Financial management of a large multisite randomized clinical trial.

PubMed

Sheffet, Alice J; Flaxman, Linda; Tom, MeeLee; Hughes, Susan E; Longbottom, Mary E; Howard, Virginia J; Marler, John R; Brott, Thomas G

2014-08-01

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years' funding ($21 112 866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2500 randomized participants at 40 sites. Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Projections of the original grant's fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant's fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2500 targeted sample size, 138 (5·5%) were randomized during the first five years and 1387 (55·5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13 845) of the projected per-patient costs ($152 992) of the fixed model. Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. © 2014 The Authors. International Journal of Stroke © 2014 World Stroke Organization.

Learning From Past Failures of Oral Insulin Trials.

PubMed

Michels, Aaron W; Gottlieb, Peter A

2018-07-01

Very recently one of the largest type 1 diabetes prevention trials using daily administration of oral insulin or placebo was completed. After 9 years of study enrollment and follow-up, the randomized controlled trial failed to delay the onset of clinical type 1 diabetes, which was the primary end point. The unfortunate outcome follows the previous large-scale trial, the Diabetes Prevention Trial-Type 1 (DPT-1), which again failed to delay diabetes onset with oral insulin or low-dose subcutaneous insulin injections in a randomized controlled trial with relatives at risk for type 1 diabetes. These sobering results raise the important question, "Where does the type 1 diabetes prevention field move next?" In this Perspective, we advocate for a paradigm shift in which smaller mechanistic trials are conducted to define immune mechanisms and potentially identify treatment responders. The stage is set for these interventions in individuals at risk for type 1 diabetes as Type 1 Diabetes TrialNet has identified thousands of relatives with islet autoantibodies and general population screening for type 1 diabetes risk is under way. Mechanistic trials will allow for better trial design and patient selection based upon molecular markers prior to large randomized controlled trials, moving toward a personalized medicine approach for the prevention of type 1 diabetes. © 2018 by the American Diabetes Association.

Study design of a cluster-randomized controlled trial to evaluate a large-scale distribution of cook stoves and water filters in Western Province, Rwanda.

PubMed

Nagel, Corey L; Kirby, Miles A; Zambrano, Laura D; Rosa, Ghislane; Barstow, Christina K; Thomas, Evan A; Clasen, Thomas F

2016-12-15

In Rwanda, pneumonia and diarrhea are the first and second leading causes of death, respectively, among children under five. Household air pollution (HAP) resultant from cooking indoors with biomass fuels on traditional stoves is a significant risk factor for pneumonia, while consumption of contaminated drinking water is a primary cause of diarrheal disease. To date, there have been no large-scale effectiveness trials of programmatic efforts to provide either improved cookstoves or household water filters at scale in a low-income country. In this paper we describe the design of a cluster-randomized trial to evaluate the impact of a national-level program to distribute and promote the use of improved cookstoves and advanced water filters to the poorest quarter of households in Rwanda. We randomly allocated 72 sectors (administratively defined units) in Western Province to the intervention, with the remaining 24 sectors in the province serving as controls. In the intervention sectors, roughly 100,000 households received improved cookstoves and household water filters through a government-sponsored program targeting the poorest quarter of households nationally. The primary outcome measures are the incidence of acute respiratory infection (ARI) and diarrhea among children under five years of age. Over a one-year surveillance period, all cases of acute respiratory infection (ARI) and diarrhea identified by health workers in the study area will be extracted from records maintained at health facilities and by community health workers (CHW). In addition, we are conducting intensive, longitudinal data collection among a random sample of households in the study area for in-depth assessment of coverage, use, environmental exposures, and additional health measures. Although previous research has examined the impact of providing household water treatment and improved cookstoves on child health, there have been no studies of national-level programs to deliver these interventions at scale in a developing country. The results of this study, the first RCT of a large-scale programmatic cookstove or household water filter intervention, will inform global efforts to reduce childhood morbidity and mortality from diarrheal disease and pneumonia. This trial is registered at Clinicaltrials.gov (NCT02239250).

Cutaneous lichen planus: A systematic review of treatments.

PubMed

Fazel, Nasim

2015-06-01

Various treatment modalities are available for cutaneous lichen planus. Pubmed, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database were searched for all the systematic reviews and randomized controlled trials related to cutaneous lichen planus. Two systematic reviews and nine relevant randomized controlled trials were identified. Acitretin, griseofulvin, hydroxychloroquine and narrow band ultraviolet B are demonstrated to be effective in the treatment of cutaneous lichen planus. Sulfasalazine is effective, but has an unfavorable safety profile. KH1060, a vitamin D analogue, is not beneficial in the management of cutaneous lichen planus. Evidence from large scale randomized trials demonstrating the safety and efficacy for many other treatment modalities used to treat cutaneous lichen planus is simply not available.

Reference Values of Within-District Intraclass Correlations of Academic Achievement by District Characteristics: Results from a Meta-Analysis of District-Specific Values

ERIC Educational Resources Information Center

Hedberg, E. C.; Hedges, Larry V.

2014-01-01

Randomized experiments are often considered the strongest designs to study the impact of educational interventions. Perhaps the most prevalent class of designs used in large scale education experiments is the cluster randomized design in which entire schools are assigned to treatments. In cluster randomized trials (CRTs) that assign schools to…

A systematic review of Investigator Global Assessment (IGA) in atopic dermatitis (AD) trials: Many options, no standards.

PubMed

Futamura, Masaki; Leshem, Yael A; Thomas, Kim S; Nankervis, Helen; Williams, Hywel C; Simpson, Eric L

2016-02-01

Investigators often use global assessments to provide a snapshot of overall disease severity in dermatologic clinical trials. Although easy to perform, the frequency of use and standardization of global assessments in studies of atopic dermatitis (AD) is unclear. We sought to assess the frequency, definitions, and methods of analysis of Investigator Global Assessment in randomized controlled trials of AD. We conducted a systematic review using all published randomized controlled trials of AD treatments in the Global Resource of Eczema Trials database (2000-2014). We determined the frequency of global scales application and defining features. Among 317 trials identified, 101 trials (32%) used an investigator-performed global assessment as an outcome measure. There was large variability in global assessments between studies in nomenclature, scale size, definitions, outcome description, and analysis. Both static and dynamic scales were identified that ranged from 4- to 7-point scales. North American studies used global assessments more commonly than studies from other countries. The search was restricted to the Global Resource of Eczema Trials database. Global assessments are used frequently in studies of AD, but their complete lack of standardized definitions and implementation preclude any meaningful comparisons between studies, which in turn impedes data synthesis to inform clinical decision-making. Standardization is urgently required. Copyright © 2015. Published by Elsevier Inc.

Age-related Cataract in a Randomized Trial of Vitamins E and C in Men

PubMed Central

Christen, William G.; Glynn, Robert J.; Sesso, Howard D.; Kurth, Tobias; MacFadyen, Jean; Bubes, Vadim; Buring, Julie E.; Manson, JoAnn E.; Michael Gaziano, J.

2010-01-01

Objective To test whether supplementation with alternate day vitamin E or daily vitamin C affects the incidence of age-related cataract in a large-scale randomized trial of men. Design Randomized, double-masked, placebo-controlled trial. Participants Eleven thousand five hundred forty-five apparently healthy US male physicians aged 50 years or older who were without a diagnosis of cataract at baseline. Intervention Participants were randomly assigned to receive 400 IU of vitamin E or placebo on alternate days, and 500 mg of vitamin C or placebo daily. Main Outcome Measure Incident cataract responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-report confirmed by medical record review. Results After 8 years of treatment and follow-up, a total of 1,174 incident cataracts were confirmed. There were 579 cataracts in the vitamin E treated group and 595 in the vitamin E placebo group (hazard ratio [HR], 0.99; 95 percent confidence interval [CI], 0.88 to 1.11). For vitamin C, there were 593 cataracts in the treated group and 581 in the placebo group (HR, 1.02; CI, 0.91 to 1.14). Conclusions In a large-scale randomized trial of US male physicians, long-term alternate day use of 400 IU of vitamin E and/or daily use of 500 mg of vitamin C had no significant beneficial or harmful effect on the risk of cataract. Application to Clinical Practice Long-term use of vitamin E and/or vitamin C supplements has no appreciable effect on cataract. PMID:21060040

The Effects of Math Video Games on Learning: A Randomized Evaluation Study with Innovative Impact Estimation Techniques. CRESST Report 841

ERIC Educational Resources Information Center

Chung, Gregory K. W. K.; Choi, Kilchan; Baker, Eva L.; Cai, Li

2014-01-01

A large-scale randomized controlled trial tested the effects of researcher-developed learning games on a transfer measure of fractions knowledge. The measure contained items similar to standardized assessments. Thirty treatment and 29 control classrooms (~1500 students, 9 districts, 26 schools) participated in the study. Students in treatment…

Culturally adaptive storytelling intervention versus didactic intervention to improve hypertension control in Vietnam: a cluster-randomized controlled feasibility trial.

PubMed

Nguyen, Hoa L; Allison, Jeroan J; Ha, Duc A; Chiriboga, Germán; Ly, Ha N; Tran, Hanh T; Nguyen, Cuong K; Dang, Diem M; Phan, Ngoc T; Vu, Nguyen C; Nguyen, Quang P; Goldberg, Robert J

2017-01-01

Vietnam is experiencing an epidemiologic transition with an increased prevalence of non-communicable diseases. Novel, large-scale, effective, and sustainable interventions to control hypertension in Vietnam are needed. We report the results of a cluster-randomized feasibility trial at 3 months follow-up conducted in Hung Yen province, Vietnam, designed to evaluate the feasibility and acceptability of two community-based interventions to improve hypertension control: a "storytelling" intervention, "We Talk about Our Hypertension," and a didactic intervention. The storytelling intervention included stories about strategies for coping with hypertension, with patients speaking in their own words, and didactic content about the importance of healthy lifestyle behaviors including salt reduction and exercise. The didactic intervention included only didactic content. The storytelling intervention was delivered by two DVDs at 3-month intervals; the didactic intervention included only one installment. The trial was conducted in four communes, equally randomized to the two interventions. The mean age of the 160 study patients was 66 years, and 54% were men. Most participants described both interventions as understandable, informative, and motivational. Between baseline and 3 months, mean systolic blood pressure declined by 8.2 mmHg (95% CI 4.1-12.2) in the storytelling group and by 5.5 mmHg (95% CI 1.4-9.5) in the didactic group. The storytelling group also reported a significant increase in hypertension medication adherence. Both interventions were well accepted in several rural communities and were shown to be potentially effective in lowering blood pressure. A large-scale randomized trial is needed to compare the effectiveness of the two interventions in controlling hypertension. ClinicalTrials.gov, NCT02483780.

Randomized Trials Built on Sand: Examples from COPD, Hormone Therapy, and Cancer

PubMed Central

Suissa, Samy

2012-01-01

The randomized controlled trial is the fundamental study design to evaluate the effectiveness of medications and receive regulatory approval. Observational studies, on the other hand, are essential to address post-marketing drug safety issues but have also been used to uncover new indications or new benefits for already marketed drugs. Hormone replacement therapy (HRT) for instance, effective for menopausal symptoms, was reported in several observational studies during the 1980s and 1990s to also significantly reduce the incidence of coronary heart disease. This claim was refuted in 2002 by the large-scale Women’s Health Initiative randomized trial. An example of a new indication for an old drug is that of metformin, an anti-diabetic medication, which is being hailed as a potential anti-cancer agent, primarily on the basis of several recent observational studies that reported impressive reductions in cancer incidence and mortality with its use. These observational studies have now sparked the conduct of large-scale randomized controlled trials currently ongoing in cancer. We show in this paper that the spectacular effects on new indications or new outcomes reported in many observational studies in chronic obstructive pulmonary disease (COPD), HRT, and cancer are the result of time-related biases, such as immortal time bias, that tend to seriously exaggerate the benefits of a drug and that eventually disappear with the proper statistical analysis. In all, while observational studies are central to assess the effects of drugs, their proper design and analysis are essential to avoid bias. The scientific evidence on the potential beneficial effects in new indications of existing drugs will need to be more carefully assessed before embarking on long and expensive unsubstantiated trials. PMID:23908838

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

PubMed

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

2016-01-14

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

Combined cognitive-strategy and task-specific training improves transfer to untrained activities in sub-acute stroke: An exploratory randomized controlled trial

PubMed Central

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

2014-01-01

Purpose The purpose of this study was to estimate the effect of the Cognitive Orientation to daily Occupational Performance (CO-OP) approach compared to usual outpatient rehabilitation on activity and participation in people less than 3 months post stroke. Methods An exploratory, single blind, randomized controlled trial with a usual care control arm was conducted. Participants referred to 2 stroke rehabilitation outpatient programs were randomized to receive either Usual Care or CO-OP. The primary outcome was actual performance of trained and untrained self-selected activities, measured using the Performance Quality Rating Scale (PQRS). Additional outcomes included the Canadian Occupational Performance Measure (COPM), the Stroke Impact Scale Participation Domain, the Community Participation Index, and the Self Efficacy Gauge. Results Thirty-five (35) eligible participants were randomized; 26 completed the intervention. Post-intervention, PQRS change scores demonstrated CO-OP had a medium effect over Usual Care on trained self-selected activities (d=0.5) and a large effect on untrained (d=1.2). At a 3 month follow-up, PQRS change scores indicated a large effect of CO-OP on both trained (d=1.6) and untrained activities (d=1.1). CO-OP had a small effect on COPM and a medium effect on the Community Participation Index perceived control and the Self-Efficacy Gauge. Conclusion CO-OP was associated with a large treatment effect on follow up performances of self-selected activities, and demonstrated transfer to untrained activities. A larger trial is warranted. PMID:25416738

Combined Cognitive-Strategy and Task-Specific Training Improve Transfer to Untrained Activities in Subacute Stroke: An Exploratory Randomized Controlled Trial.

PubMed

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

2015-07-01

The purpose of this study was to estimate the effect of the Cognitive Orientation to daily Occupational Performance (CO-OP) approach compared with usual outpatient rehabilitation on activity and participation in people <3 months poststroke. An exploratory, single-blind, randomized controlled trial, with a usual-care control arm, was conducted. Participants referred to 2 stroke rehabilitation outpatient programs were randomized to receive either usual care or CO-OP. The primary outcome was actual performance of trained and untrained self-selected activities, measured using the Performance Quality Rating Scale (PQRS). Additional outcomes included the Canadian Occupational Performance Measure (COPM), the Stroke Impact Scale Participation Domain, the Community Participation Index, and the Self-Efficacy Gauge. A total of 35 eligible participants were randomized; 26 completed the intervention. Post intervention, PQRS change scores demonstrated that CO-OP had a medium effect over usual care on trained self-selected activities (d = 0.5) and a large effect on untrained activities (d = 1.2). At a 3-month follow-up, PQRS change scores indicated a large effect of CO-OP on both trained (d = 1.6) and untrained activities (d = 1.1). CO-OP had a small effect on COPM and a medium effect on the Community Participation Index perceived control and on the Self-Efficacy Gauge. CO-OP was associated with a large treatment effect on follow-up performances of self-selected activities and demonstrated transfer to untrained activities. A larger trial is warranted. © The Author(s) 2014.

Aromatherapy for the treatment of PONV in children: a pilot RCT.

PubMed

Kiberd, Mathew B; Clarke, Suzanne K; Chorney, Jill; d'Eon, Brandon; Wright, Stuart

2016-11-09

Postoperative nausea and vomiting (PONV) is one of the most common postoperative complications of general anesthesia in pediatrics. Aromatherapy has been shown to be effective in treating PONV in adults. Given the encouraging results of the adult studies, we planned to determine feasibility of doing a large-scale study in the pediatric population. Our group conducted a pilot randomized controlled trial examining the effect of aromatherapy on post-operative nausea and vomiting in patients 4-16 undergoing ambulatory surgery at a single center. Nausea was defined as a score of 4/10 on the Baxter Retching Faces Scale (BARF scale). A clinically significant reduction was defined as a two-point reduction in Nausea. Post operatively children were administered the BARF scale in 15 min internals until discharge home or until nausea score of 4/10 or greater. Children with nausea were randomized to saline placebo group or aromatherapy QueaseEase™ (Soothing Scents, Inc, Enterprise, AL: blend of ginger, lavender, mint and spearmint). Nausea scores were recorded post intervention. A total of 162 subjects were screened for inclusion in the study. Randomization occurred in 41 subjects of which 39 were included in the final analysis. For the primary outcome, 14/18 (78 %) of controls reached primary outcome compared to 19/21 (90 %) in the aromatherapy group (p = 0.39, Eta 0.175). Other outcomes included use of antiemetic in PACU (control 44 %, aromatherapy 52 % P = 0.75, Eta 0.08), emesis (Control 11 %, 9 % aromatherapy, P = 0.87, Eta = 0.03). There was a statistically significant difference in whether subjects continued to use the intervention (control 28 %, aromatherapy 66 %, p-value 0.048, Eta 0.33). Aromatherapy had a small non-significant effect size in treating postoperative nausea and vomiting compared with control. A large-scale randomized control trial would not be feasible at our institution and would be of doubtful utility. ClinicalTrials.gov NCT02663154 .

A Data Management System Integrating Web-based Training and Randomized Trials: Requirements, Experiences and Recommendations.

PubMed

Muroff, Jordana; Amodeo, Maryann; Larson, Mary Jo; Carey, Margaret; Loftin, Ralph D

2011-01-01

This article describes a data management system (DMS) developed to support a large-scale randomized study of an innovative web-course that was designed to improve substance abuse counselors' knowledge and skills in applying a substance abuse treatment method (i.e., cognitive behavioral therapy; CBT). The randomized trial compared the performance of web-course-trained participants (intervention group) and printed-manual-trained participants (comparison group) to determine the effectiveness of the web-course in teaching CBT skills. A single DMS was needed to support all aspects of the study: web-course delivery and management, as well as randomized trial management. The authors briefly reviewed several other systems that were described as built either to handle randomized trials or to deliver and evaluate web-based training. However it was clear that these systems fell short of meeting our needs for simultaneous, coordinated management of the web-course and the randomized trial. New England Research Institute's (NERI) proprietary Advanced Data Entry and Protocol Tracking (ADEPT) system was coupled with the web-programmed course and customized for our purposes. This article highlights the requirements for a DMS that operates at the intersection of web-based course management systems and randomized clinical trial systems, and the extent to which the coupled, customized ADEPT satisfied those requirements. Recommendations are included for institutions and individuals considering conducting randomized trials and web-based training programs, and seeking a DMS that can meet similar requirements.

Review of Three Recent Randomized Trials of School-Based Mentoring: Making Sense of Mixed Findings. Social Policy Report. Volume 24, Number 3

ERIC Educational Resources Information Center

Wheeler, Marc E.; Keller, Thomas E.; DuBois, David L.

2010-01-01

Between 2007 and 2009, reports were released on the results of three separate large-scale random assignment studies of the effectiveness of school-based mentoring programs for youth. The studies evaluated programs implemented by Big Brothers Big Sisters of America (BBBSA) affiliates (Herrera et al., 2007), Communities In Schools of San Antonio,…

Pain Neurophysiology Education and Therapeutic Exercise for Patients With Chronic Low Back Pain: A Single-Blind Randomized Controlled Trial.

PubMed

Bodes Pardo, Gema; Lluch Girbés, Enrique; Roussel, Nathalie A; Gallego Izquierdo, Tomás; Jiménez Penick, Virginia; Pecos Martín, Daniel

2018-02-01

To assess the effect of a pain neurophysiology education (PNE) program plus therapeutic exercise (TE) for patients with chronic low back pain (CLBP). Single-blind randomized controlled trial. Private clinic and university. Patients with CLBP for ≥6 months (N=56). Participants were randomized to receive either a TE program consisting of motor control, stretching, and aerobic exercises (n=28) or the same TE program in addition to a PNE program (n=28), conducted in two 30- to 50-minute sessions in groups of 4 to 6 participants. The primary outcome was pain intensity rated on the numerical pain rating scale which was completed immediately after treatment and at 1- and 3-month follow-up. Secondary outcome measures were pressure pain threshold, finger-to-floor distance, Roland-Morris Disability Questionnaire, Pain Catastrophizing Scale, Tampa Scale for Kinesiophobia, and Patient Global Impression of Change. At 3-month follow-up, a large change in pain intensity (numerical pain rating scale: -2.2; -2.93 to -1.28; P<.001; d=1.37) was observed for the PNE plus TE group, and a moderate effect size was observed for the secondary outcome measures. Combining PNE with TE resulted in significantly better results for participants with CLBP, with a large effect size, compared with TE alone. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Efficacy of electroacupuncture for symptoms of menopausal transition: study protocol for a randomized controlled trial.

PubMed

Liu, Zhishun; Wang, Yang; Xu, Huanfang; Wu, Jiani; He, Liyun; Jiang, John Yi; Yan, Shiyan; Du, Ruosang; Liu, Baoyan

2014-06-21

Previous studies have shown that acupuncture can alleviate postmenopausal symptoms, such as hot flashes, but few studies have assessed symptoms during the menopausal transition (MT) period. Thus, the effect of acupuncture upon MT symptoms is unclear. We designed a large-scale trial aimed at evaluating the efficacy of electroacupuncture for MT symptoms compared with sham electroacupuncture and at observing the safety of electroacupuncture. In this multicenter randomized controlled trial, 360 women will be randomized to either an electroacupuncture group or a sham electroacupuncture group. During the 8-week-long treatment, a menopause rating scale, average 24-hour hot flash score, Menopause-Specific Quality of Life Questionnaire score, and level of female hormones will be observed. Follow-ups at the 20th and 32nd week will be made. Though there is no completely inert placebo acupuncture and blinding is difficult in acupuncture trials, the placebo effect of EA can still be partially excluded in this study. For the placebo control, we use non-points and a tailor-made sham needle. This needle is different from a retractable needle, which is usually used for sham acupuncture. The needle in this trial is more simply constructed and more acceptable to Chinese people. We expect to evaluate the efficacy of electroacupuncture for MT symptoms and clarify its effect on these symptoms. ClinicalTrials.gov Identifier: NCT01849172 (Date of registration: 05/05/2013).

Open-label placebo treatment in chronic low back pain: a randomized controlled trial

PubMed Central

Carvalho, Cláudia; Caetano, Joaquim Machado; Cunha, Lidia; Rebouta, Paula; Kaptchuk, Ted J.; Kirsch, Irving

2016-01-01

Abstract This randomized controlled trial was performed to investigate whether placebo effects in chronic low back pain could be harnessed ethically by adding open-label placebo (OLP) treatment to treatment as usual (TAU) for 3 weeks. Pain severity was assessed on three 0- to 10-point Numeric Rating Scales, scoring maximum pain, minimum pain, and usual pain, and a composite, primary outcome, total pain score. Our other primary outcome was back-related dysfunction, assessed on the Roland–Morris Disability Questionnaire. In an exploratory follow-up, participants on TAU received placebo pills for 3 additional weeks. We randomized 97 adults reporting persistent low back pain for more than 3 months' duration and diagnosed by a board-certified pain specialist. Eighty-three adults completed the trial. Compared to TAU, OLP elicited greater pain reduction on each of the three 0- to 10-point Numeric Rating Scales and on the 0- to 10-point composite pain scale (P < 0.001), with moderate to large effect sizes. Pain reduction on the composite Numeric Rating Scales was 1.5 (95% confidence interval: 1.0-2.0) in the OLP group and 0.2 (−0.3 to 0.8) in the TAU group. Open-label placebo treatment also reduced disability compared to TAU (P < 0.001), with a large effect size. Improvement in disability scores was 2.9 (1.7-4.0) in the OLP group and 0.0 (−1.1 to 1.2) in the TAU group. After being switched to OLP, the TAU group showed significant reductions in both pain (1.5, 0.8-2.3) and disability (3.4, 2.2-4.5). Our findings suggest that OLP pills presented in a positive context may be helpful in chronic low back pain. PMID:27755279

Open-label placebo treatment in chronic low back pain: a randomized controlled trial.

PubMed

Carvalho, Cláudia; Caetano, Joaquim Machado; Cunha, Lidia; Rebouta, Paula; Kaptchuk, Ted J; Kirsch, Irving

2016-12-01

This randomized controlled trial was performed to investigate whether placebo effects in chronic low back pain could be harnessed ethically by adding open-label placebo (OLP) treatment to treatment as usual (TAU) for 3 weeks. Pain severity was assessed on three 0- to 10-point Numeric Rating Scales, scoring maximum pain, minimum pain, and usual pain, and a composite, primary outcome, total pain score. Our other primary outcome was back-related dysfunction, assessed on the Roland-Morris Disability Questionnaire. In an exploratory follow-up, participants on TAU received placebo pills for 3 additional weeks. We randomized 97 adults reporting persistent low back pain for more than 3 months' duration and diagnosed by a board-certified pain specialist. Eighty-three adults completed the trial. Compared to TAU, OLP elicited greater pain reduction on each of the three 0- to 10-point Numeric Rating Scales and on the 0- to 10-point composite pain scale (P < 0.001), with moderate to large effect sizes. Pain reduction on the composite Numeric Rating Scales was 1.5 (95% confidence interval: 1.0-2.0) in the OLP group and 0.2 (-0.3 to 0.8) in the TAU group. Open-label placebo treatment also reduced disability compared to TAU (P < 0.001), with a large effect size. Improvement in disability scores was 2.9 (1.7-4.0) in the OLP group and 0.0 (-1.1 to 1.2) in the TAU group. After being switched to OLP, the TAU group showed significant reductions in both pain (1.5, 0.8-2.3) and disability (3.4, 2.2-4.5). Our findings suggest that OLP pills presented in a positive context may be helpful in chronic low back pain.

Multilingual Literacy Skill Development in Kenya: Results from Medium Scale Randomized Controlled Trials

ERIC Educational Resources Information Center

Piper, Benjamin

2016-01-01

If children do not learn how to read in the first few years of primary school, they at greater risk of dropping out. It is therefore crucial to identify and test interventions that have the potential of making a large impact, can be implemented quickly, and are affordable to be taken to scale by the Kenyan government. This paper presents the…

Buspirone versus methylphenidate in the treatment of children with attention- deficit/ hyperactivity disorder: randomized double-blind study.

PubMed

Mohammadi, Mohammad-Reza; Hafezi, Poopak; Galeiha, Ali; Hajiaghaee, Reza; Akhondzadeh, Shahin

2012-01-01

A recent randomized clinical trial showed buspirone efficacy in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children. However, results from a recent multi-site controlled clinical trial of transdermal buspirone failed to separate it from placebo in a large sample of children with ADHD. Therefore, due to these inconsistent findings, this study was designed to assess the efficacy of buspirone in the treatment of children with ADHD compared to methylphenidate in a double blind randomized clinical trial. Forty outpatients with a DSM-IV-TR diagnosis of ADHD were study population of this trial. Subjects were recruited from an outpatient child and adolescent clinic for a 6 week double blind, randomized clinical trial. All study subjects were randomly assigned to receive treatment using tablet of buspirone at a dose of 20-30 mg/day depending on weight (20 mg/day for < 30kg and 30 mg/day for > 30kg) (group 1) or methylphenidate at a dose of 20-30 mg/day depending on weight (20 mg/day for < 30kg and 30 mg/day for > 30kg (group 2) for a 6 week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent ADHD Rating Scale IV. Patients were assessed at baseline and at 21 and 42 days after the medication started. Significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores. The changes at the endpoint compared to baseline were: -8.95±8.73 (mean±SD) and -15.60±7.81 (mean±SD) for buspirone and methyphenidate, for Parent ADHD Rating Scale. The changes at the endpoint compared to baseline were: -9.80 ±7.06 (mean±SD) and -22.40±9.90 (mean±SD) for buspirone and methyphenidate, respectively for Teacher ADHD Rating Scale. The difference between the buspirone and methylphenidate groups in the frequency of side effects was not significant except for decreased appetite, headache and insomnia that were observed more frequently in the methylphenidate group. The results of this study suggest that administration of buspirone was less effective than methylphenidate in the treatment of ADHD.

Carotid artery stenting vs. carotid endarterectomy in the management of carotid artery stenosis: Lessons learned from randomized controlled trials

PubMed Central

Salem, Mohamed M.; Alturki, Abdulrahman Y.; Fusco, Matthew R.; Thomas, Ajith J.; Carter, Bob S.; Chen, Clark C.; Kasper, Ekkehard M.

2018-01-01

Background: Carotid artery stenosis, both symptomatic and asymptomatic, has been well studied with several multicenter randomized trials. The superiority of carotid endarterectomy (CEA) to medical therapy alone in both symptomatic and asymptomatic carotid artery stenosis has been well established in previous trials in the 1990s. The consequent era of endovascular carotid artery stenting (CAS) has offered another option for treating carotid artery stenosis. A series of randomized trials have now been conducted to compare CEA and CAS in the treatment of carotid artery disease. The large number of similar trials has created some confusion due to inconsistent results. Here, the authors review the trials that compare CEA and CAS in the management of carotid artery stenosis. Methods: The PubMed database was searched systematically for randomized controlled trials published in English that compared CEA and CAS. Only human studies on adult patients were assessed. The references of identified articles were reviewed for additional manuscripts to be included if inclusion criteria were met. The following terms were used during search: carotid stenosis, endarterectomy, stenting. Retrospective or single-center studies were excluded from the review. Results: Thirteen reports of seven large-scale prospective multicenter studies, comparing both interventions for symptomatic or asymptomatic extracranial carotid artery stenosis, were identified. Conclusions: While the superiority of intervention to medical management for symptomatic patients has been well established in the literatures, careful selection of asymptomatic patients for intervention should be undertaken and only be pursued after institution of appropriate medical therapy until further reports on trials comparing medical therapy to intervention in this patient group are available. PMID:29740506

Effectiveness of De Qi during acupuncture for the treatment of tinnitus: study protocol for a randomized controlled trial.

PubMed

Xie, Hui; Li, Xinrong; Lai, Jiaqin; Zhou, Yanan; Wang, Caiying; Liang, Jiao

2014-10-15

Acupuncture has been used in China to treat tinnitus for a long time. There is debate as to whether or not De Qi is a key factor in achieving the efficacy of acupuncture. However, there is no sufficient evidence obtained from randomized controlled trials to confirm the role of De Qi in the treatment of acupuncture for tinnitus. This study aims to identify the effect of De Qi for patients who receive acupuncture to alleviate tinnitus by a prospective, double-blind, randomized, sham-controlled trial. This study compares two acupuncture groups (with or without manipulation) in 292 patients with a history of subjective tinnitus. The trial will be conducted in the Teaching Hospital of Chengdu University of Traditional Chinese Medicine. In the study, the patients will be randomly assigned into two groups according to a computer-generated randomization list and assessed prior to treatment. Then, they will receive 5 daily sessions of 30 minutes each time for 4 consecutive weeks and undergo a 12-week follow-up phase. The administration of acupuncture follows the guidelines for clinical research on acupuncture (WHO Regional Publication, Western Pacific Series Number 15, 1995), and is performed double-blind by physicians well-trained in acupuncture. The measures of outcome include the subjective symptoms scores and quantitative sensations of De Qi evaluated by Visual Analog Scales (VAS) and the Chinese version of the 'modified' Massachusetts General Hospital Acupuncture Sensation Scale (C-MMASS). Furthermore, adverse events are recorded and analyzed. If any subjects are withdrawn from the trial, intention-to-treat analysis (ITT) and per-protocol (PP) analysis will be performed. The key features of this trial include the randomization procedures, large sample and the standardized protocol to evaluate De Qi qualitatively and quantitatively in the treatment of acupuncture for tinnitus. The trial will be the first study with a high evidence level in China to assess the efficacy of De Qi in the treatment of tinnitus in a randomized, double-blind, sham-controlled manner. Chinese Clinical Trial Registry: ChiCTR-TRC-14004720 (6 May 2014).

Sertraline Versus Placebo in Patients with Major Depressive Disorder Undergoing Hemodialysis: A Randomized, Controlled Feasibility Trial.

PubMed

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

2017-02-07

Depression is common in patients on hemodialysis, but data on the benefits and risks of antidepressants in this setting are limited. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of sertraline over 6 months in patients on hemodialysis with depression to determine study feasibility, safety, and effectiveness. Patients on hemodialysis at five United Kingdom renal centers completed the Beck Depression Inventory II. Those scoring ≥16 and not already on treatment for depression were invited to undergo diagnostic interview to confirm major depressive disorder. Eligible patients with major depressive disorder were randomized to receive the study medication-either sertraline or placebo. Outcomes included recruitment and dropout rates, change in the Montgomery-Asberg Depression Rating Scale and Beck Depression Inventory II, and qualitative information to guide design of a large-scale trial. In total, 709 patients were screened and enrolled between April of 2013 and October of 2014; 231 (32.6%) had Beck Depression Inventory II scores ≥16, and 68 (29%) of these were already receiving treatment for depression. Sixty-three underwent diagnostic interview, 37 were diagnosed with major depressive disorder, and 30 were randomized; 21 completed the trial: eight of 15 on sertraline and 13 of 15 on placebo (P=0.05). Dropouts due to adverse and serious adverse events were greater in the sertraline group. All occurred in the first 3 months. Over 6 months, depression scores improved in both groups. Beck Depression Inventory II score fell from 29.1±8.4 to 17.3±12.4 (P<0.001), and Montgomery-Asberg Depression Rating Scale score fell from 24.5±4.1 to 10.3±5.8 (P<0.001). There were no differences between sertraline and placebo groups. Although small, this is the largest randomized trial to date of antidepressant medication in patients on hemodialysis. Our results highlight recruitment issues. No benefit was observed, but trial size and the substantial dropout render consideration of benefit inconclusive. A definitive trial could use shorter follow-up and include depressed patients already taking antidepressants. Copyright © 2017 by the American Society of Nephrology.

Micro-Loans, Insecticide-Treated Bednets, and Malaria: Evidence from a Randomized Controlled Trial in Orissa, India.

PubMed

Tarozzi, Alessandro; Mahajan, Aprajit; Blackburn, Brian; Kopf, Dan; Krishnan, Lakshmi; Yoong, Joanne

2014-07-01

We describe findings from the first large-scale cluster randomized controlled trial in a developing country that evaluates the uptake of a health-protecting technology, insecticide-treated bednets (ITNs), through micro-consumer loans, as compared to free distribution and control conditions. Despite a relatively high price, 52 percent of sample households purchased ITNs, highlighting the role of liquidity constraints in explaining earlier low adoption rates. We find mixed evidence of improvements in malaria indices. We interpret the results and their implications within the debate about cost sharing, sustainability and liquidity constraints in public health initiatives in developing countries.

Nurse Family Partnership: Comparing Costs per Family in Randomized Trials Versus Scale-Up.

PubMed

Miller, Ted R; Hendrie, Delia

2015-12-01

The literature that addresses cost differences between randomized trials and full-scale replications is quite sparse. This paper examines how costs differed among three randomized trials and six statewide scale-ups of nurse family partnership (NFP) intensive home visitation to low income first-time mothers. A literature review provided data on pertinent trials. At our request, six well-established programs reported their total expenditures. We adjusted the costs to national prices based on mean hourly wages for registered nurses and then inflated them to 2010 dollars. A centralized data system provided utilization. Replications had fewer home visits per family than trials (25 vs. 31, p = .05), lower costs per client ($8860 vs. $12,398, p = .01), and lower costs per visit ($354 vs. $400, p = .30). Sample size limited the significance of these differences. In this type of labor intensive program, costs probably were lower in scale-up than in randomized trials. Key cost drivers were attrition and the stable caseload size possible in an ongoing program. Our estimates reveal a wide variation in cost per visit across six state programs, which suggests that those planning replications should not expect a simple rule to guide cost estimations for scale-ups. Nevertheless, NFP replications probably achieved some economies of scale.

Evaluating the Health Impact of Large-Scale Public Policy Changes: Classical and Novel Approaches

PubMed Central

Basu, Sanjay; Meghani, Ankita; Siddiqi, Arjumand

2018-01-01

Large-scale public policy changes are often recommended to improve public health. Despite varying widely—from tobacco taxes to poverty-relief programs—such policies present a common dilemma to public health researchers: how to evaluate their health effects when randomized controlled trials are not possible. Here, we review the state of knowledge and experience of public health researchers who rigorously evaluate the health consequences of large-scale public policy changes. We organize our discussion by detailing approaches to address three common challenges of conducting policy evaluations: distinguishing a policy effect from time trends in health outcomes or preexisting differences between policy-affected and -unaffected communities (using difference-in-differences approaches); constructing a comparison population when a policy affects a population for whom a well-matched comparator is not immediately available (using propensity score or synthetic control approaches); and addressing unobserved confounders by utilizing quasi-random variations in policy exposure (using regression discontinuity, instrumental variables, or near-far matching approaches). PMID:28384086

Spa therapy and balneotherapy for treating low back pain: meta-analysis of randomized trials.

PubMed

Pittler, M H; Karagülle, M Z; Karagülle, M; Ernst, E

2006-07-01

Low back pain is a major public health concern and complementary treatments are frequently used for this condition. The objective of this systematic review and meta-analysis was to assess the evidence for or against the effectiveness of spa therapy and balneotherapy for treating low back pain. Systematic searches were conducted on Medline, Embase, Amed Cochrane Central, the UK National Research Register and ClincalTrials.gov (all until July 2005). Hand searches were performed and experts contacted. Methodological quality was assessed using a standard scale. Five randomized clinical trials met all inclusion criteria. Quantitative data synthesis was performed. The data for spa therapy, assessed on a 100 mm visual analogue scale (VAS), suggest significant beneficial effects compared with waiting list control groups (weighted mean difference 26.6 mm, 95% confidence interval 20.4-32.8, n=442) for patients with chronic low back pain. For balneotherapy the data, assessed on a 100 mm VAS, also suggest beneficial effects compared with control groups (weighted mean difference 18.8 mm, 95% confidence interval 10.3-27.3, n=138). Even though the data are scarce, there is encouraging evidence suggesting that spa therapy and balneotherapy may be effective for treating patients with low back pain. These data are not compelling but warrant rigorous large-scale trials.

Feasibility, design and conduct of a pragmatic randomized controlled trial to reduce overweight and obesity in children: The electronic games to aid motivation to exercise (eGAME) study

PubMed Central

Maddison, Ralph; Foley, Louise; Ni Mhurchu, Cliona; Jull, Andrew; Jiang, Yannan; Prapavessis, Harry; Rodgers, Anthony; Vander Hoorn, Stephen; Hohepa, Maea; Schaaf, David

2009-01-01

Background Childhood obesity has reached epidemic proportions in developed countries. Sedentary screen-based activities such as video gaming are thought to displace active behaviors and are independently associated with obesity. Active video games, where players physically interact with images onscreen, may have utility as a novel intervention to increase physical activity and improve body composition in children. The aim of the Electronic Games to Aid Motivation to Exercise (eGAME) study is to determine the effects of an active video game intervention over 6 months on: body mass index (BMI), percent body fat, waist circumference, cardio-respiratory fitness, and physical activity levels in overweight children. Methods/Design Three hundred and thirty participants aged 10–14 years will be randomized to receive either an active video game upgrade package or to a control group (no intervention). Discussion An overview of the eGAME study is presented, providing an example of a large, pragmatic randomized controlled trial in a community setting. Reflection is offered on key issues encountered during the course of the study. In particular, investigation into the feasibility of the proposed intervention, as well as robust testing of proposed study procedures is a critical step prior to implementation of a large-scale trial. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12607000632493 PMID:19450288

Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial.

PubMed

Jüttler, Eric; Schwab, Stefan; Schmiedek, Peter; Unterberg, Andreas; Hennerici, Michael; Woitzik, Johannes; Witte, Steffen; Jenetzky, Ekkehart; Hacke, Werner

2007-09-01

Decompressive surgery (hemicraniectomy) for life-threatening massive cerebral infarction represents a controversial issue in neurocritical care medicine. We report here the 30-day mortality and 6- and 12-month functional outcomes from the DESTINY trial. DESTINY (ISRCTN01258591) is a prospective, multicenter, randomized, controlled, clinical trial based on a sequential design that used mortality after 30 days as the first end point. When this end point was reached, patient enrollment was interrupted as per protocol until recalculation of the projected sample size was performed on the basis of the 6-month outcome (primary end point=modified Rankin Scale score, dichotomized to 0 to 3 versus 4 to 6). All analyses were based on intention to treat. A statistically significant reduction in mortality was reached after 32 patients had been included: 15 of 17 (88%) patients randomized to hemicraniectomy versus 7 of 15 (47%) patients randomized to conservative therapy survived after 30 days (P=0.02). After 6 and 12 months, 47% of patients in the surgical arm versus 27% of patients in the conservative treatment arm had a modified Rankin Scale score of 0 to 3 (P=0.23). DESTINY showed that hemicraniectomy reduces mortality in large hemispheric stroke. With 32 patients included, the primary end point failed to demonstrate statistical superiority of hemicraniectomy, and the projected sample size was calculated to 188 patients. Despite this failure to meet the primary end point, the steering committee decided to terminate the trial in light of the results of the joint analysis of the 3 European hemicraniectomy trials.

Rationale and baseline characteristics of PREVENT: a second-generation intervention trial in subjects at-risk (prodromal) of developing first-episode psychosis evaluating cognitive behavior therapy, aripiprazole, and placebo for the prevention of psychosis.

PubMed

Bechdolf, Andreas; Müller, Hendrik; Stützer, Hartmut; Wagner, Michael; Maier, Wolfgang; Lautenschlager, Marion; Heinz, Andreas; de Millas, Walter; Janssen, Birgit; Gaebel, Wolfgang; Michel, Tanja Maria; Schneider, Frank; Lambert, Martin; Naber, Dieter; Brüne, Martin; Krüger-Özgürdal, Seza; Wobrock, Thomas; Riedel, Michael; Klosterkötter, Joachim

2011-09-01

Antipsychotics, cognitive behavioral therapy (CBT), and omega-3-fatty acids have been found superior to control conditions as regards prevention of psychosis in people at-risk of first-episode psychosis. However, no large-scale trial evaluating the differential efficacy of CBT and antipsychotics has been performed yet. In PREVENT, we evaluate CBT, aripiprazole, and clinical management (CM) as well as placebo and CM for the prevention of psychosis in a randomized, double-blind, placebo-controlled trial with regard to the antipsychotic intervention and a randomized controlled trial with regard to the CBT intervention with blinded ratings. The hypotheses are first that CBT and aripiprazole and CM are superior to placebo and CM and second that CBT is not inferior to aripiprazole and CM combined. The primary outcome is transition to psychosis. By November 2010, 156 patients were recruited into the trial. The subjects were substantially functionally compromised (Social and Occupational Functioning Assessment Scale mean score 52.5) and 78.3% presented with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition axis I comorbid diagnosis. Prior to randomization, 51.5% of the participants preferred to be randomized into the CBT arm, whereas only 12.9% preferred pharmacological treatment. First, assessments of audiotaped treatment sessions confirmed the application of CBT-specific skills in the CBT condition and the absence of those in CM. The overall quality rating of the CBT techniques applied in the CBT condition was good. When the final results of the trial are available, PREVENT will substantially expand the current limited evidence base for best clinical practice in people at-risk (prodromal) of first-episode psychosis.

What Have Researchers Learned from Project STAR?

ERIC Educational Resources Information Center

Schanzenbach, Diane Whitmore

2007-01-01

Project STAR (Student/Teacher Achievement Ratio) was a large-scale randomized trial of reduced class sizes in kindergarten through the third grade. Because of the scope of the experiment, it has been used in many policy discussions. For example, the California statewide class-size-reduction policy was justified, in part, by the successes of…

Replicating Experimental Impact Estimates Using a Regression Discontinuity Approach. NCEE 2012-4025

ERIC Educational Resources Information Center

Gleason, Philip M.; Resch, Alexandra M.; Berk, Jillian A.

2012-01-01

This NCEE Technical Methods Paper compares the estimated impacts of an educational intervention using experimental and regression discontinuity (RD) study designs. The analysis used data from two large-scale randomized controlled trials--the Education Technology Evaluation and the Teach for America Study--to provide evidence on the performance of…

Short- and Long-Term Changes in Health-Related Quality of Life with Weight Loss: Results from a Randomized Controlled Trial.

PubMed

Pearl, Rebecca L; Wadden, Thomas A; Tronieri, Jena Shaw; Berkowitz, Robert I; Chao, Ariana M; Alamuddin, Naji; Leonard, Sharon M; Carvajal, Raymond; Bakizada, Zayna M; Pinkasavage, Emilie; Gruber, Kathryn A; Walsh, Olivia A; Alfaris, Nasreen

2018-06-01

The objective of this study was to determine the effects of weight loss and weight loss maintenance (WLM) on weight-specific health-related quality of life in a 66-week trial. Adults with obesity (N = 137, 86.1% female, 68.6% black, mean age = 46.1 years) who had lost ≥ 5% of initial weight in a 14-week intensive lifestyle intervention/low-calorie diet (LCD) program were randomly assigned to lorcaserin or placebo for an additional 52-week WLM program. The Impact of Weight on Quality of Life-Lite (IWQOL-Lite) scale (including five subscales), Patient Health Questionnaire-9 (depression), and Perceived Stress Scale were administered at the start of the 14-week LCD program, randomization, and week 52 of the randomized controlled trial (i.e., 66 weeks total). Significant improvements in all outcomes, except weight-related public distress, were found following the 14-week LCD program (P values < 0.05). Improvements were largely maintained during the 52-week randomized controlled trial, despite weight regain of 2.0 to 2.5 kg across treatment groups. Participants who lost ≥ 10% of initial weight achieved greater improvements in physical function, self-esteem, sexual life, and the IWQOL-Lite total score than those who lost < 5% and did not differ from those who lost 5% to 9.9%. Improvements in weight-specific health-related quality of life were achieved with moderate weight loss and were sustained during WLM. © 2018 The Obesity Society.

Conducting pilot and feasibility studies.

PubMed

Cope, Diane G

2015-03-01

Planning a well-designed research study can be tedious and laborious work. However, this process is critical and ultimately can produce valid, reliable study findings. Designing a large-scale randomized, controlled trial (RCT)-the gold standard in quantitative research-can be even more challenging. Even the most well-planned study potentially can result in issues with research procedures and design, such as recruitment, retention, or methodology. One strategy that may facilitate sound study design is the completion of a pilot or feasibility study prior to the initiation of a larger-scale trial. This article will discuss pilot and feasibility studies, their advantages and disadvantages, and implications for oncology nursing research. 
.

Differential effects of antipsychotic drugs on insight in first episode schizophrenia: Data from the European First-Episode Schizophrenia Trial (EUFEST).

PubMed

Pijnenborg, G H M; Timmerman, M E; Derks, E M; Fleischhacker, W W; Kahn, R S; Aleman, A

2015-06-01

Although antipsychotics are widely prescribed, their effect of on improving poor illness insight in schizophrenia has seldom been investigated and therefore remains uncertain. This paper examines the effects of low dose haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on insight in first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. The effects of five antipsychotic drugs in first episode psychosis on insight were compared in a large scale open randomized controlled trial conducted in 14 European countries: the European First-Episode Schizophrenia Trial (EUFEST). Patients with at least minimal impairments in insight were included in the present study (n=455). Insight was assessed with item G12 of the Positive and Negative Syndrome Scale (PANSS), administered at baseline and at 1, 3, 6, 9, and 12 months after randomization. The use of antipsychotics was associated with clear improvements in insight over and above improvements in other symptoms. This effect was most pronounced in the first three months of treatment, with quetiapine being significantly less effective than other drugs. Effects of spontaneous improvement cannot be ruled out due to the lack of a placebo control group, although such a large spontaneous improvement of insight would seem unlikely. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Efficacy and Safety of Sipjeondaebo-Tang for Anorexia in Patients with Cancer: A Pilot, Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Cheon, Chunhoo; Yoo, Jeong-Eun; Yoo, Hwa-Seung; Cho, Chong-Kwan; Kang, Sohyeon; Kim, Mia; Jang, Bo-Hyoung; Shin, Yong-Cheol; Ko, Seong-Gyu

2017-01-01

Anorexia occurs in about half of cancer patients and is associated with high mortality rate. However, safe and long-term use of anorexia treatment is still an unmet need. The purpose of the present study was to examine the feasibility of Sipjeondaebo-tang (Juzen-taiho-to, Shi-Quan-Da-Bu-Tang) for cancer-related anorexia. A total of 32 participants with cancer anorexia were randomized to either Sipjeondaebo-tang group or placebo group. Participants were given 3 g of Sipjeondaebo-tang or placebo 3 times a day for 4 weeks. The primary outcome was a change in the Anorexia/Cachexia Subscale of Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The secondary outcomes included Visual Analogue Scale (VAS) of anorexia, FAACT scale, and laboratory tests. Anorexia and quality of life measured by FAACT and VAS were improved after 4 weeks of Sipjeondaebo-tang treatment. However, there was no significant difference between changes of Sipjeondaebo-tang group and placebo group. Sipjeondaebo-tang appears to have potential benefit for anorexia management in patients with cancer. Further large-scale studies are needed to ensure the efficacy. This trial is registered with ClinicalTrials.gov NCT02468141.

Methodological Reporting Quality of Randomized Controlled Trials in 3 Leading Diabetes Journals From 2011 to 2013 Following CONSORT Statement: A System Review.

PubMed

Zhai, Xiao; Wang, Yiran; Mu, Qingchun; Chen, Xiao; Huang, Qin; Wang, Qijin; Li, Ming

2015-07-01

To appraise the current reporting methodological quality of randomized clinical trials (RCTs) in 3 leading diabetes journals.We systematically searched the literature for RCTs in Diabetes Care, Diabetes and Diabetologia from 2011 to 2013.Characteristics were extracted based on Consolidated Standards of Reporting Trials (CONSORT) statement. Generation of allocation, concealment of allocation, intention-to-treat (ITT) analysis and handling of dropouts were defined as primary outcome and "low risk of bias." Sample size calculation, type of intervention, country, number of patients, funding source were also revealed and descriptively reported. Trials were compared among journals, study years, and other characters.A total of 305 RCTs were enrolled in this study. One hundred eight (35.4%) trials reported adequate generation of allocation, 87 (28.5%) trials reported adequate concealment of allocation, 53 (23.8%) trials used ITT analysis, and 130 (58.3%) trials were adequate in handling of dropouts. Only 15 (4.9%) were "low risk of bias" trials. Studies at a large scale (n > 100) or from European presented with more "low risk of bias" trials than those at a small scale (n ≤ 100) or from other regions. No improvements were found in these 3 years.This study shows that methodological reporting quality of RCTs in the major diabetes journals remains suboptimal. It can be further improved to meet and keep up with the standards of the CONSORT statement.

Evaluation of XIENCE V everolimus-eluting and Taxus Express2 paclitaxel-eluting coronary stents in patients with jailed side branches from the SPIRIT IV trial at 2 years.

PubMed

Forrest, John K; Lansky, Alexandra J; Meller, Stephanie M; Hou, Liming; Sood, Poornima; Applegate, Robert J; Wang, John C; Skelding, Kimberly A; Shah, Aakar; Kereiakes, Dean J; Sudhir, Krishnankutty; Cristea, Ecaterina; Yaqub, Manejeh; Stone, Gregg W

2013-06-01

The aim of this study was to determine whether patients from the Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions (SPIRIT) IV trial who underwent percutaneous coronary intervention, who had target lesions with jailed side branches, had improved clinical outcomes when treated with the XIENCE V versus Taxus Express(2) drug-eluting stent. In the SPIRIT III randomized trial, patients with target lesions with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had lower 2-year rates of major adverse cardiac events. The SPIRIT IV trial represents a larger more diverse patient population compared with SPIRIT III. In the large-scale, prospective, multicenter, randomized SPIRIT IV trial, 3,687 patients who underwent coronary stenting with up to 3 de novo native coronary artery lesions were randomized 2:1 to receive XIENCE V versus Taxus Express(2) stents. Two-year clinical outcomes of patients with or without jailed side branches after stenting were compared. A jailed side branch was defined as any side branch >1.0 mm in diameter within the target segment being stented, excluding bifurcations deemed to require treatment. Of the 3,687 patients in SPIRIT IV, a total of 1,426 had side branches that were jailed during angioplasty of the target lesion. Patients with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had significantly lower 2-year rates of target lesion failure (6.5% vs 11.9%, p = 0.001), major adverse cardiac events (6.6% vs 12.2%, p = 0.0008), ischemia-driven target vessel revascularization (4.1% vs 7.9%, p = 0.004), and stent thrombosis (0.6% vs 2.8%, p = 0.001). In conclusion, patients with jailed side branches after stenting with XIENCE V compared to Taxus Express(2) devices had superior clinical outcomes at 2 years in the large-scale randomized SPIRIT IV trial. Copyright © 2013 Elsevier Inc. All rights reserved.

Massage Therapy for Pain and Function in Patients With Arthritis: A Systematic Review of Randomized Controlled Trials.

PubMed

Nelson, Nicole L; Churilla, James R

2017-09-01

Massage therapy is gaining interest as a therapeutic approach to managing osteoarthritis and rheumatoid arthritis symptoms. To date, there have been no systematic reviews investigating the effects of massage therapy on these conditions. Systematic review was used. The primary aim of this review was to critically appraise and synthesize the current evidence regarding the effects of massage therapy as a stand-alone treatment on pain and functional outcomes among those with osteoarthritis or rheumatoid arthritis. Relevant randomized controlled trials were searched using the electronic databases Google Scholar, MEDLINE, and PEDro. The PEDro scale was used to assess risk of bias, and the quality of evidence was assessed with the GRADE approach. This review found seven randomized controlled trials representing 352 participants who satisfied the inclusion criteria. Risk of bias ranged from four to seven. Our results found low- to moderate-quality evidence that massage therapy is superior to nonactive therapies in reducing pain and improving certain functional outcomes. It is unclear whether massage therapy is more effective than other forms of treatment. There is a need for large, methodologically rigorous randomized controlled trials investigating the effectiveness of massage therapy as an intervention for individuals with arthritis.

Effects of beta-blocker therapy on mortality in patients with heart failure. A systematic overview of randomized controlled trials.

PubMed

Doughty, R N; Rodgers, A; Sharpe, N; MacMahon, S

1997-04-01

Several randomized trials have reported that beta-blocker therapy improves left ventricular function and reduces the rate of hospitalization in patients with congestive heart failure. However, most trials were individually too small to assess reliably the effects of treatment on mortality. In these circumstances a systematic overview of all trials of beta-blocker therapy in patients with congestive heart failure may provide the most reliable guide to treatment effects. Details were sought from all completed randomized trials of oral beta-blocker therapy in patients with heart failure of any aetiology. In particular, data on mortality were sought from all randomized patients for the scheduled treatment period. The typical effect of treatment on mortality was estimated from an overview in which the results of all individual trials were combined using standard statistical methods. Twenty-four randomized trials, involving 3141 patients with stable congestive heart failure were identified. Complete data on mortality were obtained from all studies, and a total of 297 deaths were documented during an average of 13 months of follow-up. Overall, there was a 31% reduction in the odds of death among patients assigned a beta-blocker (95% confidence interval 11 to 46%, 2P = 0.0035), representing an absolute reduction in mean annual mortality from 9.7% to 7.5%. The effects on mortality of vasodilating beta-blockers (47% reduction SD 15), principally carvedilol, were non-significantly greater (2P = 0.09) than those of standard agents (18% reduction SD 15), principally metoprolol. Beta-blocker therapy is likely to reduce mortality in patients with heart failure. However, large-scale, long-term randomized trials are still required to confirm and quantify more precisely the benefit suggested by this overview.

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.

Low-dose aspirin in polycythaemia vera: a pilot study. Gruppo Italiano Studio Policitemia (GISP).

PubMed

1997-05-01

In this pilot study, aimed at exploring the feasibility of a large-scale trial of low-dose aspirin in polycythaemia vera (PV), 112 PV patients (42 females, 70 males. aged 17-80 years) were selected for not having a clear indication for, or contraindication to, aspirin treatment and randomized to receive oral aspirin (40 mg/d) or placebo. Follow-up duration was 16 +/- 6 months. Measurements of thromboxane A2 production during whole blood clotting demonstrated complete inhibition of platelet cyclooxygenase activity in patients receiving aspirin. Aspirin administration was not associated with any bleeding complication. Within the limitations of the small sample size, this study indicates that a biochemically effective regimen of antiplatelet therapy is well tolerated in patients with polycythaemia vera and that a large-scale placebo-controlled trial is feasible.

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.

Fidelity of Implementation in a Large-Scale, Randomized, Field Trial: Identifying the Critical Components of Values Affirmation

ERIC Educational Resources Information Center

Bradley, Dominique; Crawford, Evan; Dahill-Brown, Sara E.

2015-01-01

Several studies suggest that values-affirmation can serve as a simple, yet powerful, tool for dramatically reducing achievement gaps. Because subtle variations in implementation procedures may explain some of the variation in these findings, it is crucial for researchers to measure the fidelity with which interventions are implemented. The authors…

Impact of a Large-Scale Science Intervention Focused on English Language Learners

ERIC Educational Resources Information Center

Llosa, Lorena; Lee, Okhee; Jiang, Feng; Haas, Alison; O'Connor, Corey; Van Booven, Christopher D.; Kieffer, Michael J.

2016-01-01

The authors evaluated the effects of P-SELL, a science curricular and professional development intervention for fifth-grade students with a focus on English language learners (ELLs). Using a randomized controlled trial design with 33 treatment and 33 control schools across three school districts in one state, we found significant and meaningfully…

Follow-up of colorectal cancer patients after resection with curative intent-the GILDA trial.

PubMed

Grossmann, Erik M; Johnson, Frank E; Virgo, Katherine S; Longo, Walter E; Fossati, Rolando

2004-01-01

Surgery remains the primary treatment of colorectal cancer. Data are lacking to delineate the optimal surveillance strategy following resection. A large-scale multi-center European study is underway to address this issue (Gruppo Italiano di Lavoro per la Diagnosi Anticipata-GILDA). Following primary surgery with curative intent, stratification, and randomization at GILDA headquarters, colon cancer patients are then assigned to a more intensive or less intensive surveillance regimen. Rectal cancer patients undergoing curative resection are similarly randomized, with their follow-up regimens placing more emphasis on detection of local recurrence. Target recruitment for the study will be 1500 patients to achieve a statistical power of 80% (assuming an alpha of 0.05 and a hazard-rate reduction of >24%). Since the trial opened in 1998, 985 patients have been randomized from 41 centers as of February 2004. There were 496 patients randomized to the less intensive regimens, and 489 randomized to the more intensive regimens. The mean duration of follow-up is 14 months. 75 relapses (15%) and 32 deaths (7%) had been observed in the two more intensive follow-up arms, while 64 relapses (13%) and 24 deaths (5%) had been observed in the two less intensive arms as of February 2004. This trial should provide the first evidence based on an adequately powered randomized trial to determine the optimal follow-up strategy for colorectal cancer patients. This trial is open to US centers, and recruitment continues.

Effect of joint mobilization techniques for primary total knee arthroplasty: Study protocol for a randomized controlled trial.

PubMed

Xu, Jiao; Zhang, Juan; Wang, Xue-Qiang; Wang, Xuan-Lin; Wu, Ya; Chen, Chan-Cheng; Zhang, Han-Yu; Zhang, Zhi-Wan; Fan, Kai-Yi; Zhu, Qiang; Deng, Zhi-Wei

2017-12-01

Total knee arthroplasty (TKA) has become the most preferred procedure by patients for the relief of pain caused by knee osteoarthritis. TKA patients aim a speedy recovery after the surgery. Joint mobilization techniques for rehabilitation have been widely used to relieve pain and improve joint mobility. However, relevant randomized controlled trials showing the curative effect of these techniques remain lacking to date. Accordingly, this study aims to investigate whether joint mobilization techniques are valid for primary TKA. We will manage a single-blind, prospective, randomized, controlled trial of 120 patients with unilateral TKA. Patients will be randomized into an intervention group, a physical modality therapy group, and a usual care group. The intervention group will undergo joint mobilization manipulation treatment once a day and regular training twice a day for a month. The physical modality therapy group will undergo physical therapy once a day and regular training twice a day for a month. The usual care group will perform regular training twice a day for a month. Primary outcome measures will be based on the visual analog scale, the knee joint Hospital for Special Surgery score, range of motion, surrounded degree, and adverse effect. Secondary indicators will include manual muscle testing, 36-Item Short Form Health Survey, Berg Balance Scale function evaluation, Pittsburgh Sleep Quality Index, proprioception, and muscle morphology. We will direct intention-to-treat analysis if a subject withdraws from the trial. The important features of this trial for joint mobilization techniques in primary TKA are randomization procedures, single-blind, large sample size, and standardized protocol. This study aims to investigate whether joint mobilization techniques are effective for early TKA patients. The result of this study may serve as a guide for TKA patients, medical personnel, and healthcare decision makers. It has been registered at http://www.chictr.org.cn/showproj.aspx?proj=15262 (Identifier:ChiCTR-IOR-16009192), Registered 11 September 2016. We also could provide the correct URL of the online registry in the WHO Trial Registration. http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR-IOR-16009192.

An analysis of the effect of funding source in randomized clinical trials of second generation antipsychotics for the treatment of schizophrenia.

PubMed

Montgomery, John H; Byerly, Matthew; Carmody, Thomas; Li, Baitao; Miller, Daniel R; Varghese, Femina; Holland, Rhiannon

2004-12-01

The effect of funding source on the outcome of randomized controlled trials has been investigated in several medical disciplines; however, psychiatry has been largely excluded from such analyses. In this article, randomized controlled trials of second generation antipsychotics in schizophrenia are reviewed and analyzed with respect to funding source (industry vs. non-industry funding). A literature search was conducted for randomized, double-blind trials in which at least one of the tested treatments was a second generation antipsychotic. In each study, design quality and study outcome were assessed quantitatively according to rating scales. Mean quality and outcome scores were compared in the industry-funded studies and non-industry-funded studies. An analysis of the primary author's affiliation with industry was similarly performed. Results of industry-funded studies significantly favored second generation over first generation antipsychotics when compared to non-industry-funded studies. Non-industry-funded studies showed a trend toward higher quality than industry-funded studies; however, the difference between the two was not significant. Also, within the industry-funded studies, outcomes of trials involving first authors employed by industry sponsors demonstrated a trend toward second generation over first generation antipsychotics to a greater degree than did trials involving first authors employed outside the industry (p=0.05). While the retrospective design of the study limits the strength of the findings, the data suggest that industry bias may occur in randomized controlled trials in schizophrenia. There appears to be several sources by which bias may enter clinical research, including trial design, control of data analysis and multiplicity/redundancy of trials.

Using the infrastructure of a conditional cash transfer program to deliver a scalable integrated early child development program in Colombia: cluster randomized controlled trial.

PubMed

Attanasio, Orazio P; Fernández, Camila; Fitzsimons, Emla O A; Grantham-McGregor, Sally M; Meghir, Costas; Rubio-Codina, Marta

2014-09-29

To assess the effectiveness of an integrated early child development intervention, combining stimulation and micronutrient supplementation and delivered on a large scale in Colombia, for children's development, growth, and hemoglobin levels. Cluster randomized controlled trial, using a 2 × 2 factorial design, with municipalities assigned to one of four groups: psychosocial stimulation, micronutrient supplementation, combined intervention, or control. 96 municipalities in Colombia, located across eight of its 32 departments. 1420 children aged 12-24 months and their primary carers. Psychosocial stimulation (weekly home visits with play demonstrations), micronutrient sprinkles given daily, and both combined. All delivered by female community leaders for 18 months. Cognitive, receptive and expressive language, and fine and gross motor scores on the Bayley scales of infant development-III; height, weight, and hemoglobin levels measured at the baseline and end of intervention. Stimulation improved cognitive scores (adjusted for age, sex, testers, and baseline levels of outcomes) by 0.26 of a standard deviation (P=0.002). Stimulation also increased receptive language by 0.22 of a standard deviation (P=0.032). Micronutrient supplementation had no significant effect on any outcome and there was no interaction between the interventions. No intervention affected height, weight, or hemoglobin levels. Using the infrastructure of a national welfare program we implemented the integrated early child development intervention on a large scale and showed its potential for improving children's cognitive development. We found no effect of supplementation on developmental or health outcomes. Moreover, supplementation did not interact with stimulation. The implementation model for delivering stimulation suggests that it may serve as a promising blueprint for future policy on early childhood development.Trial registration Current Controlled trials ISRCTN18991160. © Attanasio et al 2014.

Implementing collaborative primary care for depression and posttraumatic stress disorder: design and sample for a randomized trial in the U.S. military health system.

PubMed

Engel, Charles C; Bray, Robert M; Jaycox, Lisa H; Freed, Michael C; Zatzick, Doug; Lane, Marian E; Brambilla, Donald; Rae Olmsted, Kristine; Vandermaas-Peeler, Russ; Litz, Brett; Tanielian, Terri; Belsher, Bradley E; Evatt, Daniel P; Novak, Laura A; Unützer, Jürgen; Katon, Wayne J

2014-11-01

War-related trauma, posttraumatic stress disorder (PTSD), depression and suicide are common in US military members. Often, those affected do not seek treatment due to stigma and barriers to care. When care is sought, it often fails to meet quality standards. A randomized trial is assessing whether collaborative primary care improves quality and outcomes of PTSD and depression care in the US military health system. The aim of this study is to describe the design and sample for a randomized effectiveness trial of collaborative care for PTSD and depression in military members attending primary care. The STEPS-UP Trial (STepped Enhancement of PTSD Services Using Primary Care) is a 6 installation (18 clinic) randomized effectiveness trial in the US military health system. Study rationale, design, enrollment and sample characteristics are summarized. Military members attending primary care with suspected PTSD, depression or both were referred to care management and recruited for the trial (2592), and 1041 gave permission to contact for research participation. Of those, 666 (64%) met eligibility criteria, completed baseline assessments, and were randomized to 12 months of usual collaborative primary care versus STEPS-UP collaborative care. Implementation was locally managed for usual collaborative care and centrally managed for STEPS-UP. Research reassessments occurred at 3-, 6-, and 12-months. Baseline characteristics were similar across the two intervention groups. STEPS-UP will be the first large scale randomized effectiveness trial completed in the US military health system, assessing how an implementation model affects collaborative care impact on mental health outcomes. It promises lessons for health system change. Copyright © 2014 Elsevier Inc. All rights reserved.

Attention bias modification augments cognitive-behavioral group therapy for social anxiety disorder: a randomized controlled trial.

PubMed

Lazarov, Amit; Marom, Sofi; Yahalom, Naomi; Pine, Daniel S; Hermesh, Haggai; Bar-Haim, Yair

2017-12-20

Cognitive-behavioral group therapy (CBGT) is a first-line treatment for social anxiety disorder (SAD). However, since many patients remain symptomatic post-treatment, there is a need for augmenting procedures. This randomized controlled trial (RCT) examined the potential augmentation effect of attention bias modification (ABM) for CBGT. Fifty patients with SAD from three therapy groups were randomized to receive an 18-week standard CBGT with either ABM designed to shift attention away from threat (CBGT + ABM), or a placebo protocol not designed to modify threat-related attention (CBGT + placebo). Therapy groups took place in a large mental health center. Clinician and self-report measures of social anxiety and depression were acquired pre-treatment, post-treatment, and at 3-month follow-up. Attention bias was assessed at pre- and post-treatment. Patients randomized to the CBGT + ABM group, relative to those randomized to the CBGT + placebo group, showed greater reductions in clinician-rated SAD symptoms post-treatment, with effects maintained at 3-month follow-up. Group differences were not evident for self-report or attention-bias measures, with similar reductions in both groups. Finally, reduction in attention bias did not mediate the association between group and reduction in Liebowitz Social Anxiety Scale Structured Interview (LSAS) scores. This is the first RCT to examine the possible augmenting effect of ABM added to group-based cognitive-behavioral therapy for adult SAD. Training patients' attention away from threat might augment the treatment response to standard CBGT in SAD, a possibility that could be further evaluated in large-scale RCTs.

Baduanjin Exercise for Stroke Rehabilitation: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

PubMed Central

Wang, Chaoyi; Chen, Xiaoan; Wang, Huiru

2018-01-01

Objective: The purpose of this review was to objectively evaluate the effects of Baduanjin exercise on rehabilitative outcomes in stroke patients. Methods: Both Chinese and English electronic databases were searched for potentially relevant trials. Two review authors independently screened eligible trials against the inclusion criteria, extracted data, and assessed the methodological quality by using the revised PEDro scale. Meta-analysis was only performed for balance function. Results: In total, there were eight randomized controlled trials selected in this systematic review. The aggregated result of four trials has shown a significant benefit in favor of Baduanjin on balance function (Hedges’ g = 2.39, 95% CI 2.14 to 2.65, p < 0.001, I2 = 61.54). Additionally, Baduanjin exercise effectively improved sensorimotor function of lower extremities and ability of daily activities as well as reduced depressive level, leading to improved quality of life. Conclusion: Baduanjin exercise as an adjunctive and safe method may be conducive to help stroke patients achieve the best possible short-term outcome and should be integrated with mainstream rehabilitation programs. More rigorous randomized controlled trials with long-term intervention periods among a large sample size of stroke patients are needed to draw a firm conclusion regarding the rehabilitative effects for this population. PMID:29584623

On the Effectiveness of Pop-Up English Language Glossary Accommodations for EL Students in Large-Scale Assessments

ERIC Educational Resources Information Center

Cohen, Dale; Tracy, Ryan; Cohen, Jon

2017-01-01

This study examined the effectiveness and influence on validity of a computer-based pop-up English glossary accommodation for English learners (ELs) in grades 3 and 7. In a randomized controlled trial, we administered pop-up English glossaries with audio to students taking a statewide accountability English language arts (ELA) and mathematics…

Effects of Two Scientific Inquiry Professional Development Interventions on Teaching Practice

ERIC Educational Resources Information Center

Grigg, Jeffrey; Kelly, Kimberle A.; Gamoran, Adam; Borman, Geoffrey D.

2013-01-01

In this article, we examine classroom observations from a 3-year large-scale randomized trial in the Los Angeles Unified School District (LAUSD) to investigate the extent to which a professional development initiative in inquiry science influenced teaching practices in in 4th and 5th grade classrooms in 73 schools. During the course of the study,…

A meta-analytic review of the effects of mindfulness meditation on telomerase activity.

PubMed

Schutte, Nicola S; Malouff, John M

2014-04-01

The enzyme telomerase, through its influence on telomere length, is associated with health and mortality. Four pioneering randomized control trials, including a total of 190 participants, provided information on the effect of mindfulness meditation on telomerase. A meta-analytic effect size of d=0.46 indicated that mindfulness meditation leads to increased telomerase activity in peripheral blood mononuclear cells. These results suggest the need for further large-scale trials investigating optimal implementation of mindfulness meditation to facilitate telomerase functioning. Copyright © 2014 Elsevier Ltd. All rights reserved.

Why the evidence for outpatient commitment is good enough.

PubMed

Swanson, Jeffrey W; Swartz, Marvin S

2014-06-01

After nearly three decades of studies evaluating the legal practice of involuntary outpatient commitment, there is yet little consensus about its effectiveness and only limited implementation. Debate continues over how best to assist adults with serious mental illnesses who are unable or unwilling to participate in prescribed community treatment and as a result experience repeated involuntary hospitalizations or involvement with the criminal justice system. The authors comment on the Oxford Community Treatment Order Evaluation Trial (OCTET), a recently conducted randomized trial of outpatient commitment, and discuss the limitations of the study's design for resolving the persistent question of whether compulsory treatment is more effective than purely voluntary treatment for this difficult-to-reach target population. The authors conclude that the search for a definitive and generalizable randomized trial of outpatient commitment may be a quixotic quest; the field should, rather, welcome the results of well-conducted, large-scale, quasi-experimental and naturalistic studies with rigorous multivariable statistical controls.

Dietary interventions, lifestyle changes, and dietary supplements in preventing gestational diabetes mellitus: a literature review.

PubMed

Facchinetti, Fabio; Dante, Giulia; Petrella, Elisabetta; Neri, Isabella

2014-11-01

Gestational diabetes mellitus (GDM) is associated with increased rates of fetal morbidity and mortality, both during the pregnancy and in the postnatal life. Current treatment of GDM includes diet with or without medications, but this management is expensive and poorly cost-effective for the health care systems. Strategies to prevent such condition would be preferable with respect to its treatment. The aim of this literature review was to evaluate studies reporting the efficacy of the most used approaches to prevent GDM as well as evidences of efficacy and safety of dietary supplementations. Systematic literature searches were performed in electronic databases, covering the period January 1983 to April 2014. Randomized controlled clinical trials were included. Quality of the articles was evaluated with the Jadad scale. We did not evaluate those articles that were already entered in the most recent systematic reviews, and we completed the research with the trials published thereafter. Of 55 articles identified, 15 randomized controlled trials were eligible. Quality and heterogeneity of the studies cannot allow firm conclusions. Anyway, trials in which only intake or expenditure has been targeted mostly reported negative results. On the contrary, combined lifestyle programs including diet control (orienting food intake, restricting energy intake) associated with moderate but continuous physical activity exhibit better efficacy in reducing GDM prevalence. The results from dietary supplements with myoinositol or probiotics are promising. The actual evidences provide enough arguments for implementing large-scale, high-quality randomized controlled trials looking at the possible benefits of these new approaches for preventing GDM.

Effect of Atomoxetine on Executive Function Impairments in Adults with ADHD

ERIC Educational Resources Information Center

Brown, Thomas E.; Holdnack, James; Saylor, Keith; Adler, Lenard; Spencer, Thomas; Williams, David W.; Padival, Anoop K.; Schuh, Kory; Trzepacz, Paula T.; Kelsey, Douglas

2011-01-01

Objective: To assess the effect of atomoxetine on ADHD-related executive functions over a 6-month period using the Brown Attention-Deficit Disorder Scale (BADDS) for Adults, a normed, 40-item, self-report scale in a randomized, double-blind, placebo-controlled clinical trial. Method: In a randomized, double-blind clinical trial, adults with ADHD…

Scaling Academic Planning in Community College: A Randomized Controlled Trial. REL 2017-204

ERIC Educational Resources Information Center

Visher, Mary G.; Mayer, Alexander K.; Johns, Michael; Rudd, Timothy; Levine, Andrew; Rauner, Mary

2016-01-01

Community college students often lack an academic plan to guide their choices of coursework to achieve their educational goals, in part because counseling departments typically lack the capacity to advise students at scale. This randomized controlled trial tests the impact of guaranteed access to one of two alternative counseling sessions (group…

Using Small-Scale Randomized Controlled Trials to Evaluate the Efficacy of New Curricular Materials

ERIC Educational Resources Information Center

Drits-Esser, Dina; Bass, Kristin M.; Stark, Louisa A.

2014-01-01

How can researchers in K-12 contexts stay true to the principles of rigorous evaluation designs within the constraints of classroom settings and limited funding? This paper explores this question by presenting a small-scale randomized controlled trial (RCT) designed to test the efficacy of curricular supplemental materials on epigenetics. The…

Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: A pilot double-blind randomized trial [ISRCTN45683816

PubMed Central

Akhondzadeh, Shahin; Fallah-Pour, Hasan; Afkham, Khosro; Jamshidi, Amir-Hossein; Khalighi-Cigaroudi, Farahnaz

2004-01-01

Background The morbidity and mortality associated with depression are considerable and continue to increase. Depression currently ranks fourth among the major causes of disability worldwide, after lower respiratory infections, prenatal conditions, and HIV/AIDS. Crocus sativus L. is used to treat depression. Many medicinal plants textbooks refer to this indication whereas there is no evidence-based document. Our objective was to compare the efficacy of stigmas of Crocus sativus (saffron) with imipramine in the treatment of mild to moderate depression in a 6-week pilot double-blind randomized trial. Methods Thirty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition for major depression based on the structured clinical interview for DSM IV participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. In this double-blind, single-center trial, patients were randomly assigned to receive capsule of saffron 30 mg/day (TDS) (Group 1) and capsule of imipramine 100 mg/day (TDS) (Group 2) for a 6-week study. Results Saffron at this dose was found to be effective similar to imipramine in the treatment of mild to moderate depression (F = 2.91, d.f. = 1, P = 0.09). In the imipramine group anticholinergic effects such as dry mouth and also sedation were observed more often that was predictable. Conclusion The main overall finding from this study is that saffron may be of therapeutic benefit in the treatment of mild to moderate depression. To the best of our knowledge this is the first clinical trial that supports this indication for saffron. A large-scale trial with placebo control is warranted. PMID:15341662

The Effect of India's Total Sanitation Campaign on Defecation Behaviors and Child Health in Rural Madhya Pradesh: A Cluster Randomized Controlled Trial

PubMed Central

Patil, Sumeet R.; Arnold, Benjamin F.; Salvatore, Alicia L.; Briceno, Bertha; Ganguly, Sandipan; Colford, John M.; Gertler, Paul J.

2014-01-01

Background Poor sanitation is thought to be a major cause of enteric infections among young children. However, there are no previously published randomized trials to measure the health impacts of large-scale sanitation programs. India's Total Sanitation Campaign (TSC) is one such program that seeks to end the practice of open defecation by changing social norms and behaviors, and providing technical support and financial subsidies. The objective of this study was to measure the effect of the TSC implemented with capacity building support from the World Bank's Water and Sanitation Program in Madhya Pradesh on availability of individual household latrines (IHLs), defecation behaviors, and child health (diarrhea, highly credible gastrointestinal illness [HCGI], parasitic infections, anemia, growth). Methods and Findings We conducted a cluster-randomized, controlled trial in 80 rural villages. Field staff collected baseline measures of sanitation conditions, behaviors, and child health (May–July 2009), and revisited households 21 months later (February–April 2011) after the program was delivered. The study enrolled a random sample of 5,209 children <5 years old from 3,039 households that had at least one child <24 months at the beginning of the study. A random subsample of 1,150 children <24 months at enrollment were tested for soil transmitted helminth and protozoan infections in stool. The randomization successfully balanced intervention and control groups, and we estimated differences between groups in an intention to treat analysis. The intervention increased percentage of households in a village with improved sanitation facilities as defined by the WHO/UNICEF Joint Monitoring Programme by an average of 19% (95% CI for difference: 12%–26%; group means: 22% control versus 41% intervention), decreased open defecation among adults by an average of 10% (95% CI for difference: 4%–15%; group means: 73% intervention versus 84% control). However, the intervention did not improve child health measured in terms of multiple health outcomes (diarrhea, HCGI, helminth infections, anemia, growth). Limitations of the study included a relatively short follow-up period following implementation, evidence for contamination in ten of the 40 control villages, and bias possible in self-reported outcomes for diarrhea, HCGI, and open defecation behaviors. Conclusions The intervention led to modest increases in availability of IHLs and even more modest reductions in open defecation. These improvements were insufficient to improve child health outcomes (diarrhea, HCGI, parasite infection, anemia, growth). The results underscore the difficulty of achieving adequately large improvements in sanitation levels to deliver expected health benefits within large-scale rural sanitation programs. Trial Registration ClinicalTrials.gov NCT01465204 Please see later in the article for the Editors' Summary PMID:25157929

Bilateral robotic priming before task-oriented approach in subacute stroke rehabilitation: a pilot randomized controlled trial.

PubMed

Hsieh, Yu-Wei; Wu, Ching-Yi; Wang, Wei-En; Lin, Keh-Chung; Chang, Ku-Chou; Chen, Chih-Chi; Liu, Chien-Ting

2017-02-01

To investigate the treatment effects of bilateral robotic priming combined with the task-oriented approach on motor impairment, disability, daily function, and quality of life in patients with subacute stroke. A randomized controlled trial. Occupational therapy clinics in medical centers. Thirty-one subacute stroke patients were recruited. Participants were randomly assigned to receive bilateral priming combined with the task-oriented approach (i.e., primed group) or to the task-oriented approach alone (i.e., unprimed group) for 90 minutes/day, 5 days/week for 4 weeks. The primed group began with the bilateral priming technique by using a bimanual robot-aided device. Motor impairments were assessed by the Fugal-Meyer Assessment, grip strength, and the Box and Block Test. Disability and daily function were measured by the modified Rankin Scale, the Functional Independence Measure, and actigraphy. Quality of life was examined by the Stroke Impact Scale. The primed and unprimed groups improved significantly on most outcomes over time. The primed group demonstrated significantly better improvement on the Stroke Impact Scale strength subscale ( p = 0.012) and a trend for greater improvement on the modified Rankin Scale ( p = 0.065) than the unprimed group. Bilateral priming combined with the task-oriented approach elicited more improvements in self-reported strength and disability degrees than the task-oriented approach by itself. Further large-scale research with at least 31 participants in each intervention group is suggested to confirm the study findings.

Is the placebo powerless? Update of a systematic review with 52 new randomized trials comparing placebo with no treatment.

PubMed

Hróbjartsson, A; Gøtzsche, P C

2004-08-01

It is widely believed that placebo interventions induce powerful effects. We could not confirm this in a systematic review of 114 randomized trials that compared placebo-treated with untreated patients. To study whether a new sample of trials would reproduce our earlier findings, and to update the review. Systematic review of trials that were published since our last search (or not previously identified), and of all available trials. Data was available in 42 out of 52 new trials (3212 patients). The results were similar to our previous findings. The updated review summarizes data from 156 trials (11 737 patients). We found no statistically significant pooled effect in 38 trials with binary outcomes, relative risk 0.95 (95% confidence interval 0.89-1.01). The effect on continuous outcomes decreased with increasing sample size, and there was considerable variation in effect also between large trials; the effect estimates should therefore be interpreted cautiously. If this bias is disregarded, the pooled standardized mean difference in 118 trials with continuous outcomes was -0.24 (-0.31 to -0.17). For trials with patient-reported outcomes the effect was -0.30 (-0.38 to -0.21), but only -0.10 (-0.20 to 0.01) for trials with observer-reported outcomes. Of 10 clinical conditions investigated in three trials or more, placebo had a statistically significant pooled effect only on pain or phobia on continuous scales. We found no evidence of a generally large effect of placebo interventions. A possible small effect on patient-reported continuous outcomes, especially pain, could not be clearly distinguished from bias.

Interventions for reducing fear of childbirth: A systematic review and meta-analysis of clinical trials.

PubMed

MoghaddamHosseini, Vahideh; Nazarzadeh, Milad; Jahanfar, Shayesteh

2017-11-07

Fear of childbirth is a problematic mental health issue during pregnancy. But, effective interventions to reduce this problem are not well understood. To examine effective interventions for reducing fear of childbirth. The Cochrane Central Register of Controlled Trials, PubMed, Embase and PsycINFO were searched since inception till September 2017 without any restriction. Randomised controlled trials and quasi-randomised controlled trials comparing interventions for treatment of fear of childbirth were included. The standardized mean differences were pooled using random and fixed effect models. The heterogeneity was determined using the Cochran's test and I 2 index and was further explored in meta-regression model and subgroup analyses. Ten studies inclusive of 3984 participants were included in the meta-analysis (2 quasi-randomized and 8 randomized clinical trials). Eight studies investigated education and two studies investigated hypnosis-based intervention. The pooled standardized mean differences of fear for the education intervention and hypnosis group in comparison with control group were -0.46 (95% CI -0.73 to -0.19) and -0.22 (95% CI -0.34 to -0.10), respectively. Both types of interventions were effective in reducing fear of childbirth; however our pooled results revealed that educational interventions may reduce fear with double the effect of hypnosis. Further large scale randomized clinical trials and individual patient data meta-analysis are warranted for assessing the association. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

The National Clinical Trials Network: Conducting Successful Clinical Trials of New Therapies for Rare Cancers

PubMed Central

Schott, Anne F.; Welch, John J.; Verschraegen, Claire F.; Kurzrock, Razelle

2015-01-01

Rare cancers account for 27% of neoplasms diagnosed each year, and 25% of cancer-related deaths in the United States. However, rare cancers show some of the highest response rates to targeted therapies, probably due to identification of oncogenic drivers with little inter-patient variability. Although the low incidence of rare cancers make large scale randomized trials involving single histologies difficult to perform, drugs have been successfully developed in rare cancers utilizing clinical trial designs that combine microscopic anatomies. Such trials are being pursued within the National Clinical Trials Network (NCTN), which possesses unique qualifications to perform widespread molecular screening of tumors for patient enrollment onto therapeutic clinical trials. When larger clinical trials are needed to determine optimum treatment strategies in rare cancers, the NCTN's broad reach in North America and internationally, and ability to partner with both US-based and international research organizations, can make these challenging studies feasible. PMID:26433554

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.

Cluster Randomized Trial of a Large-Scale Education Initiative in the Democratic Republic of Congo: Pilot Year Impacts on Teacher Development

ERIC Educational Resources Information Center

Wolf, Sharon; Aber, John Lawrence; Torrente, Catalina; Rasheed, Damira; McCoy, Marissa

2014-01-01

A wealth of research, primarily in high income countries, has accumulated in recent years evaluating teacher effectiveness and the processes through which teachers' performance and job satisfaction can be improved (e.g., Pianta, Mashburn, Downer, Hamre & Justice, 2008; Ross, 1992; 1995). Much less is known about how these processes operate for…

Becoming a Manual Occupation? The Construction of a Therapy Manual for Use with Language Impaired Children in Mainstream Primary Schools

ERIC Educational Resources Information Center

McCartney, Elspeth; Boyle, James; Bannatyne, Susan; Jessiman, Emma; Campbell, Cathy; Kelsey, Cherry; Smith, Jennifer; O'Hare, Anne

2003-01-01

The construction of therapy protocols for a large-scale randomized controlled trial comparing speech and language therapists and assistants, and group and individual therapy approaches for children aged 6-11 in mainstream schools is outlined. The aim was to outline the decision-making processes that led to the construction of the research therapy…

Thinking, Fast and Slow? Some Field Experiments to Reduce Crime and Dropout in Chicago. NBER Working Paper 21178

ERIC Educational Resources Information Center

Heller, Sara B.; Shah, Anuj K.; Guryan, Jonathan; Ludwig, Jens; Mullainathan, Sendhil; Pollack, Harold A.

2015-01-01

We present the results of three large-scale randomized controlled trials (RCTs) carried out in Chicago, testing interventions to reduce crime and dropout by changing the decision-making of economically disadvantaged youth. We study a program called Becoming a Man (BAM), developed by the non-profit Youth Guidance, in two RCTs implemented in 2009-10…

Cluster Randomized Trial of a Large-Scale Education Initiative in the Democratic Republic of Congo: Baseline Findings and Lessons

ERIC Educational Resources Information Center

Aber, John Lawrence; Torrente, Catalina; Annan, Jeannie; Bundervoet, Tom; Shivshanker, Anjuli

2012-01-01

The main purpose of the current paper is to describe and discuss the scientific and practical implications of pursuing rigorous developmental research in a low-income, war-afflicted country such as DRC. In addition, the paper aims to explore the individual, household and school correlates of children's academic performance and mental health and…

Fluoxetine for Autistic Behaviors (FAB trial): study protocol for a randomized controlled trial in children and adolescents with autism.

PubMed

Mouti, Anissa; Reddihough, Dinah; Marraffa, Catherine; Hazell, Philip; Wray, John; Lee, Katherine; Kohn, Michael

2014-06-16

Serotonin reuptake inhibitors (SSRIs) are commonly prescribed off-label for children with autism. To date, clinical trials examining the use of SSRIs in autism have been limited by small sample sizes and inconclusive results. The efficacy and safety of SSRIs for moderating autistic behaviors is yet to be adequately examined to provide evidence to support current clinical practice. The aim of the Fluoxetine for Autistic Behaviors (FAB) study is to determine the efficacy and safety of low dose fluoxetine compared with placebo, for reducing the frequency and severity of repetitive stereotypic behaviors in children and adolescents with an autism spectrum disorder (ASD). The relationship between the effectiveness of fluoxetine treatment and serotonin transporter genotype will also be explored. The FAB study is a multicenter, double-blinded, randomized controlled trial, funded by the Australian Government's National Health and Medical Research Council (NHMRC) grant. Participants will be aged between 7.5 and 17 years with a confirmed diagnosis of ASD. Eligible participants will be randomized to either placebo or fluoxetine for a 16-week period. Medication will be titrated over the first four weeks. Reponses to medication will be monitored fortnightly using the Clinical Global Impressions Scale (CGI). The primary outcome measure is the Children's Yale-Brown Obsessive Compulsive Scale-Modified for Pervasive Developmental Disorders (CYBOCS-PDD), administered at baseline and 16 weeks. Secondary outcome measures include the Aberrant Behaviour Scale (ABC), the Spence Children's Anxiety Scale Parent Report (SCAS-P), and the Repetitive Behaviors Scale (RBS-R), measured at baseline and 16 weeks. Participants will be invited to undergo genetic testing for SLC6A4 allele variants using a cheek swab. Continuous outcomes, including the primary outcome will be compared between the active and placebo groups using unadjusted linear regression. Binary outcomes will be compared using unadjusted logistic regression. The FAB study is a large clinical trial to specifically investigate the efficacy of low dose fluoxetine for restricted, repetitive, and stereotyped behaviors in ASD. The outcomes of this study will contribute to evidence-based interventions used in clinical practice to assist children with ASD. Australian and New Zealand Clinical Trials Registry ACTRN12608000173392; registered on 9 April, 2008.

Ticagrelor for the treatment of atherosclerotic disease: insights from the PARTHENON clinical development program.

PubMed

Held, Peter; Himmelmann, Anders; Ditmarsch, Marc

2016-07-01

Ticagrelor (P2Y12 receptor antagonist) is presently indicated for preventing atherothrombotic events in patients with acute coronary syndrome and patients with a history of myocardial infarction. The PARTHENON clinical development program comprises five randomized, controlled, cardiovascular, indication-seeking outcome studies, aiming to evaluate ticagrelor across the spectrum of patients with atherothrombotic disease. Results of two large-scale trials support a benefit for ticagrelor in patients with acute coronary syndrome (PLATO; ClinicalTrials.gov: NCT00391872) and in patients with a history of myocardial infarction (PEGASUS-TIMI 54; ClinicalTrials.gov: NCT01225562). Ongoing trials will provide information on the efficacy and safety of ticagrelor in patients with acute ischemic stroke or transient ischemic attack (SOCRATES; ClinicalTrials.gov: NCT01994720), peripheral artery disease (EUCLID; ClinicalTrials.gov: NCT01732822) and coronary artery disease in patients with Type 2 diabetes mellitus (THEMIS: ClinicalTrials.gov: NCT01991795).

A randomized controlled pilot study of the effectiveness of occupational therapy for children with sensory modulation disorder.

PubMed

Miller, Lucy Jane; Coll, Joseph R; Schoen, Sarah A

2007-01-01

A pilot randomized controlled trial (RCT) of the effectiveness of occupational therapy using a sensory integration approach (OT-SI) was conducted with children who had sensory modulation disorders (SMDs). This study evaluated the effectiveness of three treatment groups. In addition, sample size estimates for a large scale, multisite RCT were calculated. Twenty-four children with SMD were randomly assigned to one of three treatment conditions; OT-SI, Activity Protocol, and No Treatment. Pretest and posttest measures of behavior, sensory and adaptive functioning, and physiology were administered. The OT-SI group, compared to the other two groups, made significant gains on goal attainment scaling and on the Attention subtest and the Cognitive/Social composite of the Leiter International Performance Scale-Revised. Compared to the control groups, OT-SI improvement trends on the Short Sensory Profile, Child Behavior Checklist, and electrodermal reactivity were in the hypothesized direction. Findings suggest that OT-SI may be effective in ameliorating difficulties of children with SMD.

Efficacy and safety of combined treatment of miniscalpel acupuncture and non-steroidal anti-inflammatory drugs: an assessor-blinded randomized controlled pilot study.

PubMed

Jun, Seungah; Lee, Jung Hee; Gong, Han Mi; Chung, Yeon-Joong; Kim, Ju-Ran; Park, Chung A; Choi, Seong Hun; Lee, Geon-Mok; Lee, Hyun-Jong; Kim, Jae Soo

2018-01-12

Chronic neck pain is a common musculoskeletal disease during the lifespan of an individual. With an increase in dependence on computer technology, the prevalence of chronic neck pain is expected to rise and this can lead to socioeconomic problems. We have designed the current pilot study to evaluate the efficacy and safety of miniscalpel acupuncture treatment combined with non-steroidal anti-inflammatory drugs (NSAIDs) in patients with chronic neck pain. This seven-week clinical trial has been designed as an assessor-blinded, randomized controlled trial with three parallel arms. Thirty-six patients will be recruited and randomly allocated to three treatment groups: miniscalpel acupuncture treatment; NSAIDs; and miniscalpel acupuncture treatment combined with NSAIDs. Patients in the miniscalpel acupuncture and combined treatment groups will receive three sessions of miniscalpel acupuncture over a three-week period. Patients in the NSAIDs and combined treatment groups will receive zaltoprofen (one oral tablet, three times a day for three weeks). Primary and secondary outcomes will be measured at weeks 0 (baseline), 1, 2, 3 (primary end point), and 7 (four weeks after treatment completion) using the visual analogue scale and the Neck Disability Index, EuroQol 5-dimension questionnaire, and Patients' Global Impression of Change scale, respectively. Adverse events will also be recorded. This pilot study will provide a basic foundation for a future large-scale trial as well as information about the feasibility of miniscalpel acupuncture treatment combined with NSAIDs for chronic neck pain. Korean Clinical Research Information Service registry, KCT0002258 . Registered on 9 March 2017.

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.

Implementing Mother Tongue Instruction in the Real World: Results from a Medium-Scale Randomized Controlled Trial in Kenya

ERIC Educational Resources Information Center

Piper, Benjamin; Zuilkowski, Stephanie S.; Ong'ele, Salome

2016-01-01

Research in sub-Saharan Africa investigating the effect of mother tongue (MT) literacy instruction at medium scale is limited. A randomized controlled trial of MT literacy instruction was implemented in 2013 and 2014 as part of the Primary Math and Reading (PRIMR) Initiative in Kenya. We compare the effect of two treatment groups--the base PRIMR…

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

PubMed

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

2016-01-01

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

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

PubMed

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

2017-09-18

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

Sensory integration balance training in patients with multiple sclerosis: A randomized, controlled trial.

PubMed

Gandolfi, Marialuisa; Munari, Daniele; Geroin, Christian; Gajofatto, Alberto; Benedetti, Maria Donata; Midiri, Alessandro; Carla, Fontana; Picelli, Alessandro; Waldner, Andreas; Smania, Nicola

2015-10-01

Impaired sensory integration contributes to balance disorders in patients with multiple sclerosis (MS). The objective of this paper is to compare the effects of sensory integration balance training against conventional rehabilitation on balance disorders, the level of balance confidence perceived, quality of life, fatigue, frequency of falls, and sensory integration processing on a large sample of patients with MS. This single-blind, randomized, controlled trial involved 80 outpatients with MS (EDSS: 1.5-6.0) and subjective symptoms of balance disorders. The experimental group (n = 39) received specific training to improve central integration of afferent sensory inputs; the control group (n = 41) received conventional rehabilitation (15 treatment sessions of 50 minutes each). Before, after treatment, and at one month post-treatment, patients were evaluated by a blinded rater using the Berg Balance Scale (BBS), Activities-specific Balance Confidence Scale (ABC), Multiple Sclerosis Quality of Life-54, Fatigue Severity Scale (FSS), number of falls and the Sensory Organization Balance Test (SOT). The experimental training program produced greater improvements than the control group training on the BBS (p < 0.001), the FSS (p < 0.002), number of falls (p = 0.002) and SOT (p < 0.05). Specific training to improve central integration of afferent sensory inputs may ameliorate balance disorders in patients with MS. Clinical Trial Registration (NCT01040117). © The Author(s), 2015.

Reading Skill Transfer across Languages: Outcomes from Longitudinal Bilingual Randomized Control Trials in Kenya and Haiti

ERIC Educational Resources Information Center

Piper, Benjamin; Bulat, Jennae; Johnston, Andrew

2015-01-01

If children do not learn how to read in the first few years of primary school, they will struggle to complete the cycle, and are at greater risk of dropping out. It is therefore crucial to identify and test interventions that have the potential of making a large impact, can be implemented quickly, and are affordable to be taken to scale. This is…

Impacts of Social-Emotional Curricula on Three-Year-Olds: Exploratory Findings from the Head Start CARES Demonstration. Research Snapshot. OPRE Report 2014-78

ERIC Educational Resources Information Center

Hsueh, JoAnn; Lowenstein, Amy E.; Morris, Pamela; Mattera, Shira K.; Bangser, Michael

2014-01-01

This report presents exploratory impact findings for 3-year-olds from the Head Start CARES demonstration, a large-scale randomized controlled trial implemented in Head Start centers for one academic year across the country. The study was designed primarily to test the effects of the enhancements on 4-year-olds, but it also provides an opportunity…

Integrating nutrition and early child-development interventions among infants and preschoolers in rural India.

PubMed

Fernandez-Rao, Sylvia; Hurley, Kristen M; Nair, Krishnapillai Madhavan; Balakrishna, Nagalla; Radhakrishna, Kankipati V; Ravinder, Punjal; Tilton, Nicholas; Harding, Kimberly B; Reinhart, Greg A; Black, Maureen M

2014-01-01

This article describes the development, design, and implementation of an integrated randomized double-masked placebo-controlled trial (Project Grow Smart) that examines how home/preschool fortification with multiple micronutrient powder (MNP) combined with an early child-development intervention affects child development, growth, and micronutrient status among infants and preschoolers in rural India. The 1-year trial has an infant phase (enrollment age: 6-12 months) and a preschool phase (enrollment age: 36-48 months). Infants are individually randomized into one of four groups: placebo, placebo plus early learning, MNP alone, and MNP plus early learning (integrated intervention), conducted through home visits. The preschool phase is a cluster-randomized trial conducted in Anganwadi centers (AWCs), government-run preschools sponsored by the Integrated Child Development System of India. AWCs are randomized into MNP or placebo, with the MNP or placebo mixed into the children's food. The evaluation examines whether the effects of the MNP intervention vary by the quality of the early learning opportunities and communication within the AWCs. Study outcomes include child development, growth, and micronutrient status. Lessons learned during the development, design, and implementation of the integrated trial can be used to guide large-scale policy and programs designed to promote the developmental, educational, and economic potential of children in developing countries. © 2013 New York Academy of Sciences.

The Effects of Cognitive Therapy Versus ‘Treatment as Usual’ in Patients with Major Depressive Disorder

PubMed Central

Jakobsen, Janus Christian; Lindschou Hansen, Jane; Storebø, Ole Jakob; Simonsen, Erik; Gluud, Christian

2011-01-01

Background Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Cognitive therapy may be an effective treatment option for major depressive disorder, but the effects have only had limited assessment in systematic reviews. Methods/Principal Findings Cochrane systematic review methodology, with meta-analyses and trial sequential analyses of randomized trials, are comparing the effects of cognitive therapy versus ‘treatment as usual’ for major depressive disorder. To be included the participants had to be older than 17 years with a primary diagnosis of major depressive disorder. Altogether, we included eight trials randomizing a total of 719 participants. All eight trials had high risk of bias. Four trials reported data on the 17-item Hamilton Rating Scale for Depression and four trials reported data on the Beck Depression Inventory. Meta-analysis on the data from the Hamilton Rating Scale for Depression showed that cognitive therapy compared with ‘treatment as usual’ significantly reduced depressive symptoms (mean difference −2.15 (95% confidence interval −3.70 to −0.60; P<0.007, no heterogeneity)). However, meta-analysis with both fixed-effect and random-effects model on the data from the Beck Depression Inventory (mean difference with both models −1.57 (95% CL −4.30 to 1.16; P = 0.26, I2 = 0) could not confirm the Hamilton Rating Scale for Depression results. Furthermore, trial sequential analysis on both the data from Hamilton Rating Scale for Depression and Becks Depression Inventory showed that insufficient data have been obtained. Discussion Cognitive therapy might not be an effective treatment for major depressive disorder compared with ‘treatment as usual’. The possible treatment effect measured on the Hamilton Rating Scale for Depression is relatively small. More randomized trials with low risk of bias, increased sample sizes, and broader more clinically relevant outcomes are needed. PMID:21829664

Effects of a lifestyle intervention on psychosocial well-being of severe mentally ill residential patients: ELIPS, a cluster randomized controlled pragmatic trial.

PubMed

Stiekema, Annemarie P M; Looijmans, Anne; van der Meer, Lisette; Bruggeman, Richard; Schoevers, Robert A; Corpeleijn, Eva; Jörg, Frederike

2018-03-01

Large studies investigating the psychosocial effects of lifestyle interventions in patients with a severe mental illness (SMI) are scarce, especially in residential patients. This large, randomized controlled, multicentre pragmatic trial assessed the psychosocial effects of a combined diet-and-exercise lifestyle intervention targeting the obesogenic environment of SMI residential patients. Twenty-nine sheltered and clinical care teams were randomized into intervention (n=15) or control (n=14) arm. Team tailored diet-and-exercise lifestyle plans were set up to change the obesogenic environment into a healthier setting, and team members were trained in supporting patients to make healthier choices. The control group received care-as-usual. The Calgary Depression Scale for Schizophrenia (CDSS), Positive and Negative Syndrome Scale (PANSS), Health of the Nation Outcome Scales (HoNOS) and the Manchester Short Assessment of Quality of Life (MANSA) were assessed at baseline and after three and twelve months. Data were available for 384 intervention and 386 control patients (48.6±12.5years old, 62.7% males, 73.7% psychotic disorder). Linear mixed model analysis showed no psychosocial improvements in the intervention group compared to care-as-usual; the intervention group showed a slightly reduced quality of life (overall) and a small increase in depressive symptoms (clinical care facilities) and psychotic symptoms (sheltered facilities). This may be due to difficulties with implementation, the intervention not being specifically designed for improvements in mental well-being, or the small change approach, which may take longer to reach an effect. Further research might elucidate what type of lifestyle intervention under what circumstances positively affects psychosocial outcomes in this population. Copyright © 2018 Elsevier B.V. All rights reserved.

Using the infrastructure of a conditional cash transfer program to deliver a scalable integrated early child development program in Colombia: cluster randomized controlled trial

PubMed Central

Attanasio, Orazio P; Fernández, Camila; Grantham-McGregor, Sally M; Meghir, Costas; Rubio-Codina, Marta

2014-01-01

Objective To assess the effectiveness of an integrated early child development intervention, combining stimulation and micronutrient supplementation and delivered on a large scale in Colombia, for children’s development, growth, and hemoglobin levels. Design Cluster randomized controlled trial, using a 2×2 factorial design, with municipalities assigned to one of four groups: psychosocial stimulation, micronutrient supplementation, combined intervention, or control. Setting 96 municipalities in Colombia, located across eight of its 32 departments. Participants 1420 children aged 12-24 months and their primary carers. Intervention Psychosocial stimulation (weekly home visits with play demonstrations), micronutrient sprinkles given daily, and both combined. All delivered by female community leaders for 18 months. Main outcome measures Cognitive, receptive and expressive language, and fine and gross motor scores on the Bayley scales of infant development-III; height, weight, and hemoglobin levels measured at the baseline and end of intervention. Results Stimulation improved cognitive scores (adjusted for age, sex, testers, and baseline levels of outcomes) by 0.26 of a standard deviation (P=0.002). Stimulation also increased receptive language by 0.22 of a standard deviation (P=0.032). Micronutrient supplementation had no significant effect on any outcome and there was no interaction between the interventions. No intervention affected height, weight, or hemoglobin levels. Conclusions Using the infrastructure of a national welfare program we implemented the integrated early child development intervention on a large scale and showed its potential for improving children’s cognitive development. We found no effect of supplementation on developmental or health outcomes. Moreover, supplementation did not interact with stimulation. The implementation model for delivering stimulation suggests that it may serve as a promising blueprint for future policy on early childhood development. Trial registration Current Controlled trials ISRCTN18991160. PMID:25266222

Calcium Supplements and Cardiovascular Disease: A Review.

PubMed

Waldman, Talya; Sarbaziha, Raheleh; Merz, C Noel Bairey; Shufelt, Chrisandra

2015-07-01

Dietary or supplemental calcium intake has long been encouraged for optimal bone health. However, more recently, the safety of calcium supplementation has been questioned because of a possible association between supplemental calcium and cardiovascular risk. Whereas calcium may have a beneficial or neutral effect on cardiovascular risk factors such as blood pressure, cholesterol, weight, and diabetes, available evidence does not provide a definitive answer for an association with cardiovascular disease (CVD). To date, no calcium trials have studied cardiovascular disease as a primary end point, and larger trials with longer follow-up are needed. In this review, we present results from observational studies and randomized controlled trials (RCTs) that have evaluated calcium intake (dietary or supplemental) in relation to cardiovascular risk factors and cardiovascular disease as a secondary outcome. Results from RCTs are mixed regarding CVD risk in those using supplemental calcium with or without vitamin D, and more large-scale randomized trials designed specifically with CVD as the primary end point are needed. Evidence suggests that it is reasonable to encourage adequate dietary calcium intake, especially for postmenopausal women who are at greatest risk for osteoporotic fracture.

Optimizing Implementation of Obesity Prevention Programs: A Qualitative Investigation Within a Large-Scale Randomized Controlled Trial.

PubMed

Kozica, Samantha L; Teede, Helena J; Harrison, Cheryce L; Klein, Ruth; Lombard, Catherine B

2016-01-01

The prevalence of obesity in rural and remote areas is elevated in comparison to urban populations, highlighting the need for interventions targeting obesity prevention in these settings. Implementing evidence-based obesity prevention programs is challenging. This study aimed to investigate factors influencing the implementation of obesity prevention programs, including adoption, program delivery, community uptake, and continuation, specifically within rural settings. Nested within a large-scale randomized controlled trial, a qualitative exploratory approach was adopted, with purposive sampling techniques utilized, to recruit stakeholders from 41 small rural towns in Australia. In-depth semistructured interviews were conducted with clinical health professionals, health service managers, and local government employees. Open coding was completed independently by 2 investigators and thematic analysis undertaken. In-depth interviews revealed that obesity prevention programs were valued by the rural workforce. Program implementation is influenced by interrelated factors across: (1) contextual factors and (2) organizational capacity. Key recommendations to manage the challenges of implementing evidence-based programs focused on reducing program delivery costs, aided by the provision of a suite of implementation and evaluation resources. Informing the scale-up of future prevention programs, stakeholders highlighted the need to build local rural capacity through developing supportive university partnerships, generating local program ownership and promoting active feedback to all program partners. We demonstrate that the rural workforce places a high value on obesity prevention programs. Our results inform the future scale-up of obesity prevention programs, providing an improved understanding of strategies to optimize implementation of evidence-based prevention programs. © 2015 National Rural Health Association.

A Paradox-based data collection and management system for multi-center randomized clinical trials.

PubMed

Abdellatif, Mazen; Reda, Domenic J

2004-02-01

We have developed a Paradox-based data collection and management system for large-scale multi-site randomized clinical trials. The system runs under Windows operating system and integrates Symantec pcAnywhere32 telecommunications software for data transmission and remote control sessions, PKZIP utility for the compression/decompression of transmitted data, and Stat/Transfer for exporting the centralized Paradox database for analyses. We initially developed this system for VA Cooperative Study #399 'The Effect of Antiarrhythmic Therapy in Maintaining Stability of Sinus Rhythm in Atrial Fibrillation', which collects over 1000 variables on 706 patients at 20 sites. Patient intake for this 5-year study began in March of 1998. We have also developed an enhanced version of this system, which is being used in the NIH-funded 'Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT)' that collects over 1200 variables on 1588 patients at 13 sites. Patient intake for this 4-year study began in October of 2000.

Solitaire™ with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial: protocol for a randomized, controlled, multicenter study comparing the Solitaire revascularization device with IV tPA with IV tPA alone in acute ischemic stroke.

PubMed

Saver, Jeffrey L; Goyal, Mayank; Bonafe, Alain; Diener, Hans-Christoph; Levy, Elad I; Pereira, Vitor M; Albers, Gregory W; Cognard, Christophe; Cohen, David J; Hacke, Werner; Jansen, Olav; Jovin, Tudor G; Mattle, Heinrich P; Nogueira, Raul G; Siddiqui, Adnan H; Yavagal, Dileep R; Devlin, Thomas G; Lopes, Demetrius K; Reddy, Vivek; du Mesnil de Rochemont, Richard; Jahan, Reza

2015-04-01

Early reperfusion in patients experiencing acute ischemic stroke is critical, especially for patients with large vessel occlusion who have poor prognosis without revascularization. Solitaire™ stent retriever devices have been shown to immediately restore vascular perfusion safely, rapidly, and effectively in acute ischemic stroke patients with large vessel occlusions. The aim of the study was to demonstrate that, among patients with large vessel, anterior circulation occlusion who have received intravenous tissue plasminogen activator, treatment with Solitaire revascularization devices reduces degree of disability 3 months post stroke. The study is a global multicenter, two-arm, prospective, randomized, open, blinded end-point trial comparing functional outcomes in acute ischemic stroke patients who are treated with either intravenous tissue plasminogen activator alone or intravenous tissue plasminogen activator in combination with the Solitaire device. Up to 833 patients will be enrolled. Patients who have received intravenous tissue plasminogen activator are randomized to either continue with intravenous tissue plasminogen activator alone or additionally proceed to neurothrombectomy using the Solitaire device within six-hours of symptom onset. The primary end-point is 90-day global disability, assessed with the modified Rankin Scale (mRS). Secondary outcomes include mortality at 90 days, functional independence (mRS ≤ 2) at 90 days, change in National Institutes of Health Stroke Scale at 27 h, reperfusion at 27 h, and thrombolysis in cerebral infarction 2b/3 flow at the end of the procedure. Statistical analysis will be conducted using simultaneous success criteria on the overall distribution of modified Rankin Scale (Rankin shift) and proportions of subjects achieving functional independence (mRS 0-2). © 2015 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.

Logistic random effects regression models: a comparison of statistical packages for binary and ordinal outcomes.

PubMed

Li, Baoyue; Lingsma, Hester F; Steyerberg, Ewout W; Lesaffre, Emmanuel

2011-05-23

Logistic random effects models are a popular tool to analyze multilevel also called hierarchical data with a binary or ordinal outcome. Here, we aim to compare different statistical software implementations of these models. We used individual patient data from 8509 patients in 231 centers with moderate and severe Traumatic Brain Injury (TBI) enrolled in eight Randomized Controlled Trials (RCTs) and three observational studies. We fitted logistic random effects regression models with the 5-point Glasgow Outcome Scale (GOS) as outcome, both dichotomized as well as ordinal, with center and/or trial as random effects, and as covariates age, motor score, pupil reactivity or trial. We then compared the implementations of frequentist and Bayesian methods to estimate the fixed and random effects. Frequentist approaches included R (lme4), Stata (GLLAMM), SAS (GLIMMIX and NLMIXED), MLwiN ([R]IGLS) and MIXOR, Bayesian approaches included WinBUGS, MLwiN (MCMC), R package MCMCglmm and SAS experimental procedure MCMC.Three data sets (the full data set and two sub-datasets) were analysed using basically two logistic random effects models with either one random effect for the center or two random effects for center and trial. For the ordinal outcome in the full data set also a proportional odds model with a random center effect was fitted. The packages gave similar parameter estimates for both the fixed and random effects and for the binary (and ordinal) models for the main study and when based on a relatively large number of level-1 (patient level) data compared to the number of level-2 (hospital level) data. However, when based on relatively sparse data set, i.e. when the numbers of level-1 and level-2 data units were about the same, the frequentist and Bayesian approaches showed somewhat different results. The software implementations differ considerably in flexibility, computation time, and usability. There are also differences in the availability of additional tools for model evaluation, such as diagnostic plots. The experimental SAS (version 9.2) procedure MCMC appeared to be inefficient. On relatively large data sets, the different software implementations of logistic random effects regression models produced similar results. Thus, for a large data set there seems to be no explicit preference (of course if there is no preference from a philosophical point of view) for either a frequentist or Bayesian approach (if based on vague priors). The choice for a particular implementation may largely depend on the desired flexibility, and the usability of the package. For small data sets the random effects variances are difficult to estimate. In the frequentist approaches the MLE of this variance was often estimated zero with a standard error that is either zero or could not be determined, while for Bayesian methods the estimates could depend on the chosen "non-informative" prior of the variance parameter. The starting value for the variance parameter may be also critical for the convergence of the Markov chain.

The effect of India's total sanitation campaign on defecation behaviors and child health in rural Madhya Pradesh: a cluster randomized controlled trial.

PubMed

Patil, Sumeet R; Arnold, Benjamin F; Salvatore, Alicia L; Briceno, Bertha; Ganguly, Sandipan; Colford, John M; Gertler, Paul J

2014-08-01

Poor sanitation is thought to be a major cause of enteric infections among young children. However, there are no previously published randomized trials to measure the health impacts of large-scale sanitation programs. India's Total Sanitation Campaign (TSC) is one such program that seeks to end the practice of open defecation by changing social norms and behaviors, and providing technical support and financial subsidies. The objective of this study was to measure the effect of the TSC implemented with capacity building support from the World Bank's Water and Sanitation Program in Madhya Pradesh on availability of individual household latrines (IHLs), defecation behaviors, and child health (diarrhea, highly credible gastrointestinal illness [HCGI], parasitic infections, anemia, growth). We conducted a cluster-randomized, controlled trial in 80 rural villages. Field staff collected baseline measures of sanitation conditions, behaviors, and child health (May-July 2009), and revisited households 21 months later (February-April 2011) after the program was delivered. The study enrolled a random sample of 5,209 children <5 years old from 3,039 households that had at least one child <24 months at the beginning of the study. A random subsample of 1,150 children <24 months at enrollment were tested for soil transmitted helminth and protozoan infections in stool. The randomization successfully balanced intervention and control groups, and we estimated differences between groups in an intention to treat analysis. The intervention increased percentage of households in a village with improved sanitation facilities as defined by the WHO/UNICEF Joint Monitoring Programme by an average of 19% (95% CI for difference: 12%-26%; group means: 22% control versus 41% intervention), decreased open defecation among adults by an average of 10% (95% CI for difference: 4%-15%; group means: 73% intervention versus 84% control). However, the intervention did not improve child health measured in terms of multiple health outcomes (diarrhea, HCGI, helminth infections, anemia, growth). Limitations of the study included a relatively short follow-up period following implementation, evidence for contamination in ten of the 40 control villages, and bias possible in self-reported outcomes for diarrhea, HCGI, and open defecation behaviors. The intervention led to modest increases in availability of IHLs and even more modest reductions in open defecation. These improvements were insufficient to improve child health outcomes (diarrhea, HCGI, parasite infection, anemia, growth). The results underscore the difficulty of achieving adequately large improvements in sanitation levels to deliver expected health benefits within large-scale rural sanitation programs. ClinicalTrials.gov NCT01465204. Please see later in the article for the Editors' Summary.

The Quality of Reports of Randomized Controlled Trials Varies between Subdisciplines of Physiotherapy.

PubMed

Moseley, Anne M; Elkins, Mark R; Janer-Duncan, Lee; Hush, Julia M

2014-01-01

The quality of reports of randomized trials of physiotherapy interventions varies by year of publication, language of publication and whether the intervention being assessed is a type of electrotherapy. Whether it also varies by subdiscipline of physiotherapy has not yet been systematically investigated. The purpose of this study was to determine whether the quality of trial reports varies according to the subdiscipline of physiotherapy being evaluated. Reports of physiotherapy trials were identified using the Physiotherapy Evidence Database (PEDro). Quality of the trial report was evaluated using the PEDro scale (total PEDro score and 11 individual PEDro scale items). Multiple linear and logistic regressions were used to predict the quality of trial reports, with subdisciplines, time since publication, language of publication, and evaluation of electrotherapy as independent variables in the model. Total PEDro scores are higher when trial reports are more recent; are published in English; investigate electrotherapy; and are in the subdisciplines of musculoskeletal, neurology, cardiopulmonary, gerontology, continence and women's health, orthopaedics, or paediatrics. Trials in the subdisciplines of ergonomics and occupational health, oncology, and sports are associated with lower total PEDro scores. The musculoskeletal subdiscipline had a positive association with six of the PEDro scale items, more than any other subdiscipline. There is scope to improve the quality of the conduct and reporting of randomized trials across all the physiotherapy subdisciplines. This study provides specific information about how each physiotherapy subdiscipline can improve trial quality.

The Quality of Reports of Randomized Controlled Trials Varies between Subdisciplines of Physiotherapy

PubMed Central

Elkins, Mark R.; Janer-Duncan, Lee; Hush, Julia M.

2014-01-01

ABSTRACT Purpose: The quality of reports of randomized trials of physiotherapy interventions varies by year of publication, language of publication and whether the intervention being assessed is a type of electrotherapy. Whether it also varies by subdiscipline of physiotherapy has not yet been systematically investigated. The purpose of this study was to determine whether the quality of trial reports varies according to the subdiscipline of physiotherapy being evaluated. Methods: Reports of physiotherapy trials were identified using the Physiotherapy Evidence Database (PEDro). Quality of the trial report was evaluated using the PEDro scale (total PEDro score and 11 individual PEDro scale items). Multiple linear and logistic regressions were used to predict the quality of trial reports, with subdisciplines, time since publication, language of publication, and evaluation of electrotherapy as independent variables in the model. Results: Total PEDro scores are higher when trial reports are more recent; are published in English; investigate electrotherapy; and are in the subdisciplines of musculoskeletal, neurology, cardiopulmonary, gerontology, continence and women's health, orthopaedics, or paediatrics. Trials in the subdisciplines of ergonomics and occupational health, oncology, and sports are associated with lower total PEDro scores. The musculoskeletal subdiscipline had a positive association with six of the PEDro scale items, more than any other subdiscipline. Conclusions: There is scope to improve the quality of the conduct and reporting of randomized trials across all the physiotherapy subdisciplines. This study provides specific information about how each physiotherapy subdiscipline can improve trial quality. PMID:24719507

Tryptophan for the sleeping disorder and mental symptom of new-type drug dependence: A randomized, double-blind, placebo-controlled trial.

PubMed

Wang, Dongming; Li, Wenzhen; Xiao, Yang; He, Wulong; Wei, Weiquan; Yang, Longyu; Yu, Jincong; Song, Fujian; Wang, Zengzhen

2016-07-01

New-type drugs are popular with adolescents and could lead to psychiatry disorders, but no medications have been proven to be effective for these disorders of new-type drug dependence. We aimed to evaluate the efficacy of tryptophan on sleeping disorders and mental symptoms in detoxified individuals with new-type drug dependence. This randomized, placebo-controlled trial included 80 detoxified individuals with new-type drug dependence, recruited successively from a Compulsory Residential Drug Abstinence Institution in Wuhan, China, from April 2012 to November 2012. Eligible participants were randomly allocated to be treated with tryptophan (1000 mg/d, n = 40) or placebo (n = 40) for 2 weeks. The sleeping disorders and mental symptoms were assessed using Athens Insomnia Scale and Symptom Check-List-90 at baseline and 2 weeks. Results were analyzed according to the "intention-to-treat" approach. Forty-five participants completed the 2-week study, 24 in the tryptophan group and 21 in the placebo group. There were no statistically significant differences in baseline characteristics between groups and the treatment adherence was similar between groups. The reduction in the Athens Insomnia Scale score in the tryptophan group was significantly greater than that in the placebo group (P = 0.017). However, no significant differences were found in Symptom Check-List-90 scores (either by individual dimension or the overall score) between groups (all P > 0.05). The frequency of adverse events was similar and no serious adverse events were reported during the study. Tryptophan was unlikely to be effective for mental symptoms, but could alleviate sleep disorders in short term among detoxified individuals with new-type drug dependence. Future large-scale trials are required to confirm findings from this study.

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 .

Testing cardiovascular drug safety and efficacy in randomized trials.

PubMed

FitzGerald, Garret A

2014-03-28

Randomized trials provide the gold standard evidence on which rests the decision to approve novel therapeutics for clinical use. They are large and expensive and provide average but unbiased estimates of efficacy and risk. Concern has been expressed about how unrepresentative populations and conditions that pertain in randomized trials might be of the real world, including concerns about the homogeneity of the biomedical and adherence characteristics of volunteers entered into such trials, the dose and constancy of drug administration and the mixture of additional medications that are restricted in such trials but might influence outcome in practice. A distinction has been drawn between trials that establish efficacy and those that demonstrate effectiveness, drugs that patients actually consume in the real world for clinical benefit. However, randomized controlled trials remain the gold standard for establishing efficacy and the testing of effectiveness with less rigorous approaches is a secondary, albeit important consideration. Despite this, there is an appreciation that average results may conceal considerable interindividual variation in drug response, leading to a failure to appreciate clinical value or risk in subsets of patients. Thus, attempts are now being made to individualize risk estimates by modulating those derived from large randomized trials with the individual baseline risk estimates based on demographic and biological criteria-the individual Numbers Needed to Treat to obtain a benefit, such as a life saved. Here, I will consider some reasons why large phase 3 trials-by far the most expensive element of drug development-may fail to address the unmet medical needs, which should justify such effort and investment.

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.

A randomized trial of specialized versus standard neck physiotherapy in cervical dystonia.

PubMed

Counsell, Carl; Sinclair, Hazel; Fowlie, Jillian; Tyrrell, Elaine; Derry, Natalie; Meager, Peter; Norrie, John; Grosset, Donald

2016-02-01

Anecdotal reports suggested that a specialized physiotherapy technique developed in France (the Bleton technique) improved primary cervical dystonia. We evaluated the technique in a randomized trial. A parallel-group, single-blind, two-centre randomized trial compared the specialized outpatient physiotherapy programme given by trained physiotherapists up to once a week for 24 weeks with standard physiotherapy advice for neck problems. Randomization was by a central telephone service. The primary outcome was the change in the total Toronto Western Spasmodic Torticollis Rating (TWSTR) scale, measured before any botulinum injections that were due, between baseline and 24 weeks evaluated by a clinician masked to treatment. Analysis was by intention-to-treat. 110 patients were randomized (55 in each group) with 24 week outcomes available for 84. Most (92%) were receiving botulinum toxin injections. Physiotherapy adherence was good. There was no difference between the groups in the change in TWSTR score over 24 weeks (mean adjusted difference 1.44 [95% CI -3.63, 6.51]) or 52 weeks (mean adjusted difference 2.47 [-2.72, 7.65]) nor in any of the secondary outcome measures (Cervical Dystonia Impact Profile-58, clinician and patient-rated global impression of change, mean botulinum toxin dose). Both groups showed large sustained improvements compared to baseline in the TWSTR, most of which occurred in the first four weeks. There were no major adverse events. Subgroup analysis suggested a centre effect. There was no statistically or clinically significant benefit from the specialized physiotherapy compared to standard neck physiotherapy advice but further trials are warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-05-01

Breast cancer survivors who make preference-sensitive decisions about postmastectomy breast reconstruction often have large gaps in knowledge and undergo procedures that are misaligned with their treatment goals. We evaluated the feasibility and effect of a pre-consultation educational group intervention on the decision-making process for breast reconstruction. We conducted a pilot randomized controlled trial (RCT) where participants were randomly assigned to the intervention with routine education or routine education alone. The outcomes evaluated were decisional conflict, decision self-efficacy, satisfaction with information, perceived involvement in care, and uptake of reconstruction following surgical consultation. Trial feasibility and acceptability were evaluated, and effect sizes were calculated to determine the primary outcome for the full-scale RCT. Of the 41 patients enrolled, recruitment rate was 72 %, treatment fidelity was 98 %, and retention rate was 95 %. The Cohen's d effect size in reduction of decisional conflict was moderate to high for the intervention group compared to routine education (0.69, 95 % CI = 0.02-1.42), while the effect sizes of increase in decision self-efficacy (0.05, 95 % CI = -0.60-0.71) and satisfaction with information (0.11, 95 % CI = -0.53-0.76) were small. A higher proportion of patients receiving routine education signed informed consent to undergo breast reconstruction (14/20 or 70 %) compared to the intervention group (8/21 or 38 %) P = 0.06. A pre-consultation educational group intervention improves patients' shared decision-making quality compared to routine preoperative patient education. A full-scale definitive RCT is warranted based on high feasibility outcomes, and the primary outcome for the main trial will be decisional conflict.

Study in Parkinson Disease of Exercise (SPARX): Translating high-intensity exercise from animals to humans

PubMed Central

Moore, Charity G.; Schenkman, Margaret; Kohrt, Wendy M.; Delitto, Anthony; Hall, Deborah A.; Corcos, Daniel

2013-01-01

A burgeoning literature suggests that exercise has a therapeutic benefit in persons with Parkinson disease (PD) and in animal models of PD, especially when animals exercise at high intensity. If exercise is to be prescribed as “first-line” or “add-on” therapy in patients with PD, we must demonstrate its efficacy and dose-response effects through testing phases similar to those used in the testing of pharmacologic agents. The SPARX Trial is a multicenter, randomized, controlled, single-blinded, Phase II study that we designed to test the feasibility of using high-intensity exercise to modify symptoms of PD and to simultaneously test the nonfutility of achieving a prespecified change in patients’ motor scores on the Unified Parkinson Disease Rating Scale (UPDRS). The trial began in May 2102 and is in the process of screening, enrolling, and randomly assigning 126 patients with early-stage PD to 1 of 3 groups: usual care (wait-listed controls), moderate-intensity exercise (4 days/week at 60%–65% maximal heart rate [HRmax]), or high-intensity exercise (4 days/week at 80%–85% HRmax). At 6-month follow-up, the trial is randomly reassigning usual care participants to a moderate-intensity or high-intensity exercise group for the remaining 6 months. The goals of the Phase II trial are to determine if participants can exercise at moderate and high intensities; to determine if either exercise yields benefits consistent with meaningful clinical change (nonfutility); and to document safety and attrition. The advantage of using a non-futility approach allows us to efficiently determine if moderate- or high-intensity exercise warrants further large-scale investigation in PD. PMID:23770108

A randomized controlled trial to evaluate the safety and efficacy of cardiac contractility modulation in patients with systolic heart failure: rationale, design, and baseline patient characteristics.

PubMed

Abraham, William T; Burkhoff, Daniel; Nademanee, Koonlawee; Carson, Peter; Bourge, Robert; Ellenbogen, Kenneth A; Parides, Michael; Kadish, Alan

2008-10-01

Cardiac contractility modulation (CCM) signals are nonexcitatory electrical signals delivered during the cardiac absolute refractory period that enhance the strength of cardiac muscular contraction. Prior research in experimental and human heart failure has shown that CCM signals normalize phosphorylation of key proteins and expression of genes coding for proteins involved in regulation of calcium cycling and contraction. The results of prior clinical studies of CCM have supported its safety and efficacy. A large-scale clinical study, the FIX-HF-5 study, is currently underway to test the safety and efficacy of this treatment. In this article, we provide an overview of the system used to deliver CCM signals, the implant procedure, and the details and rationale of the FIX-HF-5 study design. Baseline characteristics for patients randomized in this trial are also presented.

Comparing Mindfulness-Based Group Therapy With Treatment as Usual for Opioid Dependents: A Pilot Randomized Clinical Trial Study Protocol.

PubMed

Imani, Saeed; Atef Vahid, Mohammad Kazem; Gharraee, Banafsheh; Habibi, Mojtaba; Bowen, Sarah; Noroozi, Alireza

2015-03-01

In response to high burden of opioid abuse in Iran, Ministry of Health has launched a large-scale opioid maintenance treatment program, delivered through a network of certified drug treatment centers. To promote opioid pharmacotherapies, there is an urgent need to develop and introduce evidence-based psychosocial interventions into the network. This is a randomized clinical trial (RCT) to investigate feasibility and effectiveness of adding mindfulness-based group therapy to opioid pharmacotherapies as compared to opioid pharmacotherapies alone. The primary outcomes were treatment retention and percentage of weekly morphine, methamphetamine, and benzodiazepine negative tests. This is the first RCT that explores the effectiveness of mindfulness-based relapse prevention group therapy among opioid dependent clients in Iran. The feasibility of group therapy and comparison of outcomes in intervention and control groups should be discussed in the outcome article.

Prednisolone and acupuncture in Bell's palsy: study protocol for a randomized, controlled trial

PubMed Central

2011-01-01

Background There are a variety of treatment options for Bell's palsy. Evidence from randomized controlled trials indicates corticosteroids can be used as a proven therapy for Bell's palsy. Acupuncture is one of the most commonly used methods to treat Bell's palsy in China. Recent studies suggest that staging treatment is more suitable for Bell's palsy, according to different path-stages of this disease. The aim of this study is to compare the effects of prednisolone and staging acupuncture in the recovery of the affected facial nerve, and to verify whether prednisolone in combination with staging acupuncture is more effective than prednisolone alone for Bell's palsy in a large number of patients. Methods/Design In this article, we report the design and protocol of a large sample multi-center randomized controlled trial to treat Bell's palsy with prednisolone and/or acupuncture. In total, 1200 patients aged 18 to 75 years within 72 h of onset of acute, unilateral, peripheral facial palsy will be assessed. There are six treatment groups, with four treated according to different path-stages and two not. These patients are randomly assigned to be in one of the following six treatment groups, i.e. 1) placebo prednisolone group, 2) prednisolone group, 3) placebo prednisolone plus acute stage acupuncture group, 4) prednisolone plus acute stage acupuncture group, 5) placebo prednisolone plus resting stage acupuncture group, 6) prednisolone plus resting stage acupuncture group. The primary outcome is the time to complete recovery of facial function, assessed by Sunnybrook system and House-Brackmann scale. The secondary outcomes include the incidence of ipsilateral pain in the early stage of palsy (and the duration of this pain), the proportion of patients with severe pain, the occurrence of synkinesis, facial spasm or contracture, and the severity of residual facial symptoms during the study period. Discussion The result of this trial will assess the efficacy of using prednisolone and staging acupuncture to treat Bell's palsy, and to determine a best combination therapy with prednisolone and acupuncture for treating Bell's palsy. Trial Registration ClinicalTrials.gov: NCT01201642 PMID:21693007

The effects of using cognitive behavioural therapy to improve sleep for patients with delusions and hallucinations (the BEST study): study protocol for a randomized controlled trial.

PubMed

Freeman, Daniel; Startup, Helen; Myers, Elissa; Harvey, Allison; Geddes, John; Yu, Ly-Mee; Zaiwalla, Zenobia; Luengo-Fernandez, Ramon; Foster, Russell; Lister, Rachel

2013-07-11

Patients with psychosis frequently report difficulties getting or staying asleep (insomnia). Dissatisfaction with sleep is high. Insomnia should be treated in this group, but typically it is not even assessed. Importantly, recent evidence indicates that insomnia triggers and exacerbates delusions and hallucinations. The clinical implication is that if the insomnia is treated then the psychotic symptoms will significantly lessen. In a case series with 15 patients with persecutory delusions resistant to previous treatment this is exactly what we found: cognitive behavioural therapy for insomnia (CBT-I) led to large reductions in both the insomnia and delusions. The clear next step is a pilot randomized controlled test. The clinical aim is to test whether CBT-I can reduce both insomnia and psychotic symptoms. The trial will inform decisions for a definitive large-scale evaluation. We will carry out a randomized controlled trial (the Better Sleep Trial, or the BEST study) with 60 patients with distressing delusions or hallucinations in the context of a schizophrenia spectrum diagnosis. Half of the participants will be randomized to receive CBT-I, in addition to their standard treatment, for up to eight sessions over 12 weeks. The other half will continue with treatment as usual. Blind assessments will take place at 0 weeks, 12 weeks (post-treatment) and 24 weeks (follow-up). The primary outcome hypotheses are that CBT-I added to treatment as usual will improve sleep, delusions and hallucinations compared with only treatment as usual. All main analyses will be carried out at the end of the last follow-up assessments and will be based on the intention-to-treat principle. The trial is funded by the NHS National Institute for Health Research (NIHR) Research for Patient Benefit Programme. Data collection will be complete by the end of 2014. This will be the first controlled test of CBT-I for patients with delusions and hallucinations. It will provide significant evidence for an easily administered intervention that is likely to prove very popular with patients experiencing the difficult-to-treat problems of delusions and hallucinations. Current Controlled Trials ISRCTN 33695128.

Evaluation of the effect of Spiritual care on patients with generalized anxiety and depression: a randomized controlled study.

PubMed

Sankhe, A; Dalal, K; Save, D; Sarve, P

2017-12-01

The present study was conducted to assess the effect of spiritual care in patients with depression, anxiety or both in a randomized controlled design. The participants were randomized either to receive spiritual care or not and Hamilton anxiety rating scale-A (HAM-A), Hamilton depression rating scale-D (HAM-D), WHO-quality of life-Brief (WHOQOL-BREF) and Functional assessment of chronic illness therapy - Spiritual well-being (FACIT-Sp) were assessed before therapy and two follow-ups at 3 and 6 week. However, with regard to the spiritual care therapy group, statistically significant differences were observed in both HAM-A and HAM-D scales between the baseline and visit 2 (p < 0.001), thus significantly reducing symptoms of anxiety and depression, respectively. No statistically significant differences were observed for any of the scales during the follow-up periods for the control group of participants. When the scores were compared between the study groups, HAM-A, HAM-D and FACIT-Sp 12 scores were significantly lower in the interventional group as compared to the control group at both third and sixth weeks. This suggests a significant improvement in symptoms of anxiety and depression in the spiritual care therapy group than the control group; however, large randomized controlled trials with robust design are needed to confirm the same.

Cognitive Behavior Therapy to Treat Sleep Disturbance and Fatigue After Traumatic Brain Injury: A Pilot Randomized Controlled Trial.

PubMed

Nguyen, Sylvia; McKay, Adam; Wong, Dana; Rajaratnam, Shantha M; Spitz, Gershon; Williams, Gavin; Mansfield, Darren; Ponsford, Jennie L

2017-08-01

To evaluate the efficacy of adapted cognitive behavioral therapy (CBT) for sleep disturbance and fatigue in individuals with traumatic brain injury (TBI). Parallel 2-group randomized controlled trial. Outpatient therapy. Adults (N=24) with history of TBI and clinically significant sleep and/or fatigue complaints were randomly allocated to an 8-session adapted CBT intervention or a treatment as usual (TAU) condition. Cognitive behavior therapy. The primary outcome was the Pittsburgh Sleep Quality Index (PSQI) posttreatment and at 2-month follow-up. Secondary measures included the Insomnia Severity Index, Fatigue Severity Scale, Brief Fatigue Inventory (BFI), Epworth Sleepiness Scale, and Hospital Anxiety and Depression Scale. At follow-up, CBT recipients reported better sleep quality than those receiving TAU (PSQI mean difference, 4.85; 95% confidence interval [CI], 2.56-7.14). Daily fatigue levels were significantly reduced in the CBT group (BFI difference, 1.54; 95% CI, 0.66-2.42). Secondary improvements were significant for depression. Large within-group effect sizes were evident across measures (Hedges g=1.14-1.93), with maintenance of gains 2 months after therapy cessation. Adapted CBT produced greater and sustained improvements in sleep, daily fatigue levels, and depression compared with TAU. These pilot findings suggest that CBT is a promising treatment for sleep disturbance and fatigue after TBI. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Current screening and treatments in retinopathy of prematurity in the US

PubMed Central

Suelves, Ana M; Shulman, Julia P

2016-01-01

Retinopathy of prematurity (ROP) is a complex disease characterized by an aberrant developmental retinal angiogenesis in preterm infants and can carry significant visual morbidity, including retinal detachment and blindness. Though large scale, randomized clinical trials have improved our understanding of the pathophysiology and progression of the disease, the management of ROP remains a challenge for ophthalmologists. This review addresses the up-to-date screening approach, diagnosis, and treatment guidelines for ROP in the US. PMID:28539800

Current screening and treatments in retinopathy of prematurity in the US.

PubMed

Suelves, Ana M; Shulman, Julia P

2016-01-01

Retinopathy of prematurity (ROP) is a complex disease characterized by an aberrant developmental retinal angiogenesis in preterm infants and can carry significant visual morbidity, including retinal detachment and blindness. Though large scale, randomized clinical trials have improved our understanding of the pathophysiology and progression of the disease, the management of ROP remains a challenge for ophthalmologists. This review addresses the up-to-date screening approach, diagnosis, and treatment guidelines for ROP in the US.

Effects of rotigotine transdermal patch in patients with Parkinson's disease presenting with non-motor symptoms - results of a double-blind, randomized, placebo-controlled trial.

PubMed

Antonini, A; Bauer, L; Dohin, E; Oertel, W H; Rascol, O; Reichmann, H; Schmid, M; Singh, P; Tolosa, E; Chaudhuri, K Ray

2015-10-01

Non-motor symptoms (NMS) of Parkinson's disease (PD) have a major impact on health-related quality of life. This is the first randomized controlled trial to use the NMS Scale (NMSS) as a primary outcome to assess treatment effects on NMS in PD. In this double-blind trial (NCT01300819), patients with PD and a total NMSS score ≥40 were randomized (2:1) to rotigotine or placebo, titrated over 1-7 weeks to optimal dose (≤8 mg/24 h for patients not receiving levodopa, ≤16 mg/24 h for patients receiving levodopa), maintained for 12 weeks. The primary outcome was change in NMSS total score from baseline to end of maintenance. Secondary outcomes were the nine NMSS domains, Unified Parkinson's Disease Rating Scale (UPDRS) III (motor) and the 39-item Parkinson's Disease Questionnaire (PDQ-39). In total, 283/349 (81.1%) randomized patients completed the trial; 211 rotigotine and 122 placebo were included in the full analysis set. The NMSS total score decreased by 23 (rotigotine) and 19 (placebo) points; the treatment difference was not statistically significant (-3.58; 95% confidence interval -8.43, 1.26; P = 0.147). Numerically greater than placebo improvements were detected in the 'mood/apathy' and 'miscellaneous' NMSS domains (P < 0.05). Treatment differences in UPDRS III (-2.60; -4.27, -0.92; P = 0.002) and PDQ-39 (-2.79; -5.21, -0.37; P = 0.024) favoured rotigotine. Adverse events reported more frequently with rotigotine were nausea, application site reactions, somnolence and headache. Rotigotine improvement in the multi-domain NMSS total score was not superior to placebo. A different sensitivity of individual NMSS domains to dopaminergic therapy and a large placebo effect may have contributed to these findings. © 2015 EAN.

Non-Celiac Gluten Sensitivity Has Narrowed the Spectrum of Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial.

PubMed

Shahbazkhani, Bijan; Sadeghi, Amirsaeid; Malekzadeh, Reza; Khatavi, Fatima; Etemadi, Mehrnoosh; Kalantri, Ebrahim; Rostami-Nejad, Mohammad; Rostami, Kamran

2015-06-05

Several studies have shown that a large number of patients who are fulfilling the criteria for irritable bowel syndrome (IBS) are sensitive to gluten. The aim of this study was to evaluate the effect of a gluten-free diet on gastrointestinal symptoms in patients with IBS. In this double-blind randomized, placebo-controlled trial, 148 IBS patients fulfilling the Rome III criteria were enrolled between 2011 and 2013. However, only 72 out of the 148 commenced on a gluten-free diet for up to six weeks and completed the study; clinical symptoms were recorded biweekly using a standard visual analogue scale (VAS). In the second stage after six weeks, patients whose symptoms improved to an acceptable level were randomly divided into two groups; patients either received packages containing powdered gluten (35 cases) or patients received placebo (gluten free powder) (37 cases). Overall, the symptomatic improvement was statistically different in the gluten-containing group compared with placebo group in 9 (25.7%), and 31 (83.8%) patients respectively (p < 0.001). A large number of patients labelled as irritable bowel syndrome are sensitive to gluten. Using the term of IBS can therefore be misleading and may deviate and postpone the application of an effective and well-targeted treatment strategy in gluten sensitive patients.

European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP): a randomized trial.

PubMed

Landolfi, R; Marchioli, R

1997-01-01

Thrombotic complications characterize the clinical course of polycythemia vera (PV) and represent the main cause of morbidity and mortality. However, uncertainty still exists as to the benefit/risk ratio of aspirin prophylaxis in this setting. In vivo platelet biosynthesis of thromboxane A2 is enhanced and can be suppressed by low-dose aspirin in PV, thus providing a rationale for assessing the efficacy and safety of a low-dose aspirin regimen in these patients. The Gruppo Italiano Studio Policitemia Vera has recently performed a pilot study on 112 patients randomized to receive aspirin, 40 mg daily, or placebo and followed for 16 +/- 6 months (mean +/- SD). This study showed that low-dose aspirin is well tolerated in PV patients, and that a large-scale efficacy trial is feasible in this setting. In this article we report the protocol of the European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) study, which is a randomized trial designed to assess the risk/benefit ratio of low-dose aspirin in PV. To estimate the size and the follow-up duration required for the ECLAP trial, a retrospective analysis of the clinical epidemiology of a large PV population has recently been completed by the Gruppo Italiano Studio Policitemia Vera. On this basis, approximately 3500 patients will be enrolled in the ECLAP study with a follow-up of 3 to 4 years. The uncertainty principle will be used as the main eligibility criterion: Polycythemic patients of any age, having no clear indication for or contraindication to aspirin treatment, will be randomized in a double-blind fashion to receive oral aspirin (100 mg daily) or placebo. According to current therapeutic recommendations, the basic treatment of randomized patients should be aimed at maintaining the hematocrit value < or = 45% in subjects aged < or = 50, and hematocrit < 45% as well as platelet count < 400 x 10(9)/L in patients aged > 50. Randomization will be stratified by participating center. The study is funded by the European Union BIOMED 2 program.

Testing Cardiovascular Drug Safety and Efficacy in Randomized Trials

PubMed Central

FitzGerald, Garret A.

2014-01-01

Randomized trials provide the gold standard evidence on which rests the decision to approve novel therapeutics for clinical use. They are large and expensive and provide average, but unbiased estimates of efficacy and risk. Concern has been expressed about how “unrepresentative” populations and conditions that pertain in randomized trials might be of the “real world”, including concerns about the homogeneity of the biomedical and adherence characteristics of volunteers entered into such trials, the dose and constancy of drug administration and the mixture of additional medications that are restricted in such trials but might influence outcome in practice. A distinction has been drawn between trials which establish “efficacy” and those that demonstrate “effectiveness” - drugs that patients actually consume in the “real world” for clinical benefit1. However, randomized controlled trials remain the gold standard for establishing efficacy and the testing of “effectiveness” with less rigorous approaches is a secondary, albeit important consideration. Despite this, there is an appreciation that “average” results may conceal considerable inter-individual variation in drug response, leading to a failure to appreciate clinical value or risk in subsets of patients2,3Thus, attempts are now being made to individualize risk estimates by modulating those derived from large randomized trials with the individual baseline risk estimates based on demographic and biological criteria - the individual Numbers Needed to Treat to obtain a benefit, such as a life saved4. Here, I will consider some reasons why large phase 3 trials - by far the most expensive element of drug development - may fail to address the “unmet medical needs” which should justify such effort and investment. PMID:24677235

Osteoporosis therapies: evidence from health-care databases and observational population studies.

PubMed

Silverman, Stuart L

2010-11-01

Osteoporosis is a well-recognized disease with severe consequences if left untreated. Randomized controlled trials are the most rigorous method for determining the efficacy and safety of therapies. Nevertheless, randomized controlled trials underrepresent the real-world patient population and are costly in both time and money. Modern technology has enabled researchers to use information gathered from large health-care or medical-claims databases to assess the practical utilization of available therapies in appropriate patients. Observational database studies lack randomization but, if carefully designed and successfully completed, can provide valuable information that complements results obtained from randomized controlled trials and extends our knowledge to real-world clinical patients. Randomized controlled trials comparing fracture outcomes among osteoporosis therapies are difficult to perform. In this regard, large observational database studies could be useful in identifying clinically important differences among therapeutic options. Database studies can also provide important information with regard to osteoporosis prevalence, health economics, and compliance and persistence with treatment. This article describes the strengths and limitations of both randomized controlled trials and observational database studies, discusses considerations for observational study design, and reviews a wealth of information generated by database studies in the field of osteoporosis.

Logistic random effects regression models: a comparison of statistical packages for binary and ordinal outcomes

PubMed Central

2011-01-01

Background Logistic random effects models are a popular tool to analyze multilevel also called hierarchical data with a binary or ordinal outcome. Here, we aim to compare different statistical software implementations of these models. Methods We used individual patient data from 8509 patients in 231 centers with moderate and severe Traumatic Brain Injury (TBI) enrolled in eight Randomized Controlled Trials (RCTs) and three observational studies. We fitted logistic random effects regression models with the 5-point Glasgow Outcome Scale (GOS) as outcome, both dichotomized as well as ordinal, with center and/or trial as random effects, and as covariates age, motor score, pupil reactivity or trial. We then compared the implementations of frequentist and Bayesian methods to estimate the fixed and random effects. Frequentist approaches included R (lme4), Stata (GLLAMM), SAS (GLIMMIX and NLMIXED), MLwiN ([R]IGLS) and MIXOR, Bayesian approaches included WinBUGS, MLwiN (MCMC), R package MCMCglmm and SAS experimental procedure MCMC. Three data sets (the full data set and two sub-datasets) were analysed using basically two logistic random effects models with either one random effect for the center or two random effects for center and trial. For the ordinal outcome in the full data set also a proportional odds model with a random center effect was fitted. Results The packages gave similar parameter estimates for both the fixed and random effects and for the binary (and ordinal) models for the main study and when based on a relatively large number of level-1 (patient level) data compared to the number of level-2 (hospital level) data. However, when based on relatively sparse data set, i.e. when the numbers of level-1 and level-2 data units were about the same, the frequentist and Bayesian approaches showed somewhat different results. The software implementations differ considerably in flexibility, computation time, and usability. There are also differences in the availability of additional tools for model evaluation, such as diagnostic plots. The experimental SAS (version 9.2) procedure MCMC appeared to be inefficient. Conclusions On relatively large data sets, the different software implementations of logistic random effects regression models produced similar results. Thus, for a large data set there seems to be no explicit preference (of course if there is no preference from a philosophical point of view) for either a frequentist or Bayesian approach (if based on vague priors). The choice for a particular implementation may largely depend on the desired flexibility, and the usability of the package. For small data sets the random effects variances are difficult to estimate. In the frequentist approaches the MLE of this variance was often estimated zero with a standard error that is either zero or could not be determined, while for Bayesian methods the estimates could depend on the chosen "non-informative" prior of the variance parameter. The starting value for the variance parameter may be also critical for the convergence of the Markov chain. PMID:21605357

Baseline Factors Predicting Placebo Response to Treatment in Children and Adolescents With Autism Spectrum Disorders

PubMed Central

King, Bryan H.; Dukes, Kimberly; Donnelly, Craig L.; Sikich, Linmarie; McCracken, James T.; Scahill, Lawrence; Hollander, Eric; Bregman, Joel D.; Anagnostou, Evdokia; Robinson, Fay; Sullivan, Lisa; Hirtz, Deborah

2016-01-01

IMPORTANCE The finding of factors that differentially predict the likelihood of response to placebo over that of an active drug could have a significant impact on study design in this population. OBJECTIVE To identify possible nonspecific, baseline predictors of response to intervention in a large randomized clinical trial of children and adolescents with autism spectrum disorders. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of citalopram hydrobromide for children and adolescents with autism spectrum disorders and prominent repetitive behavior. Baseline data at study entry were examined with respect to final outcome to determine if response predictors could be identified. A total of 149 children and adolescents 5 to 17 years of age (mean [SD] age, 9.4 [3.1] years) from 6 academic centers were randomly assigned to citalopram (n = 73) or placebo (n = 76). Participants had autistic disorder, Asperger syndrome, or pervasive developmental disorder, not otherwise specified; had illness severity ratings that were moderate or more than moderate on the Clinical Global Impression–Severity scale; and scored moderate or more than moderate on compulsive behaviors measured with the modified Children’s Yale-Brown Obsessive-Compulsive Scale. INTERVENTIONS Twelve weeks of treatment with citalopram (10 mg/5 mL) or placebo. The mean (SD) maximum dose of citalopram was 16.5 (6.5) mg by mouth daily (maximum dose, 20 mg/d). MAIN OUTCOMES AND MEASURES A positive response was defined as having a score of at least much improved on the Clinical Global Impression–Improvement scale at week 12. Baseline measures included demographic (sex, age, weight, and pubertal status), clinical, and family measures. Clinical variables included baseline illness severity ratings (the Aberrant Behavior Checklist, the Child and Adolescent Symptom Inventory, the Vineland Adaptive Behavior Scales, the Repetitive Behavior Scale–Revised, and the Children’s Yale-Brown Obsessive-Compulsive Scale). Family measures included the Caregiver Strain Questionnaire. RESULTS Several baseline predictors of response were identified, and a principal component analysis yielded 3 composite measures (disruptive behavior, autism/mood, and caregiver strain) that significantly predicted response at week 12. Specifically, participants in the placebo group were significantly less likely than participants in the citalopram group to respond at week 12 if they entered the study more symptomatic on each of the 3 composite measures, and they were at least 2 times less likely to be responders. CONCLUSIONS AND RELEVANCE This analysis suggests strategies that may be useful in anticipating and potentially mitigating the nonspecific response in randomized clinical trials of children and adolescents with autism spectrum disorders. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00086645 PMID:24061784

A 'green button' for using aggregate patient data at the point of care.

PubMed

Longhurst, Christopher A; Harrington, Robert A; Shah, Nigam H

2014-07-01

Randomized controlled trials have traditionally been the gold standard against which all other sources of clinical evidence are measured. However, the cost of conducting these trials can be prohibitive. In addition, evidence from the trials frequently rests on narrow patient-inclusion criteria and thus may not generalize well to real clinical situations. Given the increasing availability of comprehensive clinical data in electronic health records (EHRs), some health system leaders are now advocating for a shift away from traditional trials and toward large-scale retrospective studies, which can use practice-based evidence that is generated as a by-product of clinical processes. Other thought leaders in clinical research suggest that EHRs should be used to lower the cost of trials by integrating point-of-care randomization and data capture into clinical processes. We believe that a successful learning health care system will require both approaches, and we suggest a model that resolves this escalating tension: a "green button" function within EHRs to help clinicians leverage aggregate patient data for decision making at the point of care. Giving clinicians such a tool would support patient care decisions in the absence of gold-standard evidence and would help prioritize clinical questions for which EHR-enabled randomization should be carried out. The privacy rule in the Health Insurance Portability and Accountability Act (HIPAA) of 1996 may require revision to support this novel use of patient data. Project HOPE—The People-to-People Health Foundation, Inc.

Direct to Public Peer Support and e-Therapy Program Versus Information to Aid Self-Management of Depression and Anxiety: Protocol for a Randomized Controlled Trial

PubMed Central

2017-01-01

Background Regardless of geography or income, effective help for depression and anxiety only reaches a small proportion of those who might benefit from it. The scale of the problem suggests a role for effective, safe, anonymized public health–driven Web-based services such as Big White Wall (BWW), which offer immediate peer support at low cost. Objective Using Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) methodology, the aim of this study was to determine the population reach, effectiveness, cost-effectiveness, and barriers and drivers to implementation of BWW compared with Web-based information compiled by UK’s National Health Service (NHS, NHS Choices Moodzone) in people with probable mild to moderate depression and anxiety disorder. Methods A pragmatic, parallel-group, single-blind randomized controlled trial (RCT) is being conducted using a fully automated trial website in which eligible participants are randomized to receive either 6 months access to BWW or signposted to the NHS Moodzone site. The recruitment of 2200 people to the study will be facilitated by a public health engagement campaign involving general marketing and social media, primary care clinical champions, health care staff, large employers, and third sector groups. People will refer themselves to the study and will be eligible if they are older than 16 years, have probable mild to moderate depression or anxiety disorders, and have access to the Internet. Results The primary outcome will be the Warwick-Edinburgh Mental Well-Being Scale at 6 weeks. We will also explore the reach, maintenance, cost-effectiveness, and barriers and drivers to implementation and possible mechanisms of actions using a range of qualitative and quantitative methods. Conclusions This will be the first fully digital trial of a direct to public online peer support program for common mental disorders. The potential advantages of adding this to current NHS mental health services and the challenges of designing a public health campaign and RCT of two digital interventions using a fully automated digital enrollment and data collection process are considered for people with depression and anxiety. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 12673428; http://www.controlled-trials.com/ISRCTN12673428/12673428 (Archived by WebCite at http://www.webcitation.org/6uw6ZJk5a) PMID:29254909

Escitalopram treatment of depression in human immunodeficiency virus/acquired immunodeficiency syndrome: a randomized, double-blind, placebo-controlled study.

PubMed

Hoare, Jacqueline; Carey, Paul; Joska, John A; Carrara, Henri; Sorsdahl, Katherine; Stein, Dan J

2014-02-01

Depression can be a chronic and impairing illness in people with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Large randomized studies of newer selective serotonin reuptake inhibitors such as escitalopram in the treatment of depression in HIV, examining comparative treatment efficacy and safety, have yet to be done in HIV-positive patients. This was a fixed-dose, placebo-controlled, randomized, double-blind study to investigate the efficacy of escitalopram in HIV-seropositive subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, major depressive disorder. One hundred two participants were randomly assigned to either 10 mg of escitalopram or placebo for 6 weeks. An analysis of covariance of the completers found that there was no advantage for escitalopram over placebo on the Montgomery-Asberg Depression Rating Scale (p = 0.93). Sixty-two percent responded to escitalopram and 59% responded to placebo on the Clinical Global Impression Scale. Given the relatively high placebo response, future trials in this area need to be selective in participant recruitment and to be adequately powered.

Patients' preferences shed light on the murky world of guideline-based medicine.

PubMed

Penston, James

2007-02-01

Concordance--that is, shared decision-making between doctors and patients--is nowadays accepted as an integral part of good clinical practice. It is of particular importance in the case of treatments with only marginal benefits such as those recommended in guidelines for the management of common, chronic diseases. However, the implementation of guideline-based medicine conflicts with that of concordance. Studies indicate that patients are not adequately informed about their treatment. Clinical guidelines for conditions such as cardiovascular disease are based on large-scale randomized trials and the complex nature of the data limits effective communication especially in an environment characterized by time constraints. But other factors may be more relevant, notably pressures to comply with guidelines and financial rewards for meeting targets: it is simply not in the interests of doctors to disclose accurate information. Studies show that patients are far from impressed by the small benefits derived from large scale trials. Indeed, faced with absolute risk reductions, patients decline treatment promoted by guidelines. To participate in clinical decisions, patients require unbiased information concerning outcomes with and without treatment, and the absolute risk reduction; they should be told that most patients receiving long-term medication obtain no benefit despite being exposed to adverse drug reactions; furthermore, they should be made aware of the questionable validity of large-scale trials and that these studies may be influenced by those with a vested interest. Genuine concordance will inevitably lead to many patients rejecting the recommendations of guidelines and encourage a more critical approach to clinical research and guideline-based medicine.

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.

Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke: A Randomized Trial.

PubMed

Tuttolomondo, Antonino; Di Raimondo, Domenico; Pecoraro, Rosaria; Maida, Carlo; Arnao, Valentina; Della Corte, Vittoriano; Simonetta, Irene; Corpora, Francesca; Di Bona, Danilo; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

2016-03-01

Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-α, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile.

After-School Multifamily Groups: A Randomized Controlled Trial Involving Low-Income, Urban, Latino Children

ERIC Educational Resources Information Center

McDonald, Lynn; Moberg, D. Paul; Brown, Roger; Rodriguez-Espiricueta, Ismael; Flores, Nydia I.; Burke, Melissa P.; Coover, Gail

2006-01-01

This randomized controlled trial evaluated a culturally representative parent engagement strategy with Latino parents of elementary school children. Ten urban schools serving low-income children from mixed cultural backgrounds participated in a large study. Classrooms were randomly assigned either either to an after-school, multifamily support…

A Randomized Controlled Pilot Trial of Oral N-Acetylcysteine in Children with Autism

PubMed Central

Hardan, Antonio Y.; Fung, Lawrence K.; Libove, Robin A.; Obukhanych, Tetyana V.; Nair, Surekha; Herzenberg, Leonore A.; Frazier, Thomas W.; Tirouvanziam, Rabindra

2016-01-01

Background An imbalance in the excitatory/inhibitory systems with abnormalities in the glutamatergic pathways has been implicated in the pathophysiology of autism. Furthermore, chronic redox imbalance was also recently linked to this disorder. The goal of this pilot study was to assess the feasibility of using oral N-acetylcysteine (NAC), a glutamatergic modulator and an antioxidant in the treatment of behavioral disturbance in children with autism. Methods This is a 12-week, double-blind, randomized, placebo-controlled study of NAC in children with autistic disorder. Subjects randomized to NAC were initiated at 900 mg daily for 4 weeks, then 900 mg twice-daily for 4 weeks and 900 mg three-times-daily for 4 weeks. The primary behavioral measure (Aberrant Behavior Checklist – Irritability subscale) and safety measures were performed at baseline, 4, 8, and 12 weeks. Secondary measures included the ABC-Stereotypy subscale, Repetitive Behavior Scale – Revised (RBS-R), and Social Responsiveness Scale (SRS). Results Thirty-three subjects (31 males, 2 females; aged 3.2–10.7 years) were randomized in the study. Follow-up data was available on fourteen subjects in the NAC group and fifteen in the placebo group. Oral NAC was well-tolerated with limited side effects. Compared to placebo, NAC resulted in significant improvements on ABC-Irritability subscale (F=6.80; p<.001; d=.96). Conclusions Data from this pilot investigation support the potential usefulness of NAC for treating irritability in children with autistic disorder. Large randomized controlled investigations are warranted. ClinicalTrials.gov Identifier NCT00627705 PMID:22342106

Mentalization-based therapy for parents in entrenched conflict: A random allocation feasibility study.

PubMed

Hertzmann, Leezah; Target, Mary; Hewison, David; Casey, Polly; Fearon, Pasco; Lassri, Dana

2016-12-01

To explore the effectiveness of a mentalization-based therapeutic intervention specifically developed for parents in entrenched conflict over their children. To the best of our knowledge, this is the first randomized controlled intervention study in the United Kingdom to work with both parents postseparation, and the first to focus on mentalization in this situation. Using a mixed-methods study design, 30 parents were randomly allocated to either mentalization-based therapy for parental conflict-Parenting Together, or the Parents' Group, a psycho-educational intervention for separated parents based on elements of the Separated Parents Information Program-part of the U.K. Family Justice System and approximating to treatment as usual. Given the challenges of recruiting parents in these difficult circumstances, the sample size was small and permitted only the detection of large differences between conditions. The data, involving repeated measures of related individuals, was explored statistically, using hierarchical linear modeling, and qualitatively. Significant findings were reported on the main predicted outcomes, with clinically important trends on other measures. Qualitative findings further contributed to the understanding of parents' subjective experience, pre- and posttreatment. Findings indicate that a larger scale randomized controlled trial would be worthwhile. These encouraging findings shed light on the dynamics maintaining these high-conflict situations known to be damaging to children. We established that both forms of intervention were acceptable to most parents, and we were able to operate a random allocation design with extensive quantitative and qualitative assessments of the kind that would make a larger-scale trial feasible and productive. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Effects of mindfulness meditation on chronic pain: a randomized controlled trial.

PubMed

la Cour, Peter; Petersen, Marian

2015-04-01

This randomized controlled clinical trial investigated the effects of mindfulness meditation on chronic pain. A total of 109 patients with nonspecific chronic pain were randomized to either a standardized mindfulness meditation program (mindfulness-based stress reduction [MBSR]) or to a wait list control. Pain, physical function, mental function, pain acceptance, and health-related quality of life were measured. The SF36 vitality scale was chosen as the primary outcome measure; the primary end point was after completing the MBSR course. Within a 2.5-year period, 43 of the 109 randomized patients completed the mindfulness program, while 47 remained in the control group. Data were compared at three time points: at baseline, after completion of the course/waiting period, and at the 6-month follow-up. Significant effect (Cohen's d = 0.39) was found on the primary outcome measure, the SF36 vitality scale. On the secondary variables, significant medium to large size effects (Cohen's d = 0.37-0.71) were found for lower general anxiety and depression, better mental quality of life (psychological well-being), feeling in control of the pain, and higher pain acceptance. Small (nonsignificant) effect sizes were found for pain measures. There were no significant differences in the measures just after the intervention vs the 6-month follow-up. A standardized mindfulness program (MBSR) contributes positively to pain management and can exert clinically relevant effects on several important dimensions in patients with long-lasting chronic pain. © 2014 American Academy of Pain Medicine.

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.

A New Zealand pilot randomized controlled trial of a web-based interactive self-management programme (MSInvigor8) with and without email support for the treatment of multiple sclerosis fatigue.

PubMed

van Kessel, Kirsten; Wouldes, Trecia; Moss-Morris, Rona

2016-05-01

To pilot and compare the efficacy of an internet-based cognitive behavioural therapy self-management programme with (MSInvigor8-Plus) and without (MSInvigor8-Only) the use of email support in reducing fatigue severity and impact (primary outcomes), and depressed and anxious mood (secondary outcomes). Randomized controlled trial using an independent randomization system built into the website and intention-to-treat analysis. Participants were recruited through the local Multiple Sclerosis Society and hospital neurological services in New Zealand. A total of 39 people (aged 31-63 years), experiencing multiple sclerosis fatigue, able to walk with and without walking aids, were randomized to MSInvigor8-Only (n = 20) or to MSInvigor8-Plus (n = 19). MSInvigor8 is an eight-session programme based on cognitive behaviour therapy principles including psycho-education, self-monitoring, and changing unhelpful activity and thought patterns. Outcome measures included fatigue severity (Chalder Fatigue Scale) and impact (Modified Fatigue Impact Scale), and anxiety and depression (Hospital Anxiety and Depression Scale). Assessments were performed at baseline and at 10 weeks. The MSInvigor8-Plus condition resulted in significantly greater reductions in fatigue severity (F [1,36] = 9.09, p < 0.01) and impact (F [1,36] = 6.03, p < 0.02) compared with the MSInvigor8-Only condition. Large between-group effect sizes for fatigue severity (d = 0.99) and fatigue impact (d = 0.81) were obtained. No significant differences were found between the groups on changes in anxiety and depression. MSInvigor8 delivered with email-based support is a potentially promising, acceptable, and cost-effective approach to treating fatigue in people with multiple sclerosis in New Zealand. © The Author(s) 2015.

Critical Analysis of the Efficacy of Meditation Therapies for Acute and Subacute Phase Treatment of Depressive Disorders: A Systematic Review

PubMed Central

Jain, Felipe A.; Walsh, Roger N.; Eisendrath, Stuart J.; Christensen, Scott; Cahn, B. Rael

2014-01-01

Background Recently, the application of meditative practices to the treatment of depressive disorders has met with increasing clinical and scientific interest, due to a lower side-effect burden, potential reduction of polypharmacy, as well as theoretical considerations that such interventions may target some of the cognitive roots of depression. We aimed to determine the state of the evidence supporting this application. Methods Randomized, controlled trials of techniques meeting the Agency for Healthcare Research and Quality (AHRQ) definition of meditation, for participants suffering from clinically diagnosed depressive disorders, not currently in remission, were selected. Meditation therapies were separated into praxis (i.e. how they were applied) components, and trial outcomes were reviewed. Results Eighteen studies meeting inclusionary criteria were identified, encompassing seven distinct techniques and 1173 patients, with Mindfulness-Based Cognitive Therapy comprising the largest proportion. Studies including patients suffering from acute major depressive episodes (N = 10 studies), and those with residual subacute clinical symptoms despite initial treatment (N = 8), demonstrated moderate to large reductions in depression symptoms within group, and relative to control groups. There was significant heterogeneity of techniques and trial designs. Conclusions A substantial body of evidence indicates that meditation therapies may have salutary effects on patients suffering from clinical depressive disorders during the acute and subacute phases of treatment. Due to methodological deficiences and trial heterogeneity, large-scale, randomized controlled trials with well-described comparator interventions and measures of expectation are needed to clarify the role of meditation in the depression treatment armamentarium. PMID:25591492

Sodium iodide associated to salicylic acid in the topical management of chronic oral candidiasis: a randomized trial.

PubMed

Petruzzi, M; Grassi, F R; Nardi, G M; Martinelli, D; Serpico, R; Luglie, P F; Baldoni, E

2010-01-01

Candidiasis is a relevant problem in oral medicine practice. We compared the antimycotic activity of nystatin with a solution of sodium iodide associated to salicylic acid (SISA) in the topical management of chronic candidiasis. Consecutive patients affected by chronic candidiasis were randomly allocated to SISA (group A) or nystatin (group B). VAS and swab scores were recorded at the beginning and at the end of the study while the healing index was evaluated at the end of the study only. Data were analyzed by STATA 10 MP. Forty patients (20 male, 20 female) were randomized. SIAS was as effective as nystatin in affecting VAS (p greater than 0.05) and swab score (p greater than 0.05). A statistically significant reduction (p less than 0.05) of healing index was observed in both groups. No side effects were reported. SISA topical application, shows a comparable efficacy to the nystatin in the management of chronic oral candidiasis. Its use could represent an adequate alternative to the nystatin above all in the cases of drug-resistance. Further large scale randomized trials are warranted to confirm these preliminary findings.

Activity groups for people with schizophrenia: a randomized controlled trial.

PubMed

Dean, Madeleine; Weston, Adam R W; Osborn, David P; Willis, Suzie; Patterson, Sue; Killaspy, Helen; Leurent, Baptiste; Crawford, Mike J

2014-08-01

UK guidelines recommend that patients with schizophrenia are offered access to social activities, however, the impact of such interventions have not been examined in a large randomized trial. To investigate the effect of an activity group intervention on mental health and global functioning 12 months after randomization compared to standard care alone. Secondary analysis of data from the MATISSE study. Primary outcomes were global functioning, assessed using the Global Assessment of Functioning (GAF), and mental health symptoms measured using the Positive and Negative Syndrome Scale (PANSS). About 140 participants were randomized to activity groups and 137 to standard care alone. Follow-up data were collected from 242 (87%) participants. Mental health improved significantly among those offered activity groups (change in PANSS score = -6.0, 95% CI -2.3 to -9.8) but global functioning did not (change in GAF score = 0.8, 95% CI -1.7 to 3.3). No significant differences were found between treatment arms. Offering activity groups to patients with schizophrenia was not associated with any additional clinical benefits. There was poor uptake and attendance at activity groups. Interventions that aim to improve negative symptoms may be useful in enabling engagement in psychosocial interventions.

What is the Optimal Strategy for Adaptive Servo-Ventilation Therapy?

PubMed

Imamura, Teruhiko; Kinugawa, Koichiro

2018-05-23

Clinical advantages in the adaptive servo-ventilation (ASV) therapy have been reported in selected heart failure patients with/without sleep-disorder breathing, whereas multicenter randomized control trials could not demonstrate such advantages. Considering this discrepancy, optimal patient selection and device setting may be a key for the successful ASV therapy. Hemodynamic and echocardiographic parameters indicating pulmonary congestion such as elevated pulmonary capillary wedge pressure were reported as predictors of good response to ASV therapy. Recently, parameters indicating right ventricular dysfunction also have been reported as good predictors. Optimal device setting with appropriate pressure setting during appropriate time may also be a key. Large-scale prospective trial with optimal patient selection and optimal device setting is warranted.

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.

Testing a workplace physical activity intervention: a cluster randomized controlled trial

PubMed Central

2011-01-01

Background Increased physical activity levels benefit both an individuals' health and productivity at work. The purpose of the current study was to explore the impact and cost-effectiveness of a workplace physical activity intervention designed to increase physical activity levels. Methods A total of 1260 participants from 44 UK worksites (based within 5 organizations) were recruited to a cluster randomized controlled trial with worksites randomly allocated to an intervention or control condition. Measurement of physical activity and other variables occurred at baseline, and at 0 months, 3 months and 9 months post-intervention. Health outcomes were measured during a 30 minute health check conducted in worksites at baseline and 9 months post intervention. The intervention consisted of a 3 month tool-kit of activities targeting components of the Theory of Planned Behavior, delivered in-house by nominated facilitators. Self-reported physical activity (measured using the IPAQ short-form) and health outcomes were assessed. Results and discussion Multilevel modelling found no significant effect of the intervention on MET minutes of activity (from the IPAQ) at any of the follow-up time points controlling for baseline activity. However, the intervention did significantly reduce systolic blood pressure (B = -1.79 mm/Hg) and resting heart rate (B = -2.08 beats) and significantly increased body mass index (B = .18 units) compared to control. The intervention was found not to be cost-effective, however the substantial variability round this estimate suggested that further research is warranted. Conclusions The current study found mixed support for this worksite physical activity intervention. The paper discusses some of the tensions involved in conducting rigorous evaluations of large-scale randomized controlled trials in real-world settings. Trial registration Current controlled trials ISRCTN08807396 PMID:21481265

Folic Acid, Vitamin B6, and Vitamin B12 in Combination and Age-Related Cataract in a Randomized Trial of Women.

PubMed

Christen, William G; Glynn, Robert J; Chew, Emily Y; Albert, Christine M; Manson, JoAnn E

2016-01-01

To examine the incidence of cataract and cataract extraction in a trial of folic acid and vitamins B6 and B12. In a randomized, double-masked, placebo-controlled trial, 5442 female health professionals aged 40 years or older with preexisting cardiovascular disease (CVD) or three or more CVD risk factors were randomly assigned to receive a combination of folic acid (2.5 mg/day), vitamin B6 (50 mg/day), and vitamin B12 (1 mg/day), or placebo. A total of 3925 of these women did not have a diagnosis of cataract at baseline and were included in this analysis. The primary endpoint was age-related cataract, defined as an incident age-related lens opacity, responsible for a reduction in best-corrected visual acuity to 20/30 or worse, based on self-report confirmed by medical record review. Extraction of incident age-related cataract was a secondary endpoint of the trial. During an average of 7.3 years of treatment and follow-up, 408 cataracts and 275 cataract extractions were documented. There were 215 cataracts in the combination treatment group and 193 in the placebo group (hazard ratio, HR, 1.10, 95% confidence interval, CI, 0.90-1.33; p = 0.36). For the secondary endpoint of cataract extraction, there were 155 in the combination treatment group and 120 in the placebo group (HR 1.28, 95% CI 1.01-1.63; p = 0.04). In this large-scale randomized trial of women at high risk of CVD, daily supplementation with a combination of folic acid, vitamin B6, and vitamin B12 had no significant effect on cataract, but may have increased the risk of cataract extraction.

The evidence for pharmacological treatment of neuropathic pain.

PubMed

Finnerup, Nanna Brix; Sindrup, Søren Hein; Jensen, Troels Staehelin

2010-09-01

Randomized, double-blind, placebo-controlled trials on neuropathic pain treatment are accumulating, so an updated review of the available evidence is needed. Studies were identified using MEDLINE and EMBASE searches. Numbers needed to treat (NNT) and numbers needed to harm (NNH) values were used to compare the efficacy and safety of different treatments for a number of neuropathic pain conditions. One hundred and seventy-four studies were included, representing a 66% increase in published randomized, placebo-controlled trials in the last 5 years. Painful poly-neuropathy (most often due to diabetes) was examined in 69 studies, postherpetic neuralgia in 23, while peripheral nerve injury, central pain, HIV neuropathy, and trigeminal neuralgia were less often studied. Tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, the anticonvulsants gabapentin and pregabalin, and opioids are the drug classes for which there is the best evidence for a clinical relevant effect. Despite a 66% increase in published trials only a limited improvement of neuropathic pain treatment has been obtained. A large proportion of neuropathic pain patients are left with insufficient pain relief. This fact calls for other treatment options to target chronic neuropathic pain. Large-scale drug trials that aim to identify possible subgroups of patients who are likely to respond to specific drugs are needed to test the hypothesis that a mechanism-based classification may help improve treatment of the individual patients. Copyright (c) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Wordless intervention for epilepsy in learning disabilities (WIELD): study protocol for a randomized controlled feasibility trial.

PubMed

Durand, Marie-Anne; Gates, Bob; Parkes, Georgina; Zia, Asif; Friedli, Karin; Barton, Garry; Ring, Howard; Oostendorp, Linda; Wellsted, David

2014-11-20

Epilepsy is the most common neurological problem that affects people with learning disabilities. The high seizure frequency, resistance to treatments, associated skills deficit and co-morbidities make the management of epilepsy particularly challenging for people with learning disabilities. The Books Beyond Words booklet for epilepsy uses images to help people with learning disabilities manage their condition and improve quality of life. Our aim is to conduct a randomized controlled feasibility trial exploring key methodological, design and acceptability issues, in order to subsequently undertake a large-scale randomized controlled trial of the Books Beyond Words booklet for epilepsy. We will use a two-arm, single-centre randomized controlled feasibility design, over a 20-month period, across five epilepsy clinics in Hertfordshire, United Kingdom. We will recruit 40 eligible adults with learning disabilities and a confirmed diagnosis of epilepsy and will randomize them to use either the Books Beyond Words booklet plus usual care (intervention group) or to receive routine information and services (control group). We will collect quantitative data about the number of eligible participants, number of recruited participants, demographic data, discontinuation rates, variability of the primary outcome measure (quality of life: Epilepsy and Learning Disabilities Quality of Life scale), seizure severity, seizure control, intervention's patterns of use, use of other epilepsy-related information, resource use and the EQ-5D-5L health questionnaire. We will also gather qualitative data about the feasibility and acceptability of the study procedures and the Books Beyond Words booklet. Ethical approval for this study was granted on 28 April 2014, by the Wales Research Ethics Committee 5. Recruitment began on 1 July 2014. The outcomes of this feasibility study will be used to inform the design and methodology of a definitive study, adequately powered to determine the impact of the Books Beyond Words intervention to improve the management of epilepsy in people with learning disabilities. http://ISRCTN80067039 (Date of ISRCTN assignation: 23 April 2014).

A single point acupuncture treatment at large intestine meridian: a randomized controlled trial in acute tonsillitis and pharyngitis.

PubMed

Fleckenstein, Johannes; Lill, Christian; Lüdtke, Rainer; Gleditsch, Jochen; Rasp, Gerd; Irnich, Dominik

2009-09-01

One out of 4 patients visiting a general practitioner reports of a sore throat associated with pain on swallowing. This study was established to examine the immediate pain alleviating effect of a single point acupuncture treatment applied to the large intestine meridian of patients with sore throat. Sixty patients with acute tonsillitis and pharyngitis were enrolled in this randomized placebo-controlled trial. They either received acupuncture, or sham laser acupuncture, directed to the large intestine meridian section between acupuncture points LI 8 and LI 10. The main outcome measure was the change of pain intensity on swallowing a sip of water evaluated by a visual analog scale 15 minutes after treatment. A credibility assessment regarding the respective treatment was performed. The pain intensity for the acupuncture group before and immediately after therapy was 5.6+/-2.8 and 3.0+/-3.0, and for the sham group 5.6+/-2.5 and 3.8+/-2.5, respectively. Despite the articulation of a more pronounced improvement among the acupuncture group, there was no significant difference between groups (Delta=0.9, confidence interval: -0.2-2.0; P=0.12; analysis of covariance). Patients' satisfaction was high in both treatment groups. The study was prematurely terminated due to a subsequent lack of suitable patients. A single acupuncture treatment applied to a selected area of the large intestine meridian was no more effective in the alleviation of pain associated with clinical sore throat than sham laser acupuncture applied to the same area. Hence, clinically relevant improvement could be achieved. Pain alleviation might partly be due to the intense palpation of the large intestine meridian. The benefit of a comprehensive acupuncture treatment protocol in this condition should be subject to further trials.

A pilot randomized placebo-controlled trial of adjunctive aripiprazole for chronic PTSD in US military Veterans resistant to antidepressant treatment.

PubMed

Naylor, Jennifer C; Kilts, Jason D; Bradford, Daniel W; Strauss, Jennifer L; Capehart, Bruce P; Szabo, Steven T; Smith, Karen D; Dunn, Charlotte E; Conner, Kathryn M; Davidson, Jonathan R T; Wagner, Henry Ryan; Hamer, Robert M; Marx, Christine E

2015-05-01

Many individuals with post-traumatic stress disorder (PTSD) experience persistent symptoms despite pharmacological treatment with antidepressants. Several open-label monotherapy and adjunctive studies have suggested that aripiprazole (a second-generation antipsychotic) may have clinical utility in PTSD. However, there have been no randomized placebo-controlled trials of aripiprazole use for PTSD. We thus conducted a pilot randomized controlled trial of adjunctive aripiprazole versus placebo among Veterans with chronic PTSD serving in the US military since 11 September 2001 to assess the feasibility, safety, tolerability, and therapeutic potential of aripiprazole. Sixteen Veterans were randomized, and 14 completed at least 4 weeks of the study; 12 completed the entire 8-week trial. Outcome measures included the Clinician-Administered PTSD Scale (CAPS), PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores. Aripiprazole was well-tolerated in this cohort, and improvements in CAPS, PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores were as hypothesized. Although CAPS change scores did not reach statistical significance, aripiprazole outperformed placebo by 9 points on the CAPS in the last observation carried forward analysis compared with the placebo group (n = 7 per group), and by 20 points in the group randomized to aripiprazole that completed the entire study (n = 5) compared with the placebo group (n = 7). Results suggest promise for aripiprazole as an adjunctive strategy for the treatment of PTSD.

The effects of using cognitive behavioural therapy to improve sleep for patients with delusions and hallucinations (the BEST study): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Patients with psychosis frequently report difficulties getting or staying asleep (insomnia). Dissatisfaction with sleep is high. Insomnia should be treated in this group, but typically it is not even assessed. Importantly, recent evidence indicates that insomnia triggers and exacerbates delusions and hallucinations. The clinical implication is that if the insomnia is treated then the psychotic symptoms will significantly lessen. In a case series with 15 patients with persecutory delusions resistant to previous treatment this is exactly what we found: cognitive behavioural therapy for insomnia (CBT-I) led to large reductions in both the insomnia and delusions. The clear next step is a pilot randomized controlled test. The clinical aim is to test whether CBT-I can reduce both insomnia and psychotic symptoms. The trial will inform decisions for a definitive large-scale evaluation. Methods/design We will carry out a randomized controlled trial (the Better Sleep Trial, or the BEST study) with 60 patients with distressing delusions or hallucinations in the context of a schizophrenia spectrum diagnosis. Half of the participants will be randomized to receive CBT-I, in addition to their standard treatment, for up to eight sessions over 12 weeks. The other half will continue with treatment as usual. Blind assessments will take place at 0 weeks, 12 weeks (post-treatment) and 24 weeks (follow-up). The primary outcome hypotheses are that CBT-I added to treatment as usual will improve sleep, delusions and hallucinations compared with only treatment as usual. All main analyses will be carried out at the end of the last follow-up assessments and will be based on the intention-to-treat principle. The trial is funded by the NHS National Institute for Health Research (NIHR) Research for Patient Benefit Programme. Data collection will be complete by the end of 2014. Discussion This will be the first controlled test of CBT-I for patients with delusions and hallucinations. It will provide significant evidence for an easily administered intervention that is likely to prove very popular with patients experiencing the difficult-to-treat problems of delusions and hallucinations. Trial registration Current Controlled Trials ISRCTN 33695128 PMID:23845104

Randomized Controlled Trial of the Resilience and Coping Intervention (RCI) with Undergraduate University Students

ERIC Educational Resources Information Center

Houston, J. Brian; First, Jennifer; Spialek, Matthew L.; Sorenson, Mary E.; Mills-Sandoval, Toby; Lockett, McKenzie; First, Nathan L.; Nitiéma, Pascal; Allen, Sandra F.; Pfefferbaum, Betty

2017-01-01

Objective: The purpose of this pilot study was to evaluate the Resilience and Coping Intervention (RCI) with college students. Participants: College students (aged 18-23) from a large Midwest US university who volunteered for a randomized controlled trial during the 2015 spring semester. Methods: College students were randomly assigned to an…

Lesson Study to Scale up Research-Based Knowledge: A Randomized, Controlled Trial of Fractions Learning

ERIC Educational Resources Information Center

Lewis, Catherine; Perry, Rebecca

2017-01-01

An understanding of fractions eludes many U.S. students, and research-based knowledge about fraction, such as the utility of linear representations, has not broadly influenced instruction. This randomized trial of lesson study supported by mathematical resources assigned 39 educator teams across the United States to locally managed lesson study…

Empirically Assessing Participant Perceptions of the Research Experience in a Randomized Clinical Trial: The Women's Self-Defense Project as a Case Example.

PubMed

Weitlauf, Julie C; Ruzek, Josef I; Westrup, Darrah A; Lee, Tina; Keller, Jennifer

2007-06-01

A growing body of empirical literature has systematically documented the reactions to research participation among participants in traumafocused research. To date, the available data has generally presented an optimistic picture regarding participants' ability to tolerate and even find benefit from their participation. However, this literature has been largely limited to cross-sectional designs. No extant literature has yet examined the perceptions of participants with psychiatric illness who are participating in randomized clinical trials (RCTs) designed to evaluate the efficacy or effectiveness of novel trauma treatments. The authors posit that negative experiences of, or poor reactions to, the research experience in the context of a trauma-focused RCT may elevate the risk of participation. Indeed, negative reactions may threaten to undermine the potential therapeutic gains of participants and promoting early drop out from the trial. Empirically assessing reactions to research participation at the pilot-study phase of a clinical trial can both provide investigators and IRB members alike with empirical evidence of some likely risks of participation. In turn, this information can be used to help shape the design and recruitment methodology of the full-scale trial. Using data from the pilot study of the Women's Self-Defense Project as a case illustration, we provide readers with concrete suggestions for empirically assessing participants' perceptions of risk involved in their participation in behaviorally oriented clinical trials.

Lamotrigine versus inert placebo in the treatment of borderline personality disorder: study protocol for a randomized controlled trial and economic evaluation.

PubMed

Crawford, Mike J; Sanatinia, Rahil; Barrett, Barbara; Byford, Sarah; Cunningham, Gillian; Gakhal, Kavi; Lawrence-Smith, Geof; Leeson, Verity; Lemonsky, Fenella; Lykomitrou, Georgia; Montgomery, Alan; Morriss, Richard; Paton, Carol; Tan, Wei; Tyrer, Peter; Reilly, Joseph G

2015-07-18

People with borderline personality disorder (BPD) experience rapid and distressing changes in mood, poor social functioning and have high rates of suicidal behaviour. Several small scale studies suggest that mood stabilizers may produce short-term reductions in symptoms of BPD, but have not been large enough to fully examine clinical and cost-effectiveness. A two parallel-arm, placebo controlled randomized trial of usual care plus either lamotrigine or an inert placebo for people aged over 18 who are using mental health services and meet diagnostic criteria for BPD. We will exclude people with comorbid bipolar affective disorder or psychosis, those already taking a mood stabilizer, those who speak insufficient English to complete the baseline assessment and women who are pregnant or contemplating becoming pregnant. Those meeting inclusion criteria and provide written informed consent will be randomized to up to 200mg of lamotrigine per day or an inert placebo (up to 400mg if taking combined oral contraceptives). Participants will be randomized via a remote web-based system using permuted stacked blocks stratified by study centre, severity of personality disorder, and level of bipolarity. Follow-up assessments will be conducted by masked researchers 12, 24 weeks, and 52 weeks after randomization. The primary outcome is the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD). The secondary outcomes are depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment, adverse events and withdrawal of trial medication due to adverse effects. The main analyses will use intention to treat without imputation of missing data. The economic evaluation will take an NHS/Personal Social Services perspective. A cost-utility analysis will compare differences in total costs and differences in quality of life using QALYs derived from the EQ-5D. The evidence base for the use of pharmacological treatments for people with borderline personality disorder is poor. In this trial we will examine the clinical and cost-effectiveness of lamotrigine to assess what if any impact offering this has on peoples' mental health, social functioning, and use of other medication and other resources. Current Controlled Trials ISRCTN90916365 (registered 01/08/2012).

Quantity and quality assessment of randomized controlled trials on orthodontic practice in PubMed.

PubMed

Shimada, Tatsuo; Takayama, Hisako; Nakamura, Yoshiki

2010-07-01

To find current high-quality evidence for orthodontic practice within a reasonable time, we tested the performance of a PubMed search. PubMed was searched using publication type randomized controlled trial and medical subject heading term "orthodontics" for articles published between 2003 and 2007. The PubMed search results were compared with those from a hand search of four orthodontic journals to determine the sensitivity of PubMed search. We evaluated the precision of the PubMed search result and assessed the quality of individual randomized controlled trials using the Jadad scale. Sensitivity and precision were 97.46% and 58.12%, respectively. In PubMed, of the 277 articles retrieved, 161 (58.12%) were randomized controlled trials on orthodontic practice, and 115 of the 161 articles (71.42%) were published in four orthodontic journals: American Journal of Orthodontics and Dentofacial Orthopedics, The Angle Orthodontist, the European Journal of Orthodontics, and the Journal of Orthodontics. Assessment by the Jadad scale revealed 60 high-quality randomized controlled trials on orthodontic practice, of which 45 (75%) were published in these four journals. PubMed is a highly desirable search engine for evidence-based orthodontic practice. To stay current and get high-quality evidence, it is reasonable to look through four orthodontic journals: American Journal of Orthodontics and Dentofacial Orthopedics, The Angle Orthodontist, the European Journal of Orthodontics, and the Journal of Orthodontics.

Development and validation of a prognostic nomogram for colorectal cancer after radical resection based on individual patient data from three large-scale phase III trials

PubMed Central

Akiyoshi, Takashi; Maeda, Hiromichi; Kashiwabara, Kosuke; Kanda, Mitsuro; Mayanagi, Shuhei; Aoyama, Toru; Hamada, Chikuma; Sadahiro, Sotaro; Fukunaga, Yosuke; Ueno, Masashi; Sakamoto, Junichi; Saji, Shigetoyo; Yoshikawa, Takaki

2017-01-01

Background Few prediction models have so far been developed and assessed for the prognosis of patients who undergo curative resection for colorectal cancer (CRC). Materials and Methods We prepared a clinical dataset including 5,530 patients who participated in three major randomized controlled trials as a training dataset and 2,263 consecutive patients who were treated at a cancer-specialized hospital as a validation dataset. All subjects underwent radical resection for CRC which was histologically diagnosed to be adenocarcinoma. The main outcomes that were predicted were the overall survival (OS) and disease free survival (DFS). The identification of the variables in this nomogram was based on a Cox regression analysis and the model performance was evaluated by Harrell's c-index. The calibration plot and its slope were also studied. For the external validation assessment, risk group stratification was employed. Results The multivariate Cox model identified variables; sex, age, pathological T and N factor, tumor location, size, lymphnode dissection, postoperative complications and adjuvant chemotherapy. The c-index was 0.72 (95% confidence interval [CI] 0.66-0.77) for the OS and 0.74 (95% CI 0.69-0.78) for the DFS. The proposed stratification in the risk groups demonstrated a significant distinction between the Kaplan–Meier curves for OS and DFS in the external validation dataset. Conclusions We established a clinically reliable nomogram to predict the OS and DFS in patients with CRC using large scale and reliable independent patient data from phase III randomized controlled trials. The external validity was also confirmed on the practical dataset. PMID:29228760

Decision aid on breast cancer screening reduces attendance rate: results of a large-scale, randomized, controlled study by the DECIDEO group

PubMed Central

Bourmaud, Aurelie; Soler-Michel, Patricia; Oriol, Mathieu; Regnier, Véronique; Tinquaut, Fabien; Nourissat, Alice; Bremond, Alain; Moumjid, Nora; Chauvin, Franck

2016-01-01

Controversies regarding the benefits of breast cancer screening programs have led to the promotion of new strategies taking into account individual preferences, such as decision aid. The aim of this study was to assess the impact of a decision aid leaflet on the participation of women invited to participate in a national breast cancer screening program. This Randomized, multicentre, controlled trial. Women aged 50 to 74 years, were randomly assigned to receive either a decision aid or the usual invitation letter. Primary outcome was the participation rate 12 months after the invitation. 16 000 women were randomized and 15 844 included in the modified intention-to-treat analysis. The participation rate in the intervention group was 40.25% (3174/7885 women) compared with 42.13% (3353/7959) in the control group (p = 0.02). Previous attendance for screening (RR = 6.24; [95%IC: 5.75-6.77]; p < 0.0001) and medium household income (RR = 1.05; [95%IC: 1.01-1.09]; p = 0.0074) were independently associated with attendance for screening. This large-scale study demonstrates that the decision aid reduced the participation rate. The decision aid activate the decision making process of women toward non-attendance to screening. These results show the importance of promoting informed patient choices, especially when those choices cannot be anticipated. PMID:26883201

Effect of Transcutaneous Electrical Nerve Stimulation on Pain, Function, and Quality of Life in Fibromyalgia: A Double-Blind Randomized Clinical Trial

PubMed Central

Noehren, Brian; Dailey, Dana L.; Rakel, Barbara A.; Vance, Carol G.T.; Zimmerman, Miriam B.; Crofford, Leslie J.

2015-01-01

Background Fibromyalgia is a common chronic pain condition that has a significant impact on quality of life and often leads to disability. To date, there have been few well-controlled trials assessing the utility of nonpharmacological treatment modalities such as transcutaneous electrical nerve stimulation (TENS) in the management of pain and improvement in function in individuals with fibromyalgia. Objectives The purpose of this study will be to complete a long-term, multicenter study to assess the effects of TENS in women with fibromyalgia. Design This will be a phase II randomized, double-blind, placebo-controlled, multicenter clinical trial. Participants Three hundred forty-three participants with fibromyalgia will be recruited for this study. Intervention Participants will be randomly assigned to 1 of 3 groups: the intervention (TENS), placebo, or no treatment. After completing the randomized period, all participants will receive the intervention for 1 month. The participants will be asked to use TENS at the highest tolerable level for at least 2 hours daily during physical activity. Measurements The primary outcome will be pain with movement, with secondary outcomes assessing functional abilities, patient-reported outcomes, and quantitative sensory testing. Limitations Because having participants refrain from their typical medications is not practical, their usage and any change in medication use will be recorded. Conclusions The results of this study will provide some of the first evidence from a large-scale, double-blind, placebo-controlled trial on the effectiveness of TENS on pain control and quality-of-life changes in patients with fibromyalgia. PMID:25212518

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

Effect of transcutaneous electrical nerve stimulation on pain, function, and quality of life in fibromyalgia: a double-blind randomized clinical trial.

PubMed

Noehren, Brian; Dailey, Dana L; Rakel, Barbara A; Vance, Carol G T; Zimmerman, Miriam B; Crofford, Leslie J; Sluka, Kathleen A

2015-01-01

Fibromyalgia is a common chronic pain condition that has a significant impact on quality of life and often leads to disability. To date, there have been few well-controlled trials assessing the utility of nonpharmacological treatment modalities such as transcutaneous electrical nerve stimulation (TENS) in the management of pain and improvement in function in individuals with fibromyalgia. The purpose of this study will be to complete a long-term, multicenter study to assess the effects of TENS in women with fibromyalgia. This will be a phase II randomized, double-blind, placebo-controlled, multicenter clinical trial. Three hundred forty-three participants with fibromyalgia will be recruited for this study. Participants will be randomly assigned to 1 of 3 groups: the intervention (TENS), placebo, or no treatment. After completing the randomized period, all participants will receive the intervention for 1 month. The participants will be asked to use TENS at the highest tolerable level for at least 2 hours daily during physical activity. The primary outcome will be pain with movement, with secondary outcomes assessing functional abilities, patient-reported outcomes, and quantitative sensory testing. Because having participants refrain from their typical medications is not practical, their usage and any change in medication use will be recorded. The results of this study will provide some of the first evidence from a large-scale, double-blind, placebo-controlled trial on the effectiveness of TENS on pain control and quality-of-life changes in patients with fibromyalgia. © 2015 American Physical Therapy Association.

Does Topical Lidocaine Reduce the Pain Associated With the Insertion of Nasal Continuous Positive Airway Pressure Prongs in Preterm Infants?: A Randomized, Controlled Pilot Trial.

PubMed

Soliman, Hasnaa; Elsharkawy, Ashraf; Abdel-Hady, Hesham

2016-11-01

To evaluate the efficacy of topical lidocaine 2% gel in reducing the pain associated with the insertion of nasal continuous positive airway pressure (nCPAP) prongs in preterm infants. A pilot randomized controlled trial. Sixty preterm infants, categorized into lidocaine (n=30) and control groups (n=30). The primary outcome was Premature Infant Pain Profile (PIPP) score, secondary outcomes included salivary cortisol, presence of cry, the duration of first cry, and adverse effects of lidocaine. There were no statistically significant differences between lidocaine and control groups regarding PIPP scores (mean±SD: 7.2±2.3 vs. 9.3±3.0, respectively, P=0.086). None of the infants in the lidocaine group had severe pain defined as a PIPP score>12, compared with 3 (10%) infants in the control group (P=0.056). Salivary cortisol concentrations were not significantly different between the lidocaine and control groups (mean±SD: 2.57±1.79 vs. 4.82±1.61 μg/dL, respectively, P=0.11). Standardized effect sizes for topical lidocaine were medium to large for reduction in PIPP scores and large for reduction in salivary cortisol (Cohen d=-0.78 and -1.32, respectively). No adverse effects were reported in infants receiving lidocaine. Our data suggest that topical lidocaine did not reduce the pain associated with the insertion of nCPAP prongs in preterm infants. However, the trends for lower PIPP scores in the lidocaine group and the effect sizes for lidocaine on PIPP scores and salivary cortisol were large enough so that a large-scale randomized clinical trial is warranted to confirm or refute our results. Such a study should compare 2 or more active pain interventions during nCPAP application, rather than evaluating a single intervention versus placebo or no treatment.

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

PubMed Central

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

2017-01-01

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

Prednisolone and acupuncture in Bell's palsy: study protocol for a randomized, controlled trial.

PubMed

Xia, Feng; Han, Junliang; Liu, Xuedong; Wang, Jingcun; Jiang, Zhao; Wang, Kangjun; Wu, Songdi; Zhao, Gang

2011-06-21

There are a variety of treatment options for Bell's palsy. Evidence from randomized controlled trials indicates corticosteroids can be used as a proven therapy for Bell's palsy. Acupuncture is one of the most commonly used methods to treat Bell's palsy in China. Recent studies suggest that staging treatment is more suitable for Bell's palsy, according to different path-stages of this disease. The aim of this study is to compare the effects of prednisolone and staging acupuncture in the recovery of the affected facial nerve, and to verify whether prednisolone in combination with staging acupuncture is more effective than prednisolone alone for Bell's palsy in a large number of patients. In this article, we report the design and protocol of a large sample multi-center randomized controlled trial to treat Bell's palsy with prednisolone and/or acupuncture. In total, 1200 patients aged 18 to 75 years within 72 h of onset of acute, unilateral, peripheral facial palsy will be assessed. There are six treatment groups, with four treated according to different path-stages and two not. These patients are randomly assigned to be in one of the following six treatment groups, i.e. 1) placebo prednisolone group, 2) prednisolone group, 3) placebo prednisolone plus acute stage acupuncture group, 4) prednisolone plus acute stage acupuncture group, 5) placebo prednisolone plus resting stage acupuncture group, 6) prednisolone plus resting stage acupuncture group. The primary outcome is the time to complete recovery of facial function, assessed by Sunnybrook system and House-Brackmann scale. The secondary outcomes include the incidence of ipsilateral pain in the early stage of palsy (and the duration of this pain), the proportion of patients with severe pain, the occurrence of synkinesis, facial spasm or contracture, and the severity of residual facial symptoms during the study period. The result of this trial will assess the efficacy of using prednisolone and staging acupuncture to treat Bell's palsy, and to determine a best combination therapy with prednisolone and acupuncture for treating Bell's palsy. ClinicalTrials.gov: NCT01201642.

A randomized clinical trial of histamine 2 receptor antagonism in treatment-resistant schizophrenia.

PubMed

Meskanen, Katarina; Ekelund, Heidi; Laitinen, Jarmo; Neuvonen, Pertti J; Haukka, Jari; Panula, Pertti; Ekelund, Jesper

2013-08-01

Histamine has important functions as regulator of several other key neurotransmitters. Patients with schizophrenia have lower histamine H1 receptor levels. Since a case report in 1990 of an effect of the H2 antagonist famotidine on negative symptoms in schizophrenia, some open-label trials have been performed, but no randomized controlled trial. Recently, it was shown that clozapine is a full inverse agonist at the H2 receptor. We performed a researcher-initiated, academically financed, double-blind, placebo-controlled, parallel-group, randomized trial with the histamine H2 antagonist famotidine in treatment-resistant schizophrenia. Thirty subjects with schizophrenia were randomized to have either famotidine (100 mg twice daily, n = 16) or placebo (n = 14) orally, added to their normal treatment regimen for 4 weeks. They were followed up weekly with the Scale for the Assessment of Negative Symptoms (SANS), the PANSS (Positive and Negative Syndrome Scale), and Clinical Global Impression (CGI) Scale. In the famotidine group, the SANS score was reduced by 5.3 (SD, 13.1) points, whereas in the placebo group the SANS score was virtually unchanged (mean change, +0.2 [SD, 9.5]). The difference did not reach statistical significance (P = 0.134) in Mann-Whitney U analysis. However, the PANSS Total score and the General subscore as well as the CGI showed significantly (P < 0.05) greater change in the famotidine group than in the placebo group. No significant adverse effects were observed. This is the first placebo-controlled, randomized clinical trial showing a beneficial effect of histamine H2 antagonism in schizophrenia. H2 receptor antagonism may provide a new alternative for the treatment of schizophrenia.

Kinetics of matching.

PubMed

Mark, T A; Gallistel, C R

1994-01-01

Rats responded on concurrent variable interval schedules of brain stimulation reward in 2-trial sessions. Between trials, there was a 16-fold reversal in the relative rate of reward. In successive, narrow time windows, the authors compared the ratio of the times spent on the 2 levers to the ratio of the rewards received. Time-allocation ratios tracked wide, random fluctuations in the reward ratio. The adjustment to the midsession reversal in relative rate of reward was largely completed within 1 interreward interval on the leaner schedule. Both results were unaffected by a 16-fold change in the combined rates of reward. The large, rapid, scale-invariant shifts in time-allocation ratios that underlie matching behavior imply that the subjective relative rate of reward can be determined by a very few of the most recent interreward intervals and that this estimate can directly determine the ratio of the expected stay durations.

A randomized controlled trial evaluating a brief parenting program with children with autism spectrum disorders.

PubMed

Tellegen, Cassandra L; Sanders, Matthew R

2014-12-01

This randomized controlled trial evaluated the efficacy of Primary Care Stepping Stones Triple P, a brief individualized parenting program, in a sample of parents of children with autism spectrum disorder (ASD). Sixty-four parents of children aged 2-9 years (M = 5.67, SD = 2.14) with an ASD diagnosis participated in the study. Eighty-six percent of children were male, and 89% of parents identified their child's ethnicity as Australian/White. Families were randomly assigned to 1 of 2 conditions (intervention or care-as-usual) and were assessed at 3 time points (preintervention, postintervention, and 6-month follow-up). Parents completed a range of questionnaires to assess changes in child behavior (Eyberg Child Behavior Inventory) and parent outcomes (Parenting Scale, Depression Anxiety Stress Scale-21, Parent Problem Checklist, Relationship Quality Inventory, Parental Stress Scale) and 30-min home observations of parent-child interactions. Relative to the care-as-usual group, significant short-term improvements were found in the intervention group on parent-reported child behavior problems, dysfunctional parenting styles, parenting confidence, and parental stress, parental conflict, and relationship happiness. No significant intervention effects were found on levels of parental depression or anxiety, or on observed child disruptive and parent aversive behavior. The effect sizes for significant variables ranged from medium to large. Short-term effects were predominantly maintained at 6-month follow-up, and parents reported high levels of goal achievement and satisfaction with the program. The results indicate that a brief low intensity version of Stepping Stones Triple P is an efficacious intervention for parents of children with ASD.

Hydrotherapy vs. conventional land-based exercise for improving walking and balance after stroke: a randomized controlled trial.

PubMed

Zhu, Zhizhong; Cui, Liling; Yin, Miaomiao; Yu, Yang; Zhou, Xiaona; Wang, Hongtu; Yan, Hua

2016-06-01

To investigate the effects of hydrotherapy on walking ability and balance in patients with chronic stroke. Single-blind, randomized controlled pilot trial. Outpatient rehabilitation clinic at a tertiary neurological hospital in China. A total of 28 participants with impairments in walking and controlling balance more than six months post-stroke. After baseline evaluations, participants were randomly assigned to a land-based therapy (control group, n = 14) or hydrotherapy (study group, n = 14). Participants underwent individual sessions for four weeks, five days a week, for 45 minutes per session. After four weeks of rehabilitation, all participants were evaluated by a blinded assessor. Functional assessments included the Functional Reach Test, Berg Balance Scale, 2-minute walk test, and Timed Up and Go Test. After four weeks of treatment, the Berg Balance Scale, functional reach test, 2-minute walk test, and the Timed Up and Go Test scores had improved significantly in each group (P < 0.05). The mean improvement of the functional reach test and 2-minute walk test were significantly higher in the aquatic group than in the control group (P < 0.01). The differences in the mean values of the improvements in the Berg Balance Scale and the Timed Up and Go Test were not statistically significant. The results of this study suggest that a relatively short programme (four weeks) of hydrotherapy exercise resulted in a large improvement in a small group (n = 14) of individuals with relatively high balance and walking function following a stroke. © The Author(s) 2015.

Many multicenter trials had few events per center, requiring analysis via random-effects models or GEEs.

PubMed

Kahan, Brennan C; Harhay, Michael O

2015-12-01

Adjustment for center in multicenter trials is recommended when there are between-center differences or when randomization has been stratified by center. However, common methods of analysis (such as fixed-effects, Mantel-Haenszel, or stratified Cox models) often require a large number of patients or events per center to perform well. We reviewed 206 multicenter randomized trials published in four general medical journals to assess the average number of patients and events per center and determine whether appropriate methods of analysis were used in trials with few patients or events per center. The median number of events per center/treatment arm combination for trials using a binary or survival outcome was 3 (interquartile range, 1-10). Sixteen percent of trials had less than 1 event per center/treatment combination, 50% fewer than 3, and 63% fewer than 5. Of the trials which adjusted for center using a method of analysis which requires a large number of events per center, 6% had less than 1 event per center-treatment combination, 25% fewer than 3, and 50% fewer than 5. Methods of analysis that allow for few events per center, such as random-effects models or generalized estimating equations (GEEs), were rarely used. Many multicenter trials contain few events per center. Adjustment for center using random-effects models or GEE with model-based (non-robust) standard errors may be beneficial in these scenarios. Copyright © 2015 Elsevier Inc. All rights reserved.

Intermittent catheterization with hydrophilic catheters as a treatment of chronic neurogenic urinary retention.

PubMed

Chartier-Kastler, Emmanuel; Denys, Pierre

2011-01-01

Neurogenic bladder can be effectively managed with intermittent catheterization (IC) to improve or restore continence, but there is no consensus on which type of catheter is preferred. Hydrophilic catheters were developed to reduce urethral friction, thereby minimizing trauma and sticking, and making them more acceptable to the patient, and easier and safer to use. The objective of this article was to review the literature on the benefits of hydrophilic catheters in patients with neurogenic bladder. A large body of experimental and observational evidence, including randomized controlled trials, was identified using PubMed. Compared with plastic catheters that have been manually lubricated with gel, hydrophilic catheters reduce urinary tract infection and microhematuria. Hydrophilic catheters are also associated with high levels of patient satisfaction because they are comfortable to use. There is a wealth of evidence, including randomized controlled trials, to support the benefits of hydrophilic catheters in terms of safety and quality of life, especially in men with spinal cord injury. More data are required for spina bifida, multiple sclerosis, and in women. Further research is warranted, especially large-scale and long-term robust comparisons of different types of catheter, and in well-defined and stratified populations. Copyright © 2010 Wiley-Liss, Inc.

Osteoporosis improvement: a large-scale randomized controlled trial of patient and primary care physician education.

PubMed

Solomon, Daniel H; Katz, Jeffrey N; Finkelstein, Joel S; Polinski, Jennifer M; Stedman, Margaret; Brookhart, M Alan; Arnold, Marilyn; Gauthier, Suzanne; Avorn, Jerry

2007-11-01

We conducted a randomized controlled trial within the setting of a large drug benefit plan for Medicare beneficiaries. Primary care physicians and their patients were randomized to usual care, patient intervention only, physician intervention only, or both interventions. There was no difference in the probability of the primary composite endpoint (BMD test or osteoporosis medication) or in either of its components comparing the combined intervention group with usual care (risk ratio = 1.04; 95% CI, 0.85-1.26). Fractures from osteoporosis are associated with substantial morbidity, mortality, and cost. However, only a minority of at-risk older adults receives screening and/or treatment for this condition. We evaluated the effect of educational interventions for osteoporosis targeting at-risk patients, primary care physicians, or both. We conducted a randomized controlled trial within the setting of a large drug benefit plan for Medicare beneficiaries. Primary care physicians and their patients were randomized to usual care, patient intervention only, physician intervention only, or both interventions. The at-risk patients were women >or=65 yr of age, men and women >or=65 yr of age with a prior fracture, and men and women >or=65 yr of age who used oral glucocorticoids. The primary outcome studied was a composite of either undergoing a BMD test or initiating a medication used for osteoporosis. The secondary outcome was a hip, humerus, spine, or wrist fracture. We randomized 828 primary care physicians and their 13,455 eligible at-risk patients into four study arms. Physician and patient characteristics were very similar across all four groups. Across all four groups, the rate of the composite outcome was 10.3 per 100 person-years and did not differ between the usual care and the combined intervention groups (p = 0.5). In adjusted Cox proportional hazards models, there was no difference in the probability of the primary composite endpoint comparing the combined intervention group with usual care (risk ratio = 1.04; 95% CI, 0.85-1.26). There was also no difference in either of the components of the composite endpoint. The probability of fracture during follow-up was 4.2 per 100 person-years and did not differ by treatment assignment (p = 0.9). In this trial, a relatively brief program of patient and/or physician education did not work to improve the management of osteoporosis. More intensive efforts should be considered for future quality improvement programs for osteoporosis.

Comparison of group-based outpatient physiotherapy with usual care after total knee replacement: a feasibility study for a randomized controlled trial.

PubMed

Artz, Neil; Dixon, Samantha; Wylde, Vikki; Marques, Elsa; Beswick, Andrew D; Lenguerrand, Erik; Blom, Ashley W; Gooberman-Hill, Rachael

2017-04-01

To evaluate the feasibility of conducting a randomized controlled trial comparing group-based outpatient physiotherapy with usual care in patients following total knee replacement. A feasibility study for a randomized controlled trial. One secondary-care hospital orthopaedic centre, Bristol, UK. A total of 46 participants undergoing primary total knee replacement. The intervention group were offered six group-based exercise sessions after surgery. The usual care group received standard postoperative care. Participants were not blinded to group allocation. Feasibility was assessed by recruitment, reasons for non-participation, attendance, and completion rates of study questionnaires that included the Lower Extremity Functional Scale and Knee Injury and Osteoarthritis Outcome Score. Recruitment rate was 37%. Five patients withdrew or were no longer eligible to participate. Intervention attendance was high (73%) and 84% of group participants reported they were 'very satisfied' with the exercises. Return of study questionnaires at six months was lower in the usual care (75%) than in the intervention group (100%). Mean (standard deviation) Lower Extremity Functional Scale scores at six months were 45.0 (20.8) in the usual care and 57.8 (15.2) in the intervention groups. Recruitment and retention of participants in this feasibility study was good. Group-based physiotherapy was acceptable to participants. Questionnaire return rates were lower in the usual care group, but might be enhanced by telephone follow-up. The Lower Extremity Functional Scale had high responsiveness and completion rates. Using this outcome measure, 256 participants would be required in a full-scale randomized controlled trial.

Rehabilitation of traumatic brain injury in active duty military personnel and veterans: Defense and Veterans Brain Injury Center randomized controlled trial of two rehabilitation approaches.

PubMed

Vanderploeg, Rodney D; Schwab, Karen; Walker, William C; Fraser, Jamie A; Sigford, Barbara J; Date, Elaine S; Scott, Steven G; Curtiss, Glenn; Salazar, Andres M; Warden, Deborah L

2008-12-01

To determine the relative efficacy of 2 different acute traumatic brain injury (TBI) rehabilitation approaches: cognitive didactic versus functional-experiential, and secondarily to determine relative efficacy for different patient subpopulations. Randomized, controlled, intent-to-treat trial comparing 2 alternative TBI treatment approaches. Four Veterans Administration acute inpatient TBI rehabilitation programs. Adult veterans or active duty military service members (N=360) with moderate to severe TBI. One and a half to 2.5 hours of protocol-specific cognitive-didactic versus functional-experiential rehabilitation therapy integrated into interdisciplinary acute Commission for Accreditation of Rehabilitation Facilities-accredited inpatient TBI rehabilitation programs with another 2 to 2.5 hours daily of occupational and physical therapy. Duration of protocol treatment varied from 20 to 60 days depending on the clinical needs and progress of each participant. The 2 primary outcome measures were functional independence in living and return to work and/or school assessed by independent evaluators at 1-year follow-up. Secondary outcome measures consisted of the FIM, Disability Rating Scale score, and items from the Present State Exam, Apathy Evaluation Scale, and Neurobehavioral Rating Scale. The cognitive-didactic and functional-experiential treatments did not result in overall group differences in the broad 1-year primary outcomes. However, analysis of secondary outcomes found differentially better immediate posttreatment cognitive function (mean+/-SD cognitive FIM) in participants randomized to cognitive-didactic treatment (27.3+/-6.2) than to functional treatment (25.6+/-6.0, t332=2.56, P=.01). Exploratory subgroup analyses found that younger participants in the cognitive arm had a higher rate of returning to work or school than younger patients in the functional arm, whereas participants older than 30 years and those with more years of education in the functional arm had higher rates of independent living status at 1 year posttreatment than similar patients in the cognitive arm. Results from this large multicenter randomized controlled trial comparing cognitive-didactic and functional-experiential approaches to brain injury rehabilitation indicated improved but similar long-term global functional outcome. Participants in the cognitive treatment arm achieved better short-term functional cognitive performance than patients in the functional treatment arm. The current increase in war-related brain injuries provides added urgency for rigorous study of rehabilitation treatments. (http://ClinicalTrials.gov ID# NCT00540020.).

From randomized controlled trials to observational studies.

PubMed

Silverman, Stuart L

2009-02-01

Randomized controlled trials are considered the gold standard in the hierarchy of research designs for evaluating the efficacy and safety of a treatment intervention. However, their results can have limited applicability to patients in clinical settings. Observational studies using large health care databases can complement findings from randomized controlled trials by assessing treatment effectiveness in patients encountered in day-to-day clinical practice. Results from these designs can expand upon outcomes of randomized controlled trials because of the use of larger and more diverse patient populations with common comorbidities and longer follow-up periods. Furthermore, well-designed observational studies can identify clinically important differences among therapeutic options and provide data on long-term drug effectiveness and safety.

Effects of pilates on patients with chronic non-specific low back pain: a systematic review

PubMed Central

Lin, Hui-Ting; Hung, Wei-Ching; Hung, Jia-Ling; Wu, Pei-Shan; Liaw, Li-Jin; Chang, Jia-Hao

2016-01-01

[Purpose] To evaluate the effects of Pilates on patients with chronic low back pain through a systematic review of high-quality articles on randomized controlled trials. [Subjects and Methods] Keywords and synonyms for “Pilates” and “Chronic low back pain” were used in database searches. The databases included PubMed, Physiotherapy Evidence Database (PEDro), Medline, and the Cochrane Library. Articles involving randomized controlled trials with higher than 5 points on the PEDro scale were reviewed for suitability and inclusion. The methodological quality of the included randomized controlled trials was evaluated using the PEDro scale. Relevant information was extracted by 3 reviewers. [Results] Eight randomized controlled trial articles were included. Patients with chronic low back pain showed statistically significant improvement in pain relief and functional ability compared to patients who only performed usual or routine health care. However, other forms of exercise were similar to Pilates in the improvement of pain relief and functional capacity. [Conclusion] In patients with chronic low back pain, Pilates showed significant improvement in pain relief and functional enhancement. Other exercises showed effects similar to those of Pilates, if waist or torso movement was included and the exercises were performed for 20 cumulative hours. PMID:27821970

Buspirone versus methylphenidate in the treatment of attention deficit hyperactivity disorder: a double-blind and randomized trial.

PubMed

Davari-Ashtiani, Rozita; Shahrbabaki, Mahin Eslami; Razjouyan, Katayoon; Amini, Homayoun; Mazhabdar, Homa

2010-12-01

The efficacy and side effects of buspirone compared with methylphenidate (MPH) in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). A total of 34 children with ADHD as defined by DSM-IV-TR were randomized to buspirone or methylphenidate dosed on weight-adjusted basis at buspirone (0.5 mg/kg/day) and methylphenidate (0.3-1 mg/kg/day) for a 6-week double-blind clinical trial. The principle measures of outcome were the teacher and parent ADHD Rating Scale. The side effects were assessed by the special side effect checklist of each drug. In both groups, the scores of teacher and parent ADHD Rating Scale significantly declined on the 6th week as compared to baseline (p = 0.001). These effects were observed in the subscales too. No significant differences were observed between the two protocols on the total scores of parent and teacher ADHD Rating Scale, but methylphenidate was superior to buspirone in decreasing the symptoms of inattention. The side effects of buspirone were mild and rare in comparison with MPH. Buspirone has a favorable side-effects profile. It also has clinically and statistically significant impacts on improving the ADHD symptoms in children. These preliminary findings of the efficacy of buspirone in children with ADHD need large and cross-over studies.

Reporting funding source or conflict of interest in abstracts of randomized controlled trials, no evidence of a large impact on general practitioners' confidence in conclusions, a three-arm randomized controlled trial.

PubMed

Buffel du Vaure, Céline; Boutron, Isabelle; Perrodeau, Elodie; Ravaud, Philippe

2014-04-28

Systematic reporting of funding sources is recommended in the CONSORT Statement for abstracts. However, no specific recommendation is related to the reporting of conflicts of interest (CoI). The objective was to compare physicians' confidence in the conclusions of abstracts of randomized controlled trials of pharmaceutical treatment indexed in PubMed. We planned a three-arm parallel-group randomized trial. French general practitioners (GPs) were invited to participate and were blinded to the study's aim. We used a representative sample of 75 abstracts of pharmaceutical industry-funded randomized controlled trials published in 2010 and indexed in PubMed. Each abstract was standardized and reported in three formats: 1) no mention of the funding source or CoI; 2) reporting the funding source only; and 3) reporting the funding source and CoI. GPs were randomized according to a computerized randomization on a secure Internet system at a 1:1:1 ratio to assess one abstract among the three formats. The primary outcome was GPs' confidence in the abstract conclusions (0, not at all, to 10, completely confident). The study was planned to detect a large difference with an effect size of 0.5. Between October 2012 and June 2013, among 605 GPs contacted, 354 were randomized, 118 for each type of abstract. The mean difference (95% confidence interval) in GPs' confidence in abstract findings was 0.2 (-0.6; 1.0) (P = 0.84) for abstracts reporting the funding source only versus no funding source or CoI; -0.4 (-1.3; 0.4) (P = 0.39) for abstracts reporting the funding source and CoI versus no funding source and CoI; and -0.6 (-1.5; 0.2) (P = 0.15) for abstracts reporting the funding source and CoI versus the funding source only. We found no evidence of a large impact of trial report abstracts mentioning funding sources or CoI on GPs' confidence in the conclusions of the abstracts. ClinicalTrials.gov identifier: NCT01679873.

Effect of physical activity on frailty and associated negative outcomes: the LIFE randomized trial

USDA-ARS?s Scientific Manuscript database

Background: Limited evidence suggests that physical activity may prevent frailty and associated negative outcomes in older adults. Definitive data from large, long-term, randomized trials are lacking. Objective: To determine whether a long-term structured moderate-intensity physical activity (PA) p...

Acupuncture lowering blood pressure for secondary prevention of stroke: a study protocol for a multicenter randomized controlled trial.

PubMed

Du, Yu-Zheng; Gao, Xin-Xin; Wang, Cheng-Ting; Zheng, Hai-Zhen; Lei, Yun; Wu, Meng-Han; Shi, Xue-Min; Ban, Hai-Peng; Gu, Wen-Long; Meng, Xiang-Gang; Wei, Mao-Ti; Hu, Chun-Xiao

2017-09-15

Stroke is the prime cause of morbidity and mortality in the general population, and hypertension will increase the recurrence and mortality of stroke. We report a protocol of a pragmatic randomized controlled trial (RCT) using blood pressure (BP)-lowering acupuncture add-on treatment to treat patients with hypertension and stroke. This is a large-scale, multicenter, subject-, assessor- and analyst-blinded, pragmatic RCT. A total of 480 patients with hypertension and ischemic stroke will be randomly assigned to two groups: an experimental group and a control group. The experimental group will receive "HuoXueSanFeng" acupuncture combined with one antihypertensive medication in addition to routine ischemic stroke treatment. The control group will only receive one antihypertensive medication and basic treatments for ischemic stroke. HuoXueSanFeng acupuncture will be given for six sessions weekly for the first 6 weeks and three times weekly for the next 6 weeks. A 9-month follow-up will, thereafter, be conducted. Antihypertensive medication will be adjusted based on BP levels. The primary outcome will be the recurrence of stroke. The secondary outcomes including 24-h ambulatory BP, the TCM syndrome score, the Short Form 36-item Health Survey (SF-36), the National Institute of Health Stroke Scale (NIHSS), as well as the Barthel Index (BI) scale will be assessed at baseline, 6 weeks and 12 weeks post initiating treatments; cardiac ultrasound, carotid artery ultrasound, transcranial Doppler, and lower extremity ultrasound will be evaluated at baseline and 12 weeks after treatment. The safety of acupuncture will also be assessed. We aim to determine the clinical effects of controlling BP for secondary prevention of stroke with acupuncture add-on treatment. ClinicalTrials.gov, ID: NCT02967484 . Registered on 13 February 2017; last updated on 27 June 2017.

Child/Adolescent Anxiety Multimodal Study (CAMS): rationale, design, and methods

PubMed Central

2010-01-01

Objective To present the design, methods, and rationale of the Child/Adolescent Anxiety Multimodal Study (CAMS), a recently completed federally-funded, multi-site, randomized placebo-controlled trial that examined the relative efficacy of cognitive-behavior therapy (CBT), sertraline (SRT), and their combination (COMB) against pill placebo (PBO) for the treatment of separation anxiety disorder (SAD), generalized anxiety disorder (GAD) and social phobia (SoP) in children and adolescents. Methods Following a brief review of the acute outcomes of the CAMS trial, as well as the psychosocial and pharmacologic treatment literature for pediatric anxiety disorders, the design and methods of the CAMS trial are described. Results CAMS was a six-year, six-site, randomized controlled trial. Four hundred eighty-eight (N = 488) children and adolescents (ages 7-17 years) with DSM-IV-TR diagnoses of SAD, GAD, or SoP were randomly assigned to one of four treatment conditions: CBT, SRT, COMB, or PBO. Assessments of anxiety symptoms, safety, and functional outcomes, as well as putative mediators and moderators of treatment response were completed in a multi-measure, multi-informant fashion. Manual-based therapies, trained clinicians and independent evaluators were used to ensure treatment and assessment fidelity. A multi-layered administrative structure with representation from all sites facilitated cross-site coordination of the entire trial, study protocols and quality assurance. Conclusions CAMS offers a model for clinical trials methods applicable to psychosocial and psychopharmacological comparative treatment trials by using state-of-the-art methods and rigorous cross-site quality controls. CAMS also provided a large-scale examination of the relative and combined efficacy and safety of the best evidenced-based psychosocial (CBT) and pharmacologic (SSRI) treatments to date for the most commonly occurring pediatric anxiety disorders. Primary and secondary results of CAMS will hold important implications for informing practice-relevant decisions regarding the initial treatment of youth with anxiety disorders. Trial registration ClinicalTrials.gov NCT00052078. PMID:20051130

Internet cognitive behavioural therapy for mixed anxiety and depression: a randomized controlled trial and evidence of effectiveness in primary care.

PubMed

Newby, J M; Mackenzie, A; Williams, A D; McIntyre, K; Watts, S; Wong, N; Andrews, G

2013-12-01

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) have the highest co-morbidity rates within the internalizing disorders cluster, yet no Internet-based cognitive behavioural therapy (iCBT) programme exists for their combined treatment. We designed a six-lesson therapist-assisted iCBT programme for mixed anxiety and depression. Study 1 was a randomized controlled trial (RCT) comparing the iCBT programme (n = 46) versus wait-list control (WLC; n = 53) for patients diagnosed by structured clinical interview with MDD, GAD or co-morbid GAD/MDD. Primary outcome measures were the Patient Health Questionnaire nine-item scale (depression), Generalized Anxiety Disorder seven-item scale (generalized anxiety), Kessler 10-item Psychological Distress scale (distress) and 12-item World Health Organization Disability Assessment Schedule II (disability). The iCBT group was followed up at 3 months post-treatment. In study 2, we investigated the adherence to, and efficacy of the same programme in a primary care setting, where patients (n = 136) completed the programme under the supervision of primary care clinicians. The RCT showed that the iCBT programme was more effective than WLC, with large within- and between-groups effect sizes found (>0.8). Adherence was also high (89%), and gains were maintained at 3-month follow-up. In study 2 in primary care, adherence to the iCBT programme was low (41%), yet effect sizes were large (>0.8). Of the non-completers, 30% experienced benefit. Together, the results show that iCBT is effective and adherence is high in research settings, but there is a problem of adherence when translated into the 'real world'. Future efforts need to be placed on developing improved adherence to iCBT in primary care settings.

Findings from a Multiyear Scale-Up Effectiveness Trial of Open Court Reading

ERIC Educational Resources Information Center

Vaden-Kiernan, Michael; Borman, Geoffrey; Caverly, Sarah; Bell, Nance; Sullivan, Kate; Ruiz de Castilla, Veronica; Fleming, Grace; Rodriguez, Debra; Henry, Chad; Long, Tracy; Hughes Jones, Debra

2018-01-01

This multiyear scale-up effectiveness study of Open Court Reading (OCR) involved approximately 4,500 students and more than 1,000 teachers per year in Grades K-5 from 49 elementary schools in seven districts across the country. Using a school-level cluster randomized trial design, we assessed the implementation and effectiveness of Open Court…

Cognitive behaviour therapy for specific phobia of vomiting (Emetophobia): A pilot randomized controlled trial.

PubMed

Riddle-Walker, Lori; Veale, David; Chapman, Cynthia; Ogle, Frank; Rosko, Donna; Najmi, Sadia; Walker, Lana M; Maceachern, Pete; Hicks, Thomas

2016-10-01

This is the first randomised controlled trial to evaluate a protocol for cognitive behaviour therapy (CBT) for a Specific Phobia of Vomiting (SPOV) compared with a wait list and to use assessment scales that are specific for a SPOV. 24 participants (23 women and 1 man) were randomly allocated to either 12 sessions of CBT or a wait list. At the end of the treatment, CBT was significantly more efficacious than the wait list with a large effect size (Cohen's d=1.53) on the Specific Phobia of Vomiting Inventory between the two groups after 12 sessions. Six (50%) of the participants receiving CBT achieved clinically significant change compared to 2 (16%) participants in the wait list group. Eight (58.3%) participants receiving CBT achieved reliable improvement compared to 2 (16%) participants in the wait list group. A SPOV is a condition treatable by CBT but further developments are required to increase efficacy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Randomized Trial of Plaque-Identifying Toothpaste: Decreasing Plaque and Inflammation.

PubMed

Fasula, Kim; Evans, Carla A; Boyd, Linda; Giblin, Lori; Belavsky, Benjamin Z; Hetzel, Scott; McBride, Patrick; DeMets, David L; Hennekens, Charles H

2017-06-01

Randomized data are sparse about whether a plaque-identifying toothpaste reduces dental plaque and nonexistent for inflammation. Inflammation is intimately involved in the pathogenesis of atherosclerosis and is accurately measured by high-sensitivity C-reactive protein (hs-CRP), a sensitive marker for cardiovascular disease. The hypotheses that Plaque HD (TJA Health LLC, Joliet, Ill), a plaque-identifying toothpaste, produces statistically significant reductions in dental plaque and hs-CRP were tested in this randomized trial. Sixty-one apparently healthy subjects aged 19 to 44 years were assigned at random to this plaque-identifying (n = 31) or placebo toothpaste (n = 30) for 60 days. Changes from baseline to follow-up in dental plaque and hs-CRP were assessed. In an intention-to-treat analysis, the plaque-identifying toothpaste reduced mean plaque score by 49%, compared with a 24% reduction in placebo (P = .001). In a prespecified subgroup analysis of 38 subjects with baseline levels >0.5 mg/L, the plaque-identifying toothpaste reduced hs-CRP by 29%, compared with a 25% increase in placebo toothpaste (P = .041). This plaque-identifying toothpaste produced statistically significant reductions in dental plaque and hs-CRP. The observed reduction in dental plaque confirms and extends a previous observation. The observed reduction in inflammation supports the hypothesis of a reduction in risks of cardiovascular disease. The direct test of this hypothesis requires a large-scale randomized trial of sufficient size and duration designed a priori to do so. Such a finding would have major clinical and public health implications. Copyright © 2017 Elsevier Inc. All rights reserved.

"Open mesh" or "strictly selected population" recruitment? The experience of the randomized controlled MeMeMe trial.

PubMed

Cortellini, Mauro; Berrino, Franco; Pasanisi, Patrizia

2017-01-01

Among randomized controlled trials (RCTs), trials for primary prevention require large samples and long follow-up to obtain a high-quality outcome; therefore the recruitment process and the drop-out rates largely dictate the adequacy of the results. We are conducting a Phase III trial on persons with metabolic syndrome to test the hypothesis that comprehensive lifestyle changes and/or metformin treatment prevents age-related chronic diseases (the MeMeMe trial, EudraCT number: 2012-005427-32, also registered on ClinicalTrials.gov [NCT02960711]). Here, we briefly analyze and discuss the reasons which may lead to participants dropping out from trials. In our experience, participants may back out of a trial for different reasons. Drug-induced side effects are certainly the most compelling reason. But what are the other reasons, relating to the participants' perception of the progress of the trial which led them to withdraw after randomization? What about the time-dependent drop-out rate in primary prevention trials? The primary outcome of this analysis is the point of drop-out from trial, defined as the time from the randomization date to the withdrawal date. Survival functions were non-parametrically estimated using the product-limit estimator. The curves were statistically compared using the log-rank test ( P =0.64, not significant). Researchers involved in primary prevention RCTs seem to have to deal with the paradox of the proverbial "short blanket syndrome". Recruiting only highly motivated candidates might be useful for the smooth progress of the trial but it may lead to a very low enrollment rate. On the other hand, what about enrolling all the eligible subjects without considering their motivation? This might boost the enrollment rate, but it can lead to biased results on account of large proportions of drop-outs. Our experience suggests that participants do not change their mind depending on the allocation group (intervention or control). There is no single answer to sort out the short blanket syndrome.

Porvoo sarcopenia and nutrition trial: effects of protein supplementation on functional performance in home-dwelling sarcopenic older people - study protocol for a randomized controlled trial.

PubMed

Bjorkman, Mikko P; Suominen, Merja H; Pitkälä, Kaisu H; Finne-Soveri, Harriet U; Tilvis, Reijo S

2013-11-14

Age-related muscle loss (that is, sarcopenia) is a common health problem among older people. Physical exercise and dietary protein have been emphasized in prevention and treatment of sarcopenia. Rigorous trials investigating the effects of protein supplementation on physical performance in sarcopenic populations are still scarce. The aim of this study is to investigate the effects of protein supplementation along with simple home-based exercises on physical performance among home-dwelling sarcopenic older people. During 2012 the entire 75 and older population (N = 3,275) living in Porvoo, Finland was contacted via a postal questionnaire. Persons at risk of sarcopenia are screened with hand grip strength and gait speed. Poorly performing persons are further examined by segmental bioimpendance spectroscopy to determine their skeletal muscle index. Sarcopenic patients (target N = 250) will be enrolled in a 12-month randomized controlled trial with three arms: 1) no supplementation, 2) protein supplementation (20 grams twice a day), and 3) isocaloric placebo. All the participants will receive instructions on simple home-based exercises, dietary protein, and vitamin D supplementation (20 μg/d). The recruitment of patients will be completed during 2013. The primary endpoint of the trial is the change in short physical performance battery score and percentage of patients maintaining or improving their physical performance. Secondary endpoints will be, among other things, changes in muscle functions, nutritional status, body composition, cognition, quality of life, use of health care services, falls, and mortality. The assessment times will be 0, 6, 12 and 24 months. To our knowledge, this is the first large scale randomized controlled trial among community dwelling older people with sarcopenia that focuses on the effects of protein supplementation on physical performance. ACTRN12612001253897, date of registration 28 October 2012, first patient was randomized 11 April 2012.

Generalizing Evidence From Randomized Clinical Trials to Target Populations

PubMed Central

Cole, Stephen R.; Stuart, Elizabeth A.

2010-01-01

Properly planned and conducted randomized clinical trials remain susceptible to a lack of external validity. The authors illustrate a model-based method to standardize observed trial results to a specified target population using a seminal human immunodeficiency virus (HIV) treatment trial, and they provide Monte Carlo simulation evidence supporting the method. The example trial enrolled 1,156 HIV-infected adult men and women in the United States in 1996, randomly assigned 577 to a highly active antiretroviral therapy and 579 to a largely ineffective combination therapy, and followed participants for 52 weeks. The target population was US people infected with HIV in 2006, as estimated by the Centers for Disease Control and Prevention. Results from the trial apply, albeit muted by 12%, to the target population, under the assumption that the authors have measured and correctly modeled the determinants of selection that reflect heterogeneity in the treatment effect. In simulations with a heterogeneous treatment effect, a conventional intent-to-treat estimate was biased with poor confidence limit coverage, but the proposed estimate was largely unbiased with appropriate confidence limit coverage. The proposed method standardizes observed trial results to a specified target population and thereby provides information regarding the generalizability of trial results. PMID:20547574

Facilitating large-scale clinical trials: in Asia.

PubMed

Choi, Han Yong; Ko, Jae-Wook

2010-01-01

The number of clinical trials conducted in Asian countries has started to increase as a result of expansion of the pharmaceutical market in this area. There is a growing opportunity for large-scale clinical trials because of the large number of patients, significant market potential, good quality of data, and the cost effective and qualified medical infrastructure. However, for carrying out large-scale clinical trials in Asia, there are several major challenges, including the quality control of data, budget control, laboratory validation, monitoring capacity, authorship, staff training, and nonstandard treatment that need to be considered. There are also several difficulties in collaborating on international trials in Asia because Asia is an extremely diverse continent. The major challenges are language differences, diversity of patterns of disease, and current treatments, a large gap in the experience with performing multinational trials, and regulatory differences among the Asian countries. In addition, there are also differences in the understanding of global clinical trials, medical facilities, indemnity assurance, and culture, including food and religion. To make regional and local data provide evidence for efficacy through the standardization of these differences, unlimited effort is required. At this time, there are no large clinical trials led by urologists in Asia, but it is anticipated that the role of urologists in clinical trials will continue to increase. Copyright © 2010 Elsevier Inc. All rights reserved.

Systematic Review and Meta-Analysis of Randomized Controlled Trials of Xingnaojing Treatment for Stroke

PubMed Central

Wang, Weihao; Xing, Zhihua

2014-01-01

Objective. Xingnaojing injection (XNJ) is a well-known traditional Chinese patent medicine (TCPM) for stroke. The aim of this study is to assess the efficacy of XNJ for stroke including ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Methods. An extensive search was performed within using eight databases up to November 2013. Randomized controlled trials (RCTs) on XNJ for treatment of stroke were collected. Study selection, data extraction, quality assessment, and meta-analysis were conducted according to the Cochrane standards, and RevMan5.0 was used for meta-analysis. Results. This review included 13 RCTs and a total of 1,514 subjects. The overall methodological quality was poor. The meta-analysis showed that XNJ combined with conventional treatment was more effective for total efficacy, neurological deficit improvement, and reduction of TNF-α levels compared with those of conventional treatment alone. Three trials reported adverse events, of these one trial reported mild impairment of kidney and liver function, whereas the other two studies failed to report specific adverse events. Conclusion. Despite the limitations of this review, we suggest that XNJ in combination with conventional medicines might be beneficial for the treatment of stroke. Currently there are various methodological problems in the studies. Therefore, high-quality, large-scale RCTs are urgently needed. PMID:24707306

Randomized Trial of Behavior Therapy for Adults with Tourette’s Disorder

PubMed Central

Wilhelm, Sabine; Peterson, Alan L.; Piacentini, John; Woods, Douglas W.; Deckersbach, Thilo; Sukhodolsky, Denis G.; Chang, Susanna; Liu, Haibei; Dziura, James; Walkup, John T.; Scahill, Lawrence

2013-01-01

Context Tics in Tourette syndrome begin in childhood, peak in early adolescence, and often decline by early adulthood. However, some adult patients continue to have impairing tics. Medications for tics are often effective but can cause adverse effects. Behavior therapy may offer an alternative but has not been examined in a large-scale controlled trial in adults. Objective To test the efficacy of a comprehensive behavioral intervention for tics in adults with Tourette syndrome of at least moderate severity. Design A randomized, controlled trial with posttreatment evaluations at 3 and 6 months for positive responders. Setting Three outpatient research clinics. Subjects Subjects (N = 122; 78 males, age 16 to 69 years) with Tourette syndrome or chronic tic disorder. Interventions Eight sessions of Comprehensive Behavioral Intervention for Tics or 8 sessions of supportive treatment delivered over 10 weeks. Subjects showing a positive response were given 3 monthly booster sessions. Main Outcome Measures Total Tic score of the Yale Global Tic Severity Scale and the Improvement scale of the Clinical Global Impression rated by a clinician blind to treatment assignment. Results Behavior therapy was associated with a significantly greater decrease on the Yale Global Tic Severity Scale (24.0 ± 6.47 to 17.8 ± 7.32) from baseline to endpoint compared to the control treatment (21.8 ± 6.59 to 19.3 ± 7.40) (P < .001; effect size = 0.57). Twenty-four of 63 subjects (38.1%) in CBIT were rated as Much Improved or Very Much Improved on the Clinical Global Impression-Improvement scale compared to 6.8% (4 of 63) in the control group (P < .0001). Attrition was 13.9% with no difference across groups. Subjects in behavior therapy available for assessment at 6 months posttreatment showed continued benefit. Conclusions Comprehensive behavior therapy is a safe and effective intervention for adults with Tourette syndrome. PMID:22868933

Evaluating large-scale health programmes at a district level in resource-limited countries.

PubMed

Svoronos, Theodore; Mate, Kedar S

2011-11-01

Recent experience in evaluating large-scale global health programmes has highlighted the need to consider contextual differences between sites implementing the same intervention. Traditional randomized controlled trials are ill-suited for this purpose, as they are designed to identify whether an intervention works, not how, when and why it works. In this paper we review several evaluation designs that attempt to account for contextual factors that contribute to intervention effectiveness. Using these designs as a base, we propose a set of principles that may help to capture information on context. Finally, we propose a tool, called a driver diagram, traditionally used in implementation that would allow evaluators to systematically monitor changing dynamics in project implementation and identify contextual variation across sites. We describe an implementation-related example from South Africa to underline the strengths of the tool. If used across multiple sites and multiple projects, the resulting driver diagrams could be pooled together to form a generalized theory for how, when and why a widely-used intervention works. Mechanisms similar to the driver diagram are urgently needed to complement existing evaluations of large-scale implementation efforts.

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.

Traditional manual acupuncture combined with rehabilitation therapy for shoulder hand syndrome after stroke within the Chinese healthcare system: a systematic review and meta-analysis.

PubMed

Peng, Le; Zhang, Chao; Zhou, Lan; Zuo, Hong-Xia; He, Xiao-Kuo; Niu, Yu-Ming

2018-04-01

To investigate the effectiveness of traditional manual acupuncture combined with rehabilitation therapy versus rehabilitation therapy alone for shoulder hand syndrome after stroke. PubMed, EMBASE, the Cochrane Library, Chinese Biomedicine Database, China National Knowledge Infrastructure, VIP Information Database, Wan Fang Database and reference lists of the eligible studies were searched up to July 2017 for relevant studies. Randomized controlled trials that compared the combined effects of traditional manual acupuncture and rehabilitation therapy to rehabilitation therapy alone for shoulder hand syndrome after stroke were included. Two reviewers independently screened the searched records, extracted the data and assessed risk of bias of the included studies. The treatment effect sizes were pooled in a meta-analysis using RevMan 5.3 software. A total of 20 studies involving 1918 participants were included in this study. Compared to rehabilitation therapy alone, the combined therapy significantly reduced pain on the visual analogue scale and improved limb movement on the Fugl-Meyer Assessment scale and the performance of activities of daily living (ADL) on the Barthel Index scale or Modified Barthel Index scale. Of these, the visual analogue scale score changes were significantly higher (mean difference = 1.49, 95% confidence interval = 1.15-1.82, P < 0.00001) favoring the combined therapy after treatment, with severe heterogeneity ( I 2  = 71%, P = 0.0005). Current evidence suggests that traditional manual acupuncture integrated with rehabilitation therapy is more effective in alleviating pain, improving limb movement and ADL. However, considering the relatively low quality of available evidence, further rigorously designed and large-scale randomized controlled trials are needed to confirm the results.

Intranasal topical local anesthetic and decongestant for flexible nasendoscopy in children: a randomized, double-blind, placebo-controlled trial.

PubMed

Chadha, Neil K; Lam, Gilbert O A; Ludemann, Jeffrey P; Kozak, Frederick K

2013-12-01

To our knowledge, the present study is the first double-blind, randomized, placebo-controlled trial in children to compare nasal preparation sprays administered before flexible nasendoscopy with placebo. To compare the degree of pain experienced by children undergoing flexible nasendoscopy after 1 of 3 intranasal sprays: placebo, decongestant with topical local anesthetic (TLA), or decongestant without TLA. A randomized placebo-controlled trial with blinding of participants, caregivers, observers, and otolaryngologists was conducted in a tertiary pediatric otolaryngology ambulatory clinic. Participants included a consecutive sample of children aged 3 to 12 years requiring flexible nasendoscopy. Exclusion criteria included concomitant respiratory tract infection, known allergy to a trial agent, or previous flexible nasendoscopy. One hundred fifty-one children were assessed for eligibility; 24 eligible children refused participation and 69 were included and block-randomized. All completed the study, and there were no adverse events. Nasal spray administration of placebo (normal saline); xylometazoline hydrochloride, 0.05% (decongestant); or lidocaine hydrochloride, 1%, with xylometazoline hydrochloride, 0.05% (TLA with decongestant) was performed 10 minutes before flexible nasendoscopy. Primary outcome measure was the child-reported Wong-Baker Faces Pain (WBFP) scale. Secondary outcomes included the caregiver-proxy WBFP scale; the Face, Legs, Activity, Cry, and Consolability (FLACC) scale; and the physician-reported Difficulty of Procedure Visual Analog Scale (DPVAS). Twenty-three children were recruited in each of the intervention arms. Baseline characteristics were comparable between groups. The mean child-rated WBFP scale scores were 2.4, 1.8, and 2.2 for the placebo, decongestant, and TLA with decongestant groups, respectively (P = .45). Although the finding was statistically nonsignificant, decongestant had the lowest mean caregiver-proxy WBFP scale score, lowest observer-rated FLACC scale score, and highest physician-rated DPVAS score. Subgroup analysis did not demonstrate any correlation between the outcomes and age or sex. This study revealed no statistically significant difference in the discomfort experienced by children undergoing flexible nasendoscopy after placebo, decongestant, or TLA with decongestant. Decongestant was associated with the least discomfort (on child, caregiver, and observer-rated pain scale scores) and the lowest rating for difficulty of procedure. With these findings, the study suggests that there is no significant benefit of topical decongestant with or without TLA compared with placebo in reducing pain associated with pediatric flexible nasendoscopy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01351298.

Lessons Learned from Large-Scale Randomized Experiments

ERIC Educational Resources Information Center

Slavin, Robert E.; Cheung, Alan C. K.

2017-01-01

Large-scale randomized studies provide the best means of evaluating practical, replicable approaches to improving educational outcomes. This article discusses the advantages, problems, and pitfalls of these evaluations, focusing on alternative methods of randomization, recruitment, ensuring high-quality implementation, dealing with attrition, and…

Randomized controlled trials and neuro-oncology: should alternative designs be considered?

PubMed

Mansouri, Alireza; Shin, Samuel; Cooper, Benjamin; Srivastava, Archita; Bhandari, Mohit; Kondziolka, Douglas

2015-09-01

Deficiencies in design and reporting of randomized controlled trials (RCTs) hinders interpretability and critical appraisal. The reporting quality of recent RCTs in neuro-oncology was analyzed to assess adequacy of design and reporting. The MEDLINE and EMBASE databases were searched to identify non-surgical RCTs (years 2005-2014, inclusive). The CONSORT and Jadad scales were used to assess the quality of design/reporting. Studies published in 2005-2010 were compared as a cohort against studies published in 2011-2014, in terms of general characteristics and reporting quality. A PRECIS-based scale was used to designate studies on the pragmatic-explanatory continuum. Spearman's test was used to assess correlations. Regression analysis was used to assess associations. Overall 68 RCTs were identified. Studies were often chemotherapy-based (n = 41 studies) focusing upon high grade gliomas (46 %) and metastases (41 %) as the top pathologies. Multi-center trials (71 %) were frequent. The overall median CONSORT and Jadad scores were 34.5 (maximum 44) and 2 (maximum 5), respectively; these scores were similar in radiation and chemotherapy-based trials. Major areas of deficiency pertained to allocation concealment, implementation of methods, and blinding whereby less than 20 % of articles fulfilled all criteria. Description of intervention, random sequence generation, and the details regarding recruitment were also deficient; less than 50 % of studies fulfilled all criteria. Description of sample size calculations and blinding improved in later published cohorts. Journal impact factor was significantly associated with higher quality (p = 0.04). Large academic consortia, multi-center designs, ITT analysis, collaboration with biostatisticians, larger sample sizes, and studies with pragmatic objectives were more likely to achieve positive primary outcomes on univariate analysis; none of these variables were significant on multivariate analysis. Deficiencies in the quality of design/reporting of RCTs in neuro-oncology persist. Quality improvement is necessary. Consideration of alternative strategies should be considered.

Inference of median difference based on the Box-Cox model in randomized clinical trials.

PubMed

Maruo, K; Isogawa, N; Gosho, M

2015-05-10

In randomized clinical trials, many medical and biological measurements are not normally distributed and are often skewed. The Box-Cox transformation is a powerful procedure for comparing two treatment groups for skewed continuous variables in terms of a statistical test. However, it is difficult to directly estimate and interpret the location difference between the two groups on the original scale of the measurement. We propose a helpful method that infers the difference of the treatment effect on the original scale in a more easily interpretable form. We also provide statistical analysis packages that consistently include an estimate of the treatment effect, covariance adjustments, standard errors, and statistical hypothesis tests. The simulation study that focuses on randomized parallel group clinical trials with two treatment groups indicates that the performance of the proposed method is equivalent to or better than that of the existing non-parametric approaches in terms of the type-I error rate and power. We illustrate our method with cluster of differentiation 4 data in an acquired immune deficiency syndrome clinical trial. Copyright © 2015 John Wiley & Sons, Ltd.

Challenges and opportunities in SLE clinical trials.

PubMed

van Vollenhoven, Ronald F

2013-09-01

To provide an update on the field of clinical trials in systemic lupus erythematosus (SLE). This review will examine failed and successful clinical trials in SLE in order to draw lessons and determine the optimal ways forward. Over the past decade, many clinical trials in SLE met with limited success, but in the past 2 years several SLE clinical trials have been successful. The two large phase III randomized controlled trials (RCTs) of belimumab achieved their primary endpoints and resulted in food and drug administration and European medicines agency approval of the drug. Characteristics of these trials were, among other things, a very large number of patients (>800 each), compound clinical endpoints, and a flexible design with regards to concomitant medication use. Likewise, large randomized controlled trials with mycophenolate mofetil, although nominally unsuccessful, clearly demonstrated the clinical benefit of this drug in lupus nephritis. Posthoc analyses of several failed trials involving abatacept and rituximab revealed design elements and/or outcomes that might have changed the outcomes of these studies. Many smaller trials have also been reported, in some instances with surprisingly positive results. An improved understanding of specific design features in SLE clinical trials combined with robust outcomes will make it possible more effectively to design and conduct clinical trials in SLE.

Effect Sizes and Primary Outcomes in Large-Budget, Cardiovascular-Related Behavioral Randomized Controlled Trials Funded by NIH Since 1980

PubMed Central

Irvin, Veronica L.; Kaplan, Robert M.

2015-01-01

Purpose We reviewed large-budget, National Institutes of Health (NIH)-supported randomized controlled trials (RCTs) with behavioral interventions to assess (1) publication rates, (2) trial registration, (3) use of objective measures, (4) significant behavior and physiological change, and (5) effect sizes. Methods We identified large-budget grants (>$500,000/year) funded by NIH (National Heart Lung and Blood Institute (NHLBI) or National Institute of Diabetes & Digestive and Kidney Diseases (NIDDK)) for cardiovascular disease (dates January 1, 1980 to December 31, 2012). Among 106 grants that potentially met inclusion criteria, 20 studies were not published and 48 publications were excluded, leaving 38 publications for analysis. ClinicalTrials.gov abstracts were used to determine whether outcome measures had been pre-specified. Results Three fourths of trials were registered in ClinicalTrials.gov and all published pre-specified outcomes. Twenty-six trials reported a behavioral outcome with 81 % reporting significant improvements for the target behavior. Thirty-two trials reported a physiological outcome. All were objectively measured, and 81 % reported significant benefit. Seventeen trials reported morbidity outcomes, and seven reported a significant benefit. Nine trials assessed mortality, and all were null for this outcome. Conclusions Behavioral trials complied with trial registration standards. Most reported a physiological benefit, but few documented morbidity or mortality benefits. PMID:26507906

Treating major depression with yoga: A prospective, randomized, controlled pilot trial

PubMed Central

Rivera, Renee; Cochran, Ashly; Tungol, Jose Gabriel; Fayazmanesh, Nima; Weinmann, Eva

2017-01-01

Background Conventional pharmacotherapies and psychotherapies for major depression are associated with limited adherence to care and relatively low remission rates. Yoga may offer an alternative treatment option, but rigorous studies are few. This randomized controlled trial with blinded outcome assessors examined an 8-week hatha yoga intervention as mono-therapy for mild-to-moderate major depression. Methods Investigators recruited 38 adults in San Francisco meeting criteria for major depression of mild-to-moderate severity, per structured psychiatric interview and scores of 14–28 on Beck Depression Inventory-II (BDI). At screening, individuals engaged in psychotherapy, antidepressant pharmacotherapy, herbal or nutraceutical mood therapies, or mind-body practices were excluded. Participants were 68% female, with mean age 43.4 years (SD = 14.8, range = 22–72), and mean BDI score 22.4 (SD = 4.5). Twenty participants were randomized to 90-minute hatha yoga practice groups twice weekly for 8 weeks. Eighteen participants were randomized to 90-minute attention control education groups twice weekly for 8 weeks. Certified yoga instructors delivered both interventions at a university clinic. Primary outcome was depression severity, measured by BDI scores every 2 weeks from baseline to 8 weeks. Secondary outcomes were self-efficacy and self-esteem, measured by scores on the General Self-Efficacy Scale (GSES) and Rosenberg Self-Esteem Scale (RSES) at baseline and at 8 weeks. Results In intent-to-treat analysis, yoga participants exhibited significantly greater 8-week decline in BDI scores than controls (p-value = 0.034). In sub-analyses of participants completing final 8-week measures, yoga participants were more likely to achieve remission, defined per final BDI score ≤ 9 (p-value = 0.018). Effect size of yoga in reducing BDI scores was large, per Cohen’s d = -0.96 [95%CI, -1.81 to -0.12]. Intervention groups did not differ significantly in 8-week change scores for either the GSES or RSES. Conclusion In adults with mild-to-moderate major depression, an 8-week hatha yoga intervention resulted in statistically and clinically significant reductions in depression severity. Trial registration ClinicalTrials.gov NCT01210651 PMID:28301561

Raloxifene Plus Antipsychotics Versus Placebo Plus Antipsychotics in Severely Ill Decompensated Postmenopausal Women With Schizophrenia or Schizoaffective Disorder: A Randomized Controlled Trial.

PubMed

Weiser, Mark; Levi, Linda; Burshtein, Shimon; Hagin, Michal; Matei, Valentin P; Podea, Delia; Micluția, Ioana; Tiugan, Alexandru; Păcală, Bogdan; Grecu, Iosif Gabos; Noy, Adam; Zamora, Daisy; Davis, John M

2017-07-01

Several single-center studies have found raloxifene, an estrogen agonist, to be effective in ameliorating symptoms of schizophrenia in stable patients as augmentation of antipsychotics. This multicenter study assessed whether raloxifene plus antipsychotic treatment, in comparison to placebo plus antipsychotics, improves symptoms or cognition in severely ill decompensated schizophrenia patients. In this 16-week, double-blind, randomized, placebo-controlled study, 200 severely ill, decompensated postmenopausal women who met DSM-IV-TR criteria for schizophrenia or schizoaffective disorder were recruited from January 2011 to December 2012 and were randomized to receive either raloxifene 120 mg/d plus antipsychotics or placebo plus antipsychotics. The primary outcome measure was Positive and Negative Syndrome Scale (PANSS) total score at the end of the trial. The placebo plus antipsychotics group experienced statistically significant improvement in PANSS total score (P < .001) compared to the raloxifene plus antipsychotics group, using mixed models for repeated measures, with results favoring placebo by 4.5 points (95% CI, 2.3-6.7). These results were clearly outside the 95% confidence interval. This negative effect was more pronounced in patients who had more frequent relapses and in those with baseline PANSS scores of 100 or higher. There were no differences between groups in Clinical Global Impression Scale-Severity scores or Composite Brief Assessment of Cognition in Schizophrenia scores at 16 weeks (P > .3). Baseline follicle-stimulating hormone and estradiol levels did not alter the drug-placebo differences. Individuals in the active treatment arm showed worse outcome than those in the placebo arm, most likely as a result of chance variation, but the results unequivocally show no benefit of antipsychotics plus raloxifene versus antipsychotics plus placebo in this large randomized, double-blind, placebo-controlled trial in postmenopausal women. These data do not support the use of raloxifene in severely decompensated schizophrenia patients until reliable research identifies what subgroup of patients or domain of outcome is benefited. ClinicalTrials.gov identifier: NCT01280305. © Copyright 2017 Physicians Postgraduate Press, Inc.

Update on worldwide efforts to prevent type 1 diabetes.

PubMed

Skyler, Jay S

2008-12-01

This paper reviews worldwide efforts to interdict the type 1 diabetes (T1D) disease process, during the stage of evolution of the disease prior to the time of disease onset. The goal of intervention before disease onset is to arrest immune destruction and thus prevent or delay clinical disease. In this regard, there have been several large-scale multicenter randomized controlled clinical trials designed to prevent T1D. These have tested nicotinamide, parenteral insulin, oral insulin, nasal insulin, and the elimination of cow's milk from infant feeding.

Whole body vibration exercise for chronic low back pain: study protocol for a single-blind randomized controlled trial.

PubMed

Wang, Xue-Qiang; Pi, Yan-Lin; Chen, Pei-Jie; Chen, Bin-Lin; Liang, Lei-Chao; Li, Xin; Wang, Xiao; Zhang, Juan

2014-04-02

Low back pain affects approximately 80% of people at some stage in their lives. Exercise therapy is the most widely used nonsurgical intervention for low back pain in practice guidelines. Whole body vibration exercise is becoming increasingly popular for relieving musculoskeletal pain and improving health-related quality of life. However, the efficacy of whole body vibration exercise for low back pain is not without dispute. This study aims to estimate the effect of whole body vibration exercise for chronic low back pain. We will conduct a prospective, single-blind, randomized controlled trial of 120 patients with chronic low back pain. Patients will be randomly assigned into an intervention group and a control group. The intervention group will participate in whole body vibration exercise twice a week for 3 months. The control group will receive general exercise twice a week for 3 months. Primary outcome measures will be the visual analog scale for pain, the Oswestry Disability Index and adverse events. The secondary outcome measures will include muscle strength and endurance of spine, trunk proprioception, transversus abdominis activation capacity, and quality of life. We will conduct intention-to-treat analysis if any participants withdraw from the trial. Important features of this study include the randomization procedures, single-blind, large sample size, and a standardized protocol for whole body vibration in chronic low back pain. This study aims to determine whether whole body vibration exercise produces more beneficial effects than general exercise for chronic low back pain. Therefore, our results will be useful for patients with chronic low back pain as well as for medical staff and health-care decision makers. Chinese Clinical Trial Registry: ChiCTR-TRC-13003708.

Changes in Brain Volume and Cognition in a Randomized Trial of Exercise and Social Interaction in a Community-Based Sample of Non-Demented Chinese Elders

PubMed Central

Mortimer, James A.; Ding, Ding; Borenstein, Amy R.; DeCarli, Charles; Guo, Qihao; Wu, Yougui; Zhao, Qianhua; Chu, Shugang

2013-01-01

Physical exercise has been shown to increase brain volume and improve cognition in randomized trials of non-demented elderly. Although greater social engagement was found to reduce dementia risk in observational studies, randomized trials of social interventions have not been reported. A representative sample of 120 elderly from Shanghai, China was randomized to four groups (Tai Chi, Walking, Social Interaction, No Intervention) for 40 weeks. Two MRIs were obtained, one before the intervention period, the other after. A neuropsychological battery was administered at baseline, 20 weeks, and 40 weeks. Comparison of changes in brain volumes in intervention groups with the No Intervention group were assessed by t-tests. Time-intervention group interactions for neuropsychological measures were evaluated with repeated-measures mixed models. Compared to the No Intervention group, significant increases in brain volume were seen in the Tai Chi and Social Intervention groups (p < 0.05). Improvements also were observed in several neuropsychological measures in the Tai Chi group, including the Mattis Dementia Rating Scale score (p = 0.004), the Trailmaking Test A (p = 0.002) and B (p = 0.0002), the Auditory Verbal Learning Test (p = 0.009), and verbal fluency for animals (p = 0.01). The Social Interaction group showed improvement on some, but fewer neuropsychological indices. No differences were observed between the Walking and No Intervention groups. The findings differ from previous clinical trials in showing increases in brain volume and improvements in cognition with a largely non-aerobic exercise (Tai Chi). In addition, intellectual stimulation through social interaction was associated with increases in brain volume as well as with some cognitive improvements. PMID:22451320

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.

Blood pressure and endothelial function in healthy, pregnant women after acute and daily consumption of flavanol-rich chocolate: a pilot, randomized controlled trial

PubMed Central

2013-01-01

Background Several randomized clinical trials (RCTs) indicate that flavanol-rich chocolate has beneficial effects on flow-mediated dilation (FMD) and blood pressure (BP). However, no RCTs have evaluated these outcomes in pregnant women. The objective of this 2-group, parallel, double-blind RCT was to examine the effects of flavanol-rich chocolate on FMD and BP in pregnant women with normal BP. Methods Forty-four healthy, pregnant women were randomized to the high-flavanol (n = 23) or low-flavanol (n = 21) chocolate consumption for 12 weeks. At randomization (0, 60, 120 and 180 min after a single 40-g dose of chocolate), 6 and 12 weeks after daily 20-g chocolate intake, we evaluated plasma concentrations of flavanols and theobromine, as well as the FMD and BP. Results Plasma epicatechin was significantly increased (p < 0.001) 180 min after the consumption of 40-g high-flavanol chocolate compared to low-flavanol chocolate. Theobromine concentrations were significantly higher 180 min and 12 weeks after the intake of experimental chocolate or low-flavanol chocolate (p < 0.001). FMD was not different between the 2 groups at all pre-defined time periods. No other significant within-group or between-group changes were observed. Conclusion These results confirm the feasibility of a large-scale RCT comparing daily consumption of flavanol-rich chocolate to an equivalent placebo during pregnancy and demonstrate higher plasma epicatechin and theobromine concentration in the intervention group after acute ingestion Trial registration ClinicalTrials.gov Identifier: NCT01659060 PMID:23565841

Changes in brain volume and cognition in a randomized trial of exercise and social interaction in a community-based sample of non-demented Chinese elders.

PubMed

Mortimer, James A; Ding, Ding; Borenstein, Amy R; DeCarli, Charles; Guo, Qihao; Wu, Yougui; Zhao, Qianhua; Chu, Shugang

2012-01-01

Physical exercise has been shown to increase brain volume and improve cognition in randomized trials of non-demented elderly. Although greater social engagement was found to reduce dementia risk in observational studies, randomized trials of social interventions have not been reported. A representative sample of 120 elderly from Shanghai, China was randomized to four groups (Tai Chi, Walking, Social Interaction, No Intervention) for 40 weeks. Two MRIs were obtained, one before the intervention period, the other after. A neuropsychological battery was administered at baseline, 20 weeks, and 40 weeks. Comparison of changes in brain volumes in intervention groups with the No Intervention group were assessed by t-tests. Time-intervention group interactions for neuropsychological measures were evaluated with repeated-measures mixed models. Compared to the No Intervention group, significant increases in brain volume were seen in the Tai Chi and Social Intervention groups (p < 0.05). Improvements also were observed in several neuropsychological measures in the Tai Chi group, including the Mattis Dementia Rating Scale score (p = 0.004), the Trailmaking Test A (p = 0.002) and B (p = 0.0002), the Auditory Verbal Learning Test (p = 0.009), and verbal fluency for animals (p = 0.01). The Social Interaction group showed improvement on some, but fewer neuropsychological indices. No differences were observed between the Walking and No Intervention groups. The findings differ from previous clinical trials in showing increases in brain volume and improvements in cognition with a largely non-aerobic exercise (Tai Chi). In addition, intellectual stimulation through social interaction was associated with increases in brain volume as well as with some cognitive improvements.

Impact of oral care with versus without toothbrushing on the prevention of ventilator-associated pneumonia: a systematic review and meta-analysis of randomized controlled trials

PubMed Central

2012-01-01

Introduction Ventilator-associated pneumonia (VAP) remains a common hazardous complication in mechanically ventilated patients and is associated with increased morbidity and mortality. We undertook a systematic review and meta-analysis of randomized controlled trials to assess the effect of toothbrushing as a component of oral care on the prevention of VAP in adult critically ill patients. Methods A systematic literature search of PubMed and Embase (up to April 2012) was conducted. Eligible studies were randomized controlled trials of mechanically ventilated adult patients receiving oral care with toothbrushing. Relative risks (RRs), weighted mean differences (WMDs), and 95% confidence intervals (CIs) were calculated and heterogeneity was assessed with the I2 test. Results Four studies with a total of 828 patients met the inclusion criteria. Toothbrushing did not significantly reduce the incidence of VAP (RR, 0.77; 95% CI, 0.50 to 1.21) and intensive care unit mortality (RR, 0.88; 95% CI, 0.70 to 1.10). Toothbrushing was not associated with a statistically significant reduction in duration of mechanical ventilation (WMD, -0.88 days; 95% CI, -2.58 to 0.82), length of intensive care unit stay (WMD, -1.48 days; 95% CI, -3.40 to 0.45), antibiotic-free day (WMD, -0.52 days; 95% CI, -2.82 to 1.79), or mechanical ventilation-free day (WMD, -0.43 days; 95% CI, -1.23 to 0.36). Conclusions Oral care with toothbrushing versus without toothbrushing does not significantly reduce the incidence of VAP and alter other important clinical outcomes in mechanically ventilated patients. However, the results should be interpreted cautiously since relevant evidence is still limited, although accumulating. Further large-scale, well-designed randomized controlled trials are urgently needed. PMID:23062250

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.

Gait retraining versus foot orthoses for patellofemoral pain: a pilot randomised clinical trial.

PubMed

Bonacci, Jason; Hall, Michelle; Saunders, Natalie; Vicenzino, Bill

2018-05-01

To determine the feasibility of a clinical trial that compares a 6-week, physiotherapist-guided gait retraining program with a foot orthoses intervention in runners with patellofemoral pain. Pilot randomised controlled trial. Runners aged 18-40 years with clinically diagnosed patellofemoral pain were randomly allocated to either a 6-week gait retraining intervention of increasing cadence and use of a minimalist shoe or prefabricated foot orthoses. Outcomes at baseline and 12-weeks included recruitment, retention, adherence, adverse events, global improvement, anterior knee pain scale, worst and average pain on a 100mm visual analogue scale. Of the 16 randomised participants, two withdrew prior to commencing treatment due to non-trial related matters (n=1 from each group) and 14 completed the pilot trial. Minor calf muscle soreness was reported by 3 participants in the gait retraining group while no adverse events were reported in the foot orthoses group. There were no deviations from the treatment protocols. There was a large between-group difference favouring gait retraining at 12-weeks in the anterior knee pain scale and the worst pain in the past week, which was reflected in the number needed-to-treat of 2. This study supports the feasibility of a trial comparing gait retraining with foot orthoses and provides point estimates of effect that informs the design and planning of a larger clinical trial. It appears that a 6-week gait retraining program has a clinically meaningful effect on runners with patellofemoral pain when compared to an evidence-based treatment of foot orthoses. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

A Blinded Randomized Controlled Trial of Motivational Interviewing to Improve Adherence with Osteoporosis Medications: Design of the OPTIMA Trial

PubMed Central

Solomon, Daniel H.; Gleeson, Timothy; Iversen, Maura; Avorn, Jerome; Brookhart, M. Alan; Lii, Joyce; Losina, Elena; May, Frank; Patrick, Amanda; Shrank, William H.; Katz, Jeffrey N.

2010-01-01

Purpose While many effective treatments exist for osteoporosis, most people do not adhere to such treatments long-term. No proven interventions exist to improve osteoporosis medication adherence. We report here on the design and initial enrollment in an innovative randomized controlled trial aimed at improving adherence to osteoporosis treatments. Methods The trial represents a collaboration between academic researchers and a state-run pharmacy benefits program for low-income older adults. Beneficiaries beginning treatment with a medication for osteoporosis are targeted for recruitment. We randomize consenting individuals to receive 12-months of mailed education (control arm) or an intervention consisting of one-on-one telephone-based counseling and the mailed education. Motivational Interviewing forms the basis for the counseling program which is delivered by seven trained and supervised health counselors over ten telephone calls. The counseling sessions include scripted dialogue, open-ended questions about medication adherence and its barriers, as well as structured questions. The primary endpoint of the trial is medication adherence measured over the 12-month intervention period. Secondary endpoints include fractures, nursing home admissions, health care resource utilization, and mortality. Results During the first 7 months of recruitment, we have screened 3,638 potentially eligible subjects. After an initial mailing, 1,115 (30.6%) opted out of telephone recruitment and 1,019 (28.0%) could not be successfully contacted. Of the remaining, 879 (24.2%) consented to participate and were randomized. Women comprise over 90% of all groups, mean ages range from 77–80 years old, and the majority in all groups was white. The distribution of osteoporosis medications was comparable across groups and the median number of different prescription drugs used in the prior year was 8–10. Conclusions We have developed a novel intervention for improving osteoporosis medication adherence. The intervention is currently being tested in a large scale randomized controlled trial. If successful, the intervention may represent a useful model for improving adherence to other chronic treatments. PMID:19436935

Sensitivity of the Modified Children's Yale-Brown Obsessive Compulsive Scale to Detect Change: Results from Two Multi-Site Trials

ERIC Educational Resources Information Center

Scahill, Lawrence; Sukhodolsky, Denis G.; Anderberg, Emily; Dimitropoulos, Anastasia; Dziura, James; Aman, Michael G.; McCracken, James; Tierney, Elaine; Hallett, Victoria; Katz, Karol; Vitiello, Benedetto; McDougle, Christopher

2016-01-01

Repetitive behavior is a core feature of autism spectrum disorder. We used 8-week data from two federally funded, multi-site, randomized trials with risperidone conducted by the Research Units on Pediatric Psychopharmacology Autism Network to evaluate the sensitivity of the Children's Yale-Brown Obsessive Compulsive Scale modified for autism…

Does Goal Attainment Scaling improve satisfaction regarding performance of activities of younger knee arthroplasty patients? Study protocol of the randomized controlled ACTION trial.

PubMed

Witjes, Suzanne; Hoorntje, Alexander; Kuijer, P Paul F M; Koenraadt, Koen L M; Blankevoort, Leendert; Kerkhoffs, Gino M M J; van Geenen, Rutger C I

2016-03-02

Knee arthroplasty is being increasingly performed, and also more often in a younger patient population (<65 years of age). Up to 20 % of patients remain dissatisfied after knee arthroplasty, despite the apparent technical success of the operation. Recent studies suggest that the fulfilment of patients' expectations plays an important role in achieving satisfaction. Thus, addressing preoperative expectations more explicitly might improve patient satisfaction. The primary aim of the present study is to investigate the effect of a multidisciplinary, goal attained and individualized rehabilitation on satisfaction of activities of younger patients (<65 years) after knee arthroplasty. A single-centre randomized controlled trial will be conducted. In total, 120 patients (<65 years of age) with knee osteoarthritis who will undergo knee arthroplasty, will be randomly allocated to either goal attainment scaling rehabilitation or usual care rehabilitation. Goal attainment scaling rehabilitation includes drafting individually set rehabilitation goals preoperatively and measuring progress of rehabilitation on a six-point scale (-3 to +2). The primary outcome is patient satisfaction concerning activities in daily life, work and leisure time, including sports. Secondary outcome measures include KOOS, OKS, SQUASH and WORQ questionnaires and activity objectively measured with the Activ8® activity monitor. The findings of this study will help to elucidate whether goal attainment scaling is an effective rehabilitation method for achieving higher levels of patient satisfaction, with a focus on activities, in younger patients after knee arthroplasty. This trial is since June 15(th) 2015 registered at the Dutch Trial Register: NTR5251 .

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.

Happy Family Kitchen II: A Cluster Randomized Controlled Trial of a Community-Based Family Intervention for Enhancing Family Communication and Well-being in Hong Kong

PubMed Central

Ho, Henry C. Y.; Mui, Moses; Wan, Alice; Ng, Yin-Lam; Stewart, Sunita M.; Yew, Carol; Lam, Tai Hing; Chan, Sophia S.

2016-01-01

Long working hours and stressful urban lifestyles pose major challenges to family communication and well-being in Hong Kong. A community-based family intervention derived from a positive psychology framework, by using cooking and dining as a platform, was developed for improving family communication and well-being. Social workers and teachers from 31 social service units and schools in collaboration with an academic partner organized and conducted the intervention programs for 2,070 individuals from 973 families in a deprived district in Hong Kong. The participants were randomly assigned into the intervention or control group in a cluster randomized controlled trial (cRCT). The core intervention covered one of five positive psychology themes: joy, gratitude, flow, savoring, and listening. Assessments at pre-intervention, immediate post-intervention, and 4 and 12 weeks post-intervention showed improved family communication and well-being with sustainable effects up to 12 weeks. Positive changes in family happiness and family health were greater in the intervention group than in the control group. The savoring intervention had the most improved outcomes among the five themes. We concluded that this large-scale brief cRCT developed and conducted in real-world settings provided evidence for the feasibility and effectiveness of a community-based family intervention. This study was registered under ClinicalTrials.gov (NCT01796275). PMID:27199864

Placebo effects in a multiple sclerosis spasticity enriched clinical trial with the oromucosal cannabinoid spray (THC/CBD): dimension and possible causes.

PubMed

Di Marzo, Vincenzo; Centonze, Diego

2015-03-01

Regulatory authorities admit clinical studies with an initial enrichment phase to select patients that respond to treatment before randomization (Enriched Design Studies; EDSs). The trial period aims to prevent long-term drug exposure risks in patients with limited chances of improvement while optimizing costs. In EDSs for symptom control therapies providing early improvements and without a wash-out period, it is difficult to show further improvements and thus large therapeutic gains versus placebo. Moreover, in trials with cannabinoids, the therapeutic gains can be further biased in the postenrichment randomized phase because of carryover and other effects. The aims of the present review article are to examine the placebo effects in the enrichment and postenrichment phases of an EDS with Δ(9) -tetrahydrocannabinol and cannabidiol (THC/CBD) oromucosal spray in patients with multiple sclerosis (MS) spasticity and to discuss the possible causes of maintained efficacy after randomization in the placebo-allocated patients. The overall mean therapeutic gain of THC/CBD spray over placebo in resistant MS spasticity after 16 weeks can be estimated as a ~1.27-point improvement on the spasticity 0-10 Numerical Rating Scale (NRS; ~-20.1% of the baseline NRS score). We conclude that careful interpretation of the results of EDSs is required, especially when cannabinoid-based medications are being investigated. © 2014 John Wiley & Sons Ltd.

Multicenter, randomized, placebo-controlled, double-blind clinical trial of escitalopram on the progression-delaying effects in Alzheimer's disease.

PubMed

Choe, Young Min; Kim, Ki Woong; Jhoo, Jin Hyeong; Ryu, Seung Ho; Seo, Eun Hyun; Sohn, Bo Kyung; Byun, Min Soo; Bak, Jae-Hwa; Lee, Jong-Min; Yun, Hyuk Jin; Han, Myeong-Il; Woo, Jong Inn; Lee, Dong Young

2016-07-01

A series of preclinical studies have suggested that selective serotonin reuptake inhibitor antidepressants not only stimulate neurogenesis but also have neuroprotective effects. The present study primarily aimed to investigate whether escitalopram would decelerate the brain atrophy of patients with mild-to-moderate Alzheimer's disease (AD). We also assessed the effects of escitalopram on the cognitive function and neuropsychiatric symptoms of these participants. Seventy-four probable AD patients without major depression were recruited from four dementia clinics of university hospitals and randomly assigned in a 1:1 ratio. Each group received 20 mg/day of escitalopram or placebo for 52 weeks. The primary outcome measures were the change rates of hippocampal and whole brain volume on magnetic resonance imaging for 52 weeks. The Alzheimer's Disease Assessment Scale-cognitive subscale, Mini-Mental State Examination, Neuropsychiatric Inventory, and Cornell Scale for Depression in Dementia (CSDD) were also applied. We did not find any significant differences in the changes of hippocampal or whole brain volume between the groups. Escitalopram showed significant beneficial effects on the CSDD score at 28 weeks compared with placebo (t = -2.17, df = 50.42, p = 0.035), but this finding did not persist throughout the study. The findings of the present study do not support the role of escitalopram as a progression-delaying treatment for AD. However, the negative results of the present trial should be interpreted cautiously because of the relatively small sample size. Further large-scale escitalopram trials targeting the earlier stages of AD, even prodromal AD, are still needed. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Unit cost analysis of training and deploying paid community health workers in three rural districts of Tanzania.

PubMed

Tani, Kassimu; Exavery, Amon; Baynes, Colin D; Pemba, Senga; Hingora, Ahmed; Manzi, Fatuma; Phillips, James F; Kanté, Almamy Malick

2016-07-08

Tanzania, like other African countries, faces significant health workforce shortages. With advisory and partnership from Columbia University, the Ifakara Health Institute and the Tanzanian Training Centre for International Health (TTCIH) developed and implemented the Connect Project as a randomized cluster experimental trial of the childhood survival impact of recruiting, training, and deploying of a new cadre of paid community health workers (CHW), named "Wawazesha wa afya ya Jamii" (WAJA). This paper presents an estimation of the cost of training and deploying WAJA in three rural districts of Tanzania. Costing data were collected by tracking project activity expenditure records and conducting in-depth interviews of TTCIH staff who have led the training and deployment of WAJA, as well as their counterparts at Public Clinical Training Centres who have responsibility for scaling up the WAJA training program. The trial is registered with the International Standard Randomized Controlled Trial Register number ( ISRCTN96819844 ). The Connect training cost was US$ 2,489.3 per WAJA, of which 40.1 % was for meals, 20.2 % for accommodation 10.2 % for tuition fees and the remaining 29.5 % for other costs including instruction and training facilities and field allowance. A comparable training program estimated unit cost for scaling-up this training via regional/district clinical training centres would be US$ 833.5 per WAJA. Of this unit cost, 50.3 % would involve the cost of meals, 27.4 % training fees, 13.7 % for field allowances, 9 % for accommodation and medical insurance. The annual running cost of WAJA in a village will cost US$ 1.16 per capita. Costs estimated by this study are likely to be sustainable on a large scale, particularly if existing regional/district institutions are utilized for this program.

Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial: Rationale and Design.

PubMed

Sheth, Kevin N; Elm, Jordan J; Beslow, Lauren A; Sze, Gordon K; Kimberly, W Taylor

2016-02-01

Patients with large territory infarction are at high risk of cerebral edema and neurological deterioration, including death. Preclinical studies have shown that a continuous infusion of glyburide blocks edema formation and improves outcome. We hypothesize that treatment with RP-1127 (Glyburide for Injection) reduces formation of brain edema in patients after large anterior circulation infarction. GAMES-RP is a prospective, randomized, double-blind, multicenter trial designed to evaluate RP-1127 in patients at high risk for the development of malignant cerebral edema. The study population consisted of subjects with a clinical diagnosis of acute severe anterior circulation ischemic stroke with a baseline diffusion-weighted image lesion between 82 and 300 cm(3) who are 18-80 years of age. The target time from symptom onset to start of study infusion was ≤10 h. Subjects were randomized to RP-1127 (glyburide for injection) or placebo and treated with a continuous infusion for 72 h. The primary efficacy outcome was a composite of the modified Rankin Scale and the incidence of decompressive craniectomy, assessed at 90 days. Safety outcomes were the frequency and severity of adverse events, with a focus on cardiac- and glucose-related serious adverse events. GAMES-RP was designed to provide critical information regarding glyburide for injection in patients with large hemispheric stroke and will inform the design of future studies.

Rationale and Design of Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) Trial.

PubMed

Miyauchi, Katsumi; Kimura, Takeshi; Shimokawa, Hiroaki; Daida, Hiroyuki; Iimuro, Satoshi; Iwata, Hiroshi; Ozaki, Yukio; Sakuma, Ichiro; Nakagawa, Yoshihisa; Hibi, Kiyoshi; Hiro, Takafumi; Fukumoto, Yoshihiro; Hokimoto, Seiji; Ohashi, Yasuo; Ohtsu, Hiroshi; Saito, Yasushi; Matsuzaki, Masunori; Nagai, Ryozo

2018-03-30

Large-scale clinical trials in patients in Western countries with coronary artery disease (CAD) have found that aggressive lipid-lowering therapy using high-dose statins reduces cardiovascular (CV) events further than low-dose statins. However, such evidence has not yet been fully established in Asian populations, including in Japan. The Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study addresses whether intensification of statin therapy improves clinical outcomes in Japanese patients with CAD.REAL-CAD is a prospective, multicenter, randomized, open-label, blinded-endpoint, physician-initiated phase 4 trial in Japan. The study will recruit up to 12,600 patients with stable CAD. Patients are assigned to receive either pitavastatin 1 mg/day or pitavastatin 4 mg/day. LDL-C levels are expected to reach approximate mean values of 100 mg/dL in the low-dose pitavastatin group and 80 mg/dL in the high-dose group. The primary endpoint is the time to occurrence of a major CV event, including CV death, non-fatal myocardial infarction, non-fatal ischemic stroke, and unstable angina requiring emergency hospitalization during an average of 5 years. The large number of patients and the long follow-up period in the REAL-CAD study should ensure that there is adequate power to definitively determine if reducing LDL-C levels to approximately 80 mg/dL by high-dose statin can provide additional clinical benefit.After the study is completed, we will have categorical evidence on the optimal statin dose and target LDL-C level for secondary prevention in Japanese patients.

Impact of intermittent fasting on glucose homeostasis.

PubMed

Varady, Krista A

2016-07-01

This article provides an overview of the most recent human trials that have examined the impact of intermittent fasting on glucose homeostasis. Our literature search retrieved one human trial of alternate day fasting, and three trials of Ramadan fasting published in the past 12 months. Current evidence suggests that 8 weeks of alternate day fasting that produces mild weight loss (4% from baseline) has no effect on glucose homeostasis. As for Ramadan fasting, decreases in fasting glucose, insulin, and insulin resistance have been noted after 4 weeks in healthy normal weight individuals with mild weight loss (1-2% from baseline). However, Ramadan fasting may have little impact on glucoregulatory parameters in women with polycystic ovarian syndrome who failed to observe weight loss. Whether intermittent fasting is an effective means of regulating glucose homeostasis remains unclear because of the scarcity of studies in this area. Large-scale, longer-term randomized controlled trials will be required before the use of fasting can be recommended for the prevention and treatment of metabolic diseases.

Alternative surgical approaches in epilepsy.

PubMed

Gigante, Paul R; Goodman, Robert R

2011-08-01

The mainstay of epilepsy surgery is the resection of a presumed seizure focus or disruption of seizure propagation pathways. These approaches cannot be applied to all patients with medically refractory epilepsy (MRE). Since 1997, vagus nerve stimulation has been a palliative adjunct to the care of MRE patients. Deep brain stimulation (DBS) in select locations has been reported to reduce seizure frequency in small studies over the past three decades. Recently published results from the SANTE (Stimulation of the Anterior Nuclei of Thalamus for Epilepsy) trial-the first large-scale, randomized, double-blind trial of bilateral anterior thalamus DBS for MRE-demonstrate a significant reduction in seizure frequency with programmed stimulation. Another surgical alternative is the RNS™ System (NeuroPace, Mountain View, CA), which uses a closed-loop system termed responsive neurostimulation to both detect apparent seizure onsets and deliver stimulation. Recently presented results from the RNS™ pivotal trial demonstrate a sustained reduction in seizure frequency with stimulation, although comprehensive trial results are pending.

HIV-related stigma and universal testing and treatment for HIV prevention and care: design of an implementation science evaluation nested in the HPTN 071 (PopART) cluster-randomized trial in Zambia and South Africa.

PubMed

Hargreaves, James R; Stangl, Anne; Bond, Virginia; Hoddinott, Graeme; Krishnaratne, Shari; Mathema, Hlengani; Moyo, Maureen; Viljoen, Lario; Brady, Laura; Sievwright, Kirsty; Horn, Lyn; Sabapathy, Kalpana; Ayles, Helen; Beyers, Nulda; Bock, Peter; Fidler, Sarah; Griffith, Sam; Seeley, Janet; Hayes, Richard

2016-12-01

Stigma and discrimination related to HIV and key populations at high risk of HIV have the potential to impede the implementation of effective HIV prevention and treatment programmes at scale. Studies measuring the impact of stigma on these programmes are rare. We are conducting an implementation science study of HIV-related stigma in communities and health settings within a large, pragmatic cluster-randomized trial of a universal testing and treatment intervention for HIV prevention in Zambia and South Africa and will assess how stigma affects, and is affected by, implementation of this intervention. A mixed-method evaluation will be nested within HIV prevention trials network (HPTN) 071/PopART (Clinical Trials registration number NCT01900977), a three-arm trial comparing universal door-to-door delivery of HIV testing and referral to prevention and treatment services, accompanied by either an immediate offer of anti-retroviral treatment to people living with HIV regardless of clinical status, or an offer of treatment in-line with national guidelines, with a standard-of-care control arm. The primary outcome of HPTN 071/PopART is HIV incidence measured among a cohort of 52 500 individuals in 21 study clusters. Our evaluation will include integrated quantitative and qualitative data collection and analysis in all trial sites. We will collect quantitative data on indicators of HIV-related stigma over 3 years from large probability samples of community members, health workers and people living with HIV. We will collect qualitative data, including in-depth interviews and observations from members of these same groups sampled purposively. In analysis, we will: (1) compare HIV-related stigma measures between study arms, (2) link data on stigma to measures of the success of implementation of the PopART intervention and (3) explore changes in the dominant drivers and manifestations of stigma in study communities and the health system. HIV-related stigma may impede the successful implementation of HIV prevention and treatment programmes. Using a novel study-design nested within a large, community randomized trial we will evaluate the extent to which HIV-related stigma affects and is affected by the implementation of a comprehensive combination HIV prevention intervention including a universal test and treatment approach. © The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Radiation proctopathy in the treatment of prostate cancer

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

Garg, Amit K.; Mai Weiyan; McGary, John E.

2006-12-01

Purpose: To compile and review data on radiation proctopathy in the treatment of prostate cancer with respect to epidemiology, clinical manifestations, pathogenesis, risk factors, and treatment. Methods: Medical literature databases including PubMed and Medline were screened for pertinent reports, and critically analyzed for relevance in the scope of our purpose. Results: Rectal toxicity as a complication of radiotherapy has received attention over the past decade, especially with the advent of dose-escalation in prostate cancer treatment. A number of clinical criteria help to define acute and chronic radiation proctopathy, but lack of a unified grading scale makes comparing studies difficult. Amore » variety of risk factors, related to either radiation delivery or patient, are the subject of intense study. Also, a variety of treatment options, including medical therapy, endoscopic treatments, and surgery have shown varied results, but a lack of large randomized trials evaluating their efficacy prevents forming concrete recommendations. Conclusion: Radiation proctopathy should be an important consideration for the clinician in the treatment of prostate cancer especially with dose escalation. With further study of possible risk factors, the advent of a standardized grading scale, and more randomized trials to evaluate treatments, patients and physicians will be better armed to make appropriate management decisions.« less

Multi-site randomized trial of behavioral interventions for women with co-occurring PTSD and substance use disorders

PubMed Central

Hien, Denise A.; Wells, Elizabeth A.; Jiang, Huiping; Suarez-Morales, Lourdes; Campbell, Aimee N. C.; Cohen, Lisa R.; Miele, Gloria M.; Killeen, Therese; Brigham, Gregory S.; Zhang, Yulei; Hansen, Cheri; Hodgkins, Candace; Hatch-Maillette, Mary; Brown, Chanda; Kulaga, Agatha; Kristman-Valente, Allison; Chu, Melissa; Sage, Robert; Robinson, James A.; Liu, David; Nunes, Edward V.

2009-01-01

We compared the effectiveness of Seeking Safety (SS), an integrated cognitive behavioral treatment for substance use disorder (SUD) and post-traumatic stress disorder (PTSD), to an active comparison health education group (Women’s Health Education [WHE]) within NIDA’s Clinical Trials Network. We randomized 353 women to receive 12 sessions of SS (M = 6.2 sessions) or WHE (M = 6.0 sessions) with follow-up assessment at post-treatment and 3-, 6-, and 12-months post-treatment. Primary outcomes were the Clinician Administered PTSD Scale (CAPS) and PTSD Symptom Scale-Self Report (PSS-SR), and substance use (self-reported abstinence in the prior 7 days and days per week of any substance use). Intention-to-treat analysis showed large, clinically significant reductions in CAPS and PSS-SR symptoms (d = 1.94 and 1.12, respectively), but no reliable difference between conditions. Substance use outcomes were not significantly different over time between the two treatments and at follow-up showed no significant change from baseline, when 46% of participants were abstinent. Study results do not favor SS over WHE as an adjunct to SUD treatment for women with PTSD and reflect considerable opportunity to improve clinical outcomes in community-based treatments for these co-occurring conditions. PMID:19634955

A Randomized Trial Investigating the Effect of a Brief Lifestyle Intervention on Freshman-Year Weight Gain

ERIC Educational Resources Information Center

Middleton, Kathryn R.; Perri, Michael G.

2014-01-01

Objective: The current study was a randomized controlled trial investigating the effect of an innovative, short-term lifestyle intervention on weight gain in female freshman college students. Participants: Ninety-five freshmen were recruited from a large public university in the United States. Methods: Participants completed baseline assessments…

[Scales to evaluate pain in elderly patients suffering from dementia. Help-tools for the physiotherapist, doctor, nurse and occupational therapist].

PubMed

Rodríguez-Mansilla, Juan; Jiménez-Palomares, María; González-López-Arza, María Victoria

2014-01-01

The purpose of this study was to determine which scales are being used to evaluate pain in old people suffering from dementia. A search strategy was developed to retrieve all articles (randomized controlled trials and clinical trials without randomization) published in MEDLINE, Cochrane Library Plus, PEDro and Dialnet and BMC Geriatrics from January 2000 to January 2012. Exclusion criteria were articles that did not use scales for evaluating pain in elderly patients suffering from dementia, and other type of articles (case studies, reviews...). Finally, 13 studies were included in this review. From the results obtained it appears that more studies are needed to confirm the pain scales used for the elderly suffering from dementia. Observational scales may be useful to evaluate pain in these patients. Copyright © 2012 SEGG. Published by Elsevier Espana. All rights reserved.

Randomized Controlled Trial of Group Cognitive Behavioural Therapy for Post-Traumatic Stress Disorder in Children and Adolescents Exposed to Tsunami in Thailand.

PubMed

Pityaratstian, Nuttorn; Piyasil, Vinadda; Ketumarn, Panom; Sitdhiraksa, Nanthawat; Ularntinon, Sirirat; Pariwatcharakul, Pornjira

2015-09-01

Post-traumatic stress disorder (PTSD) is a common and debilitating consequence of natural disaster in children and adolescents. Accumulating data show that cognitive behavioural therapy (CBT) is an effective treatment for PTSD. However, application of CBT in a large-scale disaster in a setting with limited resources, such as when the tsunami hit several Asian countries in 2004, poses a major problem. This randomized controlled trial aimed to test for the efficacy of the modified version of CBT for children and adolescents with PSTD. Thirty-six children (aged 10-15 years) who had been diagnosed with PSTD 4 years after the tsunami were randomly allocated to either CBT or wait list. CBT was delivered in 3-day, 2-hour-daily, group format followed by 1-month posttreatment self-monitoring and daily homework. Compared to the wait list, participants who received CBT demonstrated significantly greater improvement in symptoms of PTSD at 1-month follow-up, although no significant improvement was observed when the measures were done immediately posttreatment. Brief, group CBT is an effective treatment for PTSD in children and adolescents when delivered in conjunction with posttreatment self-monitoring and daily homework.

A Herbal Medicine, Gongjindan, in Subjects with Chronic Dizziness (GOODNESS Study): Study Protocol for a Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Clinical Trial for Effectiveness, Safety, and Cost-Effectiveness

PubMed Central

Kim, Jinyoung; Cho, Jae-Heung

2017-01-01

This study protocol aims to explore the effectiveness, safety, and cost-effectiveness of a herbal medication, Gongjindan (GJD), in patients with chronic dizziness. This will be a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group, clinical trial. Seventy-eight patients diagnosed with Meniere's disease, psychogenic dizziness, or dizziness of unknown cause will be randomized and allocated to either a GJD or a placebo group in a 1 : 1 ratio. Participants will be orally given 3.75 g GJD or placebo in pill form once a day for 56 days. The primary outcome measure will be the Dizziness Handicap Inventory score. Secondary outcome measures will be as follows: severity (mean vertigo scale and visual analogue scale) and frequency of dizziness, balance function (Berg Balance Scale), fatigue (Fatigue Severity Scale) and deficiency pattern/syndrome (qi blood yin yang-deficiency questionnaire) levels, and depression (Korean version of Beck's Depression Inventory) and anxiety (State-Trait Anxiety Inventory) levels. To assess safety, adverse events, including laboratory test results, will be monitored. Further, the incremental cost-effectiveness ratio will be calculated based on quality-adjusted life years (from the EuroQoL five dimensions' questionnaire) and medical expenses. Data will be statistically analyzed at a significance level of 0.05 (two-sided). This trial is registered with ClinicalTrials.gov NCT03219515, in July 2017. PMID:29387128

The effect of additional ankle and midfoot mobilizations on plantar fasciitis: a randomized controlled trial.

PubMed

Shashua, Anat; Flechter, Shlomo; Avidan, Liat; Ofir, Dani; Melayev, Alex; Kalichman, Leonid

2015-04-01

A single-blind randomized controlled trial. To evaluate the efficacy of ankle and midfoot mobilization on pain and function of patients with plantar fasciitis (PF). Plantar fasciitis is a degenerative process of the plantar fascia, with a lifetime prevalence of approximately 10%. Limited ankle dorsiflexion is a common finding and apparently acts as a contributing factor to the development of PF. Fifty patients with PF, aged 23 to 73 years, were randomly assigned to either the intervention or control group. Both groups received 8 treatments, twice a week, consisting of stretching exercises and ultrasound. In addition, the intervention group received mobilization of the ankle and midfoot joints. Dorsiflexion range of motion was measured at the beginning and at the end of treatment. The results were evaluated by 3 outcomes: the numeric pain-rating scale, Lower Extremity Functional Scale, and algometry. No significant difference was found between groups in any of the outcomes. Both groups showed a significant difference in the numeric pain-rating scale and Lower Extremity Functional Scale. Both groups significantly improved in dorsiflexion range of motion, with no difference between groups. The addition of ankle and foot joint mobilization aimed at improving dorsiflexion range of motion is not more effective than stretching and ultrasound alone in treating PF. The association between limited ankle dorsiflexion and PF is most probably due to soft tissue limitations, not the joints. Trial registered at ClinicalTrials.gov (registration number NCT01439932). Therapy, level 1b.

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.

Effectiveness of aerobic gymnastic exercise on stress, fatigue, and sleep quality during postpartum: A pilot randomized controlled trial.

PubMed

Yang, Chiu-Ling; Chen, Chung-Hey

2018-01-01

Gymnastics is a preferable safe exercise for postnatal women performing regularly. The aim of this pilot randomized controlled trial was to determine whether the aerobic gymnastic exercise improves stress, fatigue, sleep quality and depression in postpartum women. Single-blinded, randomized controlled trial held from December 2014 until September 2015. Postnatal clinic of a medical center in southern Taiwan. 140 eligible postnatal women were systematically assigned, with a random start to experimental (n=70) or a control (n=70) group. Engage in aerobic gymnastic exercise at least three times (15min per section) a week for three months using compact disc in the home. Perceived Stress Scale, Postpartum Fatigue Scale, Postpartum Sleep Quality Scale, and Edinburgh Postnatal Depression Scale. In a two-way ANOVA with repeated measures, the aerobic gymnastic exercise group showed significant decrease in fatigue after practicing exercise 4 weeks and the positive effects extended to the 12-week posttests. Paired t-tests revealed that aerobic gymnastic exercise participants had improved significantly in perceived stress and fatigue after 4 weeks gymnastic exercise; these positive effects extended to the 12-week posttests. In addition, the changes in physical symptoms-related sleep inefficiency after 12 weeks gymnastic exercise were significantly decreased in the experimental group compared with the control group. The findings can be used to encourage postnatal women to perform moderate-intensity gymnastic exercise in their daily life to reduce their stress, fatigue and improve sleep quality. Copyright © 2017 Elsevier Ltd. All rights reserved.

A large-scale field randomized trial demonstrates safety and efficacy of the vaccine LetiFend® against canine leishmaniosis.

PubMed

Fernández Cotrina, Javier; Iniesta, Virginia; Monroy, Isabel; Baz, Victoria; Hugnet, Christophe; Marañon, Francisco; Fabra, Mercedes; Gómez-Nieto, Luis Carlos; Alonso, Carlos

2018-04-05

Canine leishmaniosis is a zoonotic disease caused by Leishmania infantum. Extensive research is currently ongoing to develop safe and effective vaccines to protect from disease development. The European Commission has granted a marketing authorization for LetiFend®, a new vaccine containing recombinant Protein Q. The efficacy of LetiFend® vaccination in a large-scale dog population of both sexes, different breeds and ages in endemic areas is reported in this multicenter, randomized, double-blind, placebo-controlled field trial. Dogs (n = 549) living in France and Spain were randomly selected to receive a single subcutaneous dose of LetiFend® or placebo per year, and were naturally exposed to two L. infantum transmission seasons. Clinical examinations, blood and lymphoid organ sampling to evaluate serological, parasitological and disease status of the dogs were performed at different time points during the study. LetiFend® was very well tolerated and clearly reduced the incidence of clinical signs related to leishmaniosis. The number of confirmed cases of leishmaniosis was statistically significantly lower in the vaccine group. The number of dogs with parasites was close to be significantly reduced in the vaccine group (p = 0.0564). Re-vaccination of seropositive dogs demonstrated to be safe and not to worsen the course of the disease. The likelihood that a dog vaccinated with LetiFend® develops a confirmed case or clinical signs of leishmaniosis in areas with high pressure is, respectively, 5 and 9.8 time less than that for an unvaccinated dog. Thus, the overall efficacy of the LetiFend® vaccine in the prevention of confirmed cases of leishmaniosis in endemic areas with high disease pressure was shown to be 72%. In conclusion, this field trial demonstrates that LetiFend® is a novel, safe and effective vaccine for the active immunization of non-infected dogs from 6 months of age in reducing the risk of developing clinical leishmaniosis after natural infection with Leishmania infantum. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Web-Based and Mobile Stress Management Intervention for Employees: A Randomized Controlled Trial.

PubMed

Heber, Elena; Lehr, Dirk; Ebert, David Daniel; Berking, Matthias; Riper, Heleen

2016-01-27

Work-related stress is highly prevalent among employees and is associated with adverse mental health consequences. Web-based interventions offer the opportunity to deliver effective solutions on a large scale; however, the evidence is limited and the results conflicting. This randomized controlled trial evaluated the efficacy of guided Web- and mobile-based stress management training for employees. A total of 264 employees with elevated symptoms of stress (Perceived Stress Scale-10, PSS-10≥22) were recruited from the general working population and randomly assigned to an Internet-based stress management intervention (iSMI) or waitlist control group. The intervention (GET.ON Stress) was based on Lazarus's transactional model of stress, consisted of seven sessions, and applied both well-established problem solving and more recently developed emotion regulation strategies. Participants also had the opportunity to request automatic text messages on their mobile phone along with the iSMI. Participants received written feedback on every completed session from an e-coach. The primary outcome was perceived stress (PSS-10). Web-based self-report assessments for both groups were scheduled at baseline, 7 weeks, and 6 months. At 12 months, an extended follow-up was carried out for the iSMI group only. An intention-to-treat analysis of covariance revealed significantly large effect differences between iSMI and waitlist control groups for perceived stress at posttest (F1,261=58.08, P<.001; Cohen's d=0.83) and at the 6-month follow-up (F1,261=80.17, P<.001; Cohen's d=1.02). The effects in the iSMI group were maintained at 12-month follow-up. This Web- and mobile-based intervention has proven effective in reducing stress in employees in the long term. Internet-based stress management interventions should be further pursued as a valuable alternative to face-to-face interventions. German Clinical Trials Register (DRKS): 00004749; http://drks-neu.uniklinik-freiburg.de/ drks_web/setLocale_EN.do (Archived by WebCite at http://www.webcitation.org/6e8rl98nl).

Design and rationale of the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) Trial.

PubMed

Kidwell, Chelsea S; Jahan, Reza; Alger, Jeffry R; Schaewe, Timothy J; Guzy, Judy; Starkman, Sidney; Elashoff, Robert; Gornbein, Jeffrey; Nenov, Val; Saver, Jeffrey L

2014-01-01

Multimodal imaging has the potential to identify acute ischaemic stroke patients most likely to benefit from late recanalization therapies. The general aim of the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy Trial is to investigate whether multimodal imaging can identify patients who will benefit substantially from mechanical embolectomy for the treatment of acute ischaemic stroke up to eight-hours from symptom onset. Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy is a randomized, controlled, blinded-outcome clinical trial. Acute ischaemic stroke patients with large vessel intracranial internal carotid artery or middle cerebral artery M1 or M2 occlusion enrolled within eight-hours of symptom onset are eligible. The study sample size is 120 patients. Patients are randomized to endovascular embolectomy employing the Merci Retriever (Concentric Medical, Mountain View, CA) or the Penumbra System (Penumbra, Alameda, CA) vs. standard medical care, with randomization stratified by penumbral pattern. The primary aim of the trial is to test the hypothesis that the presence of substantial ischaemic penumbral tissue visualized on multimodal imaging (magnetic resonance imaging or computed tomography) predicts patients most likely to respond to mechanical embolectomy for treatment of acute ischaemic stroke due to a large vessel, intracranial occlusion up to eight-hours from symptom onset. This hypothesis will be tested by analysing whether pretreatment imaging pattern has a significant interaction with treatment as a determinant of functional outcome based on the distribution of scores on the modified Rankin Scale measure of global disability assessed 90 days post-stroke. Nested hypotheses test for (1) treatment efficacy in patients with a penumbral pattern pretreatment, and (2) absence of treatment benefit (equivalency) in patients without a penumbral pattern pretreatment. An additional aim will only be tested if the primary hypothesis of an interaction is negative: that patients treated with mechanical embolectomy have improved functional outcome vs. standard medical management. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Longitudinal Evaluation of a Scale-up Model for Teaching Mathematics with Trajectories and Technologies: Persistence of Effects in the Third Year

ERIC Educational Resources Information Center

Clements, Douglas H.; Sarama, Julie; Wolfe, Christopher B.; Spitler, Mary Elaine

2013-01-01

Using a cluster randomized trial design, we evaluated the persistence of effects of a research-based model for scaling up educational interventions. The model was implemented in 42 schools in two city districts serving low-resource communities, randomly assigned to three conditions. In pre-kindergarten, the two experimental interventions were…

The Use of Electronic Data Capture Tools in Clinical Trials: Web-Survey of 259 Canadian Trials

PubMed Central

Jonker, Elizabeth; Sampson, Margaret; Krleža-Jerić, Karmela; Neisa, Angelica

2009-01-01

Background Electronic data capture (EDC) tools provide automated support for data collection, reporting, query resolution, randomization, and validation, among other features, for clinical trials. There is a trend toward greater adoption of EDC tools in clinical trials, but there is also uncertainty about how many trials are actually using this technology in practice. A systematic review of EDC adoption surveys conducted up to 2007 concluded that only 20% of trials are using EDC systems, but previous surveys had weaknesses. Objectives Our primary objective was to estimate the proportion of phase II/III/IV Canadian clinical trials that used an EDC system in 2006 and 2007. The secondary objectives were to investigate the factors that can have an impact on adoption and to develop a scale to assess the extent of sophistication of EDC systems. Methods We conducted a Web survey to estimate the proportion of trials that were using an EDC system. The survey was sent to the Canadian site coordinators for 331 trials. We also developed and validated a scale using Guttman scaling to assess the extent of sophistication of EDC systems. Trials using EDC were compared by the level of sophistication of their systems. Results We had a 78.2% response rate (259/331) for the survey. It is estimated that 41% (95% CI 37.5%-44%) of clinical trials were using an EDC system. Trials funded by academic institutions, government, and foundations were less likely to use an EDC system compared to those sponsored by industry. Also, larger trials tended to be more likely to adopt EDC. The EDC sophistication scale had six levels and a coefficient of reproducibility of 0.901 (P< .001) and a coefficient of scalability of 0.79. There was no difference in sophistication based on the funding source, but pediatric trials were likely to use a more sophisticated EDC system. Conclusion The adoption of EDC systems in clinical trials in Canada is higher than the literature indicated: a large proportion of clinical trials in Canada use some form of automated data capture system. To inform future adoption, research should gather stronger evidence on the costs and benefits of using different EDC systems. PMID:19275984

Clinical outcomes and neural correlates of 20 sessions of repetitive transcranial magnetic stimulation in severe and enduring anorexia nervosa (the TIARA study): study protocol for a randomised controlled feasibility trial.

PubMed

Bartholdy, Savani; McClelland, Jessica; Kekic, Maria; O'Daly, Owen G; Campbell, Iain C; Werthmann, Jessica; Rennalls, Samantha J; Rubia, Katya; David, Anthony S; Glennon, Danielle; Kern, Nikola; Schmidt, Ulrike

2015-12-03

Anorexia nervosa (AN) is a serious mental disorder with multiple comorbidities and complications. In those with a severe and enduring form of the illness (SEED-AN), treatment responsivity is poor and the evidence base limited. Thus, there is a need for novel treatment strategies. This paper describes the theoretical background and protocol of a feasibility randomised controlled trial (RCT) of real versus sham (placebo) therapeutic repetitive transcranial magnetic stimulation (rTMS) in SEED-AN. The aim of this trial is to obtain information that will guide decision making and protocol development in relation to a future large-scale RCT of rTMS in this group of patients, and also to assess the preliminary efficacy and neural correlates of rTMS treatment. Forty-four adults from the community with a DSM-5 diagnosis of AN, an illness duration>3 years and a previous course of unsuccessful treatment will be randomly allocated to receive 20 sessions of either real or sham rTMS, in a parallel group design. As this is a feasibility study, no primary outcome has been defined and a broad range of outcome variables will be examined. These include weight/body mass index (BMI), eating disorder psychopathology, other psychopathology (for example, depression, anxiety), quality of life, neuropsychological processes (such as self-regulation, attentional bias and food choice behaviour), neuroimaging measures (that is, changes in brain structure or function), tolerability and acceptability of rTMS, and additional service utilisation. The feasibility of conducting a large-scale RCT of rTMS and the appropriateness of rTMS as a treatment for SEED-AN will be evaluated through: assessment of recruitment and retention rates, acceptability of random allocation, blinding success (allocation concealment), completion of treatment sessions and research assessments (baseline, post-treatment and follow-up assessments). The acceptability and tolerability of the treatment will be assessed via semi-structured interviews. The effect sizes generated and other findings from this trial will inform a future large-scale RCT with respect to decisions on primary outcome measures and other aspects of protocol development. Additionally, results from this study will provide a preliminary indication of the efficacy of rTMS treatment for AN, the neural correlates of the illness, and potential biomarkers of clinical response. ISRCTN14329415 . Date of registration: 23 July 2015.

An effectiveness study of an integrated, community-based package for maternal, newborn, child and HIV care in South Africa: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Progress towards MDG4 in South Africa will depend largely on scaling up effective prevention against mother to child transmission (PMTCT) of HIV and also addressing neonatal mortality. This imperative drives increasing focus on the neonatal period and particularly on the development and testing of appropriate models of sustainable, community-based care in South Africa in order to reach the poor. A number of key implementation gaps affecting progress have been identified. Implementation gaps for HIV prevention in neonates; implementation gaps for neonatal care especially home postnatal care; and implementation gaps for maternal mental health support. We have developed and are evaluating and costing an integrated and scaleable home visit package delivered by community health workers targeting pregnant and postnatal women and their newborns to provide essential maternal/newborn care as well as interventions for Prevention of Mother to Child Transmission (PMTCT) of HIV. Methods The trial is a cluster randomized controlled trial that is being implemented in Umlazi which is a peri-urban settlement with a total population of 1 million close to Durban in KwaZulu Natal, South Africa. The trial consists of 30 randomized clusters (15 in each arm). A baseline survey established the homogeneity of clusters and neither stratification nor matching was performed. Sample size was based on increasing HIV-free survival from 74% to 84%, and calculated to be 120 pregnant women per cluster. Primary outcomes are higher levels of HIV free survival and levels of exclusive and appropriate infant feeding at 12 weeks postnatally. The intervention is home based with community health workers delivering two antenatal visits, a postnatal visit within 48 hours of birth, and a further four visits during the first two months of the infants life. We are undertaking programmatic and cost effectiveness analysis to cost the intervention. Discussion The question is not merely to develop an efficacious package but also to identify and test delivery strategies that enable scaling up, which requires effectiveness studies in a health systems context, adapting and testing Asian community-based studies in various African contexts. Trial registration ISRCTN: ISRCTN41046462 PMID:22044553

iSupport, an online training and support program for caregivers of people with dementia: study protocol for a randomized controlled trial in India.

PubMed

Mehta, Kala M; Gallagher-Thompson, Dolores; Varghese, Mathew; Loganathan, Santosh; Baruah, Upasana; Seeher, Katrin; Zandi, Diana; Dua, Tarun; Pot, Anne Margriet

2018-05-08

Dementia has a huge physical, psychological, social and economic impact upon caregivers, families and societies at large. There has been a growing impetus to utilize Internet interventions given the potential scalability, and presumed cost-effectiveness and accessibility. In this paper, we describe the design of a randomized controlled trial (RCT) aiming to study the impact of online self-help programs on caregivers of people with dementia in India. The experimental group will receive an interactive training and support program and the comparison group will receive an education-only e-book. It will be among the first online support intervention RCTs for a mental health condition in a lower-middle income country. Two hundred and eight participants are expected to be recruited via several strategies (email, Internet and social media, telephone and face-to-face) starting in the Bangalore region of India. The inclusion criteria for participation in the trial are: (1) being 18 years or older, (2) being a self-reported caregiver of a person with dementia, (3) self-report that a family member has a diagnosis of dementia (AD8 ≥ 2), and experience caregiver distress (≥ 4 on a 1-item burden scale ranging from 1 to 10 or ≥ 4 or < 20 on the Center for Epidemiologic Study-Depression (CES-D) scale (10-item) or ≥ 4 or < 15 on the Generalized Anxiety Disorder Scale (7-item). The intervention group will be offered iSupport, an online self-help training and support program, enabling a personalized education plan with a maximum of 23 lessons. These modules present a range of topics from "what is dementia?" to "dealing with challenging behaviors like aggression." The comparison group will receive an education-only e-book containing similar content. The outcomes of this trial are: caregiver burden as measured by the 22-item Zarit Burden Scale, depressive symptoms, anxiety symptoms (primary outcomes), quality of life, person-centered attitude, self-efficacy and mastery (secondary outcomes). Based on the findings of this trial, we will examine the potential use and scale up of iSupport for caregiver distress in India. This style of online self-help programs could be expanded to other regions or countries or to other suitable caregiver groups. Clinical Trials Registry-India (CTRI), ID: CTRI/2017/02/007876 .

Randomized Controlled Trial of Early Versus Delayed Statin Therapy in Patients With Acute Ischemic Stroke: ASSORT Trial (Administration of Statin on Acute Ischemic Stroke Patient).

PubMed

Yoshimura, Shinichi; Uchida, Kazutaka; Daimon, Takashi; Takashima, Ryuzo; Kimura, Kazuhiro; Morimoto, Takeshi

2017-11-01

Several studies suggested that statins during hospitalization were associated with better disability outcomes in patients with acute ischemic stroke, but only 1 small randomized trial is available. We conducted a multicenter, open-label, randomized controlled trial in patients with acute ischemic strokes in 11 hospitals in Japan. Patients with acute ischemic stroke and dyslipidemia randomly received statins within 24 hours after admission in the early group or on the seventh day in the delayed group, in a 1:1 ratio. Statins were administered for 12 weeks. The primary outcome was patient disability assessed by modified Rankin Scale at 90 days. A total of 257 patients were randomized and analyzed (early 131, delayed 126). At 90 days, modified Rankin Scale score distribution did not differ between groups ( P =0.68), and the adjusted common odds ratio of the early statin group was 0.84 (95% confidence interval, 0.53-1.3; P =0.46) compared with the delayed statin group. There were 3 deaths at 90 days (2 in the early group, 1 in the delayed group) because of malignancy. Ischemic stroke recurred in 9 patients (6.9%) in the early group and 5 patients (4.0%) in the delayed group. The safety profile was similar between groups. Our randomized trial involving patients with acute ischemic stroke and dyslipidemia did not show any superiority of early statin therapy within 24 hours of admission compared with delayed statin therapy 7 days after admission to alleviate the degree of disability at 90 days after onset. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02549846. © 2017 American Heart Association, Inc.

Quality of Reporting Randomized Controlled Trials in Five Leading Neurology Journals in 2008 and 2013 Using the Modified "Risk of Bias" Tool.

PubMed

Zhai, Xiao; Cui, Jin; Wang, Yiran; Qu, Zhiquan; Mu, Qingchun; Li, Peiwen; Zhang, Chaochao; Yang, Mingyuan; Chen, Xiao; Chen, Ziqiang; Li, Ming

2017-03-01

To examine the risk of bias of methodological quality of reporting randomized clinical trials (RCTs) in major neurology journals before and after the update (2011) of Cochrane risk of bias tool. RCTs in 5 leading neurology journals in 2008 and 2013 were searched systematically. Characteristics were extracted based on the list of the modified Cochrane Collaboration's tool. Country, number of patients, type of intervention, and funding source also were examined for further analysis. A total of 138 RCTs were enrolled in this study. The rates of following a trial plan were 61.6% for the allocation generation, 52.9% for the allocation concealment, 84.8% for the blinding of the participants or the personnel, 34.8% for the blinding of outcome assessment, 78.3% for the incomplete outcome data, and 67.4% for the selective reporting. A significant setback was found in "the selective reporting" in 2013 than that in 2008. Trials performed by multi-centers and on a large scale had significantly more "low risk of bias" trials. Not only the number of surgical trials (5.8%) was much less than that of trials using drugs (73.9%), but also the reporting quality of surgical trials were worse (P = 0.008). Finally, only 17.4% trials met the criterion of "low risk of bias." The modified "risk of bias" tool is an improved version for assessment. Methodological quality of reporting RCTs in the 5neurology journals is unsatisfactory, especially that for surgical RCTs, and it could be further improved. Copyright © 2017 Elsevier Inc. All rights reserved.

Emergence times and airway reactions in general laryngeal mask airway anesthesia: study protocol for a randomized controlled trial.

PubMed

Stevanovic, Ana; Rossaint, Rolf; Keszei, András P; Fritz, Harald; Fröba, Gebhard; Pühringer, Friedrich; Coburn, Mark

2015-07-26

The use of a laryngeal mask airway (LMA) in appropriate patients supports fast-track anesthesia with a lower incidence of postoperative airway-connected adverse events. Data on the most favorable anesthetic in this context, with the lowest rate of upper airway complications and fast emergence times, are controversial and limited. Desflurane seems to match these criteria best, but large randomized controlled trials (RCTs) with a standardized study protocol are lacking. Therefore, we aim to compare desflurane with other commonly used anesthetics, sevoflurane and propofol, in a sufficiently powered RCT. We hypothesize that desflurane is noninferior regarding the frequency of upper airway events and superior regarding the emergence times to sevoflurane and propofol. A total of 351 patients undergoing surgery with an LMA will be included in this prospective, randomized, double-blind controlled, multicenter clinical trial. The patients will be randomly assigned to the three treatment arms: desflurane (n = 117), sevoflurane (n = 117), and propofol (n = 117). The emergence time (time to state the date of birth) will be the primary endpoint of this study. The secondary endpoints include further emergence times, such as time to open eyes, to remove LMA, to respond to command and to state name. Additionally, we will determine the frequency of cough and laryngospasm, measured intraoperatively and at emergence. We will assess the postoperative recovery on the first postoperative day via the Postoperative Quality Recovery Scale. Despite increasing importance of cost-effective and safe anesthesia application, we lack proof for the most advantageous anesthetic agent, when an LMA is used. There are only a few RCTs comparing desflurane to other commonly used anesthetics (sevoflurane, propofol and isoflurane) in patients with LMA. These RCTs were conducted with small sample sizes, huge interstudy variability, and some also showed strong biases. The present multicenter RCT will provide results from a large sample size with a standardized study protocol and minimized bias, which is feasible in the clinical routine. Furthermore, we will expand our knowledge regarding the most favorable recovery on the first postoperative day, which impacts patients' comfort after surgery. EudraCT Identifier: 2014-003810-96, 5 September 2014 ClinicalTrials.gov: NCT02322502, December 2014.

Rational emotive behavior therapy, cognitive therapy, and medication in the treatment of major depressive disorder: a randomized clinical trial, posttreatment outcomes, and six-month follow-up.

PubMed

David, Daniel; Szentagotai, Aurora; Lupu, Viorel; Cosman, Doina

2008-06-01

A randomized clinical trial was undertaken to investigate the relative efficacy of rational-emotive behavior therapy (REBT), cognitive therapy (CT), and pharmacotherapy in the treatment of 170 outpatients with nonpsychotic major depressive disorder. The patients were randomly assigned to one of the following: 14 weeks of REBT, 14 weeks of CT, or 14 weeks of pharmacotherapy (fluoxetine). The outcome measures used were the Hamilton Rating Scale for Depression and the Beck Depression Inventory. No differences among treatment conditions at posttest were observed. A larger effect of REBT (significant) and CT (nonsignificant) over pharmacotherapy at 6 months follow-up was noted on the Hamilton Rating Scale for Depression only. (c) 2008 Wiley Periodicals, Inc.

Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract.

PubMed

Kongkeaw, Chuenjid; Dilokthornsakul, Piyameth; Thanarangsarit, Phurit; Limpeanchob, Nanteetip; Norman Scholfield, C

2014-01-01

Bacopa monnieri has a long history in Ayurvedic medicine for neurological and behavioral defects. To assess its efficacy in improving cognitive function. MEDLINE, EMBASE, CINAHL, AMED, Cochrane Central of clinical trial, WHO registry, Thai Medical Index, Index Medicus Siriraj library and www.clinicaltrial.gov were searched from the inception date of each database to June 2013 using scientific and common synonyms of Bacopa monnieri, cognitive performance or memory. The reference lists of retrieved articles were also reviewed. Randomized, placebo controlled human intervention trials on chronic ≥ 12 weeks dosing of standardized extracts of Bacopa monnieri without any co-medication were included in this study. The methodological quality of studies was assessed using Cochrane's risk of bias assessment and Jadad's quality scales. The weighted mean difference and 95% confidence interval (95% CI) were performed using the random-effects model of the Dersimonian-Laird method. Nine studies met the inclusion criteria using 518 subjects. Overall quality of all included trials was low risk of bias and quality of reported information was high. Meta-analysis of 437 eligible subjects showed improved cognition by shortened Trail B test (-17.9 ms; 95% CI -24.6 to -11.2; p<0.001) and decreased choice reaction time (10.6 ms; 95% CI -12.1 to -9.2; p<0.001). This meta-analysis suggests that Bacopa monnieri has the potential to improve cognition, particularly speed of attention but only a large well designed 'head-to-head' trial against an existing medication will provide definitive data on its efficacy on healthy or dementia patients using a standardized preparation. © 2013 Elsevier Ireland Ltd. All rights reserved.

Study protocol: Münster tinnitus randomized controlled clinical trial-2013 based on tailor-made notched music training (TMNMT).

PubMed

Pantev, Christo; Rudack, Claudia; Stein, Alwina; Wunderlich, Robert; Engell, Alva; Lau, Pia; Wollbrink, Andreas; Shaykevich, Alex

2014-03-02

Tinnitus is a result of hyper-activity/hyper-synchrony of auditory neurons coding the tinnitus frequency, which has developed to synchronous mass activity owing the lack of inhibition. We assume that removal of exactly these frequency components from an auditory stimulus will cause the brain to reorganize around tonotopic regions coding the tinnitus frequency. Based on this assumption a novel treatment for tonal tinnitus - tailor-made notched music training (TMNMT) (Proc Natl Acad Sci USA 107:1207-1210, 2010; Ann N Y Acad Sci 1252:253-258, 2012; Frontiers Syst Neurosci 6:50, 2012) has been introduced and will be tested in this clinical trial on a large number of tinnitus patients. A randomized controlled trial (RCT) in parallel group design will be performed in a double-blinded manner. The choice of the intervention we are going to apply is based on two "proof of concept" studies in humans (Proc Natl Acad Sci USA 107:1207-1210, 2010; Ann N Y Acad Sci 1252:253-258, 2012; Frontiers Syst Neurosci 6:50, 2012; PloS One 6(9):e24685, 2011) and on a recent animal study (Front Syst Neurosci 7:21, 2013).The RCT includes 100 participants with chronic, tonal tinnitus who listened to tailor-made notched music (TMNM) for two hours a day for three months. The effect of TMNMT is assessed by the tinnitus handicap questionnaire and visual analogue scales (VAS) measuring perceived tinnitus loudness, distress and handicap. This is the first randomized controlled trial applying TMNMT on a larger number of patients with tonal tinnitus. Our data will verify more securely and reliably the effectiveness of this kind of completely non-invasive and low-cost treatment approach on tonal tinnitus. Current Controlled Trials ISRCTN04840953.

Sham-controlled, randomized, feasibility trial of acupuncture for prevention of radiation-induced xerostomia among patients with nasopharyngeal carcinoma

PubMed Central

Meng, Zhiqiang; Garcia, M. Kay; Hu, Chaosu; Chiang, Joseph; Chambers, Mark; Rosenthal, David I.; Peng, Huiting; Wu, Caijun; Zhao, Qi; Zhao, Genming; Liu, Luming; Spelman, Amy; Palmer, J. Lynn; Wei, Qi; Cohen, Lorenzo

2013-01-01

Background Xerostomia (dry mouth) after head/neck radiation is a common problem among cancer patients. Quality of life (QOL) is impaired, and available treatments are of little benefit. This trial determined the feasibility of conducting a sham-controlled trial of acupuncture and whether acupuncture could prevent xerostomia among head/neck patients undergoing radiotherapy. Methods A sham controlled, feasibility trial was conducted at Fudan University Shanghai Cancer Center, Shanghai, China among patients with nasopharyngeal carcinoma undergoing radiotherapy. To determine feasibility of a sham procedure, 23 patients were randomized to real acupuncture (N = 11) or to sham acupuncture (N = 12). Patients were treated 3 times/week during their course of radiotherapy. Subjective measures were the Xerostomia Questionnaire (XQ) and MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN). Objective measures were unstimulated whole salivary flow rates (UWSFR) and stimulated salivary flow rates (SSFR). Patients were followed for 1 month after radiotherapy. Results XQ scores for acupuncture were significantly lower than sham controls starting in week 3 and lasted through the 1-month follow-up (all P’s < 0.001 except for week 3, which was 0.006), with clinically significant differences as follows: week 6 – RR 0.28 [95% CI, 0.10, 0.79]; week 11- RR 0.17 [95% CI, 0.03, 1.07]. Similar findings were seen for MDASI-HN scores and MDASI-Intrusion scores. Group differences for UWSFR and SSFR were not found. Conclusions In this small pilot study, true acupuncture given concurrently with radiotherapy significantly reduced xerostomia symptoms and improved QOL when compared with sham acupuncture. Large-scale, multi-center, randomized, placebo-controlled trials are now needed. PMID:22285177

Conservative surgery versus colorectal resection in deep endometriosis infiltrating the rectum: a randomized trial

PubMed Central

Bubenheim, Michael; Huet, Emmanuel; Bridoux, Valérie; Zacharopoulou, Chrysoula; Daraï, Emile; Collinet, Pierre; Tuech, Jean-Jacques

2018-01-01

Abstract STUDY QUESTION Is there a difference in functional outcome between conservative versus radical rectal surgery in patients with large deep endometriosis infiltrating the rectum 2 years postoperatively? SUMMARY ANSWER No evidence was found that functional outcomes differed when conservative surgery was compared to radical rectal surgery for deeply invasive endometriosis involving the bowel. WHAT IS KNOWN ALREADY Adopting a conservative approach to the surgical management of deep endometriosis infiltrating the rectum, by employing shaving or disc excision, appears to yield improved digestive functional outcomes. However, previous comparative studies were not randomized, introducing a possible bias regarding the presumed superiority of conservative techniques due to the inclusion of patients with more severe deep endometriosis who underwent colorectal resection. STUDY DESIGN SIZE, DURATION From March 2011 to August 2013, we performed a 2-arm randomized trial, enroling 60 patients with deep endometriosis infiltrating the rectum up to 15 cm from the anus, measuring more than 20 mm in length, involving at least the muscular layer in depth and up to 50% of rectal circumference. No women were lost to follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were enroled in three French university hospitals and had either conservative surgery, by shaving or disc excision, or radical rectal surgery, by segmental resection. Randomization was performed preoperatively using sequentially numbered, opaque, sealed envelopes, and patients were informed of the results of randomization. The primary endpoint was the proportion of patients experiencing one of the following symptoms: constipation (1 stool/>5 consecutive days), frequent bowel movements (≥3 stools/day), defecation pain, anal incontinence, dysuria or bladder atony requiring self-catheterization 24 months postoperatively. Secondary endpoints were the values of the Visual Analog Scale (VAS), Knowles–Eccersley–Scott-Symptom Questionnaire (KESS), the Gastrointestinal Quality of Life Index (GIQLI), the Wexner scale, the Urinary Symptom Profile (USP) and the Short Form 36 Health Survey (SF36). MAIN RESULTS AND THE ROLE OF CHANCE A total of 60 patients were enroled. Among the 27 patients in the conservative surgery arm, two were converted to segmental resection (7.4%). In each group, 13 presented with at least one functional problem at 24 months after surgery (48.1 versus 39.4%, OR = 0.70, 95% CI 0.22–2.21). The intention-to-treat comparison of the overall scores on KESS, GIQLI, Wexner, USP and SF36 did not reveal significant differences between the two arms. Segmental resection was associated with a significant risk of bowel stenosis. LIMITATIONS REASONS FOR CAUTION The inclusion of only large infiltrations of the rectum does not allow the extrapolation of conclusions to small nodules of <20 mm in length. The presumption of a 40% difference favourable to conservative surgery in terms of postoperative functional outcomes resulted in a lack of power to demonstrate a difference for the primary endpoint. WIDER IMPLICATIONS OF THE FINDINGS Conservative surgery is feasible in patients managed for large deep rectal endometriosis. The trial does not show a statistically significant superiority of conservative surgery for mid-term functional digestive and urinary outcomes in this specific population of women with large involvement of the rectum. There is a higher risk of rectal stenosis after segmental resection, requiring additional endoscopic or surgical procedures. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a grant from the clinical research programme for hospitals (PHRC) in France. The authors declare no competing interests related to this study. TRIAL REGISTRATION NUMBER This study is registered with ClinicalTrials.gov, number NCT 01291576. TRIAL REGISTRATION DATE 31 January 2011. DATE OF FIRST PATIENT’S ENROLMENT 7 March 2011. PMID:29194531

Efficacy of a medical food in mild Alzheimer's disease: A randomized, controlled trial.

PubMed

Scheltens, Philip; Kamphuis, Patrick J G H; Verhey, Frans R J; Olde Rikkert, Marcel G M; Wurtman, Richard J; Wilkinson, David; Twisk, Jos W R; Kurz, Alexander

2010-01-01

To investigate the effect of a medical food on cognitive function in people with mild Alzheimer's disease (AD). A total of 225 drug-naïve AD patients participated in this randomized, double-blind controlled trial. Patients were randomized to active product, Souvenaid, or a control drink, taken once-daily for 12 weeks. Primary outcome measures were the delayed verbal recall task of the Wechsler Memory Scale-revised, and the 13-item modified Alzheimer's Disease Assessment Scale-cognitive subscale at week 12. At 12 weeks, significant improvement in the delayed verbal recall task was noted in the active group compared with control (P = .021). Modified Alzheimer's Disease Assessment Scale-cognitive subscale and other outcome scores (e.g., Clinician Interview Based Impression of Change plus Caregiver Input, 12-item Neuropsychiatric Inventory, Alzheimer's disease Co-operative Study-Activities of Daily Living, Quality of Life in Alzheimer's Disease) were unchanged. The control group neither deteriorated nor improved. Compliance was excellent (95%) and the product was well tolerated. Supplementation with a medical food including phosphatide precursors and cofactors for 12 weeks improved memory (delayed verbal recall) in mild AD patients. This proof-of-concept study justifies further clinical trials. 2010 The Alzheimer's Association. All rights reserved.

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

The added value of a mobile application of Community Case Management on referral, re-consultation and hospitalization rates of children aged under 5 years in two districts in Northern Malawi: study protocol for a pragmatic, stepped-wedge cluster-randomized controlled trial.

PubMed

Hardy, Victoria; O'Connor, Yvonne; Heavin, Ciara; Mastellos, Nikolaos; Tran, Tammy; O'Donoghue, John; Fitzpatrick, Annette L; Ide, Nicole; Wu, Tsung-Shu Joseph; Chirambo, Griphin Baxter; Muula, Adamson S; Nyirenda, Moffat; Carlsson, Sven; Andersson, Bo; Thompson, Matthew

2017-10-11

There is evidence to suggest that frontline community health workers in Malawi are under-referring children to higher-level facilities. Integrating a digitized version of paper-based methods of Community Case Management (CCM) could strengthen delivery, increasing urgent referral rates and preventing unnecessary re-consultations and hospital admissions. This trial aims to evaluate the added value of the Supporting LIFE electronic Community Case Management Application (SL eCCM App) compared to paper-based CCM on urgent referral, re-consultation and hospitalization rates, in two districts in Northern Malawi. This is a pragmatic, stepped-wedge cluster-randomized trial assessing the added value of the SL eCCM App on urgent referral, re-consultation and hospitalization rates of children aged 2 months and older to up to 5 years, within 7 days of the index visit. One hundred and two health surveillance assistants (HSAs) were stratified into six clusters based on geographical location, and clusters randomized to the timing of crossover to the intervention using simple, computer-generated randomization. Training workshops were conducted prior to the control (paper-CCM) and intervention (paper-CCM + SL eCCM App) in assigned clusters. Neither participants nor study personnel were blinded to allocation. Outcome measures were determined by abstraction of clinical data from patient records 2 weeks after recruitment. A nested qualitative study explored perceptions of adherence to urgent referral recommendations and a cost evaluation determined the financial and time-related costs to caregivers of subsequent health care utilization. The trial was conducted between July 2016 and February 2017. This is the first large-scale trial evaluating the value of adding a mobile application of CCM to the assessment of children aged under 5 years. The trial will generate evidence on the potential use of mobile health for CCM in Malawi, and more widely in other low- and middle-income countries. ClinicalTrials.gov, ID: NCT02763345 . Registered on 3 May 2016.

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

Considerations for Managing Large-Scale Clinical Trials.

ERIC Educational Resources Information Center

Tuttle, Waneta C.; And Others

1989-01-01

Research management strategies used effectively in a large-scale clinical trial to determine the health effects of exposure to Agent Orange in Vietnam are discussed, including pre-project planning, organization according to strategy, attention to scheduling, a team approach, emphasis on guest relations, cross-training of personnel, and preparing…

Vitamin D and type 2 diabetes.

PubMed

Lips, Paul; Eekhoff, Marelise; van Schoor, Natasja; Oosterwerff, Mirjam; de Jongh, Renate; Krul-Poel, Yvonne; Simsek, Suat

2017-10-01

Vitamin D deficiency is associated with a decreased insulin release, insulin resistance and type 2 diabetes in experimental and epidemiological studies. Animal studies show that 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) stimulates the pancreatic β-cell to secrete insulin. The relationship between vitamin D deficiency and insulin resistance could develop through inflammation, as vitamin D deficiency is associated with increased inflammatory markers. In addition, genetic polymorphisms of vitamin D -related genes may predispose to impaired glycemic control and type 2 diabetes. Epidemiologic studies showed an association between low serum 25-hydroxyvitamin D 3 (25(OH)D 3 ) concentration and an increased risk for the metabolic syndrome and type 2 diabetes. This may be partly explained by an increased fat mass. A possible causal relationship between vitamin D deficiency and type 2 diabetes should be proven by randomized clinical trials showing that either type 2 diabetes can be prevented or insulin release and insulin sensitivity can be improved by vitamin D supplements. The results of randomized clinical trials on the effect of vitamin D versus placebo, sometimes combined with calcium, in patients with impaired glucose tolerance ("prediabetes") or type 2 diabetes are inconsistent. Some studies showed a slight decrease of fasting plasma glucose or improvement of insulin resistance, but often only in posthoc analyses. These effects are mainly visible in patients with vitamin D deficiency and impaired glucose tolerance at baseline. Meta-analyses of randomized clinical trials in general did not show significant effects of vitamin D supplementation on glycemic control. Currently, several large scale randomized clinical trials with vitamin D supplementation in doses of 1600-4000IU/d are ongoing with glycemic control or incidence of diabetes mellitus as outcome. Vitamin D deficiency needs to be prevented or cured, but until the results of these trials are published, high-dose vitamin D supplementation cannot be recommended for prevention or amelioration of type 2 diabetes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chinese herbal medicine Kuntai capsule for treatment of menopausal syndrome: a systematic review of randomized clinical trials.

PubMed

Zhou, Quan; Tao, Jing; Song, Huamei; Chen, Aihua; Yang, Huaijie; Zuo, Manzhen; Li, Hairong

2016-12-01

Kuntai capsule has been widely used for the treatment of menopausal syndrome in China for long time. We conducted this review to assess efficacy and safety of Kuntai capsule for the treatment of menopausal syndrome. We searched studies in PubMed, ClinicalTrials, the Cochrane Library, China National Knowledge Infrastructure Database(CNKI), China Science and Technology Journal Database (VIP), Wan fang Database and Chinese Biomedical Literature Database(CBM) until November 20, 2014. Randomized trials on Kuntai capsule for menopausal syndrome, compared with placebo or hormone replacement therapy (HRT) were included. Two reviewers independently retrieved the randomized controlled trials (RCTs) and extracted the information. The Cochrane risk of bias method was used to assess the quality of the included studies, and a Meta-analysis was conducted with Review Manager 5.2 software. A total of 17 RCTs (1455 participants) were included. The studies were of low methodological quality. Meta-analysis indicated that there was no statistical difference in the Kupperman index (KI) [WMD=0.51, 95% CI (-0.04, 1.06)], the effective rate of KI [OR=1.21, 95% CI (0.72, 2.04)], E2 level [WMD=-15.18, 95% CI (-33.93, 3.56)], and FSH level [WMD=-3.46, 95% CI (-7.2, 0.28)] after treatment between Kuntai versus HRT group (P>0.05). However, Compared with HRT, Kuntai capsule could significantly reduce the total incidence of adverse events [OR=0.28, 95% CI (0.17, 0.45)]. Kuntai capsule may be effective for treating menopausal syndrome and lower risk of side effects. The studies we analyzed were of low methodological quality. Therefore, more strictly designed large-scale randomized clinical trials are needed to evaluate the efficacy of Kuntai capsule in menopausal syndrome. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reducing Achievement Gaps in Academic Writing for Latinos and English Learners in Grades 7-12

ERIC Educational Resources Information Center

Olson, Carol Booth; Matuchniak, Tina; Chung, Huy Q.; Stumpf, Rachel; Farkas, George

2017-01-01

This study reports 2 years of findings from a randomized controlled trial designed to replicate and demonstrate the efficacy of an existing, successful professional development program, the Pathway Project, that uses a cognitive strategies approach to text-based analytical writing. Building on an earlier randomized field trial in a large, urban,…

Effects of psychological interventions for patients with osteoarthritis: a systematic review and meta-analysis.

PubMed

Zhang, Lijuan; Fu, Ting; Zhang, Qiuxiang; Yin, Rulan; Zhu, Li; He, Yan; Fu, Wenting; Shen, Biyu

2018-01-01

The aim of this study was to determine the effects of psychological interventions (e.g. cognitive restructuring, relaxation) on physiological and psychological health in osteoarthritis patients. A systematic literature search was done using PubMed, Embase, PsycINFO, Web of Science, China National Knowledge Infrastructure, and Wanfang Database through November 2016. Studies were included if they used a randomized controlled trial designed to explore the effects of psychological interventions in osteoarthritis patients. Two independent authors assessed the methodological quality of the trials using criteria outlined by Jadad et al. Meta-analysis was done with the Revman5.0. Twelve randomized controlled trials, including 1307 osteoarthritis patients, met the study inclusion criteria. Meta-analysis showed that psychological interventions could reduce the levels of pain [standard mean difference (SMD) -0.28, 95% CI -0.48, -0.08, P-value 0.005)] and fatigue (SMD -0.18, 95% CI -0.34, -0.01, P-value 0.04). In addition, psychological interventions significantly improved osteoarthritis patients' self-efficacy (SMD 0.58, 95% CI 0.40, 0.75, P-value 0.00) and pain coping (MD 1.64, 95% CI 0.03, 3.25, P-value 0.05). Although the effects on physical function, anxiety, depression, psychological disability were in the expected direction, they were not statistically significant. In conclusion, the role of psychological interventions in the management of osteoarthritis remains equivocal. Some encouraging results were seen with regard to pain, pain coping, self-efficacy, and fatigue. We believe that more methodologically rigorous large-scale randomized controlled trials are necessary to answer this study question.

Strategies and Opportunities to STOP Colon Cancer in Priority Populations: Design of a Cluster-Randomized Pragmatic Trial

PubMed Central

Coronado, Gloria D.; Vollmer, William M.; Petrik, Amanda; Taplin, Stephen H.; Burdick, Timothy E.; Meenan, Richard T.; Green, Beverly

2014-01-01

Background Colorectal cancer is the second-leading cause of cancer deaths in the United States. The Strategies and Opportunities to Stop Colorectal Cancer (STOP CRC) in Priority Populations study is a pragmatic trial and a collaboration between two research institutions and a network of more than 200 safety net clinics. The study will assess effectiveness of a systems-based intervention designed to improve rates of colorectal-cancer screening using fecal immunochemical testing (FIT) in federally qualified health centers in Oregon and Northern California. Material and Methods STOP CRC is a cluster-randomized comparative-effectiveness pragmatic trial enrolling 26 clinics. Clinics will be randomized to one of two arms. Clinics in the intervention arm (1) will use an automated, data-driven, electronic health record-embedded program to identify patients due for colorectal screening and mail FIT kits (with pictographic instructions) to them; (2) will conduct an improvement process (e.g. Plan-Do-Study-Act) to enhance the adoption, reach, and effectiveness of the program. Clinics in the control arm will provide opportunistic colorectal-cancer screening to patients at clinic visits. The primary outcomes are: proportion of age– and screening-eligible patients completing a FIT within 12 months; and cost, cost-effectiveness, and return on investment of the intervention. Conclusions This large-scale pragmatic trial will leverage electronic health record information and existing clinic staff to enroll a broad range of patients, including many with historically low colorectal-cancer screening rates. If successful, the program will provide a model for a cost-effective and scalable method to raise colorectal-cancer screening rates. PMID:24937017

Sodium Bicarbonate for the Prevention of Contrast Induced-Acute Kidney Injury: A Systematic Review and Meta-analysis

PubMed Central

Hiremath, Swapnil; Dangas, George; Mehran, Roxana; Brar, Simerjeet K.; Leon, Martin B.

2009-01-01

Background and objectives: Infusion of sodium bicarbonate has been suggested as a preventative strategy but reports are conflicting on its efficacy. The aim of this study was to assess the effectiveness of hydration with sodium bicarbonate for the prevention of contrast-induced acute kidney injury (CI-AKI). Design, setting, participants, & measurements: Medline, EMBASE, Cochrane library, and the Internet were searched for randomized controlled trials comparing hydration between sodium bicarbonate and chloride for the prevention of CI-AKI between 1966 and November 2008. Fourteen trials that included 2290 patients were identified. There was significant heterogeneity between studies (P heterogeneity = 0.02; I2 = 47.8%), which was largely accounted for by trial size (P = 0.016). Trials were therefore classified by size. Results: Three trials were categorized as large (n = 1145) and 12 as small (n = 1145). Among the large trials, the incidence of CI-AKI for sodium bicarbonate and sodium chloride was 10.7 and 12.5%, respectively; the relative risk (RR) [95% confidence interval (CI)] was 0.85 (0.63 to 1.16) without evidence of heterogeneity (P = 0.89, I2 = 0%). The pooled RR (95% CI) among the 12 small trials was 0.50 (0.27 to 0.93) with significant between-trial heterogeneity (P = 0.01; I2 = 56%). The small trials were more likely to be of lower methodological quality. Conclusions: A significant clinical and statistical heterogeneity was observed that was largely explained by trial size and published status. Among the large randomized trials there was no evidence of benefit for hydration with sodium bicarbonate compared with sodium chloride for the prevention of CI-AKI. The benefit of sodium bicarbonate was limited to small trials of lower methodological quality. PMID:19713291

The saving and empowering young lives in Europe (SEYLE) randomized controlled trial (RCT): methodological issues and participant characteristics.

PubMed

Carli, Vladimir; Wasserman, Camilla; Wasserman, Danuta; Sarchiapone, Marco; Apter, Alan; Balazs, Judit; Bobes, Julio; Brunner, Romuald; Corcoran, Paul; Cosman, Doina; Guillemin, Francis; Haring, Christian; Kaess, Michael; Kahn, Jean Pierre; Keeley, Helen; Keresztény, Agnes; Iosue, Miriam; Mars, Ursa; Musa, George; Nemes, Bogdan; Postuvan, Vita; Reiter-Theil, Stella; Saiz, Pilar; Varnik, Peeter; Varnik, Airi; Hoven, Christina W

2013-05-16

Mental health problems and risk behaviours among young people are of great public health concern. Consequently, within the VII Framework Programme, the European Commission funded the Saving and Empowering Young Lives in Europe (SEYLE) project. This Randomized Controlled Trial (RCT) was conducted in eleven European countries, with Sweden as the coordinating centre, and was designed to identify an effective way to promote mental health and reduce suicidality and risk taking behaviours among adolescents. To describe the methodological and field procedures in the SEYLE RCT among adolescents, as well as to present the main characteristics of the recruited sample. Analyses were conducted to determine: 1) representativeness of study sites compared to respective national data; 2) response rate of schools and pupils, drop-out rates from baseline to 3 and 12 month follow-up, 3) comparability of samples among the four Intervention Arms; 4) properties of the standard scales employed: Beck Depression Inventory, Second Edition (BDI-II), Zung Self-Rating Anxiety Scale (Z-SAS), Strengths and Difficulties Questionnaire (SDQ), World Health Organization Well-Being Scale (WHO-5). Participants at baseline comprised 12,395 adolescents (M/F: 5,529/6,799; mean age=14.9±0.9) from Austria, Estonia, France, Germany, Hungary, Ireland, Israel, Italy, Romania, Slovenia and Spain. At the 3 and 12 months follow up, participation rates were 87.3% and 79.4%, respectively. Demographic characteristics of participating sites were found to be reasonably representative of their respective national population. Overall response rate of schools was 67.8%. All scales utilised in the study had good to very good internal reliability, as measured by Cronbach's alpha (BDI-II: 0.864; Z-SAS: 0.805; SDQ: 0.740; WHO-5: 0.799). SEYLE achieved its objective of recruiting a large representative sample of adolescents within participating European countries. Analysis of SEYLE data will shed light on the effectiveness of important interventions aimed at improving adolescent mental health and well-being, reducing risk-taking and self-destructive behaviour and preventing suicidality. US National Institute of Health (NIH) clinical trial registry (NCT00906620) and the German Clinical Trials Register (DRKS00000214).

Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials: a literature review and synthesis.

PubMed

Banks, Jamie L; Marotta, Charles A

2007-03-01

The modified Rankin scale (mRS), a clinician-reported measure of global disability, is widely applied for evaluating stroke patient outcomes and as an end point in randomized clinical trials. Extensive evidence on the validity of the mRS exists across a large but fragmented literature. As new treatments for acute ischemic stroke are submitted for agency approval, an appreciation of the mRS's attributes, specifically its relationship to other stroke evaluation scales, would be valuable for decision-makers to properly assess the impact of a new drug on treatment paradigms. The purpose of this report is to assemble and systematically assess the properties of the mRS to provide decision-makers with pertinent evaluative information. A Medline search was conducted to identify reports in the peer-reviewed medical literature (1957-2006) that provide information on the structure, validation, scoring, and psychometric properties of the mRS and its use in clinical trials. The selection of articles was based on defined criteria that included relevance, study design and use of appropriate statistical methods. Of 224 articles identified by the literature search, 50 were selected for detailed assessment. Inter-rater reliability with the mRS is moderate and improves with structured interviews (kappa 0.56 versus 0.78); strong test-re-test reliability (kappa=0.81 to 0.95) has been reported. Numerous studies demonstrate the construct validity of the mRS by its relationships to physiological indicators such as stroke type, lesion size, perfusion and neurological impairment. Convergent validity between the mRS and other disability scales is well documented. Patient comorbidities and socioeconomic factors should be considered in properly applying and interpreting the mRS. Recent analyses suggest that randomized clinical trials of acute stroke treatments may require a smaller sample size if the mRS is used as a primary end point rather than the Barthel Index. Multiple types of evidence attest to the validity and reliability of the mRS. The reported data support the view that the mRS is a valuable instrument for assessing the impact of new stroke treatments.

Automatic initialization and quality control of large-scale cardiac MRI segmentations.

PubMed

Albà, Xènia; Lekadir, Karim; Pereañez, Marco; Medrano-Gracia, Pau; Young, Alistair A; Frangi, Alejandro F

2018-01-01

Continuous advances in imaging technologies enable ever more comprehensive phenotyping of human anatomy and physiology. Concomitant reduction of imaging costs has resulted in widespread use of imaging in large clinical trials and population imaging studies. Magnetic Resonance Imaging (MRI), in particular, offers one-stop-shop multidimensional biomarkers of cardiovascular physiology and pathology. A wide range of analysis methods offer sophisticated cardiac image assessment and quantification for clinical and research studies. However, most methods have only been evaluated on relatively small databases often not accessible for open and fair benchmarking. Consequently, published performance indices are not directly comparable across studies and their translation and scalability to large clinical trials or population imaging cohorts is uncertain. Most existing techniques still rely on considerable manual intervention for the initialization and quality control of the segmentation process, becoming prohibitive when dealing with thousands of images. The contributions of this paper are three-fold. First, we propose a fully automatic method for initializing cardiac MRI segmentation, by using image features and random forests regression to predict an initial position of the heart and key anatomical landmarks in an MRI volume. In processing a full imaging database, the technique predicts the optimal corrective displacements and positions in relation to the initial rough intersections of the long and short axis images. Second, we introduce for the first time a quality control measure capable of identifying incorrect cardiac segmentations with no visual assessment. The method uses statistical, pattern and fractal descriptors in a random forest classifier to detect failures to be corrected or removed from subsequent statistical analysis. Finally, we validate these new techniques within a full pipeline for cardiac segmentation applicable to large-scale cardiac MRI databases. The results obtained based on over 1200 cases from the Cardiac Atlas Project show the promise of fully automatic initialization and quality control for population studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Internet-Assisted Parent Training Intervention for Disruptive Behavior in 4-Year-Old Children: A Randomized Clinical Trial.

PubMed

Sourander, Andre; McGrath, Patrick J; Ristkari, Terja; Cunningham, Charles; Huttunen, Jukka; Lingley-Pottie, Patricia; Hinkka-Yli-Salomäki, Susanna; Kinnunen, Malin; Vuorio, Jenni; Sinokki, Atte; Fossum, Sturla; Unruh, Anita

2016-04-01

There is a large gap worldwide in the provision of evidence-based early treatment of children with disruptive behavioral problems. To determine whether an Internet-assisted intervention using whole-population screening that targets the most symptomatic 4-year-old children is effective at 6 and 12 months after the start of treatment. This 2-parallel-group randomized clinical trial was performed from October 1, 2011, through November 30, 2013, at a primary health care clinic in Southwest Finland. Data analysis was performed from August 6, 2015, to December 11, 2015. Of a screened population of 4656 children, 730 met the screening criteria indicating a high level of disruptive behavioral problems. A total of 464 parents of 4-year-old children were randomized into the Strongest Families Smart Website (SFSW) intervention group (n = 232) or an education control (EC) group (n = 232). The SFSW intervention, an 11-session Internet-assisted parent training program that included weekly telephone coaching. Child Behavior Checklist version for preschool children (CBCL/1.5-5) externalizing scale (primary outcome), other CBCL/1.5-5 scales and subscores, Parenting Scale, Inventory of Callous-Unemotional Traits, and the 21-item Depression, Anxiety, and Stress Scale. All data were analyzed by intention to treat and per protocol. The assessments were made before randomization and 6 and 12 months after randomization. Of the children randomized, 287 (61.9%) were male and 79 (17.1%) lived in other than a family with 2 biological parents. At 12-month follow-up, improvement in the SFSW intervention group was significantly greater compared with the control group on the following measures: CBCL/1.5-5 externalizing scale (effect size, 0.34; P < .001), internalizing scale (effect size, 0.35; P < .001), and total scores (effect size, 0.37; P < .001); 5 of 7 syndrome scales, including aggression (effect size, 0.36; P < .001), sleep (effect size, 0.24; P = .002), withdrawal (effect size, 0.25; P = .005), anxiety (effect size, 0.26; P = .003), and emotional problems (effect size, 0.31; P = .001); Inventory of Callous-Unemotional Traits callousness scores (effect size, 0.19; P = .03); and self-reported parenting skills (effect size, 0.53; P < .001). The study reveals the effectiveness and feasibility of an Internet-assisted parent training intervention offered for parents of preschool children with disruptive behavioral problems screened from the whole population. The strategy of population-based screening of children at an early age to offering parent training using digital technology and telephone coaching is a promising public health strategy for providing early intervention for a variety of child mental health problems. clinicaltrials.gov Identifier: NCT01750996.

Blood pressure and endothelial function in healthy, pregnant women after acute and daily consumption of flavanol-rich chocolate: a pilot, randomized controlled trial.

PubMed

Mogollon, Jaime Andres; Bujold, Emmanuel; Lemieux, Simone; Bourdages, Mélodie; Blanchet, Claudine; Bazinet, Laurent; Couillard, Charles; Noël, Martin; Dodin, Sylvie

2013-04-08

Several randomized clinical trials (RCTs) indicate that flavanol-rich chocolate has beneficial effects on flow-mediated dilation (FMD) and blood pressure (BP). However, no RCTs have evaluated these outcomes in pregnant women. The objective of this 2-group, parallel, double-blind RCT was to examine the effects of flavanol-rich chocolate on FMD and BP in pregnant women with normal BP. Forty-four healthy, pregnant women were randomized to the high-flavanol (n = 23) or low-flavanol (n = 21) chocolate consumption for 12 weeks. At randomization (0, 60, 120 and 180 min after a single 40-g dose of chocolate), 6 and 12 weeks after daily 20-g chocolate intake, we evaluated plasma concentrations of flavanols and theobromine, as well as the FMD and BP. Plasma epicatechin was significantly increased (p < 0.001) 180 min after the consumption of 40-g high-flavanol chocolate compared to low-flavanol chocolate. Theobromine concentrations were significantly higher 180 min and 12 weeks after the intake of experimental chocolate or low-flavanol chocolate (p < 0.001). FMD was not different between the 2 groups at all pre-defined time periods. No other significant within-group or between-group changes were observed. These results confirm the feasibility of a large-scale RCT comparing daily consumption of flavanol-rich chocolate to an equivalent placebo during pregnancy and demonstrate higher plasma epicatechin and theobromine concentration in the intervention group after acute ingestion ClinicalTrials.gov Identifier: NCT01659060.

Non-surgical treatment of hip osteoarthritis. Hip school, with or without the addition of manual therapy, in comparison to a minimal control intervention: Protocol for a three-armed randomized clinical trial

PubMed Central

2011-01-01

Background Hip osteoarthritis is a common and chronic condition resulting in pain, functional disability and reduced quality of life. In the early stages of the disease, a combination of non-pharmacological and pharmacological treatment is recommended. There is evidence from several trials that exercise therapy is effective. In addition, single trials suggest that patient education in the form of a hip school is a promising intervention and that manual therapy is superior to exercise. Methods/Design This is a randomized clinical trial. Patients with clinical and radiological hip osteoarthritis, 40-80 years of age, and without indication for hip surgery were randomized into 3 groups. The active intervention groups A and B received six weeks of hip school, taught by a physiotherapist, for a total of 5 sessions. In addition, group B received manual therapy consisting of joint manipulation and soft-tissue therapy twice a week for six weeks. Group C received a self-care information leaflet containing advice on "live as usual" and stretching exercises from the hip school. The primary time point for assessing relative effectiveness is at the end of the six weeks intervention period with follow-ups after three and 12 months. Primary outcome measure is pain measured on an eleven-point numeric rating scale. Secondary outcome measures are the hip dysfunction and osteoarthritis outcome score, patient's global perceived effect, patient specific functional scale, general quality of life and hip range of motion. Discussion To our knowledge this is the first randomized clinical trial comparing a patient education program with or without the addition of manual therapy to a minimal intervention for patients with hip osteoarthritis. Trial registration ClinicalTrials NCT01039337 PMID:21542914

An empirical study using permutation-based resampling in meta-regression

PubMed Central

2012-01-01

Background In meta-regression, as the number of trials in the analyses decreases, the risk of false positives or false negatives increases. This is partly due to the assumption of normality that may not hold in small samples. Creation of a distribution from the observed trials using permutation methods to calculate P values may allow for less spurious findings. Permutation has not been empirically tested in meta-regression. The objective of this study was to perform an empirical investigation to explore the differences in results for meta-analyses on a small number of trials using standard large sample approaches verses permutation-based methods for meta-regression. Methods We isolated a sample of randomized controlled clinical trials (RCTs) for interventions that have a small number of trials (herbal medicine trials). Trials were then grouped by herbal species and condition and assessed for methodological quality using the Jadad scale, and data were extracted for each outcome. Finally, we performed meta-analyses on the primary outcome of each group of trials and meta-regression for methodological quality subgroups within each meta-analysis. We used large sample methods and permutation methods in our meta-regression modeling. We then compared final models and final P values between methods. Results We collected 110 trials across 5 intervention/outcome pairings and 5 to 10 trials per covariate. When applying large sample methods and permutation-based methods in our backwards stepwise regression the covariates in the final models were identical in all cases. The P values for the covariates in the final model were larger in 78% (7/9) of the cases for permutation and identical for 22% (2/9) of the cases. Conclusions We present empirical evidence that permutation-based resampling may not change final models when using backwards stepwise regression, but may increase P values in meta-regression of multiple covariates for relatively small amount of trials. PMID:22587815

A Randomized Crossover Trial Comparing Autotitrating and Continuous Positive Airway Pressure in Subjects With Symptoms of Aerophagia: Effects on Compliance and Subjective Symptoms

PubMed Central

Shirlaw, Teresa; Hanssen, Kevin; Duce, Brett; Hukins, Craig

2017-01-01

Study Objectives: To assess the benefit and tolerance of autotitrating positive airway pressure (APAP) versus continuous positive airway pressure (CPAP) in subjects who experience aerophagia. Methods: This is the report of a prospective, two-week, double-blinded, randomized crossover trial set in an Australian clinical sleep laboratory in a tertiary hospital. Fifty-six subjects who reported symptoms of aerophagia that they attributed to CPAP were recruited. Full face masks were used by 39 of the 56 subjects recruited. Subjects were randomly and blindly allocated to either CPAP at their treatment recommended pressure or APAP 6–20 cm H2O, in random order. Subjects spent two weeks on each therapy mode. Therapy usage hours, 95th centile pressure, maximum pressure, 95th centile leak, and residual apnea-hypopnea index (AHI) were reported at the end of each two-week treatment period. Functional Outcome of Sleepiness Questionnaire, Epworth Sleepiness Scale, and visual analog scale to measure symptoms of aerophagia were also completed at the end of each 2-week treatment arm. Results: The median pressure (P < .001) and 95th centile pressure (P < .001) were reduced with APAP but no differences in compliance (P = .120) and residual AHI were observed. APAP reduced the symptoms of bloating (P = .011), worst episode of bloating (P = .040), flatulence (P = .010), and belching (P = .001) compared to CPAP. There were no differences in Epworth Sleepiness Scale or Functional Outcome of Sleepiness Questionnaire outcomes between CPAP and APAP. Conclusions: APAP therapy reduces the symptoms of aerophagia while not affecting compliance when compared with CPAP therapy. Clinical Trial Registration: Australian and New Zealand Clinical Trials Registry at https://www.anzctr.org.au, trial number ACTRN12611001250921. Commentary: A commentary on this article appears in this issue on page 859. Citation: Shirlaw T, Hanssen K, Duce B, Hukins C. A randomized crossover trial comparing autotitrating and continuous positive airway pressure in subjects with symptoms of aerophagia: effects on compliance and subjective symptoms. J Clin Sleep Med. 2017;13(7):881–888. PMID:28558864

Year One Results from the Multisite Randomized Evaluation of the i3 Scale-Up of Reading Recovery

ERIC Educational Resources Information Center

May, Henry; Gray, Abigail; Sirinides, Philip; Goldsworthy, Heather; Armijo, Michael; Sam, Cecile; Gillespie, Jessica N.; Tognatta, Namrata

2015-01-01

Reading Recovery (RR) is a short-term, one-to-one intervention designed to help the lowest achieving readers in first grade. This article presents first-year results from the multisite randomized controlled trial (RCT) and implementation study under the $55 million Investing in Innovation (i3) Scale-Up Project. For the 2011-2012 school year, the…

Financial incentives for smoking cessation in low-income smokers: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Tobacco smoking is the leading avoidable cause of death in high-income countries. The smoking-related disease burden is borne primarily by the least educated and least affluent groups. Thus, there is a need for effective smoking cessation interventions that reach to, and are effective in this group. Research suggests that modest financial incentives are not very effective in helping smokers quit. What is not known is whether large financial incentives can enhance longer-term (1 year) smoking cessation rates, outside clinical and workplace settings. Trial design A randomized, parallel groups, controlled trial. Methods Participants: Eight hundred low-income smokers in Switzerland (the less affluent third of the population, based on fiscal taxation). Intervention: A smoking cessation program including: (a) financial incentives given during 6 months; and (b) Internet-based counseling. Financial rewards will be offered for biochemically verified smoking abstinence after 1, 2, and 3 weeks and 1, 3, and 6 months, for a maximum of 1,500 CHF (1,250 EUR, 1,500 USD) for those abstinent at all time-points. All participants, including controls, will receive Internet-based, individually-tailored, smoking cessation counseling and self-help booklets, but there will be no in-person or telephone counseling, and participants will not receive medications. The control group will not receive financial incentives. Objective: To increase smoking cessation rates. Outcome: Smoking abstinence after 6 and 18 months, not contradicted by biochemical tests. We will assess relapse after the end of the intervention, to test whether 6-month effects translate into sustained abstinence 12 months after the incentives are withdrawn. Randomization: Will be done using sealed envelopes drawn by participants. Blinding: Is not possible in this context. Discussion Smoking prevention policies and interventions have been least effective in the least educated, low-income groups. Combining financial incentives and Internet-based counseling is an innovative approach that, if proven acceptable and effective, could be later implemented on a large scale at a reasonable cost, decrease health disparities, and save many lives. Trial registration Current Controlled Trials ISRCTN04019434. PMID:22721577

Internet Treatment for Depression: A Randomized Controlled Trial Comparing Clinician vs. Technician Assistance

PubMed Central

Titov, Nickolai; Andrews, Gavin; Davies, Matthew; McIntyre, Karen; Robinson, Emma; Solley, Karen

2010-01-01

Background Internet-based cognitive behavioural therapy (iCBT) for depression is effective when guided by a clinician, less so if unguided. Question: Would guidance from a technician be as effective as guidance from a clinician? Method Randomized controlled non-inferiority trial comparing three groups: Clinician-assisted vs. technician-assisted vs. delayed treatment. Community-based volunteers applied to the VirtualClinic (www.virtualclinic.org.au) research program, and 141 participants with major depressive disorder were randomized. Participants in the clinician- and technician-assisted groups received access to an iCBT program for depression comprising 6 online lessons, weekly homework assignments, and weekly supportive contact over a treatment period of 8 weeks. Participants in the clinician-assisted group also received access to a moderated online discussion forum. The main outcome measures were the Beck Depression Inventory (BDI-II) and the Patient Health Questionnaire-9 Item (PHQ-9). Completion rates were high, and at post-treatment, both treatment groups reduced scores on the BDI-II (p<0.001) and PHQ-9 (p<0.001) compared to the delayed treatment group but did not differ from each other. Within group effect sizes on the BDI-II were 1.27 and 1.20 for the clinician- and technician-assisted groups respectively, and on the PHQ-9, were 1.54 and 1.60 respectively. At 4-month follow-up participants in the technician group had made further improvements and had significantly lower scores on the PHQ-9 than those in the clinician group. A total of approximately 60 minutes of clinician or technician time was required per participant during the 8-week treatment program. Conclusions Both clinician- and technician-assisted treatment resulted in large effect sizes and clinically significant improvements comparable to those associated with face-to-face treatment, while a delayed treatment control group did not improve. These results provide support for large scale trials to determine the clinical effectiveness and acceptability of technician-assisted iCBT programs for depression. This form of treatment has potential to increase the capacity of existing mental health services. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12609000559213 PMID:20544030

Internet Treatment for Generalized Anxiety Disorder: A Randomized Controlled Trial Comparing Clinician vs. Technician Assistance

PubMed Central

Robinson, Emma; Titov, Nickolai; Andrews, Gavin; McIntyre, Karen; Schwencke, Genevieve; Solley, Karen

2010-01-01

Background Internet-based cognitive behavioural therapy (iCBT) for generalized anxiety disorder (GAD) has been shown to be effective when guided by a clinician. The present study sought to replicate this finding, and determine whether support from a technician is as effective as guidance from a clinician. Method Randomized controlled non-inferiority trial comparing three groups: Clinician-assisted vs. technician-assisted vs. delayed treatment. Community-based volunteers applied to the VirtualClinic (www.virtualclinic.org.au) research program and 150 participants with GAD were randomized. Participants in the clinician- and technician-assisted groups received access to an iCBT program for GAD comprising six online lessons, weekly homework assignments, and weekly supportive contact over a treatment period of 10 weeks. Participants in the clinician-assisted group also received access to a moderated online discussion forum. The main outcome measures were the Penn State Worry Questionnaire (PSWQ) and the Generalized Anxiety Disorder-7 Item (GAD-7). Completion rates were high, and both treatment groups reduced scores on the PSWQ (p<0.001) and GAD-7 (p<0.001) compared to the delayed treatment group, but did not differ from each other. Within group effect sizes on the PSWQ were 1.16 and 1.07 for the clinician- and technician-assisted groups, respectively, and on the GAD-7 were 1.55 and 1.73, respectively. At 3 month follow-up participants in both treatment groups had sustained the gains made at post-treatment. Participants in the clinician-assisted group had made further gains on the PSWQ. Approximately 81 minutes of clinician time and 75 minutes of technician time were required per participant during the 10 week treatment program. Conclusions Both clinician- and technician-assisted treatment resulted in large effect sizes and clinically significant improvements comparable to those associated with face-to-face treatment, while a delayed treatment/control group did not improve. These results provide support for large scale trials to determine the clinical effectiveness and acceptability of technician-assisted iCBT programs for GAD. This form of treatment has potential to increase the capacity of existing mental health services. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12609000563268 PMID:20532167

The efficacy of interpersonal psychotherapy for depression among economically disadvantaged mothers.

PubMed

Toth, Sheree L; Rogosch, Fred A; Oshri, Assaf; Gravener-Davis, Julie; Sturm, Robin; Morgan-López, Antonio Alexander

2013-11-01

A randomized clinical trial was conducted to evaluate the efficacy of interpersonal psychotherapy (IPT) for ethnically and racially diverse, economically disadvantaged women with major depressive disorder. Non-treatment-seeking urban women (N = 128; M age = 25.40, SD = 4.98) with infants were recruited from the community. Participants were at or below the poverty level: 59.4% were Black and 21.1% were Hispanic. Women were screened for depressive symptoms using the Center for Epidemiologic Studies Depression Scale; the Diagnostic Interview Schedule was used to confirm major depressive disorder diagnosis. Participants were randomized to individual IPT or enhanced community standard. Depressive symptoms were assessed before, after, and 8 months posttreatment with the Beck Depression Inventory-II and the Revised Hamilton Rating Scale for Depression. The Social Support Behaviors Scale, the Social Adjustment Scale-Self-Report, and the Perceived Stress Scale were administered to examine mediators of outcome at follow-up. Treatment effects were evaluated with a growth mixture model for randomized trials using complier-average causal effect estimation. Depressive symptoms trajectories from baseline through postintervention to follow-up showed significant decreases among the IPT group compared to the enhanced community standard group. Changes on the Perceived Stress Scale and the Social Support Behaviors Scale mediated sustained treatment outcome.

Huperzine A for Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

PubMed Central

Yang, Guoyan; Wang, Yuyi; Tian, Jinzhou; Liu, Jian-Ping

2013-01-01

Background Huperzine A is a Chinese herb extract used for Alzheimer’s disease. We conducted this review to evaluate the beneficial and harmful effect of Huperzine A for treatment of Alzheimer’s disease. Methods We searched for randomized clinical trials (RCTs) of Huperzine A for Alzheimer’s disease in PubMed, Cochrane Library, and four major Chinese electronic databases from their inception to June 2013. We performed meta-analyses using RevMan 5.1 software. (Protocol ID: CRD42012003249) Results 20 RCTs including 1823 participants were included. The methodological quality of most included trials had a high risk of bias. Compared with placebo, Huperzine A showed a significant beneficial effect on the improvement of cognitive function as measured by Mini-Mental State Examination (MMSE) at 8 weeks, 12 weeks and 16 weeks, and by Hastgawa Dementia Scale (HDS) and Wechsler Memory Scale (WMS) at 8 weeks and 12 weeks. Activities of daily living favored Huperzine A as measured by Activities of Daily Living Scale (ADL) at 6 weeks, 12 weeks and 16 weeks. One trial found Huperzine A improved global clinical assessment as measured by Clinical Dementia Rating Scale (CDR). One trial demonstrated no significant change in cognitive function as measured by Alzheimer’s disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and activity of daily living as measured by Alzheimer’s disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) in Huperzine A group. Trials comparing Huperzine A with no treatment, psychotherapy and conventional medicine demonstrated similar findings. No trial evaluated quality of life. No trial reported severe adverse events of Huperzine A. Conclusions Huperzine A appears to have beneficial effects on improvement of cognitive function, daily living activity, and global clinical assessment in participants with Alzheimer’s disease. However, the findings should be interpreted with caution due to the poor methodological quality of the included trials. PMID:24086396

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.

Conservative surgery versus colorectal resection in deep endometriosis infiltrating the rectum: a randomized trial.

PubMed

Roman, Horace; Bubenheim, Michael; Huet, Emmanuel; Bridoux, Valérie; Zacharopoulou, Chrysoula; Daraï, Emile; Collinet, Pierre; Tuech, Jean-Jacques

2018-01-01

Is there a difference in functional outcome between conservative versus radical rectal surgery in patients with large deep endometriosis infiltrating the rectum 2 years postoperatively? No evidence was found that functional outcomes differed when conservative surgery was compared to radical rectal surgery for deeply invasive endometriosis involving the bowel. Adopting a conservative approach to the surgical management of deep endometriosis infiltrating the rectum, by employing shaving or disc excision, appears to yield improved digestive functional outcomes. However, previous comparative studies were not randomized, introducing a possible bias regarding the presumed superiority of conservative techniques due to the inclusion of patients with more severe deep endometriosis who underwent colorectal resection. From March 2011 to August 2013, we performed a 2-arm randomized trial, enroling 60 patients with deep endometriosis infiltrating the rectum up to 15 cm from the anus, measuring more than 20 mm in length, involving at least the muscular layer in depth and up to 50% of rectal circumference. No women were lost to follow-up. Patients were enroled in three French university hospitals and had either conservative surgery, by shaving or disc excision, or radical rectal surgery, by segmental resection. Randomization was performed preoperatively using sequentially numbered, opaque, sealed envelopes, and patients were informed of the results of randomization. The primary endpoint was the proportion of patients experiencing one of the following symptoms: constipation (1 stool/>5 consecutive days), frequent bowel movements (≥3 stools/day), defecation pain, anal incontinence, dysuria or bladder atony requiring self-catheterization 24 months postoperatively. Secondary endpoints were the values of the Visual Analog Scale (VAS), Knowles-Eccersley-Scott-Symptom Questionnaire (KESS), the Gastrointestinal Quality of Life Index (GIQLI), the Wexner scale, the Urinary Symptom Profile (USP) and the Short Form 36 Health Survey (SF36). A total of 60 patients were enroled. Among the 27 patients in the conservative surgery arm, two were converted to segmental resection (7.4%). In each group, 13 presented with at least one functional problem at 24 months after surgery (48.1 versus 39.4%, OR = 0.70, 95% CI 0.22-2.21). The intention-to-treat comparison of the overall scores on KESS, GIQLI, Wexner, USP and SF36 did not reveal significant differences between the two arms. Segmental resection was associated with a significant risk of bowel stenosis. The inclusion of only large infiltrations of the rectum does not allow the extrapolation of conclusions to small nodules of <20 mm in length. The presumption of a 40% difference favourable to conservative surgery in terms of postoperative functional outcomes resulted in a lack of power to demonstrate a difference for the primary endpoint. Conservative surgery is feasible in patients managed for large deep rectal endometriosis. The trial does not show a statistically significant superiority of conservative surgery for mid-term functional digestive and urinary outcomes in this specific population of women with large involvement of the rectum. There is a higher risk of rectal stenosis after segmental resection, requiring additional endoscopic or surgical procedures. This work was supported by a grant from the clinical research programme for hospitals (PHRC) in France. The authors declare no competing interests related to this study. This study is registered with ClinicalTrials.gov, number NCT 01291576. 31 January 2011. 7 March 2011. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Statistical analysis of mesoscale rainfall: Dependence of a random cascade generator on large-scale forcing

NASA Technical Reports Server (NTRS)

Over, Thomas, M.; Gupta, Vijay K.

1994-01-01

Under the theory of independent and identically distributed random cascades, the probability distribution of the cascade generator determines the spatial and the ensemble properties of spatial rainfall. Three sets of radar-derived rainfall data in space and time are analyzed to estimate the probability distribution of the generator. A detailed comparison between instantaneous scans of spatial rainfall and simulated cascades using the scaling properties of the marginal moments is carried out. This comparison highlights important similarities and differences between the data and the random cascade theory. Differences are quantified and measured for the three datasets. Evidence is presented to show that the scaling properties of the rainfall can be captured to the first order by a random cascade with a single parameter. The dependence of this parameter on forcing by the large-scale meteorological conditions, as measured by the large-scale spatial average rain rate, is investigated for these three datasets. The data show that this dependence can be captured by a one-to-one function. Since the large-scale average rain rate can be diagnosed from the large-scale dynamics, this relationship demonstrates an important linkage between the large-scale atmospheric dynamics and the statistical cascade theory of mesoscale rainfall. Potential application of this research to parameterization of runoff from the land surface and regional flood frequency analysis is briefly discussed, and open problems for further research are presented.

The 'Healthy Dads, Healthy Kids' community effectiveness trial: study protocol of a community-based healthy lifestyle program for fathers and their children

PubMed Central

2011-01-01

Background The 'Healthy Dads, Healthy Kids' program was designed to help overweight fathers lose weight and positively influence the health behaviors of their children. The aim of the current study was to evaluate the previously established program in a community setting, in a large effectiveness trial. Methods/Design The Healthy Dads, Healthy Kids community trial consists of three stages: (i) Stage 1 - program refinement and resource development (ii) Stage 2 - community randomized controlled trial (iii) Stage 3 - community effectiveness trial. The program will be evaluated in five Local Government Areas in the Hunter Valley Region of NSW, Australia. For the community randomized controlled trial, 50 overweight/obese men (aged 18-65 years) from one Local Government Area with a child aged between 5-12 years of age will be recruited. Families will be randomized to either the program or a 6-month wait-list control group. Fathers and their children will be assessed at baseline, post-intervention (3-months) and 6-months. Inclusion criteria are: body mass index 25-40 kg/m2; no participation in other weight loss programs during the study; pass a health-screening questionnaire; and access to a computer with Internet facilities. In the community trial, the program will be evaluated using a non-randomized, prospective design in five Local Government Areas. The exclusion criteria is body mass index < 25 kg/m2 or lack of doctor's approval. Measures will be collected at baseline, 3-, 6- and 12-months. The program involves fathers attending seven face-to-face group sessions (three with children) over 3-months. Measures: The primary outcome is fathers' weight. Secondary outcomes for both fathers and children include: waist circumference, blood pressure, resting heart rate, physical activity, sedentary behaviors and dietary intake. Father-only measures include portion size, alcohol consumption, parenting for physical activity and nutrition and parental engagement. Process evaluation will determine the fidelity, dose (delivered and received), reach, recruitment and context of the program. Discussion As a unique approach to reducing obesity prevalence in men and improving lifestyle behaviours in children, our findings will provide important evidence relating to the translation of Healthy Dads, Healthy Kids, which will enable it to be delivered on a larger scale. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000608066 PMID:22099889

Baseline adjustments for binary data in repeated cross-sectional cluster randomized trials.

PubMed

Nixon, R M; Thompson, S G

2003-09-15

Analysis of covariance models, which adjust for a baseline covariate, are often used to compare treatment groups in a controlled trial in which individuals are randomized. Such analysis adjusts for any baseline imbalance and usually increases the precision of the treatment effect estimate. We assess the value of such adjustments in the context of a cluster randomized trial with repeated cross-sectional design and a binary outcome. In such a design, a new sample of individuals is taken from the clusters at each measurement occasion, so that baseline adjustment has to be at the cluster level. Logistic regression models are used to analyse the data, with cluster level random effects to allow for different outcome probabilities in each cluster. We compare the estimated treatment effect and its precision in models that incorporate a covariate measuring the cluster level probabilities at baseline and those that do not. In two data sets, taken from a cluster randomized trial in the treatment of menorrhagia, the value of baseline adjustment is only evident when the number of subjects per cluster is large. We assess the generalizability of these findings by undertaking a simulation study, and find that increased precision of the treatment effect requires both large cluster sizes and substantial heterogeneity between clusters at baseline, but baseline imbalance arising by chance in a randomized study can always be effectively adjusted for. Copyright 2003 John Wiley & Sons, Ltd.

[Evidence of pharmacotherapy in COPD--key findings from recently-conducted randomized clinical studies].

PubMed

Shimizu, Kaoruko; Nishimura, Masaharu

2011-10-01

The primary aim of pharmachotherapy in COPD is improvement of exertional dyspnea and quality of life through its bronchodilator effects. However, there is emerging evidence that pharmacotherapy may reduce exacerbations, alleviate annual decline of pulmonary function, and even favorably affect mortality, thus changing natural history of COPD. The large-scaled randomized clinical trials, such as TORCH, UPLIFT, have revealed that combination of long acting beta2 agonist (LABA) and inhaled corticosteroids (ICS), LABA/ICS, and/or tiotropium alone may have such effects. In addition, carbocisteine, which is a mucolytic and anti-oxidant agent, has been shown to reduce exacerbations in COPD. Future directions on pharmacotherapy are personalized medicine based on phenotyping of the disease and development of new agents which may cure airway inflammation in COPD.

Is ginger effective for the treatment of irritable bowel syndrome? A double blind randomized controlled pilot trial.

PubMed

van Tilburg, Miranda A L; Palsson, Olafur S; Ringel, Yehuda; Whitehead, William E

2014-02-01

Ginger is one of the most commonly used herbal medicines for irritable bowel syndrome (IBS) but no data exists about its effectiveness. Double blind randomized controlled trial. University of North Carolina, Chapel Hill, North Carolina, USA. Forty-five IBS patients were randomly assigned to three groups: placebo, 1g of ginger, and 2g of ginger daily for 28 days. The IBS severity scale (IBS-SS) was administered, as well as adequate relief of symptoms scale. A responder was defined as having at least 25% reduction in IBS-SS post-treatment. There were 57.1% responders to placebo, 46.7% to 1g and 33.3% to 2g of ginger. Adequate relief was reported by 53.3% on placebo and 53.3% in both ginger groups combined. Side effects were mild and reported by 35.7% in the placebo and 16.7% in the ginger groups. This double blind randomized controlled pilot study suggests ginger is well tolerated but did not perform better than placebo. Larger trials are needed before any definitive conclusions can be drawn. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Saving and Empowering Young Lives in Europe (SEYLE) Randomized Controlled Trial (RCT): methodological issues and participant characteristics

PubMed Central

2013-01-01

Background Mental health problems and risk behaviours among young people are of great public health concern. Consequently, within the VII Framework Programme, the European Commission funded the Saving and Empowering Young Lives in Europe (SEYLE) project. This Randomized Controlled Trial (RCT) was conducted in eleven European countries, with Sweden as the coordinating centre, and was designed to identify an effective way to promote mental health and reduce suicidality and risk taking behaviours among adolescents. Objective To describe the methodological and field procedures in the SEYLE RCT among adolescents, as well as to present the main characteristics of the recruited sample. Methods Analyses were conducted to determine: 1) representativeness of study sites compared to respective national data; 2) response rate of schools and pupils, drop-out rates from baseline to 3 and 12 month follow-up, 3) comparability of samples among the four Intervention Arms; 4) properties of the standard scales employed: Beck Depression Inventory, Second Edition (BDI-II), Zung Self-Rating Anxiety Scale (Z-SAS), Strengths and Difficulties Questionnaire (SDQ), World Health Organization Well-Being Scale (WHO-5). Results Participants at baseline comprised 12,395 adolescents (M/F: 5,529/6,799; mean age=14.9±0.9) from Austria, Estonia, France, Germany, Hungary, Ireland, Israel, Italy, Romania, Slovenia and Spain. At the 3 and 12 months follow up, participation rates were 87.3% and 79.4%, respectively. Demographic characteristics of participating sites were found to be reasonably representative of their respective national population. Overall response rate of schools was 67.8%. All scales utilised in the study had good to very good internal reliability, as measured by Cronbach’s alpha (BDI-II: 0.864; Z-SAS: 0.805; SDQ: 0.740; WHO-5: 0.799). Conclusions SEYLE achieved its objective of recruiting a large representative sample of adolescents within participating European countries. Analysis of SEYLE data will shed light on the effectiveness of important interventions aimed at improving adolescent mental health and well-being, reducing risk-taking and self-destructive behaviour and preventing suicidality. Trial registration US National Institute of Health (NIH) clinical trial registry (NCT00906620) and the German Clinical Trials Register (DRKS00000214). PMID:23679917

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

The Relationship of Class Size Effects and Teacher Salary

ERIC Educational Resources Information Center

Peevely, Gary; Hedges, Larry; Nye, Barbara A.

2005-01-01

The effects of class size on academic achievement have been studied for decades. Although the results of small-scale, randomized experiments and large-scale, econometric studies point to positive effects of small classes, some scholars see the evidence as ambiguous. Recent analyses from a 4-year, large-scale, randomized experiment on the effects…

A Multisite Randomized Trial of a Cognitive Skills Program for Male Mentally Disordered Offenders: Violence and Antisocial Behavior Outcomes

ERIC Educational Resources Information Center

Cullen, Alexis E.; Clarke, Amory Y.; Kuipers, Elizabeth; Hodgins, Sheilagh; Dean, Kimberlie; Fahy, Tom

2012-01-01

Objective: Despite a large evidence base indicating that cognitive skills programs can reduce reoffending in individuals without mental illness, there have been no randomized controlled trials (RCTs) to determine their effectiveness in mentally disordered offenders (MDOs). In the first RCT of a cognitive skills program for MDOs, we aimed to…

Examination of Individual Differences in Outcomes from a Randomized Controlled Clinical Trial Comparing Formal and Informal Individual Auditory Training Programs

ERIC Educational Resources Information Center

Smith, Sherri L.; Saunders, Gabrielle H.; Chisolm, Theresa H.; Frederick, Melissa; Bailey, Beth A.

2016-01-01

Purpose: The purpose of this study was to determine if patient characteristics or clinical variables could predict who benefits from individual auditory training. Method: A retrospective series of analyses were performed using a data set from a large, multisite, randomized controlled clinical trial that compared the treatment effects of at-home…

Worksite health and safety climate: scale development and effects of a health promotion intervention.

PubMed

Basen-Engquist, K; Hudmon, K S; Tripp, M; Chamberlain, R

1998-01-01

Environmental influences on health and health behavior have an important place in research on worksite health promotion. We tested the validity and internal consistency of a new measure of organizational health and safety climate that was used in a large randomized trial of a worksite cancer prevention program (the Working Well Trial). The resulting scales then were applied to assess intervention effects. This study uses data from a subset of 40 worksites in the Working Well Trial. Employees at 20 natural gas pipeline worksite and 20 rural electrical cooperatives completed a cross-sectional questionnaire at baseline and 3-year follow-up. A factor analysis of this self-report instrument produced a two-factor solution. The resulting health and safety climate scales had good internal consistency (Cronbach's alpha = 0.74 and 0.82, respectively) and concurrent validity. The health climate scale was correlated more highly with organizational measures that were indicative of a supportive health climate than those indicating supportive safety climate, while the reverse was true of the safety climate scale. Changes in health climate were associated with the number of smoking and smokeless tobacco programs offered at the worksites at the time of the 3-year follow-up (r = 0.46 and 0.42, respectively). The scales were not correlated with most employee health behaviors. The health climate scores increased at intervention worksites, compared with scores at control worksites (F[1,36] = 7.57, P = 0.009). The health and safety climate scales developed for this study provide useful instruments for measuring organizational change related to worksite health promotion activities. The Working Well Intervention resulted in a significant improvement in worksite health climate.

What qualitative research can contribute to a randomized controlled trial of a complex community intervention.

PubMed

Nelson, Geoffrey; Macnaughton, Eric; Goering, Paula

2015-11-01

Using the case of a large-scale, multi-site Canadian Housing First research demonstration project for homeless people with mental illness, At Home/Chez Soi, we illustrate the value of qualitative methods in a randomized controlled trial (RCT) of a complex community intervention. We argue that quantitative RCT research can neither capture the complexity nor tell the full story of a complex community intervention. We conceptualize complex community interventions as having multiple phases and dimensions that require both RCT and qualitative research components. Rather than assume that qualitative research and RCTs are incommensurate, a more pragmatic mixed methods approach was used, which included using both qualitative and quantitative methods to understand program implementation and outcomes. At the same time, qualitative research was used to examine aspects of the intervention that could not be understood through the RCT, such as its conception, planning, sustainability, and policy impacts. Through this example, we show how qualitative research can tell a more complete story about complex community interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

Effectiveness of information and communication technologies interventions to increase mental health literacy: A systematic review.

PubMed

Tay, Jing Ling; Tay, Yi Fen; Klainin-Yobas, Piyanee

2018-06-13

Most mental health conditions affect adolescent and young adults. The onset of many mental disorders occurs in the young age. This is a critical period to implement interventions to enhance mental health literacy (MHL) and to prevent the occurrence of mental health problems. This systematic review examined the effectiveness of information and communication technologies interventions on MHL (recognition of conditions, stigma and help-seeking). The authors searched for both published and unpublished studies. Nineteen studies were included with 9 randomized controlled trials and 10 quasi-experimental studies. Informational interventions were useful to enhance MHL of less-known disorders such as anxiety disorder and anorexia, but not depression. Interventions that were effective in enhancing depression MHL comprised active component such as videos or quizzes. Interventions that successfully elevated MHL also reduced stigma. Elevated MHL levels did not improve help-seeking, and reduction in stigma levels did not enhance help-seeking behaviours. Future good quality, large-scale, multi-sites randomized controlled trials are necessary to evaluate MHL interventions. © 2018 John Wiley & Sons Australia, Ltd.

Electroacupuncture to treat painful diabetic neuropathy: study protocol for a three-armed, randomized, controlled pilot trial

PubMed Central

2013-01-01

Background The purpose of this study is to conduct a basic analysis of the effectiveness and safety of electroacupuncture in the treatment of painful diabetic neuropathy (PDN) as compared to placebo and usual care and to evaluate the feasibility of large-scale clinical research. Methods/design This study is a protocol for a three-armed, randomized, patient-assessor-blinded (to the type of treatment), controlled pilot trial. Forty-five participants with a ≥ six month history of PDN and a mean weekly pain score of ≥ 4 on the 11-point Pain Intensity Numerical Rating Scale (PI-NRS) will be assigned to the electroacupuncture group (n = 15), sham group (n = 15) or usual care group (n = 15). The participants assigned to the electroacupuncture group will receive electroacupuncture (remaining for 30 minutes with a mixed current of 2 Hz/120 Hz and 80% of the bearable intensity) at 12 standard acupuncture points (bilateral ST36, GB39, SP9, SP6, LR3 and GB41) twice per week for eight weeks (a total of 16 sessions) as well as the usual care. The participants in the sham group will receive sham electroacupuncture (no electrical current will be passed to the needle, but the light will be seen, and the sound of the pulse generator will be heard by the participants) at non-acupuncture points as well as the usual care. The participants in the usual care group will not receive electroacupuncture treatment during the study period and will receive only the usual care. The follow-up will be in the 5th, 9th and 17th weeks after random allocation. The PI-NRS score assessed at the ninth week will be the primary outcome measurement used in this study. The Short-Form McGill Pain Questionnaire (SF-MPQ), a sleep disturbance score (11-point Likert scale), the Short-Form 36v2 Health Survey (SF-36), the Beck Depression Inventory (BDI) and the Patient Global Impression of Change (PGIC) will be used as outcome variables to evaluate the effectiveness of the acupuncture. Safety will be assessed at every visit. Discussion The result of this trial will provide a basis for the effectiveness and safety of electroacupuncture for PDN. Trial registration Clinical Research information Service. Unique identifier: KCT0000466. PMID:23866906

Perceptions of Massage Therapists Participating in a Randomized Controlled Trial

PubMed Central

Perlman, Adam; Dreusicke, Mark; Keever, Teresa; Ali, Ather

2015-01-01

Background Clinical practice and randomized trials often have disparate aims, despite involving similar interventions. Attitudes and expectancies of practitioners influence patient outcomes, and there is growing emphasis on optimizing provider–patient relationships. In this study, we evaluated the experiences of licensed massage therapists involved in a randomized controlled clinical trial using qualitative methodology. Methods Seven massage therapists who were interventionists in a randomized controlled trial participated in structured interviews approximately 30 minutes in length. Interviews focused on their experiences and perceptions regarding aspects of the clinical trial, as well as recommendations for future trials. Transcribed interviews were analyzed for emergent topics and themes using standard qualitative methods. Results Six themes emerged. Therapists discussed 1) promoting the profession of massage therapy through research, 2) mixed views on using standardized protocols, 3) challenges of sham interventions, 4) participant response to the sham intervention, 5) views on scheduling and compensation, and 6) unanticipated benefits of participating in research. Conclusions Therapists largely appreciated the opportunity to promote massage through research. They demonstrated insight and understanding of the rationale for a clinical trial adhering to a standardized protocol. Evaluating the experiences and ideas of complementary and alternative medicine practitioners provides valuable insight that is relevant for the implementation and design of randomized trials. PMID:26388961

Literature Review: Herbal Medicine Treatment after Large-Scale Disasters.

PubMed

Takayama, Shin; Kaneko, Soichiro; Numata, Takehiro; Kamiya, Tetsuharu; Arita, Ryutaro; Saito, Natsumi; Kikuchi, Akiko; Ohsawa, Minoru; Kohayagawa, Yoshitaka; Ishii, Tadashi

2017-01-01

Large-scale natural disasters, such as earthquakes, tsunamis, volcanic eruptions, and typhoons, occur worldwide. After the Great East Japan earthquake and tsunami, our medical support operation's experiences suggested that traditional medicine might be useful for treating the various symptoms of the survivors. However, little information is available regarding herbal medicine treatment in such situations. Considering that further disasters will occur, we performed a literature review and summarized the traditional medicine approaches for treatment after large-scale disasters. We searched PubMed and Cochrane Library for articles written in English, and Ichushi for those written in Japanese. Articles published before 31 March 2016 were included. Keywords "disaster" and "herbal medicine" were used in our search. Among studies involving herbal medicine after a disaster, we found two randomized controlled trials investigating post-traumatic stress disorder (PTSD), three retrospective investigations of trauma or common diseases, and seven case series or case reports of dizziness, pain, and psychosomatic symptoms. In conclusion, herbal medicine has been used to treat trauma, PTSD, and other symptoms after disasters. However, few articles have been published, likely due to the difficulty in designing high quality studies in such situations. Further study will be needed to clarify the usefulness of herbal medicine after disasters.

Are orange lollies effective in preventing nausea and vomiting related to dimethyl sulfoxide? A multicenter randomized trial.

PubMed

Gonella, Silvia; Berchialla, Paola; Bruno, Benedetto; Di Giulio, Paola

2014-09-01

Nausea and vomiting (NV) related to DMSO affect patients undergoing auto-SCT despite antiemetic measures. Orange flavoring may reduce gastrointestinal symptoms. A multicenter, randomized, three-arm, open-label trial in four Italian large bone marrow transplant centers was conducted to assess the effectiveness of orange aroma in preventing NV related to DMSO. Patients were randomized to orange ice lollies, non-citrus ice lollies, and routine treatment (deep breaths) during reinfusion. Data on NV were collected up to 5 days after infusion; 69/98 patients were randomized: 23 to orange, 21 to non-citrus ice lollies, and 25 to routine treatment. Although 48 h after transplantation no differences were observed in controlled nausea (Numerical Rating Scale (NRS) 0-100, ≤25) or vomiting, significantly fewer patients had no episodes of vomiting, no antiemetic rescue therapy, and no nausea (NRS <5) in the deep breath vs lollies groups (P = 0.017). The intensity of nausea over time differed significantly between ice lollies vs routine care (P = 0.001) groups, but not between the orange and non-citrus groups (P = 0.428). The vasoconstrictive action of ice may prevent NV related to DMSO in the acute phase and reduce the need for rescue antiemetic therapy. Ice lollies offer a simple, noninvasive, and economic means for relieving nausea and vomiting related to this preservative.

Randomized clinical trial of bright light therapy for antepartum depression: preliminary findings.

PubMed

Epperson, C Neill; Terman, Michael; Terman, Jiuan Su; Hanusa, Barbara H; Oren, Dan A; Peindl, Kathleen S; Wisner, Katherine L

2004-03-01

Bright light therapy was shown to be a promising treatment for depression during pregnancy in a recent open-label study. In an extension of this work, we report findings from a double-blind placebo-controlled pilot study. Ten pregnant women with DSM-IV major depressive disorder were randomly assigned from April 2000 to January 2002 to a 5-week clinical trial with either a 7000 lux (active) or 500 lux (placebo) light box. At the end of the randomized controlled trial, subjects had the option of continuing in a 5-week extension phase. The Structured Interview Guide for the Hamilton Depression Scale-Seasonal Affective Disorder Version was administered to assess changes in clinical status. Salivary melatonin was used to index circadian rhythm phase for comparison with antidepressant results. Although there was a small mean group advantage of active treatment throughout the randomized controlled trial, it was not statistically significant. However, in the longer 10-week trial, the presence of active versus placebo light produced a clear treatment effect (p =.001) with an effect size (0.43) similar to that seen in antidepressant drug trials. Successful treatment with bright light was associated with phase advances of the melatonin rhythm. These findings provide additional evidence for an active effect of bright light therapy for antepartum depression and underscore the need for an expanded randomized clinical trial.

A combined community- and facility-based approach to improve pregnancy outcomes in low-resource settings: a Global Network cluster randomized trial.

PubMed

Pasha, Omrana; McClure, Elizabeth M; Wright, Linda L; Saleem, Sarah; Goudar, Shivaprasad S; Chomba, Elwyn; Patel, Archana; Esamai, Fabian; Garces, Ana; Althabe, Fernando; Kodkany, Bhala; Mabeya, Hillary; Manasyan, Albert; Carlo, Waldemar A; Derman, Richard J; Hibberd, Patricia L; Liechty, Edward K; Krebs, Nancy; Hambidge, K Michael; Buekens, Pierre; Moore, Janet; Jobe, Alan H; Koso-Thomas, Marion; Wallace, Dennis D; Stalls, Suzanne; Goldenberg, Robert L

2013-10-03

Fetal and neonatal mortality rates in low-income countries are at least 10-fold greater than in high-income countries. These differences have been related to poor access to and poor quality of obstetric and neonatal care. This trial tested the hypothesis that teams of health care providers, administrators and local residents can address the problem of limited access to quality obstetric and neonatal care and lead to a reduction in perinatal mortality in intervention compared to control locations. In seven geographic areas in five low-income and one middle-income country, most with high perinatal mortality rates and substantial numbers of home deliveries, we performed a cluster randomized non-masked trial of a package of interventions that included community mobilization focusing on birth planning and hospital transport, community birth attendant training in problem recognition, and facility staff training in the management of obstetric and neonatal emergencies. The primary outcome was perinatal mortality at ≥28 weeks gestation or birth weight ≥1000 g. Despite extensive effort in all sites in each of the three intervention areas, no differences emerged in the primary or any secondary outcome between the intervention and control clusters. In both groups, the mean perinatal mortality was 40.1/1,000 births (P = 0.9996). Neither were there differences between the two groups in outcomes in the last six months of the project, in the year following intervention cessation, nor in the clusters that best implemented the intervention. This cluster randomized comprehensive, large-scale, multi-sector intervention did not result in detectable impact on the proposed outcomes. While this does not negate the importance of these interventions, we expect that achieving improvement in pregnancy outcomes in these settings will require substantially more obstetric and neonatal care infrastructure than was available at the sites during this trial, and without them provider training and community mobilization will not be sufficient. Our results highlight the critical importance of evaluating outcomes in randomized trials, as interventions that should be effective may not be. ClinicalTrials.gov NCT01073488.

Practices that minimize trauma to the genital tract in childbirth: a systematic review of the literature.

PubMed

Renfrew, M J; Hannah, W; Albers, L; Floyd, E

1998-09-01

Trauma to the genital tract commonly occurs at birth, and can cause short- and long-term morbidity. Clinical measures to reduce its occurrence have not been fully identified. A systematic review of the English language literature was conducted to describe the current state of knowledge on reduction of genital tract trauma before planning a large randomized controlled trial of ways to prevent such trauma. Randomized trials and other published reports were identified from relevant databases and hand searches. Studies were reviewed and assessed using a structured format. A total of 77 papers and chapters were identified and placed into 5 categories after critical review: 25 randomized trials, 4 meta-analyses, 4 prospective studies, 36 retrospective studies, and 8 descriptions of practice from textbooks. The available evidence is conclusive in favor of restricted use of episiotomy. The contribution of maternal characteristics and attitudes to intact perineum has not been investigated. Several other topics warrant further study, including maternal position, style of pushing, and antenatal perineal massage. Strong opinions and sparse data exist regarding the role of hand maneuvers by the birth attendant for perineal management and birth of the baby. This became the topic of the planned randomized controlled trial, which was completed; results will be published soon. The case for restricting the use of episiotomy is conclusive. Several other clinical factors warrant investigation, including the role of hand maneuvers by the birth attendant in preventing birth trauma. A large randomized controlled trial will report on this topic.

A Review of Clinical Trials in Spinal Cord Injury including Biomarkers.

PubMed

Badhiwala, Jetan H; Wilson, Jefferson R; Kwon, Brian K; Casha, Steve; Fehlings, Michael G

2018-06-11

Acute traumatic spinal cord injury (SCI) entered the arena of prospective randomized clinical trials almost 40 years ago, with the undertaking of the National Acute Spinal Cord Study (NASCIS) I trial. Since then, a number of clinical trials have been conducted in the field, spurred by the devastating physical, social, and economic consequences of acute SCI for patients, families, and society at large. Many of these have been controversial and attracted criticism. The current review provides a critical summary of select past and current clinical trials in SCI, focusing in particular on the findings of prospective randomized controlled trials (RCTs), the challenges and barriers encountered, and the valuable lessons learned that can be applied to future trials.

Interferential current sensory stimulation, through the neck skin, improves airway defense and oral nutrition intake in patients with dysphagia: a double-blind randomized controlled trial.

PubMed

Maeda, Keisuke; Koga, Takayuki; Akagi, Junji

2017-01-01

Neuromuscular electrical stimulation with muscle contraction, administered through the skin of the neck, improves a patient's swallowing ability. However, the beneficial effects of transcutaneous electrical sensory stimulation (TESS), without muscle contraction, are controversial. We investigated the effect of TESS, using interferential current, in patients undergoing dysphagia rehabilitation. This double-blind, randomized controlled trial involved 43 patients who were prescribed in-hospital dysphagia rehabilitation for ≥3 weeks. Patients were randomly assigned to the sensory stimulation (SS) or sham groups; all received usual rehabilitative care plus 2 weeks of SS or sham intervention. Outcome measures included cough latency times against a 1% citric acid mist, functional oral intake scale (FOIS) scores, and oral nutritional intake - each determined after the second and third week following treatment initiation. Mean patient age was 84.3±7.5 years; 58% were women. The SS and sham groups had similar baseline characteristics. Changes in cough latency time at 2 weeks (-14.1±14.0 vs -5.2±14.2 s, p =0.047) and oral nutrition intake at 3 weeks (437±575 vs 138±315 kcal/day, p =0.042) improved more in the SS group than in the sham group. Changes in cough frequency and FOIS scores indicated better outcomes in the SS group, based on substantial effect sizes. TESS, using interferential current through the neck, improved airway defense and nutrition in patients suffering from dysphagia. Further large-scale studies are needed to confirm the technique's effect on swallowing ability.

The Baltimore Experience Corps Trial: Enhancing Generativity via Intergenerational Activity Engagement in Later Life

PubMed Central

Tanner, Elizabeth K.; Fried, Linda P.; Carlson, Michelle C.; Xue, Qian-Li; Parisi, Jeanine M.; Rebok, George W.; Yarnell, Lisa M.; Seeman, Teresa E.

2016-01-01

Objectives: Being and feeling generative, defined as exhibiting concern and behavior to benefit others, is an important developmental goal of midlife and beyond. Although a growing body of evidence suggests mental and physical health benefits of feeling generative in later life, little information exists as to the modifiability of generativity perceptions. The present study examines whether participation in the intergenerational civic engagement program, Experience Corps (EC), benefits older adults’ self-perceptions of generativity. Method: Levels of generativity were compared in older adults randomized to serve as EC volunteers or controls (usual volunteer opportunities) in the Baltimore Experience Corps Trial at 4-, 12-, and 24-month evaluation points over the 2-year trial. Analyses utilized intention-to-treat and complier average causal effects (CACE) analyses which incorporate degree of intervention exposure in analytic models. Results: Participants randomized to the EC group had significantly higher levels of generative desire and perceptions of generative achievement than controls at each follow-up point; CACE analyses indicate a dose–response effect with a greater magnitude of intervention effect with greater exposure to the EC program. Discussion: Results provide the first-ever, large-scale experimental demonstration that participation in an intergenerational civic engagement program can positively alter self-perceptions of generativity in older adulthood. PMID:25721053

The impact of grape seed extract treatment on blood pressure changes: A meta-analysis of 16 randomized controlled trials.

PubMed

Zhang, Haili; Liu, Shuang; Li, Lan; Liu, Shisong; Liu, Shuqi; Mi, Jia; Tian, Geng

2016-08-01

Several clinical trials have shown that grape seed extract can reduce blood pressure, but the results are often irreproducible. We therefore sought to systematically evaluate the impact of grape seed extract treatment on the changes of systolic/diastolic blood pressure (SBP/DBP) by meta-analyzing available randomized controlled trials. Trial selection and data extraction were completed independently by 2 investigators. Effect-size estimates were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Twelve articles involving 16 clinical trials and 810 study subjects were analyzed. Overall analyses found significant reductions for SBP (WMD = -6.077; 95% CI: -10.736 to -1.419; P = 0.011) and DBP (WMD = -2.803; 95% CI: -4.417 to -1.189; P = 0.001) after grape seed extract treatment. In subgroup analyses, there were significant reductions in younger subjects (mean age < 50 years) for SBP (WMD = -6.049; 95% CI: -10.223 to -1.875; P = 0.005) and DBP (WMD = -3.116; 95% CI: -4.773 to -1.459; P < 0.001), in obese subjects (mean body mass index ≥ 25 kg/m) for SBP (WMD = -4.469; 95% CI: -6.628 to -2.310; P < 0.001), and in patients with metabolic syndrome for SBP (WMD = -8.487; 95% CI: -11.869 to -5.106; P < 0.001). Further meta-regression analyses showed that age, body mass index, and baseline blood pressure were negatively associated with the significant reductions of SBP and DBP after treatment. There was no indication of publication bias. Our findings demonstrate that grape seed extract exerted a beneficial impact on blood pressure, and this impact was more obvious in younger or obese subjects, as well as in patients with metabolic disorders. In view of the small sample size involved, we agree that confirmation of our findings in a large-scale, long-term, multiple-dose randomized controlled trial, especially among hypertensive patients is warranted.

The role of calcium in the prevention of cardiovascular disease--a review of observational studies and randomized clinical trials.

PubMed

Rautiainen, Susanne; Wang, Lu; Manson, JoAnn E; Sesso, Howard D

2013-11-01

Calcium is a mineral that is important for bone health and has also been suggested to play a role in the prevention of cardiovascular disease (CVD). Lately, the potential effects of both inadequate and excessive calcium intake have received growing attention. In this review, we summarize the evidence from experimental, epidemiologic, and clinical studies investigating the role of calcium intake, either from the diet or from supplements, as well as blood concentrations, in relation to the risk of CVD in adults. In vitro and in vivo laboratory studies suggest that calcium may be involved in CVD development through multiple pathways, including blood cholesterol, insulin secretion and sensitivity, vasodilation, inflammatory profile, thrombosis, obesity, and vascular calcification. Several prospective epidemiologic studies have examined how dietary or supplemental calcium intake is associated with CVD incidence or mortality in middle-aged and older adults, and the results are inconsistent. Prospective studies investigating blood concentrations of calcium have also reported mixed results. However, changes in blood calcium concentrations may reflect a disturbed calcium phosphate balance, which is associated with increased risk of CVD. To date there is no randomized clinical trial that has been designed specifically to test the effect of calcium supplementation on the risk of CVD as the primary end point. Existing trials have performed secondary analyses, and most of them have been conducted among postmenopausal women. These trials suggest that calcium supplementation has no effect on CVD development; however, they do not allow a definitive conclusion to be drawn. The average daily intake of calcium is low in many populations; however, the evidence for a potential role of dietary or supplemental calcium in the prevention of CVD remains insufficient and inconclusive. Only large-scale randomized trials designed to investigate the effects of calcium supplementation on CVD events as the primary end point, as well as short-term trials investigating the effect on coronary biomarkers, can provide a definitive answer.

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

PubMed Central

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

2015-01-01

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

What's new in stroke? The top 10 studies of 2009-2011: part II.

PubMed

Hart, Robert G; Oczkowski, Wiesław J

2011-06-01

Five studies published between 2009 and 2011 are reviewed that importantly inform stroke prevention for patients with atrial fibrillation (AF) or with cervical carotid artery stenosis. Two large, phase III randomized trials tested novel oral anticoagulants for stroke prevention in patients with AF: the direct thrombin inhibitor dabigatran 150 mg twice daily was superior to adjusted-dose warfarin (RE-LY trial) and the direct factor Xa inhibitor apixaban was far superior to aspirin in patients deemed unsuitable for warfarin (AVERROES trial). For both novel anticoagulants, major bleeding rates were similar to the comparator treatment. Clopidogrel plus aspirin was more efficacious than aspirin alone for prevention of stroke in patients with AF deemed unsuitable for warfarin, but major bleeding was significantly increased with dual antiplatelet therapy (ACTIVE A trial). Two large randomized trials (CREST, ICSS) provide the best available data on the short-term risks of carotid artery stenting vs. endarterectomy. In both trials, periprocedural stroke was more frequent with stenting than with endarterectomy, but the increased risk was largely confined to patients >70 years old. For younger patients, periprocedural risks were comparable with stenting or endarterectomy, but long-term outcomes are required to assess the relative merits of the two procedures.

Dronedarone: a novel antiarrhythmic agent for the treatment of atrial fibrillation.

PubMed

Duray, Gabor Z; Ehrlich, Joachim R; Hohnloser, Stefan H

2010-01-01

To describe the electrophysiological profile and the clinical portfolio of dronedarone, a new multichannel-blocking antiarrhythmic drug developed for the treatment of atrial fibrillation. Dronedarone is a derivative of amiodarone that is free of iodine and less lipophilic. The drug has - as its predecessor - multichannel-blocking efficacy and in addition vasodilating effects. It reduces the incidence of ventricular fibrillation in several experimental models. Dronedarone has undergone thorough clinical evaluation in various patient populations. In two large trials, the drug was shown to postpone the recurrence of atrial fibrillation after cardioversion relative to placebo. In a trial in unstable heart failure patients, there was excess mortality in the dronedarone arm. This trial was stopped prematurely and prompted the conduct of a large outcome study. The ATHENA trial demonstrated a significant reduction in cardiovascular hospitalizations and death in atrial fibrillation patients randomly assigned to receive dronedarone or placebo. This large trial in more than 4600 patients revealed no signs of excess mortality or morbidity in patients receiving dronedarone. On the basis of the results of five international, multicenter, randomized clinical trials involving nearly 6300 patients, dronedarone was approved by the FDA for treatment of nonpermanent atrial fibrillation to reduce the risk of cardiovascular hospitalization.

The effect of whole body vibration on balance, gait performance and mobility in people with stroke: a systematic review and meta-analysis.

PubMed

Yang, Xiaotian; Wang, Pu; Liu, Chuan; He, Chengqi; Reinhardt, Jan D

2015-07-01

To examine the effect of whole body vibration on balance, gait performance and mobility among people with stroke. A systematic review was conducted by two independent reviewers who completed the article search and selection. We included randomized controlled trials published in English examining effects of whole body vibration on balance, gait, mobility, muscle strength and muscle tone in adults with a clinical diagnosis of stroke. Articles were excluded if they were research studies on people with other primary diagnosis, abstracts published in the conferences or books. The Cochrane risk of bias tool was used to assess the methodological quality of the selected studies. Sources included Cochrane Central Register of Controlled Trials, Pubmed, MEDLINE, CINAHL, EMBASE, PEDro, PsycINFO, Science Citation Index, ClinicalTrials.gov, Current Controlled Trials, Stroke Trials Registry, and reference lists of all relevant articles. Eight randomized controlled trials (nine articles) involving 271 participants were included in this meta-analysis. No significant improvement was found regarding Berg balance scale (SMD=-0.08, 95%CI=-1.35 to 1.19, P=0.91), mobility (SMD=0.45, 95%CI=-0.46 to 1.37, P=0.33), maximal isometric contracion of knee extension strength (SMD=0.23, 95%CI=-0.27 to 0.74, P=0.36), and maximal isometric contracion of knee extension strength (SMD=0.09, 95%CI=-0.38 to 0.56, P=0.71). There was no evidence for effects of whole body vibration on balance in people with stroke. Effects of whole body vibration on mobility and gait performance remain inconclusive. More large and high-quality trials are required. © The Author(s) 2014.

Changes of attachment characteristics during psychotherapy of patients with social anxiety disorder: Results from the SOPHO-Net trial

PubMed Central

Strauß, Bernhard; Altmann, Uwe; Manes, Susanne; Tholl, Anne; Koranyi, Susan; Nolte, Tobias; Beutel, Manfred E.; Wiltink, Jörg; Herpertz, Stephan; Hiller, Wolfgang; Hoyer, Jürgen; Joraschky, Peter; Nolting, Björn; Ritter, Viktoria; Stangier, Ulrich; Willutzki, Ulrike; Salzer, Simone; Leibing, Eric; Leichsenring, Falk; Kirchmann, Helmut

2018-01-01

Objectives Within a randomized controlled trial contrasting the outcome of manualized cognitive-behavioral (CBT) and short term psychodynamic therapy (PDT) compared to a waiting list condition (the SOPHO-Net trial), we set out to test whether self-reported attachment characteristics change during the treatments and if these changes differ between treatments. Research design and methods 495 patients from the SOPHO-Net trial (54.5% female, mean age 35.2 years) who were randomized to either CBT, PDT or waiting list (WL) completed the partner-related revised Experiences in Close Relationships Questionnaire (ECR-R) before and after treatment and at 6 and 12 months follow-up. The Liebowitz Social Anxiety Scale (LSAS) was administered at pre-treatment, post-treatment, and at 6-month and 1-year follow-up. ECR-R scores were first compared to a representative healthy sample (n = 2508) in order to demonstrate that the clinical sample differed significantly from the non-clinical sample with respect to attachment anxiety and avoidance. Results LSAS scores correlated significantly with both ECR-R subscales. Post-therapy, patients treated with CBT revealed significant changes in attachment anxiety and avoidance whereas patients treated with PDT showed no significant changes. Changes between post-treatment and the two follow-ups were significant in both conditions, with minimal (insignificant) differences between treatments at the 12- month follow-up. Conclusions The current study supports recent reviews of mostly naturalistic studies indicating changes in attachment as a result of psychotherapy. Although there were differences between conditions at the end of treatment, these largely disappeared during the follow-up period which is line with the other results of the SOPHO-NET trial. Trial registration Controlled-trials.com ISRCTN53517394 PMID:29518077

Systematic review of atorvastatin for the treatment of Alzheimer's disease★

PubMed Central

Sun, Yuan; Wang, Genfa; Pan, Zhihong; Chen, Shuyan

2012-01-01

Objective: To assess the clinical efficacy and safety of atorvastatin in the treatment of Alzheimer's disease. Data Sources: Medline (1948/2011-04), Embase (1966/2011-04), Cochrane Library (Issue 3, 2011), Chinese National Knowledge Infrastructure (1989/2011-04), and the Chinese Biomedical Literature Database (1979/2011-04) were searched for randomized clinical trials regardless of language. Abstracts of conference papers were manually searched. Furthermore, Current Controlled Trials (http://controlled-trials.com), Clinical Trials.gov (http://clinicaltrials.gov), and Chinese Clinical Trial Registry (http://www.chictr.org) were also searched. Key words included Alzheimer disease, dementia, cognition, affection, memory dysfunction, hydroxymethylglutaryl-CoA reductase inhibitors, atorvastatin and statins. Data Selection: Randomized controlled trials of grade A or B according to quality evaluation criteria of the Cochrane Collaboration were selected, in which atorvastatin and placebo were used to evaluate the effects of atorvastatin in the treatment of Alzheimer's disease. Study methodological quality was evaluated based on criteria described in Cochrane Reviewer's Handbook 5.0.1. Revman 5.1 software was used for data analysis. Main Outcome Measures: Clinical efficacy, safety, withdrawal from the studies, and withdrawal due to adverse effects. Results: Two randomized controlled trials were included, one was scale A, and the other was scale B. All patients (n = 710, age range 50–90 years) were diagnosed as probable or possible mild to moderate Alzheimer's disease according to standard criteria and treated with atorvastatin 80 mg/d or placebo. There was no difference between the two groups in the final follow-up for Clinical Global Impression of Change scale (WMD = 0.13, 95%CI: –0.15 to 0.40), the Alzheimer's Disease Assessment Scale-cognitive subscale (WMD = 1.05, 95%CI: –3.06 to 6.05), Mini-Mental State Examination Scale (WMD = 0.77, 95%CI: –0.57 to 2.10), and the Neuropsychiatric Instrument (WMD = 2.07, 95%CI: –1.59 to 5.73). The rates of abnormal liver function, withdrawal from treatment, and withdrawal due to adverse effects were higher in the treatment group (OR = 7.86, 95%CI: 2.50-24.69; OR = 4.70, 95%CI: 2.61-8.44; and OR = 5.47, 95%CI: 3.01-9.94; respectively) compared with the placebo group. Conclusion: There is insufficient evidence to recommend atorvastatin for the treatment of mild to moderate Alzheimer's disease, because there was no benefit on general function, cognitive function or mental/behavior abnormality outcome measures. Efficacy and safety need to be confirmed by larger and higher quality randomized controlled trials, especially for moderate to severe Alzheimer's disease, because results of this systematic review may be limited by selection bias, implementation bias, as well as measurement bias. PMID:25657666

The Relations of Cognitive, Behavioral, and Physical Activity Variables to Depression Severity in Traumatic Brain Injury: Reanalysis of Data From a Randomized Controlled Trial.

PubMed

Bombardier, Charles H; Fann, Jesse R; Ludman, Evette J; Vannoy, Steven D; Dyer, Joshua R; Barber, Jason K; Temkin, Nancy R

To explore the relations of cognitive, behavioral, and physical activity variables to depression severity among people with traumatic brain injury (TBI) undergoing a depression treatment trial. Community. Adults (N = 88) who sustained complicated mild to severe TBI within the past 10 years, met criteria for major depressive disorder, and completed study measures. Randomized controlled trial. Participants were randomized to cognitive-behavioral therapy (n = 58) or usual care (n = 42). Outcomes were measured at baseline and 16 weeks. We combined the groups and used regressions to explore the relations among theoretical variables and depression outcomes. Depression severity was measured with the Hamilton Depression Rating Scale and Symptom Checklist-20. Theory-based measures were the Dysfunctional Attitudes Scale (DAS), Automatic Thoughts Questionnaire (ATQ), Environmental Rewards Observation Scale (EROS), and the International Physical Activity Questionnaire (IPAQ). Compared with non-TBI norms, baseline DAS and ATQ scores were high and EROS and IPAQ scores were low. All outcomes improved from baseline to 16 weeks except the DAS. The ATQ was an independent predictor of baseline depression. An increase in EROS scores was correlated with decreased depression. Increasing participation in meaningful roles and pleasant activities may be a promising approach to treating depression after TBI.

Acceptability of potential rectal microbicide delivery systems for HIV prevention: a randomized crossover trial.

PubMed

Pines, Heather A; Gorbach, Pamina M; Weiss, Robert E; Hess, Kristen; Murphy, Ryan; Saunders, Terry; Brown, Joelle; Anton, Peter A; Cranston, Ross D

2013-03-01

We assessed the acceptability of three of over-the-counter products representative of potential rectal microbicide (RM) delivery systems. From 2009 to 2010, 117 HIV-uninfected males (79 %) and females (21 %) who engage in receptive anal intercourse participated in a 6-week randomized crossover acceptability trial. Participants received each of three products (enema, lubricant-filled applicator, suppository) every 2 weeks in a randomized sequence. CASI and T-ACASI scales assessed product acceptability via Likert responses. Factor analysis was used to identify underlying factors measured by each scale. Random effects models were fit to examine age and gender effects on product acceptability. Three underlying factors were identified: Satisfaction with Product Use, Sexual Pleasure, and Ease of Product Use. For acceptability, the applicator ranked highest; however, differences between product acceptability scores were greatest among females and younger participants. These findings indicate that RM delivery systems impact their acceptability and should be considered early in RM development to enhance potential use.

Acceptability of Potential Rectal Microbicide Delivery Systems for HIV Prevention: A Randomized Crossover Trial

PubMed Central

Gorbach, Pamina M.; Weiss, Robert E.; Hess, Kristen; Murphy, Ryan; Saunders, Terry; Brown, Joelle; Anton, Peter A.; Cranston, Ross D.

2012-01-01

We assessed the acceptability of three of over-the-counter products representative of potential rectal microbicide (RM) delivery systems. From 2009 to 2010, 117 HIV-uninfected males (79 %) and females (21 %) who engage in receptive anal intercourse participated in a 6-week randomized crossover acceptability trial. Participants received each of three products (enema, lubricant-filled applicator, suppository) every 2 weeks in a randomized sequence. CASI and T-ACASI scales assessed product acceptability via Likert responses. Factor analysis was used to identify underlying factors measured by each scale. Random effects models were fit to examine age and gender effects on product acceptability. Three underlying factors were identified: Satisfaction with Product Use, Sexual Pleasure, and Ease of Product Use. For acceptability, the applicator ranked highest; however, differences between product acceptability scores were greatest among females and younger participants. These findings indicate that RM delivery systems impact their acceptability and should be considered early in RM development to enhance potential use. PMID:23114512

Add-on treatment with N-acetylcysteine for bipolar depression: a 24-week randomized double-blind parallel group placebo-controlled multicentre trial (NACOS-study protocol).

PubMed

Ellegaard, Pernille Kempel; Licht, Rasmus Wentzer; Poulsen, Henrik Enghusen; Nielsen, René Ernst; Berk, Michael; Dean, Olivia May; Mohebbi, Mohammadreza; Nielsen, Connie Thuroee

2018-04-05

Oxidative stress and inflammation may be involved in the development and progression of mood disorders, including bipolar disorder. Currently, there is a scarcity of useful treatment options for bipolar depressive episodes, especially compared with the efficacy of treatment for acute mania. N-Acetylcysteine (NAC) has been explored for psychiatric disorders for some time given its antioxidant and anti-inflammatory properties. The current trial aims at testing the clinical effects of adjunctive NAC treatment (compared to placebo) for bipolar depression. We will also explore the biological effects of NAC in this context. We hypothesize that adjunctive NAC treatment will reduce symptoms of depression, which will be reflected by changes in selected markers of oxidative stress. In the study, we will include adults diagnosed with bipolar disorder, in a currently depressive episode. Participants will undertake a 20-week, adjunctive, randomized, double-blinded, parallel group placebo-controlled trial comparing 3 grams of adjunctive NAC daily with placebo. The primary outcome is the mean change over time from baseline to end of study on the Montgomery-Asberg Depression Rating Scale (MADRS). Among the secondary outcomes are mean changes from baseline to end of study on the Bech-Rafaelsen Melancholia Scale (MES), the Young Mania Rating Scale (YMRS), the WHO-Five Well-being Index (WHO-5), the Global Assessment of Functioning scale (GAF-F), the Global Assessment of Symptoms scale (GAF-S) and the Clinical Global Impression-Severity scale (CGI-S). The potential effects on oxidative stress by NAC treatment will be measured through urine and blood samples. DNA will be examined for potential polymorphisms related to oxidative defences. Registered at The European Clinical Trials Database, ClinicalTrials.gov: NCT02294591 and The Danish Data Protection Agency: 2008-58-0035.

Wrist-ankle acupuncture (WAA) for primary dysmenorrhea (PD) of young females: study protocol for a randomized controlled trial.

PubMed

Chen, Yingfan; Tian, Sinan; Tian, Jing; Shu, Shi

2017-08-22

Primary dysmenorrhea (PD) is one of the most common health complaints all over the world, specifically among young females. Acupuncture has been employed to relieve the pain-based symptoms and to avoid the side effects of conventional medication, and wrist-ankle acupuncture (WAA) has confirmed analgesic efficacy for various types of pain. The aim of this study is to evaluate the immediate analgesia effect of WAA on PD of young females. This study will carry out a randomized parallel controlled single-blind trial to observe the immediate analgesia effect of WAA in PD of young females. Sixty participants who meet inclusion criteria will be recruited from September 2016 to September 2017 in Changhai hospital of China. They are randomly assigned to WAA therapy or sham acupuncture groups (30 patients for each group), and then receive real or sham acupuncture treatment, respectively. In this trial, the primary outcome measure is simple form of McGill pain questionnaire (SF-MPQ), while expectation and treatment credibility scale (ETCS), safety assessment, the COX menstrual symptom scale (CMSS), questionnaire about the feeling of being punctured are included in the secondary outcomes. This trial will be the first study protocol designed to evaluate the immediate analgesia effect of WAA in PD of young females. The strengths in methodology, including rigorous randomized, sham-controlled, participants-blinded and assessors-blinded, will guarantee the quality of this study. WAA doesn't require any needling sensation, so non-penetrating sham acupuncture can serve as an effective placebo intervention in this trial. Chinese Clinical Trial Registry (identifier: ChiCTR-IOR-16008546 ; registration date: 27 May 2016).

Non-surgical treatment of hip osteoarthritis. Hip school, with or without the addition of manual therapy, in comparison to a minimal control intervention: protocol for a three-armed randomized clinical trial.

PubMed

Poulsen, Erik; Christensen, Henrik W; Roos, Ewa M; Vach, Werner; Overgaard, Søren; Hartvigsen, Jan

2011-05-04

Hip osteoarthritis is a common and chronic condition resulting in pain, functional disability and reduced quality of life. In the early stages of the disease, a combination of non-pharmacological and pharmacological treatment is recommended. There is evidence from several trials that exercise therapy is effective. In addition, single trials suggest that patient education in the form of a hip school is a promising intervention and that manual therapy is superior to exercise. This is a randomized clinical trial. Patients with clinical and radiological hip osteoarthritis, 40-80 years of age, and without indication for hip surgery were randomized into 3 groups. The active intervention groups A and B received six weeks of hip school, taught by a physiotherapist, for a total of 5 sessions. In addition, group B received manual therapy consisting of joint manipulation and soft-tissue therapy twice a week for six weeks. Group C received a self-care information leaflet containing advice on "live as usual" and stretching exercises from the hip school. The primary time point for assessing relative effectiveness is at the end of the six weeks intervention period with follow-ups after three and 12 months.Primary outcome measure is pain measured on an eleven-point numeric rating scale. Secondary outcome measures are the hip dysfunction and osteoarthritis outcome score, patient's global perceived effect, patient specific functional scale, general quality of life and hip range of motion. To our knowledge this is the first randomized clinical trial comparing a patient education program with or without the addition of manual therapy to a minimal intervention for patients with hip osteoarthritis. ClinicalTrials NCT01039337.

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

PubMed Central

Seib, Rachael; Prescott, Todd

2005-01-01

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

Comparison of Trained Clinician Ratings with Expert Ratings of Aspiration on Videofluoroscopic Images from a Randomized Clinical Trial

PubMed Central

Hind, Jacqueline A.; Gensler, Gary; Brandt, Diane K.; Miller Gardner, Patricia J.; Blumenthal, Loreen; Gramigna, Gary D.; Kosek, Steven; Lundy, Donna; McGarvey-Toler, Susan; Rockafellow, Susan; Sullivan, Paula A.; Villa, Marybell; Gill, Gary D.; Lindblad, Anne S.; Logemann, Jeri A.; Robbins, JoAnne

2009-01-01

Accurate detection and classification of aspiration is a critical component of videofluoroscopic swallowing evaluation, the most commonly utilized instrumental method for dysphagia diagnosis and treatment. Currently published literature indicates that inter-judge reliability for the identification of aspiration ranges from poor to fairly good depending on the amount of training provided to clinicians. The majority of extant studies compared judgments among clinicians. No studies included judgments made during the use of a postural compensatory strategy. The purpose of this study was to examine the accuracy of judgments made by speech-language pathologists (SLPs) practicing in hospitals compared with unblinded expert judges when identifying aspiration and using the 8-point Penetration/Aspiration Scale. Clinicians received extensive training for the detection of aspiration and minimal training on use of the Penetration/Aspiration Scale. Videofluoroscopic data were collected from 669 patients as part of a large, randomized clinical trial and include judgments of 10,200 swallows made by 76 clinicians from 44 hospitals in 11 states. Judgments were made on swallows during use of dysphagia compensatory strategies: chin down posture with thin-liquids and thickened liquids (nectar-thick and honey-thick consistencies) in a head neutral posture. The subject population included patients with Parkinson’s disease and/or dementia. Kappa statistics indicate high accuracy for all interventions by SLPs for identification of aspiration (all К > .86) and variable accuracy (range 69%–76%) using the Penetration/Aspiration Scale when compared to expert judges. It is concluded that while the accuracy of identifying the presence of aspiration by SLPs is excellent, more extensive training and/or image enhancement is recommended for precise use of the Penetration/Aspiration Scale. PMID:18953607

Quasi-experiments to establish causal effects of HIV care and treatment and to improve the cascade of care

PubMed Central

Bor, Jacob; Geldsetzer, Pascal; Venkataramani, Atheendar; Bärnighausen, Till

2015-01-01

Purpose of review Randomized, population-representative trials of clinical interventions are rare. Quasi-experiments have been used successfully to generate causal evidence on the cascade of HIV care in a broad range of real-world settings. Recent findings Quasi-experiments exploit exogenous, or quasi-random, variation occurring naturally in the world or because of an administrative rule or policy change to estimate causal effects. Well designed quasi-experiments have greater internal validity than typical observational research designs. At the same time, quasi-experiments may also have potential for greater external validity than experiments and can be implemented when randomized clinical trials are infeasible or unethical. Quasi-experimental studies have established the causal effects of HIV testing and initiation of antiretroviral therapy on health, economic outcomes and sexual behaviors, as well as indirect effects on other community members. Recent quasi-experiments have evaluated specific interventions to improve patient performance in the cascade of care, providing causal evidence to optimize clinical management of HIV. Summary Quasi-experiments have generated important data on the real-world impacts of HIV testing and treatment and on interventions to improve the cascade of care. With the growth in large-scale clinical and administrative data, quasi-experiments enable rigorous evaluation of policies implemented in real-world settings. PMID:26371463

Quasi-experiments to establish causal effects of HIV care and treatment and to improve the cascade of care.

PubMed

Bor, Jacob; Geldsetzer, Pascal; Venkataramani, Atheendar; Bärnighausen, Till

2015-11-01

Randomized, population-representative trials of clinical interventions are rare. Quasi-experiments have been used successfully to generate causal evidence on the cascade of HIV care in a broad range of real-world settings. Quasi-experiments exploit exogenous, or quasi-random, variation occurring naturally in the world or because of an administrative rule or policy change to estimate causal effects. Well designed quasi-experiments have greater internal validity than typical observational research designs. At the same time, quasi-experiments may also have potential for greater external validity than experiments and can be implemented when randomized clinical trials are infeasible or unethical. Quasi-experimental studies have established the causal effects of HIV testing and initiation of antiretroviral therapy on health, economic outcomes and sexual behaviors, as well as indirect effects on other community members. Recent quasi-experiments have evaluated specific interventions to improve patient performance in the cascade of care, providing causal evidence to optimize clinical management of HIV. Quasi-experiments have generated important data on the real-world impacts of HIV testing and treatment and on interventions to improve the cascade of care. With the growth in large-scale clinical and administrative data, quasi-experiments enable rigorous evaluation of policies implemented in real-world settings.

Effects of resistance and functional-skills training on habitual activity and constipation among older adults living in long-term care facilities: a randomized controlled trial.

PubMed

Chin A Paw, Marijke J M; van Poppel, Mireille N M; van Mechelen, Willem

2006-07-31

Large-scale RCTs comparing different types of exercise training in institutionalised older people are scarce, especially regarding effects on habitual physical activity and constipation. This study investigated the effects of different training protocols on habitual physical activity and constipation of older adults living in long-term care facilities. A randomized controlled trial with 157 participants, aged 64 to 94 years, who were randomly assigned to 1) resistance training; 2) all-round functional-skills training; 3) both; or 4) an 'educational' control condition. Habitual physical activity was assessed with a physical activity questionnaire and accelerometers. Constipation was assessed by a questionnaire. Measurements were performed at baseline and after six months of training. At baseline the median time spent sitting was 8.2 hr/d, the median time spent on activity of at least moderate intensity was 32 min/d. At baseline, about 22% of the subjects were diagnosed with constipation and 23% were taking laxatives. There were no between-group differences for changes in habitual physical activity or constipation over 6-months. Six months of moderate intensity exercise training neither enhances habitual physical activity nor affects complaints of constipation among older people living in long-term care facilities.

Experiences of being a control group: lessons from a UK-based randomized controlled trial of group singing as a health promotion initiative for older people.

PubMed

Skingley, Ann; Bungay, Hilary; Clift, Stephen; Warden, June

2014-12-01

Existing randomized controlled trials within the health field suggest that the concept of randomization is not always well understood and that feelings of disappointment may occur when participants are not placed in their preferred arm. This may affect a study's rigour and ethical integrity if not addressed. We aimed to test whether these issues apply to a healthy volunteer sample within a health promotion trial of singing for older people. Written comments from control group participants at two points during the trial were analysed, together with individual semi-structured interviews with a small sample (n = 11) of this group. We found that motivation to participate in the trial was largely due to the appeal of singing and disappointment resulted from allocation to the control group. Understanding of randomization was generally good and feelings of disappointment lessened over time and with a post-research opportunity to sing. Findings suggest that measures should be put in place to minimize the potential negative impacts of randomized controlled trials in health promotion research. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed

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

2017-01-01

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

Vitamin D and Cancer Prevention

MedlinePlus

... D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin ... the National Cancer Institute.” Please note that blog posts that are written by individuals from outside the ...

Acupuncture for acute stroke: study protocol for a multicenter, randomized, controlled trial.

PubMed

Chen, Lifang; Fang, Jianqiao; Ma, Ruijie; Froym, Ronen; Gu, Xudong; Li, Jianhua; Chen, Lina; Xu, Shouyu; Ji, Conghua

2014-06-08

Acupuncture has been widely used as a treatment for stroke in China for more than 3,000 years. However, previous research has not yet shown that acupuncture is effective as a stroke treatment. We report a protocol for a multicenter, randomized, controlled, and outcome assessor-blind trial to evaluate the efficacy and safety of acupuncture on acute ischemic stroke. In a prospective trial involving three hospitals in the Zhejiang Province (China) 250 patients with a recent (less than 1 week previous) episode of ischemic stroke will be included. Patients will be randomized into two groups: an acupuncture group given scalp acupuncture and electroacupuncture, and a control group given no acupuncture. Eighteen treatment sessions will be performed over a three-week period. The primary outcome will be measured by changes in the National Institutes of Health Stroke Scale score at the one, three, and four-week follow-up. Secondary outcome measures will be: 1) the Fugl-Meyer assessment scale for motor function; 2) the mini-mental state examination and Montreal cognitive assessment for cognitive function; 3) the video-fluoroscopic swallowing study for swallowing ability; and 4) the incidence of adverse events. This trial is expected to clarify whether or not acupuncture is effective for acute stroke. It will also show if acupuncture can improve motor, cognitive, or swallowing function. Chinese Clinical Trial Registry ChiCTR-TRC-12001971.

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

The addition of a goal-based motivational interview to treatment as usual to enhance engagement and reduce dropouts in a personality disorder treatment service: results of a feasibility study for a randomized controlled trial

PubMed Central

2013-01-01

Background There are high rates of treatment non-completion for personality disorder and those who do not complete treatment have poorer outcomes. A goal-based motivational interview may increase service users’ readiness to engage with therapy and so enhance treatment retention. We conducted a feasibility study to inform the design of a randomized controlled trial. The aims were to test the feasibility of recruitment, randomization and follow-up, and to conduct a preliminary evaluation of the effectiveness of the motivational interview. Methods Patients in an outpatient personality disorder service were randomized to receive the Personal Concerns Inventory plus treatment as usual or treatment as usual only. The main randomized controlled trial feasibility criteria were recruitment of 54% of referrals, and 80% of clients and therapists finding the intervention acceptable. Information was collected on treatment attendance, the clarity of therapy goals and treatment engagement. Results The recruitment rate was 29% (76 of 258). Of 12 interviewed at follow-up, eight (67%) were positive about the Personal Concerns Inventory. Pre-intervention interviews were conducted with 61% (23 out of 38) of the Personal Concerns Inventory group and 74% (28 out of 38) of the treatment as usual group. Participants’ therapy goals were blind-rated for clarity on a scale of 0 to 10. The mean score for the Personal Concerns Inventory group was 6.64 (SD = 2.28) and for the treatment as usual group 2.94 (SD = 1.71). Over 12 weeks, the median percentage session attendance was 83.33% for the Personal Concerns Inventory group (N = 17) and 66.67% for the treatment as usual group (N = 24). Of 59 eligible participants at follow-up, the Treatment Engagement Rating scale was completed for 40 (68%). The mean Treatment Engagement Rating scale score for the Personal Concerns Inventory group was 6.64 (SD = 2.28) and for the treatment as usual group 2.94 (SD = 1.71). Of the 76 participants, 63 (83%) completed the Client Service Receipt Inventory at baseline and 34 of 59 (58%) at follow-up. Conclusion Shortfalls in recruitment and follow-up data collection were explained by major changes to the service. However, evidence of a substantial positive impact of the Personal Concerns Inventory on treatment attendance, clarity of therapy goals and treatment engagement, make a full-scale evaluation worth pursuing. Further preparatory work is required for a multisite trial. Trial registration ClinicalTrials.Gov.UK Identifier - NCT01132976 PMID:23414174

Using the bedside wellness system during chemotherapy decreases fatigue and emesis in cancer patients.

PubMed

Oyama, H; Kaneda, M; Katsumata, N; Akechi, T; Ohsuga, M

2000-06-01

The bedside wellness system (BSW) is effective for decreasing stress and improving mental well-being and should help relieve the side effects and mental disorders of patients during cancer chemotherapy. The study was a randomized clinical trial. After giving informed consent, patients were randomly assigned to the BSW intervention or control groups. The patients were given the Hospital Anxiety and Depression Scale (HADS) test before the trial to evaluate their emotional baseline. The Cancer Fatigue Scale, which was developed at our institute, and face visual analog scale were used to measure the emotional state and subjective feelings before and after the trial. The degree of emesis was measured using a visual analogue scale after the experience. We set up the system in a room in the outpatient clinic of the National Cancer Center New Hospital Building. The decreases in the fatigue score and emesis score 3-5 days after chemotherapy were statistically significant (both p < 0.05) and carry-over effects were detected. BSW intervention therapy is an effective way to treat fatigue and emesis. This virtual reality system is a new therapeutic method that can be used in palliative medicine.

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

PubMed Central

2011-01-01

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

Strategies and Opportunities to STOP Colon Cancer in Priority Populations: design of a cluster-randomized pragmatic trial.

PubMed

Coronado, Gloria D; Vollmer, William M; Petrik, Amanda; Taplin, Stephen H; Burdick, Timothy E; Meenan, Richard T; Green, Beverly B

2014-07-01

Colorectal cancer is the second-leading cause of cancer deaths in the United States. The Strategies and Opportunities to Stop Colorectal Cancer (STOP CRC) in Priority Populations study is a pragmatic trial and a collaboration between two research institutions and a network of more than 200 safety net clinics. The study will assess the effectiveness of a system-based intervention designed to improve the rates of colorectal-cancer screening using fecal immunochemical testing (FIT) in federally qualified health centers in Oregon and Northern California. STOP CRC is a cluster-randomized comparative-effectiveness pragmatic trial enrolling 26 clinics. Clinics will be randomized to one of two arms. Clinics in the intervention arm (1) will use an automated, data-driven, electronic health record-embedded program to identify patients due for colorectal screening and mail FIT kits (with pictographic instructions) to them; (2) will conduct an improvement process (e.g. Plan-Do-Study-Act) to enhance the adoption, reach, and effectiveness of the program. Clinics in the control arm will provide opportunistic colorectal-cancer screening to patients at clinic visits. The primary outcomes are: proportion of age- and screening-eligible patients completing a FIT within 12months; and cost, cost-effectiveness, and return on investment of the intervention. This large-scale pragmatic trial will leverage electronic health record information and existing clinic staff to enroll a broad range of patients, including many with historically low colorectal-cancer screening rates. If successful, the program will provide a model for a cost-effective and scalable method to raise colorectal-cancer screening rates. Copyright © 2014 Elsevier Inc. All rights reserved.

Depression in Visual Impairment Trial (DEPVIT): A Randomized Clinical Trial of Depression Treatments in People With Low Vision.

PubMed

Nollett, Claire L; Bray, Nathan; Bunce, Catey; Casten, Robin J; Edwards, Rhiannon T; Hegel, Mark T; Janikoun, Sarah; Jumbe, Sandra E; Ryan, Barbara; Shearn, Julia; Smith, Daniel J; Stanford, Miles; Xing, Wen; Margrain, Tom H

2016-08-01

The purpose of this study was to compare two interventions for depression, problem solving treatment (PST) and referral to the patient's physician, with a waiting-list control group in people with sight loss and depressive symptoms. This was an assessor-masked, exploratory, multicenter, randomized clinical trial, with concurrent economic analysis. Of 1008 consecutive attendees at 14 low-vision rehabilitation centers in Britain, 43% (n = 430) screened positive for depressive symptoms on the Geriatric Depression Scale and 85 of these attendees participated in the trial. Eligible participants were randomized in the ratio 1:1:1 to PST, referral to their physician, or a waiting-list control arm. PST is a manualized talking intervention delivered by a trained therapist who teaches people over six to eight sessions to implement a seven-step method for solving their problems. Referral to the physician involved sending a referral letter to the person's physician, encouraging him or her to consider treatment according to the stepped care protocol recommended by the U.K.'s National Institute of Health and Care Excellence. The primary outcome was change in depressive symptoms (6 months after baseline) as determined by the Beck Depression Inventory. At 6 months, Beck Depression Inventory scores reduced by 1.05 (SD 8.85), 2.11 (SD 7.60), and 2.68 (SD 7.93) in the waiting-list control, referral, and PST arms, respectively. The cost per patient of the PST intervention was £1176 in Wales and £1296 in London. Depressive symptoms improved most in the PST group and least in the control group. However, the change was small and the uncertainty of the measurements relatively large.

Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

PubMed Central

Wahner-Roedler, Dietlind L.; Thompson, Jeffrey M.; Luedtke, Connie A.; King, Susan M.; Cha, Stephen S.; Elkin, Peter L.; Bruce, Barbara K.; Townsend, Cynthia O.; Bergeson, Jody R.; Eickhoff, Andrea L.; Loehrer, Laura L.; Sood, Amit; Bauer, Brent A.

2011-01-01

Most patients with fibromyalgia use complementary and alternative medicine (CAM). Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein) shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ) and the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02) and by 18% in the placebo group (P < .001). The difference in change in scores between the groups was not significant (P = .16). With the same analysis, CES-D scores decreased in the soy group by 16% (P = .004) and in the placebo group by 15% (P = .05). The change in scores was similar in the groups (P = .83). Results of statistical analysis using the separation test and intent-to-treat analysis revealed no benefit of soy compared with placebo. Shakes that contain soy and shakes that contain casein, when combined with a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control) shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated. PMID:18990724

PDA+: A Personal Digital Assistant for Obesity Treatment - an RCT testing the use of technology to enhance weight loss treatment for veterans.

PubMed

Duncan, Jennifer M; Janke, E Amy; Kozak, Andrea T; Roehrig, Megan; Russell, Stephanie W; McFadden, H Gene; Demott, Andrew; Pictor, Alex; Hedeker, Don; Spring, Bonnie

2011-04-11

Obese adults struggle to make the changes necessary to achieve even modest weight loss, though a decrease in weight by as little as 10% can have significant health benefits. Failure to meet weight loss goals may in part be associated with barriers to obesity treatment. Wide-spread dissemination of evidence-based obesity treatment faces multiple challenges including cost, access, and implementing the programmatic characteristics on a large scale. The PDA+: A Personal Digital Assistant for Obesity Treatment randomized controlled trial (RCT) was designed to test whether a PDA-based behavioral intervention enhances the effectiveness of the existing group weight loss treatment program at VA Medical Centers Managing Overweight/Obese Veterans Everywhere (MOVE!). We also aim to introduce technology as a way to overcome systemic barriers of traditional obesity treatment. Veterans enrolled in the MOVE! group at the Hines Hospital VAMC with BMI ≥ 25 and ≤ 40 and weigh < 400 pounds, experience chronic pain (≥ 4 on the NRS-I scale for ≥ 6 months prior to enrollment) and are able to participate in a moderate intensity exercise program will be recruited and screened for eligibility. Participants will be randomized to receive either: a) MOVE! treatment alone (Standard Care) or b) Standard Care plus PDA (PDA+). Those randomized to PDA+ will record dietary intake, physical activity, and weight on the PDA. In addition, they will also record mood and pain intensity, and receive biweekly telephone support for the first 6-months of the 12-month study. All participants will attend in-person lab sessions every three months to complete questionnaires and for the collection of anthropomorphic data. Weight loss and decrease in pain level intensity are the primary outcomes. The PDA+ trial represents an important step in understanding ways to improve the use of technology in obesity treatment. The trial will address barriers to obesity care by implementing effective behavioral components of a weight loss intervention and delivering high intensity, low cost obesity treatment. This RCT also tests an intervention approach supported by handheld technology in a population traditionally considered to have lower levels of technology literacy. ClinicalTrials.gov: NCT00371462.

Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine.

PubMed

Gibbons, Robert D; Hur, Kwan; Brown, C Hendricks; Davis, John M; Mann, J John

2012-06-01

Some meta-analyses suggest that efficacy of antidepressants for major depression is overstated and limited to severe depression. To determine the short-term efficacy of antidepressants for treating major depressive disorder in youth, adult, and geriatric populations. Reanalysis of all intent-to-treat person-level longitudinal data during the first 6 weeks of treatment of major depressive disorder from 12 adult, 4 geriatric, and 4 youth randomized controlled trials of fluoxetine hydrochloride and 21 adult trials of venlafaxine hydrochloride. All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine. Children's Depression Rating Scale-Revised scores (youth population), Hamilton Depression Rating Scale scores (adult and geriatric populations), and estimated response and remission rates at 6 weeks were analyzed for 2635 adults, 960 geriatric patients, and 708 youths receiving fluoxetine and for 2421 adults receiving immediate-release venlafaxine and 2461 adults receiving extended-release venlafaxine. Patients in all age and drug groups had significantly greater improvement relative to control patients receiving placebo. The differential rate of improvement was largest for adults receiving fluoxetine (34.6% greater than those receiving placebo). Youths had the largest treated vs control difference in response rates (24.1%) and remission rates (30.1%), with adult differences generally in the 15.6% (remission) to 21.4% (response) range. Geriatric patients had the smallest drug-placebo differences, an 18.5% greater rate of improvement, 9.9% for response and 6.5% for remission. Immediate-release venlafaxine produced larger effects than extended-release venlafaxine. Baseline severity could not be shown to affect symptom reduction. To our knowledge, this is the first research synthesis in this area to use complete longitudinal person-level data from a large set of published and unpublished studies. The results do not support previous findings that antidepressants show little benefit except for severe depression. The antidepressants fluoxetine and venlafaxine are efficacious for major depressive disorder in all age groups, although more so in youths and adults compared with geriatric patients. Baseline severity was not significantly related to degree of treatment advantage over placebo.

Sleep Apnea and Cardiovascular Disease: Lessons From Recent Trials and Need for Team Science.

PubMed

Drager, Luciano F; McEvoy, R Doug; Barbe, Ferran; Lorenzi-Filho, Geraldo; Redline, Susan

2017-11-07

Emerging research highlights the complex interrelationships between sleep-disordered breathing and cardiovascular disease, presenting clinical and research opportunities as well as challenges. Patients presenting to cardiology clinics have a high prevalence of obstructive and central sleep apnea associated with Cheyne-Stokes respiration. Multiple mechanisms have been identified by which sleep disturbances adversely affect cardiovascular structure and function. Epidemiological research indicates that obstructive sleep apnea is associated with increases in the incidence and progression of coronary heart disease, heart failure, stroke, and atrial fibrillation. Central sleep apnea associated with Cheyne-Stokes respiration predicts incident heart failure and atrial fibrillation; among patients with heart failure, it strongly predicts mortality. Thus, a strong literature provides the mechanistic and empirical bases for considering obstructive sleep apnea and central sleep apnea associated with Cheyne-Stokes respiration as potentially modifiable risk factors for cardiovascular disease. Data from small trials provide evidence that treatment of obstructive sleep apnea with continuous positive airway pressure improves not only patient-reported outcomes such as sleepiness, quality of life, and mood but also intermediate cardiovascular end points such as blood pressure, cardiac ejection fraction, vascular parameters, and arrhythmias. However, data from large-scale randomized controlled trials do not currently support a role for positive pressure therapies for reducing cardiovascular mortality. The results of 2 recent large randomized controlled trials, published in 2015 and 2016, raise questions about the effectiveness of pressure therapies in reducing clinical end points, although 1 trial supported the beneficial effect of continuous positive airway pressure on quality of life, mood, and work absenteeism. This review provides a contextual framework for interpreting the results of recent studies, key clinical messages, and suggestions for future sleep and cardiovascular research, which include further consideration of individual risk factors, use of existing and new multimodality therapies that also address adherence, and implementation of trials that are sufficiently powered to target end points and to support subgroup analyses. These goals may best be addressed through strengthening collaboration among the cardiology, sleep medicine, and clinical trial communities. © 2017 American Heart Association, Inc.

Mixed methods evaluation of a randomized control pilot trial targeting sugar-sweetened beverage behaviors.

PubMed

Zoellner, Jamie; Cook, Emily; Chen, Yvonnes; You, Wen; Davy, Brenda; Estabrooks, Paul

2013-02-01

This Excessive sugar-sweetened beverage (SSB) consumption and low health literacy skills have emerged as two public health concerns in the United States (US); however, there is limited research on how to effectively address these issues among adults. As guided by health literacy concepts and the Theory of Planned Behavior (TPB), this randomized controlled pilot trial applied the RE-AIM framework and a mixed methods approach to examine a sugar-sweetened beverage (SSB) intervention (SipSmartER), as compared to a matched-contact control intervention targeting physical activity (MoveMore). Both 5-week interventions included two interactive group sessions and three support telephone calls. Executing a patient-centered developmental process, the primary aim of this paper was to evaluate patient feedback on intervention content and structure. The secondary aim was to understand the potential reach (i.e., proportion enrolled, representativeness) and effectiveness (i.e. health behaviors, theorized mediating variables, quality of life) of SipSmartER. Twenty-five participants were randomized to SipSmartER (n=14) or MoveMore (n=11). Participants' intervention feedback was positive, ranging from 4.2-5.0 on a 5-point scale. Qualitative assessments reavealed several opportunties to improve clarity of learning materials, enhance instructions and communication, and refine research protocols. Although SSB consumption decreased more among the SipSmartER participants (-256.9 ± 622.6 kcals), there were no significant group differences when compared to control participants (-199.7 ± 404.6 kcals). Across both groups, there were significant improvements for SSB attitudes, SSB behavioral intentions, and two media literacy constructs. The value of using a patient-centered approach in the developmental phases of this intervention was apparent, and pilot findings suggest decreased SSB may be achieved through targeted health literacy and TPB strategies. Future efforts are needed to examine the potential public health impact of a large-scale trial to address health literacy and reduce SSB.

Exploring synergistic effects of aerobic exercise and mindfulness training on cognitive function in older adults: Protocol for a pilot randomized controlled trial.

PubMed

Salmoirago-Blotcher, Elena; DeCosta, Julie; Harris, Kristie; Breault, Christopher; Dunsiger, Shira; Santos, Claudia; Snyder, Peter

2018-05-01

Despite increasing evidence that aerobic exercise and cognitive training improve cognitive function among patients with cognitive impairment and dementia, few studies have focused on the effect of a combination of these approaches. This study will explore whether combining aerobic training (AT) with mindfulness training (MT), an intervention promoting the moment-to-moment awareness of physical sensations, affective states, and thoughts, improves cognitive function in individuals at risk of dementia. The primary objective is to determine the feasibility and acceptability of the intervention(s). The secondary objective is to obtain estimates of effect sizes on cognitive function and on possible mediators. Forty participants with at least 2 risk factors for dementia will be randomized (2 × 2 factorial design) to either AT (3 sessions/week for 12 weeks), MT (1 session/week for 8 weeks), both, or usual care. Assessments of cognitive function (attention, executive function, episodic, and working memory); physical activity (accelerometry), aerobic capacity (6-minute walk test), waist-to-hip ratio, blood pressure, social support (Multidimensional Scale of Perceived Social Support), depression (Hospital Anxiety and Depression Scale), and mindfulness (Five Facets of Mindfulness) will be conducted at baseline, end of treatment, and 6-months postbaseline. Rates of retention, attendance, and program satisfaction will be calculated for each of the 4 groups to determine the feasibility and acceptability of each intervention. This study has full ethical approval by The Miriam Hospital Institutional Review Board and adheres to the Standard Protocol Items: Recommendations for Interventional Trials reporting recommendations. If results from this exploratory, proof-of-concept study support our hypotheses, we will conduct a large randomized controlled trial (RCT) to determine the efficacy of combined MT and AT in improving cognitive function in individuals at risk of dementia. Results from the study will be disseminated through peer-reviewed journals and conference presentations. REGISTRATION DETAILS:: http://www.clinicalstrials.gov identifier NCT03289546.

Randomized trial of thoracic irradiation plus combination chemotherapy for unresectable adenocarcinoma and large cell carcinoma of the lung

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

Eagan, R.T.; Lee, R.E.; Frytak, S.

1979-08-01

Sixty-eight evaluable patients with unresectable adenocarcinoma and large cell carcinoma of the lung were treated on a prospective randomized trial comparing thoracic radiation therapy (TRT) plus combination chemotherapy with either cyclophosphamide, Adriamycin and cis-platinum (CAP) or cyclophosphamide, Adriamycin (same dosages) and DTIC (CAD), 34 on each arm. Patients treated with TRT plus CAP had a better overall regression rate (59% vs 47%) and a statistically significant superiority in time to disease progression (147 days vs 303 days) and survival (217 days vs 504 days).

A randomized clinical trial of high eicosapentaenoic acid omega-3 fatty acids and inositol as monotherapy and in combination in the treatment of pediatric bipolar spectrum disorders: a pilot study.

PubMed

Wozniak, Janet; Faraone, Stephen V; Chan, James; Tarko, Laura; Hernandez, Mariely; Davis, Jacqueline; Woodworth, K Yvonne; Biederman, Joseph

2015-11-01

We conducted a 12-week, randomized, double-blind, controlled clinical trial to evaluate the effectiveness and tolerability of high eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) omega-3 fatty acids and inositol as monotherapy and in combination in children with bipolar spectrum disorders. Participants were children 5-12 years of age meeting DSM-IV diagnostic criteria for bipolar spectrum disorders (bipolar I or II disorder or bipolar disorder not otherwise specified [NOS]) and displaying mixed, manic, or hypomanic symptoms. Subjects with severe illness were excluded. Subjects were randomized to 1 of 3 treatment arms: inositol plus placebo, omega-3 fatty acids plus placebo, and the combined active treatment of omega-3 fatty acids plus inositol. Data were collected from February 2012 to November 2013. Twenty-four subjects were exposed to treatment (≥ 1 week of study completed) (inositol [n = 7], omega-3 fatty acids [n = 7], and omega-3 fatty acids plus inositol [n =10]). Fifty-four percent of the subjects completed the study. Subjects randomized to the omega-3 fatty acids plus inositol arm had the largest score decrease comparing improvement from baseline to end point with respect to the Young Mania Rating Scale (P < .05). Similar results were found for the Children's Depression Rating Scale (P < .05) and the Brief Psychiatric Rating Scale (P <.05). Results of this pilot randomized, double-blind, controlled trial suggest that the combined treatment of omega-3 fatty acids plus inositol reduced symptoms of mania and depression in prepubertal children with mild to moderate bipolar spectrum disorders. Results should be interpreted in light of limitations, which include exclusion of severely ill subjects, 54% completion rate, and small sample size. ClinicalTrials.gov identifier: NCT01396486. © Copyright 2015 Physicians Postgraduate Press, Inc.

Double-blind optimization of subcallosal cingulate deep brain stimulation for treatment-resistant depression: a pilot study.

PubMed

Ramasubbu, Rajamannar; Anderson, Susan; Haffenden, Angela; Chavda, Swati; Kiss, Zelma H T

2013-09-01

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is reported to be a safe and effective new treatment for treatment-resistant depression (TRD). However, the optimal electrical stimulation parameters are unknown and generally selected by trial and error. This pilot study investigated the relationship between stimulus parameters and clinical effects in SCC-DBS treatment for TRD. Four patients with TRD underwent SCC-DBS surgery. In a double-blind stimulus optimization phase, frequency and pulse widths were randomly altered weekly, and corresponding changes in mood and depression were evaluated using a visual analogue scale (VAS) and the 17-item Hamilton Rating Scale for Depression (HAM-D-17). In the open-label postoptimization phase, depressive symptoms were evaluated biweekly for 6 months to determine long-term clinical outcomes. Longer pulse widths (270-450 μs) were associated with reductions in HAM-D-17 scores in 3 patients and maximal happy mood VAS responses in all 4 patients. Only 1 patient showed acute clinical or mood effects from changing the stimulation frequency. After 6 months of open-label therapy, 2 patients responded and 1 patient partially responded. Limitations include small sample size, weekly changes in stimulus parameters, and fixed-order and carry-forward effects. Longer pulse width stimulation may have a role in stimulus optimization for SCC-DBS in TRD. Longer pulse durations produce larger apparent current spread, suggesting that we do not yet know the optimal target or stimulus parameters for this therapy. Investigations using different stimulus parameters are required before embarking on large-scale randomized sham-controlled trials.

Goal Attainment Scaling as an Outcome Measure in Randomized Controlled Trials of Psychosocial Interventions in Autism

ERIC Educational Resources Information Center

Ruble, Lisa; McGrew, John H.; Toland, Michael D.

2012-01-01

Goal attainment scaling (GAS) holds promise as an idiographic approach for measuring outcomes of psychosocial interventions in community settings. GAS has been criticized for untested assumptions of scaling level (i.e., interval or ordinal), inter-individual equivalence and comparability, and reliability of coding across different behavioral…

Massage therapy for fibromyalgia: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Li, Yan-hui; Wang, Feng-yun; Feng, Chun-qing; Yang, Xia-feng; Sun, Yi-hua

2014-01-01

Although some studies evaluated the effectiveness of massage therapy for fibromyalgia (FM), the role of massage therapy in the management of FM remained controversial. The purpose of this systematic review is to evaluate the evidence of massage therapy for patients with FM. Electronic databases (up to June 2013) were searched to identify relevant studies. The main outcome measures were pain, anxiety, depression, and sleep disturbance. Two reviewers independently abstracted data and appraised risk of bias. The risk of bias of eligible studies was assessed based on Cochrane tools. Standardised mean difference (SMD) and 95% confidence intervals (CI) were calculated by more conservative random-effects model. And heterogeneity was assessed based on the I(2) statistic. Nine randomized controlled trials involving 404 patients met the inclusion criteria. The meta-analyses showed that massage therapy with duration ≥ 5 weeks significantly improved pain (SMD, 0.62; 95% CI 0.05 to 1.20; p = 0.03), anxiety (SMD, 0.44; 95% CI 0.09 to 0.78; p = 0.01), and depression (SMD, 0.49; 95% CI 0.15 to 0.84; p = 0.005) in patients with FM, but not on sleep disturbance (SMD, 0.19; 95% CI -0.38 to 0.75; p = 0.52). Massage therapy with duration ≥ 5 weeks had beneficial immediate effects on improving pain, anxiety, and depression in patients with FM. Massage therapy should be one of the viable complementary and alternative treatments for FM. However, given fewer eligible studies in subgroup meta-analyses and no evidence on follow-up effects, large-scale randomized controlled trials with long follow-up are warrant to confirm the current findings.

Massage Therapy for Fibromyalgia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Li, Yan-hui; Wang, Feng-yun; Feng, Chun-qing; Yang, Xia-feng; Sun, Yi-hua

2014-01-01

Background Although some studies evaluated the effectiveness of massage therapy for fibromyalgia (FM), the role of massage therapy in the management of FM remained controversial. Objective The purpose of this systematic review is to evaluate the evidence of massage therapy for patients with FM. Methods Electronic databases (up to June 2013) were searched to identify relevant studies. The main outcome measures were pain, anxiety, depression, and sleep disturbance. Two reviewers independently abstracted data and appraised risk of bias. The risk of bias of eligible studies was assessed based on Cochrane tools. Standardised mean difference (SMD) and 95% confidence intervals (CI) were calculated by more conservative random-effects model. And heterogeneity was assessed based on the I2 statistic. Results Nine randomized controlled trials involving 404 patients met the inclusion criteria. The meta-analyses showed that massage therapy with duration ≥5 weeks significantly improved pain (SMD, 0.62; 95% CI 0.05 to 1.20; p = 0.03), anxiety (SMD, 0.44; 95% CI 0.09 to 0.78; p = 0.01), and depression (SMD, 0.49; 95% CI 0.15 to 0.84; p = 0.005) in patients with FM, but not on sleep disturbance (SMD, 0.19; 95% CI −0.38 to 0.75; p = 0.52). Conclusion Massage therapy with duration ≥5 weeks had beneficial immediate effects on improving pain, anxiety, and depression in patients with FM. Massage therapy should be one of the viable complementary and alternative treatments for FM. However, given fewer eligible studies in subgroup meta-analyses and no evidence on follow-up effects, large-scale randomized controlled trials with long follow-up are warrant to confirm the current findings. PMID:24586677

A randomized trial of functional electrical stimulation for walking in incomplete spinal cord injury: Effects on walking competency

PubMed Central

Kapadia, Naaz; Masani, Kei; Catharine Craven, B.; Giangregorio, Lora M.; Hitzig, Sander L.; Richards, Kieva; Popovic, Milos R.

2014-01-01

Background Multi-channel surface functional electrical stimulation (FES) for walking has been used to improve voluntary walking and balance in individuals with spinal cord injury (SCI). Objective To investigate short- and long-term benefits of 16 weeks of thrice-weekly FES-assisted walking program, while ambulating on a body weight support treadmill and harness system, versus a non-FES exercise program, on improvements in gait and balance in individuals with chronic incomplete traumatic SCI, in a randomized controlled trial design. Methods Individuals with traumatic and chronic (≥18 months) motor incomplete SCI (level C2 to T12, American Spinal Cord Injury Association Impairment Scale C or D) were recruited from an outpatient SCI rehabilitation hospital, and randomized to FES-assisted walking therapy (intervention group) or aerobic and resistance training program (control group). Outcomes were assessed at baseline, and after 4, 6, and 12 months. Gait, balance, spasticity, and functional measures were collected. Results Spinal cord independence measure (SCIM) mobility sub-score improved over time in the intervention group compared with the control group (baseline/12 months: 17.27/21.33 vs. 19.09/17.36, respectively). On all other outcome measures the intervention and control groups had similar improvements. Irrespective of group allocation walking speed, endurance, and balance during ambulation all improved upon completion of therapy, and majority of participants retained these gains at long-term follow-ups. Conclusions Task-oriented training improves walking ability in individuals with incomplete SCI, even in the chronic stage. Further randomized controlled trials, involving a large number of participants are needed, to verify if FES-assisted treadmill training is superior to aerobic and strength training. PMID:25229735

Omega-3 and -6 fatty acid supplementation and sensory processing in toddlers with ASD symptomology born preterm: A randomized controlled trial.

PubMed

Boone, Kelly M; Gracious, Barbara; Klebanoff, Mark A; Rogers, Lynette K; Rausch, Joseph; Coury, Daniel L; Keim, Sarah A

2017-12-01

Despite advances in the health and long-term survival of infants born preterm, they continue to face developmental challenges including higher risk for autism spectrum disorder (ASD) and atypical sensory processing patterns. This secondary analysis aimed to describe sensory profiles and explore effects of combined dietary docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and gamma-linolenic acid (GLA) supplementation on parent-reported sensory processing in toddlers born preterm who were exhibiting ASD symptoms. 90-day randomized, double blinded, placebo-controlled trial. 31 children aged 18-38months who were born at ≤29weeks' gestation. Mixed effects regression analyses followed intent to treat and explored effects on parent-reported sensory processing measured by the Infant/Toddler Sensory Profile (ITSP). Baseline ITSP scores reflected atypical sensory processing, with the majority of atypical scores falling below the mean. Sensory processing sections: auditory (above=0%, below=65%), vestibular (above=13%, below=48%), tactile (above=3%, below=35%), oral sensory (above=10%; below=26%), visual (above=10%, below=16%); sensory processing quadrants: low registration (above=3%; below=71%), sensation avoiding (above=3%; below=39%), sensory sensitivity (above=3%; below=35%), and sensation seeking (above=10%; below=19%). Twenty-eight of 31 children randomized had complete outcome data. Although not statistically significant (p=0.13), the magnitude of the effect for reduction in behaviors associated with sensory sensitivity was medium to large (effect size=0.57). No other scales reflected a similar magnitude of effect size (range: 0.10 to 0.32). The findings provide support for larger randomized trials of omega fatty acid supplementation for children at risk of sensory processing difficulties, especially those born preterm. Copyright © 2017 Elsevier B.V. All rights reserved.

Online Alcohol Assessment and Feedback for Hazardous and Harmful Drinkers: Findings From the AMADEUS-2 Randomized Controlled Trial of Routine Practice in Swedish Universities.

PubMed

Bendtsen, Preben; Bendtsen, Marcus; Karlsson, Nadine; White, Ian R; McCambridge, Jim

2015-07-09

Previous research on the effectiveness of online alcohol interventions for college students has shown mixed results. Small benefits have been found in some studies and because online interventions are inexpensive and possible to implement on a large scale, there is a need for further study. This study evaluated the effectiveness of national provision of a brief online alcohol intervention for students in Sweden. Risky drinkers at 9 colleges and universities in Sweden were invited by mail and identified using a single screening question. These students (N=1605) gave consent and were randomized into a 2-arm parallel group randomized controlled trial consisting of immediate or delayed access to a fully automated online assessment and intervention with personalized feedback. After 2 months, there was no strong evidence of effectiveness with no statistically significant differences in the planned analyses, although there were some indication of possible benefit in sensitivity analyses suggesting an intervention effect of a 10% reduction (95% CI -30% to 10%) in total weekly alcohol consumption. Also, differences in effect sizes between universities were seen with participants from a major university (n=365) reducing their weekly alcohol consumption by 14% (95% CI -23% to -4%). However, lower recruitment than planned and differential attrition in the intervention and control group (49% vs 68%) complicated interpretation of the outcome data. Any effects of current national provision are likely to be small and further research and development work is needed to enhance effectiveness. International Standard Randomized Controlled Trial Number (ISRCTN): 02335307; http://www.isrctn.com/ISRCTN02335307 (Archived by WebCite at http://www.webcitation.org/6ZdPUh0R4).

Development and Evaluation of the Sugar-Sweetened Beverages Media Literacy (SSB-ML) Scale and Its Relationship With SSB Consumption.

PubMed

Chen, Yvonnes; Porter, Kathleen J; Estabrooks, Paul A; Zoellner, Jamie

2017-10-01

Understanding how adults' media literacy skill sets impact their sugar-sweetened beverage (SSB) intake provides insight into designing effective interventions to enhance their critical analysis of marketing messages and thus improve their healthy beverage choices. However, a media literacy scale focusing on SSBs is lacking. This cross-sectional study uses baseline data from a large randomized controlled trial to (a) describe the psychometric properties of an SSB Media Literacy Scale (SSB-ML) scale and its subdomains, (b) examine how the scale varies across demographic variables, and (c) explain the scale's concurrent validity to predict SSB consumption. Results from 293 adults in rural southwestern Virginia (81.6% female, 94.0% White, 54.1% receiving SNAP and/or WIC benefits, average 410 SSB kcal daily) show that overall SSB-ML scale and its subdomains have strong internal consistencies (Cronbach's alphas ranging from 0.65 to 0.83). The Representation & Reality domain significantly predicted SSB kilocalories, after controlling for demographic variables. This study has implications for the assessment and inclusion of context-specific media literacy skills in behavioral interventions.

Methods for Synthesizing Findings on Moderation Effects Across Multiple Randomized Trials

PubMed Central

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

2011-01-01

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

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

PubMed

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

2013-04-01

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

Treating major depression with yoga: A prospective, randomized, controlled pilot trial.

PubMed

Prathikanti, Sudha; Rivera, Renee; Cochran, Ashly; Tungol, Jose Gabriel; Fayazmanesh, Nima; Weinmann, Eva

2017-01-01

Conventional pharmacotherapies and psychotherapies for major depression are associated with limited adherence to care and relatively low remission rates. Yoga may offer an alternative treatment option, but rigorous studies are few. This randomized controlled trial with blinded outcome assessors examined an 8-week hatha yoga intervention as mono-therapy for mild-to-moderate major depression. Investigators recruited 38 adults in San Francisco meeting criteria for major depression of mild-to-moderate severity, per structured psychiatric interview and scores of 14-28 on Beck Depression Inventory-II (BDI). At screening, individuals engaged in psychotherapy, antidepressant pharmacotherapy, herbal or nutraceutical mood therapies, or mind-body practices were excluded. Participants were 68% female, with mean age 43.4 years (SD = 14.8, range = 22-72), and mean BDI score 22.4 (SD = 4.5). Twenty participants were randomized to 90-minute hatha yoga practice groups twice weekly for 8 weeks. Eighteen participants were randomized to 90-minute attention control education groups twice weekly for 8 weeks. Certified yoga instructors delivered both interventions at a university clinic. Primary outcome was depression severity, measured by BDI scores every 2 weeks from baseline to 8 weeks. Secondary outcomes were self-efficacy and self-esteem, measured by scores on the General Self-Efficacy Scale (GSES) and Rosenberg Self-Esteem Scale (RSES) at baseline and at 8 weeks. In intent-to-treat analysis, yoga participants exhibited significantly greater 8-week decline in BDI scores than controls (p-value = 0.034). In sub-analyses of participants completing final 8-week measures, yoga participants were more likely to achieve remission, defined per final BDI score ≤ 9 (p-value = 0.018). Effect size of yoga in reducing BDI scores was large, per Cohen's d = -0.96 [95%CI, -1.81 to -0.12]. Intervention groups did not differ significantly in 8-week change scores for either the GSES or RSES. In adults with mild-to-moderate major depression, an 8-week hatha yoga intervention resulted in statistically and clinically significant reductions in depression severity. ClinicalTrials.gov NCT01210651.

Six-month exercise training program to treat post-thrombotic syndrome: a randomized controlled two-centre trial

PubMed Central

Kahn, Susan R.; Shrier, Ian; Shapiro, Stan; Houweling, Adrielle H.; Hirsch, Andrew M.; Reid, Robert D.; Kearon, Clive; Rabhi, Khalil; Rodger, Marc A.; Kovacs, Michael J.; Anderson, David R.; Wells, Philip S.

2011-01-01

Background Exercise training may have the potential to improve post-thrombotic syndrome, a frequent, chronic complication of deep venous thrombosis. We conducted a randomized controlled two-centre pilot trial to assess the feasibility of a multicentre-based evaluation of a six-month exercise training program to treat post-thrombotic syndrome and to obtain preliminary data on the effectiveness of such a program. Methods Patients were randomized to receive exercise training (a six-month trainer-supervised program) or control treatment (an education session with monthly phone follow-ups). Levels of eligibility, consent, adherence and retention were used as indicators of study feasibility. Primary outcomes were change from baseline to six months in venous disease-specific quality of life (as measured using the Venous Insufficiency Epidemiological and Economic Study Quality of Life [VEINES-QOL] questionnaire) and severity of post-thrombotic syndrome (as measured by scores on the Villalta scale) in the exercise training group versus the control group, assessed by t tests. Secondary outcomes were change in generic quality of life (as measured using the Short-Form Health Survey-36 [SF-36] questionnaire), category of severity of post-thrombotic syndrome, leg strength, leg flexibility and time on treadmill. Results Of 95 patients with post-thrombotic syndrome, 69 were eligible, 43 consented and were randomized, and 39 completed the study. Exercise training was associated with improvement in VEINES-QOL scores (exercise training mean change 6.0, standard deviation [SD] 5.1 v. control mean change 1.4, SD 7.2; difference 4.6, 95% CI 0.54 to 8.7; p = 0.027) and improvement in scores on the Villalta scale (exercise training mean change −3.6, SD 3.7 v. control mean change −1.6, SD 4.3; difference −2.0, 95% CI −4.6 to 0.6; p = 0.14). Most secondary outcomes also showed greater improvement in the exercise training group. Interpretation Exercise training may improve post-thrombotic syndrome. It would be feasible to definitively evaluate exercise training as a treatment for post-thrombotic syndrome in a large multicentre trial. PMID:21098066

The PEDro scale had acceptably high convergent validity, construct validity, and interrater reliability in evaluating methodological quality of pharmaceutical trials.

PubMed

Yamato, Tie Parma; Maher, Chris; Koes, Bart; Moseley, Anne

2017-06-01

The Physiotherapy Evidence Database (PEDro) scale has been widely used to investigate methodological quality in physiotherapy randomized controlled trials; however, its validity has not been tested for pharmaceutical trials. The aim of this study was to investigate the validity and interrater reliability of the PEDro scale for pharmaceutical trials. The reliability was also examined for the Cochrane Back and Neck (CBN) Group risk of bias tool. This is a secondary analysis of data from a previous study. We considered randomized placebo controlled trials evaluating any pain medication for chronic spinal pain or osteoarthritis. Convergent validity was evaluated by correlating the PEDro score with the summary score of the CBN risk of bias tool. The construct validity was tested using a linear regression analysis to determine the degree to which the total PEDro score is associated with treatment effect sizes, journal impact factor, and the summary score for the CBN risk of bias tool. The interrater reliability was estimated using the Prevalence and Bias Adjusted Kappa coefficient and 95% confidence interval (CI) for the PEDro scale and CBN risk of bias tool. Fifty-three trials were included, with 91 treatment effect sizes included in the analyses. The correlation between PEDro scale and CBN risk of bias tool was 0.83 (95% CI 0.76-0.88) after adjusting for reliability, indicating strong convergence. The PEDro score was inversely associated with effect sizes, significantly associated with the summary score for the CBN risk of bias tool, and not associated with the journal impact factor. The interrater reliability for each item of the PEDro scale and CBN risk of bias tool was at least substantial for most items (>0.60). The intraclass correlation coefficient for the PEDro score was 0.80 (95% CI 0.68-0.88), and for the CBN, risk of bias tool was 0.81 (95% CI 0.69-0.88). There was evidence for the convergent and construct validity for the PEDro scale when used to evaluate methodological quality of pharmacological trials. Both risk of bias tools have acceptably high interrater reliability. Copyright © 2017 Elsevier Inc. All rights reserved.

Early Mobilization in Ischemic Stroke: A Pilot Randomized Trial of Safety and Feasibility in a Public Hospital in Brazil

PubMed Central

Poletto, Simone Rosa; Rebello, Letícia Costa; Valença, Maria Júlia Monteiro; Rossato, Daniele; Almeida, Andrea Garcia; Brondani, Rosane; Chaves, Márcia Lorena Fagundes; Nasi, Luiz Antônio; Martins, Sheila Cristina Ouriques

2015-01-01

Background The effect of early mobilization after acute stroke is still unclear, although some studies have suggested improvement in outcomes. We conducted a randomized, single-blind, controlled trial seeking to evaluate the feasibility, safety, and benefit of early mobilization for patients with acute ischemic stroke treated in a public teaching hospital in Southern Brazil. This report presents the feasibility and safety findings for the pilot phase of this trial. Methods The primary outcomes were time to first mobilization, total duration of mobilization, complications during early mobilization, falls within 3 months, mortality within 3 months, and medical complications of immobility. We included adult patients with CT- or MRI-confirmed ischemic stroke within 48 h of symptom onset who were admitted from March to November 2012 to the acute vascular unit or general emergency unit of a large urban emergency department (ED) at the Hospital de Clínicas de Porto Alegre. The severity of the neurological deficit on admission was assessed by the National Institutes of Health Stroke Scale (NIHSS). The NIHSS and modified Rankin Scale (mRS, functional outcome) scores were assessed on day 14 or at discharge as well as at 3 months. Activities of daily living (ADL) were measured with the modified Barthel Index (mBI) at 3 months. Results Thirty-seven patients (mean age 65 years, mean NIHSS score 11) were randomly allocated to an intervention group (IG) or a control group (CG). The IG received earlier (p = 0.001) and more frequent (p < 0.0001) mobilization than the CG. Of the 19 patients in the CG, only 5 (26%) underwent a physical therapy program during hospitalization. No complications (symptomatic hypotension or worsening of neurological symptoms) were observed in association with early mobilization. The rates of complications of immobility (pneumonia, pulmonary embolism, and deep vein thrombosis) and mortality were similar in the two groups. No statistically significant differences in functional independence, disability, or ADL (mBI ≥85) were observed between the groups at the 3-month follow-up. Conclusions This pilot trial conducted at a public hospital in Brazil suggests that early mobilization after acute ischemic stroke is safe and feasible. Despite some challenges and limitations, early mobilization was successfully implemented, even in the setting of a large, complex ED, and without complications. Patients from the IG were mobilized much earlier than controls receiving the standard care provided in most Brazilian hospitals. PMID:26034487

Lack of adjunctive benefit of Er:YAG laser in non-surgical periodontal treatment: a randomized split-mouth clinical trial.

PubMed

Rotundo, Roberto; Nieri, Michele; Cairo, Francesco; Franceschi, Debora; Mervelt, Jana; Bonaccini, Daniele; Esposito, Marco; Pini-Prato, Giovanpaolo

2010-06-01

This split-mouth, randomized, clinical trial aimed to evaluate the efficacy of erbium-doped:yttrium-aluminium-garnet (Er:YAG) laser application in non-surgical periodontal treatment. A total of 27 patients underwent four modalities of non-surgical therapy: supragingival debridement; scaling and root planing (SRP)+Er:YAG laser; Er:YAG laser; and SRP. Each strategy was randomly assigned and performed in one of the four quadrants. Clinical outcomes were evaluated at 3 and 6 months. Subjective benefits of patients have been evaluated by means of questionnaires. Six months after therapy, Er:YAG laser showed no statistical difference in clinical attachment gain with respect to supragingival scaling [0.15 mm (95% CI -0.16; 0.46)], while SRP showed a greater attachment gain than the supragingival scaling [0.37 mm (95% CI 0.05; 0.68)]. No difference resulted between Er:YAG laser+SRP and SRP alone [0.05 mm (95% CI -0.25; 0.36)]. The adjunctive use of Er:YAG laser to conventional SRP did not reveal a more effective result than SRP alone. Furthermore, the sites treated with Er:YAG laser showed similar results of the sites treated with supragingival scaling.

Clinical Perspectives of Genetic Analyses on Dyslipidemia and Coronary Artery Disease

PubMed Central

Kawashiri, Masa-aki; Yamagishi, Masakazu

2017-01-01

We have learned that low-density lipoprotein (LDL) cholesterol is the cause of atherosclerosis from various aspects, including a single case with familial hypercholesterolemia, other cases with different types of Mendelian dyslipidemias, large-scale randomized controlled trials using LDL cholesterol lowering therapies, and Mendelian randomization studies using common as well as rare variants associated with LDL cholesterol levels. There is no doubt that determinations of genotypes in lipid-associated genes have contributed not only to the genetic diagnosis for Mendelian dyslipidemias but also to the discoveries of novel therapeutic targets. Furthermore, recent studies have shown that such genetic information could provide useful clues for the risk prediction as well as risk stratification in general and in particular population. We provide the current understanding of genetic analyses relating to plasma lipids and coronary artery disease. PMID:28250266

Strengthening of the Hip and Core Versus Knee Muscles for the Treatment of Patellofemoral Pain: A Multicenter Randomized Controlled Trial

PubMed Central

Ferber, Reed; Bolgla, Lori; Earl-Boehm, Jennifer E.; Emery, Carolyn; Hamstra-Wright, Karrie

2015-01-01

Context: Patellofemoral pain (PFP) is the most common injury in running and jumping athletes. Randomized controlled trials suggest that incorporating hip and core strengthening (HIP) with knee-focused rehabilitation (KNEE) improves PFP outcomes. However, no randomized controlled trials have, to our knowledge, directly compared HIP and KNEE programs. Objective: To compare PFP pain, function, hip- and knee-muscle strength, and core endurance between KNEE and HIP protocols after 6 weeks of rehabilitation. We hypothesized greater improvements in (1) pain and function, (2) hip strength and core endurance for patients with PFP involved in the HIP protocol, and (3) knee strength for patients involved in the KNEE protocol. Design: Randomized controlled clinical trial. Setting: Four clinical research laboratories in Calgary, Alberta; Chicago, Illinois; Milwaukee, Wisconsin; and Augusta, Georgia. Patients or Other Participants: Of 721 patients with PFP screened, 199 (27.6%) met the inclusion criteria (66 men [31.2%], 133 women [66.8%], age = 29.0 ± 7.1 years, height = 170.4 ± 9.4 cm, weight = 67.6 ± 13.5 kg). Intervention(s): Patients with PFP were randomly assigned to a 6-week KNEE or HIP protocol. Main Outcome Measure(s): Primary variables were self-reported visual analog scale and Anterior Knee Pain Scale measures, which were conducted weekly. Secondary variables were muscle strength and core endurance measured at baseline and at 6 weeks. Results: Compared with baseline, both the visual analog scale and the Anterior Knee Pain Scale improved for patients with PFP in both the HIP and KNEE protocols (P < .001), but the visual analog scale scores for those in the HIP protocol were reduced 1 week earlier than in the KNEE group. Both groups increased in strength (P < .001), but those in the HIP protocol gained more in hip-abductor (P = .01) and -extensor (P = .01) strength and posterior core endurance (P = .05) compared with the KNEE group. Conclusions: Both the HIP and KNEE rehabilitation protocols produced improvements in PFP, function, and strength over 6 weeks. Although outcomes were similar, the HIP protocol resulted in earlier resolution of pain and greater overall gains in strength compared with the KNEE protocol. PMID:25365133

Mindfulness-based stress reduction for treating chronic headache: A systematic review and meta-analysis.

PubMed

Anheyer, Dennis; Leach, Matthew J; Klose, Petra; Dobos, Gustav; Cramer, Holger

2018-01-01

Background Mindfulness-based stress reduction/cognitive therapy are frequently used for pain-related conditions, but their effects on headache remain uncertain. This review aimed to assess the efficacy and safety of mindfulness-based stress reduction/cognitive therapy in reducing the symptoms of chronic headache. Data sources and study selection MEDLINE/PubMed, Scopus, CENTRAL, and PsychINFO were searched to 16 June 2017. Randomized controlled trials comparing mindfulness-based stress reduction/cognitive therapy with usual care or active comparators for migraine and/or tension-type headache, which assessed headache frequency, duration or intensity as a primary outcome, were eligible for inclusion. Risk of bias was assessed using the Cochrane Tool. Results Five randomized controlled trials (two on tension-type headache; one on migraine; two with mixed samples) with a total of 185 participants were included. Compared to usual care, mindfulness-based stress reduction/cognitive therapy did not improve headache frequency (three randomized controlled trials; standardized mean difference = 0.00; 95% confidence interval = -0.33,0.32) or headache duration (three randomized controlled trials; standardized mean difference = -0.08; 95% confidence interval = -1.03,0.87). Similarly, no significant difference between groups was found for pain intensity (five randomized controlled trials; standardized mean difference = -0.78; 95% confidence interval = -1.72,0.16). Conclusions Due to the low number, small scale and often high or unclear risk of bias of included randomized controlled trials, the results are imprecise; this may be consistent with either an important or negligible effect. Therefore, more rigorous trials with larger sample sizes are needed.

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.

Guided Web-Based Cognitive Behavior Therapy for Perfectionism: Results From Two Different Randomized Controlled Trials.

PubMed

Rozental, Alexander; Shafran, Roz; Wade, Tracey D; Kothari, Radha; Egan, Sarah J; Ekberg, Linda; Wiss, Maria; Carlbring, Per; Andersson, Gerhard

2018-04-26

Perfectionism can become a debilitating condition that may negatively affect functioning in multiple areas, including mental health. Prior research has indicated that internet-based cognitive behavioral therapy can be beneficial, but few studies have included follow-up data. The objective of this study was to explore the outcomes at follow-up of internet-based cognitive behavioral therapy with guided self-help, delivered as 2 separate randomized controlled trials conducted in Sweden and the United Kingdom. In total, 120 participants randomly assigned to internet-based cognitive behavioral therapy were included in both intention-to-treat and completer analyses: 78 in the Swedish trial and 62 in the UK trial. The primary outcome measure was the Frost Multidimensional Perfectionism Scale, Concern over Mistakes subscale (FMPS CM). Secondary outcome measures varied between the trials and consisted of the Clinical Perfectionism Questionnaire (CPQ; both trials), the 9-item Patient Health Questionnaire (PHQ-9; Swedish trial), the 7-item Generalized Anxiety Disorder scale (GAD-7; Swedish trial), and the 21-item Depression Anxiety Stress Scale (DASS-21; UK trial). Follow-up occurred after 6 months for the UK trial and after 12 months for the Swedish trial. Analysis of covariance revealed a significant difference between pretreatment and follow-up in both studies. Intention-to-treat within-group Cohen d effect sizes were 1.21 (Swedish trial; 95% CI 0.86-1.54) and 1.24 (UK trial; 95% CI 0.85-1.62) for the FMPS CM. Furthermore, 29 (59%; Swedish trial) and 15 (43%; UK trial) of the participants met the criteria for recovery on the FMPS CM. Improvements were also significant for the CPQ, with effect sizes of 1.32 (Swedish trial; 95% CI 0.97-1.66) and 1.49 (UK trial; 95% CI 1.09-1.88); the PHQ-9, effect size 0.60 (95% CI 0.28-0.92); the GAD-7, effect size 0.67 (95% CI 0.34-0.99); and the DASS-21, effect size 0.50 (95% CI 0.13-0.85). The results are promising for the use of internet-based cognitive behavioral therapy as a way of targeting perfectionism, but the findings need to be replicated and include a comparison condition. ©Alexander Rozental, Roz Shafran, Tracey D Wade, Radha Kothari, Sarah J Egan, Linda Ekberg, Maria Wiss, Per Carlbring, Gerhard Andersson. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 26.04.2018.

Effect of Home Care Nursing on Patients Discharged From Hospital With Self-Reported Signs of Constipation: A Randomized Trial.

PubMed

Konradsen, Hanne; Rasmussen, Marie Louise Thiese; Noiesen, Eline; Trosborg, Ingelise

Constipation is a common health problem in relation to hospitalization. This randomized controlled trial aimed to investigate whether advice from a home care nurse after discharge had an effect on self-reported signs of constipation. A total of 59 patients were included in the study on the basis of their self-reported signs of constipation evaluated using the Constipation Assessment Scale. Advice from the home care nurses was given on the intake of fiber and liquid and mobilization related to scorings on the Constipation Risk Assessment Scale, the administration of laxatives, and referral to a physician when needed. Results showed a tendency toward the visits being effective, but a more complex intervention might be needed.

Effect of acupuncture and its influence on visceral hypersensitivity in IBS-D patients: Study protocol for a randomized controlled trial.

PubMed

Pei, Lixia; Chen, Hao; Guo, Jing; Chen, Lu; Wu, Xiaoliang; Xu, Wanli; Weng, Shengjie; Yang, EunMee; Hammer, Trine; Sun, Jianhua

2018-05-01

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder associated with visceral hypersensitivity. Increased expression of colonic TRPV1 and decreased expression of microRNA-199 are implicated in the pathogenesis of visceral hypersensitivity in IBS-D patients. Acupuncture is one of the frequently used complementary and alternative therapies for the treatment of IBS. The existing clinical studies mostly use IBS-SSS or other subjective scales, so there is a lack of objective biochemical evidence regarding the effect of acupuncture on IBS. Therefore, we designed this study to investigate whether acupuncture alleviate visceral hypersensitivity by influencing the expression of TRPV1 and microRNA-199. This study is a randomized, sham-controlled trial involving 40 patients and 10 healthy volunteers. A total of 40 eligible patients with IBS-D will be randomly assigned to a traditional acupuncture group or sham acupuncture group in a 1:1 ratio. Patients will receive 3 acupuncture treatment sessions per week for 12 consecutive weeks, for a total of 36 sessions during the study. The primary outcome measure is the IBS-Symptom Severity Score (IBS-SSS). Secondary outcomes are Visceral Pain Scale and levels of TRPV1 and microRNA-199 in colonic tissues. Healthy volunteers will not receive any clinical intervention. The safety of interventions will be assessed at every visit. The purpose of this trial is to evaluate the efficacy of acupuncture for IBS-D through IBS-SSS and Visceral Pain Scale. Furthermore, we want to explore the intervention mechanism of acupuncture in improving visceral hypersensitivity by analyzing the colonic TRPV1 and microRNA-199. This trial is registered with Chinese Clinical Trials Register, ChiCTR-IOR- 17010860(http://www.chictr.org.cn/showproj.aspx?proj=18445).

Efficacy and safety of acupuncture for chronic dizziness: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Dizziness is one of the most challenging symptoms in medicine. No medication for dizziness in current use has well-established curative or prophylactic value or is suitable for long-term palliative use. Unconventional remedies, such as acupuncture, should be considered and scientifically evaluated. However, there has been relatively little evidence in randomized controlled clinical trials on acupuncture to treat chronic dizziness. The aim of our study is to evaluate the efficacy and safety of acupuncture in patients with dizziness. Methods/Design This trial is a randomized, single-blind, controlled study. A total of 80 participants will be randomly assigned to two treatment groups receiving acupuncture and sham acupuncture treatment, respectively, for 4 weeks. The primary outcome measures are the Dizziness Handicap Inventory (DHI) and the Vertigo Symptom Scale (VSS). Treatment will be conducted over a period of 4 weeks, at a frequency of two sessions per week. The assessment is at baseline (before treatment initiation), 4 weeks after the first acupuncture session, and 8 weeks after the first acupuncture session. Discussion The results from this study will provide clinical evidence on the efficacy and safety of acupuncture in patients with chronic dizziness. Trial registration International Standard Randomized Controlled Trial Number Register: ISRCTN52695239 PMID:24330810

An evaluation of biodegradable synthetic polyurethane foam in patients following septoplasty: a prospective randomized trial.

PubMed

Yilmaz, Mahmut Sinan; Guven, Mehmet; Elicora, Sultan Sevik; Kaymaz, Recep

2013-01-01

The purpose of this study is to examine the usability of biodegradable synthetic polyurethane foam (BSPF) after septoplasty by comparing it with Merocel and silicone intranasal splints as packing materials in terms of patient comfort and efficiency. A prospective, unmasked, randomized trial. A tertiary referral center. This study was designed to be a prospective, randomized clinical trial. Sixty-eight patients who underwent septoplasty were included in this study. The patients were randomized to receive Merocel, silicone intranasal septal splint (INS), or BSPF after septoplasty. Clinical efficacy on bleeding, pain, and subjective symptoms related to packing materials was evaluated. There was a statistically significant difference between the Merocel group and the other 2 groups in terms of bleeding and adhesion. The average score on the pain scale was 2.47 ± 1.01 for BSPF, 3.68 ± 1.27 for INS, and 6 ± 2.21 for Merocel. Scores on general satisfaction scales were 6.95 ± 1.42 for Merocel, 8.44 ± 2.12 for INS, and 8.28 ± 1.88 for BSPF. The efficacy of BSPF was comparable with that of Merocel and INS. Biodegradable synthetic polyurethane foam significantly reduced pain and patient discomfort during packing and removal, followed by INS, compared with Merocel.

Improving health and productivity of depressed workers: a pilot randomized controlled trial of telephone cognitive behavioral therapy delivery in workplace settings.

PubMed

Bee, Penny E; Bower, Peter; Gilbody, Simon; Lovell, Karina

2010-01-01

To examine the feasibility of telephone-delivered cognitive behavioral therapy (T-CBT) in an occupational context, with reference to participant recruitment, treatment adherence, follow-up and effect. Eligible participants comprised all employees of a large communications company with authorized work absence due to mild/moderate mental health difficulties over a 10-month period. Fifty-three consenting participants were centrally randomized to 12 weeks T-CBT or usual care, with minimization on age, gender and illness severity. Primary (symptom severity) and secondary outcomes (self-rated work performance and productivity) were measured at baseline and 3-months via postal questionnaires. Intention-to-treat analysis comprised multiple regression modeling with adjustment for missing response predictors, minimization variables and baseline values. Twenty-three employees attended one or more T-CBT sessions. T-CBT was associated with medium-large effects sizes on clinical outcomes (0.63-0.77) and work productivity scores (0.75-0.88). Twenty-one patients failed to return 3-month primary outcome data. Non-respondents were more likely to be male and more severely ill. Delivery of T-CBT in an occupational context is feasible with evidence of potential effect. Larger-scale trials are warranted. These studies demand assertive outreach or telephone-based assessment strategies in order to maximize participant recruitment and follow-up. Copyright 2010 Elsevier Inc. All rights reserved.

The efficacy and safety of Jiedu Tongluo granules for treating post-stroke depression with qi deficiency and blood stasis syndrome: study protocol for a randomized controlled trial.

PubMed

Zhao, Ai-Mei; Qiu, Wen-Ran; Mao, Li-Jun; Ren, Jun-Guo; Xu, Li; Yao, Ming-Jiang; Bilinksi, Kellie; Chang, Dennis; Liu, Jian-Xun

2018-05-10

Post-stroke depression (PSD) is the most common psychiatric complication after a stroke. The most frequently used antidepressants are selective serotonin receptor inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), however, these exhibit a series of side effects. Traditional Chinese medicine has been used to treat PSD with few side effects. The aim of this study is to evaluate the efficacy and safety of Jiedu Tongluo granules for treating PSD with qi deficiency and blood stasis syndrome. The planned study is a double-blind, randomized, placebo-controlled pilot trial. Eighty participants will be randomly assigned to receive either treatment or placebo. The treatment group will receive Jiedu Tongluo granules (JDTLG) with conventional treatment, and the placebo group will receive placebo with conventional treatment for 8 weeks. The primary outcome is the effectiveness of JDTLG on depression after 8 weeks treatment, which is defined as a decrease of 50% or more in 17-item Hamilton Depression Scale (HAMD-17) score or clinical recovery (score < 7). Secondary outcomes are improvement in neurological function, degree of independence, activities of daily living, and TCM syndrome at each visit, which will be measured with National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), Barthel Index (BI) and TCM scale, respectively. Interleukin (IL)-6, IL-8, and small-molecule metabolites will be monitored to explore the mechanism of action of JDTLG on PSD. Safety measures include vital signs, results of electrocardiography, laboratory index (full blood count, kidney and liver function tests) and adverse events. The purpose of this trial is to evaluate the therapeutic effects and safety of JDTLG in individuals with PSD with concomitant qi deficiency and blood stasis syndrome. If successful, the outcome of this trial will provide a viable treatment option for PSD patients. ClinicalTrials.gov ID: NCT03147053 . Registered on 27 April 2017.

Rationale and design of A Trial of Sertraline vs. Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression (ASCEND).

PubMed

Hedayati, S Susan; Daniel, Divya M; Cohen, Scott; Comstock, Bryan; Cukor, Daniel; Diaz-Linhart, Yaminette; Dember, Laura M; Dubovsky, Amelia; Greene, Tom; Grote, Nancy; Heagerty, Patrick; Katon, Wayne; Kimmel, Paul L; Kutner, Nancy; Linke, Lori; Quinn, Davin; Rue, Tessa; Trivedi, Madhukar H; Unruh, Mark; Weisbord, Steven; Young, Bessie A; Mehrotra, Rajnish

2016-03-01

Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343), A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes. Published by Elsevier Inc.

Rationale and Design of A Trial of Sertraline vs. Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression (ASCEND)

PubMed Central

Hedayati, S. Susan; Daniel, Divya M.; Cohen, Scott; Comstock, Bryan; Cukor, Daniel; Diaz-Linhart, Yaminette; Dember, Laura M.; Dubovsky, Amelia; Greene, Tom; Grote, Nancy; Heagerty, Patrick; Katon, Wayne; Kimmel, Paul L.; Kutner, Nancy; Linke, Lori; Quinn, Davin; Rue, Tessa; Trivedi, Madhukar H.; Unruh, Mark; Weisbord, Steven; Young, Bessie A.; Mehrotra, Rajnish

2015-01-01

Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343), A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes. PMID:26621218

PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial.

PubMed

de Ridder, Inger R; den Hertog, Heleen M; van Gemert, H Maarten A; Schreuder, A H C M L Tobien; Ruitenberg, Annemieke; Maasland, E Lisette; Saxena, Ritu; van Tuijl, Jordie H; Jansen, Ben P W; Van den Berg-Vos, Renske M; Vermeij, Frederique; Koudstaal, Peter J; Kappelle, L Jaap; Algra, Ale; van der Worp, H Bart; Dippel, Diederik W J

2017-04-01

Subfebrile body temperature and fever in the first days after stroke are strongly associated with unfavorable outcome. A subgroup analysis of a previous trial suggested that early treatment with paracetamol may improve functional outcome in patients with acute stroke and a body temperature of ≥36.5°C. In the present trial, we aimed to confirm this finding. PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2) was a multicenter, randomized, double-blind, placebo-controlled clinical trial. We aimed to include 1500 patients with acute ischemic stroke or intracerebral hemorrhage within 12 hours of symptom onset. Patients were treated with paracetamol in a daily dose of 6 g or matching placebo for 3 consecutive days. The primary outcome was functional outcome at 3 months, assessed with the modified Rankin Scale and analyzed with multivariable ordinal logistic regression. Because of slow recruitment and lack of funding, the study was stopped prematurely. Between December 2011 and October 2015, we included 256 patients, of whom 136 (53%) were allocated to paracetamol. In this small sample, paracetamol had no effect on functional outcome (adjusted common odds ratio, 1.15; 95% confidence interval, 0.74-1.79). There was no difference in the number of serious adverse events (paracetamol n=35 [26%] versus placebo n=28 [24%]). Treatment with high-dose paracetamol seemed to be safe. The effect of high-dose paracetamol on functional outcome remains uncertain. Therefore, a large trial of early treatment with high-dose paracetamol is still needed. URL: http://www.trialregister.nl. Unique identifier: NTR2365. © 2017 American Heart Association, Inc.

InsuOnline, a Serious Game to Teach Insulin Therapy to Primary Care Physicians: Design of the Game and a Randomized Controlled Trial for Educational Validation.

PubMed

Diehl, Leandro Arthur; Souza, Rodrigo Martins; Alves, Juliano Barbosa; Gordan, Pedro Alejandro; Esteves, Roberto Zonato; Jorge, Maria Lúcia Silva Germano; Coelho, Izabel Cristina Meister

2013-01-21

Physicians´ lack of knowledge contributes to underuse of insulin and poor glycemic control in adults with diabetes mellitus (DM). Traditional continuing medical education have limited efficacy, and new approaches are required. We report the design of a trial to assess the educational efficacy of InsuOnline, a game for education of primary care physicians (PCPs). The goal of InsuOnline was to improve appropriate initiation and adjustment of insulin for the treatment of DM. InsuOnline was designed to be educationally adequate, self-motivating, and attractive. A multidisciplinary team of endocrinologists, experts in medical education, and programmers, was assembled for the design and development of InsuOnline. Currently, we are conducting usability and playability tests, with PCPs and medical students playing the game on a desktop computer. Adjustments will be made based on these results. An unblinded randomized controlled trial with PCPs who work in the city of Londrina, Brazil, will be conducted to assess the educational validity of InsuOnline on the Web. In this trial, 64 PCPs will play InsuOnline, and 64 PCPs will undergo traditional instructional activities (lecture and group discussion). Knowledge on how to initiate and adjust insulin will be assessed by a Web-based multiple choice questionnaire, and attitudes regarding diabetes/insulin will be assessed by Diabetes Attitude Scale 3 at 3 time points-before, immediately after, and 6 months after the intervention. Subjects´ general impressions on the interventions will be assessed by a questionnaire. Software logs will be reviewed. To our knowledge, this is the first research with the aim of assessing the educational efficacy of a computer game for teaching PCPs about insulin therapy in DM. We describe the development criteria used for creating InsuOnline. Evaluation of the game using a randomized controlled trial design will be done in future studies. We demonstrated that the design and development of a game for PCPs education on insulin is possible with a multidisciplinary team. InsuOnline can be an attractive option for large-scale continuous medical education to help improving PCPs´ knowledge on insulin therapy and potentially improving DM patients´ care. Clinicaltrials.gov: NCT01759953; http://clinicaltrials.gov/show/NCT01759953 (Archived by WebCite at http://www.webcitation.org/6Dq8Vc7a6).

Venlafaxine versus methylphenidate in pediatric outpatients with attention deficit hyperactivity disorder: a randomized, double-blind comparison trial.

PubMed

Zarinara, Ali-Reza; Mohammadi, Mohammad-Reza; Hazrati, Nazanin; Tabrizi, Mina; Rezazadeh, Shams-Ali; Rezaie, Farzin; Akhondzadeh, Shahin

2010-11-01

The present report aimed to investigate the efficacy and tolerability of venlafaxine compared to methylphenidate in children and adolescents with Attention Deficit/Hyperactivity Disorder (ADHD). This was a 6-week, parallel group, randomized clinical trial. Thirty-eight patients (27 boys and 11 girls) with a DSM-IV-TR diagnosis of ADHD were the study population of this trial. All study subjects were randomly assigned to receive treatment using capsules of venlafaxine at doses of 50-75 mg/day depending on weight (50 mg/day for <30 kg and 75 mg/day for >30 kg (group 1) or methylphenidate at a dose of 20-30 mg/day depending on weight (group 2) for a 6-week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent Attention Deficit/Hyperactivity Disorder Rating Scale-IV. No significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores (df = 1; F = 1.77; p = 0.19 and df = 1; F = 1.64; p = 0.20, respectively). Side effects of headaches and insomnia were observed more frequently in the methylphenidate group. The results suggest that venlafaxine may be useful for the treatment of ADHD. In addition, a tolerable side-effect profile is one of the advantages of venlafaxine in the treatment of ADHD. Copyright © 2010 John Wiley & Sons, Ltd.

Amantadine versus methylphenidate in children and adolescents with attention deficit/hyperactivity disorder: a randomized, double-blind trial.

PubMed

Mohammadi, Mohammad-Reza; Kazemi, Mohammad-Reza; Zia, Ebtehal; Rezazadeh, Shams-Ali; Tabrizi, Mina; Akhondzadeh, Shahin

2010-11-01

The aim of the present study was to further evaluate, under double blind and controlled conditions, the efficacy of amantadine for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents as compared to methylphenidate. This was a 6-week randomized clinical trial. Forty patients (28 boys and 12 girls) with a DSM-IV-TR diagnosis of ADHD were the study population of this trial. All study subjects were randomly assigned to receive the treatment using capsule of amantadine at a dose of 100-150 mg/day depending on weight (100 mg/day for <30 kg and 150 mg/day for >30 kg) or methylphenidate at a dose of 20-30 mg/day for a 6-week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent Attention deficit/hyperactivity disorder Rating Scale-IV. No significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores (df = 1; F = 0.02; p = 0.86 and df = 1; F = 0.01; p = 0.89, respectively). Side effects of decreased appetite and restlessness were observed more frequently in the methylphenidate group. The results of this study indicate that amantadine significantly improved symptoms of ADHD and was well tolerated and it may be beneficial in the treatment of children with ADHD. Nevertheless, the present results do not constitute proof of efficacy. Copyright © 2010 John Wiley & Sons, Ltd.

Effects of a Herbal Medicine, Yukgunja-Tang, on Functional Dyspepsia Patients Classified by 3-Dimensional Facial Measurement: A Study Protocol for Placebo-Controlled, Double-Blind, Randomized Trial.

PubMed

Kim, Juyeon; Park, Jae-Woo; Ko, Seok-Jae; Jeon, Soo-Hyung; Kim, Jong-Won; Yeo, Inkwon; Kim, Jinsung

2017-01-01

Introduction . Functional dyspepsia (FD), a common upper gastrointestinal disease, is difficult to manage because of the limitations of current conventional treatments. Yukgunja-tang (YGJT) is widely used to treat FD in clinical practice in Korea, Japan, and China. However, YGJT significantly improves few symptoms of FD. In Korean medicine, FD is a well-known functional gastric disease that shows difference in the effect of herbal medicine depending on constitution or type of Korean medicine diagnosis. This study aims to investigate the efficacy of YGJT on FD patients classified by 3-dimensional facial measurement using a 3-dimensional facial shape diagnostic system (3-FSDS). Methods . A placebo-controlled, double-blind, randomized, two-center trial will be performed to evaluate the efficacy of YGJT on FD patients. Eligible subjects will be initially classified as two types by 3-dimensional facial measurement using the 3-FSDS. Ninety-six subjects (48 subjects per each type) will be enrolled. These subjects will be randomly allocated into treatment or control groups in a 2 : 1 ratio. YGJT or placebo will be administered to each group during the 8-week treatment period. The primary outcome is total dyspepsia symptom scale, and the secondary outcomes include single dyspepsia symptom scale, proportion of responders with adequate symptom relief, visual analog scale, Nepean dyspepsia index-Korean version, functional dyspepsia-related quality of life, and spleen qi deficiency questionnaire. Discussion . This is the first randomized controlled trial to assess the efficacy of the YGJT on FD patients classified by 3-dimensional facial measurement. We will compare the treatment effect of the YGJT on FD patients classified as two types using the 3-FSDS. The results of this trial will help the FD patients improve the symptoms and quality of life effectively and provide objective evidence for prescribing the YGJT to FD patients in clinical practice. Trial Registration . This trial is registered with Clinical Research Information Service Identifier: KCT0001920, 15 May, 2016.

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.

Ketamine rapidly relieves acute suicidal ideation in cancer patients: a randomized controlled clinical trial.

PubMed

Fan, Wei; Yang, HaiKou; Sun, Yong; Zhang, Jun; Li, Guangming; Zheng, Ying; Liu, Yi

2017-01-10

This study was designed to examine the rapid antidepressant effects of single dose ketamine on suicidal ideation and overall depression level in patients with newly-diagnosed cancer. Forty-two patients were enrolled into the controlled trial and randomized into two groups: ketamine group and midazolam group. Patients from the two groups received a sub-anesthetic dose of racemic ketamine hydrochloride or midazolam. Suicidal ideation score, measured with the Beck Scale and suicidal part of the Montgomery-Asberg Depression Rating Scale, significantly decreased on day 1 and day 3 in ketamine-treated patients when compared to those treated with midazolam. Consistently, overall depression levels measured using the Montgomery-Asberg Depression Rating Scale indicated a significant relief of overall depression on day 1 in ketamine-treated patients. Collectively, this study provides novel information about the rapid antidepressant effect of ketamine on acute depression and suicidal ideation in newly-diagnosed cancer patients.

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

PubMed

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

2014-11-20

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

Yoga vs. physical therapy vs. education for chronic low back pain in predominantly minority populations: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Chronic low back pain causes substantial morbidity and cost to society while disproportionately impacting low-income and minority adults. Several randomized controlled trials show yoga is an effective treatment. However, the comparative effectiveness of yoga and physical therapy, a common mainstream treatment for chronic low back pain, is unknown. Methods/Design This is a randomized controlled trial for 320 predominantly low-income minority adults with chronic low back pain, comparing yoga, physical therapy, and education. Inclusion criteria are adults 18–64 years old with non-specific low back pain lasting ≥12 weeks and a self-reported average pain intensity of ≥4 on a 0–10 scale. Recruitment takes place at Boston Medical Center, an urban academic safety-net hospital and seven federally qualified community health centers located in diverse neighborhoods. The 52-week study has an initial 12-week Treatment Phase where participants are randomized in a 2:2:1 ratio into i) a standardized weekly hatha yoga class supplemented by home practice; ii) a standardized evidence-based exercise therapy protocol adapted from the Treatment Based Classification method, individually delivered by a physical therapist and supplemented by home practice; and iii) education delivered through a self-care book. Co-primary outcome measures are 12-week pain intensity measured on an 11-point numerical rating scale and back-specific function measured using the modified Roland Morris Disability Questionnaire. In the subsequent 40-week Maintenance Phase, yoga participants are re-randomized in a 1:1 ratio to either structured maintenance yoga classes or home practice only. Physical therapy participants are similarly re-randomized to either five booster sessions or home practice only. Education participants continue to follow recommendations of educational materials. We will also assess cost effectiveness from the perspectives of the individual, insurers, and society using claims databases, electronic medical records, self-report cost data, and study records. Qualitative data from interviews will add subjective detail to complement quantitative data. Trial registration This trial is registered in ClinicalTrials.gov, with the ID number: NCT01343927. PMID:24568299

Effects of levosimendan on mortality in patients undergoing cardiac surgery: A systematic review and meta-analysis.

PubMed

Chen, Peili; Wu, Xiaoqiang; Wang, Zhiwei; Li, Zhenya; Tian, Xiangyong; Wang, Junpeng; Yan, Tianzhong

2018-06-01

We sought to determine the impact of levosimendan on mortality following cardiac surgery based on large-scale randomized controlled trials (RCTs). We searched PubMed, Web of Science, Cochrane databases, and ClinicalTrials.gov for RCTs published up to December 2017, on levosimendan for patients undergoing cardiac surgery. A total of 25 RCTs enrolling 2960 patients met the inclusion criteria; data from 15 placebo-controlled randomized trials were included for meta-analysis. Pooled analysis showed that the all-cause mortality rate was 6.4% (71 of 1106) in the levosimendan group and 8.4% (93 of 1108) in the placebo group (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.55-1.04; P = 0.09). There were no significant differences between the two groups in the rates of myocardial infarction (OR: 0.91; 95% CI, 0.68-1.21; P = 0.52), serious adverse events (OR: 0.84; 95% CI, 0.66-1.07; P = 0.17), hypotension (OR: 1.69; 95% CI, 0.94-3.03; P = 0.08), and low cardiac output syndrome (OR: 0.47; 95% CI, 0.22-1.02; P = 0.05). Levosimendan did not result in a reduction in mortality in adult cardiac surgery patients. Well designed, adequately powered, multicenter trials are necessary to determine the role of levosimendan in adult cardiac surgery. © 2018 The Authors. Journal of Cardiac Surgery Published by Wiley Periodicals Inc.

Direct to Public Peer Support and e-Therapy Program Versus Information to Aid Self-Management of Depression and Anxiety: Protocol for a Randomized Controlled Trial.

PubMed

Kaylor-Hughes, Catherine J; Rawsthorne, Mat; Coulson, Neil S; Simpson, Sandra; Simons, Lucy; Guo, Boliang; James, Marilyn; Moran, Paul; Simpson, Jayne; Hollis, Chris; Avery, Anthony J; Tata, Laila J; Williams, Laura; Morriss, Richard K

2017-12-18

Regardless of geography or income, effective help for depression and anxiety only reaches a small proportion of those who might benefit from it. The scale of the problem suggests a role for effective, safe, anonymized public health-driven Web-based services such as Big White Wall (BWW), which offer immediate peer support at low cost. Using Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) methodology, the aim of this study was to determine the population reach, effectiveness, cost-effectiveness, and barriers and drivers to implementation of BWW compared with Web-based information compiled by UK's National Health Service (NHS, NHS Choices Moodzone) in people with probable mild to moderate depression and anxiety disorder. A pragmatic, parallel-group, single-blind randomized controlled trial (RCT) is being conducted using a fully automated trial website in which eligible participants are randomized to receive either 6 months access to BWW or signposted to the NHS Moodzone site. The recruitment of 2200 people to the study will be facilitated by a public health engagement campaign involving general marketing and social media, primary care clinical champions, health care staff, large employers, and third sector groups. People will refer themselves to the study and will be eligible if they are older than 16 years, have probable mild to moderate depression or anxiety disorders, and have access to the Internet. The primary outcome will be the Warwick-Edinburgh Mental Well-Being Scale at 6 weeks. We will also explore the reach, maintenance, cost-effectiveness, and barriers and drivers to implementation and possible mechanisms of actions using a range of qualitative and quantitative methods. This will be the first fully digital trial of a direct to public online peer support program for common mental disorders. The potential advantages of adding this to current NHS mental health services and the challenges of designing a public health campaign and RCT of two digital interventions using a fully automated digital enrollment and data collection process are considered for people with depression and anxiety. International Standard Randomized Controlled Trial Number (ISRCTN): 12673428; http://www.controlled-trials.com/ISRCTN12673428/12673428 (Archived by WebCite at http://www.webcitation.org/6uw6ZJk5a). ©Catherine J Kaylor-Hughes, Mat Rawsthorne, Neil S Coulson, Sandra Simpson, Lucy Simons, Boliang Guo, Marilyn James, Paul Moran, Jayne Simpson, Chris Hollis, Anthony J Avery, Laila J Tata, Laura Williams, REBOOT Notts Lived Experience Advisory Panel, Richard K Morriss. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 18.12.2017.

Cost analysis of PET and comprehensive lifestyle modification for the reversal of atherosclerosis.

PubMed

Delgado, Rigoberto I; Swint, J Michael; Lairson, David R; Johnson, Nils P; Gould, K Lance; Sdringola, Stefano

2014-01-01

We present a preliminary cost analysis of a combination intervention using PET and comprehensive lifestyle modification to reverse atherosclerosis. With a sensitivity of 92%-95% and specificity of 85%-95%, PET is an essential tool for high-precision diagnosis of coronary artery disease, accurately guiding optimal treatment for both symptomatic and asymptomatic patients. PET imaging provides a powerful visual and educational aid for helping patients identify and adopt appropriate treatments. However, little is known about the operational cost of using the technology for this purpose. The analysis was done in the context of the Century Health Study for Cardiovascular Medicine (Century Trial), a 1,300-patient, randomized study combining PET imaging with lifestyle changes. Our methodology included a microcosting and time study focusing on estimating average direct and indirect costs. The total cost of the Century Trial in present-value terms is $9.2 million, which is equal to $7,058 per patient. Sensitivity analysis indicates that the present value of total costs is likely to range between $8.8 and $9.7 million, which is equivalent to $6,655-$7,606 per patient. The clinical relevance of the Century Trial is significant since it is, to our knowledge, the first randomized controlled trial to combine high-precision imaging with lifestyle strategies. The Century Trial is in its second year of a 5-y protocol, and we present preliminary findings. The results of this cost study, however, provide policy makers with an early estimate of the costs of implementing, at large scale, a combined intervention such as the Century Trial. Further, we believe that imaging-guided lifestyle management may have considerable potential for improving outcomes and reducing health-care costs by eliminating unnecessary invasive procedures.

Effects of Interventions on Survival in Acute Respiratory Distress Syndrome: an Umbrella Review of 159 Published Randomized Trials and 29 Meta-analyses

PubMed Central

Tonelli, Adriano R.; Zein, Joe; Adams, Jacob; Ioannidis, John P.A.

2014-01-01

Purpose Multiple interventions have been tested in acute respiratory distress syndrome (ARDS). We examined the entire agenda of published randomized controlled trials (RCTs) in ARDS that reported on mortality and of respective meta-analyses. Methods We searched PubMed, the Cochrane Library and Web of Knowledge until July 2013. We included RCTs in ARDS published in English. We excluded trials of newborns and children; and those on short-term interventions, ARDS prevention or post-traumatic lung injury. We also reviewed all meta-analyses of RCTs in this field that addressed mortality. Treatment modalities were grouped in five categories: mechanical ventilation strategies and respiratory care, enteral or parenteral therapies, inhaled / intratracheal medications, nutritional support and hemodynamic monitoring. Results We identified 159 published RCTs of which 93 had overall mortality reported (n= 20,671 patients) - 44 trials (14,426 patients) reported mortality as a primary outcome. A statistically significant survival benefit was observed in 8 trials (7 interventions) and two trials reported an adverse effect on survival. Among RTCs with >50 deaths in at least 1 treatment arm (n=21), 2 showed a statistically significant mortality benefit of the intervention (lower tidal volumes and prone positioning), 1 showed a statistically significant mortality benefit only in adjusted analyses (cisatracurium) and 1 (high-frequency oscillatory ventilation) showed a significant detrimental effect. Across 29 meta-analyses, the most consistent evidence was seen for low tidal volumes and prone positioning in severe ARDS. Conclusions There is limited supportive evidence that specific interventions can decrease mortality in ARDS. While low tidal volumes and prone positioning in severe ARDS seem effective, most sporadic findings of interventions suggesting reduced mortality are not corroborated consistently in large-scale evidence including meta-analyses. PMID:24667919

Mediterranean Diet Improves High-Density Lipoprotein Function in High-Cardiovascular-Risk Individuals: A Randomized Controlled Trial.

PubMed

Hernáez, Álvaro; Castañer, Olga; Elosua, Roberto; Pintó, Xavier; Estruch, Ramón; Salas-Salvadó, Jordi; Corella, Dolores; Arós, Fernando; Serra-Majem, Lluis; Fiol, Miquel; Ortega-Calvo, Manuel; Ros, Emilio; Martínez-González, Miguel Ángel; de la Torre, Rafael; López-Sabater, M Carmen; Fitó, Montserrat

2017-02-14

The biological functions of high-density lipoproteins (HDLs) contribute to explaining the cardioprotective role of the lipoprotein beyond quantitative HDL cholesterol levels. A few small-scale interventions with a single antioxidant have improved some HDL functions. However, to date, no long-term, large-scale, randomized controlled trial has been conducted to assess the effects of an antioxidant-rich dietary pattern (such as a traditional Mediterranean diet [TMD]) on HDL function in humans. This study was performed in a random subsample of volunteers from the PREDIMED Study (Prevención con Dieta Mediterránea; n=296) after a 1-year intervention. We compared the effects of 2 TMDs, one enriched with virgin olive oil (TMD-VOO; n=100) and the other enriched with nuts (TMD-Nuts; n=100), with respect to a low-fat control diet (n=96). We assessed the effects of both TMDs on the role of HDL particles on reverse cholesterol transport (cholesterol efflux capacity, HDL ability to esterify cholesterol, and cholesteryl ester transfer protein activity), HDL antioxidant properties (paraoxonase-1 arylesterase activity and total HDL antioxidant capacity on low-density lipoproteins), and HDL vasodilatory capacity (HDL ability to induce the release of nitric oxide in endothelial cells). We also studied the effects of a TMD on several HDL quality-related characteristics (HDL particle oxidation, resistance against oxidative modification, main lipid and protein composition, and size distribution). Both TMDs increased cholesterol efflux capacity relative to baseline ( P =0.018 and P =0.013 for TMD-VOO and TMD-Nuts, respectively). The TMD-VOO intervention decreased cholesteryl ester transfer protein activity (relative to baseline, P =0.028) and increased HDL ability to esterify cholesterol, paraoxonase-1 arylesterase activity, and HDL vasodilatory capacity (relative to control, P =0.039, P =0.012, and P =0.026, respectively). Adherence to a TMD induced these beneficial changes by improving HDL oxidative status and composition. The 3 diets increased the percentage of large HDL particles (relative to baseline, P <0.001). The TMD, especially when enriched with virgin olive oil, improved HDL atheroprotective functions in humans. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639. © 2017 American Heart Association, Inc.

Practice Patterns for Neurosurgical Utilization and Outcome in Acute Intracerebral Hemorrhage: Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials 1 and 2 Studies.

PubMed

Guo, Rui; Blacker, David J; Wang, Xia; Arima, Hisatomi; Lavados, Pablo M; Lindley, Richard I; Chalmers, John; Anderson, Craig S; Robinson, Thompson

2017-12-01

The prognosis in acute spontaneous intracerebral hemorrhage (ICH) is related to hematoma volume, where >30 mL is commonly used to define large ICH as a threshold for neurosurgical decompression but without clear supporting evidence. To determine the factors associated with large ICH and neurosurgical intervention among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT). We performed pooled analysis of the pilot INTERACT1 (n = 404) and main INTERACT2 (n = 2839) studies of ICH patients (<6 h of onset) with elevated systolic blood pressure (SBP, 150-220 mm Hg) who were randomized to intensive (target SBP < 140 mm Hg) or contemporaneous guideline-recommended (target SBP < 180 mm Hg) management. Neurosurgical intervention data were collected at 7 d postrandomization. Multivariable logistic regression was used to determine associations. There were 372 (13%) patients with large ICH volume (>30 mL), which was associated with nonresiding in China, nondiabetic status, severe neurological deficit (National Institutes of Health stroke scale [NIHSS] score ≥ 15), lobar location, intraventricular hemorrhage extension, raised leucocyte count, and hyponatremia. Significant predictors of those patients who underwent surgery (226 of 3233 patients overall; 83 of 372 patients with large ICH) were younger age, severe neurological deficit (lower Glasgow coma scale score, and NIHSS score ≥ 15), baseline ICH volume > 30 mL, and intraventricular hemorrhage. Early identification of severe ICH, based on age and clinical and imaging parameters, may facilitate neurosurgery and intensive monitoring of patients. Copyright © 2017 by the Congress of Neurological Surgeons

Regional or general anesthesia for fast-track hip and knee replacement - what is the evidence?

PubMed Central

Kehlet, Henrik; Aasvang, Eske Kvanner

2015-01-01

Regional anesthesia for knee and hip arthroplasty may have favorable outcome effects compared with general anesthesia by effectively blocking afferent input, providing initial postoperative analgesia, reducing endocrine metabolic responses, and providing sympathetic blockade with reduced bleeding and less risk of thromboembolic complications but with undesirable effects on lower limb motor and urinary bladder function. Old randomized studies supported the use of regional anesthesia with fewer postoperative pulmonary and thromboembolic complications, and this has been supported by recent large non-randomized epidemiological database cohort studies. In contrast, the data from newer randomized trials are conflicting, and recent studies using modern general anesthetic techniques may potentially support the use of general versus spinal anesthesia. In summary, the lack of properly designed large randomized controlled trials comparing modern general anesthesia and spinal anesthesia for knee and hip arthroplasty prevents final recommendations and calls for prospective detailed studies in this clinically important field. PMID:26918127

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.

From Efficacy Trial to Large Scale Effectiveness Trial: A Tier 2 Mathematics Intervention for First Graders with Difficulties in Mathematics

ERIC Educational Resources Information Center

Rolfhus, Eric; Clarke, Ben; Decker, Lauren E.; Williams, Chuck; Dimino, Joseph

2013-01-01

Large scale longitudinal research (Morgan, Farkas, & Wu, 2009) and a meta-analysis (Duncan et al., 2007) have found that early mathematics achievement is a strong predictor of later mathematics achievement. In fact, end of Kindergarten and end of grade 1 mathematics achievement on ECLS-K and similar mathematics proficiency measures tends to be…

A Randomized Controlled Trial of Individual Family Psychoeducational Psychotherapy and Omega-3 Fatty Acids in Youth with Subsyndromal Bipolar Disorder

PubMed Central

Young, Andrea S.; Vesco, Anthony T.; Nader, Elias S.; Healy, K. Zachary; Gardner, William; Wolfson, Hannah L.; Arnold, L. Eugene

2015-01-01

Abstract Objective: This pilot study evaluates efficacy of omega-3 fatty acid supplementation (Ω3), individual family psychoeducational psychotherapy (IF-PEP), and their combination in youth with subsyndromal bipolar disorders (bipolar disorder not otherwise specified [BP-NOS], cyclothymic disorder [CYC]). Methods: This study was a 12 week, randomized trial of Ω3 versus placebo and IF-PEP versus active monitoring (AM) using a 2 × 2 design (Ω3 + PEP: n = 5; Ω3 + AM: n = 5; placebo + PEP: n = 7; placebo + AM: n = 6). Twenty-three youth ages 7–14 with BP-NOS or CYC were recruited via community advertisements and clinician referrals. Participants could be taking stable medication for attention-deficit/hyperactivity disorder and sleep aids, but no other psychotropics. Independent evaluators assessed participants at screen, baseline, and 2, 4, 6, 9, and 12 weeks. Primary outcome measures were the Kiddie Schedule for Affective Disorders (K-SADS) Depression (KDRS) and Mania (KMRS) Rating Scales, Children's Depression Rating Scale-Revised (CDRS-R), and Young Mania Rating Scale (YMRS). Ω3/placebo conditions were double-blind; independent evaluators were blind to psychotherapy condition. Results: Most participants (83%) completed the 12 week trial. Side effects were uncommon and mild. Intent-to-treat analyses indicated significant improvement in depressive symptoms (KDRS) for combined treatment relative to placebo and AM (p = 0.01, d = 1.70). Across groups, manic symptoms improved over time without significant treatment effects. Effect of IF-PEP on child depression compared with AM was medium (d = 0.63, CDRS-R) to large (d = 1.24, KDRS). Effect of Ω3 on depression was medium (d = 0.48, KDRS). Conclusion: IF-PEP and Ω3 are well tolerated and associated with improved mood symptoms among youth with BP-NOS and CYC. Clinicaltrials.gov Identifier: NCT01507753 PMID:26682997

School-based cognitive behavioral interventions for anxious youth: study protocol for a randomized controlled trial.

PubMed

Haugland, Bente Storm Mowatt; Raknes, Solfrid; Haaland, Aashild Tellefsen; Wergeland, Gro Janne; Bjaastad, Jon Fauskanger; Baste, Valborg; Himle, Joe; Rapee, Ron; Hoffart, Asle

2017-03-04

Anxiety disorders are prevalent among adolescents and may have long-lasting negative consequences for the individual, the family and society. Cognitive behavioral therapy (CBT) is an effective treatment. However, many anxious youth do not seek treatment. Low-intensity CBT in schools may improve access to evidence-based services. We aim to investigate the efficacy of two CBT youth anxiety programs with different intensities (i.e., number and length of sessions), both group-based and administered as early interventions in a school setting. The objectives of the study are to examine the effects of school-based interventions for youth anxiety and to determine whether a less intensive intervention is non-inferior to a more intensive intervention. The present study is a randomized controlled trial comparing two CBT interventions to a waitlist control group. A total of 18 schools participate and we aim to recruit 323 adolescents (12-16 years). Youth who score above a cutoff on an anxiety symptom scale will be included in the study. School nurses recruit participants and deliver the interventions, with mental health workers as co-therapists and/or supervisors. Primary outcomes are level of anxiety symptoms and anxiety-related functional impairments. Secondary outcomes are level of depressive symptoms, quality of life and general psychosocial functioning. Non-inferiority between the two active interventions will be declared if a difference of 1.4 or less is found on the anxiety symptom measure post-intervention and a difference of 0.8 on the interference scale. Effects will be analyzed by mixed effect models, applying an intention to treat procedure. The present study extends previous research by comparing two programs with different intensity. A brief intervention, if effective, could more easily be subject to large-scale implementation in school health services. ClinicalTrials.gov, NCT02279251 . Registered on 15 October 2014. Retrospectively registered.

Add-on treatment of benzoate for schizophrenia: a randomized, double-blind, placebo-controlled trial of D-amino acid oxidase inhibitor.

PubMed

Lane, Hsien-Yuan; Lin, Ching-Hua; Green, Michael F; Hellemann, Gerhard; Huang, Chih-Chia; Chen, Po-Wei; Tun, Rene; Chang, Yue-Cung; Tsai, Guochuan E

2013-12-01

In addition to dopaminergic hyperactivity, hypofunction of the N-methyl-d-aspartate receptor (NMDAR) has an important role in the pathophysiology of schizophrenia. Enhancing NMDAR-mediated neurotransmission is considered a novel treatment approach. To date, several trials on adjuvant NMDA-enhancing agents have revealed beneficial, but limited, efficacy for positive and negative symptoms and cognition. Another method to enhance NMDA function is to raise the levels of d-amino acids by blocking their metabolism. Sodium benzoate is a d-amino acid oxidase inhibitor. To examine the clinical and cognitive efficacy and safety of add-on treatment of sodium benzoate for schizophrenia. A randomized, double-blind, placebo-controlled trial in 2 major medical centers in Taiwan composed of 52 patients with chronic schizophrenia who had been stabilized with antipsychotic medications for 3 months or longer. Six weeks of add-on treatment of 1 g/d of sodium benzoate or placebo. The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score. Clinical efficacy and adverse effects were assessed biweekly. Cognitive functions were measured before and after the add-on treatment. Benzoate produced a 21% improvement in PANSS total score and large effect sizes (range, 1.16-1.69) in the PANSS total and subscales, Scales for the Assessment of Negative Symptoms-20 items, Global Assessment of Function, Quality of Life Scale and Clinical Global Impression and improvement in the neurocognition subtests as recommended by the National Institute of Mental Health's Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative, including the domains of processing speed and visual learning. Benzoate was well tolerated without significant adverse effects. Benzoate adjunctive therapy significantly improved a variety of symptom domains and neurocognition in patients with chronic schizophrenia. The preliminary results show promise for d-amino acid oxidase inhibition as a novel approach for new drug development for schizophrenia.

Internet treatment for generalized anxiety disorder: a randomized controlled trial comparing clinician vs. technician assistance.

PubMed

Robinson, Emma; Titov, Nickolai; Andrews, Gavin; McIntyre, Karen; Schwencke, Genevieve; Solley, Karen

2010-06-03

Internet-based cognitive behavioural therapy (iCBT) for generalized anxiety disorder (GAD) has been shown to be effective when guided by a clinician. The present study sought to replicate this finding, and determine whether support from a technician is as effective as guidance from a clinician. Randomized controlled non-inferiority trial comparing three groups: Clinician-assisted vs. technician-assisted vs. delayed treatment. Community-based volunteers applied to the VirtualClinic (www.virtualclinic.org.au) research program and 150 participants with GAD were randomized. Participants in the clinician- and technician-assisted groups received access to an iCBT program for GAD comprising six online lessons, weekly homework assignments, and weekly supportive contact over a treatment period of 10 weeks. Participants in the clinician-assisted group also received access to a moderated online discussion forum. The main outcome measures were the Penn State Worry Questionnaire (PSWQ) and the Generalized Anxiety Disorder-7 Item (GAD-7). Completion rates were high, and both treatment groups reduced scores on the PSWQ (p<0.001) and GAD-7 (p<0.001) compared to the delayed treatment group, but did not differ from each other. Within group effect sizes on the PSWQ were 1.16 and 1.07 for the clinician- and technician-assisted groups, respectively, and on the GAD-7 were 1.55 and 1.73, respectively. At 3 month follow-up participants in both treatment groups had sustained the gains made at post-treatment. Participants in the clinician-assisted group had made further gains on the PSWQ. Approximately 81 minutes of clinician time and 75 minutes of technician time were required per participant during the 10 week treatment program. Both clinician- and technician-assisted treatment resulted in large effect sizes and clinically significant improvements comparable to those associated with face-to-face treatment, while a delayed treatment/control group did not improve. These results provide support for large scale trials to determine the clinical effectiveness and acceptability of technician-assisted iCBT programs for GAD. This form of treatment has potential to increase the capacity of existing mental health services. Australian New Zealand Clinical Trials Registry ACTRN12609000563268.

Internet treatment for depression: a randomized controlled trial comparing clinician vs. technician assistance.

PubMed

Titov, Nickolai; Andrews, Gavin; Davies, Matthew; McIntyre, Karen; Robinson, Emma; Solley, Karen

2010-06-08

Internet-based cognitive behavioural therapy (iCBT) for depression is effective when guided by a clinician, less so if unguided. Would guidance from a technician be as effective as guidance from a clinician? Randomized controlled non-inferiority trial comparing three groups: Clinician-assisted vs. technician-assisted vs. delayed treatment. Community-based volunteers applied to the VirtualClinic (www.virtualclinic.org.au) research program, and 141 participants with major depressive disorder were randomized. Participants in the clinician- and technician-assisted groups received access to an iCBT program for depression comprising 6 online lessons, weekly homework assignments, and weekly supportive contact over a treatment period of 8 weeks. Participants in the clinician-assisted group also received access to a moderated online discussion forum. The main outcome measures were the Beck Depression Inventory (BDI-II) and the Patient Health QUESTIONnaire-9 Item (PHQ-9). Completion rates were high, and at post-treatment, both treatment groups reduced scores on the BDI-II (p<0.001) and PHQ-9 (p<0.001) compared to the delayed treatment group but did not differ from each other. Within group effect sizes on the BDI-II were 1.27 and 1.20 for the clinician- and technician-assisted groups respectively, and on the PHQ-9, were 1.54 and 1.60 respectively. At 4-month follow-up participants in the technician group had made further improvements and had significantly lower scores on the PHQ-9 than those in the clinician group. A total of approximately 60 minutes of clinician or technician time was required per participant during the 8-week treatment program. Both clinician- and technician-assisted treatment resulted in large effect sizes and clinically significant improvements comparable to those associated with face-to-face treatment, while a delayed treatment control group did not improve. These results provide support for large scale trials to determine the clinical effectiveness and acceptability of technician-assisted iCBT programs for depression. This form of treatment has potential to increase the capacity of existing mental health services. Australian New Zealand Clinical Trials Registry ACTRN12609000559213.

A random walk model for evaluating clinical trials involving serial observations.

PubMed

Hopper, J L; Young, G P

1988-05-01

For clinical trials where the variable of interest is ordered and categorical (for example, disease severity, symptom scale), and where measurements are taken at intervals, it might be possible to achieve a greater discrimination between the efficacy of treatments by modelling each patient's progress as a stochastic process. The random walk is a simple, easily interpreted model that can be fitted by maximum likelihood using a maximization routine with inference based on standard likelihood theory. In general the model can allow for randomly censored data, incorporates measured prognostic factors, and inference is conditional on the (possibly non-random) allocation of patients. Tests of fit and of model assumptions are proposed, and application to two therapeutic trials of gastroenterological disorders are presented. The model gave measures of the rate of, and variability in, improvement for patients under different treatments. A small simulation study suggested that the model is more powerful than considering the difference between initial and final scores, even when applied to data generated by a mechanism other than the random walk model assumed in the analysis. It thus provides a useful additional statistical method for evaluating clinical trials.

Everolimus-Eluting Bioresorbable Scaffolds for Coronary Artery Disease.

PubMed

Ellis, Stephen G; Kereiakes, Dean J; Metzger, D Christopher; Caputo, Ronald P; Rizik, David G; Teirstein, Paul S; Litt, Marc R; Kini, Annapoorna; Kabour, Ameer; Marx, Steven O; Popma, Jeffrey J; McGreevy, Robert; Zhang, Zhen; Simonton, Charles; Stone, Gregg W

2015-11-12

In patients with coronary artery disease who receive metallic drug-eluting coronary stents, adverse events such as late target-lesion failure may be related in part to the persistent presence of the metallic stent frame in the coronary-vessel wall. Bioresorbable vascular scaffolds have been developed to attempt to improve long-term outcomes. In this large, multicenter, randomized trial, 2008 patients with stable or unstable angina were randomly assigned in a 2:1 ratio to receive an everolimus-eluting bioresorbable vascular (Absorb) scaffold (1322 patients) or an everolimus-eluting cobalt-chromium (Xience) stent (686 patients). The primary end point, which was tested for both noninferiority (margin, 4.5 percentage points for the risk difference) and superiority, was target-lesion failure (cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization) at 1 year. Target-lesion failure at 1 year occurred in 7.8% of patients in the Absorb group and in 6.1% of patients in the Xience group (difference, 1.7 percentage points; 95% confidence interval, -0.5 to 3.9; P=0.007 for noninferiority and P=0.16 for superiority). There was no significant difference between the Absorb group and the Xience group in rates of cardiac death (0.6% and 0.1%, respectively; P=0.29), target-vessel myocardial infarction (6.0% and 4.6%, respectively; P=0.18), or ischemia-driven target-lesion revascularization (3.0% and 2.5%, respectively; P=0.50). Device thrombosis within 1 year occurred in 1.5% of patients in the Absorb group and in 0.7% of patients in the Xience group (P=0.13). In this large-scale, randomized trial, treatment of noncomplex obstructive coronary artery disease with an everolimus-eluting bioresorbable vascular scaffold, as compared with an everolimus-eluting cobalt-chromium stent, was within the prespecified margin for noninferiority with respect to target-lesion failure at 1 year. (Funded by Abbott Vascular; ABSORB III ClinicalTrials.gov number, NCT01751906.).

Background Information | Division of Cancer Prevention

Cancer.gov

The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a large population-based randomized trial evaluating screening programs for these cancers. The primary goal of this long-term trial of the National Cancer Institute's (NCI) Division of Cancer Prevention (DCP) is to determine the effects of screening on cancer-related mortality and on secondary

Physical therapy with drug treatment in Bell palsy: a focused review.

PubMed

Ferreira, Margarida; Marques, Elisa E; Duarte, José A; Santos, Paula C

2015-04-01

The physical therapy (PT) associated with standard drug treatment (SDT) in Bell palsy has never been investigated. Randomized controlled trials or quasirandomized controlled trials have compared facial PT (except treatments such as acupuncture and osteopathic) combined with SDT against a control group with SDT alone. Participants included those older than 15 yrs with a clinical diagnosis of Bell palsy, and the primary outcome measure was motor function recovery by the House-Brackmann scale. The methodologic quality of each study was also independently assessed by two reviewers using the PEDro scale. Four studies met the inclusion criteria. Three trials indicate that PT in association with SDT supports higher motor function recovery than SDT alone between 15 days and 1 yr of follow-up. On the other hand, one trial showed that electrical stimulation added to conventional PT with SDT did not influence treatment outcomes. The present review suggests that the current practice of Bell palsy treatment by PT associated with SDT seems to have a positive effect on grade and time recovery compared with SDT alone. However, there is very little quality evidence from randomized controlled trials, and such evidence is insufficient to decide whether combined treatment is beneficial in the management of Bell palsy.

Yukmijihwang-tang for the treatment of xerostomia in the elderly: study protocol for a randomized, double-blind, placebo-controlled, two-center trial

PubMed Central

2013-01-01

Background Xerostomia, a subjective sense of dry mouth, is not generally regarded a disease despite its high prevalence among the elderly, and therefore continues to impair affected patients’ quality of life. In traditional Korean medicine, ‘Yin-Deficiency’ has been implicated in the pathogenesis of xerostomia among the elderly. Yukmijihwang-tang is a famous herbal prescription used to relieve ‘Yin-Deficiency’, and reportedly has antioxidant effects; therefore, it is postulated that Yukmijihwang-tang can be used to treat xerostomia in the elderly. However, to our knowledge, no clinical trial has been conducted on the effects of Yukmijihwang-tang on xerostomia. Thus, we designed a randomized clinical trial to investigate the effects and safety of Yukmijihwang-tang on xerostomia in the elderly. In addition, we will clarify the aforementioned assumption that ‘Yin-Deficiency’ is the major cause of xerostomia in the elderly by identifying a correlation between xerostomia and ‘Yin-Deficiency’. Methods/Design This randomized, double-blind, placebo-controlled trial will be carried out at two centers: Kyung Hee University Korean Medicine Hospital and Kyung Hee University Hospital at Gangdong. We will recruit 96 subjects aged 60-80 years who have experienced xerostomia for 3 months prior to participation. Subjects who present with score >40 on the visual analogue scale for xerostomia and unstimulated salivary flow rate under 0.3mL/min will be included and the randomization will be carried out by an independent statistician by using a random number creation program. The subjects and all researchers except the statistician will be blinded to the group assignment. Yukmijihwang-tang or placebo will be administered to each group for 8 weeks. The primary outcome is change in the scores for the visual analogue scale for xerostomia and the dry mouth symptom questionnaire from 0 to 8 weeks. Discussion It will be assessed whether Yukmijihwang-tang can be used as a new herbal treatment for xerostomia in the elderly by demonstrating its therapeutic effects in a well-designed clinical trial. Trial registration ClinicalTrials.gov Identifier: NCT01579877 PMID:24004451

Vitamin-mineral intake and intelligence: a macrolevel analysis of randomized controlled trials.

PubMed

Schoenthaler, S J; Bier, I D

1999-04-01

Two independent groups suspected that poor diets in school children might impair intelligence. Because dietary changes produce psychological effects, both groups conducted randomized trials in which children were challenged with placebo or vitamin-mineral tablets. Both reported significantly greater gains in intelligence among the actives. The findings were important because of the apparent inadequacy of diet they revealed, and the magnitude of the potential for increased intelligence. However, 5 of 11 replications were not significant, leaving the issue in doubt. To determine if school children who receive low-dose vitamin-mineral tablets produce significantly higher IQ scores than children who receive placebo. A macrolevel analysis of the 13 known randomized, double-blind trials was undertaken. A total of 15 public schools in Arizona, California, Missouri, Oklahoma, Belgium, England, Scotland, and Wales participated, with 1477 school children, aged 6 to 17 years, and 276 young adult males, aged 18 to 25 years, in 2 American correctional facilities. All studies used 1 of 3 standardized tests of nonverbal intelligence: the Wechsler Intelligence Scale for Children-Revised, the Wechsler Adult Intelligence Scale, or the Calvert Non-verbal test. The activities in each study performed better, on average, than placebo in nonverbal IQ, regardless of formula, location, age, race, gender, or research team composition. The probability of 13 randomly selected experimental groups always performing better than 13 randomly selected independent control groups is one-half to the 13th power (p = 0.000122). The mean difference across all studies is 3.2 IQ points. Furthermore, the standard deviation in the variable "IQ change" was also consistently larger in each active group when compared to its controls. This confirms that a few children in each study, presumably the poorly nourished minority, were producing large differences, rather than a 3.2 point gain in all active children. There are important health risks when school children's dietary habits depart substantially from government guidelines; poor dietary habits may lead to impaired intelligence. Low-dose vitamin-mineral supplementation may restore the cognitive abilities of these children by raising low blood nutrient concentrations. However, there is also evidence that supplementation has no measurable effect on the intelligence of well-nourished children with normal blood nutrient concentrations.

Development and Evaluation of the Sugar-Sweetened Beverages Media Literacy (SSB-ML) Scale and Its Relationship With SSB Consumption

PubMed Central

Chen, Yvonnes; Porter, Kathleen J.; Estabrooks, Paul A.; Zoellner, Jamie

2017-01-01

Understanding how adults’ media literacy skill sets impact their sugar-sweetened beverage (SSB) intake provides insight into designing effective interventions to enhance their critical analysis of marketing messages and thus improve their healthy beverage choices. However, a media literacy scale focusing on SSBs is lacking. This cross-sectional study uses baseline data from a large randomized controlled trial to (a) describe the psychometric properties of an SSB Media Literacy Scale (SSB-ML) scale and its subdomains, (b) examine how the scale varies across demographic variables, and (c) explain the scale’s concurrent validity to predict SSB consumption. Results from 293 adults in rural southwestern Virginia (81.6% female, 94.0% White, 54.1% receiving SNAP and/or WIC benefits, average 410 SSB kcal daily) show that overall SSB-ML scale and its subdomains have strong internal consistencies (Cronbach’s alphas ranging from 0.65 to 0.83). The Representation & Reality domain significantly predicted SSB kilocalories, after controlling for demographic variables. This study has implications for the assessment and inclusion of context-specific media literacy skills in behavioral interventions. PMID:27690635

Eye movement desensitization and reprocessing therapy versus supportive therapy in affective relapse prevention in bipolar patients with a history of trauma: study protocol for a randomized controlled trial.

PubMed

Moreno-Alcázar, Ana; Radua, Joaquim; Landín-Romero, Ramon; Blanco, Laura; Madre, Mercè; Reinares, Maria; Comes, Mercè; Jiménez, Esther; Crespo, Jose Manuel; Vieta, Eduard; Pérez, Victor; Novo, Patricia; Doñate, Marta; Cortizo, Romina; Valiente-Gómez, Alicia; Lupo, Walter; McKenna, Peter J; Pomarol-Clotet, Edith; Amann, Benedikt L

2017-04-04

Up to 60% of patients with bipolar disorder (BD) have a history of traumatic events, which is associated with greater episode severity, higher risk of comorbidity and higher relapse rates. Trauma-focused treatment strategies for BD are thus necessary but studies are currently scarce. The aim of this study is to examine whether Eye Movement Desensitization and Reprocessing (EMDR) therapy focusing on adherence, insight, de-idealisation of manic symptoms, prodromal symptoms and mood stabilization can reduce episode severity and relapse rates and increase cognitive performance and functioning in patients with BD. This is a single-blind, randomized controlled, multicentre trial in which 82 patients with BD and a history of traumatic events will be recruited and randomly allocated to one of two treatment arms: EMDR therapy or supportive therapy. Patients in both groups will receive 20 psychotherapeutic sessions, 60 min each, during 6 months. The primary outcome is a reduction of affective episodes after 12 and 24 months in favour of the EMDR group. As secondary outcome we postulate a greater reduction in affective symptoms in the EMDR group (as measured by the Bipolar Depression Rating Scale, the Young Mania Rating Scale and the Clinical Global Impression Scale modified for BD), and a better performance in cognitive state, social cognition and functioning (as measured by the Screen for Cognitive Impairment in Psychiatry, The Mayer-Salovey-Caruso Emotional Intelligence Test and the Functioning Assessment Short Test, respectively). Traumatic events will be evaluated by The Holmes-Rahe Life Stress Inventory, the Clinician-administered PTSD Scale and the Impact of Event Scale. The results of this study will provide evidence whether a specific EMDR protocol for patients with BD is effective in reducing affective episodes, affective symptoms and functional, cognitive and trauma symptoms. The trial is registered at ClinicalTrials.gov, identifier: NCT02634372 . Registered on 3 December 2015.

Glutamine and antioxidants in the critically ill patient: a post hoc analysis of a large-scale randomized trial.

PubMed

Heyland, Daren K; Elke, Gunnar; Cook, Deborah; Berger, Mette M; Wischmeyer, Paul E; Albert, Martin; Muscedere, John; Jones, Gwynne; Day, Andrew G

2015-05-01

The recent large randomized controlled trial of glutamine and antioxidant supplementation suggested that high-dose glutamine is associated with increased mortality in critically ill patients with multiorgan failure. The objectives of the present analyses were to reevaluate the effect of supplementation after controlling for baseline covariates and to identify potentially important subgroup effects. This study was a post hoc analysis of a prospective factorial 2 × 2 randomized trial conducted in 40 intensive care units in North America and Europe. In total, 1223 mechanically ventilated adult patients with multiorgan failure were randomized to receive glutamine, antioxidants, both glutamine and antioxidants, or placebo administered separate from artificial nutrition. We compared each of the 3 active treatment arms (glutamine alone, antioxidants alone, and glutamine + antioxidants) with placebo on 28-day mortality. Post hoc, treatment effects were examined within subgroups defined by baseline patient characteristics. Logistic regression was used to estimate treatment effects within subgroups after adjustment for baseline covariates and to identify treatment-by-subgroup interactions (effect modification). The 28-day mortality rates in the placebo, glutamine, antioxidant, and combination arms were 25%, 32%, 29%, and 33%, respectively. After adjusting for prespecified baseline covariates, the adjusted odds ratio of 28-day mortality vs placebo was 1.5 (95% confidence interval, 1.0-2.1, P = .05), 1.2 (0.8-1.8, P = .40), and 1.4 (0.9-2.0, P = .09) for glutamine, antioxidant, and glutamine plus antioxidant arms, respectively. In the post hoc subgroup analysis, both glutamine and antioxidants appeared most harmful in patients with baseline renal dysfunction. No subgroups suggested reduced mortality with supplements. After adjustment for baseline covariates, early provision of high-dose glutamine administered separately from artificial nutrition was not beneficial and may be associated with increased mortality in critically ill patients with multiorgan failure. For both glutamine and antioxidants, the greatest potential for harm was observed in patients with multiorgan failure that included renal dysfunction upon study enrollment. © 2014 American Society for Parenteral and Enteral Nutrition.

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

PubMed

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

2013-12-09

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

Comparative effectiveness of a complex Ayurvedic treatment and conventional standard care in osteoarthritis of the knee--study protocol for a randomized controlled trial.

PubMed

Witt, Claudia M; Michalsen, Andreas; Roll, Stephanie; Morandi, Antonio; Gupta, Shivnarain; Rosenberg, Mark; Kronpass, Ludwig; Stapelfeldt, Elmar; Hissar, Syed; Müller, Matthias; Kessler, Christian

2013-05-23

Traditional Indian Ayurvedic medicine uses complex treatment approaches, including manual therapies, lifestyle and nutritional advice, dietary supplements, medication, yoga, and purification techniques. Ayurvedic strategies are often used to treat osteoarthritis (OA) of the knee; however, no systematic data are available on their effectiveness in comparison with standard care. The aim of this study is to evaluate the effectiveness of complex Ayurvedic treatment in comparison with conventional methods of treating OA symptoms in patients with knee osteoarthritis. In a prospective, multicenter, randomized controlled trial, 150 patients between 40 and 70 years, diagnosed with osteoarthritis of the knee, following American College of Rheumatology criteria and an average pain intensity of ≥40 mm on a 100 mm visual analog scale in the affected knee at baseline will be randomized into two groups. In the Ayurveda group, treatment will include tailored combinations of manual treatments, massages, dietary and lifestyle advice, consideration of selected foods, nutritional supplements, yoga posture advice, and knee massage. Patients in the conventional group will receive self-care advice, pain medication, weight-loss advice (if overweight), and physiotherapy following current international guidelines. Both groups will receive 15 treatment sessions over 12 weeks. Outcomes will be evaluated after 6 and 12 weeks and 6 and 12 months. The primary endpoint is a change in the score on the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) after 12 weeks. Secondary outcome measurements will use WOMAC subscales, a pain disability index, a visual analog scale for pain and sleep quality, a pain experience scale, a quality-of-life index, a profile of mood states, and Likert scales for patient satisfaction, patient diaries, and safety. Using an adapted PRECIS scale, the trial was identified as lying mainly in the middle of the efficacy-effectiveness continuum. This trial is the first to compare the effectiveness of a complex Ayurvedic intervention with a complex conventional intervention in a Western medical setting in patients with knee osteoarthritis. During the trial design, aspects of efficacy and effectiveness were discussed. The resulting design is a compromise between rigor and pragmatism. NCT01225133.

Value of Information Analysis of Multiparameter Tests for Chemotherapy in Early Breast Cancer: The OPTIMA Prelim Trial.

PubMed

Hall, Peter S; Smith, Alison; Hulme, Claire; Vargas-Palacios, Armando; Makris, Andreas; Hughes-Davies, Luke; Dunn, Janet A; Bartlett, John M S; Cameron, David A; Marshall, Andrea; Campbell, Amy; Macpherson, Iain R; Dan Rea; Francis, Adele; Earl, Helena; Morgan, Adrienne; Stein, Robert C; McCabe, Christopher

2017-12-01

Precision medicine is heralded as offering more effective treatments to smaller targeted patient populations. In breast cancer, adjuvant chemotherapy is standard for patients considered as high-risk after surgery. Molecular tests may identify patients who can safely avoid chemotherapy. To use economic analysis before a large-scale clinical trial of molecular testing to confirm the value of the trial and help prioritize between candidate tests as randomized comparators. Women with surgically treated breast cancer (estrogen receptor-positive and lymph node-positive or tumor size ≥30 mm) were randomized to standard care (chemotherapy for all) or test-directed care using Oncotype DX™. Additional testing was undertaken using alternative tests: MammaPrint TM , PAM-50 (Prosigna TM ), MammaTyper TM , IHC4, and IHC4-AQUA™ (NexCourse Breast™). A probabilistic decision model assessed the cost-effectiveness of all tests from a UK perspective. Value of information analysis determined the most efficient publicly funded ongoing trial design in the United Kingdom. There was an 86% probability of molecular testing being cost-effective, with most tests producing cost savings (range -£1892 to £195) and quality-adjusted life-year gains (range 0.17-0.20). There were only small differences in costs and quality-adjusted life-years between tests. Uncertainty was driven by long-term outcomes. Value of information demonstrated value of further research into all tests, with Prosigna currently being the highest priority for further research. Molecular tests are likely to be cost-effective, but an optimal test is yet to be identified. Health economics modeling to inform the design of a randomized controlled trial looking at diagnostic technology has been demonstrated to be feasible as a method for improving research efficiency. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

A randomized controlled trial of single point acupuncture in primary dysmenorrhea.

PubMed

Liu, Cun-Zhi; Xie, Jie-Ping; Wang, Lin-Peng; Liu, Yu-Qi; Song, Jia-Shan; Chen, Yin-Ying; Shi, Guang-Xia; Zhou, Wei; Gao, Shu-Zhong; Li, Shi-Liang; Xing, Jian-Min; Ma, Liang-Xiao; Wang, Yan-Xia; Zhu, Jiang; Liu, Jian-Ping

2014-06-01

Acupuncture is often used for primary dysmenorrhea. But there is no convincing evidence due to low methodological quality. We aim to assess immediate effect of acupuncture at specific acupoint compared with unrelated acupoint and nonacupoint on primary dysmenorrhea. The Acupuncture Analgesia Effect in Primary Dysmenorrhoea-II is a multicenter controlled trial conducted in six large hospitals of China. Patients who met inclusion criteria were randomly assigned to classic acupoint (N = 167), unrelated acupoint (N = 167), or non-acupoint (N = 167) group on a 1:1:1 basis. They received three sessions with electro-acupuncture at a classic acupoint (Sanyinjiao, SP6), or an unrelated acupoint (Xuanzhong, GB39), or nonacupoint location, respectively. The primary outcome was subjective pain as measured by a 100-mm visual analog scale (VAS). Measurements were obtained at 0, 5, 10, 30, and 60 minutes following the first intervention. In addition, patients scored changes of general complaints using Cox retrospective symptom scales (RSS-Cox) and 7-point verbal rating scale (VRS) during three menstrual cycles. Secondary outcomes included VAS score for average pain, pain total time, additional in-bed time, and proportion of participants using analgesics during three menstrual cycles. Five hundred and one people underwent random assignment. The primary comparison of VAS scores following the first intervention demonstrated that classic acupoint group was more effective both than unrelated acupoint (-4.0 mm, 95% CI -7.1 to -0.9, P = 0.010) and nonacupoint (-4.0 mm, 95% CI -7.0 to -0.9, P = 0.012) groups. However, no significant differences were detected among the three acupuncture groups for RSS-Cox or VRS outcomes. The per-protocol analysis showed similar pattern. No serious adverse events were noted. Specific acupoint acupuncture produced a statistically, but not clinically, significant effect compared with unrelated acupoint and nonacupoint acupuncture in primary dysmenorrhea patients. Future studies should focus on effects of multiple points acupuncture on primary dysmenorrhea. Wiley Periodicals, Inc.

Addressing challenges in scaling up TB and HIV treatment integration in rural primary healthcare clinics in South Africa (SUTHI): a cluster randomized controlled trial protocol.

PubMed

Naidoo, Kogieleum; Gengiah, Santhanalakshmi; Yende-Zuma, Nonhlanhla; Padayatchi, Nesri; Barker, Pierre; Nunn, Andrew; Subrayen, Priashni; Abdool Karim, Salim S

2017-11-13

A large and compelling clinical evidence base has shown that integrated TB and HIV services leads to reduction in human immunodeficiency virus (HIV)- and tuberculosis (TB)-associated mortality and morbidity. Despite official policies and guidelines recommending TB and HIV care integration, its poor implementation has resulted in TB and HIV remaining the commonest causes of death in several countries in sub-Saharan Africa, including South Africa. This study aims to reduce mortality due to TB-HIV co-infection through a quality improvement strategy for scaling up of TB and HIV treatment integration in rural primary healthcare clinics in South Africa. The study is designed as an open-label cluster randomized controlled trial. Sixteen clinic supervisors who oversee 40 primary health care (PHC) clinics in two rural districts of KwaZulu-Natal, South Africa will be randomized to either the control group (provision of standard government guidance for TB-HIV integration) or the intervention group (provision of standard government guidance with active enhancement of TB-HIV care integration through a quality improvement approach). The primary outcome is all-cause mortality among TB-HIV patients. Secondary outcomes include time to antiretroviral therapy (ART) initiation among TB-HIV co-infected patients, as well as TB and HIV treatment outcomes at 12 months. In addition, factors that may affect the intervention, such as conditions in the clinic and staff availability, will be closely monitored and documented. This study has the potential to address the gap between the establishment of TB-HIV care integration policies and guidelines and their implementation in the provision of integrated care in PHC clinics. If successful, an evidence-based intervention comprising change ideas, tools, and approaches for quality improvement could inform the future rapid scale up, implementation, and sustainability of improved TB-HIV integration across sub-Sahara Africa and other resource-constrained settings. Clinicaltrials.gov, NCT02654613 . Registered 01 June 2015.

Efficacy and Safety of Individualized Coaching After Stroke: the LAST Study (Life After Stroke): A Pragmatic Randomized Controlled Trial.

PubMed

Askim, Torunn; Langhammer, Birgitta; Ihle-Hansen, Hege; Gunnes, Mari; Lydersen, Stian; Indredavik, Bent

2018-02-01

The evidence for interventions to prevent functional decline in the long term after stroke is lacking. The aim of this trial was to evaluate the efficacy and safety of an 18-month follow-up program of individualized regular coaching on physical activity and exercise. This was a multicentre, pragmatic, single-blinded, randomized controlled trial. Adults (age ≥18 years) with first-ever or recurrent stroke, community dwelling, with modified Rankin Scale <5, and no serious comorbidities were included 10 to 16 weeks poststroke. The intervention group received individualized regular coaching on physical activity and exercise every month for 18 consecutive months. The control group received standard care. Primary outcome was the Motor Assessment Scale at end of intervention (18-month follow-up). Secondary measures were Barthel index, modified Rankin Scale, item 14 from Berg Balance Scale, Timed Up and Go test, gait speed, 6-minute walk test, and Stroke Impact Scale. Other outcomes were adverse events and compliance to the intervention assessed by training diaries and the International Physical Activity Questionnaire. Three hundred and eighty consenting participants were randomly assigned to individualized coaching (n=186) or standard care (n=194). The mean estimated difference on Motor Assessment Scale in favor of control group was -0.70 points (95% confidence interval, -2.80, 1.39), P =0.512. There were no differences between the groups on Barthel index, modified Rankin Scale, or Berg Balance Scale. The frequency of adverse events was low in both groups. Results from International Physical Activity Questionnaire and training diaries showed increased activity levels but low intensity of the exercise in the intervention group. The regular individualized coaching did not improve maintenance of motor function or the secondary outcomes compared with standard care. The intervention should be regarded as safe. Despite the neutral results, the health costs related to the intervention should be investigated. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01467206. © 2017 American Heart Association, Inc.

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.

Band gaps and localization of surface water waves over large-scale sand waves with random fluctuations

NASA Astrophysics Data System (ADS)

Zhang, Yu; Li, Yan; Shao, Hao; Zhong, Yaozhao; Zhang, Sai; Zhao, Zongxi

2012-06-01

Band structure and wave localization are investigated for sea surface water waves over large-scale sand wave topography. Sand wave height, sand wave width, water depth, and water width between adjacent sand waves have significant impact on band gaps. Random fluctuations of sand wave height, sand wave width, and water depth induce water wave localization. However, random water width produces a perfect transmission tunnel of water waves at a certain frequency so that localization does not occur no matter how large a disorder level is applied. Together with theoretical results, the field experimental observations in the Taiwan Bank suggest band gap and wave localization as the physical mechanism of sea surface water wave propagating over natural large-scale sand waves.

The Effects of Inhalation Aromatherapy on Anxiety in Patients With Myocardial Infarction: A Randomized Clinical Trial

PubMed Central

Najafi, Zahra; Taghadosi, Mohsen; Sharifi, Khadijeh; Farrokhian, Alireza; Tagharrobi, Zahra

2014-01-01

Background: Anxiety is an important mental health problem in patients with cardiac disease. Anxiety reduces patients’ quality of life and increases the risk of different cardiac complications. Objectives: The aim of this study was to investigate the effects of inhalation aromatherapy on anxiety in patients with myocardial infarction. Patients and Methods: This was a randomized clinical trial conduced on 68 patients with myocardial infarction hospitalized in coronary care units of a large-scale teaching hospital affiliated to Kashan University of Medical Sciences, Kashan, Iran in 2013. By using the block randomization technique, patients were randomly assigned to experimental (33 patients receiving inhalation aromatherapy with lavender aroma twice a day for two subsequent days) and control (35 patients receiving routine care of study setting including no aromatherapy) groups. At the beginning of study and twenty minutes after each aromatherapy session, anxiety state of patients was assessed using the Spielberger’s State Anxiety Inventory. Data was analyzed using SPSS v. 16.0. We used Chi-square, Fisher’s exact, independent-samples T-test and repeated measures analysis of variance to analyze the study data. Results: The study groups did not differ significantly regarding baseline anxiety mean and demographic characteristics. However, after the administration of aromatherapy, anxiety mean in the experimental group was significantly lower than the control group. Conclusions: Inhalation aromatherapy with lavender aroma can reduce anxiety in patients with myocardial infarction. Consequently, healthcare providers, particularly nurses, can use this strategy to improve postmyocardial infarction anxiety management. PMID:25389481

Home-based exercise program and fall-risk reduction in older adults with multiple sclerosis: phase 1 randomized controlled trial.

PubMed

Sosnoff, Jacob J; Finlayson, Marcia; McAuley, Edward; Morrison, Steve; Motl, Robert W

2014-03-01

To determine the feasibility, safety, and efficacy of a home-based exercise intervention targeting fall risk in older adults with multiple sclerosis. A randomized controlled pilot trial. A home-based exercise program. Participants were randomly allocated to either a home-based exercise intervention group (n = 13) or a waiting list control group (n = 14). The exercise group completed exercises targeting lower muscle strength and balance three times a week for 12 weeks. The control group continued normal activity. Fall risk (Physiological Profile Assessment scores), balance (Berg Balance Scale), and walking testing prior to and immediately following the 12-week intervention. Each outcome measure was placed in an analysis of covariance with group as the between-subject factor and baseline values as the covariate. Effect sizes were calculated. Twelve participants from the control group and ten from the exercise group completed the study. There were no related adverse events. Fall risk was found to decrease in the exercise group following the intervention (1.1 SD 1.0 vs. 0.6 SD 0.6) while there was an increase in fall risk in the control group (1.9 SD 1.5 vs. 2.2 SD 1.9). Effect sizes for most outcomes were large (η(2) > 0.15). Home-based exercise was found to be feasible, safe, and effective for reducing physiological fall risk in older adults with multiple sclerosis. Our findings support the implementation of a larger trial to reduce fall risk in persons with multiple sclerosis.

Effects of Mat Pilates on Physical Functional Performance of Older Adults: A Meta-analysis of Randomized Controlled Trials.

PubMed

Bueno de Souza, Roberta Oliveira; Marcon, Liliane de Faria; Arruda, Alex Sandro Faria de; Pontes Junior, Francisco Luciano; Melo, Ruth Caldeira de

2018-06-01

The present meta-analysis aimed to examine evidence from randomized controlled trials to determine the effects of mat Pilates on measures of physical functional performance in the older population. A search was conducted in the MEDLINE/PubMed, Scopus, Scielo, and PEDro databases between February and March 2017. Only randomized controlled trials that were written in English, included subjects aged 60 yrs who used mat Pilates exercises, included a comparison (control) group, and reported performance-based measures of physical function (balance, flexibility, muscle strength, and cardiorespiratory fitness) were included. The methodological quality of the studies was analyzed according to the PEDro scale and the best-evidence synthesis. The meta-analysis was conducted with the Review Manager 5.3 software. The search retrieved 518 articles, nine of which fulfilled the inclusion criteria. High methodological quality was found in five of these studies. Meta-analysis indicated a large effect of mat Pilates on dynamic balance (standardized mean difference = 1.10, 95% confidence interval = 0.29-1.90), muscle strength (standardized mean difference = 1.13, 95% confidence interval = 0.30-1.96), flexibility (standardized mean difference = 1.22, 95% confidence interval = 0.39-2.04), and cardiorespiratory fitness (standardized mean difference = 1.48, 95% confidence interval = 0.42-2.54) of elderly subjects. There is evidence that mat Pilates improves dynamic balance, lower limb strength, hip and lower back flexibility, and cardiovascular endurance in elderly individuals. Furthermore, high-quality studies are necessary to clarify the effects of mat Pilates on other physical functional measurements among older adults.

The impact of occupational therapy in Parkinson's disease: a randomized controlled feasibility study.

PubMed

Sturkenboom, Ingrid H; Graff, Maud J; Borm, George F; Veenhuizen, Yvonne; Bloem, Bastiaan R; Munneke, Marten; Nijhuis-van der Sanden, Maria W

2013-02-01

To evaluate the feasibility of a randomized controlled trial including process and potential impact of occupational therapy in Parkinson's disease. Process and outcome were quantitatively and qualitatively evaluated in an exploratory multicentre, two-armed randomized controlled trial at three months. Forty-three community-dwelling patients with Parkinson's disease and difficulties in daily activities, their primary caregivers and seven occupational therapists. Ten weeks of home-based occupational therapy according to the Dutch guidelines of occupational therapy in Parkinson's disease versus no occupational therapy in the control group. Process evaluation measured accrual, drop-out, intervention delivery and protocol adherence. Primary outcome measures of patients assessed daily functioning: Canadian Occupational Performance Measure (COPM) and Assessment of Motor and Process Skills. Primary outcome for caregivers was caregiver burden: Zarit Burden Inventory. Participants' perspectives of the intervention were explored using questionnaires and in-depth interviews. Inclusion was 23% (43/189), drop-out 7% (3/43) and unblinding of assessors 33% (13/40). Full intervention protocol adherence was 74% (20/27), but only 60% (71/119) of baseline Canadian Occupational Performance Measure priorities were addressed in the intervention. The outcome measures revealed negligible to small effects in favour of the intervention group. Almost all patients and caregivers of the intervention group were satisfied with the results. They perceived: 'more grip on the situation' and used 'practical advices that make life easier'. Therapists were satisfied, but wished for a longer intervention period. The positive perceived impact of occupational therapy warrants a large-scale trial. Adaptations in instructions and training are needed to use the Canadian Occupational Performance Measure as primary outcome measure.

Endovascular Therapy Is Effective and Safe for Patients With Severe Ischemic Stroke: Pooled Analysis of Interventional Management of Stroke III and Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands Data.

PubMed

Broderick, Joseph P; Berkhemer, Olvert A; Palesch, Yuko Y; Dippel, Diederik W J; Foster, Lydia D; Roos, Yvo B W E M; van der Lugt, Aad; Tomsick, Thomas A; Majoie, Charles B L M; van Zwam, Wim H; Demchuk, Andrew M; van Oostenbrugge, Robert J; Khatri, Pooja; Lingsma, Hester F; Hill, Michael D; Roozenbeek, Bob; Jauch, Edward C; Jovin, Tudor G; Yan, Bernard; von Kummer, Rüdiger; Molina, Carlos A; Goyal, Mayank; Schonewille, Wouter J; Mazighi, Mikael; Engelter, Stefan T; Anderson, Craig S; Spilker, Judith; Carrozzella, Janice; Ryckborst, Karla J; Janis, L Scott; Simpson, Kit N

2015-12-01

We assessed the effect of endovascular treatment in acute ischemic stroke patients with severe neurological deficit (National Institutes of Health Stroke Scale score, ≥20) after a prespecified analysis plan. The pooled analysis of the Interventional Management of Stroke III (IMS III) and Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands (MR CLEAN) trials included participants with an National Institutes of Health Stroke Scale score of ≥20 before intravenous tissue-type plasminogen activator (tPA) treatment (IMS III) or randomization (MR CLEAN) who were treated with intravenous tPA ≤3 hours of stroke onset. Our hypothesis was that participants with severe stroke randomized to endovascular therapy after intravenous tPA would have improved 90-day outcome (distribution of modified Rankin Scale scores), when compared with those who received intravenous tPA alone. Among 342 participants in the pooled analysis (194 from IMS III and 148 from MR CLEAN), an ordinal logistic regression model showed that the endovascular group had superior 90-day outcome compared with the intravenous tPA group (adjusted odds ratio, 1.78; 95% confidence interval, 1.20-2.66). In the logistic regression model of the dichotomous outcome (modified Rankin Scale score, 0-2, or functional independence), the endovascular group had superior outcomes (adjusted odds ratio, 1.97; 95% confidence interval, 1.09-3.56). Functional independence (modified Rankin Scale score, ≤2) at 90 days was 25% in the endovascular group when compared with 14% in the intravenous tPA group. Endovascular therapy after intravenous tPA within 3 hours of symptom onset improves functional outcome at 90 days after severe ischemic stroke. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424 (IMS III) and ISRCTN10888758 (MR CLEAN). © 2015 American Heart Association, Inc.

Effect of acupuncture on insomnia following stroke: study protocol for a randomized controlled trial.

PubMed

Cao, Yan; Yin, Xuan; Soto-Aguilar, Francisca; Liu, Yiping; Yin, Ping; Wu, Junyi; Zhu, Bochang; Li, Wentao; Lao, Lixing; Xu, Shifen

2016-11-16

The incidence, mortality, and prevalence of stroke are high in China. Stroke is commonly associated with insomnia; both insomnia and stroke have been effectively treated with acupuncture for a long time. The aim of this proposed trial is to assess the therapeutic effect of acupuncture on insomnia following stroke. This proposed study is a single-center, single-blinded (patient-assessor-blinded), parallel-group randomized controlled trial. We will randomly assign 60 participants with insomnia following stroke into two groups in a 1:1 ratio. The intervention group will undergo traditional acupuncture that achieves the De-qi sensation, and the control group will receive sham acupuncture without needle insertion. The same acupoints (DU20, DU24, EX-HN3, EX-HN22, HT7, and SP6) will be used in both groups. Treatments will be given to all participants three times a week for the subsequent 4 weeks. The primary outcome will be the Pittsburgh Sleep Quality Index. The secondary outcomes will be: the Insomnia Severity Index; sleep efficacy, sleep awakenings, and total sleep time recorded via actigraphy; the National Institutes of Health Stroke Scale; the Stroke-Specific Quality of Life score; the Hospital Anxiety and Depression Scale. The use of estazolam will be permitted and regulated under certain conditions. Outcomes will be assessed at baseline, 2 weeks after treatment commencement, 4 weeks after treatment commencement, and at the 8-week follow-up. This proposed study will contribute to expanding knowledge about acupuncture treatment for insomnia following stroke. This will be a high-quality randomized controlled trial with strict methodology and few design deficits. It will investigate the effectiveness of acupuncture as an alternative treatment for insomnia following stroke. Chinese Clinical Trial Registry identifier: ChiCTR-IIC-16008382 . Registered on 28 April 2016.

A randomized double-blind, placebo-controlled trial of minocycline in children and adolescents with fragile x syndrome.

PubMed

Leigh, Mary Jacena S; Nguyen, Danh V; Mu, Yi; Winarni, Tri I; Schneider, Andrea; Chechi, Tasleem; Polussa, Jonathan; Doucet, Paul; Tassone, Flora; Rivera, Susan M; Hessl, David; Hagerman, Randi J

2013-04-01

Minocycline rescued synaptic abnormalities and improved behavior in the fragile X mouse model. Previous open-label human studies demonstrated benefits in individuals with fragile X syndrome (FXS); however, its efficacy in patients with FXS has not been assessed in a controlled trial. Randomized, double-blind, placebo-controlled, crossover trial in individuals with FXS, aged 3.5 years to 16 years (n = 55, mean age 9.2 [SD, 3.6] years). Participants were randomized to minocycline or placebo for 3 months and then switched to the other treatment. Sixty-nine subjects were screened and 66 were randomized. Fifty-five subjects (83.3%) completed at least the first period and 48 (72.7%) completed the full trial. Intention-to-treat analysis demonstrated significantly greater improvements in one primary outcome, Clinical Global Impression Scale-Improvement after minocycline compared with placebo (2.49 ± 0.13 and 2.97 ± 0.13, respectively, p = .0173) and greater improvement in ad hoc analysis of anxiety and mood-related behaviors on the Visual Analog Scale (minocycline: 5.26 cm ± 0.46 cm, placebo: 4.05 cm ± 0.46 cm; p = .0488). Side effects were not significantly different during the minocycline and placebo treatments. No serious adverse events occurred on minocycline. Results may be potentially biased by study design weaknesses, including unblinding of subjects when they completed the study, drug-related side effects unblinding, and preliminary efficacy analysis results known to investigators. Minocycline treatment for 3 months in children with FXS resulted in greater global improvement than placebo. Treatment for 3 months appears safe; however, longer trials are indicated to further assess benefits, side effects, and factors associated with a clinical response to minocycline.

A Randomized Double-Blind, Placebo-Controlled Trial of Minocycline in Children and Adolescents with Fragile X Syndrome

PubMed Central

Leigh, Mary Jacena S.; Nguyen, Danh V.; Mu, Yi; Winarni, Tri I.; Schneider, Andrea; Chechi, Tasleem; Polussa, Jonathan; Doucet, Paul; Tassone, Flora; Rivera, Susan M.; Hessl, David; Hagerman, Randi J.

2013-01-01

Objective Minocycline rescued synaptic abnormalities and improved behavior in the fragile X mouse model. Prior open-label human studies demonstrated benefits in individuals with fragile X syndrome (FXS); however, its efficacy in patients with FXS has not been assessed in a controlled trial. Method Randomized, double-blind, placebo-controlled, crossover trial in individuals with FXS, ages 3.5-16 years (n=55, mean age 9.2 (SD 3.6 years)). Participants were randomized to minocycline or placebo for three months, then switched to the other treatment. Results Sixty-nine subjects were screened and 66 were randomized. Fifty-five subjects (83.3%) completed at least the first period and 48 (72.7%) completed the full trial. Intention-to-treat analysis demonstrated significantly greater improvements in one primary outcome, Clinical Global Impression Scale-Improvement after minocycline compared to placebo (2.49 ±0.13, 2.97 ±0.13, respectively, p 0.0173) and greater improvement in ad hoc analysis of anxiety and mood-related behaviors on the Visual Analoge Scale (minocycline 5.26 cm ±0.46 cm, placebo 4.05 cm±0.46cm; p 0.0488). Side effects were not significantly different during the minocycline and placebo treatments. No serious adverse events occurred on minocycline. Results may be potentially biased by study design weaknesses, including unblinding of subjects when they completed the study, drug-related side effects unblinding and preliminary efficacy analysis results known to investigators. Conclusion Minocycline treatment for three months in children with FXS resulted in greater global improvement than placebo. Treatment for three months appears safe; however, longer trials are indicated to further assess benefits, side effects, and factors associated with a clinical response to minocycline. PMID:23572165

A double-blind, placebo-controlled, randomized trial of Ginkgo biloba extract EGb 761 in a sample of cognitively intact older adults: neuropsychological findings.

PubMed

Mix, Joseph A; Crews, W David

2002-08-01

There appears to be an absence of large-scaled clinical trials that have examined the efficacy of Ginkgo biloba extract on the neuropsychological functioning of cognitively intact older adults. The importance of such clinical research appears paramount in light of the plethora of products containing Ginkgo biloba that are currently being widely marketed to predominantly cognitively intact adults with claims of enhanced cognitive performances. The purpose of this research was to conduct the first known, large-scaled clinical trial of the efficacy of Ginkgo biloba extract (EGb 761) on the neuropsychological functioning of cognitively intact older adults. Two hundred and sixty-two community-dwelling volunteers (both male and female) 60 years of age and older, who reported no history of dementia or significant neurocognitive impairments and obtained Mini-Mental State Examination total scores of at least 26, were examined via a 6-week, randomized, double-blind, fixed-dose, placebo-controlled, parallel-group, clinical trial. Participants were randomly assigned to receive either Ginkgo biloba extract EGb 761(n = 131; 180 mg/day) or placebo (n = 131) for 6 weeks. Efficacy measures consisted of participants' raw change in performance scores from pretreatment baseline to those obtained just prior to termination of treatment on the following standardized neuropsychological measures: Selective Reminding Test (SRT), Wechsler Adult Intelligence Scale-III Block Design (WAIS-III BD) and Digit Symbol-Coding (WAIS-III DS) subtests, and the Wechsler Memory Scale-III Faces I (WMS-III FI) and Faces II (WMS-III FII) subtests. A subjective Follow-up Self-report Questionnaire was also administered to participants just prior to termination of the treatment phase. Analyses of covariance indicated that cognitively intact participants who received 180 mg of EGb 761 daily for 6 weeks exhibited significantly more improvement on SRT tasks involving delayed (30 min) free recall (p < 0.04) and recognition (p < 0.01) of noncontextual, auditory-verbal material, compared with the placebo controls. The EGb 761 group also demonstrated significantly greater improvement on the WMS-III FII subtest assessing delayed (30 min) recognition (p < 0.025) of visual material (i.e. human faces), compared with the placebo group. However, based on the significant difference (p < 0.03) found between the two groups' pretreatment baseline scores on the WMS-III FII, this result should be interpreted with caution. An examination of the participants' subjective ratings of their overall abilities to remember by treatment end on the Follow-up Self-report Questionnaire also revealed that significantly more (p = 0.05) older adults in the EGb 761 group rated their overall abilities to remember by treatment end as 'improved' compared with the placebo controls. Overall, the results from both objective, standardized, neuropsychological tests and a subjective, follow-up self-report questionnaire provided complementary evidence of the potential efficacy of Ginkgo biloba EGb 761 in enhancing certain neuropsychological/memory processes of cognitively intact older adults, 60 years of age and over. Copyright 2002 John Wiley & Sons, Ltd.

The PLCO Cancer Screening Trial: Q and A

Cancer.gov

The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a large, randomized study to determine whether the use of certain screening tests will reduce the risk of dying of those four cancers. In addition to answering questions about the

The effect of a therapeutic regimen of Traditional Chinese Medicine rehabilitation for post-stroke cognitive impairment: study protocol for a randomized controlled trial.

PubMed

Huang, Jia; Lin, Zhengkun; Wang, Qin; Liu, Feiwen; Liu, Jiao; Fang, Yunhua; Chen, Shanjia; Zhou, Xiaoxuan; Hong, Wenjun; Wu, Jinsong; Madrigal-Mora, Natalia; Zheng, Guohua; Yang, Shanli; Tao, Jing; Chen, Lidian

2015-06-16

Post-stroke cognitive impairment (PSCI) lessens quality of life, restricts the rehabilitation of stroke, and increases the social and economic burden stroke imposes on patients and their families. Therefore effective treatment is of paramount importance. However, the treatment of PSCI is very limited. The primary aim of this protocol is to propose a lower cost and more effective therapy, and to confirm the long-term effectiveness of a therapeutic regimen of Traditional Chinese Medicine (TCM) rehabilitation for PSCI. A prospective, multicenter, large sample, randomized controlled trial will be conducted. A total of 416 eligible patients will be recruited from seven inpatient and outpatient stroke rehabilitation units and randomly allocated into a therapeutic regimen of TCM rehabilitation group or cognitive training (CT) control group. The intervention period of both groups will last 12 weeks (30 minutes per day, five days per week). Primary and secondary outcomes will be measured at baseline, 12 weeks (at the end of the intervention), and 36 weeks (after the 24-week follow-up period). This protocol presents an objective design of a multicenter, large sample, randomized controlled trial that aims to put forward a lower cost and more effective therapy, and confirm the long-term effectiveness of a therapeutic regimen of TCM rehabilitation for PSCI through subjective and objective assessments, as well as highlight its economic advantages. This trial was registered with the Chinese Clinical Trial Registry (identifier: ChiCTR-TRC-14004872 ) on 23 June 2014.

A pilot randomized controlled trial comparing prenatal yoga to perinatal health education for antenatal depression.

PubMed

Uebelacker, Lisa A; Battle, Cynthia L; Sutton, Kaeli A; Magee, Susanna R; Miller, Ivan W

2016-06-01

We conducted a pilot randomized controlled trial (RCT) comparing a prenatal yoga intervention to perinatal-focused health education in pregnant women with depression. Findings document acceptability and feasibility of the yoga intervention: no yoga-related injuries were observed, instructors showed fidelity to the yoga manual, and women rated interventions as acceptable. Although improvements in depression were not statistically different between groups, they favored yoga. This study provides support for a larger scale RCT examining prenatal yoga to improve mood during pregnancy.

Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available.

PubMed

Hernán, Miguel A; Robins, James M

2016-04-15

Ideally, questions about comparative effectiveness or safety would be answered using an appropriately designed and conducted randomized experiment. When we cannot conduct a randomized experiment, we analyze observational data. Causal inference from large observational databases (big data) can be viewed as an attempt to emulate a randomized experiment-the target experiment or target trial-that would answer the question of interest. When the goal is to guide decisions among several strategies, causal analyses of observational data need to be evaluated with respect to how well they emulate a particular target trial. We outline a framework for comparative effectiveness research using big data that makes the target trial explicit. This framework channels counterfactual theory for comparing the effects of sustained treatment strategies, organizes analytic approaches, provides a structured process for the criticism of observational studies, and helps avoid common methodologic pitfalls. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Systems Training for Emotional Predictability and Problem Solving (STEPPS) for outpatients with borderline personality disorder: a randomized controlled trial and 1-year follow-up.

PubMed

Blum, Nancee; St John, Don; Pfohl, Bruce; Stuart, Scott; McCormick, Brett; Allen, Jeff; Arndt, Stephan; Black, Donald W

2008-04-01

Systems Training for Emotional Predictability and Problem Solving (STEPPS) is a 20-week manual-based group treatment program for outpatients with borderline personality disorder that combines cognitive behavioral elements and skills training with a systems component. The authors compared STEPPS plus treatment as usual with treatment as usual alone in a randomized controlled trial. Subjects with borderline personality disorder were randomly assigned to STEPPS plus treatment as usual or treatment as usual alone. Total score on the Zanarini Rating Scale for Borderline Personality Disorder was the primary outcome measure. Secondary outcomes included measures of global functioning, depression, impulsivity, and social functioning; suicide attempts and self-harm acts; and crisis utilization. Subjects were followed 1 year posttreatment. A linear mixed-effects model was used in the analysis. Data pertaining to 124 subjects (STEPPS plus treatment as usual [N=65]; treatment as usual alone [N=59]) were analyzed. Subjects assigned to STEPPS plus treatment as usual experienced greater improvement in the Zanarini Rating Scale for Borderline Personality Disorder total score and subscales assessing affective, cognitive, interpersonal, and impulsive domains. STEPPS plus treatment as usual also led to greater improvements in impulsivity, negative affectivity, mood, and global functioning. These differences yielded moderate to large effect sizes. There were no differences between groups for suicide attempts, self-harm acts, or hospitalizations. Most gains attributed to STEPPS were maintained during follow-up. Fewer STEPPS plus treatment as usual subjects had emergency department visits during treatment and follow-up. The discontinuation rate was high in both groups. STEPPS, an adjunctive group treatment, can deliver clinically meaningful improvements in borderline personality disorder-related symptoms and behaviors, enhance global functioning, and relieve depression.

Trauma-focused cognitive behavioral therapy or eye movement desensitization and reprocessing: what works in children with posttraumatic stress symptoms? A randomized controlled trial.

PubMed

Diehle, Julia; Opmeer, Brent C; Boer, Frits; Mannarino, Anthony P; Lindauer, Ramón J L

2015-02-01

To prevent adverse long-term effects, children who suffer from posttraumatic stress symptoms (PTSS) need treatment. Trauma-focused cognitive behavioral therapy (TF-CBT) is an established treatment for children with PTSS. However, alternatives are important for non-responders or if TF-CBT trained therapists are unavailable. Eye movement desensitization and reprocessing (EMDR) is a promising treatment for which sound comparative evidence is lacking. The current randomized controlled trial investigates the effectiveness and efficiency of both treatments. Forty-eight children (8-18 years) were randomly assigned to eight sessions of TF-CBT or EMDR. The primary outcome was PTSS as measured with the Clinician-Administered PTSD Scale for Children and Adolescents (CAPS-CA). Secondary outcomes included parental report of child PTSD diagnosis status and questionnaires on comorbid problems. The Children's Revised Impact of Event Scale was administered during the course of treatment. TF-CBT and EMDR showed large reductions from pre- to post-treatment on the CAPS-CA (-20.2; 95% CI -12.2 to -28.1 and -20.9; 95% CI -32.7 to -9.1). The difference in reduction was small and not statistically significant (mean difference of 0.69, 95% CI -13.4 to 14.8). Treatment duration was not significantly shorter for EMDR (p = 0.09). Mixed model analysis of monitored PTSS during treatment showed a significant effect for time (p < 0.001) but not for treatment (p = 0.44) or the interaction of time by treatment (p = 0.74). Parents of children treated with TF-CBT reported a significant reduction of comorbid depressive and hyperactive symptoms. TF-CBT and EMDR are effective and efficient in reducing PTSS in children.

A pilot study of activity-based therapy in the arm motor recovery post stroke: a randomized controlled trial.

PubMed

Rabadi, Mh; Galgano, M; Lynch, D; Akerman, M; Lesser, M; Volpe, Bt

2008-12-01

To determine the efficacy of activity-based therapies using arm ergometer or robotic or group occupational therapy for motor recovery of the paretic arm in patients with an acute stroke (< or =4 weeks) admitted to an inpatient rehabilitation facility, and to obtain information to plan a large randomized controlled trial. Prospective, randomized controlled study. Stroke unit in a rehabilitation hospital. Thirty patients with an acute stroke (< or =4 weeks) who had arm weakness (Medical Research Council grade 2 or less at the shoulder joint). Occupational therapy (OT) group (control) (n = 10), arm ergometer (n = 10) or robotic (n = 10) therapy group. All patients received standard, inpatient, post-stroke rehabilitation training for 3 hours a day, plus 12 additional 40-minute sessions of the activity-based therapy. The primary outcome measures were discharge scores in the Fugl-Meyer Assessment Scale for upper limb impairment, Motor Status Scale, total Functional Independence Measure (FIM) and FIM-motor and FIM-cognition subscores. The three groups (OT group versus arm ergometer versus robotic) were comparable on clinical demographic measures except the robotic group was significantly older and there were more haemorrhagic stroke patients in the arm ergometer group. After adjusting for age, stroke type and outcome measures at baseline, a similar degree of improvement in the discharge scores was found in all of the primary outcome measures. This study suggests that activity-based therapies using an arm ergometer or robot when used over shortened training periods have the same effect as OT group therapy in decreasing impairment and improving disability in the paretic arm of severely affected stroke patients in the subacute phase.

Interferential current sensory stimulation, through the neck skin, improves airway defense and oral nutrition intake in patients with dysphagia: a double-blind randomized controlled trial

PubMed Central

Maeda, Keisuke; Koga, Takayuki; Akagi, Junji

2017-01-01

Background Neuromuscular electrical stimulation with muscle contraction, administered through the skin of the neck, improves a patient’s swallowing ability. However, the beneficial effects of transcutaneous electrical sensory stimulation (TESS), without muscle contraction, are controversial. We investigated the effect of TESS, using interferential current, in patients undergoing dysphagia rehabilitation. Methods This double-blind, randomized controlled trial involved 43 patients who were prescribed in-hospital dysphagia rehabilitation for ≥3 weeks. Patients were randomly assigned to the sensory stimulation (SS) or sham groups; all received usual rehabilitative care plus 2 weeks of SS or sham intervention. Outcome measures included cough latency times against a 1% citric acid mist, functional oral intake scale (FOIS) scores, and oral nutritional intake – each determined after the second and third week following treatment initiation. Results Mean patient age was 84.3±7.5 years; 58% were women. The SS and sham groups had similar baseline characteristics. Changes in cough latency time at 2 weeks (−14.1±14.0 vs −5.2±14.2 s, p=0.047) and oral nutrition intake at 3 weeks (437±575 vs 138±315 kcal/day, p=0.042) improved more in the SS group than in the sham group. Changes in cough frequency and FOIS scores indicated better outcomes in the SS group, based on substantial effect sizes. Conclusion TESS, using interferential current through the neck, improved airway defense and nutrition in patients suffering from dysphagia. Further large-scale studies are needed to confirm the technique’s effect on swallowing ability. PMID:29158670

Electroacupuncture and splinting versus splinting alone to treat carpal tunnel syndrome: a randomized controlled trial.

PubMed

Chung, Vincent C H; Ho, Robin S T; Liu, Siya; Chong, Marc K C; Leung, Albert W N; Yip, Benjamin H K; Griffiths, Sian M; Zee, Benny C Y; Wu, Justin C Y; Sit, Regina W S; Lau, Alexander Y L; Wong, Samuel Y S

2016-09-06

The effectiveness of acupuncture for managing carpal tunnel syndrome is uncertain, particularly in patients already receiving conventional treatments (e.g., splinting). We aimed to assess the effects of electroacupuncture combined with splinting. We conducted a randomized parallel-group assessor-blinded 2-arm trial on patients with clinically diagnosed primary carpal tunnel syndrome. The treatment group was offered 13 sessions of electroacupuncture over 17 weeks. The treatment and control groups both received continuous nocturnal wrist splinting. Of 181 participants randomly assigned to electroacupuncture combined with splinting (n = 90) or splinting alone (n = 91), 174 (96.1%) completed all follow-up. The electroacupuncture group showed greater improvements at 17 weeks in symptoms (primary outcome of Symptom Severity Scale score mean difference [MD] -0.20, 95% confidence interval [CI] -0.36 to -0.03), disability (Disability of Arm, Shoulder and Hand Questionnaire score MD -6.72, 95% CI -10.9 to -2.57), function (Functional Status Scale score MD -0.22, 95% CI -0.38 to -0.05), dexterity (time to complete blinded pick-up test MD -6.13 seconds, 95% CI -10.6 to -1.63) and maximal tip pinch strength (MD 1.17 lb, 95% CI 0.48 to 1.86). Differences between groups were small and clinically unimportant for reduction in pain (numerical rating scale -0.70, 95% CI -1.34 to -0.06), and not significant for sensation (first finger monofilament test -0.08 mm, 95% CI -0.22 to 0.06). For patients with primary carpal tunnel syndrome, chronic mild to moderate symptoms and no indication for surgery, electroacupuncture produces small changes in symptoms, disability, function, dexterity and pinch strength when added to nocturnal splinting. Chinese Clinical Trial Register no. ChiCTR-TRC-11001655 (www.chictr.org.cn/showprojen.aspx?proj=7890); subsequently deposited in the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR-TRC-11001655). © 2016 Canadian Medical Association or its licensors.

Reduced knee joint loading with lateral and medial wedge insoles for management of knee osteoarthritis: a protocol for a randomized controlled trial.

PubMed

Lewinson, Ryan T; Collins, Kelsey H; Vallerand, Isabelle A; Wiley, J Preston; Woodhouse, Linda J; Reimer, Raylene A; Worobets, Jay T; Herzog, Walter; Stefanyshyn, Darren J

2014-12-03

Knee osteoarthritis (OA) progression has been linked to increased peak external knee adduction moments (KAMs). Although some trials have attempted to reduce pain and improve function in OA by reducing KAMs with a wedged footwear insole intervention, KAM reduction has not been specifically controlled for in trial designs, potentially explaining the mixed results seen in the literature. Therefore, the primary purpose of this trial is to identify the effects of reduced KAMs on knee OA pain and function. Forty-six patients with radiographically confirmed diagnosis medial knee OA will be recruited for this 3 month randomized controlled trial. Recruitment will be from Alberta and surrounding areas. Eligibility criteria include being between the ages of 40 and 85 years, have knee OA primarily localized to the medial tibiofemoral compartment, based on the American College of Rheumatology diagnostic criteria and be classified as having a Kellgren-Lawrence grade of 1 to 3. Patients will visit the laboratory at baseline for testing that includes dual x-ray absorptiometry, biomechanical testing, and surveys (KOOS, PASE activity scale, UCLA activity scale, comfort visual analog scale). At baseline, patients will be randomized to either a wedged insole group to reduce KAMs, or a waitlist control group where no intervention is provided. The survey tests will be repeated at 3 months, and response to wedged insoles over 3 months will be evaluated. This study represents the first step in systematically evaluating the effects of reduced KAMs on knee OA management by using a patient-specific wedged insole prescription procedure rather than providing the same insole to all patients. The results of this trial will provide indications as to whether reduced KAMs are an effective strategy for knee OA management, and whether a personalized approach to footwear insole prescription is warranted. NCT02067208.

HIV Topical Microbicides: Steer the Ship or Run Aground

PubMed Central

Gross, Michael

2004-01-01

Six HIV candidate microbicides are scheduled to enter 6 large-scale effectiveness trials in the next year. The selection of products for testing and the design of this group of trials should be reconsidered to provide an answer to a key question now before the field: Does a sulfonated polyanion, delivered intravaginally as a gel, block HIV attachment to target cells with sufficient potency to protect women from sexually acquired HIV infection? Paradoxically, entering more candidates into more trials may confuse or compromise efforts to identify an effective product. Instead, a single trial of the most promising product(s) best serves the current candidates while also preserving resources needed to promptly advance innovative new protective concepts into future large-scale trials. PMID:15226123

Qigong Exercises for the Management of Type 2 Diabetes Mellitus

PubMed Central

Close, Jacqueline R.; Lilly, Harold Ryan; Guillaume, Nathalie; Sun, Guan-Cheng

2017-01-01

Background: The purpose of this article is to clarify and define medical qigong and to identify an appropriate study design and methodology for a large-scale study looking at the effects of qigong in patients with type 2 diabetes mellitus (T2DM), specifically subject enrollment criteria, selection of the control group and study duration. Methods: A comprehensive literature review of English databases was used to locate articles from 1980–May 2017 involving qigong and T2DM. Control groups, subject criteria and the results of major diabetic markers were reviewed and compared within each study. Definitions of qigong and its differentiation from physical exercise were also considered. Results: After a thorough review, it was found that qigong shows positive effects on T2DM; however, there were inconsistencies in control groups, research subjects and diabetic markers analyzed. It was also discovered that there is a large variation in styles and definitions of qigong. Conclusions: Qigong exercise has shown promising results in clinical experience and in randomized, controlled pilot studies for affecting aspects of T2DM including blood glucose, triglycerides, total cholesterol, weight, BMI and insulin resistance. Due to the inconsistencies in study design and methods and the lack of large-scale studies, further well-designed randomized control trials (RCT) are needed to evaluate the ‘vital energy’ or qi aspect of internal medical qigong in people who have been diagnosed with T2DM. PMID:28930273

Analgesic efficacy of lidocaine for suction-assisted lipectomy with tumescent technique under general anesthesia: a randomized, double-masked, controlled trial.

PubMed

Danilla, Stefan; Fontbona, Montserrat; de Valdés, Victoria Diaz; Dagnino, Bruno; Sorolla, Juan Pablo; Israel, Guillermo; Searle, Susana; Norambuena, Hernán; Cabello, Rodrigo

2013-08-01

Suction-assisted lipectomy is one of the most common procedures performed in plastic surgery. To minimize blood loss and to obtain adequate analgesia, a liquid solution is infiltrated into the subcutaneous plane before suction. The objective of this study was to determine whether the use of lidocaine in the infiltration solution reduces postoperative pain. A prospective, randomized, double-masked, clinical trial was designed. Each side of patients' body zones to be treated with suction-assisted lipectomy was randomized to receive infiltration solution with or without lidocaine. Treatment allocation was performed using computer-generated random numbers in permuted blocks of eight. Pain was assessed using the visual analogue scale and registered 1, 6, 12, 18, and 24 hours after the procedure. The trial was stopped after a first interim analysis. The use of lidocaine in the dilute solution reduced pain by 0.5 point on the visual analogue scale (95 percent CI, 0.3 to 0.8; p<0.001). The effect was independent of the suctioned body zone (p=0.756), and lasted until 18 hours after surgery. Its analgesic effect was lost at the 24-hour postoperative control. Pain increased an average of 0.018 point on the visual analogue scale per hour (95 percent CI, 0.001 to 0.036; p=0.043). The use of lidocaine in the infiltration solution is effective in postoperative pain control until 18 hours after surgery. Nevertheless, its clinical effect is limited and clinically irrelevant, and therefore it is no longer used by the authors. Therapeutic, I.

A Randomized Controlled Trial of Cognitive-Behavior Therapy Plus Bright Light Therapy for Adolescent Delayed Sleep Phase Disorder

PubMed Central

Gradisar, Michael; Dohnt, Hayley; Gardner, Greg; Paine, Sarah; Starkey, Karina; Menne, Annemarie; Slater, Amy; Wright, Helen; Hudson, Jennifer L.; Weaver, Edward; Trenowden, Sophie

2011-01-01

Objective: To evaluate cognitive-behavior therapy plus bright light therapy (CBT plus BLT) for adolescents diagnosed with delayed sleep phase disorder (DSPD). Design: Randomized controlled trial of CBT plus BLT vs. waitlist (WL) control with comparisons at pre- and post-treatment. There was 6-month follow-up for the CBT plus BLT group only. Setting: Flinders University Child & Adolescent Sleep Clinic, Adelaide, South Australia. Patients: 49 adolescents (mean age 14.6 ± 1.0 y, 53% males) diagnosed with DSPD; mean chronicity 4 y 8 months; 16% not attending school. Eighteen percent of adolescents dropped out of the study (CBT plus BLT: N = 23 vs WL: N = 17). Interventions: CBT plus BLT consisted of 6 individual sessions, including morning bright light therapy to advance adolescents' circadian rhythms, and cognitive restructuring and sleep education to target associated insomnia and sleep hygiene. Measurements and Results: DSPD diagnosis was performed via a clinical interview and 7-day sleep diary. Measurements at each time-point included online sleep diaries and scales measuring sleepiness, fatigue, and depression symptoms. Compared to WL, moderate-to-large improvements (d = 0.65-1.24) were found at post-treatment for CBT plus BLT adolescents, including reduced sleep latency, earlier sleep onset and rise times, total sleep time (school nights), wake after sleep onset, sleepiness, and fatigue. At 6-month follow-up (N = 15), small-to-large improvements (d = 0.24-1.53) continued for CBT plus BLT adolescents, with effects found for all measures. Significantly fewer adolescents receiving CBT plus BLT met DPSD criteria at post-treatment (WL = 82% vs. CBT plus BLT = 13%, P < 0.0001), yet 13% still met DSPD criteria at the 6-month follow-up. Conclusions: CBT plus BLT for adolescent DSPD is effective for improving multiple sleep and daytime impairments in the immediate and long-term. Studies evaluating the treatment effectiveness of each treatment component are needed. Clinical Trial Information: Australia – New Zealand Trials Registry Number: ACTRN12610001041044. Citation: Gradisar M; Dohnt H; Gardner G; Paine S; Starkey K; Menne A; Slater A; Wright H; Hudson JL; Weaver E; Trenowden S. A randomized controlled trial of cognitive-behavior therapy plus bright light therapy for adolescent delayed sleep phase disorder. SLEEP 2011;34(12):1671-1680. PMID:22131604

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

PubMed

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

2010-02-01

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

Learning before leaping: integration of an adaptive study design process prior to initiation of BetterBirth, a large-scale randomized controlled trial in Uttar Pradesh, India.

PubMed

Hirschhorn, Lisa Ruth; Semrau, Katherine; Kodkany, Bhala; Churchill, Robyn; Kapoor, Atul; Spector, Jonathan; Ringer, Steve; Firestone, Rebecca; Kumar, Vishwajeet; Gawande, Atul

2015-08-14

Pragmatic and adaptive trial designs are increasingly used in quality improvement (QI) interventions to provide the strongest evidence for effective implementation and impact prior to broader scale-up. We previously showed that an on-site coaching intervention focused on the World Health Organization Safe Childbirth Checklist (SCC) improved performance of essential birth practices (EBPs) in one facility in Karnataka, India. We report on the process and outcomes of adapting the intervention prior to larger-scale implementation in a randomized controlled trial in Uttar Pradesh (UP), India. Initially, we trained a local team of physicians and nurses to coach birth attendants in SCC use at two public facilities for 4-6 weeks. Trained observers evaluated adherence to EBPs before and after coaching. Using mixed methods and a systematic adaptation process, we modified and strengthened the intervention. The modified intervention was implemented in three additional facilities. Pre/post-change in EBP prevalence aggregated across facilities was analyzed. In the first two facilities, limited improvement was seen in EBPs with the exception of post-partum oxytocin. Checklists were used <25 % of observations. We identified challenges in physicians coaching nurses, need to engage district and facility leadership to address system gaps, and inadequate strategy for motivating SCC uptake. Revisions included change to peer-to-peer coaching (nurse to nurse, physician to physician); strengthened coach training on behavior and system change; adapted strategy for effective leadership engagement; and an explicit motivation strategy to enhance professional pride and effectiveness. These modifications resulted in improvement in multiple EBPs from baseline including taking maternal blood pressure (0 to 16 %), post-partum oxytocin (36 to 97 %), early breastfeeding initiation (3 to 64 %), as well as checklist use (range 32 to 88 %), all p < 0.01. Further adaptations were implemented to increase the effectiveness prior to full trial launch. The adaptive study design of implementation, evaluation, and feedback drove iterative redesign and successfully developed a SCC-focused coaching intervention that improved EBPs in UP facilities. This work was critical to develop a replicable BetterBirth package tailored to the local context. The multi-center pragmatic trial is underway measuring impact of the BetterBirth program on EBP and maternal-neonatal morbidity and mortality. NCT02148952 .

Antioxidant supplements and mortality.

PubMed

Bjelakovic, Goran; Nikolova, Dimitrinka; Gluud, Christian

2014-01-01

Oxidative damage to cells and tissues is considered involved in the aging process and in the development of chronic diseases in humans, including cancer and cardiovascular diseases, the leading causes of death in high-income countries. This has stimulated interest in the preventive potential of antioxidant supplements. Today, more than one half of adults in high-income countries ingest antioxidant supplements hoping to improve their health, oppose unhealthy behaviors, and counteract the ravages of aging. Older observational studies and some randomized clinical trials with high risks of systematic errors ('bias') have suggested that antioxidant supplements may improve health and prolong life. A number of randomized clinical trials with adequate methodologies observed neutral or negative results of antioxidant supplements. Recently completed large randomized clinical trials with low risks of bias and systematic reviews of randomized clinical trials taking systematic errors ('bias') and risks of random errors ('play of chance') into account have shown that antioxidant supplements do not seem to prevent cancer, cardiovascular diseases, or death. Even more, beta-carotene, vitamin A, and vitamin E may increase mortality. Some recent large observational studies now support these findings. According to recent dietary guidelines, there is no evidence to support the use of antioxidant supplements in the primary prevention of chronic diseases or mortality. Antioxidant supplements do not possess preventive effects and may be harmful with unwanted consequences to our health, especially in well-nourished populations. The optimal source of antioxidants seems to come from our diet, not from antioxidant supplements in pills or tablets.

Universal statistics of vortex tangles in three-dimensional random waves

NASA Astrophysics Data System (ADS)

Taylor, Alexander J.

2018-02-01

The tangled nodal lines (wave vortices) in random, three-dimensional wavefields are studied as an exemplar of a fractal loop soup. Their statistics are a three-dimensional counterpart to the characteristic random behaviour of nodal domains in quantum chaos, but in three dimensions the filaments can wind around one another to give distinctly different large scale behaviours. By tracing numerically the structure of the vortices, their conformations are shown to follow recent analytical predictions for random vortex tangles with periodic boundaries, where the local disorder of the model ‘averages out’ to produce large scale power law scaling relations whose universality classes do not depend on the local physics. These results explain previous numerical measurements in terms of an explicit effect of the periodic boundaries, where the statistics of the vortices are strongly affected by the large scale connectedness of the system even at arbitrarily high energies. The statistics are investigated primarily for static (monochromatic) wavefields, but the analytical results are further shown to directly describe the reconnection statistics of vortices evolving in certain dynamic systems, or occurring during random perturbations of the static configuration.

Methods for sample size determination in cluster randomized trials

PubMed Central

Rutterford, Clare; Copas, Andrew; Eldridge, Sandra

2015-01-01

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

InsuOnline, a Serious Game to Teach Insulin Therapy to Primary Care Physicians: Design of the Game and a Randomized Controlled Trial for Educational Validation

PubMed Central

Souza, Rodrigo Martins; Alves, Juliano Barbosa; Gordan, Pedro Alejandro; Esteves, Roberto Zonato; Jorge, Maria Lúcia Silva Germano; Coelho, Izabel Cristina Meister

2013-01-01

Background Physicians´ lack of knowledge contributes to underuse of insulin and poor glycemic control in adults with diabetes mellitus (DM). Traditional continuing medical education have limited efficacy, and new approaches are required. Objective We report the design of a trial to assess the educational efficacy of InsuOnline, a game for education of primary care physicians (PCPs). The goal of InsuOnline was to improve appropriate initiation and adjustment of insulin for the treatment of DM. InsuOnline was designed to be educationally adequate, self-motivating, and attractive. Methods A multidisciplinary team of endocrinologists, experts in medical education, and programmers, was assembled for the design and development of InsuOnline. Currently, we are conducting usability and playability tests, with PCPs and medical students playing the game on a desktop computer. Adjustments will be made based on these results. An unblinded randomized controlled trial with PCPs who work in the city of Londrina, Brazil, will be conducted to assess the educational validity of InsuOnline on the Web. In this trial, 64 PCPs will play InsuOnline, and 64 PCPs will undergo traditional instructional activities (lecture and group discussion). Knowledge on how to initiate and adjust insulin will be assessed by a Web-based multiple choice questionnaire, and attitudes regarding diabetes/insulin will be assessed by Diabetes Attitude Scale 3 at 3 time points—before, immediately after, and 6 months after the intervention. Subjects´ general impressions on the interventions will be assessed by a questionnaire. Software logs will be reviewed. Results To our knowledge, this is the first research with the aim of assessing the educational efficacy of a computer game for teaching PCPs about insulin therapy in DM. We describe the development criteria used for creating InsuOnline. Evaluation of the game using a randomized controlled trial design will be done in future studies. Conclusions We demonstrated that the design and development of a game for PCPs education on insulin is possible with a multidisciplinary team. InsuOnline can be an attractive option for large-scale continuous medical education to help improving PCPs´ knowledge on insulin therapy and potentially improving DM patients´ care. Trial Registration Clinicaltrials.gov: NCT01759953; http://clinicaltrials.gov/show/NCT01759953 (Archived by WebCite at http://www.webcitation.org/6Dq8Vc7a6). PMID:23612462

Effect of oriental medicine music therapy on patients with Hwa-byung: a study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Hwa-byung, a Korean culture-bound syndrome with both psychological and somatic symptoms, is also known as ‘anger syndrome’. It includes various physical symptoms including anxiety, a feeling of overheating, a sensation of pressure on the chest, heart palpitations, respiratory stuffiness, insomnia, and anxiety. Methods/design The proposed study is a single-center, double-blind, randomized, controlled trial with two parallel arms: an oriental medicine music therapy (OMMT) group and a control music therapy (CMT) group. In total, 48 patients will be enrolled into the trial. The first visit will be the screening visit. At baseline (visit 2), all participants fulfilling both the inclusion and the exclusion criteria will be split and randomly divided into two equal groups: the OMMT and the CMT (n = 24 each). Each group will receive treatment sessions over the course of 4 weeks, twice per week, for eight sessions in total. The primary outcome is the State-Trait Anxiety Inventory (STAI), and the secondary outcomes are the Hwa-byung scale (H-scale), the Center for Epidemiologic Studies Depression Scale (CES-D), the Hwa-byung visual analogue scale (H-VAS) for primary symptoms, the World Health Organization Quality of Life scale, brief version (WHOQOL-BREF), and levels of salivary cortisol. Patients will be asked to complete questionnaires at the baseline visit (visit 2), after the last treatment session (visit 9), and at 4 weeks after the end of all trial sessions (visit 10). From the baseline (visit 2) through the follow-up (visit 10), the entire process will take a total of 53 days. Discussion This proposed study targets patients with Hwa-byung, especially those who have exhibited symptoms of anxiety. Therefore, the primary outcome is set to measure the level of anxiety. OMMT is music therapy combined with traditional Korean medicinal theories. Unlike previously reported music therapies, for which patients simply listen to music passively, in OMMT, patients actively move their bodies and play the music. Because Hwa-byung is caused by an accumulation of blocked emotions and anger inside the body, OMMT, because of its active component, is expected to be more efficacious than pre-existing music therapies. Trial registration Current Controlled Trials ISRCTN11939282 PMID:22963388

HIMALAIA (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA): a randomized single-blind controlled trial of induced hypertension vs. no induced hypertension in the treatment of delayed cerebral ischemia after subarachnoid hemorrhage.

PubMed

Gathier, C S; van den Bergh, W M; Slooter, A J C

2014-04-01

Delayed cerebral ischemia (DCI) is a major complication after aneurysmal subarachnoid hemorrhage (SAH). One option to treat delayed cerebral ischemia is to use induced hypertension, but its efficacy on the eventual outcome has not been proven in a randomized clinical trial. This article describes the design of the HIMALAIA trial (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA), designed to assess the effectiveness of induced hypertension on neurological outcome in patients with DCI after SAH. To investigate whether induced hypertension improves the functional outcome in patients with delayed cerebral ischemia after SAH. The HIMALAIA trial is a multicenter, singe-blinded, randomized controlled trial in patients with DCI after a recent SAH. Eligible patients will be randomized to either induced hypertension (n = 120) or to no induced hypertension (n = 120). In selected centers, the efficacy of induced hypertension in augmenting cerebral blood flow will be measured by means of cerebral perfusion computerized tomography scanning. Follow-up assessments will be performed at 3 and 12 months after randomization by trial nurses who are blinded to the treatment allocation and management. We will include patients during five years. The primary outcome is the proportion of subarachnoid hemorrhage patients with delayed cerebral ischemia with poor outcome three-months after randomization, defined as a modified Rankin scale of more than 3. Secondary outcome measures are related to treatment failure, functional outcome, adverse events, and cerebral hemodynamics. The HIMALAIA trial is registered at clinicaltrials.gov under identifier NCT01613235. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

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

The design and implementation of a randomized controlled trial of a risk reduction and human immunodeficiency virus prevention videogame intervention in minority adolescents: PlayForward: Elm City Stories.

PubMed

Fiellin, Lynn E; Kyriakides, Tassos C; Hieftje, Kimberly D; Pendergrass, Tyra M; Duncan, Lindsay R; Dziura, James D; Sawyer, Benjamin G; Fiellin, David A

2016-08-01

To address the need for risk behavior reduction and human immunodeficiency virus prevention interventions that capture adolescents "where they live," we created a tablet-based videogame to teach skills and knowledge and influence psychosocial antecedents for decreasing risk and preventing human immunodeficiency virus infection in minority youth in schools, after-school programs, and summer camps. We developed PlayForward: Elm City Stories over a 2-year period, working with researchers, commercial game designers, and staff and teens from community programs. The videogame PlayForward provides an interactive world where players, using an avatar, "travel" through time, facing challenges such as peer pressure to drink alcohol or engage in risky sexual behaviors. Players experience how their choices affect their future and then are able to go back in time and change their choices, creating different outcomes. A randomized controlled trial was designed to evaluate the efficacy of PlayForward. Participants were randomly assigned to play PlayForward or a set of attention/time control games on a tablet at their community-based program. Assessment data were collected during face-to-face study visits and entered into a web-based platform and unique real-time "in-game" PlayForward data were collected as players engaged in the game. The innovative methods of this randomized controlled trial are described. We highlight the logistical issues of conducting a large-scale trial using mobile technology such as the iPad(®), and collecting, transferring, and storing large amounts of in-game data. We outline the methods used to analyze the in-game data alone and in conjunction with standardized assessment data to establish correlations between behaviors during gameplay and those reported in real life. We also describe the use of the in-game data as a measure of fidelity to the intervention. In total, 333 boys and girls, aged 11-14 years, were randomized over a 14-month period: 166 were assigned to play PlayForward and 167 to play the control games. To date (as of 1 March 2016), 18 have withdrawn from the study; the following have completed the protocol-defined assessments: 6 weeks: 271 (83%), 3 months: 269 (84%), 6 months: 254 (79%), 12 months: 259 (82%), and 24 months: is ongoing with 152 having completed out of the 199 participants (76%) who were eligible to date (assessment windows were still open). Videogames can be developed to address complex behaviors and can be subject to empiric testing using community-based randomized controlled trials. Although mobile technologies pose challenges in their use as interventions and in the collection and storage of data they produce, they provide unique opportunities as new sources of potentially valid data and novel methods to measure the fidelity of digitally delivered behavioral interventions. © The Author(s) 2016.

The design and implementation of a randomized controlled trial of a risk reduction and human immunodeficiency virus prevention videogame intervention in minority adolescents: PlayForward: Elm City Stories

PubMed Central

Fiellin, Lynn E; Kyriakides, Tassos C; Hieftje, Kimberly D; Pendergrass, Tyra M; Duncan, Lindsay R; Dziura, James D; Sawyer, Benjamin G; Fiellin, David A

2016-01-01

Background To address the need for risk behavior reduction and HIV prevention interventions that capture adolescents “where they live,” we created a tablet-based videogame to teach skills and knowledge and influence psychosocial antecedents for decreasing risk and preventing HIV infection in minority youth in schools, after-school programs, and summer camps. Methods We developed PlayForward: Elm City Stories over a 2-year period, working with researchers, commercial game designers, and staff and teens from community programs. The videogame PlayForward provides an interactive world where players, using an avatar, “travel” through time, facing challenges such as peer pressure to drink alcohol or engage in risky sexual behaviors. Players experience how their choices affect their future and then are able to go back in time and change their choices, creating different outcomes. A randomized controlled trial was designed to evaluate the efficacy of PlayForward. Participants were randomly assigned to play PlayForward or a set of attention/time control games on a tablet at their community-based program. Assessment data were collected during face-to-face study visits and entered into a web-based platform and unique real-time “in-game” PlayForward data were collected as players engaged in the game. The innovative methods of this randomized controlled trial are described. We highlight the logistical issues of conducting a large-scale trial using mobile technology such as the iPad®, and collecting, transferring, and storing large amounts of in-game data. We outline the methods used to analyze the in-game data alone and in conjunction with standardized assessment data to establish correlations between behaviors during gameplay and those reported in real life. We also describe the use of the in-game data as a measure of fidelity to the intervention. Results In total, 333 boys and girls, aged 11–14 years, were randomized over a 14-month period: 166 were assigned to play PlayForward and 167 to play the control games. To date (as of 1 March 2016), 18 have withdrawn from the study; the following have completed the protocol-defined assessments: 6 weeks: 271 (83%); 3 months: 269 (84%); 6 months: 254 (79%); 12 months: 259 (82%); and 24 months: is ongoing with 152 having completed out of the 199 participants (76%) who were eligible to date (assessment windows were still open). Conclusion Videogames can be developed to address complex behaviors and can be subject to empiric testing using community-based randomized controlled trials. Although mobile technologies pose challenges in their use as interventions and in the collection and storage of data they produce, they provide unique opportunities as new sources of potentially valid data and novel methods to measure the fidelity of digitally delivered behavioral interventions. PMID:27013483

Efficacy and safety of olanzapine/fluoxetine combination in the treatment of treatment-resistant depression: a meta-analysis of randomized controlled trials

PubMed Central

Luan, Shuxin; Wan, Hongquan; Wang, Shijun; Li, He; Zhang, Baogang

2017-01-01

Background Whether olanzapine/fluoxetine combination (OFC) is superior to olanzapine or fluoxetine monotherapy in patients with treatment-resistant depression (TRD) remains controversial. Thus, we conducted this meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of OFC with olanzapine or fluoxetine monotherapy for patients with TRD. Materials and methods RCTs published in PubMed, Embase, Web of Science, and the ClinicalTrials.gov registry were systematically reviewed to assess the efficacy and safety of OFC. Outcomes included mean changes from baseline in Montgomery–Asberg Depression Rating Scale (MADRS), Clinical Global Impression-Severity (CGI-S), Hamilton Rating Scale for Anxiety (HAM-A), Brief Psychiatric Rating Scale (BPRS) scores, response rate, remission rate, and adverse events. Results were expressed with weighted mean difference (WMD) with 95% confidence intervals (CIs) and risk ratio (RR) with 95% CIs. Results A total of five RCTs with 3,020 patients met the inclusion criteria and were included in this meta-analysis. Compared with olanzapine or fluoxetine monotherapy, OFC was associated with greater changes from baseline in MADRS (WMD =−3.37, 95% CI: −4.76, −1.99; P<0.001), HAM-A (WMD =−1.82, 95% CI: −2.25, −1.40; P<0.001), CGI-S (WMD =−0.37, 95% CI: −0.45, −0.28; P<0.001), and BPRS scores (WMD =−1.46, 95% CI: −2.16, −0.76; P<0.001). Moreover, OFC had significantly higher response rate (RR =1.35, 95% CI: 1.12, 1.63; P=0.001) and remission rate (RR =1.71, 95% CI: 1.31, 2.23; P<0.001). The incidence of treatment-related adverse events was similar between the OFC and monotherapy groups (RR =1.01, 95% CI: 0.94, 1.08; P=0.834). Conclusion OFC is more effective than olanzapine or fluoxetine monotherapy in the treatment of patients with TRD. Our results provided supporting evidence for the use of OFC in TRD. However, considering the limitations in this study, more large-scale, well-designed RCTs are needed to confirm these findings. PMID:28280343

Sleep Telemedicine: An Emerging Field's Latest Frontier.

PubMed

Zia, Subaila; Fields, Barry G

2016-06-01

There is a widening gap between sleep provider access and patient demand for it. An American Academy of Sleep Medicine position paper recently recognized sleep telemedicine as one tool to narrow that divide. We define the term sleep telemedicine as the use of sleep-related medical information exchanged from one site to another via electronic communications to improve a patient's health. Applicable data transfer methods include telephone, video, smartphone applications, and the Internet. Their usefulness for the treatment of insomnia and sleep-disordered breathing is highlighted. Sleep telemedicine programs range in complexity from telephone-based patient feedback systems to comprehensive treatment pathways incorporating real-time video, telephone, and the Internet. While large, randomized trials are lacking, smaller studies comparing telemedicine with in-person care suggest noninferiority in terms of patient satisfaction, adherence to treatment, and symptomatic improvement. Sleep telemedicine is feasible from a technological and quality-driven perspective, but cost uncertainties, complex reimbursement structures, and variable licensing rules remain significant challenges to its feasibility on a larger scale. As legislative reform pends, larger randomized trials are needed to elucidate impact on patient outcomes, cost, and health-care system accessibility. Published by Elsevier Inc.

Evolution of Biomarker Guided Therapy for Heart Failure: Current Concepts and Trial Evidence

PubMed Central

Pruett, Amanda E; Lee, Amanda K; Patterson, Herbert; Schwartz, Todd A; Glotzer, Jana M; Adams, Jr, Kirkwood F

2015-01-01

Optimizing management of patients with heart failure remains quite challenging despite many significant advances in drug and device therapy for this syndrome. Although a large body of evidence from robust clinical trials supports multiple thera-pies, utilization of these well-established treatments remains inconsistent and outcomes suboptimal in “real-world” patients with heart failure. Disease management programs may be effective, but are difficult to implement due to cost and logistical issues. Another approach to optimizing therapy is to utilize biomarkers to guide therapeutic choices. Natriuretic peptides pro-vide additional information of significant clinical value in the diagnosis and estimation of risk inpatients with heart failure. Ongoing research suggests a potential important added role for natriuretic peptides in heart failure. Guiding therapy based on serial changes in these biomarkers may be an effective strategy to optimize treatment and achieve better outcomes in this syn-drome. Initial, innovative, proof-of-concept studies have provided encouraging results and important insights into key as-pects of this strategy, but well designed, large-scale, multicenter, randomized, outcome trials are needed to definitively estab-lish this novel approach to management. Given the immense and growing public health burden of heart failure, identification of cost-effective ways to decrease the morbidity and mortality due to this syndrome is critical. PMID:24251462

Transcranial magnetic stimulation for tinnitus: using the Tinnitus Functional Index to predict benefit in a randomized controlled trial.

PubMed

Theodoroff, Sarah M; Griest, Susan E; Folmer, Robert L

2017-02-09

Identifying characteristics associated with transcranial magnetic stimulation (TMS) benefit would offer insight as to why some individuals experience tinnitus relief following TMS treatment, whereas others do not. The purpose of this study was to use the Tinnitus Functional Index (TFI) and its subscales to identify specific factors associated with TMS treatment responsiveness. Individuals with bothersome tinnitus underwent 2000 pulses of 1-Hz TMS for 10 consecutive business days. The primary outcome measure was the TFI which yields a total score and eight individual subscale scores. Analyses were performed on baseline data from the active arm (n = 35) of a prospective, double-blind, randomized placebo-controlled clinical trial of TMS for tinnitus. Baseline total TFI score and three of the eight TFI subscales were useful in differentiating between responders and nonresponders to TMS intervention for tinnitus. These findings are not definitive, but suggest potential factors that contribute to perceived benefit following TMS. Overall, the main factor associated with TMS benefit was a higher tinnitus severity score for responders at baseline. The TFI subscales helped to clarify the factors that contributed to a higher severity score at baseline. Large-scale prospective research using systematic approaches is needed to identify and describe additional factors associated with tinnitus benefit following TMS. ClinicalTrials.gov, ID: NCT01104207 . Registered on 13 April 2010.

Safety, efficacy, actions, and patient acceptability of drospirenone/ethinyl estradiol contraceptive pills in the treatment of premenstrual dysphoric disorder.

PubMed

Breech, Lesley L; Braverman, Paula K

2010-08-09

Premenstrual dysphoric disorder (PMDD) is estimated to affect 3%-8% of reproductive age women. Multiple therapeutic modalities have been evaluated with varying efficacy for the associated somatic and mood symptoms. The majority of older studies had shown that oral contraceptive pills (OCs) were most effective for the physical symptoms. However, newer OCs containing a novel progestin, drospirenone, have shown promise in alleviating both the somatic and affective/behavioral symptoms. This progestin, which is a derivative of spironolactone, has both antimineralocorticoid and antiandrogenic activity. A 24/4 formulation containing 20 μg of ethinyl estradiol has been found effective in randomized double-blind placebo-controlled trials utilizing established scales documenting symptoms associated with PMDD. Multiple studies have shown that drospirenone-containing OCs are safe without evidence of clinically adverse effects on carbohydrate metabolism, lipids, blood pressure, weight, serum potassium or increased thrombotic events compared to other low dose OCs. In addition, significant improvements have been demonstrated in acne, hirsutism, and fluid retention symptoms. Several open label studies demonstrated good patient compliance and reported satisfaction with the method. Because of the significant placebo effect demonstrated in the blinded placebo-controlled trials, additional large randomized placebo-controlled trials are needed to confirm the efficacy of the drospirenone OCs in the treatment of PMDD. However, this OC formulation appears to be a promising therapeutic modality.

Safety, efficacy, actions, and patient acceptability of drospirenone/ethinyl estradiol contraceptive pills in the treatment of premenstrual dysphoric disorder

PubMed Central

Breech, Lesley L; Braverman, Paula K

2010-01-01

Premenstrual dysphoric disorder (PMDD) is estimated to affect 3%–8% of reproductive age women. Multiple therapeutic modalities have been evaluated with varying efficacy for the associated somatic and mood symptoms. The majority of older studies had shown that oral contraceptive pills (OCs) were most effective for the physical symptoms. However, newer OCs containing a novel progestin, drospirenone, have shown promise in alleviating both the somatic and affective/behavioral symptoms. This progestin, which is a derivative of spironolactone, has both antimineralocorticoid and antiandrogenic activity. A 24/4 formulation containing 20 μg of ethinyl estradiol has been found effective in randomized double-blind placebo-controlled trials utilizing established scales documenting symptoms associated with PMDD. Multiple studies have shown that drospirenone-containing OCs are safe without evidence of clinically adverse effects on carbohydrate metabolism, lipids, blood pressure, weight, serum potassium or increased thrombotic events compared to other low dose OCs. In addition, significant improvements have been demonstrated in acne, hirsutism, and fluid retention symptoms. Several open label studies demonstrated good patient compliance and reported satisfaction with the method. Because of the significant placebo effect demonstrated in the blinded placebo-controlled trials, additional large randomized placebo-controlled trials are needed to confirm the efficacy of the drospirenone OCs in the treatment of PMDD. However, this OC formulation appears to be a promising therapeutic modality. PMID:21072278

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.

Are there synergies from combining hygiene and sanitation promotion campaigns: Evidence from a large-scale cluster-randomized trial in rural Tanzania.

PubMed

Briceño, Bertha; Coville, Aidan; Gertler, Paul; Martinez, Sebastian

2017-01-01

The current evidence on handwashing and sanitation programs suggests limited impacts on health when at-scale interventions have been tested in isolation. However, no published experimental evidence currently exists that tests the interaction effects between sanitation and handwashing. We present the results of two large-scale, government-led handwashing and sanitation promotion campaigns in rural Tanzania, with the objective of tracing the causal chain from hygiene and sanitation promotion to changes in child health outcomes and specifically testing for potential interaction effects of combining handwashing and sanitation interventions. The study is a factorial cluster-randomized control trial where 181 rural wards from 10 districts in Tanzania were randomly assigned to receive sanitation promotion, handwashing promotion, both interventions together or neither (control). Interventions were rolled out from February 2009 to June 2011 and the endline survey was conducted from May to November 2012, approximately one year after program completion. The sample was composed of households with children under 5 years old in the two largest villages in each ward. Masking was not possible due to the nature of the intervention, but enumerators played no part in the intervention and were blinded to treatment status. The primary outcome of interest was 7-day diarrhea prevalence for children under five. Intermediate outcomes of behavior change including improved latrine construction, levels of open defecation and handwashing with soap were also analyzed. Secondary health outcomes included anemia, height-for-age and weight-for-age of children under 5. An intention-to-treat analysis was used to assess the relationship between the interventions and outcomes of interest. One year after the end of the program, ownership of improved latrines increased from 49.7% to 64.8% (95% CI 57.9%-71.7%) and regular open defecation decreased from 23.1% to 11.1% (95% CI 3.5%-18.7%) in sanitation promotion-only wards. Households in handwashing promotion-only wards showed marginal improvements in handwashing behavior related to food preparation but not at other critical junctures. There were no detectable interaction effects for the combined intervention. The associated cost-per-household gaining access to improved sanitation is estimated to be USD $194. Final effects on child health measured through diarrhea, anemia, stunting and wasting were absent in all treatment groups. Although statistically significant, the changes in intermediate outcomes achieved through each intervention in isolation were not large enough to generate meaningful health impacts. With no observable signs of interaction, the combined intervention produced similar results. The study highlights the importance of focusing on intermediate outcomes of take up and behavior change as a critical first step in large-scale programs before realizing the changes in health that sanitation and hygiene interventions aim to deliver. Clinicaltrials.gov NCT01465204.

Large-scale structure of randomly jammed spheres

NASA Astrophysics Data System (ADS)

Ikeda, Atsushi; Berthier, Ludovic; Parisi, Giorgio

2017-05-01

We numerically analyze the density field of three-dimensional randomly jammed packings of monodisperse soft frictionless spherical particles, paying special attention to fluctuations occurring at large length scales. We study in detail the two-point static structure factor at low wave vectors in Fourier space. We also analyze the nature of the density field in real space by studying the large-distance behavior of the two-point pair correlation function, of density fluctuations in subsystems of increasing sizes, and of the direct correlation function. We show that such real space analysis can be greatly improved by introducing a coarse-grained density field to disentangle genuine large-scale correlations from purely local effects. Our results confirm that both Fourier and real space signatures of vanishing density fluctuations at large scale are absent, indicating that randomly jammed packings are not hyperuniform. In addition, we establish that the pair correlation function displays a surprisingly complex structure at large distances, which is however not compatible with the long-range negative correlation of hyperuniform systems but fully compatible with an analytic form for the structure factor. This implies that the direct correlation function is short ranged, as we also demonstrate directly. Our results reveal that density fluctuations in jammed packings do not follow the behavior expected for random hyperuniform materials, but display instead a more complex behavior.

A comparison of confidence interval methods for the intraclass correlation coefficient in community-based cluster randomization trials with a binary outcome.

PubMed

Braschel, Melissa C; Svec, Ivana; Darlington, Gerarda A; Donner, Allan

2016-04-01

Many investigators rely on previously published point estimates of the intraclass correlation coefficient rather than on their associated confidence intervals to determine the required size of a newly planned cluster randomized trial. Although confidence interval methods for the intraclass correlation coefficient that can be applied to community-based trials have been developed for a continuous outcome variable, fewer methods exist for a binary outcome variable. The aim of this study is to evaluate confidence interval methods for the intraclass correlation coefficient applied to binary outcomes in community intervention trials enrolling a small number of large clusters. Existing methods for confidence interval construction are examined and compared to a new ad hoc approach based on dividing clusters into a large number of smaller sub-clusters and subsequently applying existing methods to the resulting data. Monte Carlo simulation is used to assess the width and coverage of confidence intervals for the intraclass correlation coefficient based on Smith's large sample approximation of the standard error of the one-way analysis of variance estimator, an inverted modified Wald test for the Fleiss-Cuzick estimator, and intervals constructed using a bootstrap-t applied to a variance-stabilizing transformation of the intraclass correlation coefficient estimate. In addition, a new approach is applied in which clusters are randomly divided into a large number of smaller sub-clusters with the same methods applied to these data (with the exception of the bootstrap-t interval, which assumes large cluster sizes). These methods are also applied to a cluster randomized trial on adolescent tobacco use for illustration. When applied to a binary outcome variable in a small number of large clusters, existing confidence interval methods for the intraclass correlation coefficient provide poor coverage. However, confidence intervals constructed using the new approach combined with Smith's method provide nominal or close to nominal coverage when the intraclass correlation coefficient is small (<0.05), as is the case in most community intervention trials. This study concludes that when a binary outcome variable is measured in a small number of large clusters, confidence intervals for the intraclass correlation coefficient may be constructed by dividing existing clusters into sub-clusters (e.g. groups of 5) and using Smith's method. The resulting confidence intervals provide nominal or close to nominal coverage across a wide range of parameters when the intraclass correlation coefficient is small (<0.05). Application of this method should provide investigators with a better understanding of the uncertainty associated with a point estimator of the intraclass correlation coefficient used for determining the sample size needed for a newly designed community-based trial. © The Author(s) 2015.

Effect of L-arginine and sildenafil citrate on intrauterine growth restriction fetuses: a meta-analysis.

PubMed

Chen, Juncao; Gong, Xiaoyuan; Chen, Pingyang; Luo, Kaiju; Zhang, Xiuquan

2016-08-16

Intrauterine growth restriction (IUGR) is associated with perinatal morbidity and mortality. Several clinical trials have reported L-arginine and sildenafil citrate had effect on intrauterine growth restriction fetuses. A meta-analysis of available randomized controlled trials (RCTs) was conducted to investigate the effects of L-arginine and sildenafil citrate on major clinical outcomes of IUGR fetuses. Systematically searched Medline, Embase, the Cochrane Library, and Clinical Trials, references of retrieved articles, and conference proceedings from 1960 to 2015. We included randomized controlled trials assessing the effects of L-arginine and sildenafil citrate on IUGR. Outcomes analyzed were the birth weight, gestational age at labor, Apgar score at 1and 5 min, the ratio of NRDS, the ratio of ICH and neonatal death, etc. Ten trials were included. Nine trials (576 patients) compared L-arginine with either placebo or no intervention. In the L-arginine treatment groups of the L-arginine trials, there was a significant increase in fetal birth weight (SMD 0.41, 95 % CI [0.24,0.58]), gestational age (SMD 0.30, 95 % CI [0.07,0.54]); L-arginine treatment group have a significant reduction in the ratio of neonatal respiratory distress syndrome (P = 0.009), intracranial hemorrhage of fetuses (P = 0.002), but the number of included studies and people on these outcomes are small. As only one trial (41 patients) compared sildenafil citrate with placebo, it was too small for reliable conclusions about possible differential effects could be drawn. The results of this meta-analysis showed that L-arginine increased birth weight and prolonged gestational age at labor of IUGR fetuses. However, further large-scale RCTs are needed to adequately assess the effect of L-arginine and Sildenafil citrate on clinical outcomes, because the number of study may be small.

Effectiveness of an annular closure device in a "real-world" population: stratification of registry data using screening criteria from a randomized controlled trial.

PubMed

Kuršumović, Adisa; Rath, Stefan A

2018-01-01

Increased focus has been put on the use of "'real-world" data to support randomized clinical trial (RCT) evidence for clinical decision-making. The objective of this study was to assess the performance of an annular closure device (ACD) after stratifying a consecutive series of "real-world" patients by the screening criteria of an ongoing RCT. This was a single-center registry analysis of 164 subjects who underwent limited discectomy combined with ACD for symptomatic lumbar disc herniation. Patients were stratified into two groups using the selection criteria of a pivotal RCT on the same device: Trial (met inclusion; n=44) or non-Trial (did not meet inclusion; n=120). Patient-reported outcomes, including Oswestry Disability Index (ODI) and visual analog scale (VAS) for leg and back pain, and adverse events were collected from baseline to last follow-up (mean: Trial - 15.6 months; non-Trial - 14.6 months). Statistical analyses were performed with significance set at p <0.05. Patient-reported outcomes were not significantly different between groups at last ( p ≥0.15) and clinical success (≥15-point improvement in ODI score; ≥20-point improvement in VAS scores) was achieved in both the groups. Three non-Trial (2.5%) and three Trial (6.8%) patients experienced symptomatic reherniation ( p =0.34). Rates of reoperation, ACD mesh dislocation/separation, and other radiographic findings were similar between groups ( p =1.00). Outcomes with the ACD appeared advantageous in both the groups, particularly in comparison with historical reherniation rates reported in the same high-risk, large annular defect population. Stratification of this "real-world" series on the basis of RCT screening criteria did not result in significant between-group differences. These findings suggest that the efficacy of the ACD extends beyond the strictly defined patient population being studied in the RCT of this device. Furthermore, reducing the reherniation rate following lumbar discectomy has positive clinical and economic implications.

Assessing the comparative effectiveness of Tai Chi versus physical therapy for knee osteoarthritis: design and rationale for a randomized trial.

PubMed

Wang, Chenchen; Iversen, Maura D; McAlindon, Timothy; Harvey, William F; Wong, John B; Fielding, Roger A; Driban, Jeffrey B; Price, Lori Lyn; Rones, Ramel; Gamache, Tressa; Schmid, Christopher H

2014-09-08

Knee osteoarthritis (OA) causes pain and long-term disability with annual healthcare costs exceeding $185 billion in the United States. Few medical remedies effectively influence the course of the disease. Finding effective treatments to maintain function and quality of life in patients with knee OA is one of the national priorities identified by the Institute of Medicine. We are currently conducting the first comparative effectiveness and cost-effectiveness randomized trial of Tai Chi versus a physical-therapy regimen in a sample of patients with symptomatic and radiographically confirmed knee OA. This article describes the design and conduct of this trial. A single-center, 52-week, comparative effectiveness randomized controlled trial of Tai Chi versus a standardized physical-therapy regimen is being conducted at an urban tertiary medical center in Boston, Massachusetts. The study population consists of adults ≥ 40 years of age with symptomatic and radiographic knee OA (American College of Rheumatology criteria). Participants are randomly allocated to either 12 weeks of Tai Chi (2x/week) or Physical Therapy (2x/week for 6 weeks, followed by 6 weeks of rigorously monitored home exercise). The primary outcome measure is pain (Western Ontario and McMaster Universities WOMAC) subscale at 12 weeks. Secondary outcomes include WOMAC stkiffness and function domain scores, lower extremity strength and power, functional balance, physical performance tests, psychological and psychosocial functioning, durability effects, health related quality of life, and healthcare utilization at 12, 24 and 52 weeks. This study will be the first randomized comparative-effectiveness and cost-effectiveness trial of Tai Chi versus Physical Therapy in a large symptomatic knee OA population with long-term follow up. We present here a robust and well-designed randomized comparative-effectiveness trial that also explores multiple outcomes to elucidate the potential mechanisms of mind-body effect for a major disabling disease with substantial health burdens and economic costs. Results of this study are expected to have important public health implications for the large and growing population with knee OA. ClinicalTrials.gov identifier: NCT01258985.

Some practical problems in implementing randomization.

PubMed

Downs, Matt; Tucker, Kathryn; Christ-Schmidt, Heidi; Wittes, Janet

2010-06-01

While often theoretically simple, implementing randomization to treatment in a masked, but confirmable, fashion can prove difficult in practice. At least three categories of problems occur in randomization: (1) bad judgment in the choice of method, (2) design and programming errors in implementing the method, and (3) human error during the conduct of the trial. This article focuses on these latter two types of errors, dealing operationally with what can go wrong after trial designers have selected the allocation method. We offer several case studies and corresponding recommendations for lessening the frequency of problems in allocating treatment or for mitigating the consequences of errors. Recommendations include: (1) reviewing the randomization schedule before starting a trial, (2) being especially cautious of systems that use on-demand random number generators, (3) drafting unambiguous randomization specifications, (4) performing thorough testing before entering a randomization system into production, (5) maintaining a dataset that captures the values investigators used to randomize participants, thereby allowing the process of treatment allocation to be reproduced and verified, (6) resisting the urge to correct errors that occur in individual treatment assignments, (7) preventing inadvertent unmasking to treatment assignments in kit allocations, and (8) checking a sample of study drug kits to allow detection of errors in drug packaging and labeling. Although we performed a literature search of documented randomization errors, the examples that we provide and the resultant recommendations are based largely on our own experience in industry-sponsored clinical trials. We do not know how representative our experience is or how common errors of the type we have seen occur. Our experience underscores the importance of verifying the integrity of the treatment allocation process before and during a trial. Clinical Trials 2010; 7: 235-245. http://ctj.sagepub.com.

Adjunctive minocycline for schizophrenia: A meta-analysis of randomized controlled trials.

PubMed

Xiang, Ying-Qiang; Zheng, Wei; Wang, Shi-Bin; Yang, Xin-Hu; Cai, Dong-Bin; Ng, Chee H; Ungvari, Gabor S; Kelly, Deanna L; Xu, Wei-Ying; Xiang, Yu-Tao

2017-01-01

This study aimed to conduct a meta-analysis of the efficacy and safety of adjunctive minocycline for schizophrenia. Randomized controlled trials (RCTs) comparing adjunctive minocycline with placebo in patients with schizophrenia were included in the meta-analysis. Two independent investigators extracted and synthesized data. Standard mean differences (SMDs), risk ratio (RR) ±95% confidence intervals (CIs) and the number-needed-to-harm (NNH) were calculated. Eight RCTs with 548 schizophrenia patient including 286 (52.2%) patients on minocycline (171.9±31.2mg/day) and 262 (47.8%) on placebo completed 18.5±13.4 weeks of treatment. Meta-analyses of Positive and Negative Syndrome Scale (PANSS) (7 RCTs with 8 treatment arms)/Brief Psychiatric Rating Scale (BPRS) (1 RCT) total score [SMD: -0.64, (95%CI: -1.02, -0.27), P=0.0008; I 2 =74%], positive, negative and general symptom scores [SMD: -0.69 to -0.22 (95%CI: -0.98, -0.03), P=0.02-0.00001; I 2 =7-63%] revealed a significant superiority of adjunctive minocycline treatment over the placebo. There was no significant difference regarding neurocognitive function, discontinuation rate and adverse drug reactions between the two groups. This meta-analysis showed that adjunctive minocycline appears to be efficacious and safe for schizophrenia. Due to significant heterogeneity, future studies with a large sample size are needed to confirm these findings. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

The addition of a goal-based motivational interview to treatment as usual to enhance engagement and reduce dropouts in a personality disorder treatment service: results of a feasibility study for a randomized controlled trial.

PubMed

McMurran, Mary; Cox, W Miles; Whitham, Diane; Hedges, Lucy

2013-02-17

There are high rates of treatment non-completion for personality disorder and those who do not complete treatment have poorer outcomes. A goal-based motivational interview may increase service users' readiness to engage with therapy and so enhance treatment retention. We conducted a feasibility study to inform the design of a randomized controlled trial. The aims were to test the feasibility of recruitment, randomization and follow-up, and to conduct a preliminary evaluation of the effectiveness of the motivational interview. Patients in an outpatient personality disorder service were randomized to receive the Personal Concerns Inventory plus treatment as usual or treatment as usual only. The main randomized controlled trial feasibility criteria were recruitment of 54% of referrals, and 80% of clients and therapists finding the intervention acceptable. Information was collected on treatment attendance, the clarity of therapy goals and treatment engagement. The recruitment rate was 29% (76 of 258). Of 12 interviewed at follow-up, eight (67%) were positive about the Personal Concerns Inventory. Pre-intervention interviews were conducted with 61% (23 out of 38) of the Personal Concerns Inventory group and 74% (28 out of 38) of the treatment as usual group. Participants' therapy goals were blind-rated for clarity on a scale of 0 to 10. The mean score for the Personal Concerns Inventory group was 6.64 (SD = 2.28) and for the treatment as usual group 2.94 (SD = 1.71). Over 12 weeks, the median percentage session attendance was 83.33% for the Personal Concerns Inventory group (N = 17) and 66.67% for the treatment as usual group (N = 24). Of 59 eligible participants at follow-up, the Treatment Engagement Rating scale was completed for 40 (68%). The mean Treatment Engagement Rating scale score for the Personal Concerns Inventory group was 6.64 (SD = 2.28) and for the treatment as usual group 2.94 (SD = 1.71). Of the 76 participants, 63 (83%) completed the Client Service Receipt Inventory at baseline and 34 of 59 (58%) at follow-up. Shortfalls in recruitment and follow-up data collection were explained by major changes to the service. However, evidence of a substantial positive impact of the Personal Concerns Inventory on treatment attendance, clarity of therapy goals and treatment engagement, make a full-scale evaluation worth pursuing. Further preparatory work is required for a multisite trial. ClinicalTrials.Gov.UK Identifier - NCT01132976.

Mindfulness Meditation for Chronic Pain: Systematic Review and Meta-analysis.

PubMed

Hilton, Lara; Hempel, Susanne; Ewing, Brett A; Apaydin, Eric; Xenakis, Lea; Newberry, Sydne; Colaiaco, Ben; Maher, Alicia Ruelaz; Shanman, Roberta M; Sorbero, Melony E; Maglione, Margaret A

2017-04-01

Chronic pain patients increasingly seek treatment through mindfulness meditation. This study aims to synthesize evidence on efficacy and safety of mindfulness meditation interventions for the treatment of chronic pain in adults. We conducted a systematic review on randomized controlled trials (RCTs) with meta-analyses using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. Quality of evidence was assessed using the GRADE approach. Outcomes included pain, depression, quality of life, and analgesic use. Thirty-eight RCTs met inclusion criteria; seven reported on safety. We found low-quality evidence that mindfulness meditation is associated with a small decrease in pain compared with all types of controls in 30 RCTs. Statistically significant effects were also found for depression symptoms and quality of life. While mindfulness meditation improves pain and depression symptoms and quality of life, additional well-designed, rigorous, and large-scale RCTs are needed to decisively provide estimates of the efficacy of mindfulness meditation for chronic pain.

Patient satisfaction with different interpreting methods: a randomized controlled trial.

PubMed

Gany, Francesca; Leng, Jennifer; Shapiro, Ephraim; Abramson, David; Motola, Ivette; Shield, David C; Changrani, Jyotsna

2007-11-01

Growth of the foreign-born population in the U.S. has led to increasing numbers of limited-English-proficient (LEP) patients. Innovative medical interpreting strategies, including remote simultaneous medical interpreting (RSMI), have arisen to address the language barrier. This study evaluates the impact of interpreting method on patient satisfaction. 1,276 English-, Spanish-, Mandarin-, and Cantonese-speaking patients attending the primary care clinic and emergency department of a large New York City municipal hospital were screened for enrollment in a randomized controlled trial. Language-discordant patients were randomized to RSMI or usual and customary (U&C) interpreting. Patients with language-concordant providers received usual care. Demographic and patient satisfaction questionnaires were administered to all participants. 541 patients were language-concordant with their providers and not randomized; 371 were randomized to RSMI, 167 of whom were exposed to RSMI; and 364 were randomized to U&C, 198 of whom were exposed to U&C. Patients randomized to RSMI were more likely than those with U&C to think doctors treated them with respect (RSMI 71%, U&C 64%, p < 0.05), but they did not differ in other measures of physician communication/care. In a linear regression analysis, exposure to RSMI was significantly associated with an increase in overall satisfaction with physician communication/care (beta 0.10, 95% CI 0.02-0.18, scale 0-1.0). Patients randomized to RSMI were more likely to think the interpreting method protected their privacy (RSMI 51%, U&C 38%, p < 0.05). Patients randomized to either arm of interpretation reported less comprehension and satisfaction than patients in language-concordant encounters. While not a substitute for language-concordant providers, RSMI can improve patient satisfaction and privacy among LEP patients. Implementing RSMI should be considered an important component of a multipronged approach to addressing language barriers in health care.

Patient Satisfaction with Different Interpreting Methods: A Randomized Controlled Trial

PubMed Central

Leng, Jennifer; Shapiro, Ephraim; Abramson, David; Motola, Ivette; Shield, David C.; Changrani, Jyotsna

2007-01-01

Background Growth of the foreign-born population in the U.S. has led to increasing numbers of limited-English-proficient (LEP) patients. Innovative medical interpreting strategies, including remote simultaneous medical interpreting (RSMI), have arisen to address the language barrier. This study evaluates the impact of interpreting method on patient satisfaction. Methods 1,276 English-, Spanish-, Mandarin-, and Cantonese-speaking patients attending the primary care clinic and emergency department of a large New York City municipal hospital were screened for enrollment in a randomized controlled trial. Language-discordant patients were randomized to RSMI or usual and customary (U&C) interpreting. Patients with language-concordant providers received usual care. Demographic and patient satisfaction questionnaires were administered to all participants. Results 541 patients were language-concordant with their providers and not randomized; 371 were randomized to RSMI, 167 of whom were exposed to RSMI; and 364 were randomized to U&C, 198 of whom were exposed to U&C. Patients randomized to RSMI were more likely than those with U&C to think doctors treated them with respect (RSMI 71%, U&C 64%, p < 0.05), but they did not differ in other measures of physician communication/care. In a linear regression analysis, exposure to RSMI was significantly associated with an increase in overall satisfaction with physician communication/care (β 0.10, 95% CI 0.02–0.18, scale 0–1.0). Patients randomized to RSMI were more likely to think the interpreting method protected their privacy (RSMI 51%, U&C 38%, p < 0.05). Patients randomized to either arm of interpretation reported less comprehension and satisfaction than patients in language-concordant encounters. Conclusions While not a substitute for language-concordant providers, RSMI can improve patient satisfaction and privacy among LEP patients. Implementing RSMI should be considered an important component of a multipronged approach to addressing language barriers in health care. PMID:17957417

A randomized pilot trial of a full subsidy vs. a partial subsidy for obesity treatment.

PubMed

Tsai, Adam G; Felton, Sue; Hill, James O; Atherly, Adam J

2012-09-01

Intensive obesity treatment is mandated by federal health care reform but is costly. A partial subsidy for obesity treatment could lower the cost of treatment, without reducing its efficacy. This study sought to test whether a partial subsidy for obesity treatment would be feasible, as compared to a fully subsidized intervention. The study was a pilot randomized trial. Participants (n = 50) were primary care patients with obesity and at least one comorbid condition (diabetes, hypertension, dyslipidemia, or obstructive sleep apnea). Each participant received eight weight loss counseling visits as well as portion-controlled foods for weight loss. Participants were randomized to full subsidy or partial subsidy (2 vs. 1 meal per day provided). The primary outcome was weight change after 4 months. Secondary outcomes included changes in blood pressure, waist circumference, and health-related quality of life. Participants in the full and partial subsidy groups lost 5.9 and 5.3 kg, equivalent to 5.3% and 5.1% of initial weight, respectively (P = 0.71). Changes in secondary outcomes were similar in the two groups. A partial subsidy was feasible and induced a clinically similar amount of weight loss, compared to a full subsidy. Large-scale testing of economic incentives for weight control is merited given the federal mandate to offer weight loss counseling to obese patients.

Complementary and Alternative Medicine Treatments for Generalized Anxiety Disorder: Systematic Review and Meta-analysis of Randomized Controlled Trials.

PubMed

Barić, Hrvoje; Đorđević, Veljko; Cerovečki, Ivan; Trkulja, Vladimir

2018-03-01

The objective was to evaluate efficacy/safety of complementary and alternative medicine (CAM) methods for generalized anxiety disorder (GAD) based on randomized controlled trials in adults. Data sources. Six electronic databases ("generalized anxiety (disorder)" and "randomized trial") and reference lists of identified publications were searched to March 2017. Eligibility: full-text publications (English, German language); CAM versus conventional treatment, placebo/sham or no treatment; GAD diagnosed according to standard criteria; and a validated scale for disease severity. Of the 6693 screened records, 32 were included (18 on biologically-based therapies, exclusively herbal preparations; eight on manipulative and body-based therapies; and three on alternative medical systems and three on mind-body therapies). Cochrane Collaboration methodology was used for quality assessment and data extraction. Direct comparisons of Kava Kava (Piper methysticum) extracts to placebo (4 quality trials, n = 233) were highly heterogeneous. Network meta-regression reduced heterogeneity and suggested a modest Kava effect [end-of-treatment Hamilton Anxiety scale score difference adjusted for baseline scores and trial duration: - 3.24 (95% CI - 6.65, 0.17; P = 0.059), Kava Kava 4 arms, n = 139; placebo 5 arms, n = 359]. Lavender (Lavandula angustifolia) extract (1 quality trial, 10 weeks, n = 523) and a combination of extracts of C. oxycantha, E. californica and magnesium (1 quality trial, 12 weeks, n = 264) were superior to placebo and balneotherapy was superior to paroxetine (1 quality trial, 8 weeks, n = 237) indicating efficacy. All other trials were small and/or of modest/low quality and/or lacked assay sensitivity. Safety reporting was poor. Evidence about efficacy/safety of most CAM methods in GAD is limited. Apparent efficacy of certain herbal preparations and body-based therapies requires further confirmation.

Telephone based cognitive behavioral therapy targeting major depression among urban dwelling, low income people living with HIV/AIDS: results of a randomized controlled trial.

PubMed

Himelhoch, Seth; Medoff, Deborah; Maxfield, Jennifer; Dihmes, Sarah; Dixon, Lisa; Robinson, Charles; Potts, Wendy; Mohr, David C

2013-10-01

This pilot randomized controlled trial evaluated a previously developed manualized telephone based cognitive behavioral therapy (T-CBT) intervention compared to face-to-face (f2f) therapy among low-income, urban dwelling HIV infected depressed individuals. The primary outcome was the reduction of depressive symptoms as measured by the Hamliton rating scale for depression scale. The secondary outcome was adherence to HAART as measured by random telephone based pill counts. Outcome measures were collected by trained research assistants masked to treatment allocation. Analysis was based on intention-to-treat. Thirty-four participants met eligibility criteria and were randomly assigned to receive T-CBT (n = 16) or f2f (n = 18). There was no statistically significant difference in depression treatment outcomes comparing f2f to T-CBT. Within group evaluation demonstrated that both the T-CBT and the f2f psychotherapy groups resulted in significant reductions in depressive symptoms. Those who received the T-CBT were significantly more likely to maintain their adherence to antiretroviral medication compared to the f2f treatment. None of the participants discontinued treatment due to adverse events. T-CBT can be delivered to low-income, urban dwelling HIV infected depressed individuals resulting in significant reductions in depression symptoms and improved adherence to antiretroviral medication. Clinical Trial.gov identifier: NCT01055158.

Platelet-rich plasma injection in the treatment of frozen shoulder: A randomized controlled trial with 6-month follow-up
.

PubMed

Lin, Junhong

2018-06-22

Platelet-rich plasma (PRP) has been utilized in the treatment of chronic injuries. The current study aimed to evaluate the efficiency of PRP in the treatment of frozen shoulder compared to procaine. 60 patients with frozen shoulder were randomly divided into two groups. The PRP group was injected with 2 mL prepared PRP, while in the control group procaine was used. The stretching and formal strengthening exercises were carried out in both groups during the 6-month follow-up. Visual analog scale (VAS) score was used to assess the subjective pain intensity of the patients. The general shoulder assessment instruments (University of California at Los Angeles (UCLA) shoulder scale) was applied to measure the shoulder function of the patients. The evaluation was performed before treatment and 1 week, 1 month, 3 months, and 6 months after the first injection. The efficiency of PRP was superior to and longer than procaine. VAS scores were both declined in PRP and control group after 1 week, 1 month, and 3 months of first injection. By contrast, it was elevated was elevated in the control group while continued to decline in PRP group. The UCLA scores were almost linearly improved in the PRP group, while the UCLA scores decreased to a lower level at the final follow-up visit compared to that post 3 months in the control group. PRP and procaine were effective in treating frozen shoulder. PRP was more effective and had a more prolonged efficiency than the procaine control. Nevertheless, the definite conclusion should come from further large-scale clinical trials.
.

Effect of parent training vs parent education on behavioral problems in children with autism spectrum disorder: a randomized clinical trial.

PubMed

Bearss, Karen; Johnson, Cynthia; Smith, Tristram; Lecavalier, Luc; Swiezy, Naomi; Aman, Michael; McAdam, David B; Butter, Eric; Stillitano, Charmaine; Minshawi, Noha; Sukhodolsky, Denis G; Mruzek, Daniel W; Turner, Kylan; Neal, Tiffany; Hallett, Victoria; Mulick, James A; Green, Bryson; Handen, Benjamin; Deng, Yanhong; Dziura, James; Scahill, Lawrence

2015-04-21

Disruptive behavior is common in children with autism spectrum disorder. Behavioral interventions are used to treat disruptive behavior but have not been evaluated in large-scale randomized trials. To evaluate the efficacy of parent training for children with autism spectrum disorder and disruptive behavior. This 24-week randomized trial compared parent training (n = 89) to parent education (n = 91) at 6 centers (Emory University, Indiana University, Ohio State University, University of Pittsburgh, University of Rochester, Yale University). We screened 267 children; 180 children (aged 3-7 years) with autism spectrum disorder and disruptive behaviors were randomly assigned (86% white, 88% male) between September 2010 and February 2014. Parent training (11 core, 2 optional sessions; 2 telephone boosters; 2 home visits) provided specific strategies to manage disruptive behavior. Parent education (12 core sessions, 1 home visit) provided information about autism but no behavior management strategies. Parents rated disruptive behavior and noncompliance on co-primary outcomes: the Aberrant Behavior Checklist-Irritability subscale (range, 0-45) and the Home Situations Questionnaire-Autism Spectrum Disorder (range, 0-9). On both measures, higher scores indicate greater severity and a 25% reduction indicates clinical improvement. A clinician blind to treatment assignment rated the Improvement scale of the Clinical Global Impression (range, 1-7), a secondary outcome, with a positive response less than 3. At week 24, the Aberrant Behavior Checklist-Irritability subscale declined 47.7% in parent training (from 23.7 to 12.4) compared with 31.8% for parent education (23.9 to 16.3) (treatment effect, -3.9; 95% CI, -6.2 to -1.7; P < .001, standardized effect size = 0.62). The Home Situations Questionnaire-Autism Spectrum Disorder declined 55% (from 4.0 to 1.8) compared with 34.2% in parent education (3.8 to 2.5) (treatment effect, -0.7; 95% CI, -1.1 to -0.3; P < .001, standardized effect size = 0.45). Neither measure met the prespecified minimal clinically important difference. The proportions with a positive response on the Clinical Global Impression-Improvement scale were 68.5% for parent training vs 39.6% for parent education (P < .001). For children with autism spectrum disorder, a 24-week parent training program was superior to parent education for reducing disruptive behavior on parent-reported outcomes, although the clinical significance of the improvement is unclear. The rate of positive response judged by a blinded clinician was greater for parent training vs parent education. clinicaltrials.gov Identifier: NCT01233414.

MIDAS (Modafinil in Debilitating Fatigue After Stroke): A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial.

PubMed

Bivard, Andrew; Lillicrap, Thomas; Krishnamurthy, Venkatesh; Holliday, Elizabeth; Attia, John; Pagram, Heather; Nilsson, Michael; Parsons, Mark; Levi, Christopher R

2017-05-01

This study aimed to assess the efficacy of modafinil, a wakefulness-promoting agent in alleviating post-stroke fatigue ≥3 months after stroke. We hypothesized that 200 mg of modafinil daily for 6 weeks would result in reduced symptoms of fatigue compared with placebo. This single-center phase 2 trial used a randomized, double-blind, placebo-controlled, crossover design. The key inclusion criterion was a multidimensional fatigue inventory score of ≥60. Patients were randomized to either modafinil or placebo for 6 weeks of therapy, then after a 1 week washout period swapped treatment arms for a second 6 weeks of therapy. The primary outcome was the multidimensional fatigue inventory; secondary outcomes included the Montreal cognitive assessment, the Depression, Anxiety, and Stress Scale (DASS), and the Stroke-Specific Quality of Life (SSQoL) scale. The multidimensional fatigue inventory is a self-administered questionnaire with a range of 0 to 100. Treatment efficacy was assessed using linear regression by estimating within-person, baseline-adjusted differences in mean outcomes after therapy. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000350527). A total of 232 stroke survivors were screened and 36 were randomized. Participants receiving modafinil reported a significant decrease in fatigue (multidimensional fatigue inventory, -7.38; 95% CI, -21.76 to -2.99; P <0.001) and improved quality of life (SSQoL, 11.81; 95% CI, 2.31 to 21.31; P =0.0148) compared with placebo. Montreal cognitive assessment and DASS were not significantly improved with modafinil therapy during the study period ( P >0.05). Stroke survivors with nonresolving fatigue reported reduced fatigue and improved quality of life after taking 200 mg daily treatment with modafinil. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368268. Unique identifier: ACTRN12615000350527. © 2017 The Authors.

Research protocol for a randomized controlled trial of the health effects of volunteering for seniors.

PubMed

Pettigrew, Simone; Jongenelis, Michelle; Newton, Robert U; Warburton, Jeni; Jackson, Ben

2015-06-04

A growing evidence base demonstrates that interventions that focus on participation in physical and social activities can assist in preventing and treating both physical and mental health problems. In addition, there is some evidence that engaging in volunteering activities can provide beneficial social, physical, psychological, and cognitive outcomes for older people. This study will use a randomized controlled trial approach to investigate the potential for interventions involving volunteer activities to produce positive physical and psychological outcomes for older people, thereby contributing to the limited evidence relating to the potential for volunteering to provide multiple health effects. This randomized controlled trial will involve 400 retired/non-employed individuals in good health aged 60+ years living in the metropolitan area in Perth, Western Australia. Participants will be recruited from the Perth metropolitan area using a variety of recruitment methods to achieve a diverse sample in terms of age, gender, and socioeconomic status. Consenting and eligible participants will be randomly assigned to an intervention (n = 200) or control group (n = 200). Those in the intervention group will be asked to engage in a minimum 60 min of volunteer activities per week for a period of 6 months, while those in the control group will be asked to maintain their existing lifestyle or take on new activities as they see fit. Physical and psychological outcomes will be assessed. Primary physical outcomes will include physical activity and sedentary time (measured using pedometers and Actigraph monitors) and physical health (measured using a battery of physical functioning tests, resting heart rate, blood pressure, BMI, and girth). Primary psychological outcomes will include psychological well-being, depression, self-esteem, and quality of life (measured using the Warwick-Edinburgh Mental Well-Being Scale, Center for Epidemiologic Studies Depression Scale, the Rosenberg Self-Esteem Survey, and the Global Quality of Life Scale, respectively). Secondary outcomes of interest will include attitudes to volunteering (measured via open-ended interviews) and personal growth, purpose in life, social support, and self-efficacy (measured using the Personal Growth and Purpose in Life subscales of Ryff's Psychological Well-Being Scale, the Social Provisions Scale, and the Generalized Self-Efficacy Scale, respectively). Participants will be re-assessed on these measures after 6 months. The results of this randomized controlled trial will generate new knowledge relating to the physical and psychological health benefits of different levels and types of volunteering for older people. In addition, insight will be provided into the major factors influencing the recruitment and retention of older volunteers. Understanding the full potential for volunteering to affect physical and mental well-being will provide policy makers with the evidence they require to determine appropriate investment in the volunteering sector, especially in relation to encouraging volunteering among older people who constitute an important resource for the community. Australian and New Zealand Clinical Trials Registry ACTRN12615000091505. Date registered: 3 February, 2015.

Diabetes Prevention Program (DPP)

MedlinePlus

... mass index of 35 or higher. DPP Study Design The DPP was a randomized, controlled clinical trial ... by several earlier small-scale studies. DPPOS Study Design The DPPOS follow-up study started in 2002. ...

Limited Impact of Music Therapy on Patient Anxiety with the Large Loop Excision of Transformation Zone Procedure - a Randomized Controlled Trial.

PubMed

Kongsawatvorakul, Chompunoot; Charakorn, Chuenkamon; Paiwattananupant, Krissada; Lekskul, Navamol; Rattanasiri, Sasivimol; Lertkhachonsuk, Arb-Aroon

2016-01-01

Many studies have pointed to strategies to cope with patient anxiety in colposcopy. Evidence shows that patients experienced considerable distress with the large loop excision of transformation zone (LLETZ) procedure and suitable interventions should be introduced to reduce anxiety. This study aimed to investigate the effects of music therapy in patients undergoing LLETZ. A randomized controlled trial was conducted with patients undergoing LLETZ performed under local anesthesia in an out patient setting at Ramathibodi Hospital, Bangkok, Thailand, from February 2015 to January 2016. After informed consent and demographic data were obtained, we assessed the anxiety level using State Anxiety Inventory pre and post procedures. Music group patients listened to classical songs through headphones, while the control group received the standard care. Pain score was evaluated with a visual analog scale (VAS). Statistical analysis was conducted using Pearson Chi-square, Fisher's Exact test and T-Test and p-values less than 0.05 were considered statistically significant. A total of 73 patients were enrolled and randomized, resulting in 36 women in the music group and 37 women in the non-music control group. The preoperative mean anxiety score was higher in the music group (46.8 VS 45.8 points). The postoperative mean anxiety scores in the music and the non-music groups were 38.7 and 41.3 points, respectively. VAS was lower in music group (2.55 VS 3.33). The percent change of anxiety was greater in the music group, although there was no significant difference between two groups. Music therapy did not significantly reduce anxiety in patients undergoing the LLETZ procedure. However, different interventions should be developed to ease the patients' apprehension during this procedure.

Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke

PubMed Central

Tuttolomondo, Antonino; Di Raimondo, Domenico; Pecoraro, Rosaria; Maida, Carlo; Arnao, Valentina; Corte, Vittoriano Della; Simonetta, Irene; Corpora, Francesca; Di Bona, Danilo; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

2016-01-01

Abstract Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-α, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile. PMID:27043681

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

The effect of mud therapy on pain relief in patients with knee osteoarthritis: a meta-analysis of randomized controlled trials.

PubMed

Liu, Hua; Zeng, Chao; Gao, Shu-guang; Yang, Tuo; Luo, Wei; Li, Yu-sheng; Xiong, Yi-lin; Sun, Jin-peng; Lei, Guang-hua

2013-10-01

A meta-analysis was conducted to examine the effect of mud therapy on pain relief in patients with knee osteoarthritis (OA). A detailed search of PubMed®/MEDLINE® was undertaken to identify randomized controlled trials and prospective comparative studies published before 9 March 2013 that compared mud therapy with control group treatments in patients with knee OA. A quantitative meta-analysis of seven studies (410 patients) was performed. There was a significant difference between the groups in the visual analogue scale pain score (standardized mean difference [SMD] -0.73) and Western Ontario and McMaster Universities Osteoarthritis Index pain score (SMD -0.30), with differences in favour of mud therapy. Mud therapy is a favourable option for pain relief in patients with knee OA. Additional high-quality randomized controlled trials need to be conducted to explore this issue further and to confirm this conclusion.

2D vs. 3D imaging in laparoscopic surgery-results of a prospective randomized trial.

PubMed

Buia, Alexander; Stockhausen, Florian; Filmann, Natalie; Hanisch, Ernst

2017-12-01

3D imaging is an upcoming technology in laparoscopic surgery, and recent studies have shown that the modern 3D technique is superior in an experimental setting. However, the first randomized controlled clinical trial in this context dates back to 1998 and showed no significant difference between 2D and 3D visualization using the first 3D generation technique, which is now more than 15 years old. Positive results measured in an experimental setting considering 3D imaging on surgical performance led us to initiate a randomized controlled pragmatic clinical trial to validate our findings in daily clinical routine. Standard laparoscopic operations (cholecystectomy, appendectomy) were preoperatively randomized to a 2D or 3D imaging system. We used a surgical comfort scale (Likert scale) and the Raw NASA Workload TLX for the subjective assessment of 2D and 3D imaging; the duration of surgery was also measured. The results of 3D imaging were statistically significant better than 2D imaging concerning the parameters "own felt safety" and "task efficiency"; the difficulty level of the procedures in the 2D and 3D groups did not differ. Overall, the Raw NASA Workload TLX showed no significance between the groups. 3D imaging could be a possible advantage in laparoscopic surgery. The results of our clinical trial show increased personal felt safety and efficiency of the surgeon using a 3D imaging system. Overall of the procedures, the findings assessed using Likert scales in terms of own felt safety and task efficiency were statistically significant for 3D imaging. The individually perceived workload assessed with the Raw NASA TLX shows no difference. Although these findings are subjective impressions of the performing surgeons without a clear benefit for 3D technology in clinical outcome, we think that these results show the capability that 3D laparoscopy can have a positive impact while performing laparoscopic procedures.

A Randomized Crossover Trial Comparing Autotitrating and Continuous Positive Airway Pressure in Subjects With Symptoms of Aerophagia: Effects on Compliance and Subjective Symptoms.

PubMed

Shirlaw, Teresa; Hanssen, Kevin; Duce, Brett; Hukins, Craig

2017-07-15

To assess the benefit and tolerance of autotitrating positive airway pressure (APAP) versus continuous positive airway pressure (CPAP) in subjects who experience aerophagia. This is the report of a prospective, two-week, double-blinded, randomized crossover trial set in an Australian clinical sleep laboratory in a tertiary hospital. Fifty-six subjects who reported symptoms of aerophagia that they attributed to CPAP were recruited. Full face masks were used by 39 of the 56 subjects recruited. Subjects were randomly and blindly allocated to either CPAP at their treatment recommended pressure or APAP 6-20 cm H 2 O, in random order. Subjects spent two weeks on each therapy mode. Therapy usage hours, 95th centile pressure, maximum pressure, 95th centile leak, and residual apnea-hypopnea index (AHI) were reported at the end of each two-week treatment period. Functional Outcome of Sleepiness Questionnaire, Epworth Sleepiness Scale, and visual analog scale to measure symptoms of aerophagia were also completed at the end of each 2-week treatment arm. The median pressure ( P < .001) and 95th centile pressure ( P < .001) were reduced with APAP but no differences in compliance ( P = .120) and residual AHI were observed. APAP reduced the symptoms of bloating ( P = .011), worst episode of bloating ( P = .040), flatulence ( P = .010), and belching ( P = .001) compared to CPAP. There were no differences in Epworth Sleepiness Scale or Functional Outcome of Sleepiness Questionnaire outcomes between CPAP and APAP. APAP therapy reduces the symptoms of aerophagia while not affecting compliance when compared with CPAP therapy. Australian and New Zealand Clinical Trials Registry at https://www.anzctr.org.au, trial number ACTRN12611001250921. A commentary on this article appears in this issue on page 859. © 2017 American Academy of Sleep Medicine

Review of recent non-hyperbaric oxygen interventions for mild traumatic brain injury.

PubMed

Wilson, Steffanie H; Roth, Michael; Lindblad, Anne S; Weaver, Lindell K

2016-01-01

Traumatic brain injury (TBI) affects 3.2 to 5.3 million persons in the United States (U.S.), and the impact in the U.S. military is proportionally higher. Consensus is lacking regarding an accepted outcome to measure the effectiveness of interventions to improve the symptoms associated with TBI, and no standard-of-care treatment exists for mild TBI (mTBI). A recent literature review evaluated hyperbaric oxygen therapy (HBO₂) interventions, and findings were mixed. We conducted a systematic review of non-HBO₂ mTBI interventional trials published in 2005-2015 in military and civilian populations. A total of 154 abstracts, seven randomized controlled trials (RCTs) and five pilot studies were reviewed. RCTs were evaluated using Consolidated Standards of Reporting Trials criteria. Results indicated that studies published within the period of review were small pilot studies for rehabilitation therapy and motion capture or virtual reality gaming interventions. Neuropsychological assessments were commonly specified outcomes, and most studies included a combination of symptom and neuropsychological assessments. Findings indicated a lack of large-scale, well-controlled trials to address the symptoms and sequelae of this condition, but results of small exploratory studies show evidence of potentially promising interventions. Copyright© Undersea and Hyperbaric Medical Society.

The Immunogenicity and Safety of CYD-Tetravalent Dengue Vaccine (CYD-TDV) in Children and Adolescents: A Systematic Review.

PubMed

Agarwal, Raksheeth; Wahid, Mardiastuti H; Yausep, Oliver E; Angel, Sharon H; Lokeswara, Angga W

2017-01-01

to assess the immunogenicity and safety of CYD-tetravalent dengue vaccine (CYD-TDV) in children. comprehensive literature searches were conducted on various databases. Randomized-controlled trials on children with CYD-TDV as intervention were selected based on inclusion and exclusion criteria. Data extracted from selected trials included safety of vaccine and immunogenicity in terms of Geometric Mean Titres (GMT) of antibodies.   six clinical trials were selected based on preset criteria. GMT values were obtained using 50% Plaque Reduction Neutralization Test (PRNT) and safety was semi-quantitatively assessed based on adverse effects. Additional data processing was done to obtain a better understanding on the trends among the studies. The results showed that the groups vaccinated with CYD-TDV showed higher immunogenicity against dengue virus antigens than the control groups. Safety results were satisfactory in all trials, and most severe side effects were unrelated to the vaccine. CYD-TDV is both effective and safe for patients in endemic regions. This gives promise for further development and large-scale research on this vaccine to assess its efficacy in decreasing dengue prevalence, and its pervasive implementation in endemic countries, such as Indonesia.

Yukmijihwang-tang for the treatment of xerostomia in the elderly: study protocol for a randomized, double-blind, placebo-controlled, two-center trial.

PubMed

Han, Gajin; Park, Jae-Woo; Ko, Seok-Jae; Son, Jihee; Seon, Jongki; Kim, Juyeon; Kim, Seulki; Yeo, Inkwon; Ryu, Bongha; Kim, Jinsung

2013-09-03

Xerostomia, a subjective sense of dry mouth, is not generally regarded a disease despite its high prevalence among the elderly, and therefore continues to impair affected patients' quality of life. In traditional Korean medicine, 'Yin-Deficiency' has been implicated in the pathogenesis of xerostomia among the elderly. Yukmijihwang-tang is a famous herbal prescription used to relieve 'Yin-Deficiency', and reportedly has antioxidant effects; therefore, it is postulated that Yukmijihwang-tang can be used to treat xerostomia in the elderly. However, to our knowledge, no clinical trial has been conducted on the effects of Yukmijihwang-tang on xerostomia. Thus, we designed a randomized clinical trial to investigate the effects and safety of Yukmijihwang-tang on xerostomia in the elderly. In addition, we will clarify the aforementioned assumption that 'Yin-Deficiency' is the major cause of xerostomia in the elderly by identifying a correlation between xerostomia and 'Yin-Deficiency'. This randomized, double-blind, placebo-controlled trial will be carried out at two centers: Kyung Hee University Korean Medicine Hospital and Kyung Hee University Hospital at Gangdong. We will recruit 96 subjects aged 60-80 years who have experienced xerostomia for 3 months prior to participation. Subjects who present with score >40 on the visual analogue scale for xerostomia and unstimulated salivary flow rate under 0.3mL/min will be included and the randomization will be carried out by an independent statistician by using a random number creation program. The subjects and all researchers except the statistician will be blinded to the group assignment. Yukmijihwang-tang or placebo will be administered to each group for 8 weeks. The primary outcome is change in the scores for the visual analogue scale for xerostomia and the dry mouth symptom questionnaire from 0 to 8 weeks. It will be assessed whether Yukmijihwang-tang can be used as a new herbal treatment for xerostomia in the elderly by demonstrating its therapeutic effects in a well-designed clinical trial. ClinicalTrials.gov Identifier: NCT01579877.

Assessing the Eventual Publication of Clinical Trial Abstracts Submitted to a Large Annual Oncology Meeting.

PubMed

Massey, Paul R; Wang, Ruibin; Prasad, Vinay; Bates, Susan E; Fojo, Tito

2016-03-01

Despite the ethical imperative to publish clinical trials when human subjects are involved, such data frequently remain unpublished. The objectives were to tabulate the rate and ascertain factors associated with eventual publication of clinical trial results reported as abstracts in the Proceedings of the American Society of Clinical Oncology (American Society of Clinical Oncology). Abstracts describing clinical trials for patients with breast, lung, colorectal, ovarian, and prostate cancer from 2009 to 2011 were identified by using a comprehensive online database (http://meetinglibrary.asco.org/abstracts). Abstracts included reported results of a treatment or intervention assessed in a discrete, prospective clinical trial. Publication status at 4-6 years was determined by using a standardized search of PubMed. Primary outcomes were the rate of publication for abstracts of randomized and nonrandomized clinical trials. Secondary outcomes included factors influencing the publication of results. A total of 1,075 abstracts describing 378 randomized and 697 nonrandomized clinical trials were evaluated. Across all years, 75% of randomized and 54% of nonrandomized trials were published, with an overall publication rate of 61%. Sample size was a statistically significant predictor of publication for both randomized and nonrandomized trials (odds ratio [OR] per increase of 100 participants = 1.23 [1.11-1.36], p < .001; and 1.64 [1.15-2.34], p = .006, respectively). Among randomized studies, an industry coauthor or involvement of a cooperative group increased the likelihood of publication (OR 2.37, p = .013; and 2.21, p = .01, respectively). Among nonrandomized studies, phase II trials were more likely to be published than phase I (p < .001). Use of an experimental agent was not a predictor of publication in randomized (OR 0.76 [0.38-1.52]; p = .441) or nonrandomized trials (OR 0.89 [0.61-1.29]; p = .532). This is the largest reported study examining why oncology trials are not published. The data show that 4-6 years after appearing as abstracts, 39% of oncology clinical trials remain unpublished. Larger sample size and advanced trial phase were associated with eventual publication; among randomized trials, an industry-affiliated author or a cooperative group increased likelihood of publication. Unfortunately, we found that, despite widespread recognition of the problem and the creation of central data repositories, timely publishing of oncology clinical trials results remains unsatisfactory. ©AlphaMed Press.

Randomized controlled trial comparing retroperitoneal laparoscopic pyelolithotomy versus percutaneous nephrolithotomy for the treatment of large renal pelvic calculi: a pilot study.

PubMed

Li, Sheng; Liu, Tong-Zu; Wang, Xing-Huan; Zeng, Xian-Tao; Zeng, Guang; Yang, Zhong-Hua; Weng, Hong; Meng, Zhe; Huang, Jing-Yu

2014-08-01

To evaluate the efficacy and safety of retroperitoneal laparoscopic pyelolithotomy (RLP) versus percutaneous nephrolithotomy (PCNL) for large renal pelvic calculi using a randomized controlled trial. Patients with large renal pelvic calculi were prospectively randomized using matched-pair analysis (1:1 scenario) into either the RLP group or the PCNL group. The patients in each group underwent the procedure accordingly. Treatment efficacy, safety, and complications were evaluated after surgery. Finally, 178 eligible patients were included and the demographics and mean stone size of two groups were similar. We found no significant differences in the mean postoperative hospital stay (4.5±2.3 vs. 4.3±1.3 days), rate of blood transfusion (0% vs. 1.1%), conversion rate (0% vs. 3.4%), and rate of total postoperative complication (p>0.05). The procedural duration and mean drop in hemoglobin levels were significantly lower in the RLP group as compared with the PCNL group (90.87±33.4 vs. 116.8±44.4 minutes, p<0.001; 0.9±0.5 vs. 1.7±1.3 g/dL, p<0.001, respectively). Significant differences were also observed in the stone-free rate (98% vs. 90%, p=0.03) and postoperative fever rate (3.4% vs. 13.5%, p=0.02). Current evidence suggests that PCNL and RLP are both effective and safe for the treatment of large renal pelvic calculi. Our study shows that, compared with the PCNL approach, RLP for large renal pelvic stone resulted in shorter operative time, less bleeding, less postoperative fever, and a higher stone-free rate. Data from larger, multicenter randomized controlled trials of high quality are needed to further confirm our findings.

Efficacy of prokinetics with a split-dose of polyethylene glycol in bowel preparation for morning colonoscopy: a randomized controlled trial.

PubMed

Kim, Hyoung Jun; Kim, Tae Oh; Shin, Bong Chul; Woo, Jae Gon; Seo, Eun Hee; Joo, Hee Rin; Heo, Nae-Yun; Park, Jongha; Park, Seung Ha; Yang, Sung Yeon; Moon, Young Soo; Shin, Jin-Yong; Lee, Nae Young

2012-01-01

Currently, a split-dose of polyethylene glycol (PEG) is the mainstay of bowel preparation due to its tolerability, bowel-cleansing action, and safety. However, bowel preparation with PEG is suboptimal because residual fluid reduces the polyp detection rate and requires a more thorough colon inspection. The aim of our study was to demonstrate the efficacy of a sufficient dose of prokinetics on bowel cleansing together with split-dose PEG. A prospective endoscopist-blinded study was conducted. Patients were randomly allocated to two groups: prokinetic with split-dose PEG or split-dose PEG alone. A prokinetic [100 mg itopride (Itomed)], was administered twice simultaneously with each split-dose of PEG. Bowel-cleansing efficacy was measured by endoscopists using the Ottawa scale and the segmental fluidity scale score. Each participant completed a bowel preparation survey. Mean scores from the Ottawa scale, segmental fluid scale, and rate of poor preparation were compared between both groups. Patients in the prokinetics with split-dose PEG group showed significantly lower total Ottawa and segmental fluid scores compared with patients in the split-dose of PEG alone group. A sufficient dose of prokinetics with a split-dose of PEG showed efficacy in bowel cleansing for morning colonoscopy, largely due to the reduction in colonic fluid. Copyright © 2012 S. Karger AG, Basel.

Electroacupuncture and splinting versus splinting alone to treat carpal tunnel syndrome: a randomized controlled trial

PubMed Central

Chung, Vincent C.H.; Ho, Robin S.T.; Liu, Siya; Chong, Marc K.C.; Leung, Albert W.N.; Yip, Benjamin H.K.; Griffiths, Sian M.; Zee, Benny C.Y.; Wu, Justin C.Y.; Sit, Regina W.S.; Lau, Alexander Y.L.; Wong, Samuel Y.S.

2016-01-01

Background: The effectiveness of acupuncture for managing carpal tunnel syndrome is uncertain, particularly in patients already receiving conventional treatments (e.g., splinting). We aimed to assess the effects of electroacupuncture combined with splinting. Methods: We conducted a randomized parallel-group assessor-blinded 2-arm trial on patients with clinically diagnosed primary carpal tunnel syndrome. The treatment group was offered 13 sessions of electroacupuncture over 17 weeks. The treatment and control groups both received continuous nocturnal wrist splinting. Results: Of 181 participants randomly assigned to electroacupuncture combined with splinting (n = 90) or splinting alone (n = 91), 174 (96.1%) completed all follow-up. The electroacupuncture group showed greater improvements at 17 weeks in symptoms (primary outcome of Symptom Severity Scale score mean difference [MD] −0.20, 95% confidence interval [CI] −0.36 to −0.03), disability (Disability of Arm, Shoulder and Hand Questionnaire score MD −6.72, 95% CI −10.9 to −2.57), function (Functional Status Scale score MD −0.22, 95% CI −0.38 to −0.05), dexterity (time to complete blinded pick-up test MD −6.13 seconds, 95% CI −10.6 to −1.63) and maximal tip pinch strength (MD 1.17 lb, 95% CI 0.48 to 1.86). Differences between groups were small and clinically unimportant for reduction in pain (numerical rating scale −0.70, 95% CI −1.34 to −0.06), and not significant for sensation (first finger monofilament test −0.08 mm, 95% CI −0.22 to 0.06). Interpretation: For patients with primary carpal tunnel syndrome, chronic mild to moderate symptoms and no indication for surgery, electroacupuncture produces small changes in symptoms, disability, function, dexterity and pinch strength when added to nocturnal splinting. Trial registration: Chinese Clinical Trial Register no. ChiCTR-TRC-11001655 (www.chictr.org.cn/showprojen.aspx?proj=7890); subsequently deposited in the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR-TRC-11001655). PMID:27270119

Surgery for post-vitrectomy cataract

PubMed Central

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

2014-01-01

Background Cataract formation or acceleration can occur after intraocular surgery, especially following vitrectomy, a surgical technique for removing the vitreous which is used in the treatment of disorders that affect the posterior segment of the eye. The underlying problem that led to vitrectomy may limit the benefit from cataract surgery. Objectives The objective of this review was to evaluate the effectiveness and safety of surgery for post-vitrectomy cataract with respect to visual acuity, quality of life, and other outcomes. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 4), Ovid MEDLINE, Ovid MEDLINE in-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily Update, Ovid OLDMED-LINE (January 1946 to May 2013), EMBASE (January 1980 to May 2013, Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to May 2013), PubMed (January 1946 to May 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrial.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 22 May 2013. Selection criteria We planned to include randomized and quasi-randomized controlled trials comparing cataract surgery with no surgery in adult patients who developed cataract following vitrectomy. Data collection and analysis Two authors screened the search results independently according to the standard methodological procedures expected by The Cochrane Collaboration. Main results We found no randomized or quasi-randomized controlled trials comparing cataract surgery with no cataract surgery for patients who developed cataracts following vitrectomy surgery. Authors' conclusions There is no evidence from randomized or quasi-randomized controlled trials on which to base clinical recommendations for surgery for post-vitrectomy cataract. There is a clear need for randomized controlled trials to address this evidence gap. Such trials should stratify participants by their age, the retinal disorder leading to vitrectomy, and the status of the underlying disease process in the contralateral eye. Outcomes assessed in such trials may include gain of vision on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, quality of life, and adverse events such as posterior capsular rupture. Both short-term (six-month) and long-term (one-year or two-year) outcomes should be examined. PMID:24357418

A body image and disordered eating intervention for women in midlife: a randomized controlled trial.

PubMed

McLean, Siân A; Paxton, Susan J; Wertheim, Eleanor H

2011-12-01

This study examined the outcome of a body image and disordered eating intervention for midlife women. The intervention was specifically designed to address risk factors that are pertinent in midlife. Participants were 61 women aged 30 to 60 years (M = 43.92, SD = 8.22) randomly assigned to intervention (n = 32) or (delayed treatment) control (n = 29) groups. Following an 8-session facilitated group cognitive behavioral therapy-based intervention, outcomes from the Body Shape Questionnaire; Eating Disorder Examination Questionnaire; Body Image Avoidance Questionnaire; Physical Appearance Comparison Scale; Sociocultural Attitudes Towards Appearance Scale, Internalization subscale; measures of appearance importance, cognitive reappraisal, and self-care; Dutch Eating Behavior Questionnaire; and Kessler Psychological Distress Scale were compared for statistical and clinical significance from baseline to posttest and 6-month follow-up. Following the intent-to-treat principle, mixed-model analyses with a mixed within-between design demonstrated that the intervention group had large improvements that were statistically significantly different from the control group in body image, disordered eating, and risk factor variables and that were maintained at 6-month follow-up. Furthermore, the improvements were also of clinical importance. This study provides support for the efficacy of an intervention to reduce body image and eating concerns in midlife women. Further research into interventions tailored for this population is warranted.

Radiation Therapy Intensification for Solid Tumors: A Systematic Review of Randomized Trials

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

Yamoah, Kosj; Showalter, Timothy N.; Ohri, Nitin, E-mail: ohri.nitin@gmail.com

Purpose: To systematically review the outcomes of randomized trials testing radiation therapy (RT) intensification, including both dose escalation and/or the use of altered fractionation, as a strategy to improve disease control for a number of malignancies. Methods and Materials: We performed a literature search to identify randomized trials testing RT intensification for cancers of the central nervous system, head and neck, breast, lung, esophagus, rectum, and prostate. Findings were described qualitatively. Where adequate data were available, pooled estimates for the effect of RT intensification on local control (LC) or overall survival (OS) were obtained using the inverse variance method. Results: Inmore » primary central nervous system tumors, esophageal cancer, and rectal cancer, randomized trials have not demonstrated that RT intensification improves clinical outcomes. In breast cancer and prostate cancer, dose escalation has been shown to improve LC or biochemical disease control but not OS. Radiation therapy intensification may improve LC and OS in head and neck and lung cancers, but these benefits have generally been limited to studies that did not incorporate concurrent chemotherapy. Conclusions: In randomized trials, the benefits of RT intensification have largely been restricted to trials in which concurrent chemotherapy was not used. Novel strategies to optimize the incorporation of RT in the multimodality treatment of solid tumors should be explored.« less

Yoga vs. physical therapy vs. education for chronic low back pain in predominantly minority populations: study protocol for a randomized controlled trial.

PubMed

Saper, Robert B; Sherman, Karen J; Delitto, Anthony; Herman, Patricia M; Stevans, Joel; Paris, Ruth; Keosaian, Julia E; Cerrada, Christian J; Lemaster, Chelsey M; Faulkner, Carol; Breuer, Maya; Weinberg, Janice

2014-02-26

Chronic low back pain causes substantial morbidity and cost to society while disproportionately impacting low-income and minority adults. Several randomized controlled trials show yoga is an effective treatment. However, the comparative effectiveness of yoga and physical therapy, a common mainstream treatment for chronic low back pain, is unknown. This is a randomized controlled trial for 320 predominantly low-income minority adults with chronic low back pain, comparing yoga, physical therapy, and education. Inclusion criteria are adults 18-64 years old with non-specific low back pain lasting ≥ 12 weeks and a self-reported average pain intensity of ≥ 4 on a 0-10 scale. Recruitment takes place at Boston Medical Center, an urban academic safety-net hospital and seven federally qualified community health centers located in diverse neighborhoods. The 52-week study has an initial 12-week Treatment Phase where participants are randomized in a 2:2:1 ratio into i) a standardized weekly hatha yoga class supplemented by home practice; ii) a standardized evidence-based exercise therapy protocol adapted from the Treatment Based Classification method, individually delivered by a physical therapist and supplemented by home practice; and iii) education delivered through a self-care book. Co-primary outcome measures are 12-week pain intensity measured on an 11-point numerical rating scale and back-specific function measured using the modified Roland Morris Disability Questionnaire. In the subsequent 40-week Maintenance Phase, yoga participants are re-randomized in a 1:1 ratio to either structured maintenance yoga classes or home practice only. Physical therapy participants are similarly re-randomized to either five booster sessions or home practice only. Education participants continue to follow recommendations of educational materials. We will also assess cost effectiveness from the perspectives of the individual, insurers, and society using claims databases, electronic medical records, self-report cost data, and study records. Qualitative data from interviews will add subjective detail to complement quantitative data. This trial is registered in ClinicalTrials.gov, with the ID number: NCT01343927.

Using Small-Scale Randomized Controlled Trials to Evaluate the Efficacy of New Curricular Materials

PubMed Central

Bass, Kristin M.; Stark, Louisa A.

2014-01-01

How can researchers in K–12 contexts stay true to the principles of rigorous evaluation designs within the constraints of classroom settings and limited funding? This paper explores this question by presenting a small-scale randomized controlled trial (RCT) designed to test the efficacy of curricular supplemental materials on epigenetics. The researchers asked whether the curricular materials improved students’ understanding of the content more than an alternative set of activities. The field test was conducted in a diverse public high school setting with 145 students who were randomly assigned to a treatment or comparison condition. Findings indicate that students in the treatment condition scored significantly higher on the posttest than did students in the comparison group (effect size: Cohen's d = 0.40). The paper discusses the strengths and limitations of the RCT, the contextual factors that influenced its enactment, and recommendations for others wishing to conduct small-scale rigorous evaluations in educational settings. Our intention is for this paper to serve as a case study for university science faculty members who wish to employ scientifically rigorous evaluations in K–12 settings while limiting the scope and budget of their work. PMID:25452482

Effectiveness of a School-Based Physical Activity Intervention on Cognitive Performance in Danish Adolescents: LCoMotion—Learning, Cognition and Motion – A Cluster Randomized Controlled Trial

PubMed Central

Domazet, Sidsel Louise; Froberg, Karsten; Hillman, Charles H.; Andersen, Lars Bo; Bugge, Anna

2016-01-01

Background Physical activity is associated not only with health-related parameters, but also with cognitive and academic performance. However, no large scale school-based physical activity interventions have investigated effects on cognitive performance in adolescents. The aim of this study was to describe the effectiveness of a school-based physical activity intervention in enhancing cognitive performance in 12–14 years old adolescents. Methods A 20 week cluster randomized controlled trial was conducted including seven intervention and seven control schools. A total of 632 students (mean (SD) age: 12.9 (0.6) years) completed the trial with baseline and follow-up data on primary or secondary outcomes (74% of randomized subjects). The intervention targeted physical activity during academic subjects, recess, school transportation and leisure-time. Cognitive performance was assessed using an executive functions test of inhibition (flanker task) with the primary outcomes being accuracy and reaction time on congruent and incongruent trials. Secondary outcomes included mathematics performance, physical activity levels, body-mass index, waist-circumference and cardiorespiratory fitness. Results No significant difference in change, comparing the intervention group to the control group, was observed on the primary outcomes (p’s>0.05) or mathematics skills (p>0.05). An intervention effect was found for cardiorespiratory fitness in girls (21 meters (95% CI: 4.4–38.6) and body-mass index in boys (-0.22 kg/m2 (95% CI: -0.39–0.05). Contrary to our predictions, a significantly larger change in interference control for reaction time was found in favor of the control group (5.0 milliseconds (95% CI: 0–9). Baseline to mid-intervention changes in physical activity levels did not differ significantly between groups (all p’s>0.05). Conclusions No evidence was found for effectiveness of a 20-week multi-faceted school-based physical activity intervention for enhancing executive functioning or mathematics skills compared to a control group, but low implementation fidelity precludes interpretation of the causal relationship. Trial Registration www.ClinicalTrials.gov NCT02012881 PMID:27341346

Electroacupuncture to treat painful diabetic neuropathy: study protocol for a three-armed, randomized, controlled pilot trial.

PubMed

Lee, Seunghoon; Kim, Joo-Hee; Shin, Kyung-Min; Kim, Jung-Eun; Kim, Tae-Hun; Kang, Kyung-Won; Lee, Minhee; Jung, So-Young; Shin, Mi-Suk; Kim, Ae-Ran; Park, Hyo-Ju; Hong, Kwon-Eui; Choi, Sun-Mi

2013-07-18

The purpose of this study is to conduct a basic analysis of the effectiveness and safety of electroacupuncture in the treatment of painful diabetic neuropathy (PDN) as compared to placebo and usual care and to evaluate the feasibility of large-scale clinical research. This study is a protocol for a three-armed, randomized, patient-assessor-blinded (to the type of treatment), controlled pilot trial. Forty-five participants with a ≥ six month history of PDN and a mean weekly pain score of ≥ 4 on the 11-point Pain Intensity Numerical Rating Scale (PI-NRS) will be assigned to the electroacupuncture group (n = 15), sham group (n = 15) or usual care group (n = 15). The participants assigned to the electroacupuncture group will receive electroacupuncture (remaining for 30 minutes with a mixed current of 2 Hz/120 Hz and 80% of the bearable intensity) at 12 standard acupuncture points (bilateral ST36, GB39, SP9, SP6, LR3 and GB41) twice per week for eight weeks (a total of 16 sessions) as well as the usual care. The participants in the sham group will receive sham electroacupuncture (no electrical current will be passed to the needle, but the light will be seen, and the sound of the pulse generator will be heard by the participants) at non-acupuncture points as well as the usual care. The participants in the usual care group will not receive electroacupuncture treatment during the study period and will receive only the usual care. The follow-up will be in the 5th, 9th and 17th weeks after random allocation. The PI-NRS score assessed at the ninth week will be the primary outcome measurement used in this study. The Short-Form McGill Pain Questionnaire (SF-MPQ), a sleep disturbance score (11-point Likert scale), the Short-Form 36v2 Health Survey (SF-36), the Beck Depression Inventory (BDI) and the Patient Global Impression of Change (PGIC) will be used as outcome variables to evaluate the effectiveness of the acupuncture. Safety will be assessed at every visit. The result of this trial will provide a basis for the effectiveness and safety of electroacupuncture for PDN. Clinical Research information Service. Unique identifier: KCT0000466.

The statistical pitfalls of the partially randomized preference design in non-blinded trials of psychological interventions.

PubMed

Gemmell, Isla; Dunn, Graham

2011-03-01

In a partially randomized preference trial (PRPT) patients with no treatment preference are allocated to groups at random, but those who express a preference receive the treatment of their choice. It has been suggested that the design can improve the external and internal validity of trials. We used computer simulation to illustrate the impact that an unmeasured confounder could have on the results and conclusions drawn from a PRPT. We generated 4000 observations ("patients") that reflected the distribution of the Beck Depression Index (DBI) in trials of depression. Half were randomly assigned to a randomized controlled trial (RCT) design and half were assigned to a PRPT design. In the RCT, "patients" were evenly split between treatment and control groups; whereas in the preference arm, to reflect patient choice, 87.5% of patients were allocated to the experimental treatment and 12.5% to the control. Unadjusted analyses of the PRPT data consistently overestimated the treatment effect and its standard error. This lead to Type I errors when the true treatment effect was small and Type II errors when the confounder effect was large. The PRPT design is not recommended as a method of establishing an unbiased estimate of treatment effect due to the potential influence of unmeasured confounders. Copyright © 2011 John Wiley & Sons, Ltd.

A cognitive-behavioral intervention for emotion regulation in adults with high-functioning autism spectrum disorders: study protocol for a randomized controlled trial.

PubMed

Kuroda, Miho; Kawakubo, Yuki; Kuwabara, Hitoshi; Yokoyama, Kazuhito; Kano, Yukiko; Kamio, Yoko

2013-07-23

Adults with high-functioning autism spectrum disorders (ASD) have difficulties in social communication; thus, these individuals have trouble understanding the mental states of others. Recent research also suggests that adults with ASD are unable to understand their own mental states, which could lead to difficulties in emotion-regulation. Some studies have reported the efficacy of cognitive-behavioral therapy (CBT) in improving emotion-regulation among children with ASD. The current study will investigate the efficacy of group-based CBT for adults with ASD. The study is a randomized, waitlist controlled, single-blinded trial. The participants will be 60 adults with ASD; 30 will be assigned to a CBT group and 30 to a waitlist control group. Primary outcome measures are the 20-item Toronto Alexithymia Scale, the Coping Inventory for Stressful Situations, the Motion Picture Mind-Reading task, and an ASD questionnaire. The secondary outcome measures are the Center for Epidemiological Studies Depression Scale, the World Health Organization Quality of Life Scale 26-item version, the Global Assessment of Functioning, State-trait Anxiety Inventory, Social Phobia and Anxiety Inventory, and Liebowitz Social Anxiety Scale. All will be administered during the pre- and post-intervention, and 12 week follow-up periods. The CBT group will receive group therapy over an 8 week period (one session per week) with each session lasting approximately 100 minutes. Group therapy will consist of four or five adults with ASD and two psychologists. We will be using visual materials for this program, mainly the Cognitive Affective Training kit. This trial will hopefully indicate the efficacy of group-based CBT for adults with high- functioning ASD. This trial was registered in The University Hospital Medical Information Network Clinical Trials Registry No. UMIN000006236.

A stepped strategy that aims at the nationwide implementation of the Enhanced Recovery After Surgery programme in major gynaecological surgery: study protocol of a cluster randomised controlled trial.

PubMed

de Groot, Jeanny Ja; Maessen, José Mc; Slangen, Brigitte Fm; Winkens, Bjorn; Dirksen, Carmen D; van der Weijden, Trudy

2015-07-30

Enhanced Recovery After Surgery (ERAS) programmes aim at an early recovery after surgical trauma and consequently at a reduced length of hospitalisation. This paper presents the protocol for a study that focuses on large-scale implementation of the ERAS programme in major gynaecological surgery in the Netherlands. The trial will evaluate effectiveness and costs of a stepped implementation approach that is characterised by tailoring the intensity of implementation activities to the needs of organisations and local barriers for change, in comparison with the generic breakthrough strategy that is usually applied in large-scale improvement projects in the Netherlands. All Dutch hospitals authorised to perform major abdominal surgery in gynaecological oncology patients are eligible for inclusion in this cluster randomised controlled trial. The hospitals that already fully implemented the ERAS programme in their local perioperative management or those who predominantly admit gynaecological surgery patients to an external hospital replacement care facility will be excluded. Cluster randomisation will be applied at the hospital level and will be stratified based on tertiary status. Hospitals will be randomly assigned to the stepped implementation strategy or the breakthrough strategy. The control group will receive the traditional breakthrough strategy with three educational sessions and the use of plan-do-study-act cycles for planning and executing local improvement activities. The intervention group will receive an innovative stepped strategy comprising four levels of intensity of support. Implementation starts with generic low-cost activities and may build up to the highest level of tailored and labour-intensive activities. The decision for a stepwise increase in intensive support will be based on the success of implementation so far. Both implementation strategies will be completed within 1 year and evaluated on effect, process, and cost-effectiveness. The primary outcome is length of postoperative hospital stay. Additional outcome measures are length of recovery, guideline adherence, and mean implementation costs per patient. This study takes up the challenge to evaluate an efficient strategy for large-scale implementation. Comparing effectiveness and costs of two different approaches, this study will help to define a preferred strategy for nationwide dissemination of best practices. Dutch Trial Register NTR4058.

Nifedipine vs Placebo for Treatment of Chronic Chilblains: A Randomized Controlled Trial

PubMed Central

Souwer, Ibo H.; Bor, Jacobus H. J.; Smits, Paul; Lagro-Janssen, Antoine L. M.

2016-01-01

PURPOSE Nifedipine is commonly prescribed for the treatment of chilblains (pernio, perniosis) on the basis of observational studies and a single small, older clinical trial. We aimed to confirm the proposed superiority of oral nifedipine 60 mg per day over placebo for treatment of chronic chilblains in primary care. METHODS We performed a randomized, placebo-controlled, double-blind, crossover trial, closely following the design of the older trial. A total of 32 patients with chronic chilblains were randomly assigned to nifedipine (30 mg controlled release twice a day) or placebo. The primary outcome was patient-reported complaints; the secondary outcome was patient-reported disability. Both were assessed from daily ratings on 100-mm visual analogue scales recorded in a diary. We took ambient temperatures into account and checked for a carry-over effect, and monitored for adverse effects. RESULTS After 6 weeks of treatment, mean scores on the visual analogue scale on complaints showed a nonsignificant difference of 1.84 mm (95% CI, −6.67 to 2.99 mm) in favor of nifedipine (P = .44). Mean scores on the visual analogue scale on disability showed a nonsignificant difference of 0.56 mm (95% CI, −2.97 to 4.09 mm) in favor of placebo (P = .75). There was no carry-over effect of prior study treatment. Nifedipine was associated with significantly lower systolic blood pressure and a significantly higher incidence of edema. CONCLUSIONS In our study, nifedipine was not superior to placebo for treating chronic chilblains. These findings contrast with those of the older study and do not support routine use of nifedipine for this condition. PMID:27621162