Distinct Effects of Trial-Driven and Task Set-Related Control in Primary Visual Cortex

PubMed Central

Vaden, Ryan J.; Visscher, Kristina M.

2015-01-01

Task sets are task-specific configurations of cognitive processes that facilitate task-appropriate reactions to stimuli. While it is established that the trial-by-trial deployment of visual attention to expected stimuli influences neural responses in primary visual cortex (V1) in a retinotopically specific manner, it is not clear whether the mechanisms that help maintain a task set over many trials also operate with similar retinotopic specificity. Here, we address this question by using BOLD fMRI to characterize how portions of V1 that are specialized for different eccentricities respond during distinct components of an attention-demanding discrimination task: cue-driven preparation for a trial, trial-driven processing, task-initiation at the beginning of a block of trials, and task-maintenance throughout a block of trials. Tasks required either unimodal attention to an auditory or a visual stimulus or selective intermodal attention to the visual or auditory component of simultaneously presented visual and auditory stimuli. We found that while the retinotopic patterns of trial-driven and cue-driven activity depended on the attended stimulus, the retinotopic patterns of task-initiation and task-maintenance activity did not. Further, only the retinotopic patterns of trial-driven activity were found to depend on the presence of intermodal distraction. Participants who performed well on the intermodal selective attention tasks showed strong task-specific modulations of both trial-driven and task-maintenance activity. Importantly, task-related modulations of trial-driven and task-maintenance activity were in opposite directions. Together, these results confirm that there are (at least) two different processes for top-down control of V1: One, working trial-by-trial, differently modulates activity across different eccentricity sectors—portions of V1 corresponding to different visual eccentricities. The second process works across longer epochs of task performance, and does not differ among eccentricity sectors. These results are discussed in the context of previous literature examining top-down control of visual cortical areas. PMID:26163806

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

PubMed

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

2013-08-15

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

Health Activities Project (HAP), Trial Edition III.

ERIC Educational Resources Information Center

Buller, Dave; And Others

Contained within this Health Activities Project (HAP) trial edition (set III) are a teacher information folio and numerous student activity folios which center around the idea that students in grades 5-8 can control their own health and safety. Each student folio is organized into an Overview, Health Background, Materials, Setting Up, and…

Health Activities Project (HAP), Trial Edition II.

ERIC Educational Resources Information Center

Buller, Dave; And Others

Contained within this Health Activities Project (HAP) trial edition (set II) are a teacher information folio and numerous student activity folios which center around the idea that students in grades 5-8 can control their own health and safety. Each student folio is organized into a Synopsis, Health Background, Materials, Setting Up, and Activities…

Choosing a Control Group in Effectiveness Trials of Behavioral Drug Abuse Treatments

PubMed Central

Brigham, Gregory S.; Feaster, Daniel J.; Wakim, Paul G.; Dempsey, Catherine L.

2009-01-01

Effectiveness trials are an important step in the scientific process of developing and evaluating behavioral treatments. The focus on effectiveness research presents a different set of requirements on the research design when compared with efficacy studies. The choice of a control condition has many implications for a clinical trial's internal and external validity. The purpose of this manuscript is to provide a discussion of the issues involved in choosing a control group for effectiveness trials of behavioral interventions in substance abuse treatment. The authors provide a description of four trial designs and a discussion of the advantages and disadvantages of each. PMID:19553062

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

PubMed

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

2016-01-01

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

A methodological approach for assessing the uptake of core outcome sets using ClinicalTrials.gov: findings from a review of randomised controlled trials of rheumatoid arthritis.

PubMed

Kirkham, Jamie J; Clarke, Mike; Williamson, Paula R

2017-05-17

Objective  To assess the uptake of the rheumatoid arthritis core outcome set using a new assessment method of calculating uptake from data in clinical trial registry entries. Design  Review of randomised trials. Setting  ClinicalTrials.gov. Subjects  273 randomised trials of drug interventions for the treatment of rheumatoid arthritis and registered in ClinicalTrials.gov between 2002 and 2016. Full publications were identified for completed studies from information in the trial registry or from an internet search using Google and the citation database Web of Science. Main outcome measure  The percentage of trials reporting or planning to measure the rheumatoid arthritis core outcome set calculated from the information presented in the trial registry and compared with the percentage reporting the rheumatoid arthritis core outcome set in the resulting trial publications. Results  The full rheumatoid arthritis core outcome set was reported in 81% (116/143) of trials identified on the registry as completed (or terminated) for which results were found in either the published literature or the registry. For trials identified on the registry as completed (or terminated), using information only available in the registry gives an estimate for uptake of 77% (145/189). Conclusions  The uptake of the rheumatoid arthritis core outcome set in clinical trials has continued to increase over time. Using the information on outcomes listed for completed or terminated studies in a trial registry provides a reasonable estimate of the uptake of a core outcome set and is a more efficient and up-to-date approach than examining the outcomes in published trial reports. The method proposed may provide an efficient approach for an up-to-date assessment of the uptake of the 300 core outcome sets already published. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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

PubMed Central

2013-01-01

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

Antiviral therapeutics for the treatment of Ebola virus infection.

PubMed

Cardile, Anthony P; Downey, Lydia G; Wiseman, Perry D; Warren, Travis K; Bavari, Sina

2016-10-01

There have been significant developments in Ebola virus therapeutics. While the efficacy of several products was evaluated in the recent West Africa outbreak, a licensed treatment for EBOV disease remains elusive. Factors that negatively impacted the execution of clinical trials included an overall lack of world readiness to conduct clinical trials in an outbreak setting, ethical concerns limiting implementation of the randomized controlled trials in an outbreak setting, and a decline in case numbers by the time resources were mobilized to conduct clinical trials. We summarize relevant therapeutics that underwent clinical trials during the West Africa outbreak and highlight promising candidates under advanced development. Published by Elsevier Ltd.

Informing real-world practice with real-world evidence: the value of PRECIS-2.

PubMed

Neta, Gila; Johnson, Karin E

2018-05-21

Real-world evidence is needed to inform real-world practice. Pragmatic controlled trials are intended to provide such evidence by assessing the effectiveness of medicines and other interventions in real-world settings, as opposed to explanatory trials that assess efficacy in highly controlled settings. Dal-Ré and colleagues (BMC Med 16:49, 2018) recently performed a literature review of studies published between 2014 and 2017 to assess the degree to which studies that self-identified as pragmatic were truly so. The authors found that over one-third of randomized controlled trials of drugs and biologics that were self-labeled as pragmatic used placebo controls (as opposed to usual care), tested medicines before licensing, or were conducted in a single site. Further, they proposed that, in order to improve the reliability of the 'pragmatic' label, investigators should assess their trials using the PRECIS-2 tool upon submission to funders, ethics boards, or journals. We appreciate the value of PRECIS-2 as an indicator to assess the pragmatic versus explanatory features in a trial, and we herein highlight the potential challenges and opportunities that may arise with its systematic and widespread use.

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.

Recruiting Participants for Randomized Controlled Trials

ERIC Educational Resources Information Center

Gallagher, H. Alix; Roschelle, Jeremy; Feng, Mingyu

2014-01-01

The objective of this study was to look across strategies used in a wide range of studies to build a framework for researchers to use in conceptualizing the recruitment process. This paper harvests lessons learned across 19 randomized controlled trials in K-12 school settings conducted by a leading research organization to identify strategies that…

Randomized, Controlled Trial to Examine the Impact of Providing Yogurt to Women Enrolled in WIC

ERIC Educational Resources Information Center

Fung, Ellen B.; Ritchie, Lorrene D.; Walker, Brent H.; Gildengorin, Ginny; Crawford, Patricia B.

2010-01-01

Objective: Examine the impact of providing yogurt to women enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Design: Randomized, controlled intervention trial. Setting: Two California WIC local agency sites. Participants: 511 pregnant, breast-feeding, or postpartum women. Intervention: Substitution of…

Influencing Antecedents of Adolescent Risk-Taking Behaviour in Elementary School: Results of a 4-Year Quasi-Experimental Controlled Trial

ERIC Educational Resources Information Center

Maruska, K.; Morgenstern, M.; Isensee, B.; Hanewinkel, R.

2010-01-01

Effects of the life skills programme "Eigenstandig werden" (Becoming independent) on life skills and on identified antecedents of adolescent health risk behaviour, childhood internalizing and externalizing behaviour were tested in an elementary school setting. A quasi-experimental controlled trial with five repeated measures was…

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

PubMed

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

2011-02-01

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

Design of robust iterative learning control schemes for systems with polytopic uncertainties and sector-bounded nonlinearities

NASA Astrophysics Data System (ADS)

Boski, Marcin; Paszke, Wojciech

2017-01-01

This paper deals with designing of iterative learning control schemes for uncertain systems with static nonlinearities. More specifically, the nonlinear part is supposed to be sector bounded and system matrices are assumed to range in the polytope of matrices. For systems with such nonlinearities and uncertainties the repetitive process setting is exploited to develop a linear matrix inequality based conditions for computing the feedback and feedforward (learning) controllers. These controllers guarantee acceptable dynamics along the trials and ensure convergence of the trial-to-trial error dynamics, respectively. Numerical examples illustrate the theoretical results and confirm effectiveness of the designed control scheme.

Limitations of basing screening policies on screening trials: The US Preventive Services Task Force and Prostate Cancer Screening.

PubMed

Etzioni, Ruth; Gulati, Roman; Cooperberg, Matt R; Penson, David M; Weiss, Noel S; Thompson, Ian M

2013-04-01

The US Preventive Services Task Force recently recommended against prostate-specific antigen screening for prostate cancer based primarily on evidence from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. : To examine limitations of basing screening policy on evidence from screening trials. We reviewed published modeling studies that examined population and trial data. The studies (1) project the roles of screening and changes in primary treatment in the US mortality decline; (2) extrapolate the ERSPC mortality reduction to the long-term US setting; (3) estimate overdiagnosis based on US incidence trends; and (4) quantify the impact of control arm screening on PLCO mortality results. Screening plausibly explains 45% and changes in primary treatment can explain 33% of the US prostate cancer mortality decline. Extrapolating the ERSPC results to the long-term US setting implies an absolute mortality reduction at least 5 times greater than that observed in the trial. Approximately 28% of screen-detected cases are overdiagnosed in the United States versus 58% of screen-detected cases suggested by the ERSPC results. Control arm screening can explain the null result in the PLCO trial. Modeling studies indicate that population trends and trial results extended to the long-term population setting are consistent with greater benefit of prostate-specific antigen screening-and more favorable harm-benefit tradeoffs-than has been suggested by empirical trial evidence.

Generalizability of findings from randomized controlled trials: application to the National Institute of Drug Abuse Clinical Trials Network.

PubMed

Susukida, Ryoko; Crum, Rosa M; Ebnesajjad, Cyrus; Stuart, Elizabeth A; Mojtabai, Ramin

2017-07-01

To compare randomized controlled trial (RCT) sample treatment effects with the population effects of substance use disorder (SUD) treatment. Statistical weighting was used to re-compute the effects from 10 RCTs such that the participants in the trials had characteristics that resembled those of patients in the target populations. Multi-site RCTs and usual SUD treatment settings in the United States. A total of 3592 patients in 10 RCTs and 1 602 226 patients from usual SUD treatment settings between 2001 and 2009. Three outcomes of SUD treatment were examined: retention, urine toxicology and abstinence. We weighted the RCT sample treatment effects using propensity scores representing the conditional probability of participating in RCTs. Weighting the samples changed the significance of estimated sample treatment effects. Most commonly, positive effects of trials became statistically non-significant after weighting (three trials for retention and urine toxicology and one trial for abstinence); also, non-significant effects became significantly positive (one trial for abstinence) and significantly negative effects became non-significant (two trials for abstinence). There was suggestive evidence of treatment effect heterogeneity in subgroups that are under- or over-represented in the trials, some of which were consistent with the differences in average treatment effects between weighted and unweighted results. The findings of randomized controlled trials (RCTs) for substance use disorder treatment do not appear to be directly generalizable to target populations when the RCT samples do not reflect adequately the target populations and there is treatment effect heterogeneity across patient subgroups. © 2017 Society for the Study of Addiction.

Feasibility of a multicentre, randomised controlled trial of laparoscopic versus open colorectal surgery in the acute setting: the LaCeS feasibility trial protocol.

PubMed

Harji, Deena; Marshall, Helen; Gordon, Katie; Crow, Hannah; Hiley, Victoria; Burke, Dermot; Griffiths, Ben; Moriarty, Catherine; Twiddy, Maureen; O'Dwyer, John L; Verjee, Azmina; Brown, Julia; Sagar, Peter

2018-02-22

Acute colorectal surgery forms a significant proportion of emergency admissions within the National Health Service. There is limited evidence to suggest minimally invasive surgery may be associated with improved clinical outcomes in this cohort of patients. Consequently, there is a need to assess the clinical effectiveness and cost-effectiveness of laparoscopic surgery in the acute colorectal setting. However,emergency colorectal surgical trials have previously been difficult to conduct due to issues surrounding recruitment and equipoise. The LaCeS (randomised controlled trial of Laparoscopic versus open Colorectal Surgery in the acute setting) feasibility trial will determine the feasibility of conducting a definitive, phase III trial of laparoscopic versus open acute colorectal resection. The LaCeS feasibility trial is a prospective, multicentre, single-blinded, parallel group, pragmatic randomised controlled feasibility trial. Patients will be randomised on a 1:1 basis to receive eitherlaparoscopic or open surgery. The trial aims to recruit at least 66 patients from five acute general surgical units across the UK. Patients over the age of 18 with a diagnosis of acute colorectal pathology requiring resection on clinical and radiological/endoscopic investigations, with a National Confidential Enquiry into Patient Outcome and Death classification of urgent will be considered eligible for participation. The primary outcome is recruitment. Secondary outcomes include assessing the safety profile of laparoscopic surgery using intraoperative and postoperative complication rates, conversion rates and patient-safety indicators as surrogate markers. Clinical and patient-reported outcomes will also be reported. The trial will contain an embedded qualitative study to assess clinician and patient acceptability of trial processes. The LaCeS feasibility trial is approved by the Yorkshire and The Humber, Bradford Leeds Research Ethics Committee (REC reference: 15/ YH/0542). The results from the trial will be presented at national and international colorectal conferences and will be submitted for publication to peer-reviewed journals. ISRCTN15681041; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Synergies in the space of control variables within the equilibrium-point hypothesis.

PubMed

Ambike, S; Mattos, D; Zatsiorsky, V M; Latash, M L

2016-02-19

We use an approach rooted in the recent theory of synergies to analyze possible co-variation between two hypothetical control variables involved in finger force production based on the equilibrium-point (EP) hypothesis. These control variables are the referent coordinate (R) and apparent stiffness (C) of the finger. We tested a hypothesis that inter-trial co-variation in the {R; C} space during repeated, accurate force production trials stabilizes the fingertip force. This was expected to correspond to a relatively low amount of inter-trial variability affecting force and a high amount of variability keeping the force unchanged. We used the "inverse piano" apparatus to apply small and smooth positional perturbations to fingers during force production tasks. Across trials, R and C showed strong co-variation with the data points lying close to a hyperbolic curve. Hyperbolic regressions accounted for over 99% of the variance in the {R; C} space. Another analysis was conducted by randomizing the original {R; C} data sets and creating surrogate data sets that were then used to compute predicted force values. The surrogate sets always showed much higher force variance compared to the actual data, thus reinforcing the conclusion that finger force control was organized in the {R; C} space, as predicted by the EP hypothesis, and involved co-variation in that space stabilizing total force. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Synergies in the space of control variables within the equilibrium-point hypothesis

PubMed Central

Ambike, Satyajit; Mattos, Daniela; Zatsiorsky, Vladimir M.; Latash, Mark L.

2015-01-01

We use an approach rooted in the recent theory of synergies to analyze possible co-variation between two hypothetical control variables involved in finger force production based in the equilibrium-point hypothesis. These control variables are the referent coordinate (R) and apparent stiffness (C) of the finger. We tested a hypothesis that inter-trial co-variation in the {R; C} space during repeated, accurate force production trials stabilizes the fingertip force. This was expected to correspond to a relatively low amount of inter-trial variability affecting force and a high amount of variability keeping the force unchanged. We used the “inverse piano” apparatus to apply small and smooth positional perturbations to fingers during force production tasks. Across trials, R and C showed strong co-variation with the data points lying close to a hyperbolic curve. Hyperbolic regressions accounted for over 99% of the variance in the {R; C} space. Another analysis was conducted by randomizing the original {R; C} data sets and creating surrogate data sets that were then used to compute predicted force values. The surrogate sets always showed much higher force variance compared to the actual data, thus reinforcing the conclusion that finger force control was organized in the {R; C} space, as predicted by the equilibrium-point hypothesis, and involved co-variation in that space stabilizing total force. PMID:26701299

Effectiveness and Cost-Effectiveness of Occupation-Based Occupational Therapy Using the Aid for Decision Making in Occupation Choice (ADOC) for Older Residents: Pilot Cluster Randomized Controlled Trial

PubMed Central

Nagayama, Hirofumi; Tomori, Kounosuke; Ohno, Kanta; Takahashi, Kayoko; Ogahara, Kakuya; Sawada, Tatsunori; Uezu, Sei; Nagatani, Ryutaro; Yamauchi, Keita

2016-01-01

Background Care-home residents are mostly inactive, have little interaction with staff, and are dependent on staff to engage in daily occupations. We recently developed an iPad application called the Aid for Decision-making in Occupation Choice (ADOC) to promote shared decision-making in activities and occupation-based goal setting by choosing from illustrations describing daily activities. This study aimed to evaluate if interventions based on occupation-based goal setting using the ADOC could focus on meaningful activities to improve quality of life and independent activities of daily living, with greater cost-effectiveness than an impairment-based approach as well as to evaluate the feasibility of conducting a large cluster, randomized controlled trial. Method In this single (assessor)-blind pilot cluster randomized controlled trial, the intervention group (ADOC group) received occupational therapy based on occupation-based goal setting using the ADOC, and the interventions were focused on meaningful occupations. The control group underwent an impairment-based approach focused on restoring capacities, without goal setting tools. In both groups, the 20-minute individualized intervention sessions were conducted twice a week for 4 months. Main Outcome Measures Short Form-36 (SF-36) score, SF-6D utility score, quality adjusted life years (QALY), Barthel Index, and total care cost. Results We randomized and analyzed 12 facilities (44 participants, 18.5% drop-out rate), with 6 facilities each allocated to the ADOC (n = 23) and control (n = 21) groups. After the 4-month intervention, the ADOC group had a significantly greater change in the BI score, with improved scores (P = 0.027, 95% CI 0.41 to 6.87, intracluster correlation coefficient = 0.14). No other outcome was significantly different. The incremental cost-effectiveness ratio, calculated using the change in BI score, was $63.1. Conclusion The results suggest that occupational therapy using the ADOC for older residents might be effective and cost-effective. We also found that conducting an RCT in the occupational therapy setting is feasible. Trial Registration UMIN Clinical Trials Registry UMIN000012994 PMID:26930191

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

PubMed Central

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

1996-01-01

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

Selecting promising treatments in randomized Phase II cancer trials with an active control.

PubMed

Cheung, Ying Kuen

2009-01-01

The primary objective of Phase II cancer trials is to evaluate the potential efficacy of a new regimen in terms of its antitumor activity in a given type of cancer. Due to advances in oncology therapeutics and heterogeneity in the patient population, such evaluation can be interpreted objectively only in the presence of a prospective control group of an active standard treatment. This paper deals with the design problem of Phase II selection trials in which several experimental regimens are compared to an active control, with an objective to identify an experimental arm that is more effective than the control or to declare futility if no such treatment exists. Conducting a multi-arm randomized selection trial is a useful strategy to prioritize experimental treatments for further testing when many candidates are available, but the sample size required in such a trial with an active control could raise feasibility concerns. In this study, we extend the sequential probability ratio test for normal observations to the multi-arm selection setting. The proposed methods, allowing frequent interim monitoring, offer high likelihood of early trial termination, and as such enhance enrollment feasibility. The termination and selection criteria have closed form solutions and are easy to compute with respect to any given set of error constraints. The proposed methods are applied to design a selection trial in which combinations of sorafenib and erlotinib are compared to a control group in patients with non-small-cell lung cancer using a continuous endpoint of change in tumor size. The operating characteristics of the proposed methods are compared to that of a single-stage design via simulations: The sample size requirement is reduced substantially and is feasible at an early stage of drug development.

Controlled human malaria infection trials: How tandems of trust and control construct scientific knowledge.

PubMed

Bijker, Else M; Sauerwein, Robert W; Bijker, Wiebe E

2016-02-01

Controlled human malaria infections are clinical trials in which healthy volunteers are deliberately infected with malaria under controlled conditions. Controlled human malaria infections are complex clinical trials: many different groups and institutions are involved, and several complex technologies are required to function together. This functioning together of technologies, people, and institutions is under special pressure because of potential risks to the volunteers. In this article, the authors use controlled human malaria infections as a strategic research site to study the use of control, the role of trust, and the interactions between trust and control in the construction of scientific knowledge. The authors argue that tandems of trust and control play a central role in the successful execution of clinical trials and the construction of scientific knowledge. More specifically, two aspects of tandems of trust and control will be highlighted: tandems are sites where trust and control coproduce each other, and tandems link the personal, the technical, and the institutional domains. Understanding tandems of trust and control results in setting some agendas for both clinical trial research and science and technology studies.

The Selection and Prevalence of Natural and Fortified Calcium Food Sources in the Diets of Adolescent Girls

ERIC Educational Resources Information Center

Rafferty, Karen; Watson, Patrice; Lappe, Joan M.

2011-01-01

Objective: To assess the impact of calcium-fortified food and dairy food on selected nutrient intakes in the diets of adolescent girls. Design: Randomized controlled trial, secondary analysis. Setting and Participants: Adolescent girls (n = 149) from a midwestern metropolitan area participated in randomized controlled trials of bone physiology…

Reducing Developmental Risk for Emotional/Behavioral Problems: A Randomized Controlled Trial Examining the Tools for Getting Along Curriculum

ERIC Educational Resources Information Center

Daunic, Ann P.; Smith, Stephen W.; Garvan, Cynthia W.; Barber, Brian R.; Becker, Mallory K.; Peters, Christine D.; Taylor, Gregory G.; Van Loan, Christopher L.; Li, Wei; Naranjo, Arlene H.

2012-01-01

Researchers have demonstrated that cognitive-behavioral intervention strategies--such as social problem solving--provided in school settings can help ameliorate the developmental risk for emotional and behavioral difficulties. In this study, we report the results of a randomized controlled trial of Tools for Getting Along (TFGA), a social…

Multisite Randomized Controlled Trial Examining Intelligent Tutoring of Structure Strategy for Fifth-Grade Readers

ERIC Educational Resources Information Center

Wijekumar, Kausalai; Meyer, Bonnie J. F.; Lei, Pui-Wa; Lin, Yu-Chu; Johnson, Lori A.; Spielvogel, James A.; Shurmatz, Kathryn M.; Ray, Melissa; Cook, Michael

2014-01-01

This article reports on a large scale randomized controlled trial to study the efficacy of a web-based intelligent tutoring system for the structure strategy designed to improve content area reading comprehension. The research was conducted with 128 fifth-grade classrooms within 12 school districts in rural and suburban settings. Classrooms within…

Designing a Weight Gain Prevention Trial for Young Adults: The CHOICES Study

ERIC Educational Resources Information Center

Lytle, Leslie A.; Moe, Stacey G.; Nanney, M. Susie; Laska, Melissa N.; Linde, Jennifer A.; Petrich, Christine A.; Sevcik, Sarah M.

2014-01-01

Background: Young adults are at risk for weight gain. Little is known about how to design weight control programs to meet the needs of young adults and few theory-based interventions have been evaluated in a randomized control trial. The Choosing Healthy Options in College Environments and Settings (CHOICES) study was funded to create a…

A Randomised Controlled Trial to Determine the Effectiveness of an Early Psychological Intervention with Children Involved in Road Traffic Accidents

ERIC Educational Resources Information Center

Stallard, Paul; Velleman, Richard; Salter, Emma; Howse, Imogen; Yule, William; Taylor, Gordon

2006-01-01

Objective: To determine whether an early intervention using a psychological debriefing format is effective in preventing psychological distress in child road traffic accident survivors. Design: Randomised controlled trial. Setting: Accident and Emergency Department, Royal United Hospital, Bath. Subjects: 158 children aged 7-18. Follow-up…

Maternal Dietary Counseling Reduces Consumption of Energy-Dense Foods among Infants: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Vitolo, Marcia Regina; Bortolini, Gisele Ane; Campagnolo, Paula Dal Bo; Hoffman, Daniel J.

2012-01-01

Objective: To evaluate the impact of a dietary counseling in reducing the intake of energy-dense foods by infants. Design: A randomized controlled trial. Setting and Participants: Sao Leopoldo, Brazil. Mothers and infants of a low-income-group population were randomized into intervention (n = 163) and received dietary counseling during 10 home…

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…

A Randomized Controlled Trial of a Standardized Behavior Management Intervention for Students with Externalizing Behavior

ERIC Educational Resources Information Center

Forster, Martin; Sundell, Knut; Morris, Richard J.; Karlberg, Martin; Melin, Lennart

2012-01-01

This study reports the results from a Swedish randomized controlled trial of a standardized behavior management intervention. The intervention targeted students with externalizing behavior in a regular education setting. First- and second-grade students (N = 100) from 38 schools were randomly assigned to either the intervention or an active…

Intelligence and Persisting with Medication for Two Years: Analysis in a Randomised Controlled Trial

ERIC Educational Resources Information Center

Deary, Ian J.; Gale, Catharine R.; Stewart, Marlene C. W.; Fowkes, F. Gerald R.; Murray, Gordon D.; Batty, G. David; Price, Jacqueline F.

2009-01-01

The study examined whether verbal intelligence is associated with persisting to take medication for up to two years. The design is a prospective follow-up of compliance with taking medication in high-risk individuals participating in a randomised, placebo-controlled trial set in Central Scotland. Participants were 1993 people aged between 50 and…

A pragmatic cluster randomised controlled trial to evaluate the safety, clinical effectiveness, cost effectiveness and satisfaction with point of care testing in a general practice setting - rationale, design and baseline characteristics.

PubMed

Laurence, Caroline; Gialamas, Angela; Yelland, Lisa; Bubner, Tanya; Ryan, Philip; Willson, Kristyn; Glastonbury, Briony; Gill, Janice; Shephard, Mark; Beilby, Justin

2008-08-06

Point of care testing (PoCT) may be a useful adjunct in the management of chronic conditions in general practice (GP). The provision of pathology test results at the time of the consultation could lead to enhanced clinical management, better health outcomes, greater convenience and satisfaction for patients and general practitioners (GPs), and savings in costs and time. It could also result in inappropriate testing, increased consultations and poor health outcomes resulting from inaccurate results. Currently there are very few randomised controlled trials (RCTs) in GP that have investigated these aspects of PoCT. The Point of Care Testing in General Practice Trial (PoCT Trial) was an Australian Government funded multi-centre, cluster randomised controlled trial to determine the safety, clinical effectiveness, cost effectiveness and satisfaction of PoCT in a GP setting.The PoCT Trial covered an 18 month period with the intervention consisting of the use of PoCT for seven tests used in the management of patients with diabetes, hyperlipidaemia and patients on anticoagulant therapy. The primary outcome measure was the proportion of patients within target range, a measure of therapeutic control. In addition, the PoCT Trial investigated the safety of PoCT, impact of PoCT on patient compliance to medication, stakeholder satisfaction, cost effectiveness of PoCT versus laboratory testing, and influence of geographic location. The paper provides an overview of the Trial Design, the rationale for the research methodology chosen and how the Trial was implemented in a GP environment. The evaluation protocol and data collection processes took into account the large number of patients, the broad range of practice types distributed over a large geographic area, and the inclusion of pathology test results from multiple pathology laboratories.The evaluation protocol developed reflects the complexity of the Trial setting, the Trial Design and the approach taken within the funding provided. The PoCT Trial is regarded as a pragmatic RCT, evaluating the effectiveness of implementing PoCT in GP and every effort was made to ensure that, in these circumstances, internal and external validity was maintained. 12612605000272695.

Clinical Trial Registries Are of Minimal Use for Identifying Selective Outcome and Analysis Reporting

ERIC Educational Resources Information Center

Norris, Susan L.; Holmer, Haley K.; Fu, Rongwei; Ogden, Lauren A.; Viswanathan, Meera S.; Abou-Setta, Ahmed M.

2014-01-01

Objective: This study aimed to examine selective outcome reporting (SOR) and selective analysis reporting (SAR) in randomized controlled trials (RCTs) and to explore the usefulness of trial registries for identifying SOR and SAR. Study Design and Setting: We selected one "index outcome" for each of three comparative effectiveness reviews…

Is conflict adaptation due to active regulation or passive carry-over? Evidence from eye movements.

PubMed

Hubbard, Jason; Kuhns, David; Schäfer, Theo A J; Mayr, Ulrich

2017-03-01

Conflict-adaptation effects (i.e., reduced response-time costs on high-conflict trials following high-conflict trials) supposedly represent our cognitive system's ability to regulate itself according to current processing demands. However, currently it is not clear whether these effects reflect conflict-triggered, active regulation, or passive carry-over of previous-trial control settings. We used eye movements to examine whether the degree of experienced conflict modulates conflict-adaptation effects, as the conflict-triggered regulation view predicts. Across 2 experiments in which participants had to identify a target stimulus based on an endogenous cue while-on conflict trials-having to resist a sudden-onset distractor, we found a clear indication of conflict adaptation. This adaptation effect disappeared however, when participants inadvertently fixated the sudden-onset distractor on the previous trial-that is, when they experienced a high degree of conflict. This pattern of results suggests that conflict adaptation can be explained parsimoniously in terms of a broader memory process that retains recently adopted control settings across trials. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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.

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

PubMed

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

2017-02-01

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

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2018-01-01

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

Goal-setting intervention in patients with active asthma: protocol for a pilot cluster-randomised controlled trial

PubMed Central

2013-01-01

Background Supporting self-management behaviours is recommended guidance for people with asthma. Preliminary work suggests that a brief, intensive, patient-centred intervention may be successful in supporting people with asthma to participate in life roles and activities they value. We seek to assess the feasibility of undertaking a cluster-randomised controlled trial (cRCT) of a brief, goal-setting intervention delivered in the context of an asthma review consultation. Methods/design A two armed, single-blinded, multi-centre, cluster-randomised controlled feasibility trial will be conducted in UK primary care. Randomisation will take place at the practice level. We aim to recruit a total of 80 primary care patients with active asthma from at least eight practices across two health boards in Scotland (10 patients per practice resulting in ~40 in each arm). Patients in the intervention arm will be asked to complete a novel goal-setting tool immediately prior to an asthma review consultation. This will be used to underpin a focussed discussion about their goals during the asthma review. A tailored management plan will then be negotiated to facilitate achieving their prioritised goals. Patients in the control arm will receive a usual care guideline-based review of asthma. Data on quality of life, asthma control and patient confidence will be collected from both arms at baseline and 3 and 6 months post-intervention. Data on health services resource use will be collected from all patient records 6 months pre- and post-intervention. Semi-structured interviews will be carried out with healthcare staff and a purposive sample of patients to elicit their views and experiences of the trial. The outcomes of interest in this feasibility trial are the ability to recruit patients and healthcare staff, the optimal method of delivering the intervention within routine clinical practice, and acceptability and perceived utility of the intervention among patients and staff. Trial registration ISRCTN18912042 PMID:24021033

Servo-control for maintaining abdominal skin temperature at 36C in low birth weight infants.

PubMed

Sinclair, J C

2002-01-01

Randomized trials have shown that the neonatal mortality rate of low birth-weight babies can be reduced by keeping them warm. For low birth-weight babies nursed in incubators, warm conditions may be achieved either by heating the air to a desired temperature, or by servo-controlling the baby's body temperature at a desired set-point. In low birth weight infants, to determine the effect on death and other important clinical outcomes of targeting body temperature rather than air temperature as the end-point of control of incubator heating. Standard search strategy of the Cochrane Neonatal Review Group. Searches were made of the Cochrane Controlled Trials Register (CCTR) (Cochrane Library, Issue 4, 2001) and MEDLINE, 1966 to November 2001. Randomized or quasi-randomized trials which test the effects of having the heat output of the incubator servo-controlled from body temperature compared with setting a constant incubator air temperature. Trial methodologic quality was systematically assessed. Outcome measures included death, timing of death, cause of death, and other clinical outcomes. Categorical outcomes were analyzed using relative risk and risk difference. Meta-analysis assumed a fixed effect model. Two eligible trials were found. In total, they included 283 babies and 112 deaths. Compared to setting a constant incubator air temperature of 31.8C, servo-control of abdominal skin temperature at 36C reduces the neonatal death rate among low birth weight infants: relative risk 0.72 (95% CI 0.54, 0.97); risk difference -12.7% (95% CI -1.6, -23.9). This effect is even greater among VLBW infants. During at least the first week after birth, low birth weight babies should be provided with a carefully regulated thermal environment that is near the thermoneutral point. For LBW babies in incubators, this can be achieved by adjusting incubator temperature to maintain an anterior abdominal skin temperature of at least 36C, using either servo-control or frequent manual adjustment of incubator air temperature.

Working with men to prevent intimate partner violence in a conflict-affected setting: a pilot cluster randomized controlled trial in rural Côte d’Ivoire

PubMed Central

2014-01-01

Background Evidence from armed conflict settings points to high levels of intimate partner violence (IPV) against women. Current knowledge on how to prevent IPV is limited—especially within war-affected settings. To inform prevention programming on gender-based violence in settings affected by conflict, we evaluated the impact of adding a targeted men’s intervention to a community-based prevention programme in Côte d’Ivoire. Methods We conducted a two-armed, non-blinded cluster randomized trial in Côte d’Ivoire among 12 pair-matched communities spanning government-controlled, UN buffer, and rebel–controlled zones. The intervention communities received a 16-week IPV prevention intervention using a men’s discussion group format. All communities received community-based prevention programmes. Baseline data were collected from couples in September 2010 (pre-intervention) and follow-up in March 2012 (one year post-intervention). The primary trial outcome was women’s reported experiences of physical and/or sexual IPV in the last 12 months. We also assessed men’s reported intention to use physical IPV, attitudes towards sexual IPV, use of hostility and conflict management skills, and participation in gendered household tasks. An adjusted cluster-level intention to treat analysis was used to compare outcomes between intervention and control communities at follow-up. Results At follow-up, reported levels of physical and/or sexual IPV in the intervention arm had decreased compared to the control arm (ARR 0.52, 95% CI 0.18-1.51, not significant). Men participating in the intervention reported decreased intentions to use physical IPV (ARR 0.83, 95% CI 0.66-1.06) and improved attitudes toward sexual IPV (ARR 1.21, 95% CI 0.77-1.91). Significant differences were found between men in the intervention and control arms’ reported ability to control their hostility and manage conflict (ARR 1.3, 95% CI 1.06-1.58), and participation in gendered household tasks (ARR 2.47, 95% CI 1.24-4.90). Conclusions This trial points to the value of adding interventions working with men alongside community activities to reduce levels of IPV in conflict-affected settings. The intervention significantly influenced men’s reported behaviours related to hostility and conflict management and gender equitable behaviours. The decreased mean level of IPV and the differences between intervention and control arms, while not statistically significant, suggest that IPV in conflict-affected areas can be reduced through concerted efforts to include men directly in violence prevention programming. A larger-scale trial is needed to replicate these findings and further understand the mechanisms of change. Trial registration clinicaltrials.gov NCT01803932 PMID:24716478

An implementation strategy to improve the guideline adherence of insurance physicians: an experiment in a controlled setting

PubMed Central

2011-01-01

Background The aim of this study was to investigate the efficacy of a newly developed implementation strategy for the insurance medicine guidelines for depression in the Netherlands. We hypothesized that an educational intervention would increase the insurance physicians' (IPs) guideline adherence in a controlled setting. Methods Forty IPs were allocated in a randomised controlled trial (RCT) to an intervention group (IG) (n = 21) and a control group (CG) (n = 19). The IG received tailored training in applying the guidelines for depression, while the CG received an alternative programme. Baseline (T0) and follow-up (T1) measurements were conducted before and after the intervention within a period of two weeks. The intervention consisted of a workshop in which the evidence-based theory of the guidelines was translated for use in practice, with the help of various tools. The IPs had to write a case-report on the basis of video cases, two before and two after the training. Specially trained and blinded test IPs judged the case reports independently on the basis of six performance indicators. Primary outcome measure in the controlled setting of the trial was guideline adherence measured by six performance indicators on a scale of one to seven. Secondary outcome measure was knowledge of the guidelines for depression. Analyses were performed using Linear Mixed Models, and ANCOVA. Results We found significantly higher scores in the IG than in the CG at T1 for both outcomes. The interaction effect (standard error; p-value) of group crossed with time was 0.97 (0.19; p < 0.0005) for guideline adherence in the controlled setting. The group effect at T1 for the knowledge test was 0.86 (0.40; p = 0.038). Conclusions The newly developed implementation strategy for the insurance medicine guidelines for depression improved the guideline adherence of the trained IPs in disability assessments of clients with depression when performed in a controlled setting. Furthermore, the trained IPs showed gains in knowledge of the guidelines for depression. Trial registration Netherlands' Trial Register NTR1863. PMID:22188876

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…

Beyond Binary: Using Propensity Scores to Account for Varying Levels of Program Participation in Randomized Controlled Trials

ERIC Educational Resources Information Center

Stuart, Elizabeth A.; Warkentien, Siri; Jo, Booil

2011-01-01

The purpose of the current project is to explore the use of propensity scores to estimate the effects of interventions within randomized control trials, accounting for varying levels of implementation or fidelity. This work extends that of Jo and Stuart (2009) to settings with multiple or continuous measures of implementation. Rather than focus…

Treatment of retained placenta with misoprostol: a randomised controlled trial in a low-resource setting (Tanzania).

PubMed

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

2009-10-23

Retained placenta is one of the common causes of maternal mortality in developing countries where access to appropriate obstetrical care is limited. Current treatment of retained placenta is manual removal of the placenta under anaesthesia, which can only take place in larger health care facilities. Medical treatment of retained placenta with prostaglandins E1 (misoprostol) could be cost-effective and easy-to-use and could be a life-saving option in many low-resource settings. The aim of this study is to assess the efficacy and safety of sublingually administered misoprostol in women with retained placenta in a low resource setting. Multicentered randomised, double-blind, placebo-controlled trial, to be conducted in 5 hospitals in Tanzania, Africa. Women with retained placenta, at a gestational age of 28 weeks or more and blood loss less than 750 ml, 30 minutes after delivery of the newborn despite active management of third stage of labour. Trial Entry & Randomisation & Study Medication: After obtaining informed consent, eligible women will be allocated randomly to the treatment groups using numbered envelopes that will be randomized in variable blocks containing identical capsules with either 800 microgram of misoprostol or placebo. The drugs will be given sublingually. The women, maternal care providers and researchers will be blinded to treatment allocation. 117 women, to show a 40% reduction in manual removals of the placenta (p = 0.05, 80% power). The randomization will be misoprostol: placebo = 2:1. PRIMARY STUDY OUTCOME: Expulsion of the placenta without manual removal. Secondary outcome is the number of blood transfusions. This is a protocol for a randomized trial in a low resource setting to assess if medical treatment of women with retained placenta with misoprostol reduces the incidence of manual removal of the placenta. Current Controlled Trials ISRCTN16104753.

The ABC of non-inferiority margin setting from indirect comparisons.

PubMed

Julious, Steven A

2011-01-01

In a non-inferiority trial to assess a new investigative treatment, there may need to be consideration of an indirect comparison with placebo using the active control in the current trial. We can, therefore, use the fact that there is a common active control in the comparisons of the investigative treatment and placebo. In analysing a non-inferiority trial, the ABC of: Assay sensitivity, Bias minimisation and Constancy assumption needs to be considered. It is highlighted how the ABC assumptions can potentially fail when there is placebo creep or a patient population shift. In this situation, the belief about the placebo response expressed in terms of a prior probability in Bayesian formulation could be used with the observed treatment effects to set the non-inferiority limit. Copyright © 2011 John Wiley & Sons, Ltd.

Defining a Clinically Meaningful Effect for the Design and Interpretation of Randomized Controlled Trials

PubMed Central

Kraemer, Helena C.; Epstein, Robert S.; Frank, Ellen; Haynes, Ginger; Laughren, Thomas P.; Mcnulty, James; Reed, Shelby D.; Sanchez, Juan; Leon, Andrew C.

2013-01-01

Objective: This article captures the proceedings of a meeting aimed at defining clinically meaningful effects for use in randomized controlled trials for psychopharmacological agents. Design: Experts from a variety of disciplines defined clinically meaningful effects from their perspectives along with viewpoints about how to design and interpret randomized controlled trials. Setting: The article offers relevant, practical, and sometimes anecdotal information about clinically meaningful effects and how to interpret them. Participants: The concept for this session was the work of co-chairs Richard Keefe and the late Andy Leon. Faculty included Richard Keefe, PhD; James McNulty, AbScB; Robert S. Epstein, MD, MS; Shelby D. Reed, PhD; Juan Sanchez, MD; Ginger Haynes, PhD; Andrew C. Leon, PhD; Helena Chmura Kraemer, PhD; Ellen Frank, PhD, and Kenneth L. Davis, MD. Results: The term clinically meaningful effect is an important aspect of designing and interpreting randomized controlled trials but can be particularly difficult in the setting of psychopharmacology where effect size may be modest, particularly over the short term, because of a strong response to placebo. Payers, regulators, patients, and clinicians have different concerns about clinically meaningful effects and may describe these terms differently. The use of moderators in success rate differences may help better delineate clinically meaningful effects. Conclusion: There is no clear consensus on a single definition for clinically meaningful differences in randomized controlled trials, and investigators must be sensitive to specific concerns of stakeholders in psychopharmacology in order to design and execute appropriate clinical trials. PMID:23882433

Design and implementation of a controlled clinical trial to evaluate the effectiveness and efficiency of routine opt-out rapid human immunodeficiency virus screening in the emergency department.

PubMed

Haukoos, Jason S; Hopkins, Emily; Byyny, Richard L; Conroy, Amy A; Silverman, Morgan; Eisert, Sheri; Thrun, Mark; Wilson, Michael; Boyett, Brian; Heffelfinger, James D

2009-08-01

In 2006, the Centers for Disease Control and Prevention (CDC) released revised recommendations for performing human immunodeficiency virus (HIV) testing in health care settings, including implementing routine rapid HIV screening, the use of an integrated opt-out consent, and limited prevention counseling. Emergency departments (EDs) have been a primary focus of these efforts. These revised CDC recommendations were primarily based on feasibility studies and have not been evaluated through the application of rigorous research methods. This article describes the design and implementation of a large prospective controlled clinical trial to evaluate the CDC's recommendations in an ED setting. From April 15, 2007, through April 15, 2009, a prospective quasi-experimental equivalent time-samples clinical trial was performed to compare the clinical effectiveness and efficiency of routine (nontargeted) opt-out rapid HIV screening (intervention) to physician-directed diagnostic rapid HIV testing (control) in a high-volume urban ED. In addition, three nested observational studies were performed to evaluate the cost-effectiveness and patient and staff acceptance of the two rapid HIV testing methods. This article describes the rationale, methodologies, and study design features of this program evaluation clinical trial. It also provides details regarding the integration of the principal clinical trial and its nested observational studies. Such ED-based trials are rare, but serve to provide valid comparisons between testing approaches. Investigators should consider similar methodology when performing future ED-based health services research.

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

PubMed

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

2017-04-01

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

Involving patients in setting priorities for healthcare improvement: a cluster randomized trial

PubMed Central

2014-01-01

Background Patients are increasingly seen as active partners in healthcare. While patient involvement in individual clinical decisions has been extensively studied, no trial has assessed how patients can effectively be involved in collective healthcare decisions affecting the population. The goal of this study was to test the impact of involving patients in setting healthcare improvement priorities for chronic care at the community level. Methods Design: Cluster randomized controlled trial. Local communities were randomized in intervention (priority setting with patient involvement) and control sites (no patient involvement). Setting: Communities in a canadian region were required to set priorities for improving chronic disease management in primary care, from a list of 37 validated quality indicators. Intervention: Patients were consulted in writing, before participating in face-to-face deliberation with professionals. Control: Professionals established priorities among themselves, without patient involvement. Participants: A total of 172 individuals from six communities participated in the study, including 83 chronic disease patients, and 89 health professionals. Outcomes: The primary outcome was the level of agreement between patients’ and professionals’ priorities. Secondary outcomes included professionals’ intention to use the selected quality indicators, and the costs of patient involvement. Results Priorities established with patients were more aligned with core generic components of the Medical Home and Chronic Care Model, including: access to primary care, self-care support, patient participation in clinical decisions, and partnership with community organizations (p < 0.01). Priorities established by professionals alone placed more emphasis on the technical quality of single disease management. The involvement intervention fostered mutual influence between patients and professionals, which resulted in a 41% increase in agreement on common priorities (95%CI: +12% to +58%, p < 0.01). Professionals’ intention to use the selected quality indicators was similar in intervention and control sites. Patient involvement increased the costs of the prioritization process by 17%, and required 10% more time to reach consensus on common priorities. Conclusions Patient involvement can change priorities driving healthcare improvement at the population level. Future research should test the generalizability of these findings to other contexts, and assess its impact on patient care. Trial registration The Netherlands National Trial Register #NTR2496. PMID:24555508

Performance on a strategy set shifting task in rats following adult or adolescent cocaine exposure

PubMed Central

Kantak, Kathleen M.; Barlow, Nicole; Tassin, David H.; Brisotti, Madeline F.; Jordan, Chloe J

2014-01-01

Rationale Neuropsychological testing is widespread in adult cocaine abusers, but lacking in teens. Animal models may provide insight into age-related neuropsychological consequences of cocaine exposure. Objectives Determine whether developmental plasticity protects or hinders behavioral flexibility after cocaine exposure in adolescent vs. adult rats. Methods Using a yoked-triad design, one rat controlled cocaine delivery and the other two passively received cocaine or saline. Rats controlling cocaine delivery (1.0 mg/kg) self-administered for 18 sessions (starting P37 or P77), followed by 18 drug-free days. Rats next were tested in a strategy set shifting task, lasting 11–13 sessions. Results Cocaine self-administration did not differ between age groups. During initial set formation, adolescent-onset groups required more trials to reach criterion and made more errors than adult-onset groups. During the set shift phase, rats with adult-onset cocaine self-administration experience had higher proportions of correct trials and fewer perseverative + regressive errors than age-matched yoked-controls or rats with adolescent-onset cocaine self-administration experience. During reversal learning, rats with adult-onset cocaine experience (self-administered or passive) required fewer trials to reach criterion and the self-administering rats made fewer perseverative + regressive errors than yoked-saline rats. Rats receiving adolescent-onset yoked-cocaine had more trial omissions and longer lever press reaction times than age-matched rats self-administering cocaine or receiving yoked-saline. Conclusions Prior cocaine self-administration may impair memory to reduce proactive interference during set shifting and reversal learning in adult-onset but not adolescent-onset rats (developmental plasticity protective). Passive cocaine may disrupt aspects of executive function in adolescent-onset but not adult-onset rats (developmental plasticity hinders). PMID:24800898

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

PubMed Central

2011-01-01

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

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

PubMed Central

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

2009-01-01

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

Evaluating the Implementation of a School-Based Emotional Well-Being Programme: A Cluster Randomized Controlled Trial of Zippy's Friends for Children in Disadvantaged Primary Schools

ERIC Educational Resources Information Center

Clarke, Aleisha M.; Bunting, Brendan; Barry, Margaret M.

2014-01-01

Schools are recognized as one of the most important settings for promoting social and emotional well-being among children and adolescents. This clustered randomized controlled trial evaluated Zippy's Friends, an international school-based emotional well-being programme, with 766 children from designated disadvantaged schools. The purpose of this…

The Efficacy of Web-Based and Print-Delivered Computer-Tailored Interventions to Reduce Fat Intake: Results of a Randomized, Controlled Trial

ERIC Educational Resources Information Center

Kroeze, Willemieke; Oenema, Anke; Campbell, Marci; Brug, Johannes

2008-01-01

Objective: To test and compare the efficacy of interactive- and print-delivered computer-tailored nutrition education targeting saturated fat intake reduction. Design: A 3-group randomized, controlled trial (2003-2005) with posttests at 1 and 6 months post-intervention. Setting: Worksites and 2 neighborhoods in the urban area of Rotterdam.…

The ethics of placebo-controlled trials: methodological justifications.

PubMed

Millum, Joseph; Grady, Christine

2013-11-01

The use of placebo controls in clinical trials remains controversial. Ethical analysis and international ethical guidance permit the use of placebo controls in randomized trials when scientifically indicated in four cases: (1) when there is no proven effective treatment for the condition under study; (2) when withholding treatment poses negligible risks to participants; (3) when there are compelling methodological reasons for using placebo, and withholding treatment does not pose a risk of serious harm to participants; and, more controversially, (4) when there are compelling methodological reasons for using placebo, and the research is intended to develop interventions that can be implemented in the population from which trial participants are drawn, and the trial does not require participants to forgo treatment they would otherwise receive. The concept of methodological reasons is essential to assessing the ethics of placebo controls in these controversial last two cases. This article sets out key considerations relevant to considering whether methodological reasons for a placebo control are compelling. © 2013.

A 2D systems approach to iterative learning control for discrete linear processes with zero Markov parameters

NASA Astrophysics Data System (ADS)

Hladowski, Lukasz; Galkowski, Krzysztof; Cai, Zhonglun; Rogers, Eric; Freeman, Chris T.; Lewin, Paul L.

2011-07-01

In this article a new approach to iterative learning control for the practically relevant case of deterministic discrete linear plants with uniform rank greater than unity is developed. The analysis is undertaken in a 2D systems setting that, by using a strong form of stability for linear repetitive processes, allows simultaneous consideration of both trial-to-trial error convergence and along the trial performance, resulting in design algorithms that can be computed using linear matrix inequalities (LMIs). Finally, the control laws are experimentally verified on a gantry robot that replicates a pick and place operation commonly found in a number of applications to which iterative learning control is applicable.

Promoting Activity in Geriatric Rehabilitation: A Randomized Controlled Trial of Accelerometry.

PubMed

Peel, Nancye M; Paul, Sanjoy K; Cameron, Ian D; Crotty, Maria; Kurrle, Susan E; Gray, Leonard C

2016-01-01

Low activity levels in inpatient rehabilitation are associated with adverse outcomes. The study aimed to test whether activity levels can be increased by the provision of monitored activity data to patients and clinicians in the context of explicit goal setting. A randomized controlled trial in three sites in Australia included 255 inpatients aged 60 and older who had a rehabilitation goal to become ambulant. The primary outcome was patients' walking time measured by accelerometers during the rehabilitation admission. Walking times from accelerometry were made available daily to treating therapists and intervention participants to motivate patients to improve incidental activity levels and reach set goals. For the control group, 'usual care' was followed, including the setting of mobility goals; however, for this group, neither staff nor patients received data on walking times to aid the setting of daily walking time targets. The median daily walking time in the intervention group increased from 10.3 minutes at baseline to 32.1 minutes at day 28, compared with an increase from 9.5 to 26.5 minutes per day in the control group. Subjects in the intervention group had significantly higher non-therapy walking time by about 7 minutes [mean (95% CI): 24.6 (21.7, 27.4)] compared to those in the control group [mean(95% CI): 17.3 (14.4, 20.3)] (p = 0.001). Daily feedback to patients and therapists using an accelerometer increased walking times during rehabilitation admissions. The results of this study suggest objective monitoring of activity levels could provide clinicians with information on clinically important, mobility-related activities to assist goal setting. Australian New Zealand Clinical Trials Registry ACTRN12611000034932 http://www.ANZCTR.org.au/.

Low Social Support Level Is Associated with Non-Adherence to Diet at 1 Year in the Family Intervention Trial for Heart Health (FIT Heart)

ERIC Educational Resources Information Center

Aggarwal, Brooke; Liao, Ming; Allegrante, John P.; Mosca, Lori

2010-01-01

Objective: Evaluate the relationship between low social support (SS) and adherence to diet in a cardiovascular disease (CVD) lifestyle intervention trial. Design: Prospective substudy. Setting and Participants: Blood relatives/cohabitants of hospitalized cardiac patients in a randomized controlled trial (n = 458; 66% female, 35% nonwhite, mean age…

A pilot randomised control trial of the effectiveness of a biofeedback mouse in reducing self-reported pain among office workers.

PubMed

King, Trevor K; Severin, Colette N; Van Eerd, Dwayne; Ibrahim, Selahadin; Cole, Donald; Amick, Ben; Steenstra, Ivan A

2013-01-01

A pilot study examined the effectiveness of a biofeedback mouse in reducing upper extremity pain and discomfort in office workers; in addition, relative mouse use (RMU), satisfaction and the feasibility of running a randomised controlled trial (RCT) in a workplace setting were evaluated. The mouse would gently vibrate if the hand was idle for more than 12 s. The feedback reminded users to rest the arm in neutral, supported postures. Analysis showed a statistically significant reduction in shoulder pain and discomfort for the intervention group at T2 (38.7% lower than controls). Statistically significant differences in RMU time between groups were seen post intervention (-7% at T1 and +15% at T2 for the intervention group). Fifty-five percent of the intervention group was willing to continue using the mouse. It appears feasible to perform an RCT for this type of intervention in a workplace setting. Further study including more participants is suggested. The study findings support the feasibility of conducting randomised control trials in office settings to evaluate ergonomics interventions. The intervention resulted in reduced pain and discomfort in the shoulder. The intervention could be a relevant tool in the reduction of upper extremity musculoskeletal disorder. Further research will better explain the study's preliminary findings.

Comparative efficacy of interventions to promote hand hygiene in hospital: systematic review and network meta-analysis

PubMed Central

Hongsuwan, Maliwan; Limmathurotsakul, Direk; Lubell, Yoel; Lee, Andie S; Harbarth, Stephan; Day, Nicholas P J; Graves, Nicholas; Cooper, Ben S

2015-01-01

Objective To evaluate the relative efficacy of the World Health Organization 2005 campaign (WHO-5) and other interventions to promote hand hygiene among healthcare workers in hospital settings and to summarize associated information on use of resources. Design Systematic review and network meta-analysis. Data sources Medline, Embase, CINAHL, NHS Economic Evaluation Database, NHS Centre for Reviews and Dissemination, Cochrane Library, and the EPOC register (December 2009 to February 2014); studies selected by the same search terms in previous systematic reviews (1980-2009). Review methods Included studies were randomised controlled trials, non-randomised trials, controlled before-after trials, and interrupted time series studies implementing an intervention to improve compliance with hand hygiene among healthcare workers in hospital settings and measuring compliance or appropriate proxies that met predefined quality inclusion criteria. When studies had not used appropriate analytical methods, primary data were re-analysed. Random effects and network meta-analyses were performed on studies reporting directly observed compliance with hand hygiene when they were considered sufficiently homogeneous with regard to interventions and participants. Information on resources required for interventions was extracted and graded into three levels. Results Of 3639 studies retrieved, 41 met the inclusion criteria (six randomised controlled trials, 32 interrupted time series, one non-randomised trial, and two controlled before-after studies). Meta-analysis of two randomised controlled trials showed the addition of goal setting to WHO-5 was associated with improved compliance (pooled odds ratio 1.35, 95% confidence interval 1.04 to 1.76; I2=81%). Of 22 pairwise comparisons from interrupted time series, 18 showed stepwise increases in compliance with hand hygiene, and all but four showed a trend for increasing compliance after the intervention. Network meta-analysis indicated considerable uncertainty in the relative effectiveness of interventions, but nonetheless provided evidence that WHO-5 is effective and that compliance can be further improved by adding interventions including goal setting, reward incentives, and accountability. Nineteen studies reported clinical outcomes; data from these were consistent with clinically important reductions in rates of infection resulting from improved hand hygiene for some but not all important hospital pathogens. Reported costs of interventions ranged from $225 to $4669 (£146-£3035; €204-€4229) per 1000 bed days. Conclusion Promotion of hand hygiene with WHO-5 is effective at increasing compliance in healthcare workers. Addition of goal setting, reward incentives, and accountability strategies can lead to further improvements. Reporting of resources required for such interventions remains inadequate. PMID:26220070

Benefits and problems of health-care robots in aged care settings: A comparison trial.

PubMed

Broadbent, Elizabeth; Kerse, Ngaire; Peri, Kathryn; Robinson, Hayley; Jayawardena, Chandimal; Kuo, Tony; Datta, Chandan; Stafford, Rebecca; Butler, Haley; Jawalkar, Pratyusha; Amor, Maddy; Robins, Ben; MacDonald, Bruce

2016-03-01

This study investigated whether multiple health-care robots could have any benefits or cause any problems in an aged care facility. Fifty-three residents and 53 staff participated in a non-randomised controlled trial over 12 weeks. Six robots provided entertainment, communication and health-monitoring functions in staff rooms and activity lounges. These settings were compared to control settings without robots. There were no significant differences between groups in resident or staff outcomes, except a significant increase in job satisfaction in the control group only. The intervention group perceived the robots had more agency and experience than the control group did. Perceived agency of the robots decreased over time in both groups. Overall, we received very mixed responses with positive, neutral and negative comments. The robots had no major benefits or problems. Future research could give robots stronger operational roles, use more specific outcome measures, and perform cost-benefit analyses. © 2015 AJA Inc.

A real-time freehand ultrasound calibration system with automatic accuracy feedback and control.

PubMed

Chen, Thomas Kuiran; Thurston, Adrian D; Ellis, Randy E; Abolmaesumi, Purang

2009-01-01

This article describes a fully automatic, real-time, freehand ultrasound calibration system. The system was designed to be simple and sterilizable, intended for operating-room usage. The calibration system employed an automatic-error-retrieval and accuracy-control mechanism based on a set of ground-truth data. Extensive validations were conducted on a data set of 10,000 images in 50 independent calibration trials to thoroughly investigate the accuracy, robustness, and performance of the calibration system. On average, the calibration accuracy (measured in three-dimensional reconstruction error against a known ground truth) of all 50 trials was 0.66 mm. In addition, the calibration errors converged to submillimeter in 98% of all trials within 12.5 s on average. Overall, the calibration system was able to consistently, efficiently and robustly achieve high calibration accuracy with real-time performance.

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

PubMed

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

2016-11-20

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

Effectiveness of the 'Who's Challenging Who' support staff training intervention to improve attitudes and empathy towards adults with intellectual disability and challenging behaviours: study protocol for a cluster randomised controlled trial.

PubMed

Randell, Elizabeth; Hastings, Richard P; McNamara, Rachel; Knight, Roseanna; Gillespie, David; Taylor, Zachary

2017-10-05

Findings suggest approximately one in six people with intellectual disability engage in 'challenging behaviours', which include aggression towards others/property and self-injurious actions. In residential settings, actions of staff members can make challenging behaviours more likely to occur, or make these behaviours worse. In particular, negative attitudes from members of staff and lack of understanding about the reasons for challenging behaviour are contributory factors. 'Who's Challenging Who?' (WCW) training is designed to emphasise the role of staff in residential settings as a challenge also to people with intellectual disability. The course is delivered jointly by a trainer with intellectual disability who has been labelled as having challenging behaviour, along with a trainer without intellectual disability. This is a cluster randomised two-arm trial of WCW training versus a waiting list control. Overall, 118 residential settings will be recruited and randomised on a 1:1 ratio. Within each setting, two members of staff will be invited to take part in the trial. Participants will complete assessments at baseline and at 6 and 20 weeks. WCW is a half day initial training course with some follow-on coaching to ensure implementation. The primary outcome is changes in staff empathy towards people with challenging behaviour. Secondary outcomes at the staff level include confidence, attitudes and work-related well-being. Secondary outcomes at the residential setting level include recorded incidents of aggressive challenging behaviour, and use of any restrictive practices. If the results of the cluster randomised trial are positive, we will disseminate the findings widely and make all training manuals and materials freely available for anyone in intellectual disability services (and beyond) to use. Our training approach may have wider implications in other areas of social care. It may also provide a generally applicable model for how to train people with intellectual disability to act as co-trainers in intellectual disability social care settings. People with intellectual disability and challenging behaviour have already been involved centrally with the design, development and pilot evaluation of WCW and will also be fully involved throughout this trial. Registered on the International Standard Randomised Controlled Trial Number registry on 8th December 2015: ISRCTN53763600 .

Developing a core outcome set for chronic rhinosinusitis: a systematic review of outcomes utilised in the current literature.

PubMed

Soni-Jaiswal, Archana; Lakhani, Raj; Hopkins, Claire

2017-07-11

A core outcome set (COS) is an agreed standardised collection of outcomes that should be measured and reported by all trials for a specific clinical area, in this case chronic rhinosinusitis. These are not restrictive and researchers may continue to explore other outcomes alongside these that they feel are relevant to their intervention. The aim of this systematic review was to identify the need for a COS for chronic rhinosinusitis. A sensitive search strategy was used to identify all published Cochrane systematic reviews and randomised control trials of intervention for adult patients with chronic rhinosinusitis. Two independent authors reviewed these to obtain a list of outcomes and outcome measures reported by each clinical trial. Sixty-nine randomised control trials and eight Cochrane systematic reviews were included in this study. They reported 68 individual outcomes and outcome measures, with an average of four to ten outcomes per clinical trial. These outcomes were mapped to 23 subcategories belonging to eight core categories. The key finding of this review was the heterogeneity of outcomes reported and measured by clinical trials of patients with chronic rhinosinusitis, precluding meaningful meta-analysis of data. This review supports the need for development of a COS, to be used in future trials on adult patients with chronic rhinosinusitis.

Oxytocin for preventing postpartum haemorrhage (PPH) in non-facility birth settings.

PubMed

Pantoja, Tomas; Abalos, Edgardo; Chapman, Evelina; Vera, Claudio; Serrano, Valentina P

2016-04-14

Postpartum haemorrhage (PPH) is the single leading cause of maternal mortality worldwide. Most of the deaths associated with PPH occur in resource-poor settings where effective methods of prevention and treatment - such as oxytocin - are not accessible because many births still occur at home, or in community settings, far from a health facility. Likewise, most of the evidence supporting oxytocin effectiveness comes from hospital settings in high-income countries, mainly because of the need of well-organised care for its administration and monitoring. Easier methods for oxytocin administration have been developed for use in resource-poor settings, but as far as we know, its effectiveness has not been assessed in a systematic review. To assess the effectiveness and safety of oxytocin provided in non-facility birth settings by any way in the third stage of labour to prevent PPH. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, the WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov (12 November 2015), and reference lists of retrieved reports. All published, unpublished or ongoing randomised or quasi-randomised controlled trials comparing the administration of oxytocin with no intervention, or usual/standard care for the management of the third stage of labour in non-facility birth settings were considered for inclusion.Quasi-randomised controlled trials and randomised controlled trials published in abstract form only were eligible for inclusion but none were identified. Cross-over trials were not eligible for inclusion in this review. Two review authors independently assessed studies for eligibility, assessed risk of bias and extracted the data using an agreed data extraction form. Data were checked for accuracy. We included one cluster-randomised trial conducted in four rural districts in Ghana that randomised 28 community health officers (CHOs) (serving 2404 potentially eligible pregnant women) to the intervention group and 26 CHOs (serving 3515 potentially eligible pregnant women) to the control group. Overall, the trial had a high risk of bias. CHOs delivered the intervention in the experimental group (injection of 10 IU (international units) of oxytocin in the thigh one minute following birth using a prefilled, auto-disposable syringe). In the control group, CHOs did not provide this prophylactic injection to the women they observed. CHOs had no midwifery skills and did not in any way manage the birth. All other CHO activities (outcome measurement, data collection, and early treatment and referral when necessary) were identical across the control and oxytocin CHOs.Although only one of the nine cases of severe PPH (blood loss greater or equal to 1000 mL) occurred in the oxytocin group, the effect estimate for this outcome was very imprecise and it is uncertain whether the intervention prevents severe PPH (risk ratio (RR) 0.16, 95% confidence interval (CI) 0.02 to 1.30; 1570 women (very low-quality evidence)). Similarly, because of the lack of cases of severe maternal morbidity (e.g. uterine rupture) and maternal deaths, it was not possible to obtain effect estimates for those outcomes (both very low-quality evidence).Oxytocin compared with the control group decreased the incidence of PPH (> 500 mL) in both our unadjusted (RR 0.48, 95% CI 0.28 to 0.81; 1569 women) and adjusted (RR 0.49, 95% CI 0.27 to 0.90; 1174 women (both low-quality evidence)) analyses. There was little or no difference between the oxytocin and control groups on the rates of transfer or referral of the mother to a healthcare facility (RR 0.72, 95% CI 0.34 to 1.56; 1586 women (low-quality evidence)), stillbirths (RR 1.27, 95% CI 0.67 to 2.40; 2006 infants (low-quality evidence)); andearly infant deaths (0 to three days) (RR 1.03, 95% CI 0.35 to 3.07; 1969 infants (low-quality evidence)). There were no cases of needle-stick injury or any other maternal major or minor adverse event or unanticipated harmful event. There were no cases of oxytocin use during labour.There were no data reported for some of this review's secondary outcomes: manual removal of placenta, maternal anaemia, neonatal death within 28 days, neonatal transfer to health facility for advanced care, breastfeeding rates. Similarly, the women's or the provider's satisfaction with the intervention was not reported. It is uncertain if oxytocin administered by CHO in non-facility settings compared with a control group reduces the incidence of severe PPH (>1000 mL), severe maternal morbidity or maternal deaths. However, the intervention probably decreases the incidence of PPH (> 500 mL).The quality of the one trial included in this review was limited because of the risk of attrition and recruitment biases related to limitations in the follow-up of pregnant women in both arms of the trials and some baseline imbalance on the size of babies at birth. Additionally, there was serious imprecision of the effect estimates for most of the primary outcomes mainly because of the size of the trial, very few or no events and CIs around both relative and absolute estimates of effect that include both appreciable benefit and appreciable harm.Although the trial presented data both for primary and secondary outcomes, it seemed to be underpowered to detect differences in the primary outcomes that are the ones more relevant for making judgments about the potential applicability of the intervention in other settings (especially severe PPH).Therefore, taking into account the extreme setting where the intervention was implemented, the limited role of the CHO in the trial and the lack of power for detecting effects on primary (relevant) outcomes, the applicability of the evidence found seems to be rather limited.Further well-executed and adequately-powered randomised controlled trials assessing the effects of using oxytocin in pre-filled injection devices or other new delivery systems (spray-dried ultrafine formulation of oxytocin) on severe PPH are urgently needed. Likewise, other important outcomes like possible adverse events and acceptability of the intervention by mothers and other community stakeholders should also be assessed.

A randomized controlled trial of a community health worker intervention in a population of patients with multiple chronic diseases: Study design and protocol

PubMed Central

Kangovi, Shreya; Mitra, Nandita; Turr, Lindsey; Huo, Hairong; Grande, David; Long, Judith A.

2017-01-01

Upstream interventions – e.g. housing programs and community health worker interventions-address socioeconomic and behavioral factors that influence health outcomes across diseases. Studying these types of interventions in clinical trials raises a methodological challenge: how should researchers measure the effect of an upstream intervention in a sample of patients with different diseases? This paper addresses this question using an illustrative protocol of a randomized controlled trial of collaborative-goal setting versus goal-setting plus community health worker support among patients multiple chronic diseases: diabetes, obesity, hypertension and tobacco dependence. At study enrollment, patients met with their primary care providers to select one of their chronic diseases to focus on during the study, and to collaboratively set a goal for that disease. Patients randomly assigned to a community health worker also received six months of support to address socioeconomic and behavioral barriers to chronic disease control. The primary hypothesis was that there would be differences in patients’ selected chronic disease control as measured by HbA1c, body mass index, systolic blood pressure and cigarettes per day, between the goal-setting alone and community health worker support arms. To test this hypothesis, we will conduct a stratum specific multivariate analysis of variance which allows all patients (regardless of their selected chronic disease) to be included in a single model for the primary outcome. Population health researchers can use this approach to measure clinical outcomes across diseases. PMID:27965180

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

PubMed

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

2012-02-03

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

Using an internet intervention to support self-management of low back pain in primary care: findings from a randomised controlled feasibility trial (SupportBack)

PubMed Central

Geraghty, Adam W A; Stanford, Rosie; Stuart, Beth; Little, Paul; Roberts, Lisa C; Foster, Nadine E; Hill, Jonathan C; Hay, Elaine M; Turner, David; Malakan, Wansida; Leigh, Linda; Yardley, Lucy

2018-01-01

Objective To determine the feasibility of a randomised controlled trial of an internet intervention for low back pain (LBP) using three arms: (1) usual care, (2) usual care plus an internet intervention or (3) usual care plus an internet intervention with additional physiotherapist telephone support. Design and setting A three-armed randomised controlled feasibility trial conducted in 12 general practices in England. Participants Primary care patients aged over 18 years, with current LBP, access to the internet and without indicators of serious spinal pathology or systemic illness. Interventions The ‘SupportBack’ internet intervention delivers a 6-week, tailored programme, focused on graded goal setting, self-monitoring and provision of tailored feedback to encourage physical activity. Additional physiotherapist telephone support consisted of three brief telephone calls over a 4-week period, to address any concerns and provide reassurance. Outcomes The primary outcomes were the feasibility of the trial design including recruitment, adherence and retention at follow-up. Secondary descriptive and exploratory analyses were conducted on clinical outcomes including LBP-related disability at 3 months follow-up. Results Primary outcomes: 87 patients with LBP were recruited (target 60–90) over 6 months, and there were 3 withdrawals. Adherence to the intervention was higher in the physiotherapist-supported arm, compared with the stand-alone internet intervention. Trial physiotherapists adhered to the support protocol. Overall follow-up rate on key clinical outcomes at 3 months follow-up was 84%. Conclusions This study demonstrated the feasibility of a future definitive randomised controlled trial to determine the clinical and cost-effectiveness of the SupportBack intervention in primary care patients with LBP. Trial registration number ISRCTN31034004; Results. PMID:29525768

The Salford Lung Study protocol: a pragmatic, randomised phase III real-world effectiveness trial in asthma.

PubMed

Woodcock, Ashley; Bakerly, Nawar Diar; New, John P; Gibson, J Martin; Wu, Wei; Vestbo, Jørgen; Leather, David

2015-12-10

Novel therapies need to be evaluated in normal clinical practice to allow a true representation of the treatment effectiveness in real-world settings. The Salford Lung Study is a pragmatic randomised controlled trial in adult asthma, evaluating the clinical effectiveness and safety of once-daily fluticasone furoate (100 μg or 200 μg)/vilanterol 25 μg in a novel dry-powder inhaler, versus existing asthma maintenance therapy. The study was initiated before this investigational treatment was licensed and conducted in real-world clinical practice to consider adherence, co-morbidities, polypharmacy, and real-world factors. Asthma Control Test at week 24; safety endpoints include the incidence of serious pneumonias. The study utilises the Salford electronic medical record, which allows near to real-time collection and monitoring of safety data. The Salford Lung Study is the world's first pragmatic randomised controlled trial of a pre-licensed medication in asthma. Use of patients' linked electronic health records to collect clinical endpoints offers minimal disruption to patients and investigators, and also ensures patient safety. This highly innovative study will complement standard double-blind randomised controlled trials in order to improve our understanding of the risk/benefit profile of fluticasone furoate/vilanterol in patients with asthma in real-world settings. Clinicaltrials.gov, NCT01706198; 04 October 2012.

75 FR 34997 - National Institute on Disability and Rehabilitation Research (NIDRR)-Disability and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-21

... trial research designs to evaluate the effectiveness of interventions or practices. NIDRR believes that randomized control trial research designs can be appropriate for research that involves evaluating specific interventions. However, in complex service delivery settings, other scientifically rigorous research designs may...

Building clinical trial capacity to develop a new treatment for multidrug-resistant tuberculosis.

PubMed

Tupasi, Thelma; Gupta, Rajesh; Danilovits, Manfred; Cirule, Andra; Sanchez-Garavito, Epifanio; Xiao, Heping; Cabrera-Rivero, Jose L; Vargas-Vasquez, Dante E; Gao, Mengqiu; Awad, Mohamed; Gentry, Leesa M; Geiter, Lawrence J; Wells, Charles D

2016-02-01

New drugs for infectious diseases often need to be evaluated in low-resource settings. While people working in such settings often provide high-quality care and perform operational research activities, they generally have less experience in conducting clinical trials designed for drug approval by stringent regulatory authorities. We carried out a capacity-building programme during a multi-centre randomized controlled trial of delamanid, a new drug for the treatment of multidrug-resistant tuberculosis. The programme included: (i) site identification and needs assessment; (ii) achieving International Conference on Harmonization - Good Clinical Practice (ICH-GCP) standards; (iii) establishing trial management; and (iv) increasing knowledge of global and local regulatory issues. Trials were conducted at 17 sites in nine countries (China, Egypt, Estonia, Japan, Latvia, Peru, the Philippines, the Republic of Korea and the United States of America). Eight of the 10 sites in low-resource settings had no experience in conducting the requisite clinical trials. Extensive capacity-building was done in all 10 sites. The programme resulted in improved local capacity in key areas such as trial design, data safety and monitoring, trial conduct and laboratory services. Clinical trials designed to generate data for regulatory approval require additional efforts beyond traditional research-capacity strengthening. Such capacity-building approaches provide an opportunity for product development partnerships to improve health systems beyond the direct conduct of the specific trial.

Comparing community and specialty provider-based recruitment in a randomized clinical trial: clinical trial in fecal incontinence.

PubMed

Whitebird, Robin R; Bliss, Donna Zimmaro; Savik, Kay; Lowry, Ann; Jung, Hans-Joachim G

2010-12-01

Recruitment of participants to clinical trials remains a significant challenge, especially for research addressing topics of a sensitive nature such as fecal incontinence (FI). In the Fiber Study, a randomized controlled trial on symptom management for FI, we successfully enrolled 189 community-living adults through collaborations with specialty-based and community-based settings, each employing methods tailored to the organizational characteristics of their site. Results show that using the two settings increased racial and ethnic diversity of the sample and inclusion of informal caregivers. There were no differential effects on enrollment, final eligibility, or completion of protocol by site. Strategic collaborations with complementary sites can achieve sample recruitment goals for clinical trials on topics that are sensitive or known to be underreported. Copyright © 2010 Wiley Periodicals, Inc.

Challenges of a community based pragmatic, randomised controlled trial of weight loss maintenance.

PubMed

Randell, Elizabeth; McNamara, Rachel; Shaw, Christine; Espinasse, Aude; Simpson, Sharon Anne

2015-12-18

Randomised controlled trials (RCTs) have a reputation for being inherently difficult to deliver as planned and often face unforeseen challenges and delays, particularly in relation to organisational and governance difficulties, participant interest, constraints due to allocation of costs, local investigator interest and lengthy bureaucracy. Recruitment is often difficult and the challenges faced often impact on the cost and delivery of a successful trial within the funded period. This paper reflects upon the challenges faced in delivering a pragmatic RCT of weight loss maintenance in a community setting and suggests some potential solutions. The weight loss maintenance in adults trial aimed to evaluate the impact of a 12 month, individually tailored weight maintenance intervention on BMI 3 years from randomisation. Participants were recruited primarily from participant identification centres (PICs)-GP surgeries, exercise on referral schemes and slimming world. The intervention was delivered in community settings. A recruitment strategy implementation plan was drafted to address and monitor poor recruitment. Delays in opening and recruitment were experienced early on. Some were beyond the control of the study team such as; disagreement over allocation of national health service costs and PIC classification as well as difficulties in securing support from research networks. That the intervention was delivered in community settings was often at the root of these issues. Key items to address at the design stage of future trials include feasibility of eligibility criteria. The most effective element of the recruitment implementation plan was to refocus sources of recruitment and target only those who could fulfil the eligibility criteria immediately. Learnings from this trial should be kept in mind by those designing similar studies in the future. Considering potential governance, cost and research network support implications at the design stage of pragmatic trials of any community-based complex intervention is paramount. The appropriateness and viability of inclusion criteria also require careful consideration as does use of a targeted advertising strategy. ISRCTN35774128, 12/01/2010.

Ethical challenges in cluster randomized controlled trials: experiences from public health interventions in Africa and Asia

PubMed Central

Azad, Kishwar; Fernandez, Armida; Manandhar, Dharma S; Mwansambo, Charles W; Tripathy, Prasanta; Costello, Anthony M

2009-01-01

Abstract Public health interventions usually operate at the level of groups rather than individuals, and cluster randomized controlled trials (RCTs) are one means of evaluating their effectiveness. Using examples from six such trials in Bangladesh, India, Malawi and Nepal, we discuss our experience of the ethical issues that arise in their conduct. We set cluster RCTs in the broader context of public health research, highlighting debates about the need to reconcile individual autonomy with the common good and about the ethics of public health research in low-income settings in general. After a brief introduction to cluster RCTs, we discuss particular challenges we have faced. These include the nature of – and responsibility for – group consent, and the need for consent by individuals within groups to intervention and data collection. We discuss the timing of consent in relation to the implementation of public health strategies, and the problem of securing ethical review and approval in a complex domain. Finally, we consider the debate about benefits to control groups and the standard of care that they should receive, and the issue of post-trial adoption of the intervention under test. PMID:19876544

Effectiveness and Cost-Effectiveness of Occupation-Based Occupational Therapy Using the Aid for Decision Making in Occupation Choice (ADOC) for Older Residents: Pilot Cluster Randomized Controlled Trial.

PubMed

Nagayama, Hirofumi; Tomori, Kounosuke; Ohno, Kanta; Takahashi, Kayoko; Ogahara, Kakuya; Sawada, Tatsunori; Uezu, Sei; Nagatani, Ryutaro; Yamauchi, Keita

2016-01-01

Care-home residents are mostly inactive, have little interaction with staff, and are dependent on staff to engage in daily occupations. We recently developed an iPad application called the Aid for Decision-making in Occupation Choice (ADOC) to promote shared decision-making in activities and occupation-based goal setting by choosing from illustrations describing daily activities. This study aimed to evaluate if interventions based on occupation-based goal setting using the ADOC could focus on meaningful activities to improve quality of life and independent activities of daily living, with greater cost-effectiveness than an impairment-based approach as well as to evaluate the feasibility of conducting a large cluster, randomized controlled trial. In this single (assessor)-blind pilot cluster randomized controlled trial, the intervention group (ADOC group) received occupational therapy based on occupation-based goal setting using the ADOC, and the interventions were focused on meaningful occupations. The control group underwent an impairment-based approach focused on restoring capacities, without goal setting tools. In both groups, the 20-minute individualized intervention sessions were conducted twice a week for 4 months. Short Form-36 (SF-36) score, SF-6D utility score, quality adjusted life years (QALY), Barthel Index, and total care cost. We randomized and analyzed 12 facilities (44 participants, 18.5% drop-out rate), with 6 facilities each allocated to the ADOC (n = 23) and control (n = 21) groups. After the 4-month intervention, the ADOC group had a significantly greater change in the BI score, with improved scores (P = 0.027, 95% CI 0.41 to 6.87, intracluster correlation coefficient = 0.14). No other outcome was significantly different. The incremental cost-effectiveness ratio, calculated using the change in BI score, was $63.1. The results suggest that occupational therapy using the ADOC for older residents might be effective and cost-effective. We also found that conducting an RCT in the occupational therapy setting is feasible. UMIN Clinical Trials Registry UMIN000012994.

Herd effect from influenza vaccination in non-healthcare settings: a systematic review of randomised controlled trials and observational studies

PubMed Central

Mertz, Dominik; Fadel, Shaza A.; Lam, Po-Po; Tran, Dat; Srigley, Jocelyn A; Asner, Sandra A; Science, Michelle; Kuster, Stefan P; Nemeth, Johannes; Johnstone, Jennie; Ortiz, Justin R; Loeb, Mark

2016-01-01

Influenza vaccination programmes are assumed to have a herd effect and protect contacts of vaccinated persons from influenza virus infection. We searched MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Global Health and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to March 2014 for studies assessing the protective effect of influenza vaccination vs no vaccination on influenza virus infections in contacts. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using a random-effects model. Of 43,082 screened articles, nine randomised controlled trials (RCTs) and four observational studies were eligible. Among the RCTs, no statistically significant herd effect on the occurrence of influenza in contacts could be found (OR: 0.62; 95% CI: 0.34–1.12). The one RCT conducted in a community setting, however, showed a significant effect (OR: 0.39; 95% CI: 0.26–0.57), as did the observational studies (OR: 0.57; 95% CI: 0.43–0.77). We found only a few studies that quantified the herd effect of vaccination, all studies except one were conducted in children, and the overall evidence was graded as low. The evidence is too limited to conclude in what setting(s) a herd effect may or may not be achieved. PMID:27784531

Back schools for nonspecific low back pain: a systematic review within the framework of the Cochrane Collaboration Back Review Group.

PubMed

Heymans, M W; van Tulder, M W; Esmail, R; Bombardier, C; Koes, B W

2005-10-01

A systematic review within the Cochrane Collaboration Back Review Group. To assess the effectiveness of back schools for patients with nonspecific low back pain (LBP). Since the introduction of the Swedish back school in 1969, back schools have frequently been used for treating patients with LBP. However, the content of back schools has changed and appears to vary widely today. We searched the MEDLINE and EMBASE databases and the Cochrane Central Register of Controlled Trials to November 2004 for relevant trials reported in English, Dutch, French, or German. We also screened references from relevant reviews and included trials. Randomized controlled trials that reported on any type of back school for nonspecific LBP were included. Four reviewers, blinded to authors, institution, and journal, independently extracted the data and assessed the quality of the trials. We set the high-quality level, a priori, at a trial meeting six or more of 11 internal validity criteria. Because data were clinically and statistically too heterogeneous to perform a meta-analysis, we used a qualitative review (best evidence synthesis) to summarize the results. The evidence was classified into four levels (strong, moderate, limited, or no evidence), taking into account the methodologic quality of the studies. We also evaluated the clinical relevance of the studies. Nineteen randomized controlled trials (3,584 patients) were included in this updated review. Overall, the methodologic quality was low, with only six trials considered to be high-quality. It was not possible to perform relevant subgroup analyses for LBP with radiation versus LBP without radiation. The results indicate that there is moderate evidence suggesting that back schools have better short- and intermediate-term effects on pain and functional status than other treatments for patients with recurrent and chronic LBP. There is moderate evidence suggesting that back schools for chronic LBP in an occupational setting are more effective than other treatments and placebo or waiting list controls on pain, functional status, and return to work during short- and intermediate-term follow-up. In general, the clinical relevance of the studies was rated as insufficient. There is moderate evidence suggesting that back schools, in an occupational setting, reduce pain and improve function and return-to-work status, in the short- and intermediate-term, compared with exercises, manipulation, myofascial therapy, advice, placebo, or waiting list controls, for patients with chronic and recurrent LBP. However, future trials should improve methodologic quality and clinical relevance and evaluate the cost-effectiveness of back schools.

The CONSENSUS study: protocol for a mixed methods study to establish which outcomes should be included in a core outcome set for oropharyngeal cancer

PubMed Central

2014-01-01

Background The incidence of oropharyngeal cancer is increasing in the developed world. This has led to a large rise in research activity and clinical trials in this area, yet there is no consensus on which outcomes should be measured. As a result, the outcomes measured often differ between trials of comparable interventions, making the combination or comparison of results between trials impossible. Outcomes may also be ‘cherry-picked’, such that favourable results are reported, and less favourable results withheld. The development of a minimum outcome reporting standard, known as a core outcome set, goes some way to addressing these problems. Core outcome sets are ideally developed using a patient-centred approach so that the outcomes measured are relevant to patients and clinical practice. Core outcome sets drive up the quality and relevance of research by ensuring that the right outcomes are consistently measured and reported in trials in specific areas of health or healthcare. Methods/Design This is a mixed methods study involving three phases to develop a core outcome set for oropharyngeal cancer clinical trials. Firstly, a systematic review will establish which outcomes are measured in published oropharyngeal cancer randomised controlled trials (RCTs). Secondly, qualitative interviews with patients and carers in the UK and the USA will aim to establish which outcomes are important to these stakeholders. Data from these first two stages will be used to develop a comprehensive list of outcomes to be considered for inclusion in the core outcome set. In the third stage, patients and clinicians will participate in an iterative consensus exercise known as a Delphi study to refine the contents of the core outcome set. This protocol lays out the methodology to be implemented in the CONSENSUS study. Discussion A core outcome set defines a minimum outcome reporting standard for clinical trials in a particular area of health or healthcare. Its consistent implementation in oropharyngeal cancer clinical trials will improve the quality and relevance of research. Trials and registration This study is registered at the National Institute for Health Research (NIHR) Clinical Research Network (CRN) portfolio, ID 13823 (17 January 2013). PMID:24885068

Effectiveness of Training Clinicians' Communication Skills on Patients' Clinical Outcomes: A Systematic Review.

PubMed

Oliveira, Vinicius C; Ferreira, Manuela L; Pinto, Rafael Z; Filho, Ruben F; Refshauge, Kathryn; Ferreira, Paulo H

2015-10-01

The aim of this systematic review was to investigate the literature on the effectiveness of communication skills training for clinicians on patients' clinical outcomes in primary care and rehabilitation settings. We systematically reviewed the literature for randomized controlled trials investigating the effectiveness of communication skills training for clinicians on patients' satisfaction with care and on pain and disability in primary care and rehabilitation settings. The search strategy was conducted using AMED, PsycINFO, MEDLINE, CINAHL, EMBASE, PEDro, and Cochrane Central Register of Controlled Trials through June 2015. Methodological quality of included trials was assessed by 2 independent investigators using the PEDro scale, and consensus was used to resolve disagreements. Data were extracted, and meta-analyses were performed. Nineteen randomized controlled trials were included. Of these, 16 investigated communication training for clinicians that emphasized patient participation (eg, shared decision-making approaches). Communication training had small effects on patients' satisfaction with care when compared to control (4.1 points on a 100-point scale, 95% confidence interval [CI], 1.1-7.0). Communication training also had small effects on pain and disability with pooled results showing weighted mean differences of -3.8 points (95% CI, -6.5 to -1.1) and -3.6 (95% CI, -5.4 to -1.7), respectively. Studies show that communication training for clinicians produces small effects in improving patients' satisfaction with care or reducing pain and disability in primary care and rehabilitation settings. Copyright © 2015 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

2010-01-01

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

Improving decision making about clinical trial participation - a randomised controlled trial of a decision aid for women considering participation in the IBIS-II breast cancer prevention trial.

PubMed

Juraskova, I; Butow, P; Bonner, C; Bell, M L; Smith, A B; Seccombe, M; Boyle, F; Reaby, L; Cuzick, J; Forbes, J F

2014-07-08

Decision aids may improve informed consent in clinical trial recruitment, but have not been evaluated in this context. This study investigated whether decision aids (DAs) can reduce decisional difficulties among women considering participation in the International Breast Cancer Intervention Study-II (IBIS-II) trial. The IBIS-II trial investigated breast cancer prevention with anastrazole in two cohorts: women with increased risk (Prevention), and women treated for ductal carcinoma in situ (DCIS). Australia, New Zealand and United Kingdom participants were randomised to receive a DA (DA group) or standard trial consent materials (control group). Questionnaires were completed after deciding about participation in IBIS-II (post decision) and 3 months later (follow-up). Data from 112 Prevention and 34 DCIS participants were analysed post decision (73 DA; 73 control); 95 Prevention and 24 DCIS participants were analysed at follow-up (58 DA; 61 control). There was no effect on the primary outcome of decisional conflict. The DCIS-DA group had higher knowledge post decision, and the Prevention-DA group had lower decisional regret at follow-up. This was the first study to evaluate a DA in the clinical trial setting. The results suggest DAs can potentially increase knowledge and reduce decisional regret about clinical trial participation.

Sub-Lexical Reading Intervention in a Student with Dyslexia and Asperger's Disorder

ERIC Educational Resources Information Center

Wright, Craig; Conlon, Elizabeth; Wright, Michalle; Dyck, Murray

2011-01-01

Dyslexia is a common presenting condition in clinic and educational settings. Unlike the homogenous groups used in randomised trials, educators typically manage children who have multiple developmental problems. Investigations are required into how these complex cases respond to treatment identified as efficacious by controlled trials. This study…

Causal inference as an emerging statistical approach in neurology: an example for epilepsy in the elderly.

PubMed

Moura, Lidia Mvr; Westover, M Brandon; Kwasnik, David; Cole, Andrew J; Hsu, John

2017-01-01

The elderly population faces an increasing number of cases of chronic neurological conditions, such as epilepsy and Alzheimer's disease. Because the elderly with epilepsy are commonly excluded from randomized controlled clinical trials, there are few rigorous studies to guide clinical practice. When the elderly are eligible for trials, they either rarely participate or frequently have poor adherence to therapy, thus limiting both generalizability and validity. In contrast, large observational data sets are increasingly available, but are susceptible to bias when using common analytic approaches. Recent developments in causal inference-analytic approaches also introduce the possibility of emulating randomized controlled trials to yield valid estimates. We provide a practical example of the application of the principles of causal inference to a large observational data set of patients with epilepsy. This review also provides a framework for comparative-effectiveness research in chronic neurological conditions.

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.

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

PubMed Central

2012-01-01

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

Evaluating the design and reporting of pragmatic trials in osteoarthritis research.

PubMed

Ali, Shabana Amanda; Kloseck, Marita; Lee, Karen; Walsh, Kathleen Ellen; MacDermid, Joy C; Fitzsimmons, Deborah

2018-01-01

Among the challenges in health research is translating interventions from controlled experimental settings to clinical and community settings where chronic disease is managed daily. Pragmatic trials offer a method for testing interventions in real-world settings but are seldom used in OA research. The aim of this study was to evaluate the literature on pragmatic trials in OA research up to August 2016 in order to identify strengths and weaknesses in the design and reporting of these trials. We used established guidelines to assess the degree to which 61 OA studies complied with pragmatic trial design and reporting. We assessed design according to the pragmatic-explanatory continuum indicator summary and reporting according to the pragmatic trials extension of the CONsolidated Standards of Reporting Trials guidelines. None of the pragmatic trials met all 11 criteria evaluated and most of the trials met between 5 and 8 of the criteria. Criteria most often unmet pertained to practitioner expertise (by requiring specialists) and criteria most often met pertained to primary outcome analysis (by using intention-to-treat analysis). Our results suggest a lack of highly pragmatic trials in OA research. We identify this as a point of opportunity to improve research translation, since optimizing the design and reporting of pragmatic trials can facilitate implementation of evidence-based interventions for OA care. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Randomized Controlled Trials Evaluating Effect of Television Advertising on Food Intake in Children: Why Such a Sensitive Topic is Lacking Top-Level Evidence?

PubMed

Gregori, Dario; Ballali, Simonetta; Vecchio, Maria Gabriella; Sciré, Antonella Silvia; Foltran, Francesca; Berchialla, Paola

2014-01-01

The aim of this study was to perform a systematic review of evidence coming from randomized controlled trials (RCT) aimed at assessing the effect of television advertising on food intake in children from 4 to 12 years old. Randomized controlled trials were searched in PubMed database and included if they assessed the effect of direct exposure to television food advertising over the actual energy intake of children. Seven studies out of 2166 fulfilled the inclusion criteria. The association between television advertising and energy intake is based on a very limited set of randomized researches lacking a solid ground of first-level evidence.

DeLLITE depression in late life: an intervention trial of exercise. Design and recruitment of a randomised controlled trial.

PubMed

Kerse, Ngaire; Falloon, Karen; Moyes, Simon A; Hayman, Karen J; Dowell, Tony; Kolt, Gregory S; Elley, C Raina; Hatcher, Simon; Peri, Kathy; Keeling, Sally; Robinson, Elizabeth; Parsons, John; Wiles, Janine; Arroll, Bruce

2008-05-24

Physical activity shows potential in combating the poor outcomes associated with depression in older people. Meta-analyses show gaps in the research with poor trial design compromising certainty in conclusions and few programmes showing sustained effects. The Depression in Late Life: an Intervention Trial of Exercise (DeLLITE) is a 12 month randomised controlled trial of a physical activity intervention to increase functional status in people aged 75 years and older with depressive symptoms. The intervention involves an individualised activity programme based on goal setting and progression of difficulty of activities delivered by a trained nurse during 8 home visits over 6 months. The control group received time matched home visits to discuss social contacts and networks. Baseline, 6 and 12 months measures were assessed in face to face visits with the primary outcome being functional status (SPPB, NEADL). Secondary outcomes include depressive symptoms (Geriatric Depression Scale), quality of life (SF-36), physical activity (AHS Physical Activity Questionnaire) and falls (self report). Due to report in 2008 the DeLLITE study has recruited 70% of those eligible and tests the efficacy of a home based, goal setting physical activity programme in improving function, mood and quality of life in older people with depressive symptomatology. If successful in improving function and mood this trial could prove for the first time that there are long term health benefit of physical activity, independent of social activity, in this high risk group who consume excess health related costs. Australian and New Zealand Clinical Trials Register ACTRN12605000475640.

Artificial Pancreas Device Systems for the Closed-Loop Control of Type 1 Diabetes

PubMed Central

Trevitt, Sara; Simpson, Sue; Wood, Annette

2015-01-01

Background: Closed-loop artificial pancreas device (APD) systems are externally worn medical devices that are being developed to enable people with type 1 diabetes to regulate their blood glucose levels in a more automated way. The innovative concept of this emerging technology is that hands-free, continuous, glycemic control can be achieved by using digital communication technology and advanced computer algorithms. Methods: A horizon scanning review of this field was conducted using online sources of intelligence to identify systems in development. The systems were classified into subtypes according to their level of automation, the hormonal and glycemic control approaches used, and their research setting. Results: Eighteen closed-loop APD systems were identified. All were being tested in clinical trials prior to potential commercialization. Six were being studied in the home setting, 5 in outpatient settings, and 7 in inpatient settings. It is estimated that 2 systems may become commercially available in the EU by the end of 2016, 1 during 2017, and 2 more in 2018. Conclusions: There are around 18 closed-loop APD systems progressing through early stages of clinical development. Only a few of these are currently in phase 3 trials and in settings that replicate real life. PMID:26589628

Hybrid Implementation Model of Community-Partnered Early Intervention for Toddlers with Autism: A Randomized Trial

ERIC Educational Resources Information Center

Shire, Stephanie Y.; Chang, Ya-Chih; Shih, Wendy; Bracaglia, Suzanne; Kodjoe, Maria; Kasari, Connie

2017-01-01

Background: Interventions found to be effective in research settings are often not as effective when implemented in community settings. Considering children with autism, studies have rarely examined the efficacy of laboratory-tested interventions on child outcomes in community settings using randomized controlled designs. Methods: One hundred and…

'In situ simulation' versus 'off site simulation' in obstetric emergencies and their effect on knowledge, safety attitudes, team performance, stress, and motivation: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Unexpected obstetric emergencies threaten the safety of pregnant women. As emergencies are rare, they are difficult to learn. Therefore, simulation-based medical education (SBME) seems relevant. In non-systematic reviews on SBME, medical simulation has been suggested to be associated with improved learner outcomes. However, many questions on how SBME can be optimized remain unanswered. One unresolved issue is how 'in situ simulation' (ISS) versus 'off site simulation' (OSS) impact learning. ISS means simulation-based training in the actual patient care unit (in other words, the labor room and operating room). OSS means training in facilities away from the actual patient care unit, either at a simulation centre or in hospital rooms that have been set up for this purpose. Methods and design The objective of this randomized trial is to study the effect of ISS versus OSS on individual learning outcome, safety attitude, motivation, stress, and team performance amongst multi-professional obstetric-anesthesia teams. The trial is a single-centre randomized superiority trial including 100 participants. The inclusion criteria were health-care professionals employed at the department of obstetrics or anesthesia at Rigshospitalet, Copenhagen, who were working on shifts and gave written informed consent. Exclusion criteria were managers with staff responsibilities, and staff who were actively taking part in preparation of the trial. The same obstetric multi-professional training was conducted in the two simulation settings. The experimental group was exposed to training in the ISS setting, and the control group in the OSS setting. The primary outcome is the individual score on a knowledge test. Exploratory outcomes are individual scores on a safety attitudes questionnaire, a stress inventory, salivary cortisol levels, an intrinsic motivation inventory, results from a questionnaire evaluating perceptions of the simulation and suggested changes needed in the organization, a team-based score on video-assessed team performance and on selected clinical performance. Discussion The perspective is to provide new knowledge on contextual effects of different simulation settings. Trial registration ClincialTrials.gov NCT01792674. PMID:23870501

Community-led trials: Intervention co-design in a cluster randomised controlled trial.

PubMed

Andersson, Neil

2017-05-30

In conventional randomised controlled trials (RCTs), researchers design the interventions. In the Camino Verde trial, each intervention community designed its own programmes to prevent dengue. Instead of fixed actions or menus of activities to choose from, the trial randomised clusters to a participatory research protocol that began with sharing and discussing evidence from a local survey, going on to local authorship of the action plan for vector control.Adding equitable stakeholder engagement to RCT infrastructure anchors the research culturally, making it more meaningful to stakeholders. Replicability in other conditions is straightforward, since all intervention clusters used the same engagement protocol to discuss and to mobilize for dengue prevention. The ethical codes associated with RCTs play out differently in community-led pragmatic trials, where communities essentially choose what they want to do. Several discussion groups in each intervention community produced multiple plans for prevention, recognising different time lines. Some chose fast turnarounds, like elimination of breeding sites, and some chose longer term actions like garbage disposal and improving water supplies.A big part of the skill set for community-led trials is being able to stand back and simply support communities in what they want to do and how they want to do it, something that does not come naturally to many vector control programs or to RCT researchers. Unexpected negative outcomes can come from the turbulence implicit in participatory research. One example was the gender dynamic in the Mexican arm of the Camino Verde trial. Strong involvement of women in dengue control activities seems to have discouraged men in settings where activity in public spaces or outside of the home would ordinarily be considered a "male competence".Community-led trials address the tension between one-size-fits-all programme interventions and local needs. Whatever the conventional wisdom about how prevention works at a system level, programmes have to be perceived as locally relevant and they must engage stakeholders who make them work. Locally, each participating community has to know the intervention is relevant to them; they have to want to do it. That happens much more easily if they design the programme themselves.

Effect of Sling Exercise Training on Balance in Patients with Stroke: A Meta-Analysis

PubMed Central

Peng, Qiyuan; Chen, Jingjie; Zou, Yucong; Liu, Gang

2016-01-01

Objective This study aims to evaluate the effect of sling exercise training (SET) on balance in patients with stroke. Methods PubMed, Cochrane Library, Ovid LWW, CBM, CNKI, WanFang, and VIP databases were searched for randomized controlled trials of the effect of SET on balance in patients with stroke. The study design and participants were subjected to metrological analysis. Berg balance Scale (BBS), Barthel index score (BI), and Fugl-Meyer Assessment (FMA) were used as independent parameters for evaluating balance function, activities of daily living(ADL) and motor function after stroke respectively, and were subjected to meta-analysis by RevMan5.3 software. Results Nine studies with 460 participants were analyzed. Results of meta-analysis showed that the SET treatment combined with conventional rehabilitation was superior to conventional rehabilitation treatments, with increased degrees of BBS (WMD = 3.81, 95% CI [0.15, 7.48], P = 0.04), BI (WMD = 12.98, 95% CI [8.39, 17.56], P < 0.00001), and FMA (SMD = 0.76, 95% CI [0.41, 1.11], P < 0.0001). Conclusion Based on limited evidence from 9 trials, the SET treatment combined with conventional rehabilitation was superior to conventional rehabilitation treatments, with increased degrees of BBS, BI and FMA, So the SET treatment can improvement of balance function after stroke, but the interpretation of our findings is required to be made with caution due to limitations in included trials such as small sample sizes and the risk of bias. Therefore, more multi-center and large-sampled randomized controlled trials are needed to confirm its clinical applications. PMID:27727288

DeLLITE Depression in late life: an intervention trial of exercise. Design and recruitment of a randomised controlled trial

PubMed Central

Kerse, Ngaire; Falloon, Karen; Moyes, Simon A; Hayman, Karen J; Dowell, Tony; Kolt, Gregory S; Elley, C Raina; Hatcher, Simon; Peri, Kathy; Keeling, Sally; Robinson, Elizabeth; Parsons, John; Wiles, Janine; Arroll, Bruce

2008-01-01

Background Physical activity shows potential in combating the poor outcomes associated with depression in older people. Meta-analyses show gaps in the research with poor trial design compromising certainty in conclusions and few programmes showing sustained effects. Methods/design The Depression in Late Life: an Intervention Trial of Exercise (DeLLITE) is a 12 month randomised controlled trial of a physical activity intervention to increase functional status in people aged 75 years and older with depressive symptoms. The intervention involves an individualised activity programme based on goal setting and progression of difficulty of activities delivered by a trained nurse during 8 home visits over 6 months. The control group received time matched home visits to discuss social contacts and networks. Baseline, 6 and 12 months measures were assessed in face to face visits with the primary outcome being functional status (SPPB, NEADL). Secondary outcomes include depressive symptoms (Geriatric Depression Scale), quality of life (SF-36), physical activity (AHS Physical Activity Questionnaire) and falls (self report). Discussion Due to report in 2008 the DeLLITE study has recruited 70% of those eligible and tests the efficacy of a home based, goal setting physical activity programme in improving function, mood and quality of life in older people with depressive symptomatology. If successful in improving function and mood this trial could prove for the first time that there are long term health benefit of physical activity, independent of social activity, in this high risk group who consume excess health related costs. Trial registration Australian and New Zealand Clinical Trials Register ACTRN12605000475640 PMID:18501008

Measurement, Education and Tracking in Integrated Care (METRIC): use of a culturally adapted education tool versus standard education to increase engagement in depression treatment among Hispanic patients: study protocol for a randomized control trial.

PubMed

Sanchez, Katherine; Eghaneyan, Brittany H; Killian, Michael O; Cabassa, Leopoldo; Trivedi, Madhukar H

2017-08-03

Significant mental health disparities exist for Hispanic populations, especially with regard to depression treatment. Stigma and poor communication between patients and their providers result in low use of antidepressant medications and early treatment withdrawal. Cultural factors which influence treatment decisions among Hispanics include fears about the addictive and harmful properties of antidepressants, worries about taking too many pills, and the stigma attached to taking medications. Primary care settings often are the gateway to identifying undiagnosed or untreated mental health disorders, particularly for people with co-morbid physical health conditions. Hispanics, in particular, are more likely to receive mental healthcare in primary care settings. Recent recommendations from the U.S. Preventive Services Task Force are that primary care providers screen adult patients for depression only if systems are in place to ensure adequate treatment and follow-up. We are conducting a randomized controlled trial among 150 depressed adult Hispanics in a primary care safety net setting, testing the effectiveness of a culturally appropriate depression education intervention to reduce stigma and increase uptake in depression treatment among Hispanics, and implement a Measurement-Based Integrated Care (MBIC) model with collaborative, multidisciplinary treatment and culturally tailored care management strategies. This study protocol represents the first randomized control trial of the culturally adapted depression education fotonovela, Secret Feelings, among Hispanics in a primary care setting. The education intervention will be implemented after diagnosis using an innovative screening technology and enrolled in measurement-based integrated care for the treatment of depression, which will help build the evidence around cultural adaptations in treatment to reduce mental health disparities. ClinicalTrials.gov, NCT02702596. Registered on 20 March 2016.

Back schools for non-specific low-back pain.

PubMed

Heymans, M W; van Tulder, M W; Esmail, R; Bombardier, C; Koes, B W

2004-10-18

Since the introduction of the Swedish back school in 1969, back schools have frequently been used for treating patients with low-back pain (LBP). However, the content of back schools has changed and appears to vary widely today. To assess the effectiveness of back schools for patients with non-specific LBP. We searched the MEDLINE and EMBASE databases and the Cochrane Central Register of Controlled Trials to May 2003 for relevant trials reported in English, Dutch, French or German. We also screened references from relevant reviews and included trials. Randomized controlled trials (RCTs) that reported on any type of back school for non-specific LBP were included. Four reviewers, blinded to authors, institution and journal, independently extracted the data and assessed the quality of the trials. We set the high quality level, a priori, at a trial meeting six or more of 11 internal validity criteria. As data were clinically and statistically too heterogeneous to perform a meta-analysis, we used a qualitative review (best evidence synthesis) to summarize the results. The evidence was classified into four levels (strong, moderate, limited or no evidence), taking into account the methodological quality of the studies. We also evaluated the clinical relevance of the studies. Nineteen RCTs (3584 patients) were included in this updated review. Overall, the methodological quality was low, with only six trials considered to be high quality. It was not possible to perform relevant subgroup analyses for LBP with radiation versus LBP without radiation. The results indicate that there is moderate evidence suggesting that back schools have better short and intermediate-term effects on pain and functional status than other treatments for patients with recurrent and chronic LBP. There is moderate evidence suggesting that back schools for chronic LBP in an occupational setting, are more effective than other treatments and placebo or waiting list controls on pain, functional status and return to work during short and intermediate-term follow-up. In general, the clinical relevance of the studies was rated as insufficient. There is moderate evidence suggesting that back schools, in an occupational setting, reduce pain, and improve function and return-to-work status, in the short and intermediate-term, compared to exercises, manipulation, myofascial therapy, advice, placebo or waiting list controls, for patients with chronic and recurrent LBP. However, future trials should improve methodological quality and clinical relevance and evaluate the cost-effectiveness of back schools.

Testing the Replicability of a Successful Care Management Program: Results from a Randomized Trial and Likely Explanations for Why Impacts Did Not Replicate.

PubMed

Peterson, G Greg; Zurovac, Jelena; Brown, Randall S; Coburn, Kenneth D; Markovich, Patricia A; Marcantonio, Sherry A; Clark, William D; Mutti, Anne; Stepanczuk, Cara

2016-12-01

To test whether a care management program could replicate its success in an earlier trial and determine likely explanations for why it did not. Medicare claims and nurse contact data for Medicare fee-for-service beneficiaries with chronic illnesses enrolled in the trial in eastern Pennsylvania (N = 483). A randomized trial with half of enrollees receiving intensive care management services and half receiving usual care. We developed and tested hypotheses for why impacts declined. All outcomes and covariates were derived from claims and the nurse contact data. From 2010 to 2014, the program did not reduce hospitalizations or generate Medicare savings to offset program fees that averaged $260 per beneficiary per month. These estimates are statistically different (p < .05) from the large reductions in hospitalizations and spending in the first trial (2002-2010). The treatment-control differences in the second trial disappeared because the control group's risk-adjusted hospitalization rate improved, not because the treatment group's outcomes worsened. Even if demonstrated in a randomized trial, successful results from one test may not replicate in other settings or time periods. Assessing whether gaps in care that the original program filled exist in other settings can help identify where earlier success is likely to replicate. © Health Research and Educational Trust.

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.

Hyperthermia and fever control in brain injury.

PubMed

Badjatia, Neeraj

2009-07-01

Fever in the neurocritical care setting is common and has a negative impact on outcome of all disease types. Meta-analyses have demonstrated that fever at onset and in the acute setting after ischemic brain injury, intracerebral hemorrhage, and cardiac arrest has a negative impact on morbidity and mortality. Data support that the impact of fever is sustained for longer durations after subarachnoid hemorrhage and traumatic brain injury. Recent advances have made eliminating fever and maintaining normothermia feasible. However, there are no prospective randomized trials demonstrating the benefit of fever control in these patient populations, and important questions regarding indications and timing remain. The purpose of this review is to analyze the data surrounding the impact of fever across a range of neurologic injuries to better understand the optimal timing and duration of fever control. Prospective randomized trials are needed to determine whether the beneficial impact of secondary injury prevention is outweighed by the potential risks of prolonged fever control.

Evaluating effectiveness and cost-effectiveness of a group psychological intervention using cognitive behavioural strategies for women with common mental disorders in conflict-affected rural Pakistan: study protocol for a randomised controlled trial.

PubMed

Chiumento, Anna; Hamdani, Syed Usman; Khan, Muhammad Naseem; Dawson, Katie; Bryant, Richard A; Sijbrandij, Marit; Nazir, Huma; Akhtar, Parveen; Masood, Aqsa; Wang, Duolao; van Ommeren, Mark; Rahman, Atif

2017-04-26

The impact of humanitarian disasters upon mental health is well recognised. The evidence for psychological interventions for mental health is mounting, but few interventions have been rigorously tested in humanitarian settings. To be sustainable in humanitarian settings interventions need to be short, simple, deliverable by nonspecialists under supervision, and adopt a transdiagnostic approach where an array of mental health outcomes are addressed simultaneously. These elements have been incorporated into the newly developed WHO Problem Management Plus (PM+) Group intervention. The aim of this trial is to evaluate the locally adapted PM+ Group intervention for women in Swat, Pakistan. This PM+ Group trial is a two-arm, single-blind, cluster randomised controlled trial conducted in a community-based setting with women in rural Pakistan. PM+ is delivered in partnership with the Lady Health Worker (LHW) Programme which provides community-based health care to women in Pakistan. Thirty-four LHW clusters will be randomised in a 1:1 allocation ratio using a permuted-block randomisation method. Participants screened and found to meet the inclusion criteria will be allocated to either the PM+ intervention group (n = 306), or the control arm (n = 306). The manualised PM+ intervention involves five sessions, each lasting 3 h, and introduces four strategies applied by participants to problems that they are facing. It is delivered by local female facilitators with a minimum of 16 years of education who are provided with targeted training and supervision. The primary outcome is individual psychological distress, measured by levels of anxiety and depression on the Hospital Anxiety and Depression Scale at 20 weeks after baseline. Secondary outcomes include major depression, post-traumatic stress disorder, levels of social support, levels of functioning, and economic effectiveness. Intervention acceptability will be explored through an embedded qualitative study. The PM+ Group trial will provide important evidence on the effectiveness of an empirically supported psychological treatment delivered by nonspecialists in a humanitarian setting. If proven effective, the qualitative component will inform strategies for PM+ Group scale-up in health systems in other humanitarian settings. Australian New Zealand Clinical Trials Registry, identifier: ACTRN12616000037404. Registered on 19 January 2016; WHO Protocol ID RPC705, v.4, 2 November 2015.

Implementing guidelines in nursing homes: a systematic review.

PubMed

Diehl, Heinz; Graverholt, Birgitte; Espehaug, Birgitte; Lund, Hans

2016-07-25

Research on guideline implementation strategies has mostly been conducted in settings which differ significantly from a nursing home setting and its transferability to the nursing home setting is therefore limited. The objective of this study was to systematically review the effects of interventions to improve the implementation of guidelines in nursing homes. A systematic literature search was conducted in the Cochrane Library, CINAHL, Embase, MEDLINE, DARE, HTA, CENTRAL, SveMed + and ISI Web of Science from their inception until August 2015. Reference screening and a citation search were performed. Studies were eligible if they evaluated any type of guideline implementation strategy in a nursing home setting. Eligible study designs were systematic reviews, randomised controlled trials, non-randomised controlled trials, controlled before-after studies and interrupted-time-series studies. The EPOC risk of bias tool was used to evaluate the risk of bias in the included studies. The overall quality of the evidence was rated using GRADE. Five cluster-randomised controlled trials met the inclusion criteria, evaluating a total of six different multifaceted implementation strategies. One study reported a small statistically significant effect on professional practice, and two studies demonstrated small to moderate statistically significant effects on patient outcome. The overall quality of the evidence for all comparisons was low or very low using GRADE. Little is known about how to improve the implementation of guidelines in nursing homes, and the evidence to support or discourage particular interventions is inconclusive. More implementation research is needed to ensure high quality of care in nursing homes. PROSPERO 2014: CRD42014007664.

Reaching clinically relevant outcome measures for new pharmacotherapy and immunotherapy of atopic eczema.

PubMed

Chalmers, Joanne; Deckert, Stefanie; Schmitt, Jochen

2015-06-01

This article describes the core outcome set (COS) for atopic eczema trials. COS describe a minimum set of outcomes to be assessed in a defined situation. COS are required to overcome the current situation of different trials using different endpoints with unclear/insufficient measurement properties resulting in incomparable trials. The global multi-stakeholder Harmonising Outcomes Measures for Eczema initiative developed the Harmonising Outcomes Measures for Eczema roadmap as a generic framework for COS development. Following the establishment of a panel representing all stakeholders, a core set of outcome domains need to be selected based on systematic reviews and consensus methods. Outcome measurement instruments to assess these core domains need to be valid, reliable, and feasible. There is broad global consensus that clinical signs, quality of life, symptoms, and long-term control of flares form the COS for atopic eczema trials. The Eczema Area and Severity Index is recommended to assess clinical signs in atopic eczema trials. Systematic reviews to identify adequate outcome measurement instruments for the other core outcome domains are underway. Clinical signs should be assessed in all atopic eczema trials by at least the Eczema Area and Severity Index. Quality of life, symptoms, and flares should also be assessed in all atopic eczema trials by a valid, reliable, and feasible instrument.

Assessment of the effect of larval source management and house improvement on malaria transmission when added to standard malaria control strategies in southern Malawi: study protocol for a cluster-randomised controlled trial.

PubMed

McCann, Robert S; van den Berg, Henk; Diggle, Peter J; van Vugt, Michèle; Terlouw, Dianne J; Phiri, Kamija S; Di Pasquale, Aurelio; Maire, Nicolas; Gowelo, Steven; Mburu, Monicah M; Kabaghe, Alinune N; Mzilahowa, Themba; Chipeta, Michael G; Takken, Willem

2017-09-22

Due to outdoor and residual transmission and insecticide resistance, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) will be insufficient as stand-alone malaria vector control interventions in many settings as programmes shift toward malaria elimination. Combining additional vector control interventions as part of an integrated strategy would potentially overcome these challenges. Larval source management (LSM) and structural house improvements (HI) are appealing as additional components of an integrated vector management plan because of their long histories of use, evidence on effectiveness in appropriate settings, and unique modes of action compared to LLINs and IRS. Implementation of LSM and HI through a community-based approach could provide a path for rolling-out these interventions sustainably and on a large scale. We will implement community-based LSM and HI, as additional interventions to the current national malaria control strategies, using a randomised block, 2 × 2 factorial, cluster-randomised design in rural, southern Malawi. These interventions will be continued for two years. The trial catchment area covers about 25,000 people living in 65 villages. Community participation is encouraged by training community volunteers as health animators, and supporting the organisation of village-level committees in collaboration with The Hunger Project, a non-governmental organisation. Household-level cross-sectional surveys, including parasitological and entomological sampling, will be conducted on a rolling, 2-monthly schedule to measure outcomes over two years (2016 to 2018). Coverage of LSM and HI will also be assessed throughout the trial area. Combining LSM and/or HI together with the interventions currently implemented by the Malawi National Malaria Control Programme is anticipated to reduce malaria transmission below the level reached by current interventions alone. Implementation of LSM and HI through a community-based approach provides an opportunity for optimum adaptation to the local ecological and social setting, and enhances the potential for sustainability. Registered with The Pan African Clinical Trials Registry on 3 March 2016, trial number PACTR201604001501493.

Application of a repetitive process setting to design of monotonically convergent iterative learning control

NASA Astrophysics Data System (ADS)

Boski, Marcin; Paszke, Wojciech

2015-11-01

This paper deals with the problem of designing an iterative learning control algorithm for discrete linear systems using repetitive process stability theory. The resulting design produces a stabilizing output feedback controller in the time domain and a feedforward controller that guarantees monotonic convergence in the trial-to-trial domain. The results are also extended to limited frequency range design specification. New design procedure is introduced in terms of linear matrix inequality (LMI) representations, which guarantee the prescribed performances of ILC scheme. A simulation example is given to illustrate the theoretical developments.

The CONSENSUS study: protocol for a mixed methods study to establish which outcomes should be included in a core outcome set for oropharyngeal cancer.

PubMed

Waters, Aoife Mi; Tudur Smith, Catrin; Young, Bridget; Jones, Terry M

2014-05-13

The incidence of oropharyngeal cancer is increasing in the developed world. This has led to a large rise in research activity and clinical trials in this area, yet there is no consensus on which outcomes should be measured. As a result, the outcomes measured often differ between trials of comparable interventions, making the combination or comparison of results between trials impossible. Outcomes may also be 'cherry-picked', such that favourable results are reported, and less favourable results withheld. The development of a minimum outcome reporting standard, known as a core outcome set, goes some way to addressing these problems. Core outcome sets are ideally developed using a patient-centred approach so that the outcomes measured are relevant to patients and clinical practice. Core outcome sets drive up the quality and relevance of research by ensuring that the right outcomes are consistently measured and reported in trials in specific areas of health or healthcare. This is a mixed methods study involving three phases to develop a core outcome set for oropharyngeal cancer clinical trials. Firstly, a systematic review will establish which outcomes are measured in published oropharyngeal cancer randomised controlled trials (RCTs). Secondly, qualitative interviews with patients and carers in the UK and the USA will aim to establish which outcomes are important to these stakeholders. Data from these first two stages will be used to develop a comprehensive list of outcomes to be considered for inclusion in the core outcome set. In the third stage, patients and clinicians will participate in an iterative consensus exercise known as a Delphi study to refine the contents of the core outcome set. This protocol lays out the methodology to be implemented in the CONSENSUS study. A core outcome set defines a minimum outcome reporting standard for clinical trials in a particular area of health or healthcare. Its consistent implementation in oropharyngeal cancer clinical trials will improve the quality and relevance of research. This study is registered at the National Institute for Health Research (NIHR) Clinical Research Network (CRN) portfolio, ID 13823 (17 January 2013).

Statin use and 25-hydroxyvitamin D blood level response to vitamin D treatment of older adults

USDA-ARS?s Scientific Manuscript database

Objectives: To determine whether statin use alters response of 25-hydroxyvitamin D (25(OH)D) level to vitamin D treatment. Design: Pooled analysis. Setting: Three double-blind randomized controlled trials that tested different doses of vitamin D. Participants: Participants of three trials (N = 646; ...

Moving from Efficacy to Effectiveness in Cognitive Behavioral Therapy for Psychosis: A Randomized Clinical Practice Trial

ERIC Educational Resources Information Center

Lincoln, Tania M.; Ziegler, Michael; Mehl, Stephanie; Kesting, Marie-Luise; Lullmann, Eva; Westermann, Stefan; Rief, Winfried

2012-01-01

Objective: Randomized controlled trials have attested the efficacy of cognitive behavioral therapy (CBT) in reducing psychotic symptoms. Now, studies are needed to investigate its effectiveness in routine clinical practice settings. Method: Eighty patients with schizophrenia spectrum disorders who were seeking outpatient treatment were randomized…

Is Conflict Adaptation due to Active Regulation or Passive Carry-Over? Evidence from Eye Movements

PubMed Central

Hubbard, Jason; Kuhns, David; Schäfer, Theo A.J.; Mayr, Ulrich

2017-01-01

Conflict-adaptation effects (i.e., reduced response-time costs on high-conflict trials following high-conflict trials) supposedly represent our cognitive system’s ability to regulate itself according to current processing demands. However, currently it is not clear whether these effects reflect conflict-triggered, active regulation, or passive carry-over of previous-trial control settings. We used eye movements to examine whether the degree of experienced conflict modulates conflict-adaptation effects, as the conflict-triggered regulation view predicts. Across two experiments in which participants had to identify a target stimulus based on an endogenous cue while––on conflict trials––having to resist a sudden-onset distractor, we found a clear indication of conflict adaptation. This adaptation effect disappeared however, when participants inadvertently fixated the sudden-onset distractor on the previous trial––that is, when they experienced a high degree of conflict. This pattern of results suggests that conflict adaptation can be explained parsimoniously in terms of a broader memory process that retains recently adopted control settings across trials. PMID:27656869

Muslim communities learning about second-hand smoke (MCLASS): study protocol for a pilot cluster randomised controlled trial

PubMed Central

2013-01-01

Background In the UK, 40% of Bangladeshi and 29% of Pakistani men smoke cigarettes regularly compared to the national average of 24%. As a consequence, second-hand smoking is also widespread in their households which is a serious health hazard to non-smokers, especially children. Smoking restrictions in households can help reduce exposure to second-hand smoking. This is a pilot trial of ‘Smoke Free Homes’, an educational programme which has been adapted for use by Muslim faith leaders, in an attempt to find an innovative solution to encourage Pakistani- and Bangladeshi-origin communities to implement smoking restrictions in their homes. The primary objectives for this pilot trial are to establish the feasibility of conducting such an evaluation and provide information to inform the design of a future definitive study. Methods/Design This is a pilot cluster randomised controlled trial of ‘Smoke Free Homes’, with an embedded preliminary health economic evaluation and a qualitative analysis. The trial will be carried out in around 14 Islamic religious settings. Equal randomisation will be employed to allocate each cluster to a trial arm. The intervention group will be offered the Smoke Free Homes package (Smoke Free Homes: a resource for Muslim religious teachers), trained in its use, and will subsequently implement the package in their religious settings. The remaining clusters will not be offered the package until the completion of the study and will form the control group. At each cluster, we aim to recruit around 50 households with at least one adult resident who smokes tobacco and at least one child or a non-smoking adult. Households will complete a household survey and a non-smoking individual will provide a saliva sample which will be tested for cotinine. All participant outcomes will be measured before and after the intervention period in both arms of the trial. In addition, a purposive sample of participants and religious leaders/teachers will take part in interviews and focus groups. Discussion The results of this pilot study will inform the protocol for a definitive trial. Trial registration Current Controlled Trials ISRCTN03035510 PMID:24034853

Web-Based Decision Aid to Assist Help-Seeking Choices for Young People Who Self-Harm: Outcomes From a Randomized Controlled Feasibility Trial

PubMed Central

Patel, Krisna; French, Rebecca S; Henderson, Claire; Ougrin, Dennis; Slade, Mike; Moran, Paul

2018-01-01

Background Adolescents who self-harm are often unsure how or where to get help. We developed a Web-based personalized decision aid (DA) designed to support young people in decision making about seeking help for their self-harm. Objective The aim of this study was to evaluate the feasibility and acceptability of the DA intervention and the randomized controlled trial (RCT) in a school setting. Methods We conducted a two-group, single blind, randomized controlled feasibility trial in a school setting. Participants aged 12 to 18 years who reported self-harm in the past 12 months were randomized to either a Web-based DA or to general information about mood and feelings. Feasibility of recruitment, randomization, and follow-up rates were assessed, as was acceptability of the intervention and study procedures. Descriptive data were collected on outcome measures examining decision making and help-seeking behavior. Qualitative interviews were conducted with young people, parents or carers, and staff and subjected to thematic analysis to explore their views of the DA and study processes. Results Parental consent was a significant barrier to young people participating in the trial, with only 17.87% (208/1164) of parents or guardians who were contacted for consent responding to study invitations. Where parental consent was obtained, we were able to recruit 81.7% (170/208) of young people into the study. Of those young people screened, 13.5% (23/170) had self-harmed in the past year. Ten participants were randomized to receiving the DA, and 13 were randomized to the control group. Four-week follow-up assessments were completed with all participants. The DA had good acceptability, but qualitative interviews suggested that a DA that addressed broader mental health problems such as depression, anxiety, and self-harm may be more beneficial. Conclusions A broad-based mental health DA addressing a wide range of psychosocial problems may be useful for young people. The requirement for parental consent is a key barrier to intervention research on self-harm in the school setting. Adaptations to the research design and the intervention are needed before generalizable research about DAs can be successfully conducted in a school setting. Trial Registration International Standard Randomized Controlled Trial registry: ISRCTN11230559; http://www.isrctn.com/ISRCTN11230559 (Archived by WebCite at http://www.webcitation.org/6wqErsYWG) PMID:29382626

Alternation as a form of allocation for quality improvement studies in primary healthcare settings: the on-off study design.

PubMed

Mathe, Nonsikelelo; Johnson, Steven T; Wozniak, Lisa A; Majumdar, Sumit R; Johnson, Jeffrey A

2015-08-25

Randomized controlled trials are considered the "gold standard" for scientific rigor in the assessment of benefits and harms of interventions in healthcare. They may not always be feasible, however, when evaluating quality improvement interventions in real-world healthcare settings. Non-randomized controlled trials (NCTs) are designed to answer questions of effectiveness of interventions in routine clinical practice to inform a decision or process. The on-off NCT design is a relatively new design where participant allocation is by alternation. In alternation, eligible patients are allocated to the intervention "on" or control "off " groups in time series dependent sequential clusters. We used two quality improvement studies undertaken in a Canadian primary care setting to illustrate the features of the on-off design. We also explored the perceptions and experiences of healthcare providers tasked with implementing the on-off study design. The on-off design successfully allocated patients to intervention and control groups. Imbalances between baseline variables were attributed to chance, with no detectable biases. However, healthcare providers' perspectives and experiences with the design in practice reveal some conflict. Specifically, providers described the process of allocating patients to the off group as unethical and immoral, feeling it was in direct conflict with their professional principle of providing care for all. The degree of dissatisfaction seemed exacerbated by: 1) the patient population involved (e.g., patient population viewed as high-risk (e.g., depressed or suicidal)), 2) conducting assessments without taking action (e.g., administering the PHQ-9 and not acting on the results), and 3) the (non-blinded) allocation process. Alternation, as in the on-off design, is a credible form of allocation. The conflict reported by healthcare providers in implementing the design, while not unique to the on-off design, may be alleviated by greater emphasis on the purpose of the research and having research assistants allocate patients and collect data instead of the healthcare providers implementing the trial. In addition, consultation with front-line staff implementing the trials with an on-off design on appropriateness to the setting (e.g., alignment with professional values and the patient population served) may be beneficial. Health Eating and Active Living with Diabetes: ClinicalTrials.gov identifier: NCT00991380. Date registered: 7 October 2009. Controlled trial of a collaborative primary care team model for patients with diabetes and depression: Clintrials.gov Identifier: NCT01328639 Date registered: 30 March 2011.

Evaluation of interventions for informed consent for randomised controlled trials (ELICIT): protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey.

PubMed

Gillies, Katie; Entwistle, Vikki; Treweek, Shaun P; Fraser, Cynthia; Williamson, Paula R; Campbell, Marion K

2015-10-27

The process of obtaining informed consent for participation in randomised controlled trials (RCTs) was established as a mechanism to protect participants against undue harm from research and allow people to recognise any potential risks or benefits associated with the research. A number of interventions have been put forward to improve this process. Outcomes reported in trials of interventions to improve the informed consent process for decisions about trial participation tend to focus on the 'understanding' of trial information. However, the operationalization of understanding as a concept, the tools used to measure it and the timing of the measurements are heterogeneous. A lack of clarity exists regarding which outcomes matter (to whom) and why. This inconsistency between studies results in difficulties when making comparisons across studies as evidenced in two recent systematic reviews of informed consent interventions. As such, no optimal method for measuring the impact of these interventions aimed at improving informed consent for RCTs has been identified. The project will adopt and adapt methodology previously developed and used in projects developing core outcome sets for assessment of clinical treatments. Specifically, the work will consist of three stages: 1) A systematic methodology review of existing outcome measures of trial informed consent interventions; 2) Interviews with key stakeholders to explore additional outcomes relevant for trial participation decisions; and 3) A Delphi study to refine the core outcome set for evaluation of trial informed consent interventions. All stages will include the stakeholders involved in the various aspects of RCT consent: users (that is, patients), developers (that is, trialists), deliverers (focusing on research nurses) and authorisers (that is, ethics committees). A final consensus meeting including all stakeholders will be held to review outcomes. The ELICIT study aims to develop a core outcome set for the evaluation of interventions intended to improve informed consent for RCTs for use in future RCTs and reviews, thereby improving the reliability and consistency of research in this area.

The role of randomized cluster crossover trials for comparative effectiveness testing in anesthesia: design of the Benzodiazepine-Free Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial.

PubMed

Spence, Jessica; Belley-Côté, Emilie; Lee, Shun Fu; Bangdiwala, Shrikant; Whitlock, Richard; LeManach, Yannick; Syed, Summer; Lamy, Andre; Jacobsohn, Eric; MacIsaac, Sarah; Devereaux, P J; Connolly, Stuart

2018-07-01

Increasingly, clinicians and researchers recognize that studies of interventions need to evaluate not only their therapeutic efficacy (i.e., the effect on an outcome in ideal, controlled settings) but also their real-world effectiveness in broad, unselected patient groups. Effectiveness trials inform clinical practice by comparing variations in therapeutic approaches that fall within the standard of care. In this article, we discuss the need for studies of comparative effectiveness in anesthesia and the limitations of individual patient randomized-controlled trials in determining comparative effectiveness. We introduce the concept of randomized cluster crossover trials as a means of answering questions of comparative effectiveness in anesthesia, using the design of the Benzodiazepine-Free Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial (Clinicaltrials.gov identifier NCT03053869).

Protocol for the development of a Core Outcome Set (COS) for hemorrhoidal disease: an international Delphi study.

PubMed

van Tol, R R; Melenhorst, J; Dirksen, C D; Stassen, L P S; Breukink, S O

2017-07-01

Over the last decade, many studies were performed regarding treatment options for hemorrhoidal disease. Randomised controlled trials (RCTs) should have well-defined primary and secondary outcomes. However, the reported outcome measures are numerous and diverse. The heterogeneity of outcome definition in clinical trials limits transparency and paves the way for bias. The development of a core outcome set (COS) helps minimizing this problem. A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease. The aim of this project is to generate a COS regarding the outcome of treatment after hemorrhoidal disease. A Delphi study will be performed by an international steering group healthcare professionals and patients with the intention to create a standard outcome set for future clinical trials for the treatment of hemorrhoidal disease. First, a literature review will be conducted to establish which outcomes are used in clinical trials for hemorrhoidal disease. Secondly, both healthcare professionals and patients will participate in several consecutive rounds of online questionnaires and a face-to-face meeting to refine the content of the COS. Development of a COS for hemorrhoidal disease defines a minimum outcome-reporting standard and will improve the quality of research in the future.

A Randomized Controlled Trial of an Activity Specific Exercise Program for Individuals With Alzheimer Disease in Long-term Care Settings

PubMed Central

Roach, Kathryn E.; Tappen, Ruth M.; Kirk-Sanchez, Neva; Williams, Christine L.; Loewenstein, David

2011-01-01

Objective To determine whether an activity specific exercise program could improve ability to perform basic mobility activities in long-term care residents with Alzheimer disease (AD). Design Randomized, controlled, single-blinded clinical trial. Setting Residents of 7 long-term care facilities. Participants Eighty-two long-term care residents with mild to severe AD. Intervention An activity specific exercise program was compared to a walking program and to an attention control. Measurements Ability to perform bed mobility and transfers were assessed using the subscales of the Acute Care Index of Function; functional mobility was measured using the 6-Minute Walk test. Results Subjects receiving the activity specific exercise program improved in ability to perform transfers, whereas subjects in the other 2 groups declined. PMID:21937893

Cognitive remediation therapy (CRT) in a specialist inpatient eating disorder service for children and adolescents: CAN-CRT study protocol for a pilot randomised controlled trial.

PubMed

Giombini, Lucia; Nesbitt, Sophie; Cox, Hannah; Foxall, Anna; Sharia, Teo; Easter, Abigail; Tchanturia, Kate

2018-03-26

Research on treatments for young people (YP) with anorexia nervosa (AN) is scarce. Evidence supports the use of cognitive remediation therapy (CRT) to improve central coherence and set-shifting, inefficiencies that can negatively impact on prognosis. The study aims to evaluate the feasibility of individual CRT in an inpatient setting for YP aged 10-18 years with AN and to qualitatively examine YP's and their parents experiences. In a single-centre, pilot, randomised controlled trial, 80 patients aged 10-18 years with AN will be randomly allocated to the immediate or delayed CRT group, in addition to standard treatment. A repeated measures design will be conducted across 3 time points. The data will provide evidence regarding the feasibility of individual CRT in YP with AN, informing directions of further development of CRT. The study is in preparation for a definitive randomised controlled trial. The aim of this manuscript is to describe the study protocol. Copyright © 2018 John Wiley & Sons, Ltd and Eating Disorders Association.

Continuous wound infiltration or epidural analgesia for pain prevention after hepato-pancreato-biliary surgery within an enhanced recovery program (POP-UP trial): study protocol for a randomized controlled trial.

PubMed

Mungroop, Timothy H; Veelo, Denise P; Busch, Olivier R; van Dieren, Susan; van Gulik, Thomas M; Karsten, Tom M; de Castro, Steve M; Godfried, Marc B; Thiel, Bram; Hollmann, Markus W; Lirk, Philipp; Besselink, Marc G

2015-12-09

Postoperative pain prevention is essential for the recovery of surgical patients. Continuous (thoracic) epidural analgesia (CEA) is routinely practiced for major abdominal surgery, but evidence is conflicting on its benefits in this setting. Potential disadvantages of epidural analgesia are a) perioperative hypotension, frequently requiring additional intravenous fluid boluses or prolonged use of vasopressors; b) relatively high failure rates, with periods of inadequate analgesia; and c) the risk of rare but serious, at times persistent, neurologic complications (hematoma and abscess). In recent years, continuous (subfascial) wound infiltration (CWI) plus patient-controlled analgesia (PCA) has been suggested as a safe and reliable alternative, which does not have the previously mentioned disadvantages, but evidence from multicenter trials targeting a specific surgical population is lacking. We hypothesize that CWI+PCA is equally as effective as CEA, without the mentioned disadvantages. POP-UP is a randomized controlled noninferiority multicenter trial, recruiting adult patients scheduled for elective hepato-pancreato-biliary surgery via laparotomy in an enhanced recovery setting. A total of 102 patients are being randomly allocated to CWI+PCA or (P)CEA. Our primary endpoint is the Overall Benefit of Analgesic Score (OBAS), a composite endpoint of pain intensity, opioid-related adverse effects and patient satisfaction, during postoperative days 1 to 5. Secondary endpoints include length of the hospital stay, number of patients with severe pain, and the use of rescue medication. POP-UP is a pragmatic trial that will provide evidence of whether CWI+PCA is noninferior as compared to (P)CEA after elective hepato-pancreato-biliary surgery via laparotomy in an enhanced recovery setting. If this hypothesis is confirmed, this finding could contribute to more widespread implementation of this technique, especially when the described disadvantages of epidural analgesia are less often observed with CWI+PCA. Netherlands Trial Register NTR4948 (registry date 2 January 2015).

Planned hospital birth versus planned home birth

PubMed Central

Olsen, Ole; Clausen, Jette A

2014-01-01

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

Improving decision making about clinical trial participation – a randomised controlled trial of a decision aid for women considering participation in the IBIS-II breast cancer prevention trial

PubMed Central

Juraskova, I; Butow, P; Bonner, C; Bell, M L; Smith, A B; Seccombe, M; Boyle, F; Reaby, L; Cuzick, J; Forbes, J F

2014-01-01

Background: Decision aids may improve informed consent in clinical trial recruitment, but have not been evaluated in this context. This study investigated whether decision aids (DAs) can reduce decisional difficulties among women considering participation in the International Breast Cancer Intervention Study-II (IBIS-II) trial. Methods: The IBIS-II trial investigated breast cancer prevention with anastrazole in two cohorts: women with increased risk (Prevention), and women treated for ductal carcinoma in situ (DCIS). Australia, New Zealand and United Kingdom participants were randomised to receive a DA (DA group) or standard trial consent materials (control group). Questionnaires were completed after deciding about participation in IBIS-II (post decision) and 3 months later (follow-up). Results: Data from 112 Prevention and 34 DCIS participants were analysed post decision (73 DA; 73 control); 95 Prevention and 24 DCIS participants were analysed at follow-up (58 DA; 61 control). There was no effect on the primary outcome of decisional conflict. The DCIS–DA group had higher knowledge post decision, and the Prevention-DA group had lower decisional regret at follow-up. Conclusions: This was the first study to evaluate a DA in the clinical trial setting. The results suggest DAs can potentially increase knowledge and reduce decisional regret about clinical trial participation. PMID:24892447

Clinical trials of homoeopathy.

PubMed Central

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

1991-01-01

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

Tailored Case Management for Diabetes and Hypertension (TEACH-DM) in a community population: study design and baseline sample characteristics.

PubMed

Crowley, Matthew J; Bosworth, Hayden B; Coffman, Cynthia J; Lindquist, Jennifer H; Neary, Alice M; Harris, Amy C; Datta, Santanu K; Granger, Bradi B; Pereira, Katherine; Dolor, Rowena J; Edelman, David

2013-09-01

Despite recognition of the benefits associated with well-controlled diabetes and hypertension, control remains suboptimal. Effective interventions for these conditions have been studied within academic settings, but interventions targeting both conditions have rarely been tested in community settings. We describe the design and baseline results of a trial evaluating a behavioral intervention among community patients with poorly-controlled diabetes and comorbid hypertension. Tailored Case Management for Diabetes and Hypertension (TEACH-DM) is a 24-month randomized, controlled trial evaluating a telephone-delivered behavioral intervention for diabetes and hypertension versus attention control. The study recruited from nine community practices. The nurse-administered intervention targets 3 areas: 1) cultivation of healthful behaviors for diabetes and hypertension control; 2) provision of fundamentals to support attainment of healthful behaviors; and 3) identification and correction of patient-specific barriers to adopting healthful behaviors. Hemoglobin A1c and blood pressure measured at 6, 12, and 24 months are co-primary outcomes. Secondary outcomes include self-efficacy, self-reported medication adherence, exercise, and cost-effectiveness. Of 377 randomized patients, 193 were allocated to the intervention and 184 to attention control. The cohort is balanced in terms of gender, race, education level, and income. The cohort's mean baseline hemoglobin A1c and blood pressure are above goal, and mean baseline body mass index falls in the obese range. Baseline self-reported non-adherence is high for diabetes and hypertension medications. Trial results are pending. If effective, the TEACH-DM intervention's telephone-based delivery strategy and nurse administration make it well-suited for rapid implementation and broad dissemination in community settings. © 2013.

Therapeutic Plasma Transfusion in Bleeding Patients: A Systematic Review.

PubMed

Levy, Jerrold H; Grottke, Oliver; Fries, Dietmar; Kozek-Langenecker, Sibylle

2017-04-01

Plasma products, including fresh frozen plasma, are administered extensively in a variety of settings from massive transfusion to vitamin K antagonist reversal. Despite the widespread use of plasma as a hemostatic agent in bleeding patients, its effect in comparison with other available choices of hemostatic therapies is unclear. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed Central, and databases of ongoing trials for randomized controlled trials that assessed the efficacy and/or safety of therapeutic plasma as an intervention to treat bleeding patients compared with other interventions or placebo. Of 1243 unique publications retrieved in our initial search, no randomized controlled trials were identified. Four nonrandomized studies described the effect of therapeutic plasma in bleeding patients; however, data gathered from these studies did not allow for comparison with other therapeutic interventions primarily as a result of the low number of patients and the use of different (or lack of) comparators. We identified two ongoing trials investigating the efficacy and safety of therapeutic plasma, respectively; however, no data have been released as yet. Although plasma is used extensively in the treatment of bleeding patients, evidence from randomized controlled trials comparing its effect with those of other therapeutic interventions is currently lacking.

Overcoming residual interference in mental set switching: Neural correlates and developmental trajectory

PubMed Central

Witt, Suzanne T.; Stevens, Michael C.

2012-01-01

Mental set switching is a key facet of executive control measured behaviorally through reaction time or accuracy (i.e., ‘switch costs’) when shifting among task types. One of several experimentally-dissociable influences on switch costs is ‘task set inertia’, conceptualized as the residual interference conferred when a previous stimulus-response tendency interferes with subsequent stimulus processing on a new task. Task set inertia is thought to represent the passive decay of the previous stimulus-response set from working memory, and its effects decrease with increased interstimulus interval. Closely spaced trials confer high task set inertia, while sparsely spaced trials confer low task set inertia. This functional magnetic resonance imaging (fMRI) study characterized, for the first time, two opposing brain systems engaged to resolve task set inertia: 1) a frontoparietal ‘cortical control’ network for overcoming high task set inertia interference and 2) a subcortical-motor network more active during trials with low task set inertia. These networks were distinct from brain regions showing general switching effects (i.e., switch > non-switch) and from other previously-characterized interference effects. Moreover, there were ongoing maturational effects throughout adolescence for the brain regions engaged to overcome high task set inertia not seen for generalized switching effects. These novel findings represent a new avenue of exploration of cognitive set switching neural function. PMID:22584223

Can attentional control settings be maintained for two color-location conjunctions? Evidence from an RSVP task.

PubMed

Irons, Jessica L; Remington, Roger W

2013-07-01

Previous investigations of the ability to maintain separate attentional control settings for different spatial locations have relied principally on a go/no-go spatial-cueing paradigm. The results have suggested that control of attention is accomplished only late in processing. However, the go/no-go task does not provide strong incentives to withhold attention from irrelevant color-location conjunctions. We used a modified version of the task in which failing to adopt multiple control settings would be detrimental to performance. Two RSVP streams of colored letters appeared to the left and right of fixation. Participants searched for targets that were a conjunction of color and location, so that the target color for one stream acted as a distractor when presented in the opposite stream. Distractors that did not match the target conjunctions nevertheless captured attention and interfered with performance. This was the case even when the target conjunctions were previewed early in the trial prior to the target (Exp. 2). However, distractor interference was reduced when the upcoming distractor was previewed early on in the trial (Exp. 3). Attentional selection of targets by color-location conjunctions may be effective if facilitative attentional sets are accompanied by the top-down inhibition of irrelevant items.

Lack of Interaction between Sensing-Intuitive Learning Styles and Problem-First versus Information-First Instruction: A Randomized Crossover Trial

ERIC Educational Resources Information Center

Cook, David A.; Thompson, Warren G.; Thomas, Kris G.; Thomas, Matthew R.

2009-01-01

Background: Adaptation to learning styles has been proposed to enhance learning. Objective: We hypothesized that learners with sensing learning style would perform better using a problem-first instructional method while intuitive learners would do better using an information-first method. Design: Randomized, controlled, crossover trial. Setting:…

Does recruitment source moderate treatment effectiveness? A subgroup analysis from the EVIDENT study, a randomised controlled trial of an internet intervention for depressive symptoms

PubMed Central

Gamon, Carla; Späth, Christina; Berger, Thomas; Meyer, Björn; Hohagen, Fritz; Hautzinger, Martin; Lutz, Wolfgang; Vettorazzi, Eik; Moritz, Steffen; Schröder, Johanna

2017-01-01

Objective This study aims to examine whether the effects of internet interventions for depression generalise to participants recruited in clinical settings. Design This study uses subgroup analysis of the results of a randomised, controlled, single-blind trial. Setting The study takes place in five diagnostic centres in Germany. Participants A total of 1013 people with mild to moderate depressive symptoms were recruited from clinical sources as well as internet forums, statutory insurance companies and other sources. Interventions This study uses either care-as-usual alone (control) or a 12-week internet intervention (Deprexis) plus usual care (intervention). Main outcome measures The primary outcome measure was self-rated depression severity (Patient Health Questionnaire-9) at 3 months and 6 months. Further measures ranged from demographic and clinical parameters to a measure of attitudes towards internet interventions (Attitudes towards Psychological Online Interventions Questionnaire). Results The recruitment source was only associated with very few of the examined demographic and clinical characteristics. Compared with participants recruited from clinical sources, participants recruited through insurance companies were more likely to be employed. Clinically recruited participants were as severely affected as those from other recruitment sources but more sceptical of internet interventions. The effectiveness of the intervention was not differentially associated with recruitment source (treatment by recruitment source interaction=0.28, p=0.84). Conclusion Our results support the hypothesis that the intervention we studied is effective across different recruitment sources including clinical settings. Trial registration number ClinicalTrials.gov NCT01636752. PMID:28710212

Muslim communities learning about second-hand smoke (MCLASS): study protocol for a pilot cluster randomised controlled trial.

PubMed

Ainsworth, Hannah; Shah, Sarwat; Ahmed, Faraz; Amos, Amanda; Cameron, Ian; Fairhurst, Caroline; King, Rebecca; Mir, Ghazala; Parrott, Steve; Sheikh, Aziz; Torgerson, David; Thomson, Heather; Siddiqi, Kamran

2013-09-13

In the UK, 40% of Bangladeshi and 29% of Pakistani men smoke cigarettes regularly compared to the national average of 24%. As a consequence, second-hand smoking is also widespread in their households which is a serious health hazard to non-smokers, especially children. Smoking restrictions in households can help reduce exposure to second-hand smoking. This is a pilot trial of 'Smoke Free Homes', an educational programme which has been adapted for use by Muslim faith leaders, in an attempt to find an innovative solution to encourage Pakistani- and Bangladeshi-origin communities to implement smoking restrictions in their homes. The primary objectives for this pilot trial are to establish the feasibility of conducting such an evaluation and provide information to inform the design of a future definitive study. This is a pilot cluster randomised controlled trial of 'Smoke Free Homes', with an embedded preliminary health economic evaluation and a qualitative analysis. The trial will be carried out in around 14 Islamic religious settings. Equal randomisation will be employed to allocate each cluster to a trial arm. The intervention group will be offered the Smoke Free Homes package (Smoke Free Homes: a resource for Muslim religious teachers), trained in its use, and will subsequently implement the package in their religious settings. The remaining clusters will not be offered the package until the completion of the study and will form the control group. At each cluster, we aim to recruit around 50 households with at least one adult resident who smokes tobacco and at least one child or a non-smoking adult. Households will complete a household survey and a non-smoking individual will provide a saliva sample which will be tested for cotinine. All participant outcomes will be measured before and after the intervention period in both arms of the trial. In addition, a purposive sample of participants and religious leaders/teachers will take part in interviews and focus groups. The results of this pilot study will inform the protocol for a definitive trial. Current Controlled Trials ISRCTN03035510.

'In situ simulation' versus 'off site simulation' in obstetric emergencies and their effect on knowledge, safety attitudes, team performance, stress, and motivation: study protocol for a randomized controlled trial.

PubMed

Sørensen, Jette Led; Van der Vleuten, Cees; Lindschou, Jane; Gluud, Christian; Østergaard, Doris; LeBlanc, Vicki; Johansen, Marianne; Ekelund, Kim; Albrechtsen, Charlotte Krebs; Pedersen, Berit Woetman; Kjærgaard, Hanne; Weikop, Pia; Ottesen, Bent

2013-07-17

Unexpected obstetric emergencies threaten the safety of pregnant women. As emergencies are rare, they are difficult to learn. Therefore, simulation-based medical education (SBME) seems relevant. In non-systematic reviews on SBME, medical simulation has been suggested to be associated with improved learner outcomes. However, many questions on how SBME can be optimized remain unanswered. One unresolved issue is how 'in situ simulation' (ISS) versus 'off site simulation' (OSS) impact learning. ISS means simulation-based training in the actual patient care unit (in other words, the labor room and operating room). OSS means training in facilities away from the actual patient care unit, either at a simulation centre or in hospital rooms that have been set up for this purpose. The objective of this randomized trial is to study the effect of ISS versus OSS on individual learning outcome, safety attitude, motivation, stress, and team performance amongst multi-professional obstetric-anesthesia teams.The trial is a single-centre randomized superiority trial including 100 participants. The inclusion criteria were health-care professionals employed at the department of obstetrics or anesthesia at Rigshospitalet, Copenhagen, who were working on shifts and gave written informed consent. Exclusion criteria were managers with staff responsibilities, and staff who were actively taking part in preparation of the trial. The same obstetric multi-professional training was conducted in the two simulation settings. The experimental group was exposed to training in the ISS setting, and the control group in the OSS setting. The primary outcome is the individual score on a knowledge test. Exploratory outcomes are individual scores on a safety attitudes questionnaire, a stress inventory, salivary cortisol levels, an intrinsic motivation inventory, results from a questionnaire evaluating perceptions of the simulation and suggested changes needed in the organization, a team-based score on video-assessed team performance and on selected clinical performance. The perspective is to provide new knowledge on contextual effects of different simulation settings. ClincialTrials.gov NCT01792674.

Effectiveness of a self-management program for dual sensory impaired seniors in aged care settings: study protocol for a cluster randomized controlled trial

PubMed Central

2013-01-01

Background Five to 25 percent of residents in aged care settings have a combined hearing and visual sensory impairment. Usual care is generally restricted to single sensory impairment, neglecting the consequences of dual sensory impairment on social participation and autonomy. The aim of this study is to evaluate the effectiveness of a self-management program for seniors who acquired dual sensory impairment at old age. Methods/Design In a cluster randomized, single-blind controlled trial, with aged care settings as the unit of randomization, the effectiveness of a self-management program will be compared to usual care. A minimum of 14 and maximum of 20 settings will be randomized to either the intervention cluster or the control cluster, aiming to include a total of 132 seniors with dual sensory impairment. Each senior will be linked to a licensed practical nurse working at the setting. During a five to six month intervention period, nurses at the intervention clusters will be trained in a self-management program to support and empower seniors to use self-management strategies. In two separate diaries, nurses keep track of the interviews with the seniors and their reflections on their own learning process. Nurses of the control clusters offer care as usual. At senior level, the primary outcome is the social participation of the seniors measured using the Hearing Handicap Questionnaire and the Activity Card Sort, and secondary outcomes are mood, autonomy and quality of life. At nurse level, the outcome is job satisfaction. Effectiveness will be evaluated using linear mixed model analysis. Discussion The results of this study will provide evidence for the effectiveness of the Self-Management Program for seniors with dual sensory impairment living in aged care settings. The findings are expected to contribute to the knowledge on the program’s potential to enhance social participation and autonomy of the seniors, as well as increasing the job satisfaction of the licensed practical nurses. Furthermore, an extensive process evaluation will take place which will offer insight in the quality and feasibility of the sampling and intervention process. If it is shown to be effective and feasible, this Self-Management Program could be widely disseminated. Clinical trials registration ClinicalTrials.gov, NCT01217502. PMID:24099315

Effects of methylphenidate on attentional set-shifting in a genetic model of attention-deficit/hyperactivity disorder.

PubMed

Cao, Ai-hua; Yu, Lin; Wang, Yu-wei; Wang, Jun-mei; Yang, Le-jin; Lei, Ge-Fei

2012-02-28

Although deficits of attentional set-shifting have been reported in individuals with attention deficit/hyperactivity disorder (ADHD), it is rarely examined in animal models. This study compared spontaneously hypertensive rats (SHRs; a genetic animal model of ADHD) and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats (normoactive control strains), on attentional set-shifting task (ASST) performance. Furthermore, the dose-effects of methylphenidate (MPH) on attentional set-shifting of SHR were investigated. In experiment 1, ASST procedures were conducted in SHR, WKY and SD rats of 8 each at the age of 5 weeks. Mean latencies at the initial phase, error types and numbers, and trials to criteria at each stage were recorded. In experiment 2, 24 SHR rats were randomly assigned to 3 groups of 8 each-- MPH-L (lower dose), MPH-H (higher dose), and SHR-vehicle groups. From 3 weeks, they were administered 2.5 mg/kg or 5 mg/kg MPH or saline respectively for 14 consecutive days. All rats were tested in the ASST at the age of 5 weeks. The SHRs generally exhibited poorer performance on ASST than the control WKY and SD rats. Significant strain effects on mean latency [F (2, 21) = 639.636, p < 0.001] and trials to criterion [F (2, 21) = 114.118, p < 0.001] were observed. The SHRs were found to have more perseverative and regressive errors than the control strains (p < 0.001). After MPH treatment, the two MPH treated groups exhibited significantly longer latency and fewer trials to reach criterion than the SHR-vehicle group and the MPH-L group exhibited fewer trials to reach criterion in more stages compared with the MPH-H group. Significant main effects of treatment [F (2, 21) = 52.174, p < 0.001] and error subtype [F (2, 42) = 221.635, p < 0.01] were found. The SHR may be impaired in discrimination learning, reversal learning and attentional set-shifting. Our study provides evidence that MPH may improve the SHR's performance on attentional set-shifting and lower dose is more effective than higher dose.

Effects of methylphenidate on attentional set-shifting in a genetic model of attention-deficit/hyperactivity disorder

PubMed Central

2012-01-01

Background Although deficits of attentional set-shifting have been reported in individuals with attention deficit/hyperactivity disorder (ADHD), it is rarely examined in animal models. Methods This study compared spontaneously hypertensive rats (SHRs; a genetic animal model of ADHD) and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats (normoactive control strains), on attentional set-shifting task (ASST) performance. Furthermore, the dose-effects of methylphenidate (MPH) on attentional set-shifting of SHR were investigated. In experiment 1, ASST procedures were conducted in SHR, WKY and SD rats of 8 each at the age of 5 weeks. Mean latencies at the initial phase, error types and numbers, and trials to criteria at each stage were recorded. In experiment 2, 24 SHR rats were randomly assigned to 3 groups of 8 each-- MPH-L (lower dose), MPH-H (higher dose), and SHR-vehicle groups. From 3 weeks, they were administered 2.5 mg/kg or 5 mg/kg MPH or saline respectively for 14 consecutive days. All rats were tested in the ASST at the age of 5 weeks. Results The SHRs generally exhibited poorer performance on ASST than the control WKY and SD rats. Significant strain effects on mean latency [F (2, 21) = 639.636, p < 0.001] and trials to criterion [F (2, 21) = 114.118, p < 0.001] were observed. The SHRs were found to have more perseverative and regressive errors than the control strains (p < 0.001). After MPH treatment, the two MPH treated groups exhibited significantly longer latency and fewer trials to reach criterion than the SHR-vehicle group and the MPH-L group exhibited fewer trials to reach criterion in more stages compared with the MPH-H group. Significant main effects of treatment [F (2, 21) = 52.174, p < 0.001] and error subtype [F (2, 42) = 221.635, p < 0.01] were found. Conclusions The SHR may be impaired in discrimination learning, reversal learning and attentional set-shifting. Our study provides evidence that MPH may improve the SHR's performance on attentional set-shifting and lower dose is more effective than higher dose. PMID:22369105

Artificial Pancreas Device Systems for the Closed-Loop Control of Type 1 Diabetes: What Systems Are in Development?

PubMed

Trevitt, Sara; Simpson, Sue; Wood, Annette

2016-05-01

Closed-loop artificial pancreas device (APD) systems are externally worn medical devices that are being developed to enable people with type 1 diabetes to regulate their blood glucose levels in a more automated way. The innovative concept of this emerging technology is that hands-free, continuous, glycemic control can be achieved by using digital communication technology and advanced computer algorithms. A horizon scanning review of this field was conducted using online sources of intelligence to identify systems in development. The systems were classified into subtypes according to their level of automation, the hormonal and glycemic control approaches used, and their research setting. Eighteen closed-loop APD systems were identified. All were being tested in clinical trials prior to potential commercialization. Six were being studied in the home setting, 5 in outpatient settings, and 7 in inpatient settings. It is estimated that 2 systems may become commercially available in the EU by the end of 2016, 1 during 2017, and 2 more in 2018. There are around 18 closed-loop APD systems progressing through early stages of clinical development. Only a few of these are currently in phase 3 trials and in settings that replicate real life. © 2015 Diabetes Technology Society.

A novel community-based study to address disparities in hypertension and colorectal cancer: a study protocol for a randomized control trial

PubMed Central

2013-01-01

Background Black men have the greatest burden of premature death and disability from hypertension (HTN) in the United States, and the highest incidence and mortality from colorectal cancer (CRC). While several clinical trials have reported beneficial effects of lifestyle changes on blood pressure (BP) reduction, and improved CRC screening with patient navigation (PN), the effectiveness of these approaches in community-based settings remains understudied, particularly among Black men. Methods/design MISTER B is a two-parallel-arm randomized controlled trial that will compare the effect of a motivational interviewing tailored lifestyle intervention (MINT) versus a culturally targeted PN intervention on improvement of BP and CRC screening among black men aged ≥50 with uncontrolled HTN who are eligible for CRC screening. Approximately 480 self-identified black men will be randomly assigned to one of the two study conditions. This innovative research design allows each intervention to serve as the control for the other. Specifically, the MINT arm is the control condition for the PN arm, and vice-versa. This novel, simultaneous testing of two community-based interventions in a randomized fashion is an economical and yet rigorous strategy that also enhances the acceptability of the project. Participants will be recruited during scheduled screening events at barbershops in New York City. Trained research assistants will conduct the lifestyle intervention, while trained community health workers will deliver the PN intervention. The primary outcomes will be 1) within-patient change in systolic and diastolic BP from baseline to six months and 2) CRC screening rates at six months. Discussion This innovative study will provide a unique opportunity to test two interventions for two health disparities simultaneously in community-based settings. Our study is one of the first to test culturally targeted patient navigation for CRC screening among black men in barbershops. Thus, our study has the potential to improve the reach of hypertension control and cancer prevention efforts within a high-risk population that is under-represented in primary care settings. Trial registration ClinicalTrials.gov, NCT01092078 PMID:24011142

Are There Scenarios When the Use of Non-Placebo-Control Groups in Experimental Trial Designs Increase Expected Value to Society?

PubMed

Uyei, Jennifer; Braithwaite, R Scott

2016-01-01

Despite the benefits of the placebo-controlled trial design, it is limited by its inability to quantify total benefits and harms. Such trials, for example, are not designed to detect an intervention's placebo or nocebo effects, which if detected could alter the benefit-to-harm balance and change a decision to adopt or reject an intervention. In this article, we explore scenarios in which alternative experimental trial designs, which differ in the type of control used, influence expected value across a range of pretest assumptions and study sample sizes. We developed a decision model to compare 3 trial designs and their implications for decision making: 2-arm placebo-controlled trial ("placebo-control"), 2-arm intervention v. do nothing trial ("null-control"), and an innovative 3-arm trial design: intervention v. do nothing v. placebo trial ("novel design"). Four scenarios were explored regarding particular attributes of a hypothetical intervention: 1) all benefits and no harm, 2) no biological effect, 3) only biological effects, and 4) surreptitious harm (no biological benefit or nocebo effect). Scenario 1: When sample sizes were very small, the null-control was preferred, but as sample sizes increased, expected value of all 3 designs converged. Scenario 2: The null-control was preferred regardless of sample size when the ratio of placebo to nocebo effect was >1; otherwise, the placebo-control was preferred. Scenario 3: When sample size was very small, the placebo-control was preferred when benefits outweighed harms, but the novel design was preferred when harms outweighed benefits. Scenario 4: The placebo-control was preferred when harms outweighed placebo benefits; otherwise, preference went to the null-control. Scenarios are hypothetical, study designs have not been tested in a real-world setting, blinding is not possible in all designs, and some may argue the novel design poses ethical concerns. We identified scenarios in which alternative experimental study designs would confer greater expected value than the placebo-controlled trial design. The likelihood and prevalence of such situations warrant further study. © The Author(s) 2015.

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

PubMed

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

2016-09-01

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

Protocol for a randomised controlled trial of a web-based healthy relationship tool and safety decision aid for women experiencing domestic violence (I-DECIDE).

PubMed

Hegarty, Kelsey; Tarzia, Laura; Murray, Elizabeth; Valpied, Jodie; Humphreys, Cathy; Taft, Angela; Gold, Lisa; Glass, Nancy

2015-08-01

Domestic violence is a serious problem affecting the health and wellbeing of women globally. Interventions in health care settings have primarily focused on screening and referral, however, women often may not disclose abuse to health practitioners. The internet offers a confidential space in which women can assess the health of their relationships and make a plan for safety and wellbeing for themselves and their children. This randomised controlled trial is testing the effectiveness of a web-based healthy relationship tool and safety decision aid (I-DECIDE). Based broadly on the IRIS trial in the United States, it has been adapted for the Australian context where it is conducted entirely online and uses the Psychosocial Readiness Model as the basis for the intervention. In this two arm, pragmatic randomised controlled trial, women who have experienced abuse or fear of a partner in the previous 6 months will be computer randomised to receive either the I-DECIDE website or a comparator website (basic relationship and safety advice). The intervention includes self-directed reflection exercises on their relationship, danger level, priority setting, and results in an individualised, tailored action plan. Primary self-reported outcomes are: self-efficacy (General Self-Efficacy Scale) immediately after completion, 6 and 12 months post-baseline; and depressive symptoms (Centre for Epidemiologic Studies Depression Scale, Revised, 6 and 12 months post-baseline). Secondary outcomes include mean number of helpful actions for safety and wellbeing, mean level of fear of partner and cost-effectiveness. This fully-automated trial will evaluate a web-based self-information, self-reflection and self-management tool for domestic violence. We hypothesise that the improvement in self-efficacy and mental health will be mediated by increased perceived support and awareness encouraging positive change. If shown to be effective, I-DECIDE could be easily incorporated into the community sector and health care settings, providing an alternative to formal services for women not ready or able to acknowledge abuse and access specialised services. Trial registered on 15(th) December 2014 with the Australian New Zealand Clinical Trials Registry ACTRN12614001306606.

Psychological therapy for inpatients receiving acute mental health care: A systematic review and meta-analysis of controlled trials.

PubMed

Paterson, Charlotte; Karatzias, Thanos; Dickson, Adele; Harper, Sean; Dougall, Nadine; Hutton, Paul

2018-04-16

The effectiveness of psychological therapies for those receiving acute adult mental health inpatient care remains unclear, partly because of the difficulty in conducting randomized controlled trials (RCTs) in this setting. The aim of this meta-analysis was to synthesize evidence from all controlled trials of psychological therapy carried out with this group, to estimate its effects on a number of important outcomes and examine whether the presence of randomization and rater blinding moderated these estimates. A systematic review and meta-analysis of all controlled trials of psychological therapy delivered in acute inpatient settings was conducted, with a focus on psychotic symptoms, readmissions or emotional distress (anxiety and depression). Studies were identified through ASSIA, EMBASE, CINAHL, Cochrane, MEDLINE, and PsycINFO using a combination of the key terms 'inpatient', 'psychological therapy', and 'acute'. No restriction was placed on diagnosis. The moderating effect of the use of assessor-blind RCT methodology was examined via subgroup and sensitivity analyses. Overall, psychological therapy was associated with small-to-moderate improvements in psychotic symptoms at end of therapy but the effect was smaller and not significant at follow-up. Psychological therapy was also associated with reduced readmissions, depression, and anxiety. The use of single-blind randomized controlled trial methodology was associated with significantly reduced benefits on psychotic symptoms and was also associated with reduced benefits on readmission and depression; however, these reductions were not statistically significant. The provision of psychological therapy to acute psychiatric inpatients is associated with improvements; however, the use of single-blind RCT methodology was associated with reduced therapy-attributable improvements. Whether this is a consequence of increased internal validity or reduced external validity is unclear. Trials with both high internal and external validity are now required to establish what type, format, and intensity of brief psychological therapy is required to achieve sustained benefits. Clinical implications: This review provides the first meta-analytical synthesis of brief psychological therapy delivered in acute psychiatric inpatient settings. This review suggests that brief psychological therapy may be associated with reduced emotional distress and readmissions. The evidence in this review is of limited quality. The type, format, and intensity of brief psychological therapy required to achieve sustained benefits are yet to be established. © 2018 The British Psychological Society.

Simultaneous vs. sequential treatment for smoking and weight management in tobacco quitlines: 6 and 12 month outcomes from a randomized trial.

PubMed

Bush, Terry; Lovejoy, Jennifer; Javitz, Harold; Torres, Alula Jimenez; Wassum, Ken; Tan, Marcia M; Spring, Bonnie

2018-05-31

Smoking cessation often results in weight gain which discourages many smokers from quitting and can increase health risks. Treatments to reduce cessation-related weight gain have been tested in highly controlled trials of in-person treatment, but have never been tested in a real-world setting, which has inhibited dissemination. The Best Quit Study (BQS) is a replication and "real world" translation using telephone delivery of a prior in-person efficacy trial. randomized control trial in a quitline setting. Eligible smokers (n = 2540) were randomized to the standard 5-call quitline intervention or quitline plus simultaneous or sequential weight management. Regression analyses tested effectiveness of treatments on self-reported smoking abstinence and weight change at 6 and 12 months. Study enrollees were from 10 commercial employer groups and three state quitlines. Participants were between ages 18-72, 65.8% female, 68.2% white; 23.0% Medicaid-insured, and 76.3% overweight/obese. The follow-up response rate was lower in the simultaneous group than the control group at 6 months (p = 0.01). While a completers analysis of 30-day point prevalence abstinence detected no differences among groups at 6 or 12 months, multiply imputed abstinence showed quit rate differences at 6 months for:simultaneous (40.3%) vs. sequential (48.3%), p = 0.034 and simultaneous vs. control (44.9%), p = 0.043. At 12 months, multiply imputed abstinence, was significantly lower for the simultaneous group (40.7%) vs. control (46.0%), p < 0.05 and vs. sequential (46.3%), p < 0.05. Weight gain at 6 and 12 months was minimal and not different among treatment groups. The sequential group completed fewer total calls (3.75) vs. control (4.16) and vs. simultaneous group (3.83), p = 0.01, and fewer weight calls (0.94) than simultaneous (2.33), p < 0.0001. The number of calls completed predicted 30-day abstinence, p < 0.001, but not weight outcomes. This study offers a model for evaluating population-level public health interventions conducted in partnership with tobacco quitlines. Simultaneous (vs. sequential) delivery of phone/web weight management with cessation treatment in the quitline setting may adversely affect quit rate. Neither a simultaneous nor sequential approach to addressing weight produced any benefit on suppressing weight gain. This study highlights the need and the challenges of testing intensive interventions in real-world settings. ClinicalTrials.gov Identifier: NCT01867983 . Registered: May 30, 2013.

Addressing standards of care in resource-limited settings.

PubMed

Dawson, Liza; Klingman, Karin L; Marrazzo, Jeanne

2014-01-01

: The choice between "best-known" standards of care (SOC) or "best available" standards as the control arm in a clinical trial is a fundamental dilemma in clinical research in resource-limited settings (RLS). When the health system is delivering less than an optimal level of care, using highest standard of care in a clinical trial may produce results that cannot be implemented or sustained locally. On the other hand, using interventions that are more feasible in the local setting may involve suboptimal care, and clinical outcomes may be affected. The need for improved standards in health systems in RLS, and the difficulty in securing them, has led many researchers advocate for policy changes at the national or international level to improve clinical care more systemically. SOC decisions in a clinical trial affect the level of benefit provided to study participants and the policy implications of the trial findings. SOC choices should provide high-quality care to help advance the health care system in host countries participating in the trial, but balancing the scientific and ethical objectives of SOC choices is difficult, and there is no single formula for selecting the appropriate SOC. Despite the challenges, well-designed and conducted clinical trials can and should make significant contributions to health systems in RLS.

[Shared decision-making and individualized goal setting - a pilot trial using PRISM (Pictorial Representation of Illness and Self Measure) in psychiatric inpatients].

PubMed

Büchi, S; Straub, S; Schwager, U

2010-12-01

Although there is much talk about shared decision making and individualized goal setting, there is a lack of knowledge and knowhow in their realization in daily clinical practice. There is a lack in tools for easy applicable tools to ameliorate person-centred individualized goal setting processes. In three selected psychiatric inpatients the semistructured, theory driven use of PRISM (Pictorial Representation of Illness and Self Measure) in patients with complex psychiatric problems is presented and discussed. PRISM sustains a person-centred individualized process of goal setting and treatment and reinforces the active participation of patients. The process of visualisation and synchronous documentation is validated positively by patients and clinicians. The visual goal setting requires 30 to 45 minutes. In patients with complex psychiatric illness PRISM was used successfully to ameliorate individual goal setting. Specific effects of PRISM-visualisation are actually evaluated in a randomized controlled trial.

Effect of Newborn Resuscitation Training on Health Worker Practices in Pumwani Hospital, Kenya

PubMed Central

Opiyo, Newton; Were, Fred; Govedi, Fridah; Fegan, Greg; Wasunna, Aggrey; English, Mike

2008-01-01

Background Birth asphyxia kills 0.7 to 1.6 million newborns a year globally with 99% of deaths in developing countries. Effective newborn resuscitation could reduce this burden of disease but the training of health-care providers in low income settings is often outdated. Our aim was to determine if a simple one day newborn resuscitation training (NRT) alters health worker resuscitation practices in a public hospital setting in Kenya. Methods/Principal Findings We conducted a randomised, controlled trial with health workers receiving early training with NRT (n = 28) or late training (the control group, n = 55). The training was adapted locally from the approach of the UK Resuscitation Council. The primary outcome was the proportion of appropriate initial resuscitation steps with the frequency of inappropriate practices as a secondary outcome. Data were collected on 97 and 115 resuscitation episodes over 7 weeks after early training in the intervention and control groups respectively. Trained providers demonstrated a higher proportion of adequate initial resuscitation steps compared to the control group (trained 66% vs control 27%; risk ratio 2.45, [95% CI 1.75–3.42], p<0.001, adjusted for clustering). In addition, there was a statistically significant reduction in the frequency of inappropriate and potentially harmful practices per resuscitation in the trained group (trained 0.53 vs control 0.92; mean difference 0.40, [95% CI 0.13–0.66], p = 0.004). Conclusions/Significance Implementation of a simple, one day newborn resuscitation training can be followed immediately by significant improvement in health workers' practices. However, evidence of the effects on long term performance or clinical outcomes can only be established by larger cluster randomised trials. Trial Registration Controlled-Trials.com ISRCTN92218092 PMID:18270586

Reward Motivation Enhances Task Coding in Frontoparietal Cortex

PubMed Central

Etzel, Joset A.; Cole, Michael W.; Zacks, Jeffrey M.; Kay, Kendrick N.; Braver, Todd S.

2016-01-01

Reward motivation often enhances task performance, but the neural mechanisms underlying such cognitive enhancement remain unclear. Here, we used a multivariate pattern analysis (MVPA) approach to test the hypothesis that motivation-related enhancement of cognitive control results from improved encoding and representation of task set information. Participants underwent two fMRI sessions of cued task switching, the first under baseline conditions, and the second with randomly intermixed reward incentive and no-incentive trials. Information about the upcoming task could be successfully decoded from cue-related activation patterns in a set of frontoparietal regions typically associated with task control. More critically, MVPA classifiers trained on the baseline session had significantly higher decoding accuracy on incentive than non-incentive trials, with decoding improvement mediating reward-related enhancement of behavioral performance. These results strongly support the hypothesis that reward motivation enhances cognitive control, by improving the discriminability of task-relevant information coded and maintained in frontoparietal brain regions. PMID:25601237

Three nested randomized controlled trials of peer-only or multiple stakeholder group feedback within Delphi surveys during core outcome and information set development.

PubMed

Brookes, Sara T; Macefield, Rhiannon C; Williamson, Paula R; McNair, Angus G; Potter, Shelley; Blencowe, Natalie S; Strong, Sean; Blazeby, Jane M

2016-08-17

Methods for developing a core outcome or information set require involvement of key stakeholders to prioritise many items and achieve agreement as to the core set. The Delphi technique requires participants to rate the importance of items in sequential questionnaires (or rounds) with feedback provided in each subsequent round such that participants are able to consider the views of others. This study examines the impact of receiving feedback from different stakeholder groups, on the subsequent rating of items and the level of agreement between stakeholders. Randomized controlled trials were nested within the development of three core sets each including a Delphi process with two rounds of questionnaires, completed by patients and health professionals. Participants rated items from 1 (not essential) to 9 (absolutely essential). For round 2, participants were randomized to receive feedback from their peer stakeholder group only (peer) or both stakeholder groups separately (multiple). Decisions as to which items to retain following each round were determined by pre-specified criteria. Whilst type of feedback did not impact on the percentage of items for which a participant subsequently changed their rating, or the magnitude of change, it did impact on items retained at the end of round 2. Each core set contained discordant items retained by one feedback group but not the other (3-22 % discordant items). Consensus between patients and professionals in items to retain was greater amongst those receiving multiple group feedback in each core set (65-82 % agreement for peer-only feedback versus 74-94 % for multiple feedback). In addition, differences in round 2 scores were smaller between stakeholder groups receiving multiple feedback than between those receiving peer group feedback only. Variability in item scores across stakeholders was reduced following any feedback but this reduction was consistently greater amongst the multiple feedback group. In the development of a core outcome or information set, providing feedback within Delphi questionnaires from all stakeholder groups separately may influence the final core set and improve consensus between the groups. Further work is needed to better understand how participants rate and re-rate items within a Delphi process. The three randomized controlled trials reported here were each nested within the development of a core information or outcome set to investigate processes in core outcome and information set development. Outcomes were not health-related and therefore trial registration was not applicable.

Safety of discontinuing cotrimoxazole prophylaxis among HIV infected adults on anti-retroviral therapy in Uganda (COSTOP trial): Design.

PubMed

Anywaine, Zacchaeus; Abaasa, Andrew; Levin, Jonathan; Kasirye, Ronnie; Kamali, Anatoli; Grosskurth, Heiner; Munderi, Paula; Nunn, Andrew

2015-07-01

Cotrimoxazole (CTX) prophylaxis is recommended by the World Health Organisation for HIV infected persons. However, once HIV infected patients have commenced ART in resource limited settings, the benefits of continued CTX prophylaxis are not known. The few studies that investigated the safety of discontinuing CTX prophylaxis in these settings had limitations due to their design. COSTOP is a randomised double blind placebo controlled non-inferiority trial among HIV infected Ugandan adults stabilised on anti-retroviral treatment (ART). Participants with CD4 count of 250 or more cells/mm(3) are randomised to two arms: the intervention arm in which CTX is discontinued and the control arm in which CTX prophylaxis is continued. The study aims to assess whether the intervention regimen is not inferior, with respect to the incidence of pre-defined CTX-preventable events, to the control regimen and superior with respect to the incidence of haematological adverse events. Studies that have previously evaluated the safety of discontinuing CTX prophylaxis among HIV infected adults in resource limited settings have provided moderate to low quality evidence owing in part to methodological limitations. COSTOP is designed and conducted with sufficient rigour to answer this question. The results of the trial will assist in guiding policy recommendations. This paper describes the design and methodological considerations important for the conduct of CTX cessation studies. Copyright © 2015. Published by Elsevier Inc.

Servo-control for maintaining abdominal skin temperature at 36C in low birth weight infants.

PubMed

Sinclair, J C

2000-01-01

Randomized trials have shown that the neonatal mortality rate of low birth-weight babies can be reduced by keeping them warm. For low birth-weight babies nursed in incubators, warm conditions may be achieved either by heating the air to a desired temperature, or by servo-controlling the baby's body temperature at a desired set-point. In low birth weight infants, to determine the effect on death and other important clinical outcomes of targeting body temperature rather than air temperature as the end-point of control of incubator heating. Standard search strategy of the Cochrane Neonatal Collaborative Review Group. Randomized or quasi-randomized trials which test the effects of having the heat output of the incubator servo-controlled from body temperature compared with setting a constant incubator air temperature. Trial methodologic quality was systematically assessed. Outcome measures included death, timing of death, cause of death, and other clinical outcomes. Categorical outcomes were analyzed using relative risk and risk difference. Meta-analysis assumed a fixed effect model. Compared to setting a constant incubator air temperature of 31.8C, servo-control of abdominal skin temperature at 36C reduces the neonatal death rate among low birth weight infants: relative risk 0.72 (95% CI 0.54, 0.97); risk difference -12.7% (95% CI -1.6, -23.9). This effect is even greater among VLBW infants. During at least the first week after birth, low birth weight babies should be provided with a carefully regulated thermal environment that is near the thermoneutral point. For LBW babies in incubators, this can be achieved by adjusting incubator temperature to maintain an anterior abdominal skin temperature of at least 36C, using either servo-control or frequent manual adjustment of incubator air temperature.

Surgical “Placebo” Controls

PubMed Central

Tenery, Robert; Rakatansky, Herbert; Riddick, Frank A.; Goldrich, Michael S.; Morse, Leonard J.; O’Bannon, John M.; Ray, Priscilla; Smalley, Sherie; Weiss, Matthew; Kao, Audiey; Morin, Karine; Maixner, Andrew; Seiden, Sam

2002-01-01

Objective To set ethical guidelines on the use of surgical placebo controls in the design of surgical trials. Background Data Ethical concerns recently arose from surgical trials where subjects in the control arm underwent surgical procedures that had the appearance of a therapeutic intervention, but during which the essential therapeutic maneuver was omitted. Although there are ethical guidelines on the use of a placebo in drug trials, little attention has been paid to the use of a surgical placebo control in surgical trials. Methods The Council on Ethical and Judicial Affairs developed ethical guidelines based on a wide literature search and consultation with experts. Results Surgical placebo controls should be limited to studies of new surgical procedures aimed at treating diseases that are not amenable to other surgical therapies, and are reasonably anticipated to be susceptible to substantial placebo effects. If the standard nonsurgical treatment is efficacious and acceptable to the patient, then it must be offered as part of the study design. Conclusions Surgical placebo controls should be used only when no other trial design will yield the requisite data and should always be accompanied by a rigorous informed consent process and a careful consideration of the related risks and benefits. The recommended ethical guidelines were adopted as AMA ethics policy and are now incorporated in the AMA’s Code of Medical Ethics. PMID:11807373

Exercise and mental health: a review.

PubMed

Glenister, D

1996-02-01

With the advent of programmes to raise the level of fitness in the general population, and alliances between primary health care and community leisure services, the potential of exercise in promoting mental as well as physical health deserves investigation. In contrast to USA and continental Europe, there is a paucity of British research studies systematically exploring the mental health benefits of exercise. The recent rapid growth of exercise prescription among general practitioners presents an opportunity for future research. This review of eleven randomised control trials (RCTs) suggests a causal relationship between exercise and mental health based upon studies in various settings. The methodological difficulties associated with randomised control trials of psycho-social interventions are discussed. The value of future randomised control trials which incorporate examination of perceived acceptability and health economics is indicated.

A Bayesian-frequentist two-stage single-arm phase II clinical trial design.

PubMed

Dong, Gaohong; Shih, Weichung Joe; Moore, Dirk; Quan, Hui; Marcella, Stephen

2012-08-30

It is well-known that both frequentist and Bayesian clinical trial designs have their own advantages and disadvantages. To have better properties inherited from these two types of designs, we developed a Bayesian-frequentist two-stage single-arm phase II clinical trial design. This design allows both early acceptance and rejection of the null hypothesis ( H(0) ). The measures (for example probability of trial early termination, expected sample size, etc.) of the design properties under both frequentist and Bayesian settings are derived. Moreover, under the Bayesian setting, the upper and lower boundaries are determined with predictive probability of trial success outcome. Given a beta prior and a sample size for stage I, based on the marginal distribution of the responses at stage I, we derived Bayesian Type I and Type II error rates. By controlling both frequentist and Bayesian error rates, the Bayesian-frequentist two-stage design has special features compared with other two-stage designs. Copyright © 2012 John Wiley & Sons, Ltd.

Virtual Reality and Medical Inpatients: A Systematic Review of Randomized, Controlled Trials

PubMed Central

Dascal, Julieta; Reid, Mark; IsHak, Waguih William; Spiegel, Brennan; Recacho, Jennifer; Rosen, Bradley

2017-01-01

Objective: We evaluated the evidence supporting the use of virtual reality among patients in acute inpatient medical settings. Method: We conducted a systematic review of randomized controlled trials conducted that examined virtual reality applications in inpatient medical settings between 2005 and 2015. We used PsycINFO, PubMed, and Medline databases to identify studies using the keywords virtual reality, VR therapy, treatment, and inpatient. Results: We identified 2,024 citations, among which 11 met criteria for inclusion. Studies addressed three general areas: pain management, eating disorders, and cognitive and motor rehabilitation. Studies were small and heterogeneous and utilized different designs and measures. Virtual reality was generally well tolerated by patients, and a majority of studies demonstrated clinical efficacy. Studies varied in quality, as measured by an evaluation metric developed by Reisch, Tyson, and Mize (average quality score=0.87; range=0.78–0.96). Conclusion: Virtual reality is a promising intervention with several potential applications in the inpatient medical setting. Studies to date demonstrate some efficacy, but there is a need for larger, well-controlled studies to show clinical and cost-effectiveness. PMID:28386517

Virtual Reality and Medical Inpatients: A Systematic Review of Randomized, Controlled Trials.

PubMed

Dascal, Julieta; Reid, Mark; IsHak, Waguih William; Spiegel, Brennan; Recacho, Jennifer; Rosen, Bradley; Danovitch, Itai

2017-01-01

Objective: We evaluated the evidence supporting the use of virtual reality among patients in acute inpatient medical settings. Method: We conducted a systematic review of randomized controlled trials conducted that examined virtual reality applications in inpatient medical settings between 2005 and 2015. We used PsycINFO, PubMed, and Medline databases to identify studies using the keywords virtual reality , VR therapy , treatment , and inpatient. Results: We identified 2,024 citations, among which 11 met criteria for inclusion. Studies addressed three general areas: pain management, eating disorders, and cognitive and motor rehabilitation. Studies were small and heterogeneous and utilized different designs and measures. Virtual reality was generally well tolerated by patients, and a majority of studies demonstrated clinical efficacy. Studies varied in quality, as measured by an evaluation metric developed by Reisch, Tyson, and Mize (average quality score=0.87; range=0.78-0.96). Conclusion: Virtual reality is a promising intervention with several potential applications in the inpatient medical setting. Studies to date demonstrate some efficacy, but there is a need for larger, well-controlled studies to show clinical and cost-effectiveness.

Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations.

PubMed Central

Webster, Lucy; Groskreutz, Derek; Grinbergs-Saull, Anna; Howard, Rob; O'Brien, John T; Mountain, Gail; Banerjee, Sube; Woods, Bob; Perneczky, Robert; Lafortune, Louise; Roberts, Charlotte; McCleery, Jenny; Pickett, James; Bunn, Frances; Challis, David; Charlesworth, Georgina; Featherstone, Katie; Fox, Chris; Goodman, Claire; Jones, Roy; Lamb, Sallie; Moniz-Cook, Esme; Schneider, Justine; Shepperd, Sasha; Surr, Claire; Thompson-Coon, Jo; Ballard, Clive; Brayne, Carol; Burke, Orlaith; Burns, Alistair; Clare, Linda; Garrard, Peter; Kehoe, Patrick; Passmore, Peter; Holmes, Clive; Maidment, Ian; Murtagh, Fliss; Robinson, Louise; Livingston, Gill

2017-01-01

BACKGROUND There is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials. OBJECTIVES To agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI). DATA SOURCES We included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1; (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016; and (3) hand-searches of reference lists of relevant systematic reviews from database searches. REVIEW METHODS The project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We divided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core set of outcomes. RESULTS We included 149 papers from the 22,918 papers screened, referring to 125 individual trials. Eighty-one outcomes were used across trials, including 72 scales [31 cognitive, 12 activities of daily living (ADLs), 10 global, 16 neuropsychiatric and three quality of life] and nine biological techniques. We consulted with 18 people for PPI. The conference decided that only cognition and biological markers are core measures of disease modification. Cognition should be measured by the Mini Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog), and brain changes through structural magnetic resonance imaging (MRI) in a subset of participants. All other domains are important but not core. We recommend using the Neuropsychiatric Inventory for neuropsychiatric symptoms: the Disability Assessment for Dementia for ADLs, the Dementia Quality of Life Measure for quality of life and the Clinical Dementia Rating scale to measure dementia globally. LIMITATIONS Most of the trials included participants with Alzheimer's disease, so recommendations may not apply to other types of dementia. We did not conduct economic analyses. The PPI consultation was limited to members of the Alzheimer's Society Research Network. CONCLUSIONS Cognitive outcomes and biological markers form the core outcome set for future disease modification trials, measured by the MMSE or ADAS-Cog, and structural MRI in a subset of participants. FUTURE WORK We envisage that the core set may be superseded in the future, particularly for other types of dementia. There is a need to develop an algorithm to compare scores on the MMSE and ADAS-Cog. STUDY REGISTRATION The project was registered with Core Outcome Measures in Effectiveness Trials [ www.comet-initiative.org/studies/details/819?result=true (accessed 7 April 2016)]. The systematic review protocol is registered as PROSPERO CRD42015027346. FUNDING The National Institute for Health Research Health Technology Assessment programme. PMID:28625273

Screening Children for Family Violence: A Review of the Evidence for the US Preventive Services Task Force

PubMed Central

Nygren, Peggy; Nelson, Heidi D.; Klein, Jonathan

2004-01-01

BACKGROUND We wanted to evaluate the benefits and harms of screening children in primary health care settings for abuse and neglect resulting from family violence by examining the evidence on the performance of screening instruments and the effectiveness of interventions. METHODS We searched for relevant studies in MEDLINE, PsycINFO, CINAHL, ERIC, Cochrane Controlled Trials Register, and reference lists. English language abstracts with original data about family violence against children focusing on screening and interventions initiated or based in health care settings were included. We extracted selected information about study design, patient populations and settings, methods of assessment or intervention, and outcome measures, and applied a set of criteria to evaluate study quality. RESULTS All instruments designed to screen for child abuse and neglect were directed to parents, particularly pregnant women. These instruments had fairly high sensitivity but low specificity when administered in high-risk study populations and have not been widely tested in other populations. Randomized controlled trials of frequent nurse home visitation programs beginning during pregnancy that address behavioral and psychological factors indicated improved abuse measures and outcomes. No studies were identified about interventions in older children or harms associated with screening and intervention. CONCLUSIONS No trials of the effectiveness of screening in a health care setting have been published. Clinician referrals to nurse home visitation during pregnancy and in early childhood may reduce abuse in selected populations. There are no studies about harms of screening and interventions. PMID:15083858

Testing self-regulation interventions to increase walking using factorial randomized N-of-1 trials.

PubMed

Sniehotta, Falko F; Presseau, Justin; Hobbs, Nicola; Araújo-Soares, Vera

2012-11-01

To investigate the suitability of N-of-1 randomized controlled trials (RCTs) as a means of testing the effectiveness of behavior change techniques based on self-regulation theory (goal setting and self-monitoring) for promoting walking in healthy adult volunteers. A series of N-of-1 RCTs in 10 normal and overweight adults ages 19-67 (M = 36.9 years). We randomly allocated 60 days within each individual to text message-prompted daily goal-setting and/or self-monitoring interventions in accordance with a 2 (step-count goal prompt vs. alternative goal prompt) × 2 (self-monitoring: open vs. blinded Omron-HJ-113-E pedometer) factorial design. Aggregated data were analyzed using random intercept multilevel models. Single cases were analyzed individually. The primary outcome was daily pedometer step counts over 60 days. Single-case analyses showed that 4 participants significantly increased walking: 2 on self-monitoring days and 2 on goal-setting days, compared with control days. Six participants did not benefit from the interventions. In aggregated analyses, mean step counts were higher on goal-setting days (8,499.9 vs. 7,956.3) and on self-monitoring days (8,630.3 vs. 7,825.9). Multilevel analyses showed a significant effect of the self-monitoring condition (p = .01), the goal-setting condition approached significance (p = .08), and there was a small linear increase in walking over time (p = .03). N-of-1 randomized trials are a suitable means to test behavioral interventions in individual participants.

A general method for handling missing binary outcome data in randomized controlled trials

PubMed Central

Jackson, Dan; White, Ian R; Mason, Dan; Sutton, Stephen

2014-01-01

Aims The analysis of randomized controlled trials with incomplete binary outcome data is challenging. We develop a general method for exploring the impact of missing data in such trials, with a focus on abstinence outcomes. Design We propose a sensitivity analysis where standard analyses, which could include ‘missing = smoking’ and ‘last observation carried forward’, are embedded in a wider class of models. Setting We apply our general method to data from two smoking cessation trials. Participants A total of 489 and 1758 participants from two smoking cessation trials. Measurements The abstinence outcomes were obtained using telephone interviews. Findings The estimated intervention effects from both trials depend on the sensitivity parameters used. The findings differ considerably in magnitude and statistical significance under quite extreme assumptions about the missing data, but are reasonably consistent under more moderate assumptions. Conclusions A new method for undertaking sensitivity analyses when handling missing data in trials with binary outcomes allows a wide range of assumptions about the missing data to be assessed. In two smoking cessation trials the results were insensitive to all but extreme assumptions. PMID:25171441

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

PubMed

Petosa, R L; Smith, L

2017-01-01

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

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

PubMed Central

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

2013-01-01

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

Randomized Controlled Trial of Problem-Solving Therapy for Minor Depression in Home Care

ERIC Educational Resources Information Center

Gellis, Zvi D.; McGinty, Jean; Tierney, Lynda; Jordan, Cindy; Burton, Jean; Misener, Elizabeth

2008-01-01

Objective: Data are presented from a pilot research program initiated to develop, refine, and test the outcomes of problem-solving therapy that targets the needs of older adults with minor depression in home care settings. Method: A pilot randomized clinical trial compares the impact of problem-solving therapy for home care to treatment as usual…

Prostate cancer, comorbidity, and participation in randomized controlled trials of therapy.

PubMed

Chao, Herta H; Mayer, Tina; Concato, John; Rose, Michal G; Uchio, Edward; Kelly, Wm Kevin

2010-03-01

Randomized controlled trials (RCTs) evaluate the potential benefits of chemotherapy regimens and guide clinical care for patients with cancer. Inclusion criteria for RCTs are usually stringent and may exclude many patients seen in clinical practice. Our objective was to determine the proportion of men with castrate-resistant prostate cancer (CRPC) in a clinical setting that would have been excluded from major phase 3 RCTs. We reviewed eligibility criteria from 24 phase 3 clinical trials evaluating chemotherapy for CRPC active from January, 2004, through April, 2008. We created a common list of criteria used in at least 3 studies and separately considered the criteria from a prominent RCT (TAX 327). We applied these criteria to a population of patients with CRPC treated during 2004 to 2006 at the Veterans Affairs Connecticut Healthcare System. Among 106 patients with CRPC, 99 (93%) had complete medical records, and 45 (45%) of the 99 would have been excluded from RCTs. Common reasons for exclusion were abnormal laboratory values, other malignancies, and other serious medical conditions including cardiac disease. Almost half of the CRPC patients examined in a clinical setting would have been ineligible for phase 3 RCTs, highlighting that such trials may not be applicable to general oncology practice.

Dynamics of task sets: evidence from dense-array event-related potentials.

PubMed

Poulsen, Catherine; Luu, Phan; Davey, Colin; Tucker, Don M

2005-06-01

Prior research suggests that task sets facilitate coherent, goal-directed behavior by providing an internal, contextual frame that biases selection toward context-relevant stimulus attributes and responses. Questions about how task sets are engaged, maintained, and shifted have recently become a major focus of research on executive control processes. We employed dense-array (128-channel) event-related potential (ERP) methodology to examine the dynamics of brain systems engaged during the preparation and implementation of task switching. The EEG was recorded while participants performed letter and digit judgments to pseudorandomly-ordered, univalent (#3, A%) and bivalent (G5) stimulus trials, with the appropriate task cued by a colored rectangle presented 450 ms before target onset. Results revealed spatial and temporal variations in brain activity that could be related to preparatory processes common to both switch and repeat trials, switch-specific control processes engaged to reconfigure and maintain task set under conflict, and visual priming benefits of task repetition. Despite extensive practice and improvement, both behavioral and ERP results indicated that subjects maintained high levels of executive control processing with extended task engagement. The patterns of ERP activity obtained in the present study fit well with functional neuroanatomical models of self-regulation of action. The frontopolar and right-lateralized frontal switch effects obtained in the present study are consistent with the role of these regions in adapting to changing contextual contingencies. In contrast, the centroparietal P3b and N384 effects related to the contextual ambiguity of bivalent trials are consistent with the context monitoring and updating functions associated with the posterior cingulate learning circuit.

Test-Retest Reliability and Practice Effects of the Stability Evaluation Test.

PubMed

Williams, Richelle M; Corvo, Matthew A; Lam, Kenneth C; Williams, Travis A; Gilmer, Lesley K; McLeod, Tamara C Valovich

2017-01-17

Postural control plays an essential role in concussion evaluation. The Stability Evaluation Test (SET) aims to objectively analyze postural control by measuring sway velocity on the NeuroCom's VSR portable force platform (Natus, San Carlos, CA). To assess the test-retest reliability and practice effects of the SET protocol. Cohort. Research Laboratory. Fifty healthy adults (males=20, females=30, age=25.30±3.60 years, height=166.60±12.80 cm, mass=68.80±13.90 kg). All participants completed four trials of the SET. Each trial consisted of six 20-second balance tests with eyes closed, under the following conditions: double-leg firm (DFi), single-leg firm (SFi), tandem firm (TFi), double-leg foam (DFo), single-leg foam (SFo), and tandem foam (TFo). Each trial was separated by a 5-minute seated rest period. The dependent variable was sway velocity (deg/sec), with lower values indicating better balance. Sway velocity was recorded for each of the six conditions as well as a composite score for each trial. Test-retest reliability was analyzed across four trials with Intraclass Correlation Coefficients. Practice effects analyzed with repeated measures analysis of variance, followed by Tukey post-hoc comparisons for any significant main effects (p<.05). Sway velocity reliability values were good to excellent: DFi (ICC=0.88;95%CI:0.81,0.92), SFi (ICC=0.75;95%CI:0.61,0.85), TFi (ICC=0.84;95%CI:0.75,0.90), DFo (ICC=0.83;95%CI:0.74,0.90), SFo (ICC=0.82;95%CI:0.72,0.89), TFo (ICC=0.81;95%CI:0.69,0.88), and composite score (ICC=0.93;95%CI:0.88,0.95). Significant practice effects (p<.05) were noted on the SFi, DFo, SFo, TFo conditions, and composite scores. Our results suggest the SET has good to excellent reliability for the assessment of postural control in healthy adults. Due to the practice effects noted, a familiarization session is recommended (i.e., all 6 conditions) prior to recording the data. Future studies should evaluate injured patients to determine meaningful change scores during various injuries.

A randomized controlled trial of physical activity with individual goal-setting and volunteer mentors to overcome sedentary lifestyle in older adults at risk of cognitive decline: the INDIGO trial protocol.

PubMed

Cox, Kay L; Cyarto, Elizabeth V; Etherton-Beer, Christopher; Ellis, Kathryn A; Alfonso, Helman; Clare, Linda; Liew, Danny; Ames, David; Flicker, Leon; Almeida, Osvaldo P; LoGiudice, Dina; Lautenschlager, Nicola T

2017-09-13

Increasing physical activity (PA) effectively in those who are inactive is challenging. For those who have subjective memory complaints (SMC) or mild cognitive impairment (MCI) this is a greater challenge necessitating the need for more engaging and innovative approaches. The primary aim of this trial is to determine whether a home-based 6-month PA intervention with individual goal-setting and peer mentors (GM-PA) can significantly increase PA levels in insufficiently active older adults at increased risk of developing Alzheimer's disease (AD). Community living 60-80 year olds with SMC or MCI who do not engage in more than 60 min per week of moderate intensity PA will be recruited from memory clinics and the community via media advertisements to participate in this randomized, single-blind controlled trial. All participants will receive an individually tailored home-based PA program of 150 min of moderate intensity walking/week for 6 months. The intervention group will undertake individual goal-setting and behavioral education workshops with mentor support via telephone (GM-PA). Those randomized to the control group will have standard education workshops and Physical Activity Liaison (PAL) contact via telephone (CO-PA). Increase in PA is the primary outcome, fitness, cognitive, personality, demographic and clinical parameters will be measured and a health economic analysis performed. A saliva sample will be collected for APOE e4 genotyping. All participants will have a goal-setting interview to determine their PA goals. Active volunteers aged 50-85 years will be recruited from the community randomized and trained to provide peer support as mentors (intervention group) or PALS (control group) for the 6-month intervention. Mentors and PALS will have PA, exercise self-efficacy and mentoring self-efficacy measured. Participants in both groups are asked to attend 3 workshops in 6 months. At the first workshop, they will meet their allocated Mentor or PAL who will deliver their respective programs and support via 6 telephone calls during the intervention. If the GM-PA program is successful in increasing the PA levels of the target group it will potentially provide another strategy and community resource that can be translated into practice. Australia New Zealand Clinical Trials Registry ACTRN12613001181796 . (29/10/2013) retrospectively registered.

Study protocol for the evaluation of an Infant Simulator based program delivered in schools: a pragmatic cluster randomised controlled trial

PubMed Central

2010-01-01

Background This paper presents the study protocol for a pragmatic randomised controlled trial to evaluate the impact of a school based program developed to prevent teenage pregnancy. The program includes students taking care of an Infant Simulator; despite growing popularity and an increasing global presence of such programs, there is no published evidence of their long-term impact. The aim of this trial is to evaluate the Virtual Infant Parenting (VIP) program by investigating pre-conceptual health and risk behaviours, teen pregnancy and the resultant birth outcomes, early child health and maternal health. Methods and Design Fifty-seven schools (86% of 66 eligible secondary schools) in Perth, Australia were recruited to the clustered (by school) randomised trial, with even randomisation to the intervention and control arms. Between 2003 and 2006, the VIP program was administered to 1,267 participants in the intervention schools, while 1,567 participants in the non-intervention schools received standard curriculum. Participants were all female and aged between 13-15 years upon recruitment. Pre and post-intervention questionnaires measured short-term impact and participants are now being followed through their teenage years via data linkage to hospital medical records, abortion clinics and education records. Participants who have a live birth are interviewed by face-to-face interview. Kaplan-Meier survival analysis and proportional hazards regression will test for differences in pregnancy, birth and abortion rates during the teenage years between the study arms. Discussion This protocol paper provides a detailed overview of the trial design as well as initial results in the form of participant flow. The authors describe the intervention and its delivery within the natural school setting and discuss the practical issues in the conduct of the trial, including recruitment. The trial is pragmatic and will directly inform those who provide Infant Simulator based programs in school settings. Trial registration ISRCTN24952438 PMID:20964860

Maintenance Cognitive Stimulation Therapy (CST) in practice: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Cognitive Stimulation Therapy (CST) is a psychosocial evidence-based group intervention for people with dementia recommended by the UK NICE guidelines. In clinical trials, CST has been shown to improve cognition and quality of life, but little is known about the best way of ensuring implementation of CST in practice settings. A recent pilot study found that a third of people who attend CST training go on to run CST in practice, but staff identified a lack of support as a key reason for the lack of implementation. Methods/design There are three projects in this study: The first is a pragmatic multi-centre, randomised controlled trial (RCT) of staff training, comparing CST training and outreach support with CST training only; the second, the monitoring and outreach trial, is a phase IV trial that evaluates implementation of CST in practice by staff members who have previously had the CST manual or attended training. Centres will be randomised to receive outreach support. The primary outcome measure for both of these trials is the number of CST sessions run for people with dementia. Secondary outcomes include the number of attenders at sessions, job satisfaction, dementia knowledge and attitudes, competency, barriers to change, approach to learning and a controllability of beliefs and the level of adherence. Focus groups will assess staff members’ perceptions of running CST groups and receiving outreach support. The third study involves monitoring centres running groups in their usual practice and looking at basic outcomes of cognition and quality of life for the person with dementia. Discussion These studies assess the effects of outreach support on putting CST into practice and running groups effectively in a variety of care settings with people with dementia; evaluate the effectiveness of CST in standard clinical practice; and identify key factors promoting or impeding the successful running of groups. Trial registration Clinical trial ISRCTN28793457. PMID:22735077

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

PubMed

Hussein, Norita; Weng, Stephen F; Kai, Joe; Kleijnen, Jos; Qureshi, Nadeem

2015-08-12

Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 25 June 2015.Date of latest search of all other sources: 10 December 2014. Any randomised or quasi-randomised control trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease when compared to usual care. We identified 19 papers, describing 13 unique trials which were potentially eligible for inclusion in the review. However, after assessment, no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found. No randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found. As no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis, or Tay-Sachs disease were found for inclusion in this review, the research evidence for current policy recommendations is limited to non-randomised studies.Information from well-designed, adequately powered, randomised trials is desirable in order to make more robust recommendations for practice. However, such trials must also consider the legal, ethical, and cultural barriers to implementation of preconception genetic risk assessment.

The Effects of Age and Set Size on the Fast Extraction of Egocentric Distance

PubMed Central

Gajewski, Daniel A.; Wallin, Courtney P.; Philbeck, John W.

2016-01-01

Angular direction is a source of information about the distance to floor-level objects that can be extracted from brief glimpses (near one's threshold for detection). Age and set size are two factors known to impact the viewing time needed to directionally localize an object, and these were posited to similarly govern the extraction of distance. The question here was whether viewing durations sufficient to support object detection (controlled for age and set size) would also be sufficient to support well-constrained judgments of distance. Regardless of viewing duration, distance judgments were more accurate (less biased towards underestimation) when multiple potential targets were presented, suggesting that the relative angular declinations between the objects are an additional source of useful information. Distance judgments were more precise with additional viewing time, but the benefit did not depend on set size and accuracy did not improve with longer viewing durations. The overall pattern suggests that distance can be efficiently derived from direction for floor-level objects. Controlling for age-related differences in the viewing time needed to support detection was sufficient to support distal localization but only when brief and longer glimpse trials were interspersed. Information extracted from longer glimpse trials presumably supported performance on subsequent trials when viewing time was more limited. This outcome suggests a particularly important role for prior visual experience in distance judgments for older observers. PMID:27398065

Is Performance in Task-Cuing Experiments Mediated by Task Set Selection or Associative Compound Retrieval?

ERIC Educational Resources Information Center

Forrest, Charlotte L. D.; Monsell, Stephen; McLaren, Ian P. L.

2014-01-01

Task-cuing experiments are usually intended to explore control of task set. But when small stimulus sets are used, they plausibly afford learning of the response associated with a combination of cue and stimulus, without reference to tasks. In 3 experiments we presented the typical trials of a task-cuing experiment: a cue (colored shape) followed,…

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

PubMed Central

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

2016-01-01

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

Different methods to analyze stepped wedge trial designs revealed different aspects of intervention effects.

PubMed

Twisk, J W R; Hoogendijk, E O; Zwijsen, S A; de Boer, M R

2016-04-01

Within epidemiology, a stepped wedge trial design (i.e., a one-way crossover trial in which several arms start the intervention at different time points) is increasingly popular as an alternative to a classical cluster randomized controlled trial. Despite this increasing popularity, there is a huge variation in the methods used to analyze data from a stepped wedge trial design. Four linear mixed models were used to analyze data from a stepped wedge trial design on two example data sets. The four methods were chosen because they have been (frequently) used in practice. Method 1 compares all the intervention measurements with the control measurements. Method 2 treats the intervention variable as a time-independent categorical variable comparing the different arms with each other. In method 3, the intervention variable is a time-dependent categorical variable comparing groups with different number of intervention measurements, whereas in method 4, the changes in the outcome variable between subsequent measurements are analyzed. Regarding the results in the first example data set, methods 1 and 3 showed a strong positive intervention effect, which disappeared after adjusting for time. Method 2 showed an inverse intervention effect, whereas method 4 did not show a significant effect at all. In the second example data set, the results were the opposite. Both methods 2 and 4 showed significant intervention effects, whereas the other two methods did not. For method 4, the intervention effect attenuated after adjustment for time. Different methods to analyze data from a stepped wedge trial design reveal different aspects of a possible intervention effect. The choice of a method partly depends on the type of the intervention and the possible time-dependent effect of the intervention. Furthermore, it is advised to combine the results of the different methods to obtain an interpretable overall result. Copyright © 2016 Elsevier Inc. All rights reserved.

Reflecting on the methodological challenges of recruiting to a United Kingdom-wide, multi-centre, randomised controlled trial in gynaecology outpatient settings

PubMed Central

2013-01-01

Background Successful recruitment of participants to any trial is central to its success. Trial results are routinely published, and recruitment is often cited to be slower and more difficult than anticipated. This article reflects on the methodological challenges of recruiting women with prolapse attending United Kingdom (UK) gynaecology outpatient clinics to a multi-centre randomised controlled trial (RCT) of physiotherapy, and the systems put in place in an attempt to address them. Methods Gynaecology outpatients with symptomatic prolapse were to be recruited over a 16-month period from 14 UK hospitals and one New Zealand hospital. Eligible women were informed about the trial by their gynaecologist and informed consent was obtained by the central trial office. Recruitment difficulties were encountered early on, and a number of strategies were employed to try to improve recruitment. Results Some strategies were more successful than others and they differed in the resources required. Actions that facilitated recruitment included increasing recruiting centres to 23 UK and two international hospitals, good centre support, using processes embedded in clinical practice, and good communication between the trial office, collaborators and participants. Collaborator incentives, whereby staff involved received the benefit immediately, were more successful than a nominal monetary payment per woman randomised. Barriers to recruitment included fewer eligible women than anticipated, patient’s preference to receive active treatment rather than allocation to the control group, lack of support staff and high staff turnover. Geographical variations in Primary Care Trust Research Management and Governance approval systems and general practitioner (GP) referral procedures also impacted negatively on recruitment. Conclusions Our article reflects on the methodological challenges of recruiting to a multi-centre RCT in a UK gynaecology setting. Effective interventions included increasing the number of recruiting centres and providing collaborator incentives. Barriers to recruitment included fewer eligible women than anticipated, patient’s preference to be allocated to the treatment group, lack of support staff, and variations in approval systems and GP referral procedures. To improve the evidence base on clinical trial recruitment, trialists need to publish their experiences and lessons learned. Future RCTs should evaluate, where possible, the effect of strategies designed to improve recruitment and retention. Trial registration Current Controlled Trials ISRCTN35911035 PMID:24228935

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

PubMed

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

2013-09-01

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

Reconciling the effects of screening on prostate cancer mortality in the ERSPC and PLCO trials

PubMed Central

Tsodikov, Alex; Gulati, Roman; Heijnsdijk, Eveline AM; Pinsky, Paul F; Moss, Sue M; Qiu, Sheng; de Carvalho, Tiago M; Hugosson, Jonas; Berg, Christine D; Auvinen, Anssi; Andriole, Gerald L; Roobol, Monique J; Crawford, E David; Nelen, Vera; Kwiatkowski, Maciej; Zappa, Marco; Luján, Marcos; Villers, Arnauld; Feuer, Eric J; de Koning, Harry J; Mariotto, Angela B; Etzioni, Ruth

2017-01-01

Background The European Randomized Study of Screening for Prostate Cancer (ERSPC) found screening reduced prostate cancer (PC) mortality, but the Prostate, Lung, Colorectal, and Ovarian trial (PLCO) found no reduction. Objective To evaluate whether effects of screening on PC mortality relative to no screening differed between the ERSPC and PLCO. Design Cox regression of PC death in each trial arm adjusted for age and trial, and extended analyses that accounted for increased incidence due to screening and diagnostic workup on each arm via mean lead times (MLTs). MLTs were estimated empirically and using analytic or microsimulation models. Setting Randomized controlled trials in Europe and the US. Participants Men aged 55–69 (ERSPC) or 55–74 (PLCO) at randomization. Intervention Prostate cancer screening. Measurements PC incidence and survival from randomization; PC incidence in the US before screening began. Results Estimated MLTs were similar in the ERSPC and PLCO intervention arms but were longer in the PLCO control arm than the ERSPC control arm. Extended analyses found no evidence that effects of screening differed between trials (P=0.37–0.47, range across MLT estimation approaches) but strong evidence that benefit increased with MLT (P=0.0027–0.0032). Screening was estimated to confer a 7–9% reduction in PC death per year of MLT. This translated into an estimated 25–31% and 27–32% lower risk of PC death under screening as performed in the ERSPC and PLCO intervention arms, respectively, relative to no screening. Limitations MLT is a simple metric of screening and diagnostic workup. Conclusion After accounting for differences in implementation and settings, the ERSPC and PLCO provide compatible evidence that screening reduces PC mortality. PMID:28869989

Controlled trials to improve antibiotic utilization: a systematic review of experience, 1984-2004.

PubMed

Parrino, Thomas A

2005-02-01

To review the effectiveness of interventions designed to improve antibiotic prescribing patterns in clinical practice and to draw inferences about the most practical methods for optimizing antibiotic utilization in hospital and ambulatory settings. A literature search using online databases for the years 1975-2004 identified controlled trials of strategies for improving antibiotic utilization. Due to variation in study settings and design, quantitative meta-analysis was not feasible. Therefore, a qualitative literature review was conducted. Forty-one controlled trials met the search criteria. Interventions consisted of education, peer review and feedback, physician participation, rewards and penalties, administrative methods, and combined approaches. Social marketing directed at patients and prescribers was effective in varying contexts, as was implementation of practice guidelines. Authorization systems with structured order entry, formulary restriction, and mandatory consultation were also effective. Peer review and feedback were more effective when combined with dissemination of relevant information or social marketing than when used alone. Several practices were effective in improving antibiotic utilization: social marketing, practice guidelines, authorization systems, and peer review and feedback. Online systems providing clinical information, structured order entry, and decision support may be the most promising approach. Further studies, including economic analyses, are needed to confirm or refute this hypothesis.

The feasibility of a randomized controlled trial of esophagectomy for esophageal cancer - the ROMIO (Randomized Oesophagectomy: Minimally Invasive or Open) study: protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background There is a need for evidence of the clinical effectiveness of minimally invasive surgery for the treatment of esophageal cancer, but randomized controlled trials in surgery are often difficult to conduct. The ROMIO (Randomized Open or Minimally Invasive Oesophagectomy) study will establish the feasibility of a main trial which will examine the clinical and cost-effectiveness of minimally invasive and open surgical procedures for the treatment of esophageal cancer. Methods/Design A pilot randomized controlled trial (RCT), in two centers (University Hospitals Bristol NHS Foundation Trust and Plymouth Hospitals NHS Trust) will examine numbers of incident and eligible patients who consent to participate in the ROMIO study. Interventions will include esophagectomy by: (1) open gastric mobilization and right thoracotomy, (2) laparoscopic gastric mobilization and right thoracotomy, and (3) totally minimally invasive surgery (in the Bristol center only). The primary outcomes of the feasibility study will be measures of recruitment, successful development of methods to monitor quality of surgery and fidelity to a surgical protocol, and development of a core outcome set to evaluate esophageal cancer surgery. The study will test patient-reported outcomes measures to assess recovery, methods to blind participants, assessments of surgical morbidity, and methods to capture cost and resource use. ROMIO will integrate methods to monitor and improve recruitment using audio recordings of consultations between recruiting surgeons, nurses, and patients to provide feedback for recruiting staff. Discussion The ROMIO study aims to establish efficient methods to undertake a main trial of minimally invasive surgery versus open surgery for esophageal cancer. Trial registration The pilot trial has Current Controlled Trials registration number ISRCTN59036820(25/02/2013) at http://www.controlled-trials.com; the ROMIO trial record at that site gives a link to the original version of the study protocol. PMID:24888266

Birth Control in Clinical Trials

PubMed Central

Stewart, J.; Beyer, B. K.; Chadwick, K.; De Schaepdrijver, L.; Desai, M.; Enright, B.; Foster, W.; Hui, J. Y.; Moffat, G. J.; Tornesi, B.; Van Malderen, K.; Wiesner, L.; Chen, C. L.

2015-01-01

The Health and Environmental Sciences Institute (HESI) Developmental and Reproductive Toxicology Technical Committee sponsored a pharmaceutical industry survey on current industry practices for contraception use during clinical trials. The objectives of the survey were to improve our understanding of the current industry practices for contraception requirements in clinical trials, the governance processes set up to promote consistency and/or compliance with contraception requirements, and the effectiveness of current contraception practices in preventing pregnancies during clinical trials. Opportunities for improvements in current practices were also considered. The survey results from 12 pharmaceutical companies identified significant variability among companies with regard to contraception practices and governance during clinical trials. This variability was due primarily to differences in definitions, areas of scientific uncertainty or misunderstanding, and differences in company approaches to enrollment in clinical trials. The survey also revealed that few companies collected data in a manner that would allow a retrospective understanding of the reasons for failure of birth control during clinical trials. In this article, suggestions are made for topics where regulatory guidance or scientific publications could facilitate best practice. These include provisions for a pragmatic definition of women of childbearing potential, guidance on how animal data can influence the requirements for male and female birth control, evidence-based guidance on birth control and pregnancy testing regimes suitable for low- and high-risk situations, plus practical methods to ascertain the risk of drug-drug interactions with hormonal contraceptives. PMID:27042398

Dynamic Trial-by-Trial Recoding of Task-Set Representations in the Frontoparietal Cortex Mediates Behavioral Flexibility

PubMed Central

Qiao, Lei; Zhang, Lijie

2017-01-01

Cognitive flexibility forms the core of the extraordinary ability of humans to adapt, but the precise neural mechanisms underlying our ability to nimbly shift between task sets remain poorly understood. Recent functional magnetic resonance imaging (fMRI) studies employing multivoxel pattern analysis (MVPA) have shown that a currently relevant task set can be decoded from activity patterns in the frontoparietal cortex, but whether these regions support the dynamic transformation of task sets from trial to trial is not clear. Here, we combined a cued task-switching protocol with human (both sexes) fMRI, and harnessed representational similarity analysis (RSA) to facilitate a novel assessment of trial-by-trial changes in neural task-set representations. We first used MVPA to define task-sensitive frontoparietal and visual regions and found that neural task-set representations on switch trials are less stably encoded than on repeat trials. We then exploited RSA to show that the neural representational pattern dissimilarity across consecutive trials is greater for switch trials than for repeat trials, and that the degree of this pattern dissimilarity predicts behavior. Moreover, the overall neural pattern of representational dissimilarities followed from the assumption that repeating sets, compared with switching sets, results in stronger neural task representations. Finally, when moving from cue to target phase within a trial, pattern dissimilarities tracked the transformation from previous-trial task representations to the currently relevant set. These results provide neural evidence for the longstanding assumptions of an effortful task-set reconfiguration process hampered by task-set inertia, and they demonstrate that frontoparietal and stimulus processing regions support “dynamic adaptive coding,” flexibly representing changing task sets in a trial-by-trial fashion. SIGNIFICANCE STATEMENT Humans can fluently switch between different tasks, reflecting an ability to dynamically configure “task sets,” rule representations that link stimuli to appropriate responses. Recent studies show that neural signals in frontal and parietal brain regions can tell us which of two tasks a person is currently performing. However, it is not known whether these regions are also involved in dynamically reconfiguring task-set representations when switching between tasks. Here we measured human brain activity during task switching and tracked the similarity of neural task-set representations from trial to trial. We show that frontal and parietal brain regions flexibly recode changing task sets in a trial-by-trial fashion, and that task-set similarity over consecutive trials predicts behavior. PMID:28972126

Context-dependent control over attentional capture

PubMed Central

Cosman, Joshua D.; Vecera, Shaun P.

2014-01-01

A number of studies have demonstrated that the likelihood of a salient item capturing attention is dependent on the “attentional set” an individual employs in a given situation. The instantiation of an attentional set is often viewed as a strategic, voluntary process, relying on working memory systems that represent immediate task priorities. However, influential theories of attention and automaticity propose that goal-directed control can operate more or less automatically on the basis of longer-term task representations, a notion supported by a number of recent studies. Here, we provide evidence that longer-term contextual learning can rapidly and automatically influence the instantiation of a given attentional set. Observers learned associations between specific attentional sets and specific task-irrelevant background scenes during a training session, and in the ensuing test session simply reinstating particular scenes on a trial by trial basis biased observers to employ the associated attentional set. This directly influenced the magnitude of attentional capture, suggesting that memory for the context in which a task is performed can play an important role in the ability to instantiate a particular attentional set and overcome distraction by salient, task-irrelevant information. PMID:23025581

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

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

PubMed Central

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

2015-01-01

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

Web-Based Decision Aid to Assist Help-Seeking Choices for Young People Who Self-Harm: Outcomes From a Randomized Controlled Feasibility Trial.

PubMed

Rowe, Sarah L; Patel, Krisna; French, Rebecca S; Henderson, Claire; Ougrin, Dennis; Slade, Mike; Moran, Paul

2018-01-30

Adolescents who self-harm are often unsure how or where to get help. We developed a Web-based personalized decision aid (DA) designed to support young people in decision making about seeking help for their self-harm. The aim of this study was to evaluate the feasibility and acceptability of the DA intervention and the randomized controlled trial (RCT) in a school setting. We conducted a two-group, single blind, randomized controlled feasibility trial in a school setting. Participants aged 12 to 18 years who reported self-harm in the past 12 months were randomized to either a Web-based DA or to general information about mood and feelings. Feasibility of recruitment, randomization, and follow-up rates were assessed, as was acceptability of the intervention and study procedures. Descriptive data were collected on outcome measures examining decision making and help-seeking behavior. Qualitative interviews were conducted with young people, parents or carers, and staff and subjected to thematic analysis to explore their views of the DA and study processes. Parental consent was a significant barrier to young people participating in the trial, with only 17.87% (208/1164) of parents or guardians who were contacted for consent responding to study invitations. Where parental consent was obtained, we were able to recruit 81.7% (170/208) of young people into the study. Of those young people screened, 13.5% (23/170) had self-harmed in the past year. Ten participants were randomized to receiving the DA, and 13 were randomized to the control group. Four-week follow-up assessments were completed with all participants. The DA had good acceptability, but qualitative interviews suggested that a DA that addressed broader mental health problems such as depression, anxiety, and self-harm may be more beneficial. A broad-based mental health DA addressing a wide range of psychosocial problems may be useful for young people. The requirement for parental consent is a key barrier to intervention research on self-harm in the school setting. Adaptations to the research design and the intervention are needed before generalizable research about DAs can be successfully conducted in a school setting. International Standard Randomized Controlled Trial registry: ISRCTN11230559; http://www.isrctn.com/ISRCTN11230559 (Archived by WebCite at http://www.webcitation.org/6wqErsYWG). ©Sarah L Rowe, Krisna Patel, Rebecca S French, Claire Henderson, Dennis Ougrin, Mike Slade, Paul Moran. Originally published in JMIR Mental Health (http://mental.jmir.org), 30.01.2018.

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

PubMed

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

2015-08-01

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

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

PubMed Central

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

2015-01-01

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

Proactive inhibitory control: A general biasing account☆

PubMed Central

Elchlepp, Heike; Lavric, Aureliu; Chambers, Christopher D.; Verbruggen, Frederick

2016-01-01

Flexible behavior requires a control system that can inhibit actions in response to changes in the environment. Recent studies suggest that people proactively adjust response parameters in anticipation of a stop signal. In three experiments, we tested the hypothesis that proactive inhibitory control involves adjusting both attentional and response settings, and we explored the relationship with other forms of proactive and anticipatory control. Subjects responded to the color of a stimulus. On some trials, an extra signal occurred. The response to this signal depended on the task context subjects were in: in the ‘ignore’ context, they ignored it; in the ‘stop’ context, they had to withhold their response; and in the ‘double-response’ context, they had to execute a secondary response. An analysis of event-related brain potentials for no-signal trials in the stop context revealed that proactive inhibitory control works by biasing the settings of lower-level systems that are involved in stimulus detection, action selection, and action execution. Furthermore, subjects made similar adjustments in the double-response and stop-signal contexts, indicating an overlap between various forms of proactive action control. The results of Experiment 1 also suggest an overlap between proactive inhibitory control and preparatory control in task-switching studies: both require reconfiguration of task-set parameters to bias or alter subordinate processes. We conclude that much of the top-down control in response inhibition tasks takes place before the inhibition signal is presented. PMID:26859519

Neuroreflexotherapy for nonspecific low back pain: a systematic review.

PubMed

Urrútia, Gerard; Burton, Kim; Morral, Antoni; Bonfill, Xavier; Zanoli, Gustavo

2005-03-15

Systematic review. To assess the effectiveness of neuroreflexotherapy (NRT) for low back pain (LBP). Few of the alternatives for the management of LBP have a firm base of evidence for their effectiveness. Recently, a new intervention known as NRT has been developed in Spain and has been reported to have favorable results. Searches were undertaken according to Cochrane Collaboration guidelines, and randomized controlled trials that evaluated NRT as treatment for patients with nonspecific LBP were included. A qualitative synthesis and an assessment of methodological quality were undertaken. Three randomized controlled trials were included, with 125 and 148 subjects in control and intervention groups, respectively. NRT was compared with sham in two trials and standard care in one. Individuals receiving active NRT showed significantly better outcomes for pain, mobility, disability, medication use, consumption of resources, and costs. No major side effects were reported by those receiving active NRT. NRT appears to be a safe and effective intervention for nonspecific LBP. This conclusion is limited to three trials conducted by a small number of experienced clinicians. Further trials in other settings are needed to determine whether these favorable results can be generalized.

Standardising the reporting of outcomes in gastric cancer surgery trials: protocol for the development of a core outcome set and accompanying outcome measurement instrument set (the GASTROS study).

PubMed

Alkhaffaf, Bilal; Glenny, Anne-Marie; Blazeby, Jane M; Williamson, Paula; Bruce, Iain A

2017-08-09

Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Whilst surgery is the mainstay of curative treatment, it is associated with significant risks. Surgical strategies for treating gastric cancer should be based on evidence from systematic reviews of well-designed randomised controlled trials. However, inconsistencies in the reporting of outcomes from these trials makes evidence synthesis unreliable. We present a protocol for an international consensus study to develop a standardised set of outcomes and measurement tools - a 'core outcome set' (COS) - to be used by all future trials examining therapeutic surgical interventions for gastric cancer. The GASTROS study aims to standardise the reporting of outcomes in gastric cancer surgery trials through an international consensus process of key stakeholders including health care professionals and patients. The first of three stages in the study will identify a 'long-list' of potentially important outcomes to be prioritised. These will be extracted from a systematic review of relevant academic literature and patient interviews. Stage 2 will comprise an eDelphi survey which will consider the views of patients, nurse specialists and surgeons to prioritise the most important outcomes. A meeting of stakeholder representatives will ratify the COS. Stage 3 will focus on identifying appropriate instruments to measure the prioritised outcomes by means of quality assessment of available measurement instruments and stakeholder consultation. This study aims to standardise the reporting of outcomes in future trials examining therapeutic surgical interventions for gastric cancer. It is anticipated that standardisation of outcome reporting in these surgical effectiveness trials will enhance the evidence base for clinical practice. Highlighting outcomes of greatest importance to patients will ensure that their perspectives are central to research in this field.

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

PubMed Central

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

2000-01-01

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

Exploring the costs and outcomes of sexually transmitted infection (STI) screening interventions targeting men in football club settings: preliminary cost-consequence analysis of the SPORTSMART pilot randomised controlled trial

PubMed Central

Jackson, Louise J; Roberts, Tracy E; Fuller, Sebastian S; Sutcliffe, Lorna J; Saunders, John M; Copas, Andrew J; Mercer, Catherine H; Cassell, Jackie A; Estcourt, Claudia S

2015-01-01

Background The objective of this study was to compare the costs and outcomes of two sexually transmitted infection (STI) screening interventions targeted at men in football club settings in England, including screening promoted by team captains. Methods A comparison of costs and outcomes was undertaken alongside a pilot cluster randomised control trial involving three trial arms: (1) captain-led and poster STI screening promotion; (2) sexual health advisor-led and poster STI screening promotion and (3) poster-only STI screening promotion (control/comparator). For all study arms, resource use and cost data were collected prospectively. Results There was considerable variation in uptake rates between clubs, but results were broadly comparable across study arms with 50% of men accepting the screening offer in the captain-led arm, 67% in the sexual health advisor-led arm and 61% in the poster-only control arm. The overall costs associated with the intervention arms were similar. The average cost per player tested was comparable, with the average cost per player tested for the captain-led promotion estimated to be £88.99 compared with £88.33 for the sexual health advisor-led promotion and £81.87 for the poster-only (control) arm. Conclusions Costs and outcomes were similar across intervention arms. The target sample size was not achieved, and we found a greater than anticipated variability between clubs in the acceptability of screening, which limited our ability to estimate acceptability for intervention arms. Further evidence is needed about the public health benefits associated with screening interventions in non-clinical settings so that their cost-effectiveness can be fully evaluated. PMID:25512670

Balance circuit classes to improve balance among rehabilitation inpatients: a protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Impaired balance and mobility are common among rehabilitation inpatients. Poor balance and mobility lead to an increased risk of falling. Specific balance exercise has been shown to improve balance and reduce falls within the community setting. However few studies have measured the effects of balance exercises on balance within the inpatient setting. The aim of this randomised controlled trial is to investigate whether the addition of circuit classes targeting balance to usual therapy lead to greater improvements in balance among rehabilitation inpatients than usual therapy alone. Methods/Design A single centre, randomised controlled trial with concealed allocation, assessor blinding and intention-to-treat analysis. One hundred and sixty two patients admitted to the general rehabilitation ward at Bankstown-Lidcombe Hospital will be recruited. Eligible participants will have no medical contraindications to exercise and will be able to: fully weight bear; stand unaided independently for at least 30 seconds; and participate in group therapy sessions with minimal supervision. Participants will be randomly allocated to an intervention group or usual-care control group. Both groups will receive standard rehabilitation intervention that includes physiotherapy mobility training and exercise for at least two hours on each week day. The intervention group will also receive six 1-hour circuit classes of supervised balance exercises designed to maximise the ability to make postural adjustments in standing, stepping and walking. The primary outcome is balance. Balance will be assessed by measuring the total time the participant can stand unsupported in five different positions; feet apart, feet together, semi-tandem, tandem and single-leg-stance. Secondary outcomes include mobility, self reported physical functioning, falls and hospital readmissions. Performance on the outcome measures will be assessed before randomisation and at two-weeks and three-months after randomisation by physiotherapists unaware of intervention group allocation. Discussion This study will determine the impact of additional balance circuit classes on balance among rehabilitation inpatients. The results will provide essential information to guide evidence-based physiotherapy at the study site as well as across other rehabilitation inpatient settings. Trial registration The protocol for this study is registered with the Australian New Zealand, Clinical Trials Registry: ACTRN=12611000412932 PMID:23870654

Differential Neural Correlates of Set-Shifting in the Bingeing-Purging and Restrictive Subtypes of Anorexia Nervosa: An fMRI Study.

PubMed

Van Autreve, Sara; De Baene, Wouter; Baeken, Chris; van Heeringen, Kees; Vancayseele, Nikita; Vervaet, Myriam

2016-07-01

In this study, possible differences in the neural correlates of set-shifting abilities between the restrictive (AN-R) and bingeing/purging (AN-BP) subtypes of anorexia nervosa have been explored. Three groups of participants performed a set-shifting task during functional magnetic resonance imaging: patients with AN-R (N = 16), AN-BP (N = 13) and healthy control participants (N = 15). As in a typical set-shifting experiment, participants had to switch between two easy tasks (i.e. 'Is the presented number odd/even' or 'Is the presented number smaller/larger than 5'). The trials in which the task was repeated (repeat trials) were compared with trials in which the task was switched (switch trials). With regards to the level of task performance, no significant group differences could be established. However, when comparing switch specific brain activity across study groups, a stronger activation was found in the insula and the precuneus in AN-R when compared to AN-BP and HC. These results suggest that the both subtypes of AN might have different neurobiological correlates, and thus, might benefit from different treatment approaches. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

The effect of berberine on insulin resistance in women with polycystic ovary syndrome: detailed statistical analysis plan (SAP) for a multicenter randomized controlled trial.

PubMed

Zhang, Ying; Sun, Jin; Zhang, Yun-Jiao; Chai, Qian-Yun; Zhang, Kang; Ma, Hong-Li; Wu, Xiao-Ke; Liu, Jian-Ping

2016-10-21

Although Traditional Chinese Medicine (TCM) has been widely used in clinical settings, a major challenge that remains in TCM is to evaluate its efficacy scientifically. This randomized controlled trial aims to evaluate the efficacy and safety of berberine in the treatment of patients with polycystic ovary syndrome. In order to improve the transparency and research quality of this clinical trial, we prepared this statistical analysis plan (SAP). The trial design, primary and secondary outcomes, and safety outcomes were declared to reduce selection biases in data analysis and result reporting. We specified detailed methods for data management and statistical analyses. Statistics in corresponding tables, listings, and graphs were outlined. The SAP provided more detailed information than trial protocol on data management and statistical analysis methods. Any post hoc analyses could be identified via referring to this SAP, and the possible selection bias and performance bias will be reduced in the trial. This study is registered at ClinicalTrials.gov, NCT01138930 , registered on 7 June 2010.

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

PubMed Central

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

2008-01-01

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

Care in a birth room versus a conventional setting: a controlled trial.

PubMed Central

Klein, M; Papageorgiou, A; Westreich, R; Spector-Dunsky, L; Elkins, V; Kramer, M S; Gelfand, M M

1984-01-01

A controlled clinical trial was carried out to assess whether a birth room setting would influence the care of mothers and newborns. Of the 163 low-risk women enrolled, 49 (30%) manifested some prenatal risk and were excluded. The remaining 114 were allocated by strict alternation to a birth room or a conventional setting. Of the 56 women allocated to the birth room, 63% of the primiparas and 19% of the multiparas were later transferred. The numbers in the two settings who had oxytocin stimulation, epidural anesthesia, forceps delivery or cesarean section did not show statistically significant differences. The episiotomy rates were slightly lower in the birth room than in the conventional setting, and the rates of an intact perineum were higher in the birth room. Neither the Apgar scores nor the morbidity rates of the infants showed statistically significant differences related to the setting to which the mother had been allocated, although more infants from the conventional setting were admitted to a special care unit. Both "experimental" groups of women less often received routine perineal shaving, enemas or intravenous infusions than did an obstetrically similar nonexperimental comparison group. Despite the apparent inability in this setting for the birth room to influence the rate of major obstetric procedures (except for episiotomy) and outcomes, the authors believe that a birth room is desirable in tertiary care centres as well as in community hospitals. PMID:6388776

Evaluation of Two Interventions to Reduce Aggressive and Antisocial Behavior in First and Second Graders in a Resource-Poor Setting

ERIC Educational Resources Information Center

Klevens, Joanne; Martinez, Jose William; Le, Brenda; Rojas, Carlos; Duque, Adriana; Tovar, Rafael

2009-01-01

We conducted a three-arm cluster randomized controlled trial (n = 2491) to evaluate a teacher delivered intervention to reduce aggressive and antisocial behavior and increase prosocial behavior in the classroom. A second aim of this trial was to establish whether combining this intervention with an intervention for parents was better than the…

Switching between univalent task-sets in schizophrenia: ERP evidence of an anticipatory task-set reconfiguration deficit.

PubMed

Karayanidis, Frini; Nicholson, Rebecca; Schall, Ulrich; Meem, Lydia; Fulham, Ross; Michie, Patricia T

2006-10-01

The present study used behavioral and event-related potential (ERP) indices of task-switching to examine whether schizophrenia patients have a specific deficit in anticipatory task-set reconfiguration. Participants switched between univalent tasks in an alternating runs paradigms with blocked response-stimulus interval (RSI) manipulation (150, 300, 600, and 1200ms). Nineteen high functioning people with schizophrenia were compared to controls that were matched for age, gender, education and premorbid IQ estimate. Schizophrenia patients had overall increased RT, but no increase in corrected RT switch cost. In the schizophrenia group, ERPs showed reduced activation of the differential positivity in anticipation of switch trial at the optimal 600ms RSI and reduced activation of the frontal post-stimulus switch negativity at both 600 and 1200ms RSI compared to the control group. Despite no behavioral differences in task switching performance, anticipatory and stimulus-triggered ERP indices of task-switching suggest group differences in processing of switch and repeat trials, especially at longer RSI conditions that for control participants provide opportunity for anticipatory activation of task-set reconfiguration processes. These results are compatible with impaired implementation of endogenously driven processes in schizophrenia and greater reliance on external task cues, especially at long preparation intervals.

Intrapartum amnioinfusion for meconium-stained amniotic fluid: a systematic review of randomised controlled trials.

PubMed

Xu, H; Hofmeyr, J; Roy, C; Fraser, W D

2007-04-01

Amnioinfusion (AI) is thought to dilute meconium when present in the amniotic fluid and so reduces the risk of meconium aspiration. To evaluate if AI reduces meconium aspiration syndrome (MAS) and other indicators of morbidity in babies born to women with meconium-stained amniotic fluid (MSAF). PubMed, Medline, EMBASE, and the Cochrane Controlled Trials Register from January 1980 to May 30, 2005, using the keywords 'amnioinfusion' and 'meconium'. Randomised trials comparing AI with no AI for women in labour with MSAF. Trial quality was evaluated using pre-established criteria. The following morbidity indicators were assessed: MAS, 5-minute Apgar score < 7, arterial cord pH < 7.2, and caesarean section. Studies were stratified according to the level of peripartum surveillance (standard versus limited). Typical relative risks (RRs) with their 95% confidence intervals were calculated for each outcome using a random effects model. In clinical settings with standard peripartum surveillance, we found no evidence that AI reduced the risk of MAS (RR 0.59, 95% CI 0.28-1.25), 5-minute Apgar score < 7 (RR 0.90, 95% CI 0.58-1.41), or caesarean delivery (RR 0.89, 95% CI 0.73-1.10). In clinical settings with limited peripartum surveillance, AI appeared to reduce the risk of MAS (RR 0.25, 95% CI 0.13-0.47). In clinical settings with standard peripartum surveillance, the evidence does not support the use of AI for MSAF. In settings with limited peripartum surveillance, where complications of MSAF are common, AI appears to reduce the risk of MAS. However, this finding requires confirmation by further studies.

A pilot cluster randomised trial to assess the effect of a structured communication approach on quality of life in secure mental health settings: The Comquol Study.

PubMed

MacInnes, Douglas; Kinane, Catherine; Parrott, Janet; Mansfield, Jacqueline; Craig, Tom; Eldridge, Sandra; Marsh, Ian; Chan, Claire; Hounsome, Natalia; Harrison, George; Priebe, Stefan

2016-09-29

There is a lack of research in forensic settings examining therapeutic relationships. A structured communication approach, placing patients' perspectives at the heart of discussions about their care, was used to improve patients' quality of life in secure settings. The objectives were to: • Establish the feasibility of the trial design • Determine the variability of the outcomes of interest • Estimate the costs of the intervention • If necessary, refine the intervention METHODS: A pilot cluster randomised controlled trial was conducted. Data was collected from July 2012 to January 2015 from participants in 6 medium secure in-patient services in London and Southern England. 55 patients and 47 nurses were in the intervention group with 57 patients and 45 nurses in the control group. The intervention comprised 6 nurse-patient meetings over a 6 month period. Patients rated their satisfaction with a range of domains followed by discussions on improving patient identified problems. Assessments took place at baseline, 6 months, and 12 months. Participants were not blind to their allocated group. The primary outcome was self-reported quality of life collected by a researcher blind to participants' allocation status. The randomisation procedures and intervention approach functioned well. The measures used were understood by the participants and gave relevant outcome information. The response rates were good with low patient withdrawal rates. The quality of life estimated treatment effect was 0.2 (95 % CI: -0.4 to 0.8) at 6 months and 0.4 (95 % CI: -0.3 to 1.1) indicating the likely extreme boundaries of effect in the main trial. The estimated treatment effect of the primary outcome is clinically important, and a positive effect of the intervention is not ruled out. The estimate of the ICC for the primary outcome at 6 and 12 months was 0.04 (0.00 to 0.17) and 0.05 (0.00 to 0.18). The cost of the intervention was £529 per patient. The trial design was viable as the basis for a full-scale trial. A full trial is justified to estimate the effect of the intervention with greater certainty. The variability of the outcomes could be used to calculate numbers needed for a full-scale trial. Ratings of need for therapeutic security may be useful in any future study. Current Controlled Trials ISRCTN34145189 . Retrospectively registered 22 June 2012.

A survey of facilitators and barriers to recruitment to the MAGNETIC trial.

PubMed

Kaur, Geetinder; Smyth, Rosalind L; Powell, Colin V E; Williamson, Paula

2016-12-23

Recruitment to randomised controlled trials with children is challenging. It is imperative to understand the factors that boost or hinder recruitment of children to clinical trials. We conducted a survey of facilitators and barriers to recruitment to the MAGNETIC trial, using a previously developed web-based tool. MAGNETIC is a multicentre randomised trial of nebulised magnesium in acute severe asthma, recruiting 508 children from 30 UK sites. Recruiters were asked to grade a list of factors from -3 to +3 depending on whether the factor was perceived as a strong, intermediate or weak barrier (-3 to -1) or facilitator (+1 to + 3), and using (0) if it was thought to be not applicable. Free text responses were invited on strategies applied to counter the identified barriers. The commonly identified facilitators were motivation and experience of study teams, effective communication and coordination between teams at site and between sites and the Clinical Trials Unit, the presence of designated research nurses, good trial management, clinical trial publicity, simple inclusion criteria, effective communication with parents and presentation of trial information in a simple and clear manner. The commonly identified barriers were heavy clinical workload, shift patterns of work, Good Clinical Practice (GCP) training, inadequate number of trained staff, time and setting of consent seeking, non-availability of research staff out of hours and parents' concerns about their child taking an experimental medicine. Having a designated research nurse, arranging GCP training and trial-related training sessions for staff were the most commonly reported interventions. This study highlights important generic and trial-specific facilitators and barriers to recruitment to a paediatric trial in the acute setting and provides information on the recruitment strategies or interventions that were applied to overcome these barriers. This information can be very useful in informing the design and conduct of future clinical trials with children, particularly in the acute or emergency setting. ISRCTN, ISRCTN81456894 . Registered on 15 November 2007.

Interventions in the alcohol server setting for preventing injuries.

PubMed

Ker, K; Chinnock, P

2006-04-19

Injuries are a significant public health burden and alcohol intoxication is recognised as a risk factor for injuries. There is increasing attention on supply-side interventions, which aim to modify the environment and context within which alcohol is supplied and consumed. To quantify the effectiveness of interventions implemented in the server setting for reducing injuries. We searched the Cochrane Injuries Group Specialised Register (September 2004), Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2004), MEDLINE (January 1966 to September 2004), EMBASE (1980 to 2004, wk 36), other specialised databases and reference lists of articles. We also contacted experts in the field. Randomised controlled trials (RCTs) and non-randomised controlled studies (NRS) of the effectiveness of interventions administered in the server setting which attempted to modify the conditions under which alcohol is served and consumed, to facilitate sensible alcohol consumption and reduce the occurrence of alcohol-related harm. Two authors independently screened search results and assessed the full texts of potentially relevant studies for inclusion. Data were extracted and methodological quality was examined. Due to variability in the intervention types investigated, a pooled analysis was not appropriate. Twenty studies met the inclusion criteria. Overall methodological quality was poor. Five studies used an injury outcome measure; only one of these studies was randomised. The studies were grouped into broad categories according to intervention type. One NRS investigated server training and estimated a reduction of 23% in single vehicle night-time crashes in the experimental area (controlled for crashes in the control area). Another NRS examined the impact of a drink driving service, and reported a reduction in injury road crashes of 15% in the experimental area, with no change in the control; no difference was found for fatal crashes. One NRS investigating the impact of a policy intervention, reported that pre-intervention the serious assault rate in the experimental area was 52% higher than the rate in the control area. After intervention, the serious assault rate in the experimental area was 37% lower than in the control. The only RCT targeting the server setting environment with an injury outcome compared toughened glassware (experimental) to annealed glassware (control) on number of bar staff injuries; a greater number of injuries were detected in the experimental group (relative risk 1.72, 95% CI 1.15 to 2.59). A NRS investigating the impact of a intervention aiming to reduce crime experienced by drinking premises; found a lower rate of all crime in the experimental premises (rate ratio 4.6, 95% CI 1.7 to 12, P = 0.01), no difference was found for injury (rate ratio 1.1. 95% CI 0.1 to 10, P = 0.093). The effectiveness of the interventions on patron alcohol consumption is inconclusive. One randomised trial found a statistically significant reduction in observed severe aggression exhibited by patrons. There is some indication of improved server behaviour but it is difficult to predict what effect this might have on injury risk. There is no reliable evidence that interventions in the alcohol server setting are effective in reducing injury. Compliance with interventions appears to be a problem; hence mandated interventions may be more likely to show an effect. Randomised controlled trials, with adequate allocation concealment and blinding are required to improve the evidence base. Further well conducted non-randomised trials are also needed, when random allocation is not feasible.

Interventions in the alcohol server setting for preventing injuries.

PubMed

Ker, Katharine; Chinnock, Paul

2008-07-16

Injuries are a significant public health burden and alcohol intoxication is recognised as a risk factor for injuries. There is increasing attention on supply-side interventions, which aim to modify the environment and context within which alcohol is supplied and consumed. To quantify the effectiveness of interventions implemented in the server setting for reducing injuries. We searched the Cochrane Injuries Group Specialised Register (September 2004), Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2004), MEDLINE (January 1966 to September 2004), EMBASE (1980 to 2004, wk 36), other specialised databases and reference lists of articles. We also contacted experts in the field. Randomised controlled trials (RCTs) and non-randomised controlled studies (NRS) of the effectiveness of interventions administered in the server setting which attempted to modify the conditions under which alcohol is served and consumed, to facilitate sensible alcohol consumption and reduce the occurrence of alcohol-related harm. Two authors independently screened search results and assessed the full texts of potentially relevant studies for inclusion. Data were extracted and methodological quality was examined. Due to variability in the intervention types investigated, a pooled analysis was not appropriate. Twenty studies met the inclusion criteria. Overall methodological quality was poor. Five studies used an injury outcome measure; only one of these studies was randomised. The studies were grouped into broad categories according to intervention type. One NRS investigated server training and estimated a reduction of 23% in single vehicle night-time crashes in the experimental area (controlled for crashes in the control area). Another NRS examined the impact of a drink driving service, and reported a reduction in injury road crashes of 15% in the experimental area, with no change in the control; no difference was found for fatal crashes. One NRS investigating the impact of a policy intervention, reported that pre-intervention the serious assault rate in the experimental area was 52% higher than the rate in the control area. After intervention, the serious assault rate in the experimental area was 37% lower than in the control. The only RCT targeting the server setting environment with an injury outcome compared toughened glassware (experimental) to annealed glassware (control) on number of bar staff injuries; a greater number of injuries were detected in the experimental group (relative risk 1.72, 95% CI 1.15 to 2.59). A NRS investigating the impact of a intervention aiming to reduce crime experienced by drinking premises; found a lower rate of all crime in the experimental premises (rate ratio 4.6, 95% CI 1.7 to 12, P = 0.01), no difference was found for injury (rate ratio 1.1. 95% CI 0.1 to 10, P = 0.093). The effectiveness of the interventions on patron alcohol consumption is inconclusive. One randomised trial found a statistically significant reduction in observed severe aggression exhibited by patrons. There is some indication of improved server behaviour but it is difficult to predict what effect this might have on injury risk. There is no reliable evidence that interventions in the alcohol server setting are effective in reducing injury. Compliance with interventions appears to be a problem; hence mandated interventions may be more likely to show an effect. Randomised controlled trials, with adequate allocation concealment and blinding are required to improve the evidence base. Further well conducted non-randomised trials are also needed, when random allocation is not feasible.

Mechanisms of change in control group drinking in clinical trials of brief alcohol intervention: implications for bias toward the null.

PubMed

Bernstein, Judith A; Bernstein, Edward; Heeren, Timothy C

2010-09-01

Reductions in control group consumption over time that are possibly related to research design affect the impact of brief alcohol interventions (BAI) in clinical settings. We conducted a systematic review to identify research design factors that may contribute to control group change, strategies to limit these effects and implications for researchers. Studies with control group n > 30 were selected if they published baseline and outcome consumption data, conducted trials in clinical settings in Anglophone countries and did not censor gender or age. Among 38 studies cited in 20 reviews through October 2009, 16 met criteria (n = 31-370). In 54%, controls received alcohol specific handouts, advice and/or referral. Both the number and depth of assessments were highly variable. The percentage change in consumption ranged from-0.10 to-0.84 (mean-0.32), and effect size from 0.04 to 0.70 (mean 0.37). Published data were insufficient for meta-analysis. Researchers should consider strategies to reduce the impact of research design factors, such as procedures to enhance sample diversity, blind subjects to study purpose to limit social desirability bias, reduce the number and depth of instruments (assessment reactivity), and finally, analytic techniques to decrease the impact of outliers and regression to the mean. This review identifies problems with retrospective analysis of predictors of control group change, and underscores the need to design prospective studies to permit identification, quantification and adjustment for potential sources of bias in BAI trials.

Decision aids for randomised controlled trials: a qualitative exploration of stakeholders’ views

PubMed Central

Gillies, Katie; Skea, Zoë C; Campbell, Marion K

2014-01-01

Objectives To explore stakeholders’ perceptions of decision aids designed to support the informed consent decision-making process for randomised controlled trials. Design Qualitative semistructured interviews. Participants were provided with prototype trial decision aids in advance to stimulate discussion. Interviews were analysed using an established interpretive approach. Participants 23 stakeholders: Trial Managers (n=5); Research Nurses (n=5); Ethics Committee Chairs (n=5); patients (n=4) and Clinical Principal Investigators (n=4). Setting Embedded within two ongoing randomised controlled trials. All interviews conducted with UK-based participants. Results Certain key aspects (eg, values clarification exercises, presentation of probabilities, experiences of others and balance of options) in the prototype decision aids were perceived by all stakeholders as having a significant advantage (over existing patient information leaflets) in terms of supporting well informed appropriate decisions. However, there were some important differences between the stakeholder groups on specific content (eg, language used in the section on positive and negative features of taking part in a trial and the overall length of the trial decision aids). Generally the stakeholders believed trial decision aids have the potential to better engage potential participants in the decision-making process and allow them to make more personally relevant decisions about their participation. Conclusions Compared to existing patient information leaflets, stakeholders perceived decision aids for trial participation to have the potential to promote a more ‘informed’ decision-making process. Further efforts to develop, refine and formally evaluate trial decision aids should be explored. PMID:25138811

Detailed systematic analysis of recruitment strategies in randomised controlled trials in patients with an unscheduled admission to hospital

PubMed Central

Rooshenas, Leila; Fairhurst, Katherine; Rees, Jonathan; Gamble, Carrol; Blazeby, Jane M

2018-01-01

Objectives To examine the design and findings of recruitment studies in randomised controlled trials (RCTs) involving patients with an unscheduled hospital admission (UHA), to consider how to optimise recruitment in future RCTs of this nature. Design Studies within the ORRCA database (Online Resource for Recruitment Research in Clinical TriAls; www.orrca.org.uk) that reported on recruitment to RCTs involving UHAs in patients >18 years were included. Extracted data included trial clinical details, and the rationale and main findings of the recruitment study. Results Of 3114 articles populating ORRCA, 39 recruitment studies were eligible, focusing on 68 real and 13 hypothetical host RCTs. Four studies were prospectively planned investigations of recruitment interventions, one of which was a nested RCT. Most recruitment papers were reports of recruitment experiences from one or more ‘real’ RCTs (n=24) or studies using hypothetical RCTs (n=11). Rationales for conducting recruitment studies included limited time for informed consent (IC) and patients being too unwell to provide IC. Methods to optimise recruitment included providing patients with trial information in the prehospital setting, technology to allow recruiters to cover multiple sites, screening logs to uncover recruitment barriers, and verbal rather than written information and consent. Conclusion There is a paucity of high-quality research into recruitment in RCTs involving UHAs with only one nested randomised study evaluating a recruitment intervention. Among the remaining studies, methods to optimise recruitment focused on how to improve information provision in the prehospital setting and use of screening logs. Future research in this setting should focus on the prospective evaluation of the well-developed interventions to optimise recruitment. PMID:29420230

Detailed systematic analysis of recruitment strategies in randomised controlled trials in patients with an unscheduled admission to hospital.

PubMed

Rowlands, Ceri; Rooshenas, Leila; Fairhurst, Katherine; Rees, Jonathan; Gamble, Carrol; Blazeby, Jane M

2018-02-02

To examine the design and findings of recruitment studies in randomised controlled trials (RCTs) involving patients with an unscheduled hospital admission (UHA), to consider how to optimise recruitment in future RCTs of this nature. Studies within the ORRCA database (Online Resource for Recruitment Research in Clinical TriAls; www.orrca.org.uk) that reported on recruitment to RCTs involving UHAs in patients >18 years were included. Extracted data included trial clinical details, and the rationale and main findings of the recruitment study. Of 3114 articles populating ORRCA, 39 recruitment studies were eligible, focusing on 68 real and 13 hypothetical host RCTs. Four studies were prospectively planned investigations of recruitment interventions, one of which was a nested RCT. Most recruitment papers were reports of recruitment experiences from one or more 'real' RCTs (n=24) or studies using hypothetical RCTs (n=11). Rationales for conducting recruitment studies included limited time for informed consent (IC) and patients being too unwell to provide IC. Methods to optimise recruitment included providing patients with trial information in the prehospital setting, technology to allow recruiters to cover multiple sites, screening logs to uncover recruitment barriers, and verbal rather than written information and consent. There is a paucity of high-quality research into recruitment in RCTs involving UHAs with only one nested randomised study evaluating a recruitment intervention. Among the remaining studies, methods to optimise recruitment focused on how to improve information provision in the prehospital setting and use of screening logs. Future research in this setting should focus on the prospective evaluation of the well-developed interventions to optimise recruitment. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

PubMed

Hussein, Norita; Weng, Stephen F; Kai, Joe; Kleijnen, Jos; Qureshi, Nadeem

2018-03-14

Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. This is an update of a previously published review. To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 20 June 2017.Date of latest search of all other sources: 16 November 2017. Any randomised or quasi-randomised controlled trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease when compared to usual care. We identified 25 papers, describing 16 unique trials which were potentially eligible for inclusion in the review. However, after assessment, no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found. No randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were included. One ongoing trial has been identified which may potentially eligible for inclusion once completed. As no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis, or Tay-Sachs disease were found for inclusion in this review, the research evidence for current policy recommendations is limited to non-randomised studies.Information from well-designed, adequately powered, randomised trials is desirable in order to make more robust recommendations for practice. However, such trials must also consider the legal, ethical, and cultural barriers to implementation of preconception genetic risk assessment.

Reflecting on the methodological challenges of recruiting to a United Kingdom-wide, multi-centre, randomised controlled trial in gynaecology outpatient settings.

PubMed

Dickson, Sylvia; Logan, Janet; Hagen, Suzanne; Stark, Diane; Glazener, Cathryn; McDonald, Alison M; McPherson, Gladys

2013-11-15

Successful recruitment of participants to any trial is central to its success. Trial results are routinely published, and recruitment is often cited to be slower and more difficult than anticipated. This article reflects on the methodological challenges of recruiting women with prolapse attending United Kingdom (UK) gynaecology outpatient clinics to a multi-centre randomised controlled trial (RCT) of physiotherapy, and the systems put in place in an attempt to address them. Gynaecology outpatients with symptomatic prolapse were to be recruited over a 16-month period from 14 UK hospitals and one New Zealand hospital. Eligible women were informed about the trial by their gynaecologist and informed consent was obtained by the central trial office. Recruitment difficulties were encountered early on, and a number of strategies were employed to try to improve recruitment. Some strategies were more successful than others and they differed in the resources required. Actions that facilitated recruitment included increasing recruiting centres to 23 UK and two international hospitals, good centre support, using processes embedded in clinical practice, and good communication between the trial office, collaborators and participants. Collaborator incentives, whereby staff involved received the benefit immediately, were more successful than a nominal monetary payment per woman randomised. Barriers to recruitment included fewer eligible women than anticipated, patient's preference to receive active treatment rather than allocation to the control group, lack of support staff and high staff turnover. Geographical variations in Primary Care Trust Research Management and Governance approval systems and general practitioner (GP) referral procedures also impacted negatively on recruitment. Our article reflects on the methodological challenges of recruiting to a multi-centre RCT in a UK gynaecology setting. Effective interventions included increasing the number of recruiting centres and providing collaborator incentives. Barriers to recruitment included fewer eligible women than anticipated, patient's preference to be allocated to the treatment group, lack of support staff, and variations in approval systems and GP referral procedures. To improve the evidence base on clinical trial recruitment, trialists need to publish their experiences and lessons learned. Future RCTs should evaluate, where possible, the effect of strategies designed to improve recruitment and retention. Current Controlled Trials ISRCTN35911035.

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

PubMed

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

2017-02-01

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

Healthy Homes/Healthy Kids: A Randomized Trial of a Pediatric Primary Care Based Obesity Prevention Intervention for At-Risk 5-10 Year Olds

PubMed Central

Sherwood, Nancy E.; Levy, Rona L.; Langer, Shelby L.; Senso, Meghan M.; Crain, A. Lauren; Hayes, Marcia G.; Anderson, Julie D.; Seburg, Elisabeth M.; Jeffery, Robert W.

2014-01-01

Pediatric primary care is an important setting in which to address obesity prevention, yet relatively few interventions have been evaluated and even fewer have been shown to be effective. The development and evaluation of cost-effective approaches to obesity prevention that leverage opportunities of direct access to families in the pediatric primary care setting, overcome barriers to implementation in busy practice settings, and facilitate sustained involvement of parents is an important public health priority. The goal of the Healthy Homes/Healthy Kids (HHHK 5-10) randomized controlled trial is to evaluate the efficacy of a relatively low-cost primary care-based obesity prevention intervention aimed at 5 to 10 year old children who are at risk for obesity. Four hundred twenty one parent/child dyads were recruited and randomized to either the obesity prevention arm or a contact control condition that focuses on safety and injury prevention. The HHHK 5-10 obesity prevention intervention combines brief counseling with a pediatric primary care provider during routine well-child visits and follow-up telephone coaching that supports parents in making home environmental changes to support healthful eating, activity patterns, and body weight. The contact control condition combines the same provider counseling with telephone coaching focused on safety and injury prevention messages. This manuscript describes the study design and baseline characteristics of participants enrolled in the HHHK 5-10 trial. PMID:23816490

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

PubMed Central

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

2007-01-01

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

Efficacy of the unified protocol for the treatment of emotional disorders in the Spanish public mental health system using a group format: study protocol for a multicenter, randomized, non-inferiority controlled trial.

PubMed

Osma, Jorge; Suso-Ribera, Carlos; García-Palacios, Azucena; Crespo-Delgado, Elena; Robert-Flor, Cristina; Sánchez-Guerrero, Ana; Ferreres-Galan, Vanesa; Pérez-Ayerra, Luisa; Malea-Fernández, Amparo; Torres-Alfosea, Mª Ángeles

2018-03-12

Emotional disorders, which include both anxiety and depressive disorders, are the most prevalent psychological disorders according to recent epidemiological studies. Consequently, public costs associated with their treatment have become a matter of concern for public health systems, which face long waiting lists. Because of their high prevalence in the population, finding an effective treatment for emotional disorders has become a key goal of today's clinical psychology. The Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders might serve the aforementioned purpose, as it can be applied to a variety of disorders simultaneously and it can be easily performed in a group format. The study is a multicenter, randomized, non-inferiority controlled clinical trial. Participants will be 220 individuals with emotional disorders, who are randomized to either a treatment as usual (individual cognitive behavioral therapy) or to a Unified Protocol condition in group format. Depression, anxiety, and diagnostic criteria are the primary outcome measures. Secondary measures include the assessment of positive and negative affect, anxiety control, personality traits, overall adjustment, and quality of life. An analysis of treatment satisfaction is also conducted. Assessment points include baseline, post-treatment, and three follow-ups at 3, 6, and 12 months. To control for missing data and possible biases, intention-to-treat and per-protocol analyses will be performed. This is the first randomized, controlled clinical trial to test the effectiveness of a transdiagnostic intervention in a group format for the treatment of emotional disorders in public settings in Spain. Results obtained from this study may have important clinical, social, and economic implications for public mental health settings in Spain. Retrospectively registered at https://clinicaltrials.gov/ . Trial NCT03064477 (March 10, 2017). The trial is active and recruitment is ongoing. Recruitment is expected to finish by January 2020.

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

PubMed Central

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

2000-01-01

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

Using Performance Feedback and Goal Setting to Improve Elementary Students' Writing Fluency: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Koenig, Elizabeth A.; Eckert, Tanya L.; Hier, Bridget O.

2016-01-01

Although performance feedback interventions successfully lead to improvements in students' performance, research suggests that the combination of feedback and goal setting leads to greater performance than either component alone and that graphing performance in relation to a goal can lead to improvements in academic performance. The goal of the…

The Efficacy of Conjoint Behavioral Consultation in the Home Setting: Outcomes and Mechanisms in Rural Communities

ERIC Educational Resources Information Center

Sheridan, Susan M.; Witte, Amanda L.; Holmes, Shannon; Wu, ChaoRong; Bhatia, Sonya A.; Angell, Samantha

2017-01-01

This study reports the results of a randomized controlled trial examining the effect of Conjoint Behavioral Consultation (CBC), a family-school partnership intervention, on children's behaviors, parents' skills, and parent-teacher relationships in rural community and town settings. Participants were 267 children, 267 parents, and 152 teachers in…

Evaluation of a Decision Aid for Women with Epilepsy Who Are Considering Pregnancy: A Randomized Controlled Trial.

PubMed

McGrath, Amanda; Sharpe, Louise; Lah, Suncica; Parratt, Kaitlyn

2017-07-01

For many women with epilepsy (WWE), decision making about pregnancy is complicated by considerations such as the potential teratogenicity of antiepileptic drugs, offspring risk of epilepsy, seizure occurrence during pregnancy, and the challenges of parenting amidst poorly controlled seizures. This proof-of-concept, randomized controlled trial aimed to evaluate a decision aid (DA) developed to help WWE decide if they should start or enlarge their families. Seventy-nine WWE of childbearing age were recruited from Epilepsy Action Australia between October and November 2013 and randomized to receive the intervention (the DA) or not, and to complete a set of questionnaires pre- and post- intervention. The DA, delivered as a PDF booklet, provided balanced evidence-based information about options, risks and benefits, including probabilities; as well as steps for clarifying values and considering options within one's personal situation. Compared with the control group, the DA group had statistically significant improvements in knowledge about pregnancy and epilepsy (Cohen's d = 1.24; 95%CI = 0.77 to 1.83) and reduced decisional conflict (Cohen's d = 0.59; 95%CI = 0.21 to 0.99). Changes in decision self-efficacy, certainty of choice, patient-practitioner communication abilities and value congruence with choice were comparable between the DA and control group. Importantly, women's decisions about motherhood were not biased towards either direction, and there were no adverse effects on depression or anxiety. All women who received the DA indicated they would recommend it to other WWE. The DA has the potential to serve as a useful support tool for WWE who are considering motherhood. Future research is needed to test the DA in clinical settings with guidance from a health professional. The trial was registered with the Australian New Zealand Clinical Trials Registry (ID ACTRN12613001082796).

Effect of a multifaceted educational intervention for anti-infectious measures on sepsis mortality: a cluster randomized trial.

PubMed

Bloos, Frank; Rüddel, Hendrik; Thomas-Rüddel, Daniel; Schwarzkopf, Daniel; Pausch, Christine; Harbarth, Stephan; Schreiber, Torsten; Gründling, Matthias; Marshall, John; Simon, Philipp; Levy, Mitchell M; Weiss, Manfred; Weyland, Andreas; Gerlach, Herwig; Schürholz, Tobias; Engel, Christoph; Matthäus-Krämer, Claudia; Scheer, Christian; Bach, Friedhelm; Riessen, Reimer; Poidinger, Bernhard; Dey, Karin; Weiler, Norbert; Meier-Hellmann, Andreas; Häberle, Helene H; Wöbker, Gabriele; Kaisers, Udo X; Reinhart, Konrad

2017-11-01

Guidelines recommend administering antibiotics within 1 h of sepsis recognition but this recommendation remains untested by randomized trials. This trial was set up to investigate whether survival is improved by reducing the time before initiation of antimicrobial therapy by means of a multifaceted intervention in compliance with guideline recommendations. The MEDUSA study, a prospective multicenter cluster-randomized trial, was conducted from July 2011 to July 2013 in 40 German hospitals. Hospitals were randomly allocated to receive conventional continuous medical education (CME) measures (control group) or multifaceted interventions including local quality improvement teams, educational outreach, audit, feedback, and reminders. We included 4183 patients with severe sepsis or septic shock in an intention-to-treat analysis comparing the multifaceted intervention (n = 2596) with conventional CME (n = 1587). The primary outcome was 28-day mortality. The 28-day mortality was 35.1% (883 of 2596 patients) in the intervention group and 26.7% (403 of 1587 patients; p = 0.01) in the control group. The intervention was not a risk factor for mortality, since this difference was present from the beginning of the study and remained unaffected by the intervention. Median time to antimicrobial therapy was 1.5 h (interquartile range 0.1-4.9 h) in the intervention group and 2.0 h (0.4-5.9 h; p = 0.41) in the control group. The risk of death increased by 2% per hour delay of antimicrobial therapy and 1% per hour delay of source control, independent of group assignment. Delay in antimicrobial therapy and source control was associated with increased mortality but the multifaceted approach was unable to change time to antimicrobial therapy in this setting and did not affect survival.

The SPORTSMART study: a pilot randomised controlled trial of sexually transmitted infection screening interventions targeting men in football club settings

PubMed Central

Fuller, Sebastian S; Mercer, Catherine H; Copas, Andrew J; Saunders, John; Sutcliffe, Lorna J; Cassell, Jackie A; Hart, Graham; Johnson, Anne M; Roberts, Tracy E; Jackson, Louise J; Muniina, Pamela; Estcourt, Claudia S

2015-01-01

Background Uptake of chlamydia screening by men in England has been substantially lower than by women. Non-traditional settings such as sports clubs offer opportunities to widen access. Involving people who are not medically trained to promote screening could optimise acceptability. Methods We developed two interventions to explore the acceptability and feasibility of urine-based sexually transmitted infection (STI) screening interventions targeting men in football clubs. We tested these interventions in a pilot cluster randomised control trial. Six clubs were randomly allocated, two to each of three trial arms: team captain-led and poster STI screening promotion; sexual health adviser-led and poster STI screening promotion; and poster-only STI screening promotion (control/comparator). Primary outcome was test uptake. Results Across the three arms, 153 men participated in the trial and 90 accepted the offer of screening (59%, 95% CI 35% to 79%). Acceptance rates were broadly comparable across the arms: captain-led: 28/56 (50%); health professional-led: 31/46 (67%); and control: 31/51 (61%). However, rates varied appreciably by club, precluding formal comparison of arms. No infections were identified. Process evaluation confirmed that interventions were delivered in a standardised way but the control arm was unintentionally ‘enhanced’ by some team captains actively publicising screening events. Conclusions Compared with other UK-based community screening models, uptake was high but gaining access to clubs was not always easy. Use of sexual health advisers and team captains to promote screening did not appear to confer additional benefit over a poster-promoted approach. Although the interventions show potential, the broader implications of this strategy for UK male STI screening policy require further investigation. PMID:25512674

Post-trial apomorphine at an autoreceptor dose level can eliminate apomorphine conditioning and sensitization: support for the critical role of dopamine in re-consolidation.

PubMed

Carrera, Marinete Pinheiro; Carey, Robert J; Cruz Dias, Flávia Regina; dos Santos Sampaio, Maria de Fátima; de Matos, Liana Wermelinger

2013-01-01

Re-exposure to conditioned drug stimuli triggers re-consolidation processes. In the present study post-trial apomorphine treatments were administered in order to interact with the re-consolidation of an apomorphine conditioned/sensitized locomotor response. A low (0.05 mg/kg) and a high (2.0mg/kg) dose were used to inhibit or to enhance dopamine activity, respectively. Initially, groups received 5 daily apomorphine (2.0mg/kg)/vehicle treatments either paired or unpaired to open-field placement. The paired treatments generated a progressive locomotor response. Subsequently, all groups received a 5 min non-drug test for conditioning and a conditioned locomotor response was observed in the paired group. The groups received another apomorphine (2.0mg/kg)/vehicle treatment as a re-induction treatment. At this stage the post-trial protocol was initiated. One set of paired, unpaired and vehicle groups were given a low dose of apomorphine (0.05 mg/kg) post-trial; another set received a high dose of apomorphine (2.0mg/kg) post-trial. The remaining group set received vehicle post-trial. The low dose post-trial treatment eliminated the conditioned and sensitized locomotor response and the high dose post-trial treatment enhanced the conditioned and sensitized locomotor response. The efficacy of the post-trial apomorphine treatments to modify the conditioned and the sensitized response after a brief non-drug exposure to test cues supports the proposition that exteroceptive cues control conditioning and sensitization and that the interoceptive drug cues make little or no associational contribution to apomorphine conditioning and sensitization. In addition, the findings point to the importance of dopamine activation in both the acquisition and re-consolidation of conditioning processes. Copyright © 2012 Elsevier B.V. All rights reserved.

REFINE (Reducing Falls in In-patient Elderly)--a randomised controlled trial.

PubMed

Vass, Catherine D; Sahota, Opinder; Drummond, Avril; Kendrick, Denise; Gladman, John; Sach, Tracey; Avis, Mark; Grainge, Matthew

2009-09-10

Falls in hospitals are common, resulting in injury and anxiety to patients, and large costs to NHS organisations. More than half of all in-patient falls in elderly people in acute care settings occur at the bedside, during transfers or whilst getting up to go to the toilet. In the majority of cases these falls are unwitnessed. There is insufficient evidence underpinning the effectiveness of interventions to guide clinical staff regarding the reduction of falls in the elderly inpatient. New patient monitoring technologies have the potential to offer advances in falls prevention. Bedside sensor equipment can alert staff, not in the immediate vicinity, to a potential problem and avert a fall. However no studies utilizing this assistive technology have demonstrated a significant reduction in falls rates in a randomised controlled trial setting. The research design is an individual patient randomised controlled trial of bedside chair and bed pressure sensors, incorporating a radio-paging alerting mode to alert staff to patients rising from their bed or chair, across five acute elderly care wards in Nottingham University Hospitals NHS Trust. Participants will be randomised to bedside chair and bed sensors or to usual care (without the use of sensors). The primary outcome is the number of bedside in-patient falls. The REFINE study is the first randomised controlled trial of bedside pressure sensors in elderly inpatients in an acute NHS Trust. We will assess whether falls can be successfully and cost effectively reduced using this technology, and report on its acceptability to both patients and staff.

A cluster randomised trial of a school-based resilience intervention to decrease tobacco, alcohol and illicit drug use in secondary school students: study protocol

PubMed Central

2012-01-01

Background Whilst schools provide a potentially appropriate setting for preventing substance use among young people, systematic review evidence suggests that past interventions in this setting have demonstrated limited effectiveness in preventing tobacco, alcohol and other drug use. Interventions that adopt a mental wellbeing approach to prevent substance use offer considerable promise and resilience theory provides one method to impact on adolescent mental well-being. The aim of the proposed study is to examine the efficacy of a resilience intervention in decreasing the tobacco, alcohol and illicit drug use of adolescents. Methods A cluster randomised controlled trial with schools as the unit of randomisation will be undertaken. Thirty two schools in disadvantaged areas will be allocated to either an intervention or a control group. A comprehensive resilience intervention will be implemented, inclusive of explicit program adoption strategies. Baseline surveys will be conducted with students in Grade 7 in both groups and again three years later when the student cohort is in Grade 10. The primary outcome measures will include self-reported tobacco, alcohol, marijuana and other illicit drug use. Comparisons will be made post-test between Grade 10 students in intervention and control schools to determine intervention effectiveness across all measures. Discussion To the authors’ knowledge this is the first randomised controlled trial to evaluate the effectiveness of a comprehensive school-based resilience intervention, inclusive of explicit adoption strategies, in decreasing tobacco, alcohol and illicit drug use of adolescents attending disadvantaged secondary schools. Trial registration ACTRN12611000606987 PMID:23171383

Effectiveness and implementation of an obesity prevention intervention: the HeLP-her Rural cluster randomised controlled trial.

PubMed

Lombard, Catherine B; Harrison, Cheryce L; Kozica, Samantha L; Zoungas, Sophia; Keating, Catherine; Teede, Helena J

2014-06-16

To impact on the obesity epidemic, interventions that prevent weight gain across populations are urgently needed. However, even the most efficacious interventions will have little impact on obesity prevention unless they are successfully implemented in diverse populations and settings. Implementation research takes isolated efficacy studies into practice and policy and is particularly important in obesity prevention where there is an urgent need to accelerate the evidence to practice cycle. Despite the recognised need, few obesity prevention interventions have been implemented in real life settings and to our knowledge rarely target rural communities. Here we describe the rationale, design and implementation of a Healthy Lifestyle Program for women living in small rural communities (HeLP-her Rural). The primary goal of HeLP-her Rural is to prevent weight gain using a low intensity, self-management intervention. Six hundred women from 42 small rural communities in Australia will be randomised as clusters (n-21 control towns and n = 21 intervention towns). A pragmatic randomised controlled trial methodology will test efficacy and a comprehensive mixed methods community evaluation and cost analysis will inform effectiveness and implementation of this novel prevention program. Implementing population interventions to prevent obesity is complex, costly and challenging. To address these barriers, evidence based interventions need to move beyond isolated efficacy trials and report outcomes related to effectiveness and implementation. Large pragmatic trials provide an opportunity to inform both effectiveness and implementation leading to potential for greater impact at the population level. Pragmatic trials should incorporate both effectiveness and implementation outcomes and a multidimensional methodology to inform scale-up to population level. The learnings from this trial will impact on the design and implementation of population obesity prevention strategies nationally and internationally. ANZ clinical trial registry ACTRN12612000115831. Date of registration 24/01/2012.

Study protocol for the evaluation of an Infant Simulator based program delivered in schools: a pragmatic cluster randomised controlled trial.

PubMed

Brinkman, Sally A; Johnson, Sarah E; Lawrence, David; Codde, James P; Hart, Michael B; Straton, Judith A Y; Silburn, Sven

2010-10-21

This paper presents the study protocol for a pragmatic randomised controlled trial to evaluate the impact of a school based program developed to prevent teenage pregnancy. The program includes students taking care of an Infant Simulator; despite growing popularity and an increasing global presence of such programs, there is no published evidence of their long-term impact. The aim of this trial is to evaluate the Virtual Infant Parenting (VIP) program by investigating pre-conceptual health and risk behaviours, teen pregnancy and the resultant birth outcomes, early child health and maternal health. Fifty-seven schools (86% of 66 eligible secondary schools) in Perth, Australia were recruited to the clustered (by school) randomised trial, with even randomisation to the intervention and control arms. Between 2003 and 2006, the VIP program was administered to 1,267 participants in the intervention schools, while 1,567 participants in the non-intervention schools received standard curriculum. Participants were all female and aged between 13-15 years upon recruitment. Pre and post-intervention questionnaires measured short-term impact and participants are now being followed through their teenage years via data linkage to hospital medical records, abortion clinics and education records. Participants who have a live birth are interviewed by face-to-face interview. Kaplan-Meier survival analysis and proportional hazards regression will test for differences in pregnancy, birth and abortion rates during the teenage years between the study arms. This protocol paper provides a detailed overview of the trial design as well as initial results in the form of participant flow. The authors describe the intervention and its delivery within the natural school setting and discuss the practical issues in the conduct of the trial, including recruitment. The trial is pragmatic and will directly inform those who provide Infant Simulator based programs in school settings. ISRCTN24952438.

Vector and reservoir control for preventing leishmaniasis.

PubMed

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

2015-08-05

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

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

PubMed Central

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

2015-01-01

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

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

PubMed Central

2010-01-01

Background The goal of this cluster randomized trial is to test the effectiveness of a counseling approach, Motivational Interviewing, to control dental caries in young Aboriginal children. Motivational Interviewing, a client-centred, directive counseling style, has not yet been evaluated as an approach for promotion of behaviour change in indigenous communities in remote settings. Methods/design Aboriginal women were hired from the 9 communities to recruit expectant and new mothers to the trial, administer questionnaires and deliver the counseling to mothers in the test communities. The goal is for mothers to receive the intervention during pregnancy and at their child's immunization visits. Data on children's dental health status and family dental health practices will be collected when children are 30-months of age. The communities were randomly allocated to test or control group by a random "draw" over community radio. Sample size and power were determined based on an anticipated 20% reduction in caries prevalence. Randomization checks were conducted between groups. Discussion In the 5 test and 4 control communities, 272 of the original target sample size of 309 mothers have been recruited over a two-and-a-half year period. A power calculation using the actual attained sample size showed power to be 79% to detect a treatment effect. If an attrition fraction of 4% per year is maintained, power will remain at 80%. Power will still be > 90% to detect a 25% reduction in caries prevalence. The distribution of most baseline variables was similar for the two randomized groups of mothers. However, despite the random assignment of communities to treatment conditions, group differences exist for stage of pregnancy and prior tooth extractions in the family. Because of the group imbalances on certain variables, control of baseline variables will be done in the analyses of treatment effects. This paper explains the challenges of conducting randomized trials in remote settings, the importance of thorough community collaboration, and also illustrates the likelihood that some baseline variables that may be clinically important will be unevenly split in group-randomized trials when the number of groups is small. Trial registration This trial is registered as ISRCTN41467632. PMID:20465831

21 CFR 886.1405 - Ophthalmic trial lens set.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ophthalmic trial lens set. 886.1405 Section 886...) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1405 Ophthalmic trial lens set. (a) Identification. An ophthalmic trial lens set is a device that is a set of lenses of various dioptric powers...

Supervised exercise therapy versus home-based exercise therapy versus walking advice for intermittent claudication.

PubMed

Hageman, David; Fokkenrood, Hugo Jp; Gommans, Lindy Nm; van den Houten, Marijn Ml; Teijink, Joep Aw

2018-04-06

Although supervised exercise therapy (SET) provides significant symptomatic benefit for patients with intermittent claudication (IC), it remains an underutilized tool. Widespread implementation of SET is restricted by lack of facilities and funding. Structured home-based exercise therapy (HBET) with an observation component (e.g., exercise logbooks, pedometers) and just walking advice (WA) are alternatives to SET. This is the second update of a review first published in 2006. The primary objective was to provide an accurate overview of studies evaluating effects of SET programs, HBET programs, and WA on maximal treadmill walking distance or time (MWD/T) for patients with IC. Secondary objectives were to evaluate effects of SET, HBET, and WA on pain-free treadmill walking distance or time (PFWD/T), quality of life, and self-reported functional impairment. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register (December 16, 2016) and the Cochrane Central Register of Controlled Trials (2016, Issue 11). We searched the reference lists of relevant studies identified through searches for other potential trials. We applied no restriction on language of publication. We included parallel-group randomized controlled trials comparing SET programs with HBET programs and WA in participants with IC. We excluded studies in which control groups did not receive exercise or walking advice (maintained normal physical activity). We also excluded studies comparing exercise with percutaneous transluminal angioplasty, bypass surgery, or drug therapy. Three review authors (DH, HF, and LG) independently selected trials, extracted data, and assessed trials for risk of bias. Two other review authors (MvdH and JT) confirmed the suitability and methodological quality of trials. For all continuous outcomes, we extracted the number of participants, mean outcome, and standard deviation for each treatment group through the follow-up period, if available. We extracted Medical Outcomes Study Short Form 36 outcomes to assess quality of life, and Walking Impairment Questionnaire outcomes to assess self-reported functional impairment. As investigators used different scales to present results of walking distance and time, we standardized reported data to effect sizes to enable calculation of an overall standardized mean difference (SMD). We obtained summary estimates for all outcome measures using a random-effects model. We assessed the quality of evidence using the GRADE approach. For this update, we included seven additional studies, making a total of 21 included studies, which involved a total of 1400 participants: 635 received SET, 320 received HBET, and 445 received WA. In general, SET and HBET programs consisted of three exercise sessions per week. Follow-up ranged from six weeks to two years. Most trials used a treadmill walking test to investigate effects of exercise therapy on walking capacity. However, two trials assessed only quality of life, functional impairment, and/or walking behavior (i.e., daily steps measured by pedometer). The overall methodological quality of included trials was moderate to good. However, some trials were small with respect to numbers of participants, ranging from 20 to 304.SET groups showed clear improvement in MWD/T compared with HBET and WA groups, with overall SMDs at three months of 0.37 (95% confidence interval [CI] 0.12 to 0.62; P = 0.004; moderate-quality evidence) and 0.80 (95% CI 0.53 to 1.07; P < 0.00001; high-quality evidence), respectively. This translates to differences in increased MWD of approximately 120 and 210 meters in favor of SET groups. Data show improvements for up to six and 12 months, respectively. The HBET group did not show improvement in MWD/T compared with the WA group (SMD 0.30, 95% CI -0.45 to 1.05; P = 0.43; moderate-quality evidence).Compared with HBET, SET was more beneficial for PFWD/T but had no effect on quality of life parameters nor on self-reported functional impairment. Compared with WA, SET was more beneficial for PFWD/T and self-reported functional impairment, as well as for some quality of life parameters (e.g., physical functioning, pain, and physical component summary after 12 months), and HBET had no effect.Data show no obvious effects on mortality rates. Thirteen of the 1400 participants died, but no deaths were related to exercise therapy. Overall, adherence to SET was approximately 80%, which was similar to that reported with HBET. Only limited adherence data were available for WA groups. Evidence of moderate and high quality shows that SET provides an important benefit for treadmill-measured walking distance (MWD and PFWD) compared with HBET and WA, respectively. Although its clinical relevance has not been definitively demonstrated, this benefit translates to increased MWD of 120 and 210 meters after three months in SET groups. These increased walking distances are likely to have a positive impact on the lives of patients with IC. Data provide no clear evidence of a difference between HBET and WA. Trials show no clear differences in quality of life parameters nor in self-reported functional impairment between SET and HBET. However, evidence is of low and very low quality, respectively. Investigators detected some improvements in quality of life favoring SET over WA, but analyses were limited by small numbers of studies and participants. Future studies should focus on disease-specific quality of life and other functional outcomes, such as walking behavior and physical activity, as well as on long-term follow-up.

Decision-making and goal-setting in chronic disease management: Baseline findings of a randomized controlled trial.

PubMed

Kangovi, Shreya; Mitra, Nandita; Smith, Robyn A; Kulkarni, Raina; Turr, Lindsey; Huo, Hairong; Glanz, Karen; Grande, David; Long, Judith A

2017-03-01

Growing interest in collaborative goal-setting has raised questions. First, are patients making the 'right choices' from a biomedical perspective? Second, are patients and providers setting goals of appropriate difficulty? Finally, what types of support will patients need to accomplish their goals? We analyzed goals and action plans from a trial of collaborative goal-setting among 302 residents of a high-poverty urban region who had multiple chronic conditions. Patients used a low-literacy aid to prioritize one of their chronic conditions and then set a goal for that condition with their primary care provider. Patients created patient-driven action plans for reaching these goals. Patients chose to focus on conditions that were in poor control and set ambitious chronic disease management goals. The mean goal weight loss -16.8lbs (SD 19.5), goal HbA1C reduction was -1.3% (SD 1.7%) and goal blood pressure reduction was -9.8mmHg (SD 19.2mmHg). Patient-driven action plans spanned domains including health behavior (58.9%) and psychosocial (23.5%). High-risk, low-SES patients identified high priority conditions, set ambitious goals and generate individualized action plans for chronic disease management. Practices may require flexible personnel who can support patients using a blend of coaching, social support and navigation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Moving from Efficacy to Effectiveness Trials in Prevention Research

PubMed Central

Marchand, Erica; Stice, Eric; Rohde, Paul; Becker, Carolyn Black

2013-01-01

Efficacy trials test whether interventions work under optimal, highly controlled conditions whereas effectiveness trials test whether interventions work with typical clients and providers in real-world settings. Researchers, providers, and funding bodies have called for more effectiveness trials to understand whether interventions produce effects under ecologically valid conditions, which factors predict program effectiveness, and what strategies are needed to successfully implement programs in practice settings. The transition from efficacy to effectiveness with preventive interventions involves unique considerations, some of which are not shared by treatment research. The purpose of this article is to discuss conceptual and methodological issues that arise when making the transition from efficacy to effectiveness research in primary, secondary, and tertiary prevention, drawing on the experiences of two complimentary research groups as well as the existing literature. We address (a) program of research, (b) intervention design and conceptualization, (c) participant selection and characteristics, (d) providers, (e) context, (f) measurement and methodology, (g) outcomes, (h) cost, and (i) sustainability. We present examples of research in eating disorder prevention that demonstrate the progression from efficacy to effectiveness trials. PMID:21092935

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

PubMed

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

2015-04-01

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

Academic Performance of Subsequent Schools and Impacts of Early Interventions: Evidence from a Randomized Controlled Trial in Head Start Settings

PubMed Central

Zhai, Fuhua; Raver, C. Cybele; Jones, Stephanie M.

2012-01-01

The role of subsequent school contexts in the long-term effects of early childhood interventions has received increasing attention, but has been understudied in the literature. Using data from the Chicago School Readiness Project (CSRP), a cluster-randomized controlled trial conducted in Head Start programs, we investigate whether the intervention had differential effects on academic and behavioral outcomes in kindergarten if children attended high- or low-performing schools subsequent to the preschool intervention year. To address the issue of selection bias, we adopt an innovative method, principal score matching, and control for a set of child, mother, and classroom covariates. We find that exposure to the CSRP intervention in the Head Start year had significant effects on academic and behavioral outcomes in kindergarten for children who subsequently attended high-performing schools, but no significant effects on children attending low-performing schools. Policy implications of the findings are discussed. PMID:22773872

Less is more: Patient-level meta-analysis reveals paradoxical dose-response effects of a computer-based social anxiety intervention targeting attentional bias.

PubMed

Price, Rebecca B; Kuckertz, Jennie M; Amir, Nader; Bar-Haim, Yair; Carlbring, Per; Wallace, Meredith L

2017-12-01

The past decade of research has seen considerable interest in computer-based approaches designed to directly target cognitive mechanisms of anxiety, such as attention bias modification (ABM). By pooling patient-level datasets from randomized controlled trials of ABM that utilized a dot-probe training procedure, we assessed the impact of training "dose" on relevant outcomes among a pooled sample of 693 socially anxious adults. A paradoxical effect of the number of training trials administered was observed for both posttraining social anxiety symptoms and behavioral attentional bias (AB) toward threat (the target mechanism of ABM). Studies administering a large (>1,280) number of training trials showed no benefit of ABM over control conditions, while those administering fewer training trials showed significant benefit for ABM in reducing social anxiety (P = .02). These moderating effects of dose were not better explained by other examined variables and previously identified moderators, including patient age, training setting (laboratory vs. home), or type of anxiety assessment (clinician vs. self-report). Findings inform the optimal dosing for future dot-probe style ABM applications in both research and clinical settings, and suggest several novel avenues for further research. © 2017 Wiley Periodicals, Inc.

Birth Control in Clinical Trials: Industry Survey of Current Use Practices, Governance, and Monitoring.

PubMed

Stewart, J; Breslin, W J; Beyer, B K; Chadwick, K; De Schaepdrijver, L; Desai, M; Enright, B; Foster, W; Hui, J Y; Moffat, G J; Tornesi, B; Van Malderen, K; Wiesner, L; Chen, C L

2016-03-01

The Health and Environmental Sciences Institute (HESI) Developmental and Reproductive Toxicology Technical Committee sponsored a pharmaceutical industry survey on current industry practices for contraception use during clinical trials. The objectives of the survey were to improve our understanding of the current industry practices for contraception requirements in clinical trials, the governance processes set up to promote consistency and/or compliance with contraception requirements, and the effectiveness of current contraception practices in preventing pregnancies during clinical trials. Opportunities for improvements in current practices were also considered. The survey results from 12 pharmaceutical companies identified significant variability among companies with regard to contraception practices and governance during clinical trials. This variability was due primarily to differences in definitions, areas of scientific uncertainty or misunderstanding, and differences in company approaches to enrollment in clinical trials. The survey also revealed that few companies collected data in a manner that would allow a retrospective understanding of the reasons for failure of birth control during clinical trials. In this article, suggestions are made for topics where regulatory guidance or scientific publications could facilitate best practice. These include provisions for a pragmatic definition of women of childbearing potential, guidance on how animal data can influence the requirements for male and female birth control, evidence-based guidance on birth control and pregnancy testing regimes suitable for low- and high-risk situations, plus practical methods to ascertain the risk of drug-drug interactions with hormonal contraceptives.

Defining a clinically meaningful effect for the design and interpretation of randomized controlled trials.

PubMed

Keefe, Richard S E; Kraemer, Helena C; Epstein, Robert S; Frank, Ellen; Haynes, Ginger; Laughren, Thomas P; McNulty, James; Reed, Shelby D; Sanchez, Juan; Leon, Andrew C

2013-05-01

This article captures the proceedings of a meeting aimed at defining clinically meaningful effects for use in randomized controlled trials for psychopharmacological agents. Experts from a variety of disciplines defined clinically meaningful effects from their perspectives along with viewpoints about how to design and interpret randomized controlled trials. The article offers relevant, practical, and sometimes anecdotal information about clinically meaningful effects and how to interpret them. The concept for this session was the work of co-chairs Richard Keefe and the late Andy Leon. Faculty included Richard Keefe, PhD; James McNulty, AbScB; Robert S. Epstein, MD, MS; Shelby D. Reed, PhD; Juan Sanchez, MD; Ginger Haynes, PhD; Andrew C. Leon, PhD; Helena Chmura Kraemer, PhD; Ellen Frank, PhD, and Kenneth L. Davis, MD. The term clinically meaningful effect is an important aspect of designing and interpreting randomized controlled trials but can be particularly difficult in the setting of psychopharmacology where effect size may be modest, particularly over the short term, because of a strong response to placebo. Payers, regulators, patients, and clinicians have different concerns about clinically meaningful effects and may describe these terms differently. The use of moderators in success rate differences may help better delineate clinically meaningful effects. There is no clear consensus on a single definition for clinically meaningful differences in randomized controlled trials, and investigators must be sensitive to specific concerns of stakeholders in psychopharmacology in order to design and execute appropriate clinical trials.

Effectiveness of Goal-Setting Telephone Follow-Up on Health Behaviors of Patients with Ischemic Stroke: A Randomized Controlled Trial.

PubMed

Wan, Li-Hong; Zhang, Xiao-Pei; Mo, Miao-Miao; Xiong, Xiao-Ni; Ou, Cui-Ling; You, Li-Ming; Chen, Shao-Xian; Zhang, Min

2016-09-01

Adopting healthy behaviors is critical for secondary stroke prevention, but many patients fail to follow national guidelines regarding diet, exercise, and abstinence from risk factors. Compliance often decreases with time after hospital discharge, yet few studies have examined programs promoting long-term adherence to health behaviors. Goal setting and telephone follow-up have been proven to be effective in other areas of medicine, so this study evaluated the effectiveness of a guideline-based, goal-setting telephone follow-up program for patients with ischemic stroke. This was a multicenter, assessor-blinded, parallel-group, randomized controlled trial. Ninety-one stroke patients were randomized to either a control group or an intervention group. Intervention consisted of predischarge education and 3 goal-setting follow-up sessions conducted by phone. Data were collected at baseline and during the third and sixth months after hospital discharge. Six months after discharge, patients in the intervention group exhibited significantly higher medication adherence than patients in the control group. There were no statistically significant differences in physical activity, nutrition, low-salt diet adherence, blood pressure monitoring, smoking abstinence, unhealthy use of alcohol, and modified Rankin Scale (mRS) scores between the 2 groups. Goal-setting telephone follow-up intervention for ischemic stroke patients is feasible and leads to improved medication adherence. However, the lack of group differences in other health behavior subcategories and in themRS score indicates a need for more effective intervention strategies to help patients reach guideline-recommended targets. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2005-05-01

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

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

PubMed Central

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

1999-01-01

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

Stroke Survivors' Evaluations of a Stroke Workbook-Based Intervention Designed to Increase Perceived Control over Recovery

ERIC Educational Resources Information Center

Joice, Sara; Johnston, Marie; Bonetti, Debbie; Morrison, Val; MacWalter, Ron

2012-01-01

Objective: To report stroke survivors' experiences and perceived usefulness of an effective self-help workbook-based intervention. Design: A cross-sectional study involving the intervention group of an earlier randomized controlled trial. Setting: At the participants' homes approximately seven weeks post-hospital discharge. Method: Following the…

A systematic review of training programmes for recruiters to randomised controlled trials.

PubMed

Townsend, Daisy; Mills, Nicola; Savović, Jelena; Donovan, Jenny L

2015-09-28

Recruitment to randomised controlled trials (RCTs) is often difficult. Clinician related factors have been implicated as important reasons for low rates of recruitment. Clinicians (doctors and other health professionals) can experience discomfort with some underlying principles of RCTs and experience difficulties in conveying them positively to potential trial participants. Recruiter training has been suggested to address identified problems but a synthesis of this research is lacking. The aim of our study was to systematically review the available evidence on training interventions for recruiters to randomised trials. Studies that evaluated training programmes for trial recruiters were included. Those that provided only general communication training not linked to RCT recruitment were excluded. Data extraction and quality assessment were completed by two reviewers independently, with a third author where necessary. Seventeen studies of 9615 potentially eligible titles and abstracts were included in the review: three randomised controlled studies, two non-randomised controlled studies, nine uncontrolled pre-test/post-test studies, two qualitative studies, and a post-training questionnaire survey. Most studies were of moderate or weak quality. Training programmes were mostly set within cancer trials, and usually consisted of workshops with a mix of health professionals over one or two consecutive days covering generic and trial specific issues. Recruiter training programmes were well received and some increased recruiters' self-confidence in communicating key RCT concepts to patients. There was, however, little evidence that this training increased actual recruitment rates or patient understanding, satisfaction, or levels of informed consent. There is a need to develop recruiter training programmes that can lead to improved recruitment and informed consent in randomised trials.

Wheeze as an Adverse Event in Pediatric Vaccine and Drug Randomized Controlled Trials: A Systematic Review

PubMed Central

Marangu, Diana; Kovacs, Stephanie; Walson, Judd; Bonhoeffer, Jan; Ortiz, Justin R.; John-Stewart, Grace; Horne, David J.

2016-01-01

Introduction Wheeze is an important sign indicating a potentially severe adverse event in vaccine and drug trials, particularly in children. However, there are currently no consensus definitions of wheeze or associated respiratory compromise in randomized controlled trials (RCTs). Objective To identify definitions and severity grading scales of wheeze as an adverse event in vaccine and drug RCTs enrolling children <5 years and to determine their diagnostic performance based on sensitivity, specificity and inter-observer agreement. Methods We performed a systematic review of electronic databases and reference lists with restrictions for trial settings, English language and publication date ≥ 1970. Wheeze definitions and severity grading were abstracted and ranked by a diagnostic certainty score based on sensitivity, specificity and inter-observer agreement. Results Of 1,205 articles identified using our broad search terms, we identified 58 eligible trials conducted in 38 countries, mainly in high-income settings. Vaccines made up the majority (90%) of interventions, particularly influenza vaccines (65%). Only 15 trials provided explicit definitions of wheeze. Of 24 studies that described severity, 11 described wheeze severity in the context of an explicit wheeze definition. The remaining 13 studies described wheeze severity where wheeze was defined as part of a respiratory illness or a wheeze equivalent. Wheeze descriptions were elicited from caregiver reports (14%), physical examination by a health worker (45%) or a combination (41%). There were 21/58 studies in which wheeze definitions included combined caregiver report and healthcare worker assessment. The use of these two methods appeared to have the highest combined sensitivity and specificity. Conclusion Standardized wheeze definitions and severity grading scales for use in pediatric vaccine or drug trials are lacking. Standardized definitions of wheeze are needed for assessment of possible adverse events as new vaccines and drugs are evaluated. PMID:26319071

Ketamine for Depression: Where Do We Go from Here?

PubMed Central

aan het Rot, Marije; Zarate, Carlos A.; Charney, Dennis S.; Mathew, Sanjay J.

2012-01-01

Since publication of the first randomized controlled trial describing rapid antidepressant effects of ketamine, several reports have confirmed the potential utility of this dissociative anesthetic medication for treatment of major depressive episodes, including those associated with bipolar disorder and resistant to other medications and electroconvulsive therapy. These reports have generated several questions with respect to who might respond to ketamine, how, and for how long. To start answering these questions. We used PubMed.gov and ClinicalTrials.gov to perform a systematic review of all available published data on the antidepressant effects of ketamine and of all recently completed, ongoing, and planned studies. To date, 163 patients, primarily with treatment-resistant depression, have participated in case studies, open-label investigations, or controlled trials. All controlled trials have used a within-subject, crossover design with an inactive placebo as the control. Ketamine administration has usually involved an anaesthesiologist infusing a single, subanesthetic, intravenous dose, and required hospitalization for at least 24 hours postinfusion. Response rates in the open-label investigations and controlled trials have ranged from 25% to 85% at 24 hours postinfusion and from 14% to 70% at 72 hours postinfusion. Although adverse effects have generally been mild, some patients have experienced brief changes in blood pressure, heart rate, or respiratory rate. Risk–benefit analyses support further research of ketamine for individuals with severe mood disorders. However, given the paucity of randomized controlled trials, lack of an active placebo, limited data on long-term outcomes, and potential risks, ketamine administration is not recommended outside of the hospital setting. PMID:22705040

Knowledge translation studies in paediatric emergency medicine: A systematic review of the literature.

PubMed

Wilson, Catherine L; Johnson, David; Oakley, Ed

2016-02-01

Systematic review of knowledge translation studies focused on paediatric emergency care to describe and assess the interventions used in emergency department settings. Electronic databases were searched for knowledge translation studies conducted in the emergency department that included the care of children. Two researchers independently reviewed the studies. From 1305 publications identified, 15 studies of varied design were included. Four were cluster-controlled trials, two patient-level randomised controlled trials, two interrupted time series, one descriptive study and six before and after intervention studies. Knowledge translation interventions were predominantly aimed at the treating clinician, with some targeting the organisation. Studies assessed effectiveness of interventions over 6-12 months in before and after studies, and 3-28 months in cluster or patient level controlled trials. Changes in clinical practice were variable, with studies on single disease and single treatments in a single site showing greater improvement. Evidence for effective methods to translate knowledge into practice in paediatric emergency medicine is fairly limited. More optimal study designs with more explicit descriptions of interventions are needed to facilitate other groups to effectively apply these procedures in their own setting. © 2016 The Authors Journal of Paediatrics and Child Health © 2016 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Conventional Wisdom versus Actual Outcomes: Challenges in the Conduct of an Ebola Vaccine Trial in Liberia during the International Public Health Emergency.

PubMed

Larson, Gregg S; Baseler, Beth R; Hoover, Marie L; Pierson, Jerome F; Tegli, Jemee K; Johnson, Melvin P; Kieh, Mark W S; McNay, Laura A; Njoh, Wissedi Sio

2017-07-01

Clinical trials are challenging endeavors. Planning and implementing an investigational vaccine trial in Liberia, in the midst of an Ebola virus disease (EVD) epidemic that World Health Organization classified a public health emergency of international concern, presented extraordinary challenges. Normally, years of preparation and a litany of tasks lay the groundwork for a successful, randomized, blinded, placebo-controlled trial focused on safety and efficacy. Difficult research settings, unpredictable events, and other unique circumstances can add complexity. The setting in Liberia was especially problematic due to an infrastructure still badly damaged following a lengthy civil war and a very fragile health-care system that was further devastated by the EVD outbreak. The Partnership for Research on Vaccines in Liberia I EVD vaccine trial was planned and implemented in less than 3 months by a Liberian and U.S. research partnership, and its Phase II substudy was fully enrolled 3 months later. Contrasting conventional wisdom with trial outcomes offers an opportunity to compare early assumptions, barriers encountered, and adaptive strategies used, with end results. Understanding what was learned can inform future trial responses when disease outbreaks, especially in resource-poor locations with minimal infrastructure, pose a significant threat to public health.

Conventional Wisdom versus Actual Outcomes: Challenges in the Conduct of an Ebola Vaccine Trial in Liberia during the International Public Health Emergency

PubMed Central

Larson, Gregg S.; Baseler, Beth R.; Hoover, Marie L.; Pierson, Jerome F.; Tegli, Jemee K.; Johnson, Melvin P.; Kieh, Mark W. S.; McNay, Laura A.; Njoh, Wissedi Sio

2017-01-01

Abstract. Clinical trials are challenging endeavors. Planning and implementing an investigational vaccine trial in Liberia, in the midst of an Ebola virus disease (EVD) epidemic that World Health Organization classified a public health emergency of international concern, presented extraordinary challenges. Normally, years of preparation and a litany of tasks lay the groundwork for a successful, randomized, blinded, placebo-controlled trial focused on safety and efficacy. Difficult research settings, unpredictable events, and other unique circumstances can add complexity. The setting in Liberia was especially problematic due to an infrastructure still badly damaged following a lengthy civil war and a very fragile health-care system that was further devastated by the EVD outbreak. The Partnership for Research on Vaccines in Liberia I EVD vaccine trial was planned and implemented in less than 3 months by a Liberian and U.S. research partnership, and its Phase II substudy was fully enrolled 3 months later. Contrasting conventional wisdom with trial outcomes offers an opportunity to compare early assumptions, barriers encountered, and adaptive strategies used, with end results. Understanding what was learned can inform future trial responses when disease outbreaks, especially in resource-poor locations with minimal infrastructure, pose a significant threat to public health. PMID:28719299

The use of propensity scores to assess the generalizability of results from randomized trials

PubMed Central

Stuart, Elizabeth A.; Cole, Stephen R.; Bradshaw, Catherine P.; Leaf, Philip J.

2014-01-01

Randomized trials remain the most accepted design for estimating the effects of interventions, but they do not necessarily answer a question of primary interest: Will the program be effective in a target population in which it may be implemented? In other words, are the results generalizable? There has been very little statistical research on how to assess the generalizability, or “external validity,” of randomized trials. We propose the use of propensity-score-based metrics to quantify the similarity of the participants in a randomized trial and a target population. In this setting the propensity score model predicts participation in the randomized trial, given a set of covariates. The resulting propensity scores are used first to quantify the difference between the trial participants and the target population, and then to match, subclassify, or weight the control group outcomes to the population, assessing how well the propensity score-adjusted outcomes track the outcomes actually observed in the population. These metrics can serve as a first step in assessing the generalizability of results from randomized trials to target populations. This paper lays out these ideas, discusses the assumptions underlying the approach, and illustrates the metrics using data on the evaluation of a schoolwide prevention program called Positive Behavioral Interventions and Supports. PMID:24926156

Screening and brief interventions for hazardous and harmful alcohol use among university students in South Africa: results from a randomized controlled trial.

PubMed

Pengpid, Supa; Peltzer, Karl; van der Heever, Hendry; Skaal, Linda

2013-05-21

The aim of this study was to assess the effectiveness of Screening and Brief Intervention (SBI) for alcohol problems among university students in South Africa. The study design for this efficacy study is a randomized controlled trial with 6- and 12-month follow-ups to examine the effects of a brief alcohol intervention to reduce alcohol use by hazardous and harmful drinkers in a university setting. The unit of randomization is the individual university student identified as a hazardous or harmful drinker attending public recruitment venues in a university campus. University students were screened for alcohol problems, and those identified as hazardous or harmful drinkers were randomized into an experimental or control group. The experimental group received one brief counseling session on alcohol risk reduction, while the control group received a health education leaflet. Results indicate that of the 722 screened for alcohol and who agreed to participate in the trial 152 (21.1%) tested positive for the Alcohol Use Disorder Identification Test (AUDIT) (score 8 or more). Among the 147 (96.7%) university students who also attended the 12-month follow-up session, the intervention effect on the AUDIT score was -1.5, which was statistically significant (P = 0.009). Further, the depression scores marginally significantly decreased over time across treatment groups, while other substance use (tobacco and cannabis use), self-rated health status and Posttraumatic Stress Disorder (PTSD) scores did not change over time across treatment groups. The study provides evidence of effective brief intervention by assistant nurses with hazardous and harmful drinkers in a university setting in South Africa. The short duration of the brief intervention makes it a realistic candidate for use in a university setting.

Testing a counselling intervention in antenatal care for women experiencing partner violence: a study protocol for a randomized controlled trial in Johannesburg, South Africa.

PubMed

Pallitto, Christina; García-Moreno, Claudia; Stöeckl, Heidi; Hatcher, Abigail; MacPhail, Catherine; Mokoatle, Keneoue; Woollett, Nataly

2016-11-05

Intimate partner violence (IPV) during or before pregnancy is associated with many adverse health outcomes. Pregnancy-related complications or poor infant health outcomes can arise from direct trauma as well as physiological effects of stress, both of which impact maternal health and fetal growth and development. Antenatal care can be a key entry point within the health system for many women, particularly in low-resource settings. Interventions to identify violence during pregnancy and offer women support and counselling may reduce the occurrence of violence and mitigate its consequences. Following a formative research phase, a randomized controlled trial will be conducted to test a nurse-led empowerment counselling intervention, originally developed for high-income settings and adapted for urban South Africa. The primary outcome is reduction of partner violence, and secondary outcomes include improvement in women's mental health, safety and self-efficacy. The study aims to recruit 504 pregnant women from three antenatal clinics in Johannesburg who will be randomized to the nurse-led empowerment arm (two 30-min counselling sessions) or enhanced control condition (a referral list) to determine whether participants in the intervention arm have better outcomes as compared to the those in the control arm. This research will provide much needed evidence on whether a short counselling intervention delivered by nurses is efficacious and feasible in low resource settings that have high prevalence of IPV and HIV. The study was registered in the South African Clinical Trials Registry (DOH-27-0414-4720) on 11 August 2014 and in the ISRCTN Registry ( ISRCTN35969343 ) on 23 May 2016).

A Controlled Pilot Trial of PainTracker Self-Manager, a Web-Based Platform Combined With Patient Coaching, to Support Patients' Self-Management of Chronic Pain.

PubMed

Sullivan, Mark; Langford, Dale J; Davies, Pamela Stitzlein; Tran, Christine; Vilardaga, Roger; Cheung, Gifford; Yoo, Daisy; McReynolds, Justin; Lober, William B; Tauben, David; Vowles, Kevin E

2018-03-29

The objective of this study was to develop and pilot test a chronic pain empowerment and self-management platform, derived from acceptance and commitment therapy, in a pain specialty setting. A controlled, sequential, nonrandomized study design was used to accommodate intervention development and to test the efficacy of the PainTracker Self-Manager (PTSM) intervention (Web-based educational modules and outcome tracking combined with tailored patient coaching sessions and provider guidance). Generalized estimating equations evaluated changes over time (baseline, 3 months, 6 months) in pain self-efficacy (primary outcome), chronic pain acceptance (activity engagement and pain willingness), perceived efficacy in patient-provider interactions, pain intensity and interference, and overall satisfaction with pain treatment (secondary outcomes) between intervention (n = 48) and usual care control groups (n = 51). The full study sample (N = 99) showed greater improvements over time (significant Group × Time interactions) in pain self-efficacy and satisfaction with pain treatment. Among study completers (n = 82), greater improvement in activity engagement as well as pain intensity and interference were also observed. These preliminary findings support the efficacy of the PTSM intervention in a pain specialty setting. Further research is needed to refine and expand the PTSM intervention and to test it in a randomized trial in primary care settings. We developed a Web-based patient empowerment platform that combined acceptance and commitment therapy-based educational modules and tailored coaching sessions with longitudinal tracking of treatments and patient-reported outcomes, named PTSM. Pilot controlled trial results provide preliminary support for its efficacy in improving pain self-efficacy, activity engagement, pain intensity and interference, and satisfaction with pain treatment. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

A pilot cluster randomized controlled trial of structured goal-setting following stroke.

PubMed

Taylor, William J; Brown, Melanie; William, Levack; McPherson, Kathryn M; Reed, Kirk; Dean, Sarah G; Weatherall, Mark

2012-04-01

To determine the feasibility, the cluster design effect and the variance and minimal clinical importance difference in the primary outcome in a pilot study of a structured approach to goal-setting. A cluster randomized controlled trial. Inpatient rehabilitation facilities. People who were admitted to inpatient rehabilitation following stroke who had sufficient cognition to engage in structured goal-setting and complete the primary outcome measure. Structured goal elicitation using the Canadian Occupational Performance Measure. Quality of life at 12 weeks using the Schedule for Individualised Quality of Life (SEIQOL-DW), Functional Independence Measure, Short Form 36 and Patient Perception of Rehabilitation (measuring satisfaction with rehabilitation). Assessors were blinded to the intervention. Four rehabilitation services and 41 patients were randomized. We found high values of the intraclass correlation for the outcome measures (ranging from 0.03 to 0.40) and high variance of the SEIQOL-DW (SD 19.6) in relation to the minimally importance difference of 2.1, leading to impractically large sample size requirements for a cluster randomized design. A cluster randomized design is not a practical means of avoiding contamination effects in studies of inpatient rehabilitation goal-setting. Other techniques for coping with contamination effects are necessary.

Pre-Operative nutrition In Neck of femur Trial (POINT)--carbohydrate loading in patients with fragility hip fracture: study protocol for a randomised controlled trial.

PubMed

Moppett, Iain K; Greenhaff, Paul L; Ollivere, Ben J; Joachim, Theophillus; Lobo, Dileep N; Rowlands, Martin

2014-12-04

Trauma such as hip fracture initiates a neurohumoral stress response that changes the balance between anabolism and catabolism resulting in muscle breakdown and reduced mobilisation. Various studies have demonstrated a reduction in catabolism with pre-operative carbohydrate loading but only in an elective setting. This is a two-centre, randomised double-blinded trial in the United Kingdom. Sample size will be 30 patients (approximately 15 from each centre). Randomisation will be web based using computer-generated concealed tables. Both participants and investigators will be blinded to group allocation. Participants will be >70 years of age, cognitively intact (Abbreviated Mental Score ≥ 7), able to give informed consent, and admitted directly through the emergency department with fractured neck of femur requiring hemiarthroplasty. Intervention will consist of two carbohydrate drinks (Nutricia pre-Op) given the night before, and the morning of the surgery. The control will receive two placebo drinks of equal volume. All participants will receive standard hospital care at the discretion of the clinical team. The primary outcome is the difference between groups in insulin resistance calculated by a glucose tolerance test administered pre-operatively and 24 hours postoperatively. Secondary endpoints will be changes in muscle carbohydrate metabolism (biopsy), mobility (Cumulative Ambulation Score) and subjective measures of tolerability. This is a small-scale pilot study, investigating the benefits and tolerability of carbohydrate loading in an emergency setting in a frail elderly group with known high morbidity and mortality. Positive findings will provide the basis for a larger scale study. Current Controlled Trials ISRCTN91109766 (7 April 2014); NRES ref: 13/EM/0214Trial Sponsor: University of Nottingham Ref.13036.

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

PubMed Central

Dias, Sofia; Ades, A E

2014-01-01

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

The effect of resistance exercise on the thermic effect of food.

PubMed

Denzer, Charlene M; Young, John C

2003-09-01

The thermic effect of food (TEF) is the increment in energy expenditure above resting metabolic rate associated with the cost of absorption and processing of food for storage. Previous studies have shown that TEF is enhanced by aerobic endurance exercise of sufficient duration and intensity. The purpose of this study was to determine if a similar effect occurs with a single bout of resistance exercise (weightlifting). VO2 was measured in 9 healthy volunteers (3 males and 6 females) for 2 hours after ingestion of a 2760 kJ (660 kcal) carbohydrate meal with and without prior completion of a resistance training regimen (2 sets of 10 repetitions of 10 different exercises). The meal caused an immediate and persistent thermic effect in both the control and the exercise trial. Mean oxygen consumption over baseline increased 20% in the control trial and 34% in the exercise trial. TEF calculated from VO2 and RER (total area under the response curve above baseline) was 73% greater in the exercise trial compared with the control trial (159 +/- 18 vs. 92 +/- 14 KJ/2 hrs, p < .02). These results indicate that TEF in response to a carbohydrate meal is enhanced following a single bout of resistance exercise.

The inherent paradox of clinical trials in psychiatry.

PubMed Central

Helmchen, H; Müller-Oerlinghausen, B

1975-01-01

The authors sum up the central issue of ethics in the conduct of controlled clinical trials in these two paradoxes: 'first, it is unethical to use treatment the efficacy of which has not been examined scientifically; second, it is also unethical to examine the efficacy of treatment scientifically.' In this paper they set out to demonstrate how these antithetical statements apply in controlled trials conducted in psychiatric patients. In such trials the problem of obtaining informed consent may be acute, but in these patients giving 'informed' consent might contribute to a further exacerbation of the illness. Nevertheless the problem cannot be evaded, and scientific judgments must be applied to treatment for it to be sound and improved for the further benefit of patients. These problems in the case of psychiatric controlled trials are a part of the methodology, and in Germany a new drug law has been drafted to attempt to clarify the issue. The authors briefly discuss its application, and its consequences if such a law were enacted. British psychiatrists have exactly the same problems to face but so far no attempts have been made to establish a legal framework. PMID:775089

Efficacy of Coming Out Proud to reduce stigma's impact among people with mental illness: pilot randomised controlled trial.

PubMed

Rüsch, Nicolas; Abbruzzese, Elvira; Hagedorn, Eva; Hartenhauer, Daniel; Kaufmann, Ilias; Curschellas, Jan; Ventling, Stephanie; Zuaboni, Gianfranco; Bridler, René; Olschewski, Manfred; Kawohl, Wolfram; Rössler, Wulf; Kleim, Birgit; Corrigan, Patrick W

2014-01-01

Facing frequent stigma and discrimination, many people with mental illness have to choose between secrecy and disclosure in different settings. Coming Out Proud (COP), a 3-week peer-led group intervention, offers support in this domain in order to reduce stigma's negative impact. To examine COP's efficacy to reduce negative stigma-related outcomes and to promote adaptive coping styles (Current Controlled Trials number: ISRCTN43516734). In a pilot randomised controlled trial, 100 participants with mental illness were assigned to COP or a treatment-as-usual control condition. Outcomes included self-stigma, empowerment, stigma stress, secrecy and perceived benefits of disclosure. Intention-to-treat analyses found no effect of COP on self-stigma or empowerment, but positive effects on stigma stress, disclosure-related distress, secrecy and perceived benefits of disclosure. Some effects diminished during the 3-week follow-up period. Coming Out Proud has immediate positive effects on disclosure- and stigma stress-related variables and may thus alleviate stigma's negative impact.

Chimpanzees can point to smaller amounts of food to accumulate larger amounts but they still fail the reverse-reward contingency task.

PubMed

Beran, Michael J; James, Brielle T; Whitham, Will; Parrish, Audrey E

2016-10-01

The reverse-reward contingency task presents 2 food sets to an animal, and they are required to choose the smaller of the 2 sets in order to receive the larger food set. Intriguingly, the majority of species tested on the reverse-reward task fail to learn this contingency in the absence of large trial counts, correction trials, and punishment techniques. The unique difficulty of this seemingly simple task likely reflects a failure of inhibitory control which is required to point toward a smaller and less desirable reward rather than a larger and more desirable reward. This failure by chimpanzees and other primates to pass the reverse-reward task is striking given the self-control they exhibit in a variety of other paradigms. For example, chimpanzees have consistently demonstrated a high capacity for delay of gratification in order to maximize accumulating food rewards in which foods are added item-by-item to a growing set until the subject consumes the rewards. To study the mechanisms underlying success in the accumulation task and failure in the reverse-reward task, we presented chimpanzees with several combinations of these 2 tasks to determine when chimpanzees might succeed in pointing to smaller food sets over larger food sets and how the nature of the task might determine the animals' success or failure. Across experiments, 3 chimpanzees repeatedly failed to solve the reverse-reward task, whereas they accumulated nearly all food items across all instances of the accumulation self-control task, even when they had to point to small amounts of food to accumulate larger amounts. These data indicate that constraints of these 2 related but still different tasks of behavioral inhibition are dependent upon the animals' perceptions of the choice set, their sense of control over the contents of choice sets, and the nature of the task constraints. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Postural set for balance control is normal in Alzheimer's but not in Parkinson's disease.

PubMed

Chong, R K; Jones, C L; Horak, F B

1999-03-01

It has been suggested that patients with dementia of the Alzheimer type have abnormalities in the basal ganglia, and thus, may have similar sensorimotor problems as patients with basal ganglia degeneration from Parkinson's disease. Whether the similarity extends to balance control is unknown. One distinguishing feature of balance disorder in Parkinson's disease is difficulty with changing postural set in terms of adapting the amplitude of leg muscle activity as a function of support condition. We, therefore, tested whether patients with Alzheimer's disease without extrapyramidal signs would show a similar problem in changing postural set as patients with Parkinson's disease. The ability to quickly change postural set was measured by comparing leg muscle activity under two conditions of support (free stance, versus grasping a frame, or sitting) during backward surface translations, during toes up surface rotations, and during voluntary rise to toes. Results were compared among 12 healthy adults, 8 nondemented Parkinson's patients on their usual dose of medication, and 11 Alzheimer patients without extrapyramidal signs. Subjects with Alzheimer's, but not Parkinson's, disease performed similarly to the healthy control subjects. They changed postural set immediately, by suppressing leg muscle activity to low levels when supported. Parkinson subjects did not change postural set immediately. They did not suppress the tibialis anterior in voluntary rise to toes when holding, nor the soleus in perturbed sitting as much as the healthy control and Alzheimer subjects in the first trial. Instead, the Parkinson subjects changed set more slowly, over repeated and consecutive trials in both protocols. The onset latencies of soleus responses to backward surface translations and perturbed sitting, as well as tibialis anterior responses to toes up rotations, were the same for all three groups. Alzheimer patients without extrapyramidal signs, unlike nondemented Parkinson's disease patients, have no difficulty in quickly changing postural set in response to altered support conditions. Our results, therefore, do not support the hypothesis that Parkinson's and uncomplicated Alzheimer's diseases share common postural set problems that may contribute to disordered balance control.

Does clinical equipoise apply to cluster randomized trials in health research?

PubMed Central

2011-01-01

This article is part of a series of papers examining ethical issues in cluster randomized trials (CRTs) in health research. In the introductory paper in this series, Weijer and colleagues set out six areas of inquiry that must be addressed if the cluster trial is to be set on a firm ethical foundation. This paper addresses the third of the questions posed, namely, does clinical equipoise apply to CRTs in health research? The ethical principle of beneficence is the moral obligation not to harm needlessly and, when possible, to promote the welfare of research subjects. Two related ethical problems have been discussed in the CRT literature. First, are control groups that receive only usual care unduly disadvantaged? Second, when accumulating data suggests the superiority of one intervention in a trial, is there an ethical obligation to act? In individually randomized trials involving patients, similar questions are addressed by the concept of clinical equipoise, that is, the ethical requirement that, at the start of a trial, there be a state of honest, professional disagreement in the community of expert practitioners as to the preferred treatment. Since CRTs may not involve physician-researchers and patient-subjects, the applicability of clinical equipoise to CRTs is uncertain. Here we argue that clinical equipoise may be usefully grounded in a trust relationship between the state and research subjects, and, as a result, clinical equipoise is applicable to CRTs. Clinical equipoise is used to argue that control groups receiving only usual care are not disadvantaged so long as the evidence supporting the experimental and control interventions is such that experts would disagree as to which is preferred. Further, while data accumulating during the course of a CRT may favor one intervention over another, clinical equipoise supports continuing the trial until the results are likely to be broadly convincing, often coinciding with the planned completion of the trial. Finally, clinical equipoise provides research ethics committees with formal and procedural guidelines that form an important part of the assessment of the benefits and harms of CRTs in health research. PMID:21569349

Increasing older adults’ walking through primary care: results of a pilot randomized controlled trial

PubMed Central

Mutrie, Nanette

2012-01-01

Background. Physical activity can positively influence health for older adults. Primary care is a good setting for physical activity promotion. Objective. To assess the feasibility of a pedometer-based walking programme in combination with physical activity consultations. Methods. Design: Two-arm (intervention/control) 12-week randomized controlled trial with a 12-week follow-up for the intervention group. Setting: One general practice in Glasgow, UK. Participants: Participants were aged ≥65 years. The intervention group received two 30-minute physical activity consultations from a trained practice nurse, a pedometer and a walking programme. The control group continued as normal for 12 weeks and then received the intervention. Both groups were followed up at 12 and 24 weeks. Outcome measures: Step counts were measured by sealed pedometers and an activPALTM monitor. Psychosocial variables were assessed and focus groups conducted. Results. The response rate was 66% (187/284), and 90% of those randomized (37/41) completed the study. Qualitative data suggested that the pedometer and nurse were helpful to the intervention. Step counts (activPAL) showed a significant increase from baseline to week 12 for the intervention group, while the control group showed no change. Between weeks 12 and 24, step counts were maintained in the intervention group, and increased for the control group after receiving the intervention. The intervention was associated with improved quality of life and reduced sedentary time. Conclusions. It is feasible to recruit and retain older adults from primary care and help them increase walking. A larger trial is necessary to confirm findings and consider cost-effectiveness. PMID:22843637

A Web-Based Adolescent Positive Psychology Program in Schools: Randomized Controlled Trial

PubMed Central

Manicavasagar, Vijaya; Batterham, Philip J; Miller, Leonie M; Talbot, Elizabeth; Lum, Alistair

2015-01-01

Background Adolescent mental health is characterized by relatively high rates of psychiatric disorders and low levels of help-seeking behaviors. Existing mental health programs aimed at addressing these issues in adolescents have repeated inconsistent results. Such programs have generally been based on techniques derived from cognitive behavioral therapy, which may not be ideally suited to early intervention among adolescent samples. Positive psychology, which seeks to improve well-being rather than alleviate psychological symptoms, offers an alternative approach. A previous community study of adolescents found that informal engagement in an online positive psychology program for up to 6 weeks yielded significant improvements in both well-being and depression symptoms. However, this approach had not been trialed among adolescents in a structured format and within a school setting. Objective This study examines the feasibility of an online school-based positive psychology program delivered in a structured format over a 6-week period utilizing a workbook to guide students through website content and interactive exercises. Methods Students from four high schools were randomly allocated by classroom to either the positive psychology condition, "Bite Back", or the control condition. The Bite Back condition consisted of positive psychology exercises and information, while the control condition used a series of non-psychology entertainment websites. Both interventions were delivered online for 6 hours over a period of 4-6 weeks during class time. Symptom measures and measures of well-being/flourishing and life satisfaction were administered at baseline and post intervention. Results Data were analyzed using multilevel linear modeling. Both conditions demonstrated reductions in depression, stress, and total symptom scores without any significant differences between the two conditions. Both the Bite Back and control conditions also demonstrated significant improvements in life satisfaction scores post intervention. However, only the control condition demonstrated significant increases in flourishing scores post intervention. Conclusions Results suggest that a structured online positive psychology program administered within the school curriculum was not effective when compared to the control condition. The limitations of online program delivery in school settings including logistic considerations are also relevant to the contradictory findings of this study. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN1261200057831; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362489 (Archived by Webcite at http://www.webcitation.org/6NXmjwfAy). PMID:26220564

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

PubMed

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

2009-01-30

To assess the clinical effectiveness and cost effectiveness of a policy to provide breastfeeding groups for pregnant and breastfeeding women. Cluster randomised controlled trial with prospective mixed method embedded case studies to evaluate implementation processes. Primary care in Scotland. Pregnant women, breastfeeding mothers, and babies registered with 14 of 66 eligible clusters of general practices (localities) in Scotland that routinely collect breastfeeding outcome data. Localities set up new breastfeeding groups to provide population coverage; control localities did not change group activity. any breast feeding at 6-8 weeks from routinely collected data for two pre-trial years and two trial years. any breast feeding at birth, 5-7 days, and 8-9 months; maternal satisfaction. Between 1 February 2005 and 31 January 2007, 9747 birth records existed for intervention localities and 9111 for control localities. The number of breastfeeding groups increased from 10 to 27 in intervention localities, where 1310 women attended, and remained at 10 groups in control localities. No significant differences in breastfeeding outcomes were found. Any breast feeding at 6-8 weeks declined from 27% to 26% in intervention localities and increased from 29% to 30% in control localities (P=0.08, adjusted for pre-trial rate). Any breast feeding at 6-8 weeks increased from 38% to 39% in localities not participating in the trial. Women who attended breastfeeding groups were older (P<0.001) than women initiating breast feeding who did not attend and had higher income (P=0.02) than women in the control localities who attended postnatal groups. The locality cost was pound13 400 (euro14 410; $20 144) a year. A policy for providing breastfeeding groups in relatively deprived areas of Scotland did not improve breastfeeding rates at 6-8 weeks. The costs of running groups would be similar to the costs of visiting women at home. Current Controlled Trials ISRCTN44857041.

Fire-setting performed in adolescence or early adulthood predicts schizophrenia: a register-based follow-up study of pre-trial offenders.

PubMed

Thomson, Annika; Tiihonen, Jari; Miettunen, Jouko; Virkkunen, Matti; Lindberg, Nina

2017-02-01

Aggressive and disruptive behaviours often precede the onset of serious mental illnesses. Fire-setting is a type of crime that is associated with psychotic disorders. The aim of this prospective follow-up study was to investigate if fire-setting performed in adolescence or early adulthood was associated with future diagnoses of schizophrenia or schizoaffective disorder. The consecutive sample consisted of 111 Finnish 15-25-year old males with fire-setting crimes, decreed to a pre-trial forensic psychiatric examination in 1973-1998, and showing no past nor current psychosis at the time of examination. For each firesetter, four age-, gender-, and place of birth-matched controls were randomly selected from the Central Population Register. The subjects were followed until the death of the individual, until they moved abroad, or until the end of 2012. Fourteen firesetters (12.6%) and five controls (1.1%) were diagnosed with either schizophrenia or schizoaffective disorder later in life, corresponding to a hazard ratio of 12.5. The delay between the fire-setting offense and the future diagnosis was on average nearly 10 years. Young male offenders undergoing a forensic psychiatric examination because of fire-setting crimes had a significant propensity for schizophrenia and schizoaffective disorder. Accurate assessments should be made both during imprisonment and later in life to detect possible psychotic signs in these individuals.

An Algorithm for Creating Virtual Controls Using Integrated and Harmonized Longitudinal Data.

PubMed

Hansen, William B; Chen, Shyh-Huei; Saldana, Santiago; Ip, Edward H

2018-06-01

We introduce a strategy for creating virtual control groups-cases generated through computer algorithms that, when aggregated, may serve as experimental comparators where live controls are difficult to recruit, such as when programs are widely disseminated and randomization is not feasible. We integrated and harmonized data from eight archived longitudinal adolescent-focused data sets spanning the decades from 1980 to 2010. Collectively, these studies examined numerous psychosocial variables and assessed past 30-day alcohol, cigarette, and marijuana use. Additional treatment and control group data from two archived randomized control trials were used to test the virtual control algorithm. Both randomized controlled trials (RCTs) assessed intentions, normative beliefs, and values as well as past 30-day alcohol, cigarette, and marijuana use. We developed an algorithm that used percentile scores from the integrated data set to create age- and gender-specific latent psychosocial scores. The algorithm matched treatment case observed psychosocial scores at pretest to create a virtual control case that figuratively "matured" based on age-related changes, holding the virtual case's percentile constant. Virtual controls matched treatment case occurrence, eliminating differential attrition as a threat to validity. Virtual case substance use was estimated from the virtual case's latent psychosocial score using logistic regression coefficients derived from analyzing the treatment group. Averaging across virtual cases created group estimates of prevalence. Two criteria were established to evaluate the adequacy of virtual control cases: (1) virtual control group pretest drug prevalence rates should match those of the treatment group and (2) virtual control group patterns of drug prevalence over time should match live controls. The algorithm successfully matched pretest prevalence for both RCTs. Increases in prevalence were observed, although there were discrepancies between live and virtual control outcomes. This study provides an initial framework for creating virtual controls using a step-by-step procedure that can now be revised and validated using other prevention trial data.

Effectiveness of the new 'Mobile AED Map' to find and retrieve an AED: A randomised controlled trial.

PubMed

Sakai, Tomohiko; Iwami, Taku; Kitamura, Tetsuhisa; Nishiyama, Chika; Kawamura, Takashi; Kajino, Kentaro; Tanaka, Hiroshi; Marukawa, Seishiro; Tasaki, Osamu; Shiozaki, Tadahiko; Ogura, Hiroshi; Kuwagata, Yasuyuki; Shimazu, Takeshi

2011-01-01

Although early shock with an automated external defibrillator (AED) is one of the several key elements to save out-of-hospital cardiac arrest (OHCA) victims, it is not always easy to find and retrieve a nearby AED in emergency settings. We developed a cell phone web system, the Mobile AED Map, displaying nearby AEDs located anywhere. The simulation trial in the present study aims to compare the time and travel distance required to access an AED and retrieve it with and without the Mobile AED Map. Randomised controlled trial. Two fields where it was estimated to take 2min (120-170m) to access the nearest AED. Participants were randomly assigned to either the Mobile AED Map group or the control group. We provided each participant in both groups with an OHCA scenario, and measured the time and travel distance to find and retrieve a nearby AED. Forty-three volunteers were enrolled and completed the protocol. The time to access and retrieve an AED was not significantly different between the Mobile AED Map group (400±238s) and the control group (407±256s, p=0.92). The travel distance was significantly shorter in the Mobile AED Map group (606m vs. 891m, p=0.019). Trial field conditions affected the results differently. Although the new Mobile AED Map reduced the travel distance to access and retrieve the AED, it failed to shorten the time. Further technological improvements of the system are needed to increase its usefulness in emergency settings (UMIN000002043). Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The Good Schools Toolkit to prevent violence against children in Ugandan primary schools: study protocol for a cluster randomised controlled trial

PubMed Central

2013-01-01

Background We aim to evaluate the effectiveness of the Good School Toolkit, developed by Raising Voices, in preventing violence against children attending school and in improving child mental health and educational outcomes. Methods/design We are conducting a two-arm cluster randomised controlled trial with parallel assignment in Luwero District, Uganda. We will also conduct a qualitative study, a process evaluation and an economic evaluation. A total of 42 schools, representative of Luwero District, Uganda, were allocated to receive the Toolkit plus implementation support, or were allocated to a wait-list control condition. Our main analysis will involve a cross-sectional comparison of the prevalence of past-week violence from school staff as reported by children in intervention and control primary schools at follow-up. At least 60 children per school and all school staff members will be interviewed at follow-up. Data collection involves a combination of mobile phone-based, interviewer-completed questionnaires and paper-and-pen educational tests. Survey instruments include the ISPCAN Child Abuse Screening Tools to assess experiences of violence; the Strengths and Difficulties Questionnaire to measure symptoms of common childhood mental disorders; and word recognition, reading comprehension, spelling, arithmetic and sustained attention tests adapted from an intervention trial in Kenya. Discussion To our knowledge, this is the first study to rigorously investigate the effects of any intervention to prevent violence from school staff to children in primary school in a low-income setting. We hope the results will be informative across the African region and in other settings. Trial registration clinicaltrials.gov NCT01678846 PMID:23883138

Improving the wellbeing of staff who work in palliative care settings: A systematic review of psychosocial interventions.

PubMed

Hill, Rebecca C; Dempster, Martin; Donnelly, Michael; McCorry, Noleen K

2016-10-01

Staff in palliative care settings perform emotionally demanding roles which may lead to psychological distress including stress and burnout. Therefore, interventions have been designed to address these occupational risks. To investigate quantitative studies exploring the effectiveness of psychosocial interventions that attempt to improve psychological wellbeing of palliative care staff. A systematic review was conducted according to methodological guidance from UK Centre for Reviews and Dissemination. A search strategy was developed based on the initial scans of palliative care studies. Potentially eligible research articles were identified by searching the following databases: CINAHL, MEDLINE (Ovid), PsycINFO and Web of Science. Two reviewers independently screened studies against pre-set eligibility criteria. To assess quality, both researchers separately assessed the remaining studies using the Quality Assessment Tool for Quantitative Studies. A total of 1786 potentially eligible articles were identified - nine remained following screening and quality assessment. Study types included two randomised controlled trials, two non-randomised controlled trial designs, four one-group pre-post evaluations and one process evaluation. Studies took place in the United States and Canada (5), Europe (3) and Hong Kong (1). Interventions comprised a mixture of relaxation, education, support and cognitive training and targeted stress, fatigue, burnout, depression and satisfaction. The randomised controlled trial evaluations did not improve psychological wellbeing of palliative care staff. Only two of the quasi-experimental studies appeared to show improved staff wellbeing although these studies were methodologically weak. There is an urgent need to address the lack of intervention development work and high-quality research in this area. © The Author(s) 2016.

Evaluating information prescriptions in two clinical environments*

PubMed Central

Oliver, Kathleen Burr; Lehmann, Harold P; Wolff, Antonio C; Davidson, Laurie W; Donohue, Pamela K; Gilmore, Maureen M; Craven, Catherine K.

2011-01-01

Objective: The research sought to evaluate whether providing personalized information services by libraries can improve satisfaction with information services for specific types of patients. Methods: Adult breast cancer (BrCa) clinic patients and mothers of inpatient neonatal intensive care unit (NICU) patients were randomized to receive routine information services (control) or an IRx intervention. Results: The BrCa trial randomized 211 patients and the NICU trial, 88 mothers. The BrCa trial showed no statistically significant differences in satisfaction ratings between the treatment and control groups. The IRx group in the NICU trial reported higher satisfaction than the control group regarding information received about diagnosis, treatments, respiratory tradeoffs, and medication tradeoffs. BrCa patients posed questions to librarians more frequently than did NICU mothers, and a higher percentage reported using the website. Questions asked of the librarians by BrCa patients were predominantly clinical and focused on the areas of treatment and side effects. Conclusions: Study results provide some evidence to support further efforts to both implement information prescription projects in selected settings and to conduct additional research on the costs and benefits of services. PMID:21753916

[Evidence-based obstetric conduct. Severe preeclampsia: aggressive or expectant management?].

PubMed

Briceño Pérez, Carlos; Briceño Sanabria, Liliana

2007-02-01

In severe preeclampsia, delivery is assisted immediately without thinking in fetal conditions. Some decades ago, there is agreement to hospitalize, but there is no agreement between expectant or aggressive management. Here are revised these two management evidence based medicine. Fifteen non randomized non controlled trials in English and 4 in Latin American literature highlight 10-14 days pregnancy prolongation without increase maternal morbidity with conservative management; but there were criticized by non random patient selection and non controlled. Two randomized controlled trials showed improvement in neonatal results with no change in maternal, with expectant management. One systematic review of these two trials concluded there is not sufficient data to any reliable recommendation and proposes longer trials are necessary. In United States, National Working Group in the High Blood Pressure Educational Program believes expectant management is only possible in selective women group between 23-32 weeks. The American College of Obstetricians and Gynecologist recommends this management in a tertiary care setting or in consultation with an obstetrician-gynecologist with training in high risk pregnancies. Expectant management present proposal in severe preeclampsia remote from term is summarized.

Involving patients in setting priorities for healthcare improvement: a cluster randomized trial.

PubMed

Boivin, Antoine; Lehoux, Pascale; Lacombe, Réal; Burgers, Jako; Grol, Richard

2014-02-20

Patients are increasingly seen as active partners in healthcare. While patient involvement in individual clinical decisions has been extensively studied, no trial has assessed how patients can effectively be involved in collective healthcare decisions affecting the population. The goal of this study was to test the impact of involving patients in setting healthcare improvement priorities for chronic care at the community level. Cluster randomized controlled trial. Local communities were randomized in intervention (priority setting with patient involvement) and control sites (no patient involvement). Communities in a canadian region were required to set priorities for improving chronic disease management in primary care, from a list of 37 validated quality indicators. Patients were consulted in writing, before participating in face-to-face deliberation with professionals. Professionals established priorities among themselves, without patient involvement. A total of 172 individuals from six communities participated in the study, including 83 chronic disease patients, and 89 health professionals. The primary outcome was the level of agreement between patients' and professionals' priorities. Secondary outcomes included professionals' intention to use the selected quality indicators, and the costs of patient involvement. Priorities established with patients were more aligned with core generic components of the Medical Home and Chronic Care Model, including: access to primary care, self-care support, patient participation in clinical decisions, and partnership with community organizations (p < 0.01). Priorities established by professionals alone placed more emphasis on the technical quality of single disease management. The involvement intervention fostered mutual influence between patients and professionals, which resulted in a 41% increase in agreement on common priorities (95%CI: +12% to +58%, p < 0.01). Professionals' intention to use the selected quality indicators was similar in intervention and control sites. Patient involvement increased the costs of the prioritization process by 17%, and required 10% more time to reach consensus on common priorities. Patient involvement can change priorities driving healthcare improvement at the population level. Future research should test the generalizability of these findings to other contexts, and assess its impact on patient care. The Netherlands National Trial Register #NTR2496.

The AWED trial (Applying Wolbachia to Eliminate Dengue) to assess the efficacy of Wolbachia-infected mosquito deployments to reduce dengue incidence in Yogyakarta, Indonesia: study protocol for a cluster randomised controlled trial.

PubMed

Anders, Katherine L; Indriani, Citra; Ahmad, Riris Andono; Tantowijoyo, Warsito; Arguni, Eggi; Andari, Bekti; Jewell, Nicholas P; Rances, Edwige; O'Neill, Scott L; Simmons, Cameron P; Utarini, Adi

2018-05-31

Dengue and other arboviruses transmitted by Aedes aegypti mosquitoes, including Zika and chikungunya, present an increasing public health challenge in tropical regions. Current vector control strategies have failed to curb disease transmission, but continue to be employed despite the absence of robust evidence for their effectiveness or optimal implementation. The World Mosquito Program has developed a novel approach to arbovirus control using Ae. aegypti stably transfected with Wolbachia bacterium, with a significantly reduced ability to transmit dengue, Zika and chikungunya in laboratory experiments. Modelling predicts this will translate to local elimination of dengue in most epidemiological settings. This study protocol describes the first trial to measure the efficacy of Wolbachia in reducing dengue virus transmission in the field. The study is a parallel, two-arm, non-blinded cluster randomised controlled trial conducted in a single site in Yogyakarta, Indonesia. The aim is to determine whether large-scale deployment of Wolbachia-infected Ae. aegypti mosquitoes leads to a measurable reduction in dengue incidence in treated versus untreated areas. The primary endpoint is symptomatic, virologically confirmed dengue virus infection of any severity. The 26 km 2 study area was subdivided into 24 contiguous clusters, allocated randomly 1:1 to receive Wolbachia deployments or no intervention. We use a novel epidemiological study design, the cluster-randomised test-negative design trial, in which dengue cases and arbovirus-negative controls are sampled concurrently from among febrile patients presenting to a network of primary care clinics, with case or control status classified retrospectively based on the results of laboratory diagnostic testing. Efficacy is estimated from the odds ratio of Wolbachia exposure distribution (probability of living in a Wolbachia-treated area) among virologically confirmed dengue cases compared to test-negative controls. A secondary per-protocol analysis allows for individual Wolbachia exposure levels to be assessed to account for movements outside the cluster and the heterogeneity in local Wolbachia prevalence among treated clusters. The findings from this study will provide the first experimental evidence for the efficacy of Wolbachia in reducing dengue incidence. Together with observational evidence that is accumulating from pragmatic deployments of Wolbachia in other field sites, this will provide valuable data to estimate the effectiveness of this novel approach to arbovirus control, inform future cost-effectiveness estimates, and guide plans for large-scale deployments in other endemic settings. ClinicalTrials.gov, identifier: NCT03055585 . Registered on 14 February 2017.

Efficacy of umbilical cord cleansing with a single application of 4% chlorhexidine for the prevention of newborn infections in Uganda: study protocol for a randomized controlled trial.

PubMed

Nankabirwa, Victoria; Tylleskär, Thorkild; Tumuhamye, Josephine; Tumwine, James K; Ndeezi, Grace; Martines, José C; Sommerfelt, Halvor

2017-07-12

Yearly, nearly all the estimated worldwide 2.7 million neonatal deaths occur in low- and middle-income countries. Infections, including those affecting the umbilical cord (omphalitis), are a significant factor in approximately a third of these deaths. In fact, the odds of all-cause mortality are 46% higher among neonates with omphalitis than in those without. Five large randomized controlled trials in Asia and Sub-Saharan Africa (SSA) have examined the effect of multiple cord stump applications with 4% chlorhexidine (CHX) for at least 7 days on the risk of omphalitis and neonatal death. These studies, all community-based, show that multiple CHX applications reduced the risk of omphalitis. Of these trials, only one study from South Asia (the Bangladeshi study) and none from Africa examined the effect of a single application of CHX as soon as possible after birth. In this Bangladeshi trial, CHX led to a reduction in the risk of mild-moderate omphalitis and neonatal death. It is important, in an African setting, to explore the effect of a single application among health-facility births. A single application is programmatically much simpler to implement than daily applications for 7 days. Therefore, our study compares umbilical cord cleansing with a single application of 4% CHX at birth with dry cord care among Ugandan babies born in health facilities, on the risk of omphalitis and severe neonatal illness. The CHX study is a facility-based, individually randomized controlled trial that will be conducted among 4760 newborns in Uganda. The primary outcomes are severe illness and omphalitis during the neonatal period. Analysis will be by intention-to-treat. This study will provide novel evidence, from a Sub-Saharan African setting, of the effect of umbilical cord cleansing with a single application of 4% CHX at birth and identify modifiable risk factors for omphalitis. ClinicalTrials.gov, identifier: NCT02606565 . Registered on 12 November 2015.

Assessing the feasibility of screening and providing brief advice for alcohol misuse in general dental practice: a clustered randomised control trial protocol for the DART study

PubMed Central

Ntouva, Antiopi; Porter, Jessie; Crawford, Mike J; Britton, Annie; Gratus, Christine; Newton, Tim; Tsakos, Georgios; Heilmann, Anja; Pikhart, Hynek; Watt, Richard G

2015-01-01

Introduction Alcohol misuse is a significant public health problem with major health, social and economic consequences. Systematic reviews have reported that brief advice interventions delivered in various health service settings can reduce harmful drinking. Although the links between alcohol and oral health are well established and dentists come into contact with large numbers of otherwise healthy patients regularly, no studies have been conducted in the UK to test the feasibility of delivering brief advice about alcohol in general dental settings. Methods and analysis The Dental Alcohol Reduction Trial (DART) aims to assess the feasibility and acceptability of screening for alcohol misuse and delivering brief advice in patients attending National Health Service (NHS) general dental practices in North London. DART is a cluster randomised control feasibility trial and uses a mixed methods approach throughout the development, design, delivery and evaluation of the intervention. It will be conducted in 12 NHS general dental practices across North London and will include dental patients who drink above the recommended guidance, as measured by the Alcohol Use Disorders Identification Test (AUDIT-C) screening tool. The intervention involves 5 min of tailored brief advice delivered by dental practitioners during the patient's appointment. Feasibility and acceptability measures as well as suitability of proposed primary outcomes of alcohol consumption will be assessed. Initial economic evaluation will be undertaken. Recruitment and retention rates as well as acceptability of the study procedures from screening to follow-up will be measured. Ethics and dissemination Ethical approval was obtained from the Camden and Islington Research Ethics Committee. Study outputs will be disseminated via scientific publications, newsletters, reports and conference presentations to a range of professional and patient groups and stakeholders. Based on the results of the trial, recommendations will be made on the conduct of a definitive randomised controlled trial. Trial registration number ISRCTN81193263. PMID:26443659

Critical periods after stroke study: translating animal stroke recovery experiments into a clinical trial

PubMed Central

Dromerick, Alexander W.; Edwardson, Matthew A.; Edwards, Dorothy F.; Giannetti, Margot L.; Barth, Jessica; Brady, Kathaleen P.; Chan, Evan; Tan, Ming T.; Tamboli, Irfan; Chia, Ruth; Orquiza, Michael; Padilla, Robert M.; Cheema, Amrita K.; Mapstone, Mark E.; Fiandaca, Massimo S.; Federoff, Howard J.; Newport, Elissa L.

2015-01-01

Introduction: Seven hundred ninety-five thousand Americans will have a stroke this year, and half will have a chronic hemiparesis. Substantial animal literature suggests that the mammalian brain has much potential to recover from acute injury using mechanisms of neuroplasticity, and that these mechanisms can be accessed using training paradigms and neurotransmitter manipulation. However, most of these findings have not been tested or confirmed in the rehabilitation setting, in large part because of the challenges in translating a conceptually straightforward laboratory experiment into a meaningful and rigorous clinical trial in humans. Through presentation of methods for a Phase II trial, we discuss these issues and describe our approach. Methods: In rodents there is compelling evidence for timing effects in rehabilitation; motor training delivered at certain times after stroke may be more effective than the same training delivered earlier or later, suggesting that there is a critical or sensitive period for strongest rehabilitation training effects. If analogous critical/sensitive periods can be identified after human stroke, then existing clinical resources can be better utilized to promote recovery. The Critical Periods after Stroke Study (CPASS) is a phase II randomized, controlled trial designed to explore whether such a sensitive period exists. We will randomize 64 persons to receive an additional 20 h of upper extremity therapy either immediately upon rehab admission, 2–3 months after stroke onset, 6 months after onset, or to an observation-only control group. The primary outcome measure will be the Action Research Arm Test (ARAT) at 1 year. Blood will be drawn at up to 3 time points for later biomarker studies. Conclusion: CPASS is an example of the translation of rodent motor recovery experiments into the clinical setting; data obtained from this single site randomized controlled trial will be used to finalize the design of a Phase III trial. PMID:25972803

Evaluation of a standardized treatment regimen of anti-tuberculosis drugs for patients with multi-drug-resistant tuberculosis (STREAM): study protocol for a randomized controlled trial.

PubMed

Nunn, Andrew J; Rusen, I D; Van Deun, Armand; Torrea, Gabriela; Phillips, Patrick P J; Chiang, Chen-Yuan; Squire, S Bertel; Madan, Jason; Meredith, Sarah K

2014-09-09

In contrast to drug-sensitive tuberculosis, the guidelines for the treatment of multi-drug-resistant tuberculosis (MDR-TB) have a very poor evidence base; current recommendations, based on expert opinion, are that patients should be treated for a minimum of 20 months. A series of cohort studies conducted in Bangladesh identified a nine-month regimen with very promising results. There is a need to evaluate this regimen in comparison with the currently recommended regimen in a randomized controlled trial in a variety of settings, including patients with HIV-coinfection. STREAM is a multi-centre randomized trial of non-inferiority design comparing a nine-month regimen to the treatment currently recommended by the World Health Organization in patients with MDR pulmonary TB with no evidence on line probe assay of fluoroquinolone or kanamycin resistance. The nine-month regimen includes clofazimine and high-dose moxifloxacin and can be extended to 11 months in the event of delay in smear conversion. The primary outcome is based on the bacteriological status of the patients at 27 months post-randomization. Based on the assumption that the nine-month regimen will be slightly more effective than the control regimen and, given a 10% margin of non-inferiority, a total of 400 patients are required to be enrolled. Health economics data are being collected on all patients in selected sites. The results from the study in Bangladesh and cohorts in progress elsewhere are encouraging, but for this regimen to be recommended more widely than in a research setting, robust evidence is needed from a randomized clinical trial. Results from the STREAM trial together with data from ongoing cohorts should provide the evidence necessary to revise current recommendations for the treatment for MDR-TB. This trial was registered with clincaltrials.gov (registration number: ISRCTN78372190) on 14 October 2010.

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

PubMed Central

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

2012-01-01

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

National Cancer Institute's Precision Medicine Initiatives for the new National Clinical Trials Network.

PubMed

Abrams, Jeffrey; Conley, Barbara; Mooney, Margaret; Zwiebel, James; Chen, Alice; Welch, John J; Takebe, Naoko; Malik, Shakun; McShane, Lisa; Korn, Edward; Williams, Mickey; Staudt, Louis; Doroshow, James

2014-01-01

The promise of precision medicine will only be fully realized if the research community can adapt its clinical trials methodology to study molecularly characterized tumors instead of the traditional histologic classification. Such trials will depend on adequate tissue collection, availability of quality controlled, high throughput molecular assays, and the ability to screen large numbers of tumors to find those with the desired molecular alterations. The National Cancer Institute's (NCI) new National Clinical Trials Network (NCTN) is well positioned to conduct such trials. The NCTN has the ability to seamlessly perform ethics review, register patients, manage data, and deliver investigational drugs across its many sites including both in cities and rural communities, academic centers, and private practices. The initial set of trials will focus on different questions: (1) Exceptional Responders Initiative-why do a minority of patients with solid tumors or lymphoma respond very well to some drugs even if the majority do not?; (2) NCI MATCH trial-can molecular markers predict response to targeted therapies in patients with advanced cancer resistant to standard treatment?; (3) ALCHEMIST trial-will targeted epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors improve survival for adenocarcinoma of the lung in the adjuvant setting?; and (4) Lung Cancer Master Protocol trial for advanced squamous cell lung cancer-is there an advantage to developing drugs for small subsets of molecularly characterized tumors in a single, multiarm trial design? These studies will hopefully spawn a new era of treatment trials that will carefully select the tumors that may respond best to investigational therapy.

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

PubMed

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

2015-01-01

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

Evaluation of the effectiveness of music therapy in improving the quality of life of palliative care patients: a randomised controlled pilot and feasibility study.

PubMed

McConnell, Tracey; Graham-Wisener, Lisa; Regan, Joan; McKeown, Miriam; Kirkwood, Jenny; Hughes, Naomi; Clarke, Mike; Leitch, Janet; McGrillen, Kerry; Porter, Sam

2016-01-01

Music therapy is frequently used as a palliative therapy. In consonance with the goals of palliative care, the primary aim of music therapy is to improve people's quality of life by addressing their psychological needs and facilitating communication. To date, primarily because of a paucity of robust research, the evidence for music therapy's effectiveness on patient reported outcomes is positive but weak. This pilot and feasibility study will test procedures, outcomes and validated tools; estimate recruitment and attrition rates; and calculate the sample size required for a phase III randomised trial to evaluate the effectiveness of music therapy in improving the quality of life of palliative care patients. A pilot randomised controlled trial supplemented with qualitative methods. The quantitative data collection will involve recruitment of >52 patients from an inpatient Marie Curie hospice setting over a 12-month period. Eligibility criteria include all patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 03- indicating they are medically fit to engage with music therapy and an Abbreviated Mental Test (AMT) score of ≥7 indicating they are capable of providing meaningful informed consent and accurate responses to outcome measures. Baseline data collection will include the McGill Quality of Life Questionnaire (MQOL); medical and socio-demographic data will be undertaken before randomisation to an intervention or control group. Participants in the intervention arm will be offered two 30-45 min sessions of music therapy per week for three consecutive weeks, in addition to care as usual. Participants in the control arm will receive care as usual. Follow-up measures will be administered in 1, 3 and 5 weeks. Qualitative data collection will involve focus group and individual interviews with HCPs and carers. This study will ensure a firm methodological grounding for the development of a robust phase III randomised trial of music therapy for improving quality of life in palliative care patients. By undertaking the pilot and feasibility trial under normal clinical conditions in a hospice setting, the trial will result in reliable procedures to overcome some of the difficulties in designing music therapy RCTs for palliative care settings. Clinicaltrials.gov Identifier: NCT02791048.

Effectiveness of a handwriting readiness program in head start: a two-group controlled trial.

PubMed

Lust, Carol A; Donica, Denise K

2011-01-01

This study measured skill improvement in prewriting skills, kindergarten readiness, first-name writing, and handwriting-nonspecific fine motor skills of students at Head Start who participated in Handwriting Without Tears-Get Set for School (HWT-GSS) programming. We conducted a two-group, nonrandomized controlled trial using a pretest-posttest design at a rural Head Start. The effectiveness of adding the HWT-GSS curriculum in one preschool classroom was compared with a control classroom. On posttesting, the experimental group made significant improvements compared with the control group in prewriting, kindergarten readiness, and fine motor skills. Both groups made significant improvements between pretesting and posttesting in prewriting, first name writing, and school readiness. Adding HWT-GSS to the Head Start program would be beneficial in improving handwriting readiness skills.

WWC Review of the Report "Accommodations for English Language Learner Students: The Effect of Linguistic Modification of Math Test Item Sets"

ERIC Educational Resources Information Center

What Works Clearinghouse, 2012

2012-01-01

The research described in this report is a randomized controlled trial in which seventh- and eighth-grade students were randomly assigned to complete a set of 25 math questions delivered with either standard language or language that had undergone "linguistic modification" by the research team. The purpose of the study was to assess the…

Cost-effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts: economic evaluation alongside a randomised controlled trial (EVerT trial)

PubMed Central

2012-01-01

Abstract Background Plantar warts (verrucae) are extremely common. Although many will spontaneously disappear without treatment, treatment may be sought for a variety of reasons such as discomfort. There are a number of different treatments for cutaneous warts, with salicylic acid and cryotherapy using liquid nitrogen being two of the most common forms of treatment. To date, no full economic evaluation of either salicylic acid or cryotherapy has been conducted based on the use of primary data in a pragmatic setting. This paper describes the cost-effectiveness analysis which was conducted alongside a pragmatic multicentre, randomised trial evaluating the clinical effectiveness of cryotherapy versus 50% salicylic acid of the treatment of plantar warts. Methods A cost-effectiveness analysis was undertaken alongside a pragmatic multicentre, randomised controlled trial assessing the clinical effectiveness of 50% salicylic acid and cryotherapy using liquid nitrogen at 12 weeks after randomisation of patients. Cost-effectiveness outcomes were expressed as the additional cost required to completely cure the plantar warts of one additional patient. A NHS perspective was taken for the analysis. Results Cryotherapy costs on average £101.17 (bias corrected and accelerated (BCA) 95% CI: 85.09-117.26) more per participant over the 12 week time-frame, while there is no additional benefit, in terms of proportion of patients healed compared with salicylic acid. Conclusions Cryotherapy is more costly and no more effective than salicylic acid. Trial registration Current Controlled Trials ISRCTN18994246 [controlled-trials.com] and National Research Register N0484189151. PMID:22369511

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

PubMed

Harrison, Rosamund; Veronneau, Jacques; Leroux, Brian

2010-05-13

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

Computerised cognitive–behavioural therapy for depression in adolescents: feasibility results and 4-month outcomes of a UK randomised controlled trial

PubMed Central

Wright, Barry; Tindall, Lucy; Littlewood, Elizabeth; Allgar, Victoria; Abeles, Paul; Trépel, Dominic; Ali, Shehzad

2017-01-01

Objectives Computer-administered cognitive–behavioural therapy (CCBT) may be a promising treatment for adolescents with depression, particularly due to its increased availability and accessibility. The feasibility of delivering a randomised controlled trial (RCT) comparing a CCBT program (Stressbusters) with an attention control (self-help websites) for adolescent depression was evaluated. Design Single centre RCT feasibility study. Setting The trial was run within community and clinical settings in York, UK. Participants Adolescents (aged 12–18) with low mood/depression were assessed for eligibility, 91 of whom met the inclusion criteria and were consented and randomised to Stressbusters (n=45) or websites (n=46) using remote computerised single allocation. Those with comorbid physical illness were included but those with psychosis, active suicidality or postnatal depression were not. Interventions An eight-session CCBT program (Stressbusters) designed for use with adolescents with low mood/depression was compared with an attention control (accessing low mood self-help websites). Primary and secondary outcome measures Participants completed mood and quality of life measures and a service Use Questionnaire throughout completion of the trial and 4 months post intervention. Measures included the Beck Depression Inventory (BDI) (primary outcome measure), Mood and Feelings Questionnaire (MFQ), Spence Children's Anxiety Scale (SCAS), the EuroQol five dimensions questionnaire (youth) (EQ-5D-Y) and Health Utility Index Mark 2 (HUI-2). Changes in self-reported measures and completion rates were assessed by treatment group. Results From baseline to 4 months post intervention, BDI scores and MFQ scores decreased for the Stressbusters group but increased in the website group. Quality of life, as measured by the EQ-5D-Y, increased for both groups while costs at 4 months were similar to baseline. Good feasibility outcomes were found, suggesting the trial process to be feasible and acceptable for adolescents with depression. Conclusions With modifications, a fully powered RCT is achievable to investigate a promising treatment for adolescent depression in a climate where child mental health service resources are limited. Trial registration number ISRCTN31219579. PMID:28132000

Design and baseline characteristics of the 10 Small Steps Study: a randomised controlled trial of an intervention to promote healthy behaviour using a lifestyle score and personalised feedback.

PubMed

Parekh, Sanjoti; Vandelanotte, Corneel; King, David; Boyle, Frances M

2012-03-12

Non-communicable diseases (NCDs) are the leading causes of death globally and are associated with a limited set of common, modifiable health behaviours: tobacco use, physical inactivity, harmful use of alcohol and unhealthy diet. General practice offers an ideal avenue for addressing such health behaviours on a population-wide basis. This paper describes the protocol of a multiple health behaviour change intervention designed for implementation in general practice and summarises the baseline characteristics of its participants. The 10 Small Steps (10SS) study, a randomised controlled trial, involved 4,678 adult general practice patients in Queensland, Australia. Self-reported data were collected to establish the proportion of participants meeting recommended guidelines for ten health behaviours: physical activity, body mass index, alcohol, smoking and six dietary behaviours. Participants were randomised to four groups: contact at baseline only ('single intervention' and corresponding control group) and contact at baseline and 3 months ('dual intervention' and corresponding control group). At each contact the participants received a computer-tailored feedback and one page information sheet according to their allocation to intervention or control groups. Change in the intervention group compared to the control group was assessed at 3 and12 months after baseline data collection.Responses were summed to calculate an individual lifestyle score (the Prudence Score), which ranged from 0 to 10. The baseline response was 56.5% (4678 of 8343 invited participants) and the study sample was primarily female (68.7%) with an average age of 47 years. The mean Prudence Score was 5.8 (95%CI 5.75-5.85). Baseline data from the 10SS study show that nearly all participants engage in some health behaviours but relatively few adhere simultaneously to a core set of dietary and lifestyle behaviours associated with risk of NCDs. Ample scope exists to improve health behaviour to reduce NCDs in the general practice setting and the 10SS study trial will provide data on the extent to which a minimal computer-tailored intervention can meet this objective. The protocol developed for the 10SS study has potential for translation into routine general practice as it has minimal impact on practice routine whilst contributing to primary prevention objectives. The Australian New Zealand Clinical Trials Registry ACTRN12611001213932.

Study to assess the effect of a structured communication approach on quality of life in secure mental health settings (Comquol): study protocol for a pilot cluster randomized trial.

PubMed

MacInnes, Douglas; Kinane, Catherine; Beer, Dominic; Parrott, Janet; Craig, Tom; Eldridge, Sandra; Marsh, Ian; Krotofil, Joanna; Priebe, Stefan

2013-08-16

Forensic mental health services have largely ignored examining patients' views on the nature of the services offered to them. A structured communication approach (DIALOG) has been developed with the aim of placing the patient's perspective on their care at the heart of the discussions between patients and clinicians. The effectiveness of the structured communication approach in community mental health services has been demonstrated, but no trial has taken place in a secure psychiatric setting. This pilot study is evaluating a 6-month intervention combining DIALOG with principles of solution-focused therapy on quality of life in medium-secure settings. A cluster randomized controlled trial design is being employed to conduct a 36-month pilot study. Participants are recruited from six medium-secure inpatient services, with 48 patients in the intervention group and 48 in the control group. The intervention uses a structured communication approach. It comprises six meetings between patient and nurse held monthly over a 6-month period. During each meeting, patients rate their satisfaction with a range of life and treatment domains with responses displayed on a tablet. The rating is followed by a discussion of how to improve the current situation in those domains identified by the patient. Assessments take place prior to the intervention (baseline), at 6 months (postintervention) and at 12 months (follow-up). The primary outcome is the patient's self-reported quality of life. This study aims to (1) establish the feasibility of the trial design as the basis for determining the viability of a large full-scale trial, (2) determine the variability of the outcomes of interest (quality of life, levels of satisfaction, disturbance, ward climate and engagement with services), (3) estimate the costs of the intervention and (4) refine the intervention following the outcome of the study based upon the experiences of the nurses and patients. The intervention allows patients to have a greater say in how they are treated and targets care in areas that patients identify as important to them. It is intended to establish systems that support meaningful patient and caregiver involvement and participation. Current Controlled Trials, ISRCTN34145189.

Effectiveness of a self-management program for dual sensory impaired seniors in aged care settings: study protocol for a cluster randomized controlled trial.

PubMed

Roets-Merken, Lieve M; Graff, Maud J L; Zuidema, Sytse U; Hermsen, Pieter G J M; Teerenstra, Steven; Kempen, Gertrudis I J M; Vernooij-Dassen, Myrra J F J

2013-10-07

Five to 25 percent of residents in aged care settings have a combined hearing and visual sensory impairment. Usual care is generally restricted to single sensory impairment, neglecting the consequences of dual sensory impairment on social participation and autonomy. The aim of this study is to evaluate the effectiveness of a self-management program for seniors who acquired dual sensory impairment at old age. In a cluster randomized, single-blind controlled trial, with aged care settings as the unit of randomization, the effectiveness of a self-management program will be compared to usual care. A minimum of 14 and maximum of 20 settings will be randomized to either the intervention cluster or the control cluster, aiming to include a total of 132 seniors with dual sensory impairment. Each senior will be linked to a licensed practical nurse working at the setting. During a five to six month intervention period, nurses at the intervention clusters will be trained in a self-management program to support and empower seniors to use self-management strategies. In two separate diaries, nurses keep track of the interviews with the seniors and their reflections on their own learning process. Nurses of the control clusters offer care as usual. At senior level, the primary outcome is the social participation of the seniors measured using the Hearing Handicap Questionnaire and the Activity Card Sort, and secondary outcomes are mood, autonomy and quality of life. At nurse level, the outcome is job satisfaction. Effectiveness will be evaluated using linear mixed model analysis. The results of this study will provide evidence for the effectiveness of the Self-Management Program for seniors with dual sensory impairment living in aged care settings. The findings are expected to contribute to the knowledge on the program's potential to enhance social participation and autonomy of the seniors, as well as increasing the job satisfaction of the licensed practical nurses. Furthermore, an extensive process evaluation will take place which will offer insight in the quality and feasibility of the sampling and intervention process. If it is shown to be effective and feasible, this Self-Management Program could be widely disseminated. ClinicalTrials.gov, NCT01217502.

Oral misoprostol in preventing postpartum haemorrhage in resource-poor communities: a randomised controlled trial.

PubMed

Derman, Richard J; Kodkany, Bhalchandra S; Goudar, Shivaprasad S; Geller, Stacie E; Naik, Vijaya A; Bellad, M B; Patted, Shobhana S; Patel, Ashlesha; Edlavitch, Stanley A; Hartwell, Tyler; Chakraborty, Hrishikesh; Moss, Nancy

2006-10-07

Postpartum haemorrhage is a major cause of maternal mortality in the developing world. Although effective methods for prevention and treatment of such haemorrhage exist--such as the uterotonic drug oxytocin--most are not feasible in resource-poor settings where many births occur at home. We aimed to investigate whether oral misoprostol, a potential alternative to oxytocin, could prevent postpartum haemorrhage in a community home-birth setting. In a placebo-controlled trial undertaken between September, 2002, and December, 2005, 1620 women in rural India were randomised to receive oral misoprostol (n=812) or placebo (n=808) after delivery. 25 auxiliary nurse midwives undertook the deliveries, administered the study drug, and measured blood loss. The primary outcome was the incidence of acute postpartum haemorrhage (defined as > or =500 mL bleeding) within 2 h of delivery. Analysis was by intention-to-treat. The trial was registered with the US clinical trials database (http://www. clinicaltrials.gov) as number NCT00097123. Oral misoprostol was associated with a significant reduction in the rate of acute postpartum haemorrhage (12.0% to 6.4%, p<0.0001; relative risk 0.53 [95% CI 0.39-0.74]) and acute severe postpartum haemorrhage (1.2% to 0.2%, p<0.0001; 0.20 [0.04-0.91]. One case of postpartum haemorrhage was prevented for every 18 women treated. Misoprostol was also associated with a decrease in mean postpartum blood loss (262.3 mL to 214.3 mL, p<0.0001). Postpartum haemorrhage rates fell over time in both groups but remained significantly higher in the placebo group. Women taking misoprostol had a higher rate of transitory symptoms of chills and fever than the control. Oral misoprostol was associated with significant decreases in the rate of acute postpartum haemorrhage and mean blood loss. The drug's low cost, ease of administration, stability, and a positive safety profile make it a good option in resource-poor settings.

Multilaboratory trial for determination of ceftiofur residues in bovine and swine kidney and muscle, and bovine milk.

PubMed

Hornish, Rex E; Hamlow, Philip J; Brown, Scott A

2003-01-01

A multilaboratory trial for determining ceftiofur-related residues in bovine and swine kidney and muscle, and bovine milk was conducted following regulatory guidelines of the U.S. Food and Drug Administration, Center for Veterinary Medicine. The methods convert all desfuroylceftiofur-related residues containing the intact beta-lactam ring to desfuroylceftiofur acetamide to establish ceftiofur residues in tissues. Four laboratories analyzed 5 sets of samples for each tissue. Each sample set consisted of a control/blank sample and 3 control samples fortified with ceftiofur at 0.5 Rm, Rm, and 2 Rm, respectively, where Rm is the U.S. tolerance assigned for ceftiofur residue in each tissue/matrix: 0.100 microg/mL for milk, 8.0 microg/g for kidney (both species), 1.0 microg/g for bovine muscle, and 2.0 microg/g for swine muscle. Each sample set also contained 2 samples of incurred-residue tissues (one > Rm and one < Rm) from animals treated with ceftiofur hydrochloride. All laboratories completed the method trial after a familiarization phase and test of system suitability in which they demonstrated > 80% recovery in pretrial fortified test samples. Results showed that the methods met all acceptable performance criteria for recovery, accuracy, and precision. Although sample preparation was easy, solid-phase extraction cartridge performance must be carefully evaluated before samples are processed. The liquid chromatography detection system was easily set up; however, the elution profile may require slight modifications. The procedures could clearly differentiate between violative (> Rm) and nonviolative (< Rm) ceftiofur residues. Participating laboratories found the procedures suitable for ceftiofur residue determination.

What Is Real-World Data? A Review of Definitions Based on Literature and Stakeholder Interviews.

PubMed

Makady, Amr; de Boer, Anthonius; Hillege, Hans; Klungel, Olaf; Goettsch, Wim

Despite increasing recognition of the value of real-world data (RWD), consensus on the definition of RWD is lacking. To review definitions publicly available for RWD to shed light on similarities and differences between them. A literature review and stakeholder interviews were used to compile data from eight groups of stakeholders. Data from documents and interviews were subjected to coding analysis. Definitions identified were classified into four categories: 1) data collected in a non-randomized controlled trial setting, 2) data collected in a non-interventional/non-controlled setting, 3) data collected in a non-experimental setting, and 4) others (i.e., data that do not fit into the other three categories). The frequency of definitions identified per category was recorded. Fifty-three documents and 20 interviews were assessed. Thirty-eight definitions were identified: 20 out of 38 definitions (53%) were category 1 definitions, 9 (24%) were category 2 definitions, 5 (13%) were category 3 definitions, and 4 (11%) were category 4 definitions. Differences were identified between, and within, definition categories. For example, opinions differed on the aspects of intervention with which non-interventional/non-controlled settings should abide. No definitions were provided in two interviews or identified in 33 documents. Most of the definitions defined RWD as data collected in a non-randomized controlled trial setting. A considerable number of definitions, however, diverged from this concept. Moreover, a significant number of authors and stakeholders did not have an official, institutional definition for RWD. Persisting variability in stakeholder definitions of RWD may lead to disparities among different stakeholders when discussing RWD use in decision making. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Are exergames promoting mobility an attractive alternative to conventional self-regulated exercises for elderly people in a rehabilitation setting? Study protocol of a randomized controlled trial.

PubMed

Hasselmann, Viviane; Oesch, Peter; Fernandez-Luque, Luis; Bachmann, Stefan

2015-09-07

Maintaining mobility in elderly persons has become a primary goal within healthcare services. In older adults, exercise programs significantly reduce the risk of falling and death. Long-lasting and high-intensive multi-component exercises are most effective. In a rehabilitation setting, self-regulated exercises are conventionally taught by physiotherapists, using handouts. However, the adherence of elderly persons to executing these self-administered programs varies considerably. They are often considered tedious and boring, and thus prematurely stopped. The primary aim of this clinical trial is to determine whether elderly persons in a rehabilitation setting show higher adherence to self-regulated training when using exergames than when performing conventional exercises. The second objective is to explore which mode of exercise leads to greater improvement in balance performance. The study consists of a single blind, stratified, randomized control trial with two parallel groups. Once included, study participants will be stratified according to their balance and computer skills and randomly allocated to self-regulated training with conventional exercise programs or with exergames played with the Windows Kinect® sensor and FitBit® pedometer. In both groups, self-administered exercise programs will be taught by experienced physiotherapists and performed at the patient's own discretion during the ten days of intervention. The primary outcome is the performed daily training volume, collected by the participants in a logbook. Secondary outcomes are objective and subjective balance skills measured by an activity tracker and the Fall Efficacy Scale self-administered questionnaire. Both assessments will be performed at pre- and post-intervention. According to the available literature, this study is the first to compare conventional self-regulated exercises with exergames among older patients in a rehabilitation setting. Results of this study will contribute to our understanding of its motivational potential on exercise adherence in elderly persons and provide more insight into the potential effectiveness of exergames promoting mobility. The present clinical study has been registered on ClinicalTrials.gov under the identifier number: NCT02077049. The detailed trial protocol can be accessed online on: NCT02077049.

A cluster randomized trial of routine HIV-1 viral load monitoring in Zambia: study design, implementation, and baseline cohort characteristics.

PubMed

Koethe, John R; Westfall, Andrew O; Luhanga, Dora K; Clark, Gina M; Goldman, Jason D; Mulenga, Priscilla L; Cantrell, Ronald A; Chi, Benjamin H; Zulu, Isaac; Saag, Michael S; Stringer, Jeffrey S A

2010-03-12

The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We designed a cluster randomized controlled trial to compare the use of routine VL testing at ART-initiation and at 3, 6, 12, and 18 months, versus our local standard of care (which uses immunological and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree). Dedicated study personnel were integrated into public-sector ART clinics. We collected participant information in a dedicated research database. Twelve ART clinics in Lusaka, Zambia constituted the units of randomization. Study clinics were stratified into pairs according to matching criteria (historical mortality rate, size, and duration of operation) to limit the effect of clustering, and independently randomized to the intervention and control arms. The study was powered to detect a 36% reduction in mortality at 18 months. From December 2006 to May 2008, we completed enrollment of 1973 participants. Measured baseline characteristics did not differ significantly between the study arms. Enrollment was staggered by clinic pair and truncated at two matched sites. A large clinical trial of routing VL monitoring was successfully implemented in a dynamic and rapidly growing national ART program. Close collaboration with local health authorities and adequate reserve staff were critical to success. Randomized controlled trials such as this will likely prove valuable in determining long-term outcomes in resource-constrained settings. Clinicaltrials.gov NCT00929604.

Impact of fatty acid status on immune function of children in low-income countries.

PubMed

Prentice, Andrew M; van der Merwe, Liandré

2011-04-01

In vitro and animal studies point to numerous mechanisms by which fatty acids, especially long-chain polyunsaturated fatty acids (LCPUFA), can modulate the innate and adaptive arms of the immune system. These data strongly suggest that improving the fatty acid supply of young children in low-income countries might have immune benefits. Unfortunately, there have been virtually no studies of fatty acid/immune interactions in such settings. Clinical trial registers list over 150 randomized controlled trials (RCTs) involving PUFAs, only one in a low-income setting (the Gambia). We summarize those results here. There was evidence for improved growth and nutritional status, but the primary end point of chronic environmental enteropathy showed no benefit, possibly because the infants were still substantially breastfed. In high-income settings, there have been RCTs with fatty acids (usually LCPUFAs) in relation to 18 disease end points, for some of which there have been numerous trials (asthma, inflammatory bowel disease and rheumatoid arthritis). For these diseases, the evidence is judged reasonable for risk reduction for childhood asthma (but not in adults), as yielding possible benefit in Crohn's disease (insufficient evidence in ulcerative colitis) and for convincing evidence for rheumatoid arthritis at sufficient dose levels, though formal meta-analyses are not yet available. This analysis suggests that fatty acid interventions could yield immune benefits in children in poor settings, especially in non-breastfed children and in relation to inflammatory conditions such as persistent enteropathy. Benefits might include improved responses to enteric vaccines, which frequently perform poorly in low-income settings, and these questions merit randomized trials. © 2011 Blackwell Publishing Ltd.

Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration: a methodological overview.

PubMed

Jensen, Jakob Solgaard; Bielefeldt, Andreas Ørsted; Hróbjartsson, Asbjørn

2017-07-01

Active placebos are control interventions that mimic the side effects of the experimental interventions in randomized trials and are sometimes used to reduce the risk of unblinding. We wanted to assess how often randomized clinical drug trials use active placebo control groups; to provide a catalog, and a characterization, of such trials; and to analyze methodological arguments for and against the use of active placebo. An overview consisting of three thematically linked substudies. In an observational substudy, we assessed the prevalence of active placebo groups based on a random sample of 200 PubMed indexed placebo-controlled randomized drug trials published in October 2013. In a systematic review, we identified and characterized trials with active placebo control groups irrespective of publication time. In a third substudy, we reviewed publications with substantial methodological comments on active placebo groups (searches in PubMed, The Cochrane Library, Google Scholar, and HighWirePress). The prevalence of trials with active placebo groups published in 2013 was 1 out of 200 (95% confidence interval: 0-2), 0.5% (0-1%). We identified and characterized 89 randomized trials (published 1961-2014) using active placebos, for example, antihistamines, anticholinergic drugs, and sedatives. Such trials typically involved a crossover design, the experimental intervention had noticeable side effects, and the outcomes were patient-reported. The use of active placebos was clustered in specific research settings and did not appear to reflect consistently the side effect profile of the experimental intervention, for example, selective serotonin reuptake inhibitors were compared with active placebos in pain trials but not in depression trials. We identified and analyzed 25 methods publications with substantial comments. The main argument for active placebo was to reduce risk of unblinding; the main argument against was the risk of unintended therapeutic effect. Pharmacological active placebo control interventions are rarely used in randomized clinical trials, but they constitute a methodological tool which merits serious consideration. We suggest that active placebos are used more often in trials of drugs with noticeable side effects, especially in situations where the expected therapeutic effects are modest and the risk of bias due to unblinding is high. Copyright © 2017 Elsevier Inc. All rights reserved.

Complexity in relational processing predicts changes in functional brain network dynamics.

PubMed

Cocchi, Luca; Halford, Graeme S; Zalesky, Andrew; Harding, Ian H; Ramm, Brentyn J; Cutmore, Tim; Shum, David H K; Mattingley, Jason B

2014-09-01

The ability to link variables is critical to many high-order cognitive functions, including reasoning. It has been proposed that limits in relating variables depend critically on relational complexity, defined formally as the number of variables to be related in solving a problem. In humans, the prefrontal cortex is known to be important for reasoning, but recent studies have suggested that such processes are likely to involve widespread functional brain networks. To test this hypothesis, we used functional magnetic resonance imaging and a classic measure of deductive reasoning to examine changes in brain networks as a function of relational complexity. As expected, behavioral performance declined as the number of variables to be related increased. Likewise, increments in relational complexity were associated with proportional enhancements in brain activity and task-based connectivity within and between 2 cognitive control networks: A cingulo-opercular network for maintaining task set, and a fronto-parietal network for implementing trial-by-trial control. Changes in effective connectivity as a function of increased relational complexity suggested a key role for the left dorsolateral prefrontal cortex in integrating and implementing task set in a trial-by-trial manner. Our findings show that limits in relational processing are manifested in the brain as complexity-dependent modulations of large-scale networks. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A randomized controlled trial of an activity specific exercise program for individuals with Alzheimer disease in long-term care settings.

PubMed

Roach, Kathryn E; Tappen, Ruth M; Kirk-Sanchez, Neva; Williams, Christine L; Loewenstein, David

2011-01-01

To determine whether an activity specific exercise program could improve ability to perform basic mobility activities in long-term care residents with Alzheimer disease (AD). Randomized, controlled, single-blinded clinical trial. Residents of 7 long-term care facilities. Eighty-two long-term care residents with mild to severe AD. An activity specific exercise program was compared to a walking program and to an attention control. Ability to perform bed mobility and transfers was assessed using the subscales of the Acute Care Index of Function; functional mobility was measured using the 6-Minute Walk test. Subjects receiving the activity specific exercise program improved in ability to perform transfers, whereas subjects in the other 2 groups declined.

Impact of an interprofessional shared decision-making and goal-setting decision aid for patients with diabetes on decisional conflict--study protocol for a randomized controlled trial.

PubMed

Yu, Catherine H; Ivers, Noah M; Stacey, Dawn; Rezmovitz, Jeremy; Telner, Deanna; Thorpe, Kevin; Hall, Susan; Settino, Marc; Kaplan, David M; Coons, Michael; Sodhi, Sumeet; Sale, Joanna; Straus, Sharon E

2015-06-27

Competing health concerns present real obstacles to people living with diabetes and other chronic diseases as well as to their primary care providers. Guideline implementation interventions rarely acknowledge this, leaving both patients and providers feeling overwhelmed by the volume of recommended actions. Interprofessional (IP) shared decision-making (SDM) with the use of decision aids may help to set treatment priorities. We developed an evidence-based SDM intervention for patients with diabetes and other conditions that was framed by the IP-SDM model and followed a user-centered approach. Our objective in the present study is to pilot an IP-SDM and goal-setting toolkit following the Knowledge-to-Action Framework to assess (1) intervention fidelity and the feasibility of conducting a larger trial and (2) impact on decisional conflict, diabetes distress, health-related quality of life and patient assessment of chronic illness care. A two-step, parallel-group, clustered randomized controlled trial (RCT) will be conducted, with the primary goal being to assess intervention fidelity and the feasibility of conducting a larger RCT. The first step is a provider-directed implementation only; the second (after a 6-month delay) involves both provider- and patient-directed implementation. Half of the clusters will be assigned to receive the IP-SDM toolkit, and the other will be assigned to be mailed a diabetes guidelines summary. Individual interviews with patients, their family members and health care providers will be conducted upon trial completion to explore toolkit use. A secondary purpose of this trial is to gather estimates of the toolkit's impact on decisional conflict. Secondary outcomes include diabetes distress, quality of life and chronic illness care, which will be assessed on the basis of patient-completed questionnaires of validated scales at baseline and at 6 and 12 months. Multilevel hierarchical regression models will be used to account for the clustered nature of the data. An individualized approach to patients with multiple chronic conditions using SDM and goal setting is a desirable strategy for achieving guideline-concordant treatment in a patient-centered fashion. Our pilot trial will provide insights regarding strategies for the routine implementation of such interventions in clinical practice, and it will offer an assessment of the impact of this approach. Clinicaltrials.gov Identifier: NCT02379078. Date of Registration: 11 February 2015.

Rotavirus vaccine effectiveness in low-income settings: An evaluation of the test-negative design.

PubMed

Schwartz, Lauren M; Halloran, M Elizabeth; Rowhani-Rahbar, Ali; Neuzil, Kathleen M; Victor, John C

2017-01-03

The test-negative design (TND), an epidemiologic method currently used to measure rotavirus vaccine (RV) effectiveness, compares the vaccination status of rotavirus-positive cases and rotavirus-negative controls meeting a pre-defined case definition for acute gastroenteritis. Despite the use of this study design in low-income settings, the TND has not been evaluated to measure rotavirus vaccine effectiveness. This study builds upon prior methods to evaluate the use of the TND for influenza vaccine using a randomized controlled clinical trial database. Test-negative vaccine effectiveness (VE-TND) estimates were derived from three large randomized placebo-controlled trials (RCTs) of monovalent (RV1) and pentavalent (RV5) rotavirus vaccines in sub-Saharan Africa and Asia. Derived VE-TND estimates were compared to the original RCT vaccine efficacy estimates (VE-RCTs). The core assumption of the TND (i.e., rotavirus vaccine has no effect on rotavirus-negative diarrhea) was also assessed. TND vaccine effectiveness estimates were nearly equivalent to original RCT vaccine efficacy estimates. Neither RV had a substantial effect on rotavirus-negative diarrhea. This study supports the TND as an appropriate epidemiologic study design to measure rotavirus vaccine effectiveness in low-income settings. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Effect of telecare on use of health and social care services: findings from the Whole Systems Demonstrator cluster randomised trial

PubMed Central

Steventon, Adam; Bardsley, Martin; Billings, John; Dixon, Jennifer; Doll, Helen; Beynon, Michelle; Hirani, Shashi; Cartwright, Martin; Rixon, Lorna; Knapp, Martin; Henderson, Catherine; Rogers, Anne; Hendy, Jane; Fitzpatrick, Ray; Newman, Stanton

2013-01-01

Objective: to assess the impact of telecare on the use of social and health care. Part of the evaluation of the Whole Systems Demonstrator trial. Participants and setting: a total of 2,600 people with social care needs were recruited from 217 general practices in three areas in England. Design: a cluster randomised trial comparing telecare with usual care, general practice being the unit of randomisation. Participants were followed up for 12 months and analyses were conducted as intention-to-treat. Data sources: trial data were linked at the person level to administrative data sets on care funded at least in part by local authorities or the National Health Service. Main outcome measures: the proportion of people admitted to hospital within 12 months. Secondary endpoints included mortality, rates of secondary care use (seven different metrics), contacts with general practitioners and practice nurses, proportion of people admitted to permanent residential or nursing care, weeks in domiciliary social care and notional costs. Results: 46.8% of intervention participants were admitted to hospital, compared with 49.2% of controls. Unadjusted differences were not statistically significant (odds ratio: 0.90, 95% CI: 0.75–1.07, P = 0.211). They reached statistical significance after adjusting for baseline covariates, but this was not replicated when adjusting for the predictive risk score. Secondary metrics including impacts on social care use were not statistically significant. Conclusions: telecare as implemented in the Whole Systems Demonstrator trial did not lead to significant reductions in service use, at least in terms of results assessed over 12 months. International Standard Randomised Controlled Trial Number Register ISRCTN43002091. PMID:23443509

Effectiveness of structured, hospital-based, nurse-led atrial fibrillation clinics: a comparison between a real-world population and a clinical trial population.

PubMed

Qvist, Ina; Hendriks, Jeroen M L; Møller, Dorthe S; Albertsen, Andi E; Mogensen, Helle M; Oddershede, Gitte D; Odgaard, Annette; Mortensen, Leif Spange; Johnsen, Søren Paaske; Frost, Lars

2016-01-01

A previous randomised trial showed that structured, nurse-led atrial fibrillation (AF) care is superior to conventional AF care, although further research is needed to determine the outcomes of such care in a real-world setting. We compared the outcomes of patients in real-world, nurse-led, structured hospital AF clinics with the outcomes of a randomised trial of the efficacy of a nurse-led AF clinic, with respect to a composite outcome of cardiovascular-related hospitalisation and death. All patients were referred to the AF nurse specialist by cardiologists. The AF nurse specialist provided patient education, risk-factor control and stimulated empowerment and compliance. During follow-up, treatment was adjusted according to clinical guidelines. Patient education was repeated, and compliance with medical treatment was controlled. The study size was powered as a non-inferiority study. Outcome measures were adjudicated by the same principles in both cohorts. A total of 596 patients from the real world and 356 patients from a clinical trial were included in this study. No significant difference between groups with respect to age, type of AF or CHA2DS2VASc score was found. The composite primary end point occurred with an incidence rate of 8.0 (95% CI 6.1 to 10.4) per 100 person-years in the real-world population and 8.3 (95% CI 6.3 to 10.9) per 100 person-years in the clinical trial, with a crude HR of 0.83 (95% CI 0.56 to 1.23). Structured, nurse-led, hospital-based AF care appears to be effective, and patient outcomes in an actual, hospital-based, structured AF care are as least as good as those in trial settings.

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

PubMed Central

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

2014-01-01

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

The PREEMPT study - evaluating smartphone-assisted n-of-1 trials in patients with chronic pain: study protocol for a randomized controlled trial.

PubMed

Barr, Colin; Marois, Maria; Sim, Ida; Schmid, Christopher H; Wilsey, Barth; Ward, Deborah; Duan, Naihua; Hays, Ron D; Selsky, Joshua; Servadio, Joseph; Schwartz, Marc; Dsouza, Clyde; Dhammi, Navjot; Holt, Zachary; Baquero, Victor; MacDonald, Scott; Jerant, Anthony; Sprinkle, Ron; Kravitz, Richard L

2015-02-27

Chronic pain is prevalent, costly, and clinically vexatious. Clinicians typically use a trial-and-error approach to treatment selection. Repeated crossover trials in a single patient (n-of-1 trials) may provide greater therapeutic precision. N-of-1 trials are the most direct way to estimate individual treatment effects and are useful in comparing the effectiveness and toxicity of different analgesic regimens. The goal of the PREEMPT study is to test the 'Trialist' mobile health smartphone app, which has been developed to make n-of-1 trials easier to accomplish, and to provide patients and clinicians with tools for individualizing treatments for chronic pain. A randomized controlled trial is being conducted to test the feasibility and effectiveness of the Trialist app. A total of 244 participants will be randomized to either the Trialist app intervention group (122 patients) or a usual care control group (122 patients). Patients assigned to the Trialist app will work with their clinicians to set up an n-of-1 trial comparing two pain regimens, selected from a menu of flexible options. The Trialist app provides treatment reminders and collects data entered daily by the patient on pain levels and treatment side effects. Upon completion of the n-of-1 trial, patients review results with their clinicians and develop a long-term treatment plan. The primary study outcome (comparing Trialist to usual care patients) is pain-related interference with daily functioning at 26 weeks. Trialist will allow patients and clinicians to conduct personalized n-of-1 trials. In prior studies, n-of-1 trials have been shown to encourage greater patient involvement with care, which has in turn been associated with better health outcomes. mHealth technology implemented using smartphones may offer an efficient means of facilitating n-of-1 trials so that more patients can benefit from this approach. ClinicalTrials.gov: NCT02116621 , first registered 15 April 2014.

Streamlining cardiovascular clinical trials to improve efficiency and generalisability.

PubMed

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

2017-08-01

Controlled trials provide the most valid determination of the efficacy and safety of an intervention, but large cardiovascular clinical trials have become extremely costly and complex, making it difficult to study many important clinical questions. A critical question, and the main objective of this review, is how trials might be simplified while maintaining randomisation to preserve scientific integrity and unbiased efficacy assessments. Experience with alternative approaches is accumulating, specifically with registry-based randomised controlled trials that make use of data already collected. This approach addresses bias concerns while still capitalising on the benefits and efficiencies of a registry. Several completed or ongoing trials illustrate the feasibility of using registry-based controlled trials to answer important questions relevant to daily clinical practice. Randomised trials within healthcare organisation databases may also represent streamlined solutions for some types of investigations, although data quality (endpoint assessment) is likely to be a greater concern in those settings. These approaches are not without challenges, and issues pertaining to informed consent, blinding, data quality and regulatory standards remain to be fully explored. Collaboration among stakeholders is necessary to achieve standards for data management and analysis, to validate large data sources for use in randomised trials, and to re-evaluate ethical standards to encourage research while also ensuring that patients are protected. The rapidly evolving efforts to streamline cardiovascular clinical trials have the potential to lead to major advances in promoting better care and outcomes for patients with cardiovascular disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Addressing the expected survival benefit for clinical trial design in metastatic castration-resistant prostate cancer: Sensitivity analysis of randomized trials.

PubMed

Massari, Francesco; Modena, Alessandra; Ciccarese, Chiara; Pilotto, Sara; Maines, Francesca; Bracarda, Sergio; Sperduti, Isabella; Giannarelli, Diana; Carlini, Paolo; Santini, Daniele; Tortora, Giampaolo; Porta, Camillo; Bria, Emilio

2016-02-01

We performed a sensitivity analysis, cumulating all randomized clinical trials (RCTs) in which patients with metastatic castration-resistant prostate cancer (mCRPC) received systemic therapy, to evaluate if the comparison of RCTs may drive to biased survival estimations. An overall survival (OS) significant difference according to therapeutic strategy was more likely be determined in RCTs evaluating hormonal drugs versus those studies testing immunotherapy, chemotherapy or other strategies. With regard to control arm, an OS significant effect was found for placebo-controlled trials versus studies comparing experimental treatment with active therapies. Finally, regarding to docetaxel (DOC) timing, the OS benefit was more likely to be proved in Post-DOC setting in comparison with DOC and Pre-DOC. These data suggest that clinical trial design should take into account new benchmarks such as the type of treatment strategy, the choice of the comparator and the phase of the disease in relation to the administration of standard chemotherapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cluster randomised controlled trial of a peer-led lifestyle intervention program: study protocol for the Kerala diabetes prevention program

PubMed Central

2013-01-01

Background India currently has more than 60 million people with Type 2 Diabetes Mellitus (T2DM) and this is predicted to increase by nearly two-thirds by 2030. While management of those with T2DM is important, preventing or delaying the onset of the disease, especially in those individuals at ‘high risk’ of developing T2DM, is urgently needed, particularly in resource-constrained settings. This paper describes the protocol for a cluster randomised controlled trial of a peer-led lifestyle intervention program to prevent diabetes in Kerala, India. Methods/design A total of 60 polling booths are randomised to the intervention arm or control arm in rural Kerala, India. Data collection is conducted in two steps. Step 1 (Home screening): Participants aged 30–60 years are administered a screening questionnaire. Those having no history of T2DM and other chronic illnesses with an Indian Diabetes Risk Score value of ≥60 are invited to attend a mobile clinic (Step 2). At the mobile clinic, participants complete questionnaires, undergo physical measurements, and provide blood samples for biochemical analysis. Participants identified with T2DM at Step 2 are excluded from further study participation. Participants in the control arm are provided with a health education booklet containing information on symptoms, complications, and risk factors of T2DM with the recommended levels for primary prevention. Participants in the intervention arm receive: (1) eleven peer-led small group sessions to motivate, guide and support in planning, initiation and maintenance of lifestyle changes; (2) two diabetes prevention education sessions led by experts to raise awareness on T2DM risk factors, prevention and management; (3) a participant handbook containing information primarily on peer support and its role in assisting with lifestyle modification; (4) a participant workbook to guide self-monitoring of lifestyle behaviours, goal setting and goal review; (5) the health education booklet that is given to the control arm. Follow-up assessments are conducted at 12 and 24 months. The primary outcome is incidence of T2DM. Secondary outcomes include behavioural, psychosocial, clinical, and biochemical measures. An economic evaluation is planned. Discussion Results from this trial will contribute to improved policy and practice regarding lifestyle intervention programs to prevent diabetes in India and other resource-constrained settings. Trial registration Australia and New Zealand Clinical Trials Registry: ACTRN12611000262909. PMID:24180316

"Why Didn't it Work?" Lessons From a Randomized Controlled Trial of a Web-based Personally Controlled Health Management System for Adults with Asthma.

PubMed

Lau, Annie Y S; Arguel, Amaël; Dennis, Sarah; Liaw, Siaw-Teng; Coiera, Enrico

2015-12-15

Personally controlled health management systems (PCHMS), which may include a personal health record (PHR), health management tools, and information resources, have been advocated as a next-generation technology to improve health behaviors and outcomes. There have been successful trials of PCHMS in various health settings. However, there is mixed evidence for whether consumers will use these systems over the long term and whether they ultimately lead to improved health outcomes and behaviors. The aim was to test whether use of a PCHMS by consumers can increase the uptake or updating of a written asthma action plan (AAP) among adults with asthma. A 12-month parallel 2-group randomized controlled trial was conducted. Participants living with asthma were recruited nationally in Australia between April and August 2013, and randomized 1:1 to either the PCHMS group or control group (online static educational content). The primary outcome measure was possession of an up-to-date written AAP poststudy. Secondary measures included (1) utilizing the AAP; (2) planned or unplanned visits to a health care professional for asthma-related concerns; (3) severe asthma exacerbation, inadequately controlled asthma, or worsening of asthma that required a change in treatment; and (4) number of days lost from work or study due to asthma. Ancillary analyses examined reasons for adoption or nonadoption of the intervention. Outcome measures were collected by online questionnaire prestudy, monthly, and poststudy. A total of 330 eligible participants were randomized into 1 of 2 arms (intervention: n=154; control: n=176). Access to the PCHMS was not associated with a significant difference in any of the primary or secondary outcomes. Most participants (80.5%, 124/154) did not access the intervention or accessed it only once. Despite the intervention being effective in other preventive care settings, system use was negligible and outcome changes were not seen as a result. Consumers must perceive the need for assistance with a task and assign priority to the task supported by the eHealth intervention. Additionally, the cost of adopting the intervention (eg, additional effort, time spent learning the new system) must be lower than the benefit. Otherwise, there is high risk consumers will not adopt the eHealth intervention. Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12612000716864; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362714 (Archived by WebCite® at http://www.webcitation.org/6dMV6hg4A).

A systematic review of the reporting of Data Monitoring Committees' roles, interim analysis and early termination in pediatric clinical trials

PubMed Central

2009-01-01

Background Decisions about interim analysis and early stopping of clinical trials, as based on recommendations of Data Monitoring Committees (DMCs), have far reaching consequences for the scientific validity and clinical impact of a trial. Our aim was to evaluate the frequency and quality of the reporting on DMC composition and roles, interim analysis and early termination in pediatric trials. Methods We conducted a systematic review of randomized controlled clinical trials published from 2005 to 2007 in a sample of four general and four pediatric journals. We used full-text databases to identify trials which reported on DMCs, interim analysis or early termination, and included children or adolescents. Information was extracted on general trial characteristics, risk of bias, and a set of parameters regarding DMC composition and roles, interim analysis and early termination. Results 110 of the 648 pediatric trials in this sample (17%) reported on DMC or interim analysis or early stopping, and were included; 68 from general and 42 from pediatric journals. The presence of DMCs was reported in 89 of the 110 included trials (81%); 62 papers, including 46 of the 89 that reported on DMCs (52%), also presented information about interim analysis. No paper adequately reported all DMC parameters, and nine (15%) reported all interim analysis details. Of 32 trials which terminated early, 22 (69%) did not report predefined stopping guidelines and 15 (47%) did not provide information on statistical monitoring methods. Conclusions Reporting on DMC composition and roles, on interim analysis results and on early termination of pediatric trials is incomplete and heterogeneous. We propose a minimal set of reporting parameters that will allow the reader to assess the validity of trial results. PMID:20003383

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

PubMed

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

2014-09-20

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

[Efficacy of Weitan Waifu patch on the postsurgical gastroparesis syndrome of gastrointestinal cancer: a multi-center trial].

PubMed

Zhou, Q; Zuo, M H; Li, Q W; Tian, Y T; Xie, Y B; Wang, Y B; Yang, G Y; Ye, Y J; Guo, P; Liu, J P; Liu, Z L; An, C; Zhou, T; Tian, Z; Liu, C B; Hu, Y; Chi, X Y; Shen, Y; Xia, Y; Hu, K W

2017-12-23

Objective: To investigate the safety and efficacy of the Weitan Waifu patch on the postsurgical gastroparesis syndrome (PGS) of gastrointestinal cancer. Methods: The multi-center, double-blind, randomized controlled trial was conducted with superiority design. Patients with PGS of gastrointestinal cancer diagnosed in 4 AAA hospitals and the abdominal symptom manifested as cold syndrome by Chinese local syndrome differentiation were recruited. These patients were randomly divided into two groups according to 1∶1 proportion. Placebo or Weitan Waifu patch was applied in control group or intervention group, respectively, based on the basic treatments, including nutrition support, gastrointestinal decompression, promoting gastric dynamics medicine.Two acupuncture points (Zhongwan and Shenque) were stuck with placebo in control group or patch in treatment group. The intervention course was 14 days or reached the effective standard. Results: From July 15, 2013 to Jun 3, 2015, 128 participants were recruited and 120 eligible cases were included in the full analysis set (FAS), and 60 cases in each group. 88 cases were included in the per-protocol set (PPS), including 45 cases in the treatment group and 43 cases in the control group. In the FAS, the clinical effective rate in the treatment group was 68.3%, significantly superior than 41.7% of the control group ( P =0.003). The medium time of effective therapy in the treatment group was 8 days, significantly shorter than 10 days in the control group ( P =0.017). In the FAS, 3 adverse events occurred in the treatment group, including mild to moderate decrustation, pruritus and nausea. The incidence rate of adverse events was 5.0% (3/60) and these symptoms were spontaneously remitted after drug withdrawal. No severe adverse events were observed in the control group. There was no significant difference between these two groups ( P =0.244). Conclusion: Weitan Waifu patch is a safely and effectively therapeutic method for patients with PGS (cold syndrome) of gastroenterological cancer. Trial registration: International Standard Randomized Controlled Trial Number Register, ISRCTN18291857.

A Fully Automated Diabetes Prevention Program, Alive-PD: Program Design and Randomized Controlled Trial Protocol

PubMed Central

Azar, Kristen MJ; Block, Torin J; Romanelli, Robert J; Carpenter, Heather; Hopkins, Donald; Palaniappan, Latha; Block, Clifford H

2015-01-01

Background In the United States, 86 million adults have pre-diabetes. Evidence-based interventions that are both cost effective and widely scalable are needed to prevent diabetes. Objective Our goal was to develop a fully automated diabetes prevention program and determine its effectiveness in a randomized controlled trial. Methods Subjects with verified pre-diabetes were recruited to participate in a trial of the effectiveness of Alive-PD, a newly developed, 1-year, fully automated behavior change program delivered by email and Web. The program involves weekly tailored goal-setting, team-based and individual challenges, gamification, and other opportunities for interaction. An accompanying mobile phone app supports goal-setting and activity planning. For the trial, participants were randomized by computer algorithm to start the program immediately or after a 6-month delay. The primary outcome measures are change in HbA1c and fasting glucose from baseline to 6 months. The secondary outcome measures are change in HbA1c, glucose, lipids, body mass index (BMI), weight, waist circumference, and blood pressure at 3, 6, 9, and 12 months. Randomization and delivery of the intervention are independent of clinic staff, who are blinded to treatment assignment. Outcomes will be evaluated for the intention-to-treat and per-protocol populations. Results A total of 340 subjects with pre-diabetes were randomized to the intervention (n=164) or delayed-entry control group (n=176). Baseline characteristics were as follows: mean age 55 (SD 8.9); mean BMI 31.1 (SD 4.3); male 68.5%; mean fasting glucose 109.9 (SD 8.4) mg/dL; and mean HbA1c 5.6 (SD 0.3)%. Data collection and analysis are in progress. We hypothesize that participants in the intervention group will achieve statistically significant reductions in fasting glucose and HbA1c as compared to the control group at 6 months post baseline. Conclusions The randomized trial will provide rigorous evidence regarding the efficacy of this Web- and Internet-based program in reducing or preventing progression of glycemic markers and indirectly in preventing progression to diabetes. Trial Registration ClinicalTrials.gov NCT01479062; http://clinicaltrials.gov/show/NCT01479062 (Archived by WebCite at http://www.webcitation.org/6U8ODy1vo). PMID:25608692

A review of escitalopram and citalopram in child and adolescent depression.

PubMed

Carandang, Carlo; Jabbal, Rekha; Macbride, Angela; Elbe, Dean

2011-11-01

To review the basic pharmacology and published literature regarding escitalopram and citalopram in child and adolescent depression. A LITERATURE REVIEW WAS CONDUCTED USING THE SEARCH TERMS: 'escitalopram', 'citalopram', 'depression', 'randomized controlled trial', 'open label trial' and limits set to: Human trials, English Language and All Child (Age 0-18). Additional articles were identified from reference information and poster presentation data. Three prospective, randomized controlled trials (RCT) were found for escitalopram in pediatric depression, and two RCTs were found for citalopram. One RCT each for escitalopram and citalopram showed superiority over placebo on the primary out come measure. Adverse effects in escitalopram and citalopram trials were generally mild to moderate. Suicidality was not assessed systematically in all RCTs reviewed, but did not appear to be elevated over placebo in escitalopram RCTs. One trial reported numerically higher suicide related events for citalopram compared to placebo (14 vs. 5, p=0.06). At present, escitalopram and citalopram should be considered a second-line option for adolescent depression. The US Food and Drug Administration approval of escitalopram for treatment of adolescent depression was based on a single positive RCT. This is less evidence than typically required for approval of a drug for a new indication.

Gaze-Contingent Music Reward Therapy for Social Anxiety Disorder: A Randomized Controlled Trial.

PubMed

Lazarov, Amit; Pine, Daniel S; Bar-Haim, Yair

2017-07-01

Patients with social anxiety disorder exhibit increased attentional dwelling on social threats, providing a viable target for therapeutics. This randomized controlled trial examined the efficacy of a novel gaze-contingent music reward therapy for social anxiety disorder designed to reduce attention dwelling on threats. Forty patients with social anxiety disorder were randomly assigned to eight sessions of either gaze-contingent music reward therapy, designed to divert patients' gaze toward neutral stimuli rather than threat stimuli, or to a control condition. Clinician and self-report measures of social anxiety were acquired pretreatment, posttreatment, and at 3-month follow-up. Dwell time on socially threatening faces was assessed during the training sessions and at pre- and posttreatment. Gaze-contingent music reward therapy yielded greater reductions of symptoms of social anxiety disorder than the control condition on both clinician-rated and self-reported measures. Therapeutic effects were maintained at follow-up. Gaze-contingent music reward therapy, but not the control condition, also reduced dwell time on threat, which partially mediated clinical effects. Finally, gaze-contingent music reward therapy, but not the control condition, also altered dwell time on socially threatening faces not used in training, reflecting near-transfer training generalization. This is the first randomized controlled trial to examine a gaze-contingent intervention in social anxiety disorder. The results demonstrate target engagement and clinical effects. This study sets the stage for larger randomized controlled trials and testing in other emotional disorders.

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

PubMed

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

2016-11-18

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

The Project Data Sphere Initiative: Accelerating Cancer Research by Sharing Data

PubMed Central

Reeder-Hayes, Katherine E.; Corty, Robert W.; Basch, Ethan; Milowsky, Mathew I.; Dusetzina, Stacie B.; Bennett, Antonia V.; Wood, William A.

2015-01-01

Background. In this paper, we provide background and context regarding the potential for a new data-sharing platform, the Project Data Sphere (PDS) initiative, funded by financial and in-kind contributions from the CEO Roundtable on Cancer, to transform cancer research and improve patient outcomes. Given the relatively modest decline in cancer death rates over the past several years, a new research paradigm is needed to accelerate therapeutic approaches for oncologic diseases. Phase III clinical trials generate large volumes of potentially usable information, often on hundreds of patients, including patients treated with standard of care therapies (i.e., controls). Both nationally and internationally, a variety of stakeholders have pursued data-sharing efforts to make individual patient-level clinical trial data available to the scientific research community. Potential Benefits and Risks of Data Sharing. For researchers, shared data have the potential to foster a more collaborative environment, to answer research questions in a shorter time frame than traditional randomized control trials, to reduce duplication of effort, and to improve efficiency. For industry participants, use of trial data to answer additional clinical questions could increase research and development efficiency and guide future projects through validation of surrogate end points, development of prognostic or predictive models, selection of patients for phase II trials, stratification in phase III studies, and identification of patient subgroups for development of novel therapies. Data transparency also helps promote a public image of collaboration and altruism among industry participants. For patient participants, data sharing maximizes their contribution to public health and increases access to information that may be used to develop better treatments. Concerns about data-sharing efforts include protection of patient privacy and confidentiality. To alleviate these concerns, data sets are deidentified to maintain anonymity. To address industry concerns about protection of intellectual property and competitiveness, we illustrate several models for data sharing with varying levels of access to the data and varying relationships between trial sponsors and data access sponsors. The Project Data Sphere Initiative. PDS is an independent initiative of the CEO Roundtable on Cancer Life Sciences Consortium, built to voluntarily share, integrate, and analyze comparator arms of historical cancer clinical trial data sets to advance future cancer research. The aim is to provide a neutral, broad-access platform for industry and academia to share raw, deidentified data from late-phase oncology clinical trials using comparator-arm data sets. These data are likely to be hypothesis generating or hypothesis confirming but, notably, do not take the place of performing a well-designed trial to address a specific hypothesis. Prospective providers of data to PDS complete and sign a data sharing agreement that includes a description of the data they propose to upload, and then they follow easy instructions on the website for uploading their deidentified data. The SAS Institute has also collaborated with the initiative to provide intrinsic analytic tools accessible within the website itself. As of October 2014, the PDS website has available data from 14 cancer clinical trials covering 9,000 subjects, with hopes to further expand the database to include more than 25,000 subject accruals within the next year. PDS differentiates itself from other data-sharing initiatives by its degree of openness, requiring submission of only a brief application with background information of the individual requesting access and agreement to terms of use. Data from several different sponsors may be pooled to develop a comprehensive cohort for analysis. In order to protect patient privacy, data providers in the U.S. are responsible for deidentifying data according to standards set forth by the Privacy Rule of the U.S. Health Insurance Portability and Accountability Act of 1996. Using Data Sharing to Improve Outcomes in Cancer: The “Prostate Cancer Challenge.” Control-arm data of several studies among patients with metastatic castration-resistant prostate cancer (mCRPC) are currently available through PDS. These data sets have multiple potential uses. The “Prostate Cancer Challenge” will ask the cancer research community to use clinical trial data deposited in the PDS website to address key research questions regarding mCRPC. General themes that could be explored by the cancer community are described in this article: prognostic models evaluating the influence of pretreatment factors on survival and patient-reported outcomes; comparative effectiveness research evaluating the efficacy of standard of care therapies, as illustrated in our companion article comparing mitoxantrone plus prednisone with prednisone alone; effects of practice variation in dose, frequency, and duration of therapy; level of patient adherence to elements of trial protocols to inform the design of future clinical trials; and age of subjects, regional differences in health care, and other confounding factors that might affect outcomes. Potential Limitations and Methodological Challenges. The number of data sets available and the lack of experimental-arm data limit the potential scope of research using the current PDS. The number of trials is expected to grow exponentially over the next year and may include multiple cancer settings, such as breast, colorectal, lung, hematologic malignancy, and bone marrow transplantation. Other potential limitations include the retrospective nature of the data analyses performed using PDS and its generalizability, given that clinical trials are often conducted among younger, healthier, and less racially diverse patient populations. Methodological challenges exist when combining individual patient data from multiple clinical trials; however, advancements in statistical methods for secondary database analysis offer many tools for reanalyzing data arising from disparate trials, such as propensity score matching. Despite these concerns, few if any comparable data sets include this level of detail across multiple clinical trials and populations. Conclusion. Access to large, late-phase, cancer-trial data sets has the potential to transform cancer research by optimizing research efficiency and accelerating progress toward meaningful improvements in cancer care. This type of platform provides opportunities for unique research projects that can examine relatively neglected areas and that can construct models necessitating large amounts of detailed data. The full potential of PDS will be realized only when multiple tumor types and larger numbers of data sets are available through the website. PMID:25876994

The project data sphere initiative: accelerating cancer research by sharing data.

PubMed

Green, Angela K; Reeder-Hayes, Katherine E; Corty, Robert W; Basch, Ethan; Milowsky, Mathew I; Dusetzina, Stacie B; Bennett, Antonia V; Wood, William A

2015-05-01

In this paper, we provide background and context regarding the potential for a new data-sharing platform, the Project Data Sphere (PDS) initiative, funded by financial and in-kind contributions from the CEO Roundtable on Cancer, to transform cancer research and improve patient outcomes. Given the relatively modest decline in cancer death rates over the past several years, a new research paradigm is needed to accelerate therapeutic approaches for oncologic diseases. Phase III clinical trials generate large volumes of potentially usable information, often on hundreds of patients, including patients treated with standard of care therapies (i.e., controls). Both nationally and internationally, a variety of stakeholders have pursued data-sharing efforts to make individual patient-level clinical trial data available to the scientific research community. For researchers, shared data have the potential to foster a more collaborative environment, to answer research questions in a shorter time frame than traditional randomized control trials, to reduce duplication of effort, and to improve efficiency. For industry participants, use of trial data to answer additional clinical questions could increase research and development efficiency and guide future projects through validation of surrogate end points, development of prognostic or predictive models, selection of patients for phase II trials, stratification in phase III studies, and identification of patient subgroups for development of novel therapies. Data transparency also helps promote a public image of collaboration and altruism among industry participants. For patient participants, data sharing maximizes their contribution to public health and increases access to information that may be used to develop better treatments. Concerns about data-sharing efforts include protection of patient privacy and confidentiality. To alleviate these concerns, data sets are deidentified to maintain anonymity. To address industry concerns about protection of intellectual property and competitiveness, we illustrate several models for data sharing with varying levels of access to the data and varying relationships between trial sponsors and data access sponsors. PDS is an independent initiative of the CEO Roundtable on Cancer Life Sciences Consortium, built to voluntarily share, integrate, and analyze comparator arms of historical cancer clinical trial data sets to advance future cancer research. The aim is to provide a neutral, broad-access platform for industry and academia to share raw, deidentified data from late-phase oncology clinical trials using comparator-arm data sets. These data are likely to be hypothesis generating or hypothesis confirming but, notably, do not take the place of performing a well-designed trial to address a specific hypothesis. Prospective providers of data to PDS complete and sign a data sharing agreement that includes a description of the data they propose to upload, and then they follow easy instructions on the website for uploading their deidentified data. The SAS Institute has also collaborated with the initiative to provide intrinsic analytic tools accessible within the website itself. As of October 2014, the PDS website has available data from 14 cancer clinical trials covering 9,000 subjects, with hopes to further expand the database to include more than 25,000 subject accruals within the next year. PDS differentiates itself from other data-sharing initiatives by its degree of openness, requiring submission of only a brief application with background information of the individual requesting access and agreement to terms of use. Data from several different sponsors may be pooled to develop a comprehensive cohort for analysis. In order to protect patient privacy, data providers in the U.S. are responsible for deidentifying data according to standards set forth by the Privacy Rule of the U.S. Health Insurance Portability and Accountability Act of 1996. USING DATA SHARING TO IMPROVE OUTCOMES IN CANCER THE "PROSTATE CANCER CHALLENGE": Control-arm data of several studies among patients with metastatic castration-resistant prostate cancer (mCRPC) are currently available through PDS. These data sets have multiple potential uses. The "Prostate Cancer Challenge" will ask the cancer research community to use clinical trial data deposited in the PDS website to address key research questions regarding mCRPC. General themes that could be explored by the cancer community are described in this article: prognostic models evaluating the influence of pretreatment factors on survival and patient-reported outcomes; comparative effectiveness research evaluating the efficacy of standard of care therapies, as illustrated in our companion article comparing mitoxantrone plus prednisone with prednisone alone; effects of practice variation in dose, frequency, and duration of therapy; level of patient adherence to elements of trial protocols to inform the design of future clinical trials; and age of subjects, regional differences in health care, and other confounding factors that might affect outcomes. The number of data sets available and the lack of experimental-arm data limit the potential scope of research using the current PDS. The number of trials is expected to grow exponentially over the next year and may include multiple cancer settings, such as breast, colorectal, lung, hematologic malignancy, and bone marrow transplantation. Other potential limitations include the retrospective nature of the data analyses performed using PDS and its generalizability, given that clinical trials are often conducted among younger, healthier, and less racially diverse patient populations. Methodological challenges exist when combining individual patient data from multiple clinical trials; however, advancements in statistical methods for secondary database analysis offer many tools for reanalyzing data arising from disparate trials, such as propensity score matching. Despite these concerns, few if any comparable data sets include this level of detail across multiple clinical trials and populations. Access to large, late-phase, cancer-trial data sets has the potential to transform cancer research by optimizing research efficiency and accelerating progress toward meaningful improvements in cancer care. This type of platform provides opportunities for unique research projects that can examine relatively neglected areas and that can construct models necessitating large amounts of detailed data. The full potential of PDS will be realized only when multiple tumor types and larger numbers of data sets are available through the website. ©AlphaMed Press.

Task switching in video game players: Benefits of selective attention but not resistance to proactive interference.

PubMed

Karle, James W; Watter, Scott; Shedden, Judith M

2010-05-01

Research into the perceptual and cognitive effects of playing video games is an area of increasing interest for many investigators. Over the past decade, expert video game players (VGPs) have been shown to display superior performance compared to non-video game players (nVGPs) on a range of visuospatial and attentional tasks. A benefit of video game expertise has recently been shown for task switching, suggesting that VGPs also have superior cognitive control abilities compared to nVGPs. In two experiments, we examined which aspects of task switching performance this VGP benefit may be localized to. With minimal trial-to-trial interference from minimally overlapping task set rules, VGPs demonstrated a task switching benefit compared to nVGPs. However, this benefit disappeared when proactive interference between tasks was increased, with substantial stimulus and response overlap in task set rules. We suggest that VGPs have no generalized benefit in task switching-related cognitive control processes compared to nVGPs, with switch cost reductions due instead to a specific benefit in controlling selective attention. Copyright 2009 Elsevier B.V. All rights reserved.

Reward Motivation Enhances Task Coding in Frontoparietal Cortex.

PubMed

Etzel, Joset A; Cole, Michael W; Zacks, Jeffrey M; Kay, Kendrick N; Braver, Todd S

2016-04-01

Reward motivation often enhances task performance, but the neural mechanisms underlying such cognitive enhancement remain unclear. Here, we used a multivariate pattern analysis (MVPA) approach to test the hypothesis that motivation-related enhancement of cognitive control results from improved encoding and representation of task set information. Participants underwent two fMRI sessions of cued task switching, the first under baseline conditions, and the second with randomly intermixed reward incentive and no-incentive trials. Information about the upcoming task could be successfully decoded from cue-related activation patterns in a set of frontoparietal regions typically associated with task control. More critically, MVPA classifiers trained on the baseline session had significantly higher decoding accuracy on incentive than non-incentive trials, with decoding improvement mediating reward-related enhancement of behavioral performance. These results strongly support the hypothesis that reward motivation enhances cognitive control, by improving the discriminability of task-relevant information coded and maintained in frontoparietal brain regions. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Cognitive remediation for individuals with psychosis in a supported education setting: a randomized controlled trial.

PubMed

Kidd, Sean A; Kaur, Jaswant; Virdee, Gursharan; George, Tony P; McKenzie, Kwame; Herman, Yarissa

2014-08-01

Cognitive remediation (CR) has demonstrated good outcomes when paired with supported employment, however little is known about its effectiveness when integrated into a supported education program. This randomized controlled trial examined the effectiveness of integrating CR within a supported education program compared with supported education without CR. Thirty-seven students with psychosis were recruited into the study in the 2012 academic year. Academic functioning, cognition, self-esteem, and symptomatology were assessed at baseline, at 4months following the first academic term in which CR was provided, and at 8months assessing maintenance of gains. The treatment group demonstrated better retention in the academic program and a trend of improvement across a range of academic functional domains. While both treatment and control groups showed improvement in cognitive measures, the outcomes were not augmented by CR training. CR was also associated with significant and sustained improvements in self esteem. Further research, investigating specific intervention components is required to clarify the mixed findings regarding the effectiveness of CR in an education setting. Copyright © 2014 Elsevier B.V. All rights reserved.

A modified varying-stage adaptive phase II/III clinical trial design.

PubMed

Dong, Gaohong; Vandemeulebroecke, Marc

2016-07-01

Conventionally, adaptive phase II/III clinical trials are carried out with a strict two-stage design. Recently, a varying-stage adaptive phase II/III clinical trial design has been developed. In this design, following the first stage, an intermediate stage can be adaptively added to obtain more data, so that a more informative decision can be made. Therefore, the number of further investigational stages is determined based upon data accumulated to the interim analysis. This design considers two plausible study endpoints, with one of them initially designated as the primary endpoint. Based on interim results, another endpoint can be switched as the primary endpoint. However, in many therapeutic areas, the primary study endpoint is well established. Therefore, we modify this design to consider one study endpoint only so that it may be more readily applicable in real clinical trial designs. Our simulations show that, the same as the original design, this modified design controls the Type I error rate, and the design parameters such as the threshold probability for the two-stage setting and the alpha allocation ratio in the two-stage setting versus the three-stage setting have a great impact on the design characteristics. However, this modified design requires a larger sample size for the initial stage, and the probability of futility becomes much higher when the threshold probability for the two-stage setting gets smaller. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Alternatives for discounting in the analysis of noninferiority trials.

PubMed

Snapinn, Steven M

2004-05-01

Determining the efficacy of an experimental therapy relative to placebo on the basis of an active-control noninferiority trial requires reference to historical placebo-controlled trials. The validity of the resulting comparison depends on two key assumptions: assay sensitivity and constancy. Since the truth of these assumptions cannot be verified, it seems logical to raise the standard of evidence required to declare efficacy; this concept is referred to as discounting. It is not often recognized that two common design and analysis approaches, setting a noninferiority margin and requiring preservation of a fraction of the standard therapy's effect, are forms of discounting. The noninferiority margin is a particularly poor approach, since its degree of discounting depends on an irrelevant factor. Preservation of effect is more reasonable, but it addresses only the constancy assumption, not the issue of assay sensitivity. Gaining consensus on the most appropriate approach to the design and analysis of noninferiority trials will require a common understanding of the concept of discounting.

Heparin in acute ischemic stroke revisited.

PubMed

Chamorro, A

2008-10-01

The evidence gathered in clinical trials of low molecular weight heparins (LMWHs) or with unfractionated heparin (UH) given subcutaneously at low or medium doses to patients with acute stroke cannot be extrapolated to the insufficiently tested effects of intravenous, weight-adjusted UH. Recent small studies have provided encouraging results but are potentially confounded and deserve confirmation in larger randomized controlled trials. In accordance with the current understanding of the biology of acute ischemic stroke and the pharmacology of UH, the new randomized controlled trials on heparin should give appropriate credit to the importance of a short therapeutic window, adequate dose adjustment of the drug, intravenous administration, and close monitoring of biological effects. UH is an orphan drug and only an academic driven trial would be able to face such an enterprise. Meanwhile, recommendations against the value of "early" anticoagulation with full dose of weight adjusted UH in the setting of acute ischemic stroke are not based on direct evidence but on extrapolations.

Rationale and methods of a randomized controlled trial of immunogenicity, safety and impact on carriage of pneumococcal conjugate and polysaccharide vaccines in infants in Papua New Guinea.

PubMed

Lehmann, Deborah; Kirarock, Wendy; van den Biggelaar, Anita H J; Passey, Megan; Jacoby, Peter; Saleu, Gerard; Masiria, Geraldine; Nivio, Birunu; Greenhill, Andrew; Orami, Tilda; Francis, Jacinta; Ford, Rebecca; Kirkham, Lea-Ann; Solomon, Vela; Richmond, Peter C; Pomat, William S

2017-01-01

Children in third-world settings including Papua New Guinea (PNG) experience early onset of carriage with a broad range of pneumococcal serotypes, resulting in a high incidence of severe pneumococcal disease and deaths in the first 2 years of life. Vaccination trials in high endemicity settings are needed to provide evidence and guidance on optimal strategies to protect children in these settings against pneumococcal infections. This report describes the rationale, objectives, methods, study population, follow-up and specimen collection for a vaccination trial conducted in an endemic and logistically challenging setting in PNG. The trial aimed to determine whether currently available pneumococcal conjugate vaccines (PCV) are suitable for use under PNG's accelerated immunization schedule, and that a schedule including pneumococcal polysaccharide vaccine (PPV) in later infancy is safe and immunogenic in this high-risk population. This open randomized-controlled trial was conducted between November 2011 and March 2016, enrolling 262 children aged 1 month between November 2011 and April 2014. The participants were randomly allocated (1:1) to receive 10-valent PCV (10vPCV) or 13-valent PCV (13vPCV) in a 1-2-3-month schedule, with further randomization to receive PPV or no PPV at age 9 months, followed by a 1/5 th PPV challenge at age 23 months. A total of 1229 blood samples were collected to measure humoral and cellular immune responses and 1238 nasopharyngeal swabs to assess upper respiratory tract colonization and carriage load. Serious adverse events were monitored throughout the study. Of the 262 children enrolled, 87% received 3 doses of PCV, 79% were randomized to receive PPV or no PPV at age 9 months, and 67% completed the study at 24 months of age with appropriate immunization and challenge. Laboratory testing of the many samples collected during this trial will determine the impact of the different vaccine schedules and formulations on nasopharyngeal carriage, antibody production and function, and immune memory. The final data will inform policy on pneumococcal vaccine schedules in countries with children at high risk of pneumococcal disease by providing direct comparison of an accelerated schedule of 10vPCV and 13vPCV and the potential advantages of PPV following PCV immunization. ClinicalTrials.gov CTN NCT01619462, retrospectively registered on May 28, 2012.

Grass residues as a sustainable carbon source in application of anaerobic soil disinfestation for control of apple nursery replant disease

USDA-ARS?s Scientific Manuscript database

Studies were conducted to assess the efficacy of anaerobic soil disinfestation (ASD) for control of replant disease in an apple nursery setting. Treatments applied in a field trial conducted at an experimental orchard in Washington State included ASD using orchard grass residues (GR; 20 t ha-1) as ...

Childhood Obesity: Concept, Feasibility, and Interim Results of a Local Group-Based, Long-Term Treatment Program

ERIC Educational Resources Information Center

Weigel, Corina; Kokocinski, Kathrin; Lederer, Peter; Dotsch, Jorg; Rascher, Wolfgang; Knerr, Ina

2008-01-01

Objective: The authors performed a group-based program for obese children and adolescents in Bavaria, Germany to enable them to establish a health-oriented lifestyle and to reduce overweight. The authors compared this program with a control approach based on the patients' own initiative. Design: This is a controlled clinical trial. Setting: A…

INVESTIGATING THE MANAGEMENT OF CARIOUS PRIMARY TEETH IN GENERAL DENTAL PRACTICE: AN OVERVIEW OF THE DEVELOPMENT AND CONDUCT OF THE FICTION TRIAL.

PubMed

Stewart, Matthew; Keightley, Alexander; Maguire, Anne; Chadwick, Barbara; Vale, Luke; Homer, Tara; Douglas, Gail; Deery, Chris; Marshman, Zoe; Ryan, Vicky; Innes, Nicola

2015-11-01

The management of carious primary teeth is a challenge for patients, parents and clinicians. Most evidence supporting different management strategies originates from a specialist setting and therefore its relevance to the primary care setting is questionable. The UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) has commissioned the FiCTION (Filling Children's Teeth: Indicated Or Not?) trial; a multi-centre primary dental care randomised controlled trial (RCT) to determine the most clinically and cost- effective approach to managing caries in the primary dentition in the UK. This large trial began in 2012, is due to be completed in late 2017 and involves 72 practices and 1,124 children initially aged three to seven years with dentine caries, following randomisation to one of three caries management strategies. Clinical, radiographic, quality of life, treatment acceptability and health economics data are collected during the three-year follow up period. This article provides an overview of the development and conduct of FiCTION and discusses some approaches adopted to manage challenges and achieve the patient recruitment target.

Psychological interventions for post-traumatic stress disorder in people living with HIV in Resource poor settings: a systematic review.

PubMed

Verhey, Ruth; Chibanda, Dixon; Brakarsh, Jonathan; Seedat, Soraya

2016-10-01

Post-traumatic stress disorder is pervasive in low- and middle-income countries. There is evidence to suggest that post-traumatic stress disorder is more common among people living with HIV than non-infected matched controls. We carried out a systematic review of interventions for adult post-traumatic stress disorder from resource poor settings with a focus on people living with HIV. We included all studies that investigated interventions for adult post-traumatic stress disorder from resource poor settings with a focus on interventions that were either randomised controlled trials or observational cohort studies carried out from 1980 to May 2015. Of the 25 articles that were identified for full review, two independent reviewers identified seven studies that met our study inclusion criteria. All randomised controlled trials (RCT) (n = 6) used cognitive behavioural therapy-based interventions and focused on people living with HIV in resource poor settings. There was only one study focusing on the use of lay counsellors to address post-traumatic stress disorder but core competencies were not described. There were no intervention studies from Africa, only an observational cohort study from Rwanda. Rigorously evaluated interventions for adult post-traumatic stress disorder in people living with HIV are rare. Most were undertaken in resource poor settings located in high-income countries. There is a need for research on the development and implementation of appropriate interventions for post-traumatic stress disorder in people living with HIV in low- and middle-income countries. © 2016 John Wiley & Sons Ltd.

Impact of a social franchising program on uptake of oral rehydration solution plus zinc for childhood diarrhea in myanmar: a community-level randomized controlled trial.

PubMed

Aung, Tin; Montagu, Dominic; Su Su Khin, Hnin; Win, Zaw; San, Ang Kyaw; McFarland, Willi

2014-06-01

Diarrhea's impact on childhood morbidity can be reduced by administering oral rehydration solution (ORS) with zinc; challenges to wider use are changing health-seeking behavior and ensuring access. We conducted a randomized controlled trial to increase ORS plus zinc uptake in rural Myanmar. Village tracts, matched in 52 pairs, were randomized to standard ORS access vs. a social franchising program training community educators and supplying ORS plus zinc. Intervention and control communities were comparable on demographics, prevalence of diarrhea and previous use of ORS. One year after randomization, ORS plus zinc use was 13.7% in the most recent case of diarrhea in intervention households compared with 1.8% in control households (p < 0.001) (N = 3605). A significant increase in ORS plus zinc use was noted in the intervention (p = 0.044) but not in the control (p = 0.315) group. Social franchising increased optimal treatment of childhood diarrhea in rural Myanmar. Scale-up stands to reduce morbidity among children in similar settings. Current Controlled Trials ISRCTN73606238. © The Author [2014]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Interventions to Promote Colorectal Cancer Screening: An Integrative Review

PubMed Central

Rawl, Susan M.; Menon, Usha; Burness, Allison; Breslau, Erica S.

2012-01-01

Behavior change interventions to promote colorectal cancer (CRC) screening have targeted people in community and primary care settings, health care providers, and health systems. Randomized controlled trials provide the strongest evidence of intervention efficacy. The purpose of this integrative review was to evaluate trials of CRC screening interventions published between 1997 and 2007 and to identify knowledge gaps and future directions for research. Thirty-three randomized trials that met inclusion criteria were evaluated using a modified version of the TREND criteria. Significant intervention effects were reported in six out of ten trials focused on increasing fecal occult blood testing, four of seven trials focused on sigmoidoscopy or colonoscopy completion, and nine of 16 focused on completion of any screening test. Several effective interventions to promote CRC screening were identified. Future trials need to use theory to guide interventions, examine moderators and mediators, consistently report results, and use comparable outcome measures. PMID:22261002

Improving adolescent mental health and resilience through a resilience-based intervention in schools: study protocol for a randomised controlled trial

PubMed Central

2014-01-01

Background Research investigating the effectiveness of universal interventions to reduce the risk of mental health problems remains limited. Schools are a promising setting within which adolescents can receive interventions aimed at promoting their mental health. The aim of this study is to assess the effectiveness of a resilience-based prevention-focused intervention in reducing the risk of mental health problems among adolescents attending secondary school in socio-economically disadvantaged areas. Methods/design A cluster randomised control trial will be conducted, with schools as the unit of randomisation. Initially, 32 secondary schools will be randomly allocated to a control or intervention group (12 control and 20 intervention). An intervention focused on improving student internal and external resilience factors will be implemented in intervention schools. A survey of students in Grade 7 in both intervention and control schools will be conducted (baseline) and repeated three years later when the students are in Grade 10. The Strengths and Difficulties Questionnaire will be used to measure the risk of mental health problems. At follow-up, the risk of mental health problems will be compared between Grade 10 students in intervention and control schools to determine intervention effectiveness. Discussion The study presents an opportunity to determine the effectiveness of a comprehensive resilience-based intervention in reducing the risk of mental health problems in adolescents attending secondary schools. The outcomes of the trial are of importance to youth, schools, mental health clinicians and policymakers. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12611000606987, registered 14 June 2011. PMID:25037455

Generalizing from clinical trial data: A case study. The risk of suicidality among pediatric antidepressant users

PubMed Central

Greenhouse, Joel B.; Kaizar, Eloise E.; Kelleher, Kelly; Seltman, Howard; Gardner, William

2010-01-01

Summary For the results of randomized controlled clinical trials (RCTs) and related meta-analyses to be useful in practice, they must be relevant to a definable group of patients in a particular clinical setting. To the extent this is so, we say that the trial is generalizable or externally valid. Although concern about the generalizability of the results of RCTs is often discussed, there are few examples of methods for assessing the generalizability of clinical trial data. In this paper, we describe and illustrate an approach for making what we call generalizability judgments and illustrate the approach in the context of a case study of the risk of suicidality among pediatric antidepressant users. PMID:18381709

Preventative Reading Interventions Teaching Direct Mapping of Graphemes in Texts and Set-for-Variability Aid At-Risk Learners

ERIC Educational Resources Information Center

Savage, Robert; Georgiou, George; Parrila, Rauno; Maiorino, Kristina

2018-01-01

We evaluated two experimenter-delivered, small-group word reading programs among at-risk poor readers in Grade 1 classes of regular elementary schools using a two-arm, dual-site-matched control trial intervention. At-risk poor word readers (n = 201) were allocated to either (a) Direct Mapping and Set-for-Variability (DMSfV) or (b) Current or…

Left atrial concomitant surgical ablation for treatment of atrial fibrillation in cardiac surgery: A meta-analysis of randomized controlled trials

PubMed Central

Wang, Chunguo; Ye, Minhua; Lin, Jiang; Jin, Jiang; Hu, Quanteng; Zhu, Chengchu; Chen, Baofu

2018-01-01

Introduction Surgical ablation is a generally established treatment for patients with atrial fibrillation undergoing concomitant cardiac surgery. Left atrial (LA) lesion set for ablation is a simplified procedure suggested to reduce the surgery time and morbidity after procedure. The present meta-analysis aims to explore the outcomes of left atrial lesion set versus no ablative treatment in patients with AF undergoing cardiac surgery. Methods A literature research was performed in six database from their inception to July 2017, identifying all relevant randomized controlled trials (RCTs) comparing left atrial lesion set versus no ablative treatment in AF patient undergoing cardiac surgery. Data were extracted and analyzed according to predefined clinical endpoints. Results Eleven relevant RCTs were included for analysis in the present study. The prevalence of sinus rhythm in ablation group was significantly higher at discharge, 6-month and 1-year follow-up period. The morbidity including 30 day mortality, late all-cause mortality, reoperation for bleeding, permanent pacemaker implantation and neurological events were of no significant difference between two groups. Conclusions The result of our meta-analysis demonstrates that left atrial lesion set is an effective and safe surgical ablation strategy for AF patients undergoing concomitant cardiac surgery. PMID:29360851

Feasibility and Efficacy of the Nintendo Wii Gaming System to Improve Balance Performance Post-Stroke: Protocol of a Phase II Randomized Controlled Trial in an Inpatient Rehabilitation Setting.

PubMed

Bower, Kelly J; Clark, Ross A; McGinley, Jennifer L; Martin, Clarissa L; Miller, Kimberly J

2013-04-01

Balance deficits following stroke are common and debilitating. Commercially available gaming systems, such as the Nintendo(®) (Kyoto, Japan) Wii™, have been widely adopted clinically; however, there is limited evidence supporting their feasibility and efficacy for improving balance performance following stroke. The aim of this trial is to investigate the clinical feasibility and efficacy of using the Nintendo Wii gaming system as an adjunct to standard care to improve balance performance following stroke in an inpatient rehabilitation setting. Thirty participants undergoing inpatient stroke rehabilitation will be recruited into this Phase II, single-blind, randomized controlled trial. Participants will be allocated into a Balance or Upper Limb Group, and both groups will perform activities using the Nintendo Wii in addition to their standard care. Participants will attend three 45-minute sessions per week, for a minimum of 2 and a maximum of 4 weeks. The main focus of the study is to investigate the feasibility of the intervention protocol. This will be evaluated through recruitment, retention, adherence, acceptability, and safety. The Step Test and Functional Reach Test will be the primary efficacy outcomes. Secondary outcomes will include force platform, mobility, and upper limb measures. Assessments will occur at baseline, 2 weeks, and 4 weeks after study entry. To the authors' knowledge, this will be the largest randomized clinical trial to investigate the feasibility and efficacy of the Nintendo Wii gaming system for improving balance performance in a stroke population. The results will inform the design of a Phase III multicenter trial.

Methodological quality of randomized controlled trials of spinal manipulation and mobilization in tension-type headache, migraine, and cervicogenic headache.

PubMed

Fernández-de-las-Peñas, César; Alonso-Blanco, Cristina; San-Roman, Jesús; Miangolarra-Page, Juan C

2006-03-01

Literature review of quality of clinical trials. To determine the methodological quality of published randomized controlled trials that used spinal manipulation and/or mobilization to treat patients with tension-type headache (TTH), cervicogenic headache (CeH), and migraine (M) in the last decade. TTH, CeH, and M are the most prevalent types of headaches seen in adults. Individuals who have headaches frequently use physical therapy, manual therapy, or chiropractic care. Randomized controlled trials are considered an optimal method with which to assess the efficacy of any intervention. Computerized literature searches were performed in MEDLINE, EMBASE, COCHRANE, AMED, MANTIS, CINHAL, and PEDro databases. Randomized controlled trials in which spinal manipulation and/or mobilization had been used for TTH, CeH, and M published in a peer-reviewed journal as full text, and with at least 1 clinically relevant outcome measure (ie, headache intensity, duration, or frequency) were reviewed. The methodological quality of the studies was assessed independently by 2 reviewers using a set of predefined criteria. Only 8 studies met all the inclusion criteria. One clinical trial evaluated spinal manipulation and mobilization together, and the remaining 7 assessed spinal manipulative therapy. No controlled trials analyzing exclusively the effects of spinal mobilization were found. Methodological scores ranged from 35 to 56 points out of a theoretical maximum of 100 points, indicating an overall poor methodology of the studies. Only 2 studies obtained a high-quality score (greater than 50 points). No significant differences in quality scores were found based on the type of headache investigated. Methodological quality was not associated with the year of publication (before 2000, or later) nor with the results (positive, neutral, negative) reported in the studies. The most common flaws were a small sample size, the absence of a placebo control group, lack of blinded patients, and no description of the manipulative procedure. There are few published randomized controlled trials analyzing the effectiveness of spinal manipulation and/or mobilization for TTH, CeH, and M in the last decade. In addition, the methodological quality of these papers is typically low. Clearly, there is a need for high-quality randomized controlled trials assessing the effectiveness of these interventions in these headache disorders.

Recruiting Filipino Immigrants in a Randomized Controlled Trial Promoting Enrollment in an Evidence-Based Parenting Intervention.

PubMed

Javier, Joyce R; Reyes, Angela; Coffey, Dean M; Schrager, Sheree M; Samson, Allan; Palinkas, Lawrence; Kipke, Michele D; Miranda, Jeanne

2018-05-17

Filipinos, the second largest Asian subgroup in the U.S., experience significant youth behavioral health disparities but remain under-represented in health research. We describe lessons learned from using the Matching Model of Recruitment to recruit 215 Filipinos to participate in a large, randomized controlled trial of a culturally tailored video aimed at increasing enrollment in the Incredible Years® Parent Program. We recruited participants from schools, churches, clinics, community events, and other community-based locations. Facilitators of participation included: partnership with local community groups, conducting research in familiar settings, building on existing social networks, and matching perspectives of community members and researchers. Findings suggest recruitment success occurs when there is a match between goals of Filipino parents, grandparents and the research community. Understanding the perspectives of ethnic minority communities and effectively communicating goals of research studies are critical to successful recruitment of hard-to-reach immigrant populations in randomized controlled trials.

Does a strategy to promote shared decision-making reduce medical practice variation in the choice of either single or double embryo transfer after in vitro fertilisation? A secondary analysis of a randomised controlled trial.

PubMed

Brabers, Anne E M; van Dijk, Liset; Groenewegen, Peter P; van Peperstraten, Arno M; de Jong, Judith D

2016-05-06

The hypothesis that shared decision-making (SDM) reduces medical practice variations is increasingly common, but no evidence is available. We aimed to elaborate further on this, and to perform a first exploratory analysis to examine this hypothesis. This analysis, based on a limited data set, examined how SDM is associated with variation in the choice of single embryo transfer (SET) or double embryo transfer (DET) after in vitro fertilisation (IVF). We examined variation between and within hospitals. A secondary analysis of a randomised controlled trial. 5 hospitals in the Netherlands. 222 couples (woman aged <40 years) on a waiting list for a first IVF cycle, who could choose between SET and DET (ie, ≥2 embryos available). SDM via a multifaceted strategy aimed to empower couples in deciding how many embryos should be transferred. The strategy consisted of decision aid, support of IVF nurse and the offer of reimbursement for an extra treatment cycle. Control group received standard IVF care. Difference in variation due to SDM in the choice of SET or DET, both between and within hospitals. There was large variation in the choice of SET or DET between hospitals in the control group. Lower variation between hospitals was observed in the group with SDM. Within most hospitals, variation in the choice of SET or DET appeared to increase due to SDM. Variation particularly increased in hospitals where mainly DET was chosen in the control group. Although based on a limited data set, our study gives a first insight that including patients' preferences through SDM results in less variation between hospitals, and indicates another pattern of variation within hospitals. Variation that results from patient preferences could be potentially named the informed patient rate. Our results provide the starting point for further research. NCT00315029; Post-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Systematic Review of Community-Based Childhood Obesity Prevention Studies

PubMed Central

Segal, Jodi; Wu, Yang; Wilson, Renee; Wang, Youfa

2013-01-01

OBJECTIVE: This study systematically reviewed community-based childhood obesity prevention programs in the United States and high-income countries. METHODS: We searched Medline, Embase, PsychInfo, CINAHL, clinicaltrials.gov, and the Cochrane Library for relevant English-language studies. Studies were eligible if the intervention was primarily implemented in the community setting; had at least 1 year of follow-up after baseline; and compared results from an intervention to a comparison group. Two independent reviewers conducted title scans and abstract reviews and reviewed the full articles to assess eligibility. Each article received a double review for data abstraction. The second reviewer confirmed the first reviewer’s data abstraction for completeness and accuracy. RESULTS: Nine community-based studies were included; 5 randomized controlled trials and 4 non–randomized controlled trials. One study was conducted only in the community setting, 3 were conducted in the community and school setting, and 5 were conducted in the community setting in combination with at least 1 other setting such as the home. Desirable changes in BMI or BMI z-score were found in 4 of the 9 studies. Two studies reported significant improvements in behavioral outcomes (1 in physical activity and 1 in vegetable intake). CONCLUSIONS: The strength of evidence is moderate that a combined diet and physical activity intervention conducted in the community with a school component is more effective at preventing obesity or overweight. More research and consistent methods are needed to understand the comparative effectiveness of childhood obesity prevention programs in the community setting. PMID:23753099

Improving practice in community-based settings: a randomized trial of supervision – study protocol

PubMed Central

2013-01-01

Background Evidence-based treatments for child mental health problems are not consistently available in public mental health settings. Expanding availability requires workforce training. However, research has demonstrated that training alone is not sufficient for changing provider behavior, suggesting that ongoing intervention-specific supervision or consultation is required. Supervision is notably under-investigated, particularly as provided in public mental health. The degree to which supervision in this setting includes ‘gold standard’ supervision elements from efficacy trials (e.g., session review, model fidelity, outcome monitoring, skill-building) is unknown. The current federally-funded investigation leverages the Washington State Trauma-focused Cognitive Behavioral Therapy Initiative to describe usual supervision practices and test the impact of systematic implementation of gold standard supervision strategies on treatment fidelity and clinical outcomes. Methods/Design The study has two phases. We will conduct an initial descriptive study (Phase I) of supervision practices within public mental health in Washington State followed by a randomized controlled trial of gold standard supervision strategies (Phase II), with randomization at the clinician level (i.e., supervisors provide both conditions). Study participants will be 35 supervisors and 130 clinicians in community mental health centers. We will enroll one child per clinician in Phase I (N = 130) and three children per clinician in Phase II (N = 390). We use a multi-level mixed within- and between-subjects longitudinal design. Audio recordings of supervision and therapy sessions will be collected and coded throughout both phases. Child outcome data will be collected at the beginning of treatment and at three and six months into treatment. Discussion This study will provide insight into how supervisors can optimally support clinicians delivering evidence-based treatments. Phase I will provide descriptive information, currently unavailable in the literature, about commonly used supervision strategies in community mental health. The Phase II randomized controlled trial of gold standard supervision strategies is, to our knowledge, the first experimental study of gold standard supervision strategies in community mental health and will yield needed information about how to leverage supervision to improve clinician fidelity and client outcomes. Trial registration ClinicalTrials.gov NCT01800266 PMID:23937766

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

PubMed

Shern, David L; Moran, Hazel

2009-11-01

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

The effects of asking a fertility intention question in primary care settings: a systematic review protocol.

PubMed

Henning, Paul A; Burgess, Carolyne K; Jones, Heidi E; Norman, Wendy V

2017-01-19

Planning for pregnancy has been associated with reduced unwanted pregnancies and improved pregnancy outcomes. Despite the benefits of planned pregnancy, there are no guideline recommendations on routine counseling regarding pregnancy intention in primary care settings. The objective of the systematic review is to determine the effectiveness of incorporating questions of pregnancy intention into primary care. A systematic search of the literature will be conducted for any studies comparing questions of pregnancy intention in primary care settings with no intervention or a control intervention. Types of studies will include randomized controlled trials, non-randomized trials, and observation studies. Participants will include patients of reproductive age presenting to primary health care settings. Interventions will include any assessment of fertility intention and follow-up care compared with a control group or no intervention. Outcomes will include quantitative data with rates for contraceptive uptake, and any pregnancy related outcome. Databases (Ovid MEDLINE; Pubmed; CINAHL; EMBASE; CDR/DARE databases; Web of Science; ISRCTN registry; Clinicaltrials.gov; Cochrane Library) will be searched from the year 2000 to current. Screening of identified articles and data extraction will be conducted in duplicate by two independent reviewers. Methodological quality will be assessed using the Jadad scale. Methodological quality of observational and non-randomized trials will be assessed using the Newcastle-Ottawa scale. Discrepancies will be resolved by consensus or by consulting a third author. Meta-analyses will be performed if appropriate. Determining the effect of including questions of pregnancy intention into primary care can provide evidence for the development of clinical practice guidelines and inform primary care providers if this simple and low-cost intervention should be routinely employed. This review will also identify any gaps in the current literature on this topic and provide direction for future research in this area of study. Systematic Review Registration: PROSPERO CRD42015019726.

The Efficacy of Mindfulness-Based Interventions in Primary Care: A Meta-Analytic Review.

PubMed

Demarzo, Marcelo M P; Montero-Marin, Jesús; Cuijpers, Pim; Zabaleta-del-Olmo, Edurne; Mahtani, Kamal R; Vellinga, Akke; Vicens, Caterina; López-del-Hoyo, Yolanda; García-Campayo, Javier

2015-11-01

Positive effects have been reported after mindfulness-based interventions (MBIs) in diverse clinical and nonclinical populations. Primary care is a key health care setting for addressing common chronic conditions, and an effective MBI designed for this setting could benefit countless people worldwide. Meta-analyses of MBIs have become popular, but little is known about their efficacy in primary care. Our aim was to investigate the application and efficacy of MBIs that address primary care patients. We performed a meta-analytic review of randomized controlled trials addressing the effect of MBIs in adult patients recruited from primary care settings. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane guidelines were followed. Effect sizes were calculated with the Hedges g in random effects models. The meta-analyses were based on 6 trials having a total of 553 patients. The overall effect size of MBI compared with a control condition for improving general health was moderate (g = 0.48; P = .002), with moderate heterogeneity (I(2) = 59; P <.05). We found no indication of publication bias in the overall estimates. MBIs were efficacious for improving mental health (g = 0.56; P = .007), with a high heterogeneity (I(2) = 78; P <.01), and for improving quality of life (g = 0.29; P = .002), with a low heterogeneity (I(2) = 0; P >.05). Although the number of randomized controlled trials applying MBIs in primary care is still limited, our results suggest that these interventions are promising for the mental health and quality of life of primary care patients. We discuss innovative approaches for implementing MBIs, such as complex intervention and stepped care. © 2015 Annals of Family Medicine, Inc.

Using road markings as a continuous cue for speed choice.

PubMed

Charlton, Samuel G; Starkey, Nicola J; Malhotra, Neha

2018-08-01

The potential for using road markings to indicate speed limits was investigated in a driving simulator over the course of two sessions. Two types of experimental road markings, an "Attentional" set designed to provide visually distinct cues to indicate speed limits of 60, 80 and 100 km/h, and a "Perceptual" set designed to also affect drivers' perception of speed, were compared to a standard undifferentiated set of markings. Participants (n = 20 per group) were assigned to one of four experimental groups (Attentional-Explicit, Attentional-Implicit, Perceptual-Explicit, Perceptual-Implicit) or a Control group (n = 22; standard road markings). The Explicit groups were instructed about the meaning of the road markings while those in the Implicit and Control groups did not receive any explanation. Participants drove five 10 km simulated roads containing three speed zones (60, 80 and 100 km/h) during the first session. The participants returned to the laboratory approximately 3 days later to drive five more trials including roads they had not seen before, a trial that included a secondary task, and a trial where speed signs were removed and only markings were present. The findings indicated that both types of road markings improved drivers' compliance with speed limits compared to the control group, but that explicit instruction as to the meaning of the markings was needed to realise their full benefit. Although previous research has indicated the benefit of road markings used as warnings to indicate speed reductions in advance of horizontal or vertical curves, the findings of the present experiment also suggest that systematically associating road markings with specific speed limits may be a useful way to improve speed limit compliance and increase speed homogeneity. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

MultiComponent Exercise and theRApeutic lifeStyle (CERgAS) intervention to improve physical performance and maintain independent living among urban poor older people--a cluster randomised controlled trial.

PubMed

Loh, Debbie Ann; Hairi, Noran Naqiah; Choo, Wan Yuen; Mohd Hairi, Farizah; Peramalah, Devi; Kandiben, Shathanapriya; Lee, Pek Ling; Gani, Norlissa; Madzlan, Mohamed Faris; Abd Hamid, Mohd Alif Idham; Akram, Zohaib; Chu, Ai Sean; Bulgiba, Awang; Cumming, Robert G

2015-02-11

The ability of older people to function independently is crucial as physical disability and functional limitation have profound impacts on health. Interventions that either delay the onset of frailty or attenuate its severity potentially have cascading benefits for older people, their families and society. This study aims to develop and evaluate the effectiveness of a multiComponent Exercise and theRApeutic lifeStyle (CERgAS) intervention program targeted at improving physical performance and maintaining independent living as compared to general health education among older people in an urban poor setting in Malaysia. This cluster randomised controlled trial will be a 6-week community-based intervention programme for older people aged 60 years and above from urban poor settings. A minimum of 164 eligible participants will be recruited from 8 clusters (low-cost public subsidised flats) and randomised to the intervention and control arm. This study will be underpinned by the Health Belief Model with an emphasis towards self-efficacy. The intervention will comprise multicomponent group exercise sessions, nutrition education, oral care education and on-going support and counselling. These will be complemented with a kit containing practical tips on exercise, nutrition and oral care after each session. Data will be collected over four time points; at baseline, immediately post-intervention, 3-months and 6-months follow-up. Findings from this trial will potentially provide valuable evidence to improve physical function and maintain independence among older people from low-resource settings. This will inform health policies and identify locally acceptable strategies to promote healthy aging, prevent and delay functional decline among older Malaysian adults. ISRCTN22749696.

The Efficacy of Mindfulness-Based Interventions in Primary Care: A Meta-Analytic Review

PubMed Central

Demarzo, Marcelo M.P.; Montero-Marin, Jesús; Cuijpers, Pim; Zabaleta-del-Olmo, Edurne; Mahtani, Kamal R.; Vellinga, Akke; Vicens, Caterina; López-del-Hoyo, Yolanda; García-Campayo, Javier

2015-01-01

PURPOSE Positive effects have been reported after mindfulness-based interventions (MBIs) in diverse clinical and nonclinical populations. Primary care is a key health care setting for addressing common chronic conditions, and an effective MBI designed for this setting could benefit countless people worldwide. Meta-analyses of MBIs have become popular, but little is known about their efficacy in primary care. Our aim was to investigate the application and efficacy of MBIs that address primary care patients. METHODS We performed a meta-analytic review of randomized controlled trials addressing the effect of MBIs in adult patients recruited from primary care settings. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane guidelines were followed. Effect sizes were calculated with the Hedges g in random effects models. RESULTS The meta-analyses were based on 6 trials having a total of 553 patients. The overall effect size of MBI compared with a control condition for improving general health was moderate (g = 0.48; P = .002), with moderate heterogeneity (I2 = 59; P <.05). We found no indication of publication bias in the overall estimates. MBIs were efficacious for improving mental health (g = 0.56; P = .007), with a high heterogeneity (I2 = 78; P <.01), and for improving quality of life (g = 0.29; P = .002), with a low heterogeneity (I2 = 0; P >.05). CONCLUSIONS Although the number of randomized controlled trials applying MBIs in primary care is still limited, our results suggest that these interventions are promising for the mental health and quality of life of primary care patients. We discuss innovative approaches for implementing MBIs, such as complex intervention and stepped care. PMID:26553897

Efficacy of Coming Out Proud to reduce stigma’s impact among people with mental illness: pilot randomised controlled trial

PubMed Central

Rüsch, Nicolas; Abbruzzese, Elvira; Hagedorn, Eva; Hartenhauer, Daniel; Kaufmann, Ilias; Curschellas, Jan; Ventling, Stephanie; Zuaboni, Gianfranco; Bridler, René; Olschewski, Manfred; Kawohl, Wolfram; Rössler, Wulf; Kleim, Birgit; Corrigan, Patrick W.

2014-01-01

Background Facing frequent stigma and discrimination, many people with mental illness have to choose between secrecy and disclosure in different settings. Coming Out Proud (COP), a 3-week peer-led group intervention, offers support in this domain in order to reduce stigma’s negative impact. Aims To examine COP’s efficacy to reduce negative stigma-related outcomes and to promote adaptive coping styles (Current Controlled Trials number: ISRCTN43516734). Method In a pilot randomised controlled trial, 100 participants with mental illness were assigned to COP or a treatment-as-usual control condition. Outcomes included self-stigma, empowerment, stigma stress, secrecy and perceived benefits of disclosure. Results Intention-to-treat analyses found no effect of COP on self-stigma or empowerment, but positive effects on stigma stress, disclosure-related distress, secrecy and perceived benefits of disclosure. Some effects diminished during the 3-week follow-up period. Conclusions Coming Out Proud has immediate positive effects on disclosure- and stigma stress-related variables and may thus alleviate stigma’s negative impact. PMID:24434073

Audio-visual presentation of information for informed consent for participation in clinical trials.

PubMed

Ryan, R E; Prictor, M J; McLaughlin, K J; Hill, S J

2008-01-23

Informed consent is a critical component of clinical research. Different methods of presenting information to potential participants of clinical trials may improve the informed consent process. Audio-visual interventions (presented for example on the Internet, DVD, or video cassette) are one such method. To assess the effects of providing audio-visual information alone, or in conjunction with standard forms of information provision, to potential clinical trial participants in the informed consent process, in terms of their satisfaction, understanding and recall of information about the study, level of anxiety and their decision whether or not to participate. We searched: the Cochrane Consumers and Communication Review Group Specialised Register (searched 20 June 2006); the Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library, issue 2, 2006; MEDLINE (Ovid) (1966 to June week 1 2006); EMBASE (Ovid) (1988 to 2006 week 24); and other databases. We also searched reference lists of included studies and relevant review articles, and contacted study authors and experts. There were no language restrictions. Randomised and quasi-randomised controlled trials comparing audio-visual information alone, or in conjunction with standard forms of information provision (such as written or oral information as usually employed in the particular service setting), with standard forms of information provision alone, in the informed consent process for clinical trials. Trials involved individuals or their guardians asked to participate in a real (not hypothetical) clinical study. Two authors independently assessed studies for inclusion and extracted data. Due to heterogeneity no meta-analysis was possible; we present the findings in a narrative review. We included 4 trials involving data from 511 people. Studies were set in the USA and Canada. Three were randomised controlled trials (RCTs) and the fourth a quasi-randomised trial. Their quality was mixed and results should be interpreted with caution. Considerable uncertainty remains about the effects of audio-visual interventions, compared with standard forms of information provision (such as written or oral information normally used in the particular setting), for use in the process of obtaining informed consent for clinical trials. Audio-visual interventions did not consistently increase participants' levels of knowledge/understanding (assessed in four studies), although one study showed better retention of knowledge amongst intervention recipients. An audio-visual intervention may transiently increase people's willingness to participate in trials (one study), but this was not sustained at two to four weeks post-intervention. Perceived worth of the trial did not appear to be influenced by an audio-visual intervention (one study), but another study suggested that the quality of information disclosed may be enhanced by an audio-visual intervention. Many relevant outcomes including harms were not measured. The heterogeneity in results may reflect the differences in intervention design, content and delivery, the populations studied and the diverse methods of outcome assessment in included studies. The value of audio-visual interventions for people considering participating in clinical trials remains unclear. Evidence is mixed as to whether audio-visual interventions enhance people's knowledge of the trial they are considering entering, and/or the health condition the trial is designed to address; one study showed improved retention of knowledge amongst intervention recipients. The intervention may also have small positive effects on the quality of information disclosed, and may increase willingness to participate in the short-term; however the evidence is weak. There were no data for several primary outcomes, including harms. In the absence of clear results, triallists should continue to explore innovative methods of providing information to potential trial participants. Further research should take the form of high-quality randomised controlled trials, with clear reporting of methods. Studies should conduct content assessment of audio-visual and other innovative interventions for people of differing levels of understanding and education; also for different age and cultural groups. Researchers should assess systematically the effects of different intervention components and delivery characteristics, and should involve consumers in intervention development. Studies should assess additional outcomes relevant to individuals' decisional capacity, using validated tools, including satisfaction; anxiety; and adherence to the subsequent trial protocol.

Application of local policy to prevent alcohol problems: experiences from a community trial.

PubMed

Holder, H D; Reynolds, R I

1997-06-01

Alcohol policy conventionally has been established at the national or regional, state and provincial levels. Alcohol policy at any level is not actually limited to the regulation and control of alcohol production, wholesale distribution, and retail sales. There are a number of alternatives for setting alcohol policies within a local community. Building upon existing national and state/provincial laws, policy makers at the community level can set priorities for allocating resources and enforcing laws related to drinking and driving, underage alcohol sales, alcohol serving practices of bars and restaurants and geographical density of alcohol outlets in the community. This paper concludes from the Community Trials Project that policies established at the local level can reduce alcohol problems.

Randomised controlled trial of thermostatic mixer valves in reducing bath hot tap water temperature in families with young children in social housing: A protocol

PubMed Central

Kendrick, Denise; Stewart, Jane; Coupland, Carol; Hayes, Michael; Hopkins, Nick; McCabe, Debbie; Murphy, Robert; O'Donnell, George; Phillips, Ceri; Radford, David; Ryan, Jackie; Smith, Sherie; Groom, Lindsay; Towner, Elizabeth

2008-01-01

Background Each year in the UK 2000 children attend emergency departments and 500 are admitted to hospital following a bath water scald. The long term effects can include disability, disfigurement or psychological harm and repeated skin grafts may be required as the child grows. The costs of treating a severe scald are estimated at 250,000 GBP. Children living in the most deprived wards are at greatest risk of thermal injuries; hospital admission rates are three times that for children living in the least deprived wards. Domestic hot water, which is usually stored at around 60 degrees Celsius, can result in a second-degree burn after 3 seconds and a third-degree burn after 5 seconds. Educational strategies to encourage testing of tap water temperature and reduction of hot water thermostat settings have largely proved unsuccessful. Legislation in the USA mandating pre-setting hot water heater thermostats at 49 degrees Celsius was effective in reducing scald injuries, suggesting passive measures may have a greater impact. Thermostatic mixer valves (TMVs), recently developed for the domestic market, fitted across the hot and cold water supply pipes of the bath, allow delivery of water set at a fixed temperature from the hot bath tap. These valves therefore offer the potential to reduce scald injuries. Design/Methods A pragmatic, randomised controlled trial to assess the effectiveness of TMVs in reducing bath hot tap water temperatures in the homes of families with young children in rented social housing. Two parallel arms include an intervention group and a control group where the intervention will be deferred. The intervention will consist of fitting a TMV (set at 44 degrees Celsius) by a qualified plumber and provision of educational materials. The control arm will not receive a TMV or the educational materials for the study duration but will be offered the intervention after collection of follow-up data 12 months post randomisation. The primary outcome measure will be the bath hot tap water temperature. Fifteen families per arm are required to detect a reduction in the mean bath hot tap water temperature from 60.4 degrees Celsius (SD 9.1) in the control group to 46 degrees Celsius in the intervention group, with 90% power and a 5% significance level (2 sided). Secondary outcome measures including acceptability will require a sample size of 120 participants. Discussion Whilst TMVs have the potential to reduce scald injuries, to date there have been no randomised controlled trials assessing their effectiveness, acceptability and cost effectiveness. Trial Registration ISRCTN21179067 PMID:18348736

Position control of an industrial robot using fractional order controller

NASA Astrophysics Data System (ADS)

Clitan, Iulia; Muresan, Vlad; Abrudean, Mihail; Clitan, Andrei; Miron, Radu

2017-02-01

This paper presents the design of a control structure that ensures no overshoot for the movement of an industrial robot, used for the evacuation of round steel blocks from inside a rotary hearth furnace. First, a mathematical model for the positioning system is derived from a set of experimental data, and further, the paper focuses on obtaining a PID type controller, using the relay method as tuning method in order to obtain a stable closed loop system. The controller parameters are further tuned in order to achieve the imposed set of performances for the positioning of the industrial robot through computer simulation, using trial and error method. Further, a fractional - order PID controller is obtained in order to improve the control signal variation, so as to fit within the range of unified current's variation, 4 to 20 mA.

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

PubMed

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

2018-05-01

The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open-angle glaucoma (POAG) or ocular hypertension (OHT). The LiGHT Trial is a prospective, unmasked, multicentre, pragmatic, randomised controlled trial. 718 previously untreated patients with POAG or OHT were recruited at six collaborating centres in the UK between 2012 and 2014. The trial comprises two treatment arms: initial SLT followed by conventional medical therapy as required, and medical therapy without laser therapy. Randomisation was provided online by a web-based randomisation service. Participants will be monitored for 3 years, according to routine clinical practice. The target intraocular pressure (IOP) was set at baseline according to an algorithm, based on disease severity and lifetime risk of loss of vision at recruitment, and subsequently adjusted on the basis of IOP control, optic disc and visual field. The primary outcome measure is health-related quality of life (HRQL) (EQ-5D five-level). Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index, Glaucoma Symptom Scale, Glaucoma Quality of Life, objective measures of pathway effectiveness, visual function and safety profiles and concordance. A single main analysis will be performed at the end of the trial on an intention-to-treat basis. The LiGHT Trial is a multicentre, pragmatic, randomised clinical trial that will provide valuable data on the relative HRQL, clinical effectiveness and cost-effectiveness of SLT and topical IOP-lowering medication. ISRCTN32038223, Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Why all randomised controlled trials produce biased results.

PubMed

Krauss, Alexander

2018-06-01

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

Cluster randomised controlled trial of a peer-led lifestyle intervention program: study protocol for the Kerala diabetes prevention program.

PubMed

Sathish, Thirunavukkarasu; Williams, Emily D; Pasricha, Naanki; Absetz, Pilvikki; Lorgelly, Paula; Wolfe, Rory; Mathews, Elezebeth; Aziz, Zahra; Thankappan, Kavumpurathu Raman; Zimmet, Paul; Fisher, Edwin; Tapp, Robyn; Hollingsworth, Bruce; Mahal, Ajay; Shaw, Jonathan; Jolley, Damien; Daivadanam, Meena; Oldenburg, Brian

2013-11-04

India currently has more than 60 million people with Type 2 Diabetes Mellitus (T2DM) and this is predicted to increase by nearly two-thirds by 2030. While management of those with T2DM is important, preventing or delaying the onset of the disease, especially in those individuals at 'high risk' of developing T2DM, is urgently needed, particularly in resource-constrained settings. This paper describes the protocol for a cluster randomised controlled trial of a peer-led lifestyle intervention program to prevent diabetes in Kerala, India. A total of 60 polling booths are randomised to the intervention arm or control arm in rural Kerala, India. Data collection is conducted in two steps. Step 1 (Home screening): Participants aged 30-60 years are administered a screening questionnaire. Those having no history of T2DM and other chronic illnesses with an Indian Diabetes Risk Score value of ≥60 are invited to attend a mobile clinic (Step 2). At the mobile clinic, participants complete questionnaires, undergo physical measurements, and provide blood samples for biochemical analysis. Participants identified with T2DM at Step 2 are excluded from further study participation. Participants in the control arm are provided with a health education booklet containing information on symptoms, complications, and risk factors of T2DM with the recommended levels for primary prevention. Participants in the intervention arm receive: (1) eleven peer-led small group sessions to motivate, guide and support in planning, initiation and maintenance of lifestyle changes; (2) two diabetes prevention education sessions led by experts to raise awareness on T2DM risk factors, prevention and management; (3) a participant handbook containing information primarily on peer support and its role in assisting with lifestyle modification; (4) a participant workbook to guide self-monitoring of lifestyle behaviours, goal setting and goal review; (5) the health education booklet that is given to the control arm. Follow-up assessments are conducted at 12 and 24 months. The primary outcome is incidence of T2DM. Secondary outcomes include behavioural, psychosocial, clinical, and biochemical measures. An economic evaluation is planned. Results from this trial will contribute to improved policy and practice regarding lifestyle intervention programs to prevent diabetes in India and other resource-constrained settings. Australia and New Zealand Clinical Trials Registry: ACTRN12611000262909.

Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis.

PubMed

Schuetz, Philipp; Wirz, Yannick; Sager, Ramon; Christ-Crain, Mirjam; Stolz, Daiana; Tamm, Michael; Bouadma, Lila; Luyt, Charles E; Wolff, Michel; Chastre, Jean; Tubach, Florence; Kristoffersen, Kristina B; Burkhardt, Olaf; Welte, Tobias; Schroeder, Stefan; Nobre, Vandack; Wei, Long; Bucher, Heiner C; Annane, Djillali; Reinhart, Konrad; Falsey, Ann R; Branche, Angela; Damas, Pierre; Nijsten, Maarten; de Lange, Dylan W; Deliberato, Rodrigo O; Oliveira, Carolina F; Maravić-Stojković, Vera; Verduri, Alessia; Beghé, Bianca; Cao, Bin; Shehabi, Yahya; Jensen, Jens-Ulrik S; Corti, Caspar; van Oers, Jos A H; Beishuizen, Albertus; Girbes, Armand R J; de Jong, Evelien; Briel, Matthias; Mueller, Beat

2018-01-01

In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute respiratory infections. This meta-analysis of patient data from 26 randomised controlled trials was designed to assess safety of procalcitonin-guided treatment in patients with acute respiratory infections from different clinical settings. Based on a prespecified Cochrane protocol, we did a systematic literature search on the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, and pooled individual patient data from trials in which patients with respiratory infections were randomly assigned to receive antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or control. The coprimary endpoints were 30-day mortality and setting-specific treatment failure. Secondary endpoints were antibiotic use, length of stay, and antibiotic side-effects. We identified 990 records from the literature search, of which 71 articles were assessed for eligibility after exclusion of 919 records. We collected data on 6708 patients from 26 eligible trials in 12 countries. Mortality at 30 days was significantly lower in procalcitonin-guided patients than in control patients (286 [9%] deaths in 3336 procalcitonin-guided patients vs 336 [10%] in 3372 controls; adjusted odds ratio [OR] 0·83 [95% CI 0·70 to 0·99], p=0·037). This mortality benefit was similar across subgroups by setting and type of infection (p interactions >0·05), although mortality was very low in primary care and in patients with acute bronchitis. Procalcitonin guidance was also associated with a 2·4-day reduction in antibiotic exposure (5·7 vs 8·1 days [95% CI -2·71 to -2·15], p<0·0001) and a reduction in antibiotic-related side-effects (16% vs 22%, adjusted OR 0·68 [95% CI 0·57 to 0·82], p<0·0001). Use of procalcitonin to guide antibiotic treatment in patients with acute respiratory infections reduces antibiotic exposure and side-effects, and improves survival. Widespread implementation of procalcitonin protocols in patients with acute respiratory infections thus has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance. National Institute for Health Research. Copyright © 2018 Elsevier Ltd. All rights reserved.

Artemisinin-based combination therapy for treating uncomplicated Plasmodium vivax malaria.

PubMed

Gogtay, Nithya; Kannan, Sridharan; Thatte, Urmila M; Olliaro, Piero L; Sinclair, David

2013-10-25

Plasmodium vivax is an important cause of malaria in many parts of Asia and South America, and parasite resistance to the standard treatment (chloroquine) is now high in some parts of Oceania. This review aims to assess the current treatment options in the light of increasing chloroquine resistance. To compare artemisinin-based combination therapies (ACTs) with alternative antimalarial regimens for treating acute uncomplicated P. vivax malaria. We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS; and the metaRegister of Controlled Trials (mRCT) up to 28 March 2013 using "vivax" and "arte* OR dihydroarte*" as search terms. Randomized controlled trials comparing ACTs versus standard therapy, or comparing alternative ACTs, in adults and children with uncomplicated P. vivax malaria. Two authors independently assessed trials for eligibility and risk of bias, and extracted data. We used recurrent parasitaemia prior to day 28 as a proxy for effective treatment of the blood stage parasite, and compared drug treatments using risk ratios (RR) and 95% confidence intervals (CIs). We used trials following patients for longer than 28 days to assess the duration of the post-treatment prophylactic effect of ACTs. We assessed the quality of the evidence using the GRADE approach. We included 14 trials, that enrolled 2592 participants, and were all conducted in Asia and Oceania between 2002 and 2011. ACTs versus chloroquine: ACTs clear parasites from the peripheral blood quicker than chloroquine monotherapy (parasitaemia after 24 hours of treatment: RR 0.42, 95% CI 0.36 to 0.50, four trials, 1652 participants, high quality evidence).In settings where chloroquine remains effective, ACTs are as effective as chloroquine at preventing recurrent parasitaemias before day 28 (RR 0.58, 95% CI 0.18 to 1.90, five trials, 1622 participants, high quality evidence). In four of these trials, recurrent parasitaemias before day 28 were very low following treatment with both chloroquine and ACTs. The fifth trial, from Thailand in 2011, found increased recurrent parasitaemias following treatment with chloroquine (9%), while they remained low following ACT (2%) (RR 0.25, 95% CI 0.09 to 0.66, one trial, 437 participants).ACT combinations with long half-lives probably also provide a longer prophylactic effect after treatment, with significantly fewer recurrent parasitaemias between day 28 and day 42 or day 63 (RR 0.57, 95% CI 0.40 to 0.82, three trials, 1066 participants, moderate quality evidence). One trial, from Cambodia, Thailand, India and Indonesia, gave additional primaquine to both treatment groups to reduce the risk of spontaneous relapses. Recurrent parasitaemias after day 28 were lower than seen in the trials that did not give primaquine, but the ACT still appeared to have an advantage (RR 0.27, 95% CI 0.08 to 0.94, one trial, 376 participants, low quality evidence). ACTs versus alternative ACTs: In high transmission settings, dihydroartemisinin-piperaquine is probably superior to artemether-lumefantrine, artesunate plus sulphadoxine-pyrimethamine and artesunate plus amodiaquine at preventing recurrent parasitaemias before day 28 (RR 0.20, 95% CI 0.08 to 0.49, three trials, 334 participants, moderate quality evidence).Dihydroartemisinin-piperaquine may also have an improved post-treatment prophylactic effect lasting for up to six weeks, and this effect may be present even when primaquine is also given to achieve radical cure (RR 0.21, 95% CI 0.10 to 0.46, two trials, 179 participants, low quality evidence).The data available from low transmission settings is too limited to reliably assess the relative effectiveness of ACTs. ACTs appear at least equivalent to chloroquine at effectively treating the blood stage of P. vivax infection. Even in areas where chloroquine remains effective, this finding may allow for simplified protocols for treating all forms of malaria with ACTs. In areas where chloroquine no longer cures the infection, ACTs offer an effective alternative.Dihydroartemisinin-piperaquine is the most studied ACT. It may provide a longer period of post-treatment prophylaxis than artemether-lumefantrine or artesunate plus amodiaquine. This effect may be clinically important in high transmission settings whether primaquine is also given or not.

Alternatives to inpatient mental health care for children and young people

PubMed Central

Shepperd, Sasha; Doll, Helen; Gowers, Simon; James, Anthony; Fazel, Mina; Fitzpatrick, Ray; Pollock, Jon

2014-01-01

Background Current policy in the UK and elsewhere places emphasis on the provision of mental health services in the least restrictive setting, whilst also recognising that some children will require inpatient care. As a result, there are a range of mental health services to manage young people with serious mental health problems who are at risk of being admitted to an inpatient unit in community or outpatient settings. Objectives 1. To assess the effectiveness, acceptability and cost of mental health services that provide an alternative to inpatient care for children and young people. 2. To identify the range and prevalence of different models of service that seek to avoid inpatient care for children and young people. Search methods Our search included the Cochrane Effective Practice and Organisation of Care Group Specialised Register (2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, issue 4), MEDLINE (1966 to 2007), EMBASE (1982 to 2006), the British Nursing Index (1994 to 2006), RCN database (1985 to 1996), CINAHL (1982 to 2006) and PsycInfo (1972 to 2007). Selection criteria Randomised controlled trials of mental health services providing specialist care, beyond the scope of generic outpatient provision, as an alternative to inpatient mental health care, for children or adolescents aged from five to 18 years who have a serious mental health condition requiring specialist services beyond the capacity of generic outpatient provision. The control group received mental health services in an inpatient or equivalent setting. Data collection and analysis Two authors independently extracted data and assessed study quality. We grouped studies according to the intervention type but did not pool data because of differences in the interventions and measures of outcome. Where data were available we calculated confidence intervals (CIs) for differences between groups at follow up. We also calculated standardised mean differences (SMDs) and 95% CIs for each outcome in terms of mean change from baseline to follow up using the follow-up SDs. We calculated SMDs (taking into account the direction of change and the scoring of each instrument) so that negative SMDs indicate results that favour treatment and positive SMDs favour the control group. Main results We included seven randomised controlled trials (recruiting a total of 799 participants) evaluating four distinct models of care: multi-systemic therapy (MST) at home, specialist outpatient service, intensive home treatment and intensive home-based crisis intervention (‘Homebuilders’ model for crisis intervention). Young people receiving home-based MST experienced some improved functioning in terms of externalising symptoms and they spent fewer days out of school and out-of-home placement. At short term follow up the control group had a greater improvement in terms of adaptability and cohesion; this was not sustained at four months follow up. There were small, significant patient improvements reported in both groups in the trial evaluating the intensive home-based crisis intervention using the ‘Homebuilders’ model. No differences at follow up were reported in the two trials evaluating intensive home treatment, or in the trials evaluating specialist outpatient services. Authors’ conclusions The quality of the evidence base currently provides very little guidance for the development of services. If randomised controlled trials are not feasible then consideration should be given to alternative study designs, such as prospective systems of audit conducted across several centres, as this has the potential to improve the current level of evidence. These studies should include baseline measurement at admission along with demographic data, and outcomes measured using a few standardised robust instruments. PMID:19370634

Hand washing promotion for preventing diarrhoea

PubMed Central

Ejemot-Nwadiaro, Regina I; Ehiri, John E; Arikpo, Dachi; Meremikwu, Martin M; Critchley, Julia A

2015-01-01

Background Diarrhoea accounts for 1.8 million deaths in children in low- and middle-income countries (LMICs). One of the identified strategies to prevent diarrhoea is hand washing. Objectives To assess the effects of hand washing promotion interventions on diarrhoeal episodes in children and adults. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register (27 May 2015); CENTRAL (published in the Cochrane Library 2015, Issue 5); MEDLINE (1966 to 27 May 2015); EMBASE (1974 to 27 May 2015); LILACS (1982 to 27 May 2015); PsycINFO (1967 to 27 May 2015); Science Citation Index and Social Science Citation Index (1981 to 27 May 2015); ERIC (1966 to 27 May 2015); SPECTR (2000 to 27 May 2015); Bibliomap (1990 to 27 May 2015); RoRe, The Grey Literature (2002 to 27 May 2015); World Health Organization (WHO) International Clinical Trial Registry Platform (ICTRP), metaRegister of Controlled Trials (mRCT), and reference lists of articles up to 27 May 2015. We also contacted researchers and organizations in the field. Selection criteria Individually randomized controlled trials (RCTs) and cluster-RCTs that compared the effects of hand washing interventions on diarrhoea episodes in children and adults with no intervention. Data collection and analysis Three review authors independently assessed trial eligibility, extracted data, and assessed risk of bias. We stratified the analyses for child day-care centres or schools, community, and hospital-based settings. Where appropriate, incidence rate ratios (IRR) were pooled using the generic inverse variance method and random-effects model with 95% confidence intervals (CIs). We used the GRADE approach to assess the quality of evidence. Main results We included 22 RCTs: 12 trials from child day-care centres or schools in mainly high-income countries (54,006 participants), nine community-based trials in LMICs (15,303 participants), and one hospital-based trial among people with acquired immune deficiency syndrome (AIDS) (148 participants). Hand washing promotion (education activities, sometimes with provision of soap) at child day-care facilities or schools prevents around one-third of diarrhoea episodes in high income countries (rate ratio 0.70; 95% CI 0.58 to 0.85; nine trials, 4664 participants, high quality evidence), and may prevent a similar proportion in LMICs but only two trials from urban Egypt and Kenya have evaluated this (rate ratio 0.66, 95% CI 0.43 to 0.99; two trials, 45,380 participants, low quality evidence). Only three trials reported measures of behaviour change and the methods of data collection were susceptible to bias. In one trial from the USA hand washing behaviour was reported to improve; and in the trial from Kenya that provided free soap, hand washing did not increase, but soap use did (data not pooled; three trials, 1845 participants, low quality evidence). Hand washing promotion among communities in LMICs probably prevents around one-quarter of diarrhoea episodes (rate ratio 0.72, 95% CI 0.62 to 0.83; eight trials, 14,726 participants, moderate quality evidence). However, six of these eight trials were from Asian settings, with only single trials from South America and sub-Saharan Africa. In six trials, soap was provided free alongside hand washing education, and the overall average effect size was larger than in the two trials which did not provide soap (soap provided: rate ratio 0.66, 95% CI 0.56 to 0.78; six trials, 11,422 participants; education only: rate ratio: 0.84, 95% CI 0.67 to 1.05; two trials, 3304 participants). There was increased hand washing at major prompts (before eating/cooking, after visiting the toilet or cleaning the baby's bottom), and increased compliance to hand hygiene procedure (behavioural outcome) in the intervention groups than the control in community trials (data not pooled: three trials, 3490 participants, high quality evidence). Hand washing promotion for the one trial conducted in a hospital among high-risk population showed significant reduction in mean episodes of diarrhoea (1.68 fewer) in the intervention group (Mean difference 1.68, 95% CI 1.93 to 1.43; one trial, 148 participants, moderate quality evidence). There was increase in hand washing frequency, seven times per day in the intervention group versus three times in the control in this hospital trial (one trial, 148 participants, moderate quality evidence). We found no trials evaluating or reporting the effects of hand washing promotions on diarrhoea-related deaths, all-cause-under five mortality, or costs. Authors' conclusions Hand washing promotion probably reduces diarrhoea episodes in both child day-care centres in high-income countries and among communities living in LMICs by about 30%. However, less is known about how to help people maintain hand washing habits in the longer term. PLAIN LANGUAGE SUMMARY Hand washing promotion for preventing diarrhoea Review question This Cochrane Review summarises trials evaluating the effects of promoting hand washing on the incidence of diarrhoea among children and adults in day-care centres, schools, communities, or hospitals. After searching for relevant trials up to 27 May 2015, we included 22 randomized controlled trials conducted in both high-income countries (HICs) and low- and middle-income countries (LMICs). These trials enrolled 69,309 children and 148 adults. How does hand washing prevent diarrhoea and how might hand washing be promoted Diarrhoea causes many deaths in children below five years of age, mostly in LMICs. The organisms causing diarrhoea are transmitted from person to person through food and water contaminated with faeces, or through person-to-person contact. Hand washing after defecation, or after cleaning a baby's bottom, and before preparing and eating food, can therefore reduce the risk of diarrhoea. Hand washing can be promoted through group or individual training on hygiene education, germ-health awareness, use of posters, leaflets, comic books, songs, and drama. What this review says Hand washing promotion at child day-care facilities or schools in HICs probably prevents around 30% of diarrhoea episodes (high quality evidence), and may prevent a similar proportion in schools in LMICs (low quality evidence). Among communities in LMICs hand washing promotion prevents around 28% of diarrhoea episodes (moderate quality evidence). In the only hospital-based trial included in this review, hand washing promotion also had important reduction in the mean episodes of diarrhoea (moderate quality evidence). This is based on only a single trial with few participants and thus there is need for more trials to confirm this. Effects of hand washing promotion on related hand hygiene behaviour changes improved more in the intervention groups than in the control in all the settings (low to high quality evidence). None of the included trials assessed the effect of handwashing promotion on diarrhoeal-related deaths, all-cause under-five mortality, or the cost-effectiveness of hand washing promotions. Conclusion Hand washing promotion in HICs and LMICs settings may reduce incidence of diarrhoea by about 30%. However, less is known about how to help people maintain hand washing habits in the longer term. PMID:26346329

Lessons from the field: the conduct of randomized controlled trials in Botswana.

PubMed

Bonsu, Janice M; Frasso, Rosemary; Curry, Allison E

2017-10-27

The conduct of randomized controlled trials (RCTs) in low-resource settings may present unique financial, logistic, and process-related challenges. Middle-income countries that have comparable disease burdens to low-income countries, but greater availability of resources, may be conducive settings for RCTs. Indeed, the country of Botswana is experiencing a rapid increase in the conduct of RCTs. Our objective was to explore the experiences of individuals conducting RCTs in Botswana to gain an understanding of the challenges and adaptive strategies to their work. We conducted in-depth interviews with 14 national and international individuals working on RCTs in Botswana. Participants included principal investigators, research coordinators, lab technicians, research assistants, and other healthcare professionals. Interviews were audiotaped, transcribed verbatim, and coded for thematic analysis. Five primary themes were identified: ethics board relationships (including delays in the process); research staff management (including staff attrition and career development); study recruitment and retention (including the use of reimbursements); resource availability (including challenges accessing laboratory equipment); and capacity-building (including issues of exporting locally sourced samples). These themes were explored to discuss key challenges and adaptive strategies. This study offers a first-hand account of individuals engaged in conducting RCTs in Botswana, a nation that is experiencing a rapid increase in research activities. Findings provide a foundational understanding for researchers in Botswana and trial managers in similar settings when planning RCTs so that the conduct of research does not outpace the ability to manage, support, and regulate it.

Effect of Information and Telephone-Guided Access to Community Support for People with Chronic Kidney Disease: Randomised Controlled Trial

PubMed Central

Blakeman, Tom; Blickem, Christian; Kennedy, Anne; Reeves, David; Bower, Peter; Gaffney, Hannah; Gardner, Caroline; Lee, Victoria; Jariwala, Praksha; Dawson, Shoba; Mossabir, Rahena; Brooks, Helen; Richardson, Gerry; Spackman, Eldon; Vassilev, Ivaylo; Chew-Graham, Carolyn; Rogers, Anne

2014-01-01

Background Implementation of self-management support in traditional primary care settings has proved difficult, encouraging the development of alternative models which actively link to community resources. Chronic kidney disease (CKD) is a common condition usually diagnosed in the presence of other co-morbidities. This trial aimed to determine the effectiveness of an intervention to provide information and telephone-guided access to community support versus usual care for patients with stage 3 CKD. Methods and Findings In a pragmatic, two-arm, patient level randomised controlled trial 436 patients with a diagnosis of stage 3 CKD were recruited from 24 general practices in Greater Manchester. Patients were randomised to intervention (215) or usual care (221). Primary outcome measures were health related quality of life (EQ-5D health questionnaire), blood pressure control, and positive and active engagement in life (heiQ) at 6 months. At 6 months, mean health related quality of life was significantly higher for the intervention group (adjusted mean difference = 0.05; 95% CI = 0.01, 0.08) and blood pressure was controlled for a significantly greater proportion of patients in the intervention group (adjusted odds-ratio = 1.85; 95% CI = 1.25, 2.72). Patients did not differ significantly in positive and active engagement in life. The intervention group reported a reduction in costs compared with control. Conclusions An intervention to provide tailored information and telephone-guided access to community resources was associated with modest but significant improvements in health related quality of life and better maintenance of blood pressure control for patients with stage 3 CKD compared with usual care. However, further research is required to identify the mechanisms of action of the intervention. Trial Registration Controlled-Trials.com ISRCTN45433299 PMID:25330169

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

Closed loop ventilation mode in Intensive Care Unit: a randomized controlled clinical trial comparing the numbers of manual ventilator setting changes.

PubMed

Arnal, Jean-Michel; Garnero, Aude; Novotni, Dominik; Corno, Gaëlle; Donati, Stéphane-Yannis; Demory, Didier; Quintana, Gabrielle; Ducros, Laurent; Laubscher, Thomas; Durand-Gasselin, Jacques

2018-01-01

There is an equipoise regarding closed-loop ventilation modes and the ability to reduce workload for providers. On one hand some settings are managed by the ventilator but on another hand the automatic mode introduces new settings for the user. This randomized controlled trial compared the number of manual ventilator setting changes between a full closed loop ventilation and oxygenation mode (INTELLiVENT-ASV®) and conventional ventilation modes (volume assist control and pressure support) in Intensive Care Unit (ICU) patients. The secondary endpoints were to compare the number of arterial blood gas analysis, the sedation dose and the user acceptance. Sixty subjects with an expected duration of mechanical ventilation of at least 48 hours were randomized to be ventilated using INTELLiVENT-ASV® or conventional modes with a protocolized weaning. All manual ventilator setting changes were recorded continuously from inclusion to successful extubation or death. Arterial blood gases were performed upon decision of the clinician in charge. User acceptance score was assessed for nurses and physicians once daily using a Likert Scale. The number of manual ventilator setting changes per 24 h-period per subject was lower in INTELLiVENT-ASV® as compared to conventional ventilation group (5 [4-7] versus 10 [7-17]) manuals settings per subject per day [P<0.001]). The number of arterial blood gas analysis and the sedation doses were not significantly different between the groups. Nurses and physicians reported that INTELLiVENT-ASV® was significantly easier to use as compared to conventional ventilation (P<0.001 for nurses and P<0.01 for physicians). For mechanically ventilated ICU patients, INTELLiVENT-ASV® significantly reduces the number of manual ventilator setting changes with the same number of arterial blood gas analysis and sedation dose, and is easier to use for the caregivers as compared to conventional ventilation modes.

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

PubMed Central

2013-01-01

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

Real-time, ultrasound-based control of a virtual hand by a trans-radial amputee.

PubMed

Baker, Clayton A; Akhlaghi, Nima; Rangwala, Huzefa; Kosecka, Jana; Sikdar, Siddhartha

2016-08-01

Advancements in multiarticulate upper-limb prosthetics have outpaced the development of intuitive, non-invasive control mechanisms for implementing them. Surface electromyography is currently the most popular non-invasive control method, but presents a number of drawbacks including poor deep-muscle specificity. Previous research established the viability of ultrasound imaging as an alternative means of decoding movement intent, and demonstrated the ability to distinguish between complex grasps in able-bodied subjects via imaging of the anterior forearm musculature. In order to translate this work to clinical viability, able-bodied testing is insufficient. Amputation-induced changes in muscular geometry, dynamics, and imaging characteristics are all likely to influence the effectiveness of our existing techniques. In this work, we conducted preliminary trials with a transradial amputee participant to assess these effects, and potentially elucidate necessary refinements to our approach. Two trials were performed, the first using a set of three motion types, and the second using four. After a brief training period in each trial, the participant was able to control a virtual prosthetic hand in real-time; attempted grasps were successfully classified with a rate of 77% in trial 1, and 71% in trial 2. While the results are sub-optimal compared to our previous able-bodied testing, they are a promising step forward. More importantly, the data collected during these trials can provide valuable information for refining our image processing methods, especially via comparison to previously acquired data from able-bodied individuals. Ultimately, further work with amputees is a necessity for translation towards clinical application.

Life- and person-centred help in Mecklenburg-Western Pomerania, Germany (DelpHi): study protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background The provision of appropriate medical and nursing care for people with dementia is a major challenge for the healthcare system in Germany. New models of healthcare provision need to be developed, tested and implemented on the population level. Trials in which collaborative care for dementia in the primary care setting were studied have demonstrated its effectiveness. These studies have been conducted in different healthcare systems, however, so it is unclear whether these results extend to the specific context of the German healthcare system. The objective of this population-based intervention trial in the primary care setting is to test the efficacy and efficiency of implementing a subsidiary support system on a population level for persons with dementia who live at home. Methods and study design The study was designed to assemble a general physician-based epidemiological cohort of people above the age of 70 who live at home (DelpHi cohort). These people are screened for eligibility to participate in a trial of dementia care management (DelpHi trial). The trial is a cluster-randomised, controlled intervention trial with two arms (intervention and control) designed to test the efficacy and efficiency of implementing a subsidiary support system for persons with dementia who live at home. This subsidiary support system is initiated and coordinated by a dementia care manager: a nurse with dementia-specific qualifications who delivers the intervention according to a systematic, detailed protocol. The primary outcome is quality of life and healthcare for patients with dementia and their caregivers. This is a multidimensional outcome with a focus on four dimensions: (1) quality of life, (2) caregiver burden, (3) behavioural and psychological symptoms of dementia and (4) pharmacotherapy with an antidementia drug and prevention or suspension of potentially inappropriate medication. Secondary outcomes include the assessment of dementia syndromes, activities of daily living, social support health status, utilisation of health care resources and medication. Discussion The results will provide evidence for specific needs in ambulatory care for persons with dementia and will show effective ways to meet those needs. Qualification requirements will be evaluated, and the results will help to modify existing guidelines and treatment paths. Trial registration NCT01401582 PMID:22575023

Study protocol for a phase II dose evaluation randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).

PubMed

McNally, Dayre; Amrein, Karin; O'Hearn, Katharine; Fergusson, Dean; Geier, Pavel; Henderson, Matt; Khamessan, Ali; Lawson, Margaret L; McIntyre, Lauralyn; Redpath, Stephanie; Weiler, Hope A; Menon, Kusum

2017-01-01

Clinical research has recently demonstrated that vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (PICU) and associated with worse clinical course. Multiple adult ICU trials have suggested that optimization of vitamin D status through high-dose supplementation may reduce mortality and improve other clinically relevant outcomes; however, there have been no trials of rapid normalization in the PICU setting. The objective of this study is to evaluate the safety and efficacy of an enteral weight-based cholecalciferol loading dose regimen in critically ill children with VDD. The VITdAL-PICU pilot study is designed as a multicenter placebo-controlled phase II dose evaluation pilot randomized controlled trial. We aim to randomize 67 VDD critically ill children using a 2:1 randomization schema to receive loading dose enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or a placebo solution. Participants, caregivers and outcome assessors will be blinded to allocation. Eligibility criteria include ICU patient, aged 37 weeks to 18 years, expected ICU length of stay more than 48 h, anticipated access to bloodwork at 7 days, and VDD (blood total 25 hydroxyvitamin D < 50 nmol/L). The primary objective is to determine whether the dosing protocol normalizes vitamin D status, defined as a blood total 25(OH)D concentration above 75 nmol/L. Secondary objectives include an examination of the safety of the dosing regimen (e.g. hypercalcemia, hypercalciuria, nephrocalcinosis), measures of vitamin D axis function (e.g. calcitriol levels, immune function), and protocol feasibility (eligibility criteria, protocol deviations, blinding). Despite significant observational literature suggesting VDD to be a modifiable risk factor in the PICU setting, there is no robust clinical trial evidence evaluating the benefits of rapid normalization. This phase II clinical trial will evaluate an innovative weight-based dosing regimen intended to rapidly and safely normalize vitamin D levels in critically ill children. Study findings will be used to inform the design of a multicenter phase III trial evaluating the clinical and economic benefits to rapid normalization. Recruitment for this trial was initiated in January 2016 and is expected to continue until November 30, 2017. Clinicaltrials.gov NCT02452762.

Tsetse Control and Gambian Sleeping Sickness; Implications for Control Strategy.

PubMed

Tirados, Inaki; Esterhuizen, Johan; Kovacic, Vanja; Mangwiro, T N Clement; Vale, Glyn A; Hastings, Ian; Solano, Philippe; Lehane, Michael J; Torr, Steve J

2015-01-01

Gambian sleeping sickness (human African trypanosomiasis, HAT) outbreaks are brought under control by case detection and treatment although it is recognised that this typically only reaches about 75% of the population. Vector control is capable of completely interrupting HAT transmission but is not used because it is considered too expensive and difficult to organise in resource-poor settings. We conducted a full scale field trial of a refined vector control technology to determine its utility in control of Gambian HAT. The major vector of Gambian HAT is the tsetse fly Glossina fuscipes which lives in the humid zone immediately adjacent to water bodies. From a series of preliminary trials we determined the number of tiny targets required to reduce G. fuscipes populations by more than 90%. Using these data for model calibration we predicted we needed a target density of 20 per linear km of river in riverine savannah to achieve >90% tsetse control. We then carried out a full scale, 500 km2 field trial covering two HAT foci in Northern Uganda to determine the efficacy of tiny targets (overall target density 5.7/km2). In 12 months, tsetse populations declined by more than 90%. As a guide we used a published HAT transmission model and calculated that a 72% reduction in tsetse population is required to stop transmission in those settings. The Ugandan census suggests population density in the HAT foci is approximately 500 per km2. The estimated cost for a single round of active case detection (excluding treatment), covering 80% of the population, is US$433,333 (WHO figures). One year of vector control organised within the country, which can completely stop HAT transmission, would cost US$42,700. The case for adding this method of vector control to case detection and treatment is strong. We outline how such a component could be organised.

Tsetse Control and Gambian Sleeping Sickness; Implications for Control Strategy

PubMed Central

Kovacic, Vanja; Mangwiro, T. N. Clement; Vale, Glyn A.; Hastings, Ian; Solano, Philippe; Lehane, Michael J.; Torr, Steve J.

2015-01-01

Background Gambian sleeping sickness (human African trypanosomiasis, HAT) outbreaks are brought under control by case detection and treatment although it is recognised that this typically only reaches about 75% of the population. Vector control is capable of completely interrupting HAT transmission but is not used because it is considered too expensive and difficult to organise in resource-poor settings. We conducted a full scale field trial of a refined vector control technology to determine its utility in control of Gambian HAT. Methods and Findings The major vector of Gambian HAT is the tsetse fly Glossina fuscipes which lives in the humid zone immediately adjacent to water bodies. From a series of preliminary trials we determined the number of tiny targets required to reduce G. fuscipes populations by more than 90%. Using these data for model calibration we predicted we needed a target density of 20 per linear km of river in riverine savannah to achieve >90% tsetse control. We then carried out a full scale, 500 km2 field trial covering two HAT foci in Northern Uganda to determine the efficacy of tiny targets (overall target density 5.7/km2). In 12 months, tsetse populations declined by more than 90%. As a guide we used a published HAT transmission model and calculated that a 72% reduction in tsetse population is required to stop transmission in those settings. Interpretation The Ugandan census suggests population density in the HAT foci is approximately 500 per km2. The estimated cost for a single round of active case detection (excluding treatment), covering 80% of the population, is US$433,333 (WHO figures). One year of vector control organised within the country, which can completely stop HAT transmission, would cost US$42,700. The case for adding this method of vector control to case detection and treatment is strong. We outline how such a component could be organised. PMID:26267814

Trial type mixing substantially reduces the response set effect in the Stroop task.

PubMed

Hasshim, Nabil; Parris, Benjamin A

2017-03-20

The response set effect refers to the finding that an irrelevant incongruent colour-word produces greater interference when it is one of the response options (referred to as a response set trial), compared to when it is not (a non-response set trial). Despite being a key effect for models of selective attention, the magnitude of the effect varies considerably across studies. We report two within-subjects experiments that tested the hypothesis that presentation format modulates the magnitude of the response set effect. Trial types (e.g. response set, non-response set, neutral) were either presented in separate blocks (pure) or in blocks containing trials from all conditions presented randomly (mixed). In the first experiment we show that the response set effect is substantially reduced in the mixed block context as a result of a decrease in RTs to response set trials. By demonstrating the modulation of the response set effect under conditions of trial type mixing we present evidence that is difficult for models of the effect based on strategic, top-down biasing of attention to explain. In a second experiment we tested a stimulus-driven account of the response set effect by manipulating the number of colour-words that make up the non-response set of distractors. The results show that the greater the number of non-response set colour concepts, the smaller the response set effect. Alternative accounts of the data and its implications for research debating the automaticity of reading are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Health Education: Effects on Classroom Climate and Physical Activity

ERIC Educational Resources Information Center

Efstathiou, Nicholas T.; Risvas, Grigorios S.; Theodoraki, Eleni-Maria M.; Galanaki, Evangelia P.; Zampelas, Antonios D.

2016-01-01

Objective: The objective of this study was to investigate the relationship between classroom psychological climate and the physical and sedentary behaviour of primary school students after the implementation of an innovative education programme regarding nutrition and physical activity. Design: Randomised controlled trial. Setting: Study…

Efficacy of Eight Months of Nightly Zolpidem: A Prospective Placebo-Controlled Study

PubMed Central

Randall, Surilla; Roehrs, Timothy A.; Roth, Thomas

2012-01-01

Study Objectives: To evaluate the long-term (8 months) efficacy of zolpidem in adults with chronic primary insomnia using polysomnography. Design: Randomized, double-blind, placebo-controlled clinical trial. Setting: Sleep disorders and research center. Participants: Healthy participants (n = 91), ages 23-70, meeting DSM-IV-TR criteria for primary insomnia. Interventions: Nightly zolpidem, 10 mg (5 mg for patients > 60 yrs) or placebo 30 minutes before bedtime for 8 months. Measurements and Results: Polysomnographic sleep parameters and morning subject assessments of sleep on 2 nights in months 1 and 8. Relative to placebo, zolpidem significantly increased overall total sleep time and sleep efficiency, reduced sleep latency and wake after sleep onset when assessed at months 1 and 8. Overall, subjective evaluations of efficacy were not shown among treatment groups. Conclusions: In adults with primary insomnia, nightly zolpidem administration remained efficacious across 8 months of nightly use. Clinical Trial Information: ClinicalTrials.gov Identifier: NCT01006525; Trial Name: Safety and Efficacy of Chronic Hypnotic Use; http://clinicaltrials.gov/ct2/show/NCT01006525. Citation: Randall S; Roehrs TA; Roth T. Efficacy of eight months of nightly zolpidem: a prospective placebo-controlled study. SLEEP 2012;35(11):1551-1557. PMID:23115404

Health insurance status and control of diabetes and coronary artery disease risk factors on enrollment into the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.

PubMed

Grogan, Mary; Jenkins, Margaret; Sansing, Veronica V; MacGregor, Joan; Brooks, Maria Mori; Julien-Williams, Patricia; Amendola, Angela; Abbott, J Dawn

2010-01-01

The purpose of this study was to examine measures of chronic disease severity and treatment according to insurance status in a clinical trial setting. Baseline insurance status of 776 patients with type 2 diabetes and stable coronary artery disease (CAD) enrolled in the United States in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial was analyzed with regard to measures of metabolic and cardiovascular risk factor control. Compared with patients with private or public insurance, the uninsured were younger, more often female, and less often white non-Hispanic. Uninsured patients had the greatest burden of CAD. Patients with public insurance were treated with the greatest number of medications, had the greatest self-reported functional status, and the lowest mean glycosylated hemoglobin and low-density lipoprotein (LDL) cholesterol values. Overall, for 5 measured risk factor targets, the mean number above goal was 2.49 ± 1.18. After adjustment for demographic and clinical variables, insurance status was not associated with a difference in risk factor control. In the BARI 2D trial, we did not observe a difference in baseline cardiovascular risk factor control according to insurance status. An important observation, however, was that risk factor control overall was suboptimal, which highlights the difficulty in treating type 2 diabetes and CAD irrespective of insurance status.

Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective, Randomized, Controlled Trials

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

Logan, Jennifer K.; Tang, Chad; Liao, Zhongxing

Purpose: Challenges can arise when attempting to maximize patient enrollment in clinical trials. There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to clinical trial enrollment, particularly the influence of timing, in context of three prospective, randomized oncology trials where one arm was considered more aggressive than the other. Methods and Materials: From June 2011 to March 2015, patients who were enrolled on 3 prospective institutional protocols (an oligometastatic non-small cell lung cancer [NSCLC] trial and 2 proton vs intensity modulated radiation therapy trials inmore » NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher's exact test, Student's t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. Results: A total of 309 eligible patients were approached about trial enrollment. The enrollment success rate during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligometastatic protocol: 5 vs 3 appointments [P<.001]; NSCLC protocol: 4 vs 3 appointments [P=.0018]; esophageal protocol: 3 vs 2 appointments [P=.0086]). No other factors or patient characteristics significantly affected enrollment success rate. Conclusion: Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success and may help overcome accrual barriers without compromising trial design.« less

Family-led rehabilitation after stroke in India (ATTEND): a randomised controlled trial.

PubMed

2017-08-05

Most people with stroke in India have no access to organised rehabilitation services. The effectiveness of training family members to provide stroke rehabilitation is uncertain. Our primary objective was to determine whether family-led stroke rehabilitation, initiated in hospital and continued at home, would be superior to usual care in a low-resource setting. The Family-led Rehabilitation after Stroke in India (ATTEND) trial was a prospectively randomised open trial with blinded endpoint done across 14 hospitals in India. Patients aged 18 years or older who had had a stroke within the past month, had residual disability and reasonable expectation of survival, and who had an informal family-nominated caregiver were randomly assigned to intervention or usual care by site coordinators using a secure web-based system with minimisation by site and stroke severity. The family members of participants in the intervention group received additional structured rehabilitation training-including information provision, joint goal setting, carer training, and task-specific training-that was started in hospital and continued at home for up to 2 months. The primary outcome was death or dependency at 6 months, defined by scores 3-6 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) as assessed by masked observers. Analyses were by intention to treat. This trial is registered with Clinical Trials Registry-India (CTRI/2013/04/003557), Australian New Zealand Clinical Trials Registry (ACTRN12613000078752), and Universal Trial Number (U1111-1138-6707). Between Jan 13, 2014, and Feb 12, 2016, 1250 patients were randomly assigned to intervention (n=623) or control (n=627) groups. 33 patients were lost to follow-up (14 intervention, 19 control) and five patients withdrew (two intervention, three control). At 6 months, 285 (47%) of 607 patients in the intervention group and 287 (47%) of 605 controls were dead or dependent (odds ratio 0·98, 95% CI 0·78-1·23, p=0·87). 72 (12%) patients in the intervention group and 86 (14%) in the control group died (p=0·27), and we observed no difference in rehospitalisation (89 [14%]patients in the intervention group vs 82 [13%] in the control group; p=0·56). We also found no difference in total non-fatal events (112 events in 82 [13%] intervention patients vs 110 events in 79 [13%] control patients; p=0·80). Although task shifting is an attractive solution for health-care sustainability, our results do not support investment in new stroke rehabilitation services that shift tasks to family caregivers, unless new evidence emerges. A future avenue of research should be to investigate the effects of task shifting to health-care assistants or team-based community care. The National Health and Medical Research Council of Australia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rationale, study design and analysis plan of the lung imaging morphology for ventilator settings in acute respiratory distress syndrome study (LIVE study): Study protocol for a randomised controlled trial.

PubMed

Jabaudon, Matthieu; Godet, Thomas; Futier, Emmanuel; Bazin, Jean-Étienne; Sapin, Vincent; Roszyk, Laurence; Pereira, Bruno; Constantin, Jean-Michel

2017-10-01

Different acute respiratory distress syndrome (ARDS) phenotypes may explain controversial results in clinical trials. Lung-morphology is one of the ARDS-phenotypes and physiological studies suggest different responses in terms of positive-end-expiratory-pressure (PEEP) and recruitment-manoeuvres (RM) according to loss of aeration. To evaluate whether tailored ventilator regimens may impact ARDS outcomes, our group has designed a randomised-clinical-trial of ventilator settings according to lung morphology in moderate-to-severe ARDS (LIVE study). Patients will be enrolled within the first 12hours of ARDS onset. In both groups, volume-controlled ventilation with low tidal-volumes (Vt) will be used to target a plateau pressure≤30 cmH 2 O. In the control group, the PEEP level and inspired fraction of oxygen (FiO 2 ) will be set using the ARDSNet table; a Vt of 6 mL/kg of predicted body weight (PBW) will be set and prone position (PP) will be applied. In the intervention arm, the ventilator will be set according to lung morphology (focal/non-focal) that will be assessed according to CT-scan±chest x-ray+lung echography. For focal ARDS patients, a Vt of 8 mL/kg PBW will be used along with low PEEP and PP. For non-focal ARDS patients, a Vt of 6 mL/kg PBW will be used with RM and PEEP to reach a plateau pressure≤30 cmH 2 O. The primary outcome is all-cause 90-day mortality and the secondary outcomes are: in-hospital mortality, mortality at day 28, 60, 180 and 365; ventilator-free days at day 30, quality of life at one year; ventilator-associated pneumonia rate; barotrauma; ICU and hospital length of stay. This RCT is registered on Clinicaltrials.gov under identifier NCT02149589. Copyright © 2017 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

New approaches to trials in glomerulonephritis.

PubMed

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

2017-01-01

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

Congruency sequence effect in cross-task context: evidence for dimension-specific modulation.

PubMed

Lee, Jaeyong; Cho, Yang Seok

2013-11-01

The congruency sequence effect refers to a reduced congruency effect after incongruent trials relative to congruent trials. This modulation is thought to be, at least in part, due to the control mechanisms resolving conflict. The present study examined the nature of the control mechanisms by having participants perform two different tasks in an alternating way. When participants performed horizontal and vertical Simon tasks in Experiment 1A, and horizontal and vertical spatial Stroop task in Experiment 1B, no congruency sequence effect was obtained between the task congruencies. When the Simon task and spatial Stroop task were performed with different response sets in Experiment 2, no congruency sequence effect was obtained. However, in Experiment 3, in which the participants performed the horizontal Simon and spatial Stroop tasks with an identical response set, a significant congruency sequence effect was obtained between the task congruencies. In Experiment 4, no congruency sequence effect was obtained when participants performed two tasks having different task-irrelevant dimensions with the identical response set. The findings suggest inhibitory processing between the task-irrelevant dimension and response mode after conflict. © 2013 Elsevier B.V. All rights reserved.

Assessing Health Promotion Interventions: Limitations of Traditional Research Methods in Community-Based Studies.

PubMed

Dressel, Anne; Schneider, Robert; DeNomie, Melissa; Kusch, Jennifer; Welch, Whitney; Sosa, Mirtha; Yeldell, Sally; Maida, Tatiana; Wineberg, Jessica; Holt, Keith; Bernstein, Rebecca

2017-09-01

Most low-income Americans fail to meet physical activity recommendations. Inactivity and poor diet contribute to obesity, a risk factor for multiple chronic diseases. Health promotion activities have the potential to improve health outcomes for low-income populations. Measuring the effectiveness of these activities, however, can be challenging in community settings. A "Biking for Health" study tested the impact of a bicycling intervention on overweight or obese low-income Latino and African American adults to reduce barriers to cycling and increase physical activity and fitness. A randomized controlled trial was conducted in Milwaukee, Wisconsin, in summer 2015. A 12-week bicycling intervention was implemented at two sites with low-income, overweight, or obese Latino and African American adults. We found that randomized controlled trial methodology was suboptimal for use in this small pilot study and that it negatively affected participation. More discussion is needed about the effectiveness of using traditional research methods in community settings to assess the effectiveness of health promotion interventions. Modifications or alternative methods may yield better results. The aim of this article is to discuss the effectiveness and feasibility of using traditional research methods to assess health promotion interventions in community-based settings.

A Web-Based Adolescent Positive Psychology Program in Schools: Randomized Controlled Trial.

PubMed

Burckhardt, Rowan; Manicavasagar, Vijaya; Batterham, Philip J; Miller, Leonie M; Talbot, Elizabeth; Lum, Alistair

2015-07-28

Adolescent mental health is characterized by relatively high rates of psychiatric disorders and low levels of help-seeking behaviors. Existing mental health programs aimed at addressing these issues in adolescents have repeated inconsistent results. Such programs have generally been based on techniques derived from cognitive behavioral therapy, which may not be ideally suited to early intervention among adolescent samples. Positive psychology, which seeks to improve well-being rather than alleviate psychological symptoms, offers an alternative approach. A previous community study of adolescents found that informal engagement in an online positive psychology program for up to 6 weeks yielded significant improvements in both well-being and depression symptoms. However, this approach had not been trialed among adolescents in a structured format and within a school setting. This study examines the feasibility of an online school-based positive psychology program delivered in a structured format over a 6-week period utilizing a workbook to guide students through website content and interactive exercises. Students from four high schools were randomly allocated by classroom to either the positive psychology condition, "Bite Back", or the control condition. The Bite Back condition consisted of positive psychology exercises and information, while the control condition used a series of non-psychology entertainment websites. Both interventions were delivered online for 6 hours over a period of 4-6 weeks during class time. Symptom measures and measures of well-being/flourishing and life satisfaction were administered at baseline and post intervention. Data were analyzed using multilevel linear modeling. Both conditions demonstrated reductions in depression, stress, and total symptom scores without any significant differences between the two conditions. Both the Bite Back and control conditions also demonstrated significant improvements in life satisfaction scores post intervention. However, only the control condition demonstrated significant increases in flourishing scores post intervention. Results suggest that a structured online positive psychology program administered within the school curriculum was not effective when compared to the control condition. The limitations of online program delivery in school settings including logistic considerations are also relevant to the contradictory findings of this study. Australian New Zealand Clinical Trials Registry: ACTRN1261200057831; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362489 (Archived by Webcite at http://www.webcitation.org/6NXmjwfAy).

Vector and reservoir control for preventing leishmaniasis

PubMed Central

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

2015-01-01

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

The effectiveness and cost-effectiveness of the peer-delivered Thinking Healthy Programme for perinatal depression in Pakistan and India: the SHARE study protocol for randomised controlled trials.

PubMed

Sikander, Siham; Lazarus, Anisha; Bangash, Omer; Fuhr, Daniela C; Weobong, Benedict; Krishna, Revathi N; Ahmad, Ikhlaq; Weiss, Helen A; Price, LeShawndra; Rahman, Atif; Patel, Vikram

2015-11-25

Rates of perinatal depression (antenatal and postnatal depression) in South Asia are among the highest in the world. The delivery of effective psychological treatments for perinatal depression through existing health systems is a challenge due to a lack of human resources. This paper reports on a trial protocol that aims to evaluate the effectiveness and cost-effectiveness of the Thinking Healthy Programme delivered by peers (Thinking Healthy Programme Peer-delivered; THPP), for women with moderate to severe perinatal depression in rural and urban settings in Pakistan and India. THPP is evaluated with two randomised controlled trials: a cluster trial in Rawalpindi, Pakistan, and an individually randomised trial in Goa, India. Trial participants are pregnant women who are registered with the lady health workers in the study area in Pakistan and pregnant women attending outpatient antenatal clinics in India. They will be screened using the patient health questionnaire-9 (PHQ-9) for depression symptoms and will be eligible if their PHQ-9 is equal to or greater than 10 (PHQ-9 ≥ 10). The sample size will be 560 and 280 women in Pakistan and India, respectively. Women in the intervention arm (THPP) will be offered ten individual and four group sessions (Pakistan) or 6-14 individual sessions (India) delivered by a peer (defined as a mother from the same community who is trained and supervised in delivering the intervention). Women in the control arm (enhanced usual care) will receive health care as usual, enhanced by providing the gynaecologist or primary-health facilities with adapted WHO mhGAP guidelines for depression treatment, and providing the woman with her diagnosis and information on how to seek help for herself. The primary outcomes are remission and severity of depression symptoms at the 6-month postnatal follow-up. Secondary outcomes include remission and severity of depression symptoms at the 3-month postnatal follow-up, functional disability, perceived social support, breastfeeding rates, infant height and weight, and costs of health care at the 3- and 6-month postnatal follow-ups. The primary analysis will be intention-to-treat. The trials have the potential to strengthen the evidence on the effectiveness and cost-effectiveness of an evidence-based psychological treatment recommended by the World Health Organisation and delivered by peers for perinatal depression. The trials have the unique opportunity to overcome the shortage of human resources in global mental health and may advance our understanding about the use of peers who work in partnership with the existing health systems in low-resource settings. Pakistan Trial: ClinicalTrials.gov Identifier: NCT02111915 (9 April 2014) India Trial: ClinicalTrials.gov Identifier: NCT02104232 (1 April 2014).

Primary Prevention of Parent-Child Conflict and Abuse in Iranian Mothers: A Randomized-Controlled Trial

ERIC Educational Resources Information Center

Oveisi, Sonia; Ardabili, Hassan Eftekhare; Dadds, Mark R.; Majdzadeh, Reza; Mohammadkhani, Parvaneh; Rad, Javad Alaqband; Shahrivar, Zahra

2010-01-01

Objective: The aim of this study was to assess whether primary health care settings can be used to engage and provide a preventive intervention to mothers of young children. Methods: Two hundred and twenty-four mothers who had come to the health centers were randomly assigned to either control group (CG: n=116) or intervention group (IG: n = 108).…

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

PubMed

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

2015-09-11

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

The effectiveness of peer health coaching in improving glycemic control among low-income patients with diabetes: protocol for a randomized controlled trial.

PubMed

Ghorob, Amireh; Vivas, Maria Mercedes; De Vore, Diana; Ngo, Victoria; Bodenheimer, Thomas; Chen, Ellen; Thom, David H

2011-04-01

Although self-management support improves diabetes outcomes, it is not consistently provided in health care settings strained for time and resources. One proposed solution to personnel and funding shortages is to utilize peer coaches, patients trained to provide diabetes education and support to other patients. Coaches share similar experiences about living with diabetes and are able to reach patients within and beyond the health care setting. Given the limited body of evidence that demonstrates peer coaching significantly improves chronic disease care, this present study examines the impact of peer coaching delivered in a primary care setting on diabetes outcomes. The aim of this multicenter, randomized control trial is to evaluate the effectiveness of utilizing peer coaches to improve clinical outcomes and self-management skills in low-income patients with poorly controlled diabetes. A total of 400 patients from six primary health centers based in San Francisco that serve primarily low-income populations will be randomized to receive peer coaching (n = 200) or usual care (n = 200) over 6 months. Patients in the peer coach group receive coaching from patients with diabetes who are trained and mentored as peer coaches. The primary outcome is change in HbA1c. Secondary outcomes include change in: systolic blood pressure, body mass index (BMI), LDL cholesterol, diabetes self-care activities, medication adherence, diabetes-related quality of life, diabetes self-efficacy, and depression. Clinical values (HbA1c, LDL cholesterol and blood pressure) and self-reported diabetes self-efficacy and self-care activities are measured at baseline and after 6 months for patients and coaches. Peer coaches are also assessed at 12 months. Patients with diabetes, who are trained as peer health coaches, are uniquely poised to provide diabetes self management support and education to patients. This study is designed to investigate the impact of peer health coaching in patients with poorly controlled diabetes. Additionally, we will assess disease outcomes in patients with well controlled diabetes who are trained and work as peer health coaches. ClinicalTrials.gov identifier: NCT01040806.

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

PubMed

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

2014-06-01

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

The Perils of Ignoring Design Effects in Experimental Studies: Lessons from a Mammography Screening Trial

PubMed Central

Glenn, Beth A.; Bastani, Roshan; Maxwell, Annette E.

2013-01-01

Objective Threats to external validity including pretest sensitization and the interaction of selection and an intervention are frequently overlooked by researchers despite their potential to significantly influence study outcomes. The purpose of this investigation was to conduct secondary data analyses to assess the presence of external validity threats in the setting of a randomized trial designed to promote mammography use in a high risk sample of women. Design During the trial, recruitment and intervention implementation took place in three cohorts (with different ethnic composition), utilizing two different designs (pretest-posttest control group design; posttest only control group design). Results Results reveal that the intervention produced different outcomes across cohorts, dependent upon the research design used and the characteristics of the sample. Conclusion These results illustrate the importance of weighing the pros and cons of potential research designs before making a selection and attending more closely to issues of external validity. PMID:23289517

The perils of ignoring design effects in experimental studies: lessons from a mammography screening trial.

PubMed

Glenn, Beth A; Bastani, Roshan; Maxwell, Annette E

2013-01-01

Threats to external validity, including pretest sensitisation and the interaction of selection and an intervention, are frequently overlooked by researchers despite their potential to significantly influence study outcomes. The purpose of this investigation was to conduct secondary data analyses to assess the presence of external validity threats in the setting of a randomised trial designed to promote mammography use in a high-risk sample of women. During the trial, recruitment and intervention, implementation took place in three cohorts (with different ethnic composition), utilising two different designs (pretest-posttest control group design and posttest only control group design). Results reveal that the intervention produced different outcomes across cohorts, dependent upon the research design used and the characteristics of the sample. These results illustrate the importance of weighing the pros and cons of potential research designs before making a selection and attending more closely to issues of external validity.

Core outcome sets and trial registries.

PubMed

Clarke, Mike; Williamson, Paula

2015-05-14

Some reasons for registering trials might be considered as self-serving, such as satisfying the requirements of a journal in which the researchers wish to publish their eventual findings or publicising the trial to boost recruitment. Registry entries also help others, including systematic reviewers, to know about ongoing or unpublished studies and contribute to reducing research waste by making it clear what studies are ongoing. Other sources of research waste include inconsistency in outcome measurement across trials in the same area, missing data on important outcomes from some trials, and selective reporting of outcomes. One way to reduce this waste is through the use of core outcome sets: standardised sets of outcomes for research in specific areas of health and social care. These do not restrict the outcomes that will be measured, but provide the minimum to include if a trial is to be of the most use to potential users. We propose that trial registries, such as ISRCTN, encourage researchers to note their use of a core outcome set in their entry. This will help people searching for trials and those worried about selective reporting in closed trials. Trial registries can facilitate these efforts to make new trials as useful as possible and reduce waste. The outcomes section in the entry could prompt the researcher to consider using a core outcome set and facilitate the specification of that core outcome set and its component outcomes through linking to the original core outcome set. In doing this, registries will contribute to the global effort to ensure that trials answer important uncertainties, can be brought together in systematic reviews, and better serve their ultimate aim of improving health and well-being through improving health and social care.

Food incentives to improve completion of tuberculosis treatment: randomised controlled trial in Dili, Timor-Leste

PubMed Central

Martins, Nelson; Morris, Peter

2009-01-01

Objective To determine the effectiveness of the provision of whole food to enhance completion of treatment for tuberculosis. Design Parallel group randomised controlled trial. Setting Three primary care clinics in Dili, Timor-Leste. Participants 270 adults aged ≥18 with previously untreated newly diagnosed pulmonary tuberculosis. Main outcome measures Completion of treatment (including cure). Secondary outcomes included adherence to treatment, weight gain, and clearance of sputum smears. Outcomes were assessed remotely, blinded to allocation status. Interventions Participants started standard tuberculosis treatment and were randomly assigned to intervention (nutritious, culturally appropriate daily meal (weeks 1-8) and food package (weeks 9-32) (n=137) or control (nutritional advice, n=133) groups. Randomisation sequence was computer generated with allocation concealment by sequentially numbered, opaque, sealed envelopes. Results Most patients with tuberculosis were poor, malnourished men living close to the clinics; 265/270 (98%) contributed to the analysis. The intervention had no significant beneficial or harmful impact on the outcome of treatment (76% v 78% completion, P=0.7) or adherence (93% for both groups, P=0.7) but did lead to improved weight gain at the end of treatment (10.1% v 7.5% improvement, P=0.04). Itch was more common in the intervention group (21% v 9%, P<0.01). In a subgroup analysis of patients with positive results on sputum smears, there were clinically important improvements in one month sputum clearance (85% v 67%, P=0.13) and completion of treatment (78% v 68%, P=0.3). Conclusion Provision of food did not improve outcomes with tuberculosis treatment in these patients in Timor-Leste. Further studies in different settings and measuring different outcomes are required. Trial registration Clinical Trials NCT0019256. PMID:19858174

Implementing a Complex Intervention to Support Personal Recovery: A Qualitative Study Nested within a Cluster Randomised Controlled Trial

PubMed Central

Leamy, Mary; Clarke, Eleanor; Le Boutillier, Clair; Bird, Victoria; Janosik, Monika; Sabas, Kai; Riley, Genevieve; Williams, Julie; Slade, Mike

2014-01-01

Objective To investigate staff and trainer perspectives on the barriers and facilitators to implementing a complex intervention to help staff support the recovery of service users with a primary diagnosis of psychosis in community mental health teams. Design Process evaluation nested within a cluster randomised controlled trial (RCT). Participants 28 interviews with mental health care staff, 3 interviews with trainers, 4 focus groups with intervention teams and 28 written trainer reports. Setting 14 community-based mental health teams in two UK sites (one urban, one semi-rural) who received the intervention. Results The factors influencing the implementation of the intervention can be organised under two over-arching themes: Organisational readiness for change and Training effectiveness. Organisational readiness for change comprised three sub-themes: NHS Trust readiness; Team readiness; and Practitioner readiness. Training effectiveness comprised three sub-themes: Engagement strategies; Delivery style and Modelling recovery principles. Conclusions Three findings can inform future implementation and evaluation of complex interventions. First, the underlying intervention model predicted that three areas would be important for changing practice: staff skill development; intention to implement; and actual implementation behaviour. This study highlighted the importance of targeting the transition from practitioners' intent to implement to actual implementation behaviour, using experiential learning and target setting. Second, practitioners make inferences about organisational commitment by observing the allocation of resources, Knowledge Performance Indicators and service evaluation outcome measures. These need to be aligned with recovery values, principles and practice. Finally, we recommend the use of organisational readiness tools as an inclusion criteria for selecting both organisations and teams in cluster RCTs. We believe this would maximise the likelihood of adequate implementation and hence reduce waste in research expenditure. Trial Registration Controlled-Trials.com ISRCTN02507940 PMID:24875748

A sudden death risk score specifically for hypertension: based on 25 648 individual patient data from six randomized controlled trials.

PubMed

Le, Hai-Ha; Subtil, Fabien; Cerou, Marc; Marchant, Ivanny; Al-Gobari, Muaamar; Fall, Mor; Mimouni, Yanis; Kassaï, Behrouz; Lindholm, Lars; Thijs, Lutgarde; Gueyffier, François

2017-11-01

To construct a sudden death risk score specifically for hypertension (HYSUD) patients with or without cardiovascular history. Data were collected from six randomized controlled trials of antihypertensive treatments with 8044 women and 17 604 men differing in age ranges and blood pressure eligibility criteria. In total, 345 sudden deaths (1.35%) occurred during a mean follow-up of 5.16 years. Risk factors of sudden death were examined using a multivariable Cox proportional hazards model adjusted on trials. The model was transformed to an integer system, with points added for each factor according to its association with sudden death risk. Antihypertensive treatment was not associated with a reduction of the sudden death risk and had no interaction with other factors, allowing model development on both treatment and placebo groups. A risk score of sudden death in 5 years was built with seven significant risk factors: age, sex, SBP, serum total cholesterol, cigarette smoking, diabetes, and history of myocardial infarction. In terms of discrimination performance, HYSUD model was adequate with areas under the receiver operating characteristic curve of 77.74% (confidence interval 95%, 74.13-81.35) for the derivation set, of 77.46% (74.09-80.83) for the validation set, and of 79.17% (75.94-82.40) for the whole population. Our work provides a simple risk-scoring system for sudden death prediction in hypertension, using individual data from six randomized controlled trials of antihypertensive treatments. HYSUD score could help assessing a hypertensive individual's risk of sudden death and optimizing preventive therapeutic strategies for these patients.

Familias Unidas for high risk adolescents: Study design of a cultural adaptation and randomized controlled trial of a U.S. drug and sexual risk behavior intervention in Ecuador.

PubMed

Jacobs, Petra; Estrada, Yannine A; Tapia, Maria I; Quevedo Terán, Ana M; Condo Tamayo, Cecilia; Albán García, Mónica; Valenzuela Triviño, Gilda M; Pantin, Hilda; Velazquez, Maria R; Horigian, Viviana E; Alonso, Elizabeth; Prado, Guillermo

2016-03-01

Developing, testing and implementing evidence-based prevention interventions are important in decreasing substance use and sexual risk behavior among adolescents. This process requires research expertise, infrastructure, resources and decades of research testing, which might not always be feasible for low resource countries. Adapting and testing interventions proven to be efficacious in similar cultures might circumvent the time and costs of implementing evidence-based interventions in new settings. This paper describes the two-phase study, including training and development of the research infrastructure in the Ecuadorian university necessary to implement a randomized controlled trial. Familias Unidas is a multilevel parent-centered intervention designed in the U.S. to prevent drug use and sexual risk behaviors in Hispanic adolescents. The current study consisted of Phase 1 feasibility study (n=38) which adapted the intervention and study procedures within a single-site school setting in an area with a high prevalence of drug use and unprotected sexual behavior among adolescents in Ecuador, and Phase 2 randomized controlled trial of the adapted intervention in two public high schools with a target population of families with adolescents from 12 to 14 years old. The trial is currently in Phase 2. Study recruitment was completed with 239 parent-youth dyads enrolling. The intervention phase and the first follow-up assessment have been completed. The second and third follow-up assessments will be completed in 2016. This project has the potential of benefitting a large population of families in areas of Ecuador that are disproportionally affected by drug trafficking and its consequences. MSP-DIS-2015-0055-0, Ministry of Public Health (MSP), Quito, Ecuador. Copyright © 2016 Elsevier Inc. All rights reserved.

A stepped wedge cluster randomized control trial of dried blood spot testing to improve the uptake of hepatitis C antibody testing within UK prisons

PubMed Central

Whitaker, Rhiannon; Perrett, Stephanie; Zou, Lu; Hickman, Matthew; Lyons, Marion

2015-01-01

Background: The prevalence of hepatitis C (HCV) is elevated within prison populations, yet diagnosis in prisons remains low. Dried blood spot testing (DBST) is a simple procedure for the detection of HCV antibodies; its impact on testing in the prison context is unknown. Methods: We carried out a stepped-wedge cluster-randomized control trial of DBST for HCV among prisoners within five male prisons and one female prison. Each prison was a separate cluster. The order in which the intervention (training in use of DBST for HCV testing and logistic support) was introduced was randomized across clusters. The outcome measure was the HCV testing rate by prison. Imputation analysis was carried out to account for missing data. Planned and actual intervention times differed in some prisons; data were thus analysed by intention to treat (ITT) and by observed step times. Results: There was insufficient evidence of an effect of the intervention on testing rate using either the ITT intervention time (OR: 0.84; 95% CI: 0.68–1.03; P = 0.088) or using the actual intervention time (OR: 0.86; 95% CI: 0.71–1.06; P = 0.153). This was confirmed by the pooled results of five imputed data sets. Conclusions: DBST as a stand-alone intervention was insufficient to increase HCV diagnosis within the UK prison setting. Factors such as staff training and allocation of staff time for regular clinics are key to improving service delivery. We demonstrate that prisons can conduct rigorous studies of new interventions, but data collection can be problematic. Trial registration: International Standard Randomized Controlled Trial Number Register (ISRCTN number ISRCTN05628482). PMID:25061233

Assessing Clinical Trial-Associated Workload in Community-Based Research Programs Using the ASCO Clinical Trial Workload Assessment Tool.

PubMed

Good, Marjorie J; Hurley, Patricia; Woo, Kaitlin M; Szczepanek, Connie; Stewart, Teresa; Robert, Nicholas; Lyss, Alan; Gönen, Mithat; Lilenbaum, Rogerio

2016-05-01

Clinical research program managers are regularly faced with the quandary of determining how much of a workload research staff members can manage while they balance clinical practice and still achieve clinical trial accrual goals, maintain data quality and protocol compliance, and stay within budget. A tool was developed to measure clinical trial-associated workload, to apply objective metrics toward documentation of work, and to provide clearer insight to better meet clinical research program challenges and aid in balancing staff workloads. A project was conducted to assess the feasibility and utility of using this tool in diverse research settings. Community-based research programs were recruited to collect and enter clinical trial-associated monthly workload data into a web-based tool for 6 consecutive months. Descriptive statistics were computed for self-reported program characteristics and workload data, including staff acuity scores and number of patient encounters. Fifty-one research programs that represented 30 states participated. Median staff acuity scores were highest for staff with patients enrolled in studies and receiving treatment, relative to staff with patients in follow-up status. Treatment trials typically resulted in higher median staff acuity, relative to cancer control, observational/registry, and prevention trials. Industry trials exhibited higher median staff acuity scores than trials sponsored by the National Institutes of Health/National Cancer Institute, academic institutions, or others. The results from this project demonstrate that trial-specific acuity measurement is a better measure of workload than simply counting the number of patients. The tool was shown to be feasible and useable in diverse community-based research settings. Copyright © 2016 by American Society of Clinical Oncology.

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

PubMed

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

2017-07-12

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

Rapid testing for malaria in settings where microscopy is available and peripheral clinics where only presumptive treatment is available: a randomised controlled trial in Ghana.

PubMed

Ansah, Evelyn K; Narh-Bana, Solomon; Epokor, Michael; Akanpigbiam, Samson; Quartey, Alberta Amu; Gyapong, John; Whitty, Christopher J M

2010-03-05

To test in West Africa the impact of rapid diagnostic tests on the prescription of antimalarials and antibiotics both where microscopy is used for the diagnosis of malaria and in clinical (peripheral) settings that rely on clinical diagnosis. Randomised, controlled, open label clinical trial. Four clinics in the rural Dangme West district of southern Ghana, one in which microscopy is used for diagnosis of malaria ("microscopy setting") and three where microscopy is not available and diagnosis of malaria is made on the basis of clinical symptoms ("clinical setting"). Patients with suspected malaria. Interventions Patients were randomly assigned to either a rapid diagnostic test or the current diagnostic method at the clinic (microscopy or clinical diagnosis). A blood sample for a research microscopy slide was taken for all patients. The primary outcome was the prescription of antimalarials to patients of any age whose double read research slide was negative for malaria. The major secondary outcomes were the correct prescription of antimalarials, the impact of test results on antibiotic prescription, and the correct prescription of antimalarials in children under 5 years. Of the 9236 patients screened, 3452 were randomised in the clinical setting and 3811 in the microscopy setting. Follow-up to 28 days was 97.6% (7088/7263). In the microscopy setting, 722 (51.6%) of the 1400 patients with negative research slides in the rapid diagnostic test arm were treated for malaria compared with 764 (55.0%) of the 1389 patients in the microscopy arm (adjusted odds ratio 0.87, 95% CI 0.71 to 1.1; P=0.16). In the clinical setting, 578 (53.9%) of the 1072 patients in the rapid diagnostic test arm with negative research slides were treated for malaria compared with 982 (90.1%) of the 1090 patients with negative slides in the clinical diagnosis arm (odds ratio 0.12, 95% CI 0.04 to 0.38; P=0.001). The use of rapid diagnostic tests led to better targeting of antimalarials and antibiotics in the clinical but not the microscopy setting, in both children and adults. There were no deaths in children under 5 years at 28 days follow-up in either arm. Where microscopy already exists, introducing rapid diagnostic tests had limited impact on prescriber behaviour. In settings where microscopy was not available, however, using rapid diagnostic tests led to a significant reduction in the overprescription of antimalarials, without any evidence of clinical harm, and to better targeting of antibiotics. Trial registration ClinicalTrials.gov NCT00493922.

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

PubMed

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

2012-08-01

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

A cluster-randomised controlled trial of a physical activity and nutrition programme in retirement villages: a study protocol

PubMed Central

Holt, Anne-Marie; Jancey, Jonine; Lee, Andy H; Kerr, Deborah A; Hills, Andrew P; Anderson, Annie S; Howat, Peter A

2014-01-01

Introduction Physical activity levels of Australia's ageing population are declining and coincidentally rates of overweight and obesity are increasing. Adequate levels of physical activity and a healthy diet are recognised as important lifestyle factors for the maintenance of a healthy weight and prevention of chronic diseases. Retirement village (RV) residents rarely engage in physical activity and nutrition programmes offered, with poor attendance and low use of existing facilities such as on-site fitness centres and classes and nutrition seminars. The RV provides a unique setting to access and engage with this older target group, to test the effectiveness of strategies to increase levels of physical activity, improve nutrition and maintain a healthy weight. Method and analysis This cluster-randomised controlled trial will evaluate a physical activity, nutrition and healthy weight management intervention for insufficiently active (‘not achieving 150 min of moderate-intensity physical activity per week’) adults aged 60–75 residing in RV's. A total of 400 participants will be recruited from 20 randomly selected RV's in Perth, Western Australia. Villages will be assigned to either the intervention group (n=10) or the control group (n=10) each containing 200 participants. The Retirement Village Physical Activity and Nutrition for Seniors (RVPANS) programme is a home-based physical activity and nutrition programme that includes educational resources, along with facilitators who will motivate and guide the participants during the 6-month intervention. Descriptive statistics and mixed regression models will be performed to assess the intervention effects. This trial will evaluate an intervention for the modification of health risk factors in the RV setting. Such research conducted in RV's has been limited. Ethics and dissemination Curtin University Human Research Ethics Committee (approval number: HR128/2012). Dissemination of the study results will occur through publications, reports, conference presentations and community seminars. Trial registration number Australia and New Zealand Clinical Trial Registry (ACTRN12612001168842) PMID:25256185

Population-centered Risk- and Evidence-based Dental Interprofessional Care Team (PREDICT): study protocol for a randomized controlled trial.

PubMed

Cunha-Cruz, Joana; Milgrom, Peter; Shirtcliff, R Michael; Bailit, Howard L; Huebner, Colleen E; Conrad, Douglas; Ludwig, Sharity; Mitchell, Melissa; Dysert, Jeanne; Allen, Gary; Scott, JoAnna; Mancl, Lloyd

2015-06-20

To improve the oral health of low-income children, innovations in dental delivery systems are needed, including community-based care, the use of expanded duty auxiliary dental personnel, capitation payments, and global budgets. This paper describes the protocol for PREDICT (Population-centered Risk- and Evidence-based Dental Interprofessional Care Team), an evaluation project to test the effectiveness of new delivery and payment systems for improving dental care and oral health. This is a parallel-group cluster randomized controlled trial. Fourteen rural Oregon counties with a publicly insured (Medicaid) population of 82,000 children (0 to 21 years old) and pregnant women served by a managed dental care organization are randomized into test and control counties. In the test intervention (PREDICT), allied dental personnel provide screening and preventive services in community settings and case managers serve as patient navigators to arrange referrals of children who need dentist services. The delivery system intervention is paired with a compensation system for high performance (pay-for-performance) with efficient performance monitoring. PREDICT focuses on the following: 1) identifying eligible children and gaining caregiver consent for services in community settings (for example, schools); 2) providing risk-based preventive and caries stabilization services efficiently at these settings; 3) providing curative care in dental clinics; and 4) incentivizing local delivery teams to meet performance benchmarks. In the control intervention, care is delivered in dental offices without performance incentives. The primary outcome is the prevalence of untreated dental caries. Other outcomes are related to process, structure and cost. Data are collected through patient and staff surveys, clinical examinations, and the review of health and administrative records. If effective, PREDICT is expected to substantially reduce disparities in dental care and oral health. PREDICT can be disseminated to other care organizations as publicly insured clients are increasingly served by large practice organizations. ClinicalTrials.gov NCT02312921 6 December 2014. The Robert Wood Johnson Foundation and Advantage Dental Services, LLC, are supporting the evaluation.

The impact of dermatology consultation on diagnostic accuracy and antibiotic use among patients with suspected cellulitis seen at outpatient internal medicine offices: a randomized clinical trial.

PubMed

Arakaki, Ryan Y; Strazzula, Lauren; Woo, Elaine; Kroshinsky, Daniela

2014-10-01

Cellulitis is a common and costly problem, often diagnosed in the outpatient setting. Many cutaneous conditions may clinically mimic cellulitis, but little research has been done to assess the magnitude of the problem. To determine if obtaining dermatology consultations in the outpatient primary care setting could assist in the diagnosis of pseudocellulitic conditions and reduce the rate of unnecessary antibiotic use. Nonblinded randomized clinical trial of competent adults who were diagnosed as having cellulitis by their primary care physicians (PCPs), conducted at outpatient internal medical primary care offices affiliated with a large academic medical center. Outpatient dermatology consultation. Primary outcomes were final diagnosis, antibiotic use, and need for hospitalization. A total of 29 patients (12 male and 17 female) were enrolled for participation in this trial. Nine patients were randomized to continue with PCP management (control group), and 20 patients were randomized to receive a dermatology consultation (treatment group). Of the 20 patients in the dermatology consultation group, 2 (10%) were diagnosed as having cellulitis. In the control group, all 9 patients were diagnosed as having cellulitis by PCPs, but dermatologist evaluation determined that 6 (67%) of these patients had a psuedocellulitis rather than true infection. All 9 patients (100%) in the control group were treated for cellulitis with antibiotics vs 2 patients (10%) in the treatment group (P < .001). One patient in the control group was hospitalized. All patients in the treatment group reported improvement of their cutaneous condition at the 1-week follow-up examination. Dermatology consultation in the primary care setting improves the diagnostic accuracy of suspected cellulitis and decreases unnecessary antibiotic use in patients with pseudocellulitic conditions. Obtaining an outpatient dermatology consultation may be a cost-effective strategy that improves quality of care. clinicaltrials.gov Identifier:NCT01795092.

The Good Schools Toolkit to prevent violence against children in Ugandan primary schools: study protocol for a cluster randomised controlled trial.

PubMed

Devries, Karen M; Allen, Elizabeth; Child, Jennifer C; Walakira, Eddy; Parkes, Jenny; Elbourne, Diana; Watts, Charlotte; Naker, Dipak

2013-07-24

We aim to evaluate the effectiveness of the Good School Toolkit, developed by Raising Voices, in preventing violence against children attending school and in improving child mental health and educational outcomes. We are conducting a two-arm cluster randomised controlled trial with parallel assignment in Luwero District, Uganda. We will also conduct a qualitative study, a process evaluation and an economic evaluation. A total of 42 schools, representative of Luwero District, Uganda, were allocated to receive the Toolkit plus implementation support, or were allocated to a wait-list control condition. Our main analysis will involve a cross-sectional comparison of the prevalence of past-week violence from school staff as reported by children in intervention and control primary schools at follow-up.At least 60 children per school and all school staff members will be interviewed at follow-up. Data collection involves a combination of mobile phone-based, interviewer-completed questionnaires and paper-and-pen educational tests. Survey instruments include the ISPCAN Child Abuse Screening Tools to assess experiences of violence; the Strengths and Difficulties Questionnaire to measure symptoms of common childhood mental disorders; and word recognition, reading comprehension, spelling, arithmetic and sustained attention tests adapted from an intervention trial in Kenya. To our knowledge, this is the first study to rigorously investigate the effects of any intervention to prevent violence from school staff to children in primary school in a low-income setting. We hope the results will be informative across the African region and in other settings. clinicaltrials.gov NCT01678846.

A cluster randomised trial of a school-based resilience intervention to decrease tobacco, alcohol and illicit drug use in secondary school students: study protocol.

PubMed

Hodder, Rebecca K; Freund, Megan; Bowman, Jenny; Wolfenden, Luke; Campbell, Elizabeth; Wye, Paula; Hazell, Trevor; Gillham, Karen; Wiggers, John

2012-11-21

Whilst schools provide a potentially appropriate setting for preventing substance use among young people, systematic review evidence suggests that past interventions in this setting have demonstrated limited effectiveness in preventing tobacco, alcohol and other drug use. Interventions that adopt a mental wellbeing approach to prevent substance use offer considerable promise and resilience theory provides one method to impact on adolescent mental well-being. The aim of the proposed study is to examine the efficacy of a resilience intervention in decreasing the tobacco, alcohol and illicit drug use of adolescents. A cluster randomised controlled trial with schools as the unit of randomisation will be undertaken. Thirty two schools in disadvantaged areas will be allocated to either an intervention or a control group. A comprehensive resilience intervention will be implemented, inclusive of explicit program adoption strategies. Baseline surveys will be conducted with students in Grade 7 in both groups and again three years later when the student cohort is in Grade 10. The primary outcome measures will include self-reported tobacco, alcohol, marijuana and other illicit drug use. Comparisons will be made post-test between Grade 10 students in intervention and control schools to determine intervention effectiveness across all measures. To the authors' knowledge this is the first randomised controlled trial to evaluate the effectiveness of a comprehensive school-based resilience intervention, inclusive of explicit adoption strategies, in decreasing tobacco, alcohol and illicit drug use of adolescents attending disadvantaged secondary schools. ACTRN12611000606987.

The Aspirin Regimens in Essential Thrombocythemia (ARES) phase II randomized trial design: Implementation of the serum thromboxane B2 assay as an evaluation tool of different aspirin dosing regimens in the clinical setting.

PubMed

De Stefano, Valerio; Rocca, Bianca; Tosetto, Alberto; Soldati, Denise; Petrucci, Giovanna; Beggiato, Eloise; Bertozzi, Irene; Betti, Silvia; Carli, Giuseppe; Carpenedo, Monica; Cattaneo, Daniele; Cavalca, Viviana; Dragani, Alfredo; Elli, Elena; Finazzi, Guido; Iurlo, Alessandra; Lanzarone, Giuseppe; Lissandrini, Laura; Palandri, Francesca; Paoli, Chiara; Rambaldi, Alessandro; Ranalli, Paola; Randi, Maria Luigia; Ricco, Alessandra; Rossi, Elena; Ruggeri, Marco; Specchia, Giorgina; Timillero, Andrea; Turnu, Linda; Vianelli, Nicola; Vannucchi, Alessandro M; Rodeghiero, Francesco; Patrono, Carlo

2018-06-01

Once-daily (od), low-dose aspirin (75-100 mg) is recommended to reduce the thrombotic risk of patients with essential thrombocytemia (ET). This practice is based on data extrapolated from other high-risk patients and an aspirin trial in polycythemia vera, with the assumption of similar aspirin pharmacodynamics in the two settings. However, the pharmacodynamics of low-dose aspirin is impaired in ET, reflecting accelerated renewal of platelet cyclooxygenase (COX)-1. ARES is a parallel-arm, placebo-controlled, randomized, dose-finding, phase II trial enrolling 300 ET patients to address two main questions. First, whether twice or three times 100 mg aspirin daily dosing is superior to the standard od regimen in inhibiting platelet thromboxane (TX)A 2 production, without inhibiting vascular prostacyclin biosynthesis. Second, whether long-term persistence of superior biochemical efficacy can be safely maintained with multiple vs. single dosing aspirin regimen. Considering that the primary study end point is serum TXB 2 , a surrogate biomarker of clinical efficacy, a preliminary exercise of reproducibility and validation of this biomarker across all the 11 participating centers was implemented. The results of this preliminary phase demonstrate the importance of controlling reproducibility of biomarkers in multicenter trials and the feasibility of using serum TXB 2 as a reliable end point for dose-finding studies of novel aspirin regimens.

Impact of improved recording of work-relatedness in primary care visits at occupational health services on sickness absences: study protocol for a randomised controlled trial.

PubMed

Atkins, Salla; Ojajärvi, Ulla; Talola, Nina; Viljamaa, Mervi; Nevalainen, Jaakko; Uitti, Jukka

2017-07-26

Employment protects and fosters health. Occupational health services, particularly in Finland, have a central role in protecting employee health and preventing work ability problems. However, primary care within occupational health services is currently underused in informing preventive activities. This study was designed to assess whether the recording of work ability problems and improvement of follow-up of work-related primary care visits can reduce sickness absences and work disability pensions after 1 year. A pragmatic trial will be conducted using patient electronic registers and registers of the central pensions agency in Finland. Twenty-two occupational health centres will be randomised to intervention and control groups. Intervention units will receive training to improve recording of work ability illnesses in the primary care setting and improved follow-up procedures. The intervention impact will be assessed through examining rates of sickness absence across intervention and control clinics as well as before and after the intervention. The trial will develop knowledge of the intervention potential of primary care for preventing work disability pensions and sickness absence. The use of routine patient registers and pensions registers to assess the outcomes of a randomised controlled trial will bring forward trial methodology, particularly when using register-based data. If successful, the intervention will improve the quality of occupational health care primary care and contribute to reducing work disability. ISRCTN Registry reference number ISRCTN45728263 . Registered on 18 April 2016.

Procalcitonin-guided protocol is not useful to manage antibiotic therapy in febrile neutropenia: a randomized controlled trial.

PubMed

Lima, Stella Sala Soares; Nobre, Vandack; de Castro Romanelli, Roberta Maia; Clemente, Wanessa Trindade; da Silva Bittencourt, Henrique Neves; Melo, Ana Catarina Mourão; Salomão, Luciana Caetano Botelho; Serufo, José Carlos

2016-06-01

Febrile neutropenia (FN) requires immediate use of antibiotics (ATB), and procalcitonin (PCT) is proven to be useful in guiding antibiotic therapy in different settings. This study investigated the use of PCT as a guide for the duration of ATB in FN. A randomized controlled trial was carried out from January-December 2010. A total of 62 hematological adult patients with FN were randomized, in 1:1 ratio, into two groups: (1) PCT group: length of ATB guided by institutional protocol plus PCT dynamics, and (2) control group: duration of ATB in accordance with institutional protocol. There was no difference between groups regarding the use of ATB for the first episode of fever (HR 1.14, 95 % CI 0.66-1.95, p = 0.641), with equivalent median duration of ATB therapy (PCT group 9.0 days and control group 8.0 days, p = 0.67), and median number of days without ATB (0 days, IQR 0-2 days for both groups, p = 0.96). We observed no difference in clinical cure rate (p = 0.68), infection relapse (p = 1.0), superinfection (p = 0.85), length of hospitalization (p = 0.64), and mortality at 28 days (p = 0.39) and at 90 days (p = 0.72). Considering the cut-off of 0.5 ng/ml, PCT was correlated with bacteremia (sensitivity of 51.9 % and specificity of 76.5 %). In this randomized controlled trial, adding a PCT-guided protocol to the standard recommendations did not reduce the use of antibiotics in febrile neutropenia, although no apparent harm was caused. PCT proved to be a marker of bacteremia in this setting.

Clinical Knowledge from Observational Studies: Everything You Wanted to Know but Were Afraid to Ask.

PubMed

Gershon, Andrea S; Jafarzadeh, S Reza; Wilson, Kevin C; Walkey, Allan J

2018-05-07

Well-done randomized trials provide accurate estimates of treatment effect by producing groups that are similar on all measures except for the intervention of interest. However, inferences of efficacy in tightly-controlled experimental settings may not translate into similar effectiveness in real-world settings. Observational studies generally enable inferences over a wider range of patient characteristics and evaluation of a broader range of outcomes over a longer period than randomized trials. However, clinicians are often reluctant to incorporate the findings of observational studies into clinical practice. Reason for uncertainty regarding observational studies include a lack of familiarity with observational research methods, occasional disagreements between results of observational studies and randomized trials, the perceived risk of spurious results from systematic bias, and prior teaching that randomized trials are the most reliable source of medical evidence. We propose that a better understanding of observational research will enhance clinicians' ability to distinguish reliable observational studies from those that are subjected to biases and, therefore, provide more confidence to apply observational research results into clinical practice when appropriate. Herein, we explain why observational studies may be perceived as less conclusive than randomized trials, address situations in which observational research and randomized trials produced different findings, and provide information on observational study design so that quality can be evaluated. We conclude that observational research is a valuable source of medical evidence and that clinical action is strongest when supported by both high quality observational studies and randomized trials.

Effect of early statin therapy after acute coronary syndromes: a concise review of the recent data.

PubMed

Bybee, Kevin A; Wright, R Scott; Kopecky, Stephen L

2002-01-01

HMG Co-A reductase inhibitors(statins) have been shown, in three large randomized trials, to decrease adverse cardiac events in patients with clinically evident coronary artery disease. All of these trials have excluded patients with an acute coronary syndrome within the three months prior to enrollment. Statin therapy is thought to stabilize coronary plaque and decrease the risk of plaque rupture. Statins have been shown to quickly reduce levels of LDL-C in addition to altering systemic inflammatory responses, improving endothelial function, and reducing platelet aggregation and activation. These mechanisms are potentially beneficial in the setting of acute coronary syndromes, a time of profound plaque instability. There is a growing body of evidence supporting the early initiation of statin therapy in the setting of acute coronary syndromes. This paper reviews the available data from randomized-controlled trials and observational studies evaluating the effect of early statin initiation during, or soon following, an acute coronary syndrome.

An Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective Randomized Control Trials

PubMed Central

Logan, Jennifer K; Tang, Chad; Liao, Zhongxing; Lee, J. Jack; Heymach, John V.; Swisher, Stephen G.; Welsh, James W.; Zhang, Jianjun; Lin, Steven H.; Gomez, Daniel R.

2018-01-01

Purpose Effective clinical trial enrollment can be difficult in a protocol designs that contain one treatment arm that is perceived as being more “aggressive” or “favorable.” There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to enrollment, particularly the influence of timing, in context of three prospective randomized oncology trials where one arm was considered more aggressive. Methods and materials From June 2011 to March 2015, patients who were enrolled on three prospective institutional protocols (an oligometastatic non-small cell lung cancer (NSCLC) trial, and two proton vs. intensity-modulated radiation therapy (IMRT) trials in NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher’s exact test, Student’s t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. Results 309 eligible patients were approached about trial enrollment. The enrollment success rate (ESR) during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligomet protocol: 5 vs. 3 appointments (P<0.001), NSCLC protocol: 4 vs. 3 appointments (P = 0.0018), esophageal protocol: 3 vs. 2 appointments (P = 0.0086No other factors or patient characteristics significantly affected ESR. Conclusion Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success, and may help overcome accrual barriers without compromising trial design. PMID:28244413

Effects of an aquatic physical exercise program on glycemic control and perinatal outcomes of gestational diabetes: study protocol for a randomized controlled trial.

PubMed

da Silva, José Roberto; Borges, Paulo Sérgio; Agra, Karine F; Pontes, Isabelle Albuquerque; Alves, João Guilherme Bezerra

2013-11-19

Gestational diabetes mellitus (GDM) is increasing worldwide and has been associated with adverse perinatal outcomes and high risk for chronic disease both for the mother and for the child. Physical exercise is feasible for diabetic pregnant women and contributes to better glycemic control and to a decrease in adverse perinatal outcomes. However, there are no randomized controlled trials (RCT) assessing the effects of aquatic physical exercise on GDM control and adverse maternal and fetal outcomes. An RCT will be conducted at Instituto de Medicina Integral Prof Fernando Figueira (IMIP), Brazil. A total of 72 pregnant women will be studied; 36 gestational diabetics will undergo an aquatic physical exercise program in a thermal pool, 3 times per week over 2 months. The primary endpoint will be glucose level control and use of insulin; secondary endpoints will be the following maternal and fetal outcomes: weight gain during pregnancy, blood pressure, pre-eclampsia diagnosis, intrauterus growth restriction, preterm birth, Cesarean section, macrosomia and maternal or neonatal intensive care admission. Endpoints between intervention and control group will analyzed by t test for unpaired data and χ² test, and the level of significance will set at <0.05. The physical proprieties of water make aquatic exercises ideal for pregnant women. An aquatic physical exercise program developed for GDM women will be trialed in a thermal pool and under the supervision of physiotherapist to ensure compliance. It is expected that this study will provide evidence as to the effect of aquatic physical exercise on GDM control. ClinicalTrial.gov, NCT01940003.

Community involvement in dengue vector control: cluster randomised trial.

PubMed

Vanlerberghe, V; Toledo, M E; Rodríguez, M; Gómez, D; Baly, A; Benítez, J R; Van der Stuyft, P

2010-01-01

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

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

PubMed

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

2015-07-01

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

Effects of self-management health information technology on glycaemic control for patients with diabetes: a meta-analysis of randomized controlled trials.

PubMed

Tao, Da; Or, Calvin Kl

2013-04-01

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) which had evaluated self-management health information technology (SMHIT) for glycaemic control in patients with diabetes. A total of 43 RCTs was identified, which reported on 52 control-intervention comparisons. The glycosylated haemoglobin (HbA 1c ) data were pooled using a random effects meta-analysis method, followed by a meta-regression and subgroup analyses to examine the effects of a set of moderators. The meta-analysis showed that use of SMHITs was associated with a significant reduction in HbA 1c compared to usual care, with a pooled standardized mean difference of -0.30% (95% CI -0.39 to -0.21, P < 0.001). Sample size, age, study setting, type of application and method of data entry significantly moderated the effects of SMHIT use. The review supports the use of SMHITs as a self-management approach to improve glycaemic control. The effect of SMHIT use is significantly greater when the technology is a web-based application, when a mechanism for patients' health data entry is provided (manual or automatic) and when the technology is operated in the home or without location restrictions. Integrating these variables into the design of SMHITs may augment the effectiveness of the interventions. © SAGE Publications Ltd, 2013.

A randomized controlled trial of water-based exercise for cardiovascular fitness in individuals with chronic stroke

PubMed Central

Chu, Kelly S; Eng, Janice J; Dawson, Andrew S; Harris, Jocelyn E.; Ozkaplan, Atila; Gylfadóttir, Sif

2011-01-01

Objective To evaluate the effect of an 8-week water-based exercise program (experimental group) over an upper extremity function program (control group) to increase cardiovascular fitness within a community setting for individuals with stroke. Design Single-blind randomized controlled trial Setting Public community centre Participants 12 community-dwelling individuals who have had a stroke with mild to moderate motor deficits; volunteer sample Intervention Experimental and control groups participated in group exercise programs undertaken in one hour sessions, three times per week for 8 weeks. The experimental group undertook chest deep water exercises at targeted heart rates. The control group performed arm and hand exercises while sitting. Main Outcome Measures The primary outcome measure was cardiovascular fitness (VO2max). Secondary measures were maximal workload, muscle strength, gait speed, and the Berg Balance Score. Results The experimental group attained significant improvements over the control group in cardiovascular fitness, maximal workload, gait speed, and paretic lower extremity muscle strength. The relatively short program (8 weeks) of water-based exercise resulted in a large improvement (22%) in cardiovascular fitness in a small group of individuals with stroke with relatively high function. Conclusions A water-based exercise program can be undertaken in the community as a group program and may be an effective means to promote fitness in individuals with stroke. PMID:15179638

Design and methods for a cluster-controlled trial conducted at sixty-eight daycare facilities evaluating the impact of "JolinchenKids - Fit and Healthy in Daycare", a program for health promotion in 3- to 6-year-old children.

PubMed

Steenbock, Berit; Zeeb, Hajo; Rach, Stefan; Pohlabeln, Hermann; Pischke, Claudia R

2017-07-11

The prevention of overweight and obesity during infancy is a highly relevant public health topic given the significant impact of childhood obesity on acute and chronic diseases, general health, and well-being in later stages of life. Apart from the family setting, daycare facilities (DFs) represent a key setting for health promotion among children under the age of six years. "JolinchenKids - Fit and Healthy in Daycare" is a multi-component program promoting physical activity (PA), healthy eating, and mental well-being in 3- to 6-year-old preschoolers at DFs, originally designed by the German health insurance AOK. To evaluate program effectiveness, a cluster-controlled trial involving 68 DFs is currently conducted. The objective of this article is to describe the background, study design, and aims of this trial. Sixty-eight DFs across Germany will be recruited to take part in the study, half of them serving as intervention DFs and half of them as delayed intervention control DFs (which receive the program upon completion of the study). At each DF, height, weight, and body composition, as well as motor skills, will be assessed in twenty 3- to 6-year-old children. Children's eating and PA habits, and mental well-being will be assessed via parental questionnaires. A subsample of children (i.e., at 24 DFs which are randomly selected within a geographic region) will be asked to wear accelerometers at their wrists to objectively measure PA over the course of seven days. To compare changes in body composition, motor skills, eating and PA habits, and mental well-being of children at intervention DFs with those observed among children at delayed intervention control DFs over one year, all measurements will take place at baseline and twelve months after the launch of the program at all DFs. This study investigates the influence of a health promotion program in the daycare setting on various outcomes, including body composition and objectively measured PA, in a nationwide sample of 3- to 6-year-old preschoolers. This study will provide evidence regarding the effectiveness of a multi-component program for health promotion in this setting and may provide insights into new strategies for preventing obesity in early life. German Clinical Trials Register DRKS00011065 (Date of registration 16-09-2016).

Iodine supplementation for women during the preconception, pregnancy and postpartum period.

PubMed

Harding, Kimberly B; Peña-Rosas, Juan Pablo; Webster, Angela C; Yap, Constance My; Payne, Brian A; Ota, Erika; De-Regil, Luz Maria

2017-03-05

Iodine is an essential nutrient required for the biosynthesis of thyroid hormones, which are responsible for regulating growth, development and metabolism. Iodine requirements increase substantially during pregnancy and breastfeeding. If requirements are not met during these periods, the production of thyroid hormones may decrease and be inadequate for maternal, fetal and infant needs. The provision of iodine supplements may help meet the increased iodine needs during pregnancy and the postpartum period and prevent or correct iodine deficiency and its consequences. To assess the benefits and harms of supplementation with iodine, alone or in combination with other vitamins and minerals, for women in the preconceptional, pregnancy or postpartum period on their and their children's outcomes. We searched Cochrane Pregnancy and Childbirth's Trials Register (14 November 2016), and the WHO International Clinical Trials Registry Platform (ICTRP) (17 November 2016), contacted experts in the field and searched the reference lists of retrieved studies and other relevant papers. Randomized and quasi-randomized controlled trials with randomisation at either the individual or cluster level comparing injected or oral iodine supplementation (such as tablets, capsules, drops) during preconception, pregnancy or the postpartum period irrespective of iodine compound, dose, frequency or duration. Two review authors independently assessed trial eligibility, risk of bias, extracted data and conducted checks for accuracy. We used the GRADE approach to assess the quality of the evidence for primary outcomes.We anticipated high heterogeneity among trials, and we pooled trial results using random-effects models and were cautious in our interpretation of the pooled results. We included 14 studies and excluded 48 studies. We identified five ongoing or unpublished studies and two studies are awaiting classification. Eleven trials involving over 2700 women contributed data for the comparisons in this review (in three trials, the primary or secondary outcomes were not reported). Maternal primary outcomesIodine supplementation decreased the likelihood of the adverse effect of postpartum hyperthyroidism by 68% (average risk ratio (RR) 0.32; 95% confidence interval (CI) 0.11 to 0.91, three trials in mild to moderate iodine deficiency settings, 543 women, no statistical heterogeneity, low-quality evidence) and increased the likelihood of the adverse effect of digestive intolerance in pregnancy by 15 times (average RR 15.33; 95% CI 2.07 to 113.70, one trial in a mild-deficiency setting, 76 women, very low-quality evidence).There were no clear differences between groups for hypothyroidism in pregnancy or postpartum (pregnancy: average RR 1.90; 95% CI 0.57 to 6.38, one trial, 365 women, low-quality evidence, and postpartum: average RR 0.44; 95% CI 0.06 to 3.42, three trials, 540 women, no statistical heterogeneity, low-quality evidence), preterm birth (average RR 0.71; 95% CI 0.30 to 1.66, two trials, 376 women, statistical heterogeneity, low-quality evidence) or the maternal adverse effects of elevated thyroid peroxidase antibodies (TPO-ab) in pregnancy or postpartum (average RR 0.95; 95% CI 0.44 to 2.07, one trial, 359 women, low-quality evidence, average RR 1.01; 95% CI 0.78 to 1.30, three trials, 397 women, no statistical heterogeneity, low-quality evidence), or hyperthyroidism in pregnancy (average RR 1.90; 95% CI 0.57 to 6.38, one trial, 365 women, low-quality evidence). All of the trials contributing data to these outcomes took place in settings with mild to moderate iodine deficiency. Infant/child primary outcomesCompared with those who did not receive iodine, those who received iodine supplements had a 34% lower likelihood of perinatal mortality, however this difference was not statistically significant (average RR 0.66; 95% CI 0.42 to 1.03, two trials, 457 assessments, low-quality evidence). All of the perinatal deaths occurred in one trial conducted in a severely iodine-deficient setting. There were no clear differences between groups for low birthweight (average RR 0.56; 95% CI 0.26 to 1.23, two trials, 377 infants, no statistical heterogeneity, low-quality evidence), neonatal hypothyroidism/elevated thyroid-stimulating hormone (TSH) (average RR 0.58; 95% CI 0.11 to 3.12, two trials, 260 infants, very low-quality evidence) or the adverse effect of elevated neonatal thyroid peroxidase antibodies (TPO-ab) (average RR 0.61; 95% CI 0.07 to 5.70, one trial, 108 infants, very low-quality evidence). All of the trials contributing data to these outcomes took place in areas with mild to moderate iodine deficiency. No trials reported on hypothyroidism/elevated TSH or any adverse effect beyond the neonatal period. There were insufficient data to reach any meaningful conclusions on the benefits and harms of routine iodine supplementation in women before, during or after pregnancy. The available evidence suggested that iodine supplementation decreases the likelihood of postpartum hyperthyroidism and increases the likelihood of the adverse effect of digestive intolerance in pregnancy - both considered potential adverse effects. We considered evidence for these outcomes low or very low quality, however, because of study design limitations and wide confidence intervals. In addition, due to the small number of trials and included women in our meta-analyses, these findings must be interpreted with caution. There were no clear effects on other important maternal or child outcomes though these findings must also be interpreted cautiously due to limited data and low-quality trials. Additionally, almost all of the evidence came from settings with mild or moderate iodine deficiency and therefore may not be applicable to settings with severe deficiency.More high-quality randomised controlled trials are needed on iodine supplementation before, during and after pregnancy on maternal and infant/child outcomes. However, it may be unethical to compare iodine to placebo or no treatment in severe deficiency settings. Trials may also be unfeasible in settings where pregnant and lactating women commonly take prenatal supplements with iodine. Information is needed on optimal timing of initiation as well as supplementation regimen and dose. Future trials should consider the outcomes in this review and follow children beyond the neonatal period. Future trials should employ adequate sample sizes, assess potential adverse effects (including the nature and extent of digestive intolerance), and be reported in a way that allows assessment of risk of bias, full data extraction and analysis by the subgroups specified in this review.

Internet-delivered treatment for older adults with anxiety and depression: implementation of the Wellbeing Plus Course in routine clinical care and comparison with research trial outcomes.

PubMed

Staples, Lauren G; Fogliati, Vincent J; Dear, Blake F; Nielssen, Olav; Titov, Nickolai

2016-09-01

The Wellbeing Plus Course is an internet-delivered psychological intervention for older adults with anxiety or depression. To compare the effectiveness of the Wellbeing Plus Course in a public health setting (clinic group) with its efficacy in a randomised controlled trial (research group). Participants ( n =949) were Australian adults aged 60 and above. Primary outcome measures were the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder scale (GAD-7). Initial symptom severity was higher in the clinic group and course completion was lower. Both groups showed significant symptom reductions at post-treatment and were satisfied with the treatment. Results were maintained at 3-month follow-up. Within-group symptom changes were comparable between settings; there were no between-group differences on primary outcomes or satisfaction. The Wellbeing Plus Course is as effective and acceptable in routine clinical care, as it is in controlled research trials. N.T. and B.F.D developed the Wellbeing Plus Course but derived no financial benefit from it. © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Design and methods for evaluating an early childhood obesity prevention program in the childcare center setting

PubMed Central

2013-01-01

Background Many unhealthy dietary and physical activity habits that foster the development of obesity are established by the age of five. Presently, approximately 70 percent of children in the United States are currently enrolled in early childcare facilities, making this an ideal setting to implement and evaluate childhood obesity prevention efforts. We describe here the methods for conducting an obesity prevention randomized trial in the child care setting. Methods/design A randomized, controlled obesity prevention trial is currently being conducted over a three year period (2010-present). The sample consists of 28 low-income, ethnically diverse child care centers with 1105 children (sample is 60% Hispanic, 15% Haitian, 12% Black, 2% non-Hispanic White and 71% of caregivers were born outside of the US). The purpose is to test the efficacy of a parent and teacher role-modeling intervention on children’s nutrition and physical activity behaviors. . The Healthy Caregivers-Healthy Children (HC2) intervention arm schools received a combination of (1) implementing a daily curricula for teachers/parents (the nutritional gatekeepers); (2) implementing a daily curricula for children; (3) technical assistance with meal and snack menu modifications such as including more fresh and less canned produce; and (4) creation of a center policy for dietary requirements for meals and snacks, physical activity and screen time. Control arm schools received an attention control safety curriculum. Major outcome measures include pre-post changes in child body mass index percentile and z score, fruit and vegetable and other nutritious food intake, amount of physical activity, and parental nutrition and physical activity knowledge, attitudes, and beliefs, defined by intentions and behaviors. All measures were administered at the beginning and end of the school year for year one and year two of the study for a total of 4 longitudinal time points for assessment. Discussion Although few attempts have been made to prevent obesity during the first years of life, this period may represent the best opportunity for obesity prevention. Findings from this investigation will inform both the fields of childhood obesity prevention and early childhood research about the effects of an obesity prevention program housed in the childcare setting. Trial registration Trial registration number: NCT01722032 PMID:23356862

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

PubMed Central

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

2017-01-01

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

Influence of Hydration on Physiological Function and Performance During Trail Running in the Heat

PubMed Central

Casa, Douglas J.; Stearns, Rebecca L.; Lopez, Rebecca M.; Ganio, Matthew S.; McDermott, Brendon P.; Walker Yeargin, Susan; Yamamoto, Linda M.; Mazerolle, Stephanie M.; Roti, Melissa W.; Armstrong, Lawrence E.; Maresh, Carl M.

2010-01-01

Abstract Context: Authors of most field studies have not observed decrements in physiologic function and performance with increases in dehydration, although authors of well-controlled laboratory studies have consistently reported this relationship. Investigators in these field studies did not control exercise intensity, a known modulator of body core temperature. Objective: To directly examine the effect of moderate water deficit on the physiologic responses to various exercise intensities in a warm outdoor setting. Design: Semirandomized, crossover design. Setting: Field setting. Patients or Other Participants: Seventeen distance runners (9 men, 8 women; age  =  27 ± 7 years, height  =  171 ± 9 cm, mass  =  64.2 ± 9.0 kg, body fat  =  14.6% ± 5.5%). Intervention(s): Participants completed four 12-km runs (consisting of three 4-km loops) in the heat (average wet bulb globe temperature  =  26.5°C): (1) a hydrated, race trial (HYR), (2) a dehydrated, race trial (DYR), (3) a hydrated, submaximal trial (HYS), and (4) a dehydrated, submaximal trial (DYS). Main Outcome Measure(s): For DYR and DYS trials, dehydration was measured by body mass loss. In the submaximal trials, participants ran at a moderate pace that was matched by having them speed up or slow down based on pace feedback provided by researchers. Intestinal temperature was recorded using ingestible thermistors, and participants wore heart rate monitors to measure heart rate. Results: Body mass loss in relation to a 3-day baseline was greater for the DYR (−4.30% ± 1.25%) and DYS trials (−4.59% ± 1.32%) than for the HYR (−2.05% ± 1.09%) and HYS (−2.0% ± 1.24%) trials postrun (P < .001). Participants ran faster for the HYR (53.15 ± 6.05 minutes) than for the DYR (55.7 ± 7.45 minutes; P < .01), but speed was similar for HYS (59.57 ± 5.31 minutes) and DYS (59.44 ± 5.44 minutes; P > .05). Intestinal temperature immediately postrun was greater for DYR than for HYR (P < .05), the only significant difference. Intestinal temperature was greater for DYS than for HYS postloop 2, postrun, and at 10 and 20 minutes postrun (all: P < .001). Intestinal temperature and heart rate were 0.22°C and 6 beats/min higher, respectively, for every additional 1% body mass loss during the DYS trial compared with the HYS trial. Conclusions: A small decrement in hydration status impaired physiologic function and performance while trail running in the heat. PMID:20210618

Warm-up for Sprint Swimming: Race-Pace or Aerobic Stimulation? A Randomized Study.

PubMed

Neiva, Henrique P; Marques, Mário C; Barbosa, Tiago M; Izquierdo, Mikel; Viana, João L; Teixeira, Ana M; Marinho, Daniel A

2017-09-01

Neiva, HP, Marques, MC, Barbosa, TM, Izquierdo, M, Viana, JL, Teixeira, AM, and Marinho, DA. Warm-up for sprint swimming: race-pace or aerobic stimulation? A randomized study. J Strength Cond Res 31(9): 2423-2431, 2017-The aim of this study was to compare the effects of 2 different warm-up intensities on 100-m swimming performance in a randomized controlled trial. Thirteen competitive swimmers performed two 100-m freestyle time-trials on separate days after either control or experimental warm-up in a randomized design. The control warm-up included a typical race-pace set (4 × 25 m), whereas the experimental warm-up included an aerobic set (8 × 50 m at 98-102% of critical velocity). Cortisol, testosterone, blood lactate ([La]), oxygen uptake (V[Combining Dot Above]O2), heart rate, core (Tcore and Tcorenet) and tympanic temperatures, and rating of perceived exertion (RPE) were monitored. Stroke length (SL), stroke frequency (SF), stroke index (SI), and propelling efficiency (ηp) were assessed for each 50-m lap. We found that V[Combining Dot Above]O2, heart rate, and Tcorenet were higher after experimental warm-up (d > 0.73), but only the positive effect for Tcorenet was maintained until the trial. Performance was not different between conditions (d = 0.07). Experimental warm-up was found to slow SF (mean change ±90% CL = 2.06 ± 1.48%) and increase SL (1.65 ± 1.40%) and ηp (1.87 ± 1.33%) in the first lap. After the time-trials, this warm-up had a positive effect on Tcorenet (d = 0.69) and a negative effect on [La] (d = 0.56). Although the warm-ups had similar outcomes in the 100-m freestyle, performance was achieved through different biomechanical strategies. Stroke length and efficiency were higher in the first lap after the experimental warm-up, whereas SF was higher after control warm-up. Physiological adaptations were observed mainly through an increased Tcore after experimental warm-up. In this condition, the lower [La] after the trial suggests lower dependency on anaerobic metabolism.

Feasibility intervention trial of two types of improved cookstoves in three resource-limited settings: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Exposure to biomass fuel smoke is one of the leading risk factors for disease burden worldwide. International campaigns are currently promoting the widespread adoption of improved cookstoves in resource-limited settings, yet little is known about the cultural and social barriers to successful improved cookstove adoption and how these barriers affect environmental exposures and health outcomes. Design We plan to conduct a one-year crossover, feasibility intervention trial in three resource-limited settings (Kenya, Nepal and Peru). We will enroll 40 to 46 female primary cooks aged 20 to 49 years in each site (total 120 to 138). Methods At baseline, we will collect information on sociodemographic characteristics and cooking practices, and measure respiratory health and blood pressure for all participating women. An initial observational period of four months while households use their traditional, open-fire design cookstoves will take place prior to randomization. All participants will then be randomized to receive one of two types of improved, ventilated cookstoves with a chimney: a commercially-constructed cookstove (Envirofit G3300/G3355) or a locally-constructed cookstove. After four months of observation, participants will crossover and receive the other improved cookstove design and be followed for another four months. During each of the three four-month study periods, we will collect monthly information on self-reported respiratory symptoms, cooking practices, compliance with cookstove use (intervention periods only), and measure peak expiratory flow, forced expiratory volume at 1 second, exhaled carbon monoxide and blood pressure. We will also measure pulmonary function testing in the women participants and 24-hour kitchen particulate matter and carbon monoxide levels at least once per period. Discussion Findings from this study will help us better understand the behavioral, biological, and environmental changes that occur with a cookstove intervention. If this trial indicates that reducing indoor air pollution is feasible and effective in resource-limited settings like Peru, Kenya and Nepal, trials and programs to modify the open burning of biomass fuels by installation of low-cost ventilated cookstoves could significantly reduce the burden of illness and death worldwide. Trial registration ClinicalTrials.gov NCT01686867 PMID:24112419

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

PubMed Central

2013-01-01

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

Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer

PubMed Central

Katz, Matthew H. G.; Shi, Qian; Ahmad, Syed A.; Herman, Joseph M.; Marsh, Robert de W.; Collisson, Eric; Schwartz, Lawrence; Frankel, Wendy; Martin, Robert; Conway, William; Truty, Mark; Kindler, Hedy; Lowy, Andrew M.; Bekaii-Saab, Tanios; Philip, Philip; Talamonti, Mark; Cardin, Dana; LoConte, Noelle; Shen, Perry; Hoffman, John P.; Venook, Alan P.

2016-01-01

IMPORTANCE Although consensus statements support the preoperative treatment of borderline resectable pancreatic cancer, no prospective, quality-controlled, multicenter studies of this strategy have been conducted. Existing studies are retrospective and confounded by heterogeneity in patients studied, therapeutic algorithms used, and outcomes reported. OBJECTIVE To determine the feasibility of conducting studies of multimodality therapy for borderline resectable pancreatic cancer in the cooperative group setting. DESIGN, SETTING, AND PARTICIPANTS A prospective, multicenter, single-arm trial of a multimodality treatment regimen administered within a study framework using centralized quality control with the cooperation of 14 member institutions of the National Clinical Trials Network. Twenty-nine patients with biopsy-confirmed pancreatic cancer preregistered, and 23 patients with tumors who met centrally reviewed radiographic criteria registered. Twenty-two patients initiated therapy (median age, 64 years [range, 50–76 years]; 55% female). Patients registered between May 29, 2013, and February 7,2014. INTERVENTIONS Patients received modified FOLFIRINOX treatment (85 mg/m2 of oxaliplatin, 180 mg/m2 of irinotecan hydrochloride, 400 mg/m2 of leucovorin calcium, and then 2400 mg/m2 of 5-fluorouracil for 4 cycles) followed by 5.5 weeks of external-beam radiation (50.4 Gy delivered in 28 daily fractions) with capecitabine (825 mg/m2 orally twice daily) prior to pancreatectomy. MAIN OUTCOMES AND MEASURES Feasibility, defined by the accrual rate, the safety of the preoperative regimen, and the pancreatectomy rate. RESULTS The accrual rate of 2.6 patients per month was superior to the anticipated rate. Although 14 of the 22 patients (64% [95% CI, 41%–83%]) had grade 3 or higher adverse events, 15 of the 22 patients (68% [95% CI, 49%–88%]) underwent pancreatectomy. Of these 15 patients, 12 (80%) required vascular resection, 14 (93%) had microscopically negative margins, 5 (33%) had specimens that had less than 5% residual cancer cells, and 2 (13%) had specimens that had pathologic complete responses. The median overall survival of all patients was 21.7 months (95% CI, 15.7 to not reached) from registration. CONCLUSIONS AND RELEVANCE The successful completion of this collaborative study demonstrates the feasibility of conducting quality-controlled trials for this disease stage in the multi-institutional setting. The data generated by this study and the logistical elements that facilitated the trial's completion are currently being used to develop cooperative group trials with the goal of improving outcomes for this subset of patients. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01821612 PMID:27275632

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

PubMed

Koopmeiners, Joseph S; Hobbs, Brian P

2018-05-01

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

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

PubMed Central

Koopmeiners, Joseph S.; Hobbs, Brian P.

2016-01-01

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

A Randomized Controlled Trial Determining Variances in Ostomy Skin Conditions and the Economic Impact (ADVOCATE Trial)

PubMed Central

Pittman, Joyce; Raizman, Rose; Salvadalena, Ginger

2018-01-01

PURPOSE: To compare ostomy-related costs and incidence of peristomal skin complications (PSCs) for ceramide-infused ostomy skin barriers and control skin barriers. DESIGN: The ADVOCATE trial is a multi-centered randomized controlled trial, and double-blinded international study with an adaptive design. SUBJECTS AND SETTING: The sample comprised 153 adults from 25 sites from the United States, Canada, and Europe. Participants were seen in hospital and outpatient care settings. METHODS: Data were collected by investigators at each site during face-to-face visits and during telephone check-in calls between visits. Cost of care data were collected using a questionnaire developed specifically for the study. The peristomal skin was assessed using the Ostomy Skin Tool. Health-related quality of life was measured using the SF-12v2. Patient-reported outcomes were collected using a patient-centered study-specific questionnaire. Cost of care was analyzed via analysis of covariance comparing total cost of care for 12 weeks between the 2 groups. The incidence of PSC was analyzed via Barnard's exact test comparing the incidence of PSCs between the control and treatment groups. Tertiary outcomes were exploratory in nature and not statistically powered. RESULTS: Use of the ceramide-infused barrier significantly reduced stoma-related cost of care over a 12-week period, resulting in a $36.46 decrease in cost (14% relative decrease). The adjusted average costs were $223.73 in the treatment group and $260.19 in the control group (P = .017). The overall incidence of PSCs in the study was 47.7%; PSC incidence was 40.5% for the treatment group versus 55.4% for controls (P = .069, 95% confidence interval of the difference: −1.2 to 30.4). Significantly more participants using the ceramide-infused skin barrier were “very satisfied” with barrier performance (75% vs 55%; P = .033), prevention of leakage (63% vs 38%; P < .01), and prevention of itching (53% vs 31%; P = .016). General postoperative improvement in health-related quality of life was noted in both groups. CONCLUSIONS: The use of a ceramide-infused barrier significantly decreased cost and increased satisfaction with patient-reported outcomes. PMID:29300287

Cluster randomized controlled trial of a peer support program for people with diabetes: study protocol for the Australasian peers for progress study

PubMed Central

2012-01-01

Background Well managed diabetes requires active self-management in order to ensure optimal glycaemic control and appropriate use of available clinical services and other supports. Peer supporters can assist people with their daily diabetes self-management activities, provide emotional and social support, assist and encourage clinical care and be available when needed. Methods A national database of Australians diagnosed with type 2 diabetes is being used to invite people in pre-determined locations to participate in community-based peer support groups. Peer supporters are self-identified from these communities. All consenting participants receive diabetes self-management education and education manual prior to randomization by community to a peer support intervention or usual care. This multi-faceted intervention comprises four interconnected components for delivering support to the participants. (1) Trained supporters lead 12 monthly group meetings. Participants are assisted to set goals to improve diabetes self-management, discuss with and encourage each other to strengthen linkages with local clinical services (including allied health services) as well as provide social and emotional support. (2) Support through regular supporter-participant or participant-participant contact, between monthly sessions, is also promoted in order to maintain motivation and encourage self-improvement and confidence in diabetes self-management. (3) Participants receive a workbook containing diabetes information, resources and community support services, key diabetes management behaviors and monthly goal setting activity sheets. (4) Finally, a password protected website contains further resources for the participants. Supporters are mentored and assisted throughout the intervention by other supporters and the research team through attendance at a weekly teleconference. Data, including a self-administered lifestyle survey, anthropometric and biomedical measures are collected on all participants at baseline, 6 and 12 months. The primary outcome is change in cardiovascular disease risk using the UKPDS risk equation. Secondary outcomes include biomedical, quality of life, psychosocial functioning, and other lifestyle measures. An economic evaluation will determine whether the program is cost effective. Discussion This manuscript presents the protocol for a cluster randomized controlled trial of group-based peer support for people with type 2 diabetes in a community setting. Results from this trial will contribute evidence about the effectiveness of peer support in achieving effective self-management of diabetes. Trial registration number Australian New Zealand Clinical Trials Registry (ANZCTR); ACTRN12609000469213 PMID:23035666

Routine antibiotic prophylaxis after normal vaginal birth for reducing maternal infectious morbidity.

PubMed

Bonet, Mercedes; Ota, Erika; Chibueze, Chioma E; Oladapo, Olufemi T

2017-11-13

Infectious morbidities contribute to considerable maternal and perinatal morbidity and mortality, including women at no apparent increased risk of infection. To reduce the incidence of infections, antibiotics are often administered to women after uncomplicated childbirth, particularly in settings where women are at higher risk of puerperal infectious morbidities. To assess whether routine administration of prophylactic antibiotics to women after normal (uncomplicated) vaginal birth, compared with placebo or no antibiotic prophylaxis, reduces postpartum maternal infectious morbidities and improves outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2017), LILACS, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (22 August 2017) and reference lists of retrieved studies. We planned to include randomised or quasi-randomised trials evaluating the use of prophylactic antibiotics versus placebo or no antibiotic prophylaxis. Trials using a cluster-randomised design would have been eligible for inclusion, but we found none.In future updates of this review, we will include studies published in abstract form only, provided sufficient information is available to assess risks of bias. We will consider excluded abstracts for inclusion once the full publication is available, or the authors provide more information.Trials using a cross-over design are not eligible for inclusion in this review. Two review authors conducted independent assessment of trials for inclusion and risks of bias. They independently extracted data and checked them for accuracy, resolving differences in assessments by discussion. They evaluated methodological quality using standard Cochrane criteria and the GRADE approach.We present the summaries as risk ratios (RRs) and mean difference (MDs) using fixed- or random-effect models. For one primary outcome we found considerable heterogeneity and interaction. We explored further using subgroup analysis to investigate the effects of the randomisation unit. All review authors discussed and interpreted the results. One randomised controlled trial (RCT) and two quasi-RCTs contributed data on 1779 women who had uncomplicated vaginal births, comparing different antibiotic regimens with placebo or no treatment. The included trials took place in the 1960s (one trial) and 1990s (two trials). The trials were conducted in France, the USA and Brazil. Antibiotics administered included: oral sulphamethoxypyridazine or chloramphenicol for three to five days, and intravenous amoxicillin and clavulanic acid in a single dose one hour after birth. We rated most of the domains for risk of bias as high risk, with the exception of reporting bias and other potential bias.The quality of evidence ranged from low to very low, based on the GRADE quality assessment, given very serious design limitations of the included studies, few events and wide confidence intervals (CIs) of effect estimates.We found a decrease in the risk of endometritis (RR 0.28, 95% CI 0.09 to 0.83, two trials, 1364 women,very low quality). However, one trial reported zero events for this outcome and we rate the evidence as very low quality. There was little or no difference between groups for the risk of urinary tract infection (RR 0.25, 95% CI 0.05 to 1.19, two trials, 1706 women,low quality), wound infection after episiotomy (reported as wound dehiscence in the included trials) (RR 0.78, 95% CI 0.31 to 1.96, two trials, 1364 women, very low quality) and length of maternal hospital stay in days (MD -0.15, 95% CI -0.31 to 0.01, one trial, 1291 women, very low quality). Cost of care in US dollar equivalent was 2½ times higher in the control group compared to the group receiving antibiotics prophylaxis (USD 3600: USD 9000, one trial, 1291 women). There were few or no differences between treated and control groups for adverse effects of antibiotics (skin rash) reported in one woman in each of the two trials (RR 3.03, 95% CI 0.32 to 28.95, two trials, 1706 women, very low quality). The incidence of severe maternal infectious morbidity, antimicrobial resistance or women's satisfaction with care were not addressed by any of the included studies. Routine administration of antibiotics may reduce the risk of endometritis after uncomplicated vaginal birth. The small number and nature of the trials limit the interpretation of the evidence for application in practice, particularly in settings where women may be at higher risk of developing endometritis. The use of antibiotics did not reduce the incidence of urinary tract infections, wound infection or the length of maternal hospital stay. Antibiotics are not a substitute for infection prevention and control measures around the time of childbirth and the postpartum period. The decision to routinely administer prophylactic antibiotics after normal vaginal births needs to be balanced by patient features, childbirth setting and provider experience, including considerations of the contribution of indiscriminate use of antibiotics to raising antimicrobial resistance. Well-designed and high-powered randomised controlled trials would help to evaluate the added value of routine antibiotic administration as a measure to prevent maternal infections after normal vaginal delivery.

The CEA Second-Look Trial: a randomised controlled trial of carcinoembryonic antigen prompted reoperation for recurrent colorectal cancer

PubMed Central

Treasure, Tom; Monson, Kathryn; Fiorentino, Francesca; Russell, Christopher

2014-01-01

Objective In patients who have undergone a potentially curative resection of colorectal cancer, does a ‘second-look’ operation to resect recurrence, prompted by monthly monitoring of carcinoembryonic antigen, confer a survival benefit? Design A randomised controlled trial recruiting patients from 1982 to 1993 was recovered under the Restoring Invisible and Abandoned Trials (RIAT) initiative. Setting 58 hospitals in the UK. Participants From 1982 to 1993, 1447 patients were enrolled. Of these 216 met the criteria for carcinoembryonic antigen (CEA) elevation and were randomised to ‘Aggressive’ or ‘Conventional’ arms. Interventions ‘Second-look’ surgery with intention to remove any recurrence discovered. Primary outcome measure Survival. Results By February 1993, 91/108 patients had died in the ‘Aggressive arm’ and 88/108 in the ‘Conventional’ arm (relative risk=1.16, 95% CI 0.87 to 1.37). By 2011 a further 25 randomised patients had died. Kaplan-Meier analysis showed no difference in long-term survival. Conclusions The trial was closed in 1993 following a recommendation from the Data Monitoring Committee that it was highly unlikely that any survival advantage would be demonstrated for CEA prompted second-look surgery. This conclusion was confirmed by repeat analysis of survival times after 20 years. Trial registration number ISRCTN76694943. PMID:24823671

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

PubMed Central

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

1991-01-01

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

Barbiturates for the treatment of alcohol withdrawal syndrome: A systematic review of clinical trials.

PubMed

Mo, Yoonsun; Thomas, Michael C; Karras, George E

2016-04-01

To perform a systematic review of the clinical trials concerning the use of barbiturates for the treatment of acute alcohol withdrawal syndrome (AWS). A literature search of MEDLINE, EMBASE, and the Cochrane Library, together with a manual citation review was conducted. We selected English-language clinical trials (controlled and observational studies) evaluating the efficacy and safety of barbiturates compared with benzodiazepine (BZD) therapy for the treatment of AWS in the acute care setting. Data extracted from the included trials were duration of delirium, number of seizures, length of intensive care unit and hospital stay, cumulated doses of barbiturates and BZDs, and respiratory or cardiac complications. Seven studies consisting of 4 prospective controlled and 3 retrospective trials were identified. Results from all the included studies suggest that barbiturates alone or in combination with BZDs are at least as effective as BZDs in the treatment of AWS. Furthermore, barbiturates appear to have acceptable tolerability and safety profiles, which were similar to those of BZDs in patients with AWS. Although the evidence is limited, based on our findings, adding phenobarbital to a BZD-based regimen is a reasonable option, particularly in patients with BZD-refractory AWS. Copyright © 2015 Elsevier Inc. All rights reserved.

Working memory component processes: isolating BOLD signal changes.

PubMed

Motes, Michael A; Rypma, Bart

2010-01-15

The chronology of the component processes subserving working memory (WM) and hemodynamic response lags has hindered the use of fMRI for exploring neural substrates of WM. In the present study, however, participants completed full trials that involved encoding two or six letters, maintaining the memory set over a delay, and then deciding whether a probe was in the memory set or not. Additionally, they completed encode-only, encode-and-maintain, and encode-and-decide partial trials intermixed with the full trials. The inclusion of partial trials allowed for the isolation of BOLD signal changes to the different trial periods. The results showed that only lateral and medial prefrontal cortex regions differentially responded to the 2- and 6-letter memory sets over the trial periods, showing greater activation to 6-letter sets during the encode and maintain trial periods. Thus, the data showed the differential involvement of PFC in the encoding and maintenance of supra- and sub-capacity memory sets and show the efficacy of using fMRI partial trial methods to study WM component processes.

Working Memory Component Processes: Isolating BOLD Signal-Changes

PubMed Central

Motes, Michael A.; Rypma, Bart

2009-01-01

The chronology of the component processes subserving working memory (WM) and hemodynamic response lags have hindered the use of fMRI for exploring neural substrates of WM. In the present study, however, participants completed full trials that involved encoding two or six letters, maintaining the memory-set over a delay, and then deciding whether a probe was in the memory-set or not. Additionally, they completed encode only, encode and maintain, and encode and decide partial-trials intermixed with the full-trials. The inclusion of partial-trials allowed for the isolation of BOLD signal-changes to the different trial-periods. The results showed that only lateral and medial prefrontal cortex regions differentially responded to the 2- and 6-letter memory-sets over the trial-periods, showing greater activation to 6-letter sets during the encode and maintain trial-periods. Thus, the data showed the differential involvement of PFC in the encoding and maintenance of supra- and sub-capacity memory-sets and show the efficacy of using fMRI partial-trial methods to study WM component processes. PMID:19732840

Social Stories™ to alleviate challenging behaviour and social difficulties exhibited by children with autism spectrum disorder in mainstream schools: design of a manualised training toolkit and feasibility study for a cluster randomised controlled trial with nested qualitative and cost-effectiveness components.

PubMed

Wright, Barry; Marshall, David; Adamson, Joy; Ainsworth, Hannah; Ali, Shehzad; Allgar, Victoria; Collingridge Moore, Danielle; Cook, Elizabeth; Dempster, Paul; Hackney, Lisa; McMillan, Dean; Trepél, Dominic; Williams, Chris

2016-01-01

A Social Story™ (Carol Gray) is a child-friendly intervention that is used to give children with autism spectrum disorders (ASDs) social information in situations where they have social difficulties. Limited evidence mainly using single-case designs suggests that they can reduce anxiety and challenging behaviour. The objectives were to conduct a systematic review, use this to develop a manualised intervention and run a feasibility trial to inform a fully powered randomised controlled trial (RCT) on their clinical effectiveness and cost-effectiveness in schools. This is a three-stage study following the Medical Research Council framework for complex interventions. Specifically, it involved a theoretical phase, a qualitative stage and a feasibility trial stage. Qualitative interviews and focus groups took place in Child and Adolescent Mental Health Service and primary care settings. The feasibility study took place in 37 local mainstream schools. Fifty children (aged 5-15 years) in mainstream school settings with a diagnosis of ASD were entered into the trial. For each child, an associated teacher and parent was also recruited. The intervention was a goal-setting session followed by a manualised toolkit (including a training session) for creating Social Stories™ for use with school-aged children. The comparator treatment was a goal-setting session followed by an attention control. Both arms received treatment as usual. Outcomes tested as part of the feasibility study included child- and proxy-completed questionnaires for mental health, quality of life and goal-based outcome measures. Adults additionally completed behaviour diaries and the parental stress index. The review found that the research into social stories is predominantly based in the USA, carried out in under-12-year-olds and using single-case designs. Most studies either did not follow established Social Story criteria or did not report if they did. The assessment of effectiveness presents a largely positive picture but is limited by methodological issues. There were no adequate RCTs and insufficient information to assess a number of important sources of potential bias in most studies. A manualised intervention was produced using an iterative process between user focus groups and a writing team, and assessed in the feasibility study. All 50 participant groups were recruited within the study time frame. Two outcome measures, the Social Responsiveness Scale-2 and the custom-made goal-based measure, showed high levels of completion rates and appeared to be capturing social and behaviour skills targeted by the use of Social Stories. Detailed recommendations for a full trial are provided. Blinding of participants was not feasible. Treatment fidelity was not assessed because of low levels of story return rates. The study showed that a fully powered RCT is feasible with an extended geographical footprint. A large amount of data and information has helped to inform the design of this RCT, which will be the subject of a future research grant application. Future work could focus on developing an appropriate blinded outcome measure for this population. This study is registered as PROSPERO CRD42011001440. Current Controlled Trials ISRCTN96286707. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 6. See the NIHR Journals Library website for further project information.

Effect of Integrated Approach of Yoga Therapy on Male Obesity and Psychological Parameters-A Randomised Controlled Trial

PubMed Central

Subramanya, Pailoor

2016-01-01

Introduction Obesity is a growing global epidemic and cause of non-communicable diseases. Yoga is one of the effective ways to reduce stress which is one of the causes of obesity. Aim To assess the effect of Integrated Approach of Yoga Therapy (IAYT) yoga module on adult male obesity in an urban setting. Materials and Methods RCT (Randomized Controlled Trial) was conducted for 14 weeks on obese male subjects with yoga and control groups. Total number of subjects were 72 and they were randomized into two groups (Yoga n=37, Control n=35). The subjects were from an urban setting of Mumbai and were doing yoga for the first time. Special yoga training of IAYT was given to yoga group for one and half hour for 5 days in a week for 14 weeks. The control group continued regular physical activities and no specific physical activity was given. The assessments were anthropometric parameters of weight, Body Mass Index (BMI), MAC (Mid Upper Arm Circumferences) of Left and Right Arm, Waist Circumference (WC), HC (Hip Circumference), WHR (Waist Hip Ratio), SKF(Skin Fold Thickness of Biceps, Triceps, Sub scapular, suprailiac and cumulative), Percentage body fat based on SKF and Psychological Questionnaires of Perceived Stress Scale (PSS) and AAQW (Acceptance and Action Questionnaire for Weight Related Difficulty). These were taken before and after intervention for both yoga and control groups. Within and between group analysis & correlation of differences from post to pre readings among the variables, were carried out using SPSS 21. Results The anthropometric and psychological parameters were improved in both the groups but changes were significant in yoga group. Conclusion Incorporating the IAYT for obese male in urban setting will be effective for obesity treatment and for reducing the obesity related problems. PMID:27891357

Feasibility of a patient-centred nutrition intervention to improve oral intakes of patients at risk of pressure ulcer: a pilot randomised control trial.

PubMed

Roberts, Shelley; Desbrow, Ben; Chaboyer, Wendy

2016-06-01

Nutrition is important for pressure ulcer prevention. This randomised control pilot study assessed the feasibility of conducting a larger trial to test the effectiveness of a patient-centred intervention for improving the dietary intakes of patients at risk of pressure ulcer in hospital. A 3-day intervention targeting patients at risk of pressure ulcer was developed, based on three main foundations: patient education, patient participation and guided goal setting. The intervention was piloted in three wards in a metropolitan hospital in Queensland, Australia. Participants were randomised into control or intervention groups and had their oral intakes monitored. A subset of intervention patients was interviewed on their perceptions of the intervention. Feasibility was tested against three criteria: ≥75% recruitment; ≥80% retention; and ≥80% intervention fidelity. Secondary outcomes related to effects on energy and protein intakes. Eighty patients participated in the study and 66 were included in final analysis. The recruitment rate was 82%, retention rate was 88%, and 100% of intervention patients received the intervention. Patients viewed the intervention as motivating and met significantly more of their estimated energy and protein requirements over time. This pilot study indicates that the intervention is feasible and acceptable by patients at risk of pressure ulcer. A larger trial is needed to confirm the effectiveness of the intervention in the clinical setting. © 2015 Nordic College of Caring Science.

Dissociative Global and Local Task-Switching Costs Across Younger Adults, Middle-Aged Adults, Older Adults, and Very Mild Alzheimer Disease Individuals

PubMed Central

Huff, Mark J.; Balota, David A.; Minear, Meredith; Aschenbrenner, Andrew J.; Duchek, Janet M.

2015-01-01

A task-switching paradigm was used to examine differences in attentional control across younger adults, middle-aged adults, healthy older adults, and individuals classified in the earliest detectable stage of Alzheimer's disease (AD). A large sample of participants (570) completed a switching task in which participants were cued to classify the letter (consonant/vowel) or number (odd/even) task-set dimension of a bivalent stimulus (e.g., A 14), respectively. A Pure block consisting of single-task trials and a Switch block consisting of nonswitch and switch trials were completed. Local (switch vs. nonswitch trials) and global (nonswitch vs. pure trials) costs in mean error rates, mean response latencies, underlying reaction time distributions, along with stimulus-response congruency effects were computed. Local costs in errors were group invariant, but global costs in errors systematically increased as a function of age and AD. Response latencies yielded a strong dissociation: Local costs decreased across groups whereas global costs increased across groups. Vincentile distribution analyses revealed that the dissociation of local and global costs primarily occurred in the slowest response latencies. Stimulus-response congruency effects within the Switch block were particularly robust in accuracy in the very mild AD group. We argue that the results are consistent with the notion that the impaired groups show a reduced local cost because the task sets are not as well tuned, and hence produce minimal cost on switch trials. In contrast, global costs increase because of the additional burden on working memory of maintaining two task sets. PMID:26652720

A complex breastfeeding promotion and support intervention in a developing country: study protocol for a randomized clinical trial

PubMed Central

2014-01-01

Background Breastfeeding has countless benefits to mothers, children and community at large, especially in developing countries. Studies from Lebanon report disappointingly low breastfeeding exclusivity and continuation rates. Evidence reveals that antenatal breastfeeding education, professional lactation support, and peer lay support are individually effective at increasing breastfeeding duration and exclusivity, particularly in low-income settings. Given the complex nature of the breastfeeding ecosystem and its barriers in Lebanon, we hypothesize that a complex breastfeeding support intervention, which is centered on the three components mentioned above, would significantly increase breastfeeding rates. Methods/Design A multi-center randomized controlled trial. Study population: 443 healthy pregnant women in their first trimester will be randomized to control or intervention group. Intervention: A “prenatal/postnatal” professional and peer breastfeeding support package continuing till 6 months postpartum, guided by the Social Network and Social Support Theory. Control group will receive standard prenatal and postnatal care. Mothers will be followed up from early pregnancy till five years after delivery. Outcome measures: Total and exclusive breastfeeding rates, quality of life at 1, 3 and 6 months postpartum, maternal breastfeeding knowledge and attitudes at 6 months postpartum, maternal exclusive breastfeeding rates of future infants up to five years from baseline, cost-benefit and cost-effectiveness analyses of the intervention. Statistical analysis: Descriptive and regression analysis will be conducted under the intention to treat basis using the most recent version of SPSS. Discussion Exclusive breastfeeding is a cost-effective public health measure that has a significant impact on infant morbidity and mortality. In a country with limited healthcare resources like Lebanon, developing an effective breastfeeding promotion and support intervention that is easily replicated across various settings becomes a priority. If positive, the results of this study would provide a generalizable model to bolster breastfeeding promotion efforts and contribute to improved child health in Lebanon and the Middle East and North Africa (MENA) region. Trial registration Current Controlled Trials ISRCTN17875591 PMID:24428951

Comparison of Urinary Tract Infection Rates Associated with Transurethral Catheterization, Suprapubic Tube and Clean Intermittent Catheterization in the Postoperative Setting: A Network Meta-Analysis.

PubMed

Han, Christopher S; Kim, Sinae; Radadia, Kushan D; Zhao, Philip T; Elsamra, Sammy E; Olweny, Ephrem O; Weiss, Robert E

2017-12-01

We performed a network meta-analysis of available randomized, controlled trials to elucidate the risks of urinary tract infection associated with transurethral catheterization, suprapubic tubes and intermittent catheterization in the postoperative setting. PubMed®, EMBASE® and Google Scholar™ searches were performed for eligible randomized, controlled trials from January 1980 to July 2015 that included patients who underwent transurethral catheterization, suprapubic tube placement or intermittent catheterization at the time of surgery and catheterization lasting up to postoperative day 30. The primary outcome of comparison was the urinary tract infection rate via a network meta-analysis with random effects model using the netmeta package in R 3.2 (www.r-project.org/). Included in analysis were 14 randomized, controlled trials in a total of 1,391 patients. Intermittent catheterization and suprapubic tubes showed no evidence of decreased urinary tract infection rates compared to transurethral catheterization. Suprapubic tubes and intermittent catheterization had comparable urinary tract infection rates (OR 0.903, 95% CI 0.479-2.555). On subgroup analysis of 10 randomized, controlled trials with available mean catheterization duration data in a total of 928 patients intermittent catheterization and suprapubic tube were associated with significantly decreased risk of urinary tract infection compared to transurethral catheterization when catheterization duration was greater than 5 days (OR 0.173, 95% CI 0.073-0.412 and OR 0.142, 95% CI 0.073-0.276, respectively). Transurethral catheterization is not associated with an increased urinary tract infection risk compared to suprapubic tubes and intermittent catheterization if catheterization duration is 5 days or less. However, a suprapubic tube or intermittent catheterization is associated with a lower rate of urinary tract infection if longer term catheterization is expected in the postoperative period. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2015-01-01

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

A Powered Prosthetic Intervention for Bilateral Transfemoral Amputees

PubMed Central

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

2014-01-01

This paper presents the design and validation of a control system for a pair of powered knee and ankle prostheses to be used as a prosthetic intervention for bilateral transfemoral amputees. The control system leverages communication between the prostheses for enhanced awareness and stability, along with power generation at the knee and ankle joints to better restore biomechanical functionality in level ground walking. The control methodology employed is a combination of an impedance-based framework for weight-bearing portions of gait and a trajectory-based approach for the non-weight-bearing portions. The control system was implemented on a pair of self-contained powered knee and ankle prostheses, and the ability of the prostheses and control approach to provide walking functionality was assessed in a set of experimental trials with a bilateral transfemoral amputee subject. Specifically, experimental data from these trials indicate that the powered prostheses and bilateral control architecture provide gait kinematics that reproduce healthy gait kinematics to a greater extent than the subject’s daily-use passive prostheses. PMID:25014950

Mechanisms underlying flexible adaptation of cognitive control: behavioral and neuroimaging evidence in a flanker task.

PubMed

Zurawska Vel Grajewska, Blandyna; Sim, Eun-Jin; Hoenig, Klaus; Herrnberger, Bärbel; Kiefer, Markus

2011-11-03

Cognitive control can be adapted flexibly according to the conflict level in a given situation. In the Eriksen flanker task, interference evoked by flankers is larger in conditions with a higher, rather than a lower proportion of compatible trials. Such compatibility ratio effects also occur for stimuli presented at two spatial locations suggesting that different cognitive control settings can be simultaneously maintained. However, the conditions and the neural correlates of this flexible adaptation of cognitive control are only poorly understood. In the present study, we further elucidated the mechanisms underlying the simultaneous maintenance of two cognitive control settings. In behavioral experiments, stimuli were presented centrally above and below fixation and hence processed by both hemispheres or lateralized to stimulate hemispheres differentially. The different compatibility ratio at two stimulus locations had a differential influence on the flanker effect in both experiments. In an fMRI experiment, blocks with an identical compatibility ratio at two central spatial locations elicited stronger activity in a network of prefrontal and parietal brain areas, which are known to be involved in conflict resolution and cognitive control, as compared with blocks with a different compatibility ratio at the same spatial locations. This demonstrates that the simultaneous maintenance of two conflicting control settings vs. one single setting does not recruit additional neural circuits suggesting the involvement of one single cognitive control system. Instead a crosstalk between multiple control settings renders adaptation of cognitive control more efficient when only one uniform rather than two different control settings has to be simultaneously maintained. Copyright © 2011 Elsevier B.V. All rights reserved.

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

HIV prevention trial design in an era of effective pre-exposure prophylaxis.

PubMed

Cutrell, Amy; Donnell, Deborah; Dunn, David T; Glidden, David V; Grobler, Anneke; Hanscom, Brett; Stancil, Britt S; Meyer, R Daniel; Wang, Ronnie; Cuffe, Robert L

2017-01-01

Pre-exposure prophylaxis (PrEP) has demonstrated remarkable effectiveness protecting at-risk individuals from HIV-1 infection. Despite this record of effectiveness, concerns persist about the diminished protective effect observed in women compared with men and the influence of adherence and risk behaviors on effectiveness in targeted subpopulations. Furthermore, the high prophylactic efficacy of the first PrEP agent, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), presents challenges for demonstrating the efficacy of new candidates. Trials of new agents would typically require use of non-inferiority (NI) designs in which acceptable efficacy for an experimental agent is determined using pre-defined margins based on the efficacy of the proven active comparator (i.e. TDF/FTC) in placebo-controlled trials. Setting NI margins is a critical step in designing registrational studies. Under- or over-estimation of the margin can call into question the utility of the study in the registration package. The dependence on previous placebo-controlled trials introduces the same issues as external/historical controls. These issues will need to be addressed using trial design features such as re-estimated NI margins, enrichment strategies, run-in periods, crossover between study arms, and adaptive re-estimation of sample sizes. These measures and other innovations can help to ensure that new PrEP agents are made available to the public using stringent standards of evidence.

Effects of preparation time and trial type probability on performance of anti- and pro-saccades.

PubMed

Pierce, Jordan E; McDowell, Jennifer E

2016-02-01

Cognitive control optimizes responses to relevant task conditions by balancing bottom-up stimulus processing with top-down goal pursuit. It can be investigated using the ocular motor system by contrasting basic prosaccades (look toward a stimulus) with complex antisaccades (look away from a stimulus). Furthermore, the amount of time allotted between trials, the need to switch task sets, and the time allowed to prepare for an upcoming saccade all impact performance. In this study the relative probabilities of anti- and pro-saccades were manipulated across five blocks of interleaved trials, while the inter-trial interval and trial type cue duration were varied across subjects. Results indicated that inter-trial interval had no significant effect on error rates or reaction times (RTs), while a shorter trial type cue led to more antisaccade errors and faster overall RTs. Responses following a shorter cue duration also showed a stronger effect of trial type probability, with more antisaccade errors in blocks with a low antisaccade probability and slower RTs for each saccade task when its trial type was unlikely. A longer cue duration yielded fewer errors and slower RTs, with a larger switch cost for errors compared to a short cue duration. Findings demonstrated that when the trial type cue duration was shorter, visual motor responsiveness was faster and subjects relied upon the implicit trial probability context to improve performance. When the cue duration was longer, increased fixation-related activity may have delayed saccade motor preparation and slowed responses, guiding subjects to respond in a controlled manner regardless of trial type probability. Copyright © 2016 Elsevier B.V. All rights reserved.

Highly Efficient Training, Refinement, and Validation of a Knowledge-based Planning Quality-Control System for Radiation Therapy Clinical Trials

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

Li, Nan; Carmona, Ruben; Sirak, Igor

Purpose: To demonstrate an efficient method for training and validation of a knowledge-based planning (KBP) system as a radiation therapy clinical trial plan quality-control system. Methods and Materials: We analyzed 86 patients with stage IB through IVA cervical cancer treated with intensity modulated radiation therapy at 2 institutions according to the standards of the INTERTECC (International Evaluation of Radiotherapy Technology Effectiveness in Cervical Cancer, National Clinical Trials Network identifier: 01554397) protocol. The protocol used a planning target volume and 2 primary organs at risk: pelvic bone marrow (PBM) and bowel. Secondary organs at risk were rectum and bladder. Initial unfiltered dose-volumemore » histogram (DVH) estimation models were trained using all 86 plans. Refined training sets were created by removing sub-optimal plans from the unfiltered sample, and DVH estimation models… and DVH estimation models were constructed by identifying 30 of 86 plans emphasizing PBM sparing (comparing protocol-specified dosimetric cutpoints V{sub 10} (percentage volume of PBM receiving at least 10 Gy dose) and V{sub 20} (percentage volume of PBM receiving at least 20 Gy dose) with unfiltered predictions) and another 30 of 86 plans emphasizing bowel sparing (comparing V{sub 40} (absolute volume of bowel receiving at least 40 Gy dose) and V{sub 45} (absolute volume of bowel receiving at least 45 Gy dose), 9 in common with the PBM set). To obtain deliverable KBP plans, refined models must inform patient-specific optimization objectives and/or priorities (an auto-planning “routine”). Four candidate routines emphasizing different tradeoffs were composed, and a script was developed to automatically re-plan multiple patients with each routine. After selection of the routine that best met protocol objectives in the 51-patient training sample (KBP{sub FINAL}), protocol-specific DVH metrics and normal tissue complication probability were compared for original versus KBP{sub FINAL} plans across the 35-patient validation set. Paired t tests were used to test differences between planning sets. Results: KBP{sub FINAL} plans outperformed manual planning across the validation set in all protocol-specific DVH cutpoints. The mean normal tissue complication probability for gastrointestinal toxicity was lower for KBP{sub FINAL} versus validation-set plans (48.7% vs 53.8%, P<.001). Similarly, the estimated mean white blood cell count nadir was higher (2.77 vs 2.49 k/mL, P<.001) with KBP{sub FINAL} plans, indicating lowered probability of hematologic toxicity. Conclusions: This work demonstrates that a KBP system can be efficiently trained and refined for use in radiation therapy clinical trials with minimal effort. This patient-specific plan quality control resulted in improvements on protocol-specific dosimetric endpoints.« less

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

PubMed

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

2015-08-17

The purpose of this paper is to examine potential threats to generalisability of the results of a multicentre randomised controlled trial using data from A Very Early Rehabilitation Trial (AVERT). AVERT is a prospective, parallel group, assessor-blinded randomised clinical trial. This paper presents data assessing the generalisability of AVERT. Acute stroke units at 44 hospitals in 8 countries. The first 20,000 patients screened for AVERT, of whom 1158 were recruited and randomised. We use the Proximal Similarity Model, which considers the person, place, and setting and practice, as a framework for considering generalisability. As well as comparing the recruited patients with the target population, we also performed an exploratory analysis of the demographic, clinical, site and process factors associated with recruitment. The demographics and stroke characteristics of the included patients in the trial were broadly similar to population-based norms, with the exception that AVERT had a greater proportion of men. The most common reason for non-recruitment was late arrival to hospital (ie, >24 h). Overall, being older and female reduced the odds of recruitment to the trial. More women than men were excluded for most of the reasons, including refusal. The odds of exclusion due to early deterioration were particularly high for those with severe stroke (OR=10.4, p<0.001, 95% CI 9.27 to 11.65). A model which explores person, place, and setting and practice factors can provide important information about the external validity of a trial, and could be applied to other clinical trials. Australian New Zealand Clinical Trials Registry (ACTRN12606000185561) and Clinicaltrials.gov (NCT01846247). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Contextual control over task-set retrieval.

PubMed

Crump, Matthew J C; Logan, Gordon D

2010-11-01

Contextual cues signaling task likelihood or the likelihood of task repetition are known to modulate the size of switch costs. We follow up on the finding by Leboe, Wong, Crump, and Stobbe (2008) that location cues predictive of the proportion of switch or repeat trials modulate switch costs. Their design employed one cue per task, whereas our experiment employed two cues per task, which allowed separate assessment of modulations to the cue-repetition benefit, a measure of lower level cue-encoding processes, and to the task-alternation cost, a measure of higher level processes representing task-set information. We demonstrate that location information predictive of switch proportion modulates performance at the level of task-set representations. Furthermore, we demonstrate that contextual control occurs even when subjects are unaware of the associations between context and switch likelihood. We discuss the notion that contextual information provides rapid, unconscious control over the extent to which prior task-set representations are retrieved in the service of guiding online performance.

Enhanced curriculum intervention did not result in increased postnatal physical activity in rural, Southern, primarily African American women

USDA-ARS?s Scientific Manuscript database

Purpose. To test the impact of two home visiting curricula on postnatal physical activity in rural, Southern, African American mothers. Design. Randomized controlled trial. Setting. Three rural counties in Mississippi. Subjects. Between September 2013 and May 2016, 54 postpartum women randomized...

A Systematic Review of Stress-Management Programs for Medical Students

ERIC Educational Resources Information Center

Shiralkar, Malan T.; Harris, Toi B.; Eddins-Folensbee, Florence F.; Coverdale, John H.

2013-01-01

Objective: Because medical students experience a considerable amount of stress during training, academic leaders have recognized the importance of developing stress-management programs for medical students. The authors set out to identify all controlled trials of stress-management interventions and determine the efficacy of those interventions.…

Pilot evaluation of a walking school bus program in a low-income, urban community

USDA-ARS?s Scientific Manuscript database

Our objective was to evaluate the impact of a walking school bus (WSB) program on student transport in a low-income, urban neighborhood. The design was a controlled, quasi-experimental trial with consecutive cross-sectional assessments. The setting was three urban, socioeconomically disadvantaged, p...

Methodological Foundations for the Empirical Evaluation of Non-Experimental Methods in Field Settings

ERIC Educational Resources Information Center

Wong, Vivian C.; Steiner, Peter M.

2015-01-01

Across the disciplines of economics, political science, public policy, and now, education, the randomized controlled trial (RCT) is the preferred methodology for establishing causal inference about program impacts. But randomized experiments are not always feasible because of ethical, political, and/or practical considerations, so non-experimental…

A Randomized Control Trial Of A community Mental Health Intervention For Military Personnel

DTIC Science & Technology

2011-10-01

findings for this study for this reporting period. Mental health literacy , Mental Health First Aid (MHFA), curriculum adaptation 6 DMohatt@wiche.edu 3...collection instruments to assess impact of mental health literacy program in the military setting. REPORTABLE OUTCOMES: None at this time

Conducting Randomized Controlled Trials with Offenders in an Administrative Setting

ERIC Educational Resources Information Center

Ahlin, Eileen M.

2015-01-01

Evaluation research conducted in agencies that sanction law violators is often challenging and due process may preclude evaluators from using experimental methods in traditional criminal justice agencies such as police, courts, and corrections. However, administrative agencies often deal with the same population but are not bound by due process…

Neural Correlates of Set-Shifting in Children With Autism.

PubMed

Yerys, Benjamin E; Antezana, Ligia; Weinblatt, Rachel; Jankowski, Kathryn F; Strang, John; Vaidya, Chandan J; Schultz, Robert T; Gaillard, William D; Kenworthy, Lauren

2015-08-01

Autism spectrum disorder (ASD) is often associated with high levels of inflexible thinking and rigid behavior. The neural correlates of these behaviors have been investigated in adults and older adolescents, but not children. Prior studies utilized set-shifting tasks that engaged multiple levels of shifting, and depended on learning abstract rules and establishing a strong prepotent bias. These additional demands complicate simple interpretations of the results. We used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of set-shifting in 20 children (ages 7-14) with ASD and 19 typically developing, matched, control children. Participants completed a set-shifting task that minimized nonshifting task demands through the use of concrete instructions that provide spatial mapping of stimuli-responses. The shift/stay sets were given an equal number of trials to limit the prepotent bias. Both groups showed an equivalent "switch cost," responding less accurately and slower to Switch stimuli than Stay stimuli, although the ASD group was less accurate overall. Both groups showed activation in prefrontal, striatal, parietal, and cerebellum regions known to govern effective set-shifts. Compared to controls, children with ASD demonstrated decreased activation of the right middle temporal gyrus across all trials, but increased activation in the mid-dorsal cingulate cortex/superior frontal gyrus, left middle frontal, and right inferior frontal gyri during the Switch vs. Stay contrast. The successful behavioral switching performance of children with ASD comes at the cost of requiring greater engagement of frontal regions, suggesting less efficiency at this lowest level of shifting. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Neural correlates of set-shifting in children with autism

PubMed Central

Yerys, Benjamin E.; Antezana, Ligia; Weinblatt, Rachel; Jankowski, Kathryn F.; Strang, John; Vaidya, Chandan J.; Schultz, Robert T.; Gaillard, William D.; Kenworthy, Lauren

2015-01-01

Autism spectrum disorder (ASD) is often associated with high levels of inflexible thinking and rigid behavior. The neural correlates of these behaviors have been investigated in adults and older adolescents, but not children. Prior studies utilized set-shifting tasks that engaged multiple levels of shifting, and depended on learning abstract rules and establishing a strong prepotent bias. These additional demands complicate simple interpretations of the results. We used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of set-shifting in 20 children (ages 7-14) with ASD and 19 typically developing, matched, control children. Participants completed a set-shifting task that minimized non-shifting task demands through the use of concrete instructions that provide spatial mapping of stimuli-responses. The shift/stay sets were given an equal number of trials to limit the prepotent bias. Both groups showed an equivalent ‘switch cost’, responding less accurately and slower to Switch stimuli than Stay stimuli, although the ASD group was less accurate overall. Both groups showed activation in prefrontal, striatal, parietal, and cerebellum regions known to govern effective set-shifts. Compared to controls, children with ASD demonstrated decreased activation of the right middle temporal gyrus across all trials, but increased activation in the mid-dorsal cingulate cortex/superior frontal gyrus, left middle frontal and right inferior frontal gyri during the Switch vs. Stay contrast. The successful behavioral switching performance of children with ASD comes at the cost of requiring greater engagement of frontal regions, suggesting less efficiency at this lowest level of shifting. PMID:25599972

Learning Dynamic Control of Body Roll Orientation

PubMed Central

Vimal, Vivekanand Pandey; Lackner, James R.; DiZio, Paul

2016-01-01

Our objective was to examine how the control of orientation is learned in a task involving dynamically balancing about an unstable equilibrium point, the gravitational vertical, in the absence of leg reflexes and muscle stiffness. Subjects (n=10) used a joystick to set themselves to the gravitational vertical while seated in a multi-axis rotation system device (MARS) programmed with inverted pendulum dynamics. The MARS is driven by powerful servomotors and can faithfully follow joystick commands up to 2.5 Hz with a 30 ms latency. To make the task extremely difficult, the pendulum constant was set to 600°/sec2. Each subject participated in 5 blocks of 4 trials, with a trial ending after a cumulative 100 s of balancing, excluding reset times when a subject lost control. To characterize performance and learning, we used metrics derived from joystick movements, phase portraits (joystick deflections vs MARS position and MARS velocity vs angular position), and stabilogram diffusion functions. We found that as subjects improved their balancing performance they did so by making fewer destabilizing joystick movements and reducing the number and duration of joystick commands. The control strategy they acquired involved making more persistent short-term joystick movements, waiting longer before making changes to ongoing motion, and only intervening intermittently. PMID:26525709

Supervising for Home Safety Program: A Randomized Controlled Trial (RCT) Testing Community-Based Group Delivery.

PubMed

Morrongiello, Barbara A; Hou, Sharon; Bell, Melissa; Walton, Kathryn; Filion, A Jordan; Haines, Jess

2017-08-01

The individually delivered Supervising for Home Safety (SHS) program improves caregivers' injury-related beliefs and supervision practices. The current randomized controlled trial used a group delivery in a community setting and assessed program impact, feasibility, and acceptance. Caregivers of 2-5-year-olds were randomized to receive either the SHS or an attention-matched control program. In the SHS group only, there were increases from baseline to postintervention in the following: beliefs about children's vulnerability to injury, caregiver preventability of injuries, and self-efficacy to do so; readiness for change in supervision; and watchful supervision. Face-to-face recruitment by staff at community organizations proved most successful. Caregivers' satisfaction ratings were high, as was caregiver engagement (95% completed at least seven of the nine sessions). The SHS program can be delivered to groups of caregivers in community settings, is positively received by caregivers, and produces desirable changes that can be expected to improve caregivers' home safety practices. © The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

The impact of a home visitation programme on household hazards associated with unintentional childhood injuries: a randomised controlled trial.

PubMed

Odendaal, Willem; van Niekerk, Ashley; Jordaan, Esme; Seedat, Mohamed

2009-01-01

The continued high mortality and morbidity rates for unintentional childhood injuries remain a public health concern. This article reports on the influence of a home visitation programme (HVP) on household hazards associated with unintentional childhood injuries in a South African low-income setting. A randomised controlled trial (n=211 households) was conducted in a South African informal settlement. Community members were recruited and trained as paraprofessional visitors. Four intervention visits were conducted over 3 months, focusing on child development, and the prevention of burn, poison, and fall injuries. The HVP, a multi-component intervention, included educational inputs, provision of safety devices, and an implicit enforcement strategy. The intervention effect (IE) was measured with a standardised risk assessment index that compared post-intervention scores for intervention and control households. A significant reduction was observed in the hazards associated with electrical and paraffin appliances, as well as in hazards related to poisoning. Non-significant changes were observed for burn safety household practices and fall injury hazards. This study confirmed that a multi-component HVP effectively reduced household hazards associated with electrical and paraffin appliances and poisoning among children in a low-income South African setting.

Generalizing attentional control across dimensions and tasks: evidence from transfer of proportion-congruent effects.

PubMed

Wühr, Peter; Duthoo, Wout; Notebaert, Wim

2015-01-01

Three experiments investigated transfer of list-wide proportion congruent (LWPC) effects from a set of congruent and incongruent items with different frequency (inducer task) to a set of congruent and incongruent items with equal frequency (diagnostic task). Experiments 1 and 2 mixed items from horizontal and vertical Simon tasks. Tasks always involved different stimuli that varied on the same dimension (colour) in Experiment 1 and on different dimensions (colour, shape) in Experiment 2. Experiment 3 mixed trials from a manual Simon task with trials from a vocal Stroop task, with colour being the relevant stimulus in both tasks. There were two major results. First, we observed transfer of LWPC effects in Experiments 1 and 3, when tasks shared the relevant dimension, but not in Experiment 2. Second, sequential modulations of congruency effects transferred in Experiment 1 only. Hence, the different transfer patterns suggest that LWPC effects and sequential modulations arise from different mechanisms. Moreover, the observation of transfer supports an account of LWPC effects in terms of list-wide cognitive control, while being at odds with accounts in terms of stimulus-response (contingency) learning and item-specific control.

Use of a goal setting intervention to increase adherence to low back pain rehabilitation: a randomized controlled trial.

PubMed

Coppack, Russell J; Kristensen, Jakob; Karageorghis, Costas I

2012-11-01

To examine the effects of a goal setting intervention on self-efficacy, treatment efficacy, adherence and treatment outcome in patients undergoing low back pain rehabilitation. A mixed-model 2 (time) × 3 (group) randomized controlled trial. A residential rehabilitation centre for military personnel. UK military personnel volunteers (N = 48); mean age was 32.9 (SD 7.9) with a diagnosis of non-specific low back pain. Subjects were randomly assigned to either a goal setting experimental group (Exp, n = 16), therapist-led exercise therapy group (C1, n = 16) or non-therapist-led exercise therapy group (C2, n = 16). Treatment duration for all groups was three weeks. Self-efficacy, treatment efficacy and treatment outcome were recorded before and after the treatment period. Adherence was rated during regularly scheduled treatment sessions using the Sports Injury Rehabilitation Adherence Scale (SIRAS). The Biering-Sørensen test was used as the primary measure of treatment outcome. ANCOVA results showed that adherence scores were significantly higher in the experimental group (13.70 ± 1.58) compared with C2 (11.74 ± 1.35), (P < 0.025). There was no significant difference for adherence between the experimental group and C1 (P = 0.13). Self-efficacy was significantly higher in the experimental group compared to both C1 and C2 (P < 0.05), whereas no significant difference was found for treatment efficacy. Treatment outcome did not differ significantly between the experimental and two control groups. The findings provide partial support for the use of goal setting to enhance adherence in clinical rehabilitation.

Simulated impact of RTS,S/AS01 vaccination programs in the context of changing malaria transmission.

PubMed

Brooks, Alan; Briët, Olivier J T; Hardy, Diggory; Steketee, Richard; Smith, Thomas A

2012-01-01

The RTS,S/AS01 pre-erythrocytic malaria vaccine is in phase III clinical trials. It is critical to anticipate where and how it should be implemented if trials are successful. Such planning may be complicated by changing levels of malaria transmission. Computer simulations were used to examine RTS,S/AS01 impact, using a vaccine profile based on phase II trial results, and assuming that protection decays only slowly. Settings were simulated in which baseline transmission (in the absence of vaccine) was fixed or varied between 2 and 20 infectious mosquito bites per person per annum (ibpa) over ten years. Four delivery strategies were studied: routine infant immunization (EPI), EPI plus infant catch-up, EPI plus school-based campaigns, and EPI plus mass campaigns. Impacts in changing transmission settings were similar to those in fixed settings. Assuming a persistent effect of vaccination, at 2 ibpa, the vaccine averted approximately 5-7 deaths per 1000 doses of vaccine when delivered via mass campaigns, but the benefit was less at higher transmission levels. EPI, catch-up and school-based strategies averted 2-3 deaths per 1000 doses in settings with 2 ibpa. In settings where transmission was decreasing or increasing, EPI, catch-up and school-based strategies averted approximately 3-4 deaths per 1000 doses. Where transmission is changing, it appears to be sufficient to consider simulations of pre-erythrocytic vaccine impact at a range of initial transmission levels. At 2 ibpa, mass campaigns averted the most deaths and reduced transmission, but this requires further study. If delivered via EPI, RTS,S/AS01 could avert approximately 6-11 deaths per 1000 vaccinees in all examined settings, similar to estimates for pneumococcal conjugate vaccine in African infants. These results support RTS,S/AS01 implementation via EPI, for example alongside vector control interventions, providing that the phase III trials provide support for our assumptions about efficacy.

Best (but oft-forgotten) practices: designing, analyzing, and reporting cluster randomized controlled trials.

PubMed

Brown, Andrew W; Li, Peng; Bohan Brown, Michelle M; Kaiser, Kathryn A; Keith, Scott W; Oakes, J Michael; Allison, David B

2015-08-01

Cluster randomized controlled trials (cRCTs; also known as group randomized trials and community-randomized trials) are multilevel experiments in which units that are randomly assigned to experimental conditions are sets of grouped individuals, whereas outcomes are recorded at the individual level. In human cRCTs, clusters that are randomly assigned are typically families, classrooms, schools, worksites, or counties. With growing interest in community-based, public health, and policy interventions to reduce obesity or improve nutrition, the use of cRCTs has increased. Errors in the design, analysis, and interpretation of cRCTs are unfortunately all too common. This situation seems to stem in part from investigator confusion about how the unit of randomization affects causal inferences and the statistical procedures required for the valid estimation and testing of effects. In this article, we provide a brief introduction and overview of the importance of cRCTs and highlight and explain important considerations for the design, analysis, and reporting of cRCTs by using published examples. © 2015 American Society for Nutrition.

Best strategies to implement clinical pathways in an emergency department setting: study protocol for a cluster randomized controlled trial

PubMed Central

2013-01-01

Background The clinical pathway is a tool that operationalizes best evidence recommendations and clinical practice guidelines in an accessible format for ‘point of care’ management by multidisciplinary health teams in hospital settings. While high-quality, expert-developed clinical pathways have many potential benefits, their impact has been limited by variable implementation strategies and suboptimal research designs. Best strategies for implementing pathways into hospital settings remain unknown. This study will seek to develop and comprehensively evaluate best strategies for effective local implementation of externally developed expert clinical pathways. Design/methods We will develop a theory-based and knowledge user-informed intervention strategy to implement two pediatric clinical pathways: asthma and gastroenteritis. Using a balanced incomplete block design, we will randomize 16 community emergency departments to receive the intervention for one clinical pathway and serve as control for the alternate clinical pathway, thus conducting two cluster randomized controlled trials to evaluate this implementation intervention. A minimization procedure will be used to randomize sites. Intervention sites will receive a tailored strategy to support full clinical pathway implementation. We will evaluate implementation strategy effectiveness through measurement of relevant process and clinical outcomes. The primary process outcome will be the presence of an appropriately completed clinical pathway on the chart for relevant patients. Primary clinical outcomes for each clinical pathway include the following: Asthma—the proportion of asthmatic patients treated appropriately with corticosteroids in the emergency department and at discharge; and Gastroenteritis—the proportion of relevant patients appropriately treated with oral rehydration therapy. Data sources include chart audits, administrative databases, environmental scans, and qualitative interviews. We will also conduct an overall process evaluation to assess the implementation strategy and an economic analysis to evaluate implementation costs and benefits. Discussion This study will contribute to the body of evidence supporting effective strategies for clinical pathway implementation, and ultimately reducing the research to practice gaps by operationalizing best evidence care recommendations through effective use of clinical pathways. Trial registration ClinicalTrials.gov: NCT01815710 PMID:23692634

Implementing trials of complex interventions in community settings: the USC-Rancho Los Amigos pressure ulcer prevention study (PUPS).

PubMed

Clark, Florence; Pyatak, Elizabeth A; Carlson, Mike; Blanche, Erna Imperatore; Vigen, Cheryl; Hay, Joel; Mallinson, Trudy; Blanchard, Jeanine; Unger, Jennifer B; Garber, Susan L; Diaz, Jesus; Florindez, Lucia I; Atkins, Michal; Rubayi, Salah; Azen, Stanley Paul

2014-04-01

Randomized trials of complex, non-pharmacologic interventions implemented in home and community settings, such as the University of Southern California (USC)-Rancho Los Amigos National Rehabilitation Center (RLANRC) Pressure Ulcer Prevention Study (PUPS), present unique challenges with respect to (1) participant recruitment and retention, (2) intervention delivery and fidelity, (3) randomization and assessment, and (4) potential inadvertent treatment effects. We describe the methods employed to address the challenges confronted in implementing PUPS. In this randomized controlled trial, we are assessing the efficacy of a complex, preventive intervention in reducing the incidence of, and costs associated with, the development of medically serious pressure ulcers in people with spinal cord injury. Individuals with spinal cord injury recruited from RLANRC were assigned to either a 12-month preventive intervention group or a standard care control group. The primary outcome is the incidence of serious pressure ulcers with secondary endpoints including ulcer-related surgeries, medical treatment costs, and quality of life. These outcomes are assessed at 12 and 24 months after randomization. Additionally, we are studying the mediating mechanisms that account for intervention outcomes. PUPS has been successfully implemented, including recruitment of the target sample size of 170 participants, assurance of the integrity of intervention protocol delivery with an average 90% treatment adherence rate, and enactment of the assessment plan. However, implementation has been replete with challenges. To meet recruitment goals, we instituted a five-pronged approach customized for an underserved, ethnically diverse population. In intervention delivery, we increased staff time to overcome economic and cultural barriers to retention and adherence. To ensure treatment fidelity and replicability, we monitored intervention protocol delivery in accordance with a rigorous plan. Finally, we have overcome unanticipated assessment and design concerns related to (1) determining pressure ulcer incidence/severity, (2) randomization imbalance, and (3) inadvertent potential control group contamination. We have addressed the most daunting challenges encountered in the recruitment, assessment, and intervention phases of PUPS. Some challenges and solutions may not apply to trials conducted in other settings. Overcoming challenges has required a multifaceted approach incorporating individualization, flexibility, and persistence, as well as the ability to implement needed mid-course corrections.

Oral health promotion reduces plaque and gingival bleeding in the short term.

PubMed

Hausen, Hannu

2005-01-01

Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database, UK National Health Service Economic Evaluation Database, Cochrane Central Register of Controlled Trials and Medline. There were no date limits or language restriction. Systematic reviews and controlled trials (randomised or quasi-randomised) assessing reductions in dental plaque levels and/or gingival bleeding (gingivitis) and comparing health education/health promotion interventions that did not involve clinical professional input or the use of pharmacological interventions, such as antiplaque agents were included. Studies involving only special groups, such as orthodontic or medically compromised patients or assessing only denture plaque, were excluded. A range of data were extracted from systematic reviews and trials, quality assessment was undertaken, and a qualitative overview of the findings was provided. Twenty-six potentially relevant studies were identified. Six reports of five systematic reviews and 13 trials were discussed: four studies were not assessed as one was published in Polish and three could not be located.A wide range of educational and behavioural interventions were considered. These did not generally include clinical interventions and social or environmental approaches. The reviews have a number of limitations so their conclusions should be viewed with a degree of caution. However, the majority of studies achieved short-term reductions in plaque and gingival bleeding. Precise estimates of the improvement are difficult to assess because of the range and diversity of outcome measures used. The results of two meta-analyses indicate a reduction in plaque levels of 32-37%. Of 13 recently published trials evaluating educational interventions, five were set in schools, four focused on adults either in a clinical or workplace setting, three targeted older people, and one, infants. The design quality of the trials was variable. Allocation concealment was clearly described in two trials only, but blind outcome assessment was described in most of the trials and so were dropout rates. Other problems included a lack of controls, use of single blinding and relatively short follow-up. Positive effects on plaque and/or bleeding outcomes were seen in eight studies with no difference in five studies, of which only two employed a control group. Nevertheless, for the two trials that compared various approaches, reductions in plaque and gingival bleeding were generally observed in all groups over the trial period. None of the studies produced a negative effect. Although all the studies evaluated educational interventions, there was no clear indication that any particular type or style of educational approach was more effective than any other. Reductions in plaque and gingival bleeding were seen in the short term in the majority of studies reviewed. The clinical and public health significance of these changes is, however, questionable. Future studies should use longer follow-up periods to assess whether short-term beneficial changes are sustained. Other forms of oral health promotion require better quality evaluation if they are to be used to improve periodontal health.

Group-sequential three-arm noninferiority clinical trial designs

PubMed Central

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

2016-01-01

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

Development and Evaluation of a Psychosocial Intervention for Children and Teenagers Experiencing Diabetes (DEPICTED): a protocol for a cluster randomised controlled trial of the effectiveness of a communication skills training programme for healthcare professionals working with young people with type 1 diabetes

PubMed Central

2010-01-01

Background Diabetes is the third most common chronic condition in childhood and poor glycaemic control leads to serious short-term and life-limiting long-term complications. In addition to optimal medical management, it is widely recognised that psychosocial and educational factors play a key role in improving outcomes for young people with diabetes. Recent systematic reviews of psycho-educational interventions recognise the need for new methods to be developed in consultation with key stakeholders including patients, their families and the multidisciplinary diabetes healthcare team. Methods/design Following a development phase involving key stakeholders, a psychosocial intervention for use by paediatric diabetes staff and not requiring input from trained psychologists has been developed, incorporating a communication skills training programme for health professionals and a shared agenda-setting tool. The effectiveness of the intervention will be evaluated in a cluster-randomised controlled trial (RCT). The primary outcome, to be measured in children aged 4-15 years diagnosed with type 1 diabetes for at least one year, is the effect on glycaemic control (HbA1c) during the year after training of the healthcare team is completed. Secondary outcomes include quality of life for patients and carers and cost-effectiveness. Patient and carer preferences for service delivery will also be assessed. Twenty-six paediatric diabetes teams are participating in the trial, recruiting a total of 700 patients for evaluation of outcome measures. Half the participating teams will be randomised to receive the intervention at the beginning of the trial and remaining centres offered the training package at the end of the one year trial period. Discussion The primary aim of the trial is to determine whether a communication skills training intervention for specialist paediatric diabetes teams will improve clinical and psychological outcomes for young people with type 1 diabetes. Previous research indicates the effectiveness of specialist psychological interventions in achieving sustained improvements in glycaemic control. This trial will evaluate an intervention which does not require the involvement of trained psychologists, maximising the potential feasibility of delivery in a wider NHS context. Trial registration Current Controlled Trials ISRCTN61568050. PMID:20144218

Economic evaluation of adult rehabilitation: a systematic review and meta-analysis of randomized controlled trials in a variety of settings.

PubMed

Brusco, Natasha Kareem; Taylor, Nicholas F; Watts, Jennifer J; Shields, Nora

2014-01-01

To report if there is a difference in costs from a societal perspective between adults receiving rehabilitation in an inpatient rehabilitation setting versus an alternative setting. If there are cost differences, to report whether opting for the least expensive program setting adversely affects patient outcomes. Electronic databases from the earliest possible date until May 2011. All languages were included. Multiple reviewers identified randomized controlled trials with a full economic evaluation that compared adult inpatient rehabilitation with an alternative. There were 29 included trials with 6746 participants. Multiple observers extracted data independently. Trial appraisal included a risk of bias assessment and a checklist to report the strength of the economic evaluation. Results were synthesized using standardized mean differences (SMDs) and meta-analyses for the primary outcome of cost. The Grading of Recommendations Assessment, Development, and Evaluation was applied to assess for risk of bias across studies for meta-analyses. There was high-quality evidence that cost was significantly reduced for rehabilitation in the home versus inpatient rehabilitation in a meta-analysis of 732 patients poststroke (pooled SMD [δ]=-.28; 95% confidence interval [CI], -.47 to -.09), without compromise to patient outcomes. Results of individual trials in other patient groups (orthopedic, rheumatoid arthritis, and geriatric) receiving rehabilitation in the home or community were generally consistent with the meta-analysis. There was moderate quality evidence that cost was significantly reduced for inpatient rehabilitation (stroke unit) versus general acute care in a meta-analysis of 463 patients poststroke (δ=.31; 95% CI, .15-.48), with improvement to patient outcomes. These results were not replicated in 2 individual trials with a geriatric and a mixed cohort, where costs did not differ between general acute care and inpatient rehabilitation. Three of the 4 individual trials, inclusive of a stroke or orthopedic population, reported less cost for an intensive inpatient rehabilitation program compared with usual inpatient rehabilitation. Sensitivity analysis included a health service perspective and varied inflation rates with no change to the significant findings of the meta-analyses. Based on this systematic review and meta-analyses, a single rehabilitation service may not provide health economic benefits for all patient groups and situations. For some patients, inpatient rehabilitation may be the most cost-effective method of providing rehabilitation; yet, for other patients, rehabilitation in the home or community may be the most cost-effective model of care. To achieve cost-effective outcomes, the ideal combination of rehabilitation services and patient inclusion criteria, as well as further data for nonstroke populations, warrants further research. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Exploring patients' treatment journeys following randomisation in mental health trials to improve future trial conduct: a synthesis of multiple qualitative data sets.

PubMed

Turner, Katrina M; Percival, John; Kessler, David; Donovan, Jenny

2017-06-15

The way in which pragmatic trials are designed suggests that there are differences between the experiences of participants randomised to usual care and intervention arms. These potential differences relate not only to which treatment participants receive but also how they access and engage with their allocated treatment. Such differences could affect trial results. The aim of this study was to assess whether such differences exist and, if they do, to consider their implications for the design of future trials. Interview transcripts were sampled from data sets gathered during three qualitative studies, all of which had been nested within large, primary care depression trials. Each study had explored trial participants' views and experiences of treatments received following randomisation. Transcripts from 37 participants were purposefully sampled, 20 of which were from interviews held with individuals allocated to receive usual GP care. Data were analysed thematically. There was evidence of differences between trial arms across all three data sets. Intervention participants were willing and able to engage with the treatment to which they had been allocated. Randomisation had led to them embarking upon a clear treatment pathway and receiving care in a context where they felt comfortable discussing their mental health and had sufficient time to do so. Intervention participants also had continuity with and confidence in the practitioners they saw. A few usual-care participants talked about having continuity with and confidence in their GPs. However, most of the usual-care participants reported a reluctance to consult GPs about mental health, difficulties in securing treatment appointments, and little or no changes in care following randomisation. Additionally, most reported a lack of continuity of care and a lack confidence in the treatment available to them. There are important differences between usual-care and intervention arms that go beyond treatment received, and they relate to how participants experience accessing and engaging with their allocated care. As these differences could affect trial results, researchers may want to measure or reduce them in order to fully appreciate or control for the range of factors that might affect treatment outcomes.

The process of developing and implementing a telephone-based peer support program for postpartum depression: evidence from two randomized controlled trials

PubMed Central

2014-01-01

Background A randomized controlled trial evaluated the effect of telephone-based peer support on preventing postpartum depression (PPD) among high-risk mothers. The results indicated that support provided by peer volunteers may be an effective preventative strategy. The purpose of this paper is to outline the process of developing, implementing, maintaining, and evaluating the peer support program that we used in this PPD prevention trial. Methods The peer support program had been used successfully in a pilot trial and a previous breastfeeding peer support trial. Based on our experience and lessons learned, we developed a 4-phase, 12-step approach so that the peer support model could be copied and used by different health providers in various settings. We will use the PPD prevention trial to demonstrate the suggested steps. Results The trial aim to prevent the onset of PPD was established. Peer volunteers who previously experienced and recovered from self-reported PPD were recruited and attended a four-hour training session. Volunteers were screened and those identified as appropriate to provide support to postpartum mothers were selected. Women who scored more than 9 on the Edinburgh Postnatal Depression Scale within the first two weeks after childbirth were recruited to participate in the trial and proactive, individualized, telephone-based peer support (mother-to-mother) was provided to those randomized to the intervention group. Peer volunteers maintained the intervention, supported other volunteers, and evaluated the telephone-based support program. Possible negative effects of the intervention were assessed. An in-depth assessment of maternal perspectives of the program at 12 weeks postpartum was performed. Conclusions The 4-phase, 12-step approach delineated in this paper provides clear and concise guidelines for health professionals to follow in creating and implementing community-based, peer-support interventions with the potential to prevent PPD. Trial registration Current Controlled Trials ISRCTN68337727. PMID:24742217

Early phase clinical trials with human immunodeficiency virus-1 and malaria vectored vaccines in The Gambia: frontline challenges in study design and implementation.

PubMed

Afolabi, Muhammed O; Adetifa, Jane U; Imoukhuede, Egeruan B; Viebig, Nicola K; Kampmann, Beate; Bojang, Kalifa

2014-05-01

Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and malaria are among the most important infectious diseases in developing countries. Existing control strategies are unlikely to curtail these diseases in the absence of efficacious vaccines. Testing of HIV and malaria vaccines candidates start with early phase trials that are increasingly being conducted in developing countries where the burden of the diseases is high. Unique challenges, which affect planning and implementation of vaccine trials according to internationally accepted standards have thus been identified. In this review, we highlight specific challenges encountered during two early phase trials of novel HIV-1 and malaria vectored vaccine candidates conducted in The Gambia and how some of these issues were pragmatically addressed. We hope our experience will be useful for key study personnel involved in day-to-day running of similar clinical trials. It may also guide future design and implementation of vaccine trials in resource-constrained settings.

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

PubMed

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

2016-06-01

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

An overview of the Families Improving Together (FIT) for weight loss randomized controlled trial in African American families.

PubMed

Wilson, Dawn K; Kitzman-Ulrich, Heather; Resnicow, Ken; Van Horn, M Lee; St George, Sara M; Siceloff, E Rebekah; Alia, Kassandra A; McDaniel, Tyler; Heatley, VaShawn; Huffman, Lauren; Coulon, Sandra; Prinz, Ron

2015-05-01

The Families Improving Together (FIT) randomized controlled trial tests the efficacy of integrating cultural tailoring, positive parenting, and motivational strategies into a comprehensive curriculum for weight loss in African American adolescents. The overall goal of the FIT trial is to test the effects of an integrated intervention curriculum and the added effects of a tailored web-based intervention on reducing z-BMI in overweight African American adolescents. The FIT trial is a randomized group cohort design the will involve 520 African American families with an overweight adolescent between the ages of 11-16 years. The trial tests the efficacy of an 8-week face-to-face group randomized program comparing M + FWL (Motivational Plus Family Weight Loss) to a comprehensive health education program (CHE) and re-randomizes participants to either an 8-week on-line tailored intervention or control on-line program resulting in a 2 (M + FWL vs. CHE group) × 2 (on-line intervention vs. control on-line program) factorial design to test the effects of the intervention on reducing z-BMI at post-treatment and at 6-month follow-up. The interventions for this trial are based on a theoretical framework that is novel and integrates elements from cultural tailoring, Family Systems Theory, Self-Determination Theory and Social Cognitive Theory. The intervention targets positive parenting skills (parenting style, monitoring, communication); cultural values; teaching parents to increase youth motivation by encouraging youth to have input and choice (autonomy-support); and provides a framework for building skills and self-efficacy through developing weight loss action plans that target goal setting, monitoring, and positive feedback. Copyright © 2015. Published by Elsevier Inc.

A protocol for a pragmatic randomized controlled trial evaluating outcomes of emergency nurse practitioner service.

PubMed

Jennings, Natasha; Gardner, Glenn; O'Reilly, Gerard

2014-09-01

To evaluate emergency nurse practitioner service effectiveness on outcomes related to quality of care and service responsiveness. Increasing service pressures in the emergency setting have resulted in the adoption of service innovation models; the most common and rapidly expanding of these is the emergency nurse practitioner. The delivery of high quality patient care in the emergency department is one of the most important service indicators to be measured in health services today. The rapid uptake of emergency nurse practitioner service in Australia has outpaced the capacity to evaluate this model in outcomes related to safety and quality of patient care. Pragmatic randomized controlled trial at one site with 260 participants. This protocol describes a definitive prospective randomized controlled trial, which will examine the impact of emergency nurse practitioner service on key patient care and service indicators. The study control will be standard emergency department care. The intervention will be emergency nurse practitioner service. The primary outcome measure is pain score reduction and time to analgesia. Secondary outcome measures are waiting time, number of patients who did not wait, length of stay in the emergency department and representations within 48 hours. Scant research enquiry evaluating emergency nurse practitioner service on patient effectiveness and service responsiveness exists currently. This study is a unique trial that will test the effectiveness of the emergency nurse practitioner service on patients who present to the emergency department with pain. The research will provide an opportunity to further evaluate emergency nurse practitioner models of care and build research capacity into the workforce. Trial registration details: Australian and New Zealand Clinical Trials Registry dated 18th August 2013, ACTRN12613000933752. © 2014 John Wiley & Sons Ltd.

Reconciling research and implementation in micro health insurance experiments in India: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Microinsurance or Community-Based Health Insurance is a promising healthcare financing mechanism, which is increasingly applied to aid rural poor persons in low-income countries. Robust empirical evidence on the causal relations between Community-Based Health Insurance and healthcare utilisation, financial protection and other areas is scarce and necessary. This paper contains a discussion of the research design of three Cluster Randomised Controlled Trials in India to measure the impact of Community-Based Health Insurance on several outcomes. Methods/Design Each trial sets up a Community-Based Health Insurance scheme among a group of micro-finance affiliate families. Villages are grouped into clusters which are congruous with pre-existing social groupings. These clusters are randomly assigned to one of three waves of implementation, ensuring the entire population is offered Community-Based Health Insurance by the end of the experiment. Each wave of treatment is preceded by a round of mixed methods evaluation, with quantitative, qualitative and spatial evidence on impact collected. Improving upon practices in published Cluster Randomised Controlled Trial literature, we detail how research design decisions have ensured that both the households offered insurance and the implementers of the Community-Based Health Insurance scheme operate in an environment replicating a non-experimental implementation. Discussion When a Cluster Randomised Controlled Trial involves randomizing within a community, generating adequate and valid conclusions requires that the research design must be made congruous with social structures within the target population, to ensure that such trials are conducted in an implementing environment which is a suitable analogue to that of a non-experimental implementing environment. PMID:21988774

Attitudes towards fever amongst UK paediatric intensive care staff.

PubMed

Brick, Thomas; Agbeko, Rachel S; Davies, Patrick; Davis, Peter J; Deep, Akash; Fortune, Peter-Marc; Inwald, David P; Jones, Amy; Levin, Richard; Morris, Kevin P; Pappachan, John; Ray, Samiran; Tibby, Shane M; Tume, Lyvonne N; Peters, Mark J

2017-03-01

The role played by fever in the outcome of critical illness in children is unclear. This survey of medical and nursing staff in 35 paediatric intensive care units and transport teams in the United Kingdom and Ireland established attitudes towards the management of children with fever. Four hundred sixty-two medical and nursing staff responded to a web-based survey request. Respondents answered eight questions regarding thresholds for temperature control in usual clinical practice, indications for paracetamol use, and readiness to participate in a clinical trial of permissive temperature control. The median reported threshold for treating fever in clinical practice was 38 °C (IQR 38-38.5 °C). Paracetamol was reported to be used as an analgesic and antipyretic but also for non-specific comfort indications. There was a widespread support for a clinical trial of a permissive versus a conservative approach to fever in paediatric intensive care units. Within a trial, 58% of the respondents considered a temperature of 39 °C acceptable without treatment. Staff on paediatric intensive care units in the United Kingdom and Ireland tends to treat temperatures within the febrile range. There was a willingness to conduct a randomized controlled trial of treatment of fever. What is known: • The effect of fever on the outcome in paediatric critical illness is unknown. • Paediatricians have traditionally been reluctant to allow fever in sick children. What is new: • Paediatric intensive care staff report a tendency towards treating fever, with a median reported treatment threshold of 38 °C. • There is widespread support amongst PICU staff in the UK for a randomized controlled trial of temperature in critically ill children. • Within a trial setting, PICU staff attitudes to fever are more permissive than in clinical practice.

Reconciling research and implementation in micro health insurance experiments in India: study protocol for a randomized controlled trial.

PubMed

Doyle, Conor; Panda, Pradeep; Van de Poel, Ellen; Radermacher, Ralf; Dror, David M

2011-10-11

Microinsurance or Community-Based Health Insurance is a promising healthcare financing mechanism, which is increasingly applied to aid rural poor persons in low-income countries. Robust empirical evidence on the causal relations between Community-Based Health Insurance and healthcare utilisation, financial protection and other areas is scarce and necessary. This paper contains a discussion of the research design of three Cluster Randomised Controlled Trials in India to measure the impact of Community-Based Health Insurance on several outcomes. Each trial sets up a Community-Based Health Insurance scheme among a group of micro-finance affiliate families. Villages are grouped into clusters which are congruous with pre-existing social groupings. These clusters are randomly assigned to one of three waves of implementation, ensuring the entire population is offered Community-Based Health Insurance by the end of the experiment. Each wave of treatment is preceded by a round of mixed methods evaluation, with quantitative, qualitative and spatial evidence on impact collected. Improving upon practices in published Cluster Randomised Controlled Trial literature, we detail how research design decisions have ensured that both the households offered insurance and the implementers of the Community-Based Health Insurance scheme operate in an environment replicating a non-experimental implementation. When a Cluster Randomised Controlled Trial involves randomizing within a community, generating adequate and valid conclusions requires that the research design must be made congruous with social structures within the target population, to ensure that such trials are conducted in an implementing environment which is a suitable analogue to that of a non-experimental implementing environment. © 2011 Doyle et al; licensee BioMed Central Ltd.

Care delivery and self-management strategies for children with epilepsy.

PubMed

Lindsay, Bruce; Bradley, Peter M

2010-12-08

Epilepsy care for children has been criticised for its lack of impact. Various service models and strategies have been developed in response to perceived inadequacies in care provision for children and their families. We set out to compare the effectiveness of specialist or dedicated teams or individuals in the care of children with epilepsy with usual care services. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library February issue, 2010), MEDLINE (1950 to March 2010), EMBASE (1988 to May 2006*), PsycINFO (1806 to March 2010) and CINAHL (1982 to March 2010).*Please note that as we currently do not have access to EMBASE, we have been unable to update this aspect of our searching. We included randomised controlled trials, controlled or matched trials, cohort studies or other prospective studies with a control group, or time series studies. Each review author independently selected studies, extracted data and assessed the quality of included studies. Four trials and five reports are included in this review. They report on four different education and counselling programmes for children, children and parents, or teenagers and parents. Each programme showed some benefits for the well-being of children with epilepsy, but each trial had methodological flaws and no single programme was evaluated by more than one study. While each of the programmes in this review showed some benefit to children with epilepsy their impacts were extremely variable. No programme showed benefits across the full range of outcomes. No study appears to have demonstrated any detrimental effects but the evidence in favour of any single programme is insufficient to make it possible to recommend one programme rather than another. More trials, carried out by independent research teams, are needed.

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

PubMed Central

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

2016-01-01

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

User and Provider Acceptability of Intermittent Screening and Treatment and Intermittent Preventive Treatment with Dihydroartemisinin-Piperaquine to Prevent Malaria in Pregnancy in Western Kenya.

PubMed

Hill, Jenny; Hoyt, Jenna; Achieng, Florence; Ouma, Peter; L'lanziva, Anne; Kariuki, Simon; Desai, Meghna; Webster, Jayne

2016-01-01

The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) alongside long-lasting insecticide-treated nets (LLIN) and case management for reducing the risks associated with malaria in pregnancy in areas of moderate-to-high transmission in sub-Saharan Africa. Due to increasing Plasmodium falciparum resistance to SP, the search for alternative drugs or strategies to control malaria in pregnancy is a priority. We assessed the acceptability among pregnant women and health providers of intermittent screening and treatment (ISTp) and IPTp with dihydroartemisinin-piperaquine (DP) as alternative strategies in the context of an un-blinded clinical trial. Qualitative data were collected through ten focus group discussions with women participating in a randomized controlled trial to evaluate ISTp or IPTp with DP (multi-day regimen) versus IPTp with SP (single dose) in western Kenya. Individual in-depth interviews were conducted with 26 health providers working in the trial facilities and trial staff. Women appreciated the advantages of being tested with a rapid diagnostic test (RDT) at every ANC visit (although a few women disliked finger pricks) and accepted that they would not receive any antimalarial when tested RDT-negative. There were differences in women's experiences of the efficacy of antimalarials between the trial arms, with more women in the IPTp-SP arm reporting they had experienced malaria episodes. Side effects were experienced among women taking DP and SP. Although women and trial staff reported adherence to the full DP regimen within the trial, health providers were not confident that women would adhere to multi-day regimens in non-trial settings. Health providers recognized the advantages of ISTp in reducing unnecessary exposure to drugs, but lacked confidence in the reliability of RDTs compared to microscopy. Our findings indicate that, within a trial context, ISTp-DP and IPTp-DP were generally acceptable among both users and providers and were regarded as potentially valuable alternatives to IPTp-SP. Several challenges were identified the most important of which was concerns with achieving adherence to DP in non-trial settings, requiring operational feasibility studies in routine health systems. Policy adoption of ISTp with RDTs would require a major shift in thinking among health providers due to lack of confidence in RDTs.

Development of a core outcome set for clinical trials in inflammatory bowel disease: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey.

PubMed

Ma, Christopher; Panaccione, Remo; Fedorak, Richard N; Parker, Claire E; Khanna, Reena; Levesque, Barrett G; Sandborn, William J; Feagan, Brian G; Jairath, Vipul

2017-06-09

Crohn's disease (CD) and ulcerative colitis (UC), the main forms of inflammatory bowel disease (IBD), are chronic, progressive and disabling disorders of the gastrointestinal tract. Although data from randomised controlled trials (RCTs) provide the foundation of evidence that validates medical therapy for IBD, considerable heterogeneity exists in the measured outcomes used in these studies. Furthermore, in recent years, there has been a paradigm shift in IBD treatment targets, moving from symptom-based scoring to improvement or normalisation of objective measures of inflammation such as endoscopic appearance, inflammatory biomarkers and histological and radiographic end points. The abundance of new treatment options and evolving end points poses opportunities and challenges for all stakeholders involved in drug development. Accordingly, there exists a need to harmonise measures used in clinical trials through the development of a core outcome set (COS). The development of an IBD-specific COS includes four steps. First, a systematic literature review is performed to identify outcomes previously used in IBD RCTs. Second, semistructured qualitative interviews are conducted with key stakeholders, including patients, clinicians, researchers, pharmaceutical industry representatives, healthcare payers and regulators to identify additional outcomes of importance. Using the outcomes generated from literature review and stakeholder interviews, an international two-round Delphi survey is conducted to prioritise outcomes for inclusion in the COS. Finally, a consensus meeting is held to ratify the COS and disseminate findings for application in future IBD trials. Given that over 30 novel therapeutic compounds are in development for IBD treatment, the design of robust clinical trials measuring relevant and standardised outcomes is crucial. Standardising outcomes through a COS will reduce heterogeneity in trial reporting, facilitate valid comparisons of new therapies and improve clinical trial quality. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.