Mixing a Grounded Theory Approach with a Randomized Controlled Trial Related to Intimate Partner Violence: What Challenges Arise for Mixed Methods Research?

PubMed Central

Catallo, Cristina; Jack, Susan M.; Ciliska, Donna; MacMillan, Harriet L.

2013-01-01

Little is known about how to systematically integrate complex qualitative studies within the context of randomized controlled trials. A two-phase sequential explanatory mixed methods study was conducted in Canada to understand how women decide to disclose intimate partner violence in emergency department settings. Mixing a RCT (with a subanalysis of data) with a grounded theory approach required methodological modifications to maintain the overall rigour of this mixed methods study. Modifications were made to the following areas of the grounded theory approach to support the overall integrity of the mixed methods study design: recruitment of participants, maximum variation and negative case sampling, data collection, and analysis methods. Recommendations for future studies include: (1) planning at the outset to incorporate a qualitative approach with a RCT and to determine logical points during the RCT to integrate the qualitative component and (2) consideration for the time needed to carry out a RCT and a grounded theory approach, especially to support recruitment, data collection, and analysis. Data mixing strategies should be considered during early stages of the study, so that appropriate measures can be developed and used in the RCT to support initial coding structures and data analysis needs of the grounded theory phase. PMID:23577245

Perinatal nutrition interventions and post-partum depressive symptoms.

PubMed

Gould, Jacqueline F; Best, Karen; Makrides, Maria

2017-12-15

Postpartum depression (PPD) is the most prevalent mood disorder associated with childbirth. No single cause of PPD has been identified, however the increased risk of nutritional deficiencies incurred through the high nutritional requirements of pregnancy may play a role in the pathology of depressive symptoms. Three nutritional interventions have drawn particular interest as possible non-invasive and cost-effective prevention and/or treatment strategies for PPD; omega-3 (n-3) long chain polyunsaturated fatty acids (LCPUFA), vitamin D and overall diet. We searched for meta-analyses of randomised controlled trials (RCT's) of nutritional interventions during the perinatal period with PPD as an outcome, and checked for any trials published subsequently to the meta-analyses. Fish oil: Eleven RCT's of prenatal fish oil supplementation RCT's show null and positive effects on PPD symptoms. Vitamin D: no relevant RCT's were identified, however seven observational studies of maternal vitamin D levels with PPD outcomes showed inconsistent associations. Diet: Two Australian RCT's with dietary advice interventions in pregnancy had a positive and null result on PPD. With the exception of fish oil, few RCT's with nutritional interventions during pregnancy assess PPD. Further research is needed to determine whether nutritional intervention strategies during pregnancy can protect against symptoms of PPD. Given the prevalence of PPD and ease of administering PPD measures, we recommend future prenatal nutritional RCT's include PPD as an outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

Internet-based self-help smoking cessation and alcohol moderation interventions for cancer survivors: a study protocol of two RCTs.

PubMed

Mujcic, Ajla; Blankers, Matthijs; Boon, Brigitte; Engels, Rutger; van Laar, Margriet

2018-04-02

Brief interventions for smoking cessation and alcohol moderation may contribute considerably to the prevention of cancer among populations at risk, such as cancer survivors, in addition to improving their general wellbeing. There is accumulating evidence for the effectiveness of internet-based brief health behaviour interventions. The objective of this study is to assess the effectiveness, patient-level cost-effectiveness and cost-utility of two new online theory-based self-help interventions among adult cancer survivors in the Netherlands. One of the interventions focuses on alcohol moderation, the other on smoking cessation. Both interventions are tailored to cancer survivors. Effectiveness will be assessed in two separate, nearly identical 2-armed RCTs: alcohol moderation (AM RCT) and smoking cessation (SC RCT). Participants are randomly allocated to either the intervention groups or the control groups. In the intervention groups, participants have access to one of the newly developed interventions. In the control groups, participants receive an online static information brochure on alcohol (AM RCT) or smoking (SC RCT). Main study outcome parameters are the number of drinks post-randomisation (AM RCT) and tobacco abstinence (SC RCT). In addition, cost-data and possible effect moderators and mediators will be assessed. Both treatments are internet-based minimally guided self-help interventions: MyCourse - Moderate Drinking (in Dutch: MijnKoers - Minderen met Drinken) and MyCourse - Quit Smoking (MijnKoers - Stoppen met Roken). They are based on cognitive behaviour therapy (CBT), motivational interviewing (MI) and acceptance and commitment therapy (ACT). Both interventions are optimized in collaboration with the target population of cancer survivors in focus groups and interviews, and in collaboration with several experts on eHealth, smoking cessation, alcohol misuse and cancer survivorship. The present study will add to scientific knowledge on the (cost-)effectiveness of internet-based self-help interventions to aid in smoking cessation or alcohol moderation, working mechanisms and impact on quality of life of cancer survivors. If found effective, these interventions can contribute to providing evidence-based psychosocial oncology care to a growing population of cancer survivors. Trials are prospectively registered in The Netherlands Trial Register (NTR): NTR6011 (SC RCT), NTR6010 (AM RCT) on 1 September 2016.

A randomized controlled trial of an electronic informed consent process.

PubMed

Rothwell, Erin; Wong, Bob; Rose, Nancy C; Anderson, Rebecca; Fedor, Beth; Stark, Louisa A; Botkin, Jeffrey R

2014-12-01

A pilot study assessed an electronic informed consent model within a randomized controlled trial (RCT). Participants who were recruited for the parent RCT project were randomly selected and randomized to either an electronic consent group (n = 32) or a simplified paper-based consent group (n = 30). Results from the electronic consent group reported significantly higher understanding of the purpose of the study, alternatives to participation, and who to contact if they had questions or concerns about the study. However, participants in the paper-based control group reported higher mean scores on some survey items. This research suggests that an electronic informed consent presentation may improve participant understanding for some aspects of a research study. © The Author(s) 2014.

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

PubMed

Nelson, Geoffrey; Macnaughton, Eric; Goering, Paula

2015-11-01

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

The regression discontinuity design showed to be a valid alternative to a randomized controlled trial for estimating treatment effects.

PubMed

Maas, Iris L; Nolte, Sandra; Walter, Otto B; Berger, Thomas; Hautzinger, Martin; Hohagen, Fritz; Lutz, Wolfgang; Meyer, Björn; Schröder, Johanna; Späth, Christina; Klein, Jan Philipp; Moritz, Steffen; Rose, Matthias

2017-02-01

To compare treatment effect estimates obtained from a regression discontinuity (RD) design with results from an actual randomized controlled trial (RCT). Data from an RCT (EVIDENT), which studied the effect of an Internet intervention on depressive symptoms measured with the Patient Health Questionnaire (PHQ-9), were used to perform an RD analysis, in which treatment allocation was determined by a cutoff value at baseline (PHQ-9 = 10). A linear regression model was fitted to the data, selecting participants above the cutoff who had received the intervention (n = 317) and control participants below the cutoff (n = 187). Outcome was PHQ-9 sum score 12 weeks after baseline. Robustness of the effect estimate was studied; the estimate was compared with the RCT treatment effect. The final regression model showed a regression coefficient of -2.29 [95% confidence interval (CI): -3.72 to -.85] compared with a treatment effect found in the RCT of -1.57 (95% CI: -2.07 to -1.07). Although the estimates obtained from two designs are not equal, their confidence intervals overlap, suggesting that an RD design can be a valid alternative for RCTs. This finding is particularly important for situations where an RCT may not be feasible or ethical as is often the case in clinical research settings. Copyright © 2016 Elsevier Inc. All rights reserved.

The effectiveness of dopamine agonists for treatment of neuropsychiatric symptoms post brain injury and stroke.

PubMed

Sami, Musa Basseer; Faruqui, Rafey

2015-12-01

Traumatic brain injury and stroke are among the leading causes of neurological disability worldwide. Although dopaminergic agents have long been associated with improvement of neuropsychiatric outcomes, to date much of the evidence to date has been in case reports and case series or open label trials. We undertook a systematic review of double-blinded randomised controlled trials (RCT) to determine the effect of dopaminergic agents on pre-defined outcomes of (a) apathy; (b) psychomotor retardation; (c) behavioural management and (d) cognitive function. Databases searched were: Medline, EMBASE, and PsychInfo for human studies. The Cochrane Clinical Trials Database and the TRIP Medical database were also searched. All identified studies, were further hand-searched. We identified six studies providing data on 227 participants, 150 of whom received dopaminergic therapy. Trials were compromised by cross-over design, inadequate wash out period, small numbers and heterogeneous outcome measures. However one good quality RCT demonstrates the efficacy of amantadine in behavioural management. One further RCT shows methylphenidate-levodopa is efficacious for mood post-stroke. One study shows rotigotine to improve hemi-inattention caused by prefrontal damage. Our systematic review demonstrates an evolving evidence base to suggest some benefits in agitation and aggression, mood and attentional deficits. However, there are key limitations of the studies undertaken to date involving small numbers of participants, heterogeneous outcome measures, and variable study designs. There is a need for on-going large prospective double-blind RCTs in these medications using standardised criteria and outcomes to fully understand their effectiveness in this patient group.

RCT: Module 2.06, Air Sampling Program and Methods, Course 8772

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

Hillmer, Kurt T.

The inhalation of radioactive particles is the largest cause of an internal radiation dose. Airborne radioactivity measurements are necessary to ensure that the control measures are and continue to be effective. Regulations govern the allowable effective dose equivalent to an individual. The effective dose equivalent is determined by combining the external and internal dose equivalent values. Typically, airborne radioactivity levels are maintained well below allowable levels to keep the total effective dose equivalent small. This course will prepare the student with the skills necessary for RCT qualification by passing quizzes, tests, and the RCT Comprehensive Phase 1, Unit 2 Examinationmore » (TEST 27566) and will provide in-the-field skills.« less

Effect of Robot-Assisted Game Training on Upper Extremity Function in Stroke Patients

PubMed Central

2017-01-01

Objective To determine the effects of combining robot-assisted game training with conventional upper extremity rehabilitation training (RCT) on motor and daily functions in comparison with conventional upper extremity rehabilitation training (OCT) in stroke patients. Methods Subjects were eligible if they were able to perform the robot-assisted game training and were divided randomly into a RCT and an OCT group. The RCT group performed one daily session of 30 minutes of robot-assisted game training with a rehabilitation robot, plus one daily session of 30 minutes of conventional rehabilitation training, 5 days a week for 2 weeks. The OCT group performed two daily sessions of 30 minutes of conventional rehabilitation training. The effects of training were measured by a Manual Function Test (MFT), Manual Muscle Test (MMT), Korean version of the Modified Barthel Index (K-MBI) and a questionnaire about satisfaction with training. These measurements were taken before and after the 2-week training. Results Both groups contained 25 subjects. After training, both groups showed significant improvements in motor and daily functions measured by MFT, MMT, and K-MBI compared to the baseline. Both groups demonstrated similar training effects, except motor power of wrist flexion. Patients in the RCT group were more satisfied than those in the OCT group. Conclusion There were no significant differences in changes in most of the motor and daily functions between the two types of training. However, patients in the RCT group were more satisfied than those in the OCT group. Therefore, RCT could be a useful upper extremity rehabilitation training method. PMID:28971037

Incorporating external evidence in trial-based cost-effectiveness analyses: the use of resampling methods

PubMed Central

2014-01-01

Background Cost-effectiveness analyses (CEAs) that use patient-specific data from a randomized controlled trial (RCT) are popular, yet such CEAs are criticized because they neglect to incorporate evidence external to the trial. A popular method for quantifying uncertainty in a RCT-based CEA is the bootstrap. The objective of the present study was to further expand the bootstrap method of RCT-based CEA for the incorporation of external evidence. Methods We utilize the Bayesian interpretation of the bootstrap and derive the distribution for the cost and effectiveness outcomes after observing the current RCT data and the external evidence. We propose simple modifications of the bootstrap for sampling from such posterior distributions. Results In a proof-of-concept case study, we use data from a clinical trial and incorporate external evidence on the effect size of treatments to illustrate the method in action. Compared to the parametric models of evidence synthesis, the proposed approach requires fewer distributional assumptions, does not require explicit modeling of the relation between external evidence and outcomes of interest, and is generally easier to implement. A drawback of this approach is potential computational inefficiency compared to the parametric Bayesian methods. Conclusions The bootstrap method of RCT-based CEA can be extended to incorporate external evidence, while preserving its appealing features such as no requirement for parametric modeling of cost and effectiveness outcomes. PMID:24888356

Incorporating external evidence in trial-based cost-effectiveness analyses: the use of resampling methods.

PubMed

Sadatsafavi, Mohsen; Marra, Carlo; Aaron, Shawn; Bryan, Stirling

2014-06-03

Cost-effectiveness analyses (CEAs) that use patient-specific data from a randomized controlled trial (RCT) are popular, yet such CEAs are criticized because they neglect to incorporate evidence external to the trial. A popular method for quantifying uncertainty in a RCT-based CEA is the bootstrap. The objective of the present study was to further expand the bootstrap method of RCT-based CEA for the incorporation of external evidence. We utilize the Bayesian interpretation of the bootstrap and derive the distribution for the cost and effectiveness outcomes after observing the current RCT data and the external evidence. We propose simple modifications of the bootstrap for sampling from such posterior distributions. In a proof-of-concept case study, we use data from a clinical trial and incorporate external evidence on the effect size of treatments to illustrate the method in action. Compared to the parametric models of evidence synthesis, the proposed approach requires fewer distributional assumptions, does not require explicit modeling of the relation between external evidence and outcomes of interest, and is generally easier to implement. A drawback of this approach is potential computational inefficiency compared to the parametric Bayesian methods. The bootstrap method of RCT-based CEA can be extended to incorporate external evidence, while preserving its appealing features such as no requirement for parametric modeling of cost and effectiveness outcomes.

Exercise for anxiety disorders: systematic review.

PubMed

Jayakody, Kaushadh; Gunadasa, Shalmini; Hosker, Christian

2014-02-01

Anxiety disorders are commonly treated with antidepressants and psychological treatments. Some patients may prefer alternative approaches such as exercise. To investigate the treatment effects of exercise compared with other treatments for anxiety disorders. Randomised controlled trials (RCTs) of exercise interventions for anxiety disorders were identified by searching six online databases (July 2011). A number of journals were also hand searched. Eight RCTs were included. For panic disorder: exercise appears to reduce anxiety symptoms but it is less effective than antidepressant medication (1 RCT); exercise combined with antidepressant medication improves the Clinical Global Impression outcomes (1 RCT, p<0.05); exercise combined with occupational therapy and lifestyle changes reduces Beck Anxiety Inventory outcomes (1 RCT, p=0.0002). For social phobias, added benefits of exercise when combined with group cognitive behavioural therapy (CBT) were shown (p<0.05). There was no significant difference between aerobic and anaerobic exercise groups (1 RCT, p>0.1) with both seeming to reduce anxiety symptoms (1 RCT, p<0.001). It remains unclear as to which type of exercise; moderate to hard or very light to light, is more effective in anxiety reduction (2 RCTs). Exercise seems to be effective as an adjunctive treatment for anxiety disorders but it is less effective compared with antidepressant treatment. Both aerobic and non-aerobic exercise seems to reduce anxiety symptoms. Social phobics may benefit from exercise when combined with group CBT. Further well-conducted RCTs are needed.

'Healthy Eating and Lifestyle in Pregnancy (HELP)' trial: Process evaluation framework.

PubMed

Simpson, Sharon A; Cassidy, Dunla; John, Elinor

2014-07-01

We developed and tested in a cluster RCT a theory-driven group-based intervention for obese pregnant women. It was designed to support women to moderate weight gain during pregnancy and reduce BMI one year after birth, in addition to targeting secondary health and wellbeing outcomes. In line with MRC guidance on developing and evaluating complex interventions in health, we conducted a process evaluation alongside the trial. This paper describes the development of the process evaluation framework. This cluster RCT recruited 598 pregnant women. Women in the intervention group were invited to attend a weekly weight-management group. Following a review of relevant literature, we developed a process evaluation framework which outlined key process indicators that we wanted to address and how we would measure these. Central to the process evaluation was to understand the mechanism of effect of the intervention. We utilised a logic-modelling approach to describe the intervention which helped us focus on what potential mediators of intervention effect to measure, and how. The resulting process evaluation framework was designed to address 9 core elements; context, reach, exposure, recruitment, fidelity, recruitment, retention, contamination and theory-testing. These were assessed using a variety of qualitative and quantitative approaches. The logic model explained the processes by which intervention components bring about change in target outcomes through various mediators and theoretical pathways including self-efficacy, social support, self-regulation and motivation. Process evaluation is a key element in assessing the effect of any RCT. We developed a process evaluation framework and logic model, and the results of analyses using these will offer insights into why the intervention is or is not effective. Copyright © 2014.

The feasibility of a randomised controlled trial of physiotherapy for adults with joint hypermobility syndrome.

PubMed

Palmer, Shea; Cramp, Fiona; Clark, Emma; Lewis, Rachel; Brookes, Sara; Hollingworth, William; Welton, Nicky; Thom, Howard; Terry, Rohini; Rimes, Katharine A; Horwood, Jeremy

2016-06-01

Joint hypermobility syndrome (JHS) is a heritable disorder associated with laxity and pain in multiple joints. Physiotherapy is the mainstay of treatment, but there is little research investigating its clinical effectiveness. To develop a comprehensive physiotherapy intervention for adults with JHS; to pilot the intervention; and to conduct a pilot randomised controlled trial (RCT) to determine the feasibility of conducting a future definitive RCT. Patients' and health professionals' perspectives on physiotherapy for JHS were explored in focus groups (stage 1). A working group of patient research partners, clinicians and researchers used this information to develop the physiotherapy intervention. This was piloted and refined on the basis of patients' and physiotherapists' feedback (stage 2). A parallel two-arm pilot RCT compared 'advice' with 'advice and physiotherapy' (stage 3). Random allocation was via an automated randomisation service, devised specifically for the study. Owing to the nature of the interventions, it was not possible to blind clinicians or patients to treatment allocation. Stage 1 - focus groups were conducted in four UK locations. Stages 2 and 3 - piloting of the intervention and the pilot RCT were conducted in two UK secondary care NHS trusts. Stage 1 - patient focus group participants (n = 25, three men) were aged > 18 years, had a JHS diagnosis and had received physiotherapy within the preceding 12 months. The health professional focus group participants (n = 16, three men; 14 physiotherapists, two podiatrists) had experience of managing JHS. Stage 2 - patient participants (n = 8) were aged > 18 years, had a JHS diagnosis and no other musculoskeletal conditions causing pain. Stage 3 - patient participants for the pilot RCT (n = 29) were as for stage 2 but the lower age limit was 16 years. For the pilot RCT (stage 3) the advice intervention was a one-off session, supplemented by advice booklets. All participants could ask questions specific to their circumstances and receive tailored advice. Participants were randomly allocated to 'advice' (no further advice or physiotherapy) or 'advice and physiotherapy' (an additional six 30-minute sessions over 4 months). The physiotherapy intervention was supported by a patient handbook and was delivered on a one-to-one patient-therapist basis. It aimed to increase patients' physical activity through developing knowledge, understanding and skills to better manage their condition. Data from patient and health professional focus groups formed the main outcome from stage 1. Patient and physiotherapist interview data also formed a major component of stages 2 and 3. The primary outcome in stage 3 related to the feasibility of a future definitive RCT [number of referrals, recruitment and retention rates, and an estimate of the value of information (VOI) of a future RCT]. Secondary outcomes included clinical measures (physical function, pain, global status, self-reported joint count, quality of life, exercise self-efficacy and adverse events) and resource use (to estimate cost-effectiveness). Outcomes were recorded at baseline, 4 months and 7 months. Stage 1 - JHS is complex and unpredictable. Physiotherapists should take a long-term holistic approach rather than treating acutely painful joints in isolation. Stage 2 - a user-informed physiotherapy intervention was developed and evaluated positively. Stage 3 - recruitment to the pilot RCT was challenging, primarily because of a perceived lack of equipoise between advice and physiotherapy. The qualitative evaluation provided very clear guidance to inform a future RCT, including enhancement of the advice intervention. Some patients reported that the advice intervention was useful and the physiotherapy intervention was again evaluated very positively. The rate of return of questionnaires was low in the advice group but reasonable in the physiotherapy group. The physiotherapy intervention showed evidence of promise in terms of primary and secondary clinical outcomes. The advice arm experienced more adverse events. The VOI analysis indicated the potential for high value from a future RCT. Such a trial should form the basis of future research efforts. A future definitive RCT of physiotherapy for JHS seems feasible, although the advice intervention should be made more robust to address perceived equipoise and subsequent attrition. Current Controlled Trials ISRCTN29874209. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 47. See the NIHR Journals Library website for further project information.

Randomized controlled drug trials on very elderly subjects: descriptive and methodological analysis of trials published between 1990 and 2002 and comparison with trials on adults.

PubMed

Le Quintrec, Jean-Laurent; Bussy, Caroline; Golmard, Jean-Louis; Hervé, Christian; Baulon, Alain; Piette, François

2005-03-01

Very elderly subjects (VES; aged 80 years or older) constitute a special population as they frequently present multiple diseases (polypathology). Results from trials on general adult populations therefore cannot be extrapolated to VES. We performed a census of randomized controlled trials (RCT) on VES published between 1990 and 2002, and carried out a descriptive and methodological analysis of these RCT/VES, comparing them with matched RCT on general adult populations (control RCT, RCT/C). We searched for RCT/VES in two international databases (EMBASE and MEDLINE) and then manually. RCT/C were matched to RCT/VES for disease area and year of publication. The methodological quality of each RCT was assessed with Chalmers' scale. We identified 84 RCT/VES, 63 of which were conclusive and 21, inconclusive. Subjects were institutionalized in 48 RCT, and community dwelling in 11 RCT (unspecified in 25 RCT). Efficacy was the main criterion in 75 RCT; tolerance in 9 RCT. Twenty-six RCT were published by geriatrics journals, and 58 by general medical journals. The RCT/VES covered most of the disease areas of geriatrics. The 84 RCT/VES had a mean methodological quality score of 0.578 +/- 0.157. The matched 84 RCT/C had a mean methodological quality score of 0.592 +/- 0.116 (p = .466). The methodological quality score of RCT/VES increased with the number of included subjects (p = .004) and the year of publication (p = .001). The methodological quality of RCT/VES is equivalent to that of RCT in general adult populations. Nevertheless, RCT/VES remain very scarce, and neglect certain diseases. RCT/VES and the inclusion of very elderly subjects in RCT on adults should be strongly encouraged.

The experience of adolescents participating in a randomised clinical trial in the field of mental health: a qualitative study.

PubMed

Midgley, Nick; Isaacs, Danny; Weitkamp, Katharina; Target, Mary

2016-07-28

This descriptive study aimed to investigate adolescents' motivations for participating in a randomised controlled trial (RCT), to explore the understanding that the young people had regarding a number of aspects of the trial design, to examine whether or not they found participation in the trial to be acceptable and what affected this, and to identify whether and how the young people felt that their participation in the RCT impacted on their experience of therapy and on therapeutic change. Seventy-six adolescents who were taking part in a large-scale RCT to evaluate the clinical and cost effectiveness of psychological therapies for depression were interviewed at two time-points after completing therapy. The semi-structured interviews, which included a focus on the young people's experience of the research study, were analysed using framework analysis. The vast majority of adolescents found it acceptable to participate in the clinical trial, and many agreed to participate for reasons of 'conditional altruism'. However consent was often given without great understanding of the key elements of the trial, including the difference between treatment arms and the randomisation process. Although the adolescents were largely positive about their experiences from taking part, the study raises questions about whether clinical outcomes may be influenced by participation in the research elements of the trial. Although adolescents are under-represented in clinical trials, those who do participate are generally positive about the experience; however, careful thought needs to be given to key elements of the trial design and the potential impact of the research participation on clinical outcomes. ISRCTN registry, ISRCTN83033550 . Registered on 15 October 2009.

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

PubMed

Viksveen, Petter; Relton, Clare; Nicholl, Jon

2017-07-06

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

Regression Discontinuity and Randomized Controlled Trial Estimates: An Application to The Mycotic Ulcer Treatment Trials.

PubMed

Oldenburg, Catherine E; Venkatesh Prajna, N; Krishnan, Tiruvengada; Rajaraman, Revathi; Srinivasan, Muthiah; Ray, Kathryn J; O'Brien, Kieran S; Glymour, M Maria; Porco, Travis C; Acharya, Nisha R; Rose-Nussbaumer, Jennifer; Lietman, Thomas M

2018-08-01

We compare results from regression discontinuity (RD) analysis to primary results of a randomized controlled trial (RCT) utilizing data from two contemporaneous RCTs for treatment of fungal corneal ulcers. Patients were enrolled in the Mycotic Ulcer Treatment Trials I and II (MUTT I & MUTT II) based on baseline visual acuity: patients with acuity ≤ 20/400 (logMAR 1.3) enrolled in MUTT I, and >20/400 in MUTT II. MUTT I investigated the effect of topical natamycin versus voriconazole on best spectacle-corrected visual acuity. MUTT II investigated the effect of topical voriconazole plus placebo versus topical voriconazole plus oral voriconazole. We compared the RD estimate (natamycin arm of MUTT I [N = 162] versus placebo arm of MUTT II [N = 54]) to the RCT estimate from MUTT I (topical natamycin [N = 162] versus topical voriconazole [N = 161]). In the RD, patients receiving natamycin had mean improvement of 4-lines of visual acuity at 3 months (logMAR -0.39, 95% CI: -0.61, -0.17) compared to topical voriconazole plus placebo, and 2-lines in the RCT (logMAR -0.18, 95% CI: -0.30, -0.05) compared to topical voriconazole. The RD and RCT estimates were similar, although the RD design overestimated effects compared to the RCT.

Effect of sulfonylurea agents on reverse cholesterol transport in vitro and vivo.

PubMed

Terao, Yoshio; Ayaori, Makoto; Ogura, Masatsune; Yakushiji, Emi; Uto-Kondo, Harumi; Hisada, Tetsuya; Ozasa, Hideki; Takiguchi, Shunichi; Nakaya, Kazuhiro; Sasaki, Makoto; Komatsu, Tomohiro; Iizuka, Maki; Horii, Shunpei; Mochizuki, Seibu; Yoshimura, Michihiro; Ikewaki, Katsunori

2011-01-01

Reverse cholesterol transport (RCT) is a critical mechanism for the anti-atherogenic property of HDL. The inhibitory effect of the sulfonylurea agent (SUA) glibenclamide on ATP binding-cassette transporter (ABC) A1 may decrease HDL function but it remains unclear whether it attenuates RCT in vivo. We therefore investigated how the SUAs glibenclamide and glimepiride affected the functionality of ABCA1/ABCG1 and scavenger receptor class B type I (SR-BI) expression in macrophages in vitro and overall RCT in vivo. RAW264.7, HEK293 and BHK-21 cells were used for in vitro studies. To investigate RCT in vivo, 3H-cholesterol-labeled and acetyl LDL-loaded RAW264.7 cells were injected into mice. High dose (500µM) of glibenclamide inhibited ABCA1 function and apolipoprotein A-I (apoA-I)-mediated cholesterol efflux, and attenuated ABCA1 expression. Although glimepiride maintained apoA-I-mediated cholesterol efflux from RAW264.7 cells, like glibenclamide, it inhibited ABCA1-mediated cholesterol efflux from transfected HEK293 cells. Similarly, the SUAs inhibited SR-BI-mediated cholesterol efflux from transfected BHK-21 cells. High doses of SUAs increased ABCG1 expression in RAW264.7 cells, promoting HDL-mediated cholesterol efflux in an ABCG1-independent manner. Low doses (0.1-100 µM) of SUAs did not affect cholesterol efflux from macrophages despite dose-dependent increases in ABCA1/G1 expression. Furthermore, they did not change RCT or plasma lipid levels in mice. High doses of SUAs inhibited the functionality of ABCA1/SR-BI, but not ABCG1. At lower doses, they had no unfavorable effects on cholesterol efflux or overall RCT in vivo. These results indicate that SUAs do not have adverse effects on atherosclerosis contrary to previous findings for glibenclamide.

RCT: Module 2.07, Respiratory Protection, Course 8773

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

Hillmer, Kurt T.

Internal dosimetry controls require the use of engineering controls to prevent the internal deposition of radioactive and nonradiological contaminants. However, when engineering and administrative controls are not available or feasible, respiratory protection may be necessary. The radiation control technician (RCT) should know and apply the considerations used in determining the respiratory protection equipment that is most appropriate for the job. The inappropriate use of or the use of the wrong respiratory protection equipment may result in undesirable health effects. This course will prepare the student with the skills necessary for RCT qualification by passing quizzes, tests, and the RCT Comprehensivemore » Phase 1, Unit 2 Examination (TEST 27566) and will provide in-the-field skills.« less

Understanding factors that inhibit or promote the utilization of telecare in chronic lung disease.

PubMed

Mair, Frances S; Hiscock, Julia; Beaton, Susan C

2008-06-01

To perform a process evaluation of a randomized controlled trial (RCT) of home telecare for the management of acute exacerbations of chronic obstructive pulmonary disease (COPD), using the normalization process model (NPM) as an explanatory framework. Semi-structured interviews were carried out with patients (n = 9) and nurses (n = 11) participating in a RCT. A framework approach to data analysis was used. The telecare service did not provide an interactional advantage for the nurses providing this service and did not fit with the nurses' views of the most appropriate or preferred use of their skills. The telecare service seemed unlikely to become normalized as part of routine healthcare delivery, because the nursing team lacked confidence that it was a safe way to provide healthcare in this context and it was not perceived as improving efficiency. The NPM effectively mapped onto the study findings and explained those factors that inhibited the routine delivery of COPD services by telecare.

A Mock Randomized Controlled Trial With Audience Response Technology for Teaching and Learning Epidemiology.

PubMed

Baker, Philip R A; Francis, Daniel P; Cathcart, Abby

2017-04-01

The study's objective was to apply and assess an active learning approach to epidemiology and critical appraisal. Active learning comprised a mock, randomized controlled trial (RCT) conducted with learners in 3 countries. The mock trial consisted of blindly eating red Smarties candy (intervention) compared to yellow Smarties (control) to determine whether red Smarties increase happiness. Audience response devices were employed with the 3-fold purposes to produce outcome data for analysis of the effects of red Smarties, identify baseline and subsequent changes in participant's knowledge and confidence in understanding of RCTs, and assess the teaching approach. Of those attending, 82% (117 of 143 learners) participated in the trial component. Participating in the mock trial was a positive experience, and the use of the technology aided learning. The trial produced data that learners analyzed in "real time" during the class. The mock RCT is a fun and engaging approach to teaching RCTs and helping students to develop skills in critical appraisal.

Tofacitinib restores the inhibition of reverse cholesterol transport induced by inflammation: understanding the lipid paradox associated with rheumatoid arthritis.

PubMed

Pérez-Baos, S; Barrasa, J I; Gratal, P; Larrañaga-Vera, A; Prieto-Potin, I; Herrero-Beaumont, G; Largo, R

2017-09-01

Patients with active rheumatoid arthritis (RA) have increased cardiovascular mortality, paradoxically associated with reduced circulating lipid levels. The JAK inhibitor tofacitinib ameliorates systemic and joint inflammation in RA with a concomitant increase in serum lipids. We analysed the effect of tofacitinib on the lipid profile of hyperlipidaemic rabbits with chronic arthritis (CA) and on the changes in reverse cholesterol transport (RCT) during chronic inflammation. CA was induced in previously immunized rabbits, fed a high-fat diet, by administering four intra-articular injections of ovalbumin. A group of rabbits received tofacitinib (10 mg·kg -1 ·day -1 ) for 2 weeks. Systemic and synovial inflammation and lipid content were evaluated. For in vitro studies, THP-1-derived macrophages were exposed to high lipid concentrations and then stimulated with IFNγ in the presence or absence of tofacitinib in order to study mediators of RCT. Tofacitinib decreased systemic and synovial inflammation and increased circulating lipid levels. Although it did not modify synovial macrophage density, it reduced the lipid content within synovial macrophages. In foam macrophages in culture, IFNγ further stimulated intracellular lipid accumulation, while the JAK/STAT inhibition provoked by tofacitinib induced lipid release by increasing the levels of cellular liver X receptor α and ATP-binding cassette transporter (ABCA1) synthesis. Active inflammation could be associated with lipid accumulation within macrophages of CA rabbits. JAK inhibition induced lipid release through RCT activation, providing a plausible explanation for the effect of tofacitinib on the lipid profile of RA patients. © 2017 The British Pharmacological Society.

Integration of physical abuse clinical decision support into the electronic health record at a Tertiary Care Children's Hospital.

PubMed

Suresh, Srinivasan; Saladino, Richard A; Fromkin, Janet; Heineman, Emily; McGinn, Tom; Richichi, Rudolph; Berger, Rachel P

2018-04-12

To evaluate the effect of a previously validated electronic health record-based child abuse trigger system on physician compliance with clinical guidelines for evaluation of physical abuse. A randomized controlled trial (RCT) with comparison to a preintervention group was performed. RCT-experimental subjects' providers received alerts with a direct link to a physical abuse-specific order set. RCT-control subjects' providers had no alerts, but could manually search for the order set. Preintervention subjects' providers had neither alerts nor access to the order set. Compliance with clinical guidelines was calculated. Ninety-nine preintervention subjects and 130 RCT subjects (73 RCT-experimental and 57 RCT-control) met criteria to undergo a physical abuse evaluation. Full compliance with clinical guidelines was 84% pre-intervention, 86% in RCT-control group, and 89% in RCT-experimental group. The physical abuse order set was used 43 times during the 7-month RCT. When the abuse order set was used, full compliance was 100%. The proportion of cases in which there was partial compliance decreased from 10% to 3% once the order set became available (P = .04). Male gender, having >10 years of experience and completion of a pediatric emergency medicine fellowship were associated with increased compliance. A child abuse clinical decision support system comprised of a trigger system, alerts and a physical abuse order set was quickly accepted into clinical practice. Use of the physical abuse order set always resulted in full compliance with clinical guidelines. Given the high baseline compliance at our site, evaluation of this alert system in hospitals with lower baseline compliance rates will be more valuable in assessing the efficacy in adherence to clinical guidelines for the evaluation of suspected child abuse.

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

PubMed

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

2013-08-01

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

An Approach to Assess Generalizability in Comparative Effectiveness Research: A Case Study of the Whole Systems Demonstrator Cluster Randomized Trial Comparing Telehealth with Usual Care for Patients with Chronic Health Conditions.

PubMed

Steventon, Adam; Grieve, Richard; Bardsley, Martin

2015-11-01

Policy makers require estimates of comparative effectiveness that apply to the population of interest, but there has been little research on quantitative approaches to assess and extend the generalizability of randomized controlled trial (RCT)-based evaluations. We illustrate an approach using observational data. Our example is the Whole Systems Demonstrator (WSD) trial, in which 3230 adults with chronic conditions were assigned to receive telehealth or usual care. First, we used novel placebo tests to assess whether outcomes were similar between the RCT control group and a matched subset of nonparticipants who received usual care. We matched on 65 baseline variables obtained from the electronic medical record. Second, we conducted sensitivity analysis to consider whether the estimates of treatment effectiveness were robust to alternative assumptions about whether "usual care" is defined by the RCT control group or nonparticipants. Thus, we provided alternative estimates of comparative effectiveness by contrasting the outcomes of the RCT telehealth group and matched nonparticipants. For some endpoints, such as the number of outpatient attendances, the placebo tests passed, and the effectiveness estimates were robust to the choice of comparison group. However, for other endpoints, such as emergency admissions, the placebo tests failed and the estimates of treatment effect differed markedly according to whether telehealth patients were compared with RCT controls or matched nonparticipants. The proposed placebo tests indicate those cases when estimates from RCTs do not generalize to routine clinical practice and motivate complementary estimates of comparative effectiveness that use observational data. Future RCTs are recommended to incorporate these placebo tests and the accompanying sensitivity analyses to enhance their relevance to policy making. © The Author(s) 2015.

In vivo clinical and radiological effects of platelet-rich plasma on interstitial supraspinatus lesion: Case series.

PubMed

Lädermann, A; Zumstein, M A; Kolo, F C; Grosclaude, M; Koglin, L; Schwitzguebel, A J P

2016-12-01

Rotator cuff tear (RCT) is a frequent condition of clinical relevance that can be managed with a symptomatic conservative treatment, but surgery is often needed. Biological components like leukocytes and platelet rich plasma (L-PRP) could represent an alternative curative method for interstitial RCT. It has been hypothesized that an ultrasound guided L-PRP injection in supraspinatus interstitial RCT could induce radiological healing. A prospective case series including 25 patients was performed in order to assess the effect of L-PRP infiltration into supraspinatus interstitial RCTs. Primary outcome was tear size change determined by magnetic resonance imaging arthrogram (MRA) before and 6 months after L-PRP infiltration. Secondary outcomes were Constant score, SANE score, and pain visual analog scale (VAS) after L-PRP infiltration. Tear volume diminution was statistically significant (P=.007), and a >50% tear volume diminution was observed in 15 patients. A statistically significant improvement of Constant score (P<.001), SANE score (P=.001), and VAS (P<.001) was observed. In 21 patients, Constant score improvement reached the minimal clinical important difference of 10.4 points. We observed a statistically significant and clinically relevant effect on RCT size and clinical parameters after L-PRP infiltration. Such an important improvement of supraspinatus interstitial RCT with conservative management is uncommon, therefore intratendinous L-PRP infiltrations could have been beneficial. This encouraging result could pave the way for future randomized studies in order to formally determinate whether L-PRP infiltrations are a possible alternative to surgical treatment of interstitial RCT. Prospective observational study; Level of evidence II. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Factorial Experiments: Efficient Tools for Evaluation of Intervention Components

PubMed Central

Collins, Linda M.; Dziak, John J.; Kugler, Kari C.; Trail, Jessica B.

2014-01-01

Background An understanding of the individual and combined effects of a set of intervention components is important for moving the science of preventive medicine interventions forward. This understanding can often be achieved in an efficient and economical way via a factorial experiment, in which two or more independent variables are manipulated. The factorial experiment is a complement to the randomized controlled trial (RCT); the two designs address different research questions. Purpose This article offers an introduction to factorial experiments aimed at investigators trained primarily in the RCT. Method The factorial experiment is compared and contrasted with other experimental designs used commonly in intervention science to highlight where each is most efficient and appropriate. Results Several points are made: factorial experiments make very efficient use of experimental subjects when the data are properly analyzed; a factorial experiment can have excellent statistical power even if it has relatively few subjects per experimental condition; and when conducting research to select components for inclusion in a multicomponent intervention, interactions should be studied rather than avoided. Conclusions Investigators in preventive medicine and related areas should begin considering factorial experiments alongside other approaches. Experimental designs should be chosen from a resource management perspective, which states that the best experimental design is the one that provides the greatest scientific benefit without exceeding available resources. PMID:25092122

Clinical Inquiry: Is megestrol acetate safe and effective for malnourished nursing home residents?

PubMed

Wen, Frances K; Millar, James; Oberst-Walsh, Linda; Nashelsky, Joan

2018-02-01

No. Megestrol acetate (MA) is neither safe nor effective for stimulating appetite in malnourished nursing home residents. It increases the risk of deep vein thrombosis (strength of recommendation [SOR]: C, 2 retrospective chart reviews), but isn't associated with other new or worsening events or disorders (SOR: B, single randomized controlled trial [RCT]). Over a 25-week period, MA wasn't associated with increased mortality (SOR: B, single RCT). After 44 months, however, MA-treated patients showed decreased median survival (SOR: B, single case-control study). Consistent, meaningful weight gain was not observed with MA treatment (SOR: B, single case-control study, single RCT, 2 retrospective chart reviews, single prospective case-series).

Miscellaneous treatments for antipsychotic-induced tardive dyskinesia.

PubMed

Soares-Weiser, Karla; Rathbone, John; Ogawa, Yusuke; Shinohara, Kiyomi; Bergman, Hanna

2018-03-19

Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. Its use, however, is associated with adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. This review, one in a series examining the treatment of TD, covers miscellaneous treatments not covered elsewhere. To determine whether drugs, hormone-, dietary-, or herb-supplements not covered in other Cochrane reviews on TD treatments, surgical interventions, electroconvulsive therapy, and mind-body therapies were effective and safe for people with antipsychotic-induced TD. We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including trial registers (16 July 2015 and 26 April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information. We included reports if they were randomised controlled trials (RCTs) dealing with people with antipsychotic-induced TD and schizophrenia or other chronic mental illnesses who remained on their antipsychotic medication and had been randomly allocated to the interventions listed above versus placebo, no intervention, or any other intervention. We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CIs). We assumed that people who left early had no improvement. We assessed risk of bias and created 'Summary of findings' tables using GRADE. We included 31 RCTs of 24 interventions with 1278 participants; 22 of these trials were newly included in this 2017 update. Five trials are awaiting classification and seven trials are ongoing. All participants were adults with chronic psychiatric disorders, mostly schizophrenia, and antipsychotic-induced TD. Studies were primarily of short (three to six6 weeks) duration with small samples size (10 to 157 participants), and most (61%) were published more than 20 years ago. The overall risk of bias in these studies was unclear, mainly due to poor reporting of allocation concealment, generation of the sequence, and blinding.Nineteen of the 31 included studies reported on the primary outcome 'No clinically important improvement in TD symptoms'. Two studies found moderate-quality evidence of a benefit of the intervention compared with placebo: valbenazine (RR 0.63, 95% CI 0.46 to 0.86, 1 RCT, n = 92) and extract of Ginkgo biloba (RR 0.88, 95% CI 0.81 to 0.96, 1 RCT, n = 157), respectively. However, due to small sample sizes we cannot be certain of these effects.We consider the results for the remaining interventions to be inconclusive: Low- to very low-quality evidence of a benefit was found for buspirone (RR 0.53, 95% CI 0.33 to 0.84, 1 RCT, n = 42), dihydrogenated ergot alkaloids (RR 0.45, 95% CI 0.21 to 0.97, 1 RCT, n = 28), hypnosis or relaxation, (RR 0.45, 95% CI 0.21 to 0.94, 1 study, n = 15), pemoline (RR 0.48, 95% CI 0.29 to 0.77, 1 RCT, n = 46), promethazine (RR 0.24, 95% CI 0.11 to 0.55, 1 RCT, n = 34), insulin (RR 0.52, 95% CI 0.29 to 0.96, 1 RCT, n = 20), branched chain amino acids (RR 0.79, 95% CI 0.63 to 1.00, 1 RCT, n = 52), and isocarboxazid (RR 0.24, 95% CI 0.08 to 0.71, 1 RCT, n = 20). There was low- to very low-certainty evidence of no difference between intervention and placebo or no treatment for the following interventions: melatonin (RR 0.89, 95% CI 0.71 to 1.12, 2 RCTs, n = 32), lithium (RR 1.59, 95% CI 0.79 to 3.23, 1 RCT, n = 11), ritanserin (RR 1.00, 95% CI 0.70 to 1.43, 1 RCT, n = 10), selegiline (RR 1.37, 95% CI 0.96 to 1.94, 1 RCT, n = 33), oestrogen (RR 1.18, 95% CI 0.76 to 1.83, 1 RCT, n = 12), and gamma-linolenic acid (RR 1.00, 95% CI 0.69 to 1.45, 1 RCT, n = 16).None of the included studies reported on the other primary outcome, 'no clinically significant extrapyramidal adverse effects'. This review has found that the use of valbenazine or extract of Ginkgo biloba may be effective in relieving the symptoms of tardive dyskinesia. However, since only one RCT has investigated each one of these compounds, we are awaiting results from ongoing trials to confirm these results. Results for the remaining interventions covered in this review must be considered inconclusive and these compounds probably should only be used within the context of a well-designed evaluative study.

The impact of clinical trial design on cost-effectiveness analyses: illustration from a published study of the one-touch ultrasmart blood glucose meter for insulin-using diabetes patients.

PubMed

Tunis, Sandra L; Minshall, Michael E

2008-06-01

One source of variation in cost-effectiveness analyses stems from the characteristics of the study upon which each is based. This report provides cost-effectiveness analyses using data from a recently published randomized clinical trial (RCT) comparing an integrated glucose meter/electronic logbook to a conventional glucose meter/paper logbook in helping to control hemoglobin A1c in type 1 or type 2 diabetes. RCT participants and health care professionals (HCPs) were "blinded" to results of meter downloads until week 16, when participants chose systems. They returned to "usual care" and could obtain meter results and share them with their HCPs. Those eligible returned 26-65 weeks later for an observational visit. The CORE Diabetes Model was used to estimate the 60-year cost-effectiveness of the electronic (vs. conventional) meter. With no price premium, the newer technology represented a dominant strategy (greater effectiveness/lower costs) based on the RCT alone or on the RCT + observational visit. With a $100.00/year premium, the incremental cost-effectiveness ratio was $28,053 based on the RCT, but the electronic monitor was dominant when simulations included observational visit results. One plausible reason for the greater benefits of the electronic monitor with the observational period included was the ability of patients and HCPs to make better clinical and lifestyle modifications based on fully available, formatted data. Because the advantages of the electronic meter are based on timely access to accurate feedback, the importance of naturalistic, unblinded studies for technology assessments can be appreciated. Addressing the methodological issues discussed here can help integrate clinical and economic outcomes for diabetes care innovations.

Evaluation of HDL-modulating interventions for cardiovascular risk reduction using a systems pharmacology approach[S

PubMed Central

Gadkar, Kapil; Lu, James; Sahasranaman, Srikumar; Davis, John; Mazer, Norman A.; Ramanujan, Saroja

2016-01-01

The recent failures of cholesteryl ester transport protein inhibitor drugs to decrease CVD risk, despite raising HDL cholesterol (HDL-C) levels, suggest that pharmacologic increases in HDL-C may not always reflect elevations in reverse cholesterol transport (RCT), the process by which HDL is believed to exert its beneficial effects. HDL-modulating therapies can affect HDL properties beyond total HDL-C, including particle numbers, size, and composition, and may contribute differently to RCT and CVD risk. The lack of validated easily measurable pharmacodynamic markers to link drug effects to RCT, and ultimately to CVD risk, complicates target and compound selection and evaluation. In this work, we use a systems pharmacology model to contextualize the roles of different HDL targets in cholesterol metabolism and provide quantitative links between HDL-related measurements and the associated changes in RCT rate to support target and compound evaluation in drug development. By quantifying the amount of cholesterol removed from the periphery over the short-term, our simulations show the potential for infused HDL to treat acute CVD. For the primary prevention of CVD, our analysis suggests that the induction of ApoA-I synthesis may be a more viable approach, due to the long-term increase in RCT rate. PMID:26522778

Evaluation of HDL-modulating interventions for cardiovascular risk reduction using a systems pharmacology approach.

PubMed

Gadkar, Kapil; Lu, James; Sahasranaman, Srikumar; Davis, John; Mazer, Norman A; Ramanujan, Saroja

2016-01-01

The recent failures of cholesteryl ester transport protein inhibitor drugs to decrease CVD risk, despite raising HDL cholesterol (HDL-C) levels, suggest that pharmacologic increases in HDL-C may not always reflect elevations in reverse cholesterol transport (RCT), the process by which HDL is believed to exert its beneficial effects. HDL-modulating therapies can affect HDL properties beyond total HDL-C, including particle numbers, size, and composition, and may contribute differently to RCT and CVD risk. The lack of validated easily measurable pharmacodynamic markers to link drug effects to RCT, and ultimately to CVD risk, complicates target and compound selection and evaluation. In this work, we use a systems pharmacology model to contextualize the roles of different HDL targets in cholesterol metabolism and provide quantitative links between HDL-related measurements and the associated changes in RCT rate to support target and compound evaluation in drug development. By quantifying the amount of cholesterol removed from the periphery over the short-term, our simulations show the potential for infused HDL to treat acute CVD. For the primary prevention of CVD, our analysis suggests that the induction of ApoA-I synthesis may be a more viable approach, due to the long-term increase in RCT rate. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

Inflammation modulates human HDL composition and function in vivo

USDA-ARS?s Scientific Manuscript database

Inflammation may directly impair HDL functions, in particular reverse cholesterol transport (RCT), but limited data support this concept in humans. Our study was designed to investigate this relationship. We employed low-dose human endotoxemia to assess the effects of inflammation on HDL and RCT-rel...

The Effect of the Dental Operating Microscope on the Outcome of Nonsurgical Root Canal Treatment: A Retrospective Case-control Study.

PubMed

Khalighinejad, Navid; Aminoshariae, Anita; Kulild, James C; Williams, Kristin A; Wang, Jeannie; Mickel, Andre

2017-05-01

The aim of the current investigation was to assess the effect of the use of a dental operating microscope on the outcome of nonsurgical root canal treatment (NS RCT) while treating the mesiobuccal (MB) root of the maxillary first molar. This retrospective investigation included endodontically treated maxillary first molars (ETMs) with apparent adequate previous NS RCT and restorations referred for endodontic retreatment at the endodontic graduate clinic. Inclusion criteria were ETMs that were diagnosed with irreversible pulpitis and normal periapical tissues before the initial NS RCT and ETMs that presented with a minimum of 1 identifiable periapical lesion (PAR) at 1 of the roots at the time of retreatment. One hundred ninety-five ETMs were included and divided into 2 groups: (1) the initial NS RCT had been performed using a microscope (n = 83) and (2) NS RCT had been performed without the use of a microscope (n = 112). Data extracted were whether the second MB (MB2) canal was located initially and the presence of an MB PAR at the time of retreatment. Data were statistically analyzed using binary logistic regression (α = 0.05). The MB root was 3 times more likely to present with a PAR at the time of retreatment if the initial NS RCT was performed without the use of a microscope (P < .05, odds ratio = 3.1). There was a significant association between a missed MB2 canal and an MB PAR in the group in which the initial NS RCT was performed without the use of a microscope (P < .05, odds ratio = 5.1). However, in cases in which the initial NS RCT was performed using a microscope, a missed MB2 canal was not associated with the presence of an MB PAR. With proper education, dentists can gain further insight into recognizing limitations in treating cases that require advanced training and advanced optics such as a microscope. Based on this strategy, it would appear that the outcome of NS RCT can be improved. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Sustaining program effectiveness after implementation: The case of the self-management of well-being group intervention for older adults.

PubMed

Goedendorp, Martine M; Kuiper, Daphne; Reijneveld, Sijmen A; Sanderman, Robbert; Steverink, Nardi

2017-06-01

The Self-Management of Well-being (SMW) group intervention for older women was implemented in health and social care. Our aim was to assess whether effects of the SMW intervention were comparable with the original randomized controlled trial (RCT). Furthermore, we investigated threats to effectiveness, such as participant adherence, group reached, and program fidelity. In the implementation study (IMP) 287 and RCT 142 women participated. We compared scores on self-management ability and well-being of the IMP and RCT. For adherence, drop-out rates and session attendance were compared. Regarding reach, we compared participants' baseline characteristics. Professionals completed questions regarding program fidelity. No significant differences were found on effect outcomes and adherence between IMP and RCT (all p≥0.135). Intervention effect sizes were equal (0.47-0.59). IMP participants were significantly less lonely and more likely to be married, but had lower well-being. Most professionals followed the protocol, with only minimal deviations. The effectiveness of the SMW group intervention was reproduced after implementation, with similar participant adherence, minimal changes in the group reached, and high program fidelity. The SMW group intervention can be transferred to health and social care without loss of effectiveness. Implementation at a larger scale is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

Xanthohumol, a hop-derived prenylated flavonoid, promotes macrophage reverse cholesterol transport.

PubMed

Hirata, Hiroshi; Uto-Kondo, Harumi; Ogura, Masatsune; Ayaori, Makoto; Shiotani, Kazusa; Ota, Ami; Tsuchiya, Youichi; Ikewaki, Katsunori

2017-09-01

Xanthohumol, a prominent prenyl flavonoid from the hop plant (Humulus lupulus L.), is suggested to be antiatherogenic since it reportedly increases high-density lipoprotein (HDL) cholesterol levels. It is not clear whether xanthohumol promotes reverse cholesterol transport (RCT), the most important antiatherogenic property of HDL; therefore, we investigated the effects of xanthohumol on macrophage-to-feces RCT using a hamster model as a CETP-expressing species. In vivo RCT experiments showed that xanthohumol significantly increased fecal appearance of the tracer derived from intraperitoneally injected [ 3 H]-cholesterol-labeled macrophages. Ex vivo experiments were then employed to investigate the detailed mechanism by which xanthohumol enhanced RCT. Cholesterol efflux capacity from macrophages was 1.5-fold higher in xanthohumol-fed hamsters compared with the control group. In addition, protein expression and lecithin-cholesterol acyltransferase activity in the HDL fraction were significantly higher in xanthohumol-fed hamsters compared with the control, suggesting that xanthohumol promoted HDL maturation. Hepatic transcript analysis revealed that xanthohumol increased mRNA expression of abcg8 and cyp7a1. In addition, protein expressions of liver X receptor α and bile pump export protein were increased in the liver by xanthohumol administration when compared with the control, implying that it stimulated bile acid synthesis and cholesterol excretion to feces. In conclusion, our data demonstrate that xanthohumol improves RCT in vivo through cholesterol efflux from macrophages and excretion to feces, leading to antiatherosclerosis effects. It remains to be elucidated whether enhancement of RCT by xanthohumol could prove valuable in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

Facilitating Representation Change in Insight Problems through Training

ERIC Educational Resources Information Center

Patrick, John; Ahmed, Afia

2014-01-01

Our aim in this article is to elaborate the role of training in representational change theory (RCT), particularly in terms of Ohlsson's (2011) spread of activation explanation (named "redistribution theory"), and to develop novel training manipulations that effect the re-encoding mechanism proposed by RCT (Ohlsson, 1992). Two…

Generated effect modifiers (GEM’s) in randomized clinical trials

PubMed Central

Petkova, Eva; Tarpey, Thaddeus; Su, Zhe; Ogden, R. Todd

2017-01-01

In a randomized clinical trial (RCT), it is often of interest not only to estimate the effect of various treatments on the outcome, but also to determine whether any patient characteristic has a different relationship with the outcome, depending on treatment. In regression models for the outcome, if there is a non-zero interaction between treatment and a predictor, that predictor is called an “effect modifier”. Identification of such effect modifiers is crucial as we move towards precision medicine, that is, optimizing individual treatment assignment based on patient measurements assessed when presenting for treatment. In most settings, there will be several baseline predictor variables that could potentially modify the treatment effects. This article proposes optimal methods of constructing a composite variable (defined as a linear combination of pre-treatment patient characteristics) in order to generate an effect modifier in an RCT setting. Several criteria are considered for generating effect modifiers and their performance is studied via simulations. An example from a RCT is provided for illustration. PMID:27465235

Increasing Access to Mental Health Care With Breathe, an Internet-Based Program for Anxious Adolescents: Study Protocol for a Pilot Randomized Controlled Trial

PubMed Central

Wozney, Lori; Bagnell, Alexa; Fitzpatrick, Eleanor; Curtis, Sarah; Jabbour, Mona; Johnson, David; Rosychuk, Rhonda J; Young, Michael; Ohinmaa, Arto; Joyce, Anthony; McGrath, Patrick

2016-01-01

Background There is a demand to make first-line treatments, including cognitive behavioural therapy (CBT) for adolescent anxiety disorders, more widely available. Internet-based CBT is proposed to circumvent access and availability barriers and reduce health care system costs. Recent reviews suggest more evidence is needed to establish the treatment effects of Internet-based CBT in children and adolescents and to determine related economic impacts. Objective This pilot trial aims to collect the necessary data to inform the planning of a full-scale RCT to test the effectiveness of the Internet-based CBT program Breathe (Being Real, Easing Anxiety: Tools Helping Electronically). Methods We are conducting a 27-month, 2-arm parallel-group, pilot randomized controlled trial (RCT). Outcomes will inform the planning of a full-scale RCT aimed to test the effectiveness of Internet-based CBT with a population of adolescents with moderate to mild anxiety problems. In the pilot RCT we will: (1) define a minimal clinically important difference (MCID) for the primary outcome measure (total anxiety score using the Multidimensional Anxiety Scale for Children); (2) determine a sample size for the full-scale RCT; (3) estimate recruitment and retention rates; (4) measure intervention acceptability to inform critical intervention changes; (5) determine the use of co-interventions; and (6) conduct a cost-consequence analysis to inform a cost-effectiveness analysis in the full-scale RCT. Adolescents aged 13-17 years seeking care for an anxiety complaint from a participating emergency department, mobile or school-based crisis team, or primary care clinic are being screened for interest and eligibility. Enrolled adolescents are being randomly allocated to either 8 weeks of Internet-based CBT with limited telephone and e-mail support, or a control group with access to a static webpage listing anxiety resources. Adolescents are randomly assigned using a computer generated allocation sequence. Data are being collected at baseline, treatment completion, and at a 3-month follow-up. Results Currently, adolescents are being enrolled in the study. Enrolment is taking place between March 2014 and February 2016; data collection will conclude May 2016. We expect that analysis and results will be available by August 2016. Conclusions In many communities, the resources available for front-line anxiety treatment are outweighed by the need for care. This pilot RCT is an essential step to designing a robust RCT to evaluate the effectiveness of an Internet-based CBT program for adolescents with moderate to mild anxiety problems. Trial Registration Clinicaltrials.gov NCT02059226; http://clinicaltrials.gov/ct2/show/NCT02059226 (Archived by WebCite at http://www.webcitation.org/6epF8v7k4) PMID:26825111

Obtaining real-world evidence: the Salford Lung Study

PubMed Central

New, John P; Bakerly, Nawar Diar; Leather, David; Woodcock, Ashley

2014-01-01

We need to assess clinical treatments in real-life settings outside of randomised controlled trials (RCTs). Pragmatic RCT (pRCT) data can supplement RCTs by providing effectiveness information to support healthcare decisions. Electronic health records can facilitate concurrent safety monitoring and data collection without direct patient contact for large randomised study populations in pRCTs. The Salford Lung Study is the world's first phase III pRCT in asthma and chronic obstructive pulmonary disease (COPD), which aims to randomise over 7000 patients. This paper describes the hurdles overcome and the enormous effort and resource required to establish this comparative effectiveness study of a prelicence intervention. GlaxoSmithKline protocol HZC115151 Asthma study clinicaltrials.gov registration NCT01706198 COPD study clinicaltrials.gov registration NCT01551758 PMID:24603195

One-stage surgical treatment for concomitant rotator cuff tears with shoulder stiffness has comparable results with isolated rotator cuff tears: a systematic review.

PubMed

Sabzevari, Soheil; Kachooei, Amir Reza; Giugale, Juan; Lin, Albert

2017-08-01

Addressing preoperative shoulder stiffness before rotator cuff repair (RCR) is advocated, but the effectiveness of this approach is debatable. We hypothesized that 1-stage treatment of concomitant rotator cuff tear (RCT) with shoulder stiffness has comparable results with isolated RCT. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the databases including MEDLINE, Embase, Cochrane Library, and Scopus were searched using the keywords of "shoulder stiffness" OR "adhesive capsulitis" OR "frozen shoulder" AND "rotator cuff." Studies that met all the criteria compared the 2 arms of isolated RCT vs. RCT with concomitant shoulder stiffness, received no physical therapy before surgery, and reported data of preoperative and postoperative range of motion (ROM) and functional outcomes after surgery. Four level III studies met the inclusion criteria. The non-stiff group (isolated RCT) included 460 patients who underwent RCR; the stiff group (RCT with concomitant shoulder stiffness) included 111 patients who underwent RCR and manipulation under anesthesia with or without capsular release. There were significant differences in preoperative ROM between stiff and non-stiff groups. At final follow-up, there were no statistical differences in all ROM between the 2 groups. There was no significant difference in comparing preoperative and postoperative outcome scores including visual analog scale for pain, Constant, modified American Shoulder and Elbow Surgeons, and University of California-Los Angeles scores. Concomitant surgical treatment of nonmassive RCT and moderate shoulder stiffness in 1 stage may have comparable results to the surgical treatment of RCT in patients without preoperative stiffness. Therefore, a physical therapy regimen before surgical intervention may not be necessary. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Dental Care in an Equal Access System Valuing Equity: Are There Racial Disparities?

PubMed

Boehmer, Ulrike; Glickman, Mark; Jones, Judith A; Orner, Michelle B; Wheler, Carolyn; Berlowitz, Dan R; Kressin, Nancy R

2016-11-01

Racial disparities in dental care have previously been shown in the Veterans Health Administration (VA)-a controlled access setting valuing equitable, high-quality care. The aim of this study is to examine current disparities in dental care by focusing on the receipt of root canal therapy (RCT) versus tooth extraction. This is a retrospective analysis of data contained in the VA's electronic health records. We performed logistic regressions on the independent measures along with a facility-specific random effect, using dependent binary variables that distinguished RCT from tooth extraction procedures. VA outpatients who had at least 1 tooth extraction or RCT visit in the VA in fiscal year 2011. A dependent binary measure of tooth extraction or RCT. Other measures are medical record data on medical comorbidities, dental morbidity, prior dental utilization, and demographic characteristics. The overall rate of preferred tooth-preserving RCT was 18.1% during the study period. Black and Asian patients were most dissimilar with respect to dental morbidity, medical and psychological disorders, and black patients had the least amount of eligibility for comprehensive dental care. After adjustment for known confounding factors of RCT, black patients had the lowest RCT rates, whereas Asians had the highest. Current quality improvement efforts and a value to improve the equity of care are not sufficient to address racial/ethnic disparities in VA dental care; rather more targeted efforts will be needed to achieve equity for all.

Hepatic Overexpression of Endothelial Lipase Lowers HDL (High-Density Lipoprotein) but Maintains Reverse Cholesterol Transport in Mice: Role of SR-BI (Scavenger Receptor Class B Type I)/ABCA1 (ATP-Binding Cassette Transporter A1)-Dependent Pathways.

PubMed

Takiguchi, Shunichi; Ayaori, Makoto; Yakushiji, Emi; Nishida, Takafumi; Nakaya, Kazuhiro; Sasaki, Makoto; Iizuka, Maki; Uto-Kondo, Harumi; Terao, Yoshio; Yogo, Makiko; Komatsu, Tomohiro; Ogura, Masatsune; Ikewaki, Katsunori

2018-05-10

Reverse cholesterol transport (RCT) is a major mechanism by which HDL (high-density lipoprotein) protects against atherosclerosis. Endothelial lipase (EL) reportedly reduces HDL levels, which, in theory, would increase atherosclerosis. However, it remains unclear whether EL affects RCT in vivo. Adenoviral vectors expressing EL or luciferase were intravenously injected into mice, and a macrophage RCT assay was performed. As expected, hepatic EL overexpression markedly reduced HDL levels. In parallel, plasma 3 H-cholesterol counts from the EL-expressing mice decreased by 85% compared with control. Surprisingly, there was no difference in fecal 3 H-cholesterol excretion between the groups. Kinetic studies revealed increased catabolism/hepatic uptake of 3 HDL-cholesteryl ether, resulting in no change in fecal HDL-cholesteryl ester excretion in the mice. To explore underlying mechanisms for the preservation of RCT despite low HDL levels in the EL-expressing mice, we investigated the effects of hepatic SR-BI (scavenger receptor class B type I) knockdown. RCT assay revealed that knockdown of SR-BI alone reduced fecal excretion of macrophage-derived 3 H-cholesterol. Interestingly, hepatic EL overexpression under SR-BI inhibition further attenuated fecal tracer counts as compared with control. Finally, we observed that EL overexpression enhanced in vivo RCT under pharmacological inhibition of hepatic ABCA1 (ATP-binding cassette transporter A1) by probucol. Hepatic EL expression compensates for reduced macrophage-derived cholesterol efflux to plasma because of low HDL levels by promoting cholesterol excretion to bile/feces via an SR-BI pathway, maintaining overall RCT in vivo. In contrast, EL-modified HDL might negatively regulate RCT via hepatic ABCA1. Despite extreme hypoalphalipoproteinemia, RCT is maintained in EL-expressing mice via SR-BI/ABCA1-dependent pathways. © 2018 American Heart Association, Inc.

Single-case experimental design yielded an effect estimate corresponding to a randomized controlled trial.

PubMed

Shadish, William R; Rindskopf, David M; Boyajian, Jonathan G

2016-08-01

We reanalyzed data from a previous randomized crossover design that administered high or low doses of intravenous immunoglobulin (IgG) to 12 patients with hypogammaglobulinaemia over 12 time points, with crossover after time 6. The objective was to see if results corresponded when analyzed as a set of single-case experimental designs vs. as a usual randomized controlled trial (RCT). Two blinded statisticians independently analyzed results. One analyzed the RCT comparing mean outcomes of group A (high dose IgG) to group B (low dose IgG) at the usual trial end point (time 6 in this case). The other analyzed all 12 time points for the group B patients as six single-case experimental designs analyzed together in a Bayesian nonlinear framework. In the randomized trial, group A [M = 794.93; standard deviation (SD) = 90.48] had significantly higher serum IgG levels at time six than group B (M = 283.89; SD = 71.10) (t = 10.88; df = 10; P < 0.001), yielding a mean difference of MD = 511.05 [standard error (SE) = 46.98]. For the single-case experimental designs, the effect from an intrinsically nonlinear regression was also significant and comparable in size with overlapping confidence intervals: MD = 495.00, SE = 54.41, and t = 495.00/54.41 = 9.10. Subsequent exploratory analyses indicated that how trend was modeled made a difference to these conclusions. The results of single-case experimental designs accurately approximated results from an RCT, although more work is needed to understand the conditions under which this holds. Copyright © 2016 Elsevier Inc. All rights reserved.

Theory-Driven Hints in the Cheap Necklace Problem: A Preliminary Investigation

ERIC Educational Resources Information Center

Chu, Yun; Dewald, Andrew D.; Chronicle, Edward P.

2007-01-01

Three experiments investigated the effects of two hints derived from the Criterion for Satisfactory Progress theory (CSP) and Representational Change Theory (RCT) on the cheap necklace problem (insight problem). In Experiment 1, fewer participants given the CSP hint used an incorrect (maximizing) first move than participants given the RCT hint or…

Short communication: influence of composite casein genotypes on additive genetic variation of milk production traits and coagulation properties in Holstein-Friesian cows.

PubMed

Penasa, M; Cassandro, M; Pretto, D; De Marchi, M; Comin, A; Chessa, S; Dal Zotto, R; Bittante, G

2010-07-01

The aim of the study was to quantify the effects of composite beta- and kappa-casein (CN) genotypes on genetic variation of milk coagulation properties (MCP); milk yield; fat, protein, and CN contents; somatic cell score; pH; and titratable acidity (TA) in 1,042 Italian Holstein-Friesian cows. Milk coagulation properties were defined as rennet coagulation time (RCT) and curd firmness (a(30)). Variance components were estimated using 2 animal models: model 1 included herd, days in milk, and parity as fixed effects and animal and residual as random effects, and model 2 was model 1 with the addition of composite beta- and kappa-CN genotype as a fixed effect. Genetic correlations between RCT and a(30) and between these traits and milk production traits were obtained with bivariate analyses, based on the same models. The inclusion of casein genotypes led to a decrease of 47, 68, 18, and 23% in the genetic variance for RCT, a(30), pH, and TA, respectively, and less than 6% for other traits. Heritability of RCT and a(30) decreased from 0.248 to 0.143 and from 0.123 to 0.043, respectively. A moderate reduction was found for pH and TA, whereas negligible changes were detected for other milk traits. Estimates of genetic correlations were comparable between the 2 models. Results show that composite beta- and kappa-CN genotypes are important for RCT and a(30) but cannot replace the recording of MCP themselves. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Art participation for psychosocial wellbeing during stroke rehabilitation: a feasibility randomised controlled trial.

PubMed

Morris, Jacqui H; Kelly, Chris; Joice, Sara; Kroll, Thilo; Mead, Gillian; Donnan, Peter; Toma, Madalina; Williams, Brian

2017-08-30

To examine the feasibility of undertaking a pragmatic single-blind randomised controlled trial (RCT) of a visual arts participation programme to evaluate effects on survivor wellbeing within stroke rehabilitation. Stroke survivors receiving in-patient rehabilitation were randomised to receive eight art participation sessions (n = 41) or usual care (n = 40). Recruitment, retention, preference for art participation and change in selected outcomes were evaluated at end of intervention outcome assessment and three-month follow-up. Of 315 potentially eligible participants 81 (29%) were recruited. 88% (n = 71) completed outcome and 77% (n = 62) follow-up assessments. Of eight intervention group non-completers, six had no preference for art participation. Outcome completion varied between 97% and 77%. Running groups was difficult because of randomisation timing. Effectiveness cannot be determined from this feasibility study but effects sizes suggested art participation may benefit emotional wellbeing, measured on the positive and negative affect schedule, and self-efficacy for Art (d = 0.24-0.42). Undertaking a RCT of art participation within stroke rehabilitation was feasible. Art participation may enhance self-efficacy and positively influence emotional wellbeing. These should be outcomes in a future definitive trial. A cluster RCT would ensure art groups could be reliably convened. Fewer measures, and better retention strategies are required. Implications for Rehabilitation This feasibility randomised controlled trial (RCT) showed that recruiting and retaining stroke survivors in an RCT of a visual arts participation intervention within stroke rehabilitation was feasible. Preference to participate in art activities may influence recruitment and drop-out rates, and should be addressed and evaluated fully. Art participation as part of rehabilitation may improve some aspects of post-stroke wellbeing, including positive affect and self-efficacy for art. A future definitive cluster RCT would facilitate full evaluation of the value art participation can add to rehabilitation.

Stroke prevention by percutaneous closure of patent foramen ovale: a systematic review and meta-analysis.

PubMed

Wolfrum, Mathias; Froehlich, Georg M; Knapp, Guido; Casaubon, Leanne K; DiNicolantonio, James J; Lansky, Alexandra J; Meier, Pascal

2014-03-01

The role of percutaneous closure of patent foramen oval (PFO) in patients with cryptogenic stroke has been very controversial for years due to a lack of clear evidence. Systematic review and meta-analysis of the effect of percutaneous PFO closure for secondary prevention of cryptogenic strokes as compared to best medical therapy (BMT). Trials were identified through a literature search until 28 May 2013. Controlled clinical trials (randomised and non-randomised) comparing percutaneous PFO closure with BMT. Main end point of interest was stroke. A random effects model was used to calculate the pooled relative risks (RR) with 95% CIs. A total of 14 studies (three randomised controlled trials (RCT) and 11 non-randomised observational studies (non-RCT)), and a total of 4335 patients were included for this analysis. There was no significant treatment effect of PFO closure regarding stroke among the RCT (RR 0.66, 95% CI 0.37 to 1.19, p=0.171). However, among non-RCT stroke was reduced (RR 0.37, 95% CI 0.20 to 0.67, p<0.001) after PFO closure. A time-to-event (stroke) analysis, combining all three RCT and the two non-RCT which applied strict multivariate adjustments, showed a borderline significant risk reduction after PFO closure (HR 0.58, 95% CI 0.33 to 0.99, p=0.047). Neither risk of bleeding nor mortality differed significantly between the groups. However, there was a higher incidence of new onset atrial fibrillation in the closure group (RR 3.50, 95% CI 1.47 to 8.35, p=0.005). Percutaneous closure of PFO in patients with cryptogenic stroke does not appear superior to medical therapy according to currently available randomised data. Furthermore, it is associated with an increased incidence of atrial fibrillation. However, there are signals pointing towards a potential benefit and more research should be strongly encouraged.

Effects of reiki in clinical practice: a systematic review of randomised clinical trials.

PubMed

Lee, M S; Pittler, M H; Ernst, E

2008-06-01

The aim of this systematic review is to summarise and critically evaluate the evidence for the effectiveness of reiki. We searched the literature using 23 databases from their respective inceptions through to November 2007 (search again 23 January 2008) without language restrictions. Methodological quality was assessed using the Jadad score. The searches identified 205 potentially relevant studies. Nine randomised clinical trials (RCTs) met our inclusion criteria. Two RCTs suggested beneficial effects of reiki compared with sham control on depression, while one RCT did not report intergroup differences. For pain and anxiety, one RCT showed intergroup differences compared with sham control. For stress and hopelessness a further RCT reported effects of reiki and distant reiki compared with distant sham control. For functional recovery after ischaemic stroke there were no intergroup differences compared with sham. There was also no difference for anxiety between groups of pregnant women undergoing amniocentesis. For diabetic neuropathy there were no effects of reiki on pain. A further RCT failed to show the effects of reiki for anxiety and depression in women undergoing breast biopsy compared with conventional care. In total, the trial data for any one condition are scarce and independent replications are not available for each condition. Most trials suffered from methodological flaws such as small sample size, inadequate study design and poor reporting. In conclusion, the evidence is insufficient to suggest that reiki is an effective treatment for any condition. Therefore the value of reiki remains unproven.

Factorial experiments: efficient tools for evaluation of intervention components.

PubMed

Collins, Linda M; Dziak, John J; Kugler, Kari C; Trail, Jessica B

2014-10-01

An understanding of the individual and combined effects of a set of intervention components is important for moving the science of preventive medicine interventions forward. This understanding can often be achieved in an efficient and economical way via a factorial experiment, in which two or more independent variables are manipulated. The factorial experiment is a complement to the RCT; the two designs address different research questions. To offer an introduction to factorial experiments aimed at investigators trained primarily in the RCT. The factorial experiment is compared and contrasted with other experimental designs used commonly in intervention science to highlight where each is most efficient and appropriate. Several points are made: factorial experiments make very efficient use of experimental subjects when the data are properly analyzed; a factorial experiment can have excellent statistical power even if it has relatively few subjects per experimental condition; and when conducting research to select components for inclusion in a multicomponent intervention, interactions should be studied rather than avoided. Investigators in preventive medicine and related areas should begin considering factorial experiments alongside other approaches. Experimental designs should be chosen from a resource management perspective, which states that the best experimental design is the one that provides the greatest scientific benefit without exceeding available resources. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Understanding the Importance of Context: A Qualitative Study of a Location-Based Exergame to Enhance School Childrens Physical Activity.

PubMed

Robertson, Judy; Jepson, Ruth; Macvean, Andrew; Gray, Stuart

2016-01-01

Many public health interventions are less effective than expected in 'real life settings', yet little work is undertaken to understand the reasons why. The effectiveness of complex public health interventions can often be traced back to a robust programme theory (how and why an intervention brings about a change in outcome(s)) and assumptions that are made about the context in which it is implemented. Understanding whether effectiveness (or lack thereof) is due to the intervention or the context is hugely helpful in decisions about whether to a) modify the intervention; b) modify the context; c) stop providing the intervention. Exergames-also known as Active Video Games or AVGS-are video games which use the player's bodily movements as input and have potential to increase physical activity in children. However, the results of a recent pilot randomised controlled trial (RCT) of a location-based exergame (FitQuest) in a school setting were inconclusive; no significant effect was detected for any of the outcome measures. The aim of this study was to explore whether the programme theory for FitQuest was correct with respect to how and why it would change children's perceptions of physical activity (PA) and exercise self-efficacy in the school setting. A further aim was to investigate the features of the school setting (context) that may impact on FitQuest's implementation and effectiveness. Qualitative data (gathered during the RCT) were gathered from interviews with teachers and children, and observation of sessions using FitQuest. Thematic analysis indicated that whilst children enjoyed playing the game, engaged with goal setting within the game context and undertook low to vigorous physical activity, there were significant contextual factors that prevented it from being played as often as intended. These included environmental factors (e.g. size of the playground), school factors (cancellations due to other activities), school technology policy (rules relating to mobile phone usage) and teacher factors (engagement with the intervention). A revised logic model for the FitQuest intervention indicates how both the design of exergame technology (intervention) and features of the school environment (context) could be improved to increase chances of effectiveness in the future.

Overexpression and deletion of phospholipid transfer protein reduce HDL mass and cholesterol efflux capacity but not macrophage reverse cholesterol transport[S

PubMed Central

Kuwano, Takashi; Bi, Xin; Cipollari, Eleonora; Yasuda, Tomoyuki; Lagor, William R.; Szapary, Hannah J.; Tohyama, Junichiro; Millar, John S.; Billheimer, Jeffrey T.; Lyssenko, Nicholas N.; Rader, Daniel J.

2017-01-01

Phospholipid transfer protein (PLTP) may affect macrophage reverse cholesterol transport (mRCT) through its role in the metabolism of HDL. Ex vivo cholesterol efflux capacity and in vivo mRCT were assessed in PLTP deletion and PLTP overexpression mice. PLTP deletion mice had reduced HDL mass and cholesterol efflux capacity, but unchanged in vivo mRCT. To directly compare the effects of PLTP overexpression and deletion on mRCT, human PLTP was overexpressed in the liver of wild-type animals using an adeno-associated viral (AAV) vector, and control and PLTP deletion animals were injected with AAV-null. PLTP overexpression and deletion reduced plasma HDL mass and cholesterol efflux capacity. Both substantially decreased ABCA1-independent cholesterol efflux, whereas ABCA1-dependent cholesterol efflux remained the same or increased, even though preβ HDL levels were lower. Neither PLTP overexpression nor deletion affected excretion of macrophage-derived radiocholesterol in the in vivo mRCT assay. The ex vivo and in vivo assays were modified to gauge the rate of cholesterol efflux from macrophages to plasma. PLTP activity did not affect this metric. Thus, deviations in PLTP activity from the wild-type level reduce HDL mass and ex vivo cholesterol efflux capacity, but not the rate of macrophage cholesterol efflux to plasma or in vivo mRCT. PMID:28137768

Generated effect modifiers (GEM's) in randomized clinical trials.

PubMed

Petkova, Eva; Tarpey, Thaddeus; Su, Zhe; Ogden, R Todd

2017-01-01

In a randomized clinical trial (RCT), it is often of interest not only to estimate the effect of various treatments on the outcome, but also to determine whether any patient characteristic has a different relationship with the outcome, depending on treatment. In regression models for the outcome, if there is a non-zero interaction between treatment and a predictor, that predictor is called an "effect modifier". Identification of such effect modifiers is crucial as we move towards precision medicine, that is, optimizing individual treatment assignment based on patient measurements assessed when presenting for treatment. In most settings, there will be several baseline predictor variables that could potentially modify the treatment effects. This article proposes optimal methods of constructing a composite variable (defined as a linear combination of pre-treatment patient characteristics) in order to generate an effect modifier in an RCT setting. Several criteria are considered for generating effect modifiers and their performance is studied via simulations. An example from a RCT is provided for illustration. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Design of an international multicentre RCT on group schema therapy for borderline personality disorder.

PubMed

Wetzelaer, Pim; Farrell, Joan; Evers, Silvia M A A; Jacob, Gitta A; Lee, Christopher W; Brand, Odette; van Breukelen, Gerard; Fassbinder, Eva; Fretwell, Heather; Harper, R Patrick; Lavender, Anna; Lockwood, George; Malogiannis, Ioannis A; Schweiger, Ulrich; Startup, Helen; Stevenson, Teresa; Zarbock, Gerhard; Arntz, Arnoud

2014-11-18

Borderline personality disorder (BPD) is a severe and highly prevalent mental disorder. Schema therapy (ST) has been found effective in the treatment of BPD and is commonly delivered through an individual format. A group format (group schema therapy, GST) has also been developed. GST has been found to speed up and amplify the treatment effects found for individual ST. Delivery in a group format may lead to improved cost-effectiveness. An important question is how GST compares to treatment as usual (TAU) and what format for delivery of schema therapy (format A; intensive group therapy only, or format B; a combination of group and individual therapy) produces the best outcomes. An international, multicentre randomized controlled trial (RCT) will be conducted with a minimum of fourteen participating centres. Each centre will recruit multiple cohorts of at least sixteen patients. GST formats as well as the orders in which they are delivered to successive cohorts will be balanced. Within countries that contribute an uneven number of sites, the orders of GST formats will be balanced within a difference of one. The RCT is designed to include a minimum of 448 patients with BPD. The primary clinical outcome measure will be BPD severity. Secondary clinical outcome measures will include measures of BPD and general psychiatric symptoms, schemas and schema modes, social functioning and quality of life. Furthermore, an economic evaluation that consists of cost-effectiveness and cost-utility analyses will be performed using a societal perspective. Lastly, additional investigations will be carried out that include an assessment of the integrity of GST, a qualitative study on patients' and therapists' experiences with GST, and studies on variables that might influence the effectiveness of GST. This trial will compare GST to TAU for patients with BPD as well as two different formats for the delivery of GST. By combining an evaluation of clinical effectiveness, an economic evaluation and additional investigations, it will contribute to an evidence-based understanding of which treatment should be offered to patients with BPD from clinical, economic, and stakeholders' perspectives. Netherlands Trial Register NTR2392. Registered 25 June 2010.

Protocol for the economic evaluation of a community-based intervention to improve growth among children under two in rural India (CARING trial)

PubMed Central

Sinha, Rajesh; Kumar Ojha, Amit; Sarangi, Soumendra; Nair, Nirmala; Tripathy, Prasanta; Sachdev, H S; Bhattacharyya, Sanghita; Gope, Rajkumar; Rath, Shibanand; Rath, Suchitra; Srivastava, Aradhana; Pulkki-Brännström, Anni-Maria; Costello, Anthony; Copas, Andrew; Saville, Naomi; Prost, Audrey; Haghparast-Bidgoli, Hassan

2016-01-01

Introduction Undernutrition affects ∼165 million children globally and contributes up to 45% of all child deaths. India has the highest proportion of global undernutrition-related morbidity and mortality. This protocol describes the planned economic evaluation of a community-based intervention to improve growth in children under 2 years of age in two rural districts of eastern India. The intervention is being evaluated through a cluster-randomised controlled trial (cRCT, the CARING trial). Methods and analysis A cost-effectiveness and cost–utility analysis nested within a cRCT will be conducted from a societal perspective, measuring programme, provider, household and societal costs. Programme costs will be collected prospectively from project accounts using a standardised tool. These will be supplemented with time sheets and key informant interviews to inform the allocation of joint costs. Direct and indirect costs incurred by providers will be collected using key informant interviews and time use surveys. Direct and indirect household costs will be collected prospectively, using time use and consumption surveys. Incremental cost-effectiveness ratios (ICERs) will be calculated for the primary outcome measure, that is, cases of stunting prevented, and other outcomes such as cases of wasting prevented, cases of infant mortality averted, life years saved and disability-adjusted life years (DALYs) averted. Sensitivity analyses will be conducted to assess the robustness of results. Ethics and dissemination There is a shortage of robust evidence regarding the cost-effectiveness of strategies to improve early child growth. As this economic evaluation is nested within a large scale, cRCT, it will contribute to understanding the fiscal space for investment in early child growth, and the relative (in)efficiency of prioritising resources to this intervention over others to prevent stunting in this and other comparable contexts. The protocol has all necessary ethical approvals and the findings will be disseminated within academia and the wider policy sphere. Trial registration number ISRCTN51505201; pre-results. PMID:27807084

Integrating evidence-based teaching into to clinical practice should improve outcomes.

PubMed

Richards, Derek

2005-01-01

Sources used were Medline, Embase, the Education Resources Information Centre , Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, Health Technology Assessment database, Best Evidence, Best Evidence Medical Education and Science Citation Index, along with reference lists of known systematic reviews. Studies were chosen for inclusion if they evaluated the effects of postgraduate evidence-based medicine (EBM) or critical appraisal teaching in comparison with a control group or baseline before teaching, using a measure of participants' learning achievements or patients' health gains as outcomes. Articles were graded as either level 1 (randomised controlled trials (RCT)) or level 2 (non-randomised studies that either had a comparison with a control group), or a before and after comparison without a control group. Learning achievement was assessed separately for knowledge, critical appraisal skills, attitudes and behaviour. Because of obvious heterogeneity in the features of individual studies, their quality and assessment tools used, a meta-analysis could not be carried out. Conclusions were weighted by methodological quality. Twenty-three relevant studies were identified, comprising four RCT, seven non-RCT, and 12 before and after comparison studies. Eighteen studies (including two RCT) evaluated a standalone teaching method and five studies (including two RCT) evaluated a clinically integrated teaching method. Standalone teaching improved knowledge but not skills, attitudes or behaviour. Clinically integrated teaching improved knowledge, skills, attitudes and behaviour. Teaching of EBM should be moved from classrooms to clinical practice to achieve improvements in substantial outcomes.

Comparison of a Self-Directed and Therapist-Assisted Telehealth Parent-Mediated Intervention for Children with ASD: A Pilot RCT

ERIC Educational Resources Information Center

Ingersoll, Brooke; Wainer, Allison L.; Berger, Natalie I.; Pickard, Katherine E.; Bonter, Nicole

2016-01-01

This pilot RCT compared the effect of a self-directed and therapist-assisted telehealth-based parent-mediated intervention for young children with ASD. Families were randomly assigned to a self-directed or therapist-assisted program. Parents in both groups improved their intervention fidelity, self-efficacy, stress, and positive perceptions of…

Retention Strategies for Health Disparities Preventive Trials: Findings from the Early Childhood Caries Collaborating Centers

PubMed Central

Garcia, Raul I.; Tiwari, Tamanna; Ramos-Gomez, Francisco; Heaton, Brenda; Orozco, Mario; Rasmussen, Margaret; Braun, Patricia; Henshaw, Michelle; Borrelli, Belinda; Albino, Judith; Vargas, Clemencia; Diamond, Courtney; Gebel, Christina; Batliner, Terrence S.; Barker, Judith; Gregorich, Steven; Gansky, Stuart A.

2017-01-01

Objectives To identify successful strategies for retention of participants in multi-year, community-based randomized controlled trials (RCTs) aiming to reduce early childhood caries in health disparities populations from diverse racial/ethnic backgrounds and across diverse geographic settings. Methods Four RCTs conducted by the Early Childhood Caries Collaborating Centers (EC4), an initiative of the National Institute of Dental and Craniofacial Research, systematically collected information on the success of various strategies implemented to promote participant retention in each RCT. The observational findings from this case series of four RCTs were tabulated and the strategies rated by study staff. Results Participant retention at 12 months of follow-up ranged from 52.8% to 91.7%, and at 24 months ranged from 53.6% to 85.9, across the four RCT. For the three RCT that had a 36 month follow-up, retention ranged from 53.6% to 85.1%. Effectiveness of different participant retention strategies varied widely across the RCT. Conclusions Findings from this case series study may help to guide the design of future RCTs to maximize retention of study participants and yield needed data on effective interventions to reduce oral health disparities. PMID:27759164

Effects of Astaxanthin on Reverse Cholesterol Transport and Atherosclerosis in Mice

PubMed Central

Zou, Tang-Bin; Zhu, Shan-Shan; Luo, Fei; Li, Wei-Qiao

2017-01-01

High plasma level of HDL-cholesterol (HDL-C) has been consistently associated with a decreased risk of atherosclerosis (AS); thus, HDL-C is considered to be an antiatherogenic lipoprotein. The development of novel therapies to enhance the atheroprotective properties of HDL may have the possibility of further reducing the residual AS risk. Reverse cholesterol transport (RCT) is believed to be a primary atheroprotective activity of HDL, which has been shown to promote the efflux of excess cholesterol from macrophage-derived foam cells via ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor class B type I (SR-BI) and then transport it back to the liver for excretion into bile and eventually into the feces. In the current study, we investigated the effects of astaxanthin on RCT and AS progression in mice. The results showed that short- and long-term supplementation of astaxanthin promote RCT in C57BL/6J and ApoE−/− mice, respectively. Moreover, astaxanthin can relieve the plaque area of the aortic sinus and aortic cholesterol in mice. These findings suggest that astaxanthin is beneficial for boosting RCT and preventing the development of AS. PMID:29226138

Psychosocial interventions for people with both severe mental illness and substance misuse.

PubMed

Cleary, M; Hunt, G; Matheson, S; Siegfried, N; Walter, G

2008-01-23

Even low levels of substance misuse by people with a severe mental illness can have detrimental effects. To assess the effects of psychosocial interventions for substance reduction in people with a serious mental illness. For this update (2007) we searched the Cochrane Schizophrenia Group Trials Register (May 2006) which is based on regular searches of major databases. We included all randomised controlled trials (RCTs) comparing psychosocial interventions for substance misuse with standard care in people with serious mental illness. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where data were homogeneous. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. Evaluation of long-term integrated care included 4 RCTs (total n=735). We found no significant difference on measures of substance use (n=85, 1 RCT, RR 0.89 CI 0.6 to 1.3) or loss to treatment (n=603, 3 RCTs, RR 1.09 CI 0.8 to 1.5). For the non-integrated intensive case management trials (4 RCTs, total n=151) we also found no significant difference for loss (n=134, 3 RCTs, RR 1.35 CI 0.8 to 2.2). Motivational interviewing plus cognitive behavioural therapy (3 RCTs, total n=276) did not reveal any advantage for retaining participants (n=36, 1 RCT, RR lost to treatment 0.50 CI 0.1 to 5.0) or for relapse (n=36, 1 RCT, RR 0.58 CI 0.3 to 1.1), and no benefit for reducing substance use (n=119, 1 RCT, RR 0.19 CI -0.2 to 0.6). Cognitive behavioural therapy alone (4 trials, total n=260) showed fewer participants lost from treatment (n=260, 4 RCTs, p=0.02, RR 0.61 CI 0.4 to 0.9). No benefits were observed on measures of lessening cannabis use (n=47, 1 RCT, RR 1.30 CI 0.8 to 2.2) or on the number of participants using substances (alcohol; n=46, 1 RCT, RR 5.88 CI 0.8 to 44.0, drugs; n=46, 1 RCT, RR 2.02 CI 0.9 to 4.8) and no differences were observed on measures of mental state (n=105, 1 RCT, RR 0.52 CI -0.8 to 1.8). We found no advantage for motivational interviewing alone (5 trials, total n=338) in reducing 'lost to evaluation' (n=338, 5 RCTs, RR 0.96 CI 0.6 to 1.5) compared with treatment as usual, although significantly more participants in the motivational interviewing group reported for their first aftercare appointment (n=93, 1 RCT, RR 0.69 CI 0.5 to 0.9, NNT 4 CI 3 to 12). Some differences were observed in abstaining from alcohol favouring treatment (n=28, 1 RCT, RR 0.36 CI 0.2 to 0.8, NNT 2 CI 2 to 5), but not other substances (n=89, 1 RCT, RR -0.07 CI -0.6 to 0.4) and no differences were observed in mental state (n=30, 1 RCT, WMD -4.20 CI -18.7 to 10.3). Finally, we found no significant differences for skills training in the numbers lost to treatment by 12 months (n=94, 2 RCTs, RR 0.70 CI 0.4 to 1.1). We included 25 RCTs and found no compelling evidence to support any one psychosocial treatment over another to reduce substance use (or improve mental state) by people with serious mental illnesses. Furthermore, methodological difficulties exist which hinder pooling and interpreting results; high drop out rates, varying fidelity of interventions, varying outcome measures, settings and samples and comparison groups may have received higher levels of treatment than standard care. Further studies are required which address these concerns and improve the evidence in this important area.

Developing a Reporting Guideline for Social and Psychological Intervention Trials

ERIC Educational Resources Information Center

Grant, Sean; Montgomery, Paul; Hopewell, Sally; Macdonald, Geraldine; Moher, David; Mayo-Wilson, Evan

2013-01-01

Social and psychological interventions are often complex. Understanding randomized controlled trials (RCTs) of these complex interventions requires a detailed description of the interventions tested and the methods used to evaluate them; however, RCT reports often omit, or inadequately report, this information. Incomplete and inaccurate reporting…

Whole Grain Intake and Glycaemic Control in Healthy Subjects: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Marventano, Stefano; Vetrani, Claudia; Vitale, Marilena; Godos, Justyna; Riccardi, Gabriele; Grosso, Giuseppe

2017-07-19

There is growing evidence from both observational and intervention studies that Whole Grain (WG) cereals exert beneficial effects on human health, especially on the metabolic profile. The aim of this study was to perform a meta-analysis of randomised controlled trials (RCT) to assess the acute and medium/long-term effect of WG foods on glycaemic control and insulin sensitivity in healthy individuals. A search for all the published RCT on the effect of WG food intake on glycaemic and insulin response was performed up to December 2016. Effect size consisted of mean difference (MD) and 95% CI between the outcomes of intervention and the control groups using the generic inverse-variance random effects model. The meta-analysis of the 14 studies testing the acute effects of WG foods showed significant reductions of the post-prandial values of the glucose iAUC (0-120 min) by -29.71 mmol min/L (95% CI: -43.57, -15.85 mmol min/L), the insulin iAUC (0-120 min) by -2.01 nmol min/L (95% CI: -2.88, -1.14 nmol min/L), and the maximal glucose and insulin response. In 16 medium- and long-term RCTs, effects of WG foods on fasting glucose and insulin and homeostatic model assessment-insulin resistance values were not significant. The consumption of WG foods is able to improve acutely the postprandial glucose and insulin homeostasis compared to similar refined foods in healthy subjects. Further research is needed to better understand the long-term effects and the biological mechanisms.

Mothers' perceptions of their child's enrollment in a randomized clinical trial: poor understanding, vulnerability and contradictory feelings.

PubMed

Carvalho, Adriana Assis; Costa, Luciane Rezende

2013-12-10

Little is known about the views of mothers when their children are invited to participate in randomized clinical trials (RCTs) investigating medicines and/or invasive procedures. Our goal was to understand mothers' perceptions of the processes of informed consent and randomization in a RCT that divided uncooperative children into three intervention groups (physical restraint, sedation, and general anesthesia) for dental rehabilitation. This is a qualitative study based on semi-structured interviews with mothers accompanying children under 3 years old presenting severe early childhood caries. Their responses were analyzed using content analysis. We identified one major theme from 15 mothers' responses - "Understanding of, attitudes toward, and feelings about consenting to participate in a RCT involving advanced behavior guidance techniques and about randomization" - that was derived from the following subcategories: confusion in defining techniques, questions after signing the consent form, lack of knowledge about the techniques, acceptance or questioning of the drawing, sharing responsibility with the child during the drawing, and feelings of faith in God, fear, powerlessness to choose, and relief from or an increase in pressure. Despite mothers' misunderstanding, vulnerability, and contradictory feelings, they were willing to overlook their thoughts in order to complete their children's dental treatment.

Neighborhood Effects in a Behavioral Randomized Controlled Trial

PubMed Central

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

2015-01-01

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

Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer.

PubMed

Staar, S; Rudat, V; Stuetzer, H; Dietz, A; Volling, P; Schroeder, M; Flentje, M; Eckel, H E; Mueller, R P

2001-08-01

To demonstrate the efficacy of radiochemotherapy (RCT) as the first choice of treatment for advanced unresectable head-and-neck cancer. To prove an expected benefit of simultaneously given chemotherapy, a two-arm randomized study with hyperfractionated accelerated radiochemotherapy (HF-ACC-RCT) vs. hyperfractionated accelerated radiotherapy (HF-ACC-RT) was initiated. The primary endpoint was 1-year survival with local control (SLC). Patients with Stage III and IV (UICC) unresectable oro- and hypopharyngeal carcinomas were randomized for HF-ACC-RCT with 2 cycles of 5-FU (600 mg/m(2)/day)/carboplatinum (70 mg/m(2)) on days 1--5 and 29--33 (arm A) or HF-ACC-RT alone (arm B). In both arms, there was a second randomization for testing the effect of prophylactically given G-CSF (263 microg, days 15--19) on mucosal toxicity. Total RT dose in both arms was 69.9 Gy in 38 days, with a concomitant boost regimen (weeks 1--3: 1.8 Gy/day, weeks 4 and 5: b.i.d. RT with 1.8 Gy/1.5 Gy). Between July 1995 and May 1999, 263 patients were randomized (median age 56 years; 96% Stage IV tumors, 4% Stage III tumors). This analysis is based on 240 patients: 113 patients with RCT and 127 patients with RT, qualified for protocol and starting treatment. There were 178 oropharyngeal and 62 hypopharyngeal carcinomas. Treatment was tolerable in both arms, with a higher mucosal toxicity after RCT. Restaging showed comparable nonsignificant different CR + PR rates of 92.4% after RCT and 87.9% after RT (p = 0.29). After a median observed time of 22.3 months, l- and 2-year local-regional control (LRC) rates were 69% and 51% after RCT and 58% and 45% after RT (p = 0.14). There was a significantly better 1-year SLC after RCT (58%) compared with RT (44%, p = 0.05). Patients with oropharyngeal carcinomas showed significantly better SLC after RCT (60%) vs. RT (40%, p = 0.01); the smaller group of hypopharyngeal carcinomas had no statistical benefit of RCT (p = 0.84). For both tumor locations, prophylactically given G-CSF was a poor prognostic factor (Cox regression), and resulted in reduced LRC (log-rank test: +/- G-CSF, p = 0.0072). With accelerated radiotherapy, the efficiency of simultaneously given chemotherapy may be not as high as expected when compared to standard fractionated RT. Oropharyngeal carcinomas showed better LRC after HF-ACC-RCT vs. HF-ACC-RT; hypopharyngeal carcinomas did not. Prophylactic G-CSF resulted in an unexpected reduced local control and should be given in radiotherapy regimen only with strong hematologic indication.

A systematic review of the use of aromatherapy in treatment of behavioral problems in dementia.

PubMed

Fung, Jo Kamen K M; Tsang, Hector W H; Chung, Raymond C K

2012-07-01

We aimed to fill the literature gap by identifying the clinical benefits of aromatherapy in older adults with dementia, and its efficacy in reducing behavioral and psychological symptoms of dementia (BPSD) based on available randomized controlled trials (RCT). A systematic review of 11 clinical trials shortlisted from electronic databases from 1995 to 2011 was carried out. The RCT showed that aromatherapy had positive effects on reduction of BPSD, improvement in cognitive functions, increasing quality of life, enhancing independence of activities of daily living and so on. However, adverse effects were noted in some studies. Limitations on methodology are discussed and suggestions on directions of further studies are made. It is recommended that aromatherapy shows the potential to be applied as a therapeutic and safe complementary and alternative therapy for the management of BPSD on more evidence collected from better designed RCT. © 2012 Japan Geriatrics Society.

Implications of clinical trial design on sample size requirements.

PubMed

Leon, Andrew C

2008-07-01

The primary goal in designing a randomized controlled clinical trial (RCT) is to minimize bias in the estimate of treatment effect. Randomized group assignment, double-blinded assessments, and control or comparison groups reduce the risk of bias. The design must also provide sufficient statistical power to detect a clinically meaningful treatment effect and maintain a nominal level of type I error. An attempt to integrate neurocognitive science into an RCT poses additional challenges. Two particularly relevant aspects of such a design often receive insufficient attention in an RCT. Multiple outcomes inflate type I error, and an unreliable assessment process introduces bias and reduces statistical power. Here we describe how both unreliability and multiple outcomes can increase the study costs and duration and reduce the feasibility of the study. The objective of this article is to consider strategies that overcome the problems of unreliability and multiplicity.

Effects of behavioural exercise therapy on the effectiveness of a multidisciplinary rehabilitation for chronic non-specific low back pain: study protocol for a randomised controlled trial.

PubMed

Hofmann, Jana; Peters, Stefan; Geidl, Wolfgang; Hentschke, Christian; Pfeifer, Klaus

2013-03-11

In Germany, a multidisciplinary rehabilitation named "behavioural medical rehabilitation" (BMR) is available for treatment of chronic low back pain (clbp). A central component of BMR is standard exercise therapy (SET), which is directed mainly to improve physical fitness. There is a need to address psychosocial factors within SET and therefore to improve behavior change with a focus on the development of self-management skills in dealing with clbp. Furthermore, short-term effectiveness of BMR with a SET has been proven, but the impact of a behavioural exercise therapy (BET) for improvement of the long-term effectiveness of BMR is unclear. To compare the effectiveness of two exercise programs with different approaches within BMR on the effects of BMR a prospective randomized controlled trial (RCT) in two rehabilitation centres will be performed. 214 patients aged 18-65 with clbp will be, based on an "urn randomisation"-algorithm, randomly assigned to a BMR with SET (function-oriented, n=107) and BMR with BET (behaviour-oriented, n=107). Both exercise programs have a mean duration of 26 hours in three weeks and are delivered by a limited number of not-blinded study therapists in closed groups with six to twelve patients who will be masked regarding study group. The main differences of BET lie in its detailed manualised program with a theory-based, goal-orientated combination of exercise, education and behavioural elements, active participation of patients and consideration of their individual preferences and previous experiences with exercise. The primary outcome is functional ability assessed with the Hannover Functional Ability Questionnaire directly before and after the rehabilitation program, as well as a six and twelve-month follow-up. This RCT is designed to explore the effects of BET on the effectiveness of a BMR compared to a BMR with SET in the management of patients with clbp. Methodological challenges arise from conducting a RCT within routine health care as well as from ensuring high treatment integrity. Findings of this study might contribute to a better understanding of the mechanism of action of BMR and the special effects of BET and may be used to improve the quality of these interventions in routine care, therefore reducing the burden to patients with disabling clbp. Current controlled trials NCT01666639.

Interventions for treating burning mouth syndrome.

PubMed

McMillan, Roddy; Forssell, Heli; Buchanan, John Ag; Glenny, Anne-Marie; Weldon, Jo C; Zakrzewska, Joanna M

2016-11-18

Burning mouth syndrome (BMS) is a term used for oral mucosal pain (burning pain or discomfort in the tongue, lips or entire oral cavity) without identifiable cause. General population prevalence varies from 0.1% to 3.9%. Many BMS patients indicate anxiety, depression, personality disorders and impaired quality of life (QoL). This review updates the previous versions published in 2000 and 2005. To determine the effectiveness and safety of any intervention versus placebo for symptom relief and changes in QoL, taste, and feeling of dryness in people with BMS. Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 31 December 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 11) in the Cochrane Library (searched 31 December 2015), MEDLINE Ovid (1946 to 31 December 2015), and Embase Ovid (1980 to 31 December 2015). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. We placed no restrictions on the language or date of publication when searching the electronic databases SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any treatment against placebo in people with BMS. The primary outcomes were symptom relief (pain/burning) and change in QoL. Secondary outcomes included change in taste, feeling of dryness, and adverse effects. We used standard methodological procedures expected by Cochrane. Outcome data were analysed as short-term (up to three months) or long-term (three to six months). We included 23 RCTs (1121 analysed participants; 83% female). Interventions were categorised as: antidepressants and antipsychotics, anticonvulsants, benzodiazepines, cholinergics, dietary supplements, electromagnetic radiation, physical barriers, psychological therapies, and topical treatments.Only one RCT was assessed at low risk of bias overall, four RCTs' risk of bias was unclear, and 18 studies were at high risk of bias. Overall quality of the evidence for effectiveness was very low for all interventions and all outcomes.Twenty-one RCTs assessed short-term symptom relief. There is very low-quality evidence of benefit from electromagnetic radiation (one RCT, 58 participants), topical benzodiazepines (two RCTs, 111 participants), physical barriers (one RCT, 50 participants), and anticonvulsants (one RCT, 100 participants). We found insufficient/contradictory evidence regarding the effectiveness of antidepressants, cholinergics, systemic benzodiazepines, dietary supplements or topical treatments. No RCT assessing psychological therapies evaluated short-term symptom relief.Four studies assessed long-term symptom relief. There is very low-quality evidence of a benefit from psychological therapies (one RCT, 30 participants), capsaicin oral rinse (topical treatment) (one RCT, 18 participants), and topical benzodiazepines (one RCT, 66 participants). We found no evidence of a difference for dietary supplements or lactoperoxidase oral rinse. No studies assessing antidepressants, anticonvulsants, cholinergics, electromagnetic radiation or physical barriers evaluated long-term symptom relief.Short-term change in QoL was assessed by seven studies (none long-term).The quality of evidence was very low. A benefit was found for electromagnetic radiation (one RCT, 58 participants), however findings were inconclusive for antidepressants, benzodiazepines, dietary supplements and physical barriers.Secondary outcomes (change in taste and feeling of dryness) were only assessed short-term, and the findings for both were also inconclusive.With regard to adverse effects, there is very low-quality evidence that antidepressants increase dizziness and drowsiness (one RCT, 37 participants), and that alpha lipoic acid increased headache (two RCTs, 118 participants) and gastrointestinal complaints (3 RCTs, 138 participants). We found insufficient/contradictory evidence regarding adverse events for anticonvulsants or benzodiazepines. Adverse events were poorly reported or unreported for cholinergics, electromagnetic radiation, and psychological therapies. No adverse events occurred from physical barriers or topical therapy use. Given BMS' potentially disabling nature, the need to identify effective modes of treatment for sufferers is vital. Due to the limited number of clinical trials at low risk of bias, there is insufficient evidence to support or refute the use of any interventions in managing BMS. Further clinical trials, with improved methodology and standardised outcome sets are required in order to establish which treatments are effective. Future studies are encouraged to assess the role of treatments used in other neuropathic pain conditions and psychological therapies in the treatment of BMS.

Effect of Dysphagia Screening Strategies on Clinical Outcomes After Stroke: A Systematic Review for the 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke.

PubMed

Smith, Eric E; Kent, David M; Bulsara, Ketan R; Leung, Lester Y; Lichtman, Judith H; Reeves, Mathew J; Towfighi, Amytis; Whiteley, William N; Zahuranec, Darin B

2018-03-01

Dysphagia screening protocols have been recommended to identify patients at risk for aspiration. The American Heart Association convened an evidence review committee to systematically review evidence for the effectiveness of dysphagia screening protocols to reduce the risk of pneumonia, death, or dependency after stroke. The Medline, Embase, and Cochrane databases were searched on November 1, 2016, to identify randomized controlled trials (RCTs) comparing dysphagia screening protocols or quality interventions with increased dysphagia screening rates and reporting outcomes of pneumonia, death, or dependency. Three RCTs were identified. One RCT found that a combined nursing quality improvement intervention targeting fever and glucose management and dysphagia screening reduced death and dependency but without reducing the pneumonia rate. Another RCT failed to find evidence that pneumonia rates were reduced by adding the cough reflex to routine dysphagia screening. A smaller RCT randomly assigned 2 hospital wards to a stroke care pathway including dysphagia screening or regular care and found that patients on the stroke care pathway were less likely to require intubation and mechanical ventilation; however, the study was small and at risk for bias. There were insufficient RCT data to determine the effect of dysphagia screening protocols on reducing the rates of pneumonia, death, or dependency after stroke. Additional trials are needed to compare the validity, feasibility, and clinical effectiveness of different screening methods for dysphagia. © 2018 American Heart Association, Inc.

Clinical audit training improves undergraduates' performance in root canal therapy.

PubMed

Fong, J Y M; Tan, V J H; Lee, J R; Tong, Z G M; Foong, Y K; Tan, J M E; Parolia, A; Pau, A

2017-12-20

To evaluate the effectiveness of clinical audit-feedback cycle as an educational tool in improving the technical quality of root canal therapy (RCT) and compliance with record keeping performed by dental undergraduates. Clinical audit learning was introduced in Year 3 of a 5-year curriculum for dental undergraduates. During classroom activities, students were briefed on clinical audit, selected their audit topics in groups of 5 or 6 students, and prepared and presented their audit protocols. One chosen topic was RCT, in which 3 different cohorts of Year 3 students conducted retrospective audits of patients' records in 2012, 2014 and 2015 for their compliance with recommended record keeping criteria and their performance in RCT. Students were trained by and calibrated against an endodontist (κ ≥ 0.8). After each audit, the findings were reported in class, and recommendations were made for improvement in performance of RCT and record keeping. Students' compliance with published guidelines was presented and their RCT performances in each year were compared using the chi-square test. Overall compliance with of record keeping guidelines was 44.1% in 2012, 79.6% in 2014 and 94.6% in 2015 (P = .001). In the 2012 audit, acceptable extension, condensation and the absence of mishap were observed in 72.4, 75.7% and 91.5%; in the 2014 audit, 95.1%, 64.8% and 51.4%; and in 2015 audit, 96.4%, 82.1% and 92.8% of cases, respectively. In 2015, 76.8% of root canal fillings met all 3 technical quality criteria when compared to 48.6% in 2014 and 44.7% in 2012 (P = .001). Clinical audit-feedback cycle is an effective educational tool for improving dental undergraduates' compliance with record keeping and performance in the technical quality of RCT. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed Central

Bass, Kristin M.; Stark, Louisa A.

2014-01-01

How can researchers in K–12 contexts stay true to the principles of rigorous evaluation designs within the constraints of classroom settings and limited funding? This paper explores this question by presenting a small-scale randomized controlled trial (RCT) designed to test the efficacy of curricular supplemental materials on epigenetics. The researchers asked whether the curricular materials improved students’ understanding of the content more than an alternative set of activities. The field test was conducted in a diverse public high school setting with 145 students who were randomly assigned to a treatment or comparison condition. Findings indicate that students in the treatment condition scored significantly higher on the posttest than did students in the comparison group (effect size: Cohen's d = 0.40). The paper discusses the strengths and limitations of the RCT, the contextual factors that influenced its enactment, and recommendations for others wishing to conduct small-scale rigorous evaluations in educational settings. Our intention is for this paper to serve as a case study for university science faculty members who wish to employ scientifically rigorous evaluations in K–12 settings while limiting the scope and budget of their work. PMID:25452482

Effectiveness and Patient Acceptability of Stellate Ganglion Block (SGB) for Treatment of Posttraumatic Stress Disorder (PTSD) Symptoms among Active Duty Military Members

DTIC Science & Technology

PTSD) symptoms. We will conduct two parallel studies: a randomized, controlled trial (RCT) to evaluate the effectiveness of SGB for treating PTSD, and a...study, individuals enrolled in the RCT will be asked to participate either in a focus group or an interview with their spouse. In addition, we will...conduct focus groups and key informant interviews with providers: those who refer individuals to the study, and those who provide SGB to service members.

Effects of total fat intake on bodyweight in children.

PubMed

Naude, Celeste E; Visser, Marianne E; Nguyen, Kim A; Durao, Solange; Schoonees, Anel

2018-02-15

As part of efforts to prevent childhood overweight and obesity, we need to understand the relationship between total fat intake and body fatness in generally healthy children. To assess the effects of total fat intake on measures of weight and body fatness in children and young people not aiming to lose weight. For this update we revised the previous search strategy and ran it over all years in the Cochrane Library, MEDLINE (Ovid), MEDLINE (PubMed), and Embase (Ovid) (current to 23 May 2017). No language and publication status limits were applied. We searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov for ongoing and unpublished studies (5 June 2017). We included randomised controlled trials (RCTs) in children aged 24 months to 18 years, with or without risk factors for cardiovascular disease, randomised to a lower fat (30% or less of total energy (TE)) versus usual or moderate-fat diet (greater than 30%TE), without the intention to reduce weight, and assessed a measure of weight or body fatness after at least six months. We included prospective analytical cohort studies in these children if they related baseline total fat intake to weight or body fatness at least 12 months later. We duplicated inclusion decisions and resolved disagreement by discussion with other authors. We extracted data on participants, interventions or exposures, controls and outcomes, and trial or cohort quality characteristics, as well as data on potential effect modifiers, and assessed risk of bias for all included studies. We extracted outcome data using the following time point ranges, when available: RCTs: baseline to six months, six to 12 months, one to two years, two to five years and more than five years; cohort studies: baseline to one year, one to two years, two to five years, five to 10 years and more than 10 years. We planned to perform random-effects meta-analyses with relevant subgrouping, and sensitivity and funnel plot analyses where data allowed. We included 24 studies comprising three parallel-group RCTs (n = 1054 randomised) and 21 prospective analytical cohort studies (about 25,059 children completed). Twenty-three were conducted in high-income countries. No meta-analyses were possible, since only one RCT reported the same outcome at each time point range for all outcomes, and cohort studies were too heterogeneous.For the RCTs, concerns about imprecision and poor reporting limited our confidence in our findings. In addition, the inclusion of hypercholesteraemic children in two trials raised concerns about applicability. Lower versus usual or modified total fat intake may have made little or no difference to weight over a six- to twelve month period (mean difference (MD) -0.50 kg, 95% confidence interval (CI) -1.78 to 0.78; 1 RCT; n = 620; low-quality evidence), nor a two- to five-year period (MD -0.60 kg, 95% CI -2.39 to 1.19; 1 RCT; n = 612; low-quality evidence). Compared to controls, lower total fat intake (30% or less TE) probably decreased BMI in children over a one- to two-year period (MD -1.5 kg/m 2 , 95% CI -2.45 to -0.55; 1 RCT; n = 191; moderate-quality evidence), with no other differences evident across the other time points (two to five years: MD 0.00 kg/m 2 , 95% CI -0.63 to 0.63; 1 RCT; n = 541; greater than five years; MD -0.10 kg/m 2 , 95% CI -0.75 to 0.55; 1 RCT; n = 576; low-quality evidence). Lower fat intake probably slightly reduced total cholesterol over six to 12 months compared to controls (MD -0.15 mmol/L, 95% CI -0.24 to -0.06; 1 RCT; n = 618; moderate-quality evidence), but may make little or no difference over longer time periods. Lower fat intake probably slightly decreased low-density lipoprotein (LDL) cholesterol over six to 12 months (MD -0.12 mmol/L, 95% CI -0.20 to -0.04; 1 RCT; n = 618, moderate-quality evidence) and over two to five years (MD -0.09, 95% CI -0.17 to -0.01; 1 RCT; n = 623; moderate-quality evidence), compared to controls. However, lower total fat intake probably made little or no difference to HDL-C over a six- to 12-month period (MD -0.03 mmol/L, 95% CI -0.08 to 0.02; 1 RCT; n = 618; moderate-quality evidence), nor a two- to five-year period (MD -0.01 mmol/L, 95% CI -0.06 to 0.04; 1 RCT; n = 522; moderate-quality evidence). Likewise, lower total fat intake probably made little or no difference to triglycerides in children over a six- to 12-month period (MD -0.01 mmol/L, 95% CI -0.08 to 0.06; 1 RCT; n = 618; moderate-quality evidence). Lower versus usual or modified fat intake may make little or no difference to height over more than five years (MD -0.60 cm, 95% CI -2.06 to 0.86; 1 RCT; n = 577; low-quality evidence).Over half the cohort analyses that reported on primary outcomes suggested that as total fat intake increases, body fatness measures may move in the same direction. However, heterogeneous methods and reporting across cohort studies, and predominantly very low-quality evidence, made it difficult to draw firm conclusions and true relationships may be substantially different. We were unable to reach firm conclusions. Limited evidence from three trials that randomised children to a lower total fat intake (30% or less TE) versus usual or modified fat intake, but with no intention to reduce weight, showed small reductions in body mass index, total- and LDL-cholesterol at some time points with lower fat intake compared to controls, and no consistent differences in effects on weight, high-density lipoprotein (HDL) cholesterol or height. Associations in cohort studies that related total fat intake to later measures of body fatness in children were inconsistent and the quality of this evidence was mostly very low. Twenty-three out of 24 included studies were conducted in high-income countries, and may not be applicable in low- and middle-income settings. High-quality, longer-term studies are needed, that include low- and middle-income settings and look at both possible benefits and risks.

Nevasic audio program for the prevention of chemotherapy induced nausea and vomiting: A feasibility study using a randomized controlled trial design.

PubMed

Moradian, Saeed; Walshe, Catherine; Shahidsales, Soodabeh; Ghavam Nasiri, Mohammad Reza; Pilling, Mark; Molassiotis, Alexander

2015-06-01

Pharmacological therapy is only partially effective in preventing or treating chemotherapy induced nausea and vomiting (CINV). Therefore, exploring the complementary role of non-pharmacological approaches used in addition to pharmacological agents is important. Nevasic uses specially constructed audio signals hypothesized to generate an antiemetic reaction. The aim of this study was to examine the feasibility of conducting a randomized controlled trial (RCT) to evaluate the effectiveness of Nevasic to control CINV. A mixed methods design incorporating an RCT and focus group interviews. For the RCT, female breast cancer patients were randomized to receive either Nevasic plus usual care, music plus usual care, or usual care only. Data were analysed using descriptive statistics and linear mixed-effects models. Five focus group interviews were conducted to obtain participants' views regarding the acceptability of the interventions in the trial. 99 participants were recruited to the RCT and 15 participated in focus group interviews. Recruitment targets were achieved. Issues of Nevasic acceptability were highlighted as weaknesses of the program. This study did not detect any evidence for the effectiveness of Nevasic; however, the results showed statistically significant less use of anti-emetics (p = 0.003) and borderline non-significant improvement in quality of life (p = 0.06). Conducting a non-pharmacological intervention using such an audio program is feasible, although difficulties and limitations exist with its use. Further studies are required to investigate the effectiveness of Nevasic from perspectives such as anti-emetic use, as well as its overall effect on the levels of nausea and vomiting. Copyright © 2014 Elsevier Ltd. All rights reserved.

Do School-Based Programs Prevent HIV and Other Sexually Transmitted Infections in Adolescents? A Systematic Review and Meta-analysis.

PubMed

Mirzazadeh, Ali; Biggs, M Antonia; Viitanen, Amanda; Horvath, Hacsi; Wang, Li Yan; Dunville, Richard; Barrios, Lisa C; Kahn, James G; Marseille, Elliot

2018-05-01

We systematically reviewed the literature to assess the effectiveness of school-based programs to prevent HIV and other sexually transmitted infections (STI) among adolescents in the USA. We searched six databases including PubMed for studies published through May 2017. Eligible studies included youth ages 10-19 years and assessed any school-based programs in the USA that reported changes in HIV/STI incidence or testing. We used Cochrane tool to assess the risk of bias and GRADE to determine the evidence quality for each outcome. Three RCTs and six non-RCTs, describing seven interventions, met study inclusion criteria. No study reported changes in HIV incidence or prevalence. One comprehensive intervention, assessed in a non-RCT and delivered to pre-teens, reduced STI incidence into adulthood (RR 0.36, 95% CI 0.23-0.56). A non-RCT examining chlamydia and gonorrhea incidence before and after a condom availability program found a significant effect at the city level among young men 3 years later (RR 0.43, 95% CI 0.23-0.80). The remaining four interventions found no effect. The effect on STI prevalence was also not significant (pooled RR 0.83 from two non-RCTs, RR 0.70 from one RCT). Only one non-RCT showed an increase in HIV testing (RR 3.19, 95% CI 1.24-8.24). The quality of evidence for all outcomes was very low. Studies, including the RCTs, were of low methodological quality and had mixed findings, thus offering no persuasive evidence for the effectiveness of school-based programs. The most effective intervention spanned 6 years, was a social development-based intervention with multiple components, rather than a sex education program, and started in first grade.

Conducting rigorous research with subgroups of at-risk youth: lessons learned from a teen pregnancy prevention project in Alaska.

PubMed

Hohman-Billmeier, Kathryn; Nye, Margaret; Martin, Stephanie

2016-01-01

In 2010, Alaska Department of Health and Social Services (DHSS) received federal funding to test an evidence-based teen pregnancy prevention program. The grant required a major modification to an existing program and a randomized control trial (RCT) to test its effectiveness. As the major modifications, Alaska used peer educators instead of adults to deliver the program to youth aged 14-19 instead of the original curriculum intended age range of 12-14. Cultural and approach adaptations were included as well. After 4 years of implementation and data collection, the sample was too small to provide statistically significant results. The lack of findings gave no information about the modification, nor any explanation of how the curriculum was received, or reasons for the small sample. This paper reports on a case study follow-up to the RCT to better understand outcome and implementation results. For this study, researchers reviewed project documents and interviewed peer educators, state and local staff, and evaluators. Three themes emerged from the data: (a) the professional growth of peer educators and development of peer education, (b) difficulties resulting from curriculum content, especially for subpopulations of sexually active youth, youth identified as lesbian, gay, bisexual, transgender, queer, intersex and/or asexual, pregnant, and parenting youth and (c) the appropriateness of an RCT with subpopulations of at-risk youth. Three recommendations emerged from the case study. First, including as many stakeholders as possible in the program and evaluation design phases is essential, and must be supported by appropriate funding streams and training. Second, there must be recognition of the multiple small subpopulations found in Alaska when adapting programs designed for a larger and more homogeneous population. Third, RCTs may not be appropriate for all population subgroups.

Neighborhood effects in a behavioral randomized controlled trial.

PubMed

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

2014-11-01

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

Recruitment of older adults to three preventative lifestyle improvement studies.

PubMed

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

2018-02-20

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

Anthropometrics and body composition by dual energy X-ray in children of obese women: a follow-up of a randomized controlled trial (the Lifestyle in Pregnancy and Offspring [LiPO] study).

PubMed

Tanvig, Mette; Vinter, Christina A; Jørgensen, Jan S; Wehberg, Sonja; Ovesen, Per G; Lamont, Ronald F; Beck-Nielsen, Henning; Christesen, Henrik T; Jensen, Dorte M

2014-01-01

In obese women, 1) to assess whether lower gestational weight gain (GWG) during pregnancy in the lifestyle intervention group of a randomized controlled trial (RCT) resulted in differences in offspring anthropometrics and body composition, and 2) to compare offspring outcomes to a reference group of children born to women with a normal Body Mass Index (BMI). The LiPO (Lifestyle in Pregnancy and Offspring) study was an offspring follow-up of a RCT with 360 obese pregnant women with a lifestyle intervention during pregnancy including dietary advice, coaching and exercise. The trial was completed by 301 women who were eligible for follow-up. In addition, to the children from the RCT, a group of children born to women with a normal BMI were included as a reference group. At 2.8 (range 2.5-3.2) years, anthropometrics were measured in 157 children of the RCT mothers and in 97 reference group children with Body Mass Index (BMI) Z-score as a primary outcome. Body composition was estimated by Dual Energy X-ray (DEXA) in 123 successful scans out of 147 (84%). No differences between randomized groups were seen in mean (95% C.I.) BMI Z-score (intervention group 0.06 [-0.17; 0.29] vs. controls -0.18 [-0.43; 0.05]), in the percentage of overweight or obese children (10.9% vs. 6.7%), in other anthropometrics, or in body composition values by DEXA. Outcomes between children from the RCT and the reference group children were not significantly different. The RCT with lifestyle intervention in obese pregnant women did not result in any detectable effect on offspring anthropometrics or body composition by DEXA at 2.8 years of age. This may reflect the limited difference in GWG between intervention and control groups. Offspring of obese mothers from the RCT were comparable to offspring of mothers with a normal BMI.

Planning Future Clinical Trials for Machado-Joseph Disease.

PubMed

Saute, Jonas Alex Morales; Jardim, Laura Bannach

2018-01-01

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

Benefits and Disadvantages of Neoadjuvant Radiochemotherapy (RCT) in the Multimodal Therapy of Squamous Esophageal Cancer (ESC).

PubMed

Hanna, Adrian; Birla, Rodica; Iosif, Cristina; Boeriu, Marius; Constantinoiu, Silviu

2016-01-01

The purpose of this paper is to present the advantages and disadvantages of neoadjuvant RCT in multimodal therapyof ESC. Between 1998-2014 221 patients were treated with ESC, 85 of whom received neoadjuvant RCT. For these we have made imaging and pathologic assessment of response using RECIST and MANDARD criteria and statistical data were interpreted in terms of the factors that influence the response. Also, they were evaluated statistical correlations between RCT and resectability, postoperative morbidity, mortality and long-term survival. 45 patients were imagistic responders and 34 underwent surgery, 40 non-responders of which 14 underwent surgery. Of the 48 surgical patients with preoperative RCT, histopathological evaluation showed that 32 were pathological responders and 16 non responders. There were performed statistical analyzes of correlations between RCT and resectability, stage, location of ESC, morbidity, mortality and survival. RCT increase resectability, improves survival and maximum duration of survival, more in responders than in nonresponders and does not affect postoperative complications and postoperative mortality, nor among the responders or nonresponders. Imaging evaluation result of the response to RCT overestimate responders. Celsius.

Status of the contralateral rotator cuff in patients undergoing rotator cuff repair.

PubMed

Ro, Kyung-Han; Park, Jong-Hoon; Lee, Soon-Hyuck; Song, Dong-Ik; Jeong, Ha-Joon; Jeong, Woong-Kyo

2015-05-01

Although the prevalence of rotator cuff tear (RCT) in the general population has been analyzed, little information is available on the status of the opposite-side rotator cuff in patients who have undergone arthroscopic rotator cuff repair. To identify the characteristics of the contralateral shoulder and to identify factors associated with RCT of the contralateral shoulder in patients who underwent surgery for symptomatic RCT. The hypothesis was that the prevalence of RCT in the contralateral shoulder would be higher in patients with increasingly larger cuff tears requiring surgical intervention. Case series; Level of evidence, 4. The study cohort consisted of 140 patients with RCT who underwent arthroscopic rotator cuff repair. Opposite-shoulder rotator cuff tendons of all patients were evaluated by ultrasonography. Demographic information and factors related to contralateral RCT were investigated, and risk factors associated with contralateral RCT were assessed. Of the 140 patients who underwent arthroscopic rotator cuff repair, 54 (38.6%) had an RCT of the contralateral shoulder. Of 51 patients with partial-thickness and small-sized full-thickness tears of the operated shoulder, 35 (68.6%) had no tears; 14 (27.5%) had partial-thickness tears; and 2 (3.9%) had small-sized full-thickness tears of the contralateral shoulder. Of 75 patients with medium-sized full-thickness tears, 43 (57.3%) had no tears; 12 (16%) had partial-thickness tears; and 20 (26.7%) had full-thickness tears of the contralateral shoulder. Of 14 patients with large to massive full-thickness tears, 8 (57.1%) had no tears; 1 (7.1%) had a partial-thickness tear; and 5 (35.7%) had full-thickness tears of the contralateral shoulder. The prevalence of RCT of the contralateral shoulder differed significantly among groups classified by tear size (P=.007). The mean American Shoulder and Elbow Surgeons score was significantly lower in the RCT than in the nontear group (55.8±16.9 vs 61.6±13.3; P=.03). Of 29 subjects with symptomatic tears involving the nondominant arm, 17 (58.6%) had contralateral asymptomatic RCT, compared with 37 of 111 (33.3%) subjects with symptomatic tears involving the dominant arm (P=.007). The prevalence of RCT of the contralateral asymptomatic shoulder tends to be higher in patients with more symptomatic RCT on one side, in patients with medium-sized or larger RCT in the operated shoulder, and in patients with symptomatic RCT in the nondominant arm. © 2015 The Author(s).

The post-trial effect of oral periodic presumptive treatment for vaginal infections on the incidence of bacterial vaginosis and Lactobacillus colonization

PubMed Central

Balkus, Jennifer E.; Jaoko, Walter; Mandaliya, Kishorchandra; Richardson, Barbra A.; Masese, Linnet; Gitau, Ruth; Kiarie, James; Marrazzo, Jeanne; Farquhar, Carey; McClelland, R. Scott

2012-01-01

Background We previously demonstrated a decrease in bacterial vaginosis (BV) and an increase in Lactobacillus colonization among randomized controlled trial (RCT) participants who received monthly oral periodic presumptive treatment (PPT) [2g metronidazole + 150mg fluconazole]. Post-trial data were analyzed to test the hypothesis that the treatment effect would persist following completion of one year of PPT. Methods Data were obtained from women who completed all 12 RCT visits and attended ≥1 post-trial visit within 120 days following completion of the RCT. We used Andersen-Gill proportional hazards models to estimate the post-trial effect of the intervention on the incidence of BV by Gram stain and detection of Lactobacillus species by culture. Results The analysis included 165 subjects (83 active and 82 placebo). The post-trial incidence of BV was 260 per 100 person-years in the intervention arm versus 358 per 100 person-years in the placebo arm (hazard ratio [HR]=0.76; 95% confidence interval [CI]: 0.51–1.12). The post-trial incidence of Lactobacillus colonization was 180 per 100 person-years in the intervention arm versus 127 per 100 person-years in the placebo arm (HR=1.42; 95% CI: 0.85–2.71). Conclusions Despite a decrease in BV and an increase in Lactobacillus colonization during the RCT, the effect of PPT was not sustained at the same level following cessation of the intervention. New interventions that reduce BV recurrence and promote Lactobacillus colonization without the need for ongoing treatment are needed. PMID:22504600

A Bayesian Analysis of a Randomized Clinical Trial Comparing Antimetabolite Therapies for Non-Infectious Uveitis.

PubMed

Browne, Erica N; Rathinam, Sivakumar R; Kanakath, Anuradha; Thundikandy, Radhika; Babu, Manohar; Lietman, Thomas M; Acharya, Nisha R

2017-02-01

To conduct a Bayesian analysis of a randomized clinical trial (RCT) for non-infectious uveitis using expert opinion as a subjective prior belief. A RCT was conducted to determine which antimetabolite, methotrexate or mycophenolate mofetil, is more effective as an initial corticosteroid-sparing agent for the treatment of intermediate, posterior, and pan-uveitis. Before the release of trial results, expert opinion on the relative effectiveness of these two medications was collected via online survey. Members of the American Uveitis Society executive committee were invited to provide an estimate for the relative decrease in efficacy with a 95% credible interval (CrI). A prior probability distribution was created from experts' estimates. A Bayesian analysis was performed using the constructed expert prior probability distribution and the trial's primary outcome. A total of 11 of the 12 invited uveitis specialists provided estimates. Eight of 11 experts (73%) believed mycophenolate mofetil is more effective. The group prior belief was that the odds of treatment success for patients taking mycophenolate mofetil were 1.4-fold the odds of those taking methotrexate (95% CrI 0.03-45.0). The odds of treatment success with mycophenolate mofetil compared to methotrexate was 0.4 from the RCT (95% confidence interval 0.1-1.2) and 0.7 (95% CrI 0.2-1.7) from the Bayesian analysis. A Bayesian analysis combining expert belief with the trial's result did not indicate preference for one drug. However, the wide credible interval leaves open the possibility of a substantial treatment effect. This suggests clinical equipoise necessary to allow a larger, more definitive RCT.

Understanding the Importance of Context: A Qualitative Study of a Location-Based Exergame to Enhance School Childrens Physical Activity

PubMed Central

Jepson, Ruth; Macvean, Andrew; Gray, Stuart

2016-01-01

Many public health interventions are less effective than expected in ‘real life settings’, yet little work is undertaken to understand the reasons why. The effectiveness of complex public health interventions can often be traced back to a robust programme theory (how and why an intervention brings about a change in outcome(s)) and assumptions that are made about the context in which it is implemented. Understanding whether effectiveness (or lack thereof) is due to the intervention or the context is hugely helpful in decisions about whether to a) modify the intervention; b) modify the context; c) stop providing the intervention. Exergames–also known as Active Video Games or AVGS–are video games which use the player's bodily movements as input and have potential to increase physical activity in children. However, the results of a recent pilot randomised controlled trial (RCT) of a location-based exergame (FitQuest) in a school setting were inconclusive; no significant effect was detected for any of the outcome measures. The aim of this study was to explore whether the programme theory for FitQuest was correct with respect to how and why it would change children’s perceptions of physical activity (PA) and exercise self-efficacy in the school setting. A further aim was to investigate the features of the school setting (context) that may impact on FitQuest’s implementation and effectiveness. Qualitative data (gathered during the RCT) were gathered from interviews with teachers and children, and observation of sessions using FitQuest. Thematic analysis indicated that whilst children enjoyed playing the game, engaged with goal setting within the game context and undertook low to vigorous physical activity, there were significant contextual factors that prevented it from being played as often as intended. These included environmental factors (e.g. size of the playground), school factors (cancellations due to other activities), school technology policy (rules relating to mobile phone usage) and teacher factors (engagement with the intervention). A revised logic model for the FitQuest intervention indicates how both the design of exergame technology (intervention) and features of the school environment (context) could be improved to increase chances of effectiveness in the future. PMID:27548504

Whole Grain Intake and Glycaemic Control in Healthy Subjects: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Marventano, Stefano; Vetrani, Claudia; Vitale, Marilena; Riccardi, Gabriele; Grosso, Giuseppe

2017-01-01

Backgrounds: There is growing evidence from both observational and intervention studies that Whole Grain (WG) cereals exert beneficial effects on human health, especially on the metabolic profile. The aim of this study was to perform a meta-analysis of randomised controlled trials (RCT) to assess the acute and medium/long-term effect of WG foods on glycaemic control and insulin sensitivity in healthy individuals. Methods: A search for all the published RCT on the effect of WG food intake on glycaemic and insulin response was performed up to December 2016. Effect size consisted of mean difference (MD) and 95% CI between the outcomes of intervention and the control groups using the generic inverse-variance random effects model. Results: The meta-analysis of the 14 studies testing the acute effects of WG foods showed significant reductions of the post-prandial values of the glucose iAUC (0–120 min) by −29.71 mmol min/L (95% CI: −43.57, −15.85 mmol min/L), the insulin iAUC (0–120 min) by −2.01 nmol min/L (95% CI: −2.88, −1.14 nmol min/L), and the maximal glucose and insulin response. In 16 medium- and long-term RCTs, effects of WG foods on fasting glucose and insulin and homeostatic model assessment-insulin resistance values were not significant. Conclusions: The consumption of WG foods is able to improve acutely the postprandial glucose and insulin homeostasis compared to similar refined foods in healthy subjects. Further research is needed to better understand the long-term effects and the biological mechanisms. PMID:28753929

Treatment Trials for Neonatal Seizures: The Effect of Design on Sample Size

PubMed Central

Stevenson, Nathan J.; Boylan, Geraldine B.; Hellström-Westas, Lena; Vanhatalo, Sampsa

2016-01-01

Neonatal seizures are common in the neonatal intensive care unit. Clinicians treat these seizures with several anti-epileptic drugs (AEDs) to reduce seizures in a neonate. Current AEDs exhibit sub-optimal efficacy and several randomized control trials (RCT) of novel AEDs are planned. The aim of this study was to measure the influence of trial design on the required sample size of a RCT. We used seizure time courses from 41 term neonates with hypoxic ischaemic encephalopathy to build seizure treatment trial simulations. We used five outcome measures, three AED protocols, eight treatment delays from seizure onset (Td) and four levels of trial AED efficacy to simulate different RCTs. We performed power calculations for each RCT design and analysed the resultant sample size. We also assessed the rate of false positives, or placebo effect, in typical uncontrolled studies. We found that the false positive rate ranged from 5 to 85% of patients depending on RCT design. For controlled trials, the choice of outcome measure had the largest effect on sample size with median differences of 30.7 fold (IQR: 13.7–40.0) across a range of AED protocols, Td and trial AED efficacy (p<0.001). RCTs that compared the trial AED with positive controls required sample sizes with a median fold increase of 3.2 (IQR: 1.9–11.9; p<0.001). Delays in AED administration from seizure onset also increased the required sample size 2.1 fold (IQR: 1.7–2.9; p<0.001). Subgroup analysis showed that RCTs in neonates treated with hypothermia required a median fold increase in sample size of 2.6 (IQR: 2.4–3.0) compared to trials in normothermic neonates (p<0.001). These results show that RCT design has a profound influence on the required sample size. Trials that use a control group, appropriate outcome measure, and control for differences in Td between groups in analysis will be valid and minimise sample size. PMID:27824913

Effects of Direct-to-Consumer Advertising on Patient Prescription Requests and Physician Prescribing: A Systematic Review of Psychiatry-Relevant Studies

PubMed Central

Becker, Sara J.; Midoun, Miriam M.

2017-01-01

Objective To systematically analyze the effects of direct-to-consumer advertising (DTCA) on patient requests for medication and physician prescribing across psychiatry-relevant studies. Data Sources MEDLINE, PsychINFO, ISI Thompson's Web of Knowledge, and Google Scholar were searched from 1999 through 2014 using variations of the terms direct-to-consumer advertising and psychiatric. Reference lists and an online repository of DTCA manuscripts were also scrutinized. Study Selection English-language studies collecting data at the point of service, focusing on or including psychiatric medication, and assessing DTCA's effects on patient and/or physician behavior were included. Of 989 articles identified, 69 received full-text review. Four studies across five manuscripts met inclusion criteria. Data Extraction Data were extracted on participants, study design, methodological quality, and results. Methodological quality of individual studies was assessed using adapted criteria from the Effective Public Health Practice Project. Confidence in conclusions across studies was determined using principles from the well-established GRADE system. Findings Due to lack of replication across strong randomized controlled trials (RCTs), no conclusions merited high confidence. With moderate confidence, we concluded that DTCA requests: 1) are granted most of the time [1 RCT, 3 observational]; 2) prompt higher prescribing volume [1 RCT, 1 observational]; 3) promote greater adherence to minimally acceptable treatment guidelines for patients with depression [1 RCT], and 4) stimulate overprescribing among patients with an adjustment disorder [1 RCT]. Conclusions Findings suggest that DTCA requests are typically accommodated, promote higher prescribing volume, and have competing effects on treatment quality. More methodologically strong studies are needed to increase confidence in conclusions. PMID:27631149

Effects of Direct-To-Consumer Advertising on Patient Prescription Requests and Physician Prescribing: A Systematic Review of Psychiatry-Relevant Studies.

PubMed

Becker, Sara J; Midoun, Miriam M

2016-10-01

To systematically analyze the effects of direct-to-consumer advertising (DTCA) on patient requests for medication and physician prescribing across psychiatry-relevant studies. MEDLINE, PsycINFO, Thomson Reuters' ISI Web of Knowledge, and Google Scholar were searched (1999-2014) using variations of the terms direct-to-consumer advertising and psychiatric. Reference lists and an online repository of DTCA manuscripts were also scrutinized. English-language studies collecting data at the point of service, focusing on or including psychiatric medication, and assessing the effects of DTCA on patient and/or physician behavior were included. Of 989 articles identified, 69 received full-text review. Four studies across 5 manuscripts met inclusion criteria. Data were extracted on participants, study design, methodological quality, and results. Methodological quality of individual studies was assessed using adapted criteria from the Effective Public Health Practice Project. Confidence in conclusions across studies was determined using principles from the well-established GRADE system. Due to lack of replication across strong randomized controlled trials (RCTs), no conclusions merited high confidence. With moderate confidence, we concluded that DTCA requests (1) are granted most of the time (1 RCT, 3 observational), (2) prompt higher prescribing volume (1 RCT, 1 observational), (3) promote greater adherence to minimally acceptable treatment guidelines for patients with depression (1 RCT), and (4) stimulate overprescribing among patients with an adjustment disorder (1 RCT). Findings suggest that DTCA requests are typically accommodated, promote higher prescribing volume, and have competing effects on treatment quality. More methodologically strong studies are needed to increase confidence in conclusions. © Copyright 2016 Physicians Postgraduate Press, Inc.

How to influence patient oral hygiene behavior effectively.

PubMed

Clarkson, J E; Young, L; Ramsay, C R; Bonner, B C; Bonetti, D

2009-10-01

Considerable resources are expended in dealing with dental disease easily prevented with better oral hygiene. The study hypothesis was that an evidence-based intervention, framed with psychological theory, would improve patients' oral hygiene behavior. The impact of trial methodology on trial outcomes was also explored by the conducting of two independent trials, one randomized by patient and one by dentist. The study included 87 dental practices and 778 patients (Patient RCT = 37 dentists/300 patients; Cluster RCT = 50 dentists/478 patients). Controlled for baseline differences, pooled results showed that patients who experienced the intervention had better behavioral (timing, duration, method), cognitive (confidence, planning), and clinical (plaque, gingival bleeding) outcomes. However, clinical outcomes were significantly better only in the Cluster RCT, suggesting that the impact of trial design on results needs to be further explored.

Melodic Intonation Therapy in Chronic Aphasia: Evidence from a Pilot Randomized Controlled Trial

PubMed Central

Van Der Meulen, Ineke; Van De Sandt-Koenderman, Mieke W. M. E.; Heijenbrok, Majanka H.; Visch-Brink, Evy; Ribbers, Gerard M.

2016-01-01

Melodic Intonation Therapy (MIT) is a language production therapy for severely non-fluent aphasic patients using melodic intoning and rhythm to restore language. Although many studies have reported its beneficial effects on language production, randomized controlled trials (RCT) examining the efficacy of MIT are rare. In an earlier publication, we presented the results of an RCT on MIT in subacute aphasia and found that MIT was effective on trained and untrained items. Further, we observed a clear trend in improved functional language use after MIT: subacute aphasic patients receiving MIT improved considerably on language tasks measuring connected speech and daily life verbal communication. Here, we present the results of a pilot RCT on MIT in chronic aphasia and compare these to the results observed in subacute aphasia. We used a multicenter waiting-list RCT design. Patients with chronic (>1 year) post-stroke aphasia were randomly allocated to the experimental group (6 weeks MIT) or to the control group (6 weeks no intervention followed by 6 weeks MIT). Assessments were done at baseline (T1), after 6 weeks (T2), and 6 weeks later (T3). Efficacy was evaluated at T2 using univariable linear regression analyses. Outcome measures were chosen to examine several levels of therapy success: improvement on trained items, generalization to untrained items, and generalization to verbal communication. Of 17 included patients, 10 were allocated to the experimental condition and 7 to the control condition. MIT significantly improved repetition of trained items (β = 13.32, p = 0.02). This effect did not remain stable at follow-up assessment. In contrast to earlier studies, we found only a limited and temporary effect of MIT, without generalization to untrained material or to functional communication. The results further suggest that the effect of MIT in chronic aphasia is more restricted than its effect in earlier stages post stroke. This is in line with studies showing larger effects of aphasia therapy in earlier compared to later stages post stroke. The study was designed as an RCT, but was underpowered. The results therefore have to be interpreted cautiously and future larger studies are needed. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NTR 1961. PMID:27847473

Demographic, tumor and clinical features of clinical trials versus clinical practice patients with HER2-positive early breast cancer: results of a prospective study.

PubMed

Arpino, Grazia; Michelotti, Andrea; Truini, Mauro; Montemurro, Filippo; Russo, Stefania; Palumbo, Raffaella; Zamagni, Claudio; Latorre, Agnese; Bruzzese, Dario; Riccardi, Ferdinando; De Laurentiis, Michelino; Beano, Alessandra; Biganzoli, Laura; Zaniboni, Alberto; Laudadio, Lucio; Malagoli, Maria; Bilancia, Domenico; Schettini, Francesco; Giuliano, Mario; Cazzaniga, Marina Elena; De Placido, Sabino

2016-03-01

Several randomized clinical trials (RCTs) have demonstrated the efficacy of trastuzumab-based adjuvant therapy in HER2-positive breast cancer (BC). However, RCT patients may not invariably be representative of patients routinely seen in clinical practice (CP). To address this issue, we compared the clinical and tumor features of RCT and CP patients with HER2-positive BC. From January to December 2012, 650 consecutive patients with HER2-positive early BC, treated in 36 different types of Italian healthcare facilities, were enrolled in this study. Age, treatment, tumor size (T), nodes (N), grade (G), estrogen receptor (ER) and progesterone receptor (PgR) status were prospectively collected in these CP patients. The same data were extracted from the main adjuvant trastuzumab RCTs and pooled using the random-effects model of DerSimonian and Laird. RCT and CP patients were compared by using the Cochran Q statistics. Versus RCT patients, CP patients were more likely to be older than 50 years (65 vs. 49 %; p < 0.0001) and to have HR (ER and/or PgR)-positive (72 vs. 54 %; p < 0.0001) BC and less likely to have tumor >2 cm (T ≥ 2 cm 39 vs. 59 %; p < 0.0001), positive N (47 vs. 89 %; p < 0.0001) and a high G (61 vs. 67 %; p = 0.0241). CP patients more frequently received adjuvant endocrine therapy (70 vs. 57 %; p < 0.0003) and less frequently adjuvant chemotherapy (97 vs. 99.7 %; p < 0.0001). Most tumor and clinical features differed significantly between CP and RCT patients. These data raise concerns about the applicability of RCT results to CP patients.

Tolerability and safety of Souvenaid in patients with mild Alzheimer's disease: results of multi-center, 24-week, open-label extension study.

PubMed

Olde Rikkert, Marcel G M; Verhey, Frans R; Blesa, Rafael; von Arnim, Christine A F; Bongers, Anke; Harrison, John; Sijben, John; Scarpini, Elio; Vandewoude, Maurits F J; Vellas, Bruno; Witkamp, Renger; Kamphuis, Patrick J G H; Scheltens, Philip

2015-01-01

The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to improve synapse formation and function in patients with Alzheimer's disease (AD). Two double-blind randomized controlled trials (RCT) with Souvenaid of 12 and 24 week duration (Souvenir I and Souvenir II) showed that memory performance was improved in drug-naïve mild AD patients, whereas no effects on cognition were observed in a 24-week RCT (S-Connect) in mild to moderate AD patients using AD medication. Souvenaid was well-tolerated in all RCTs. In this 24-week open-label extension (OLE) study to the 24-week Souvenir II RCT, long-term safety and intake adherence of the medical food Souvenaid was evaluated. Patients with mild AD (n = 201) received Souvenaid once-daily during the OLE. Main outcome parameters were safety and product intake adherence. The memory domain z-score from a revised neuropsychological test battery was continued as exploratory parameter. Compared to the RCT, a similar (low) incidence and type of adverse events was observed, being mainly (68.3%) of mild intensity. Pooled data (RCT and OLE) showed that 48-week use of Souvenaid was well tolerated with high intake adherence (96.1%). Furthermore, a significant increase in the exploratory memory outcome was observed in both the active-active and control-active groups during Souvenaid intervention. Souvenaid use for up to 48-weeks was well tolerated with a favorable safety profile and high intake adherence. The findings in this OLE study warrant further investigation toward the long-term safety and efficacy of Souvenaid in a well-controlled, double-blind RCT.

Benefits of simulation based training for neonatal resuscitation education: a systematic review.

PubMed

Rakshasbhuvankar, A A; Patole, S K

2014-10-01

Simulation-based training (SBT) is being more frequently recommended for neonatal resuscitation education (NRE). It is important to assess if SBT improves clinical outcomes as neonatal resuscitation aims to improve survival without long-term neurodevelopmental impairment. We aimed to assess the evidence supporting benefits of SBT in NRE. A systematic review was conducted using the Cochrane methodology. PubMed, Embase, PsycInfo and Cochrane databases were searched. Related abstracts were scanned and full texts of the potentially relevant articles were studied. Randomised controlled trials (RCT) and quasi-experimental studies with controls (non-RCT) assessing SBT for NRE were eligible for inclusion in the review. Four small studies [three RCT (n=126) and one non-RCT (n=60)] evaluated SBT for NRE. Participants included medical students (one RCT and one non-RCT), residents (one RCT) and nursing staff (one RCT). Outcomes included performance in a simulation scenario, theoretical knowledge, and confidence in leading a resuscitation scenario. One RCT favoured simulation [improved resuscitation score (p=0.016), 2.31 more number of critical actions (p=0.017) and decreased time to achieve resuscitation steps (p=<0.001)]. The remaining two RCTs and the non-RCT did not find any difference between SBT and alternate methods of instruction. None of the four studies reported clinical outcomes. Evidence regarding benefits of SBT for NRE is limited. There are no data on clinical outcomes following SBT for NRE. Large RCTs assessing clinically important outcomes are required before SBT can be recommended widely for NRE. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Protocol for the economic evaluation of a community-based intervention to improve growth among children under two in rural India (CARING trial).

PubMed

Skordis-Worrall, Jolene; Sinha, Rajesh; Kumar Ojha, Amit; Sarangi, Soumendra; Nair, Nirmala; Tripathy, Prasanta; Sachdev, H S; Bhattacharyya, Sanghita; Gope, Rajkumar; Rath, Shibanand; Rath, Suchitra; Srivastava, Aradhana; Batura, Neha; Pulkki-Brännström, Anni-Maria; Costello, Anthony; Copas, Andrew; Saville, Naomi; Prost, Audrey; Haghparast-Bidgoli, Hassan

2016-11-02

Undernutrition affects ∼165 million children globally and contributes up to 45% of all child deaths. India has the highest proportion of global undernutrition-related morbidity and mortality. This protocol describes the planned economic evaluation of a community-based intervention to improve growth in children under 2 years of age in two rural districts of eastern India. The intervention is being evaluated through a cluster-randomised controlled trial (cRCT, the CARING trial). A cost-effectiveness and cost-utility analysis nested within a cRCT will be conducted from a societal perspective, measuring programme, provider, household and societal costs. Programme costs will be collected prospectively from project accounts using a standardised tool. These will be supplemented with time sheets and key informant interviews to inform the allocation of joint costs. Direct and indirect costs incurred by providers will be collected using key informant interviews and time use surveys. Direct and indirect household costs will be collected prospectively, using time use and consumption surveys. Incremental cost-effectiveness ratios (ICERs) will be calculated for the primary outcome measure, that is, cases of stunting prevented, and other outcomes such as cases of wasting prevented, cases of infant mortality averted, life years saved and disability-adjusted life years (DALYs) averted. Sensitivity analyses will be conducted to assess the robustness of results. There is a shortage of robust evidence regarding the cost-effectiveness of strategies to improve early child growth. As this economic evaluation is nested within a large scale, cRCT, it will contribute to understanding the fiscal space for investment in early child growth, and the relative (in)efficiency of prioritising resources to this intervention over others to prevent stunting in this and other comparable contexts. The protocol has all necessary ethical approvals and the findings will be disseminated within academia and the wider policy sphere. ISRCTN51505201; pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Is resin infiltration an effective esthetic treatment for enamel development defects and white spot lesions? A systematic review.

PubMed

Borges, A B; Caneppele, T M F; Masterson, D; Maia, L C

2017-01-01

To determine if resin infiltration is an effective treatment for improving the esthetic appearance of tooth discoloration resulting from development defects of enamel (EDD) and white spot lesions (WSL) by means of a systematic review. A comprehensive search was performed in PubMed, Scopus, Web of Science, LILACS, BBO Library, Cochrane Library, and SIGLE, as well as in the abstracts of IADR conference, and in the clinical trials registry. Clinical studies in patients with whitish tooth discoloration, in which the resin infiltration technique was applied, were included. Color masking was the primary outcome. The methodological quality and risk of biases of included papers was assessed using MINORS criteria for non-randomized (NRS) comparative studies and Cochrane Collaboration for randomized clinical trials (RCT). From a total of 2930 articles, 17 were assessed for eligibility and 11 remained in the qualitative synthesis. Four NRS and seven RCT studies were selected, the latter consisting of four full-text studies and three conference abstracts. Two studies were excluded from the quality assessment, due to overlapping results. The number of participants (treated teeth) ranged from 18 to 21 (38-74) in the NRS, and 20-83 (20-231) in the RCT studies. Post-orthodontic WSL were the most frequent treated lesions. Initial condition was used as control in the NR studies. In the RCT, resin infiltration was compared to non treatment, remineralization, or bleaching. Overall, partial or complete color masking of affected teeth was reported immediately after resin infiltration. Only two studies followed original outcomes up to one year and reported maintenance of original color masking. Two NR studies were assessed as "moderate" and one as "high" quality. Two RCT were classified as "low" risk of bias in the chosen key domains. The remaining four studies were considered "unclear" or "high" risk of bias. Although the partial or total masking effect of enamel whitish discoloration has been shown with resin infiltration, there is no strong evidence to support this technique based on the present clinical studies. Enamel whitish discolorations in esthetically compromised areas are clinically undesirable. Minimally invasive approaches used as attempts to minimize the discoloration include the resin infiltration technique. The evidence for clinical recommendation of this technique is not strong, thus, further RCT studies with long-term follow-ups should be conducted. Copyright © 2016 Elsevier Ltd. All rights reserved.

A pilot randomised controlled trial of a Telehealth intervention in patients with chronic obstructive pulmonary disease: challenges of clinician-led data collection.

PubMed

Bentley, Claire L; Mountain, Gail A; Thompson, Jill; Fitzsimmons, Deborah A; Lowrie, Kinga; Parker, Stuart G; Hawley, Mark S

2014-08-06

The increasing prevalence and associated cost of treating chronic obstructive pulmonary disease (COPD) is unsustainable, and focus is needed on self-management and prevention of hospital admissions. Telehealth monitoring of patients' vital signs allows clinicians to prioritise their workload and enables patients to take more responsibility for their health. This paper reports the results of a pilot randomised controlled trial (RCT) of Telehealth-supported care within a community-based COPD supported-discharge service. A two-arm pragmatic pilot RCT was conducted comparing the standard service with a Telehealth-supported service and assessed the potential for progressing into a full RCT. The co-primary outcome measures were the proportion of COPD patients readmitted to hospital and changes in patients' self-reported quality of life. The objectives were to assess the suitability of the methodology, produce a sample size calculation for a full RCT, and to give an indication of cost-effectiveness for both pathways. Sixty three participants were recruited (n = 31 Standard; n = 32 Telehealth); 15 participants were excluded from analysis due to inadequate data completion or withdrawal from the Telehealth arm. Recruitment was slow with significant gaps in data collection, due predominantly to an unanticipated 60% reduction of staff capacity within the clinical team. The sample size calculation was guided by estimates of clinically important effects and COPD readmission rates derived from the literature. Descriptive analyses showed that the standard service group had a lower proportion of patients with hospital readmissions and a greater increase in self-reported quality of life compared to the Telehealth-supported group. Telehealth was cost-effective only if hospital admissions data were excluded. Slow recruitment rates and service reconfigurations prevented progression to a full RCT. Although there are advantages to conducting an RCT with data collection conducted by a frontline clinical team, in this case, challenges arose when resources within the team were reduced by external events. Gaps in data collection were resolved by recruiting a research nurse. This study reinforces previous findings regarding the difficulty of undertaking evaluation of complex interventions, and provides recommendations for the introduction and evaluation of complex interventions within clinical settings, such as prioritisation of research within the clinical remit. Current Controlled Trials ISRCTN68856013, registered Nov 2010.

Regulation of reverse cholesterol transport - a comprehensive appraisal of available animal studies

PubMed Central

2012-01-01

Plasma levels of high density lipoprotein (HDL) cholesterol are strongly inversely correlated to the risk of atherosclerotic cardiovascular disease. A major recognized functional property of HDL particles is to elicit cholesterol efflux and consequently mediate reverse cholesterol transport (RCT). The recent introduction of a surrogate method aiming at determining specifically RCT from the macrophage compartment has facilitated research on the different components and pathways relevant for RCT. The current review provides a comprehensive overview of studies carried out on macrophage-specific RCT including a quick reference guide of available data. Knowledge and insights gained on the regulation of the RCT pathway are summarized. A discussion of methodological issues as well as of the respective relevance of specific pathways for RCT is also included. PMID:22458435

[Meta-analysis of needle-knife treatment on cervical spondylosis].

PubMed

Kan, Li-Li; Wang, Hai-Dong; Liu, An-Guo

2013-11-01

To assess the efficacy of cervical spondylosis by needle-knife treatment according to the correlated literature of RCT,to compare advantages of needle-knife treatment. Randomized Controlled Trials about needle-knife treatment of cervical spondylosis were indexed from Chinese HowNet (CNKI) and Wanfang (WF) from 2000 to 2012, then were analyzed the efficacy by Review Manager 5.1 software. A total of 13 RCT literatures and 1 419 patients were included. The methods of included studies were poor in quality evaluation because of large sample and multi-center RCT studies was lacked, randomization method was not accurate enough, diagnostic criteria and efficacy evaluation were various, only four studies described long-term efficacy, most of the literature didn't describe the adverse event and fall off,all studies did not use the blind method. The Meta analysis outcome showed overall efficiency of needle-knife therapy was better than acupuncture and traction. Needle-knife therapy compared with Acupuncture, the total RR = 0.19, 95% confidence interval was (0.15, 0.24), P < 0.000.01. Compared with traction therapy the total RR = 1.30, 95% confidence intervalwas (1.18,1.42), P < 0.00001. Compared with acupuncture therapy,the overall effectiveness of needle-knife therapy is higher;compared with traction therapy, although,needle-knife therapy has a high overall effectiveness, but because of the loss of total sample size, the outcome RCT researches to confirm.

The social play, social skills and parent-child relationships of children with ADHD 12 months following a RCT of a play-based intervention.

PubMed

Barnes, Gabrielle; Wilkes-Gillan, Sarah; Bundy, Anita; Cordier, Reinie

2017-12-01

There is an urgent need to investigate the long-term impact of social skill interventions for children with attention deficit hyperactivity disorder (ADHD). Interventions targeting the social skills of children with ADHD have limited short-term effectiveness and rarely investigate the long-term impact. Furthermore, these interventions are most frequently conducted in the clinic setting, without including the child's natural settings and interactants, such as their regular playmates and parents. The present study investigated the social play, social skills and parent-child relationships of children with ADHD and their playmates (n = 13/group) aged 5-13 years. A two-group before and after design with a longitudinal component was applied. Participant data compared over two time points, immediately following a randomised, controlled trial (RCT) of a play-based intervention and 12 months post-RCT. From immediately following the RCT to the 12-month follow-up, children with ADHD maintained social play skill gains in the home environment. Playmates maintained social play skill gains across the home and clinic environments. Children scored within a developmentally appropriate range, falling within 1 standard deviation of the mean for social skills and most parent-child relationship scales using norm-based assessments. Results support the long-term effectiveness of the intervention. © 2017 Occupational Therapy Australia.

Benefits and Harms of Sacubitril in Adults With Heart Failure and Reduced Left Ventricular Ejection Fraction.

PubMed

Aronow, Wilbert S; Shamliyan, Tatyana A

2017-10-01

The quality of evidence regarding patient-centered outcomes in adults with heart failure (HF) after sacubitril combined with valsartan has not been systematically appraised. We searched 4 databases in February 2017 and graded the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation working group approach. We reviewed 1 meta-analysis and multiple publications of 2 randomized controlled trials (RCT) and 1 unpublished RCT. In adults with HF and reduced ejection fraction, low-quality evidence from 1 RCT of 8,432 patients suggests that sacubitril combined with valsartan reduces all-cause (number needed to treat [NNT] to prevent 1 event [NNTp] = 35) and cardiovascular mortality (NNTp = 32), hospitalization (NNTp = 11), emergency visits (NNTp = 69), and serious adverse effects, leading to treatment discontinuation (NNTp = 63) and improves quality of life when compared with enalapril. In adults with HF and preserved ejection fraction, very low-quality evidence from 1 RCT of 301 patients suggests that there are no differences in mortality, morbidity, or adverse effects between sacubitril combined with valsartan and valsartan alone. In conclusion, in adults with HF and reduced ejection fraction, to reduce cardiovascular mortality and hospitalizations and improve quality of life, clinicians may recommend sacubitril combined with valsartan over angiotensin-converting enzyme inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

Management of oral lesions in HIV-positive patients.

PubMed

Baccaglini, Lorena; Atkinson, Jane C; Patton, Lauren L; Glick, Michael; Ficarra, Giuseppe; Peterson, Douglas E

2007-03-01

HIV/AIDS is currently the leading cause of death in Africa and the fourth leading cause of death worldwide. This systematic review of the literature was conducted to evaluate the evidence for treatment of the most common oral lesions associated with HIV: oral candidiasis with or without oropharyngeal involvement (OPC), oral hairy leukoplakia (OHL), recurrent aphthous-like ulcerations (RAU), oral Kaposi's sarcoma (OKS), orolabial herpes simplex infection (HSV), oral herpes zoster infection (VZV), intraoral or perioral warts (HPV), and HIV-associated periodontal diseases. Treatment of HIV-associated salivary gland disease is addressed in a different section of this World Workshop. We found the largest body of evidence for treatment of OPC in HIV patients. Future trials will be needed to test drugs currently in development for treatment of Candida strains that are resistant to existing therapies. There were no double blind, placebo-controlled randomized clinical trials (RCT) for topical treatment of OHL, and only one RCT for systemic treatment of the lesion with desciclovir. Systemic thalidomide was the only drug tested in RCT for treatment or prevention of RAU. Only 1 double-blind RCT comparing vinblastine and sodium tetradecyl sulfate was identified for localized treatment of OKS. Three drugs (famciclovir, acyclovir, and valaciclovir) were shown to be effective in randomized, double-blind trials for treatment or suppression of mucocutaneous HSV lesions in HIV patients. In all 3 trials, the effects of these medications on orolabial HSV lesions were not reported separately. There were no double-blind, placebo-controlled RCT testing topical treatments for orolabial HSV lesions in HIV patients. No trials testing treatments of oral VZV were identified. There were no double-blind, placebo-controlled RCT for treatment of HIV-associated intraoral or perioral warts or periodontal diseases. In conclusion, there is a need for well-designed RCTs to assess the safety and efficacy of topical and systemic treatments of most oral mucosal and perioral lesions in HIV patients. There is also a need to develop newer drugs for treatment of resistant fungal and viral microorganisms. Finally, standardized outcome measures should be developed for future clinical trials to allow comparisons of studies using different populations.

The effect of a sit-stand workstation intervention on daily sitting, standing and physical activity: protocol for a 12 month workplace randomised control trial.

PubMed

Hall, Jennifer; Mansfield, Louise; Kay, Tess; McConnell, Alison K

2015-02-15

A lack of physical activity and excessive sitting can contribute to poor physical health and wellbeing. The high percentage of the UK adult population in employment, and the prolonged sitting associated with desk-based office-work, make these workplaces an appropriate setting for interventions to reduce sedentary behaviour and increase physical activity. This pilot study aims to determine the effect of an office-based sit-stand workstation intervention, compared with usual desk use, on daily sitting, standing and physical activity, and to examine the factors that underlie sitting, standing and physical activity, within and outside, the workplace. A randomised control trial (RCT) comparing the effects of a sit-stand workstation only and a multi-component sit-stand workstation intervention, with usual desk-based working practice (no sit-stand workstation) will be conducted with office workers across two organisations, over a 12 month period (N = 30). The multicomponent intervention will comprise organisational, environmental and individual elements. Objective data will be collected at baseline, and after 2-weeks, 3-months, 6-months and 12-months of the intervention. Objective measures of sitting, standing, and physical activity will be made concurrently (ActivPAL3™ and ActiGraph (GT3X+)). Activity diaries, ethnographic participant observation, and interviews with participants and key organisational personnel will be used to elicit understanding of the influence of organisational culture on sitting, standing and physical activity behaviour in the workplace. This study will be the first long-term sit-stand workstation intervention study utilising an RCT design, and incorporating a comprehensive process evaluation. The study will generate an understanding of the factors that encourage and restrict successful implementation of sit-stand workstation interventions, and will help inform future occupational wellbeing policy and practice. Other strengths include the objective measurement of physical activity during both work and non-work hours. Clinicaltrials.gov identifier NCT02172599, 22nd June 2014.

Comparison of Aflibercept, Bevacizumab, and Ranibizumab for Treatment of Diabetic Macular Edema: Extrapolation of Data to Clinical Practice.

PubMed

Heier, Jeffrey S; Bressler, Neil M; Avery, Robert L; Bakri, Sophie J; Boyer, David S; Brown, David M; Dugel, Pravin U; Freund, K Bailey; Glassman, Adam R; Kim, Judy E; Martin, Daniel F; Pollack, John S; Regillo, Carl D; Rosenfeld, Philip J; Schachat, Andrew P; Wells, John A

2016-01-01

The Diabetic Retinopathy Clinical Research Network (DRCR Network), sponsored by the National Eye Institute, reported the results of a comparative effectiveness randomized clinical trial (RCT) evaluating the 3 anti-vascular endothelial growth factor (anti-VEGF) agents aflibercept (2.0 mg), bevacizumab (1.25 mg), and ranibizumab (0.3 mg) for treatment of diabetic macular edema (DME) involving the center of the retina and associated with visual acuity loss. The many important findings of the RCT prompted the American Society of Retina Specialists to convene a group of experts to provide their perspective regarding clinically relevant findings of the study. To describe specific outcomes of the RCT judged worthy of highlighting, to discuss how these and other clinically relevant results should be considered by specialists treating DME, and to identify unanswered questions that merit consideration before treatment. The DRCR Network-authored publication on primary outcomes of the comparative effectiveness RCT at 89 sites in the United States. The study period of the RCT was August 22, 2012, to August 28, 2013. On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and with visual acuity impairment, including mean (SD) improvements by +13.3 (11.1) letters with aflibercept vs +9.7 (10.1) letters with bevacizumab (P < .001) and +11.2 (9.4) letters with ranibizumab (P = .03). Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept (+18.9 [11.5]) over bevacizumab (+11.8 [12.0]) or ranibizumab (14.2 [10.6]) 1 year later (P < .001 for interaction with visual acuity as a continuous variable, and P = .002 for interaction with visual acuity as a categorical variable). It is unknown whether different visual acuity outcomes associated with the use of the 3 anti-VEGF agents would be noted with other treatment regimens or with adequately repackaged bevacizumab, as well as in patients with criteria that excluded them from the RCT, such as persistent DME despite recent anti-VEGF treatment. On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and visual acuity impairment. Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept over bevacizumab or ranibizumab 1 year later. Care needs to be taken when attempting to extrapolate outcomes of this RCT to differing treatment regimens. With access to adequately repackaged bevacizumab, many specialists might initiate therapy with bevacizumab when visual acuity is good (ie, 20/32 to 20/40 as measured in the DRCR Network), recognizing that the cost-effectiveness of bevacizumab outweighs that of aflibercept or ranibizumab.

Comparison of surgical effect and postoperative patient experience between laparoendoscopic single-site and conventional laparoscopic varicocelectomy: a systematic review and meta-analysis

PubMed Central

Zhang, Zheng; Zheng, Shu-Juan; Yu, Wen; Han, You-Feng; Chen, Hai; Chen, Yun; Dai, Yu-Tian

2017-01-01

The present meta-analysis was conducted to compare the clinical effect and patient experience of laparoendoscopic single-site varicocelectomy (LESSV) and conventional laparoscopic varicocelectomy. The candidate studies were included after literature search of database Cochrane Library, PubMed, EMBASE, and MEDLINE. Related information on essential data and outcome measures was extracted from the eligible studies by two independent authors, and a meta-analysis was conducted using STATA 12.0 software. Subgroup analyses were conducted by study design (RCT and non-RCT). The odds ratio (OR) or standardized mean difference (SMD) and their 95% confidence intervals (95% CIs) were used to estimate the outcome measures. Seven articles were included in our meta-analysis. The results indicated that patient who had undergone LESSV had a shorter duration of back to work (overall: SMD = −1.454, 95% CI: −2.502–−0.405, P = 0.007; non-RCT: SMD = −2.906, 95% CI: −3.796–−2.017, P = 0.000; and RCT: SMD = −0.841, 95% CI: −1.393–−0.289, P = 0.003) and less pain experience at 3 h or 6 h (SMD = −0.447, 95% CI: −0.754–−0.139, P = 0.004), day 1 (SMD = −0.477, 95% CI: −0.905–−0.05, P = 0.029), and day 2 (SMD = −0.612, 95% CI: −1.099–−0.125, P = 0.014) postoperatively based on RCT studies. However, the meta-analyses based on operation time, clinical effect (improvement of semen quality and scrotal pain relief), and complications (hydrocele and recurrence) yielded nonsignificant results. In conclusion, LESSV had a rapid recovery and less pain experience over conventional laparoscopic varicocelectomy. However, there was no statistically significant difference between the two varicocelectomy techniques in terms of the clinical effect and the incidence of hydrocele and varicocele recurrence. More high-quality studies are warranted for a comprehensive conclusion. PMID:27212128

Intensive home treatment for patients in acute psychiatric crisis situations: a multicentre randomized controlled trial.

PubMed

Cornelis, Jurgen; Barakat, Ansam; Dekker, Jack; Schut, Tessy; Berk, Sandra; Nusselder, Hans; Ruhl, Nikander; Zoeteman, Jeroen; Van, Rien; Beekman, Aartjan; Blankers, Matthijs

2018-02-27

Hospitalization is a common method to intensify care for patients experiencing a psychiatric crisis. A short-term, specialised, out-patient crisis intervention by a Crisis Resolution Team (CRT) in the Netherlands, called Intensive Home Treatment (IHT), is a viable intervention which may help reduce hospital admission days. However, research on the (cost-)effectiveness of alternatives to hospitalisation such as IHT are scarce. In the study presented in this protocol, IHT will be compared to care-as-usual (CAU) in a randomized controlled trial (RCT). CAU comprises low-intensity outpatient care and hospitalisation if necessary. In this RCT it is hypothesized that IHT will reduce inpatient days by 33% compared to CAU while safety and clinical outcomes will be non-inferior. Secondary hypotheses are that treatment satisfaction of patients and their relatives are expected to be higher in the IHT condition compared to CAU. A 2-centre, 2-arm Zelen double consent RCT will be employed. Participants will be recruited in the Amsterdam area, the Netherlands. Clinical assessments will be carried out at baseline and at 6, 26 and 52 weeks post treatment allocation. The primary outcome measure is the number of admission days. Secondary outcomes include psychological well-being, safety and patients' and their relatives' treatment satisfaction. Alongside this RCT an economic evaluation will be carried out to assess the cost-effectiveness and cost-utility of IHT compared to CAU. RCTs on the effectiveness of crisis treatment in psychiatry are scarce and including patients in studies performed in acute psychiatric crisis care is a challenge due to the ethical and practical hurdles. The Zelen design may offer a feasible opportunity to carry out such an RCT. If our study finds that IHT is a safe and cost-effective alternative for CAU it may help support a further decrease of in-patient bed days and may foster the widespread implementation of IHT by mental health care organisations internationally. The trial is registered in the Netherlands Trial Register as # NTR-6151 . Registered 23 November 2016.

Risperidone versus other antipsychotics for people with severe mental illness and co-occurring substance misuse.

PubMed

Temmingh, Henk S; Williams, Taryn; Siegfried, Nandi; Stein, Dan J

2018-01-22

Up to 75% of people with serious mental illness (SMI) such as schizophrenia and bipolar disorder have co-occurring substance use disorders (dual diagnosis). Dual diagnosis can have an adverse effect on treatment and prognosis of SMI. To evaluate the effects of risperidone compared to treatment with other antipsychotics (first-generation and other second-generation antipsychotics) used in people with serious mental illness and co-occurring substance misuse. On 6 January 2016 and 9 October 2017, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (including trial registers). We selected randomised trials of risperidone versus any other antipsychotic in people with SMI and substance abuse (dual diagnosis). We included trials meeting our inclusion criteria and reporting useable data. We excluded trials that either did not meet our inclusion criteria or met our inclusion criteria but did not report any useable data. We independently inspected citations and selected studies. For included studies, we independently extracted data and appraised study quality. For binary outcomes we calculated the risk ratios (RRs) and their 95% confidence intervals. For continuous outcomes we calculated the mean differences (MDs) and their 95% confidence intervals. We pooled data using random-effects meta-analyses and assessed the quality of evidence, creating a 'Summary of findings' table using the GRADE approach. We identified eight randomised trials containing a total of 1073 participants with SMI and co-occurring substance misuse. Seven of these contributed useable data to the review. There was heterogeneity in trial design and measurement. Risperidone was compared to clozapine, olanzapine, perphenazine, quetiapine and ziprasidone. Few trials compared risperidone with first-generation agents. Few trials examined participants with a dual diagnosis from the outset and most trials only contained separate analyses of subgroups with a dual diagnosis or were secondary data analyses of subgroups of people with a dual diagnosis from existing larger trials.For risperidone versus clozapine we found no clear differences between these two antipsychotics in the reduction of positive psychotic symptoms (1 randomised controlled trial (RCT), n = 36, mean difference (MD) 0.90, 95% CI -2.21 to 4.01, very low quality evidence), or reduction in cannabis use (1 RCT, n = 14, risk ratio (RR) 1.00, 95% CI 0.30 to 3.35, very low quality evidence), improvement in subjective well-being (1 RCT, n = 36, MD -6.00, 95% CI -14.82 to 2.82, very low quality evidence), numbers discontinuing medication (1 RCT, n = 36, RR 4.05, 95% CI 0.21 to 78.76, very low quality evidence), extrapyramidal side-effects (2 RCTs, n = 50, RR 2.71, 95% CI 0.30 to 24.08; I² = 0%, very low quality evidence), or leaving the study early (2 RCTs, n = 45, RR 0.49, 95% CI 0.10 to 2.51; I² = 34%, very low quality evidence). Clozapine was associated with lower levels of craving for cannabis (1 RCT, n = 28, MD 7.00, 95% CI 2.37 to 11.63, very low quality evidence).For risperidone versus olanzapine we found no clear differences in the reduction of positive psychotic symptoms (1 RCT, n = 37, MD -1.50, 95% CI -3.82 to 0.82, very low quality evidence), reduction in cannabis use (1 RCT, n = 41, MD 0.40, 95% CI -4.72 to 5.52, very low quality evidence), craving for cannabis (1 RCT, n = 41, MD 5.00, 95% CI -4.86 to 14.86, very low quality evidence), parkinsonism (1 RCT, n = 16, MD -0.08, 95% CI -1.21 to 1.05, very low quality evidence), or leaving the study early (2 RCT, n = 77, RR 0.68, 95% CI 0.34 to 1.35; I² = 0%, very low quality evidence).For risperidone versus perphenazine, we found no clear differences in the number of participants leaving the study early (1 RCT, n = 281, RR 1.05, 95% CI 0.92 to 1.20, low-quality evidence).For risperidone versus quetiapine, we found no clear differences in the number of participants leaving the study early (1 RCT, n = 294, RR 0.96, 95% CI 0.86 to 1.07, low-quality evidence).For risperidone versus ziprasidone, we found no clear differences in the number of participants leaving the study early (1 RCT, n = 240, RR 0.96, 95% CI 0.85 to 1.10, low-quality evidence).For many comparisons, important outcomes were missing; and no data were reported in any study for metabolic disturbances, global impression of illness severity, quality of life or mortality. There is not sufficient good-quality evidence available to determine the effects of risperidone compared with other antipsychotics in people with a dual diagnosis. Few trials compared risperidone with first-generation agents, leading to limited applicability to settings where access to second-generation agents is limited, such as in low- and middle-income countries. Moreover, heterogeneity in trial design and measurement of outcomes precluded the use of many trials in our analyses. Future trials in this area need to be sufficiently powered but also need to conform to consistent methods in study population selection, use of measurement scales, definition of outcomes, and measures to counter risk of bias. Investigators should adhere to CONSORT guidelines in the reporting of results.

Decision Making in the PICU: An Examination of Factors Influencing Participation Decisions in Phase III Randomized Clinical Trials

PubMed Central

Slosky, Laura E.; Burke, Natasha L.; Siminoff, Laura A.

2014-01-01

Background. In stressful situations, decision making processes related to informed consent may be compromised. Given the profound levels of distress that surrogates of children in pediatric intensive care units (PICU) experience, it is important to understand what factors may be influencing the decision making process beyond the informed consent. The purpose of this study was to evaluate the role of clinician influence and other factors on decision making regarding participation in a randomized clinical trial (RCT). Method. Participants were 76 children under sedation in a PICU and their surrogate decision makers. Measures included the Post Decision Clinician Survey, observer checklist, and post-decision interview. Results. Age of the pediatric patient was related to participation decisions in the RCT such that older children were more likely to be enrolled. Mentioning the sponsoring institution was associated with declining to participate in the RCT. Type of health care provider and overt recommendations to participate were not related to enrollment. Conclusion. Decisions to participate in research by surrogates of children in the PICU appear to relate to child demographics and subtleties in communication; however, no modifiable characteristics were related to increased participation, indicating that the informed consent process may not be compromised in this population. PMID:25161672

A Bayesian Analysis of a Randomized Clinical Trial Comparing Antimetabolite Therapies for Non-Infectious Uveitis

PubMed Central

Browne, Erica N; Rathinam, Sivakumar R; Kanakath, Anuradha; Thundikandy, Radhika; Babu, Manohar; Lietman, Thomas M; Acharya, Nisha R

2017-01-01

Purpose To conduct a Bayesian analysis of a randomized clinical trial (RCT) for non-infectious uveitis using expert opinion as a subjective prior belief. Methods A RCT was conducted to determine which antimetabolite, methotrexate or mycophenolate mofetil, is more effective as an initial corticosteroid-sparing agent for the treatment of intermediate, posterior, and pan- uveitis. Before the release of trial results, expert opinion on the relative effectiveness of these two medications was collected via online survey. Members of the American Uveitis Society executive committee were invited to provide an estimate for the relative decrease in efficacy with a 95% credible interval (CrI). A prior probability distribution was created from experts’ estimates. A Bayesian analysis was performed using the constructed expert prior probability distribution and the trial’s primary outcome. Results 11 of 12 invited uveitis specialists provided estimates. Eight of 11 experts (73%) believed mycophenolate mofetil is more effective. The group prior belief was that the odds of treatment success for patients taking mycophenolate mofetil were 1.4-fold the odds of those taking methotrexate (95% CrI 0.03 – 45.0). The odds of treatment success with mycophenolate mofetil compared to methotrexate was 0.4 from the RCT (95% confidence interval 0.1–1.2) and 0.7 (95% CrI 0.2–1.7) from the Bayesian analysis. Conclusions A Bayesian analysis combining expert belief with the trial’s result did not indicate preference for one drug. However, the wide credible interval leaves open the possibility of a substantial treatment effect. This suggests clinical equipoise necessary to allow a larger, more definitive RCT. PMID:27982726

Red blood cells play a role in reverse cholesterol transport.

PubMed

Hung, Kimberly T; Berisha, Stela Z; Ritchey, Brian M; Santore, Jennifer; Smith, Jonathan D

2012-06-01

Reverse cholesterol transport (RCT) involves the removal of cholesterol from peripheral tissue for excretion in the feces. Here, we determined whether red blood cells (RBCs) can contribute to RCT. We performed a series of studies in apolipoprotein AI-deficient mice where the high-density lipoprotein-mediated pathway of RCT is greatly diminished. RBCs carried a higher fraction of whole blood cholesterol than plasma in apolipoprotein AI-deficient mice, and as least as much of the labeled cholesterol derived from injected foam cells appeared in RBCs compared with plasma. To determine whether RBCs mediate RCT to the fecal compartment, we measured RCT in anemic and control apolipoprotein AI-deficient mice and found that anemia decreased RCT to the feces by over 35% after correcting for fecal mass. Transfusion of [(3)H]cholesterol-labeled RBCs led to robust delivery of the labeled cholesterol to the feces in apolipoprotein AI-deficient hosts. In wild-type mice, the majority of the blood cholesterol mass, as well as [(3)H]cholesterol derived from the injected foam cells, was found in plasma, and anemia did not significantly alter RCT to the feces after correction for fecal mass. The RBC cholesterol pool is dynamic and facilitates RCT of peripheral cholesterol to the feces, particularly in the low high-density lipoprotein state.

A randomised controlled trial evaluating the utility of a patient Decision Aid to improve clinical trial (RAVES 08.03) related decision-making.

PubMed

Sundaresan, Puma; Ager, Brittany; Turner, Sandra; Costa, Dan; Kneebone, Andrew; Pearse, Maria; Woo, Henry; Tesson, Stephanie; Juraskova, Ilona; Butow, Phyllis

2017-10-01

Randomised controlled trials (RCTs) are considered the 'gold-standard' for evaluating medical treatments. However, patients and clinicians report difficulties with informed consent and recruitment. We evaluated the utility of a Decision Aid (DA) in reducing RCT-related decisional conflict, and improving RCT knowledge and recruitment. Potential participants for a radiotherapy RCT were invited to participate in the current study. Participants were randomised to receive the RCT's participant information sheet with or without a DA. Questionnaires were administered at baseline, one and six months. The primary outcome measure was decisional conflict. Secondary outcome measures included knowledge regarding and recruitment to the RCT. 129 men were randomised to the DA (63) and control (66) arms. Decisional conflict was significantly lower over 6-months (p=0.048) in the DA arm. Knowledge regarding the RCT was significantly higher at 6months (p=0.033) in the DA arm. 20.6% of the DA arm (13 of 63) and 9% of the control arm (6 of 66) entered the RCT. This study demonstrates the utility of a DA in reducing decisional conflict and improving trial knowledge in men with cancer who are making decisions regarding RCT participation. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Effectiveness of Platelet-rich Plasma Injection for Rotator Cuff Tendinopathy: A Prospective Open-label Study.

PubMed

Scarpone, Michael; Rabago, David; Snell, Edward; Demeo, Patrick; Ruppert, Kristine; Pritchard, Perry; Arbogast, Gennie; Wilson, John J; Balzano, John F

2013-03-01

Assess platelet rich plasma (PRP) injection for rotator cuff tendinopathy (RCT). Prospective open label study with 1-year follow-up. Participants recruited from an outpatient sports medicine clinic had clinically and magnetic resonance image (MRI)-demonstrated RCT refractory to physical therapy and corticosteroid injection. They received one ultrasound-guided injection of 3.0 mL of 1% xylocaine followed by 3.5 mL of PRP at the lesion and surrounding tendon. 0-10 visual analog scale (VAS; baseline, 8, 12, and 52 weeks). functional shoulder tests assessing rotator cuff strength and endurance (at baseline and 8 and 12 weeks), MRI severity (1-5 points [at baseline and 4 and 8 weeks]), and patient satisfaction (52 weeks). Eighteen participants with 19 assessed shoulders reported VAS pain score improvement from 7.5 ± 0.3 points to 0.5 ± 0.3 points by week 12 and 0.4 ± 0.2 (P = .0001) points at week 52. Functional outcomes significantly improved; the largest effect was seen in the external rotation test: 33.5 ± 5.7 seconds to 62.6 ± 7.2 seconds at week 12 (P = .0001). MRI appearance improved by 1 to 3 points in 16 of 18 assessed shoulders. Seventeen participants were "completely satisfied" (12) or "satisfied" (5). One participant was "unsatisfied." A single ultrasound-guided, intralesional injection of PRP resulted in safe, significant, sustained improvement of pain, function, and MRI outcomes in participants with refractory RCT. Randomized multidisciplinary effectiveness trials that add ultrasound and validated clinical outcome measures are needed to further assess PRP for RCT.

Long-term follow-up of disability pensioners having musculoskeletal disorders.

PubMed

Magnussen, Liv H; Strand, Liv I; Skouen, Jan S; Eriksen, Hege R

2009-11-10

Previously we have conducted a randomised controlled trial (RCT) to evaluate the effect of a brief cognitive behavioural program with a vocational approach aiming to return disability pensioners with back pain to work, as compared to no intervention. One year after the intervention, 10 participants (22%) who received the program and 5 (11%) in the control group reported to have entered a return to work process. The aims of this study were to evaluate long-term effects of the intervention, and compare this effect to 2 reference populations not participating in the original trial. Three groups of disability pensioners were investigated: 1) Disability pensioners having back pain (n = 89) previously participating in the RCT (randomized to either a brief cognitive behavioural intervention or to a control group), 2) 342 disability pensioners having back pain, but refusing to participate in the study and 3) 449 disability pensioners having other musculoskeletal disorders than back pain. Primary outcome was return to work, defined as a reduction in payment of disability pension. Only 2 of 89 (2.3%) participants from the RCT had reduced disability pension at 3-years follow-up, both from the control group. None of the participants that had been in a process of returning to work after 1 year had actually gained employment at 3-years follow-up. In the 2 groups not participating in the previous RCT, only 4 (1.2%) and 8 (1.6%) had returned to work after 3 years respectively. The number of pensioners who returned to work was negligible in all groups regardless of having participated in a cognitive behavioural intervention or not.

Genetics and the Placebo Effect: the Placebome

PubMed Central

Hall, Kathryn T.; Loscalzo, Joseph; Kaptchuk, Ted J.

2015-01-01

Placebos are indispensable controls in randomized clinical trials (RCTs), and placebo responses significantly contribute to routine clinical outcomes. Recent neurophysiological studies reveal neurotransmitter pathways that mediate placebo effects. Evidence that genetic variations in these pathways can modify placebo effects raises the possibility of using genetic screening to identify placebo responders and thereby increase RCT efficacy and improve therapeutic care. Furthermore, the possibility of interaction between placebo and drug molecular pathways warrants consideration in RCT design. The study of genomic effects on placebo response, “the placebome”, is in its infancy. Here, we review evidence from placebo studies and RCTs to identify putative genes in the placebome, examine evidence for placebo-drug interactions, and discuss implications for RCTs and clinical care. PMID:25883069

An RCT of Nurse Coaching vs. Herbal CAM for Soldier Weight Reduction

DTIC Science & Technology

2015-12-08

Coaching vs. Herbal CAM for Soldier Weight Reduction 5b. GRANT NUMBER HT9404-12-1-TS03 5c. PROGRAM ELEMENT NUMBER N/A 6. AUTHOR(S) 5d...coaching intervention and an herbal supplement for Service Member (SM) weight reduction over a 12-week period to evaluate their effectiveness...Title of Research Study or Evidence-Based Practice (EBP) Project An RCT of Nurse Coaching vs. Herbal CAM for Soldier Weight Reduction Period of Award

Human papillomavirus vaccination among adolescents in Georgia.

PubMed

Underwood, Natasha L; Weiss, Paul; Gargano, Lisa M; Seib, Katherine; Rask, Kimberly J; Morfaw, Christopher; Murray, Dennis; DiClemente, Ralph J; Hughes, James M; Sales, Jessica M

2015-01-01

Human papillomavirus (HPV) vaccination coverage for adolescent females and males remains low in the United States. We conducted a 3-arm randomized controlled trial (RCT) conducted in middle and high schools in eastern Georgia from 2011-2013 to determine the effect of 2 educational interventions used to increase adolescent vaccination coverage for the 4 recommended adolescent vaccines: Tdap, MCV4, HPV and influenza. As part of this RCT, this article focuses on: 1) describing initiation and completion of HPV vaccine series among a diverse population of male and female adolescents; 2) assessing parental attitudes toward HPV vaccine; and 3) examining correlates of HPV vaccine series initiation and completion. Parental attitude score was the strongest predictor of HPV vaccine initiation among adolescents (adjusted odds ratio (aOR): 2.08; 95% confidence interval (CI): 1.80, 2.39). Other correlates that significantly predicted HPV series initiation were gender, study year, and intervention arm. Parental attitudes remained a significant predictor of receipt of 3 doses of HPV vaccine along with gender, race, school type and insurance type. This study demonstrates that positive parental attitudes are important predictors of HPV vaccination and critical to increasing coverage rates. Our findings suggest that more research is needed to understand how parental attitudes are developed and evolve over time.

EMDR beyond PTSD: A Systematic Literature Review

PubMed Central

Valiente-Gómez, Alicia; Moreno-Alcázar, Ana; Treen, Devi; Cedrón, Carlos; Colom, Francesc; Pérez, Víctor; Amann, Benedikt L.

2017-01-01

Background: Eye Movement Desensitization and Reprocessing (EMDR) is a psychotherapeutic approach that has demonstrated efficacy in the treatment of Post-traumatic Stress Disorder (PTSD) through several randomized controlled trials (RCT). Solid evidence shows that traumatic events can contribute to the onset of severe mental disorders and can worsen their prognosis. The aim of this systematic review is to summarize the most important findings from RCT conducted in the treatment of comorbid traumatic events in psychosis, bipolar disorder, unipolar depression, anxiety disorders, substance use disorders, and chronic back pain. Methods: Using PubMed, ScienceDirect, and Scopus, we conducted a systematic literature search of RCT studies published up to December 2016 that used EMDR therapy in the mentioned psychiatric conditions. Results: RCT are still scarce in these comorbid conditions but the available evidence suggests that EMDR therapy improves trauma-associated symptoms and has a minor effect on the primary disorders by reaching partial symptomatic improvement. Conclusions: EMDR therapy could be a useful psychotherapy to treat trauma-associated symptoms in patients with comorbid psychiatric disorders. Preliminary evidence also suggests that EMDR therapy might be useful to improve psychotic or affective symptoms and could be an add-on treatment in chronic pain conditions. PMID:29018388

A retrospective study of root canal therapy in non-vital primary molars.

PubMed

Stallaert, K M; Sigal, M J; Titley, K C; Andrews, P B

2016-12-01

This study was performed to assess the clinical and radiographic success rates of a formocresol and zinc oxide eugenol (ZOE) primary molar root canal therapy (RCT) technique. The effects of this treatment on the permanent successors and on exfoliation times were also investigated. Study design: the retrospective study included 161 patients with 211 primary molars treated by RCT by a single operator in a private paediatric dental office in the Toronto area. Data were coded and entered into a Microsoft Excel database and analysis undertaken using SPSS software. Predominantly non-parametric tests were used to evaluate statistical differences (p < 0.05). A clinical success rate of 90% (190/211) and a radiographic success rate of 77.3% (136/176) were obtained. Following RCT in a primary molar, enamel defects were found in 6.8% (7/103) of premolars, all of which occurred in first premolars, and in patients treated at a mean age of 54.1 months (p < 0.005). Treated molars exfoliated on average 7.6 months sooner than contralateral teeth (p < 0.005). This formocresol and ZOE RCT is a viable treatment for necrotic primary molars and yielded very high clinical and acceptable radiographic success rates.

Does oral polio vaccine have non-specific effects on all-cause mortality? Natural experiments within a randomised controlled trial of early measles vaccine.

PubMed

Aaby, Peter; Andersen, Andreas; Martins, Cesário L; Fisker, Ane B; Rodrigues, Amabelia; Whittle, Hilton C; Benn, Christine S

2016-12-23

BCG and measles vaccine (MV) may have beneficial non-specific effects (NSEs). If an unplanned intervention with a vaccine (a natural experiment) modifies the estimated effect in a randomised controlled trial (RCT), this suggests NSEs. We used this approach to test NSEs of triple oral polio vaccine (OPV). During an RCT of 2 doses of MV at 4.5 and 9 months versus 1 dose of MV at 9 months of age, we experienced 2 natural experiments with OPV. We assessed whether these OPV experiments modified the effect of 2-dose MV in the MV trial. MV RCT conducted in urban Guinea-Bissau 2003-2009. Natural experiments with OPV due to missing vaccine and the implementation of OPV campaigns. Changes in the mortality rate ratio (MRR) for 2-dose MV versus 1-dose MV. First, the MRR (2-dose/1-dose MV) overall was 0.70 (0.52 to 0.94), but the MRR was 1.04 (0.53 to 2.04) when OPV at birth (OPV0) was not given, suggesting that early priming with OPV was important for the effect of 2-dose MV. The effect of OPV0 depended on age of administration; the MRR (2-dose/1-dose MV) was 0.45 (0.29 to 0.71) for children receiving OPV0 in the first week of life, but 3.63 (0.87 to 15.2) for those receiving OPV0 after the first month of life (p=0.007, test of no interaction). Second, campaign-OPV may have reduced the difference between the randomisation groups since the MRR (2-dose/1-dose MV) was 0.60 (0.42 to 0.85) for children who had not received campaign-OPV before RCT-enrolment versus 0.72 (0.23 to 2.31) and 1.42 (0.70 to 2.90) for children who had received 1 or 2 doses of campaign-OPV-before-enrolment, respectively. Bissau had no polio infection during this trial, so OPV0 and campaign-OPV may have NSEs since they modified the effect of 2-dose MV in an RCT. Different interventions may interact to a much larger effect than usually assumed. 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/.

Intervention for First Graders with Limited Number Knowledge: Large-Scale Replication of a Randomized Controlled Trial

ERIC Educational Resources Information Center

Gersten, Russell; Rolfhus, Eric; Clarke, Ben; Decker, Lauren E.; Wilkins, Chuck; Dimino, Joseph

2015-01-01

Replication studies are extremely rare in education. This randomized controlled trial (RCT) is a scale-up replication of Fuchs et al., which in a sample of 139 found a statistically significant positive impact for Number Rockets, a small-group intervention for at-risk first graders that focused on building understanding of number operations. The…

Stopping randomized trials early for benefit: a protocol of the Study Of Trial Policy Of Interim Truncation-2 (STOPIT-2)

PubMed Central

Briel, Matthias; Lane, Melanie; Montori, Victor M; Bassler, Dirk; Glasziou, Paul; Malaga, German; Akl, Elie A; Ferreira-Gonzalez, Ignacio; Alonso-Coello, Pablo; Urrutia, Gerard; Kunz, Regina; Culebro, Carolina Ruiz; da Silva, Suzana Alves; Flynn, David N; Elamin, Mohamed B; Strahm, Brigitte; Murad, M Hassan; Djulbegovic, Benjamin; Adhikari, Neill KJ; Mills, Edward J; Gwadry-Sridhar, Femida; Kirpalani, Haresh; Soares, Heloisa P; Elnour, Nisrin O Abu; You, John J; Karanicolas, Paul J; Bucher, Heiner C; Lampropulos, Julianna F; Nordmann, Alain J; Burns, Karen EA; Mulla, Sohail M; Raatz, Heike; Sood, Amit; Kaur, Jagdeep; Bankhead, Clare R; Mullan, Rebecca J; Nerenberg, Kara A; Vandvik, Per Olav; Coto-Yglesias, Fernando; Schünemann, Holger; Tuche, Fabio; Chrispim, Pedro Paulo M; Cook, Deborah J; Lutz, Kristina; Ribic, Christine M; Vale, Noah; Erwin, Patricia J; Perera, Rafael; Zhou, Qi; Heels-Ansdell, Diane; Ramsay, Tim; Walter, Stephen D; Guyatt, Gordon H

2009-01-01

Background Randomized clinical trials (RCTs) stopped early for benefit often receive great attention and affect clinical practice, but pose interpretational challenges for clinicians, researchers, and policy makers. Because the decision to stop the trial may arise from catching the treatment effect at a random high, truncated RCTs (tRCTs) may overestimate the true treatment effect. The Study Of Trial Policy Of Interim Truncation (STOPIT-1), which systematically reviewed the epidemiology and reporting quality of tRCTs, found that such trials are becoming more common, but that reporting of stopping rules and decisions were often deficient. Most importantly, treatment effects were often implausibly large and inversely related to the number of the events accrued. The aim of STOPIT-2 is to determine the magnitude and determinants of possible bias introduced by stopping RCTs early for benefit. Methods/Design We will use sensitive strategies to search for systematic reviews addressing the same clinical question as each of the tRCTs identified in STOPIT-1 and in a subsequent literature search. We will check all RCTs included in each systematic review to determine their similarity to the index tRCT in terms of participants, interventions, and outcome definition, and conduct new meta-analyses addressing the outcome that led to early termination of the tRCT. For each pair of tRCT and systematic review of corresponding non-tRCTs we will estimate the ratio of relative risks, and hence estimate the degree of bias. We will use hierarchical multivariable regression to determine the factors associated with the magnitude of this ratio. Factors explored will include the presence and quality of a stopping rule, the methodological quality of the trials, and the number of total events that had occurred at the time of truncation. Finally, we will evaluate whether Bayesian methods using conservative informative priors to "regress to the mean" overoptimistic tRCTs can correct observed biases. Discussion A better understanding of the extent to which tRCTs exaggerate treatment effects and of the factors associated with the magnitude of this bias can optimize trial design and data monitoring charters, and may aid in the interpretation of the results from trials stopped early for benefit. PMID:19580665

Experimental protocol of a randomized controlled clinical trial investigating the effects of personalized exercise rehabilitation on kidney transplant recipients' outcomes.

PubMed

Kastelz, Alexandra; Tzvetanov, Ivo G; Fernhall, Bo; Shetty, Aneesha; Gallon, Lorenzo; West-Thielke, Patricia; Hachaj, Greg; Grazman, Mark; Benedetti, Enrico

2015-11-01

This randomized controlled trial (RCT) will investigate the effects of a personalized exercise rehabilitation regimen on return to work and find work rate, vascular health, functional capacity, quality of life, kidney function, and body composition in kidney transplant (KT) recipients. This RCT will recruit 120 men and/or women who have had a KT to participate in a 12 month exercise intervention or control (standard clinical care only) group. The 12 month exercise intervention will consist of one-on-one, progressive exercise rehabilitation sessions twice a week, for 60 min each session. The control group will continue standard clinical care as recommended by their post-transplant medical team without any intervention. The primary outcomes will be assessments of vascular structure and function, walking and strength measures to assess functional capacity, blood markers to assess kidney function, questionnaires to assess quality of life, DXA body scan to assess body composition, and a 1-week free living physical activity assessment. Additionally, employment status will be assessed. These assessments will be performed at baseline, 6 months, and 12 months. This investigation will increase the understanding of the role exercise rehabilitation has on managing the physiological and psychological health of the individual as well as on the individual's personal economic impact (via employment status). This study design has the potential to assist in constructing an effective exercise rehabilitation program that can be incorporated into part of standard post-transplant care. Copyright © 2015 Elsevier Inc. All rights reserved.

Ubiquinol-10 supplementation improves autonomic nervous function and cognitive function in chronic fatigue syndrome.

PubMed

Fukuda, Sanae; Nojima, Junzo; Kajimoto, Osami; Yamaguti, Kouzi; Nakatomi, Yasuhito; Kuratsune, Hirohiko; Watanabe, Yasuyoshi

2016-07-08

The aim of this study was to evaluate the benefit of oral ubiquinol-10 supplementation in CFS patients using an open-label study and a randomized, double-blinded, placebo-controlled (RCT) study. Twenty patients with CFS were randomly enrolled in an 8-week open-label oral ubiquinol-10 (150 mg ubiquinol-10/day) study. The patients and the attending physicians were not blinded to the supplementation. Forty-three patients with CFS were randomly assigned to receive either ubiquinol-10 (150 mg/day) or placebo every day for 12 weeks. The patients and the attending physicians were blinded to the supplementation, and a total of 31 patients (N = 17 in the ubiquinol group and 14 in the placebo group) completed the study. The beneficial effects of ubiquinol-10 were observed in the open-label study we conducted prior to the RCT. The RCT results suggest that supplementation with ubiquinol-10 for 12 weeks is effective for improving several CFS symptoms. © 2016 BioFactors, 42(4):431-440, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

Clinical outcomes after elective repair for small umbilical and epigastric hernias.

PubMed

Christoffersen, Mette Maria Willaume

2015-11-01

Repair for an umbilical or epigastric hernia is one of the most frequently conducted gastrointestinal surgical procedures. Al-though it is a minor procedure, there is no consensus on the optimal repair technique. The readmission rate is surprisingly high due to postoperative pain, wound-related complications, and long-term results in terms of recurrence and chronic pain is not well investigated. The overall objective of this thesis was to improve early and long-term postoperative outcomes after repair for umbilical or epigastric hernias. The present thesis consisted of one RCT, one protocol article for a running RCT, and two register-based cohort studies. An abdominal binder had no analgesic effects or impact on seroma formation. We await early and late post-operative outcomes from a running RCT studying clinical effect of closing the hernia defect (inclusion is expected to end in October 2015). The two cohort studies included in the present theses found that mesh repair halved the long-term risk of recurrence compared with sutured repair. Mesh repair did not increase the risk of chronic pain or rate of reoperation for complications.

PD-L1 is upregulated by radiochemotherapy in rectal adenocarcinoma patients and associated with a favourable prognosis.

PubMed

Hecht, Markus; Büttner-Herold, Maike; Erlenbach-Wünsch, Katharina; Haderlein, Marlen; Croner, Roland; Grützmann, Robert; Hartmann, Arndt; Fietkau, Rainer; Distel, Luitpold V

2016-09-01

The influence of neoadjuvant radiochemotherapy (RCT) on programmed death-ligand 1 (PD-L1) expression, a predictive marker for programmed cell death protein 1 (PD-1) inhibitor therapy, was studied on tumour and inflammatory cells in rectal adenocarcinoma patients along with its prognostic value. PD-L1 immunohistochemistry was performed on tissue microarrays of 103 pre-RCT biopsies and 159 post-RCT surgical specimens (central tumour, invasive front and normal tissue) of 199 patients. In 63 patients, both samples were available. Proportion and maximum intensity of PD-L1-positive (PD-L1+) cells were evaluated. RCT increased the proportion of PD-L1-expressing cancer cells from 2.1% to 7.8% in the central tumour (p < 0.001) or 9.3% in the invasive front (p < 0.001). Cancer cell PD-L1 on its own could not predict prognosis. High PD-L1 expression on pre-RCT inflammatory cells (maximum intensity: p = 0.048) and post-RCT invasive front inflammatory cells (p = 0.010) correlated with improved no evidence of disease survival. In multivariate analysis, the combination of low PD-L1 in cancer and inflammatory cells was an independent negative prognostic marker for overall survival (OS) pre-RCT (Cox's proportional hazard ratio 0.438, p = 0.045) and in the invasive front post-RCT (Cox's proportional hazard ratio 0.257, p = 0.030). Neoadjuvant RCT is associated with an increased PD-L1 expression in rectal adenocarcinoma patients, which should prompt clinical trials combining radiotherapy and PD-1/PD-L1 pathway blockade. Combined low PD-L1 expression on tumour and inflammatory cells is an independent negative prognostic marker for OS in RCT of rectal adenocarcinoma. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comprehension of Randomization and Uncertainty in Cancer Clinical Trials Decision Making Among Rural, Appalachian Patients.

PubMed

Krieger, Janice L; Palmer-Wackerly, Angela; Dailey, Phokeng M; Krok-Schoen, Jessica L; Schoenberg, Nancy E; Paskett, Electra D

2015-12-01

Comprehension of randomization is a vital, but understudied, component of informed consent to participate in cancer randomized clinical trials (RCTs). This study examines patient comprehension of the randomization process as well as sources of ongoing uncertainty that may inhibit a patient's ability to provide informed consent to participate in RCTs. Cancer patients living in rural Appalachia who were offered an opportunity to participate in a cancer treatment RCT completed in-depth interviews and a brief survey. No systematic differences in randomization comprehension between patients who consented and those who declined participation in a cancer RCT were detected. Comprehension is conceptually distinct from uncertainty, with patients who had both high and low comprehension experiencing randomization-related uncertainty. Uncertainty about randomization was found to have cognitive and affective dimensions. Not all patients enrolling in RCTs have a sufficient understanding of the randomization process to provide informed consent. Healthcare providers need to be aware of the different types of randomization-related uncertainty. Efforts to improve informed consent to participate in RCTs should focus on having patients teach back their understanding of randomization. This practice could yield valuable information about the patient's cognitive and affective understanding of randomization as well as opportunities to correct misperceptions. Education about RCTs should reflect patient expectations of individualized care by explaining how all treatments being compared are appropriate to the specifics of a patient's disease.

[On-site quality control of acupuncture randomized controlled trial: design of content and checklist of quality control based on PICOST].

PubMed

Li, Hong-Jiao; He, Li-Yun; Liu, Zhi-Shun; Sun, Ya-Nan; Yan, Shi-Yan; Liu, Jia; Zhao, Ye; Liu, Bao-Yan

2014-02-01

To effectively guarantee quality of randomized controlld trial (RCT) of acupuncture and develop reasonable content and checklist of on-site quality control, influencing factors on quality of acupuncture RCT are analyzed and scientificity of quality control content and feasibility of on-site manipulation are put into overall consideration. Based on content and checklist of on-site quality control in National 11th Five-Year Plan Project Optimization of Comprehensive Treatment Plan for TCM in Prevention and Treatment of Serious Disease and Clinical Assessment on Generic Technology and Quality Control Research, it is proposed that on-site quality control of acupuncture RCT should be conducted with PICOST (patient, intervention, comparison, out come, site and time) as core, especially on quality control of interveners' skills and outcome assessment of blinding, and checklist of on-site quality control is developed to provide references for undertaking groups of the project.

Evaluation of occupational health interventions using a randomized controlled trial: challenges and alternative research designs.

PubMed

Schelvis, Roosmarijn M C; Oude Hengel, Karen M; Burdorf, Alex; Blatter, Birgitte M; Strijk, Jorien E; van der Beek, Allard J

2015-09-01

Occupational health researchers regularly conduct evaluative intervention research for which a randomized controlled trial (RCT) may not be the most appropriate design (eg, effects of policy measures, organizational interventions on work schedules). This article demonstrates the appropriateness of alternative designs for the evaluation of occupational health interventions, which permit causal inferences, formulated along two study design approaches: experimental (stepped-wedge) and observational (propensity scores, instrumental variables, multiple baseline design, interrupted time series, difference-in-difference, and regression discontinuity). For each design, the unique characteristics are presented including the advantages and disadvantages compared to the RCT, illustrated by empirical examples in occupational health. This overview shows that several appropriate alternatives for the RCT design are feasible and available, which may provide sufficiently strong evidence to guide decisions on implementation of interventions in workplaces. Researchers are encouraged to continue exploring these designs and thus contribute to evidence-based occupational health.

Evaluating the Effectiveness of Website Content Features Using Retrospective Pretest Methodology: An Experimental Test.

PubMed

Mueller, Christoph Emanuel

2015-06-01

In order to assess website content effectiveness (WCE), investigations have to be made into whether the reception of website contents leads to a change in the characteristics of website visitors or not. Because randomized controlled trials (RCTs) are not always the method of choice, researchers may have to follow other strategies such as using retrospective pretest methodology (RPM), a straightforward and easy-to-implement tool for estimating intervention effects. This article aims to introduce RPM in the context of website evaluation and test its viability under experimental conditions. Building on the idea that RCTs deliver unbiased estimates of the true causal effects of website content reception, I compared the performance of RPM with that of an RCT within the same study. Hence, if RPM provides effect estimates similar to those of the RCT, it can be considered a viable tool for assessing the effectiveness of the website content features under study. RPM was capable of delivering comparatively resilient estimates of the effects of a YouTube video and a text feature on knowledge and attitudes. With regard to all of the outcome variables considered, the differences between the sizes of the effects estimated by the RCT and RPM were not significant. Additionally, RPM delivered relatively accurate effect size estimates in most of the cases. Therefore, I conclude that RPM could be a viable alternative for assessing WCE in cases where RCTs are not the preferred method. © The Author(s) 2015.

Phenotypic and genetic relationships between indicators of the mammary gland health status and milk composition, coagulation, and curd firming in dairy sheep.

PubMed

Pazzola, Michele; Cipolat-Gotet, Claudio; Bittante, Giovanni; Cecchinato, Alessio; Dettori, Maria L; Vacca, Giuseppe M

2018-04-01

The present study investigated the effect of somatic cell count, lactose, and pH on sheep milk composition, coagulation properties (MCP), and curd firming (CF) parameters. Individual milk samples were collected from 1,114 Sarda ewes reared in 23 farms. Milk composition, somatic cell count, single point MCP (rennet coagulation time, RCT; curd firming time, k 20 ; and curd firmness, a 30 , a 45 , and a 60 ), and CF model parameters were achieved. Phenotypic traits were statistically analyzed using a mixed model to estimate the effects of the different levels of milk somatic cell score (SCS), lactose, and pH, respectively. Additive genetic, herd, and residual correlations among these 3 traits, and with milk composition, MCP and CF parameters, were inferred using a Bayesian approach. From a phenotypic point of view, higher SCS levels caused a delayed gelification of milk. Lactose concentration and pH were significant for many milk quality traits, with a very intense effect on both coagulation times and curd firming. These traits (RCT, RCT estimated using the curd firming over time equation, and k 20 ) showed an unfavorable increase of about 20% from the highest to the lowest level of lactose. Milk samples with pH values lower than 6.56 versus higher than 6.78 were characterized by an increase of RCT (from 6.00 to 14.3 min) and k 20 (from 1.65 to 2.65 min) and a decrease of all the 3 curd firmness traits. From a genetic point of view, the marginal posterior distribution of heritability estimates evidenced a large and exploitable variability for all 3 phenotypes. The mean intra-farm heritability estimates were 0.173 for SCS, 0.418 for lactose content, and 0.206 for pH. Lactose (favorably), and SCS and pH (unfavorably), at phenotypic and genetic levels, were correlated mainly with RCT and RCT estimated using the curd firming over time equation and scarcely with the other curd firming traits. The SCS, lactose, and pH were significantly correlated with each other's. In conclusion, results reported in the present study suggest that SCS, pH, and lactose affect, contemporarily and independently, milk quality and MCP. These phenotypes, easily available during milk recording schemes measured by infrared spectra prediction, could be used as potential indicators traits for improving cheese-making ability of ovine milk. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Vaccines for preventing anthrax.

PubMed

Donegan, Sarah; Bellamy, Richard; Gamble, Carrol L

2009-04-15

Anthrax is a bacterial zoonosis that occasionally causes human disease and is potentially fatal. Anthrax vaccines include a live-attenuated vaccine, an alum-precipitated cell-free filtrate vaccine, and a recombinant protein vaccine. To evaluate the effectiveness, immunogenicity, and safety of vaccines for preventing anthrax. We searched the following databases (November 2008): Cochrane Infectious Diseases Group Specialized Register; CENTRAL (The Cochrane Library 2008, Issue 4); MEDLINE; EMBASE; LILACS; and mRCT. We also searched reference lists. We included randomized controlled trials (RCTs) of individuals and cluster-RCTs comparing anthrax vaccine with placebo, other (non-anthrax) vaccines, or no intervention; or comparing administration routes or treatment regimens of anthrax vaccine. Two authors independently considered trial eligibility, assessed risk of bias, and extracted data. We presented cases of anthrax and seroconversion rates using risk ratios (RR) and 95% confidence intervals (CI). We summarized immunoglobulin G (IgG) concentrations using geometric means. We carried out a sensitivity analysis to investigate the effect of clustering on the results from one cluster-RCT. No meta-analysis was undertaken. One cluster-RCT (with 157,259 participants) and four RCTs of individuals (1917 participants) met the inclusion criteria. The cluster-RCT from the former USSR showed that, compared with no vaccine, a live-attenuated vaccine (called STI) protected against clinical anthrax whether given by a needleless device (RR 0.16; 102,737 participants, 154 clusters) or the scarification method (RR 0.25; 104,496 participants, 151 clusters). Confidence intervals were statistically significant in unadjusted calculations, but when a small amount of association within clusters was assumed, the differences were not statistically significant. The four RCTs (of individuals) of inactivated vaccines (anthrax vaccine absorbed and recombinant protective antigen) showed a dose response relationship for the anti-protective antigen IgG antibody titre. Intramuscular administration was associated with fewer injection site reactions than subcutaneous injection, and injection site reaction rates were lower when the dosage interval was longer. One cluster-RCT provides limited evidence that a live-attenuated vaccine is effective in preventing cutaneous anthrax. Vaccines based on anthrax antigens are immunogenic in most vaccinees with few adverse events or reactions. Ongoing randomized controlled trials are investigating the immunogenicity and safety of anthrax vaccines.

Translating effective web-based self-help for problem drinking into the real world.

PubMed

Riper, Heleen; Kramer, Jeannet; Conijn, Barbara; Smit, Filip; Schippers, Gerard; Cuijpers, Pim

2009-08-01

Drinking Less (DL) is a 24/7 free-access anonymous interactive web-based self-help intervention without therapeutic guidance for adult problem drinkers in the community. In a randomized controlled trial (referred to here as DL-RCT), DL has been shown effective in reducing risky alcohol consumption. To assess whether the findings of DL-RCT are generalizable to a naturalistic setting (DL-RW) in terms of ability to reach the target group and alcohol treatment response. Pretest-posttest study with 6-month follow-up. An online survey was conducted of 378 of the 1,625 people who used DL-RW from May to November 2007. Primary outcome measures were (1) problem drinking, defined as alcohol consumption in the previous 4 weeks averaging >21 or >14 standard units (male/female) per week or >or=6 or >or=4 units (m/f) on 1 or more days per week; and (2) mean weekly alcohol consumption. DL-RW and DL-RCT data were compared and pooled. Intention-to-treat (ITT) analysis was performed to analyze and compare changes in drinking from baseline to follow-up. In the DL-RW group, 18.8% (n = 71) were drinking successfully within the limits of the Dutch guideline for low-risk drinking (p < 0.001) 6 months after baseline (ITT). The DL-RW group also decreased its mean weekly alcohol intake by 7.4 units, t(377) = 6.67, p < 0.001, d = 0.29. Drinking reduction in DL-RW was of a similar magnitude to that in the DL-RCT condition in terms of drinking within the guideline [chi(2)(1) = 1.83, CI: 0.82-3.00, p = 0.18, RD = 0.05, OR = 1.55] and mean weekly consumption (a negligible difference of d = 0.03 in favor of DL-RW group). The results from DL-RCT and DL-RW were similar, and they demonstrate that web-based self-help without therapeutic guidance is feasible, well accepted, and effective for curbing adult problem drinking in the community.

Volumetric evaluation of the rotator cuff musculature in massive rotator cuff tears with pseudoparalysis.

PubMed

Rhee, Yong Girl; Cho, Nam Su; Song, Jong Hoon; Park, Jung Gwan; Kim, Tae Yong

2017-09-01

If the balance of the rotator cuff force couple is disrupted, pseudoparalysis may occur, but the exact mechanism remains unknown. This study investigated the effect of rotator cuff force couple disruption on active range of motion in massive rotator cuff tear (mRCT) by rotator cuff muscle volume analysis. The study included 53 patients with irreparable mRCT: 22 in the nonpseudoparalysis group and 31 in the pseudoparalysis group. The volumes of the subscapularis (SBS), infraspinatus (ISP), and teres minor (TM) muscles were measured using magnetic resonance imaging (MRI), and the ratios of each muscle volume to the anatomic external rotator (aER) volume were calculated. A control group of 25 individuals with normal rotator cuffs was included. Anterior-to-posterior cuff muscle volume ratio (SBS/ISP + TM) was imbalanced in both mRCT groups (1.383 nonpseudoparalysis and 1.302 pseudoparalysis). Between the 2 groups, the ISP/aER ratio (0.277 vs. 0.249) and the inferior SBS/aER ratio (0.426 vs. 0.390) were significantly decreased in the pseudoparalysis group (P= .022 and P= .040, respectively). However, neither the TM/aER ratio (0.357 vs. 0.376) nor the superior SBS/aER ratio (0.452 vs. 0.424) showed a significant difference between the two groups (P= .749 and P= .068, respectively). If the inferior SBS was torn, a high frequency of pseudoparalysis was noted (81.0%, P= .010). The disruption of transverse force couple was noted in both irreparable mRCT groups, although no significant difference was found between the nonpseudoparalysis and pseudoparalysis groups. ISP and inferior SBS muscle volumes showed a significant decrease in pseudoparalysis group and, therefore, were considered to greatly influence the loss of active motion in mRCT. The TM did not exert significant effect on the incidence of pseudoparalysis. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

The effectiveness of occlusal splints for sleep bruxism.

PubMed

Jagger, Robert

2008-01-01

Searches were made using the Cochrane Oral Health Group's Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, LILACS (Latin American & Caribbean Health Sciences Literature), Biblioteca Brasileira de Odontologia, and Dissertations, Theses and Abstracts. Hand searches were made of abstracts of particular importance to this review. Additional reports were identified from the reference lists of retrieved reports and from article reviews about treating sleep bruxism. There were no language restrictions. Randomised controlled trials (RCT) or quasi-RCT were chosen that compared splint therapy concurrently with no treatment, other occlusal appliances, or any other intervention in participants who had sleep bruxism. Data extraction was carried out independently and in duplicate. Validity assessment of the included trials was carried out at the same time as data extraction. Discrepancies were discussed and a third review author consulted. The author of the primary study was contacted when necessary. Thirty-two potentially relevant RCT were identified of which five were eventually included. In these, use of an occlusal splint was compared with palatal splint, mandibular advancement device, transcutaneous electric nerve stimulation, and no treatment. There was just one common outcome (arousal index) which was combined in a meta-analysis. No statistically significant difference between the occlusal splint and control groups were found in meta-analysis. There is not enough evidence to state that the occlusal splint is effective for treating sleep bruxism. Indication of its use is questionable with regard to sleep outcomes, but there may be some benefit with regard to tooth wear. This systematic review suggests the need for further investigation in more controlled RCT that pay attention to method of allocation, outcome assessment, large sample size, and sufficient duration of followup. The study design must be parallel in order to eliminate the bias provided by studies of crossover type. A standardisation of the outcomes of the treatment of sleep bruxism should be established in the RCT.

Right-sided rhabdoid colorectal tumors might be related to the Serrated Pathway

PubMed Central

2013-01-01

Background Rhabdoid colorectal tumor (RCT) is a rare, highly aggressive neoplasm recurrent in elderly patients, commonly at the caecum. The molecular mechanisms underlying RCT pathogenesis remain poorly elucidated. The differential diagnosis is with the malignant rhabdoid tumors of infancy characterized by genetic inactivation of SMARCB1 (INI1) or deletions of chromosome 22q12 locus. Materials and methods To shed light on RCT pathogenesis, we investigated genetic and epigenetic alterations in two cases of pure and composite RCT and compared them with the profiles of matched adenomas and normal mucosa. Immunohistochemical analysis, FISH, methylation specific PCR and DNA sequencing analysis were performed on paraffin-embedded tissues. Results Loss of epithelial markers, (CK20, CDX2 and E-cadherin) and intense vimentin expression was observed in RCTs but neither in the normal mucosa or adenomas. INI1 expression was detected in normal mucosa, adenomas and retained in pure RCT, while it was undetected in composite RCT. Rearrangement of the 22q12 locus was found only in pure RCT. The APC/β-catenin pathway was not altered, while MLH1 immunostaining was negative in RCTs and positive in adenomas and normal mucosa. These expression profiles were associated with V600E BRAF mutation, a progressive accumulation of promoter methylation at specific CIMP loci and additional genes from the normal mucosa to tubular adenoma and RCT. Conclusions Right-sided RCT could be characterized by epigenetic events and molecular features likely similar to those occurring in the serrated pathway and associated with epithelial-mesenchymal transition. These extremely rare tumors may benefit from the use of new biological molecules specific for colorectal carcinoma. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1641385210804556 PMID:23425390

Dropout from exercise randomized controlled trials among people with depression: A meta-analysis and meta regression.

PubMed

Stubbs, Brendon; Vancampfort, Davy; Rosenbaum, Simon; Ward, Philip B; Richards, Justin; Soundy, Andrew; Veronese, Nicola; Solmi, Marco; Schuch, Felipe B

2016-01-15

Exercise has established efficacy in improving depressive symptoms. Dropouts from randomized controlled trials (RCT's) pose a threat to the validity of this evidence base, with dropout rates varying across studies. We conducted a systematic review and meta-analysis to investigate the prevalence and predictors of dropout rates among adults with depression participating in exercise RCT's. Three authors identified RCT's from a recent Cochrane review and conducted updated searches of major electronic databases from 01/2013 to 08/2015. We included RCT's of exercise interventions in people with depression (including major depressive disorder (MDD) and depressive symptoms) that reported dropout rates. A random effects meta-analysis and meta regression were conducted. Overall, 40 RCT's were included reporting dropout rates across 52 exercise interventions including 1720 people with depression (49.1 years (range=19-76 years), 72% female (range=0-100)). The trim and fill adjusted prevalence of dropout across all studies was 18.1% (95%CI=15.0-21.8%) and 17.2% (95%CI=13.5-21.7, N=31) in MDD only. In MDD participants, higher baseline depressive symptoms (β=0.0409, 95%CI=0.0809-0.0009, P=0.04) predicted greater dropout, whilst supervised interventions delivered by physiotherapists (β=-1.2029, 95%CI=-2.0967 to -0.3091, p=0.008) and exercise physiologists (β=-1.3396, 95%CI=-2.4478 to -0.2313, p=0.01) predicted lower dropout. A comparative meta-analysis (N=29) established dropout was lower in exercise than control conditions (OR=0.642, 95%CI=0.43-0.95, p=0.02). Exercise is well tolerated by people with depression and drop out in RCT's is lower than control conditions. Thus, exercise is a feasible treatment, in particular when delivered by healthcare professionals with specific training in exercise prescription. Copyright © 2015 Elsevier B.V. All rights reserved.

Is Escitalopram Really Relevantly Superior to Citalopram in Treatment of Major Depressive Disorder? A Meta-analysis of Head-to-head Randomized Trials

PubMed Central

Trkulja, Vladimir

2010-01-01

Aim To evaluate clinical relevance of differences between escitalopram and citalopram (equimolar) for major depressive disorder. Methods Review and meta-analysis of comparative randomized controlled trials (RCT). Comparisons were in relation to Montgomery-Asberg depression rating scale (MADRS) score reduction at weeks 1 (5 RCTs), 4 (5 RCTs), 6 (4 RCTs), 8 (5 RCTs), and 24 (1 RCT); proportion of responders at weeks 2, 4, 6 (2 RCTs for each time point), 8 (5 RCTs), and 24 (1 RCT); clinical global impression-severity (CGI-S) reduction at weeks 6 (1 RCT), 8 (5 RCTs), and 24 (1 RCT), and discontinuation due to adverse events or inefficacy during short-term (up to 8 weeks) and medium-term (24 weeks) treatment. Results MADRS reduction was greater with escitalopram, but 95% confidence intervals (CI) around the mean difference were entirely or largely below 2 scale points (minimally important difference) and CI around the effect size (ES) was below 0.32 (“small”) at all time points. Risk of response was higher with escitalopram at week 8 (relative risk, 1.14; 95% CI, 1.04 to 1.26) but number needed to treat was 14 (95% CI, 7 to 111). All 95% CIs around the mean difference and ES of CGI-S reduction at week 8 were below 0.32 points and the limit of “small,” respectively. Data for severe patients (MADRS≥30) are scarce (only 1 RCT), indicating somewhat greater efficacy (response rate and MADRS reduction at week 8, but not CGI-S reduction) of escitalopram, but without compelling evidence of clinically relevant differences. Discontinuations due to adverse events or inefficacy up to 8 weeks of treatment were comparable. Data for the period up to 24 weeks are scarce and inconclusive. Conclusion Presently, the claims about clinically relevant superiority of escitalopram over citalopram in short-to-medium term treatment of major depressive disorder are not supported by evidence. PMID:20162747

Is escitalopram really relevantly superior to citalopram in treatment of major depressive disorder? A meta-analysis of head-to-head randomized trials.

PubMed

Trkulja, Vladimir

2010-02-01

To evaluate clinical relevance of differences between escitalopram and citalopram (equimolar) for major depressive disorder. Review and meta-analysis of comparative randomized controlled trials (RCT). Comparisons were in relation to Montgomery-Asberg depression rating scale (MADRS) score reduction at weeks 1 (5 RCTs), 4 (5 RCTs), 6 (4 RCTs), 8 (5 RCTs), and 24 (1 RCT); proportion of responders at weeks 2, 4, 6 (2 RCTs for each time point), 8 (5 RCTs), and 24 (1 RCT); clinical global impression-severity (CGI-S) reduction at weeks 6 (1 RCT), 8 (5 RCTs), and 24 (1 RCT), and discontinuation due to adverse events or inefficacy during short-term (up to 8 weeks) and medium-term (24 weeks) treatment. MADRS reduction was greater with escitalopram, but 95% confidence intervals (CI) around the mean difference were entirely or largely below 2 scale points (minimally important difference) and CI around the effect size (ES) was below 0.32 ("small") at all time points. Risk of response was higher with escitalopram at week 8 (relative risk, 1.14; 95% CI, 1.04 to 1.26) but number needed to treat was 14 (95% CI, 7 to 111). All 95% CIs around the mean difference and ES of CGI-S reduction at week 8 were below 0.32 points and the limit of "small," respectively. Data for severe patients (MADRS> or =30) are scarce (only 1 RCT), indicating somewhat greater efficacy (response rate and MADRS reduction at week 8, but not CGI-S reduction) of escitalopram, but without compelling evidence of clinically relevant differences. Discontinuations due to adverse events or inefficacy up to 8 weeks of treatment were comparable. Data for the period up to 24 weeks are scarce and inconclusive. Presently, the claims about clinically relevant superiority of escitalopram over citalopram in short-to-medium term treatment of major depressive disorder are not supported by evidence.

Critical appraisal of arguments for the delayed-start design proposed as alternative to the parallel-group randomized clinical trial design in the field of rare disease.

PubMed

Spineli, Loukia M; Jenz, Eva; Großhennig, Anika; Koch, Armin

2017-08-17

A number of papers have proposed or evaluated the delayed-start design as an alternative to the standard two-arm parallel group randomized clinical trial (RCT) design in the field of rare disease. However the discussion is felt to lack a sufficient degree of consideration devoted to the true virtues of the delayed start design and the implications either in terms of required sample-size, overall information, or interpretation of the estimate in the context of small populations. To evaluate whether there are real advantages of the delayed-start design particularly in terms of overall efficacy and sample size requirements as a proposed alternative to the standard parallel group RCT in the field of rare disease. We used a real-life example to compare the delayed-start design with the standard RCT in terms of sample size requirements. Then, based on three scenarios regarding the development of the treatment effect over time, the advantages, limitations and potential costs of the delayed-start design are discussed. We clarify that delayed-start design is not suitable for drugs that establish an immediate treatment effect, but for drugs with effects developing over time, instead. In addition, the sample size will always increase as an implication for a reduced time on placebo resulting in a decreased treatment effect. A number of papers have repeated well-known arguments to justify the delayed-start design as appropriate alternative to the standard parallel group RCT in the field of rare disease and do not discuss the specific needs of research methodology in this field. The main point is that a limited time on placebo will result in an underestimated treatment effect and, in consequence, in larger sample size requirements compared to those expected under a standard parallel-group design. This also impacts on benefit-risk assessment.

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

PubMed

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

2011-04-11

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

Secular trends and smoke-free policy development in rural Kentucky

PubMed Central

Fallin, Amanda; Parker, Lindsay; Lindgreen, Janine; Riker, Carol; Kercsmar, Sarah; Hahn, Ellen J.

2011-01-01

Secondhand smoke (SHS) exposure causes cardiovascular disease, lung cancer and pulmonary disorders. Smoke-free policies are the most effective way to prevent exposure to SHS. A 5-year community-based randomized control trial (RCT) is in progress to assess factors associated with smoke-free policy development in rural communities. Considering secular trends is critical when conducting community-based RCTs as they may threaten the internal validity of the study. For the purposes of this paper, secular trends are defined as patterns or recurring events that are not directly related to smoke-free policy but have the potential to influence policy development. There are no established protocols to monitor secular trends in the study of smoke-free policy in rural communities. The purpose of this paper is to (i) describe the development of a protocol to identify and monitor secular trends that may threaten the internal validity of a community-based RCT to promote smoke-free policy development and (ii) describe secular trends identified in the first 2 years of the RCT. The sample includes 854 secular events captured from media outlets covering the 40 study counties over the first 2 years of the RCT. Of these 854 events, there were 281 secular events in Year 1 and 573 in Year 2. This paper focuses on five specific categories: ‘tobacco use and cessation activities’, ‘farming’, ‘economics’, ‘city/county infrastructure’ and ‘wellness’. This protocol is a feasible yet time-intensive method of identifying events that may threaten the internal validity of a community-based RCT. PMID:21558440

Reports of unintended consequences of financial incentives to improve management of hypertension.

PubMed

Hysong, Sylvia J; SoRelle, Richard; Broussard Smitham, Kristen; Petersen, Laura A

2017-01-01

Given the increase in financial-incentive programs nationwide, many physicians and physician groups are concerned about potential unintended consequences of providing financial incentives to improve quality of care. However, few studies examine whether actual unintended consequences result from providing financial incentives to physicians. We sought to document the extent to which the unintended consequences discussed in the literature were observable in a randomized clinical trial (RCT) of financial incentives. We conducted a qualitative observational study nested within a larger RCT of financial incentives to improve hypertension care. We conducted 30-minute telephone interviews with primary care personnel at facilities participating in the RCT housed at12 geographically dispersed Veterans Affairs Medical Centers nationwide. Participants answered questions about unintended effects, clinic team dynamics, organizational impact on care delivery, study participation. We employed a blend of inductive and deductive qualitative techniques for analysis. Sixty-five participants were recruited from RCT enrollees and personnel not enrolled in the larger RCT, plus one primary care leader per site. Emergent themes included possible patient harm, emphasis on documentation over improving care, reduced professional morale, and positive spillover. All discussions of unintended consequences involving patient harm were only concerns, not actual events. Several unintended consequences concerned ancillary initiatives for quality improvement (e.g., practice guidelines and performance measurement systems) rather than financial incentives. Many unintended consequences of financial incentives noted were either only concerns or attributable to ancillary quality-improvement initiatives. Actual unintended consequences included improved documentation of care without necessarily improving actual care, and positive unintended consequences. Clinicaltrials.gov Identifier: NCT00302718.

Health Facility Staff Training for Improving Breastfeeding Outcome: A Systematic Review for Step 2 of the Baby-Friendly Hospital Initiative.

PubMed

Balogun, Olukunmi O; Dagvadorj, Amarjargal; Yourkavitch, Jennifer; da Silva Lopes, Katharina; Suto, Maiko; Takemoto, Yo; Mori, Rintaro; Rayco-Solon, Pura; Ota, Erika

2017-11-01

The Baby-Friendly Hospital Initiative (BFHI) implemented through the "Ten Steps to Successful Breastfeeding" has been widely promoted as an intervention that improves breastfeeding rates. Step 2 requires the training of all healthcare staff in skills that are necessary to implement the policy. This systematic review provides evidence about the effect of training healthcare staff in hospitals and birth centers on breastfeeding outcomes. Randomized controlled trials (RCT), quasi-RCT, and controlled before and after (CBA) studies comparing training of healthcare staff on breastfeeding and supportive feeding practices with no training were included in this review. We searched CENTRAL PubMed, EMBASE, CINAHL, Web of Science, and the British Nursing Index for studies. Studies were screened against predetermined criteria, and risk of bias of included studies was assessed using the Risk of Bias Assessment tool for Non-Randomized Studies for non-RCT studies and the Cochrane Handbook for Systematic Reviews of Interventions for RCT studies. Of the six studies included in this review, three were RCT whereas three were CBA studies. The studies were conducted in 5 countries and involved 390 healthcare staff. Provision of educational interventions aimed at increasing knowledge and practice of BFHI and support was found to improve health worker's knowledge, attitude, and compliance with the BFHI practices. In one study, the rate of exclusive breastfeeding increased at the intervention site but no differences were found for breastfeeding initiation rates. All included studies had methodological limitations, and study designs and methodologies lacked comparability.

Study protocol on comparative effectiveness of mindfulness meditation and qigong on psychophysiological outcomes for patients with colorectal cancer: a randomized controlled trial.

PubMed

Ho, Rainbow T H; Wan, Adrian H Y; Chan, Jessie S M; Ng, S M; Chung, K F; Chan, Cecilia L W

2017-08-08

Colorectal cancer imposes threats to patients' well-being. Although most physical symptoms can be managed by medication, psychosocial stressors may complicate survival and hamper quality of life. Mindfulness and Qigong, two kinds of mind-body exercise rooted in Eastern health philosophy, has been found effective in symptoms management, improving mental health, and reducing stress. With these potential benefits, a randomized controlled trial (RCT) is planned to investigate the comparative effectiveness of mindfulness and Baduanjin intervention on the bio-psychosocial wellbeing of people with colorectal cancer. A 3-arm RCT with waitlist control design will be used in this study. One hundred eighty-nine participants will be randomized into (i) Mindfulness, (ii) Baduanjin, or (iii) waitlist control groups. Participants in both the Baduanjin and mindfulness groups will receive 8-weeks of specific intervention. All three groups will undergo four assessment phases: (i) at baseline, (ii) at 4-week, (iii) at 8-week (post-intervention), and 6-month post-intervention (maintenance). All participants will be assessed in terms of cancer-related symptoms and symptom distress, mental health status, quality of life, stress level based on physiological marker. Based on prior research studies, participants in both the mindfulness and Baduanjn intervention group are expected to have better symptoms management, lower stress level, better mental health, and higher level of quality of life than the control group. This study contributes to better understanding on the common and unique effectiveness of mindfulness and Baduanjin qigong, as such patients and qualified healthcare professionals can select or provide practices which will produce maximum benefits, satisfaction, adherence, and sustainability. The trial has been registered in the Clinical Trials Centre of the University of Hong Kong ( HKCTR-2198 ) on 08 March 2017.

The interrelationship between sleep and depression: a secondary analysis of a randomized controlled trial on mind-body-spirit intervention.

PubMed

Ji, Xiao Wen; Chan, Celia H Y; Lau, Bobo H P; Chan, Jessie S M; Chan, Cecilia L W; Chung, Ka-Fai

2017-01-01

To conduct a secondary analysis of a randomized controlled trial (RCT) that aims to understand the mediating effects embedded in a mind-body-spirit intervention for sleep and mood disturbances. 126 adults with mild to moderate depression and subjective sleep disturbance, defined as Center for Epidemiologic Studies Depression Scale (CESD) scores from 10 to 34 and Pittsburgh Sleep Quality Index (PSQI) score > 5, participated in a waitlist-controlled RCT of an integrative mind-body-spirit intervention (I-BMS). Holistic well-being scale (HWS), a measure of the state of affliction and equanimity in mind, body and spirit, was included as a possible mediator. Data was collected at baseline and three-month follow-up. Mediation analyses were adopted to examine the pathways leading to sleep and mood improvements. After adjustments of baseline severities, changes in depressive symptoms partially mediated the effect of I-BMS on nighttime symptoms of insomnia (95% CI: 0.12-0.96), while exerting a full mediating effect on daytime symptoms of insomnia (95% CI: 0.14-0.64). The effect of I-BMS on mood was mediated by daytime symptoms of insomnia and spiritual orientation, but not by nighttime symptoms of insomnia (95% CI: 0.93-4.62). A bidirectional relationship was found between sleep disturbances and depressive symptoms following a mind-body-spirit intervention. The relationship between daytime symptoms and depressive symptoms was especially strong. Of the HWS variables, spiritual orientation was the only significant mediator of mood improvement following I-BMS. Our findings suggest that efforts to optimize the treatment of comorbid sleep disturbances and depression are needed, especially the treatment of daytime impairments along with sleep and mood disruptions. Copyright © 2016 Elsevier B.V. All rights reserved.

Cognitive rehabilitation and mindfulness in multiple sclerosis (REMIND-MS): a study protocol for a randomised controlled trial.

PubMed

Nauta, Ilse M; Speckens, Anne E M; Kessels, Roy P C; Geurts, Jeroen J G; de Groot, Vincent; Uitdehaag, Bernard M J; Fasotti, Luciano; de Jong, Brigit A

2017-11-21

Cognitive problems frequently occur in patients with multiple sclerosis (MS) and profoundly affect their quality of life. So far, the best cognitive treatment options for MS patients are a matter of debate. Therefore, this study aims to investigate the effectiveness of two promising non-pharmacological treatments: cognitive rehabilitation therapy (CRT) and mindfulness-based cognitive therapy (MBCT). Furthermore, this study aims to gain additional knowledge about the aetiology of cognitive problems among MS patients, since this may help to develop and guide effective cognitive treatments. In a dual-centre, single-blind randomised controlled trial (RCT), 120 MS patients will be randomised into one of three parallel groups: CRT, MBCT or enhanced treatment as usual (ETAU). Both CRT and MBCT consist of a structured 9-week program. ETAU consists of one appointment with an MS specialist nurse. Measurements will be performed at baseline, post-intervention and 6 months after the interventions. The primary outcome measure is the level of subjective cognitive complaints. Secondary outcome measures are objective cognitive function, functional brain network measures (using magnetoencephalography), psychological symptoms, well-being, quality of life and daily life functioning. To our knowledge, this will be the first RCT that investigates the effect of MBCT on cognitive function among MS patients. In addition, studying the effect of CRT on cognitive function may provide direction to the contradictory evidence that is currently available. This study will also provide information on changes in functional brain networks in relation to cognitive function. To conclude, this study may help to understand and treat cognitive problems among MS patients. This trial was prospectively registered at the Dutch Trial Registration (number NTR6459 , registered on 31 May 2017).

Can Comprehensive Chromosome Screening Technology Improve IVF/ICSI Outcomes? A Meta-Analysis

PubMed Central

Quan, Song

2015-01-01

Objective To examine whether comprehensive chromosome screening (CCS) for preimplantation genetic screening (PGS) has an effect on improving in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes compared to traditional morphological methods. Methods A literature search was conducted in PubMed, EMBASE, CNKI and ClinicalTrials.gov up to May 2015. Two reviewers independently evaluated titles and abstracts, extracted data and assessed quality. We included studies that compared the IVF/ICSI outcomes of CCS-based embryo selection with those of the traditional morphological method. Relative risk (RR) values with corresponding 95% confidence intervals (CIs) were calculated in RevMan 5.3, and subgroup analysis and Begg’s test were used to assess heterogeneity and potential publication bias, respectively. Results Four RCTs and seven cohort studies were included. A meta-analysis of the outcomes showed that compared to morphological criteria, euploid embryos identified by CCS were more likely to be successfully implanted (RCT RR 1.32, 95% CI 1.18–1.47; cohort study RR 1.74, 95% CI 1.35–2.24). CCS-based PGS was also related to an increased clinical pregnancy rate (RCT RR 1.26, 95% CI 0.83–1.93; cohort study RR 1.48, 95% CI 1.20–1.83), an increased ongoing pregnancy rate (RCT RR 1.31, 95% CI 0.64–2.66; cohort study RR 1.61, 95% CI 1.30–2.00), and an increased live birth rate (RCT RR 1.26, 95% CI 1.05–1.50; cohort study RR 1.35, 95% CI 0.85–2.13) as well as a decreased miscarriage rate (RCT RR 0.53, 95% CI 0.24–1.15; cohort study RR 0.31, 95% CI 0.21–0.46) and a decreased multiple pregnancy rate (RCT RR 0.02, 95% CI 0.00–0.26; cohort study RR 0.19, 95% CI 0.07–0.51). The results of the subgroup analysis also showed a significantly increased implantation rate in the CCS group. Conclusions The effectiveness of CCS-based PGS is comparable to that of traditional morphological methods, with better outcomes for women receiving IVF/ICSI technology. The transfer of both trophectoderm-biopsied and blastomere-biopsied CCS-euploid embryos can improve the implantation rate. PMID:26470028

Technical Note: MRI only prostate radiotherapy planning using the statistical decomposition algorithm

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

Siversson, Carl, E-mail: carl.siversson@med.lu.se; Nordström, Fredrik; Department of Radiation Physics, Skåne University Hospital, Lund 214 28

2015-10-15

Purpose: In order to enable a magnetic resonance imaging (MRI) only workflow in radiotherapy treatment planning, methods are required for generating Hounsfield unit (HU) maps (i.e., synthetic computed tomography, sCT) for dose calculations, directly from MRI. The Statistical Decomposition Algorithm (SDA) is a method for automatically generating sCT images from a single MR image volume, based on automatic tissue classification in combination with a model trained using a multimodal template material. This study compares dose calculations between sCT generated by the SDA and conventional CT in the male pelvic region. Methods: The study comprised ten prostate cancer patients, for whommore » a 3D T2 weighted MRI and a conventional planning CT were acquired. For each patient, sCT images were generated from the acquired MRI using the SDA. In order to decouple the effect of variations in patient geometry between imaging modalities from the effect of uncertainties in the SDA, the conventional CT was nonrigidly registered to the MRI to assure that their geometries were well aligned. For each patient, a volumetric modulated arc therapy plan was created for the registered CT (rCT) and recalculated for both the sCT and the conventional CT. The results were evaluated using several methods, including mean average error (MAE), a set of dose-volume histogram parameters, and a restrictive gamma criterion (2% local dose/1 mm). Results: The MAE within the body contour was 36.5 ± 4.1 (1 s.d.) HU between sCT and rCT. Average mean absorbed dose difference to target was 0.0% ± 0.2% (1 s.d.) between sCT and rCT, whereas it was −0.3% ± 0.3% (1 s.d.) between CT and rCT. The average gamma pass rate was 99.9% for sCT vs rCT, whereas it was 90.3% for CT vs rCT. Conclusions: The SDA enables a highly accurate MRI only workflow in prostate radiotherapy planning. The dosimetric uncertainties originating from the SDA appear negligible and are notably lower than the uncertainties introduced by variations in patient geometry between imaging sessions.« less

Aripiprazole (intramuscular) for psychosis-induced aggression or agitation (rapid tranquillisation).

PubMed

Ostinelli, Edoardo G; Jajawi, Salwan; Spyridi, Styliani; Sayal, Kamlaj; Jayaram, Mahesh B

2018-01-08

People experiencing psychosis may become aggressive. Antipsychotics, such as aripiprazole in intramuscular form, can be used in such situations. To evaluate the effects of intramuscular aripiprazole in the treatment of psychosis-induced aggression or agitation (rapid tranquillisation). On 11 December 2014 and 11 April 2017, we searched the Cochrane Schizophrenia Group's Study-based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. All randomised controlled trials (RCTs) that randomised people with psychosis-induced aggression or agitation to receive either intramuscular aripiprazole or another intramuscular intervention. We independently inspected citations and, where possible, abstracts, ordered papers and re-inspected and quality assessed these. We included studies that met our selection criteria. At least two review authors independently extracted data from the included studies. We chose a fixed-effect model. We analysed dichotomous data using risk ratio (RR) and the 95% confidence intervals (CI). We analysed continuous data using mean differences (MD) and their CIs. We assessed risk of bias for included studies and used GRADE to create 'Summary of findings' tables. Searching found 63 records referring to 21 possible trials. We could only include three studies, all completed over the last decade, with 885 participants, of which 707 were included for quantitative analyses in this systematic review. Due to limited comparisons, small size of trials and a paucity of investigated and reported 'pragmatic' outcomes, evidence was mostly graded as low or very low quality. No trials reported useful data for one of our primary outcomes of tranquil or asleep by 30 minutes. Economic outcomes were also not reported in the trials.When compared with placebo, fewer people in the aripiprazole group needed additional injections compared to the placebo group (2 RCTs, n = 382, RR 0.69, 95% CI 0.56 to 0.85, very low-quality evidence). Clinically important improvement in agitation at two hours favoured the aripiprazole group (2 RCTs, n = 382, RR 1.50, 95% CI 1.17 to 1.92, very low-quality evidence). The numbers of non-responders after the first injection also favoured aripiprazole (1 RCT, n = 263, RR 0.49, 95% CI 0.34 to 0.71, low-quality evidence). Although no effect was found, more people in the aripiprazole compared to the placebo group experienced adverse effects (1 RCT, n = 117, RR 1.51, 95% CI 0.93 to 2.46, very low-quality evidence).Aripiprazole required more injections compared to haloperidol (2 RCTs, n = 477, RR 1.28, 95% CI 1.00 to 1.63, very low-quality evidence), with no significant difference in agitation (2 RCTs, n = 477, RR 0.94, 95% CI 0.80 to 1.11, very low-quality evidence), and similar non-responders after first injection (1 RCT, n = 360, RR 1.18, 95% CI 0.78 to 1.79, low-quality evidence). Aripiprazole and haloperidol did not differ when taking into account the overall number of people that experienced at least one adverse effect (1 RCT, n = 113, RR 0.91, 95% CI 0.61 to 1.35, very low-quality evidence).Compared to aripiprazole, olanzapine was better at reducing agitation (1 RCT, n = 80, RR 0.77, 95% CI 0.60 to 0.99, low-quality evidence) and had a more favourable effect on global state change scores (1 RCT, n = 80, MD 0.58, 95% CI 0.01 to 1.15, low-quality evidence), both at two hours. No differences were found in terms of experiencing at least one adverse effect during the 24 hours after treatment (1 RCT, n = 80, RR 0.75, 95% CI 0.45 to 1.24, very low-quality evidence). However, participants allocated to aripiprazole experienced less somnolence (1 RCT, n = 80, RR 0.25, 95% CI 0.08 to 0.82, low-quality evidence). The available evidence is of poor quality but there is some evidence aripiprazole is effective compared to placebo and haloperidol, but not when compared to olanzapine. However, considering that evidence comes from only three studies, caution is required in generalising these results to real-world practice. This review firmly highlights the need for more high-quality trials on intramuscular aripiprazole in the management of people with acute aggression or agitation.

Psychosocial interventions for people with both severe mental illness and substance misuse.

PubMed

Hunt, Glenn E; Siegfried, Nandi; Morley, Kirsten; Sitharthan, Thiagarajan; Cleary, Michelle

2013-10-03

Even low levels of substance misuse by people with a severe mental illness can have detrimental effects. To assess the effects of psychosocial interventions for reduction in substance use in people with a serious mental illness compared with standard care. For this update (2013), the Trials Search Co-ordinator of the Cochrane Schizophrenia Group (CSG) searched the CSG Trials Register (July 2012), which is based on regular searches of major medical and scientific databases. The principal authors conducted two further searches (8 October 2012 and 15 January 2013) of the Cochrane Database of Systematic Reviews, MEDLINE and PsycINFO. A separate search for trials of contingency management was completed as this was an additional intervention category for this update. We included all randomised controlled trials (RCTs) comparing psychosocial interventions for substance misuse with standard care in people with serious mental illness. We independently selected studies, extracted data and appraised study quality. For binary outcomes, we calculated standard estimates of relative risk (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis. For continuous outcomes, we calculated the mean difference (MD) between groups. For all meta-analyses we pooled data using a random-effects model. Using the GRADE approach, we identified seven patient-centred outcomes and assessed the quality of evidence for these within each comparison. We included 32 trials with a total of 3165 participants. Evaluation of long-term integrated care included four RCTs (n = 735). We found no significant differences on loss to treatment (n = 603, 3 RCTs, RR 1.09 CI 0.82 to 1.45, low quality of evidence), death by 3 years (n = 421, 2 RCTs, RR 1.18 CI 0.39 to 3.57, low quality of evidence), alcohol use (not in remission at 36 months) (n = 143, 1 RCT, RR 1.15 CI 0.84 to 1.56,low quality of evidence), substance use (n = 85, 1 RCT, RR 0.89 CI 0.63 to 1.25, low quality of evidence), global assessment of functioning (n = 171, 1 RCT, MD 0.7 CI 2.07 to 3.47, low quality of evidence), or general life satisfaction (n = 372, 2 RCTs, MD 0.02 higher CI 0.28 to 0.32, moderate quality of evidence).For evaluation of non-integrated intensive case management with usual treatment (4 RCTs, n = 163) we found no statistically significant difference for loss to treatment at 12 months (n = 134, 3 RCTs, RR 1.21 CI 0.73 to 1.99, very low quality of evidence).Motivational interviewing plus cognitive behavioural therapy compared to usual treatment (7 RCTs, total n = 878) did not reveal any advantage for retaining participants at 12 months (n = 327, 1 RCT, RR 0.99 CI 0.62 to 1.59, low quality of evidence) or for death (n = 493, 3 RCTs, RR 0.72 CI 0.22 to 2.41, low quality of evidence), and no benefit for reducing substance use (n = 119, 1 RCT, MD 0.19 CI -0.22 to 0.6, low quality of evidence), relapse (n = 36, 1 RCT, RR 0.5 CI 0.24 to 1.04, very low quality of evidence) or global functioning (n = 445, 4 RCTs, MD 1.24 CI 1.86 to 4.34, very low quality of evidence).Cognitive behavioural therapy alone compared with usual treatment (2 RCTs, n = 152) showed no significant difference for losses from treatment at 3 months (n = 152, 2 RCTs, RR 1.12 CI 0.44 to 2.86, low quality of evidence). No benefits were observed on measures of lessening cannabis use at 6 months (n = 47, 1 RCT, RR 1.30 CI 0.79 to 2.15, very low quality of evidence) or mental state (n = 105, 1 RCT, Brief Psychiatric Rating Scale MD 0.52 CI -0.78 to 1.82, low quality of evidence).We found no advantage for motivational interviewing alone compared with usual treatment (8 RCTs, n = 509) in reducing losses to treatment at 6 months (n = 62, 1 RCT, RR 1.71 CI 0.63 to 4.64, very low quality of evidence), although significantly more participants in the motivational interviewing group reported for their first aftercare appointment (n = 93, 1 RCT, RR 0.69 CI 0.53 to 0.9). Some differences, favouring treatment, were observed in abstaining from alcohol (n = 28, 1 RCT, RR 0.36 CI 0.17 to 0.75, very low quality of evidence) but not other substances (n = 89, 1 RCT, RR -0.07 CI -0.56 to 0.42, very low quality of evidence), and no differences were observed in mental state (n = 30, 1 RCT, MD 0.19 CI -0.59 to 0.21, very low quality of evidence).We found no significant differences for skills training in the numbers lost to treatment by 12 months (n = 94, 2 RCTs, RR 0.70 CI 0.44 to 1.1, very low quality of evidence).We found no differences for contingency management compared with usual treatment (2 RCTs, n = 206) in numbers lost to treatment at 3 months (n = 176, 1 RCT, RR 1.65 CI 1.18 to 2.31, low quality of evidence), number of stimulant positive urine tests at 6 months (n = 176, 1 RCT, RR 0.83 CI 0.65 to 1.06, low quality of evidence) or hospitalisations (n = 176, 1 RCT, RR 0.21 CI 0.05 to 0.93, low quality of evidence).We were unable to summarise all findings due to skewed data or because trials did not measure the outcome of interest. In general, evidence was rated as low or very low due to high or unclear risks of bias because of poor trial methods, or poorly reported methods, and imprecision due to small sample sizes, low event rates and wide confidence intervals. We included 32 RCTs and found no compelling evidence to support any one psychosocial treatment over another for people to remain in treatment or to reduce substance use or improve mental state in people with serious mental illnesses. Furthermore, methodological difficulties exist which hinder pooling and interpreting results. Further high quality trials are required which address these concerns and improve the evidence in this important area.

The ethics of public policy RCTs: The principle of policy equipoise.

PubMed

MacKay, Douglas

2018-01-01

In this article, I ask whether a principle analogous to the principle of clinical equipoise should govern the design and conduct of RCTs evaluating the effectiveness of policy interventions. I answer this question affirmatively, and introduce and defend the principle of policy equipoise. According to this principle, all arms of a policy RCT must be, at minimum, in a state of equipoise with the best proven policy that is also morally and practically attainable and sustainable. For all arms of a policy RCT, policy experts must either (1) reasonably disagree about whether the trial arms are more effective than this policy, or (2) know that they are. © 2017 John Wiley & Sons Ltd.

Rubber dam use during root canal treatment: findings from The Dental Practice-Based Research Network

PubMed Central

Anabtawi, Mona F.; Gilbert, Gregg H.; Bauer, Michael R.; Reams, Gregg; Makhija, Sonia K.; Benjamin, Paul L.; Williams, O. Dale

2012-01-01

Background The Dental Practice-Based Research Network (DPBRN) provides a venue to investigate whether certain procedures are performed routinely. Study objectives were to: (1) quantify rubber dam use during root canal treatment (RCT) among general dentists; (2) test the hypothesis that certain dentist or practice characteristics are associated with its use. Methods DPBRN practitioner-investigators participated in a questionnaire that included items about rubber dam use and other forms of isolation during root RCT. DPBRN Enrollment Questionnaire data provided certain practitioner and practice characteristics. Results A total of 729 practitioners responded (74%); 524 were general dentists and indicated they do RCT and the percentage of RCT in which they use a rubber dam. Of these 524, 44% use rubber dam for all RCTs; 24% use it for 51%–99% of RCTs; 17% use it for 1%–50%; 15% never use it during RCT. Usage varied significantly by geographic region and practice type. Cotton rolls and other forms of isolation were also reported. Conclusions Similar to other reports in the literature, not all DPBRN general dentists use a rubber dam during RCT. Clinical implications Because the current clinical standard of care is to use a rubber dam during RCT, increasing its use may be important. PMID:23372134

Targeting the Replication Initiator of the Second Vibrio Chromosome: Towards Generation of Vibrionaceae-Specific Antimicrobial Agents

PubMed Central

Yamaichi, Yoshiharu; Duigou, Stéphane; Shakhnovich, Elizabeth A.; Waldor, Matthew K.

2009-01-01

The Vibrionaceae is comprised of numerous aquatic species and includes several human pathogens, such as Vibrio cholerae, the cause of cholera. All organisms in this family have two chromosomes, and replication of the smaller one depends on rctB, a gene that is restricted to the Vibrionaceae. Given the increasing prevalence of multi-drug resistance in pathogenic vibrios, there is a need for new targets and drugs to combat these pathogens. Here, we carried out a high throughput cell-based screen to find small molecule inhibitors of RctB. We identified a compound that blocked growth of an E. coli strain bearing an rctB-dependent plasmid but did not influence growth of E. coli lacking this plasmid. This compound, designated vibrepin, had potent cidal activity against V. cholerae and inhibited the growth of all vibrio species tested. Vibrepin blocked RctB oriCII unwinding, apparently by promoting formation of large non-functional RctB complexes. Although vibrepin also appears to have targets other than RctB, our findings suggest that RctB is an attractive target for generation of novel antibiotics that only block growth of vibrios. Vibrio-specific agents, unlike antibiotics currently used in clinical practice, will not engender resistance in the normal human flora or in non-vibrio environmental microorganisms. PMID:19936046

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.

Do brief alcohol motivational interventions work like we think they do?

PubMed

Bertholet, Nicolas; Palfai, Tibor; Gaume, Jacques; Daeppen, Jean-Bernard; Saitz, Richard

2014-03-01

Questions remain about how brief motivational interventions (BMIs) for unhealthy alcohol use work, and addressing these questions may be important for improving their efficacy. Therefore, we assessed the effects of various characteristics of BMIs on drinking outcomes across 3 randomized controlled trials (RCTs). Audio recordings of 314 BMIs were coded. We used the global rating scales of the Motivational Interviewing Skills Code (MISC) 2.1: counselor's acceptance, empathy, and motivational interviewing (MI) spirit, and patient's self-exploration were rated. MI proficiency was defined as counselor's rating scale scores ≥5. We also used the structure, confrontation, and advice subscale scores of the Therapy Process Rating Scale and the Working Alliance Inventory. We examined these process characteristics in interventions across 1 U.S. RCT of middle-aged medical inpatients with unhealthy alcohol use (n = 124) and 2 Swiss RCTs of young men with binge drinking in a nonclinical setting: Swiss-one (n = 62) and Swiss-two (n = 128). We assessed the associations between these characteristics and drinks/d reported by participants 3 to 6 months after study entry. In all 3 RCTs, mean MISC counselor's rating scales scores were consistent with MI proficiency. In overdispersed Poisson regression models, most BMI characteristics were not significantly associated with drinks/d in follow-up. In the U.S. RCT, confrontation and self-exploration were associated with more drinking. Giving advice was significantly associated with less drinking in the Swiss-one RCT. Contrary to expectations, MI spirit was not consistently associated with drinking across studies. Across different populations and settings, intervention characteristics viewed as central to efficacious BMIs were neither robust nor consistent predictors of drinking outcome. Although there may be alternative reasons why the level of MI processes was not predictive of outcomes in these studies (limited variability in scores), efforts to understand what makes BMIs efficacious may require attention to factors beyond intervention process characteristics typically examined. Copyright © 2013 by the Research Society on Alcoholism.

Do Brief Alcohol Motivational Interventions Work Like We Think They Do?

PubMed Central

Bertholet, Nicolas; Palfai, Tibor; Gaume, Jacques; Daeppen, Jean-Bernard; Saitz, Richard

2016-01-01

Background Questions remain about how brief motivational interventions (BMIs) for unhealthy alcohol use work and addressing these questions may be important for improving their efficacy. Therefore, we assessed the effects of various characteristics of BMIs on drinking outcomes across three randomized controlled trials (RCTs). Methods Audio recordings of 314 BMIs were coded. We used the global rating scales of the Motivational Interviewing Skills Code (MISC) 2.1: counselor’s acceptance, empathy, and motivational interviewing (MI) spirit, and patient’s self-exploration were rated. MI proficiency was defined as counselor’s rating scale scores ≥5. We also used the structure, confrontation and advice sub-scale scores of the Therapy Process Rating Scale; and the Working Alliance Inventory. We examined these process characteristics in interventions across: one US RCT of middle-aged medical inpatients with unhealthy alcohol use (n=124) and two Swiss RCTs of young men with binge drinking in a non-clinical setting: Swiss-one (n=62) and Swiss-two (n=128). We assessed the associations between these characteristics and drinks/day reported by participants 3–6 months after study entry. Results In all 3 RCTs, mean MISC counselor’s rating scales scores were consistent with MI proficiency. In overdispersed Poisson regression models, most BMI characteristics were not significantly associated with drinks/day in follow-up. In the US RCT, confrontation and self-exploration were associated with more drinking. Giving advice was significantly associated with less drinking in the Swiss-one RCT. Contrary to expectations, MI spirit was not consistently associated with drinking across studies. Conclusions Across different populations and settings, intervention characteristics viewed as central to efficacious BMIs were neither robust nor consistent predictors of drinking outcome. Although there may be alternative reasons why the level of MI processes were not predictive of outcomes in these studies (limited variability in scores), efforts to understand what makes BMIs efficacious may require attention to factors beyond intervention process characteristics typically examined. PMID:24125097

Effects of Screening for Psychological Distress on Patient Outcomes in Cancer: a Systematic Review

PubMed Central

Meijer, Anna; Roseman, Michelle; Delisle, Vanessa C.; Milette, Katherine; Levis, Brooke; Syamchandra, Achyuth; Stefanek, Michael E.; Stewart, Donna E.; de Jonge, Peter; Coyne, James C.; Thombs, Brett D.

2013-01-01

Objective Several practice guidelines recommend routine screening for psychological distress in cancer care. The objective was to evaluate the effect of screening cancer patients for psychological distress by assessing the (1) effectiveness of interventions to reduce distress among patients identified as distressed; and (2) effects of screening for distress on distress outcomes. Methods CINAHL, Cochrane, EMBASE, ISI, MEDLINE, PsycINFO, and SCOPUS databases were searched through April 6, 2011 with manual searches of 45 relevant journals, reference list review, citation tracking of included articles, and trial registry reviews through June 30, 2012. Articles in any language on cancer patients were included if they (1) compared treatment for patients with psychological distress to placebo or usual care in a randomized controlled trial (RCT); or (2) assessed the effect of screening on psychological distress in a RCT. Results There were 14 eligible RCTs for treatment of distress, and 1 RCT on the effects of screening on patient distress. Pharmacological, psychotherapy and collaborative care interventions generally reduced distress with small to moderate effects. One study investigated effects of screening for distress on psychological outcomes, and it found no improvement. Conclusion Treatment studies reported modest improvement in distress symptoms, but only a single eligible study was found on the effects of screening cancer patients for distress, and distress did not improve in screened patients versus those receiving usual care. Because of the lack of evidence of beneficial effects of screening cancer patients for distress, it is premature to recommend or mandate implementation of routine screening. PMID:23751231

CONTRACT Study - CONservative TReatment of Appendicitis in Children (feasibility): study protocol for a randomised controlled Trial.

PubMed

Hutchings, Natalie; Wood, Wendy; Reading, Isabel; Walker, Erin; Blazeby, Jane M; Van't Hoff, William; Young, Bridget; Crawley, Esther M; Eaton, Simon; Chorozoglou, Maria; Sherratt, Frances C; Beasant, Lucy; Corbett, Harriet; Stanton, Michael P; Grist, Simon; Dixon, Elizabeth; Hall, Nigel J

2018-03-02

Currently, the routine treatment for acute appendicitis in the United Kingdom is an appendicectomy. However, there is increasing scientific interest and research into non-operative treatment of appendicitis in adults and children. While a number of studies have investigated non-operative treatment of appendicitis in adults, this research cannot be applied to the paediatric population. Ultimately, we aim to perform a UK-based multicentre randomised controlled trial (RCT) to test the clinical and cost effectiveness of non-operative treatment of acute uncomplicated appendicitis in children, as compared with appendicectomy. First, we will undertake a feasibility study to assess the feasibility of performing such a trial. The study involves a feasibility RCT with a nested qualitative research to optimise recruitment as well as a health economic substudy. Children (aged 4-15 years inclusive) diagnosed with acute uncomplicated appendicitis that would normally be treated with an appendicectomy are eligible for the RCT. Exclusion criteria include clinical/radiological suspicion of perforated appendicitis, appendix mass or previous non-operative treatment of appendicitis. Participants will be randomised into one of two arms. Participants in the intervention arm are treated with antibiotics and regular clinical assessment to ensure clinical improvement. Participants in the control arm will receive appendicectomy. Randomisation will be minimised by age, sex, duration of symptoms and centre. Children and families who are approached for the RCT will be invited to participate in the embedded qualitative substudy, which includes recording of recruitment consultants and subsequent interviews with participants and non-participants and their families and recruiters. Analyses of these will inform interventions to optimise recruitment. The main study outcomes include recruitment rate (primary outcome), identification of strategies to optimise recruitment, performance of trial treatment pathways, clinical outcomes and safety of non-operative treatment. We have involved children, young people and parents in study design and delivery. In this study we will explore the feasibility of performing a full efficacy RCT comparing non-operative treatment with appendicectomy in children with acute uncomplicated appendicitis. Factors determining success of the present study include recruitment rate, safety of non-operative treatment and adequate interest in the future RCT. Ultimately this feasibility study will form the foundation of the main RCT and reinforce its design. ISRCTN15830435 . Registered on 8 February 2017.

Worldwide trends in volume and quality of published protocols of randomized controlled trials

PubMed Central

Alldinger, Ingo; Cieslak, Kasia P.; Wennink, Roos; Clarke, Mike; Ali, Usama Ahmed; Besselink, Marc G. H.

2017-01-01

Introduction Publishing protocols of randomized controlled trials (RCT) facilitates a more detailed description of study rational, design, and related ethical and safety issues, which should promote transparency. Little is known about how the practice of publishing protocols developed over time. Therefore, this study describes the worldwide trends in volume and methodological quality of published RCT protocols. Methods A systematic search was performed in PubMed and EMBASE, identifying RCT protocols published over a decade from 1 September 2001. Data were extracted on quality characteristics of RCT protocols. The primary outcome, methodological quality, was assessed by individual methodological characteristics (adequate generation of allocation, concealment of allocation and intention-to-treat analysis). A comparison was made by publication period (First, September 2001- December 2004; Second, January 2005-May 2008; Third, June 2008-September 2011), geographical region and medical specialty. Results The number of published RCT protocols increased from 69 in the first, to 390 in the third period (p<0.0001). Internal medicine and paediatrics were the most common specialty topics. Whereas most published RCT protocols in the first period originated from North America (n = 30, 44%), in the second and third period this was Europe (respectively, n = 65, 47% and n = 190, 48%, p = 0.02). Quality of RCT protocols was higher in Europe and Australasia, compared to North America (OR = 0.63, CI = 0.40–0.99, p = 0.04). Adequate generation of allocation improved with time (44%, 58%, 67%, p = 0.001), as did concealment of allocation (38%, 53%, 55%, p = 0.03). Surgical protocols had the highest quality among the three specialty topics used in this study (OR = 1.94, CI = 1.09–3.45, p = 0.02). Conclusion Publishing RCT protocols has become popular, with a five-fold increase in the past decade. The quality of published RCT protocols also improved, although variation between geographical regions and across medical specialties was seen. This emphasizes the importance of international standards of comprehensive training in RCT methodology. PMID:28296925

Effectiveness versus efficacy trials in COPD: how study design influences outcomes and applicability.

PubMed

Woodcock, Ashley; Boucot, Isabelle; Leather, David A; Crawford, Jodie; Collier, Susan; Bakerly, Nawar Diar; Hilton, Emma; Vestbo, Jørgen

2018-02-01

Guidelines for chronic obstructive pulmonary disease (COPD) management are based largely on results from double-blind randomised controlled trials (RCTs) of efficacy. These trials have high internal validity and test whether a drug is efficacious, but they are conducted in highly selected populations that may differ significantly from patients with COPD seen in routine practice.We compared the baseline characteristics, healthcare use and outcomes between the Salford Lung Study (SLS), an open-label effectiveness RCT, with six recent large-scale efficacy RCTs. We also calculated the proportion of SLS patients who would have been eligible for inclusion in an efficacy RCT by applying the inclusion criteria used in efficacy trials of combination treatments.SLS patients were older, included more females and more current smokers, had more comorbidities (including asthma), and had more often experienced exacerbations prior to inclusion. In the SLS, rates of moderate or severe exacerbations, incidence of overall serious adverse events (SAEs), and SAEs of pneumonia were more frequent. A maximum of 30% of patients enrolled in the SLS would have been eligible for a phase IIIa regulatory exacerbation study.Patients in large COPD efficacy RCTs have limited representativeness compared with an effectiveness trial. This should be considered when interpreting efficacy RCT outcomes and their inclusion into guidelines. Copyright ©ERS 2018.

Simulation can contribute a part of cardiorespiratory physiotherapy clinical education: two randomized trials.

PubMed

Blackstock, Felicity C; Watson, Kathryn M; Morris, Norman R; Jones, Anne; Wright, Anthony; McMeeken, Joan M; Rivett, Darren A; O'Connor, Vivienne; Peterson, Raymond F; Haines, Terry P; Watson, Geoffrey; Jull, Gwendolen Anne

2013-02-01

Simulated learning environments (SLEs) are used worldwide in health professional education, including physiotherapy, to train certain attributes and skills. To date, no randomized controlled trial (RCT) has evaluated whether education in SLEs can partly replace time in the clinical environment for physiotherapy cardiorespiratory practice. Two independent single-blind multi-institutional RCTs were conducted in parallel using a noninferiority design. Participants were volunteer physiotherapy students (RCT 1, n = 176; RCT 2, n = 173) entering acute care cardiorespiratory physiotherapy clinical placements. Two SLE models were investigated as follows: RCT 1, 1 week in SLE before 3 weeks of clinical immersion; RCT 2, 2 weeks of interspersed SLE/clinical immersion (equivalent to 1 SLE week) within the 4-week clinical placement. Students in each RCT were stratified on academic grade and randomly allocated to an SLE plus clinical immersion or clinical immersion control group. The primary outcome was competency to practice measured in 2 clinical examinations using the Assessment of Physiotherapy Practice. Secondary outcomes were student perception of experience and clinical educator and patient rating of student performance. There were no significant differences in student competency between the SLE and control groups in either RCT, although students in the interspersed group (RCT 2) achieved a higher score in 5 of 7 Assessment of Physiotherapy Practice standards (all P < 0.05). Students rated the SLE experience positively. Clinical educators and patients reported comparability between groups. An SLE can replace clinical time in cardiorespiratory physiotherapy practice. Part education in the SLE satisfied clinical competency requirements, and all stakeholders were satisfied.

Zuclopenthixol dihydrochloride for schizophrenia.

PubMed

Bryan, Edward J; Purcell, Marie Ann; Kumar, Ajit

2017-11-16

Oral zuclopenthixol dihydrochloride (Clopixol) is an anti-psychotic treatment for people with psychotic symptoms, especially those with schizophrenia. It is associated with neuroleptic malignant syndrome, a prolongation of the QTc interval, extra-pyramidal reactions, venous thromboembolism and may modify insulin and glucose responses. To determine the effects of zuclopenthixol dihydrochloride for treatment of schizophrenia. We searched the Cochrane Schizophrenia Group's Trials Register (latest search 09 June 2015). There were no language, date, document type, or publication status limitations for inclusion of records in the register. All randomised controlled trials (RCTs) focusing on zuclopenthixol dihydrochloride for schizophrenia. We included trials meeting our inclusion criteria and reporting useable data. We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a random-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. We included 20 trials, randomising 1850 participants. Data were reported for 12 comparisons, predominantly for the short term (up to 12 weeks) and inpatient populations. Overall risk of bias for included studies was low to unclear.Data were unavailable for many of our pre-stated outcomes of interest. No data were available, across all comparisons, for death, duration of stay in hospital and general functioning.Zuclopenthixol dihydrochloride versus: 1. placeboMovement disorders (EPSEs) were similar between groups (1 RCT, n = 28, RR 6.07 95% CI 0.86 to 43.04 very low-quality evidence). There was no clear difference in numbers leaving the study early (2 RCTs, n = 100, RR 0.29, 95% CI 0.01 to 6.60, very low-quality evidence). 2. chlorpromazineNo clear differences were found for the outcomes of global state (average CGI-SI endpoint score) (1 RCT, n = 60, MD 0.00, 95% CI -0.49 to 0.49) or movement disorders (EPSEs) (3 RCTs, n = 199, RR 0.94, 95% CI 0.61 to 1.45), both very low-quality evidence. More people left the study early for any reason from the zuclopenthixol group (6 RCTs, n = 766, RR 0.54, 95% CI 0.36 to 0.81, low-quality evidence). 3. chlorprothixeneThere was no clear difference in numbers leaving the study early for any reason (1 RCT, n = 20, RR 1.00, 95% CI 0.34 to 2.93, very low-quality evidence). 4. clozapineNo useable data were presented. 5. haloperidolNo clear differences between treatment groups were found for the outcomes global state score (average CGI endpoint score) (1 RCT, n = 49, MD 0.13, 95% CI -0.30 to 0.55) or leaving the study early (2 RCTs, n = 141, RR 0.99, 95% CI 0.72 to 1.35), both very low-quality evidence. 6. perphenazineThose receiving zuclopenthixol were more likely to require medication in the short term for EPSEs than perphenazine (1 RCT, n = 50, RR 1.90, 95% CI 1.12 to 3.22, very low-quality evidence). Similar numbers left the study early (2 RCTs, n = 104, RR 0.63, 95% CI 0.27 to 1.47, very low-quality evidence). 7. risperidoneThose receiving zuclopenthixol were more likely to require medications for EPSEs than risperidone (1 RCT, n = 98,RR 1.92, 95% CI 1.12 to 3.28, very low quality evidence). There was no clear difference in numbers leaving the study early ( 3 RCTs, n = 154, RR 1.30, 95% CI 0.84 to 2.02) or in mental state (average PANSS total endpoint score) (1 RCT, n = 25, MD -3.20, 95% CI -7.71 to 1.31), both very low-quality evidence). 8. sulpirideNo clear differences were found for global state (average CGI endpoint score) ( 1 RCT, n = 61, RR 1.18, 95% CI 0.49 to 2.85, very low-quality evidence), requiring hypnotics/sedatives (1 RCT, n = 61, RR 0.60, 95% CI 0.27 to 1.32, very low-quality evidence) or leaving the study early (1 RCT, n = 61, RR 2.07 95% CI 0.97 to 4.40, very low-quality evidence). 9. thiothixeneNo clear differences were found for the outcomes of 'global state (average CGI endpoint score) (1 RCT, n = 20, RR 0.50, 95% CI 0.17 to 1.46) or leaving the study early (1 RCT, n = 20, RR 0.57, 95% CI 0.24 to 1.35), both very low-quality evidence). 10. trifluoperazineNo useable data were presented. 11. zuclopenthixol depotThere was no clear difference in numbers leaving the study early (1 RCT, n = 46, RR 1.95, 95% CI 0.36 to 10.58, very low-quality evidence). 12. Zuclopenthixol dihydrochloride (cis z isomer) versus zuclopenthixol (cis z/trans e isomer)There were no clear differences in reported side-effects ( 1 RCT, n = 57, RR 1.34, 95% CI 0.82 to 2.18, very low-quality evidence) and in numbers leaving the study early (4 RCTs, n = 140, RR 2.15, 95% CI 0.49 to 9.41, very low-quality evidence). Zuclopenthixol dihydrochloride appears to cause more EPSEs than clozapine, risperidone or perphenazine, but there was no difference in EPSEs when compared to placebo or chlorpromazine. Similar numbers required hypnotics/sedatives when zuclopenthixol dihydrochloride was compared to sulpiride, and similar numbers of reported side-effects were found when its isomers were compared. The other comparisons did not report adverse-effect data.Reported data indicate zuclopenthixol dihydrochloride demonstrates no difference in mental or global states compared to placebo, chlorpromazine, chlorprothixene, clozapine, haloperidol, perphenazine, sulpiride, thiothixene, trifluoperazine, depot and isomers. Zuclopenthixol dihydrochloride, when compared with risperidone, is favoured when assessed using the PANSS in the short term, but not in the medium term.The data extracted from the included studies are mostly equivocal, and very low to low quality, making it difficult to draw firm conclusions. Prescribing practice is unlikely to change based on this meta-analysis. Recommending any particular course of action about side-effect medication other than monitoring, using rating scales and clinical assessment, and prescriptions on a case-by-case basis, is also not possible.There is a need for further studies covering this topic with more antipsychotic comparisons for currently relevant outcomes.

Pilot Randomized Controlled Trial of Titrated Subcutaneous Ketamine in Older Patients with Treatment-Resistant Depression.

PubMed

George, Duncan; Gálvez, Verònica; Martin, Donel; Kumar, Divya; Leyden, John; Hadzi-Pavlovic, Dusan; Harper, Simon; Brodaty, Henry; Glue, Paul; Taylor, Rohan; Mitchell, Philip B; Loo, Colleen K

2017-11-01

To assess the efficacy and safety of subcutaneous ketamine for geriatric treatment-resistant depression. Secondary aims were to examine if repeated treatments were safe and more effective in inducing or prolonging remission than a single treatment. In this double-blind, controlled, multiple-crossover study with a 6-month follow-up (randomized controlled trial [RCT] phase), 16 participants (≥60 years) with treatment-resistant depression who relapsed after remission or did not remit in the RCT were administered an open-label phase. Up to five subcutaneous doses of ketamine (0.1, 0.2, 0.3, 0.4, and 0.5 mg/kg) were administered in separate sessions (≥1 week apart), with one active control (midazolam) randomly inserted (RCT phase). Twelve ketamine treatments were given in the open-label phase. Mood, hemodynamic, and psychotomimetic outcomes were assessed by blinded raters. Remitters in each phase were followed for 6 months. Seven of 14 RCT-phase completers remitted with ketamine treatment. Five remitted at doses below 0.5 mg/kg. Doses ≥ 0.2 mg/kg were significantly more effective than midazolam. Ketamine was well tolerated. Repeated treatments resulted in higher likelihood of remission or longer time to relapse. Results provide preliminary evidence for the efficacy and safety of ketamine in treating elderly depressed. Dose titration is recommended for optimizing antidepressant and safety outcomes on an individual basis. Subcutaneous injection is a practical method for giving ketamine. Repeated treatments may improve remission rates (clinicaltrials.gov; NCT01441505). Copyright © 2017 American Association for Geriatric Psychiatry. All rights reserved.

Evidence for Neuroplastic Compensation in the Cerebral Cortex of Persons with Depressive Illness

PubMed Central

Bansal, Ravi; Hellerstein, David J.; Peterson, Bradley S.

2017-01-01

We yoked anatomical brain Magnetic Resonance Imaging to a randomized, double-blind, placebo-controlled trial (RCT) of antidepressant medication for 10-week’s duration in patients with dysthymia. The RCT study design mitigated ascertainment bias by randomizing patients to receive either duloxetine or placebo, and it supported true causal inferences about treatment effects on the brain by controlling treatment assignment experimentally. We acquired 121 anatomical scans: at baseline and endpoint in 41 patients, and once in 39 healthy controls. At baseline, patients had diffusely thicker cortices than did healthy participants, and patients who had thicker cortices had proportionately less severe symptoms. During the trial, symptoms improved significantly more in medication- compared with placebo-treated patients; concurrently, thicknesses in medication-treated patients declined toward values in healthy controls, but they increased slightly, away from control values, in placebo-treated patients. Changes in symptom severity during the trial mediated the association of treatment assignment with the change in thickness, suggesting that the beneficial effects of medication on symptom severity were at least partially responsible for normalizing cortical thickness. Together our findings suggest that baseline cortical hypertrophy in medication-free patients likely represented a compensatory, neuroplastic response that attenuated symptom severity. Medication then reduced symptoms and lessened the need for compensation, thereby normalizing thickness. This is to the best of our knowledge the first study to report within an RCT a differential change in cortical morphology during medication treatment for depressive illness and the first to provide within an RCT in vivo evidence for the presence of neuroanatomical plasticity in humans. PMID:28265119

A Relational Cultural Approach to Working with Clients with Eating Disorders

ERIC Educational Resources Information Center

Trepal, Heather C.; Boie, Ioana; Kress, Victoria E.

2012-01-01

The authors examine eating disorders through the conceptual framework of relational cultural theory (RCT). Taking into account the importance of relationships and connection, it is suggested that RCT may be a useful lens for conceptualizing and working with people who are experiencing eating disorders. Ways that RCT can be applied to enhance…

Cautionary tales in the interpretation of observational studies of effects of clinical interventions.

PubMed

Scott, I A; Attia, J

2017-02-01

Observational studies of the effectiveness of clinical interventions are proliferating as more 'real-world' clinical data (so called 'big data') are gathered from clinical registries, administrative datasets and electronic health records. While well-conducted randomised controlled trials (RCT) remain the scientific standard in assessing the efficacy of clinical interventions, well-designed observational studies may add to the evidence base of effectiveness in situations where RCT are of limited value or very difficult to perform. Rather than dismissing observational studies, we need to determine what circumstances may justify doing an observational study and when the study is sufficiently rigorous to be considered reasonably trustworthy. This article proposes criteria by which users of the literature might make such determinations. © 2016 Royal Australasian College of Physicians.

The Physiotherapy for Femoroacetabular Impingement Rehabilitation STudy (physioFIRST): A Pilot Randomized Controlled Trial.

PubMed

Kemp, Joanne L; Coburn, Sally L; Jones, Denise M; Crossley, Kay M

2018-04-01

Study Design A pilot double-blind randomized controlled trial (RCT). Background The effectiveness of physical therapy for femoroacetabular impingement syndrome (FAIS) is unknown. Objectives To determine the feasibility of an RCT investigating the effectiveness of a physical therapy intervention for FAIS. Methods Participants were 17 women and 7 men (mean ± SD age, 37 ± 8 years; body mass index, 25.4 ± 3.4 kg/m 2 ) with FAIS who received physical therapy interventions provided over 12 weeks. The FAIS-specific physical therapy group received personalized progressive strengthening and functional retraining. The control group received standardized stretching exercises. In addition, both groups received manual therapy, progressive physical activity, and education. The primary outcome was feasibility, including integrity of the protocol, recruitment and retention, outcome measures, randomization procedure, and sample-size estimate. Secondary outcomes included hip pain and function (international Hip Outcome Tool-33 [iHOT-33]) and hip muscle strength. Poststudy interviews were conducted to determine potential improvements for future studies. Results Twenty-four (100%) patients with known eligibility agreed to participate. Four patients (17%) were lost to follow-up. All participants and the tester remained blinded, and the control intervention was acceptable to participants. The between-group mean differences in change scores were 16 (95% confidence interval [CI]: -9, 38) for the iHOT-33 and 0.24 (95% CI: 0.02, 0.47) Nm/kg for hip adduction strength, favoring the FAIS-specific physical therapy group. Using an effect size of 0.61, between-group improvements for the iHOT-33 suggest that 144 participants are required for a full-scale RCT. Conclusion A full-scale RCT of physical therapy for FAIS is feasible. A FAIS-specific physical therapy program has the potential for a moderate to large positive effect on hip pain, function, and hip adductor strength. Level of Evidence Therapy, level 2b. J Orthop Sports Phys Ther 2018;48(4):307-315. doi:10.2519/jospt.2018.7941.

[SPA therapy for pain of patients with chronic low back pain, knee osteo-arthritis and fibromyalgia].

PubMed

Roques, Christian-François; Queneau, Patrice

2016-03-01

The data of 33 randomized controlled trials suggest that chronic pain of patients with chronic low back pain, knee osteo-arthritis, fibromyalgia is significantly improved by balneotherapy and significantly better improved than by control treatments. For chronic low back pain (10 RCT, 1192 patients) pain was better improved in balneotherapy group and the weighted mean of the differential improvement was 19.66 (95 % CI: 16.6 ; 22.8) and the effect size was 1.1 (95 %CI: 0.82 ; 1.38) favouring balneotherapy. For knee osteo-arthritis pain (17 RCT, 1428 patients) pain was better improved in balneotherapy group and the weighted mean of the differential improvement was 13.24 (95 % CI: 5.52 ; 20.96) and the effect size was 0.72 (95 %CI: 0.51 ; 0.93) favouring balneotherapy. For fibromyalgia (6 RCT, 398 patients) pain was better improved in balneotherapy group and the weighted mean of the differential improvement was 19.32 (95 % CI: 10.62 ; 29.2) and the effect size was 0.79 (95 %CI: 0.27 ; 1.31) favouring balneotherapy. Mineral waters and healing muds appear to have a more powerful analgesic action: 13 RCT (701) patients) compared mineral water bathing to tap water bathing or peloid application to hot-apcks or neutral muds application : the effect size was 0.75 (95 % CI :0.71 ; 0.79) favouring balneotherapy. Balneotherapy is a safe treatment as only 1 % of the patients receiving balneotherapy had to interrupt the treatment. However several methodological biases were observed in many trials, mainly a lack of statistical power due to a limited enrolment of patients, an insufficient duration of follow-up, an inhomogeneity of treatments. The clinical benefit has to be confirmed by stronger data of evidence but these data are sufficient to perform a more complete scientific analysis (meta-analysis) ; but further clinical investigations with a better methodological quality remain necessary.

Enalapril versus losartan for adults with chronic kidney disease: a systematic review and meta-analysis.

PubMed

He, Yuan-Mei; Feng, Li; Huo, Dong-Mei; Yang, Zhen-Hua; Liao, Yun-Hua

2013-09-01

Both enalapril and losartan are effective and widely used in patients with chronic kidney disease (CKD). This review aimed to evaluate the benefits of enalapril and losartan in adults with CKD. PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov were searched, without language limitations, for randomized controlled trials (RCT), in which enalapril and losartan were compared in adults with CKD. Standard methods, consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, were used. Reviewer Manager software, ver. 5.2, was used for meta-analysis. Of 318 citations retrieved, 17 RCT (14 parallel-group and three cross-over) met our inclusion criteria. The pooled analysis for parallel RCT showed that the effects of enalapril and losartan on blood pressure, renal function and serum uric acid (UA) were similar. Meta-analysis indicated that patients taking enalapril had a higher risk of dry cough (risk ratio, 2.88; 95% CI, 1.11-7.48; P=0.03). Sensitivity analysis showed good robustness of these findings. Enalapril has similar effects to losartan on systemic blood pressure, renal function and serum UA in patients with CKD, but carries a higher risk of dry cough. Larger trials are required to evaluate the effects of these medications on clinical outcomes. © 2013 The Authors. Nephrology © 2013 Asian Pacific Society of Nephrology.

A pilot randomised controlled trial of an Internet-based cognitive behavioural therapy self-management programme (MS Invigor8) for multiple sclerosis fatigue.

PubMed

Moss-Morris, Rona; McCrone, Paul; Yardley, Lucy; van Kessel, Kirsten; Wills, Gary; Dennison, Laura

2012-06-01

The majority of people affected by Multiple Sclerosis (paMS) experience severe and disabling fatigue. A recent randomised controlled trial (RCT) showed that cognitive behaviour therapy with a clinical psychologist was an effective treatment for MS fatigue. An Internet-based version of this intervention, MS Invigor8, was developed for the current study using agile design and input from paMS. MS Invigor8 includes eight tailored, interactive sessions. The aim was to test the feasibility and potential efficacy and cost-effectiveness of the programme in a pilot RCT. 40 patients were randomised to MS Invigor8 (n=23) or standard care (n=17). The MS Invigor8 group accessed sessions over 8-10 weeks and received up to three 30-60min telephone support sessions. Participants completed online standardised questionnaires assessing fatigue, mood, quality of life and service use at baseline and 10 weeks follow-up. Large between group treatment effects were found for the primary outcomes of fatigue severity (d=1.19) and impact (d=1.02). The MS Invigor8 group also reported significantly greater improvements in anxiety, depression and quality-adjusted life years. These data suggest that Internet-based CBT may be a clinically and cost-effective treatment for MS fatigue. A larger RCT with longer term follow-up is warranted. Copyright © 2012 Elsevier Ltd. All rights reserved.

Crystal structures of resorcin[4]arene and pyrogallol[4]arene complexes with DL-pipecolinic acid. Model compounds for the recognition of the pipecolinyl ring, a key fragment of FK506, through C-H⋯π interaction

NASA Astrophysics Data System (ADS)

Fujisawa, Ikuhide; Kitamura, Yuji; Kato, Ryo; Murayama, Kazutaka; Aoki, Katsuyuki

2014-01-01

Resorcin[4]arene (resorcinol cyclic tetramer, abbreviated as RCT) or pyrogallol[4]arene (pyrogallol cyclic tetramer, PCT) form host-guest 1:1 complexes with DL-pipecolinic acid (DL-pipeH), RCT·DL-pipeH·EtOH·8H2O (1), PCT DL-pipeH·EtOH·4H2O (2), and PCT·DL-pipeH·3H2O (3), whose crystal structures have been determined. In each complex, the pipeH ligand is incorporated into the bowl-shaped cavity of the RCT or PCT host molecules through C-H⋯π interactions between alkyl protons of the piperidine ring of pipeH and π-rings of RCT or PCT, forming an [(RCT/PCT)·pipeH] structural fragment. In 1 and 3, two [(RCT/PCT) pipeH] fragments self-associate across an inversion center to form a guest-mediated, obliquely declined dimeric structure [(RCT/PCT)·L-pipeH·D-pipeH (RCT/PCT)]. In 2, each PCT-capped pipeH ligand bridges to two adjacent PCT molecules to form guest-mediated, optically-discrete helical polymers [PCT·L-pipeH]n or [PCT·D-pipeH]n. An 1H NMR experiment shows that the complexation through C-H⋯π interaction between the piperidine ring of pipeH and π-rings of RCT or PCT occurs also in solution, with the binding constants of 9.7 ± 0.6 M-1 for RCT and 26.5 ± 1.5 M-1 for PCT. These complexes provide a synthetic model for the recognition of the pipecolinyl-ring moiety, a key constituent of immunosuppressant drugs such as FK506, FK520 or rapamycin, by their binding proteins through C-H⋯π interaction.

Predictors of outcome in residential cognitive and interpersonal treatment for social phobia: do cognitive and social dysfunction moderate treatment outcome?

PubMed

Borge, Finn-Magnus; Hoffart, Asle; Sexton, Harold

2010-09-01

The predictors of residential cognitive (RCT) and residential interpersonal Treatment (RIPT) for social phobia were explored. (1) Sotsky et al. (1991) found differential effects of CT and IPT for depression, suggesting that the level of cognitive or social dysfunction predicted differential outcome. We examined whether an analogous effect could be demonstrated in 10 weeks of residential treatment of 80 social phobia subjects. (2) We also included expectations, age of onset, severity of illness, concurrent anxiety, mood, avoidant personality disorder, and body dysmorphic disorder as predictors in this exploratory study. Main outcome was the social phobia subscale of Social Phobia and Anxiety Inventory (SPAI SP). DSM-IV axis I and II interviews were completed. (1) Sotsky et al. (1991) findings were not reproduced. However, RIPT subjects with poor general functioning were less improved following treatment. Subjects with concurrent agoraphobia responded better with RCT than subjects without agoraphobia. (2) Age of onset and expectations were the most powerful predictors of post treatment outcome. Some patient characteristics appear to impact outcome with RIPT and RCT differentially. The findings are discussed. (c) 2010 Elsevier Ltd. All rights reserved.

Internet Interventions for Hearing Loss.

PubMed

Thorén, Elisabet Sundewall; Öberg, Marie; Andersson, Gerhard; Lunner, Thomas

2015-09-01

The purpose of the two studies presented in this research forum article was to develop audiological rehabilitation programs for experienced hearing aid users and evaluate them in online versions. In this research forum article, the differences between the two studies are discussed. Two randomized controlled trials (RCTs) were performed evaluating the efficacy of online rehabilitation, including professional guidance by an audiologist. In each RCT, the effects of the online programs were compared with the effects measured in a control group. The results from the first RCT showed a significant increase in activity and participation for both groups with participants in the intervention group improving more than those in the control group. At the 6-month follow-up, after the study, the significant increase was maintained; however, amounts of increase in the two groups were no longer significantly different. The results from the second RCT showed significant increase in activity and participation for the intervention group, although the control group did not improve. The results from the RCTs provide evidence that the Internet can be used to deliver rehabilitation to hearing-aid users and that their problems are reduced by the intervention; however, the content of the online rehabilitation program requires further investigation.

Root Canal Therapy Reduces Multiple Dimensions of Pain: A National Dental PBRN Study

PubMed Central

Law, Alan S.; Nixdorf, Donald R.; Rabinowitz, Ira; Reams, Gregory J.; Smith, James A.; Torres, Anibal V.; Harris, D. Robert

2014-01-01

Background Initial orthograde root canal therapy (RCT) is used to treat dentoalveolar pathosis. The affect RCT has on pain intensity has been frequently reported, but the affect on other dimensions of pain has not. Also, the lack of large prospective studies involving diverse groups of patients and practitioners that are not involved in data collection suggest that there are multiple opportunities for bias to be introduced when this data is systematically aggregated. Method This prospective observational study assessed pain intensity, duration, and its interference with daily activities among RCT patients. Sixty-two practitioners (46 general dentists, 16 endodontists) in the National Dental Practice-Based Research Network enrolled patients requiring RCT. Patient reported data were collected before, immediately following, and one week after treatment using the Graded Chronic Pain Scale. Results Enrollment of 708 patients was completed over 6 months with 655 patients (93%) providing one-week follow-up data. Prior to treatment, patients reported a mean (±standard deviation) worst pain intensity of 5.3±3.8 (0-10 scale), 50% had “severe” pain (≥7), and mean days in pain and days pain interfered with activities were 3.6±2.7 and 0.5±1.2, respectively. Following treatment, patients reported a mean worst pain intensity of 3.0±3.2, 19% had “severe” pain, and mean days in pain and days with pain interference were 2.1±2.4 and 0.4±1.1, respectively. All changes were statistically significant (p<0.0001). Conclusions RCT is an effective treatment for patients experiencing pain, significantly reducing pain intensity, duration, and related interference. Further research is needed to reduce the proportion of patients reporting “severe” post-operative pain. PMID:25190605

Systematic review of complementary and alternative medicine treatments in inflammatory bowel diseases.

PubMed

Langhorst, J; Wulfert, H; Lauche, R; Klose, P; Cramer, H; Dobos, G J; Korzenik, J

2015-01-01

We performed a systematic review for Complementary and Alternative Medicine [CAM] as defined by the National Institute of Health in Inflammatory Bowel Disease [IBD], ie Crohn's disease [CD] and ulcerative colitis [UC], with the exception of dietary and nutritional supplements, and manipulative therapies. A computerized search of databases [Cochrane Library, Pubmed/Medline, PsychINFO, and Scopus] through March 2014 was performed. We screened the reference sections of original studies and systematic reviews in English language for CAM in IBD, CD and UC. Randomized controlled trials [RCT] and controlled trials [CT] were referred and assessed using the Cochrane risk of bias tool. A total of: 26 RCT and 3 CT for herbal medicine, eg aloe-vera gel, andrographis paniculata, artemisia absinthium, barley foodstuff, boswellia serrata, cannabis, curcumin, evening primrose oil, Myrrhinil intest®, plantago ovata, silymarin, sophora, tormentil, wheatgrass-juice and wormwood; 1 RCT for trichuris suis ovata; 7 RCT for mind/body interventions such as lifestyle modification, hypnotherapy, relaxation training and mindfulness; and 2 RCT in acupuncture; were found. Risk of bias was quite heterogeneous. Best evidence was found for herbal therapy, ie plantago ovata and curcumin in UC maintenance therapy, wormwood in CD, mind/body therapy and self-intervention in UC, and acupuncture in UC and CD. Complementary and alternative therapies might be effective for the treatment of inflammatory bowel diseases; however, given the low number of trials and the heterogeneous methodological quality of trials, further in-depth research is necessary. Copyright © 2014 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Systematic review of interventions for children with Fetal Alcohol Spectrum Disorders

PubMed Central

Peadon, Elizabeth; Rhys-Jones, Biarta; Bower, Carol; Elliott, Elizabeth J

2009-01-01

Background Children with Fetal Alcohol Spectrum Disorders (FASD) may have significant neurobehavioural problems persisting into adulthood. Early diagnosis may decrease the risk of adverse life outcomes. However, little is known about effective interventions for children with FASD. Our aim is to conduct a systematic review of the literature to identify and evaluate the evidence for pharmacological and non-pharmacological interventions for children with FASD. Methods We did an electronic search of the Cochrane Library, MEDLINE, EMBASE, PsychINFO, CINAHL and ERIC for clinical studies (Randomized controlled trials (RCT), quasi RCT, controlled trials and pre- and post-intervention studies) which evaluated pharmacological, behavioural, speech therapy, occupational therapy, physiotherapy, psychosocial and educational interventions and early intervention programs. Participants were aged under 18 years with a diagnosis of a FASD. Selection of studies for inclusion and assessment of study quality was undertaken independently by two reviewers. Meta-analysis was not possible due to diversity in the interventions and outcome measures. Results Twelve studies met the inclusion criteria. Methodological weaknesses were common, including small sample sizes; inadequate study design and short term follow up. Pharmacological interventions, evaluated in two studies (both RCT) showed some benefit from stimulant medications. Educational and learning strategies (three RCT) were evaluated in seven studies. There was some evidence to suggest that virtual reality training, cognitive control therapy, language and literacy therapy, mathematics intervention and rehearsal training for memory may be beneficial strategies. Three studies evaluating social communication and behavioural strategies (two RCT) suggested that social skills training may improve social skills and behaviour at home and Attention Process Training may improve attention. Conclusion There is limited good quality evidence for specific interventions for managing FASD, however seven randomized controlled trials that address specific functional deficits of children with FASD are underway or recently completed. PMID:19463198

Compensatory hypertrophy of the teres minor muscle after large rotator cuff tear model in adult male rat.

PubMed

Ichinose, Tsuyoshi; Yamamoto, Atsushi; Kobayashi, Tsutomu; Shitara, Hitoshi; Shimoyama, Daisuke; Iizuka, Haku; Koibuchi, Noriyuki; Takagishi, Kenji

2016-02-01

Rotator cuff tear (RCT) is a common musculoskeletal disorder in the elderly. The large RCT is often irreparable due to the retraction and degeneration of the rotator cuff muscle. The integrity of the teres minor (TM) muscle is thought to affect postoperative functional recovery in some surgical treatments. Hypertrophy of the TM is found in some patients with large RCTs; however, the process underlying this hypertrophy is still unclear. The objective of this study was to determine if compensatory hypertrophy of the TM muscle occurs in a large RCT rat model. Twelve Wistar rats underwent transection of the suprascapular nerve and the supraspinatus and infraspinatus tendons in the left shoulder. The rats were euthanized 4 weeks after the surgery, and the cuff muscles were collected and weighed. The cross-sectional area and the involvement of Akt/mammalian target of rapamycin (mTOR) signaling were examined in the remaining TM muscle. The weight and cross-sectional area of the TM muscle was higher in the operated-on side than in the control side. The phosphorylated Akt/Akt protein ratio was not significantly different between these sides. The phosphorylated-mTOR/mTOR protein ratio was significantly higher on the operated-on side. Transection of the suprascapular nerve and the supraspinatus and infraspinatus tendons activates mTOR signaling in the TM muscle, which results in muscle hypertrophy. The Akt-signaling pathway may not be involved in this process. Nevertheless, activation of mTOR signaling in the TM muscle after RCT may be an effective therapeutic target of a large RCT. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Quality of randomized controlled trials published in the International Urogynecology Journal 2007-2016.

PubMed

Kim, Kyu Shik; Chung, Jae Hoon; Jo, Jung Ki; Kim, Jae Heon; Kim, Seungjun; Cho, Jeoung Man; Cho, Hee Ju; Choi, Hong Yong; Lee, Seung Wook

2018-07-01

Randomized controlled trials (RCTs) provide the best quality clinical evidence. The aim of this study was to assess the quality of RCTs published by the International Urogynecology Journal (IUJ) in 2007-2016. RCTs in original articles were extracted from PubMed and IUJ homepage. Change in RCT quality over time was assessed with Jadad and van Tulder scales and Cochrane Collaboration's risk of bias tool (CCRBT). Jadad scores of 3-5 or van Tulder scores of >5 indicated high-quality RCTs. The effect on RCT quality of including funding source and institutional review board (IRB) approval statements and describing the intervention was assessed. In addition, changes in RCT topics over time were assessed. Annual RCT frequencies did not change significantly (6.7-15.7%): 36.1% and 25.7% described blinding and allocation concealment, respectively. Both tended to increase between 2013 and 2016, particularly 2013 and 2014. Funding statement inclusion (39.1% overall) and intervention description (78.2% overall) tended to increase steadily. IRB statement inclusion (60.4% overall) increased significantly (p < 0.01). Jadad scores and van Tulder rose significantly until 2014 (p < 0.01). Frequencies of high-quality RCTs tended to rise. CCRBT indicated that RCTs with a low risk of bias tended to increase until 2014. However, from 2015, Jadad scores, van Tulder, and CCRBT the low risk tended to decreased. RCTs with funding and IRB approval statements had higher Jadad and van Tulder scores than unfunded RCTs (p < 0.01 and p < 0.01, respectively). Intervention description did not associate with better quality. RCT quality improved over time, but a dip in quality was observed in 2015-2016 because of decreased blinding and allocation concealment.

Rectal Chlamydia in heterosexual women: more questions than answers.

PubMed

Ding, Alvin; Challenor, Rachel

2014-07-01

The aim of this study was to observe the proportion of concurrent rectal Chlamydia (RCt) infection in women who have cervical Chlamydia (CCt) and to observe whether there was any correlation with receptive anal intercourse (RAI). Untreated CCt-positive women were invited to take part. Women chose either to have a physician-collected or self-taken rectal swab. Treatment was then commenced. 17 samples were physician-collected and 80 were self-collected. 75/97 (77.3%, 95% Confidence Interval [95%CI] 69.0-85.7%) were RCt positive. 25/97 (25.8%, 95%CI 17.1-34.5%) reported RAI. There was no difference in the positivity rate whether RAI was reported (80%) or not (76%) (P = 0.71); or whether swabs were physician-collected (65%) or self-taken (80%) (P = 0.17). Only one of those with RCt reported rectal symptoms. One woman had concurrent gonococcal infection. 34/97 (35%) had a history of past sexually transmitted infections. Verified contact attendance was 0.52 and 72% of verified contacts were Chlamydia positive. Reported RAI may not be helpful in guiding RCt testing. RCt infection in women may be more prevalent than previously thought. We do not know whether RCt infections are clinically significant or whether they may act as a reservoir for re-infection. RCt infections in women require further study. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Recruitment to online therapies for depression: pilot cluster randomized controlled trial.

PubMed

Jones, Ray B; Goldsmith, Lesley; Hewson, Paul; Williams, Christopher J

2013-03-05

Raising awareness of online cognitive behavioral therapy (CBT) could benefit many people with depression, but we do not know how purchasing online advertising compares to placing free links from relevant local websites in increasing uptake. To pilot a cluster randomized controlled trial (RCT) comparing purchase of Google AdWords with placing free website links in raising awareness of online CBT resources for depression in order to better understand research design issues. We compared two online interventions with a control without intervention. The pilot RCT had 4 arms, each with 4 British postcode areas: (A) geographically targeted AdWords, (B) adverts placed on local websites by contacting website owners and requesting links be added, (C) both interventions, (D) control. Participants were directed to our research project website linking to two freely available online CBT resource sites (Moodgym and Living Life To The Full (LLTTF)) and two other depression support sites. We used data from (1) AdWords, (2) Google Analytics for our project website and for LLTTF, and (3) research project website. We compared two outcomes: (1) numbers with depression accessing the research project website, and then chose an onward link to one of the two CBT websites, and (2) numbers registering with LLTTF. We documented costs, and explored intervention and assessment methods to make general recommendations to inform researchers aiming to use similar methodologies in future studies. Trying to place local website links appeared much less cost effective than AdWords and although may prove useful for service delivery, was not worth pursuing in the context of the current study design. Our AdWords intervention was effective in recruiting people to the project website but our location targeting "leaked" and was not as geographically specific as claimed. The impact on online CBT was also diluted by offering participants other choices of destinations. Measuring the impact on LLTTF use was difficult as the total number using LLTTF was less than 5% of all users and record linkage across websites was impossible. Confounding activity may have resulted in some increase in registrations in the control arm. Practitioners should consider online advertising to increase uptake of online therapy but need to check its additional value. A cluster RCT using location targeted adverts is feasible and this research design provides the best evidence of cost-effectiveness. Although our British pilot study is limited to online CBT for depression, a cluster RCT with similar design would be appropriate for other online treatments and countries and our recommendations may apply. They include ways of dealing with possible contamination (buffer zones and AdWords techniques), confounding factors (large number of clusters), advertising dose (in proportion to total number of users), record linkage (landing within target website), and length of study (4-6 months). clinicaltrials.gov (Registration No. NCT01469689); http://clinicaltrials.gov/ct2/show/NCT01469689 (Archived by WebCite at http://www.webcitation.org/6EtTthDOp).

Information and communication technology in patient education and support for people with schizophrenia.

PubMed

Välimäki, Maritta; Hätönen, Heli; Lahti, Mari; Kuosmanen, Lauri; Adams, Clive E

2012-10-17

Poor compliance with treatment often means that many people with schizophrenia or other severe mental illness relapse and may need frequent and repeated hospitalisation. Information and communication technology (ICT) is increasingly being used to deliver information, treatment or both for people with severe mental disorders. To evaluate the effects of psychoeducational interventions using ICT as a means of educating and supporting people with schizophrenia or related psychosis. We searched the Cochrane Schizophrenia Group Trials Register (2008, 2009 and September 2010), inspected references of identified studies for further trials and contacted authors of trials for additional information. All clinical randomised controlled trials (RCTs) comparing ICT as a psychoeducational and supportive tool with any other type of psychoeducation and supportive intervention or standard care. We selected trials and extracted data independently. For homogenous dichotomous data we calculated fixed-effect risk ratios (RR) with 95% confidence intervals (CI). For continuous data, we calculated mean differences (MD). We assessed risk of bias using the criteria described in the Cochrane Handbook for Systematic Reviews of Interventions. We included six trials with a total of 1063 participants. We found no significant differences in the primary outcomes (patient compliance and global state) between psychoeducational interventions using ICT and standard care.Technology-mediated psychoeducation improved mental state in the short term (n = 84, 1 RCT, RR 0.75, 95% CI 0.56 to 1.00; n = 30, 1 RCT, MD -0.51, 95% CI -0.90 to -0.12) but not global state (n = 84, 1 RCT, RR 1.07, 95% CI 0.82 to 1.42). Knowledge and insight were not effected (n = 84, 1 RCT, RR 0.89, 95% CI 0.68 to 1.15; n = 84, 1 RCT, RR 0.77, 95% CI 0.58 to 1.03). People allocated to technology-mediated psychoeducation perceived that they received more social support than people allocated to the standard care group (n = 30, 1 RCT, MD 0.42, 95% CI 0.04 to 0.80).When technology-mediated psychoeducation was used as an adjunct to standard care it did not improve general compliance in the short term (n = 291, 3 RCTs, RR for leaving the study early 0.81, 95% CI 0.55 to 1.19) or in the long term (n = 434, 2 RCTs, RR for leaving the study early 0.70, 95% CI 0.39 to 1.25). However, it did improve compliance with medication in the long term (n = 71, 1 RCT, RR 0.45, 95% CI 0.27 to 0.77). Adding technology-mediated psychoeducation on top of standard care did not clearly improve either general mental state, negative or positive symptoms, global state, level of knowledge or quality of life. However, the results were not consistent regarding level of knowledge and satisfaction with treatment.When technology-mediated psychoeducation plus standard care was compared with patient education not using technology the only outcome reported was satisfaction with treatment. There were no differences between groups. Using ICT to deliver psychoeducational interventions has no clear effects compared with standard care, other methods of delivering psychoeducation and support, or both. Researchers used a variety of methods of delivery and outcomes, and studies were few and underpowered. ICT remains a promising method of delivering psychoeducation; the equivocal findings of this review should not postpone high-quality research in this area.

A web-based multidomain lifestyle intervention with connected devices for older adults: research protocol of the eMIND pilot randomized controlled trial.

PubMed

Pothier, Kristell; Soriano, G; Lussier, M; Naudin, A; Costa, N; Guyonnet, S; Piau, A; Ousset, P J; Nourhashemi, F; Vellas, B; de Souto Barreto, P

2018-01-24

Multidomain interventions composed of nutritional counseling, exercise and cognitive trainings have shown encouraging results as effective preventive strategies delaying age-related declines. However, these interventions are time- and resource-consuming. The use of Information and Communication Technologies (ICT) might facilitate the translation from research into real-world practice and reach a massive number of people. This article describes the protocol of the eMIND study, a randomized controlled trial (RCT) using a web-based multidomain intervention for older adults. One hundred and twenty older adults (≥ 65 years), with a spontaneous memory complaint, will be randomly assigned to a six-month web-based multidomain (nutritional counseling, physical and cognitive trainings) intervention group with a connected accelerometer (number of steps, energy expenditure), or to a control group with access to general information on healthy aging plus the accelerometer, but no access to the multidomain intervention. The main outcome is the feasibility/acceptability of the web-based intervention. Secondary clinical outcomes include: cognitive functions, physical performance, nutritional status and cost-effectiveness. We expect a high amount of adherers (ie, > 75% compliance to the protocol) to reflect the feasibility. Acceptability, assessed through interviews, should allow us to understand motivators and barriers to this ICT intervention. We also expect to provide data on its effects on various clinical outcomes and efficiency. The eMIND study will provide crucial information to help developing a future and larger web-based multidomain lifestyle RCT, which should facilitate the translation of this ICT intervention from the research world into real-life clinical practice for the healthcare of older adults.

Preventing lower extremity injury in elite orienteerers: study protocol for a randomised controlled trial

PubMed Central

Halvarsson, Bodil

2018-01-01

Background The high physical load associated with running through uneven terrain contributes toorienteerers being exposed to high injury risk, where the majority of injuries are located in the lower extremities. Specific training programmes have been effective at reducing injury risk in sports. Yet no trial has been conducted in elite orienteering. The aim of this study is to investigate the effectiveness of a specific training programme in preventing lower extremity injury in adult elite orienteerers. Study design Randomised controlled trial (RCT). Methods Seventy-two Swedish elite orienteerers, aged 18–40 years, are allocated to an intervention or control group. The intervention group performs four specific exercises, with three difficult levels intensified every second week over the first 4 weeks, targeting strength, flexibility and coordination of the lower extremity. The exercises are completed four times a week (10 min per session) in conjunction with normal training over 14 weeks. Injury data are collected every second week using a valid injury questionnaire distributed by text messages over 14 weeks. The primary outcome is number of substantial injuries in the lower extremity. The secondary outcomes are incidence of ankle sprains and the average substantial injury prevalence across 14 weeks. Discussion Due to high injury risk and lack of injury prevention trials in orienteering, an RCT investigating the effect of a specific exercise programme in preventing lower extremity injury is warranted. The results of this trial will be beneficial to orienteerers, clubs and federations, and increase our understanding on how lower extremity injuries can be prevented in a physically challenging sport. Trial registration number NCT03408925. PMID:29707231

Communication skills training for mental health professionals working with people with severe mental illness.

PubMed

Papageorgiou, Alexia; Loke, Yoon K; Fromage, Michelle

2017-06-13

Research evidence suggests that both mental health professionals and people with severe mental health illness such as schizophrenia or schizoaffective disorder find it difficult to communicate with each other effectively about symptoms, treatments and their side effects so that they reach a shared understanding about diagnosis, prognosis and treatment. Effective use of communication skills in mental health interactions could be associated with increased patient satisfaction and adherence to treatment. To review the effectiveness of communication skills training for mental health professionals who work with people with severe mental illness. We searched the Cochrane Schizophrenia Trials Register (latest search 17 February, 2016) which is compiled by systematic searches of major resources (including AMED, BIOSIS, CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings. There are no language, date, document type, or publication status limitations for inclusion of records into the register. All relevant randomised clinical trials (RCTs) that focused on communication skills training (CST) for mental health professionals who work with people with severe mental illness compared with those who received standard or no training. We sought a number of primary (patient adherence to treatment and attendance at scheduled appointments as well as mental health professionals' satisfaction with the training programme) and secondary outcomes (patients' global state, service use, mental state, patient satisfaction, social functioning, quality of life). RCTs where the unit of randomisation was by cluster (e.g. healthcare facility) were also eligible for inclusion. We included one trial that met our inclusion criteria and reported useable data. We independently selected studies, quality assessed them and extracted data. For binary outcomes, we planned to calculate standard estimates of the risk ratio (RR) and their 95% confidence intervals (CI) using a fixed-effect model. For continuous outcomes, we planned to estimate the mean difference (MD) between groups, or obtain the adjusted mean difference (aMD) where available for cluster-randomised trials. If heterogeneity had been identified, we would have explored this using a random-effects model. We used GRADE to create a 'Summary of findings' table and we assessed risk of bias for the one included study. We included one pilot cluster-RCT that recruited a total of 21 psychiatrists and 97 patients. The psychiatrists were randomised to a training programme in communication skills, compared to a no specific training (NST) programme. The trial provided useable data for only one of our prestated outcomes of interest, patient satisfaction. The trial did not report global state but did report mental state and, as global state data were not available, we included these mental state data in the 'Summary of findings' table. There was high risk of bias from attrition because of substantial losses to follow-up and incomplete outcome data.Patient satisfaction was measured as satisfaction with treatment and 'experience of therapeutic relationship' at medium term (five months). Satisfaction with treatment was similar between the CST and NST group using the Client Satisfaction Questionnaire (CSQ-8) (1 RCT, n = 66/97*, aMD 1.77 95% CI - 0.13 to 3.68, low-quality evidence). When comparing patient experience of the therapeutic relationship using the STAR-P scale, participants in the CST group rated the therapeutic relationship more positively than participants in the NST group (1 RCT, n = 63/97, aMD 0.21 95% CI 0.01 to 0.41, low-quality evidence).Mental state scores on the Positive and Negative Syndrome Scale (PANSS) were similar between treatment groups for general symptoms (1 RCT, n = 59/97, aMD 4.48 95% CI -2.10 to 11.06, low-quality evidence), positive symptoms (1 RCT, n = 59/97, aMD -0.23, 95% CI -2.91 to 2.45, low-quality evidence) and negative symptoms (1 RCT, n = 59/97, aMD 3.42, 95%C CI -0.24 to 7.09, low-quality evidence).No data were available for adherence to treatment, service use or quality of life.* Of the total of 97 randomised participants, 66 provided data. The evidence available is from one pilot cluster-randomised controlled trial, it is not adequate enough to draw any robust conclusions. There were relatively few good quality data and the trial is too small to highlight differences in most outcome measures. Adding a CST programme appears to have a modest positive effect on patients' experiences of the therapeutic relationship. More high-quality research is needed in this area.

How does routinely delivered cognitive-behavioural therapy for gambling disorder compare to "gold standard" clinical trial?

PubMed

Smith, David P; Fairweather-Schmidt, A Kate; Harvey, Peter W; Battersby, Malcolm W

2018-03-01

Currently, it is unknown whether treatment outcomes derived from randomized controlled trials (RCTs) of cognitive-behavioural therapy (CBT) for problem gamblers still hold when applied to patients seen in routine practice. Thus, data from an RCT of cognitive therapy versus exposure therapy for problem gambling versus patients of a gambling help service were compared. Assessments of problem gambling severity, psychosocial impairment, and alcohol use were undertaken at baseline and post-treatment and evaluated within a counterfactual framework. Findings showed that the contrast between routine CBT for pokies and horse betting had a significant effect, indicative of a 62% lower gambling urge score if routine CBT recipients had all been horse/track betters opposed to gambling with "pokies." However, the majority of contrasts indicated therapeutic outcomes achieved in routine CBT treatments were of equivalent robustness relative to RCT conditions. The present findings infer routine practice treatment outcomes are as efficacious as those generated in RCT contexts. Copyright © 2017 John Wiley & Sons, Ltd.

Returning to the bedside: using the history and physical examination to identify rotator cuff tears.

PubMed

Litaker, D; Pioro, M; El Bilbeisi, H; Brems, J

2000-12-01

To determine the value of elements of the bedside history and physical examination in predicting arthrography results in older patients with suspected rotator cuff tear (RCT). Retrospective chart review Orthopedic practice limited to disorders of the shoulder 448 consecutive patients with suspected RCT referred for arthrography over a 4-year period Presence of partial or complete RCT on arthrogram 301 patients (67.2%) had evidence of complete or partial RCT. Clinical findings in the univariate analysis most closely associated with rotator cuff tear included infra- and supraspinatus atrophy (P < .001), weakness with either elevation (P < .001) or external rotation (P < .001), arc of pain (P = .004), and impingement sign (P = .01). Stepwise logistic regression based on a derivation dataset (n = 191) showed that weakness with external rotation (Adjusted Odds Ratio (AOR) 6.96 (3.09, 13.03)), age > or = 65 (AOR 4.05(2.47, 16.07)), and night pain (AOR 2.61 (1.004, 7.39)) best predicted the presence of RCT. A five-point scoring system developed from this model was applied in the remaining patient sample (n = 216) to test validity. No significant differences in performance were noted using ROC curve comparison. Using likelihood ratios, a clinical score = 4 was superior in predicting RCT to the diagnostic prediction of an expert clinician. This score had specificity equivalent to magnetic resonance imaging or ultrasonography in diagnosis of RCT. The presence of three simple features in the history and physical examination of the shoulder can identify RCT efficiently. This approach offers a valuable strategy to diagnosis at the bedside without compromising sensitivity or specificity.

Statistical Power for the Comparative Regression Discontinuity Design With a Pretest No-Treatment Control Function: Theory and Evidence From the National Head Start Impact Study.

PubMed

Tang, Yang; Cook, Thomas D

2018-01-01

The basic regression discontinuity design (RDD) has less statistical power than a randomized control trial (RCT) with the same sample size. Adding a no-treatment comparison function to the basic RDD creates a comparative RDD (CRD); and when this function comes from the pretest value of the study outcome, a CRD-Pre design results. We use a within-study comparison (WSC) to examine the power of CRD-Pre relative to both basic RDD and RCT. We first build the theoretical foundation for power in CRD-Pre, then derive the relevant variance formulae, and finally compare them to the theoretical RCT variance. We conclude from this theoretical part of this article that (1) CRD-Pre's power gain depends on the partial correlation between the pretest and posttest measures after conditioning on the assignment variable, (2) CRD-Pre is less responsive than basic RDD to how the assignment variable is distributed and where the cutoff is located, and (3) under a variety of conditions, the efficiency of CRD-Pre is very close to that of the RCT. Data from the National Head Start Impact Study are then used to construct RCT, RDD, and CRD-Pre designs and to compare their power. The empirical results indicate (1) a high level of correspondence between the predicted and obtained power results for RDD and CRD-Pre relative to the RCT, and (2) power levels in CRD-Pre and RCT that are very close. The study is unique among WSCs for its focus on the correspondence between RCT and observational study standard errors rather than means.

Interventions for the prevention of postoperative ear discharge after insertion of ventilation tubes (grommets) in children.

PubMed

Syed, Mohammed Iqbal; Suller, Sharon; Browning, George G; Akeroyd, Michael A

2013-04-30

Grommets are frequently inserted in children's ears for acute otitis media and otitis media with effusion. A common complication is postoperative ear discharge (otorrhoea). A wide range of treatments are used to prevent the discharge, but there is no consensus on whether or not intervention is necessary nor which is the most effective intervention. To assess the effectiveness of prophylactic interventions, both topical and systemic, in reducing the incidence of otorrhoea following the surgical insertion of grommets in children. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 3 July 2012. We included randomised controlled trials (RCTs) that compared the efficacy of prophylactic interventions against placebo/control and/or with other prophylactic interventions for postoperative otorrhoea in children. Two review authors independently assessed study eligibility and risk of bias, and extracted data. The outcome data were dichotomous for all the included trials. We calculated individual and pooled risk ratios (RR) using the Mantel-Haenszel fixed-effect method. We also calculated the numbers needed to treat to benefit (NNTB). We found 15 eligible RCTs (2476 children, aged from four months to 17 years). We graded seven RCTs as being at a low risk of bias (n = 926 children) and for an eighth RCT we also graded two of the arms as being at a low risk of bias. We graded the other seven trials as being at a high risk of bias.For a single application at surgery, there was evidence from two low risk of bias trials that at two weeks postoperatively the risk of otorrhoea was reduced by multiple saline washouts (from 30% to 16%; RR 0.52, 95% confidence interval (CI) 0.27 to 1.00; NNTB 7; one RCT; 140 children) and antibiotic/steroid ear drops (from 9% to 1%; RR 0.13, 95% CI 0.03 to 0.57; NNTB 13; one RCT; 322 ears). A meta-analysis of two low risk of bias trials (222 ears) failed to find an effect of a single application of antibiotic/steroid ear drops at four to six weeks postoperatively.For a prolonged application of an intervention, there was evidence from four low risk of bias trials that the risk of otorrhoea was reduced two weeks postoperatively by antibiotic ear drops (from 15% to 8%; RR 0.54, 95% CI 0.30 to 0.97; NNTB 15; one RCT; 372 children), antibiotic/steroid ear drops (from 39% to 5%; RR 0.13, 95% CI 0.05 to 0.31; NNTB 3; one RCT; 200 children), aminoglycoside/steroid ear drops (from 15% to 5%; RR 0.37, 95% CI 0.18 to 0.74; NNTB 11; one RCT; 356 children) or oral antibacterial agents/steroids (from 39% to 5%; RR 0.13, 95% CI 0.03 to 0.51; NNTB 3; one RCT; 77 children).Only one trial assessed the secondary outcome of ototoxicity, but no effect was found. There were no trials that assessed quality of life. Our review found that each of the following were effective at reducing the rate of otorrhoea up to two weeks following surgery: (1) multiple saline washouts at surgery, (2) a single application of topical antibiotic/steroid drops at surgery, (3) a prolonged application of topical drops (namely antibiotic ear drops, antibiotic/steroid eardrops or aminoglycoside/steroid ear drops) and (4) a prolonged application of oral antibacterial agents/steroids. However, the rate of otorrhoea between RCTs varied greatly and the higher the rates of otorrhoea within a RCT, the smaller the NNTB for therapy.We conclude that if a surgeon has a high rate of postoperative otorrhoea in children then either saline irrigation or antibiotic ear drops at the time of surgery would significantly reduce that rate. If topical drops are chosen, it is suggested that to reduce the cost and potential for ototoxic damage this be a single application at the time of surgery and not prolonged thereafter.

What can economics add to health technology assessment? Please not just another cost-effectiveness analysis!

PubMed

Bridges, John Fp

2006-02-01

Evidence based medicine is not only important for clinical practice, but national governments have embraced it through health technology assessment (HTA). HTA combines data from randomized controlled trials (RCT) and observational studies with an economic component (among other issues). HTA, however, is not taking full advantage of economics. This paper presents five areas in which economics may improve not only HTA, but the RCT methods that underpin it. HTA needs to live up to its original agenda of being a interdisciplinary field and draw methods not just from biostatistics, but from a range of discipline, including economics. By focusing only on cost effectiveness analysis (CEA), however, we go nowhere close to fulfilling this potential.

Evidence-based medicine in obstetrics: can levels B and C recommendations be elevated to level A recommendations?

PubMed Central

Chauhan, Suneet P; Chang, Eugene; Brost, Brian; Assel, Barbara; Baxter, Jason; Smith, James A; Grobman, Robert; Berghella, Vincenzo; Scardo, James A; Magann, Everett F; Morrison, John C

2009-01-01

In this study, 65% (132/195) of level B/C obstetric recommendations are amenable to randomized clinical trials (RCTs) and seven were identified as most needed. The purpose of the survey was to evaluate levels B and C recommendations in obstetric practice bulletins (PBs) regarding the feasibility of performing RCT to elevate each subject to level A evidence. Eleven geographically dispersed physicians with experience in research reviewed levels B and C recommendations for the ethical and logistical feasibility of performing an RCT. In the 35 obstetric PBs, 195 level B/C recommendations were reviewed. The majority considered 47 (24%) topics unethical for an RCT and thought 16 (11%) did not need an RCT, thus leaving 132 (67%) levels B and C recommendations available for an RCT. Two-thirds of levels B and C recommendations in obstetric PB are amenable to RCTs and potentially becoming level A evidence. PMID:27582813

Degree of tendon degeneration and stage of rotator cuff disease.

PubMed

Jo, Chris Hyunchul; Shin, Won Hyoung; Park, Ji Wan; Shin, Ji Sun; Kim, Ji Eun

2017-07-01

While tendon degeneration has been known to be an important cause of rotator cuff disease, few studies have objectively proven the association of tendon degeneration and rotator cuff disease. The purpose of this study was to investigate changes of tendon degeneration with respect to the stage of rotator cuff disease. A total of 48 patients were included in the study: 12 with tendinopathy, 12 with a partial-thickness tear (pRCT), 12 with a full-thickness tear (fRCT), and 12 as the control. A full-thickness supraspinatus tendon sample was harvested en bloc from the middle portion between the lateral edge and the musculotendinous junction of the tendon using a biopsy punch with a diameter of 3 mm. Harvested samples were evaluated using a semi-quantitative grading scale with 7 parameters after haematoxylin and eosin staining. There was no significant difference in age, gender, symptom duration, and Kellgren-Lawrence grade between the groups except for the global fatty degeneration index. All of the seven parameters were significantly different between the groups and could be categorized as follows: early responders (fibre structure and arrangement), gradual responder (rounding of the nuclei), after-tear responders (cellularity, vascularity, and stainability), and late responder (hyalinization). The total degeneration scores were not significantly different between the control (6.08 ± 1.16) and tendinopathy (6.67 ± 1.83) (n.s.). However, the score of pRCT group (10.42 ± 1.31) was greater than that of tendinopathy (P < 0.001), and so was the score of fRCT (12.33 ± 1.15) than that of pRCT (p = 0.009). This study showed that the degeneration of supraspinatus tendon increases as the stage of rotator cuff disease progresses from tendinopathy to pRCT, and then to fRCT. The degree of degeneration of tendinopathy was not different from that of normal but aged tendons, and significant tendon degeneration began from the stage of pRCT. The clinical relevance of the study is that strategies and goals of the treatment for rotator cuff disease should be specific to its stage, in order to prevent disease progression for tendinopathy and pRCT, as well to restore the structural integrity for fRCT. Diagnostic, Level I.

Platelet-rich plasma injections in the treatment of chronic rotator cuff tendinopathy: a randomized controlled trial with 1-year follow-up.

PubMed

Kesikburun, Serdar; Tan, Arif Kenan; Yilmaz, Bilge; Yaşar, Evren; Yazicioğlu, Kamil

2013-11-01

Rotator cuff tendinopathy (RCT) is a significant source of disability and loss of work. Platelet-rich plasma (PRP) has been suggested to be beneficial in the treatment of RCT. To investigate the effect of PRP injections on pain and shoulder functions in patients with chronic RCT. Randomized controlled trial; Level of evidence, 1. A total of 40 patients, 18 to 70 years of age, with (1) a history of shoulder pain for >3 months during overhead-throwing activities, (2) MRI findings of RCT or partial tendon ruptures, and (3) a minimum 50% reduction in shoulder pain with subacromial injections of an anesthetic were included in this placebo-controlled, double-blind randomized clinical trial. Patients were randomized into a PRP group (n = 20) or placebo group (n = 20). Patients received an ultrasound-guided injection into the subacromial space that contained either 5 mL of PRP prepared from autologous venous blood or 5 mL of saline solution. All patients underwent a 6-week standard exercise program. Outcome measures (Western Ontario Rotator Cuff Index [WORC], Shoulder Pain and Disability Index [SPADI], 100-mm visual analog scale [VAS] of shoulder pain with the Neer test, and shoulder range of motion) were assessed at baseline and at 3, 6, 12, and 24 weeks and 1 year after injection. Comparison of the patients revealed no significant difference between the groups in WORC, SPADI, and VAS scores at 1-year follow-up (P = .174, P = .314, and P = .904, respectively). Similar results were found at other assessment points. Within each group, the WORC, SPADI, and VAS scores showed significant improvements compared with baseline at all time points (P < .001). In the range of motion measures, there were no significant group × time interactions. At 1-year follow-up, a PRP injection was found to be no more effective in improving quality of life, pain, disability, and shoulder range of motion than placebo in patients with chronic RCT who were treated with an exercise program.

The effect of an outdoor activities' intervention delivered by older volunteers on the quality of life of older people with severe mobility limitations: a randomized controlled trial.

PubMed

Rantanen, Taina; Äyräväinen, Irma; Eronen, Johanna; Lyyra, Tiinamari; Törmäkangas, Timo; Vaarama, Marja; Rantakokko, Merja

2015-04-01

Older community-living disabled people often have unmet activity needs and participation restrictions potentially reducing their quality of life (QoL). We examined the effects of an individualized out-of-home activity intervention delivered by volunteers on QoL among community-living older people, who have difficulty accessing the outdoors independently. Volunteering, Access to Outdoor Activities and Wellbeing in Older People (VOW; ISRCTN56847832) was a two-arm randomized single-blinded, controlled effectiveness trial (RCT) in Jyväskylä, Finland. The inclusion criteria were: age 65 or over, severe mobility limitation, able to communicate, and agree to participate in a RCT. Each intervention group member was assigned a trained volunteer with whom out-of-home activities were done once a week for 3 months (e.g., running errands or recreational activities). The primary outcome was the environmental subscore of QoL assessed with WHOQOL-BREF. Secondary outcomes were the overall QoL, physical capacity, psychological well-being, and social relationships assessed with WHOQOL_BREF and lower-extremity performance assessed with Short Physical Performance Battery (SPPB). 121 people aged 67-92 years (mean age 81.9 years, SD 5.9, 90 % women) were randomized. No treatment effect on the environmental QoL subscore was observed, but for physical capacity subscore a significant treatment effect was observed (General Linear Model, Group by Time p = 0.001). No effects were observed for the other QoL subscores or for SPPB score. This study suggests that individualized out-of-home activity intervention delivered by volunteers may influence the QoL of old severely mobility-limited community-living people in a positive way. Further studies are needed to better understand how to improve QoL of older disabled community-living people and potentially buffer them against more severe care needs and institutionalization.

Does rectal indomethacin eliminate the need for prophylactic pancreatic stent placement in patients undergoing high-risk ERCP? Post hoc efficacy and cost-benefit analyses using prospective clinical trial data.

PubMed

Elmunzer, B Joseph; Higgins, Peter D R; Saini, Sameer D; Scheiman, James M; Parker, Robert A; Chak, Amitabh; Romagnuolo, Joseph; Mosler, Patrick; Hayward, Rodney A; Elta, Grace H; Korsnes, Sheryl J; Schmidt, Suzette E; Sherman, Stuart; Lehman, Glen A; Fogel, Evan L

2013-03-01

A recent large-scale randomized controlled trial (RCT) demonstrated that rectal indomethacin administration is effective in addition to pancreatic stent placement (PSP) for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. We performed a post hoc analysis of this RCT to explore whether rectal indomethacin can replace PSP in the prevention of PEP and to estimate the potential cost savings of such an approach. We retrospectively classified RCT subjects into four prevention groups: (1) no prophylaxis, (2) PSP alone, (3) rectal indomethacin alone, and (4) the combination of PSP and indomethacin. Multivariable logistic regression was used to adjust for imbalances in the prevalence of risk factors for PEP between the groups. Based on these adjusted PEP rates, we conducted an economic analysis comparing the costs associated with PEP prevention strategies employing rectal indomethacin alone, PSP alone, or the combination of both. After adjusting for risk using two different logistic regression models, rectal indomethacin alone appeared to be more effective for preventing PEP than no prophylaxis, PSP alone, and the combination of indomethacin and PSP. Economic analysis revealed that indomethacin alone was a cost-saving strategy in 96% of Monte Carlo trials. A prevention strategy employing rectal indomethacin alone could save approximately $150 million annually in the United States compared with a strategy of PSP alone, and $85 million compared with a strategy of indomethacin and PSP. This hypothesis-generating study suggests that prophylactic rectal indomethacin could replace PSP in patients undergoing high-risk ERCP, potentially improving clinical outcomes and reducing healthcare costs. A RCT comparing rectal indomethacin alone vs. indomethacin plus PSP is needed.

Effect of phylloquinone (vitamin K1) supplementation for 12 months on the indices of vitamin K status and bone health in adult patients with Crohn's disease.

PubMed

O'Connor, Eibhlís M; Grealy, Geraldine; McCarthy, Jane; Desmond, Alan; Craig, Orla; Shanahan, Fergus; Cashman, Kevin D

2014-10-14

Although epidemiological findings support a role for vitamin K status in the improvement of bone indices in adult patients with Crohn's disease (CD), this needs to be confirmed in double-blind, randomised controlled trials (RCT) with phylloquinone (vitamin K1). By conducting two RCT, the present study aimed to first establish whether supplementation with 1000 μg of phylloquinone daily near-maximally suppresses the percentage of undercarboxylated osteocalcin in serum (%ucOC; marker of vitamin K status) in adult patients with CD currently in remission as it does in healthy adults and second determine the effect of supplementation with phylloquinone at this dose for 12 months on the indices of bone turnover and bone mass. The initial dose-ranging RCT was conducted in adult patients with CD (n 10 per group) using 0 (placebo), 1000 or 2000 μg of phylloquinone daily for 2 weeks. In the main RCT, the effect of placebo v. 1000 μg vitamin K/d (both co-administered with Ca (500 mg/d) and vitamin D3 (10 μg/d)) for 12 months (n 43 per group) on the biochemical indices of bone turnover (determined by enzyme immunoassay) and bone mass (determined by dual-energy X-ray absorptiometry) were investigated. At baseline, the mean %ucOC was 47 %, and this was suppressed upon supplementation with 1000 μg of phylloquinone daily ( - 81 %; P< 0·01) and not suppressed further by 2000 μg of phylloquinone daily. Compared with the placebo, supplementation with 1000 μg of phylloquinone daily for 12 months had no significant effect (P>0·1) on bone turnover markers or on the bone mass of the lumbar spine or femur, but modestly increased (P< 0·05) the bone mass of the total radius. Despite near maximal suppression of serum %ucOC, supplementation with 1000 μg of phylloquinone daily (with Ca and vitamin D3) had no effect on the indices of bone health in adult CD patients with likely vitamin K insufficiency.

Promoting the uptake of HIV testing among men who have sex with men: systematic review of effectiveness and cost-effectiveness.

PubMed

Lorenc, Theo; Marrero-Guillamón, Isaac; Aggleton, Peter; Cooper, Chris; Llewellyn, Alexis; Lehmann, Angela; Lindsay, Catriona

2011-06-01

What interventions are effective and cost-effective in increasing the uptake of HIV testing among men who have sex with men (MSM)? A systematic review was conducted of the following databases: AEGIS, ASSIA, BL Direct, BNI, Centre for Reviews and Dissemination, Cochrane Database of Systematic Reviews, CINAHL, Current Contents Connect, EconLit, EMBASE, ERIC, HMIC, Medline, Medline In-Process, NRR, PsychINFO, Scopus, SIGLE, Social Policy and Practice, Web of Science, websites, journal hand-searching, citation chasing and expert recommendations. Prospective studies of the effectiveness or cost-effectiveness of interventions (randomised controlled trial (RCT), controlled trial, one-group or any economic analysis) were included if the intervention aimed to increase the uptake of HIV testing among MSM in a high-income (Organization for Economic Co-operation and Development) country. Quality was assessed and data were extracted using standardised tools. Results were synthesised narratively. Twelve effectiveness studies and one cost-effectiveness study were located, covering a range of intervention types. There is evidence that rapid testing and counselling in community settings (one RCT), and intensive peer counselling (one RCT), can increase the uptake of HIV testing among MSM. There are promising results regarding the introduction of opt-out testing in sexually transmitted infection clinics (two one-group studies). Findings regarding other interventions, including bundling HIV tests with other tests, peer outreach in community settings, and media campaigns, are inconclusive. Findings indicate several promising approaches to increasing HIV testing among MSM. However, there is limited evidence overall, and evidence for the effectiveness of key intervention types (particularly peer outreach and media campaigns) remains lacking.

A Kantian claim permitting the randomised clinical trial.

PubMed

Katz, P

2001-01-01

Among the most contested aspects of medical research is the randomized clinical trial (RCT). While the majority of arguments justifying the RCT and its use in medical research rest within a utilitarian framework, many Kantians claim that a deontological ethical framework is prohibitive of the use RCTs in medical research. This paper argues that, in fact, the RCT is permissible within a deontological framework.

Effects of Dietary Flavonoids on Reverse Cholesterol Transport, HDL Metabolism, and HDL Function12

PubMed Central

Millar, Courtney L; Duclos, Quinn

2017-01-01

Strong experimental evidence confirms that HDL directly alleviates atherosclerosis. HDL particles display diverse atheroprotective functions in reverse cholesterol transport (RCT), antioxidant, anti-inflammatory, and antiapoptotic processes. In certain inflammatory disease states, however, HDL particles may become dysfunctional and proatherogenic. Flavonoids show the potential to improve HDL function through their well-documented effects on cellular antioxidant status and inflammation. The aim of this review is to summarize the basic science and clinical research examining the effects of dietary flavonoids on RCT and HDL function. Based on preclinical studies that used cell culture and rodent models, it appears that many flavonoids (e.g., anthocyanidins, flavonols, and flavone subclasses) influence RCT and HDL function beyond simple HDL cholesterol concentration by regulating cellular cholesterol efflux from macrophages and hepatic paraoxonase 1 expression and activity. In clinical studies, dietary anthocyanin intake is associated with beneficial changes in serum biomarkers related to HDL function in a variety of human populations (e.g., in those who are hyperlipidemic, hypertensive, or diabetic), including increased HDL cholesterol concentration, as well as HDL antioxidant and cholesterol efflux capacities. However, clinical research on HDL functionality is lacking for some flavonoid subclasses (e.g., flavanols, flavones, flavanones, and isoflavones). Although there has been a tremendous effort to develop HDL-targeted drug therapies, more research is warranted on how the intake of foods or specific nutrients affects HDL function. PMID:28298268

[Education for patients with fibromyalgia. A systematic review of randomised clinical trials].

PubMed

Elizagaray-Garcia, Ignacio; Muriente-Gonzalez, Jorge; Gil-Martinez, Alfonso

2016-01-16

To analyse the effectiveness of education about pain, quality of life and functionality in patients with fibromyalgia. The search for articles was carried out in electronic databases. Eligibility criteria were: controlled randomised clinical trials (RCT), published in English and Spanish, that had been conducted on patients with fibromyalgia, in which the therapeutic procedure was based on patient education. Two independent reviewers analysed the methodological quality using the PEDro scale. Five RCT were selected, of which four offered good methodological quality. In three of the studies, patient education, in combination with another intervention based on therapeutic exercise, improved the outcomes in the variables assessing pain and quality of life as compared with the same procedures performed separately. Moreover, an RCT with a high quality methodology showed that patient education activated inhibitory neural pathways capable of lowering the level of pain. The quantitative analysis yields strong-moderate evidence that patient education, in combination with other therapeutic exercise procedures, offers positive results in the variables pain, quality of life and functionality. Patient education in itself has not proved to be effective for pain, quality of life or functionality in patients with fibromyalgia. There is strong evidence, however, of the effectiveness of combining patient education with exercise and active strategies for coping with pain, quality of life and functionality in the short, medium and long term in patients with fibromyalgia.

Role of oral zinc supplementation for reduction of neonatal hyperbilirubinemia: a systematic review of current evidence.

PubMed

Sharma, Deepak; Farahbakhsh, Nazanin; Sharma, Pradeep; Shastri, Sweta

2017-08-01

Neonatal hyperbilirubinemia is frequently seen condition in the NICU. Oral zinc has been tried for the prevention of hyperbilirubinemia. To evaluate the role of oral zinc supplementation for reduction of neonatal hyperbilirubinemia in term and preterm infants. The literature search was done for various randomized control trial (RCT) by searching the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Scopus, Index Copernicus, African Index Medicus (AIM), Thomson Reuters (ESCI), Chemical Abstracts Service (CAS) and other data base. This review included six RCT that fulfilled inclusion criteria. One study evaluated the role of zinc in very low birth weight (VLBW) infants and remaining enrolled neonates  ≥35 weeks of gestation. The dose of zinc varied from 5 to 20 mg/day and duration from 5-7 days. All the studies used zinc sulfate, only one study used zinc gluconate. The total neonates enrolled in these different RCT are 749. Role of zinc in the prevention of neonatal hyperbilirubinemia is not supported by the current evidence. Only one study was able to show reduction in the mean TSB level and requirement of phototherapy with zinc, and the remaining studies did not report any positive effect. None of the studies showed any effect on the duration of phototherapy, incidence of phototherapy, age of starting of phototherapy and any serious adverse effect.

Anthropometrics and Body Composition by Dual Energy X-Ray in Children of Obese Women: A Follow-Up of a Randomized Controlled Trial (the Lifestyle in Pregnancy and Offspring [LiPO] Study)

PubMed Central

Tanvig, Mette; Vinter, Christina A.; Jørgensen, Jan S.; Wehberg, Sonja; Ovesen, Per G.; Lamont, Ronald F.; Beck-Nielsen, Henning

2014-01-01

Objective In obese women, 1) to assess whether lower gestational weight gain (GWG) during pregnancy in the lifestyle intervention group of a randomized controlled trial (RCT) resulted in differences in offspring anthropometrics and body composition, and 2) to compare offspring outcomes to a reference group of children born to women with a normal Body Mass Index (BMI). Research design and methods The LiPO (Lifestyle in Pregnancy and Offspring) study was an offspring follow-up of a RCT with 360 obese pregnant women with a lifestyle intervention during pregnancy including dietary advice, coaching and exercise. The trial was completed by 301 women who were eligible for follow-up. In addition, to the children from the RCT, a group of children born to women with a normal BMI were included as a reference group. At 2.8 (range 2.5–3.2) years, anthropometrics were measured in 157 children of the RCT mothers and in 97 reference group children with Body Mass Index (BMI) Z-score as a primary outcome. Body composition was estimated by Dual Energy X-ray (DEXA) in 123 successful scans out of 147 (84%). Results No differences between randomized groups were seen in mean (95% C.I.) BMI Z-score (intervention group 0.06 [−0.17; 0.29] vs. controls −0.18 [−0.43; 0.05]), in the percentage of overweight or obese children (10.9% vs. 6.7%), in other anthropometrics, or in body composition values by DEXA. Outcomes between children from the RCT and the reference group children were not significantly different. Conclusions The RCT with lifestyle intervention in obese pregnant women did not result in any detectable effect on offspring anthropometrics or body composition by DEXA at 2.8 years of age. This may reflect the limited difference in GWG between intervention and control groups. Offspring of obese mothers from the RCT were comparable to offspring of mothers with a normal BMI. Trial registration clinicaltrials.gov NCT00530439, NCT01918319 and NCT01918423. URL: NCT00530439?term = NCT00530439&rank = 1, NCT01918319?term = NCT00530439&rank = 2 and NCT01918423?term = NCT00530439&rank = 3. PMID:24586896

A randomized clinical trial in preterm infants on the effects of a home-based early intervention with the 'CareToy System'

PubMed Central

Sgandurra, Giuseppina; Lorentzen, Jakob; Inguaggiato, Emanuela; Bartalena, Laura; Beani, Elena; Cecchi, Francesca; Dario, Paolo; Giampietri, Matteo; Greisen, Gorm; Herskind, Anna; Nielsen, Jens Bo; Rossi, Giuseppe; Cioni, Giovanni

2017-01-01

CareToy system is an innovative tele-rehabilitative tool, useful in providing intensive, individualized, home-based, family-centred Early Intervention (EI) in infants. Our aim was to evaluate, through a Randomized Clinical Trial (RCT) study, the effects of CareToy intervention on early motor and visual development in preterm infants. 41 preterm infants (range age: 3.0–5.9 months of corrected age) were enrolled and randomized into two groups, CareToy and Standard Care. 19 infants randomized in CareToy group performed a 4-week CareToy program, while 22 allocated to control group completed 4 weeks of Standard Care. Infant Motor Profile (IMP) was primary outcome measure, Alberta Infant Motor Scale (AIMS) and Teller Acuity Cards were secondary ones. Assessments were carried out at baseline (T0) and at the end of CareToy training or Standard Care period (T1). T1 was the primary endpoint. After RCT phase, 17 infants from control group carried out a 4-week CareToy program, while 18 infants from the CareToy group continued with Standard Care. At the end of this phase, infants were re-assessed at T2. In RCT phase, delta IMP total score and variation and performance sub-domains were significantly higher (P<0.050) in CareToy group if compared to Standard Care group. Similar results were found for Teller Acuity Cards, while no differences between groups were found for AIMS. No differences were found in any outcome measure results (T2-T0), between infants who started CareToy training before or after one month of standard care. This RCT study confirms the results of a previous pilot study, indicating that CareToy system can provide effective home-based EI. Trial Registration: This trial has been registered at www.clinicaltrials.gov (Identifier NCT01990183). PMID:28328946

The incidence and effect of fatty atrophy, positive tangent sign, and rotator cuff tears on outcomes after total shoulder arthroplasty.

PubMed

Choate, W Stephen; Shanley, Ellen; Washburn, Richard; Tolan, Stefan J; Salim, Tariq I; Tadlock, Josh; Shealy, Elizabeth C; Long, Catherine D; Crawford, Ashley E; Kissenberth, Michael J; Lonergan, Keith T; Hawkins, Richard J; Tokish, John M

2017-12-01

Treatment choices for total shoulder arthroplasty (TSA) in the absence of full-thickness rotator cuff tears (RCTs) are not clearly defined in current literature. This study investigated the prevalence and effect of preoperative partial-thickness RCTs and muscular degenerative changes on postoperative outcomes after TSA. Medical records and magnetic resonance imaging studies were reviewed for patients who underwent TSA for primary glenohumeral osteoarthritis with minimum 2-year follow-up to determine preoperative tear classification, Goutallier grade, and supraspinatus tangent sign. Postoperative pain on the visual analog scale, range of motion, and patient outcomes scores were obtained to correlate preoperative RCT status, Goutallier grading, tangent sign, and postoperative outcomes. Patients with full-thickness RCT on preoperative magnetic resonance imaging were excluded. Forty-five patients met all inclusion criteria (average age, 65 ± 10 years; average follow-up, 43 months). Of the patients undergoing TSA, 40% had a significant (>50% thickness) partial RCT. Grade 3 to 4 Goutallier changes were noted in 22% of all patients, and 13% demonstrated grade 3 to 4 changes in the context of no tear. Positive tangent sign was present in 7% of all patients. The preoperative Goutallier grade of the infraspinatus was significantly negatively correlated with postoperative forward elevation (P = .02) and external rotation (P = .05), but rotator cuff pathology, including tear status, Goutallier grade, and the presence of a tangent sign, did not correlate with postoperative functional outcome scores. Even in the absence of a full-thickness RCT, rotator cuff atrophy, fatty infiltration, and partial thickness tearing are common findings. Although postoperative range of motion is correlated to Goutallier changes of the infraspinatus, rotator cuff pathology is not correlated to outcomes after TSA; therefore, one may proceed with TSA without concern of their effect on postoperative outcomes. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Actor-partner effects associated with experiencing intimate partner violence or coercion among male couples enrolled in an HIV prevention trial

PubMed Central

2014-01-01

Background Intimate partner violence (IPV) and coercion have been associated with negative health outcomes, including increased HIV risk behaviors, among men who have sex with men (MSM). This is the first study to describe the prevalence and factors associated with experiencing IPV or coercion among US MSM dyads using the actor-partner interdependence model (APIM), an analytic framework to describe interdependent outcomes within dyads. Methods Among MSM couples enrolled as dyads in an HIV prevention randomized controlled trial (RCT), two outcomes are examined in this cross-sectional analysis: 1) the actor experiencing physical or sexual IPV from the study partner in the past 3-months and 2) the actor feeling coerced to participate in the RCT by the study partner. Two multilevel APIM logistic regression models evaluated the association between each outcome and actor, partner, and dyad-level factors. Results Of 190 individuals (95 MSM couples), 14 reported experiencing physical or sexual IPV from their study partner in the past 3 months (7.3%) and 12 reported feeling coerced to participate in the RCT by their study partner (6.3%). Results of multivariate APIM analyses indicated that reporting experienced IPV was associated (p < 0.1) with non-Black/African American actor race, lower actor education, and lower partner education. Reporting experienced coercion was associated (p < 0.1) with younger actor age and lower partner education. Conclusions These findings from an HIV prevention RCT for MSM show considerable levels of IPV experienced in the past 3-months and coercion to participate in the research study, indicating the need for screening tools and support services for these behaviors. The identification of factors associated with IPV and coercion demonstrate the importance of considering actor and partner effects, as well as dyadic-level effects, to improve development of screening tools and support services for these outcomes. PMID:24580732

Evidence for the effectiveness of Alexander Technique lessons in medical and health-related conditions: a systematic review.

PubMed

Woodman, J P; Moore, N R

2012-01-01

Complementary medicine and alternative approaches to chronic and intractable health conditions are increasingly being used, and require critical evaluation. The aim of this review was to systematically evaluate available evidence for the effectiveness and safety of instruction in the Alexander Technique in health-related conditions. PUBMED, EMBASE, PSYCHINFO, ISI Web-of-Knowledge, AMED, CINHAL-plus, Cochrane library and Evidence-based Medicine Reviews were searched to July 2011. Inclusion criteria were prospective studies evaluating Alexander Technique instruction (individual lessons or group delivery) as an intervention for any medical indication/health-related condition. Studies were categorised and data extracted on study population, randomisation method, nature of intervention and control, practitioner characteristics, validity and reliability of outcome measures, completeness of follow-up and statistical analyses.   Of 271 publications identified, 18 were selected: three randomised, controlled trials (RCTs), two controlled non-randomised studies, eight non-controlled studies, four qualitative analyses and one health economic analysis. One well-designed, well-conducted RCT demonstrated that, compared with usual GP care, Alexander Technique lessons led to significant long-term reductions in back pain and incapacity caused by chronic back pain. The results were broadly supported by a smaller, earlier RCT in chronic back pain. The third RCT, a small, well-designed, well-conducted study in individuals with Parkinson's disease, showed a sustained increased ability to carry out everyday activities following Alexander lessons, compared with usual care. The 15 non-RCT studies are also reviewed. Strong evidence exists for the effectiveness of Alexander Technique lessons for chronic back pain and moderate evidence in Parkinson's-associated disability. Preliminary evidence suggests that Alexander Technique lessons may lead to improvements in balance skills in the elderly, in general chronic pain, posture, respiratory function and stuttering, but there is insufficient evidence to support recommendations in these areas. © 2011 Blackwell Publishing Ltd.

Mediating the distal crime-drug relationship with proximal reactive criminal thinking.

PubMed

Walters, Glenn D

2016-02-01

This article describes the results of a study designed to test whether reactive criminal thinking (RCT) does a better job of mediating the crime → drug relationship than it does mediating the drug → crime relationship after the direct effects of crime on drug use/dependency and of drug use/dependency on crime have been rendered nonsignificant by control variables. All 1,170 male members of the Pathways to Desistance study (Mulvey, 2012) served as participants in the current investigation. As predicted, the total (unmediated) effects of crime on substance use/dependence and of substance use/dependence on crime were nonsignificant when key demographic and third variables were controlled, although the indirect (RCT-mediated) effect of crime on drug use was significant. Proactive criminal thinking (PCT), by comparison, failed to mediate either relationship. The RCT continued to mediate the crime → drug relationship and the PCT continued to not mediate either relationship when more specific forms of offending (aggressive, income) and substance use/dependence (drug use, substance-use dependency symptoms) were analyzed. This offers preliminary support for the notion that even when the total crime-drug effect is nonsignificant the indirect path from crime to reactive criminal thinking to drugs can still be significant. Based on these results, it is concluded that mediation by proximal reactive criminal thinking is a mechanism by which distal measures of crime and drug use/dependence are connected. (c) 2016 APA, all rights reserved).

A Yoga Intervention for Posttraumatic Stress: A Preliminary Randomized Control Trial.

PubMed

Jindani, Farah; Turner, Nigel; Khalsa, Sat Bir S

2015-01-01

Yoga may be effective in the reduction of PTSD symptomology. The purpose of this study was to evaluate the impact of a Kundalini Yoga (KY) treatment on PTSD symptoms and overall wellbeing. To supplement the current field of inquiry, a pilot randomized control trial (RCT) was conducted comparing an 8-session KY intervention with a waitlist control group. 80 individuals with current PTSD symptoms participated. Both groups demonstrated changes in PTSD symptomology but yoga participants showed greater changes in measures of sleep, positive affect, perceived stress, anxiety, stress, and resilience. Between-groups effect sizes were small to moderate (0.09-0.25). KY may be an adjunctive or alternative intervention for PTSD. Findings indicate the need for further yoga research to better understand the mechanism of yoga in relation to mental and physical health, gender and ethnic comparisons, and short- and long-term yoga practice for psychiatric conditions.

A Yoga Intervention for Posttraumatic Stress: A Preliminary Randomized Control Trial

PubMed Central

Jindani, Farah; Turner, Nigel; Khalsa, Sat Bir S.

2015-01-01

Yoga may be effective in the reduction of PTSD symptomology. The purpose of this study was to evaluate the impact of a Kundalini Yoga (KY) treatment on PTSD symptoms and overall wellbeing. To supplement the current field of inquiry, a pilot randomized control trial (RCT) was conducted comparing an 8-session KY intervention with a waitlist control group. 80 individuals with current PTSD symptoms participated. Both groups demonstrated changes in PTSD symptomology but yoga participants showed greater changes in measures of sleep, positive affect, perceived stress, anxiety, stress, and resilience. Between-groups effect sizes were small to moderate (0.09–0.25). KY may be an adjunctive or alternative intervention for PTSD. Findings indicate the need for further yoga research to better understand the mechanism of yoga in relation to mental and physical health, gender and ethnic comparisons, and short- and long-term yoga practice for psychiatric conditions. PMID:26366179

Exercise therapy for schizophrenia

PubMed Central

Gorczynski, Paul; Faulkner, Guy

2014-01-01

Background The health benefits of physical activity and exercise are well documented and these effects could help people with schizophrenia. Objectives To determine the mental health effects of exercise/physical activity programmes for people with schizophrenia or schizophrenia-like illnesses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (December 2008) which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. We also inspected references within relevant papers. Selection criteria We included all randomised controlled trials comparing any intervention where physical activity or exercise was considered to be the main or active ingredient with standard care or other treatments for people with schizophrenia or schizophrenia-like illnesses. Data collection and analysis We independently inspected citations and abstracts, ordered papers, quality assessed and data extracted. For binary outcomes we calculated a fixed-effect risk ratio (RR) and its 95% confidence interval (CI). Where possible, the weighted number needed to treat/ harm statistic (NNT/H) and its 95% confidence interval (CI), was also calculated. For continuous outcomes, endpoint data were preferred to change data. We synthesised non-skewed data from valid scales using a weighted mean difference (WMD). Main results Three randomised controlled trials met the inclusion criteria. Trials assessed the effects of exercise on physical and mental health. Overall numbers leaving the trials were similar. Two trials compared exercise to standard care and both found exercise to significantly improve negative symptoms of mental state (Mental Health Inventory Depression:1RCT, n=10, MD 17.50 CI 6.70 to 28.30, PANSS negative: 1RCT, n=10, MD -8.50 CI -11.11 to -5.89). No absolute effects were found for positive symptoms of mental state. Physical health improved significantly in the exercise group compared to those in standard care (1RCT, n=13, MD 79.50 CI 33.82 to 125.18), but no effect on peoples’ weight/BMI was apparent. One trial compared exercise with yoga and found that yoga had a better outcome for mental state (PANSS total: 1RCT, n=41, MD 14.95 CI 2.60 to 27.30). The same trial also found those in the yoga group had significantly better quality of life scores (WHOQOL Physical: 1RCT, n=41, MD -9.22 CI -18.86 to 0.42). Adverse effects (AIMS total scores) were, however, similar. Authors’ conclusions Results of this Cochrane review are similar to existing reviews that have examined the health benefits of exercise in this population. Although studies included in this review are small and used various measures of physical and mental health, results indicated that regular exercise programmes are possible in this population, and that they can have healthful effects on both the physical and mental health and well-being of individuals with schizophrenia. Larger randomised studies are required before any definitive conclusions can be drawn. PMID:20464730

Direct evidence for radiative charge transfer after inner-shell excitation and ionization of large clusters

NASA Astrophysics Data System (ADS)

Hans, Andreas; Stumpf, Vasili; Holzapfel, Xaver; Wiegandt, Florian; Schmidt, Philipp; Ozga, Christian; Reiß, Philipp; Ben Ltaief, Ltaief; Küstner-Wetekam, Catmarna; Jahnke, Till; Ehresmann, Arno; Demekhin, Philipp V.; Gokhberg, Kirill; Knie, André

2018-01-01

We directly observe radiative charge transfer (RCT) in Ne clusters by dispersed vacuum-ultraviolet photon detection. The doubly ionized Ne2+-{{{N}}{{e}}}n-1 initial states of RCT are populated after resonant 1s-3p photoexcitation or 1s photoionization of Ne n clusters with < n> ≈ 2800. These states relax further producing Ne+-Ne+-{{{N}}{{e}}}n-2 final states, and the RCT photon is emitted. Ab initio calculations assign the observed RCT signal to the{}{{{N}}{{e}}}2+(2{{{p}}}-2{[}1{{D}}]){--}{{{N}}{{e}}}n-1 initial state, while transitions from other possible initial states are proposed to be quenched by competing relaxation processes. The present results are in agreement with the commonly discussed scenario, where the doubly ionized atom in a noble gas cluster forms a dimer which dissipates its vibrational energy on a picosecond timescale. Our study complements the picture of the RCT process in weakly bound clusters, providing information which is inaccessible by charged particle detection techniques.

Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice.

PubMed

Martel, Catherine; Li, Wenjun; Fulp, Brian; Platt, Andrew M; Gautier, Emmanuel L; Westerterp, Marit; Bittman, Robert; Tall, Alan R; Chen, Shu-Hsia; Thomas, Michael J; Kreisel, Daniel; Swartz, Melody A; Sorci-Thomas, Mary G; Randolph, Gwendalyn J

2013-04-01

Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic drainage from skin--1 surgical and the other genetic--to quantitatively track RCT following injection of [3H]-cholesterol-loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analog (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aortae of donor atherosclerotic Apoe-deficient mice with [2H]6-labeled cholesterol and surgically transplanting these aortae into recipient Apoe-deficient mice that were treated with anti-VEGFR3 antibody to block lymphatic regrowth or with control antibody to allow such regrowth. [2H]-Cholesterol was retained in aortae of anti-VEGFR3-treated mice. Thus, the lymphatic vessel route is critical for RCT from multiple tissues, including the aortic wall. These results suggest that supporting lymphatic transport function may facilitate cholesterol clearance in therapies aimed at reversing atherosclerosis.

Correlation between anatomy of the scapula and the incidence of rotator cuff tear and glenohumeral osteoarthritis via radiological study.

PubMed

Miswan, Mohd Fairudz Bin Mohd; Saman, Mohd Shahril Bin Ahmad; Hui, Teo Seow; Al-Fayyadh, Mohamed Zubair Mohamed; Ali, Mohamed Razif Bin Mohamed; Min, Ng Wuey

2017-01-01

We conducted a study to elucidate the correlation between the anatomy of the shoulder joint with the development of rotator cuff tear (RCT) and glenohumeral osteoarthritis (GHOA) by using acromioglenoid angle (AGA). The AGA is a new measured angle formed between the line from midglenoid to lateral end of the acromion with the line parallel to the glenoid surface. The AGA was measured in a group of 85 shoulders with RCT, 49 with GHOA and 103 non-RCT/GHOA control shoulders. The AGA was compared with other radiological parameters, such as, the critical shoulder angle (CSA), the acromion index (AI) and the acromiohumeral interval (AHI). Correlational and regression analysis were performed using SPSS 20. The mean AGA was 50.9° (45.2-56.5°) in the control group, 53.3° (47.6-59.1°) in RCT group and 45.5° (37.7-53.2°) in OA group. Among patients with AGA > 51.5°, 61% were in the RCT group and among patients with AGA < 44.5°, 56% were in OA group. Pearson correlation analysis had shown significant correlation between AGA and CSA ( r = 0.925, p < 0.001). It was also significant of AHI in RCT group with mean 6.6 mm (4.7-8.5 mm) and significant AI in OA group with mean 0.68 (0.57-0.78) with p value < 0.001 respectively. The AGA method of measurement is an excellent predictive parameter for diagnosing RCT and GHOA.

The feasibility of conducting a randomised controlled trial comparing arthroscopic hip surgery to conservative care for patients with femoroacetabular impingement syndrome: the FASHIoN feasibility study.

PubMed

Griffin, D R; Dickenson, E J; Wall, P D H; Realpe, A; Adams, A; Parsons, N; Hobson, R; Achten, J; Costa, M L; Foster, N E; Hutchinson, C E; Petrou, S; Donovan, J L

2016-10-01

To determine whether it was feasible to perform a randomized controlled trial (RCT) comparing arthroscopic hip surgery to conservative care in patients with femoroacetabular impingement (FAI). This study had two phases: a pre-pilot and pilot RCT. In the pre-pilot, we conducted interviews with clinicians who treated FAI and with FAI patients to determine their views about an RCT. We developed protocols for operative and conservative care. In the pilot RCT, we determined the rates of patient eligibility, recruitment and retention, to investigate the feasibility of the protocol and we established methods to assess treatment fidelity. In the pre-pilot phase, 32 clinicians were interviewed, of which 26 reported theoretical equipoise, but in example scenarios 7 failed to show clinical equipoise. Eighteen patients treated for FAI were also interviewed, the majority of whom felt that surgery and conservative care were acceptable treatments. Surgery was viewed by patients as a 'definitive solution'. Patients were motivated to participate in research but were uncomfortable about randomization. Randomization was more acceptable if the alternative was available at the end of the trial. In the pilot phase, 151 patients were assessed for eligibility. Sixty were eligible and invited to take part in the pilot RCT; 42 consented to randomization. Follow-up was 100% at 12 months. Assessments of treatment fidelity were satisfactory. An RCT to compare arthroscopic hip surgery with conservative care in patients with FAI is challenging but feasible. Recruitment has started for a full RCT.

Impact of spine alignment on the rotator cuff in long-term wheelchair users.

PubMed

Kentar, Yasser; Brunner, Manuela; Bruckner, Thomas; Hug, Andreas; Raiss, Patric; Zeifang, Felix; Loew, Markus; Almansour, Haidara; Akbar, Michael

2018-06-01

We investigated the impact of poor seated posture on the prevalence of rotator cuff tears (RCTs) among wheelchair-dependent individuals with long-standing paraplegia. The study included 319 patients. Lateral radiographs of the spine were collected from a database and analyzed to assess the global spinopelvic alignment (SPA). Magnetic resonance images of both shoulders were obtained to detect the presence of cuff tears. Patients were divided into 2 groups: Group RCT-I included all patients with cuff tears (right, left, or bilateral), whereas group RCT-II consisted exclusively of patients with bilateral cuff tears. We used the classification systems developed by Kendall et al and Roussouly et al to assess the sagittal spine alignment and SPA, respectively. Univariate and multivariate analyses were performed. To fit both models (groups RCT-I and RCT-II) to the data, the 4 spine curves according to Roussouly et al were subdivided into 2 groups: Group SPA-I included both type 1 and type 2, whereas group SPA-II included both type 3 and type 4. Magnetic resonance images showed a cuff tear in 192 patients (60.19%) (group RCT-I). Among those, 37 patients (11.60%) had tears in both shoulders (group RCT-II). In group RCT-I, 70.31% of the patients had a kyphotic-lordotic posture. The kyphotic-lordotic posture, a longer duration, and a more rostral neurologic level of injury were highly associated with cuff tear prevalence. In group RCT-II, the multivariate analysis showed that only the duration of spinal cord injury was significantly associated with RCTs. Thoracic hyperkyphosis was associated with a markedly high rate of RCTs. The data from this study may provide support for developing preventive strategies. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Enhancing Recruitment Using Teleconference and Commitment Contract (ERUTECC): study protocol for a randomised, stepped-wedge cluster trial within the EFFECTS trial.

PubMed

Lundström, Erik; Isaksson, Eva; Wester, Per; Laska, Ann-Charlotte; Näsman, Per

2018-01-08

Many randomised controlled trials (RCTs) fail to meet their recruitment goals in time. Trialists are advised to include study recruitment strategies within their trials. EFFECTS is a Swedish, academic-led RCT of fluoxetine for stroke recovery. The trial's primary objective is to investigate whether 20 mg fluoxetine daily compared with placebo for 6 months after an acute stroke improves the patient's functional outcome. The first patient was included on 20 October 2014 and, as of 31 August 2017, EFFECTS has included 810 of planned 1500 individuals. EFFECTS currently has 32 active centres. The primary objective of the ERUTECC (Enhancing Recruitment Using Teleconference and Commitment Contract) study is to investigate whether a structured teleconference re-visit with the study personnel at the centres, accompanied by a commitment contract, can enhance recruitment by 20% at 60 days post intervention, compared with 60 days pre-intervention, in an ongoing RCT. ERUTECC is a randomised, stepped-wedge cluster trial embedded in EFFECTS. The plan is to start ERUTECC with a running-in period of September 2017. The first intervention is due in October 2017, and the study will continue for 12 months. We are planning to intervene at all active centres in EFFECTS, except the five top recruiting centres (n = 27). The rationale for not intervening at the top recruiting centres is that we believe they have reached their full potential and the intervention would be too weak for them. The hypothesis of this study is that a structured teleconference re-visit with the study personnel at the centres, accompanied by a commitment contract, can enhance recruitment by 20% 60 days post intervention, compared to 60 days pre-intervention, in an ongoing RCT. EFFECTS is a large, pragmatic RCT of stroke in Sweden. Results from the embedded ERUTECC study could probably be generalised to high-income Western countries, and is relevant to trial management and could improve trial management in the future. It might also be useful in clinical settings outside the field of stroke. The ERUTECC study was registered in the Northern Ireland Hub for Trials Methodology Research Studies Within a Trial repository ( SWAT58 ) on 30 April 2017. ClinicalTrials.gov, ID: NCT02683213 . Retrospectively registered on 2 February 2016.

Rapid distortion theory and the 'problems' of turbulence

NASA Astrophysics Data System (ADS)

Hunt, J. C. R.; Carruthers, D. J.

1990-03-01

This paper describes some developments in the techniques of the rapid distortion theory (RDT) and in the general understanding of how it can be used. It is noted in particular that the theory provides a rational basis for analyzing rapidly changing turbulent flows (RCT), and a heuristic method for estimating certain features of slowly changing turbulent flows (SCT). Recent developments of the RDT are reviewed, including criteria for its validity and new solutions allowing for the effects of inhomogeneities and boundaries. The problems associated with analyzing different kinds of turbulent flow and different methods of solution are classified and discussed with reference to how the turbulent structure in a flow domain depends on the scale and geometry of the domain's boundary, and on the information provided in the boundary conditions.

Risperidone (depot) for schizophrenia.

PubMed

Sampson, Stephanie; Hosalli, Prakash; Furtado, Vivek A; Davis, John M

2016-04-14

Risperidone is the first new generation antipsychotic drug made available in a long-acting injection formulation. To examine the effects of depot risperidone for treatment of schizophrenia or related psychoses in comparison with placebo, no treatment or other antipsychotic medication.To critically appraise and summarise current evidence on the resource use, cost and cost-effectiveness of risperidone (depot) for schizophrenia. We searched the Cochrane Schizophrenia Group's Register (December 2002, 2012, and October 28, 2015). We also checked the references of all included studies, and contacted industry and authors of included studies. Randomised clinical trials comparing depot risperidone with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. Two review authors independently selected trials, assessed trial quality and extracted data. For dichotomous data, we calculated the risk ratio (RR), with 95% confidence interval (CI). For continuous data, we calculated mean differences (MD). We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. Twelve studies, with a total of 5723 participants were randomised to the following comparison treatments: Risperidone depot versus placebo Outcomes of relapse and improvement in mental state were neither measured or reported. In terms of other primary outcomes, more people receiving placebo left the study early by 12 weeks (1 RCT, n=400, RR 0.74 95% CI 0.63 to 0.88, very low quality evidence), experienced severe adverse events in short term (1 RCT, n=400, RR 0.59 95% CI 0.38 to 0.93, very low quality evidence). There was however, no difference in levels of weight gain between groups (1 RCT, n=400, RR 2.11 95% CI 0.48 to 9.18, very low quality evidence). Risperidone depot versus general oral antipsychotics The outcome of improvement in mental state was not presented due to high levels of attrition, nor were levels of severe adverse events explicitly reported. Most primary outcomes of interest showed no difference between treatment groups. However, more people receiving depot risperidone experienced nervous system disorders (long-term:1 RCT, n=369, RR 1.34 95% CI 1.13 to 1.58, very-low quality evidence). Risperidone depot versus oral risperidoneData for relapse and severe adverse events were not reported. All outcomes of interest were rated as moderate quality evidence. Main results showed no differences between treatment groups with equivocal data for change in mental state, numbers leaving the study early, any extrapyramidal symptoms, weight increase and prolactin-related adverse events. Risperidone depot versus oral quetiapine Relapse rates and improvement in mental state were not reported. Fewer people receiving risperidone depot left the study early (long-term: 1 RCT, n=666, RR 0.84 95% CI 0.74 to 0.95, moderate quality evidence). Experience of serious adverse events was similar between groups (low quality evidence), but more people receiving depot risperidone experienced EPS (1 RCT, n=666, RR 1.83 95% CI 1.07 to 3.15, low quality evidence), had greater weight gain (1 RCT, n=666, RR 1.25 95% CI 0.25 to 2.25, low quality evidence) and more prolactin-related adverse events (1 RCT, n=666, RR 3.07 95% CI 1.13 to 8.36, very low quality evidence). Risperidone depot versus oral aripiprazoleRelapse rates, mental state using PANSS, leaving the study early, serious adverse events and weight increase were similar between groups. However more people receiving depot risperidone experienced prolactin-related adverse events compared to those receiving oral aripiprazole (2 RCTs, n=729, RR 9.91 95% CI 2.78 to 35.29, very low quality of evidence). Risperidone depot versus oral olanzapineRelapse rates were not reported in any of the included studies for this comparison. Improvement in mental state using PANSS and instances of severe adverse events were similar between groups. More people receiving depot risperidone left the study early than those receiving oral olanzapine (1 RCT, n=618, RR 1.32 95% CI 1.10 to 1.58, low quality evidence) with those receiving risperidone depot also experiencing more extrapyramidal symptoms (1 RCT, n=547, RR 1.67 95% CI 1.19 to 2.36, low quality evidence). However, more people receiving oral olanzapine experienced weight increase (1 RCT, n=547, RR 0.56 95% CI 0.42 to 0.75, low quality evidence). Risperidone depot versus atypical depot antipsychotics (specifically paliperidone palmitate)Relapse rates were not reported and rates of response using PANSS, weight increase, prolactin-related adverse events and glucose-related adverse events were similar between groups. Fewer people left the study early due to lack of efficacy from the risperidone depot group (long term: 1 RCT, n=749, RR 0.60 95% CI 0.45 to 0.81, low quality evidence), but more people receiving depot risperidone required use of EPS-medication (2 RCTs, n=1666, RR 1.46 95% CI 1.18 to 1.8, moderate quality evidence). Risperidone depot versus typical depot antipsychoticsOutcomes of relapse, severe adverse events or movement disorders were not reported. Outcomes relating to improvement in mental state demonstrated no difference between groups (low quality evidence). However, more people receiving depot risperidone compared to other typical depots left the study early (long-term:1 RCT, n=62, RR 3.05 95% CI 1.12 to 8.31, low quality evidence). Depot risperidone may be more acceptable than placebo injection but it is hard to know if it is any more effective in controlling the symptoms of schizophrenia. The active drug, especially higher doses, may be associated with more movement disorders than placebo. People already stabilised on oral risperidone may continue to maintain benefit if treated with depot risperidone and avoid the need to take tablets, at least in the short term. In people who are happy to take oral medication the depot risperidone is approximately equal to oral risperidone. It is possible that the depot formulation, however, can bring a second-generation antipsychotic to people who do not reliably adhere to treatment. People with schizophrenia who have difficulty adhering to treatment, however, are unlikely to volunteer for a clinical trial. Such people may gain benefit from the depot risperidone with no increased risk of extrapyramidal side effects.

Observational studies are complementary to randomized controlled trials.

PubMed

Grootendorst, Diana C; Jager, Kitty J; Zoccali, Carmine; Dekker, Friedo W

2010-01-01

Randomized controlled trials (RCTs) are considered the gold standard study design to investigate the effect of health interventions, including treatment. However, in some situations, it may be unnecessary, inappropriate, impossible, or inadequate to perform an RCT. In these special situations, well-designed observational studies, including cohort and case-control studies, may provide an alternative to doing nothing in order to obtain estimates of treatment effect. It should be noted that such studies should be performed with caution and correctly. The aims of this review are (1) to explain why RCTs are considered the optimal study design to evaluate treatment effects, (2) to describe the situations in which an RCT is not possible and observational studies are an adequate alternative, and (3) to explain when randomization is not needed and can be approximated in observational studies. Examples from the nephrology literature are used for illustration. Copyright 2009 S. Karger AG, Basel.

A randomized controlled trial for families with preschool children - promoting healthy eating and active playtime by connecting to nature.

PubMed

Sobko, Tanja; Tse, Michael; Kaplan, Matthew

2016-06-13

Promotion of healthy lifestyles in children focuses predominantly on proper nutrition and physical activity, elements now widely recognised as essential for a healthy life. Systematic reviews have shown that nature-related activities also enhance general well-being as reflected in increased physical activity, a healthier diet, reduced stress and better sleep. Recent research suggests that many young children in Hong Kong between the ages of two and four in Hong Kong are more sedentary than recommended and seldom participate in active play, placing them at risk of becoming overweight or obese. The proposed project aims to investigate whether connecting families to nature positively influences physical activity (i.e., active playtime) and healthy eating routines in children aged 2 to 4. We recently conducted a pilot study in Hong Kong to develop a programme, Play & Grow, based on the most successful evidence-based international preschool interventions. In addition to adopting the healthy eating and physical activity elements of these interventions, this project will additionally include a third novel element of Connectedness to nature: discovering nature through games and awareness of sounds, touch, smells, and temperature. To test the effectiveness of this modified intervention, a randomised controlled trial (RCT) involving 240 families with children aged 2 to 4 will be conducted. Families and children will take part in weekly one-hour activity sessions for 10-weeks. Lifestyle-related habits will be assessed before and immediately after the 10-week intervention, with follow up testing at 6 and 12 months' post intervention. A novel measuring tool created specifically for assessing Connectedness to nature, Nature Relatedness Scale (NRS), will be validated and tested for reliability prior to the RCT. The results of the RCT are intended to be used to understand which components of the intervention are most effective. The objectives of this project will be achieved over a 30-month period and will contribute to the research that examines key components of successful healthy lifestyle promotion programmes during early childhood. We predict that the inclusion of Connectedness to nature will significantly improve recognised preschool interventions. Finally, the aim of targeting family involvement will hopefully increase the sustainability of longer-term lifestyle modifications in children. ClinicalTrials.gov, NCT02715544 . Registered 22 March 2016.

Educational interventions to improve quality of life in people with chronic inflammatory skin diseases: systematic reviews of clinical effectiveness and cost-effectiveness.

PubMed

Pickett, Karen; Loveman, Emma; Kalita, Neelam; Frampton, Geoff K; Jones, Jeremy

2015-10-01

Inflammatory skin diseases include a broad range of disorders. For some people, these conditions lead to psychological comorbidities and reduced quality of life (QoL). Patient education is recommended in the management of these conditions and may improve QoL. To assess the clinical effectiveness and cost-effectiveness of educational interventions to improve health-related quality of life (HRQoL) in people with chronic inflammatory skin diseases. Twelve electronic bibliographic databases, including The Cochrane Library, MEDLINE and EMBASE, were searched to July 2014. Bibliographies of retrieved papers were searched and an Advisory Group contacted. Systematic reviews were conducted following standard methodologies. Clinical effectiveness studies were included if they were undertaken in people with a chronic inflammatory skin condition. Educational interventions that aimed to, or could, improve HRQoL were eligible. Studies were required to measure HRQoL, and other outcomes such as disease severity were also included. Randomised controlled trials (RCTs) or controlled clinical trials were eligible. For the review of cost-effectiveness, studies were eligible if they were full economic evaluations, cost-consequence or cost analyses. Seven RCTs were included in the review of clinical effectiveness. Two RCTs focused on children with eczema and their carers. Five RCTs were in adults. Of these, two were of people with psoriasis, one was of people with acne and two were of people with a range of conditions. There were few similarities in the interventions (e.g. the delivery mode, the topics covered, the duration of the education), which precluded any quantitative synthesis. Follow-up ranged from 4 weeks to 12 months, samples sizes were generally small and, overall, the study quality was poor. There appeared to be positive effects on HRQoL in participants with psoriasis in one trial, but no difference between groups in another trial in which participants had less severe psoriasis. Carers of children in one RCT of eczema showed improvement in HRQoL; however, in a RCT evaluating a website intervention there were no demonstrable effects on HRQoL. Neither the RCT in those adults with acne nor the RCT in those adults with mixed skin conditions demonstrated an effect on HRQoL. One RCT reported subgroups with atopic dermatitis or psoriasis and education was effective for psoriasis only. Other outcomes also showed mixed results. It is unclear how clinically meaningful any of the observed improvements are. Three studies of cost-effectiveness were included. The interventions, comparators and populations varied across the studies and, overall, the studies provided limited information on cost-effectiveness. The studies did provide detailed information on resources and costs that could be useful to inform a future cost-effectiveness evaluation in this area. The application of the inclusion criterion around whether the interventions were aimed at improving HRQoL or the inference that they could improve HRQoL was difficult as information was rarely reported. There is uncertainty regarding whether educational interventions addressing issues that could improve HRQoL in people with chronic skin conditions are effective. Tentative conclusions about the best approach to delivering these kinds of interventions are that face-to-face, group, sessions may be beneficial; however, text messages may also be effective. Delivery over a period of time and by a multidisciplinary team may also be associated with positive outcomes. There is uncertainty over whether or not educational interventions are cost-effective. This study is registered as PROSPERO CRD42014007426. The National Institute for Health Research Health Technology Assessment programme.

Implementation research design: integrating participatory action research into randomized controlled trials

PubMed Central

Leykum, Luci K; Pugh, Jacqueline A; Lanham, Holly J; Harmon, Joel; McDaniel, Reuben R

2009-01-01

Background A gap continues to exist between what is known to be effective and what is actually delivered in the usual course of medical care. The goal of implementation research is to reduce this gap. However, a tension exists between the need to obtain generalizeable knowledge through implementation trials, and the inherent differences between healthcare organizations that make standard interventional approaches less likely to succeed. The purpose of this paper is to explore the integration of participatory action research and randomized controlled trial (RCT) study designs to suggest a new approach for studying interventions in healthcare settings. Discussion We summarize key elements of participatory action research, with particular attention to its collaborative, reflective approach. Elements of participatory action research and RCT study designs are discussed and contrasted, with a complex adaptive systems approach used to frame their integration. Summary The integration of participatory action research and RCT design results in a new approach that reflects not only the complex nature of healthcare organizations, but also the need to obtain generalizeable knowledge regarding the implementation process. PMID:19852784

Passing the baton: Community-based ethnography to design a randomized clinical trial on the effectiveness of oral pre-exposure prophylaxis for HIV prevention among Black men who have sex with men.

PubMed

Garcia, Jonathan; Colson, Paul W; Parker, Caroline; Hirsch, Jennifer S

2015-11-01

Although HIV interventions and clinical trials increasingly report the use of mixed methods, studies have not reported on the process through which ethnographic or qualitative findings are incorporated into RCT designs. We conducted a community-based ethnography on social and structural factors that may affect the acceptance of and adherence to oral pre-exposure prophylaxis (PrEP) among Black men who have sex with men (BMSM). We then devised the treatment arm of an adherence clinical trial drawing on findings from the community-based ethnography. This article describes how ethnographic findings informed the RCT and identifies distilled themes and findings that could be included as part of an RCT. The enhanced intervention includes in-person support groups, online support groups, peer navigation, and text message reminders. By describing key process-related facilitators and barriers to conducting meaningful mixed methods research, we provide important insights for the practice of designing clinical trials for 'real-world' community settings. Copyright © 2015 Elsevier Inc. All rights reserved.

Passing the Baton: Community-based ethnography to design a randomized clinical trial on the effectiveness of oral pre-exposure prophylaxis for HIV prevention among Black men who have sex with men

PubMed Central

Garcia, Jonathan; Colson, Paul W.; Parker, Caroline; Hirsch, Jennifer S.

2015-01-01

Although HIV interventions and clinical trials increasingly report the use of mixed methods, studies have not reported on the process through which ethnographic or qualitative findings are incorporated into RCT designs. We conducted a community-based ethnography on social and structural factors that may affect the acceptance of and adherence to oral pre-exposure prophylaxis (PrEP) among Black men who have sex with men (BMSM). We then devised the treatment arm of an adherence clinical trial drawing on findings from the community-based ethnography. This article describes how ethnographic findings informed the RCT and identifies distilled themes and findings that could be included as part of an RCT. The enhanced intervention includes in-person support groups, online support groups, peer navigation, and text message reminders. By describing key process-related facilitators and barriers to conducting meaningful mixed methods research, we provide important insights for the practice of designing clinical trials for ‘real-world’ community settings. PMID:26476286

Advanced glycation end products affect cholesterol homeostasis by impairing ABCA1 expression on macrophages.

PubMed

Kamtchueng Simo, Olivier; Ikhlef, Souade; Berrougui, Hicham; Khalil, Abdelouahed

2017-08-01

Reverse cholesterol transport (RCT), which is intimately linked to high-density lipoproteins (HDLs), plays a key role in cholesterol homeostasis and the prevention of atherosclerosis. The goal of the present study was to investigate the effect of aging and advanced glycation end products (AGEs) on RCT as well as on other factors that may affect the antiatherogenic property of HDLs. The transfer of macrophage-derived cholesterol to the plasma and liver and then to the feces for elimination was significantly lower in aged mice than in young mice. Chronic injection of d -galactose (D-gal) or AGEs also significantly reduced RCT (65.3% reduction in [ 3 H]cholesterol levels in the plasma of D-gal-treated mice after 48 h compared with control mice, P < 0.01). The injection of both D-gal and aminoguanidine hydrochloride increased [ 3 H]cholesterol levels in the plasma, although the levels were lower than those of control mice. The in vitro incubation of HDLs with dicarbonyl compounds increased the carbonyl and conjugated diene content of HDLs and significantly reduced PON1 paraoxonase activity (87.4% lower than control HDLs, P < 0.0001). Treating J774A.1 macrophages with glycated fetal bovine serum increased carbonyl formation (39.5% increase, P < 0.003) and reduced ABCA1 protein expression and the capacity of macrophages to liberate cholesterol (69.1% decrease, P < 0.0001). Our results showed, for the first time, that RCT is altered with aging and that AGEs contribute significantly to this alteration.

Best practice guidance for the use of strategies to improve retention in randomized trials developed from two consensus workshops

PubMed Central

Brueton, Valerie; Stenning, Sally P.; Stevenson, Fiona; Tierney, Jayne; Rait, Greta

2017-01-01

Objectives To develop best practice guidance for the use of retention strategies in randomized clinical trials (RCTs). Study Design and Setting Consensus development workshops conducted at two UK Clinical Trials Units. Sixty-six statisticians, clinicians, RCT coordinators, research scientists, research assistants, and data managers associated with RCTs participated. The consensus development workshops were based on the consensus development conference method used to develop best practice for treatment of medical conditions. Workshops commenced with a presentation of the evidence for incentives, communication, questionnaire format, behavioral, case management, and methodological retention strategies identified by a Cochrane review and associated qualitative study. Three simultaneous group discussions followed focused on (1) how convinced the workshop participants were by the evidence for retention strategies, (2) barriers to the use of effective retention strategies, (3) types of RCT follow-up that retention strategies could be used for, and (4) strategies for future research. Summaries of each group discussion were fed back to the workshop. Coded content for both workshops was compared for agreement and disagreement. Agreed consensus on best practice guidance for retention was identified. Results Workshop participants agreed best practice guidance for the use of small financial incentives to improve response to postal questionnaires in RCTs. Use of second-class post was thought to be adequate for postal communication with RCT participants. The most relevant validated questionnaire was considered best practice for collecting RCT data. Barriers identified for the use of effective retention strategies were: the small improvements seen in questionnaire response for the addition of monetary incentives, and perceptions among trialists that some communication strategies are outdated. Furthermore, there was resistance to change existing retention practices thought to be effective. Face-to-face and electronic follow-up technologies were identified as retention strategies for further research. Conclusions We developed best practice guidance for the use of retention strategies in RCTs and identified potential barriers to the use of effective strategies. The extent of agreement on best practice is limited by the variability in the currently available evidence. This guidance will need updating as new retention strategies are developed and evaluated. PMID:28546093

Best practice guidance for the use of strategies to improve retention in randomized trials developed from two consensus workshops.

PubMed

Brueton, Valerie; Stenning, Sally P; Stevenson, Fiona; Tierney, Jayne; Rait, Greta

2017-08-01

To develop best practice guidance for the use of retention strategies in randomized clinical trials (RCTs). Consensus development workshops conducted at two UK Clinical Trials Units. Sixty-six statisticians, clinicians, RCT coordinators, research scientists, research assistants, and data managers associated with RCTs participated. The consensus development workshops were based on the consensus development conference method used to develop best practice for treatment of medical conditions. Workshops commenced with a presentation of the evidence for incentives, communication, questionnaire format, behavioral, case management, and methodological retention strategies identified by a Cochrane review and associated qualitative study. Three simultaneous group discussions followed focused on (1) how convinced the workshop participants were by the evidence for retention strategies, (2) barriers to the use of effective retention strategies, (3) types of RCT follow-up that retention strategies could be used for, and (4) strategies for future research. Summaries of each group discussion were fed back to the workshop. Coded content for both workshops was compared for agreement and disagreement. Agreed consensus on best practice guidance for retention was identified. Workshop participants agreed best practice guidance for the use of small financial incentives to improve response to postal questionnaires in RCTs. Use of second-class post was thought to be adequate for postal communication with RCT participants. The most relevant validated questionnaire was considered best practice for collecting RCT data. Barriers identified for the use of effective retention strategies were: the small improvements seen in questionnaire response for the addition of monetary incentives, and perceptions among trialists that some communication strategies are outdated. Furthermore, there was resistance to change existing retention practices thought to be effective. Face-to-face and electronic follow-up technologies were identified as retention strategies for further research. We developed best practice guidance for the use of retention strategies in RCTs and identified potential barriers to the use of effective strategies. The extent of agreement on best practice is limited by the variability in the currently available evidence. This guidance will need updating as new retention strategies are developed and evaluated. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Design and rationale for NOURISH-T: a randomized control trial targeting parents of overweight children off cancer treatment.

PubMed

Stern, Marilyn; Ewing, Lin; Davila, Esther; Thompson, Amanda L; Hale, Gregory; Mazzeo, Suzanne

2015-03-01

Approximately 40% of off-treatment pediatric cancer survivors (PCS) are overweight or obese, which increases their risk for negative long-term physical health complications. Consistent with the Institute of Medicine's (IOM) emphasis on patients transitioning from treatment to cancer survivorship and increasing long-term healthy behaviors in these survivors, we plan to conduct a pilot RCT to address the increasing overweight/obesity rates among PCS by targeting their caregivers as agents for PCS behavior change. We plan to focus on parents' behaviors, attitudes and roles in promoting healthier eating and physical activity (PA) in PCS and adapt an evidence-informed, manualized parent intervention - NOURISH - found to be effective for parents of overweight and obese children and adolescents in reducing child and adolescent BMI. We plan to adapt NOURISH for caregivers of 5-12 year old PCS (6 months-4 years off active cancer treatment). Our pilot feasibility RCT - NOURISH-T (Nourishing Our Understanding of Role modeling to Improve Support for Healthy Transitions) evaluates: 1) the preliminary efficacy of NOURISH-T for PCS, compared with an Enhanced Usual Care (EUC) control condition, and 2) factors to consider to improve future adaptations of the intervention. The project will enroll caregivers of PCS at two pediatric oncology clinics into the 6-week intervention (or EUC) with assessments occurring pre- and post-6 weeks of intervention, and at a 4-month follow-up. Copyright © 2015 Elsevier Inc. All rights reserved.

A randomized controlled trial of a smoking cessation self-help intervention for dual users of tobacco cigarettes and E-cigarettes: Intervention development and research design.

PubMed

Meltzer, Lauren R; Simmons, Vani N; Sutton, Steven K; Drobes, David J; Quinn, Gwendolyn P; Meade, Cathy D; Unrod, Marina; Brandon, Karen O; Harrell, Paul T; Eissenberg, Thomas; Bullen, Christopher R; Brandon, Thomas H

2017-09-01

Electronic Nicotine Delivery Systems, also called electronic cigarettes or e-cigarettes, have been available for over a decade and use has been increasing dramatically. The primary reported reasons for use are to aid smoking cessation or reduction, yet a significant proportion appear to be long-term users of both products ("dual users"). Dual users may be motivated to quit smoking and might benefit from a behavioral intervention for smoking cessation. This paper describes the intervention development, as well as the design, methods, and data analysis plans for an ongoing randomized controlled trial (RCT). Formative research and learner verification were conducted to create a usable, understandable, and acceptable self-help intervention targeting dual users. The efficacy is being tested in an RCT with current dual users (N=2900) recruited nationally and randomized to one of three conditions. The Assessment Only (ASSESS) group only completes assessments. The Generic Self-Help (GENERIC) group receives non-targeted smoking cessation booklets and supplemental materials sent monthly over 18months. The e-cigarette Targeted Self-Help (eTARGET) group receives the newly developed intervention (targeted booklets and supplemental materials) sent over the same period. All participants complete self-report surveys every 3months over 2years. The primary study outcome is self-reported 7-day point prevalence abstinence. Cost-effectiveness metrics for the GENERIC and eTARGET interventions will also be calculated. Copyright © 2017 Elsevier Inc. All rights reserved.

Using routinely recorded data in the UK to assess outcomes in a randomised controlled trial: The Trials of Access.

PubMed

Powell, G A; Bonnett, L J; Tudur-Smith, C; Hughes, D A; Williamson, P R; Marson, A G

2017-08-23

In the UK, routinely recorded data may benefit prospective studies including randomised controlled trials (RCTs). In an on-going study, we aim to assess the feasibility of access and agreement of routinely recorded clinical and non-clinical data compared to data collected during a RCT using standard prospective methods. This paper will summarise available UK routinely recorded data sources and discuss our experience with the feasibility of accessing routinely recorded data for participants of a RCT before finally proposing recommendations for improving the access and implementation of routinely recorded data in RCTs. Setting: the case study RCT is the Standard and New Antiepileptic Drugs II (SANAD II) trial, a pragmatic, UK, multicentre, phase IV RCT assessing the clinical and cost-effectiveness of antiepileptic drug treatments for newly diagnosed epilepsy. 98 participants have provided written consent to permit the request of routinely recorded data. Study procedures: routinely recorded clinical and non-clinical data were identified and data requested through formal applications from available data holders for the duration that participants have been recruited into SANAD II. The feasibility of accessing routinely recorded data during a RCT is assessed and recommendations for improving access proposed. Secondary-care clinical and socioeconomic data is recorded on a national basis and can be accessed, although there are limitations in the application process. Primary-care data are recorded by a number of organisations on a de-identified basis but access for specific individuals has not been feasible. Access to data recorded by non-clinical sources, including The Department for Work and Pensions and The Driving and Vehicle Licensing Agency, was not successful. Recommendations discussed include further research to assess the attributes of routinely recorded data, an assessment of public perceptions and the development of strategies to collaboratively improve access to routinely recorded data for research. International Standard Randomised Controlled Trials, ISRCTN30294119 . Registered on 3 July 2012. EudraCT No: 2012-001884-64. Registered on 9 May 2012.

The impact of surgery on survival of patients with cutaneous melanoma: revisiting the role of primary tumor excision margins.

PubMed

Mocellin, Simone; Pasquali, Sandro; Nitti, Donato

2011-02-01

To quantify the impact of excision margins on disease-specific survival of patients with primary cutaneous melanoma. Current guidelines recommend narrow margins for the treatment of primary melanoma, although available evidence on this subject is not unequivocal and not always appropriately analyzed. A systematic review of randomized controlled trials (RCT) addressing the issue of wide versus narrow excision margins was performed. Meta-analysis methods for time-to-event data were used to extract hazard ratios(HR) and their 95% confidence intervals (CI) from eligible studies, and ultimately to estimate the summary effect of excision margins on patients' survival. The 5 eligible RCT enrolled a total of 3295 patients who were allocated to wide (3-5 cm) or narrow (1-2 cm) excision of their primary tumor. The data of locoregional disease-free (LDFS), disease-free (DFS),disease-specific (DSS), and overall (OS) survival were available for 3, 5, 3, and 5 RCT, respectively. The meta-analysis suggested that narrow margins might be associated with an increased risk of both locoregional disease recurrence (HR: 1.30, CI: 1.07-1.57; P = 0.01) and death by disease (HR: 1.28, CI:1.07-1.53, P = 0.01). As regards DFS, the borderline disadvantage (HR:1.13, CI: 0.995-1.28; P = 0.06) becomes significant when considering RCT that enrolled patients with thicker melanoma (HR: 1.19, CI: 1.02-1.39, P =0.03). When death by any cause (OS) was analyzed, no risk difference was found. The lack of DSS data from all the available RCT does not allow to draw definitive conclusions. However, current evidence appears sufficient to question the common belief that narrow excision margins are as safe as wide margins in the management of primary melanoma, that calls for further investigation in this field.

Effectiveness of an annular closure device in a "real-world" population: stratification of registry data using screening criteria from a randomized controlled trial.

PubMed

Kuršumović, Adisa; Rath, Stefan A

2018-01-01

Increased focus has been put on the use of "'real-world" data to support randomized clinical trial (RCT) evidence for clinical decision-making. The objective of this study was to assess the performance of an annular closure device (ACD) after stratifying a consecutive series of "real-world" patients by the screening criteria of an ongoing RCT. This was a single-center registry analysis of 164 subjects who underwent limited discectomy combined with ACD for symptomatic lumbar disc herniation. Patients were stratified into two groups using the selection criteria of a pivotal RCT on the same device: Trial (met inclusion; n=44) or non-Trial (did not meet inclusion; n=120). Patient-reported outcomes, including Oswestry Disability Index (ODI) and visual analog scale (VAS) for leg and back pain, and adverse events were collected from baseline to last follow-up (mean: Trial - 15.6 months; non-Trial - 14.6 months). Statistical analyses were performed with significance set at p <0.05. Patient-reported outcomes were not significantly different between groups at last ( p ≥0.15) and clinical success (≥15-point improvement in ODI score; ≥20-point improvement in VAS scores) was achieved in both the groups. Three non-Trial (2.5%) and three Trial (6.8%) patients experienced symptomatic reherniation ( p =0.34). Rates of reoperation, ACD mesh dislocation/separation, and other radiographic findings were similar between groups ( p =1.00). Outcomes with the ACD appeared advantageous in both the groups, particularly in comparison with historical reherniation rates reported in the same high-risk, large annular defect population. Stratification of this "real-world" series on the basis of RCT screening criteria did not result in significant between-group differences. These findings suggest that the efficacy of the ACD extends beyond the strictly defined patient population being studied in the RCT of this device. Furthermore, reducing the reherniation rate following lumbar discectomy has positive clinical and economic implications.

Recruitment to Online Therapies for Depression: Pilot Cluster Randomized Controlled Trial

PubMed Central

Goldsmith, Lesley; Hewson, Paul; Williams, Christopher J

2013-01-01

Background Raising awareness of online cognitive behavioral therapy (CBT) could benefit many people with depression, but we do not know how purchasing online advertising compares to placing free links from relevant local websites in increasing uptake. Objective To pilot a cluster randomized controlled trial (RCT) comparing purchase of Google AdWords with placing free website links in raising awareness of online CBT resources for depression in order to better understand research design issues. Methods We compared two online interventions with a control without intervention. The pilot RCT had 4 arms, each with 4 British postcode areas: (A) geographically targeted AdWords, (B) adverts placed on local websites by contacting website owners and requesting links be added, (C) both interventions, (D) control. Participants were directed to our research project website linking to two freely available online CBT resource sites (Moodgym and Living Life To The Full (LLTTF)) and two other depression support sites. We used data from (1) AdWords, (2) Google Analytics for our project website and for LLTTF, and (3) research project website. We compared two outcomes: (1) numbers with depression accessing the research project website, and then chose an onward link to one of the two CBT websites, and (2) numbers registering with LLTTF. We documented costs, and explored intervention and assessment methods to make general recommendations to inform researchers aiming to use similar methodologies in future studies. Results Trying to place local website links appeared much less cost effective than AdWords and although may prove useful for service delivery, was not worth pursuing in the context of the current study design. Our AdWords intervention was effective in recruiting people to the project website but our location targeting “leaked” and was not as geographically specific as claimed. The impact on online CBT was also diluted by offering participants other choices of destinations. Measuring the impact on LLTTF use was difficult as the total number using LLTTF was less than 5% of all users and record linkage across websites was impossible. Confounding activity may have resulted in some increase in registrations in the control arm. Conclusions Practitioners should consider online advertising to increase uptake of online therapy but need to check its additional value. A cluster RCT using location targeted adverts is feasible and this research design provides the best evidence of cost-effectiveness. Although our British pilot study is limited to online CBT for depression, a cluster RCT with similar design would be appropriate for other online treatments and countries and our recommendations may apply. They include ways of dealing with possible contamination (buffer zones and AdWords techniques), confounding factors (large number of clusters), advertising dose (in proportion to total number of users), record linkage (landing within target website), and length of study (4-6 months). Trial Registration clinicaltrials.gov (Registration No. NCT01469689); http://clinicaltrials.gov/ct2/show/NCT01469689 (Archived by WebCite at http://www.webcitation.org/6EtTthDOp) PMID:23462072

Experimental protocol of a randomized controlled clinical trial investigating exercise, subclinical atherosclerosis, and walking mobility in persons with multiple sclerosis.

PubMed

Griffith, Garett; Klaren, Rachel E; Motl, Robert W; Baynard, Tracy; Fernhall, Bo

2015-03-01

This randomized controlled trial (RCT) will investigate the effects of a home-based aerobic exercise training regimen (i.e., cycle ergometry) on subclinical atherosclerosis and walking mobility in persons with multiple sclerosis (MS) and minimal disability. This RCT will recruit 54 men and women who have an Expanded Disability Status Scale characteristic of the 1st stage of MS (i.e., 0-4.0) to participate in a 3 month exercise or stretching intervention, with assessments of subclinical atherosclerosis and walking mobility conducted at baseline, week 6 (midpoint), and week 12 (conclusion) of the program. The exercise intervention will consist of 3 days/week of cycling, with a gradual increase of duration followed by an increase in intensity across the 3 month period. The attention-control condition will incorporate stretching activities and will require the same contact time commitment as the exercise condition. Both study groups will participate in weekly video chat sessions with study personnel in order to monitor and track program adherence. Primary outcomes will consist of assessments of vascular structure and function, as well as several walking tasks. Additional outcomes will include questionnaires, cardiorespiratory fitness assessment, and a 1-week free-living physical activity assessment. This investigation will increase understanding of the role of aerobic exercise as part of a treatment plan for managing subclinical atherosclerosis and improving walking mobility persons in the 1st stage of MS. Overall, this study design has the potential to lead to effective aerobic exercise intervention strategies for this population and improve program adherence. Copyright © 2015 Elsevier Inc. All rights reserved.

Behavior in children with Prader-Willi syndrome before and during growth hormone treatment: a randomized controlled trial and 8-year longitudinal study.

PubMed

Lo, Sin T; Siemensma, Elbrich P C; Festen, Dederieke A M; Collin, Philippe J L; Hokken-Koelega, Anita C S

2015-09-01

Information on behavior of children with Prader-Willi syndrome (PWS) and the effect of growth hormone (GH) treatment is scarce. Parents report less problem behavior during GH treatment. Forty-two pre-pubertal children, aged 3.5-14 years were studied in a randomized controlled GH trial (RCT) during 2 years, followed by a longitudinal study during 8 years of GH treatment. Behavior was measured annually by the Developmental Behavior Checklist for children with intellectual disability (DBC) and a Dutch questionnaire to evaluate social behavioral problems in children, the Children's Social Behavior Questionnaire (CSBQ). Problem behavior measured by the DBC in children with PWS was similar compared to peers with comparable intellectual disability. Scores on 'Social disabilities' subscale were however significantly higher compared to the DBC total score (p < 0.01). A lower IQ was associated with more self-absorbed behavior, more communication problems and more problem behavior in general. Problem behavior measured by the CSBQ was similar compared to peers with a comparable intellectual disability, but children with PWS scored significantly higher on the 'Not tuned', 'Understanding', and 'Stereotyped' subscales than the CSBQ total score (p < 0.05 for all subscales and p = 0.001 for the 'Not tuned'-subscale). There were no significant effects of GH treatment during the RCT and 8 years of GH treatment. Children with PWS showed similar problem behavior as a reference population with a comparable intellectual disability. Social problems were the most pronounced within-problem behavior in PWS. In contrast to our expectations and parents reports, our study shows no improvement but also no deterioration of behavioral problems in children with PWS during long-term GH treatment.

Crystal structures of resorcin[4]arene and pyrogallol[4]arene complexes with proline: A model for proline recognition through Csbnd H···π interaction

NASA Astrophysics Data System (ADS)

Fujisawa, Ikuhide; Kitamura, Yuji; Kato, Ryo; Aoki, Katsuyuki

2018-07-01

Resorcin[4]arene (resorcinol cyclic tetramer, abbreviated as RCT) or pyrogallol[4]arene (pyrogallol cyclic tetramer, PCT) form host-guest 1:1 complexes with DL-proline (DL-Pro) or L-proline (L-Pro), [RCT·DL-Pro]·2MeOH·3.5H2O (1) and 2[PCT·L-Pro]·2EtOH·10H2O (2), whose crystal structures have been determined. In each complex, the proline ligand is incorporated into the bowl-shaped cavity of RCT or PCT host molecules through Csbnd H … π interactions between alkyl protons of the pyrrolidine ring of proline and π-rings of RCT or PCT, forming an [RCT/PCT·Pro] structural fragment. In the crystal lattice, two [RCT/PCT·Pro] fragments self-associate to form a ligand-mediated dimeric structure, [RCT·D-Pro·L-Pro·RCT] in 1 or [PCT·L-Pro·L-Pro·PCT] in 2. A 1H NMR solution study gave the host‒ligand binding constants of 10.0 ± 1.1 M-1 for the RCT-DL-Pro system and 17.3 ± 1.3 M-1 for the PCT-L-Pro system. These complexes provide a synthetic model for the recognition of the proline residue in proline-containing substrates or inhibitors by enzymes through Csbnd H … π interaction. The CSD survey revealed that the absolute value of the torsion angle N-Cα-Csbnd O1 (O1 is cis to N) about the carboxyl Cα-C bond of proline is significantly smaller than that of the Cβ-Cα-Csbnd O2 (O2 is cis to Cβ) torsion angle.

Radiotherapy induced dermatitis is a strong predictor for late fibrosis in head and neck cancer. The development of a predictive model for late fibrosis.

PubMed

Nevens, Daan; Duprez, Fréderic; Daisne, Jean Francois; Laenen, Annouschka; De Neve, Wilfried; Nuyts, Sandra

2017-02-01

To determine if the severity of radiodermatitis at the end of radio(chemo)therapy (R(C)T) for head and neck cancer (HNC) is a predictive factor for late fibrosis of the neck and to find a model to predict neck fibrosis grade⩾2 (fibrosis RTOG 2-4 ) at 6months following R(C)T for HNC. 161 patients were prospectively included. We correlated radiodermatitis at the end of RCT, age, sex, T/N stage, tumor site, concomitant chemotherapy, upfront neck dissection, neo-adjuvant chemotherapy, accelerated RT, smoking, alcohol consumption, HPV status and the dose prescribed to the elective neck with fibrosis RTOG 2-4 6months after the end of treatment. Radiodermatitis at the end of R(C)T ⩾grade 3 proved to be associated with the incidence of fibrosis RTOG 2-4 at 6months (p<0.01). Furthermore, upfront neck dissection (p<0.01), increasing N stage (p<0.01) and tumor site (p=0.02) are significantly associated in univariate analysis with fibrosis RTOG 2-4 at 6months of follow-up. Upfront neck dissection and radiodermatitis grade⩾3 at the end of R(C)T were identified by our multivariate model. Additionally, increasing N stage was selected as an independent predictor variable. The AUC for this model was 0.92. A model for the prediction of fibrosis RTOG 2-4 following R(C)T for head and neck cancer is presented with an AUC of 0.92. Interestingly, radiodermatitis grade⩾3 at the end of R(C)T is associated with RTOG 2-4 fibrosis at 6months. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Short communication: Genetic correlation and heritability of milk coagulation traits within and across lactations in Holstein cows using multiple-lactation random regression animal models.

PubMed

Pretto, D; Vallas, M; Pärna, E; Tänavots, A; Kiiman, H; Kaart, T

2014-12-01

Genetic parameters of milk rennet coagulation time (RCT) and curd firmness (a30) among the first 3 lactations in Holstein cows were estimated. The data set included 39,960 test-day records from 5,216 Estonian Holstein cows (the progeny of 306 sires), which were recorded from April 2005 to May 2010 in 98 herds across the country. A multiple-lactation random regression animal model was used. Individual milk samples from each cow were collected during routine milk recording. These samples were analyzed for milk composition and coagulation traits with intervals of 2 to 3 mo in each lactation (7 to 305 DIM) and from first to third lactation. Mean heritabilities were 0.36, 0.32, and 0.28 for log-transformed RCT [ln(RCT)] and 0.47, 0.40, and 0.62 for a30 for parities 1, 2, and 3, respectively. Mean repeatabilities for ln(RCT) were 0.53, 0.55, and 0.56, but 0.59, 0.61, and 0.68 for a30 for parities 1, 2 and 3, respectively. Mean genetic correlations between ln(RCT) and a30 were -0.19, -0.14, and 0.02 for parities 1, 2, and 3, respectively. Mean genetic correlations were 0.91, 0.79, and 0.99 for ln(RCT), and 0.95, 0.94, and 0.94 for a30 between parities 1 and 2, 1 and 3, and 2 and 3, respectively. Due to these high genetic correlations, we concluded that for a proper genetic evaluation of milk coagulation properties it is sufficient to record RCT and a30 only in the first lactation. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Healing of intrabony defects and its relationship to root canal therapy. A histologic and histometric study in dogs.

PubMed

Lima, L A; Anderson, G B; Wang, M M; Nasjleti, C E; Morrison, E C; Kon, S; Caffesse, R G

1997-03-01

The purpose of this study was to evaluate the importance of root canal therapy in the healing process of severe intrabony defects. Four beagle dogs were used and 32 interproximal intrabony defects, up to the apical third, were created. Wire ligatures were placed into these defects for plaque accumulation. Three weeks later, the ligatures were removed and 4 different treatment modalities were employed: group 1) scaling and root planing (SRP); group 2) modified Widman flap (MWF); group 3) modified Widman flap and root canal therapy performed at the same time (RCT/MWF); and group 4) modified Widman flap and root canal therapy performed 3 weeks after the surgical procedure (MWF + RCT). Postoperative oral hygiene was obtained by spraying a 0.12% chlorhexidine solution 3 times a week. The animals were sacrificed 7 weeks after treatment. Blocks were obtained and processed for routine histology. Results were expressed as a percentage of the total defect length (TDL). No differences were observed when SRP was compared to MWF. New bone formation (BF) presented better results for SRP (43.4%) and MWF (53.4%) when compared to RCT/MWF (15.5%). New cementum formation (CF) presented better results for SRP (59.8%) and MWF (64.6%) when compared to RCT/MWF (19.3%) and MWF + RCT (31.5%). Connective tissue repair (CTR) presented better results for SRP (72.4%) and MWF (74.2%) when compared to RCT/MWF (47.5%) and MWF + RCT (44.4%). Results were statistically significant at the level of 0.05. Within the limits of this study, it was concluded that root canal therapy performed simultaneously or 3 weeks after surgery modified the healing of intrabony defects, impairing new bone formation, new cementum formation and new attachment.

[Effects of Cognitive Behavioral Therapy on Attention Deficit Hyperactivity Disorder among School-aged Children in Korea: A Meta-Analysis].

PubMed

Park, Wan-Ju; Park, Shin-Jeong; Hwang, Sung-Dong

2015-04-01

This study was a meta-analysis designed to identify effects of Cognitive Behavioral Therapy (CBT) interventions in alleviating main symptoms of Attention Deficit Hyperactivity Disorder (ADHD) among school-aged children in Korea. Examination of several databases including Research Information Sharing Service, Korean Studies Information Service System, Data Base Periodical Information Academic and hand-searched article references, resulted in identification of 1,298 studies done between 2000 and 2013 of which 21 met the inclusion criteria. Comprehensive Meta-Analysis version 2.0 was used to analyze effect sizes, explore possible causes of heterogeneity, and check publication bias with a funnel plot and its trim-and-fill analysis. Overall effect size of CBT intervention was large (g=1.08) along with each outcome of self-control (g=1.26), lack of attention (g=1.02), social skills (g=0.92), and hyperactivity (g=0.92). For heterogeneity, moderator analysis was performed, but no significant differences were found between the RCT (Randomized Controlled Trials) group and the NRCT (Non RCT) group. Also, meta-regression was performed using sample size, number of sessions, and length of session as predictors, but no statistically significant moderators were found. Finally, a funnel plot along with trim-and-fill analysis was produced to check for publication bias, but no significant bias was detected. Based on these findings, there is clear evidence that CBT intervention has significant positive effects on the main symptoms of school-aged children suffering ADHD. Further research is needed to target diverse age groups with ADHD along with more RCT studies to improve the effectiveness of the CBT intervention.

Dissemination of a Web-Based Tool for Supporting Health Insurance Plan Decisions (Show Me Health Plans): Cross-Sectional Observational Study.

PubMed

Zhao, Jingsong; Mir, Nageen; Ackermann, Nicole; Kaphingst, Kimberly A; Politi, Mary C

2018-06-20

The rate of uninsured people has decreased dramatically since the Affordable Care Act was passed. To make an informed decision, consumers need assistance to understand the advantages and disadvantages of health insurance plans. The Show Me Health Plans Web-based decision support tool was developed to improve the quality of health insurance selection. In response to the promising effectiveness of Show Me Health Plans in a randomized controlled trial (RCT) and the growing need for Web-based health insurance decision support, the study team used expert recommendations for dissemination and implementation, engaged external stakeholders, and made the Show Me Health Plans tool available to the public. The purpose of this study was to implement the public dissemination of the Show Me Health Plans tool in the state of Missouri and to evaluate its impact compared to the RCT. This study used a cross-sectional observational design. Dissemination phase users were compared with users in the RCT study across the same outcome measures. Time spent using the Show Me Health Plans tool, knowledge, importance rating of 9 health insurance features, and intended plan choice match with algorithm predictions were examined. During the dissemination phase (November 2016 to January 2017), 10,180 individuals visited the SMHP website, and the 1069 users who stayed on the tool for more than one second were included in our analyses. Dissemination phase users were more likely to live outside St. Louis City or County (P<.001), were less likely to be below the federal poverty level (P<.001), and had a higher income (P=.03). Overall, Show Me Health Plans users from St. Louis City or County spent more time on the Show Me Health Plans tool than those from other Missouri counties (P=.04); this association was not observed in the RCT. Total time spent on the tool was not correlated with knowledge scores, which were associated with lower poverty levels (P=.009). The users from the RCT phase were more likely to select an insurance plan that matched the tool's recommendations (P<.001) compared with the dissemination phase users. The study suggests that a higher income population may be more likely to seek information and online help when making a health insurance plan decision. We found that Show Me Health Plans users in the dissemination phase were more selective in the information they reviewed. This study illustrates one way of disseminating and implementing an empirically tested Web-based decision aid tool. Distributing Web-based tools is feasible and may attract a large number of potential users, educate them on basic health insurance information, and make recommendations based on personal information and preference. However, using Web-based tools may differ according to the demographics of the general public compared to research study participants. ©Jingsong Zhao, Nageen Mir, Nicole Ackermann, Kimberly A Kaphingst, Mary C Politi. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 20.06.2018.

Comparison of Ferric Sulfate Combined Mineral Trioxide Aggregate Pulpotomy and Zinc Oxide Eugenol Pulpectomy of Primary Maxillary Incisors: An 18-month Randomized, Controlled Trial.

PubMed

Nguyen, Trang D; Judd, Peter L; Barrett, Edward J; Sidhu, Nicole; Casas, Michael J

2017-01-15

The purpose of this study was to compare outcomes and survival of ferric sulfate with mineral trioxide aggregate (FS+MTA) pulpotomy and root canal therapy (RCT) in carious vital primary maxillary incisors. In this parallel group noninferiority trial, asymptomatic carious vital primary incisors with pulp exposure in healthy 18- to 46-month-olds were allocated randomly to receive FS+MTA pulpotomy or RCT between September 2010 and September 2012. Each incisor was classified into one of the following radiographic outcomes: N (incisor without pathologic change); Po (pathologic change present, follow-up recommended); Px (pathologic change present, extract.) Clinical findings and incisor survival were secondary outcomes. Seventy subjects were enrolled with a total of 172 incisors. Twelve- and 18-month radiographic outcomes demonstrated no statistical difference between FS+MTA pulpotomy and RCT incisors for Px outcomes (P=0.38; odds ratio equals 0.60; 95 percent confidence interval equals 0.19 to 1.89; chi-square test). There was no statistical differences in clinical outcomes for FS+MTA pulpotomy and RCT at 12 and 18 months (P=0.51; Fisher's exact test) or survival for FS+MTA pulpotomy and RCT incisors (P=0.11; log-rank test). Ferric Sulfate with Mineral Trioxide Aggregate (FS+MTA) is an alternative to RCT for vital primary incisors.

Connective Tissue Disease-associated Interstitial Lung Diseases (CTD-ILD) - Report from OMERACT CTD-ILD Working Group.

PubMed

Khanna, Dinesh; Mittoo, Shikha; Aggarwal, Rohit; Proudman, Susanna M; Dalbeth, Nicola; Matteson, Eric L; Brown, Kevin; Flaherty, Kevin; Wells, Athol U; Seibold, James R; Strand, Vibeke

2015-11-01

Interstitial lung disease (ILD) is common in connective tissue disease (CTD) and is the leading cause of mortality. Investigators have used certain outcome measures in randomized controlled trials (RCT) in CTD-ILD, but the lack of a systematically developed, CTD-specific index that captures all measures relevant and meaningful to patients with CTD-ILD has left a large and conspicuous gap in CTD-ILD research. The CTD-ILD working group, under the aegis of the Outcome Measures in Rheumatology (OMERACT) initiative, has completed a consensus group exercise to reach harmony on core domains and items for inclusion in RCT in CTD-ILD. During the OMERACT 12 meeting, consensus was sought on domains and core items for inclusion in RCT. In addition, consensus was pursued on a definition of response in RCT. Consensus was defined as ≥ 75% agreement among the participants. OMERACT 12 participants endorsed the domains with minimal modifications. Clinically meaningful progression for CTD-ILD was proposed as ≥ 10% relative decline in forced vital capacity (FVC) or ≥ 5% to < 10% relative decline in FVC and ≥ 15% relative decline in DLCO. There is consensus on domains for inclusion in RCT in CTD-ILD and on a definition of clinically meaningful progression. Data-driven approaches to validate these results in different cohorts and RCT are needed.

Knowledge, attitudes and decision-making preferences of men considering participation in the TROG RAVES Prostate Cancer Trial (TROG 08.03).

PubMed

Tesson, Stephanie; Sundaresan, Puma; Ager, Brittany; Butow, Phyllis; Kneebone, Andrew; Costa, Daniel; Woo, Henry; Pearse, Maria; Juraskova, Ilona; Turner, Sandra

2016-04-01

The RAVES (Trans-Tasman Radiation Oncology Group 08.03) randomised controlled trial (RCT), compares adjuvant radiotherapy with early salvage radiotherapy in men with high risk histopathological features at prostatectomy. The RAVES Decision Aid study evaluates the utility of a decision aid for men considering participation in the RAVES RCT. We report the RAVES Decision Aid study participants' attitudes and knowledge regarding RCTs, decision-making preferences and decisional-conflict. Baseline questionnaires assessed knowledge and attitudes towards RCTs and RAVES RCT. Sociodemographic and clinical predictors of knowledge were examined. Involvement in decision-making and difficulties with the decision-making process were assessed using validated tools. 127 men (median age=63years) were recruited through urologists (n=91) and radiation oncologists (n=36). Men preferred collaborative (35%) or semi-active (35%) decision-making roles. Most (>75%) felt the RAVES RCT was worthwhile and important with participation being wise. However, nearly half had high decisional-conflict regarding participation. Scores of objective knowledge regarding RCTs and RAVES RCT were low. Most men with high-risk histopathological features at prostatectomy desire active involvement in decision-making regarding further management. Despite positive attitudes towards RCTs and the RAVES RCT, there were gaps in knowledge and high decisional-conflict surrounding participation. Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.

A prospective cohort and extended comprehensive-cohort design provided insights about the generalizability of a pragmatic trial: the ProtecT prostate cancer trial.

PubMed

Donovan, Jenny L; Young, Grace J; Walsh, Eleanor I; Metcalfe, Chris; Lane, J Athene; Martin, Richard M; Tazewell, Marta K; Davis, Michael; Peters, Tim J; Turner, Emma L; Mills, Nicola; Khazragui, Hanan; Khera, Tarnjit K; Neal, David E; Hamdy, Freddie C

2018-04-01

Randomized controlled trials (RCTs) deliver robust internally valid evidence but generalizability is often neglected. Design features built into the Prostate testing for cancer and Treatment (ProtecT) RCT of treatments for localized prostate cancer (PCa) provided insights into its generalizability. Population-based cluster randomization created a prospective study of prostate-specific antigen (PSA) testing and a comprehensive-cohort study including groups choosing treatment or excluded from the RCT, as well as those randomized. Baseline information assessed selection and response during RCT conduct. The prospective study (82,430 PSA-tested men) represented healthy men likely to respond to a screening invitation. The extended comprehensive cohort comprised 1,643 randomized, 997 choosing treatment, and 557 excluded with advanced cancer/comorbidities. Men choosing treatment were very similar to randomized men except for having more professional/managerial occupations. Excluded men were similar to the randomized socio-demographically but different clinically, representing less healthy men with more advanced PCa. The design features of the ProtecT RCT provided data to assess the representativeness of the prospective cohort and generalizability of the findings of the RCT. Greater attention to collecting data at the design stage of pragmatic trials would better support later judgments by clinicians/policy-makers about the generalizability of RCT findings in clinical practice. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

MTHFR C677T Polymorphism is Associated with Tumor Response to Preoperative Chemoradiotherapy: A Result Based on Previous Reports.

PubMed

Zhao, Yue; Li, Xingde; Kong, Xiangjun

2015-10-12

Preoperative chemoradiotherapy (pRCT) followed by surgery has been widely practiced in locally advanced rectal cancer, esophageal cancer, gastric cancer and other cancers. However, the therapy also exerts some severe adverse effects and some of the patients show poor or no response. It is very important to develop biomarkers (e.g., gene polymorphisms) to identify patients who have a higher likelihood of responding to pRCT. Recently, a series of reports have investigated the association of the genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and epidermal growth factor receptor (EGFR) genes with the tumor response to pRCT; however, the results were inconsistent and inconclusive. A systematic review and meta-analysis was performed by searching relevant studies about the association of MTHFR and EGFR polymorphisms with the tumor regression grade (TRG) in response to pRCT in databases of PubMed, EMBAS, Web of science, Chinese National Knowledge Infrastructure, and Wanfang database up to March 30, 2015. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were calculated to assess the strength of the association under 5 genetic models. A total of 11 eligible articles were included in the present meta-analysis, of which 8 studies were performed in rectal cancer and 3 studies were performed in esophageal cancer. We finally included 8 included studies containing 839 cases for MTHFR C677T, 5 studies involving 634 cases for MTHFR A1298C, 3 studies containing 340 cases for EGFR G497A, and 4 studies containing 396 cases for EGFR CA repeat. The pooled analysis results indicated that MTHFR C677T might be correlated with the tumor response to pRCT under the recessive model (CC vs. CTTT) in overall analysis (OR=1.426(1.074-1.894), P=0.014), rectal cancer (OR=1.483(1.102-1.996), P=0.009), and TRG 1-2 vs. 3-5 group (OR=1.423(1.046-1.936), P=0.025), while other polymorphism including MTHFR A1298C, EGFR G497A, and EGFR CA repeat polymorphisms exerted significant association under all genetic models in overall analysis or subgroup analysis. MTHFR C677T might be correlated with the tumor response to pRCT. Further well-designed, larger-scale epidemiological studies are needed to validate our results.

Patient-centered clinical trials.

PubMed

Chaudhuri, Shomesh E; Ho, Martin P; Irony, Telba; Sheldon, Murray; Lo, Andrew W

2018-02-01

We apply Bayesian decision analysis (BDA) to incorporate patient preferences in the regulatory approval process for new therapies. By assigning weights to type I and type II errors based on patient preferences, the significance level (α) and power (1-β) of a randomized clinical trial (RCT) for a new therapy can be optimized to maximize the value to current and future patients and, consequently, to public health. We find that for weight-loss devices, potentially effective low-risk treatments have optimal αs larger than the traditional one-sided significance level of 5%, whereas potentially less effective and riskier treatments have optimal αs below 5%. Moreover, the optimal RCT design, including trial size, varies with the risk aversion and time-to-access preferences and the medical need of the target population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of EULAR recommendations for the reporting of clinical trial extension studies in rheumatology

PubMed Central

Buch, Maya H; Silva-Fernandez, Lucia; Carmona, Loreto; Aletaha, Daniel; Christensen, Robin; Combe, Bernard; Emery, Paul; Ferraccioli, Gianfranco; Guillemin, Francis; Kvien, Tore K; Landewe, Robert; Pavelka, Karel; Saag, Kenneth; Smolen, Josef S; Symmons, Deborah; van der Heijde, Désirée; Welling, Joep; Wells, George; Westhovens, Rene; Zink, Angela; Boers, Maarten

2015-01-01

Objectives Our initiative aimed to produce recommendations on post-randomised controlled trial (RCT) trial extension studies (TES) reporting using European League Against Rheumatism (EULAR) standard operating procedures in order to achieve more meaningful output and standardisation of reports. Methods We formed a task force of 22 participants comprising RCT experts, clinical epidemiologists and patient representatives. A two-stage Delphi survey was conducted to discuss the domains of evaluation of a TES and definitions. A ‘0–10’ agreement scale assessed each domain and definition. The resulting set of recommendations was further refined and a final vote taken for task force acceptance. Results Seven key domains and individual components were evaluated and led to agreed recommendations including definition of a TES (100% agreement), minimal data necessary (100% agreement), method of data analysis (agreement mean (SD) scores ranging between 7.9 (0.84) and 9.0 (2.16)) and reporting of results as well as ethical issues. Key recommendations included reporting of absolute numbers at each stage from the RCT to TES with reasons given for drop-out at each stage, and inclusion of a flowchart detailing change in numbers at each stage and focus (mean (SD) agreement 9.9 (0.36)). A final vote accepted the set of recommendations. Conclusions This EULAR task force provides recommendations for implementation in future TES to ensure a standardised approach to reporting. Use of this document should provide the rheumatology community with a more accurate and meaningful output from future TES, enabling better understanding and more confident application in clinical practice towards improving patient outcomes. PMID:24827533

Perineal resuturing versus expectant management following vaginal delivery complicated by a dehisced wound (PREVIEW): a nested qualitative study.

PubMed

Dudley, L; Kettle, C; Waterfield, J; Ismail, Khaled M K

2017-02-10

To explore women's lived experiences of a dehisced perineal wound following childbirth and how they felt participating in a pilot and feasibility randomised controlled trial (RCT). A nested qualitative study using semistructured interviews, underpinned by descriptive phenomenology. A purposive sample of six women at 6-9 months postnatal who participated in the RCT were interviewed in their own homes. Following Giorgi's analytical framework the verbatim transcripts were analysed for key themes. Women's lived experiences revealed 4 emerging themes: (1) Physical impact, with sub-themes focusing upon avoiding infection, perineal pain and the impact of the wound dehiscence upon daily activities; (2) Psychosocial impact, with sub-themes of denial, sense of failure or self-blame, fear, isolation and altered body image; (3) Sexual impact; and (4) Satisfaction with wound healing. A fifth theme 'participating in the RCT' was 'a priori' with sub-themes centred upon understanding the randomisation process, completing the trial questionnaires, attending for hospital appointments and acceptability of the treatment options. To the best of our knowledge, this is the first qualitative study to grant women the opportunity to voice their personal experiences of a dehisced perineal wound and their views on the management offered. The powerful testimonies presented disclose the extent of morbidity experienced while also revealing a strong preference for a treatment option. ISRCTN05754020; 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/.

Evaluation of the effectiveness of robotic gait training and gait-focused physical therapy programs for children and youth with cerebral palsy: a mixed methods RCT.

PubMed

Wiart, Lesley; Rosychuk, Rhonda J; Wright, F Virginia

2016-06-02

Robot assisted gait training (RAGT) is considered to be a promising approach for improving gait-related gross motor function of children and youth with cerebral palsy. However, RAGT has yet to be empirically demonstrated to be effective. This knowledge gap is particularly salient given the strong interest in this intensive therapy, the high cost of the technology, and the requirement for specialized rehabilitation centre resources. This is a research protocol describing a prospective, multi-centre, concurrent mixed methods study comprised of a randomized controlled trial (RCT) and an interpretive descriptive qualitative design. It is a mixed methods study designed to determine the relative effectiveness of three physical therapy treatment conditions (i.e., RAGT, a functional physical therapy program conducted over-ground (fPT), and RAGT + fPT) on gait related motor skills of ambulatory children with cerebral palsy. Children with cerebral palsy aged 5-18 years who are ambulatory (Gross Motor Function Classification System Levels II and III) will be randomly allocated to one of four treatment conditions: 1) RAGT, 2) fPT, 3) RAGT and fPT combined, or 4) a maintenance therapy only control group. The qualitative component will explicate child and parent experiences with the interventions, provide insight into the values that underlie their therapy goals, and assist with interpretation of the results of the RCT. n/a. NCT02391324 Registered March 12, 2015.

[Witch hunt and hypotheses loss].

PubMed

Köhler, Dieter

2015-12-01

At this time randomized controlled studies (RCT) in clinical trials usually have high quality. But this quality is only true for the included patients (intrinsic validity). It is common to generalize the results to more or less similar patients. This inductive method is prohibited in epistemology what is known for 250 years (D Hume, K R Popper). Therefore the external validity for the data of RCT is low. To solve this problem additional clinical and pathophysiological based data are necessary to generalize the results. Unfortunately RCT show less quality in their premises. This is partly due to the influence of the pharmaceutical industry. A loss of universality of the hypothesis for RCT decreases basically the extrinsic validity. The articles describe this problem with examples. © Georg Thieme Verlag KG Stuttgart · New York.

Virtual reality exposure therapy for the treatment of anxiety disorders: an evaluation of research quality.

PubMed

McCann, Russell A; Armstrong, Christina M; Skopp, Nancy A; Edwards-Stewart, Amanda; Smolenski, Derek J; June, Jennifer D; Metzger-Abamukong, Melinda; Reger, Greg M

2014-08-01

Randomized controlled trials (RCTs) support the effectiveness of virtual reality exposure therapy (VRET) for anxiety disorders; however, the overall quality of the VRET RCT literature base has yet to be evaluated. This study reviewed 27 VRET RCTs and the degree of adherence to 8 RCT research design criteria derived from existing standards. Adherence to the study quality criteria was generally low as the articles met an average 2.85 criteria (SD=1.56). None of the studies met more than six quality criteria. Study quality did not predict effect size; however, a reduction in effect size magnitude was observed for studies with larger sample sizes when comparing VRET to non-active control groups. VRET may be an effective method of treatment but caution should be exercised in interpreting the existing body of literature supporting VRET relative to existing standards of care. The need for well-designed VRET research is discussed. Copyright © 2014. Published by Elsevier Ltd.

Aromatherapy for treatment of hypertension: a systematic review.

PubMed

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

2012-02-01

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

Instrumental variables I: instrumental variables exploit natural variation in nonexperimental data to estimate causal relationships.

PubMed

Rassen, Jeremy A; Brookhart, M Alan; Glynn, Robert J; Mittleman, Murray A; Schneeweiss, Sebastian

2009-12-01

The gold standard of study design for treatment evaluation is widely acknowledged to be the randomized controlled trial (RCT). Trials allow for the estimation of causal effect by randomly assigning participants either to an intervention or comparison group; through the assumption of "exchangeability" between groups, comparing the outcomes will yield an estimate of causal effect. In the many cases where RCTs are impractical or unethical, instrumental variable (IV) analysis offers a nonexperimental alternative based on many of the same principles. IV analysis relies on finding a naturally varying phenomenon, related to treatment but not to outcome except through the effect of treatment itself, and then using this phenomenon as a proxy for the confounded treatment variable. This article demonstrates how IV analysis arises from an analogous but potentially impossible RCT design, and outlines the assumptions necessary for valid estimation. It gives examples of instruments used in clinical epidemiology and concludes with an outline on estimation of effects.

Instrumental variables I: instrumental variables exploit natural variation in nonexperimental data to estimate causal relationships

PubMed Central

Rassen, Jeremy A.; Brookhart, M. Alan; Glynn, Robert J.; Mittleman, Murray A.; Schneeweiss, Sebastian

2010-01-01

The gold standard of study design for treatment evaluation is widely acknowledged to be the randomized controlled trial (RCT). Trials allow for the estimation of causal effect by randomly assigning participants either to an intervention or comparison group; through the assumption of “exchangeability” between groups, comparing the outcomes will yield an estimate of causal effect. In the many cases where RCTs are impractical or unethical, instrumental variable (IV) analysis offers a nonexperimental alternative based on many of the same principles. IV analysis relies on finding a naturally varying phenomenon, related to treatment but not to outcome except through the effect of treatment itself, and then using this phenomenon as a proxy for the confounded treatment variable. This article demonstrates how IV analysis arises from an analogous but potentially impossible RCT design, and outlines the assumptions necessary for valid estimation. It gives examples of instruments used in clinical epidemiology and concludes with an outline on estimation of effects. PMID:19356901

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

PubMed

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

2007-01-01

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

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

PubMed Central

2013-01-01

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

Effects of Souvenaid on plasma micronutrient levels and fatty acid profiles in mild and mild-to-moderate Alzheimer's disease.

PubMed

Rijpma, Anne; Meulenbroek, Olga; van Hees, Anneke M J; Sijben, John W C; Vellas, Bruno; Shah, Raj C; Bennett, David A; Scheltens, Philip; Olde Rikkert, Marcel G M

2015-01-01

Circulating levels of uridine, selenium, vitamins B12, E and C, folate, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been shown to be lower in patients with Alzheimer's disease (AD) than in healthy individuals. These low levels may affect disease pathways involved in synapse formation and neural functioning. Here, we investigated whether, and to what extent, circulating levels of micronutrients and fatty acids can be affected by oral supplementation with Souvenaid (containing a specific nutrient combination), using data derived from three randomized clinical trials (RCT) and an open-label extension (OLE) study with follow-up data from 12 to 48 weeks. Subjects with mild (RCT1, RCT2) or mild-to-moderate AD (RCT3) received active or control product once daily for 12-24 weeks or active product during the 24-week OLE following RCT2 (n = 212-527). Measurements included plasma levels of B vitamins, choline, vitamin E, selenium, uridine and homocysteine and proportions of DHA, EPA and total n-3 long-chain polyunsaturated fatty acids in plasma and erythrocytes. Between-group comparisons were made using t tests or non-parametric alternatives. We found that 12-24-week active product intake increased plasma and/or erythrocyte micronutrients: uridine; choline; selenium; folate; vitamins B6, B12 and E; and fatty acid levels of DHA and EPA (all p < 0.001). In the OLE study, similar levels were reached in former control product/initial active product users, whereas 24-week continued active product intake showed no suggestion of a further increase in nutrient levels. These data show that circulating levels of nutrients known to be decreased in the AD population can be increased in patients with mild and mild-tomoderate AD by 24-48-week oral supplementation with Souvenaid. In addition, to our knowledge, this is the first report of the effects of sustained dietary intake of uridine monophosphate on plasma uridine levels in humans. Uptake of nutrients is observed within 6 weeks, and a plateau phase is reached for most nutrients during prolonged intake, thus increasing the availability of precursors and cofactors in the circulation that may be used for the formation and function of neuronal membranes and synapses in the brain.

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

PubMed

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

2013-07-15

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

Genetic parameters of coagulation properties, milk yield, quality, and acidity estimated using coagulating and noncoagulating milk information in Brown Swiss and Holstein-Friesian cows.

PubMed

Cecchinato, A; Penasa, M; De Marchi, M; Gallo, L; Bittante, G; Carnier, P

2011-08-01

The aim of this study was to estimate heritabilities of rennet coagulation time (RCT) and curd firmness (a(30)) and their genetic correlations with test-day milk yield, composition (fat, protein, and casein content), somatic cell score, and acidity (pH and titratable acidity) using coagulating and noncoagulating (NC) milk information. Data were from 1,025 Holstein-Friesian (HF) and 1,234 Brown Swiss (BS) cows, which were progeny of 54 HF and 58 BS artificial insemination sires, respectively. Milk coagulation properties (MCP) of each cow were measured once using a computerized renneting meter and samples not exhibiting coagulation within 31 min after rennet addition were classified as NC milk. For NC samples, RCT was unobserved. Multivariate analyses, using Bayesian methodology, were performed to estimate the genetic relationships of RCT or a(30) with the other traits and statistical inference was based on the marginal posterior distributions of parameters of concern. For analyses involving RCT, a right-censored Gaussian linear model was used and records of NC milk samples, being censored records, were included as unknown parameters in the model implementing a data augmentation procedure. Rennet coagulation time was more heritable [heritability (h(2))=0.240 and h(2)=0.210 for HF and BS, respectively] than a(30) (h(2)=0.148 and h(2)=0.168 for HF and BS, respectively). Milk coagulation properties were more heritable than a single test-day milk yield (h(2)=0.103 and h(2)=0.097 for HF and BS, respectively) and less heritable than milk composition traits whose heritability ranged from 0.275 to 0.275, with the only exception of fat content of BS milk (h(2)=0.108). A negative genetic correlation, lower than -0.85, was estimated between RCT and a(30) for both breeds. Genetic relationships of MCP with yield and composition were low or moderate and favorable. The genetic correlation of somatic cell score with RCT in BS cows was large and positive and even more positive were those of RCT with pH and titratable acidity in both breeds, ranging from 0.80 to 0.94. Including NC milk information in the data affected the estimated correlations and decreased the uncertainty associated with the estimation process. On the basis of the estimated heritabilities and genetic correlations, enhancement of MCP through selective breeding with no detrimental effects on yield and composition seems feasible in both breeds. Milk acidity may play a role as an indicator trait for indirect enhancement of MCP. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Psychological interventions for post-traumatic stress disorder (PTSD) in people with severe mental illness.

PubMed

Sin, Jacqueline; Spain, Debbie; Furuta, Marie; Murrells, Trevor; Norman, Ian

2017-01-24

Increasing evidence indicates that individuals who develop severe mental illness (SMI) are also vulnerable to developing post-traumatic stress disorder (PTSD), due to increased risk of exposure to traumatic events and social adversity. The effectiveness of trauma-focused psychological interventions (TFPIs) for PTSD in the general population is well-established. TFPIs involve identifying and changing unhelpful beliefs about traumatic experiences, processing of traumatic memories, and developing new ways of responding to cues associated with trauma. Little is known about the potential feasibility, acceptability and effectiveness of TFPIs for individuals who have a SMI and PTSD. To evaluate the effectiveness of psychological interventions for PTSD symptoms or other symptoms of psychological distress arising from trauma in people with SMI. We searched the Cochrane Schizophrenia Group's Trials Study-Based Register (up until March 10, 2016), screened reference lists of relevant reports and reviews, and contacted trial authors for unpublished and/or specific outcome data. We included all relevant randomised controlled trials (RCTs) which investigated TFPIs for people with SMI and PTSD, and reported useable data. Three review authors (DS, MF, IN) independently screened the titles and abstracts of all references identified, and read short-listed full text papers. We assessed risk of bias in each case. We calculated the risk ratio (RR) and 95% confidence interval (CI) for binary outcomes, and the mean difference (MD) and 95% CI for continuous data, on an intention-to-treat basis. We assessed quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and created 'Summary of findings' tables. Four trials involving a total of 300 adults with SMI and PTSD are included. These trials evaluated three active intervention therapies: trauma-focused cognitive behavioural therapy (TF-CBT), eye movement desensitisation and reprocessing (EMDR), and brief psychoeducation for PTSD, all delivered via individual sessions. Our main outcomes of interest were PTSD symptoms, quality of life/well-being, symptoms of co-morbid psychosis, anxiety symptoms, depressive symptoms, adverse events and health economic outcomes. 1. TF-CBT versus usual care/waiting list Three trials provided data for this comparison, however, continuous outcome data available were more often found to be skewed than unskewed, leading to the necessity of conducting analyses separately for the two types of continuous data. Using the unskewed data only, results showed no significant differences between TF-CBT and usual care in reducing clinician-rated PTSD symptoms at short term (1 RCT, n =13, MD 13.15, 95% CI -4.09 to 30.39,low-quality evidence). Limited unskewed data showed equivocal results between groups in terms of general quality of life (1 RCT, n = 39, MD -0.60, 95% CI -4.47 to 3.27, low-quality evidence), symptoms of psychosis (1 RCT, n = 9, MD -6.93, 95% CI -34.17 to 20.31, low-quality evidence), and anxiety (1 RCT, n = 9, MD 12.57, 95% CI -5.54 to 30.68, very low-quality evidence), at medium term. The only available data on depression symptoms were skewed and were equivocal across groups at medium term (2 RCTs, n = 48, MD 3.26, 95% CI -3.66 to 10.18, very low-quality evidence). TF-CBT was not associated with more adverse events (1 RCT, n = 100, RR 0.44, 95% CI 0.09 to 2.31, low-quality evidence) at medium term. No data were available for health economic outcomes. Very limited data for PTSD and other symptoms were available over the long term. 2. EMDR versus waiting listOne trial provided data for this comparison. Favourable effects were found for EMDR in terms of PTSD symptom severity at medium term but data were skewed (1 RCT, n = 83, MD -12.31, 95% CI -22.72 to -1.90, very low-quality evidence). EMDR was not associated with more adverse events (1 RCT, n = 102, RR 0.21, 95% CI 0.02 to 1.85, low-quality evidence). No data were available for quality of life, symptoms of co-morbid psychosis, depression, anxiety and health economics.3. TF-CBT versus EMDROne trial compared TF-CBT with EMDR. PTSD symptom severity, based on skewed data (1 RCT, n = 88, MD -1.69, 95% CI -12.63 to 9.23, very low-quality evidence) was similar between treatment groups. No data were available for the other main outcomes.4. TF-CBT versus psychoeducationOne trial compared TF-CBT with psychoeducation. Results were equivocal for PTSD symptom severity (1 RCT, n = 52, MD 0.23, 95% CI -14.66 to 15.12, low-quality evidence) and general quality of life (1 RCT, n = 49, MD 0.11, 95% CI -0.74 to 0.95, low-quality evidence) by medium term. No data were available for the other outcomes of interest. Very few trials have investigated TFPIs for individuals with SMI and PTSD. Results from trials of TF-CBT are limited and inconclusive regarding its effectiveness on PTSD, or on psychotic symptoms or other symptoms of psychological distress. Only one trial evaluated EMDR and provided limited preliminary evidence favouring EMDR compared to waiting list. Comparing TF-CBT head-to-head with EMDR and brief psychoeducation respectively, showed no clear effect for either therapy. Both TF-CBT and EMDR do not appear to cause more (or less) adverse effects, compared to waiting list or usual care; these findings however, are mostly based on low to very low-quality evidence. Further larger scale trials are now needed to provide high-quality evidence to confirm or refute these preliminary findings, and to establish which intervention modalities and techniques are associated with improved outcomes, especially in the long term.

[Analysis on quality of articles published in Chinese Acupuncture and Moxibustion from 2000 to 2006].

PubMed

Chen, Wen; Huang, Juan; Huang, Ai-ming

2008-01-01

To understand the quality of the papers issued in Chinese Acupuncture and Moxibustion in past 7 years, so as to provide reference for its development. Analyze information quality of the papers based on the treatises issued in Chinese Acupuncture and Moxibustion between 2000-2006. (1) Most of the authors come from medical schools and their affiliated hospitals (including scientific research units), accounting for 61. 0%; (2) Authors of each paper mainly range between 2-3 persons, accounting for 40.0%; (3) There are 405 papers with support of funds (mainly from provincial and ministerial funds) in the 7 years, accounting for 26. 2% of the total number of the papers; (4) Publication delay shortens annually, averaging 255. 3 days in the past 7 years and 210.5 days in 2006; (5) RCT papers of clinical researches account for 30.4% and show a raising tendency year by year. Chinese Acupuncture and Moxibustion has considerable advantages in the above-mentioned four aspects, showing the high quality of "key periodical", but the proportion of RCT papers still needs to be further increased.

Baseline participant characteristics and risk for dropout from ten obesity randomized controlled trials: a pooled analysis of individual level data.

PubMed

Kaiser, Kathryn A; Affuso, Olivia; Desmond, Renee; Allison, David B

Understanding participant demographic characteristics that inform the optimal design of obesity RCTs have been examined in few studies. The objective of this study was to investigate the association of individual participant characteristics and dropout rates (DORs) in obesity randomized controlled trials (RCT) by pooling data from several publicly available datasets for analyses. We comprehensively characterize DORs and patterns in obesity RCTs at the individual study level, and describe how such rates and patterns vary as a function of individual-level characteristics. We obtained and analyzed nine publicly-available, obesity RCT datasets that examined weight loss or weight gain prevention as a primary or secondary endpoint. Four risk factors for dropout were examined by Cox proportional hazards including sex, age, baseline BMI, and race/ethnicity. The individual study data were pooled in the final analyses with a random effect for study, and HR and 95% CIs were computed. Results of the multivariate analysis indicated that the risk of dropout was significantly higher for females compared to males (HR= 1.24, 95% CI = 1.05, 1.46). Hispanics and Non-Hispanic blacks had a significantly higher dropout rate compared to non-Hispanic whites (HR= 1.62, 95% CI = 1.37, 1.91; HR= 1.22, 95% CI = 1.11, 1.35, respectively). There was a significantly increased risk of dropout associated with advancing age (HR= 1.02, 95% CI = 1.01, 1.02) and increasing BMI (HR= 1.03, 95% CI = 1.03, 1.04). As more studies may focus on special populations, researchers designing obesity RCTs may wish to oversample in certain demographic groups if attempting to match comparison groups based on generalized estimates of expected dropout rates, or otherwise adjust a priori power estimates. Understanding true reasons for dropout may require additional methods of data gathering not generally employed in obesity RCTs, e.g. time on treatment.

Effectiveness of Virtual Reality in Children With Cerebral Palsy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Chen, Yuping; Fanchiang, HsinChen D; Howard, Ayanna

2018-01-01

Researchers recently investigated the effectiveness of virtual reality (VR) in helping children with cerebral palsy (CP) to improve motor function. A systematic review of randomized controlled trials (RCTs) using a meta-analytic method to examine the effectiveness of VR in children with CP was thus needed. The purpose of this study was to update the current evidence about VR by systematically examining the research literature. A systematic literature search of PubMed, CINAHL, Cochrane Central Register of Controlled Trials, ERIC, PsycINFO, and Web of Science up to December 2016 was conducted. Studies with an RCT design, children with CP, comparisons of VR with other interventions, and movement-related outcomes were included. A template was created to systematically code the demographic, methodological, and miscellaneous variables of each RCT. The Physiotherapy Evidence Database (PEDro) scale was used to evaluate the study quality. Effect size was computed and combined using meta-analysis software. Moderator analyses were also used to explain the heterogeneity of the effect sizes in all RCTs. . The literature search yielded 19 RCT studies with fair to good methodological quality. Overall, VR provided a large effect size (d = 0.861) when compared with other interventions. A large effect of VR on arm function (d = 0.835) and postural control (d = 1.003) and a medium effect on ambulation (d = 0.755) were also found. Only the VR type affected the overall VR effect: an engineer-built system was more effective than a commercial system. The RCTs included in this study were of fair to good quality, had a high level of heterogeneity and small sample sizes, and used various intervention protocols. Then compared with other interventions, VR seems to be an effective intervention for improving motor function in children with CP. © 2017 American Physical Therapy Association

SU-F-J-156: The Feasibility of MR-Only IMRT Planning for Prostate Anatomy

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

Vaitheeswaran, R; Sivaramakrishnan, KR; Kumar, Prashant

Purpose: For prostate anatomy, previous investigations have shown that simulated CT (sCT) generated from MR images can be used for accurate dose computation. In this study, we demonstrate the feasibility of MR-only IMRT planning for prostate case. Methods: Regular CT (rCT) and MR images of the same patient were acquired for prostate anatomy. Regions-of-interest (ROIs) i.e. target and risk structures are delineated on the rCT. A simulated CT (sCT) is generated from the MR image using the method described by Schadewaldt N et al. Their work establishes the clinical acceptability of dose calculation results on the sCT when compared tomore » rCT. rCT and sCT are rigidly registered to ensure proper alignment between the two images. rCT and sCT are overlaid on each other and slice-wise visual inspection confirms excellent agreement between the two images. ROIs on the rCT are copied over to sCT. Philips AutoPlanning solution is used for generating treatment plans. The same treatment technique protocol (plan parameters and clinical goals) is used to generate AutoPlan-rCT and AutoPlan-sCT respectively for rCT and and sCT. DVH comparison on ROIs and slice-wise evaluation of dose is performed between AutoPlan-rCT and AutoPlan-sCT. Delivery parameters i.e. beam and corresponding segments from the AutoPlan-sCT are copied over to rCT and dose is computed to get AutoPlan-sCT-on-rCT. Results: Plan evaluation is done based on Dose Volume Histogram (DVH) of ROIs and manual slice-wise inspection of dose distribution. Both AutoPlan-rCT and AutoPlan-sCT provide a clinically acceptable plan. Also, AutoPlan-sCT-on-rCT shows excellent agreement with AutoPlan-sCT. Conclusion: The study demonstrates that it is feasible to do IMRT planning on the simulated CT image obtained from MR image for prostate anatomy. The research is supported by Philips India Ltd.« less

Acute heart failure: perspectives from a randomized trial and a simultaneous registry.

PubMed

Ezekowitz, Justin A; Hu, Jia; Delgado, Diego; Hernandez, Adrian F; Kaul, Padma; Leader, Rolland; Proulx, Guy; Virani, Sean; White, Michel; Zieroth, Shelley; O'Connor, Christopher; Westerhout, Cynthia M; Armstrong, Paul W

2012-11-01

Randomized controlled trials (RCT) are limited by their generalizability to the broader nontrial population. To provide a context for Acute Study of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial, we designed a complementary registry to characterize clinical characteristics, practice patterns, and in-hospital outcomes of acute heart failure patients. Eligible patients for the registry included those with a principal diagnosis of acute heart failure (ICD-9-CM 402 and 428; ICD-10 I50.x, I11.0, I13.0, I13.2) from 8 sites participating in ASCEND-HF (n=697 patients, 2007-2010). Baseline characteristics, treatments, and hospital outcomes from the registy were compared with ASCEND-HF RCT patients from 31 Canadian sites (n=465, 2007-2010). Patients in the registry were older, more likely to be female, and have chronic respiratory disease, less likely to have diabetes mellitus: they had a similar incidence of ischemic HF, atrial fibrillation, and similar B-type natriuretic peptide levels. Registry patients had higher systolic blood pressure (registry: median 132 mm Hg [interquartile range 115-151 mm Hg]; RCT: median 120 mm Hg [interquartile range 110-135 mm Hg]) and ejection fraction (registry: median 40% [interquartile range 27-58%]; RCT: median 29% [interquartile range 20-40 mm Hg]) than RCT patients. Registry patients presented more often via ambulance and had a similar total length of stay as RCT patients. In-hospital mortality was significantly higher in the registry compared with the RCT patients (9.3% versus 1.3%,P<0.001), and this remained after multivariable adjustment (odds ratio 6.6, 95% CI 2.6-16.8, P<0.001). Patients enrolled in a large RCT of acute heart failure differed significantly based on clinical characteristics, treatments, and inpatient outcomes from contemporaneous patients participating in a registry. These results highlight the need for context of RCTs to evaluate generalizability of results and especially the need to improve clinical outcomes in acute heart failure. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00475852.

The association between body fat and rotator cuff tear: the influence on rotator cuff tear sizes.

PubMed

Gumina, Stefano; Candela, Vittorio; Passaretti, Daniele; Latino, Gianluca; Venditto, Teresa; Mariani, Laura; Santilli, Valter

2014-11-01

Rotator cuff tear (RCT) has a multifactorial etiology. We hypothesized that obesity may increase the risk of RCT and influence tear size. A case-control design study was used. We studied 381 consecutive patients (180 men, 201 women; mean age ± standard deviation, 65.5 ± 8.52 years; range, 43-78 years) who underwent arthroscopic rotator cuff repair. Tear size was determined intraoperatively. The control group included 220 subjects (103 men, 117 women; mean age ± standard deviation, 65.16 ± 7.24 years; range, 42-77 years) with no RCT. Body weight, height, and bicipital, tricipital, subscapularis, and suprailiac skinfolds of all participants were measured to obtain body mass index (BMI) and the percentage of body fat (%BF). For the purposes of the study, the 601 participants were divided into 2 groups by BMI (group A, BMI ≥ 25; group B, BMI < 25). The odds ratios (ORs) were calculated to investigate whether adiposity affects the risk of RCT. Data were stratified according to gender and age. Multiple linear regression analyses were applied to explore the association between obesity and tear size. The highest ORs for both men (OR, 2.49; 95% confidence interval, 1.41-3.90; P = .0037) and women (OR, 2.31; 95% confidence interval, 1.38-3.62; P = .0071) were for individuals with a BMI ≥ 30; 69% (N = 303) of group A and 48% (N = 78) of group B had RCTs. Patients with RCT had a BMI higher than that of subjects with no RCT in both groups (P = .031, group A; P = .02, group B). BMI and %BF significantly increased from patients with a small tear (BMI, 27.85; %BF, 37.63) to those with a massive RCT (BMI, 29.93; %BF, 39.43). Significant differences were found (P = .004; P = .031). Our results provide evidence that obesity, measured through BMI and %BF, is a significant risk factor for the occurrence and severity of RCT. Copyright © 2014. Published by Elsevier Inc.

Genetic parameters for milk coagulation properties in Estonian Holstein cows.

PubMed

Vallas, M; Bovenhuis, H; Kaart, T; Pärna, K; Kiiman, H; Pärna, E

2010-08-01

The objective of this study was to estimate heritabilities and repeatabilities for milk coagulation traits [milk coagulation time (RCT) and curd firmness (E(30))] and genetic and phenotypic correlations between milk yield and composition traits (milk fat percentage and protein percentage, urea, somatic cell count, pH) in first-lactation Estonian Holstein dairy cattle. A total of 17,577 test-day records from 4,191 Estonian Holstein cows in 73 herds across the country were collected during routine milk recordings. Measurements of RCT and E(30) determined with the Optigraph (Ysebaert, Frepillon, France) are based on an optical signal in the near-infrared region. The cows had at least 3 measurements taken during the period from April 2005 to January 2009. Data were analyzed using a repeatability animal model. There was substantial variation in milk coagulation traits with a coefficient of variation of 27% for E(30) and 9% for the log-transformed RCT. The percentage of variation explained by herd was 3% for E(30) and 4% for RCT, suggesting that milk coagulation traits are not strongly affected by herd conditions (e.g., feeding). Heritability was 0.28 for RCT and 0.41 for E(30), and repeatability estimates were 0.45 and 0.50, respectively. Genetic correlation between both milk coagulation traits was negligible, suggesting that RCT and E(30) have genetically different foundations. Milk coagulation time had a moderately high positive genetic (0.69) and phenotypic (0.61) correlation with milk pH indicating that a high pH is related to a less favorable RCT. Curd firmness had a moderate positive genetic (0.48) and phenotypic (0.45) correlation with the protein percentage. Therefore, a high protein percentage is associated with favorable curd firmness. All reported genetic parameters were statistically significantly different from zero. Additional univariate random regression analysis for milk coagulation traits yielded slightly higher average heritabilities of 0.38 and 0.47 for RCT and E(30) compared with the heritabilities of the repeatability model. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Influence of Study Design on Outcomes Following Reflexology Massage: An Integrative and Critical Review of Interventional Studies.

PubMed

McVicar, Andrew; Greenwood, Christina; Ellis, Carol; LeForis, Chantelle

2016-09-01

Interpretation of the efficacy of reflexology is hindered by inconsistent research designs and complicated by professional views that criteria of randomized controlled trials (RCTs)are not ideal to research holistic complementary and alternative medicine practice. The influence of research designs on study outcomes is not known. This integrative review sought to evaluate this possibility. Thirty-seven interventional studies (2000-2014) were identified; they had RCT or non-RCT design and compared reflexology outcomes against a control/comparison group. Viability of integrating RCT and non-RCT studies into a single database was first evaluated by appraisal of 16 reporting fields related to study setting and objectives, sample demographics, methodologic design, and treatment fidelity and assessment against Jadad score quality criteria for RCTs. For appraisal, the database was stratified into RCT/non-RCT or Jadad score of 3 or more or less than 3. Deficits in reporting were identified for blind assignment of participants, dropout/completion rate, and School of Reflexology. For comparison purposes, these fields were excluded from subsequent analysis for evidence of association between design fields and of fields with study outcomes. Thirty-one studies applied psychometric tools and 20 applied biometric tools (14 applied both). A total of 116 measures were used. Type of measure was associated with study objectives (p < 0.001; chi-square), in particular of psychometric measures with a collated "behavioral/cognitive" objective. Significant outcomes were more likely (p < 0.001; chi-square) for psychometric than for biometric measures. Neither type of outcome was associated with choice of RCT or non-RCT method, but psychometric responses were associated (p = 0.007) with a nonmassage control strategy. The review supports psychometric responses to reflexology when study design uses a nonmassage control strategy. Findings suggest that an evaluation of outcomes against sham reflexology massage and other forms of massage, as well as a narrower focus of study objective, may clarify whether there is a relationship between study design and efficacy of reflexology.

Comparison between treatment effects in a randomised controlled trial and an observational study using propensity scores in primary care.

PubMed

Stuart, Beth L; Grebel, Louise En; Butler, Christopher C; Hood, Kerenza; Verheij, Theo J M; Little, Paul

2017-09-01

Although randomised controlled trials (RCTs) are considered 'gold standard' evidence, they are not always feasible or appropriate, and may represent a select population. Observational studies provide a useful alternative to enhance applicability, but results can be biased due to confounding. To explore the utility of propensity scores for causal inference in an observational study. Comparison of the effect of amoxicillin on key outcomes in an international RCT and observational study of lower respiratory tract infections. Propensity scores were calculated and applied as probability weights in the analyses. The adjusted results were compared with the effects reported in the RCT. Groups were well balanced in the RCT but significantly imbalanced in the observational study, with evidence of confounding by indication: patients receiving antibiotics tended to be older and more unwell at baseline consultation. In the trial duration of symptoms (hazard ratio 1.06, 95% CI = 0.96 to 1.18) and symptom severity (-0.07, 95% CI = -0.15 to 0.007) did not differ between groups. Weighting by propensity score in the observational study resulted in very similar estimates of effect: duration of symptoms (hazard ratio 1.06, 95% CI = 0.80 to 1.40) and difference for symptom severity (-0.07, 95% CI = -0.34 to 0.20). The observational study, after conditioning on propensity score, echoed the trial results. Provided that detailed information is available on potential sources of confounding, effects of interventions can probably be assessed reasonably well in observational datasets, allowing them to be more directly compared with the results of RCTs. © British Journal of General Practice 2017.

Cost effectiveness of a multi-stage return to work program for workers on sick leave due to low back pain, design of a population based controlled trial [ISRCTN60233560].

PubMed

Steenstra, Ivan A; Anema, Johannes R; Bongers, Paulien M; de Vet, Henrica C W; van Mechelen, Willem

2003-11-21

To describe the design of a population based randomized controlled trial (RCT), including a cost-effectiveness analysis, comparing participative ergonomics interventions between 2-8 weeks of sick leave and Graded Activity after 8 weeks of sick leave with usual care, in occupational back pain management. An RCT and cost-effectiveness evaluation in employees sick-listed for a period of 2 to 6 weeks due to low back pain. Interventions used are 1. Communication between general practitioner and occupational physician plus Participative Ergonomics protocol performed by an ergonomist. 2. Graded Activity based on cognitive behavioural principles by a physiotherapist. 3. Usual care, provided by an occupational physician according to the Dutch guidelines for the occupational health management of workers with low back pain. The primary outcome measure is return to work. Secondary outcome measures are pain intensity, functional status and general improvement. Intermediate variables are kinesiophobia and pain coping. The cost-effectiveness analysis includes the direct and indirect costs due to low back pain. The outcome measures are assessed before randomization (after 2-6 weeks on sick leave) and 12 weeks, 26 weeks and 52 weeks after first day of sick leave. The combination of these interventions has been subject of earlier research in Canada. The results of the current RCT will: 1. crossvalidate the Canadian findings in an different sociocultural environment; 2. add to the cost-effectiveness on treatment options for workers in the sub acute phase of low back pain. Results might lead to alterations of existing (inter)national guidelines.

Effect of soya protein on blood pressure: a meta-analysis of randomised controlled trials.

PubMed

Dong, Jia-Yi; Tong, Xing; Wu, Zhi-Wei; Xun, Peng-Cheng; He, Ka; Qin, Li-Qiang

2011-08-01

Observational studies have indicated that soya food consumption is inversely associated with blood pressure (BP). Evidence from randomised controlled trials (RCT) on the BP-lowering effects of soya protein intake is inconclusive. We aimed to evaluate the effectiveness of soya protein intake in lowering BP. The PubMed database was searched for published RCT in the English language through to April 2010, which compared a soya protein diet with a control diet. We conducted a random-effects meta-analysis to examine the effects of soya protein on BP. Subgroup and meta-regression analyses were performed to explore possible explanations for heterogeneity among trials. Meta-analyses of twenty-seven RCT showed a mean decrease of 2·21 mmHg (95 % CI - 4·10, - 0·33; P = 0·021) for systolic BP (SBP) and 1·44 mmHg (95 % CI - 2·56, - 0·31; P = 0·012) for diastolic BP (DBP), comparing the participants in the soya protein group with those in the control group. Soya protein consumption significantly reduced SBP and DBP in both hypertensive and normotensive subjects, and the reductions were markedly greater in hypertensive subjects. Significant and greater BP reductions were also observed in trials using carbohydrate, but not milk products, as the control diet. Meta-regression analyses further revealed a significantly inverse association between pre-treatment BP and the level of BP reductions. In conclusion, soya protein intake, compared with a control diet, significantly reduces both SBP and DBP, but the BP reductions are related to pre-treatment BP levels of subjects and the type of control diet used as comparison.

The Cost-Effectiveness of Real-Time Continuous Glucose Monitoring (RT-CGM) in Type 2 Diabetes.

PubMed

Fonda, Stephanie J; Graham, Claudia; Munakata, Julie; Powers, Julia M; Price, David; Vigersky, Robert A

2016-07-01

This analysis models the cost-effectiveness of real-time continuous glucose monitoring (RT-CGM) using evidence from a randomized controlled trial (RCT) that demonstrated RT-CGM reduced A1C, for up to 9 months after using the technology, among patients with type 2 diabetes not on prandial insulin. RT-CGM was offered short-term and intermittently as a self-care tool to inform patients' behavior. The analyses projected lifetime clinical and economic outcomes for RT-CGM versus self-monitoring of blood glucose by fingerstick only. The base-case analysis was consistent with the RCT (RT-CGM for 2 weeks on/1 week off over 3 months). A scenario analysis simulated outcomes of an RT-CGM "refresher" after the active intervention of the RCT. Analyses used the IMS CORE Diabetes Model and were conducted from a US third-party payer perspective, including direct costs obtained from published sources and inflated to 2011 US dollars. Costs and health outcomes were discounted at 3% per annum. Life expectancy (LE) and quality-adjusted life expectancy (QALE) from RT-CGM were 0.10 and 0.07, with a cost of $653/patient over a lifetime. Incremental LE and QALE from a "refresher" were 0.14 and 0.10, with a cost of $1312/patient over a lifetime, and incremental cost-effectiveness ratios were $9319 and $13 030 per LY and QALY gained. RT-CGM, as a self-care tool, is a cost-effective disease management option in the US for people with type 2 diabetes not on prandial insulin. Repeated use of RT-CGM may result in additional cost-effectiveness. © 2016 Diabetes Technology Society.

Effects and safety of combination therapy with gonadotropin-releasing hormone analogue and growth hormone in girls with idiopathic central precocious puberty: a meta-analysis.

PubMed

Liu, S; Liu, Q; Cheng, X; Luo, Y; Wen, Y

2016-10-01

This meta-analysis is to evaluate the effects and safety of the combination therapy for girls with idiopathic central precocious puberty (ICPP). Electronic databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) that adopted gonadotropin-releasing hormone analogue (GnRHa) therapy and GnRHa plus growth hormone (GH) combination therapy to treat ICPP girls. A total of six RCTs (162 patients) and six CCTs (247 patients) were included. Compared to the GnRHa therapy group, the combination therapy group achieved taller final height (mean difference, MD = 2.81 cm, 95 % CI 1.76-3.87, four CCTs; MD = 4.30 cm, 95 % CI 0.59-8.01, one RCT); greater progression of final height compared with target height (MD = 3.92 cm, 95 % CI 3.12-4.73, four CCTs; MD = 4.00 cm, 95 % CI 1.93-6.07, One RCT) and larger height gains (MD = 3.49 cm, 95 % CI 0.97-6.01, four CCTs; MD = 3.88 cm, 95 % CI 0.15-7.61, one RCT). No severe adverse effects of treatment were reported. For ICPP girls, the GnRHa and GH combination therapy had advantages over GnRHa alone on final height and no severe adverse effects were reported. We recommend comprehensive assessment of the individual growth rate, patient compliance, the clinical effects, the height expectations of individual patients and the treatment cost to the family in order to identify the best therapy for individual patients.

The Norwegian Healthy Life Study: protocol for a pragmatic RCT with longitudinal follow-up on physical activity and diet for adults.

PubMed

Abildsnes, Eirik; Meland, Eivind; Mildestvedt, Thomas; Stea, Tonje H; Berntsen, Sveinung; Samdal, Gro Beate

2017-01-05

The Norwegian Directorate of Health recommends that Healthy Life Centres (HLCs) be established in primary health care to support behaviour change and reduce the risk of non-communicable diseases. The aim of the present study protocol is to present the rationale, design and methods of a combined pragmatic randomized controlled trial (RCT) and longitudinal cohort study of the effects of attending HLCs concerning physical activity, sedentary behaviour and diet and to explore how psychological well-being and motivational factors may mediate short- and long-term effects. The present study will combine a 6-month RCT with a longitudinal cohort study (24 months from baseline) conducted at six HLCs from June 2014 to Sept 2017. Participants are randomized to behavioural change interventions or a 6-month waiting list control group. A randomized trial of interventions in HLCs has the potential to influence the development of policy and practice for behaviour change interventions and patient education programmes in Norway. We discuss some of the important preconditions for obtaining valid results from a complex intervention and outline some of the characteristics of ecological approaches in health care research that can enable a pragmatic intervention study. The study was retrospectively registered on September 19, 2014 and is available online at ClinicalTrials.gov (ID: NCT02247219 ).

Effectiveness and safety of moderate-intensity aerobic water exercise during pregnancy for reducing use of epidural analgesia during labor: protocol for a randomized clinical trial.

PubMed

Navas, Araceli; Artigues, Catalina; Leiva, Alfonso; Portells, Elena; Soler, Aina; Cladera, Antonia; Ortas, Silvia; Alomar, Margarita; Gual, Marina; Manzanares, Concepción; Brunet, Marina; Julià, Magdalena; López, Lidia; Granda, Lorena; Bennasar-Veny, Miquel; Carrascosa, Mari Carmen

2018-04-11

Epidural analgesia during labor can provide effective pain relief, but can also lead to adverse effects. The practice of moderate exercise during pregnancy is associated with an increased level of endorphins in the blood, and this could also provide pain relief during labor. Aerobic water exercises, rather than other forms of exercise, do not negatively impact articulations, reduce edema, blood pressure, and back pain, and increase diuresis. We propose a randomized controlled trial (RCT) to evaluate the effectiveness and safety of a moderate water exercise program during pregnancy on the need for epidural analgesia during labor. A multi-center, parallel, randomized, evaluator blinded, controlled trial in a primary care setting. We will randomised 320 pregnant women (14 to 20 weeks gestation) who have low risk of complications to a moderate water exercise program or usual care. The findings of this research will contribute toward understanding of the effects of a physical exercise program on pain and the need for analgesia during labor. ISRCTN Registry identifier: 14097513 register on 04 September 2017. Retrospectively registered.

What works best for whom? An exploratory, subgroup analysis in a randomized, controlled trial on the effectiveness of a workplace intervention in low back pain patients on return to work.

PubMed

Steenstra, Ivan A; Knol, Dirk L; Bongers, Paulien M; Anema, Johannes R; van Mechelen, Willem; de Vet, Henrica C W

2009-05-20

Exploratory subgroup analysis in a randomized controlled trial (RCT). To detect possible moderators in the effectiveness of a workplace intervention in a population of workers with sick leave due to sub acute nonspecific low back pain. In a recently published RCT, a workplace intervention was effective on return to work, compared to usual care. Examining the heterogeneity of effect sizes within the population in this RCT (n = 196) can lead to information on the effectiveness of the intervention in subgroups of patients. A subgroup analysis was performed by adding interaction terms to the statistical model. Before analysis the following possible moderators for treatment were identified: age, gender, pain, functional status, heavy work, and sick leave in the previous 12 months. Cox regression analyses were performed and survival curves were plotted. The interaction (P = 0.02) between age (dichotomized at the median value) and the workplace intervention indicates a modifying effect. The workplace intervention is more effective for workers > or =44 years (HR, 95% CI = 2.5, [1.6, 4.1] vs. 1.2 [0.8, 1.8] for workers <44 years old). The interaction between sick leave in the previous 12 months and the workplace intervention is significant (P = 0.02). The intervention is more effective for workers with previous sick leave (HR, 95% CI = 2.8 [1.7, 4.9] vs. 1.3 [0.8, 2.0]). A modifying effect of gender, heavy work, and pain score and functional status on the effectiveness of this intervention was not found. The findings from these exploratory analyses should be tested in future RCTs. This workplace intervention seems very suitable for return to work of older workers and workers with previous sick leave. Gender, perceived heavy work, and baseline scores in pain and functional status should not be a basis for assignment to this intervention.

Providing NHS staff with height-adjustable workstations and behaviour change strategies to reduce workplace sitting time: protocol for the Stand More AT (SMArT) Work cluster randomised controlled trial.

PubMed

O'Connell, S E; Jackson, B R; Edwardson, C L; Yates, T; Biddle, S J H; Davies, M J; Dunstan, D; Esliger, D; Gray, L; Miller, P; Munir, F

2015-12-09

High levels of sedentary behaviour (i.e., sitting) are a risk factor for poor health. With high levels of sitting widespread in desk-based office workers, office workplaces are an appropriate setting for interventions aimed at reducing sedentary behaviour. This paper describes the development processes and proposed intervention procedures of Stand More AT (SMArT) Work, a multi-component randomised control (RCT) trial which aims to reduce occupational sitting time in desk-based office workers within the National Health Service (NHS). SMArT Work consists of 2 phases: 1) intervention development: The development of the SMArT Work intervention takes a community-based participatory research approach using the Behaviour Change Wheel. Focus groups will collect detailed information to gain a better understanding of the most appropriate strategies, to sit alongside the provision of height-adjustable workstations, at the environmental, organisational and individual level that support less occupational sitting. 2) intervention delivery and evaluation: The 12 month cluster RCT aims to reduce workplace sitting in the University Hospitals of Leicester NHS Trust. Desk-based office workers (n = 238) will be randomised to control or intervention clusters, with the intervention group receiving height-adjustable workstations and supporting techniques based on the feedback received from the development phase. Data will be collected at four time points; baseline, 3, 6 and 12 months. The primary outcome is a reduction in sitting time, measured by the activPAL(TM) micro at 12 months. Secondary outcomes include objectively measured physical activity and a variety of work-related health and psycho-social measures. A process evaluation will also take place. This study will be the first long-term, evidence-based, multi-component cluster RCT aimed at reducing occupational sitting within the NHS. This study will help form a better understanding and knowledge base of facilitators and barriers to creating a healthier work environment and contribute to health and wellbeing policy. ISRCTN10967042 . Registered 2 February 2015.

Patient information leaflets (PILs) for UK randomised controlled trials: a feasibility study exploring whether they contain information to support decision making about trial participation.

PubMed

Gillies, Katie; Huang, Wan; Skea, Zoë; Brehaut, Jamie; Cotton, Seonaidh

2014-02-18

Informed consent is regarded as a cornerstone of ethical healthcare research and is a requirement for most clinical research studies. Guidelines suggest that prospective randomised controlled trial (RCT) participants should understand a basic amount of key information about the RCTs they are being asked to enrol in in order to provide valid informed consent. This information is usually provided to potential participants in a patient information leaflet (PIL). There is evidence that some trial participants fail to understand key components of trial processes or rationale. As such, the existing approach to information provision for potential RCT participants may not be optimal. Decision aids have been used for a variety of treatment and screening decisions to improve knowledge, but focus more on overall decision quality, and may be helpful to those making decisions about participating in an RCT. We investigated the feasibility of using a tool to identify which items recommended for good quality decision making are present in UK PILs. PILs were sampled from UK registered Clinical Trials Unit websites across a range of clinical areas. The evaluation tool, which is based on standards for supporting decision making, was applied to 20 PILs. Two researchers independently rated each PIL using the tool. In addition, word count and readability were assessed. PILs scored poorly on the evaluation tool with the majority of leaflets scoring less than 50%. Specifically, presenting probabilities, clarifying and expressing values and structured guidance in deliberation and communication sub-sections scored consistently poorly. Tool score was associated with word count (r=0.802, P <0.01); there was no association between score and readability (r=-0.372, P=0.106). The tool was feasible to use to evaluate PILs for UK RCTs. PILs did not meet current standards of information to support good quality decision making. Writers of information leaflets could use the evaluation tool as a framework during PIL development to help ensure that items are included which promote and support more informed decisions about trial participation. Further research is required to evaluate the inclusion of such information.

Development of an implementation plan for the 6-PACK falls prevention programme as part of a randomised controlled trial: protocol for a series of preimplementation studies.

PubMed

Barker, Anna L; Morello, Renata T; Ayton, Darshini R; Hill, Keith D; Landgren, Fiona S; Brand, Caroline A

2016-12-01

Inhospital falls cause morbidity, staff burden and increased healthcare costs. It is unclear if the persistent problem of inhospital falls is due to the use of ineffective interventions or their suboptimal implementation. The 6-PACK programme appears to reduce fall injuries and a randomised controlled trial (RCT) was undertaken to confirm effects. This paper describes the protocol for the preimplementation studies that aimed to identify moderators of the effective use of the 6-PACK programme to inform the development of an implementation plan to be applied in the RCT. The 6-PACK project included five preimplementation studies: (1) a profile of safety climate; (2) review of current falls prevention practice; (3) epidemiology of inhospital falls; (4) acceptability of the 6-PACK programme; and (5) barriers and enablers to implementation of the 6-PACK programme. The Theoretical Domain Framework that includes 12 behaviour change domains informed the design of these studies that involved 540 staff and 8877 patients from 24 wards from six Australian hospitals. Qualitative and quantitative methods were applied with data collected via: structured bedside observation; daily nurse unit manager verbal report of falls; audit of medical records, incident reporting and hospital administrative data; surveys of ward nurses; focus groups with ward nurses; and key informant interviews with senior staff. Information on contextual, system, intervention, patient and provider level factors is critical to the development of an implementation plan. Information gained from these studies was used to develop a plan applied in the RCT that addressed the barriers and harnessed enablers. The RCT is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000332921. 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/.

Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol.

PubMed

Calderone, Alicia; Stevens, Wendy; Prior, David; Nandurkar, Harshal; Gabbay, Eli; Proudman, Susanna M; Williams, Trevor; Celermajer, David; Sahhar, Joanne; Wong, Peter K K; Thakkar, Vivek; Dwyer, Nathan; Wrobel, Jeremy; Chin, Weng; Liew, Danny; Staples, Margaret; Buchbinder, Rachelle; Nikpour, Mandana

2016-12-08

Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12-15% of patients with SSc and accounts for 30-40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals. ACTRN12614000418673, Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol

PubMed Central

Calderone, Alicia; Stevens, Wendy; Prior, David; Nandurkar, Harshal; Gabbay, Eli; Proudman, Susanna M; Williams, Trevor; Celermajer, David; Sahhar, Joanne; Wong, Peter K K; Thakkar, Vivek; Dwyer, Nathan; Wrobel, Jeremy; Chin, Weng; Liew, Danny; Staples, Margaret; Buchbinder, Rachelle; Nikpour, Mandana

2016-01-01

Introduction Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12–15% of patients with SSc and accounts for 30–40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. Methods and analysis This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. Ethics and dissemination Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals. Trial registration number ACTRN12614000418673, Pre-results. PMID:27932335

Clinical review: Statins and trauma - a systematic review

PubMed Central

2013-01-01

Statins, in addition to their lipid-lowering properties, have anti-inflammatory actions. The aim of this review is to evaluate the effect of pre-injury statin use, and statin treatment following injury. MEDLINE, EMBASE, and CENTRAL databases were searched to January 2012 for randomised and observational studies of statins in trauma patients in general, and in patients who have suffered traumatic brain injury, burns, and fractures. Of 985 identified citations, 7 (4 observational studies and 3 randomised controlled trials (RCTs)) met the inclusion criteria. Two studies (both observational) were concerned with trauma patients in general, two with patients who had suffered traumatic brain injury (one observational, one RCT), two with burns patients (one observational, one RCT), and one with fracture healing (RCT). Two of the RCTs relied on surrogate outcome measures. The observational studies were deemed to be at high risk of confounding, and the RCTs at high risk of bias. Three of the observational studies suggested improvements in a number of clinical outcomes in patients taking statins prior to injury (mortality, infection, and septic shock in burns patients; mortality in trauma patients in general; mortality in brain injured patients) whereas one, also of trauma patients in general, showed no difference in mortality or infection, and an increased risk of multi-organ failure. Two of three RCTs on statin treatment in burns patients and brain injured patients showed improvements in E-selectin levels and cognitive function. The third, of patients with radial fractures, showed no acceleration in fracture union. In conclusion, there is some evidence that pre-injury statin use and post-injury statin treatment may have a beneficial effect in patients who have suffered general trauma, traumatic brain injury, and burns. However, these studies are at high risk of confounding and bias, and should be regarded as 'hypothesisgenerating'. A well-designed RCT is required to determine the therapeutic efficacy in improving outcomes in this patient population. PMID:23751018

Reporting quality of randomised controlled trial abstracts on age-related macular degeneration health care: a cross-sectional quantification of the adherence to CONSORT abstract reporting recommendations.

PubMed

Baulig, Christine; Krummenauer, Frank; Geis, Berit; Tulka, Sabrina; Knippschild, Stephanie

2018-05-22

To assess the reporting quality of randomised controlled trial (RCT) abstracts on age-related macular degeneration (AMD) healthcare, to evaluate the adherence to the Consolidated Standards of Reporting Trials (CONSORT) statement's recommendations on minimum abstract information and to identify journal characteristics associated with abstract reporting quality. Cross-sectional evaluation of RCT abstracts on AMD healthcare. A PubMed search was implemented to identify RCT abstracts on AMD healthcare published in the English language between January 2004 and December 2013. Data extraction was performed by two parallel readers independently by means of a documentation format in accordance with the 16 items of the CONSORT checklist for abstracts. The total number of criteria fulfilled by an abstract was derived as primary endpoint of the investigation; incidence rate ratios (IRRs) with unadjusted 95% CI were estimated by means of multiple Poisson regression to identify journal and article characteristics (publication year, multicentre design, structured abstract recommendations, effective sample size, effective abstract word counts and journal impact factor) possibly associated with the total number of fulfilled items. 136 of 673 identified abstracts (published in 36 different journals) fulfilled all eligibility criteria. The median number of fulfilled items was 7 (95% CI 7 to 8). No abstract reported all 16 recommended items; the maximum total number was 14, the minimum 3 of 16 items. Multivariate analysis only demonstrated the abstracts' word counts as being significantly associated with a better reporting of abstracts (Poisson regression-based IRR 1.002, 95% CI 1.001 to 1.003). Reporting quality of RCT abstracts on AMD investigations showed a considerable potential for improvement to meet the CONSORT abstract reporting recommendations. Furthermore, word counts of abstracts were identified as significantly associated with the overall abstract reporting quality. © 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.

Current Issues in Randomized Clinical Trials of Neurodegenerative Disorders at Enrolment and Reporting: Diagnosis, Recruitment, Representativeness of Patients, Ethnicity, and Quality of Reporting.

PubMed

Logroscino, Giancarlo; Capozzo, Rosa; Tortelli, Rosanna; Marin, Benoît

2016-01-01

The investigator is faced with several challenges when planning a randomized clinical trial (RCT). In the early phase, issues are particularly challenging for RCTs in neurodegenerative disorders (NDD). At the time of inclusion in the study, an early and accurate diagnosis is mandatory. Variability of diagnostic criteria, mostly based on clinical grounds, lag time between onset and enrolment, and phenotypic heterogeneity are the main drivers of diagnostic complexity. High-quality data in terms of diagnostic reliability, phenotypic description, follow-up, and evaluation of outcomes are key determinants and are highly conditioned by the expertise of the investigators and center recruitment rate. Representativeness of NDD patients is mandatory to postulate the generalizability of the results of RCTs. There is, however, a systematic selection bias in terms of age (more likely to be younger), sex (more likely to be male), ethnicity (more likely to be of European/Caucasian origin), and other prognostic factors (more likely to be favorable). In the publication phase, researchers need to report properly all of the main features of the RCT. Consolidated Standards of Reporting Trials (CONSORT) facilitates the report and interpretation of RCTs, but adherence to these guidelines needs to be improved. Several issues discussed in this review may alter the internal and external validity of an RCT. To date, the impact on phenotype at study entry has often been overlooked. A differential effect of the selection of subjects and of specific clinical and nonclinical features needs to be systematically explored in the RCT planning phase. © 2016 S. Karger AG, Basel.

Randomized clinical trials in pediatric critical care: Rarely done but desperately needed.

PubMed

Randolph, Adrienne G.; Lacroix, Jacques

2002-04-01

OBJECTIVE: To review the benefits and challenges of using the randomized, controlled trial (RCT) study design to evaluate preventive and therapeutic interventions in pediatric critical care medicine. CONCLUSIONS: The RCT design is able to control for many sources of potential bias that other types of study designs cannot. The findings of RCTs often contradict the findings of less rigorous study designs. Before performing an RCT, there must exist a state of clinical equipoise, a sufficient number of eligible patients must be available, and the epidemiology of the disorder in question must be well studied. There are many challenges to performing high-quality RCTs. Studying multiple element support strategies in the critically ill patient population is more complex than studying a single drug therapy. High patient and practice variability and hazy diagnostic definitions can dilute the signal-to-noise ratio. Most interventions in critical care are expected to have a modest or small effect. This markedly increases the requisite sample size. There is a paucity of accepted clinically important measurements of the outcome of critical care, making mortality a common outcome to evaluate with a not-so-common incidence. Developmental issues, the inability to give informed consent, and the failure to perform the appropriate pharmacokinetic and safety studies are additional challenges facing pediatric investigators. Despite these limitations, a good RCT remains the best way to prove that an intervention is working or not. Indeed, RCTs are and will remain the "gold standard" method to estimate the efficacy of a therapeutic or prophylactic intervention.

Aggregated N-of-1 randomized controlled trials: modern data analytics applied to a clinically valid method of intervention effectiveness.

PubMed

Cushing, Christopher C; Walters, Ryan W; Hoffman, Lesa

2014-03-01

Aggregated N-of-1 randomized controlled trials (RCTs) combined with multilevel modeling represent a methodological advancement that may help bridge science and practice in pediatric psychology. The purpose of this article is to offer a primer for pediatric psychologists interested in conducting aggregated N-of-1 RCTs. An overview of N-of-1 RCT methodology is provided and 2 simulated data sets are analyzed to demonstrate the clinical and research potential of the methodology. The simulated data example demonstrates the utility of aggregated N-of-1 RCTs for understanding the clinical impact of an intervention for a given individual and the modeling of covariates to explain why an intervention worked for one patient and not another. Aggregated N-of-1 RCTs hold potential for improving the science and practice of pediatric psychology.

Why did an effective Dutch complex psycho-social intervention for people with dementia not work in the German healthcare context? Lessons learnt from a process evaluation alongside a multicentre RCT.

PubMed

Voigt-Radloff, Sebastian; Graff, Maud; Leonhart, Rainer; Hüll, Michael; Rikkert, Marcel Olde; Vernooij-Dassen, Myrra

2011-08-09

Background The positive effects of the Dutch Community Occupational Therapy in Dementia programme on patients' daily functioning were not found in a multicentre randomised controlled trial (RCT) in Germany. Objectives To evaluate possible effect modification on the primary outcome within the German RCT with regard to (1) participant characteristics, (2) treatment performance and (3) healthcare service utilisation; and (4) to compare the design and primary outcome between the German and the original Dutch study. Methods (1) The impact of participant baseline data on the primary outcome was analysed in exploratory ANCOVA and regression analyses. (2) Therapists completed questionnaires on context and performance problems. The main problems were identified by a qualitative content analysis and focus-group discussion. Associations of the primary outcome with scores of participant adherence and treatment performance were evaluated by regression analysis. (3) Utilisation rates of healthcare services were controlled for significant group differences. (4) Differences in the Dutch and German study design were identified, and the primary outcome was contrasted at the item level. Results (1) Participant characteristics could not explain more than 5% of outcome variance. (2) The treatment performance of some active intervention components was poor but not significantly associated with the primary outcome. (3) There were no significant group differences in the utilisation of healthcare resources. (4) In contrast to the Dutch waiting-control group, the active intervention in the German control group may have reduced group differences in the current RCT. The German patients demonstrated a higher independence at baseline and less improvement in instrumental activities of daily living. Conclusion The differences in outcome may be explained by a more active control treatment, partially poor experimental treatment and less room for improvement in the German sample. Future cross-national transfers should be prepared by pilot studies assessing the applicability of the intervention and patient needs specific to the target country. Trial registration International Clinical Trials Registry Platform, DRKS00000053.

Secukinumab Versus Adalimumab for Psoriatic Arthritis: Comparative Effectiveness up to 48 Weeks Using a Matching-Adjusted Indirect Comparison.

PubMed

Nash, Peter; McInnes, Iain B; Mease, Philip J; Thom, Howard; Hunger, Matthias; Karabis, Andreas; Gandhi, Kunal; Mpofu, Shephard; Jugl, Steffen M

2018-06-01

Secukinumab and adalimumab are approved for adults with active psoriatic arthritis (PsA). In the absence of direct randomized controlled trial (RCT) data, matching-adjusted indirect comparison can estimate the comparative effectiveness in anti-tumor necrosis factor (TNF)-naïve populations. Individual patient data from the FUTURE 2 RCT (secukinumab vs. placebo; N = 299) were adjusted to match baseline characteristics of the ADEPT RCT (adalimumab vs. placebo; N = 313). Logistic regression determined adjustment weights for age, body weight, sex, race, methotrexate use, psoriasis affecting ≥ 3% of body surface area, Psoriasis Area and Severity Index score, Health Assessment Questionnaire Disability Index score, presence of dactylitis and enthesitis, and previous anti-TNF therapy. Recalculated secukinumab outcomes were compared with adalimumab outcomes at weeks 12 (placebo-adjusted), 16, 24, and 48 (nonplacebo-adjusted). After matching, the effective sample size for FUTURE 2 was 101. Week 12 American College of Rheumatology (ACR) response rates were not significantly different between secukinumab and adalimumab. Week 16 ACR 20 and 50 response rates were higher for secukinumab 150 mg than for adalimumab (P = 0.017, P = 0.033), as was ACR 50 for secukinumab 300 mg (P = 0.030). Week 24 ACR 20 and 50 were higher for secukinumab 150 mg than for adalimumab (P = 0.001, P = 0.019), as was ACR 20 for secukinumab 300 mg (P = 0.048). Week 48 ACR 20 was higher for secukinumab 150 and 300 mg than for adalimumab (P = 0.002, P = 0.027), as was ACR 50 for secukinumab 300 mg (P = 0.032). In our analysis, patients with PsA receiving secukinumab were more likely to achieve higher ACR responses through 1 year (weeks 16-48) than those treated with adalimumab. Although informative, these observations rely on a subgroup of patients from FUTURE 2 and thus should be considered interim until the ongoing head-to-head RCT EXCEED can validate these findings. Novartis Pharma AG.

Probiotic supplementation in children with cystic fibrosis-a systematic review.

PubMed

Ananthan, Anitha; Balasubramanian, Haribalakrishna; Rao, Shripada; Patole, Sanjay

2016-10-01

Probiotics may benefit in cystic fibrosis (CF) as gut dysbiosis is associated with gastrointestinal symptoms and exacerbation of respiratory symptoms in CF. We conducted a systematic review of randomized controlled trials (RCTs) and non-RCTs of probiotic supplementation in children with CF, using the Cochrane methodology, preferred reporting items for systematic reviews (PRISMA) statement, and meta-analysis of observational studies in epidemiology (MOOSE) guidelines. Primary outcomes were pulmonary exacerbations, duration of hospitalization and antibiotics, and all-cause mortality. Secondary outcomes included gastrointestinal symptoms, markers of gut inflammation, and intestinal microbial balance. A total of nine studies (RCTs, 6, non-RCTs, 3; N = 275) with some methodological weaknesses were included in the review. The pooled estimate showed significant reduction in the rate of pulmonary exacerbation (fixed effects model, two parallel group RCTs and one cross-over trial: relative risk (RR) 0.25, (95 % confidence interval (95 % CI) 0.15,0.41); p < 0.00001; level of evidence: low) and decrease in fecal calprotectin (FCLP) levels (fixed effect model, three RCTs: mean difference (MD) -16.71, 95 % CI -27.30,-6.13); p = 0.002; level of evidence: low) after probiotic supplementation. Probiotic supplementation significantly improved gastrointestinal symptoms (one RCT, one non-RCT) and gut microbial balance (decreased Proteobacteria, increased Firmicutes, and Bacteroides in one RCT, one non-RCT). Limited low-quality evidence exists on the effects of probiotics in children with CF. Well-designed adequately powered RCTs assessing clinically meaningful outcomes are required to study this important issue. • Gut dysbiosis is frequent in children with cystic fibrosis due to frequent exposure to pathogens and antibiotics. • Probiotics decrease gut dysbiosis and improve gut maturity and function. What is New: • This comprehensive systematic review shows that current evidence on the safety and efficacy of probiotics in children with cystic fibrosis is limited and of low quality. • Well-designed and adequately powered trials assessing clinically important outcomes are required considering the health burden of cystic fibrosis and the potential benefits of probiotics.

The three stages of building and testing mid-level theories in a realist RCT: a theoretical and methodological case-example.

PubMed

Jamal, Farah; Fletcher, Adam; Shackleton, Nichola; Elbourne, Diana; Viner, Russell; Bonell, Chris

2015-10-15

Randomised controlled trials (RCTs) of social interventions are often criticised as failing to open the 'black box' whereby they only address questions about 'what works' without explaining the underlying processes of implementation and mechanisms of action, and how these vary by contextual characteristics of person and place. Realist RCTs are proposed as an approach to evaluation science that addresses these gaps while preserving the strengths of RCTs in providing evidence with strong internal validity in estimating effects. In the context of growing interest in designing and conducting realist trials, there is an urgent need to offer a worked example to provide guidance on how such an approach might be practically taken forward. The aim of this paper is to outline a three-staged theoretical and methodological process of undertaking a realist RCT using the example of the evaluation of a whole-school restorative intervention aiming to reduce aggression and bullying in English secondary schools. First, informed by the findings of our initial pilot trial and sociological theory, we elaborate our theory of change and specific a priori hypotheses about how intervention mechanisms interact with context to produce outcomes. Second, we describe how we will use emerging findings from the integral process evaluation within the RCT to refine, and add to, these a priori hypotheses before the collection of quantitative, follow-up data. Third, we will test our hypotheses using a combination of process and outcome data via quantitative analyses of effect mediation (examining mechanisms) and moderation (examining contextual contingencies). The results are then used to refine and further develop the theory of change. The aim of the realist RCT approach is thus not merely to assess whether the intervention is effective or not, but to develop empirically informed mid-range theory through a three-stage process. There are important implications for those involved with reporting and reviewing RCTs, including the use of new, iterative protocols. Current Controlled Trials ISRCTN10751359 (Registered 11 March 2014).

[Using an ovarian drilling by hydrolaparoscopy or recombinant follicle stimulating hormone plus metformin to treat polycystic ovary syndrome: Why a randomized controlled trial fail?].

PubMed

Fernandez, H; Cedrin-Durnerin, I; Gallot, V; Rongieres, C; Watrelot, A; Mayenga-Mankezi, J-M; Arnoux, A

2015-10-01

To evaluate pregnancy rates after randomized controlled trial (RCT) between ovarian drilling by fertiloscopy or ovarian hyperstimulation+insemination+metformine after clomifène citrate (cc) treatment fails. Randomized controlled trial with 126 patients in each arm in 9 university centers. After 6-9 months of stimulation by cc, 2 groups were randomized: group 1, ovarian drilling with bipolar energy versus group 2: 3 months treatment by metformine followed by 3 hyperstimulation by FSH+insemination. The success rate was pregnancy rate above 12 weeks. RCT was stopped after the screening of 40 patients. In spite of the low number of patients, the pregnancy rate is significantly higher in medical group 8/16 versus 3/18 (p=0.04). The causes of fail of RCT were in relationship with difficulties of inclusion, with absence of final agreement by team included. Moreover, RCT between medical and surgical management is often root of difficulties for patients who decline surgical strategy. However, medical treatment appeared better than drilling in this RCT. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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

PubMed

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

2015-03-01

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

Smartphone app design for the wireless control of a neuromuscular electrical stimulator device with integrated randomization allocation process for RCT applications.

PubMed

Sweeney, Dean; Quinlan, Leo R; OLaighin, Gearoid

2015-08-01

The use of NMES has evolved over the last five decades. Technological advancements have transformed these once complex systems into user-friendly devices with enhanced control functions, leading to new applications of NMES being investigated. The use of Randomized Control Trial (RCT) methodology in evaluating the effectiveness of new and existing applications of NMES is a demanding process adding time and cost to a translation into clinical practice. Poor quality trials may result in poor evidence of NMES effectiveness. In this paper some of the key challenges encountered in NMES clinical trials are identified with the aim of purposing a solution to address these challenges through the adoption of Smartphone technology. The design and evaluation of a smartphone application to provide automatic blind randomization control and facilitating the wireless temporal control of a portable Bluetooth enabled NMES is presented.

[Computer-assisted cardiovascular disease management: better implementation of care but no improvement in clinical outcomes].

PubMed

de Wit, Niek J

2012-01-01

Computer support is considered by many to be a promising strategy for improving healthcare interventions, especially in the management of chronic diseases. So far, however, evidence of the effectiveness of ICT support in healthcare is limited. Recently, computer-supported cardiovascular disease management was compared with usual care during an RCT comprised of 1100 primary care patients. This trial demonstrated that neither the clinical outcome nor the cardiovascular morbidity rate improved, even though management of the risk factors improved over 1 year of follow-up. The pragmatic design of the RCT in daily general practice may have restricted implementing the computer support, and may also have hampered the evaluation of the cardiovascular effects. The results demonstrate that although computer support may help improve the performance of disease management, its impact on disease outcomes is questionable. ICT innovations in healthcare require rigorous investigative evaluation before their implementation in daily practice can be justified.

Cost-effectiveness of cervical total disc replacement vs fusion for the treatment of 2-level symptomatic degenerative disc disease.

PubMed

Ament, Jared D; Yang, Zhuo; Nunley, Pierce; Stone, Marcus B; Kim, Kee D

2014-12-01

Cervical total disc replacement (CTDR) was developed to treat cervical spondylosis, while preserving motion. While anterior cervical discectomy and fusion (ACDF) has been the standard of care for 2-level disease, a randomized clinical trial (RCT) suggested similar outcomes. Cost-effectiveness of this intervention has never been elucidated. To determine the cost-effectiveness of CTDR compared with ACDF. Data were derived from an RCT that followed up 330 patients over 24 months. The original RCT consisted of multi-institutional data including private and academic institutions. Using linear regression for the current study, health states were constructed based on the stratification of the Neck Disability Index and a visual analog scale. Data from the 12-item Short-Form Health Survey questionnaires were transformed into utilities values using the SF-6D mapping algorithm. Costs were calculated by extracting Diagnosis-Related Group codes from institutional billing data and then applying 2012 Medicare reimbursement rates. The costs of complications and return-to-work data were also calculated. A Markov model was built to evaluate quality-adjusted life-years (QALYs) for both treatment groups. The model adopted a third-party payer perspective and applied a 3% annual discount rate. Patients included in the original RCT had to be diagnosed as having radiculopathy or myeloradiculopathy at 2 contiguous levels from C3-C7 that was unresponsive to conservative treatment for at least 6 weeks or demonstrated progressive symptoms. Incremental cost-effectiveness ratio of CTDR compared with ACDF. A strong correlation (R2 = 0.6864; P < .001) was found by projecting a visual analog scale onto the Neck Disability Index. Cervical total disc replacement had an average of 1.58 QALYs after 24 months compared with 1.50 QALYs for ACDF recipients. Cervical total disc replacement was associated with $2139 greater average cost. The incremental cost-effectiveness ratio of CTDR compared with ACDF was $24,594 per QALY at 2 years. Despite varying input parameters in the sensitivity analysis, the incremental cost-effectiveness ratio value stays below the threshold of $50,000 per QALY in most scenarios (range, -$58,194 to $147,862 per QALY). The incremental cost-effectiveness ratio of CTDR compared with traditional ACDF is lower than the commonly accepted threshold of $50,000 per QALY. This remains true with varying input parameters in a robust sensitivity analysis, reaffirming the stability of the model and the sustainability of this intervention.

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.

Preservation of the capacity to appoint a proxy decision maker: implications for dementia research.

PubMed

Kim, Scott Y H; Karlawish, Jason H; Kim, H Myra; Wall, Ian F; Bozoki, Andrea C; Appelbaum, Paul S

2011-02-01

Research involving persons with impaired decision-making capacity (such as persons with Alzheimer disease [AD]) remains ethically challenging, especially when the research involves significant risk. If individuals incapable of consenting to research studies were able to appoint a research proxy, it would allow for an appointed surrogate (rather than a de facto surrogate) to represent the subject. To assess the extent to which persons with AD retain their capacity to appoint a research proxy. Interview study. Academic research. One hundred eighty-eight persons with AD were interviewed for their capacity to appoint a proxy for research and to provide consent to 2 hypothetical research scenarios, a lower-risk randomized clinical trial testing a new drug (drug RCT) and a higher-risk randomized clinical trial testing neurosurgical cell implants using a sham control condition (neurosurgical RCT). Categorical capacity status for each subject was determined by independent videotaped reviews of capacity interviews by 5 experienced psychiatrists. Categorical capacity determinations for the capacity to appoint a research proxy, capacity to consent to a drug RCT, and capacity to consent to a neurosurgical RCT. Data showed that 37.7% (40 of 106) of those deemed incapable of consenting to the drug RCT and 54.8% (86 of 157) of those deemed incapable of consenting to the neurosurgical RCT were found capable of appointing a research proxy. Only 7 of 186 (3.8%) were deemed capable of consenting to the neurosurgical RCT by all 5 psychiatrists. A substantial proportion of persons with AD who were thought incapable of consenting to lower-risk or higher-risk studies have preserved capacity for appointing a research proxy. Because few persons are found to be unequivocally capable of providing independent consent to higher-risk AD research, providing for an appointed surrogate even after the onset of AD, which might best be done in the early stages of the illness, may help address key ethical challenges to AD research.

Management of shoulder pain by UK general practitioners (GPs): a national survey

PubMed Central

Artus, Majid; van der Windt, Danielle A; Afolabi, Ebenezer K; Buchbinder, Rachelle; Chesterton, Linda S; Hall, Alison; Roddy, Edward; Foster, Nadine E

2017-01-01

Objectives Studies in Canada, the USA and Australia suggested low confidence among general practitioners (GPs) in diagnosing and managing shoulder pain, with frequent use of investigations. There are no comparable studies in the UK; our objective was to describe the diagnosis and management of shoulder pain by GPs in the UK. Methods A national survey of a random sample of 5000 UK GPs collected data on shoulder pain diagnosis and management using two clinical vignettes that described primary care presentations with rotator cuff tendinopathy (RCT) and adhesive capsulitis (AdhC). Results Seven hundred and fourteen (14.7%) responses were received. 56% and 83% of GPs were confident in their diagnosis of RCT and AdhC, respectively, and a wide range of investigations and management options were reported. For the RCT presentation, plain radiographs of the shoulder were most common (60%), followed by blood tests (42%) and ultrasound scans (USS) (38%). 19% of those who recommended a radiograph and 76% of those who recommended a USS did so ‘to confirm the diagnosis’. For the AdhC presentation, the most common investigations were blood tests (60%), plain shoulder radiographs (58%) and USS (31%). More than two-thirds of those recommending a USS did so ‘to confirm the diagnosis’. The most commonly recommended treatment for both presentations was physiotherapy (RCT 77%, AdhC 71%) followed by non-steroidal anti-inflammatory drugs (RCT 58%, AdhC 74%). 17% opted to refer the RCT to secondary care (most often musculoskeletal interface service), compared with 31% for the AdhC. Conclusions This survey of GPs in the UK highlights reliance on radiographs and blood tests in the management of common shoulder pain presentations. GPs report referring more than 7 out of 10 patients with RCT and AdhC to physiotherapists. These findings need to be viewed in the context of low response to the survey and, therefore, potential non-response bias. PMID:28637737

Automated confidence ranked classification of randomized controlled trial articles: an aid to evidence-based medicine

PubMed Central

Smalheiser, Neil R; McDonagh, Marian S; Yu, Clement; Adams, Clive E; Davis, John M; Yu, Philip S

2015-01-01

Objective: For many literature review tasks, including systematic review (SR) and other aspects of evidence-based medicine, it is important to know whether an article describes a randomized controlled trial (RCT). Current manual annotation is not complete or flexible enough for the SR process. In this work, highly accurate machine learning predictive models were built that include confidence predictions of whether an article is an RCT. Materials and Methods: The LibSVM classifier was used with forward selection of potential feature sets on a large human-related subset of MEDLINE to create a classification model requiring only the citation, abstract, and MeSH terms for each article. Results: The model achieved an area under the receiver operating characteristic curve of 0.973 and mean squared error of 0.013 on the held out year 2011 data. Accurate confidence estimates were confirmed on a manually reviewed set of test articles. A second model not requiring MeSH terms was also created, and performs almost as well. Discussion: Both models accurately rank and predict article RCT confidence. Using the model and the manually reviewed samples, it is estimated that about 8000 (3%) additional RCTs can be identified in MEDLINE, and that 5% of articles tagged as RCTs in Medline may not be identified. Conclusion: Retagging human-related studies with a continuously valued RCT confidence is potentially more useful for article ranking and review than a simple yes/no prediction. The automated RCT tagging tool should offer significant savings of time and effort during the process of writing SRs, and is a key component of a multistep text mining pipeline that we are building to streamline SR workflow. In addition, the model may be useful for identifying errors in MEDLINE publication types. The RCT confidence predictions described here have been made available to users as a web service with a user query form front end at: http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/RCT_Tagger.cgi. PMID:25656516

The long-term (24-month) effect on health and well-being of the Lifestyle Matters community-based intervention in people aged 65 years and over: a qualitative study

PubMed Central

Chatters, Robin; Roberts, Jennifer; Mountain, Gail; Cook, Sarah; Windle, Gill; Craig, Claire; Sprange, Kirsty

2017-01-01

Objectives To assess the long-term effect on health and well-being of the Lifestyle Matters programme. Design Qualitative study of a subset of intervention arm participants who participated in the Lifestyle Matters randomised controlled trial (RCT). Setting The intervention took place at community venues within two sites in the UK. Participants A purposeful sample of 13 participants aged between 66 and 88 years from the intervention arm of the RCT were interviewed at 24 months post randomisation. Interviews aimed to understand how participants had used their time in the preceding 2 years and whether the intervention had any impact on their lifestyle choices, participation in meaningful activities and well-being. Intervention Lifestyle Matters is a 4-month occupational therapy intervention, consisting of group and individual sessions, designed to enable community living older people to make positive lifestyle choices and participate in new or neglected activities through increasing self-efficacy. Results Interviews revealed that the majority of interviewed participants were reportedly active at 24 months, with daily routines and lifestyles not changing significantly over time. All participants raised some form of benefit from attending Lifestyle Matters, including an improved perspective on life, trying new hobbies and meeting new friends. A number of intervention participants spoke of adapting to their changing circumstances, but there were significant and lasting benefits for 2 of 13 intervention participants interviewed. Conclusion The majority of those who experienced the Lifestyle Matters intervention reported minor benefits and increases in self-efficacy, but they did not perceive that it significantly improved their health and well-being. The two participants who had experienced major benefits also reported having had life-changing events, suggesting that this intervention is most effective at the time when lifestyle has to be reconsidered if mental well-being is to be sustained. Trial registration ISRCTN, ISRCTN67209155, post results. PMID:28947449

Downhole vacuum cleans up tough fishing, milling jobs

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

LaLande, P.; Flanders, B.

1996-02-01

A unique tool developed to effect reverse circulation downhole is being used successfully in problem milling and fishing operations where conventional techniques fail to recover junk in the hole. Jointly developed by several major operators in conjunction with Baker Oil Tools, the patented Reverse Circulating Tool (RCT) acts as a downhole vacuum cleaner, catching and retaining debris circulated from the wellbore while allowing fishing, milling and washover operations to continue uninterrupted. As described in several case histories overviewed, the unique vacuuming action efficiently cleans up junk and debris in even the most difficult fishing and milling applications. Downhole operations proceedmore » normally, but without threat of damage from milled debris. Developers hold both mechanical and method patents on the RCT.« less

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

PubMed

Kobalava, Zh D; Kotovskaia, Iu V

2011-01-01

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

2016 ASE undergraduate essay competition candidate information.

PubMed

Chen, Alice

2018-04-01

The aim of this review is to discuss the role of medicaments and materials used in teeth undergoing root canal treatment and how they affect the overall prognosis of root canal treated teeth. Irrigants, medicaments and materials play a vital role in RCT. They reduce the overall microbial load within the root canal system, help reduce inter-appointment pain, and induce apexification during RCT of permanent teeth with immature apices. In addition, they also help create a hermetic coronal and periradicular seal to entomb any residual microorganisms within the canals and prevent future ingress of contaminants into the root canal system and subsequent reinfection. Whilst the role of various materials in RCT has been thoroughly investigated, the available literature and longitudinal clinical studies evaluating the affect of such materials on the prognosis of RCT is scarce, and requires further investigation. © 2017 Australian Society of Endodontology Inc.

Effects of dairy factory, milk casein content and titratable acidity on coagulation properties in Trentingrana dairy industry.

PubMed

Penasa, Mauro; Toffanin, Valentina; Cologna, Nicola; Cassandro, Martino; De Marchi, Massimo

2016-05-01

The objective of the present study was to investigate the effect of environmental factors, milk casein content and titratable acidity on milk coagulation properties (MCP) of samples routinely collected in the Trento province (northeast Italy) under field conditions. Rennet coagulation time (RCT, min), curd-firming time (k20, min) and curd firmness (a30, mm) were determined by Formagraph on 14 971 samples from 635 herds associated to 17 dairy factories. Besides MCP, fat, protein, and casein percentages, titratable acidity (TA), and somatic cell and bacterial counts were available. A standardised index of milk aptitude to coagulate (IAC) was derived using information of RCT and a30. An analysis of variance was conducted on MCP and IAC using a fixed effects linear model. Approximately 3% of milk samples did not form a curd within the testing time (30 min) and k20 was missing for 26% of milks. The percentage of samples without information on k20 largely differed among dairy factories (1·7-20·9%). Significant differences were estimated between the best and the worst dairy factory for RCT (-2 min), k20 (-1·2 min), a30 (+3·4 mm) and IAC (+2·6 points). Milk casein content and TA were important factors in explaining the variation of MCP and IAC, supporting the central role of these two traits on technological properties. The Trento province is heterogeneous in terms of dairy systems and this could explain the differences among dairy factories.

Challenges and Innovations in a Community-Based Participatory Randomized Controlled Trial.

PubMed

Goodkind, Jessica R; Amer, Suha; Christian, Charlisa; Hess, Julia Meredith; Bybee, Deborah; Isakson, Brian L; Baca, Brandon; Ndayisenga, Martin; Greene, R Neil; Shantzek, Cece

2017-02-01

Randomized controlled trials (RCTs) are a long-standing and important design for conducting rigorous tests of the effectiveness of health interventions. However, many questions have been raised about the external validity of RCTs, their utility in explicating mechanisms of intervention and participants' intervention experiences, and their feasibility and acceptability. In the current mixed-methods study, academic and community partners developed and implemented an RCT to test the effectiveness of a collaboratively developed community-based advocacy, learning, and social support intervention. The goals of the intervention were to address social determinants of health and build trust and connections with other mental health services in order to reduce mental health disparities among Afghan, Great Lakes Region African, and Iraqi refugee adults and to engage and retain refugees in trauma-focused treatment, if needed. Two cohorts completed the intervention between 2013 and 2015. Ninety-three adult refugees were randomly assigned to intervention or control group and completed four research interviews (pre-, mid-, and postintervention, and follow-up). Several challenges to conducting a community-based RCT emerged, including issues related to interviewer intervention to assist participants in the control group, diffusion of intervention resources throughout the small refugee communities, and staff and community concerns about the RCT design and what evidence is meaningful to demonstrate intervention effectiveness. These findings highlight important epistemological, methodological, and ethical challenges that should be considered when conducting community-based RCTs and interpreting results from them. In addition, several innovations were developed to address these challenges, which may be useful for other community-academic partnerships engaged in RCTs.

CHALLENGES AND INNOVATIONS IN A COMMUNITY-BASED PARTICIPATORY RANDOMIZED CONTROLLED TRIAL

PubMed Central

Goodkind, Jessica R.; Amer, Suha; Christian, Charlisa; Hess, Julia Meredith; Bybee, Deborah; Isakson, Brian; Baca, Brandon; Ndaysenga, Martin; Greene, R. Neil; Shantzek, Cece

2016-01-01

Randomized controlled trials (RCTs) are a long-standing and important design for conducting rigorous tests of the effectiveness of health interventions. However, many questions have been raised about the external validity of RCTs, their utility in explicating mechanisms of intervention and participants’ intervention experiences, and their feasibility and acceptability. In the current mixed methods study, academic and community partners developed and implemented an RCT to test the effectiveness of a collaboratively developed community-based advocacy, learning, and social support intervention. The goals of the intervention were to address social determinants of health and build trust and connections with other mental health services in order to reduce mental health disparities among Afghan, Great Lakes Region African and Iraqi refugee adults and engage and retain refugees in trauma-focused treatment, if needed. Two cohorts completed the intervention between 2013-2015. Ninety-three adult refugees were randomly assigned to intervention or control group and completed four research interviews (pre-, mid-, post-intervention, and follow-up). Several challenges to conducting a community-based RCT emerged, including issues related to interviewer intervention to assist participants in the control group, diffusion of intervention resources throughout the small refugee communities, and staff and community concerns about the RCT design and what evidence is meaningful to demonstrate intervention effectiveness. These findings highlight important epistemological, methodological, and ethical challenges that should be considered when conducting community-based RCTs and interpreting results from them. In addition, several innovations were developed to address these challenges, which may be useful for other community-academic partnerships engaged in RCTs. PMID:27179291

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

PubMed

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

2015-05-01

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

Alcohol assessment & feedback by e-mail for university student hazardous and harmful drinkers: study protocol for the AMADEUS-2 randomised controlled trial.

PubMed

McCambridge, Jim; Bendtsen, Marcus; Karlsson, Nadine; White, Ian R; Bendtsen, Preben

2013-10-10

Alcohol is responsible for a large and growing proportion of the global burden of disease, as well as being the cause of social problems. Brief interventions are one component of comprehensive policy measures necessary to reduce these harms. Brief interventions increasingly take advantage of the Internet to reach large numbers of high risk groups such as students. The research literature on the efficacy and effectiveness of online interventions is developing rapidly. Although many studies show benefits in the form of reduced consumption, other intervention studies show no effects, for reasons that are unclear. Sweden became the first country in the world to implement a national system in which all university students are offered a brief online intervention via an e-mail. This randomized controlled trial (RCT) aims to evaluate the effectiveness of this national system comprising a brief online intervention among university students who are hazardous and harmful drinkers. This study employs a conventional RCT design in which screening to determine eligibility precedes random allocation to immediate or delayed access to online intervention. The online intervention evaluated comprises three main components; assessment, normative feedback and advice on reducing drinking. Screening is confined to a single question in order to minimise assessment reactivity and to prevent contamination. Outcomes will be evaluated after 2 months, with total weekly alcohol consumption being the primary outcome measure. Invitations to participate are provided by e-mail to approximately 55,000 students in 9 Swedish universities. This RCT evaluates routine service provision in Swedish universities via a delay in offer of intervention to the control group. It evaluates effects in the key population for whom this intervention has been designed. Study findings will inform the further development of the national service provision. ISRCTN02335307.

The Effectiveness of Exercise on Recovery and Clinical Outcomes in Patients With Soft Tissue Injuries of the Hip, Thigh, or Knee: A Systematic Review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.

PubMed

Brown, Courtney K; Southerst, Danielle; Côté, Pierre; Shearer, Heather M; Randhawa, Kristi; Wong, Jessica J; Yu, Hainan; Varatharajan, Sharanya; Sutton, Deborah; Stern, Paula J; D'Angelo, Kevin; Dion, Sarah; Cox, Jocelyn; Goldgrub, Rachel; Stupar, Maja; Carroll, Linda J; Taylor-Vaisey, Anne

2016-02-01

The purpose of this systematic review was to determine the effectiveness of exercise for the management of soft tissue injuries of the hip, thigh, and knee. We conducted a systematic review and searched MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials, and CINAHL Plus with Full Text from January 1, 1990, to April 8, 2015, for randomized controlled trials (RCTs), cohort studies, and case-control studies evaluating the effect of exercise on pain intensity, self-rated recovery, functional recovery, health-related quality of life, psychological outcomes, and adverse events. Random pairs of independent reviewers screened titles and abstracts and assessed risk of bias using the Scottish Intercollegiate Guidelines Network criteria. Best evidence synthesis methodology was used. We screened 9494 citations. Eight RCTs were critically appraised, and 3 had low risk of bias and were included in our synthesis. One RCT found statistically significant improvements in pain and function favoring clinic-based progressive combined exercises over a "wait and see" approach for patellofemoral pain syndrome. A second RCT suggests that supervised closed kinetic chain exercises may lead to greater symptom improvement than open chain exercises for patellofemoral pain syndrome. One RCT suggests that clinic-based group exercises may be more effective than multimodal physiotherapy in male athletes with persistent groin pain. We found limited high-quality evidence to support the use of exercise for the management of soft tissue injuries of the lower extremity. The evidence suggests that clinic-based exercise programs may benefit patients with patellofemoral pain syndrome and persistent groin pain. Further high-quality research is needed. Copyright © 2016 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2015-01-01

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

Long-Term Effects of a Home-Visiting Intervention for Depressed Mothers and Their Infants

ERIC Educational Resources Information Center

Kersten-Alvarez, Laura E.; Hosman, Clemens M. H.; Riksen-Walraven, J. Marianne; Van Doesum, Karin T. M.; Hoefnagels, Cees

2010-01-01

Background: Whereas preventive interventions for depressed mothers and their infants have yielded positive short-term outcomes, few studies have examined their long-term effectiveness. The present follow-up of a randomised controlled trial (RCT) is one of the first to examine the longer-term effects of an intervention for mothers with postpartum…

Subgroup effects of occupational therapy-based intervention for people with advanced cancer.

PubMed

Sampedro Pilegaard, Marc; Oestergaard, Lisa Gregersen; la Cour, Karen; Thit Johnsen, Anna; Brandt, Åse

2018-03-23

Many people with advanced cancer have decreased ability to perform activities of daily living (ADL). We recently performed a randomized, controlled trial (RCT) assessing the efficacy of an occupational therapy-based program, the 'Cancer Home-Life Intervention' in people with advanced cancer (N = 242) and found no overall effects on ADL ability. However, heterogeneity of treatment effect may disguise subgroup differences. To investigate whether subgroups of people with advanced cancer gain positive effects from the 'Cancer Home-Life Intervention' on ADL ability. An exploratory subgroup analysis including 191 participants from a RCT. The outcome was ADL motor ability measured by the Assessment of Motor and Process Skills (AMPS). Subgroups were defined by age, gender, years of education, type of primary tumor, functional level, and activity problems. The 'Cancer Home-Life Intervention' had no statistically significant effect in the six subgroups. Modifying effects of age (0.30 [95% CI: -0.05 to 0.64]) and gender (0.23 [95% CI: -0.11 to 0.57]) were not found. There were no subgroup effects of the 'Cancer Home-Life Intervention'on ADL motor ability. Some indications suggest greater effects for those aged below 69 years; however, this result should be interpreted with caution.

Rationale and design of a randomized trial comparing initial stress echocardiography versus coronary CT angiography in low-to-intermediate risk emergency department patients with chest pain.

PubMed

Levsky, Jeffrey M; Haramati, Linda B; Taub, Cynthia C; Spevack, Daniel M; Menegus, Mark A; Travin, Mark I; Vega, Shayna; Lerer, Rikah; Brown-Manhertz, Durline; Hirschhorn, Esther; Tobin, Jonathan N; Garcia, Mario J

2014-07-01

Comparative effectiveness research (CER) has become a major focus of cardiovascular disease investigation to optimize diagnosis and treatment paradigms and decrease healthcare expenditures. Acute chest pain is a highly prevalent reason for evaluation in the Emergency Department (ED) that results in hospital admission for many patients and excess expense. Improvement in noninvasive diagnostic algorithms can potentially reduce unnecessary admissions. To compare the performance of treadmill stress echocardiography (SE) and coronary computed tomography angiography (CTA) in ED chest pain patients with low-to-intermediate risk of significant coronary artery disease. This is a single-center, randomized controlled trial (RCT) comparing SE and CTA head-to-head as the initial noninvasive imaging modality. The primary outcome measured is the incidence of hospitalization. The study is powered to detect a reduction in admissions from 28% to 15% with a sample size of 400. Secondary outcomes include length of stay in the ED/hospital and estimated cost of care. Safety outcomes include subsequent visits to the ED and hospitalizations, as well as major adverse cardiovascular events at 30 days and 1 year. Patients who do not meet study criteria or do not consent for randomization are offered entry into an observational registry. This RCT will add to our understanding of the roles of different imaging modalities in triaging patients with suspected angina. It will increase the CER evidence base comparing SE and CTA and provide insight into potential benefits and limitations of appropriate use of treadmill SE in the ED. © 2013, Wiley Periodicals, Inc.

The pathway to RCTs: how many roads are there? Examining the homogeneity of RCT justification.

PubMed

Chow, Jeffrey Tin Yu; Lam, Kevin; Naeem, Abdul; Akanda, Zarique Z; Si, Francie Fengqin; Hodge, William

2017-02-02

Randomized controlled trials (RCTs) form the foundational background of modern medical practice. They are considered the highest quality of evidence, and their results help inform decisions concerning drug development and use, preventive therapies, and screening programs. However, the inputs that justify an RCT to be conducted have not been studied. We reviewed the MEDLINE and EMBASE databases across six specialties (Ophthalmology, Otorhinolaryngology (ENT), General Surgery, Psychiatry, Obstetrics-Gynecology (OB-GYN), and Internal Medicine) and randomly chose 25 RCTs from each specialty except for Otorhinolaryngology (20 studies) and Internal Medicine (28 studies). For each RCT, we recorded information relating to the justification for conducting RCTs such as average study size cited, number of studies cited, and types of studies cited. The justification varied widely both within and between specialties. For Ophthalmology and OB-GYN, the average study sizes cited were around 1100 patients, whereas they were around 500 patients for Psychiatry and General Surgery. Between specialties, the average number of studies cited ranged from around 4.5 for ENT to around 10 for Ophthalmology, but the standard deviations were large, indicating that there was even more discrepancy within each specialty. When standardizing by the sample size of the RCT, some of the discrepancies between and within specialties can be explained, but not all. On average, Ophthalmology papers cited review articles the most (2.96 studies per RCT) compared to less than 1.5 studies per RCT for all other specialties. The justifications for RCTs vary widely both within and between specialties, and the justification for conducting RCTs is not standardized.

Prolonged remission from hepatic encephalopathy with rifaximin: results of a placebo crossover analysis

PubMed Central

Bajaj, J S; Barrett, A C; Bortey, E; Paterson, C; Forbes, W P

2015-01-01

Background Rifaximin therapy reduced risk of hepatic encephalopathy (HE) recurrence and HE-related hospitalisations during a 6-month, randomised, placebo-controlled trial (RCT) and a 24-month open-label maintenance (OLM) study. However, the impact of crossover from placebo to rifaximin therapy is unclear. Aim To study the impact of crossing over from placebo to rifaximin treatment on breakthrough HE and hospitalisation rates using a within-subjects design. Methods Adults with cirrhosis and history of overt HE episodes, currently in HE remission, received placebo during the RCT and crossed over to rifaximin 550 mg twice daily during the OLM study. Rate of breakthrough overt HE episodes, hospitalisations and incidence and rate of adverse events (AEs) were analysed during RCT and first 6 months of OLM. Results Of 82 patients randomised to placebo in the RCT who crossed over to the OLM study, 39 experienced an HE episode during the RCT compared with 14 during the OLM study (P < 0.0001). Significantly lower rates of HE events were observed with rifaximin treatment compared with placebo treatment (P < 0.0001). Rates of HE-related hospitalisation were numerically lower during rifaximin treatment compared with placebo treatment, although not significant. Rates of most common AEs, serious AEs and infection-related AEs were similar between the two treatments. Conclusions This analysis confirms the repeatability of results from the RCT on safety and efficacy of rifaximin 550 mg twice daily in reducing the risk of hepatic encephalopathy recurrence, and suggests these findings are translatable outside of a rigorous, controlled trial setting. PMID:25339518

The Popularity of Outcome Measures for Hip and Knee Arthroplasties.

PubMed

Lovelock, Thomas M; Broughton, Nigel S; Williams, Cylie M

2018-01-01

The optimal methods of determining outcomes following hip and knee arthroplasty remain controversial. The objectives of this study were to determine the most frequently used outcome measures in randomized controlled trials (RCT) and study protocols registered with clinical trials registries (CTR) on hip and knee arthroplasty. A systematic search strategy was undertaken to identify the outcome measures used in RCT and CTR following joint arthroplasty. Databases searched included Embase, Ovid MEDLINE (including In-Process), Cochrane Central Register of Controlled Trials, CINAHL Plus, clinicaltrials.gov, ISRCTN registry, and ANZCTR. Differences in the use of outcome measures between RCT and CTR were assessed using logistic regression. There were 291 RCT and 113 CTR on hip arthroplasty and 452 RCT and 184 CTR on knee arthroplasty that met the inclusion criteria. The most popular outcome measures were the Harris Hip Score and the Knee Society Score. Multiple outcome measures were used in greater than 50% of the included studies. The Oxford Hip Score, Oxford Knee Score, EuroQol-5D, and Knee Injury and Osteoarthritis Outcome Score (all P < .001) were used in significantly more CTR than RCT. There is a clear preference for the use of the Harris Hip Score and Knee Society Score, contrary to existing international guidelines and reviews on the topic. Both measures require clinician input, which potentially influences their validity and increases their overall administration cost. Some patient-reported outcome measures, such as the Oxford Hip and Knee Scores, EuroQol-5D, and KOOS, appear to be increasing in popularity. Copyright © 2017 Elsevier Inc. All rights reserved.

Rationale and design of the Atrial Fibrillation health Literacy Information Technology Trial: (AF-LITT).

PubMed

Guhl, Emily N; Schlusser, Courtney L; Henault, Lori E; Bickmore, Timothy W; Kimani, Everlyne; Paasche-Orlow, Michael K; Magnani, Jared W

2017-11-01

Atrial Fibrillation (AF) is a common cardiac arrhythmia that is challenging for patients and adversely impacts health-related quality of life (HRQoL). Long-term management of AF requires that patients adhere to complex therapies, understand difficult terminology, navigate subspecialty care, and have continued symptom monitoring with the goal of preventing adverse outcomes. Continued interventions to ameliorate the patient experience of AF are essential. The Atrial Fibrillation health Literacy Information Technology Trial (AF-LITT; NCT03093558) is an investigator-initiated, 2-arm randomized clinical trial (RCT). This RCT is a pilot in order to implement a novel, smartphone-based intervention to address the patient experience of AF. This pilot RCT will compare a combination of the Embodied Conversational Agent (ECA) and the Alive Cor Kardia Mobile heart rhythm monitor to the current standard of care. The study will enroll 180 adults with non-valvular AF who are receiving anticoagulation for stroke prevention and randomize them to receive a 30-day intervention (smartphone-based ECA/Kardia) or standard of care, which will include a symptom and adherence journal. The primary end-points are improvement in HRQoL and self-reported adherence to anticoagulation. The secondary end-points are the acceptability of the intervention to participants, its use by participants, and acceptability to referring physicians. The AF-LITT pilot aims to evaluate the efficacy of the ECA/Kardia to improve HRQoL and anticoagulant adherence, and to guide its implementation in a larger, multicenter clinical trial. The intervention has potential to improve HRQoL, adherence, and health care utilization in individuals with chronic AF. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of EULAR recommendations for the reporting of clinical trial extension studies in rheumatology.

PubMed

Buch, Maya H; Silva-Fernandez, Lucia; Carmona, Loreto; Aletaha, Daniel; Christensen, Robin; Combe, Bernard; Emery, Paul; Ferraccioli, Gianfranco; Guillemin, Francis; Kvien, Tore K; Landewe, Robert; Pavelka, Karel; Saag, Kenneth; Smolen, Josef S; Symmons, Deborah; van der Heijde, Désirée; Welling, Joep; Wells, George; Westhovens, Rene; Zink, Angela; Boers, Maarten

2015-06-01

Our initiative aimed to produce recommendations on post-randomised controlled trial (RCT) trial extension studies (TES) reporting using European League Against Rheumatism (EULAR) standard operating procedures in order to achieve more meaningful output and standardisation of reports. We formed a task force of 22 participants comprising RCT experts, clinical epidemiologists and patient representatives. A two-stage Delphi survey was conducted to discuss the domains of evaluation of a TES and definitions. A '0-10' agreement scale assessed each domain and definition. The resulting set of recommendations was further refined and a final vote taken for task force acceptance. Seven key domains and individual components were evaluated and led to agreed recommendations including definition of a TES (100% agreement), minimal data necessary (100% agreement), method of data analysis (agreement mean (SD) scores ranging between 7.9 (0.84) and 9.0 (2.16)) and reporting of results as well as ethical issues. Key recommendations included reporting of absolute numbers at each stage from the RCT to TES with reasons given for drop-out at each stage, and inclusion of a flowchart detailing change in numbers at each stage and focus (mean (SD) agreement 9.9 (0.36)). A final vote accepted the set of recommendations. This EULAR task force provides recommendations for implementation in future TES to ensure a standardised approach to reporting. Use of this document should provide the rheumatology community with a more accurate and meaningful output from future TES, enabling better understanding and more confident application in clinical practice towards improving patient outcomes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Rationale and design of the Atrial Fibrillation health Literacy Information Technology Trial: (AF-LITT)

PubMed Central

Guhl, Emily N.; Schlusser, Courtney L.; Henault, Lori E.; Bickmore, Timothy W.; Kimani, Everlyne; Paasche-Orlow, Michael K.; Magnani, Jared W.

2017-01-01

Background Atrial Fibrillation (AF) is a common cardiac arrhythmia that is challenging for patients and adversely impacts health-related quality of life (HRQoL). Long-term management of AF requires that patients adhere to complex therapies, understand difficult terminology, navigate subspecialty care, and have continued symptom monitoring with the goal of preventing adverse outcomes. Continued interventions to ameliorate the patient experience of AF are essential. Design The Atrial Fibrillation health Literacy Information Technology Trial (AF-LITT; NCT03093558) is an investigator-initiated, 2-arm randomized clinical trial (RCT). This RCT is a pilot in order to implement a novel, smartphone-based intervention to address the patient experience of AF. This pilot RCT will compare a combination of the embodied conversational agent (ECA) and the Alive Cor Kardia Mobile heart rhythm monitor to the current standard of care. The study will enroll 180 adults with non-valvular AF who are receiving anticoagulation for stroke prevention and randomize them to receive a 30-day intervention (smartphone-based ECA/Kardia) or standard of care, which will include a symptom and adherence journal. The primary end-points are improvement in HRQoL and self-reported adherence to anticoagulation. The secondary end-points are the acceptability of the intervention to participants, its use by participants, and acceptability to referring physicians. Conclusions The AF-LITT pilot aims to evaluate the efficacy of the ECA/Kardia to improve HRQoL and anticoagulant adherence, and to guide its implementation in a larger, multicenter clinical trial. The intervention has potential to improve HRQoL, adherence, and health care utilization in individuals with chronic AF. PMID:28923492

DIgital Alcohol Management ON Demand (DIAMOND) feasibility randomised controlled trial of a web-based intervention to reduce alcohol consumption in people with hazardous and harmful use versus a face-to-face intervention: protocol.

PubMed

Hamilton, Fiona L; Hornby, Jo; Sheringham, Jessica; Kerry, Sally; Linke, Stuart; Solmi, Francesca; Ashton, Charlotte; Moore, Kevin; Murray, Elizabeth

2015-01-01

"Hazardous and harmful" drinkers make up approximately 23 % of the adult population in England. However, only around 10 % of these people access specialist care, such as face-to-face extended brief treatment in community alcohol services. This may be due to stigma, difficulty accessing services during working hours, a shortage of trained counsellors and limited provision of services in many places. Web-based alcohol treatment programmes may overcome these barriers and may better suit people who are reluctant or unable to attend face-to-face services, but there is a gap in the evidence base for the acceptability, effectiveness and cost-effectiveness of these programmes compared with treatment as usual (TAU) in community alcohol services. This study aims investigate the feasibility of all parts of a randomised controlled trial (RCT) of a psychologically informed web-based alcohol treatment programme called Healthy Living for People who use Alcohol (HeLP-Alcohol) versus TAU in community alcohol services, e.g. recruitment and retention, online data collection methods, and the use and acceptability of the intervention to participants. A feasibility RCT delivered in north London community alcohol services, comparing HeLP-Alcohol with TAU. Potential participants are aged ≥18 years referred or self-referred for hazardous and harmful use of alcohol, without co-morbidities or other complex problems. The main purpose of this study is to demonstrate the feasibility of recruiting participants to the study and will test online methods for collecting baseline demographic and outcome questionnaire data, randomising participants and collecting 3-month follow-up data. The acceptability of this intervention will be measured by recruitment and retention rates, automated log-in data collection and an online service satisfaction questionnaire. The feasibility of using tailored text message, email or phone prompt to maintain engagement with the intervention will also be explored. Results of the study will inform a definitive Phase 3 RCT. Recruitment started on 26 September 2014 and will run for 1 year. The proposed trial will provide data to inform a fully powered non-inferiority effectiveness and cost-effectiveness RCT comparing HeLP-Alcohol with TAU. ISRCTN31789096.

Rapid evidence review of the comparative effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment versus usual care for major depressive disorder.

PubMed

Peterson, Kimberly; Dieperink, Eric; Anderson, Johanna; Boundy, Erin; Ferguson, Lauren; Helfand, Mark

2017-06-01

This study aims to conduct an evidence review of the effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment for major depressive disorder. We searched MEDLINE®, the Cochrane Central Registry of Controlled Trials, and PsycINFO through February 2017. We used prespecified criteria to select studies, abstract data, and rate internal validity and strength of the evidence (PROSPERO number CRD42016036358). We included two randomized trials (RCT), five controlled cohort studies, and six modeling studies of mostly women in their mid-40s with few comorbidities. CNSDose (ABCB1, ABCC1, CYP2C19, CYP2D6, UGT1A1) is the only pharmacogenomics test that significantly improved remission (one additional remitting patient in 12 weeks per three genotyped, 95% CI 1.7 to 3.5) and reduced intolerability in an RCT. ABCB1 genotyping leads to one additional remitting patient in 5 weeks per three genotyped (95% CI 3 to 20), but tolerability was not reported. In an RCT, GeneSight (CYP2D6, CYPC19, CYP1A2, SLC6A4, HTR2A) did not statistically significantly improve remission, and evidence is inconclusive about its tolerability. Evidence is generally low strength because RCTs were few and underpowered. Cost-effectiveness is unclear due to lack of directly observed cost-effectiveness outcomes. We found no studies that evaluated whether pharmacogenomics shortens time to optimal treatment, whether improvements were due to switches to genetically congruent medication, or whether effectiveness varies based on test and patient characteristics. Certain pharmacogenomics tools show promise of improving short-term remission rates in women in their mid-40s with few comorbidities. But, important evidence limitations preclude recommending their widespread use and indicate a need for further research.

Effects of in-season circuit training on physical abilities in male handball players.

PubMed

Hermassi, Souhail; Wollny, Rainer; Schwesig, René; Shephard, Roy J; Chelly, Mohamed Souhaiel

2017-10-07

This study analyzed the effects of a resistance-type circuit training program (RCT) (30-35 minutes, performed twice a week for 10 weeks) on male handball players. Twenty-two males were divided into experimental (E; age 20.3 ± 0.5 years) and control groups (C; age 20.1± 0.5 years). Measures before and after RCT included squat (SJ) and countermovement jumps (CMJ), one repetition maximum (1-RM) ofbench press, pull-over and back half-squats, throwing velocity (a 3-step throw with run (RT), and a jump throw (JT)), repeated-sprint ability (six 2 x 15-m shuttle sprints with recording of best time for a single trial), anthropometric estimates of leg and thigh muscle volumes and mean thigh cross-sectional area (CSA), and a test of agility. The agility T-half test showed a significant interaction effect (p=0.001; η=0.422), with an inter-group difference in effect size (d) of 1.27 (dTG=1.24 vs. dCG=-0.03). The SJ displayed no interaction effect. The interaction effects for half back-squat (d=2.73, η=0.740) and CMJ (d=3.76, η=0.700) were large, but that for RT was smaller (η=0.460) than that for JT (η=0.745). The throwing velocity of C decreased for both measures, with negative effect sizes (d=-0.18 and d=-0.93 respectively). Upper body, leg, and thigh muscle volumes and thigh CSA increased significantly after resistance training. However, repeated-sprint parameters showed no significant changes. During the competitive season, 10 weeks of RCT with only 2 training sessions per week improved numerous measures of athletic performance in handball players, and such conditioning can be highly recommended as part of the annual training program for elite handball players.

Music therapy for schizophrenia or schizophrenia-like illnesses.

PubMed

Gold, C; Heldal, T O; Dahle, T; Wigram, T

2005-04-18

Music therapy is a psychotherapeutic method that uses musical interaction as a means of communication and expression. The aim of the therapy is to help people with serious mental illness to develop relationships and to address issues they may not be able to using words alone. To review the effects of music therapy, or music therapy added to standard care, compared to placebo, standard care or no treatment for people with serious mental illnesses such as schizophrenia. The Cochrane Schizophrenia Group's Register (July 2002) was searched. This was supplemented by hand searching of music therapy journals, manual searches of reference lists, and contacting relevant authors. All randomised controlled trials that compared music therapy with standard care or other psychosocial interventions for schizophrenia. Studies were reliably selected, quality assessed and data extracted. Data were excluded where more than 30% of participants in any group were lost to follow up. Non-skewed continuous endpoint data from valid scales were synthesised using a standardised mean difference (SMD). If statistical heterogeneity was found, treatment 'dosage' and treatment approach were examined as possible sources of heterogeneity. Four studies were included. These examined the effects of music therapy over the short to medium term (1 to 3 months), with treatment 'dosage' varying from 7 to 78 sessions. Music therapy added to standard care was superior to standard care alone for global state (medium term, 1 RCT, n = 72, RR 0.10 CI 0.03 to 0.31, NNT 2 CI 1.2 to 2.2). Continuous data suggested some positive effects on general mental state (1 RCT, n=69, SMD average endpoint PANSS -0.36 CI -0.85 to 0.12; 1 RCT, n=70, SMD average endpoint BPRS -1.25 CI -1.77 to -0.73),on negative symptoms (3 RCTs, n=180, SMD average endpoint SANS -0.86 CI -1.17 to -0.55) and social functioning (1 RCT, n=70, SMD average endpoint SDSI score -0.78 CI -1.27 to -0.28). However these latter effects were inconsistent across studies and depended on the number of music therapy sessions. All results were for the 1-3 month follow up. Music therapy as an addition to standard care helps people with schizophrenia to improve their global state and may also improve mental state and functioning if a sufficient number of music therapy sessions are provided. Further research should address the dose-effect relationship and the long-term effects of music therapy.

Integrating data from randomized controlled trials and observational studies to predict the response to pregabalin in patients with painful diabetic peripheral neuropathy.

PubMed

Alexander, Joe; Edwards, Roger A; Savoldelli, Alberto; Manca, Luigi; Grugni, Roberto; Emir, Birol; Whalen, Ed; Watt, Stephen; Brodsky, Marina; Parsons, Bruce

2017-07-20

More patient-specific medical care is expected as more is learned about variations in patient responses to medical treatments. Analytical tools enable insights by linking treatment responses from different types of studies, such as randomized controlled trials (RCTs) and observational studies. Given the importance of evidence from both types of studies, our goal was to integrate these types of data into a single predictive platform to help predict response to pregabalin in individual patients with painful diabetic peripheral neuropathy (pDPN). We utilized three pivotal RCTs of pregabalin (398 North American patients) and the largest observational study of pregabalin (3159 German patients). We implemented a hierarchical cluster analysis to identify patient clusters in the Observational Study to which RCT patients could be matched using the coarsened exact matching (CEM) technique, thereby creating a matched dataset. We then developed autoregressive moving average models (ARMAXs) to estimate weekly pain scores for pregabalin-treated patients in each cluster in the matched dataset using the maximum likelihood method. Finally, we validated ARMAX models using Observational Study patients who had not matched with RCT patients, using t tests between observed and predicted pain scores. Cluster analysis yielded six clusters (287-777 patients each) with the following clustering variables: gender, age, pDPN duration, body mass index, depression history, pregabalin monotherapy, prior gabapentin use, baseline pain score, and baseline sleep interference. CEM yielded 1528 unique patients in the matched dataset. The reduction in global imbalance scores for the clusters after adding the RCT patients (ranging from 6 to 63% depending on the cluster) demonstrated that the process reduced the bias of covariates in five of the six clusters. ARMAX models of pain score performed well (R 2 : 0.85-0.91; root mean square errors: 0.53-0.57). t tests did not show differences between observed and predicted pain scores in the 1955 patients who had not matched with RCT patients. The combination of cluster analyses, CEM, and ARMAX modeling enabled strong predictive capabilities with respect to pain scores. Integrating RCT and Observational Study data using CEM enabled effective use of Observational Study data to predict patient responses.

CONSORT to community: translation of an RCT to a large-scale community intervention and learnings from evaluation of the upscaled program.

PubMed

Moores, Carly Jane; Miller, Jacqueline; Perry, Rebecca Anne; Chan, Lily Lai Hang; Daniels, Lynne Allison; Vidgen, Helen Anna; Magarey, Anthea Margaret

2017-11-29

Translation encompasses the continuum from clinical efficacy to widespread adoption within the healthcare service and ultimately routine clinical practice. The Parenting, Eating and Activity for Child Health (PEACH™) program has previously demonstrated clinical effectiveness in the management of child obesity, and has been recently implemented as a large-scale community intervention in Queensland, Australia. This paper aims to describe the translation of the evaluation framework from a randomised controlled trial (RCT) to large-scale community intervention (PEACH™ QLD). Tensions between RCT paradigm and implementation research will be discussed along with lived evaluation challenges, responses to overcome these, and key learnings for future evaluation conducted at scale. The translation of evaluation from PEACH™ RCT to the large-scale community intervention PEACH™ QLD is described. While the CONSORT Statement was used to report findings from two previous RCTs, the REAIM framework was more suitable for the evaluation of upscaled delivery of the PEACH™ program. Evaluation of PEACH™ QLD was undertaken during the project delivery period from 2013 to 2016. Experiential learnings from conducting the evaluation of PEACH™ QLD to the described evaluation framework are presented for the purposes of informing the future evaluation of upscaled programs. Evaluation changes in response to real-time changes in the delivery of the PEACH™ QLD Project were necessary at stages during the project term. Key evaluation challenges encountered included the collection of complete evaluation data from a diverse and geographically dispersed workforce and the systematic collection of process evaluation data in real time to support program changes during the project. Evaluation of large-scale community interventions in the real world is challenging and divergent from RCTs which are rigourously evaluated within a more tightly-controlled clinical research setting. Constructs explored in an RCT are inadequate in describing the enablers and barriers of upscaled community program implementation. Methods for data collection, analysis and reporting also require consideration. We present a number of experiential reflections and suggestions for the successful evaluation of future upscaled community programs which are scarcely reported in the literature. PEACH™ QLD was retrospectively registered with the Australian New Zealand Clinical Trials Registry on 28 February 2017 (ACTRN12617000315314).

[Results of 30 children treated under dental general anesthesia in pediatric dentistry].

PubMed

Chen, Xu; Liu, Yao; Jin, Shi-fu; Zhang, Qian; Jin, Xuan-yu

2008-12-01

To determine the age and sex characteristics of the children and type of dental procedures performed under dental general anesthesia (DGA) and to assess the results after six months to one year's follow-up. A sample of 30 patients treated under dental general anesthesia (DGA) during 2006-2007 in the Department of Pediatric Dentistry of China Medical University was reviewed. All the teeth were treated one time. The dental procedures performed included caries restoration, indirect pulp capping, pulpotomy, root canal therapy (RCT) and dental extraction. Oral prophylaxis and topical fluoride applications were performed on all teeth. Pit and fissure sealing was performed on all healthy premolars and molars. SPSS10.0 software package was used for statistical analysis. Chi-square test was used to analyze the difference of the sex distribution in different age group and the difference of dental procedures performed between the primary teeth and the permanent teeth. The age of the patients ranged from 19 months to 14 years. The mental retardation patients accounted for 10% and mental healthy patients accounted for 90% of the sample studied. Males were more than females with the ratio about 2 to 1 in each age group. The dental procedures performed were caries restoration (18.67%), indirect pulp capping (23.26%), pulpotomy (0.77%), RCT (29.16%), dental extractions (2.05%) and fissure sealants (26.09%). The percentage of RCT was higher than that of caries restoration in the primary teeth, whereas the result was opposite as for the permanent teeth as indicated by Chi-square test (X(2)=11.630, P=0.001). New dental caries was not found except 2 patients who suffered from dysnoesia and were not cooperative to have regular examination. Fillings were lost in 3 cases, with 3 anterior teeth and 2 posterior teeth after RCT. All the children could cooperate except two mental retardation patients during the follow-up visit. Caries restoration and RCT are the most frequently performed procedures in pediatric patients using DGA. This indicates the need to design and implement integrate control and prevention programs for special pediatric patients. DGA is a safe and effective behavior management technique to treat uncooperative children.

RCT: Module 2.11, Radiological Work Coverage, Course 8777

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

Hillmer, Kurt T.

2017-07-20

Radiological work is usually approved and controlled by radiation protection personnel by using administrative and procedural controls, such as radiological work permits (RWPs). In addition, some jobs will require working in, or will have the potential for creating, very high radiation, contamination, or airborne radioactivity areas. Radiological control technicians (RCTs) providing job coverage have an integral role in controlling radiological hazards. This course will prepare the student with the skills necessary for RCT qualification by passing quizzes, tests, and the RCT Comprehensive Phase 1, Unit 2 Examination (TEST 27566) and will provide in-the-field skills.

Study sponsorship and the nutrition research agenda: analysis of randomized controlled trials included in systematic reviews of nutrition interventions to address obesity.

PubMed

Fabbri, Alice; Chartres, Nicholas; Scrinis, Gyorgy; Bero, Lisa A

2017-05-01

To categorize the research topics covered by a sample of randomized controlled trials (RCT) included in systematic reviews of nutrition interventions to address obesity; to describe their funding sources; and to explore the association between funding sources and nutrition research topics. Cross-sectional study. RCT included in Cochrane Reviews of nutrition interventions to address obesity and/or overweight. Two hundred and thirteen RCT from seventeen Cochrane Reviews were included. Funding source and authors' conflicts of interest were disclosed in 82·6 and 29·6 % of the studies, respectively. RCT were more likely to test an intervention to manipulate nutrients in the context of reduced energy intake (44·2 % of studies) than food-level (11·3 %) and dietary pattern-level (0·9 %) interventions. Most of the food industry-sponsored studies focused on interventions involving manipulations of specific nutrients (66·7 %). Only 33·1 % of the industry-funded studies addressed dietary behaviours compared with 66·9 % of the non-industry-funded ones (P=0·002). The level of food processing was poorly considered across all funding sources. The predominance of RCT examining nutrient-specific questions could limit the public health relevance of rigorous evidence available for systematic reviews and dietary guidelines.

Guidelines for time-to-event end point definitions in sarcomas and gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

PubMed

Bellera, C A; Penel, N; Ouali, M; Bonvalot, S; Casali, P G; Nielsen, O S; Delannes, M; Litière, S; Bonnetain, F; Dabakuyo, T S; Benjamin, R S; Blay, J-Y; Bui, B N; Collin, F; Delaney, T F; Duffaud, F; Filleron, T; Fiore, M; Gelderblom, H; George, S; Grimer, R; Grosclaude, P; Gronchi, A; Haas, R; Hohenberger, P; Issels, R; Italiano, A; Jooste, V; Krarup-Hansen, A; Le Péchoux, C; Mussi, C; Oberlin, O; Patel, S; Piperno-Neumann, S; Raut, C; Ray-Coquard, I; Rutkowski, P; Schuetze, S; Sleijfer, S; Stoeckle, E; Van Glabbeke, M; Woll, P; Gourgou-Bourgade, S; Mathoulin-Pélissier, S

2015-05-01

The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks uniformity across trials. End point definition can impact trial results by affecting estimation of treatment effect and statistical power. The DATECAN initiative (Definition for the Assessment of Time-to-event End points in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for RCT in sarcomas and gastrointestinal stromal tumors (GIST). We first carried out a literature review to identify TTE end points (primary or secondary) reported in publications of RCT. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points. Recommendations were developed through a validated consensus method formalizing the degree of agreement among experts. Recommended guidelines for the definition of TTE end points commonly used in RCT for sarcomas and GIST are provided for adjuvant and metastatic settings, including DFS, TTF, time to progression and others. Use of standardized definitions should facilitate comparison of trials' results, and improve the quality of trial design and reporting. These guidelines could be of particular interest to research scientists involved in the design, conduct, reporting or assessment of RCT such as investigators, statisticians, reviewers, editors or regulatory authorities. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Novel therapies for resistant focal segmental glomerulosclerosis (FONT) phase II clinical trial: study design.

PubMed

Trachtman, Howard; Vento, Suzanne; Gipson, Debbie; Wickman, Larysa; Gassman, Jennifer; Joy, Melanie; Savin, Virginia; Somers, Michael; Pinsk, Maury; Greene, Tom

2011-02-10

The lack of adequate randomized clinical trials (RCT) has hindered identification of new therapies that are safe and effective for patients with primary focal segmental glomerulosclerosis (FSGS), especially in patients who fail to respond to corticosteroids and immunosuppressive therapies. Recent basic science advances have led to development of alternative treatments that specifically target aberrant pathways of fibrosis which are relevant to disease progression in FSGS. There is a need for a flexible Phase II study design which will test such novel antifibrotic strategies in order to identify agents suitable for phase III testing. The Novel Therapies for Resistant Focal Segmental Glomerulosclerosis (FONT) project is a multicenter Phase I/II RCT designed to investigate the potential efficacy of novel therapies for resistant FSGS. Adalimumab and galactose will be evaluated against conservative therapy consisting of the combination of lisinopril, losartan and atorvastatin. The sample size is defined to assure that if one of the treatments has a superior response rate compared to that of the other treatments, it will be selected with high probability for further evaluation. Comparison of primary and secondary endpoints in each study arm will enable a choice to be made of which treatments are worthy of further study in future Phase III RCT. This report highlights the key features of the FONT II RCT including the two-step outcome analysis that will expedite achievement of the study objectives. The proposed phase II study design will help to identify promising agents for further testing while excluding ineffective agents. This staged approach can help to prevent large expenditures on unworthy therapeutic agents in the management of serious but rare kidney diseases.

Mobile phones support adherence and retention of indigenous participants in a randomised controlled trial: strategies and lessons learnt.

PubMed

McCallum, Gabrielle B; Versteegh, Lesley A; Morris, Peter S; Mckay, Clare C; Jacobsen, Nerida J; White, Andrew V; D'Antoine, Heather A; Chang, Anne B

2014-06-18

Ensuring adherence to treatment and retention is important in clinical trials, particularly in remote areas and minority groups. We describe a novel approach to improve adherence, retention and clinical review rates of Indigenous children. This descriptive study was nested within a placebo-controlled, randomised trial (RCT) on weekly azithromycin (or placebo) for 3-weeks. Indigenous children aged ≤24-months hospitalised with acute bronchiolitis were recruited from two tertiary hospitals in northern Australia (Darwin and Townsville). Using mobile phones embedded within a culturally-sensitive approach and framework, we report our strategies used and results obtained. Our main outcome measure was rates of adherence to medications, retention in the RCT and self-presentation (with child) to clinic for a clinical review on day-21. Of 301 eligible children, 76 (21%) families declined participation and 39 (13%) did not have access to a mobile phone. 186 Indigenous children were randomised and received dose one under supervision in hospital. Subsequently, 182 (99%) children received dose two (day-7), 169 (93%) dose three (day-14) and 180 (97%) attended their clinical review (day-21). A median of 2 calls (IQR 1-3) were needed to verify adherence. Importantly, over 97% of children remained in the RCT until their clinical endpoint at day-21. In our setting, the use of mobile phones within an Indigenous-appropriate framework has been an effective strategy to support a clinical trial involving Australian Indigenous children in urban and remote Australia. Further research is required to explore other applications of this approach, including the impact on clinical outcomes. ACTRN12608000150347 (RCT component).

Statistical power in parallel group point exposure studies with time-to-event outcomes: an empirical comparison of the performance of randomized controlled trials and the inverse probability of treatment weighting (IPTW) approach.

PubMed

Austin, Peter C; Schuster, Tibor; Platt, Robert W

2015-10-15

Estimating statistical power is an important component of the design of both randomized controlled trials (RCTs) and observational studies. Methods for estimating statistical power in RCTs have been well described and can be implemented simply. In observational studies, statistical methods must be used to remove the effects of confounding that can occur due to non-random treatment assignment. Inverse probability of treatment weighting (IPTW) using the propensity score is an attractive method for estimating the effects of treatment using observational data. However, sample size and power calculations have not been adequately described for these methods. We used an extensive series of Monte Carlo simulations to compare the statistical power of an IPTW analysis of an observational study with time-to-event outcomes with that of an analysis of a similarly-structured RCT. We examined the impact of four factors on the statistical power function: number of observed events, prevalence of treatment, the marginal hazard ratio, and the strength of the treatment-selection process. We found that, on average, an IPTW analysis had lower statistical power compared to an analysis of a similarly-structured RCT. The difference in statistical power increased as the magnitude of the treatment-selection model increased. The statistical power of an IPTW analysis tended to be lower than the statistical power of a similarly-structured RCT.

Effects of Rate on Analgesia in Kilohertz Frequency Spinal Cord Stimulation: Results of the PROCO Randomized Controlled Trial

PubMed Central

Tavakkolizadeh, Moein; Love‐Jones, Sarah; Patel, Nikunj K.; Gu, Jianwen Wendy; Bains, Amarpreet; Doan, Que; Moffitt, Michael

2017-01-01

Objective The PROCO RCT is a multicenter, double‐blind, crossover, randomized controlled trial (RCT) that investigated the effects of rate on analgesia in kilohertz frequency (1–10 kHz) spinal cord stimulation (SCS). Materials and Methods Patients were implanted with SCS systems and underwent an eight‐week search to identify the best location (“sweet spot”) of stimulation at 10 kHz within the searched region (T8–T11). An electronic diary (e‐diary) prompted patients for pain scores three times per day. Patients who responded to 10 kHz per e‐diary numeric rating scale (ED‐NRS) pain scores proceeded to double‐blind rate randomization. Patients received 1, 4, 7, and 10 kHz SCS at the same sweet spot found for 10 kHz in randomized order (four weeks at each frequency). For each frequency, pulse width and amplitude were titrated to optimize therapy. Results All frequencies provided equivalent pain relief as measured by ED‐NRS (p ≤ 0.002). However, mean charge per second differed across frequencies, with 1 kHz SCS requiring 60–70% less charge than higher frequencies (p ≤ 0.0002). Conclusions The PROCO RCT provides Level I evidence for equivalent pain relief from 1 to 10 kHz with appropriate titration of pulse width and amplitude. 1 kHz required significantly less charge than higher frequencies. PMID:29220121

Does a parent-administrated early motor intervention influence general movements and movement character at 3months of age in infants born preterm?

PubMed

Fjørtoft, Toril; Ustad, Tordis; Follestad, Turid; Kaaresen, Per Ivar; Øberg, Gunn Kristin

2017-09-01

Studies of preterm and term-born infants have shown absent fidgety movements and an abnormal movement character to be related to brain lesions and unfavourable neurological outcomes. The present study examines what effect a parent-administered early intervention program applied to preterm infants in a randomised control trial (RCT) between 34 and 36weeks gestational age has on their fidgety movements and overall movement character at three months of age. The study was part of the RCT in an early intervention programme including preterm infants born between 2010 and 2014 at three Norwegian university hospitals. 130 preterm infants participated in the study, with 59 of them in the control group and 71 in the intervention group. Fidgety movements and overall movement character at three months corrected age. No difference was found between the intervention group and the control group in terms of fidgety movements or movement character. Approximately half of the infants in both groups showed an abnormal movement character. No evidence was found in this RCT to suggest that an intervention at 34 to 37weeks gestational age has a significant effect on the fidgety movements or overall movement character of preterm infants. This is in line with the assumption that absent fidgety movements and an abnormal movement character are due to permanent brain injury and are therefore good predictors for later neurological impairments. Copyright © 2017 Elsevier B.V. All rights reserved.

Variability of the caprine whey protein genes and their association with milk yield, composition and renneting properties in the Sarda breed: 2. The BLG gene.

PubMed

Dettori, Maria Luisa; Pazzola, Michele; Pira, Emanuela; Puggioni, Ornella; Vacca, Giuseppe Massimo

2015-11-01

The variability of the promoter region and the 3'UTR (exon-7) of the BLG gene, encoding the β-lactoglobulin, was investigated by sequencing in 263 lactating Sarda goats in order to assess its association with milk traits. Milk traits included: milk yield, fat, total protein and lactose content, pH, daily fat and protein yield (DFPY), freezing point, milk energy, somatic cell count, total microbial mesophilic count, rennet coagulation time (RCT), curd firming rate (k20) and curd firmness (a30). A total of 7 polymorphic sites were detected and the sequence analysed was given accession number KM817769. Only three SNPs (c.-381C>T, c.-323C>T and c.*420C>A) had minor allele frequency higher than 0.05. The effects of farm, stage of lactation and the interaction farm × stage of lactation significantly influenced all the milk traits (P T and c.*420C>A (P T (P < 0.001). The c.-381TT homozygous goats showed lower pH, RCT and k20 than c.-381CT (P < 0.05). In conclusion the polymorphism of the goat BLG gene did not affect the total protein content of the Sarda goat milk, and only weakly influenced RCT and k20. On the other hand, an interesting effect on milk yields and DFPY emerged in two SNPs. This information might be useful in dairy goat breeding programs.

Differential effects of gemfibrozil and fenofibrate on reverse cholesterol transport from macrophages to feces in vivo.

PubMed

Rotllan, Noemí; Llaverías, Gemma; Julve, Josep; Jauhiainen, Matti; Calpe-Berdiel, Laura; Hernández, Cristina; Simó, Rafael; Blanco-Vaca, Francisco; Escolà-Gil, Joan Carles

2011-02-01

Gemfibrozil and fenofibrate, two of the fibrates most used in clinical practice, raise HDL cholesterol (HDLc) and are thought to reduce the risk of atherosclerotic cardiovascular disease. These drugs act as PPARα agonists and upregulate the expression of genes crucial in reverse cholesterol transport (RCT). In the present study, we determined the effects of these two fibrates on RCT from macrophages to feces in vivo in human apoA-I transgenic (hApoA-ITg) mice. [(3)H]cholesterol-labeled mouse macrophages were injected intraperitoneally into hApoA-ITg mice treated with intragastric doses of fenofibrate, gemfibrozil or a vehicle solution for 17days, and radioactivity was determined in plasma, liver and feces. Fenofibrate, but not gemfibrozil, enhanced [(3)H]cholesterol flux to plasma and feces of female hApoA-ITg mice. Fenofibrate significantly increased plasma HDLc, HDL phospholipids, hApoA-I levels and phospholipid transfer protein activity, whereas these parameters were not altered by gemfibrozil treatment. Unlike gemfibrozil, fenofibrate also induced the generation of larger HDL particles, which were more enriched in cholesteryl esters, together with higher potential to generate preβ-HDL formation and caused a significant increase in [(3)H]cholesterol efflux to plasma. Our findings demonstrate that fenofibrate promotes RCT from macrophages to feces in vivo and, thus, highlight a differential action of this fibrate on HDL. Copyright © 2010 Elsevier B.V. All rights reserved.

An RCT into the effects of neurofeedback on neurocognitive functioning compared to stimulant medication and physical activity in children with ADHD.

PubMed

Geladé, Katleen; Bink, Marleen; Janssen, Tieme W P; van Mourik, Rosa; Maras, Athanasios; Oosterlaan, Jaap

2017-04-01

Neurofeedback (NFB) is a potential alternative treatment for children with ADHD that aims to optimize brain activity. Whereas most studies into NFB have investigated behavioral effects, less attention has been paid to the effects on neurocognitive functioning. The present randomized controlled trial (RCT) compared neurocognitive effects of NFB to (1) optimally titrated methylphenidate (MPH) and (2) a semi-active control intervention, physical activity (PA), to control for non-specific effects. Using a multicentre three-way parallel group RCT design, children with ADHD, aged 7-13, were randomly allocated to NFB (n = 39), MPH (n = 36) or PA (n = 37) over a period of 10-12 weeks. NFB comprised theta/beta training at CZ. The PA intervention was matched in frequency and duration to NFB. MPH was titrated using a double-blind placebo controlled procedure to determine the optimal dose. Neurocognitive functioning was assessed using parameters derived from the auditory oddball-, stop-signal- and visual spatial working memory task. Data collection took place between September 2010 and March 2014. Intention-to-treat analyses showed improved attention for MPH compared to NFB and PA, as reflected by decreased response speed during the oddball task [η p 2  = 0.21, p < 0.001], as well as improved inhibition, impulsivity and attention, as reflected by faster stop signal reaction times, lower commission and omission error rates during the stop-signal task (range η p 2  = 0.09-0.18, p values <0.008). Working memory improved over time, irrespective of received treatment (η p 2  = 0.17, p < 0.001). Overall, stimulant medication showed superior effects over NFB to improve neurocognitive functioning. Hence, the findings do not support theta/beta training applied as a stand-alone treatment in children with ADHD.

Ezetimibe inhibits hepatic Niemann-Pick C1-Like 1 to facilitate macrophage reverse cholesterol transport in mice.

PubMed

Xie, Ping; Jia, Lin; Ma, Yinyan; Ou, Juanjuan; Miao, Hongming; Wang, Nanping; Guo, Feng; Yazdanyar, Amirfarbod; Jiang, Xian-Cheng; Yu, Liqing

2013-05-01

Controversies have arisen from recent mouse studies about the essential role of biliary sterol secretion in reverse cholesterol transport (RCT). The objective of this study was to examine the role of biliary cholesterol secretion in modulating macrophage RCT in Niemann-Pick C1-Like 1 (NPC1L1) liver only (L1(LivOnly)) mice, an animal model that is defective in both biliary sterol secretion and intestinal sterol absorption, and determine whether NPC1L1 inhibitor ezetimibe facilitates macrophage RCT by inhibiting hepatic NPC1L1. L1(LivOnly) mice were generated by crossing NPC1L1 knockout (L1-KO) mice with transgenic mice overexpressing human NPC1L1 specifically in liver. Macrophage-to-feces RCT was assayed in L1-KO and L1(LivOnly) mice injected intraperitoneally with [(3)H]-cholesterol-labeled peritoneal macrophages isolated from C57BL/6 mice. Inhibition of biliary sterol secretion by hepatic overexpression of NPC1L1 substantially reduced transport of [(3)H]-cholesterol from primary peritoneal macrophages to the neutral sterol fraction in bile and feces in L1(LivOnly) mice without affecting tracer excretion in the bile acid fraction. Ezetimibe treatment for 2 weeks completely restored both biliary and fecal excretion of [(3)H]-tracer in the neutral sterol fraction in L1(LivOnly) mice. High-density lipoprotein kinetic studies showed that L1(LivOnly) mice compared with L1-KO mice had a significantly reduced fractional catabolic rate without altered hepatic and intestinal uptake of high-density lipoprotein-cholesterol ether. In mice lacking intestinal cholesterol absorption, macrophage-to-feces RCT depends on efficient biliary sterol secretion, and ezetimibe promotes macrophage RCT by inhibiting hepatic NPC1L1 function.

Preoperative Radiotherapy of Advanced Rectal Cancer With Capecitabine and Oxaliplatin With or Without Cetuximab: A Pooled Analysis of Three Prospective Phase I-II Trials

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

Weiss, Christian, E-mail: christian.weiss@kgu.d; Arnold, Dirk; Dellas, Kathrin

2010-10-01

Purpose: A pooled analysis of three prospective trials of preoperative radiochemotherapy (RCT) for rectal cancer by using oxaliplatin and capecitabine with or without cetuximab was performed to evaluate the impact of additional cetuximab on pathologic complete response (pCR) rates and tumor regression (TRG) grades. Methods and Materials: Of 202 patients, 172 patients met the inclusion criteria (primary tumor stage II/III, M0). All patients received concurrent RCT, and 46 patients received additional cetuximab therapy. A correlation of pretreatment clinicopathologic factors and cetuximab treatment with early pCR rates (TRG > 50%) was performed with univariate and multivariate analyses. Toxicity data were recordedmore » for all patients. Results: Of 172 patients, 24 (14%) patients achieved a pCR, and 84 of 172 (71%) patients showed a TRG of >50% in the surgical specimen assessment after preoperative treatment. Age, gender, and T/N stages, as well as localization of the tumor, were not associated with pCR or good TRG. The pCR rate was 16% after preoperative RCT alone and 9% with concurrent cetuximab therapy (p = 0.32). A significantly reduced TRG of >50% was found after RCT with cetuximab compared to RCT alone (p = 0.0035). This was validated by a multivariate analysis with all available clinical factors (p = 0.0037). Acute toxicity and surgical complications were not increased with additional cetuximab. Conclusions: Triple therapy with RCT and cetuximab seems to be feasible, with no unexpected toxicity. Early response assessment (TRG), however, suggests subadditive interaction. A longer follow-up (and finally randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates.« less

Prolonged remission from hepatic encephalopathy with rifaximin: results of a placebo crossover analysis.

PubMed

Bajaj, J S; Barrett, A C; Bortey, E; Paterson, C; Forbes, W P

2015-01-01

Rifaximin therapy reduced risk of hepatic encephalopathy (HE) recurrence and HE-related hospitalisations during a 6-month, randomised, placebo-controlled trial (RCT) and a 24-month open-label maintenance (OLM) study. However, the impact of crossover from placebo to rifaximin therapy is unclear. To study the impact of crossing over from placebo to rifaximin treatment on breakthrough HE and hospitalisation rates using a within-subjects design. Adults with cirrhosis and history of overt HE episodes, currently in HE remission, received placebo during the RCT and crossed over to rifaximin 550 mg twice daily during the OLM study. Rate of breakthrough overt HE episodes, hospitalisations and incidence and rate of adverse events (AEs) were analysed during RCT and first 6 months of OLM. Of 82 patients randomised to placebo in the RCT who crossed over to the OLM study, 39 experienced an HE episode during the RCT compared with 14 during the OLM study (P < 0.0001). Significantly lower rates of HE events were observed with rifaximin treatment compared with placebo treatment (P < 0.0001). Rates of HE-related hospitalisation were numerically lower during rifaximin treatment compared with placebo treatment, although not significant. Rates of most common AEs, serious AEs and infection-related AEs were similar between the two treatments. This analysis confirms the repeatability of results from the RCT on safety and efficacy of rifaximin 550 mg twice daily in reducing the risk of hepatic encephalopathy recurrence, and suggests these findings are translatable outside of a rigorous, controlled trial setting. © 2014 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Generalisability of an online randomised controlled trial: an empirical analysis.

PubMed

Wang, Cheng; Mollan, Katie R; Hudgens, Michael G; Tucker, Joseph D; Zheng, Heping; Tang, Weiming; Ling, Li

2018-02-01

Investigators increasingly use online methods to recruit participants for randomised controlled trials (RCTs). However, the extent to which participants recruited online represent populations of interest is unknown. We evaluated how generalisable an online RCT sample is to men who have sex with men in China. Inverse probability of sampling weights (IPSW) and the G-formula were used to examine the generalisability of an online RCT using model-based approaches. Online RCT data and national cross-sectional study data from China were analysed to illustrate the process of quantitatively assessing generalisability. The RCT (identifier NCT02248558) randomly assigned participants to a crowdsourced or health marketing video for promotion of HIV testing. The primary outcome was self-reported HIV testing within 4 weeks, with a non-inferiority margin of -3%. In the original online RCT analysis, the estimated difference in proportions of HIV tested between the two arms (crowdsourcing and health marketing) was 2.1% (95% CI, -5.4% to 9.7%). The hypothesis that the crowdsourced video was not inferior to the health marketing video to promote HIV testing was not demonstrated. The IPSW and G-formula estimated differences were -2.6% (95% CI, -14.2 to 8.9) and 2.7% (95% CI, -10.7 to 16.2), with both approaches also not establishing non-inferiority. Conducting generalisability analysis of an online RCT is feasible. Examining the generalisability of online RCTs is an important step before an intervention is scaled up. NCT02248558. © 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.

Designing a field trial of an equine grass sickness vaccine: A questionnaire-based feasibility study.

PubMed

Ireland, Joanne L; McGorum, Bruce C; Proudman, Christopher J; Newton, J Richard

2016-07-01

Without an experimental model of equine grass sickness (EGS), a randomised controlled field trial (RCT) represents the only method of evaluating the efficacy of Clostridium botulinum type C vaccination in preventing naturally occurring disease. Clinical trial feasibility is an important aspect of preliminary work undertaken prior to initiating RCTs, estimating parameters that are important for study design. This cross-sectional study aimed to assess the feasibility of conducting a nationwide RCT of a candidate vaccine for EGS based on responses from a sample of British equine veterinary practices (n = 119/284). Seventy-three percent of practices had attended ≥1 EGS case within the preceding 2 years (median four cases), and 51.3% regularly attended recurrently affected premises. Veterinary surgeons had greater confidence diagnosing acute/subacute EGS based solely on history and clinical signs compared to chronic EGS. Ninety-one percent of respondents (n = 103/113) considered the proposed RCT to be important/very important to equine veterinary research. Ninety-one percent of respondents (n = 102/112) indicated preparedness to assist in owner recruitment and 92.9% (n = 104/112) indicated willingness to participate in a RCT. The most frequent reasons for practices declining to participate were low incidence of EGS (n = 4), did not believe clients would wish to participate (n = 3) and amount of paperwork/data collection involved (n = 2). There was considerable support amongst participating veterinary practices for a RCT evaluating the efficacy of Clostridium botulinum vaccination for the prevention of EGS in Britain. Substantial proportions of participating practices would be prepared to participate in the RCT and regularly attended EGS-affected premises that would meet trial inclusion criteria. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cycle regimens for frozen-thawed embryo transfer.

PubMed

Ghobara, Tarek; Gelbaya, Tarek A; Ayeleke, Reuben Olugbenga

2017-07-05

Among subfertile couples undergoing assisted reproductive technology (ART), pregnancy rates following frozen-thawed embryo transfer (FET) treatment cycles have historically been found to be lower than following embryo transfer undertaken two to five days following oocyte retrieval. Nevertheless, FET increases the cumulative pregnancy rate, reduces cost, is relatively simple to undertake and can be accomplished in a shorter time period than repeated in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles with fresh embryo transfer. FET is performed using different cycle regimens: spontaneous ovulatory (natural) cycles; cycles in which the endometrium is artificially prepared by oestrogen and progesterone hormones, commonly known as hormone therapy (HT) FET cycles; and cycles in which ovulation is induced by drugs (ovulation induction FET cycles). HT can be used with or without a gonadotrophin releasing hormone agonist (GnRHa). This is an update of a Cochrane review; the first version was published in 2008. To compare the effectiveness and safety of natural cycle FET, HT cycle FET and ovulation induction cycle FET, and compare subtypes of these regimens. On 13 December 2016 we searched databases including Cochrane Gynaecology and Fertility's Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL. Other search sources were trials registers and reference lists of included studies. We included randomized controlled trials (RCTs) comparing the various cycle regimens and different methods used to prepare the endometrium during FET. We used standard methodological procedures recommended by Cochrane. Our primary outcomes were live birth rates and miscarriage. We included 18 RCTs comparing different cycle regimens for FET in 3815 women. The quality of the evidence was low or very low. The main limitations were failure to report important clinical outcomes, poor reporting of study methods and imprecision due to low event rates. We found no data specific to non-ovulatory women. 1. Natural cycle FET comparisons Natural cycle FET versus HT FETNo study reported live birth rates, miscarriage or ongoing pregnancy.There was no evidence of a difference in multiple pregnancy rates between women in natural cycles and those in HT FET cycle (odds ratio (OR) 2.48, 95% confidence interval (CI) 0.09 to 68.14, 1 RCT, n = 21, very low-quality evidence). Natural cycle FET versus HT plus GnRHa suppressionThere was no evidence of a difference in rates of live birth (OR 0.77, 95% CI 0.39 to 1.53, 1 RCT, n = 159, low-quality evidence) or multiple pregnancy (OR 0.58, 95% CI 0.13 to 2.50, 1 RCT, n = 159, low-quality evidence) between women who had natural cycle FET and those who had HT FET cycles with GnRHa suppression. No study reported miscarriage or ongoing pregnancy. Natural cycle FET versus modified natural cycle FET (human chorionic gonadotrophin (HCG) trigger)There was no evidence of a difference in rates of live birth (OR 0.55, 95% CI 0.16 to 1.93, 1 RCT, n = 60, very low-quality evidence) or miscarriage (OR 0.20, 95% CI 0.01 to 4.13, 1 RCT, n = 168, very low-quality evidence) between women in natural cycles and women in natural cycles with HCG trigger. However, very low-quality evidence suggested that women in natural cycles (without HCG trigger) may have higher ongoing pregnancy rates (OR 2.44, 95% CI 1.03 to 5.76, 1 RCT, n = 168). There were no data on multiple pregnancy. 2. Modified natural cycle FET comparisons Modified natural cycle FET (HCG trigger) versus HT FETThere was no evidence of a difference in rates of live birth (OR 1.34, 95% CI 0.88 to 2.05, 1 RCT, n = 959, low-quality evidence) or ongoing pregnancy (OR 1.21, 95% CI 0.80 to 1.83, 1 RCT, n = 959, low-quality evidence) between women in modified natural cycles and those who received HT. There were no data on miscarriage or multiple pregnancy. Modified natural cycle FET (HCG trigger) versus HT plus GnRHa suppressionThere was no evidence of a difference between the two groups in rates of live birth (OR 1.11, 95% CI 0.66 to 1.87, 1 RCT, n = 236, low-quality evidence) or miscarriage (OR 0.74, 95% CI 0.25 to 2.19, 1 RCT, n = 236, low-quality evidence) rates. There were no data on ongoing pregnancy or multiple pregnancy. 3. HT FET comparisons HT FET versus HT plus GnRHa suppressionHT alone was associated with a lower live birth rate than HT with GnRHa suppression (OR 0.10, 95% CI 0.04 to 0.30, 1 RCT, n = 75, low-quality evidence). There was no evidence of a difference between the groups in either miscarriage (OR 0.64, 95% CI 0.37 to 1.12, 6 RCTs, n = 991, I 2 = 0%, low-quality evidence) or ongoing pregnancy (OR 1.72, 95% CI 0.61 to 4.85, 1 RCT, n = 106, very low-quality evidence).There were no data on multiple pregnancy. 4. Comparison of subtypes of ovulation induction FET Human menopausal gonadotrophin(HMG) versus clomiphene plus HMG HMG alone was associated with a higher live birth rate than clomiphene combined with HMG (OR 2.49, 95% CI 1.07 to 5.80, 1 RCT, n = 209, very low-quality evidence). There was no evidence of a difference between the groups in either miscarriage (OR 1.33, 95% CI 0.35 to 5.09,1 RCT, n = 209, very low-quality evidence) or multiple pregnancy (OR 1.41, 95% CI 0.31 to 6.48, 1 RCT, n = 209, very low-quality evidence).There were no data on ongoing pregnancy. This review did not find sufficient evidence to support the use of one cycle regimen in preference to another in preparation for FET in subfertile women with regular ovulatory cycles. The most common modalities for FET are natural cycle with or without HCG trigger or endometrial preparation with HT, with or without GnRHa suppression. We identified only four direct comparisons of these two modalities and there was insufficient evidence to support the use of either one in preference to the other.

Acupuncture/Moxibustion RCT for Distal Sensory Peripheral Neuropathy in HIV/AIDS

PubMed Central

Anastasi, Joyce K.; Capili, Bernadette; Chung, Ann M.; Hammerschlag, Richard

2017-01-01

Distal sensory peripheral neuropathy is a common neurological complication experienced by people living with the human immunodeficiency virus (HIV). Traditional Chinese medicine (TCM) may offer effective interventions in the management of its symptoms. To improve the quality and transparency of reporting acupuncture clinical trials, the Consolidated Standards of Reporting Trials (CONSORT) guidelines were developed in 1996 and the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) recommendations were introduced in 2001. Incorporating international guidelines, this paper describes the development of a RCT including rationale, design, methods, procedures and logistics for a pilot study aimed at evaluating acupuncture and moxibustion for neuropathy associated with HIV. Using STRICTA guidelines as a template, aspects of clinical research design are explored to further optimise future studies of TCM. PMID:29756126

Matrix metalloproteinase-8 and substance P levels in gingival crevicular fluid during endodontic treatment of painful, nonvital teeth.

PubMed

Shin, Su-Jung; Lee, Woocheol; Lee, Jae-Il; Baek, Seung-Ho; Kum, Kee-Yeon; Shon, Won-Jun; Bae, Kwang-Shik

2011-10-01

The aim of this study was to investigate levels of matrix metalloproteinase-8 (MMP-8) and substance P (SP) in gingival crevicular fluid (GCF) during root canal treatment (RCT) of nonvital teeth. Patients scheduled for nonsurgical RCT were prospectively selected; all patients provided informed consent. GCF samples were collected from teeth scheduled for RCT and their contralateral teeth across 3 different time periods. MMP-8 and SP levels were measured using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using a mixed model analysis and the Pearson correlation analysis. Patients' subjective pain levels were significantly related to both MMP-8 and SP levels. MMP-8 and SP levels in GCF were decreased during RCT, and they showed a positive correlation with each other (P < .05). This study demonstrated that periradicular inflammation of endodontic origin can elevate SP and MMP-8 levels in GCF. Copyright © 2011 Mosby, Inc. All rights reserved.

General Dentists’ Use of Isolation Techniques During Root Canal Treatment: from the National Dental Practice-Based Research Network

PubMed Central

Lawson, Nathaniel C.; Gilbert, Gregg H.; Funkhouser, Ellen; Eleazer, Paul D.; Benjamin, Paul L.; Worley, Donald C.

2015-01-01

Introduction A preliminary study done by a National Dental Practice-Based Research Network precursor observed that 44% of general dentists (GDs) reported always using a rubber dam (RD) during root canal treatment (RCT). This full-scale study quantified use of all isolation techniques, including RD use. Methods Network practitioners completed a questionnaire about isolation techniques used during RCT. Network Enrollment Questionnaire data provided practitioner characteristics. Results 1,490 of 1,716 eligible GDs participated (87%); 697 (47%) reported always using a RD. This percentage varied by tooth type. These GDs were more likely to always use a RD: do not own a private practice; perform less than 10 RCT/month; have postgraduate training. Conclusions Most GDs do not use a RD all the time. Ironically, RDs are used more frequently by GDs who do not perform molar RCT. RD use varies with tooth type and certain dentist, practice, and patient characteristics. PMID:26015159

Relaxation training for anxiety: a ten-years systematic review with meta-analysis.

PubMed

Manzoni, Gian Mauro; Pagnini, Francesco; Castelnuovo, Gianluca; Molinari, Enrico

2008-06-02

Relaxation training is a common treatment for anxiety problems. Lacking is a recent quantitative meta-analysis that enhances understanding of the variability and clinical significance of anxiety reduction outcomes after relaxation treatment. All studies (1997-2007), both RCT, observational and without control group, evaluating the efficacy of relaxation training (Jacobson's progressive relaxation, autogenic training, applied relaxation and meditation) for anxiety problems and disorders were identified by comprehensive electronic searches with Pubmed, Psychinfo and Cochrane Registers, by checking references of relevant studies and of other reviews. Our primary outcome was anxiety measured with psychometric questionnaires. Meta-analysis was undertaken synthesizing the data from all trials, distinguishing within and between effect sizes. 27 studies qualified for the inclusion in the meta-analysis. As hypothesized, relaxation training showed a medium-large effect size in the treatment of anxiety. Cohen's d was .57 (95% CI: .52 to .68) in the within analysis and .51 (95% CI: .46 to .634) in the between group analysis. Efficacy was higher for meditation, among volunteers and for longer treatments. Implications and limitations are discussed. The results show consistent and significant efficacy of relaxation training in reducing anxiety. This meta-analysis extends the existing literature through facilitation of a better understanding of the variability and clinical significance of anxiety improvement subsequent to relaxation training.

Comparison of Solomon technique with selective laser ablation for twin-twin transfusion syndrome: a systematic review.

PubMed

Dhillon, R K; Hillman, S C; Pounds, R; Morris, R K; Kilby, M D

2015-11-01

To compare the Solomon and selective techniques for fetoscopic laser ablation (FLA) for the treatment of twin-twin transfusion syndrome (TTTS) in monochorionic-diamniotic twin pregnancies. This was a systematic review conducted in accordance with the PRISMA statement. Electronic searches were performed for relevant citations published from inception to September 2014. Selected studies included pregnancies undergoing FLA for TTTS that reported on recurrence of TTTS, occurrence of twin anemia-polycythemia sequence (TAPS) or survival. From 270 possible citations, three studies were included, two cohort studies and one randomized controlled trial (RCT), which directly compared the Solomon and selective techniques for FLA. The odds ratios (OR) of recurrent TTTS when using the Solomon vs the selective technique in the two cohort studies (n = 249) were 0.30 (95% CI, 0.00-4.46) and 0.45 (95% CI, 0.07-2.20). The RCT (n = 274) demonstrated a statistically significant reduction in risk of recurrent TTTS with the Solomon technique (OR, 0.21 (95% CI, 0.04-0.98); P = 0.03). The ORs for the development of TAPS following the Solomon and the selective techniques were 0.20 (95% CI, 0.00-2.46) and 0.61 (95% CI, 0.05-5.53) in the cohort studies and 0.16 (95% CI, 0.05-0.49) in the RCT, with statistically significant differences for the RCT only (P < 0.001). Observational evidence suggested overall better survival with the Solomon technique, which was statistically significant for survival of at least one twin. The RCT did not demonstrate a significant difference in survival between the two techniques, most probably owing to the small sample size and lack of power. This systematic review of observational, comparative cohort and RCT data suggests a trend towards a reduction in TAPS and recurrent TTTS and an increase in twin survival, with no increase in the occurrence of complications or adverse events, when using the Solomon compared to the selective technique for the treatment of TTTS. These findings need to be confirmed by an appropriately-powered RCT with long-term neurological follow-up. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

The Southeast Scotland Foundation Doctor Teaching Programme--is "near-peer" teaching feasible, efficacious and sustainable on a regional scale?

PubMed

Rodrigues, Jeremy; Sengupta, Anshuman; Mitchell, Alana; Kane, Christopher; Kane, Clare; Maxwell, Simon; Cameron, Helen; Ross, Michael; Ford, Michael

2009-02-01

Peer-assisted learning has advantages for students and tutors. We aimed to establish a novel 'near-peer' teaching scheme delivered by junior doctors for final-year medical students in Southeast Scotland. We report feedback from students regarding the perceived utility of this scheme, the results of a randomized controlled trial (RCT) of its impact, and mechanisms for quality assurance and sustainability. The scheme was devised by newly qualified doctors. Following open recruitment and tutor training, junior doctor-led sessions were provided on clinical examination and practical prescribing in 2006-2008. Feedback was sought using anonymized questionnaires. An RCT was performed to assess the effect of attendance at a prescribing tutorial on performance in a mock assessment. Of 271 students in 2006-2007, 234 (86%) completed voluntary feedback and 233 (99%) expressed interest in attending more tutorials. In the RCT, students who received a tutorial made fewer dosing errors (9 vs. 22, p = 0.049). The majority of tutors attending the training symposium felt the experience was useful and helped prepare them for teaching. 'Near-peer' teaching is a popular adjunct to the undergraduate programme and may promote junior doctors' professional development. Such schemes can be devised and delivered by juniors in conjunction with university staff.

A Review of Escitalopram and Citalopram in Child and Adolescent Depression

PubMed Central

Carandang, Carlo; Jabbal, Rekha; MacBride, Angela; Elbe, Dean

2011-01-01

Objective: To review the basic pharmacology and published literature regarding escitalopram and citalopram in child and adolescent depression. Methods: 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. Results: 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). Conclusion: 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. PMID:22114615

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

PubMed

Sim, Julius; Lewis, Martyn

2012-03-01

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

Effects of corticosteroids and hyaluronic acid on torn rotator cuff tendons in vitro and in rats.

PubMed

Nakamura, Hidehiro; Gotoh, Masafumi; Kanazawa, Tomonoshin; Ohta, Keisuke; Nakamura, Keiichirou; Honda, Hirokazu; Ohzono, Hiroki; Shimokobe, Hisao; Mitsui, Yasuhiro; Shirachi, Isao; Okawa, Takahiro; Higuchi, Fujio; Shirahama, Masahiro; Shiba, Naoto; Matsueda, Satoko

2015-10-01

Corticosteroids (CS) or hyaluronic acid (HA) is used in subacromial injection for the conservative treatment of rotator cuff tears (RCT); this study addresses the question of how CS and HA affect the tendon tissue and fibroblasts in vitro and in rats. Cell proliferation assays were performed in human tendon fibroblasts from RCT. Rats underwent surgery to create RCT, and the surgical sites were injected with CS or HA. The rotator cuff tendons were subjected to biomechanical testing, microscopic and immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), and ultrastructural analysis. Cell proliferation was significantly decreased with CS in vitro (p < 0.05). Maximal load of CS-treated tendons was significantly decreased compared with that of HA-treated tendons (p < 0.05), as well as PCNA(+) cells at 2 weeks (p < 0.05). Ultrastructural observations of the CS-treated rats detected apoptosis of tendon fibroblasts 24 h after surgery. Histological and biomechanical data 4 weeks after surgery were not significant among the three groups. Unlike HA, CS caused cell death, and inhibition of the proliferation of tendon fibroblasts, leading to a delay of tendon healing involved and a subsequent decrease of biomechanical strength at the surgical site. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Early intervention for psychosis

PubMed Central

Marshall, Max; Rathbone, John

2014-01-01

Background Proponents of early intervention have argued that outcomes might be improved if more therapeutic efforts were focused on the early stages of schizophrenia or on people with prodromal symptoms. Early intervention in schizophrenia has two elements that are distinct from standard care: early detection, and phase-specific treatment (phase-specific treatment is a psychological, social or physical treatment developed, or modified, specifically for use with people at an early stage of the illness). Early detection and phase-specific treatment may both be offered as supplements to standard care, or may be provided through a specialised early intervention team. Early intervention is now well established as a therapeutic approach in America, Europe and Australasia. Objectives To evaluate the effects of: (a) early detection; (b) phase-specific treatments; and (c) specialised early intervention teams in the treatment of people with prodromal symptoms or first-episode psychosis. Search methods We searched the Cochrane Schizophrenia Group Trials Register (March 2009), inspected reference lists of all identified trials and reviews and contacted experts in the field. Selection criteria We included all randomised controlled trials (RCTs) designed to prevent progression to psychosis in people showing prodromal symptoms, or to improve outcome for people with first-episode psychosis. Eligible interventions, alone and in combination, included: early detection, phase-specific treatments, and care from specialised early intervention teams. We accepted cluster-randomised trials but excluded non-randomised trials. Data collection and analysis We reliably selected studies, quality rated them and extracted data. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis (ITT). Main results Studies were diverse, mostly small, undertaken by pioneering researchers and with many methodological limitations (18 RCTs, total n=1808). Mostly, meta-analyses were inappropriate. For the six studies addressing prevention of psychosis for people with prodromal symptoms, olanzapine seemed of little benefit (n=60, 1 RCT, RR conversion to psychosis 0.58 CI 0.3 to 1.2), and cognitive behavioural therapy (CBT) equally so (n=60, 1 RCT, RR conversion to psychosis 0.50 CI 0.2 to 1.7). A risperidone plus CBT plus specialised team did have benefit over specialist team alone at six months (n=59, 1 RCT, RR conversion to psychosis 0.27 CI 0.1 to 0.9, NNT 4 CI 2 to 20), but this was not seen by 12 months (n=59, 1 RCT, RR 0.54 CI 0.2 to 1.3). Omega 3 fatty acids (EPA) had advantage over placebo (n=76, 1 RCT, RR transition to psychosis 0.13 CI 0.02 to 1.0, NNT 6 CI 5 to 96). We know of no replications of this finding. The remaining trials aimed to improve outcome in first-episode psychosis. Phase-specific CBT for suicidality seemed to have little effect, but the single study was small (n=56, 1 RCT, RR suicide 0.81 CI 0.05 to 12.26). Family therapy plus a specialised team in the Netherlands did not clearly affect relapse (n=76, RR 1.05 CI 0.4 to 3.0), but without the specialised team in China it may (n=83, 1 RCT, RR admitted to hospital 0.28 CI 0.1 to 0.6, NNT 3 CI 2 to 6). The largest and highest quality study compared specialised team with standard care. Leaving the study early was reduced (n=547, 1 RCT, RR 0.59 CI 0.4 to 0.8, NNT 9 CI 6 to 18) and compliance with treatment improved (n=507, RR stopped treatment 0.20 CI 0.1 to 0.4, NNT 9 CI 8 to 12). The mean number of days spent in hospital at one year were not significantly different (n=507, WMD, −1.39 CI −2.8 to 0.1), neither were data for ‘Not hospitalised’ by five years (n=547, RR 1.05 CI 0.90 to 1.2). There were no significant differences in numbers ‘not living independently’ by one year (n=507, RR 0.55 CI 0.3 to 1.2). At five years significantly fewer participants in the treatment group were ‘not living independently’ (n=547, RR 0.42 CI 0.21 to 0.8, NNT 19 CI 14 to 62). When phase-specific treatment (CBT) was compared with befriending no significant differences emerged in the number of participants being hospitalised over the 12 months (n=62, 1 RCT, RR 1.08 CI 0.59 to 1.99). Phase-specific treatment E-EPA oils suggested no benefit (n=80, 1 RCT, RR no response 0.90 CI 0.6 to 1.4) as did phase-specific treatment brief intervention (n=106, 1 RCT, RR admission 0.86 CI 0.4 to 1.7). Phase-specific ACE found no benefit but participants given vocational intervention were more likely to be employed (n=41, 1 RCT, RR 0.39 CI 0.21 to 0.7, NNT 2 CI 2 to 4). Phase-specific cannabis and psychosis therapy did not show benefit (n=47, RR cannabis use 1.30 CI 0.8 to 2.2) and crisis assessment did not reduce hospitalisation (n=98, RR 0.85 CI 0.6 to 1.3). Weight was unaffected by early behavioural intervention. Authors’ conclusions There is emerging, but as yet inconclusive evidence, to suggest that people in the prodrome of psychosis can be helped by some interventions. There is some support for specialised early intervention services, but further trials would be desirable, and there is a question of whether gains are maintained. There is some support for phase-specific treatment focused on employment and family therapy, but again, this needs replicating with larger and longer trials. PMID:21678345

The effect of macronutrients on glycaemic control: a systematic review of dietary randomised controlled trials in overweight and obese adults with type 2 diabetes in which there was no difference in weight loss between treatment groups.

PubMed

Emadian, Amir; Andrews, Rob C; England, Clare Y; Wallace, Victoria; Thompson, Janice L

2015-11-28

Weight loss is crucial for treating type 2 diabetes mellitus (T2DM). It remains unclear which dietary intervention is best for optimising glycaemic control, or whether weight loss itself is the main reason behind observed improvements. The objective of this study was to assess the effects of various dietary interventions on glycaemic control in overweight and obese adults with T2DM when controlling for weight loss between dietary interventions. A systematic review of randomised controlled trials (RCT) was conducted. Electronic searches of Medline, Embase, Cinahl and Web of Science databases were conducted. Inclusion criteria included RCT with minimum 6 months duration, with participants having BMI≥25·0 kg/m2, a diagnosis of T2DM using HbA1c, and no statistically significant difference in mean weight loss at the end point of intervention between dietary arms. Results showed that eleven studies met the inclusion criteria. Only four RCT indicated the benefit of a particular dietary intervention over another in improving HbA1c levels, including the Mediterranean, vegan and low glycaemic index (GI) diets. However the findings from one of the four studies showing a significant benefit are questionable because of failure to control for diabetes medications and poor adherence to the prescribed diets. In conclusion there is currently insufficient evidence to suggest that any particular diet is superior in treating overweight and obese patients with T2DM. Although the Mediterranean, vegan and low-GI diets appear to be promising, further research that controls for weight loss and the effects of diabetes medications in larger samples is needed.

Preoperative intra-aortic balloon pump use in high-risk patients prior to coronary artery bypass graft surgery decreases the risk for morbidity and mortality-A meta-analysis of 9,212 patients.

PubMed

Deppe, Antje-Christin; Weber, Carolyn; Liakopoulos, Oliver J; Zeriouh, Mohamed; Slottosch, Ingo; Scherner, Maximilian; Kuhn, Elmar W; Choi, Yeong-Hoon; Wahlers, Thorsten

2017-03-01

Prophylactic intra-aortic balloon pump (IABP) support for high-risk patients before coronary artery bypass grafting (CABG) is controversial. This meta-analysis sought to determine the current role of preoperative IABP support. We performed a meta-analysis of randomized (RCT) and observational trials (OT) that fulfilled the following criteria: (1) Group comparison of patients with prophylactic IABP implantation before CABG with a control group; (2) reporting at least one desired clinical endpoint, including all-cause mortality, myocardial infarction, cerebrovascular accident (CVA), and renal failure. Pooled treatment effects (odds ratio [OR] or weighted mean difference, and 95% confidence intervals [95%CI]) were assessed using a fixed or random effects model. A total of 9,212 patients from 23 studies (7 RCT, 16 OT) were identified after a literature search of major databases using a predefined keyword list. Absolute risk reduction for mortality in RCTs was 4.4% (OR 0.43; 95%CI 0.25-0.73; p = 0.0025). Prophylactic IABP use before CABG surgery also decreased the risk for myocardial infarction (OR 0.58; 95%CI 0.43-0.78; p = 0.004), CVA (OR 0.67; 95%CI 0.47-0.97; p = 0.042), and renal failure (OR 0.62; 95%CI 0.47-0.83; p = 0.0014). Length of intensive care unit stay (p < 0.0001) and length of hospital stay (p < 0.0001) were significantly reduced in patients with preoperative IABP use. Current evidence from RCT and OT suggests beneficial effects for the IABP in high-risk patients before CABG surgery. © 2017 Wiley Periodicals, Inc.

Health-related quality of life in senior adults with epilepsy: what we know from randomized clinical trials and suggestions for future research.

PubMed

Martin, Roy; Vogtle, Laura; Gilliam, Frank; Faught, Edward

2003-12-01

The goal of this work was to review the randomized controlled trial (RCT) literature on antiepileptic medication effects on health-related quality of life in seniors with epilepsy. Studies published from 1998 to June 2002 were identified by searching through Medline and the Cochrane Clinical Trials Register. Pre-1998 RCTs identified by Baker et al. [Epilepsia 41 (2003) 1357] were also examined for relevance to the present review. Studies were reviewed if they included a RCT design and included epilepsy patients over the age of 60. A total of 85 clinical trials were reviewed. Of the 85 studies reviewed only 37 RCT studies included patients over the age of 60. However, formal quality-of-life outcome assessment was not performed in any of the RCTs that included senior adults, and only six studies provided formal quantitative analyses of AED effects in the form of adverse events incidence and participant withdrawal rates. For the most part, early study withdrawal rates were substantial for seniors and adverse events were very common. Two studies reporting on the cognitive and behavioral effects of study AEDs indicated only modest impact when AED monotherapy was kept at therapeutic levels. Despite growing appreciation for quality-of-life, issues in the management of epilepsy little current empirical guidance is available for elderly with epilepsy. There exists virtually no information on elderly patient preferences and goals for epilepsy treatment outcomes, and available data primarily concerns younger adults. Despite some encouraging preliminary evidence from this review suggesting that conservative AED treatment may have a more favorable quality of life-related outcome, more conclusive statements await further systematic investigation.

Feasibility study of a randomized controlled trial of a telephone-delivered problem-solving-occupational therapy intervention to reduce participation restrictions in rural breast cancer survivors undergoing chemotherapy.

PubMed

Hegel, Mark T; Lyons, Kathleen D; Hull, Jay G; Kaufman, Peter; Urquhart, Laura; Li, Zhongze; Ahles, Tim A

2011-10-01

Breast cancer patients receiving adjuvant chemotherapy often experience functional effects of treatment that limit participation in life activities. The purpose of this study was to examine the feasibility of conducting a randomized controlled trial (RCT) of a novel intervention for these restrictions, determine acceptability of the intervention, and preliminarily assess its effects. A pilot RCT of a telephone-delivered Problem-solving and Occupational Therapy intervention (PST-OT) to improve participation restrictions in rural breast cancer patients undergoing chemotherapy. Thirty-one participants with Stages 1-3 breast cancer were randomized to 6 weekly sessions of PST-OT (n = 15) and usual care (n = 16). The primary study outcome was the feasibility of conducting the trial. Secondary outcomes were functional, quality of life and emotional status as assessed at baseline, 6 and 12 weeks. Of 46 patients referred 31 were enrolled (67% recruitment rate), of which 6 participants withdrew (81% retention rate). Twenty-four participants completed all study-related assessments (77%). Ninety-two percent of PST-OT participants were highly satisfied with the intervention, and 92% reported PST-OT to be helpful/very helpful for overcoming participation restrictions. Ninety-seven percent of planned PST-OT treatment sessions were completed. Completion rates for PST-OT homework tasks were high. Measures of functioning, quality of life, and emotional state favored the PST-OT condition. This pilot study suggests that an RCT of the PST-OT intervention is feasible to conduct with rural breast cancer patients undergoing adjuvant chemotherapy and that PST-OT may have positive effects on function, quality of life, and emotional state. 2010 John Wiley & Sons, Ltd.

Effects of standard training in the use of closed-circuit televisions in visually impaired adults: design of a training protocol and a randomized controlled trial.

PubMed

Burggraaff, Marloes C; van Nispen, Ruth M A; Melis-Dankers, Bart J M; van Rens, Ger H M B

2010-03-10

Reading problems are frequently reported by visually impaired persons. A closed-circuit television (CCTV) can be helpful to maintain reading ability, however, it is difficult to learn how to use this device. In the Netherlands, an evidence-based rehabilitation program in the use of CCTVs was lacking. Therefore, a standard training protocol needed to be developed and tested in a randomized controlled trial (RCT) to provide an evidence-based training program in the use of this device. To develop a standard training program, information was collected by studying literature, observing training in the use of CCTVs, discussing the content of the training program with professionals and organizing focus and discussion groups. The effectiveness of the program was evaluated in an RCT, to obtain an evidence-based training program. Dutch patients (n = 122) were randomized into a treatment group: normal instructions from the supplier combined with training in the use of CCTVs, or into a control group: instructions from the supplier only. The effect of the training program was evaluated in terms of: change in reading ability (reading speed and reading comprehension), patients' skills to operate the CCTV, perceived (vision-related) quality of life and tasks performed in daily living. The development of the CCTV training protocol and the design of the RCT in the present study may serve as an example to obtain an evidence-based training program. The training program was adjusted to the needs and learning abilities of individual patients, however, for scientific reasons it might have been preferable to standardize the protocol further, in order to gain more comparable results. http://www.trialregister.nl, identifier: NTR1031.

Nurse Home Visits Improve Maternal-Infant Interaction and Decrease Severity of Postpartum Depression

PubMed Central

Horowitz, June Andrews; Murphy, Christine A.; Gregory, Katherine; Wojcik, Joanne; Pulcini, Joyce; Solon, Lori

2013-01-01

Objective To test the efficacy of the relationship-focused behavioral coaching intervention Communicating and Relating Effectively (CARE) in increasing maternal-infant relational effectiveness between depressed mothers and their infants during the first nine months postpartum. Design Randomized clinical trial (RCT) with three phases. Methods In this three-phase study, women were screened for postpartum depression (PPD) in Phase I at 6 weeks postpartum. In Phase II, women were randomly assigned to treatment or control conditions and maternal-infant interaction was video-recorded at four intervals postpartum: 6 weeks, 3 months, 6 months, and 9 months. Phase III involved focus group and individual interviews with study participants. Setting Phase I mothers were recruited from obstetric units of two major medical centers. Phase II involved the RCT, a series of nurse-led home visits beginning at 6 weeks and ending at 9 months postpartum. Phase III focus groups were conducted at the university and personal interviews were conducted by telephone or in participants’ homes. Participants Postpartum mother-infant dyads (134) representative of southeastern New England, United States participated in the RCT. One hundred and twenty-five mother-infant dyads were fully retained in the 9-month protocol. Results Treatment and control groups had significant increases in quality of mother-infant interaction and decreases in depression severity. Qualitative findings indicated presence of the nurse, empathic listening, focused attention and self-reflection during data collection, directions for video-recorded interaction, and assistance with referrals likely contributed to improvements for both groups. Conclusions Efficacy of the CARE intervention was only partially supported. Nurse attention given to the control group and the data collection process likely confounded results and constituted an unintentional treatment. Results suggest that nurse-led home visits had a positive effect on outcomes for all participants. PMID:23682696

Policy-into-practice for rheumatoid arthritis: randomized controlled trial and cohort study of e-learning targeting improved physiotherapy management.

PubMed

Fary, Robyn E; Slater, Helen; Chua, Jason; Ranelli, Sonia; Chan, Madelynn; Briggs, Andrew M

2015-07-01

To examine the effectiveness of a physiotherapy-specific, web-based e-learning platform, "RAP-el," in best-practice management of rheumatoid arthritis (RA) using a single-blind, randomized controlled trial (RCT) and prospective cohort study. Australian-registered physiotherapists were electronically randomized into intervention and control groups. The intervention group accessed RAP-eL over 4 weeks. Change in self-reported confidence in knowledge and skills was compared between groups at the end of the RCT using linear regression conditioned for baseline scores by a blinded assessor, using intent-to-treat analysis. Secondary outcomes included physiotherapists' satisfaction with RA management and responses to RA-relevant clinical statements and practice-relevant vignettes. Retention was evaluated in a cohort study 8 weeks after the RCT. Eighty physiotherapists were randomized into the intervention and 79 into the control groups. Fifty-six and 48, respectively, provided baseline data. Significant between-group differences were observed for change in confidence in knowledge (mean difference 8.51; 95% confidence interval [95% CI] 6.29, 10.73; effect size 1.62) and skills (mean difference 7.26; 95% CI 5.1, 9.4; effect size 1.54), with the intervention group performing better. Satisfaction in ability to manage RA, 4 of the 6 clinical statements, and responses to vignettes demonstrated significant improvement in the intervention group. Although 8-week scores showed declines in most outcomes, their clinical significance remains uncertain. RAP-eL can improve self-reported confidence, likely practice behaviors and satisfaction in physiotherapists' ability to manage people with RA, and improve their clinical knowledge in several areas of best-practice RA management in the short term. © 2015, American College of Rheumatology.

Effects of a GABA-ergic medication combination and initial alcohol withdrawal severity on cue-elicited brain activation among treatment-seeking alcoholics.

PubMed

Schacht, Joseph P; Anton, Raymond F; Randall, Patrick K; Li, Xingbao; Henderson, Scott; Myrick, Hugh

2013-06-01

Many studies have reported medication effects on alcohol cue-elicited brain activation or associations between such activation and subsequent drinking. However, few have combined the methodological rigor of a randomized clinical trial (RCT) with follow-up assessments to determine whether cue-elicited activation predicts relapse during treatment, the crux of alcoholism. This study analyzed functional magnetic resonance imaging (fMRI) data from 48 alcohol-dependent subjects enrolled in a 6-week RCT of an investigational pharmacotherapy. Subjects were randomized, based on their level of alcohol withdrawal (AW) at study entry, to receive either a combination of gabapentin (GBP; up to 1,200 mg for 39 days) and flumazenil (FMZ) infusions (2 days) or two placebos. Midway through the RCT, subjects were administered an fMRI alcohol cue reactivity task. There were no main effects of medication or initial AW status on cue-elicited activation, but these factors interacted, such that the GBP/FMZ/higher AW and placebo/lower AW groups, which had previously been shown to have relatively reduced drinking, demonstrated greater dorsal anterior cingulate cortex (dACC) activation to alcohol cues. Further analysis suggested that this finding represented differences in task-related deactivation and was associated with greater control over alcohol-related thoughts. Among study completers, regardless of medication or AW status, greater left dorsolateral prefrontal cortex (DLPFC) activation predicted more post-scan heavy drinking. These data suggest that alterations in task-related deactivation of dACC, a component of the default mode network, may predict better alcohol treatment response, while activation of DLPFC, an area associated with selective attention, may predict relapse drinking.

A EUropean study on effectiveness and sustainability of current Cardiac Rehabilitation programmes in the Elderly: Design of the EU-CaRE randomised controlled trial.

PubMed

Prescott, Eva; Meindersma, Esther P; van der Velde, Astrid E; Gonzalez-Juanatey, Jose R; Iliou, Marie Christine; Ardissino, Diego; Zoccai, Giuseppe Biondi; Zeymer, Uwe; Prins, Leonie F; Van't Hof, Arnoud Wj; Wilhelm, Matthias; de Kluiver, Ed P

2016-10-01

Cardiac rehabilitation (CR) is an evidence-based intervention to increase survival and quality of life. Yet studies consistently show that elderly patients are less frequently referred to CR, show less uptake and more often drop out of CR programmes. The European study on effectiveness and sustainability of current cardiac rehabilitation programmes in the elderly (EU-CaRE) project consists of an observational study and an open prospective, investigator-initiated multicentre randomised controlled trial (RCT) involving mobile telemonitoring guided CR (mCR). The aim of EU-CaRE is to map the efficiency of current CR of the elderly in Europe, and to investigate whether mCR is an effective alternative in terms of efficacy, adherence and sustainability. The EU-CaRE study includes patients aged 65 years or older with ischaemic heart disease or who have undergone heart valve surgery. A total of 1760 patients participating in existing CR programmes in eight regions of Europe will be included. Of patients declining regular CR, 238 will be included in the RCT and randomised in two study arms. The experimental group (mCR) will receive a personalised home-based programme while the control group will receive no advice or coaching throughout the study period. Outcomes will be assessed after the end of CR and at 12 months follow-up. The primary outcome is VO 2peak and secondary outcomes include variables describing CR uptake, adherence, efficacy and sustainability. The study will provide important information to improve CR in the elderly. The EU-CaRE RCT is the first European multicentre study of mCR as an alternative for elderly patients not attending usual CR. © The European Society of Cardiology 2016.

Effects of standard training in the use of closed-circuit televisions in visually impaired adults: design of a training protocol and a randomized controlled trial

PubMed Central

2010-01-01

Background Reading problems are frequently reported by visually impaired persons. A closed-circuit television (CCTV) can be helpful to maintain reading ability, however, it is difficult to learn how to use this device. In the Netherlands, an evidence-based rehabilitation program in the use of CCTVs was lacking. Therefore, a standard training protocol needed to be developed and tested in a randomized controlled trial (RCT) to provide an evidence-based training program in the use of this device. Methods/Design To develop a standard training program, information was collected by studying literature, observing training in the use of CCTVs, discussing the content of the training program with professionals and organizing focus and discussion groups. The effectiveness of the program was evaluated in an RCT, to obtain an evidence-based training program. Dutch patients (n = 122) were randomized into a treatment group: normal instructions from the supplier combined with training in the use of CCTVs, or into a control group: instructions from the supplier only. The effect of the training program was evaluated in terms of: change in reading ability (reading speed and reading comprehension), patients' skills to operate the CCTV, perceived (vision-related) quality of life and tasks performed in daily living. Discussion The development of the CCTV training protocol and the design of the RCT in the present study may serve as an example to obtain an evidence-based training program. The training program was adjusted to the needs and learning abilities of individual patients, however, for scientific reasons it might have been preferable to standardize the protocol further, in order to gain more comparable results. Trial registration http://www.trialregister.nl, identifier: NTR1031 PMID:20219120

Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients with FHA[S

PubMed Central

Kootte, Ruud S.; Smits, Loek P.; van der Valk, Fleur M.; Dasseux, Jean-Louis; Keyserling, Constance H.; Barbaras, Ronald; Paolini, John F.; Santos, Raul D.; van Dijk, Theo H.; Dallinga-van Thie, Geesje M.; Nederveen, Aart J.; Mulder, Willem J. M.; Hovingh, G. Kees; Kastelein, John J. P.; Groen, Albert K.; Stroes, Erik S.

2015-01-01

Reverse cholesterol transport (RCT) contributes to the anti-atherogenic effects of HDL. Patients with the orphan disease, familial hypoalphalipoproteinemia (FHA), are characterized by decreased tissue cholesterol removal and an increased atherogenic burden. We performed an open-label uncontrolled proof-of-concept study to evaluate the effect of infusions with a human apoA-I-containing HDL-mimetic particle (CER-001) on RCT and the arterial vessel wall in FHA. Subjects received 20 infusions of CER-001 (8 mg/kg) during 6 months. Efficacy was assessed by measuring (apo)lipoproteins, plasma-mediated cellular cholesterol efflux, fecal sterol excretion (FSE), and carotid artery wall dimension by MRI and artery wall inflammation by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography scans. We included seven FHA patients: HDL-cholesterol (HDL-c), 13.8 [1.8–29.1] mg/dl; apoA-I, 28.7 [7.9–59.1] mg/dl. Following nine infusions in 1 month, apoA-I and HDL-c increased directly after infusion by 27.0 and 16.1 mg/dl (P = 0.018). CER-001 induced a 44% relative increase (P = 0.018) in in vitro cellular cholesterol efflux with a trend toward increased FSE (P = 0.068). After nine infusions of CER-001, carotid mean vessel wall area decreased compared with baseline from 25.0 to 22.8 mm2 (P = 0.043) and target-to-background ratio from 2.04 to 1.81 (P = 0.046). In FHA-subjects, CER-001 stimulates cholesterol mobilization and reduces artery wall dimension and inflammation, supporting further evaluation of CER-001 in FHA patients. PMID:25561459

Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients with FHA.

PubMed

Kootte, Ruud S; Smits, Loek P; van der Valk, Fleur M; Dasseux, Jean-Louis; Keyserling, Constance H; Barbaras, Ronald; Paolini, John F; Santos, Raul D; van Dijk, Theo H; Dallinga-van Thie, Geesje M; Nederveen, Aart J; Mulder, Willem J M; Hovingh, G Kees; Kastelein, John J P; Groen, Albert K; Stroes, Erik S

2015-03-01

Reverse cholesterol transport (RCT) contributes to the anti-atherogenic effects of HDL. Patients with the orphan disease, familial hypoalphalipoproteinemia (FHA), are characterized by decreased tissue cholesterol removal and an increased atherogenic burden. We performed an open-label uncontrolled proof-of-concept study to evaluate the effect of infusions with a human apoA-I-containing HDL-mimetic particle (CER-001) on RCT and the arterial vessel wall in FHA. Subjects received 20 infusions of CER-001 (8 mg/kg) during 6 months. Efficacy was assessed by measuring (apo)lipoproteins, plasma-mediated cellular cholesterol efflux, fecal sterol excretion (FSE), and carotid artery wall dimension by MRI and artery wall inflammation by (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography scans. We included seven FHA patients: HDL-cholesterol (HDL-c), 13.8 [1.8-29.1] mg/dl; apoA-I, 28.7 [7.9-59.1] mg/dl. Following nine infusions in 1 month, apoA-I and HDL-c increased directly after infusion by 27.0 and 16.1 mg/dl (P = 0.018). CER-001 induced a 44% relative increase (P = 0.018) in in vitro cellular cholesterol efflux with a trend toward increased FSE (P = 0.068). After nine infusions of CER-001, carotid mean vessel wall area decreased compared with baseline from 25.0 to 22.8 mm(2) (P = 0.043) and target-to-background ratio from 2.04 to 1.81 (P = 0.046). In FHA-subjects, CER-001 stimulates cholesterol mobilization and reduces artery wall dimension and inflammation, supporting further evaluation of CER-001 in FHA patients. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

Study protocol for a randomized controlled pilot-trial on the semiocclusive treatment of fingertip amputation injuries using a novel finger cap

PubMed Central

Schultz, Jurek; Leupold, Susann; Grählert, Xina; Pfeiffer, Roland; Schwanebeck, Uta; Schröttner, Percy; Djawid, Barbara; Artsimovich, Wladislav; Kozak, Karol; Fitze, Guido

2017-01-01

Abstract Introduction: Fingertip amputation injuries are common in all ages. Conservatively treated fingertips can regenerate skin and soft tissues to form a functionally and cosmetically excellent new fingertip. Little is known about this ability that, in humans, is confined to the fingertips. Even less is known about the role of the bacteria that regularly colonize these wounds without negative impact on regeneration and healing. As an alternative to surgery, self-adhesive film dressings are commonly used to establish a wet chamber around the injury. These dressings leak malodorous wound fluid eventually until the wound is dry. Having that into consideration, we have therefore developed a silicone finger cap that forms a mechanically protected, wet chamber around the injury for optimal regeneration conditions. It contains a puncturable reservoir for excess wound fluid, which can be thus routinely analyzed for diagnostic and research purposes. This study protocol explains the first randomized controlled trial (RCT) on the semiocclusive treatment of fingertip amputations in both children and adults comparing traditional film dressings with the novel silicone finger cap. Being the first RCT using 2 medical devices not yet certified for this indication, it will gather valuable information for the understanding of fingertip regeneration and the design of future definitive studies. Methods and analysis: By employing an innovative pseudo-cross-over-design with a dichotomous primary endpoint based on patients preference, this pilot study will gain statistically significant data with a very limited sample size. Our RCT will investigate acceptance, safety, effectiveness, and efficacy of this novel medical device while gathering information on the clinical course and outcome of conservatively treated fingertip injuries. A total of 22 patients older than 2 years will be randomly assigned to start the conservative treatment with either the traditional film-dressing or the novel finger cap. The treatment will be changed to the other alternative for another 2 weeks before the patient or the guardian is confronted with the decision of which method they would prefer for the rest of the treatment (if required). Ethics and dissemination: Ethical approval (EK 148042015) of the study protocol has been obtained from Institutional Review Board at the TU Dresden. The trial is registered at the European Database on Medical Devices (EUDAMED-No.: CIV-15-03-013246) and at ClinicalTrials.gov (NCT03089060). PMID:29019891

The handsearching of 2 medical journals of Bahrain for reports of randomized controlled trials.

PubMed

Al-Hajeri, Amani A; Fedorowicz, Zbigniew; Amin, Fawzi A; Eisinga, Anne

2006-04-01

To identify reports of randomized trials by handsearching 2 Bahrain medical journals, which are indexed in the biomedical database EMBASE and to determine any added value of the handsearching by comparing the reports found by handsearching with what would have been found by searching EMBASE to examine (i) the precision and sensitivity of the EMBASE index term Randomized Controlled Trial (RCT) and (ii) The Cochrane Collaboration's systematic electronic search of EMBASE (which uses 4 index terms and 9 free-text terms). All issues of the Bahrain Medical Bulletin (BMB) (1979-2004) and the Journal of the Bahrain Medical Society (JBMS) (1989-2004) were handsearched in February 2005 for reports of RCTs or Controlled Clinical Trials (CCTs), according to Cochrane eligibility criteria. Out of 395 articles in BMB we found reports of 12 RCTs and 4 CCTs. Distribution by country of corresponding author: Jordan (4 RCTs, one CCT), Bahrain (one RCT, one CCT), India (3 RCTs, one CCT), Kuwait (one CCT), Saudi Arabia (2 RCTs), USA/Bahrain (one RCT), and Oman (one RCT); and by specialty: Anesthesia (8), Surgery (1) Pediatrics (1), Radiotherapy (1), Community Medicine (1), Sports Medicine (1), Obstetrics/Gynecology (3). The Journal of the Bahrain Medical Society included reports of 14 RCTs and 3 CCTs, out of 97 articles. Distribution by country of corresponding author: Jordan (9 RCTs, 2 CCTs), Bahrain (3 RCTs), Egypt (one RCT), Kuwait (one RCT), and Saudi Arabia (one RCT); and by specialty: Anesthesia (7), General Surgery (3), Obstetrics/Gynecology (1), Radiotherapy (1), Pediatrics (1), Orthopaedic Surgery (1), Education (1) Ear Nose and Throat (1) Ophthalmology (1). Overall, of the 33 reports of trials found by handsearching both journals, only 23 were included in EMBASE of which only 6 had been indexed with the term RCT. Of the 23 reports of trials included in EMBASE, 16 had been identified in the Collaboration s systematic search of EMBASE. Two reports of trials could have been retrieved by this search but there was insufficient information in the title and abstract to code these as trials. The EMBASE records for the remaining 5 reports of trials did not contain terms currently used by The Cochrane Collaboration to identify reports of randomized trials in this database. The handsearching of these journals will help minimize publication bias by locating randomized trials not previously identified and, through their inclusion in the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, will ensure reports of randomized trials will not remain buried through indexing bias.

Investigating rennet coagulation properties of recombined highly concentrated micellar casein concentrate and cream for use in cheese making.

PubMed

Lu, Y; McMahon, D J; Vollmer, A H

2017-02-01

Highly concentrated micellar casein concentrate (HC-MCC) contains ∼18% casein with ∼70% of whey proteins removed by microfiltration and diafiltration of skim milk, followed by vacuum evaporation for further concentration. When blended with cream, HC-MCC forms recombined concentrated milk (RCM), which could be used as a starting material in cheese making. Our objective was to investigate the rennet coagulation properties of RCM while varying parameters such as casein level, pH, rennet level, and coagulation temperature. The HC-MCC was mixed with cream using low shear at 50°C for 10 min, followed by cooling to 31, 28, or 25°C and adding rennet, and rheological properties were determined. Rennet coagulation time [RCT, the time at which storage modulus (G') = loss modulus (G″)] decreased from 8.7 to 7.4 min as casein level increased from 3.2 to 5.7%, without a significant additional difference in RCT at casein levels >5.7%. The initial G″ (G″ 0 ) increased about 10-fold when casein levels were increased from 3.2 to 10.9%, whereas no change in initial G' (G' 0 ) was observed. When G' was measured relative to RCT (i.e., 1, 1.5, or 2 times RCT after RCT was reached, and expressed as G' 1 , G' 1.5 , and G' 2 ), log relationship was found between relative G' and casein level (R 2 > 0.94). Lowering coagulation temperature from 31 to 25°C increased G″ 0 by 6 fold and extended RCT from 7.4 to 9.5 min. After coagulation, relative G' was initially higher at the lower temperature with G' 1 of 3.6 Pa at 25°C and 2.0 Pa at 31°C, but delayed in further development with G' 2 of 0.8 kPa at 25°C and 1.1 kPa at 31°C. Lowering pH of RCM from 6.6 to 6.2 resulted in reduced RCT from 11.9 to 6.5 min with increased relative G' after coagulation. When less rennet was used, RCT increased in a linear inverse relationship without changes in relative G' or G″. The microstructure of RCM coagulum (∼11% casein), observed using transmission electron microscopy, confirmed that RCM curd had a rigid protein matrix containing extensively cross-linked protein strands. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

3D scapular orientation on healthy and pathologic subjects using stereoradiographs during arm elevation.

PubMed

Ohl, Xavier; Hagemeister, Nicola; Zhang, Cheng; Billuart, Fabien; Gagey, Olivier; Bureau, Nathalie J; Skalli, Wafa

2015-11-01

Alterations of the scapular kinematics in different pathologic conditions have been widely studied. However, results have shown considerable discrepancies concerning the direction and the amplitude of scapular movement. The lack of consistency in the literature probably has several explanations. The purpose of this study was to analyze scapular orientation with the arm at rest and with 90° lateral elevation in healthy and pathologic subjects by use of stereoradiographs. All participants (n = 65) underwent a clinical examination and magnetic resonance imaging of the shoulder to assess rotator cuff status. Participants were separated into 3 groups: healthy, rotator cuff tear (RCT), and RCT and subacromial impingement syndrome (RCT+ SIS). A 3-dimensional model of the scapula was fitted to each low-dose stereoradiograph acquired with the arm at rest and 90° arm elevation. Orientation of the scapula with the arm at rest was not significantly different between groups. During lateral elevation, scapular orientation was not significantly different between the healthy group and the RCT group. However, upward rotation was significantly reduced in the RCT + SIS group. Alterations of scapular kinematics in symptomatic subjects are multifactorial. We observed a link between clinically assessed subacromial impingement and scapular orientation during lateral elevation of the arm. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

The randomised controlled trial design: unrecognized opportunities for health sciences librarianship.

PubMed

Eldredge, Jonathan D

2003-06-01

to describe the essential components of the Randomised Controlled Trial (RCT) and its major variations; to describe less conventional applications of the RCT design found in the health sciences literature with potential relevance to health sciences librarianship; to discuss the limited number of RCTs within health sciences librarianship. narrative review supported to a limited extent with PubMed and Library Literature database searches consistent with specific search parameters. In addition, more systematic methods, including handsearching of specific journals, to identify health sciences librarianship RCTs. While many RCTs within the health sciences follow more conventional patterns, some RCTs assume certain unique features. Selected examples illustrate the adaptations of this experimental design to answering questions of possible relevance to health sciences librarians. The author offers several strategies for controlling bias in library and informatics applications of the RCT and acknowledges the potential of the electronic era in providing many opportunities to utilize the blinding aspects of RCTs. RCTs within health sciences librarianship inhabit a limited number of subject domains such as education. This limited scope offers both advantages and disadvantages for making Evidence-Based Librarianship (EBL) a reality. The RCT design offers the potential to answer far more EBL questions than have been addressed by the design to date. Librarians need only extend their horizons through use of the versatile RCT design into new subject domains to facilitate making EBL a reality.

Atheroprotective Effects of Methotrexate on Reverse Cholesterol Transport Proteins and Foam Cell Transformation in THP-1 Human Monocytes/Macrophages

PubMed Central

Reiss, Allison B.; Carsons, Steven E.; Anwar, Kamran; Rao, Soumya; Edelman, Sari D.; Zhang, Hongwei; Fernandez, Patricia; Cronstein, Bruce N.; Chan, Edwin S.L.

2008-01-01

OBJECTIVE: To determine whether MTX can overcome the atherogenic effect of COX-2 inhibitors and IFN-γ, both of which suppress cholesterol efflux protein levels and promote foam cell transformation in THP-1 human monocytes/macrophages. METHODS: Message and protein level of the reverse cholesterol transport (RCT) proteins cholesterol 27-hydroxylase and ABCA1 in THP-1 cells were evaluated by real-time polymerase chain reaction and immunoblot, respectively. Expression was evaluated in cells incubated in the presence or absence of the COX-2 inhibitor NS398 or IFN-γ with/without MTX. Foam cell transformation of lipid-loaded THP-1 macrophages was detected with oil red O staining and light microscopy. RESULTS: MTX increased 27-hydroxylase message and completely blocked NS398-induced downregulation of 27-hydroxylase (112.8±13.1% for NS398+MTX versus 71.1±4.3% for NS398 alone, with untreated as 100%, n=3, p<0.01). MTX also negated COX-2 inhibitor-mediated downregulation of ABCA1. Reversal of inhibitory effects on 27-hydroxylase and ABCA1 in the presence of MTX were blocked by the adenosine A2A receptor-specific antagonist ZM-241385. MTX also prevented NS398 and IFN-γ from increasing transformation of lipid-loaded THP-1 macrophages into foam cells. CONCLUSIONS: This study provides evidence supporting the atheroprotective effect of MTX. Through adenosine A2A receptor activation, MTX promotes RCT and limits foam cell formation in THP-1 macrophages. This is the first evidence that any commonly used medication can increase expression of anti-atherogenic RCT proteins and can counteract the effects of COX-2 inhibition. Our results suggest that one mechanism by which MTX protects against cardiovascular mortality in RA patients is through facilitation of cholesterol outflow from cells of the artery wall. PMID:19035488

Feasibility of a multidimensional home-based exercise programme for the elderly with structured support given by the general practitioner's surgery: Study protocol of a single arm trial preparing an RCT [ISRCTN58562962

PubMed Central

2009-01-01

Background Physical activity programmes can help to prevent functional decline in the elderly. Until now, such programmes use to target either on healthy community-dwelling seniors or on elderly living in special residences or care institutions. Sedentary or frail people, however, are difficult to reach when they live in their own homes. The general practitioner's (GP) practice offers a unique opportunity to acquire these people for participation in activity programmes. We conceptualised a multidimensional home-based exercise programme that shall be delivered to the target group through cooperation between GPs and exercise therapists. In order to prepare a randomised controlled trial (RCT), a feasibility study is being conducted. Methods The study is designed as a single arm interventional trial. We plan to recruit 90 patients aged 70 years and above through their GPs. The intervention lasts 12 weeks and consists of physical activity counselling, a home-exercise programme, and exercise consultations provided by an exercise therapist in the GP's practice and via telephone. The exercise programme consists of two main components: 1. a combination of home-exercises to improve strength, flexibility and balance, 2. walking for exercise to improve aerobic capacity. Primary outcome measures are: appraisal by GP, undesirable events, drop-outs, adherence. Secondary outcome measures are: effects (a. motor tests: timed-up-and-go, chair rising, grip strength, tandem stand, tandem walk, sit-and-reach; b. telephone interview: PRISCUS-Physical Activity Questionnaire, Short Form-8 Health Survey, three month recall of frequency of falls, Falls Efficacy Scale), appraisal by participant, exercise performance, focus group discussion. Data analyses will focus on: 1. decision-making concerning the conduction of a RCT, 2. estimation of the effects of the programme, detection of shortcomings and identification of subgroups with contrary results, 3. feedback to participants and to GPs. Conclusion A new cooperation between GPs and exercise therapists to approach community-dwelling seniors and to deliver a home-exercise programme is object of research with regard to feasibility and acceptance. In case of success, an RCT should examine the effects of the programme. A future implementation within primary medical care may take advantage from the flexibility of the programme. Trial registration Current Controlled Trials ISRCTN58562962. PMID:19686587

The effects of testosterone on body composition in obese men are not sustained after cessation of testosterone treatment.

PubMed

Ng Tang Fui, Mark; Hoermann, Rudolf; Zajac, Jeffrey D; Grossmann, Mathis

2017-10-01

Testosterone treatment in obese dieting men augments the diet-associated loss of fat mass, but protects against loss of lean mass. We assessed whether body composition changes are maintained following withdrawal of testosterone treatment. We conducted a prespecified double-blind randomized placebo-controlled observational follow-up study of a randomized controlled trial (RCT). Participants were men with baseline obesity (body mass index >30 kg/m 2 ) and a repeated total testosterone level <12 nmol/L, previously enrolled in a 56-week testosterone treatment trial combined with a weight loss programme. Main outcome measures were mean adjusted differences (MAD) (95% confidence interval), in body composition between testosterone- and placebo-treated men at the end of the observation period. Of the 100 randomized men, 82 completed the RCT and 64 the subsequent observational study. Median [IQR] observation time after completion of the RCT was 82 weeks [74; 90] in men previously receiving testosterone (cases) and 81 weeks [67;91] in men previously receiving placebo (controls), P=.51. At the end of the RCT, while losing similar amounts of weight, cases had, compared to controls, lost more fat mass, MAD -2.9 kg (-5.7, -0.2), P=.04, but had lost less lean mass MAD 3.4 kg (1.3, 5.5), P=.002. At the end of the observation period, the former between-group differences in fat mass, MAD -0.8 kg (-3.6, 2.0), P=1.0, in lean mass, MAD -1.3 kg (-3.0, 0.5), P=.39, and in appendicular lean mass, MAD -0.1 kg/m 2 (-0.3, 0.1), P=.45, were no longer apparent. During observation, cases lost more lean mass, MAD -3.7 kg (-5.5, -1.9), P=.0005, and appendicular lean mass, MAD -0.5 kg/m 2 (-0.8, -0.3), P<.0001 compared to controls. The favourable effects of testosterone on body composition in men subjected to a concomitant weight loss programme were not maintained at 82 weeks after testosterone treatment cessation. © 2017 John Wiley & Sons Ltd.

One year follow-up after a randomized controlled trial of a 130 g/day low-carbohydrate diet in patients with type 2 diabetes mellitus and poor glycemic control

PubMed Central

Kanazawa, Akio; Hatae, Chie; Makita, Sumiko; Komiya, Koji; Shimizu, Tomoaki; Ikeda, Fuki; Tamura, Yoshifumi; Ogihara, Takeshi; Mita, Tomoya; Goto, Hiromasa; Uchida, Toyoyoshi; Miyatsuka, Takeshi; Ohmura, Chie; Watanabe, Takehito; Kobayashi, Kiyoe; Miura, Yoshiko; Iwaoka, Manami; Hirashima, Nao; Watada, Hirotaka

2017-01-01

Background & aims Recently, we conducted a prospective randomized controlled trial (RCT) showing that a 6-month 130g/day low-carbohydrate diet (LCD) reduced HbA1c and BMI more than a calorie restricted diet (CRD). [1] To assess whether the benefits of the LCD persisted after the intensive intervention, we compared HbA1c and BMI between the LCD and CRD groups at 1 year after the end of the 6-month RCT. Methods Following the end of the 6-month RCT, patients were allowed to manage their own diets with periodic outpatient visits. One year later, we analyzed clinical and nutrition data. Results Of the 66 participants in the original study, 27 in the CRD group and 22 in the LCD group completed this trial. One year after the end of the original RCT, the carbohydrate intake was comparable between the groups (215 [189–243]/day in the CRD group and 214 (176–262) g/day in the LCD group). Compared with the baseline data, HbA1c and BMI were decreased in both groups (CRD: HbA1c -0.4 [-0.9 to 0.3] % and BMI -0.63 [-1.20 to 0.18] kg/m2; LCD: HbA1c -0.35 [-1.0 to 0.35] % and BMI -0.77 [-1.15 to -0.12] kg/m2). There were no significant differences in HbA1c and BMI between the groups. Conclusions One year after the diet therapy intervention, the beneficial effect of the LCD on reduction of HbA1c and BMI did not persist in comparison with CRD. However, combining the data of both groups, significant improvements in HbA1c and BMI from baseline were observed. Although the superiority of the LCD disappeared 1 year after the intensive intervention, these data suggest that well-constructed nutrition therapy programs, both CRD and LCD, were equally effective in improving HbA1c for at least 1 year. Trial registration University Hospital Medical Information Network (UMIN) ID000010663 PMID:29206237

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.

Using Randomized Controlled Trials to Evaluate Interventions for Releasing Prisoners

ERIC Educational Resources Information Center

Pettus-Davis, Carrie; Howard, Matthew Owen; Dunnigan, Allison; Scheyett, Anna M.; Roberts-Lewis, Amelia

2016-01-01

Randomized controlled trials (RCTs) are rarely used to evaluate social and behavioral interventions designed for releasing prisoners. Objective: We use a pilot RCT of a social support intervention (Support Matters) as a case example to discuss obstacles and strategies for conducting RCT intervention evaluations that span prison and community…

RCT: 2.02 Communication Systems, Course #33339

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

Hillmer, Kurt T.

This unit will present an overview of communication systems at LANL. Good communication skills are essential to an RCT. RCTs should develop an ability to communicate, using both verbal and nonverbal media. These skills will ensure that important information is transmitted to the proper individuals in a clear and concise manner.

RCT of a Manualized Social Treatment for High-Functioning Autism Spectrum Disorders

ERIC Educational Resources Information Center

Lopata, Christopher; Thomeer, Marcus L.; Volker, Martin A.; Toomey, Jennifer A.; Nida, Robert E.; Lee, Gloria K.; Smerbeck, Audrey M.; Rodgers, Jonathan D.

2010-01-01

This RCT examined the efficacy of a manualized social intervention for children with HFASDs. Participants were randomly assigned to treatment or wait-list conditions. Treatment included instruction and therapeutic activities targeting social skills, face-emotion recognition, interest expansion, and interpretation of non-literal language. A…

Clinical effectiveness of a patient decision aid to improve decision quality and glycaemic control in people with diabetes making treatment choices: a cluster randomised controlled trial (PANDAs) in general practice

PubMed Central

Mathers, Nigel; Ng, Chirk Jenn; Campbell, Michael Joseph; Colwell, Brigitte; Brown, Ian; Bradley, Alastair

2012-01-01

Objective To determine the effectiveness of a patient decision aid (PDA) to improve decision quality and glycaemic control in people with diabetes making treatment choices using a cluster randomised controlled trial (RCT). Design A cluster RCT. Setting 49 general practices in UK randomised into intervention (n=25) and control (n=24). Participants General practices Inclusion criteria: >4 medical partners; list size >7000; and a diabetes register with >1% of practice population. 191 practices assessed for eligibility, and 49 practices randomised and completed the study. Patients People with type 2 diabetes mellitus (T2DM) taking at least two oral glucose-lowering drugs with maximum tolerated dose with a glycosolated haemoglobin (HbA1c) greater than 7.4% (IFCC HbA1c >57 mmol/mol) or advised in the preceeding 6 months to add or consider changing to insulin therapy. Exclusion criteria: currently using insulin therapy; difficulty reading or understanding English; difficulty in understanding the purpose of the study; visual or cognitive impairment or mentally ill. A total of 182 assessed for eligibility, 175 randomised to 95 intervention and 80 controls, and 167 completion and analysis. Intervention Brief training of clinicians and use of PDA with patients in single consultation. Primary outcomes Decision quality (Decisional Conflict Scores, knowledge, realistic expectations and autonomy) and glycaemic control (glycosolated haemoglobin, HbA1c). Secondary outcomes Knowledge and realistic expectations of the risks and benefits of insulin therapy and diabetic complications. Results Intervention group: lower total Decisional Conflict Scores (17.4 vs 25.2, p<0.001); better knowledge (51.6% vs 28.8%, p<0.001); realistic expectations (risk of ‘hypo’, ‘weight gain’, ‘complications’; 81.0% vs 5.2%, 70.5% vs 5.3%, 26.3% vs 5.0% respectively, p<0.001); and were more autonomous in decision-making (64.1% vs 42.9%, p=0.012). No significant difference in the glycaemic control between the two groups. Conclusions Use of the PANDAs decision aid reduces decisional conflict, improves knowledge, promotes realistic expectations and autonomy in people with diabetes making treatment choices in general practice. ISRCTN Trials Register Number 14842077. PMID:23129571

Music therapy for people with schizophrenia and schizophrenia-like disorders.

PubMed

Mössler, Karin; Chen, Xijing; Heldal, Tor Olav; Gold, Christian

2011-12-07

Music therapy is a therapeutic method that uses musical interaction as a means of communication and expression. The aim of the therapy is to help people with serious mental disorders to develop relationships and to address issues they may not be able to using words alone. To review the effects of music therapy, or music therapy added to standard care, compared with 'placebo' therapy, standard care or no treatment for people with serious mental disorders such as schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register (December 2010) and supplemented this by contacting relevant study authors, handsearching of music therapy journals and manual searches of reference lists. All randomised controlled trials (RCTs) that compared music therapy with standard care, placebo therapy, or no treatment. Studies were reliably selected, quality assessed and data extracted. We excluded data where more than 30% of participants in any group were lost to follow-up. We synthesised non-skewed continuous endpoint data from valid scales using a standardised mean difference (SMD). If statistical heterogeneity was found, we examined treatment 'dosage' and treatment approach as possible sources of heterogeneity. We included eight studies (total 483 participants). These examined effects of music therapy over the short- to medium-term (one to four months), with treatment 'dosage' varying from seven to 78 sessions. Music therapy added to standard care was superior to standard care for global state (medium-term, 1 RCT, n = 72, RR 0.10 95% CI 0.03 to 0.31, NNT 2 95% CI 1.2 to 2.2). Continuous data identified good effects on negative symptoms (4 RCTs, n = 240, SMD average endpoint Scale for the Assessment of Negative Symptoms (SANS) -0.74 95% CI -1.00 to -0.47); general mental state (1 RCT, n = 69, SMD average endpoint Positive and Negative Symptoms Scale (PANSS) -0.36 95% CI -0.85 to 0.12; 2 RCTs, n=100, SMD average endpoint Brief Psychiatric Rating Scale (BPRS) -0.73 95% CI -1.16 to -0.31); depression (2 RCTs, n = 90, SMD average endpoint Self-Rating Depression Scale (SDS) -0.63 95% CI -1.06 to -0.21; 1 RCT, n = 30, SMD average endpoint Hamilton Depression Scale (Ham-D) -0.52 95% CI -1.25 to -0.21 ); and anxiety (1 RCT, n = 60, SMD average endpoint SAS -0.61 95% CI -1.13 to -0.09). Positive effects were also found for social functioning (1 RCT, n = 70, SMD average endpoint Social Disability Schedule for Inpatients (SDSI) score -0.78 95% CI -1.27 to -0.28). Furthermore, some aspects of cognitive functioning and behaviour seem to develop positively through music therapy. Effects, however, were inconsistent across studies and depended on the number of music therapy sessions as well as the quality of the music therapy provided. Music therapy as an addition to standard care helps people with schizophrenia to improve their global state, mental state (including negative symptoms) and social functioning if a sufficient number of music therapy sessions are provided by qualified music therapists. Further research should especially address the long-term effects of music therapy, dose-response relationships, as well as the relevance of outcomes measures in relation to music therapy.

'The trial is owned by the team, not by an individual': a qualitative study exploring the role of teamwork in recruitment to randomised controlled trials in surgical oncology.

PubMed

Strong, Sean; Paramasivan, Sangeetha; Mills, Nicola; Wilson, Caroline; Donovan, Jenny L; Blazeby, Jane M

2016-04-26

Challenges exist in recruitment to trials involving interventions delivered by different clinical specialties. Collaboration is required between clinical specialty and research teams. The aim of this study was to explore how teamwork influences recruitment to a multicentre randomised controlled trial (RCT) involving interventions delivered by different clinical specialties. Semi-structured interviews were conducted in three centres with a purposeful sample of members of the surgical, oncology and research teams recruiting to a feasibility RCT comparing definitive chemoradiotherapy with chemoradiotherapy and surgery for oesophageal squamous cell carcinoma. Interviews explored factors known to influence healthcare team effectiveness and were audio-recorded and thematically analysed. Sampling, data collection and analysis were undertaken iteratively and concurrently. Twenty-one interviews were conducted. Factors that influenced how team working impacted upon trial recruitment were centred on: (1) the multidisciplinary team (MDT) meeting, (2) leadership of the trial, and (3) the recruitment process. The weekly MDT meeting was reported as central to successful recruitment and formed the focus for creating a 'study team', bringing together clinical and research teams. Shared study leadership positively influenced healthcare professionals' willingness to participate. Interviewees perceived their clinical colleagues to have strong treatment preferences which led to scepticism regarding whether the treatments were being described to patients in a balanced manner. This study has highlighted a number of aspects of team functioning that are important for recruitment to RCTs that span different clinical specialties. Understanding these issues will aid the production of guidance on team-relevant issues that should be considered in trial management and the development of interventions that will facilitate teamwork and improve recruitment to these challenging RCTs. International Standard Randomised Controlled Trial Number (ISRCTN): ISRCTN89052791 .

Carbohydrates for improving the cognitive performance of independent-living older adults with normal cognition or mild cognitive impairment.

PubMed

Ooi, Cheow Peng; Loke, Seng Cheong; Yassin, Zaitun; Hamid, Tengku-Aizan

2011-04-13

Mild cognitive impairment (MCI) is an intermediate state between normal cognition and dementia in which daily function is largely intact. This condition may present an opportunity for research into the prevention of dementia. Carbohydrate is an essential and easily accessible macronutrient which influences cognitive performance. A better understanding of carbohydrate-driven cognitive changes in normal cognition and mild cognitive impairment may suggest ways to prevent or reduce cognitive decline. To assess the effectiveness of carbohydrates in improving cognitive function in older adults. We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register on 22 June 2010 using the terms: carbohydrates OR carbohydrate OR monosaccharides OR disaccharides OR oligosaccharides OR polysaccharides OR CARBS. ALOIS contains records from all major healthcare databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many trial databases and grey literature sources. All randomised controlled trials (RCT) that have examined the efficacy of any form of carbohydrates in normal cognition and MCI. One review author selected and retrieved relevant articles for further assessment. The remaining authors independently assessed whether any of the retrieved trials should be included. Disagreements were resolved by discussion.  There is no suitable RCT of any form of carbohydrates involving independent-living older adults with normal cognition or mild cognitive impairment. There are no suitable RCTs on which to base any recommendations about the use of any form of carbohydrate for enhancing cognitive performance in older adults with normal cognition or mild cognitive impairment. More studies of many different carbohydrates are needed to tease out complex nutritional issues and further evaluate memory improvement.

Walk well: a randomised controlled trial of a walking intervention for adults with intellectual disabilities: study protocol

PubMed Central

2013-01-01

Background Walking interventions have been shown to have a positive impact on physical activity (PA) levels, health and wellbeing for adult and older adult populations. There has been very little work carried out to explore the effectiveness of walking interventions for adults with intellectual disabilities. This paper will provide details of the Walk Well intervention, designed for adults with intellectual disabilities, and a randomised controlled trial (RCT) to test its effectiveness. Methods/design This study will adopt a RCT design, with participants allocated to the walking intervention group or a waiting list control group. The intervention consists of three PA consultations (baseline, six weeks and 12 weeks) and an individualised 12 week walking programme. A range of measures will be completed by participants at baseline, post intervention (three months from baseline) and at follow up (three months post intervention and six months from baseline). All outcome measures will be collected by a researcher who will be blinded to the study groups. The primary outcome will be steps walked per day, measured using accelerometers. Secondary outcome measures will include time spent in PA per day (across various intensity levels), time spent in sedentary behaviour per day, quality of life, self-efficacy and anthropometric measures to monitor weight change. Discussion Since there are currently no published RCTs of walking interventions for adults with intellectual disabilities, this RCT will examine if a walking intervention can successfully increase PA, health and wellbeing of adults with intellectual disabilities. Trial registration ISRCTN: ISRCTN50494254 PMID:23816316

Regression discontinuity was a valid design for dichotomous outcomes in three randomized trials.

PubMed

van Leeuwen, Nikki; Lingsma, Hester F; Mooijaart, Simon P; Nieboer, Daan; Trompet, Stella; Steyerberg, Ewout W

2018-06-01

Regression discontinuity (RD) is a quasi-experimental design that may provide valid estimates of treatment effects in case of continuous outcomes. We aimed to evaluate validity and precision in the RD design for dichotomous outcomes. We performed validation studies in three large randomized controlled trials (RCTs) (Corticosteroid Randomization After Significant Head injury [CRASH], the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO], and PROspective Study of Pravastatin in elderly individuals at risk of vascular disease [PROSPER]). To mimic the RD design, we selected patients above and below a cutoff (e.g., age 75 years) randomized to treatment and control, respectively. Adjusted logistic regression models using restricted cubic splines (RCS) and polynomials and local logistic regression models estimated the odds ratio (OR) for treatment, with 95% confidence intervals (CIs) to indicate precision. In CRASH, treatment increased mortality with OR 1.22 [95% CI 1.06-1.40] in the RCT. The RD estimates were 1.42 (0.94-2.16) and 1.13 (0.90-1.40) with RCS adjustment and local regression, respectively. In GUSTO, treatment reduced mortality (OR 0.83 [0.72-0.95]), with more extreme estimates in the RD analysis (OR 0.57 [0.35; 0.92] and 0.67 [0.51; 0.86]). In PROSPER, similar RCT and RD estimates were found, again with less precision in RD designs. We conclude that the RD design provides similar but substantially less precise treatment effect estimates compared with an RCT, with local regression being the preferred method of analysis. Copyright © 2018 Elsevier Inc. All rights reserved.

Decision making and executive function in male adolescents with early-onset or adolescence-onset conduct disorder and control subjects.

PubMed

Fairchild, Graeme; van Goozen, Stephanie H M; Stollery, Sarah J; Aitken, Michael R F; Savage, Justin; Moore, Simon C; Goodyer, Ian M

2009-07-15

Although conduct disorder (CD) is associated with an increased susceptibility to substance use disorders, little is known about decision-making processes or reward mechanisms in CD. This study investigated decision making under varying motivational conditions in CD. Performances on the Risky Choice Task (RCT) and the Wisconsin Card Sorting Test (WCST) were assessed in 156 adolescents (84 control subjects, 34 with adolescence-onset CD, and 38 with early-onset CD). The RCT was performed twice, once under normal motivational conditions and once under conditions of increased motivation and psychosocial stress. Increased motivation and stress led to more cautious decision making and changes in framing effects on the RCT in all groups, although such effects were least pronounced in the early-onset CD group. Participants from both CD subgroups selected the risky choice more frequently than control subjects. Under normal motivational conditions, early-onset CD participants chose the risky choice more frequently in trials occurring after small gains, relative to control subjects and adolescence-onset CD participants. Following adjustment for IQ differences, the groups did not differ significantly in terms of WCST performance. Differences in decision making between control subjects and individuals with CD suggest that the balance between sensitivity to reward and punishment is shifted in this disorder, particularly the early-onset form. Our data on modulation of decision making according to previous outcomes suggest altered reward mechanisms in early-onset CD. The WCST data suggest that impairments in global executive function do not underlie altered decision making in CD.

Twenty-year Follow-up of Kangaroo Mother Care Versus Traditional Care.

PubMed

Charpak, Nathalie; Tessier, Rejean; Ruiz, Juan G; Hernandez, Jose Tiberio; Uriza, Felipe; Villegas, Julieta; Nadeau, Line; Mercier, Catherine; Maheu, Francoise; Marin, Jorge; Cortes, Darwin; Gallego, Juan Miguel; Maldonado, Dario

2017-01-01

Kangaroo mother care (KMC) is a multifaceted intervention for preterm and low birth weight infants and their parents. Short- and mid-term benefits of KMC on survival, neurodevelopment, breastfeeding, and the quality of mother-infant bonding were documented in a randomized controlled trial (RCT) conducted in Colombia from 1993 to 1996. The aim of the present study was to evaluate the persistence of these results in young adulthood. From 2012 to 2014, a total of 494 (69%) of the 716 participants of the original RCT known to be alive were identified; 441 (62% of the participants in the original RCT) were re-enrolled, and results for the 264 participants weighing ≤1800 g at birth were analyzed. The KMC and control groups were compared for health status and neurologic, cognitive, and social functioning with the use of neuroimaging, neurophysiological, and behavioral tests. The effects of KMC at 1 year on IQ and home environment were still present 20 years later in the most fragile individuals, and KMC parents were more protective and nurturing, reflected by reduced school absenteeism and reduced hyperactivity, aggressiveness, externalization, and socio-deviant conduct of young adults. Neuroimaging showed larger volume of the left caudate nucleus in the KMC group. This study indicates that KMC had significant, long-lasting social and behavioral protective effects 20 years after the intervention. Coverage with this efficient and scientifically based health care intervention should be extended to the 18 million infants born each year who are candidates for the method. Copyright © 2017 by the American Academy of Pediatrics.

Treatment for Stable Coronary Artery Disease: A Network Meta-Analysis of Cost-Effectiveness Studies

PubMed Central

Caruba, Thibaut; Katsahian, Sandrine; Schramm, Catherine; Charles Nelson, Anaïs; Durieux, Pierre; Bégué, Dominique; Juillière, Yves; Dubourg, Olivier

2014-01-01

Introduction and Objectives Numerous studies have assessed cost-effectiveness of different treatment modalities for stable angina. Direct comparisons, however, are uncommon. We therefore set out to compare the efficacy and mean cost per patient after 1 and 3 years of follow-up, of the following treatments as assessed in randomized controlled trials (RCT): medical therapy (MT), percutaneous coronary intervention (PCI) without stent (PTCA), with bare-metal stent (BMS), with drug-eluting stent (DES), and elective coronary artery bypass graft (CABG). Methods RCT comparing at least two of the five treatments and reporting clinical and cost data were identified by a systematic search. Clinical end-points were mortality and myocardial infarction (MI). The costs described in the different trials were standardized and expressed in US $ 2008, based on purchasing power parity. A network meta-analysis was used to compare costs. Results Fifteen RCT were selected. Mortality and MI rates were similar in the five treatment groups both for 1-year and 3-year follow-up. Weighted cost per patient however differed markedly for the five treatment modalities, at both one year and three years (P<0.0001). MT was the least expensive treatment modality: US $3069 and 13 864 after one and three years of follow-up, while CABG was the most costly: US $27 003 and 28 670 after one and three years. PCI, whether with plain balloon, BMS or DES came in between, but was closer to the costs of CABG. Conclusions Appreciable savings in health expenditures can be achieved by using MT in the management of patients with stable angina. PMID:24896266

Controlled clinical studies of homeopathy.

PubMed

Mathie, Robert T

2015-10-01

Observations about controlled clinical trials expressed by Max Haidvogl in the book Ultra High Dilution (1994) have been appraised from a perspective two decades later. The present commentary briefly examines changes in homeopathy research evidence since 1994 as regards: the published number of randomised controlled trials (RCTs), the use of individualised homeopathic intervention, the 'proven efficacy of homeopathy', and the quality of the evidence. The commentary reflects the details of RCTs that are available in a recently published literature review and by scrutiny of systematic reviews of RCTs in homeopathy. The homeopathy RCT literature grew by 309 records in the 18 years that immediately followed Haidvogl's article, with more than a doubling of the proportion that investigated individualised homeopathy. Discounting one prior publication, the entire systematic review literature on homeopathy RCTs post-dates 1994. A total of 36 condition-specific systematic reviews have been identified in the peer-reviewed literature: 16 of them reported positive, or tentatively positive, conclusions about homeopathy's clinical effectiveness; the other 20 were negative or non-conclusive. Reviews typically have been restricted in the strength of their conclusions by the low quality of the original RCT evidence. Three comprehensive systematic reviews concluded, cautiously, that homeopathy may differ from placebo; a fourth such review reached negative conclusions. A recent high-quality meta-analysis concluded that medicines prescribed in individualised homeopathic treatment may have small, specific, effects. Despite important growth in research activity since 1994, concerns about study quality limit the interpretation of available RCT data. The question whether homeopathic intervention differs from placebo awaits decisive answer. Copyright © 2015 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Symptomatic treatments for amyotrophic lateral sclerosis/motor neuron disease.

PubMed

Ng, Louisa; Khan, Fary; Young, Carolyn A; Galea, Mary

2017-01-10

Motor neuron disease (MND), which is also known as amyotrophic lateral sclerosis (ALS), causes a wide range of symptoms but the evidence base for the effectiveness of the symptomatic treatment therapies is limited. To summarise the evidence from Cochrane Systematic Reviews of all symptomatic treatments for MND. We searched the Cochrane Database of Systematic Reviews (CDSR) on 15 November 2016 for systematic reviews of symptomatic treatments for MND. We assessed the methodological quality of the included reviews using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the GRADE approach. We followed standard Cochrane study (review) selection and data extraction procedures. We reported findings narratively and in tables. We included nine Cochrane Systematic Reviews of interventions to treat symptoms in people with MND. Three were empty reviews with no included randomised controlled trials (RCTs); however, all three reported on non-RCT evidence and the remaining six included mostly one or two studies. We deemed all of the included reviews of high methodological quality. Drug therapy for painThere is no RCT evidence in a Cochrane Systematic Review exploring the efficacy of drug therapy for pain in MND. Treatment for crampsThere is evidence (13 RCTs, N = 4012) that for the treatment of cramps in MND, compared to placebo:- memantine and tetrahydrocannabinol (THC) are probably ineffective (moderate-quality evidence);- vitamin E may have little or no effect (low-quality evidence); and- the effects of L-threonine, gabapentin, xaliproden, riluzole, and baclofen are uncertain as the evidence is either very low quality or the trial specified the outcome but did not report numerical data.The review reported adverse effects of riluzole, but it is not clear whether other interventions had adverse effects. Treatment for spasticityIt is uncertain whether an endurance-based exercise programme improved spasticity or quality of life, measured at three months after the programme, as the quality of evidence is very low (1 RCT, comparison "usual activities", N = 25). The review did not evaluate other approaches, such as use of baclofen as no RCTs were available. Mechanical ventilation for supporting respiratory functionNon-invasive ventilation (NIV) probably improves median survival and quality of life in people with respiratory insufficiency and normal to moderately impaired bulbar function compared to standard care, and improves quality of life but not survival for people with poor bulbar function (1 RCT, N = 41, moderate-quality evidence; a second RCT did not provide data). The review did not evaluate other approaches such as tracheostomy-assisted ('invasive') ventilation, or assess timing of NIV initiation. Treatment for sialorrhoeaA single session of botulinum toxin type B injections to parotid and submandibular glands probably improves sialorrhoea and quality of life at up to 4 weeks compared to placebo injections, but not at 8 or 12 weeks after the injections (moderate-quality evidence from 1 placebo-controlled RCT, N = 20). The review authors found no trials of other approaches. Enteral tube feeding for supporting nutritionThere is no RCT evidence in a Cochrane Systematic Review to support benefit or harms of enteral tube feeding in supporting nutrition in MND. Repetitive transcranial magnetic stimulationIt is uncertain whether repetitive transcranial magnetic stimulation (rTMS) improves disability or limitation in activity in MND in comparison with sham rTMS (3 RCTs, very low quality evidence, N = 50). Therapeutic exerciseThere is evidence that exercise may improve disability in MND at three months after the exercise programme, but not quality of life, in comparison with "usual activities" or "usual care" including stretching (2 RCTs, low-quality evidence, N = 43). Multidisciplinary careThere is no RCT evidence in a Cochrane Systematic Review to demonstrate any benefit or harm for multidisciplinary care in MND.None of the reviews, other than the review of treatment for cramps, reported that adverse events occurred. However, the trials were too small for reliable adverse event reporting. This overview has highlighted the lack of robust evidence in Cochrane Systematic Reviews on interventions to manage symptoms resulting from MND. It is important to recognise that clinical trials may fail to demonstrate efficacy of an intervention for reasons other than a true lack of efficacy, for example because of insufficient statistical power, the wrong choice of dose, insensitive outcome measures or inappropriate participant eligibility. The trials were mostly too small to reliably assess adverse effects of the treatments. The nature of MND makes it difficult to research clinically accepted or recommended practice, regardless of the level of evidence supporting the practice. It would not be ethical, for example, to design a placebo-controlled trial for treatment of pain in MND or to withhold multidisciplinary care where such care is available. It is therefore highly unlikely that there will ever be classically designed placebo-controlled RCTs in these areas.We need more research with appropriate study designs, robust methodology, and of sufficient duration to address the changing needs-of people with MND and their caregivers-associated with MND disease progression and mortality. There is a significant gap in studies assessing the effectiveness of interventions for symptoms relating to MND, such as pseudobulbar emotional lability and cognitive and behavioural difficulties. Future studies should use appropriate outcome measures that are reliable, have internal and external validity, and are sensitive to change in what is being measured (such as quality of life).

Effectiveness and cost effectiveness of cognitive behavioral therapy (CBT) in clinically depressed adolescents: individual CBT versus treatment as usual (TAU).

PubMed

Stikkelbroek, Yvonne; Bodden, Denise Hm; Deković, Maja; van Baar, Anneloes L

2013-11-21

Depressive disorders occur in 2 to 5% of the adolescents and are associated with a high burden of disease, a high risk of recurrence and a heightened risk for development of other problems, like suicide attempts. The effectiveness of cognitive behaviour therapy (CBT), cost-effectiveness of this treatment and the costs of illness of clinical depression in adolescents are still unclear. Although several Randomized Controlled Trials (RCT) have been conducted to establish the efficacy of CBT, the effectiveness has not been established yet. Aim of this study is to conduct a RCT to test the effectiveness of CBT and to establish the cost-effectiveness of CBT under rigorous conditions within routine care provided by professionals already working in mental health institutions. CBT is investigated with a multi-site, RCT using block randomisation. The targeted population is 140 clinically referred depressed adolescents aged 12 to 21 years old. Adolescents are randomly assigned to the experimental (N = 70, CBT) or control condition (N = 70, TAU). Four assessments (pre, post, follow up at 6 and 12 months) and two mediator assessments during treatment are conducted. Primary outcome measure is depression diagnosis based on a semi-structured interview namely the K-SADS-PL. Secondary outcome measures include depressive symptoms, severity and improvement of the depression, global functioning, quality of life, suicide risk, comorbidity, alcohol and drug use, parental depression and psychopathology, parenting and conflicts. Costs and treatment characteristics will also be assessed. Furthermore, moderator and mediator analyses will be conducted. This trial will be the first to compare CBT with TAU under rigorous conditions within routine care and with a complex sample. Furthermore, cost-effectiveness of treatment and cost-of-illness of clinical depression are established which will provide new insights on depression as a disorder and its treatment. Dutch Trial register number NTR2676. The study was financially supported by a grant from ZonMw, the Netherlands organization for health research and development, grant number 157004005.

A New Social Communication Intervention for Children with Autism: Pilot Randomised Controlled Treatment Study Suggesting Effectiveness

ERIC Educational Resources Information Center

Aldred, Catherine; Green, Jonathan; Adams, Catherine

2004-01-01

Background: Psychosocial treatments are the mainstay of management of autism in the UK but there is a notable lack of a systematic evidence base for their effectiveness. Randomised controlled trial (RCT) studies in this area have been rare but are essential because of the developmental heterogeneity of the disorder. We aimed to test a new…

Training Professionals to Implement a Group Model for Alleviating Loneliness among Older People--10-Year Follow-Up Study

ERIC Educational Resources Information Center

Jansson, Anu H.; Savikko, Niina M.; Pitkälä, Kaisu H.

2018-01-01

Background and objectives: Although randomized controlled trials (RCTs) have been performed to alleviate loneliness among older people, little is known about how they have been implemented, or whether they are effective in real life. Our RCT-based model, "Circle of Friends" (CoF) proved to be effective in improving the wellbeing, health…

Degrees of Freedom and Degrees of Certainty: A Developmental Model for the Establishment of Evidence-Based Youth Care

ERIC Educational Resources Information Center

Veerman, Jan W.; van Yperen, Tom A.

2007-01-01

There are many psychosocial interventions for children and adolescents. The effects of these interventions in day-to-day practice are nevertheless often unclear. Researchers typically take the randomized controlled trial (RCT) as the "gold standard" for the supply of evidence regarding the effectiveness of an intervention. However, such trials are…

Haloperidol plus promethazine for psychosis-induced aggression.

PubMed

Huf, Gisele; Alexander, Jacob; Gandhi, Pinky; Allen, Michael H

2016-11-25

Health services often manage agitated or violent people, and such behaviour is particularly prevalent in emergency psychiatric services (10%). The drugs used in such situations should ensure that the person becomes calm swiftly and safely. To examine whether haloperidol plus promethazine is an effective treatment for psychosis-induced aggression. On 6 May 2015 we searched the Cochrane Schizophrenia Group's Register of Trials, which is compiled by systematic searches of major resources (including MEDLINE, EMBASE, AMED, BIOSIS, CINAHL, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings. All randomised clinical trials with useable data focusing on haloperidol plus promethazine for psychosis-induced aggression. We independently extracted data. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. We found two new randomised controlled trials (RCTs) from the 2015 update searching. The review now includes six studies, randomising 1367 participants and presenting data relevant to six comparisons.When haloperidol plus promethazine was compared with haloperidol alone for psychosis-induced aggression for the outcome not tranquil or asleep at 30 minutes, the combination treatment was clearly more effective (n=316, 1 RCT, RR 0.65, 95% CI 0.49 to 0.87, high-quality evidence). There were 10 occurrences of acute dystonia in the haloperidol alone arm and none in the combination group. The trial was stopped early as haloperidol alone was considered to be too toxic.When haloperidol plus promethazine was compared with olanzapine, high-quality data showed both approaches to be tranquillising. It was suggested that the combination of haloperidol plus promethazine was more effective, but the difference between the two approaches did not reach conventional levels of statistical significance (n=300, 1 RCT, RR 0.60, 95% CI 0.22 to 1.61, high-quality evidence). Lower-quality data suggested that the risk of unwanted excessive sedation was less with the combination approach (n=116, 2 RCTs, RR 0.67, 95% CI 0.12 to 3.84).When haloperidol plus promethazine was compared with ziprasidone all data were of lesser quality. We identified no binary data for the outcome tranquil or asleep. The average sedation score (Ramsay Sedation Scale) was lower for the combination approach but not to conventional levels of statistical significance (n=60, 1 RCT, MD -0.1, 95% CI - 0.58 to 0.38). These data were of low quality and it is unclear what they mean in clinical terms. The haloperidol plus promethazine combination appeared to cause less excessive sedation but again the difference did not reach conventional levels of statistical significance (n=111, 2 RCTs, RR 0.30, 95% CI 0.06 to 1.43).We found few data for the comparison of haloperidol plus promethazine versus haloperidol plus midazolam. Average Ramsay Sedation Scale scores suggest the combination of haloperidol plus midazolam to be the most sedating (n=60, 1 RCT, MD - 0.6, 95% CI -1.13 to -0.07, low-quality evidence). The risk of excessive sedation was considerably less with haloperidol plus promethazine (n=117, 2 RCTs, RR 0.12, 95% CI 0.03 to 0.49, low-quality evidence). Haloperidol plus promethazine seemed to decrease the risk of needing restraints by around 12 hours (n=60, 1 RCT, RR 0.24, 95% CI 0.10 to 0.55, low-quality evidence). It may be that use of midazolam with haloperidol sedates swiftly, but this effect does not last long.When haloperidol plus promethazine was compared with lorazepam, haloperidol plus promethazine seemed to more effectively cause sedation or tranquillisation by 30 minutes (n=200, 1 RCT, RR 0.26, 95% CI 0.10 to 0.68, high-quality evidence). The secondary outcome of needing restraints or seclusion by 12 hours was not clearly different between groups, with about 10% in each group needing this intrusive intervention (moderate-quality evidence). Sedation data were not reported, however, the combination group did have less 'any serious adverse event' in 24-hour follow-up, but there were not clear differences between the groups and we are unsure exactly what the adverse effect was. There were no deaths.When haloperidol plus promethazine was compared with midazolam, there was clear evidence that midazolam is more swiftly tranquillising of an aggressive situation than haloperidol plus promethazine (n=301, 1 RCT, RR 2.90, 95% CI 1.75 to 4.8, high-quality evidence). On its own, midazolam seems to be swift and effective in tranquillising people who are aggressive due to psychosis. There was no difference in risk of serious adverse event overall (n=301, 1 RCT, RR 1.01, 95% CI 0.06 to 15.95, high-quality evidence). However, 1 in 150 participants allocated haloperidol plus promethazine had a swiftly reversed seizure, and 1 in 151 given midazolam had swiftly reversed respiratory arrest. Haloperidol plus promethazine is effective and safe, and its use is based on good evidence. Benzodiazepines work, with midazolam being particularly swift, but both midazolam and lorazepam cause respiratory depression. Olanzapine intramuscular and ziprasidone intramuscular do seem to be viable options and their action is swift, but resumption of aggression with subsequent need to re-inject was more likely than with haloperidol plus promethazine. Haloperidol used on its own without something to offset its frequent and serious adverse effects does seem difficult to justify.

Outcomes in a Randomised Controlled Trial of Mathematics Tutoring

ERIC Educational Resources Information Center

Topping, K. J.; Miller, D.; Murray, P.; Henderson, S.; Fortuna, C.; Conlin, N.

2011-01-01

Background: Large-scale randomised controlled trials (RCT) are relatively rare in education. The present study was an attempt to scale up previous small peer tutoring projects, while investing only modestly in continuing professional development for teachers. Purpose: A two-year RCT of peer tutoring in mathematics was undertaken in one local…

Advanced Microbial Fuel Cell Development, Miniaturization and Energy and Power Density Enhancement

DTIC Science & Technology

2007-04-30

of the pure polyaniline. Since there were no glucose and bateria in the eletrolyte, the Rct should be ascribed to the doping/dedoping redox...CNT/PANI composite was much lower than that of the pure polyaniline. Since there were no glucose and bateria in the eletrolyte, the Rct should be

Are adolescent treatment studies of eating disorders utilizing clinically relevant samples? A comparison of RCT and clinic treatment-seeking youth with eating disorders.

PubMed

Stiles-Shields, Colleen; Goldschmidt, Andrea B; Lock, James; Le Grange, Daniel

2013-09-01

To assess potential selection bias in participant recruitment for randomized controlled trials (RCTs) of adolescent eating disorders (EDs), we compared participants recruited for RCTs evaluating psychosocial treatments with individuals seeking fee-for-service outpatient ED treatment [clinic treatment-seeking (CTS)]. Participants were 214 adolescents presenting to an outpatient ED research-clinical program (92.1% female; M age = 15.4 ± 1.8 years). ANOVA and chi-square tests assessed differences between CTS participants and those presenting for no-cost treatment through RCTs. A secondary analysis compared RCT participants to participants eligible for the RCTs that opted for fee-for-service treatment. RCT participants had greater baseline ED and general psychopathology (p < .001); however, CTS participants were more likely to present with a comorbid psychiatric disorder (p < .05) and higher family income (p < .05). Results suggest that RCT participants did not have less pathology than CTS participants. While preliminary, results do not indicate a systematic population bias in selecting healthier patients for RCTs involving adolescent ED. Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.

The RCT 1.3 m robotic telescope: broadband color transformation and extinction calibration

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

Strolger, L.-G.; Gott, A. M.; Carini, M.

2014-03-01

The Robotically Controlled Telescope (RCT) 1.3 m telescope, formerly known as the Kitt Peak National Observatory (KPNO) 50 inch telescope, has been refurbished as a fully robotic telescope, with an autonomous scheduler to take full advantage of the observing site without the requirement of a human presence. Here we detail the current configuration of the RCT and present, as a demonstration of its high-priority science goals, the broadband UBVRI photometric calibration of the optical facility. In summary, we find the linear color transformation and extinction corrections to be consistent with similar optical KPNO facilities, to within a photometric precision ofmore » 10% (at 1σ). While there were identified instrumental errors that likely added to the overall uncertainty, associated with since-resolved issues in engineering and maintenance of the robotic facility, a preliminary verification of this calibration gave a good indication that the solution is robust, perhaps to a higher precision than this initial calibration implies. The RCT has been executing regular science operations since 2009 and is largely meeting the science requirements set during its acquisition and redesign.« less

A multifunctional label-free electrochemical impedance biosensor for Hg(2+), adenosine triphosphate and thrombin.

PubMed

Chen, Lifen; Chen, Zhong-Ning

2015-01-01

A multifunctional label-free biosensor for the detection of Hg(2+), adenosine triphosphate and thrombin has been developed based on the changing of the electrochemical impedance spectroscopy (EIS) from the modified electrodes when nucleic acid subunits interacting with different targets. The modified electrode consists of three interaction sections, including DNA with T-T mismatch recognizing Hg(2+) to form T-Hg(2+)-T complex, split DNA chip against ATP, and DNA domin against thrombin to form G-quadruplex. Upon DNA interaction with thrombin or ATP, an increased charge transfer resistance (Rct) had been detected. However, a decreased Rct against Hg(2+) was obtained. The Rct difference (ΔRct) has relationship with the concentration of the different targets, Hg(2+), ATP and thrombin can be selectively detected with the detection limit of 0.03, 0.25, and 0.20 nmol L(-1), respectively. To separately detect the three analytes existing in the same sample, ATP aptamer, G-rich DNA strands and EDTA were applied to mask ATP, Hg(2+) or thrombin separately. Copyright © 2014 Elsevier B.V. All rights reserved.

Establishment of an attenuated strain of porcine parvovirus by serial passage at low temperature.

PubMed

Fujisaki, Y; Murakami, Y; Suzuki, H

1982-01-01

To prepare a live virus vaccine strain for the prevention of porcine parvovirus infection, the 90HS strain, isolated from the brain of a stillborn porcine fetus, was subjected to the first 45 serial passages in swine kidney established (ESK) cells of porcine kidney origin at 30-35 degrees C and to the 46th and later serial passages in the same cells as these at 32 degrees C. When swine were inoculated with the strain at the 38th passage level possessing such properties as expressed with rct/37+ and rct/40-, they presented viremia, virus discharge, and the transmission of virus to other swine. When swine were inoculated with the strain at the 54th and 55th passage level possessing such properties as expressed with rct/37- and rct/40-, they failed to exhibit viremia, virus discharge, and the transmission of virus to other swine, but retained for a long time hemagglutination-inhibiting antibody which had been produced after inoculation. A low virulent variant strain was obtained after 54 serial passages at low temperature. It was called the HT- strain.

Re-activation of degraded nickel cermet anodes - Nano-particle formation via reverse current pulses

NASA Astrophysics Data System (ADS)

Hauch, A.; Marchese, M.; Lanzini, A.; Graves, C.

2018-02-01

The Ni/yttria-stabilized-zirconia (YSZ) cermet is the most commonly applied fuel electrode for solid oxide cells (SOCs). Loss of Ni/YSZ electrode activity is a key life-time limiting factor of the SOC. Developing means to mitigate this loss of performance or re-activate a fuel electrode is therefore important. In this work, we report a series of five tests on state-of-the-art Ni/YSZ-YSZ-CGObarrier-LSC/CGO cells. All cells were deliberately degraded via gas stream impurities in CO2/CO or harsh steam electrolysis operation. The cells were re-activated via a variety of reverse current treatments (RCTs). Via electrochemical impedance spectroscopy, we found that the Ni/YSZ electrode performance could be recovered via RCT, but not via constant fuel cell operation. For optimized RCT, we obtained a lower Ni/YSZ electrode resistance than the initial resistance. E.g. at 700 °C we measured fuel electrode resistance of 180 mΩ cm2, 390 mΩ cm2, and 159 mΩ cm2 before degradation, after degradation and after re-activation via RCT, respectively. Post-test SEM revealed that the RCT led to formation of nano-particles in the fuel electrode. Besides the remarkable improvement, the results also showed that RCTs can weaken Ni/YSZ interfaces and the electrode/electrolyte interface. This indicates that finding an optimum RCT profile is crucial for achieving maximum benefit.

Implantable miniature telescope (IMT) for vision loss due to end-stage age-related macular degeneration.

PubMed

Gupta, Amisha; Lam, Jessica; Custis, Peter; Munz, Stephen; Fong, Donald; Koster, Marguerite

2018-05-30

Age-related macular degeneration (AMD) causes progressive and irreversible damage to the retina, resulting in loss of central vision. AMD is the third leading cause of irreversible visual impairment worldwide and the leading cause of blindness in industrialized countries. Since AMD is more common in older individuals, the number of affected individuals will increase significantly as the population ages. The implantable miniature telescope (IMT) is an ophthalmic device developed to improve vision in individuals who have lost vision due to AMD. Once implanted, the IMT is used to enlarge objects in the central visual field and focus them onto healthy areas of the retina not affected by AMD, allowing individuals to recognize objects that they otherwise could not see. It is unclear whether and how much the IMT can improve vision in individuals with end-stage AMD. To assess the effectiveness and safety of the IMT in improving visual acuity and quality of life in people with late or advanced AMD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 11); Ovid MEDLINE; Embase.com; PubMed; LILACS; AMED; Web of Science Conference Proceedings Citation Index-Science; OpenSIGLE; the metaRegister of Controlled Trials (mRCT) (last searched 27 June 2014); ClinicalTrials.gov; the ICTRP and the US Food and Drug Administration (FDA) Medical Devices database. The date of the search was 2 November 2017, with the exception of mRCT which is no longer in service. We planned to include randomized controlled trials (RCTs) and quasi-randomized trials that compared the IMT versus no IMT. Two review authors independently assessed all studies for inclusion, using standard methodological procedures expected by Cochrane. Our search yielded 1042 unique records. We removed irrelevant studies after screening titles and abstracts, and evaluated five full-text reports from four studies; three were non-randomized studies. There was one ongoing RCT that compared the OriLens intraocular telescope with standard low vision training in eyes with end-stage AMD. Results for this study are expected in 2020. We found no RCT or quasi-RCT and can draw no conclusion about the effectiveness and safety of the IMT in improving visual acuity in individuals with late or advanced AMD. Since the IMT is typically implanted monocularly based upon which eye has better best-corrected distance visual acuity, randomization between eyes within an individual may not be acceptable. Studies are needed that compare outcomes between individuals randomized to the device versus individuals not implanted, at least during study follow-up, who serve as controls.

Temporal Trends in Quality of Life Outcomes after Transapical TAVR: A PARTNER Trial Substudy

PubMed Central

Gada, Hemal; Kirtane, Ajay J; Wang, Kaijun; Lei, Yang; Magnuson, Elizabeth; Reynolds, Matthew R; Williams, Mathew R; Kodali, Susheel; Vahl, Torsten P; Arnold, Suzanne V; Leon, Martin B; Thourani, Vinod; Szeto, Wilson Y; Cohen, David J

2016-01-01

Background In the PARTNER randomized controlled trial (RCT), which represented the first exposure to transapical transcatheter aortic valve replacement (TA-TAVR) for many clinical sites, high risk patients undergoing TA-TAVR derived similar health-related quality-of-life (HRQoL) outcomes when compared with surgical AVR (SAVR). With increasing experience, it is possible that HRQoL outcomes of TA-TAVR may have improved. Methods and Results We evaluated HRQoL outcomes at 1-, 6-, and 12-month follow-up among 875 patients undergoing TA-TAVR in the PARTNER non-randomized continued access (NRCA) registry, and compared these outcomes with those of the TA-TAVR and SAVR patients in the PARTNER RCT. HRQoL was assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Medical Outcomes Study Short Form-12, and the EuroQoL-5D, with the KCCQ overall summary score serving as the primary endpoint. The NRCA TA-TAVR and RCT TA-TAVR and SAVR groups were generally similar. The primary outcome, the KCCQ summary score, did not differ between the NRCA TA-TAVR and the RCT TA-TAVR group at any follow-up timepoints, although there were small differences in favor of the NRCA cohort on several KCCQ subscales at 1 month. There were no significant differences in follow-up HRQOL between the NRCA-TAVR and the RCT SAVR cohorts on the KCCQ overall summary scale or any of the disease-specific or generic subscales. Conclusions Despite greater experience with TA-TAVR in the NRCA registry, HRQoL outcomes remained similar to those of TA-TAVR in the original RCT cohort and no better than those with SAVR. These findings have important implications for patient selection for TAVR when transfemoral access is not an option. Clinical Trial Registration Placement of AoRTic TraNscathetER Valve [PARTNER] trial; NCT00530894; http://clinicaltrials.gov/show/NCT00530894 PMID:26058718

A clinical carepath for obese pregnant women: A pragmatic pilot cluster randomized controlled trial.

PubMed

McDonald, Sarah D; Viaje, Kristen A; Rooney, Rebecca A; Jarde, Alexander; Giglia, Lucia; Maxwell, Cynthia V; Small, David; Kelly, Tracy Pearce; Midwifery, B H Sc; Sabatino, Lisa; Thabane, Lehana

2018-05-17

Obese women are at increased risks for complications during pregnancy, birth and in their infants. Although guidelines have been established for the clinical care of obese pregnant women, management is sometimes suboptimal. Our goal was to determine the feasibility of implementing and testing a clinical carepath for obese pregnant women compared to standard care, in a pilot cluster randomized controlled trial (RCT). A pragmatic pilot cluster RCT was conducted, randomly allocating eight clinics to the carepath or standard care for obese pregnant women. Women were eligible if they had a prepregnancy body mass index of ≥ 30 kg/m 2 and a viable singleton < 21 weeks. The primary outcomes were the feasibility of conducting a full-scale cluster RCT (defined as > 80%: randomization of clinics, use in eligible women, and completeness of follow-up) and of the intervention (defined as > 80%: compliance with each step in the carepath, and recommendation of the carepath by clinicians to a colleague). All eight approached clinics agreed to participate and were randomized. Half of the intervention clinics used the carepath, resulting in < 80% uptake of eligible women. High follow-up (99.5%) was achieved, in 188 of 189 women. The carepath was feasible for numerous guideline-directed recommendations for screening, but less so for counselling topics. When the carepath was used in the majority of women, all clinicians, most of whom were midwives, reported they would recommend it to a colleague. The intervention group had significantly higher overall adherence to the guideline recommendations compared to control (relative risk 1.71, 95% confidence interval 1.57-1.87). In this pragmatic pilot cluster RCT, a guideline-directed clinical carepath improved some aspects of care of obese pregnant women and was recommended by clinicians, particularly midwives. A cluster RCT may not be feasible in a mix of obstetric and midwifery clinics, but may be feasible in midwifery clinics. This pragmatic pilot cluster RCT was registered on clinicaltrials.gov (identifier: NCT02534051 ).

Can rheumatoid arthritis (RA) registries provide contextual safety data for modern RA clinical trials? The case for mortality and cardiovascular disease.

PubMed

Michaud, Kaleb; Berglind, Niklas; Franzén, Stefan; Frisell, Thomas; Garwood, Christopher; Greenberg, Jeffrey D; Ho, Meilien; Holmqvist, Marie; Horne, Laura; Inoue, Eisuke; Nyberg, Fredrik; Pappas, Dimitrios A; Reed, George; Symmons, Deborah; Tanaka, Eiichi; Tran, Trung N; Verstappen, Suzanne M M; Wesby-van Swaay, Eveline; Yamanaka, Hisashi; Askling, Johan

2016-10-01

We implemented a novel method for providing contextual adverse event rates for a randomised controlled trial (RCT) programme through coordinated analyses of five RA registries, focusing here on cardiovascular disease (CVD) and mortality. Each participating registry (Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (East Europe, Latin America, India) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan)) defined a main cohort from January 2000 onwards. To address comparability and potential bias, we harmonised event definitions and defined several subcohorts for sensitivity analyses based on disease activity, treatment, calendar time, duration of follow-up and RCT exclusions. Rates were standardised for age, sex and, in one sensitivity analysis, also HAQ. The combined registry cohorts included 57 251 patients with RA (234 089 person-years)-24.5% men, mean (SD) baseline age 58.2 (13.8) and RA duration 8.2 (11.7) years. Standardised registry mortality rates (per 100 person-years) varied from 0.42 (CORRONA) to 0.80 (NOAR), with 0.60 for RCT patients. Myocardial infarction and major adverse cardiovascular events (MACE) rates ranged from 0.09 and 0.31 (IORRA) to 0.39 and 0.77 (SRR), with RCT rates intermediate (0.18 and 0.42), respectively. Additional subcohort analyses showed small and mostly consistent changes across registries, retaining reasonable consistency in rates across the Western registries. Additional standardisation for HAQ returned higher mortality and MACE registry rates. This coordinated approach to contextualising RA RCT safety data demonstrated reasonable differences and consistency in rates for mortality and CVD across registries, and comparable RCT rates, and may serve as a model method to supplement clinical trial analyses for drug development programmes. 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/

Interpreting febrile neutropenia rates from randomized, controlled trials for consideration of primary prophylaxis in the real world: a systematic review and meta-analysis.

PubMed

Truong, J; Lee, E K; Trudeau, M E; Chan, K K W

2016-04-01

Guidelines recommend primary prophylaxis (PP) with granulocyte-colony-stimulating factors (G-CSF) for patients above a febrile neutropenia (FN) risk threshold of 20%. Practitioners often use FN rates of regimens based on data from randomized, controlled trials (RCTs), which are often comprised of highly selected patients. Patients in the community setting may be at higher risk of FN. A systematic literature search was conducted for full-length articles reporting FN rates for breast cancer-related chemotherapies between January 1996 and February 2014. A regimen was included if there was at least one RCT and one observational study. Meta-regression was used to model the odds of FN. 130 studies involving 29 regimens and 50 069 patients were identified. Sixty-five observational study (n = 7812) and 110 RCT (n = 42 257) cohorts were included. The unadjusted FN rate was 11.7% in observational and 7.9% in RCT cohorts. The univariable odds ratio (OR) for FN in the observational study compared with RCT cohorts was 1.58 [95% confidence interval (CI) 1.09-2.28; P = 0.017]. The FN rates remained significantly higher in the observational study compared with RCT cohorts (OR = 1.74; 95% CI 1.15-2.62; P = 0.012) after adjusting for age, chemotherapy intent, and regimen; this meant that a 13% (95% CI 8.7% to 17.9%) FN rate in RCT would translate into 20% FN rate in observational study. FN rates in the observational studies are significantly higher than suggested by RCTs. Guidelines should clarify how FN rates from RCTs should be applied in clinical practice. Large population-based studies are needed to confirm FN rates in the real world. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Moderating Effects of Parental Characteristics on the Effectiveness of a Theory of Mind Training for Children with Autism: A Randomized Controlled Trial

ERIC Educational Resources Information Center

de Veld, Danielle M. J.; Howlin, Patricia; Hoddenbach, Elske; Mulder, Fleur; Wolf, Imke; Koot, Hans M.; Lindauer, Ramón; Begeer, Sander

2017-01-01

This RCT investigated whether the effect of a Theory of Mind (ToM) intervention for children with ASD was moderated by parental education level and employment, family structure, and parental ASD. Children with autism aged 8-13 years (n = 136) were randomized over a waitlist control or treatment condition. At posttest, children in the treatment…

Antenatal and intrapartum interventions for preventing cerebral palsy: an overview of Cochrane systematic reviews.

PubMed

Shepherd, Emily; Salam, Rehana A; Middleton, Philippa; Makrides, Maria; McIntyre, Sarah; Badawi, Nadia; Crowther, Caroline A

2017-08-08

Cerebral palsy is an umbrella term encompassing disorders of movement and posture, attributed to non-progressive disturbances occurring in the developing fetal or infant brain. As there are diverse risk factors and causes, no one strategy will prevent all cerebral palsy. Therefore, there is a need to systematically consider all potentially relevant interventions for their contribution to prevention. To summarise the evidence from Cochrane reviews regarding the effects of antenatal and intrapartum interventions for preventing cerebral palsy. We searched the Cochrane Database of Systematic Reviews on 7 August 2016, for reviews of antenatal or intrapartum interventions reporting on cerebral palsy. Two authors assessed reviews for inclusion, extracted data, assessed review quality, using AMSTAR and ROBIS, and quality of the evidence, using the GRADE approach. We organised reviews by topic, and summarised findings in text and tables. We categorised interventions as effective (high-quality evidence of effectiveness); possibly effective (moderate-quality evidence of effectiveness); ineffective (high-quality evidence of harm or of lack of effectiveness); probably ineffective (moderate-quality evidence of harm or of lack of effectiveness); and no conclusions possible (low- to very low-quality evidence). We included 15 Cochrane reviews. A further 62 reviews pre-specified the outcome cerebral palsy in their methods, but none of the included randomised controlled trials (RCTs) reported this outcome. The included reviews were high quality and at low risk of bias. They included 279 RCTs; data for cerebral palsy were available from 27 (10%) RCTs, involving 32,490 children. They considered interventions for: treating mild to moderate hypertension (two) and pre-eclampsia (two); diagnosing and preventing fetal compromise in labour (one); preventing preterm birth (four); preterm fetal maturation or neuroprotection (five); and managing preterm fetal compromise (one). Quality of evidence ranged from very low to high. Effective interventions: high-quality evidence of effectiveness There was a reduction in cerebral palsy in children born to women at risk of preterm birth who received magnesium sulphate for neuroprotection of the fetus compared with placebo (risk ratio (RR) 0.68, 95% confidence interval (CI) 0.54 to 0.87; five RCTs; 6145 children). Probably ineffective interventions: moderate-quality evidence of harm There was an increase in cerebral palsy in children born to mothers in preterm labour with intact membranes who received any prophylactic antibiotics versus no antibiotics (RR 1.82, 95% CI 0.99 to 3.34; one RCT; 3173 children). There was an increase in cerebral palsy in children, who as preterm babies with suspected fetal compromise, were born immediately compared with those for whom birth was deferred (RR 5.88, 95% CI 1.33 to 26.02; one RCT; 507 children). Probably ineffective interventions: moderate-quality evidence of lack of effectiveness There was no clear difference in the presence of cerebral palsy in children born to women at risk of preterm birth who received repeat doses of corticosteroids compared with a single course (RR 1.03, 95% CI 0.71 to 1.50; four RCTs; 3800 children). No conclusions possible: low- to very low-quality evidence Low-quality evidence found there was a possible reduction in cerebral palsy for children born to women at risk of preterm birth who received antenatal corticosteroids for accelerating fetal lung maturation compared with placebo (RR 0.60, 95% CI 0.34 to 1.03; five RCTs; 904 children). There was no clear difference in the presence of cerebral palsy with interventionist care for severe pre-eclampsia versus expectant care (RR 6.01, 95% CI 0.75 to 48.14; one RCT; 262 children); magnesium sulphate for pre-eclampsia versus placebo (RR 0.34, 95% CI 0.09 to 1.26; one RCT; 2895 children); continuous cardiotocography for fetal assessment during labour versus intermittent auscultation (average RR 1.75, 95% CI 0.84 to 3.63; two RCTs; 13,252 children); prenatal progesterone for prevention of preterm birth versus placebo (RR 0.14, 95% CI 0.01 to 3.48; one RCT; 274 children); and betamimetics for inhibiting preterm labour versus placebo (RR 0.19, 95% CI 0.02 to 1.63; one RCT; 246 children).Very low-quality found no clear difference for the presence of cerebral palsy with any antihypertensive drug (oral beta-blockers) for treatment of mild to moderate hypertension versus placebo (RR 0.33, 95% CI 0.01 to 8.01; one RCT; 110 children); magnesium sulphate for prevention of preterm birth versus other tocolytic agents (RR 0.13, 95% CI 0.01 to 2.51; one RCT; 106 children); and vitamin K and phenobarbital prior to preterm birth for prevention of neonatal periventricular haemorrhage versus placebo (RR 0.77, 95% CI 0.33 to 1.76; one RCT; 299 children). This overview summarises evidence from Cochrane reviews on the effects of antenatal and intrapartum interventions on cerebral palsy, and can be used by researchers, funding bodies, policy makers, clinicians and consumers to aid decision-making and evidence translation. We recommend that readers consult the included Cochrane reviews to formally assess other benefits or harms of included interventions, including impacts on risk factors for cerebral palsy (such as the reduction in intraventricular haemorrhage for preterm babies following exposure to antenatal corticosteroids).Magnesium sulphate for women at risk of preterm birth for fetal neuroprotection can prevent cerebral palsy. Prophylactic antibiotics for women in preterm labour with intact membranes, and immediate rather than deferred birth of preterm babies with suspected fetal compromise, may increase the risk of cerebral palsy. Repeat doses compared with a single course of antenatal corticosteroids for women at risk of preterm birth do not clearly impact the risk of cerebral palsy.Cerebral palsy is rarely diagnosed at birth, has diverse risk factors and causes, and is diagnosed in approximately one in 500 children. To date, only a small proportion of Cochrane reviews assessing antenatal and intrapartum interventions have been able to report on this outcome. There is an urgent need for long-term follow-up of RCTs of interventions addressing risk factors for cerebral palsy, and consideration of the use of relatively new interim assessments (including the General Movements Assessment). Such RCTs must be rigorous in their design, and aim for consistency in cerebral palsy outcome measurement and reporting to facilitate pooling of data, to focus research efforts on prevention.

Evaluation of an Internet-Based Behavioral Intervention to Improve Psychosocial Health Outcomes in Children With Insomnia (Better Nights, Better Days): Protocol for a Randomized Controlled Trial

PubMed Central

Reid, Graham J; Hall, Wendy A; Godbout, Roger; Stremler, Robyn; Weiss, Shelly K; Gruber, Reut; Witmans, Manisha; Chambers, Christine T; Begum, Esmot Ara; Andreou, Pantelis; Rigney, Gabrielle

2018-01-01

Background Up to 25% of 1- to 10-year-old children experience insomnia (ie, resisting bedtime, trouble falling asleep, night awakenings, and waking too early in the morning). Insomnia can be associated with excessive daytime sleepiness and negative effects on daytime functioning across multiple domains (eg, behavior, mood, attention, and learning). Despite robust evidence supporting the effectiveness of behavioral treatments for insomnia in children, very few children with insomnia receive these treatments, primarily due to a shortage of available treatment resources. Objective The Better Nights, Better Days (BNBD) internet-based program provides a readily accessible electronic health (eHealth) intervention to support parents in providing evidence-based care for insomnia in typically developing children. The purpose of the randomized controlled trial (RCT) is to evaluate the effectiveness of BNBD in treating insomnia in children aged between 1 and 10 years. Methods BNBD is a fully automated program, developed based on evidence-based interventions previously tested by the investigators, as well as on the extant literature on this topic. We describe the 2-arm RCT in which participants (500 primary caregivers of children with insomnia residing in Canada) are assigned to intervention or usual care. Results The effects of this behavioral sleep eHealth intervention will be assessed at 4 and 8 months postrandomization. Assessment includes both sleep (actigraphy, sleep diary) and daytime functioning of the children and daytime functioning of their parents. Results will be reported using the standards set out in the Consolidated Standards of Reporting Trials statement. Conclusions If the intervention is supported by the results of the RCT, we plan to commercialize this program so that it is sustainable and available at a low cost to all families with internet access. Trial Registration ClinicalTrials.gov NCT02243501; https://clinicaltrials.gov/show/NCT02243501 (Archived by WebCite at http://www.webcitation.org/6x8Z5pBui) PMID:29581089

Measuring skin necrosis in a randomised controlled feasibility trial of heat preconditioning on wound healing after reconstructive breast surgery: study protocol and statistical analysis plan for the PREHEAT trial.

PubMed

Cro, Suzie; Mehta, Saahil; Farhadi, Jian; Coomber, Billie; Cornelius, Victoria

2018-01-01

Essential strategies are needed to help reduce the number of post-operative complications and associated costs for breast cancer patients undergoing reconstructive breast surgery. Evidence suggests that local heat preconditioning could help improve the provision of this procedure by reducing skin necrosis. Before testing the effectiveness of heat preconditioning in a definitive randomised controlled trial (RCT), we must first establish the best way to measure skin necrosis and estimate the event rate using this definition. PREHEAT is a single-blind randomised controlled feasibility trial comparing local heat preconditioning, using a hot water bottle, against standard care on skin necrosis among breast cancer patients undergoing reconstructive breast surgery. The primary objective of this study is to determine the best way to measure skin necrosis and to estimate the event rate using this definition in each trial arm. Secondary feasibility objectives include estimating recruitment and 30 day follow-up retention rates, levels of compliance with the heating protocol, length of stay in hospital and the rates of surgical versus conservative management of skin necrosis. The information from these objectives will inform the design of a larger definitive effectiveness and cost-effectiveness RCT. This article describes the PREHEAT trial protocol and detailed statistical analysis plan, which includes the pre-specified criteria and process for establishing the best way to measure necrosis. This study will provide the evidence needed to establish the best way to measure skin necrosis, to use as the primary outcome in a future RCT to definitively test the effectiveness of local heat preconditioning. The pre-specified statistical analysis plan, developed prior to unblinded data extraction, sets out the analysis strategy and a comparative framework to support a committee evaluation of skin necrosis measurements. It will increase the transparency of the data analysis for the PREHEAT trial. ISRCTN ISRCTN15744669. Registered 25 February 2015.

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

PubMed

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

2015-08-21

The outcome of the effects of transitioning to minimalist running shoes is a topic of interest for runners and scientists. However, few studies have investigated the longer term effects of running in minimalist shoes. The purpose of this randomised controlled trial (RCT) is to investigate the effects of a 26 week transition to minimalist shoes on running performance and injury risk in trained runners unaccustomed to minimalist footwear. A randomised parallel intervention design will be used. Seventy-six trained male runners will be recruited. To be eligible, runners must be aged 18-40 years, run with a habitual rearfoot footfall pattern, train with conventional shoes and have no prior experience with minimalist shoes. Runners will complete a standardised transition to either minimalist or control shoes and undergo assessments at baseline, 6 and 26 weeks. 5 km time-trial performance (5TT), running economy, running biomechanics, triceps surae muscle strength and lower limb bone mineral density will be assessed at each time point. Pain and injury will be recorded weekly. Training will be standardised during the first 6 weeks. Primary statistical analysis will compare 5TT between shoe groups at the 6-week time point and injury incidence across the entire 26-week study period. This RCT has been approved by the Human Research Ethics Committee of the University of South Australia. Participants will be required to provide their written informed consent prior to participation in the study. Study findings will be disseminated in the form of journal publications and conference presentations after completion of planned data analysis. This RCT has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613000642785). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Fluoropyrimidine-HAI (hepatic arterial infusion) versus systemic chemotherapy (SCT) for unresectable liver metastases from colorectal cancer.

PubMed

Mocellin, Simone; Pasquali, Sandro; Nitti, Donato

2009-07-08

Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the metastatic organ as compared to systemic chemotherapy (SCT), the benefit in terms of overall survival (OS) is unclear. We quantitatively summarized the results of randomised controlled trials (RCT) comparing HAI to SCT for the treatment of unresectable liver metastatic disease from colorectal cancer (CRC). The aim of this work is to quantitatively summarize the results of RCT comparing HAI to SCT for the treatment of unresectable hepatic metastases from CRC. A systematic review of reports published until September 2008 on the findings of RCT that compared HAI to SCT for the treatment of unresectable CRC liver metastases was performed by searching the MEDLINE, Embase, Cancerlit, Cochrane and GoogleScholar electronic databases as well as other databanks collecting information on clinical trials. Inclusion criteria were patients with unresectable CRC liver metastases enrolled in RCT comparing HAI to SCT. The outcome measures were tumor response rate and overall survival. Two authors independently carried out study selection and assessment of methodological quality. A third author performed a concordance analysis in order to unravel potential systematic biases. Ten RCT were identified that met the eligibility criteria. HAI regimens were based on floxuridine (FUDR), 5-fluorouracil or either one of these two fluoropyrimidines in eight and one RCT, respectively. SCT consisted of FUDR or 5-fluorouracil in three and seven RCT, respectively. By pooling the summary data, tumor response rate resulted 42.9% and 18.4% for HAI and SCT, respectively (RR = 2.26; 95% CI, 1.80 to 2.84; P < 0.0001). Mean weighted median OS times were 15.9 and 12.4 months for HAI and SCT, respectively: the meta-risk of death was not statistically different between the two treatment groups (HR = 0.90; 95% CI, 0.76 to 1.07; P = 0.24). Currently available evidence does not support the clinical or investigational use of fluoropyrimidine-based HAI alone for the treatment of patients with unresectable CRC liver metastases: in fact, the greater tumor response rate obtained with this HAI regimen does not translate into a survival advantage over fluoropyrimidine alone SCT.

CeasIng Cpap At standarD criteriA (CICADA): Implementation improves neonatal outcomes.

PubMed

Heath Jeffery, Rachael C; Broom, Margaret; Shadbolt, Bruce; Todd, David A

2016-03-01

A previous randomised controlled trial (RCT) in babies born < 30 weeks gestation found the so-called CICADA method (ceasing continuous positive airways pressure (CPAP) with a view to remain off rather than slow weaning) significantly reduced CPAP time. Post-RCT we introduced the CICADA method and evaluated whether the improved outcomes of the CICADA method during the RCT were replicated in clinical practice. The aim of the study is to compare cardio-respiratory outcomes in PBs < 30 weeks GA over three epochs: (i) pre RCT, (ii) during RCT and (iii) post RCT implementation. The study used prospective data to compare baseline characteristics and cardio-respiratory outcomes over the three epochs. There were 270/393(69%) PBs < 30 weeks GA who fulfilled the inclusion criteria over the three epochs. No significant differences were found in GA or birthweight between the three epochs (27.9 ± 1.3, 27.7 ± 1.4, 28.0 ± 1.3 (weeks ± 1 standard deviation); and 1100 ± 252, 1086 ± 251, 1094 ± 320 (grams ± 1 standard deviation)). There were significant decreases in CPAP days and corrected GA to cease CPAP post implementation (20.5 ± 2.1, 21.1 ± 2.1, 16.5 ± 1.8 (days ± SE); P = 0.006 and 33.3 ± 0.4, 33.5 ± 0.4, 32.6 ± 0.4 (weeks ± SE); P = 0.01). Compared with the pre RCT epoch, there were significant reductions in patent ductus arteriosus (36/78 (46%), 33/87 (37%), 18/103 (17%); P < 0.001) and chronic lung disease (40/78 (51%), 19/87 (21%), 30/103 (29%); P < 0.001). CPAP time, corrected GA to cease CPAP, patent ductus arteriosus and chronic lung disease significantly reduced following the introduction of the CICADA method. Early cessation of CPAP expedites the transition from neonatal intensive care to special care. © 2016 The Author. Journal of Paediatrics and Child Health © 2016 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Fatty acid‐binding protein 4 regulates fatty infiltration after rotator cuff tear by hypoxia‐inducible factor 1 in mice

PubMed Central

Lee, Yong‐Soo; Kim, Ja‐Yeon; Oh, Kyung‐Soo

2017-01-01

Abstract Background Fatty infiltration in skeletal muscle is directly linked to loss of muscle strength and is associated with various adverse physical outcomes such as muscle atrophy, inflammation, insulin resistance, mobility impairments, and even mortality in the elderly. Aging, mechanical unloading, muscle injury, and hormonal imbalance are main causes of muscle fat accumulation, and the fat cells are derived from muscle stem cells via adipogenic differentiation. However, the pathogenesis and molecular mechanisms of fatty infiltration in muscles are still not fully defined. Fatty acid‐binding protein 4 (FABP4) is a carrier protein for fatty acids and is involved in fatty acid uptake, transport, and lipid metabolism. Rotator cuff tear (RCT) usually occurs in the elderly and is closely related with fatty infiltration in injured muscle. To investigate potential mechanisms for fatty infiltration other than adipogenic differentiation of muscle stem cells, we examined the role of FABP4 in muscle fatty infiltration in an RCT mouse model. Methods In the RCT model, we evaluated the expression of FABP4 by qRT‐PCR, western blotting, and immunohistochemical analyses. Histological changes such as inflammation and fat accumulation in the injured muscles were examined immunohistochemically. To evaluate whether hypoxia induces FABP4 expression, the levels of FABP4 mRNA and protein in C3H10T1/2 cells after hypoxia were examined. Using a transient transfection assay in 293T cells, we assessed the promoter activity of FABP4 by hypoxia‐inducible factors (HIFs). Additionally, we evaluated the reduction in FABP4 expression and fat accumulation using specific inhibitors for HIF1 and FABP4, respectively. Results FABP4 expression was significantly increased after RCT in mice, and its expression was localized in the intramuscular fatty region. Rotator cuff tear‐induced FABP4 expression was up‐regulated by hypoxia. HIF1α, which is activated by hypoxia, augmented the promoter activity of FABP4, together with HIF1β. Hypoxia‐induced FABP4 expression was significantly decreased by HIF1 inhibitor treatment. Furthermore, in RCT model mice, fat accumulation was remarkably reduced by FABP4 inhibitor treatment. Conclusions This study shows that RCT induces FABP4 expression, leading to fat accumulation in injured muscle. FABP4 transcription is regulated by the direct binding of HIF1 to the FABP4 promoter in the hypoxic condition induced by RCT. Fat accumulation in injured muscle was reduced by the inhibition of FABP4. Ultimately, in the RCT model, we identified a novel mechanism for fatty infiltration by FABP4, which differs from adipogenic differentiation of muscle stem cells, and we found that fatty infiltration might be regulated by inhibition of HIF1 or FABP4. PMID:28382782

Foster Youth and Social Support: The First RCT of Independent Living Services

ERIC Educational Resources Information Center

Greeson, Johanna K. P.; Garcia, Antonio R.; Kim, Minseop; Courtney, Mark E.

2015-01-01

Objective: Conduct secondary data analysis to evaluate the effectiveness of Massachusetts' Adolescent Outreach Program for Youths in Intensive Foster Care (Outreach) for increasing social support (SS) among enrolled youth. Participants: 194 youth in intensive foster care under the guardianship of the Massachusetts Department of Children and…

Antipsychotic switching for people with schizophrenia who have neuroleptic-induced weight or metabolic problems.

PubMed

Mukundan, Anitha; Faulkner, Guy; Cohn, Tony; Remington, Gary

2010-12-08

Weight gain is common for people with schizophrenia and this has serious implications for a patient's health and well being. Switching strategies have been recommended as a management option. To determine the effects of antipsychotic medication switching as a strategy for reducing or preventing weight gain and metabolic problems in people with schizophrenia. We searched key databases and the Cochrane Schizophrenia Group's trials register (January 2005 and June 2007), reference sections within relevant papers and contacted the first author of each relevant study and other experts to collect further information. All clinical randomised controlled trials comparing switching of antipsychotic medication as an intervention for antipsychotic induced weight gain and metabolic problems with continuation of medication and/or other weight loss treatments (pharmacological and non pharmacological) in people with schizophrenia or schizophrenia-like illnesses. Studies were reliably selected, quality assessed and data extracted. For dichotomous data we calculated risk ratio (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effect model. The primary outcome measures were weight loss, metabolic syndrome, relapse and general mental state. We included four studies for the review with a total of 636 participants. All except one study had a duration of 26 weeks or less. There was a mean weight loss of 1.94 kg (2 RCT, n = 287, CI -3.9 to 0.08) when switched to aripiprazole or quetiapine from olanzapine. BMI also decreased when switched to quetiapine (1 RCT, n = 129, MD -0.52 CI -1.26 to 0.22) and aripiprazole (1 RCT, n = 173, RR 0.28 CI 0.13 to 0.57) from olanzapine.Fasting blood glucose showed a significant decrease when switched to aripiprazole or quetiapine from olanzapine. (2 RCT, MD -2.53 n = 280 CI -2.94 to -2.11). One RCT also showed a favourable lipid profile when switched to aripiprazole but these measures were reported as percentage changes, rather than means with standard deviation.People are less likely to leave the study early if they remain on olanzapine compared to switching to quetiapine or aripiprazole.There was no significant difference in outcomes of mental state, global state, and adverse events between groups which switched medications and those that remained on previous medication. Three different switching strategies were compared and no strategy was found to be superior to the others for outcomes of weight gain, mental state and global state. Evidence from this review suggests that switching antipsychotic medication to one with lesser potential for causing weight gain or metabolic problems could be an effective way to manage these side effects, but the data were weak due to the limited number of trials in this area and small sample sizes. Poor reporting of data also hindered using some trials and outcomes. There was no difference in mental state, global state and other treatment related adverse events between switching to another medication and continuing on the previous one. When the three switching strategies were compared none of them had an advantage over the others in their effects on the primary outcomes considered in this review. Better designed trials with adequate power would provide more convincing evidence for using medication switching as an intervention strategy.

Managing with Learning Disability and Diabetes: OK-Diabetes - a case-finding study and feasibility randomised controlled trial.

PubMed

House, Allan; Bryant, Louise; Russell, Amy M; Wright-Hughes, Alexandra; Graham, Liz; Walwyn, Rebecca; Wright, Judy M; Hulme, Claire; O'Dwyer, John L; Latchford, Gary; Meer, Shaista; Birtwistle, Jacqueline C; Stansfield, Alison; Ajjan, Ramzi; Farrin, Amanda

2018-05-01

Obesity and type 2 diabetes are common in adults with a learning disability. It is not known if the principles of self-management can be applied in this population. To develop and evaluate a case-finding method and undertake an observational study of adults with a learning disability and type 2 diabetes, to develop a standardised supported self-management (SSM) intervention and measure of adherence and to undertake a feasibility randomised controlled trial (RCT) of SSM versus treatment as usual (TAU). Observational study and an individually randomised feasibility RCT. Three cities in West Yorkshire, UK. In the observational study: adults aged > 18 years with a mild or moderate learning disability, who have type 2 diabetes that is not being treated with insulin and who are living in the community. Participants had mental capacity to consent to research and to the intervention. In the RCT participants had glycated haemoglobin (HbA 1c ) levels of > 6.5% (48 mmol/mol), a body mass index (BMI) of > 25 kg/m 2 or self-reported physical activity below national guideline levels. Standardised SSM. TAU supported by an easy-read booklet. (1) The number of eligible participants identified and sources of referral; (2) current living and support arrangements; (3) current health state, including level of HbA 1c , BMI and waist circumference, blood pressure and lipids; (4) mood, preferences for change; (5) recruitment and retention in RCT; (6) implementation and adherence to the intervention; (7) completeness of data collection and values for candidate primary outcomes; and (8) qualitative data on participant experience of the research process and intervention. In the observational study we identified 147 eligible consenting participants. The mean age was 54.4 years. In total, 130 out of 147 (88%) named a key supporter, with 113 supporters (77%) being involved in diabetes management. The mean HbA 1c level was 54.5 mmol/mol [standard deviation (SD) 14.8 mmol/mol; 7.1%, SD 1.4%]. The BMI of 65% of participants was > 30 kg/m 2 and of 21% was > 40 kg/m 2 . Many participants reported low mood, dissatisfaction with lifestyle and diabetes management and an interest in change. Non-response rates were high (45/147, 31%) for medical data requested from the primary care team. In the RCT, 82 participants were randomised. The mean baseline HbA 1c level was 56 mmol/mol (SD 16.5 mmol/mol; 7.3%, SD 1.5%) and the mean BMI was 34 kg/m 2 (SD 7.6 kg/m 2 ). All SSM sessions were completed by 35 out of 41 participants. The adherence measure was obtained in 37 out of 41 participants. The follow-up HbA 1c level and BMI was obtained for 75 out of 82 (91%) and 77 out of 82 (94%) participants, respectively. Most participants reported a positive experience of the intervention. A low response rate and difficulty understanding the EuroQol-5 Dimensions were challenges in obtaining data for an economic analysis. We recruited from only 60% of eligible general practices, and 90% of participants were on a general practice learning disability register, which meant that we did not recruit many participants from the wider population with milder learning disability. A definitive RCT is feasible and would need to recruit 194 participants per arm. The main barrier is the resource-intensive nature of recruitment. Future research is needed into the effectiveness of obesity treatments in this population, particularly estimating the longer-term outcomes that are important for health benefit. Research is also needed into improving ways of assessing quality of life in adults with a learning disability. Current Controlled Trials ISRCTN41897033. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 22, No. 26. See the NIHR Journals Library website for further project information.

Individualized FSH dosing based on ovarian reserve testing in women starting IVF/ICSI: a multicentre trial and cost-effectiveness analysis.

PubMed

van Tilborg, Theodora C; Oudshoorn, Simone C; Eijkemans, Marinus J C; Mochtar, Monique H; van Golde, Ron J T; Hoek, Annemieke; Kuchenbecker, Walter K H; Fleischer, Kathrin; de Bruin, Jan Peter; Groen, Henk; van Wely, Madelon; Lambalk, Cornelis B; Laven, Joop S E; Mol, Ben Willem J; Broekmans, Frank J M; Torrance, Helen L

2017-12-01

Is there a difference in live birth rate and/or cost-effectiveness between antral follicle count (AFC)-based individualized FSH dosing or standard FSH dosing in women starting IVF or ICSI treatment? In women initiating IVF/ICSI, AFC-based individualized FSH dosing does not improve live birth rates or reduce costs as compared to a standard FSH dose. In IVF or ICSI, ovarian reserve testing is often used to adjust the FSH dose in order to normalize ovarian response and optimize live birth rates. However, no robust evidence for the (cost-)effectiveness of this practice exists. Between May 2011 and May 2014 we performed a multicentre prospective cohort study with two embedded RCTs in women scheduled for IVF/ICSI. Based on the AFC, women entered into one of the two RCTs (RCT1: AFC < 11; RCT2: AFC > 15) or the cohort (AFC 11-15). The primary outcome was ongoing pregnancy achieved within 18 months after randomization resulting in a live birth (delivery of at least one live foetus after 24 weeks of gestation). Data from the cohort with weight 0.5 were combined with both RCTs in order to conduct a strategy analysis. Potential half-integer numbers were rounded up. Differences in costs and effects between the two treatment strategies were compared by bootstrapping. In both RCTs women were randomized to an individualized (RCT1:450/225 IU, RCT2:100 IU) or standard FSH dose (150 IU). Women in the cohort all received the standard dose (150 IU). Anti-Müllerian hormone (AMH) was measured to assess AMH post-hoc as a biomarker to individualize treatment. For RCT1 dose adjustment was allowed in subsequent cycles based on pre-specified criteria in the standard group only. For RCT2 dose adjustment was allowed in subsequent cycles in both groups. Both effectiveness and cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. We included 1515 women, of whom 483 (31.9%) entered the cohort, 511 (33.7%) RCT1 and 521 (34.4%) RCT2. Live births occurred in 420/747 (56.3%) women in the individualized strategy and 447/769 (58.2%) women in the standard strategy (risk difference -0.019 (95% CI, -0.06 to 0.02), P = 0.39; a total of 1516 women due to rounding up the half integer numbers). The individualized strategy was more expensive (delta costs/woman = €275 (95% CI, 40 to 499)). Individualized dosing reduced the occurrence of mild and moderate ovarian hyperstimulation syndrome (OHSS) and subsequently the costs for management of these OHSS categories (costs saved/woman were €35). The analysis based on AMH as a tool for dose individualization suggested comparable results. Despite a training programme, the AFC might have suffered from inter-observer variation. In addition, although strict cancel criteria were provided, selective cancelling in the individualized dose group (for poor response in particular) cannot be excluded as observers were not blinded for the FSH dose and small dose adjustments were allowed in subsequent cycles. However, as both first cycle live birth rates and cumulative live birth rates show no difference between strategies, the open design probably did not mask a potential benefit for the individualized group. Despite increasing consensus on using GnRH antagonist co-treatment in women predicted for a hyper response in particular, GnRH agonists were used in almost 80% of the women in this study. Hence, in those women, the AFC and bloodsampling for the post-hoc AMH analysis were performed during pituitary suppression. As the correlation between AFC and ovarian response is not compromised during GnRH agonist use, this will probably not have influenced classification of response. Individualized FSH dosing for the IVF/ICSI population as a whole should not be pursued as it does not improve live birth rates and it increases costs. Women scheduled for IVF/ICSI with a regular menstrual cycle are therefore recommended a standard FSH starting dose of 150 IU per day. Still, safety management by individualized dosing in predicted hyper responders is open for further research. This study was funded by The Netherlands Organisation for Health Research and Development (ZonMW number 171102020). AMH measurements were performed free of charge by Roche Diagnostics. TCT, HLT and SCO received an unrestricted personal grant from Merck BV. AH declares that the department of Obstetrics and Gynecology, University Medical Centre Groningen receives an unrestricted research grant from Ferring pharmaceutics BV, The Netherlands. CBL receives grants from Merck, Ferring and Guerbet. BWJM is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for OvsEva, Merck and Guerbet. FJMB receives monetary compensation as a member of the external advisory board for Ferring pharmaceutics BV (the Netherlands) and Merck Serono (the Netherlands) for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics on automated AMH assay development (Switzerland) and for a research cooperation with Ansh Labs (USA). All other autors have nothing to declare. Registered at the ICMJE-recognized Dutch Trial Registry (www.trialregister.nl). Registration number: NTR2657. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

The Trouble with the Gold Standard: School Libraries & Research

ERIC Educational Resources Information Center

Gordon, Carol

2007-01-01

Although science has provided empirical evidence for centuries, it's only as recently as the 1940s that a scientific method called randomized controlled trials (RCT) emerged as a technique to test the efficacy of drugs and medical procedures. Since RCT is unique in that it can claim causality, it's considered the "gold standard" of research…

Relational-Cultural Theory: A Framework for Relational Competencies and Movement in Group Work with Female Adolescents

ERIC Educational Resources Information Center

Cannon, Kristi B.; Hammer, Tonya R.; Reicherzer, Stacee; Gilliam, Billie J.

2012-01-01

Relational-cultural theory (RCT) is an evolving feminist model of human development that places emphasis on growth-fostering relationships as building blocks for wellness. This article demonstrates the use of RCT in addressing relational aggression, including cyberbullying, in counseling a group of adolescent girls. The group counselor's…

Liberia's Experiment with Privatising Education: A Critical Analysis of the RCT Study

ERIC Educational Resources Information Center

Klees, Steven J.

2018-01-01

To experiment with the possible privatisation of its primary education system, Liberia initiated the Partnership Schools of Liberia (PSL), which turned over the management of 93 public schools to eight private contractors. A randomised controlled trial (RCT) study was initiated comparing the PSL schools with matched public schools and the results…

[Worker's life before and after repetive cumulative trauma (RCT) and osteomuscular work-related disease (OWRD)].

PubMed

Barbosa, Maria do Socorro Alécio; dos Santos, Regina Maria; Trezza, Maria Cristina Soares Figueiredo

2007-01-01

This is a qualitative work, which focused on workers routine before and after being affected by RCT/ OWRD. The study aimed at verifying and analyzing if workers' lives had changed after the disease diagnostic. The research took place at sections of the TRT-AL--a Court responsible for labor conciliations in Maceió - Alagoas. The information was collected based on semi-structured interviews and data were analyzed based on the following tematics: life before RCT/OWRD; the activity that caused it; the diagnosis; an answer to the repetitive work and a new perspective to the horizon. Results enabled researchers to suggest preventive care, as well as to contribute for reducing damages caused by repetitive activities and high pressure on workers.

Different methods and settings for glucose monitoring for gestational diabetes during pregnancy.

PubMed

Raman, Puvaneswary; Shepherd, Emily; Dowswell, Therese; Middleton, Philippa; Crowther, Caroline A

2017-10-29

Incidence of gestational diabetes mellitus (GDM) is increasing worldwide. Blood glucose monitoring plays a crucial part in maintaining glycaemic control in women with GDM and is generally recommended by healthcare professionals. There are several different methods for monitoring blood glucose which can be carried out in different settings (e.g. at home versus in hospital). The objective of this review is to compare the effects of different methods and settings for glucose monitoring for women with GDM on maternal and fetal, neonatal, child and adult outcomes, and use and costs of health care. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (30 September 2016) and reference lists of retrieved studies. Randomised controlled trials (RCTs) or quasi-randomised controlled trials (qRCTs) comparing different methods (such as timings and frequencies) or settings, or both, for blood glucose monitoring for women with GDM. Two authors independently assessed study eligibility, risk of bias, and extracted data. Data were checked for accuracy.We assessed the quality of the evidence for the main comparisons using GRADE, for:- primary outcomes for mothers: that is, hypertensive disorders of pregnancy; caesarean section; type 2 diabetes; and- primary outcomes for children: that is, large-for-gestational age; perinatal mortality; death or serious morbidity composite; childhood/adulthood neurosensory disability;- secondary outcomes for mothers: that is, induction of labour; perineal trauma; postnatal depression; postnatal weight retention or return to pre-pregnancy weight; and- secondary outcomes for children: that is, neonatal hypoglycaemia; childhood/adulthood adiposity; childhood/adulthood type 2 diabetes. We included 11 RCTs (10 RCTs; one qRCT) that randomised 1272 women with GDM in upper-middle or high-income countries; we considered these to be at a moderate to high risk of bias. We assessed the RCTs under five comparisons. For outcomes assessed using GRADE, we downgraded for study design limitations, imprecision and inconsistency. Three trials received some support from commercial partners who provided glucose meters or financial support, or both. Main comparisons Telemedicine versus standard care for glucose monitoring (five RCTs): we observed no clear differences between the telemedicine and standard care groups for the mother, for:- pre-eclampsia or pregnancy-induced hypertension (risk ratio (RR) 1.49, 95% confidence interval (CI) 0.69 to 3.20; 275 participants; four RCTs; very low quality evidence);- caesarean section (average RR 1.05, 95% CI 0.72 to 1.53; 478 participants; 5 RCTs; very low quality evidence); and- induction of labour (RR 1.06, 95% CI 0.63 to 1.77; 47 participants; 1 RCT; very low quality evidence);or for the child, for:- large-for-gestational age (RR 1.41, 95% CI 0.76 to 2.64; 228 participants; 3 RCTs; very low quality evidence);- death or serious morbidity composite (RR 1.06, 95% CI 0.68 to 1.66; 57 participants; 1 RCT; very low quality evidence); and- neonatal hypoglycaemia (RR 1.14, 95% CI 0.48 to 2.72; 198 participants; 3 RCTs; very low quality evidence).There were no perinatal deaths in two RCTs (131 participants; very low quality evidence). Self-monitoring versus periodic glucose monitoring (two RCTs): we observed no clear differences between the self-monitoring and periodic glucose monitoring groups for the mother, for:- pre-eclampsia (RR 0.17, 95% CI 0.01 to 3.49; 58 participants; 1 RCT; very low quality evidence); and- caesarean section (average RR 1.18, 95% CI 0.61 to 2.27; 400 participants; 2 RCTs; low quality evidence);or for the child, for:- perinatal mortality (RR 1.54, 95% CI 0.21 to 11.24; 400 participants; 2 RCTs; very low quality evidence);- large-for-gestational age (RR 0.82, 95% CI 0.50 to 1.37; 400 participants; 2 RCTs; low quality evidence); and- neonatal hypoglycaemia (RR 0.64, 95% CI 0.39 to 1.06; 391 participants; 2 RCTs; low quality evidence). Continuous glucose monitoring system (CGMS) versus self-monitoring of glucose (two RCTs): we observed no clear differences between the CGMS and self-monitoring groups for the mother, for:- caesarean section (RR 0.91, 95% CI 0.68 to 1.20; 179 participants; 2 RCTs; very low quality evidence);or for the child, for:- large-for-gestational age (RR 0.67, 95% CI 0.43 to 1.05; 106 participants; 1 RCT; very low quality evidence) and- neonatal hypoglycaemia (RR 0.79, 95% CI 0.35 to 1.78; 179 participants; 2 RCTs; very low quality evidence).There were no perinatal deaths in the two RCTs (179 participants; very low quality evidence). Other comparisons Modem versus telephone transmission for glucose monitoring (one RCT): none of the review's primary outcomes were reported in this trial Postprandial versus preprandial glucose monitoring (one RCT): we observed no clear differences between the postprandial and preprandial glucose monitoring groups for the mother, for:- pre-eclampsia (RR 1.00, 95% CI 0.15 to 6.68; 66 participants; 1 RCT);- caesarean section (RR 0.62, 95% CI 0.29 to 1.29; 66 participants; 1 RCT); and- perineal trauma (RR 0.38, 95% CI 0.11 to 1.29; 66 participants; 1 RCT);or for the child, for:- neonatal hypoglycaemia (RR 0.14, 95% CI 0.02 to 1.10; 66 participants; 1 RCT).There were fewer large-for-gestational-age infants born to mothers in the postprandial compared with the preprandial glucose monitoring group (RR 0.29, 95% CI 0.11 to 0.78; 66 participants; 1 RCT). Evidence from 11 RCTs assessing different methods or settings for glucose monitoring for GDM suggests no clear differences for the primary outcomes or other secondary outcomes assessed in this review.However, current evidence is limited by the small number of RCTs for the comparisons assessed, small sample sizes, and the variable methodological quality of the RCTs. More evidence is needed to assess the effects of different methods and settings for glucose monitoring for GDM on outcomes for mothers and their children, including use and costs of health care. Future RCTs may consider collecting and reporting on the standard outcomes suggested in this review.

DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY - Registry (DESTINY-R): design and protocols.

PubMed

Neugebauer, Hermann; Heuschmann, Peter U; Jüttler, Eric

2012-10-02

Randomized controlled trials (RCT) on the treatment of severe space-occupying infarction of the middle cerebral artery (malignant MCA infarction) showed that early decompressive hemicraniectomy (DHC) is life saving and improves outcome without promoting most severe disablity in patients aged 18-60 years. It is, however, unknown whether the results obtained in the randomized trials are reproducible in a broader population in and apart from an academical setting and whether hemicraniectomy has been implemented in clinical practice as recommended by national and international guidelines. In addition, they were not powered to answer further relevant questions, e.g. concerning the selection of patients eligible for and the timing of hemicraniectomy. Other important issues such as the acceptance of disability following hemicraniectomy, the existence of specific prognostic factors, the value of conservative therapeutic measures, and the overall complication rate related to hemicraniectomy have not been sufficiently studied yet. DESTINY-R is a prospective, multicenter, open, controlled registry including a 12 months follow-up. The only inclusion criteria is unilateral ischemic MCA stroke affecting more than 50% of the MCA-territory. The primary study hypothesis is to confirm the results of the RCT (76% mRS ≤ 4 after 12 months) in the subgroup of patients additionally fulfilling the inclusion cirteria of the RCT in daily routine. Assuming a calculated proportion of 0.76 for successes and a sample size of 300 for this subgroup, the width of the 95% CI, calculated using Wilson's method, will be 0.096 with the lower bound 0.709 and the upper bound 0.805. The results of this study will provide information about the effectiveness of DHC in malignant MCA infarction in a broad population and a real-life situation in addition to and beyond RCT. Further prospectively obtained data will give crucial information on open questions and will be helpful in the plannig of upcomming treatment studies. (ICTRP and DRKS): DRKS00000624.

Chiropractic spinal manipulative therapy for migraine: a study protocol of a single-blinded placebo-controlled randomised clinical trial

PubMed Central

Chaibi, Aleksander; Šaltytė Benth, Jūratė; Tuchin, Peter J; Russell, Michael Bjørn

2015-01-01

Introduction Migraine affects 15% of the population, and has substantial health and socioeconomic costs. Pharmacological management is first-line treatment. However, acute and/or prophylactic medicine might not be tolerated due to side effects or contraindications. Thus, we aim to assess the efficacy of chiropractic spinal manipulative therapy (CSMT) for migraineurs in a single-blinded placebo-controlled randomised clinical trial (RCT). Method and analysis According to the power calculations, 90 participants are needed in the RCT. Participants will be randomised into one of three groups: CSMT, placebo (sham manipulation) and control (usual non-manual management). The RCT consists of three stages: 1 month run-in, 3 months intervention and follow-up analyses at the end of the intervention and 3, 6 and 12 months. The primary end point is migraine frequency, while migraine duration, migraine intensity, headache index (frequency x duration x intensity) and medicine consumption are secondary end points. Primary analysis will assess a change in migraine frequency from baseline to the end of the intervention and follow-up, where the groups CSMT and placebo and CSMT and control will be compared. Owing to two group comparisons, p values below 0.025 will be considered statistically significant. For all secondary end points and analyses, a p value below 0.05 will be used. The results will be presented with the corresponding p values and 95% CIs. Ethics and dissemination The RCT will follow the clinical trial guidelines from the International Headache Society. The Norwegian Regional Committee for Medical Research Ethics and the Norwegian Social Science Data Services have approved the project. Procedure will be conducted according to the declaration of Helsinki. The results will be published at scientific meetings and in peer-reviewed journals. Trial registration number NCT01741714. PMID:26586317

Learning from failure - rationale and design for a study about discontinuation of randomized trials (DISCO study)

PubMed Central

2012-01-01

Background Randomized controlled trials (RCTs) may be discontinued because of apparent harm, benefit, or futility. Other RCTs are discontinued early because of insufficient recruitment. Trial discontinuation has ethical implications, because participants consent on the premise of contributing to new medical knowledge, Research Ethics Committees (RECs) spend considerable effort reviewing study protocols, and limited resources for conducting research are wasted. Currently, little is known regarding the frequency and characteristics of discontinued RCTs. Methods/Design Our aims are, first, to determine the prevalence of RCT discontinuation for specific reasons; second, to determine whether the risk of RCT discontinuation for specific reasons differs between investigator- and industry-initiated RCTs; third, to identify risk factors for RCT discontinuation due to insufficient recruitment; fourth, to determine at what stage RCTs are discontinued; and fifth, to examine the publication history of discontinued RCTs. We are currently assembling a multicenter cohort of RCTs based on protocols approved between 2000 and 2002/3 by 6 RECs in Switzerland, Germany, and Canada. We are extracting data on RCT characteristics and planned recruitment for all included protocols. Completion and publication status is determined using information from correspondence between investigators and RECs, publications identified through literature searches, or by contacting the investigators. We will use multivariable regression models to identify risk factors for trial discontinuation due to insufficient recruitment. We aim to include over 1000 RCTs of which an anticipated 150 will have been discontinued due to insufficient recruitment. Discussion Our study will provide insights into the prevalence and characteristics of RCTs that were discontinued. Effective recruitment strategies and the anticipation of problems are key issues in the planning and evaluation of trials by investigators, Clinical Trial Units, RECs and funding agencies. Identification and modification of barriers to successful study completion at an early stage could help to reduce the risk of trial discontinuation, save limited resources, and enable RCTs to better meet their ethical requirements. PMID:22928744

A Narrative Review of Social Media and Game-Based Nutrition Interventions Targeted at Young Adults.

PubMed

Nour, Monica; Yeung, Sin Hang; Partridge, Stephanie; Allman-Farinelli, Margaret

2017-05-01

The increased popularity of social media and mobile gaming among young adults provides an opportunity for innovative nutrition programs. This review evaluated the efficacy of these strategies in interventions targeted at 18- to 35-year-olds. The protocol was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Ten scientific databases, information technology conference proceedings, and gray literature were searched. Two reviewers conducted screening, data extraction, and quality assessments. Interventions were included if they used social media or electronic games. Comparisons were made pre- to post-intervention, or between intervention and control arms. Outcomes of interest included change in nutrition knowledge, attitudes, behavior, or weight and/or body composition. Eleven social media-based (randomized controlled trials [RCT] n=7) and six game-based [RCT n=1]) interventions were included. Overall quality of studies was low. Social media-based strategies included forum/blogs (n=5), Facebook (n=5), Twitter (n=1), YouTube (n=1), and chat rooms (n=1). Eight (RCT n=6) of 11 social media-based studies demonstrated improvements in outcomes. Findings suggested that social media may be more effective when combined with other strategies. Virtual reality games (n=3), web-based games (n=2), and a mobile application (n=1) were used in the gaming interventions. While a significant increase in knowledge was reported by three gaming studies (RCT=1), two used nonvalidated tools and longer-term measures of weight and behavioral outcomes were limited. The use of social media and gaming for nutrition promotion is in its infancy. Preliminary evidence suggests that these strategies have some utility for intervening with young adults. Further research using high-quality study designs is required, with measurement of outcomes over longer time periods. The systematic review protocol is registered with PROSPERO (registration number: CRD42015025427). Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Do Children with Uncomplicated Severe Acute Malnutrition Need Antibiotics? A Systematic Review and Meta-Analysis

PubMed Central

Alcoba, Gabriel; Kerac, Marko; Breysse, Serge; Salpeteur, Cécile; Galetto-Lacour, Annick; Briend, André; Gervaix, Alain

2013-01-01

Background Current (1999) World Health Organization guidelines recommend giving routine antibiotics (AB) for all children with severe acute malnutrition (SAM), even if they have uncomplicated disease with no clinically obvious infections. We examined the evidence behind this recommendation. Methods and Findings OVID-MEDLINE, EMBASE, COCHRANE, GLOBAL-HEALTH, CINAHL, POPLINE, AFRICA-WIDE-NiPAD, and LILACS were searched for AB efficacy, bacterial resistance, and infection rates in SAM. Following PRISMA guidelines, a systematic review and meta-analysis were performed. Three randomised controlled trials (RCT), five Cochrane reviews, and 37 observational studies were identified. One cohort-study showed no increase in nutritional-cure and mortality in uncomplicated SAM where no AB were used. (p>0.05). However, an unpublished RCT in this setting did show mortality benefits. Another RCT did not show superiority of ceftriaxone over amoxicilllin for these same outcomes, but adressed SAM children with and without complications (p = 0.27). Another RCT showed no difference between amoxicillin and cotrimoxazole efficacies for pneumonia in underweight, but not SAM. Our meta-analysis of 12 pooled susceptibility-studies for all types of bacterial isolates, including 2767 stricly SAM children, favoured amoxicillin over cotrimoxazole for susceptibility medians: 42% (IQR 27–55%) vs 22% (IQR 17–23%) and population-weighted-means 52.9% (range 23–57%) vs 35.4% (range 6.7–42%). Susceptibilities to second-line AB were better, above 80%. Prevalence of serious infections in SAM, pooled from 24 studies, ranged from 17% to 35.2%. No study infered any association of infection prevalence with AB regimens in SAM. Conclusions The evidence underlying current antibiotic recommendations for uncomplicated SAM is weak. Susceptibility-studies favour amoxicillin over cotrimoxazole. However, given that these antibiotics have side-effects, costs, and risks as well as benefits, their routine use needs urgent testing. With reliable monitoring, we believe that there is sufficient equipoise for placebo controlled RCTs, the only robust way to demonstrate true efficacy. PMID:23326395

Protocol for a feasibility study and randomised pilot trial of a low-intensity psychological intervention for depression in adults with autism: the Autism Depression Trial (ADEPT)

PubMed Central

Russell, Ailsa; Cooper, Kate; Barton, Stephen; Ensum, Ian; Gaunt, Daisy; Horwood, Jeremy; Ingham, Barry; Kessler, David; Metcalfe, Chris; Parr, Jeremy; Rai, Dheeraj; Wiles, Nicola

2017-01-01

Introduction High rates of co-occurring depression are reported in autism spectrum disorder (ASD), a neurodevelopmental condition characterised by social communication impairments and repetitive behaviours. Cognitive-behavioural interventions adapted for ASD have been effective for anxiety problems. There have been evaluation studies of group cognitive-behavioural therapy for co-occurring depression, but no randomised trials investigating low-intensity psychological interventions as recommended in clinical guidelines for mild-moderate depression. Methods and analysis A feasibility study comprising a randomised controlled trial (RCT) and nested qualitative evaluation is under way as preparation for a definitive RCT. Participants (n=70) will be randomised to Guided Self-Help: a low-intensity psychological intervention based on behavioural activation adapted for ASD or treatment as usual. Outcomes including depression symptoms, anxiety, social function and service use will be measured at 10, 16 and 24 weeks postrandomisation and will be blind to group allocation for measures that are not self-administered. The analysis will aim to establish the rates of recruitment and retention for a larger-scale RCT as well as the most appropriate measure of depression to serve as primary outcome. The qualitative study will purposively sample up to 24 participants from each treatment group to consider the acceptability and feasibility of the intervention and the trial design. Ethics and dissemination Ethical approval has been received from WALES REC 3 (IRAS project ID: 191558) and the Health Research Authority with R&D approval from Avon and Wiltshire Mental Health Partnership and Northumberland, Tyne and Wear Foundation NHS Trusts. To our knowledge, this is the first study of a low-intensity intervention for depression in adults with autism. The results will inform the design of a definitive RCT. Dissemination will include peer-reviewed journal publications reporting the quantitative and qualitative research findings of the study and presentations at national and international conferences. Trial registration number ISRCTN54650760; Pre-results. PMID:29203509

Interventions for American Cutaneous and Mucocutaneous Leishmaniasis: A Systematic Review Update

PubMed Central

Reveiz, Ludovic; Maia-Elkhoury, Ana Nilce Silveira; Nicholls, Rubén Santiago; Sierra Romero, Gustavo Adolfo; Yadon, Zaida E.

2013-01-01

Introduction Leishmaniasis is an important public health problem in the Americas. A Cochrane review published in 2009 analyzed 38 randomized controlled trials (RCT). We conducted a systematic review to evaluate the effects of therapeutic interventions for American cutaneous and mucocutaneous leishmaniasis. Methods All studies were extracted from PubMed, Embase, Lilacs (2009 to July, 2012 respectively), the Cochrane Central Register of Controlled Trials (6-2012) and references of identified publications. RCTs’ risk of bias was assessed. Results We identified 1865 references of interest; we finally included 10 new RCTs. The risk of bias scored low or unclear for most domains. Miltefosine was not significantly different from meglumine antimoniate in the complete cure rate at 6 months (4 RCT; 584 participants; ITT; RR: 1.12; 95%CI: 0.85 to 1.47; I2 78%). However a significant difference in the rate of complete cure favoring miltefosine at 6 months was found in L. panamensis and L. guyanensis (2 RCTs, 206 participants; ITT; RR: 1.22; 95%CI: 1.02 to 1.46; I2 0%). One RCT found that meglumine antimoniate was superior to pentamidine in the rate of complete cure for L. braziliensis (80 participants, ITT; RR: 2.21; 95%CI: 1.41 to 3.49), while another RCT assessing L. guyanensis did not find any significant difference. Although meta-analysis of three studies found a significant difference in the rate of complete cure at 3 months favoring imiquimod versus placebo (134 participants; ITT; RR: 1.45; 95%CI: 1.12 to 1.88; I2 0%), no significant differences were found at 6 and 12 months. Thermotherapy and nitric oxide were not superior to meglumine antimoniate. Conclusion Therapeutic interventions for American cutaneous and mucocutaneous leishmaniasis are varied and should be decided according to the context. Since mucosal disease is the more neglected form of leishmaniasis a multicentric trial should be urgently considered. PMID:23637917

RCT of a 6-month programmed sports therapy (PST) in patients with haemophilia - Improvement of physical fitness.

PubMed

Runkel, B; Czepa, D; Hilberg, T

2016-09-01

Physical fitness is of major importance for patients with haemophilia (PwH) but is highly influenced by bleeding episodes. Although some cohort studies describe an improvement of physical fitness after training intervention, randomized controlled studies (RCT) in PwH are still rare. The aim of this study was to prove the enhancement of physical work capacity in PwH by programmed sports therapy (PST). This RCT includes a training period over six months. Sixty-four PwH with moderate (n = 5) to severe (n = 59) haemophilia A (n = 57) and B (n = 7) were randomized into two groups - training intervention group (IG) and control group (CG) by block randomization. Complex strength measurements, joint score, coordination check and a 12-min walking test were carried out before and after training intervention. Significant differences were tested in M. triceps brachii (Δ+0.62 N kg(-1) ), biceps brachii (Δ+1.25 N kg(-1) ), latissimus dorsi (Δ+0.59 N kg(-1) ), rectus abdominis (Δ+0.51 N kg(-1) ), biceps femoris (right: Δ+0.68 N kg(-1) ; left: Δ+0.59 N kg(-1) ) and the quadriceps femoris (right: Δ+0.71 N kg(-1) ; left: Δ+0.55 N kg(-1) ) after intervention between the two groups (all p ≤ 0.003). Furthermore, an increase in distance (Δ+171.5 m) covered in the 12-min walking test (P = 0.011) was observed. Regarding one-leg stand, a significant improvement (P = 0.037) in the IG (Δ+2.2 s right leg) after intervention could be determined. For the first time, a study with a corresponding number of adult PwH in a RCT-design showed that programmed sport therapy with specific instructions over 6 months has a positive effect on physical performance of PwH, independent of constitution and disease process. © 2016 John Wiley & Sons Ltd.

A State-of-the-Science Overview of Randomized Controlled Trials Evaluating Acute Management of Moderate-to-Severe Traumatic Brain Injury

PubMed Central

Synnot, Anneliese; Maas, Andrew I.; Menon, David K.; Cooper, D. James; Rosenfeld, Jeffrey V.; Gruen, Russell L.

2016-01-01

Abstract Moderate-to-severe traumatic brain injury (TBI) remains a major global challenge, with rising incidence, unchanging mortality and lifelong impairments. State-of-the-science reviews are important for research planning and clinical decision support. This review aimed to identify randomized controlled trials (RCTs) evaluating interventions for acute management of moderate/severe TBI, synthesize key RCT characteristics and findings, and determine their implications on clinical practice and future research. RCTs were identified through comprehensive database and other searches. Key characteristics, outcomes, risk of bias, and analysis approach were extracted. Data were narratively synthesized, with a focus on robust (multi-center, low risk of bias, n > 100) RCTs, and three-dimensional graphical figures also were used to explore relationships between RCT characteristics and findings. A total of 207 RCTs were identified. The 191 completed RCTs enrolled 35,340 participants (median, 66). Most (72%) were single center and enrolled less than 100 participants (69%). There were 26 robust RCTs across 18 different interventions. For 74% of 392 comparisons across all included RCTs, there was no significant difference between groups. Positive findings were broadly distributed with respect to RCT characteristics. Less than one-third of RCTs demonstrated low risk of bias for random sequence generation or allocation concealment, less than one-quarter used covariate adjustment, and only 7% employed an ordinal analysis approach. Considerable investment of resources in producing 191 completed RCTs for acute TBI management has resulted in very little translatable evidence. This may result from broad distribution of research effort, small samples, preponderance of single-center RCTs, and methodological shortcomings. More sophisticated RCT design, large multi-center RCTs in priority areas, increased focus on pre-clinical research, and alternatives to RCTs, such as comparative effectiveness research and precision medicine, are needed to fully realize the potential of acute TBI research to benefit patients. PMID:26711675

Systematic Review and Meta-analysis of Indirect Protection Afforded by Vaccinating Children Against Seasonal Influenza: Implications for Policy.

PubMed

Yin, J Kevin; Heywood, Anita E; Georgousakis, Melina; King, Catherine; Chiu, Clayton; Isaacs, David; Macartney, Kristine K

2017-09-01

Universal childhood vaccination is a potential solution to reduce seasonal influenza burden. We reviewed systematically the literature on "herd"/indirect protection from vaccinating children aged 6 months to 17 years against influenza. Of 30 studies included, 14 (including 1 cluster randomized controlled trial [cRCT]) used live attenuated influenza vaccine, 11 (7 cRCTs) used inactivated influenza vaccine, and 5 (1 cRCT) compared both vaccine types. Twenty of 30 studies reported statistically significant indirect protection effectiveness (IPE) with point estimates ranging from 4% to 66%. Meta-regression suggests that studies with high quality and/or sufficiently large sample size are more likely to report significant IPE. In meta-analyses of 6 cRCTs with full randomization (rated as moderate quality overall), significant IPE was found in 1 cRCT in closely connected communities where school-aged children were vaccinated: 60% (95% confidence interval [CI], 41%-72%; I2 = 0%; N = 2326) against laboratory-confirmed influenza, and 3 household cRCTs in which preschool-aged children were vaccinated: 22% (95% CI, 1%-38%; I2 = 0%; N = 1903) against acute respiratory infections or influenza-like illness. Significant IPE was also reported in a large-scale cRCT (N = 8510) that was not fully randomized, and 3 ecological studies (N > 10000) of moderate quality including 36% reduction in influenza-related mortality among the elderly in a Japanese school-based program. Data on IPE in other settings are heterogeneous and lacked power to draw a firm conclusion. The available evidence suggests that influenza vaccination of children confers indirect protection in some but not all settings. Robust, large-scaled studies are required to better quantify the indirect protection from vaccinating children for different settings/endpoints. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

What do letters to the editor publish about randomized controlled trials? A cross-sectional study

PubMed Central

2013-01-01

Background To identify published letters to the editor (LTE) written in response to randomized controlled trials (RCTs), determine the topics addressed in the letters, and to examine if these topics were affected by the characteristics and results of the RCTs. Methods Comparative cross-sectional study of a representative sample of RCTs from a set of high-impact medical journals (BMJ, Lancet, NEJM, JAMA, and Annals of Internal Medicine). RCTs and their published LTE were searched from these 5 journals in 2007. Data were collected on RCTs and their characteristics (author affiliation, funding source, intervention, and effect on the primary outcome) and the topics addressed in published LTE related to these RCTs. Analysis included chi-square and regression analysis (RCT characteristics) and thematic analysis (LTE topics). Results Of 334 identified RCTs, 175 trials had at least one LTE. Of these, 381 published LTE were identified. Most RCTs, tested drug interventions (68%), were funded by government (54%) or industry (33%), and described an intervention that had a positive impact on the primary outcome (62%). RCT authors were primarily affiliated with an academic centre (78%). Ninety percent of the 623 LTE topics concerned methodological issues regarding the analysis, intervention, and population in the RCT. There was a significant association between funding source and impact on outcomes (p = 0.002) or type of intervention tested (p = 0.001) in these trials. Clinical and “Other” LTE topics were more likely to be published in response to a government funded RCT (p = 0.005 and p = 0.033, respectively); no other comparisons were significant. Conclusions This study showed that most LTE are about methodological topics, but found little evidence to support that these topics are affected by the characteristics or results of the RCTs. The lack of association may be explained by editorial censorship as a small proportion of LTE that are submitted are actually published. PMID:24124753

What do letters to the editor publish about randomized controlled trials? A cross-sectional study.

PubMed

Kastner, Monika; Menon, Anita; Straus, Sharon E; Laupacis, Andreas

2013-10-14

To identify published letters to the editor (LTE) written in response to randomized controlled trials (RCTs), determine the topics addressed in the letters, and to examine if these topics were affected by the characteristics and results of the RCTs. Comparative cross-sectional study of a representative sample of RCTs from a set of high-impact medical journals (BMJ, Lancet, NEJM, JAMA, and Annals of Internal Medicine). RCTs and their published LTE were searched from these 5 journals in 2007. Data were collected on RCTs and their characteristics (author affiliation, funding source, intervention, and effect on the primary outcome) and the topics addressed in published LTE related to these RCTs. Analysis included chi-square and regression analysis (RCT characteristics) and thematic analysis (LTE topics). Of 334 identified RCTs, 175 trials had at least one LTE. Of these, 381 published LTE were identified. Most RCTs, tested drug interventions (68%), were funded by government (54%) or industry (33%), and described an intervention that had a positive impact on the primary outcome (62%). RCT authors were primarily affiliated with an academic centre (78%). Ninety percent of the 623 LTE topics concerned methodological issues regarding the analysis, intervention, and population in the RCT. There was a significant association between funding source and impact on outcomes (p = 0.002) or type of intervention tested (p = 0.001) in these trials. Clinical and "Other" LTE topics were more likely to be published in response to a government funded RCT (p = 0.005 and p = 0.033, respectively); no other comparisons were significant. This study showed that most LTE are about methodological topics, but found little evidence to support that these topics are affected by the characteristics or results of the RCTs. The lack of association may be explained by editorial censorship as a small proportion of LTE that are submitted are actually published.

Electrochemical determination of the glass transition temperature of thin polyelectrolyte brushes at solid-liquid interfaces by impedance spectroscopy.

PubMed

Alonso-García, Teodoro; Rodríguez-Presa, María José; Gervasi, Claudio; Moya, Sergio; Azzaroni, Omar

2013-07-16

Devising strategies to assess the glass transition temperature (Tg) of polyelectrolyte assemblies at solid-electrolyte interfaces is very important to understand and rationalize the temperature-dependent behavior of polyelectrolyte films in a wide range of settings. Despite the evolving perception of the importance of measuring Tg under aqueous conditions in thin film configurations, its straightforward measurement poses a challenging situation that still remains elusive in polymer and materials science. Here, we describe a new method based on electrochemical impedance spectroscopy (EIS) to estimate the glass transition temperature of planar polyelectrolyte brushes at solid-liquid interfaces. To measure Tg, the charge transfer resistance (Rct) of a redox probe diffusing through the polyelectrolyte brush was measured, and the temperature corresponding to the discontinuous change in Rct was identified as Tg. Furthermore, we demonstrate that impedance measurements not only facilitate the estimation of Tg but also enable a reliable evaluation of the transport properties of the polymeric interface, i.e., determination of diffusion coefficients, close to the thermal transition. We consider that this approach bridges the gap between electrochemistry and the traditional tools used in polymer science and offers new opportunities to characterize the thermal behavior of complex polymeric interfaces and macromolecular assemblies.

Personal health and consumer informatics. The impact of health oriented social media applications on health outcomes.

PubMed

Gibbons, M C

2013-01-01

The rapid evolution in the world-wide use of Social Media tools suggests the emergence of a global phenomenon that may have implications in the Personal Health and Consumer Health Informatics domains. However the impact of these tools on health outcomes is not known. The goal of this research was to review the randomized controlled trial (RCT) evidence of the impact of health oriented Social Media informatics tools on health outcomes. Evaluations of Social Media consumer health tools were systematically reviewed. Research was limited to studies published in the English language, published in Medline, published in the calendar year 2012 and limited to studies that utilized a RCT methodological design. Two high quality Randomized Controlled Trials among over 600 articles published in Medline were identified. These studies indicate that Social Media interventions may be able to significantly improve pain control among patients with chronic pain and enhance weight loss maintenance among individuals attempting to lose weight. Significantly more research needs to be done to confirm these early findings, evaluate additional health outcomes and further evaluate emerging health oriented Social Media interventions. Chronic pain and weight control have both socially oriented determinants. These studies suggest that understanding the social component of a disease may ultimately provide novel therapeutic targets and socio-clinical interventional strategies.

A cost effectiveness analysis of maintenance cognitive stimulation therapy (MCST) for people with dementia: examining the influence of cognitive ability and living arrangements.

PubMed

Brown, Heather; D'Amico, Francesco; Knapp, Martin; Orrell, Martin; Rehill, Amritpal; Vale, Luke; Robinson, Louise

2018-03-12

Identify if cost-effectiveness of Maintenance Cognitive Simulation Therapy (MCST) differs by type of living arrangement and cognitive ability of the person with dementia. Next, a value of information analysis is performed to inform decisions about future research. Incremental cost-effectiveness analysis applying seemingly unrelated regressions using data from a multicentre RCT of MCST versus treatment as usual in a population which had already received 7 weeks of CST for dementia (ISRCTN: 26286067). The findings from the cost-effectiveness analysis are used to inform a value of information analysis. The results are dependent upon how quality adjusted life years (QALYs) are measured. MCST might be cost-effective compared to standard treatment for those who live alone and those with higher levels of cognitive functioning. If a further RCT was to be conducted for this sub-group of the population, value of information analysis suggests a total sample of 48 complete cases for both sub-groups would be required for a two-arm trial. The expected net gain of conducting this future research is £920 million. Preliminary results suggest that MCST may be most cost-efficient for people with dementia who live alone and/or who have higher cognition. Future research in this area is needed.

An exercise trial for wheelchair users: Project Workout on Wheels

PubMed Central

Froehlich-Grobe, Katherine; Aaronson, Lauren S.; Washburn, Richard A.; Little, Todd D.; Lee, Jaehoon; Nary, Dorothy E.; VanSciver, Angela; Nesbitt, Jill; Norman, Sarah E.

2011-01-01

There is growing interest in promoting health for people with disabilities, yet evidence regarding community-based interventions is sparse. This paper describes the design details of a randomized controlled trial (RCT) that will test the effectiveness of a multi-component behaviorally-based, intervention to promote exercise adoption (over 6 months) and maintenance (up to one year) among wheelchair users and includes descriptive data on participant characteristics at baseline. Participants were randomly assigned to either a staff-supported intervention group or a self-guided comparison group. The primary study aim is to assess the effectiveness of the multi-component behaviorally-based intervention for promoting physical activity adoption and maintenance. The RCT will also assess the physical and psychosocial effects of the intervention and the complex interplay of factors that influence the effectiveness of the intervention. Therefore, the primary outcome derives from participant reports of weekly exercise (type, frequency, duration) over 52 weeks. Secondary outcomes collected on four occasions (baseline, 3 months, 6 months, 12 months) included physiological outcomes (VO2 peak, strength), disability-related outcomes (pain, fatigue, participation), and psychosocial outcomes (exercise self-efficacy, exercise barriers, quality of life, depression, mood). This study will provide evidence regarding the effectiveness of a multi-component behaviorally-based intervention for promoting exercise adoption among people with mobility impairments that necessitate wheelchair use. PMID:22101206

Comparing Treatment Effect Measurements in Narcolepsy: The Sustained Attention to Response Task, Epworth Sleepiness Scale and Maintenance of Wakefulness Test.

PubMed

van der Heide, Astrid; van Schie, Mojca K M; Lammers, Gert Jan; Dauvilliers, Yves; Arnulf, Isabelle; Mayer, Geert; Bassetti, Claudio L; Ding, Claire-Li; Lehert, Philippe; van Dijk, J Gert

2015-07-01

To validate the Sustained Attention to Response Task (SART) as a treatment effect measure in narcolepsy, and to compare the SART with the Maintenance of Wakefulness Test (MWT) and the Epworth Sleepiness Scale (ESS). Validation of treatment effect measurements within a randomized controlled trial (RCT). Ninety-five patients with narcolepsy with or without cataplexy. The RCT comprised a double-blind, parallel-group, multicenter trial comparing the effects of 8-w treatments with pitolisant (BF2.649), modafinil, or placebo (NCT01067222). MWT, ESS, and SART were administered at baseline and after an 8-w treatment period. The severity of excessive daytime sleepiness and cataplexy was also assessed using the Clinical Global Impression scale (CGI-C). The SART, MWT, and ESS all had good reliability, obtained for the SART and MWT using two to three sessions in 1 day. The ability to distinguish responders from nonresponders, classified using the CGI-C score, was high for all measures, with a high performance for the SART (r = 0.61) and the ESS (r = 0.54). The Sustained Attention to Response Task is a valid and easy-to-administer measure to assess treatment effects in narcolepsy, enhanced by combining it with the Epworth Sleepiness Scale. © 2015 Associated Professional Sleep Societies, LLC.

TargetCOPD: a pragmatic randomised controlled trial of targeted case finding for COPD versus routine practice in primary care: protocol.

PubMed

Jordan, Rachel E; Adab, Peymané; Jowett, Sue; Marsh, Jen L; Riley, Richard D; Enocson, Alexandra; Miller, Martin R; Cooper, Brendan G; Turner, Alice M; Ayres, Jon G; Cheng, Kar Keung; Jolly, Kate; Stockley, Robert A; Greenfield, Sheila; Siebert, Stanley; Daley, Amanda; Fitzmaurice, David A

2014-10-04

Many people with clinically significant chronic obstructive pulmonary disease (COPD) remain undiagnosed worldwide. There are a number of small studies which have examined possible methods of case finding through primary care, but no large RCTs that have adequately assessed the most cost-effective approach. In this study, using a cluster randomised controlled trial (RCT) in 56 general practices in the West Midlands, we plan to investigate the effectiveness and cost-effectiveness of a Targeted approach to case finding for COPD compared with routine practice. Using an individual patient RCT nested in the Targeted arm, we plan also to compare the effectiveness and cost-effectiveness of Active case finding using a postal questionnaire (with supplementary opportunistic questionnaires), and Opportunistic-only case finding during routine surgery consultations.All ever-smoking patients aged 40-79 years, without a current diagnosis of COPD and registered with participating practices will be eligible. Patients in the Targeted arm who report positive respiratory symptoms (chronic cough or phlegm, wheeze or dyspnoea) using a brief questionnaire will be invited for further spirometric assessment to ascertain whether they have COPD or not. Post-bronchodilator spirometry will be conducted to ATS standards using an Easy One spirometer by trained research assistants.The primary outcomes will be new cases of COPD and cost per new case identified, comparing targeted case finding with routine care, and two types of targeted case finding (active versus opportunistic). A multilevel logistic regression model will be used to model the probability of detecting a new case of COPD for each treatment arm, with clustering of patients (by practice and household) accounted for using a multi-level structure.A trial-based analysis will be undertaken using costs and outcomes collected during the trial. Secondary outcomes include the feasibility, efficiency, long-term cost-effectiveness, patient and primary care staff views of each approach. This will be the largest RCT of its kind, and should inform how best to identify undiagnosed patients with COPD in the UK and other similar healthcare systems. Sensitivity analyses will help local policy-makers decide which sub-groups of the population to target first. Current controlled trials ISRCTN14930255.

A comparison of cost effectiveness using data from randomized trials or actual clinical practice: selective cox-2 inhibitors as an example.

PubMed

van Staa, Tjeerd-Pieter; Leufkens, Hubert G; Zhang, Bill; Smeeth, Liam

2009-12-01

Data on absolute risks of outcomes and patterns of drug use in cost-effectiveness analyses are often based on randomised clinical trials (RCTs). The objective of this study was to evaluate the external validity of published cost-effectiveness studies by comparing the data used in these studies (typically based on RCTs) to observational data from actual clinical practice. Selective Cox-2 inhibitors (coxibs) were used as an example. The UK General Practice Research Database (GPRD) was used to estimate the exposure characteristics and individual probabilities of upper gastrointestinal (GI) events during current exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) or coxibs. A basic cost-effectiveness model was developed evaluating two alternative strategies: prescription of a conventional NSAID or coxib. Outcomes included upper GI events as recorded in GPRD and hospitalisation for upper GI events recorded in the national registry of hospitalisations (Hospital Episode Statistics) linked to GPRD. Prescription costs were based on the prescribed number of tables as recorded in GPRD and the 2006 cost data from the British National Formulary. The study population included over 1 million patients prescribed conventional NSAIDs or coxibs. Only a minority of patients used the drugs long-term and daily (34.5% of conventional NSAIDs and 44.2% of coxibs), whereas coxib RCTs required daily use for at least 6-9 months. The mean cost of preventing one upper GI event as recorded in GPRD was US$104k (ranging from US$64k with long-term daily use to US$182k with intermittent use) and US$298k for hospitalizations. The mean costs (for GPRD events) over calendar time were US$58k during 1990-1993 and US$174k during 2002-2005. Using RCT data rather than GPRD data for event probabilities, the mean cost was US$16k with the VIGOR RCT and US$20k with the CLASS RCT. The published cost-effectiveness analyses of coxibs lacked external validity, did not represent patients in actual clinical practice, and should not have been used to inform prescribing policies. External validity should be an explicit requirement for cost-effectiveness analyses.

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.

The effect of active video games by ethnicity, sex and fitness: subgroup analysis from a randomised controlled trial.

PubMed

Foley, Louise; Jiang, Yannan; Ni Mhurchu, Cliona; Jull, Andrew; Prapavessis, Harry; Rodgers, Anthony; Maddison, Ralph

2014-04-03

The prevention and treatment of childhood obesity is a key public health challenge. However, certain groups within populations have markedly different risk profiles for obesity and related health behaviours. Well-designed subgroup analysis can identify potential differential effects of obesity interventions, which may be important for reducing health inequalities. The study aim was to evaluate the consistency of the effects of active video games across important subgroups in a randomised controlled trial (RCT). A two-arm, parallel RCT was conducted in overweight or obese children (n=322; aged 10-14 years) to determine the effect of active video games on body composition. Statistically significant overall treatment effects favouring the intervention group were found for body mass index, body mass index z-score and percentage body fat at 24 weeks. For these outcomes, pre-specified subgroup analyses were conducted among important baseline demographic (ethnicity, sex) and prognostic (cardiovascular fitness) groups. No statistically significant interaction effects were found between the treatment and subgroup terms in the main regression model (p=0.36 to 0.93), indicating a consistent treatment effect across these groups. Preliminary evidence suggests an active video games intervention had a consistent positive effect on body composition among important subgroups. This may support the use of these games as a pragmatic public health intervention to displace sedentary behaviour with physical activity in young people.

Differential Diagnoses for Persistent Pain Following Root Canal Treatment: A Study in the National Dental PBRN

PubMed Central

Nixdorf, Donald R.; Law, Alan S.; John, Mike T.; Sobieh, Radwa M.; Kohli, Richie; Nguyen, Ruby H.N.

2015-01-01

Introduction Pain present 6 months following root canal treatment (RCT) may be either of odontogenic or nonodontogenic origin. This is importance because treatments and prognoses are different; therefore the aim of this study was to provide specific diagnoses of patients reporting pain 6 months after receiving initial orthograde RCT. Methods We enrolled patients from the Midwest region of an existing prospective observational study of pain after RCT. Pain at 6 months was defined as ≥1 day of pain and average pain intensity of at least 1/10 over the preceding month. An Endodontist and an Orofacial Pain practitioner independently performed clinical evaluations, which included periapical and cone-beam CT radiographs, to determine diagnoses. Results Thirty-eight out of the 354 eligible patients in the geographic area (11%) met the pain criteria, with 19 (50%) consenting to be clinically evaluated. As the sole reason for pain, 7 patients (37%) were given odontogenic diagnoses (4 involving the RCT tooth, 3 involving an adjacent tooth). Eight patients (42%) were given nonodontogenic pain diagnoses (7 from referred temporomandibular disorder (TMD) pain, 1 from persistent dentoalveolar pain disorder (PDAP)). Two patients (11%) had both odontogenic and nonodontogenic diagnoses, while 2 (11%) no longer fit the pain criteria at the time of the clinical evaluation. Conclusion Patients reporting “tooth” pain 6 months following RCT had a nonodontogenic pain diagnosis accounting for some of this pain, with TMD being the most frequent nonodonotgenic diagnosis. Dentists should have the necessary knowledge to differentiate between these diagnoses to adequately manage their patients. PMID:25732400

Evaluation of complications of root canal treatment performed by undergraduate dental students.

PubMed

AlRahabi, Mothanna K

2017-12-01

This study evaluated the technical quality of root canal treatment (RCT) and detected iatrogenic errors in an undergraduate dental clinic at the College of Dentistry, Taibah University, Saudi Arabia. Dental records of 280 patients who received RCT between 2013 and 2016 undertaken by dental students were investigated by retrospective chart review. Root canal obturation was evaluated on the basis of the length of obturation being ≤2 mm from the radiographic apex, with uniform radiodensity and good adaptation to root canal walls. Inadequate root canal obturation included cases containing procedural errors such as furcal perforation, ledge, canal transportation, strip perforation, root perforation, instrument separation, voids in the obturation, or underfilling or overfilling of the obturation. In 193 (68.9%) teeth, RCT was adequate and without procedural errors. However, in 87 (31.1%) teeth, RCT was inadequate and contained procedural errors. The frequency of procedural errors in the entire sample was 31.1% as follows: underfilling, 49.9%; overfilling, 24.1%; voids, 12.6%; broken instruments, 9.2%; apical perforation, 2.3%; and root canal transportation, 2.3%. There were no significant differences (p > 0.05) in the type or frequency of procedural errors between the fourth- and fifth-year students. Lower molars (43.1%) and upper incisors (19.2%) exhibited the highest and lowest frequencies of procedural errors, respectively. The technical quality of RCT performed by undergraduate dental students was classified as 'adequate' in 68.9% of the cases. There is a need for improvement in the training of students at the preclinical and clinical levels.

Relaxation training for anxiety: a ten-years systematic review with meta-analysis

PubMed Central

Manzoni, Gian Mauro; Pagnini, Francesco; Castelnuovo, Gianluca; Molinari, Enrico

2008-01-01

Background Relaxation training is a common treatment for anxiety problems. Lacking is a recent quantitative meta-analysis that enhances understanding of the variability and clinical significance of anxiety reduction outcomes after relaxation treatment. Methods All studies (1997–2007), both RCT, observational and without control group, evaluating the efficacy of relaxation training (Jacobson's progressive relaxation, autogenic training, applied relaxation and meditation) for anxiety problems and disorders were identified by comprehensive electronic searches with Pubmed, Psychinfo and Cochrane Registers, by checking references of relevant studies and of other reviews. Our primary outcome was anxiety measured with psychometric questionnaires. Meta-analysis was undertaken synthesizing the data from all trials, distinguishing within and between effect sizes. Results 27 studies qualified for the inclusion in the meta-analysis. As hypothesized, relaxation training showed a medium-large effect size in the treatment of anxiety. Cohen's d was .57 (95% CI: .52 to .68) in the within analysis and .51 (95% CI: .46 to .634) in the between group analysis. Efficacy was higher for meditation, among volunteers and for longer treatments. Implications and limitations are discussed. Conclusion The results show consistent and significant efficacy of relaxation training in reducing anxiety. This meta-analysis extends the existing literature through facilitation of a better understanding of the variability and clinical significance of anxiety improvement subsequent to relaxation training. PMID:18518981

Diversity and antioxidant activity of culturable endophytic fungi from alpine plants of Rhodiola crenulata, R. angusta, and R. sachalinensis.

PubMed

Cui, Jin-Long; Guo, Ting-Ting; Ren, Zhen-Xing; Zhang, Na-Sha; Wang, Meng-Liang

2015-01-01

Rhodiola spp. are rare and endangered alpine plants widely used as medicines and food additives by many civilizations since ancient times. Their main effective ingredients (such as salidroside and p-tyrosol) are praised to exhibit pharmacologic effects on high-altitude sickness and possess anti-aging and other adaptogenic capacities based on their antioxidant properties. In this study, 347 endophytic fungi were isolated from R. crenulata, R. angusta, and R. sachalinensis, and the molecular diversity and antioxidant activities of these fungi were investigated for the first time. These fungi were categorized into 180 morphotypes based on cultural characteristics, and their rRNA gene ITS sequences were analyzed by BLAST search in the GenBank database. Except for 12 unidentified fungi (6.67%), all others were affiliated to at least 57 genera in 20 orders of four phyla, namely, Ascomycota (88.89%), Basidiomycota (2.78%), Zygomycota (1.11%), and Glomeromycota (0.56%), which exhibited high abundance and diversity. Antioxidant assay showed that the DPPH radical-scavenging rates of 114 isolates (63.33%) were >50%, and those of five isolates (Rct45, Rct63, Rct64, Rac76, and Rsc57) were >90%. The EC50 values of five antioxidant assays suggested significant potential of these fungi on scavenging DPPH•, O2-•, and OH• radicals, as well as scavenging nitrite and chelating Fe2+, which showed preference and selection between endophytic fungi and their hosts. Further research also provided the first evidence that Rac12 could produce salidrosides and p-tyrosol. Results suggested that versatile endophytic fungi associated with Rhodiola known as antioxidants could be exploited as potential sources of novel antioxidant products.

Cognitive behavioural therapy for psychopathology in relatives of missing persons: study protocol for a pilot randomised controlled trial.

PubMed

Lenferink, Lonneke I M; Wessel, Ineke; de Keijser, Jos; Boelen, Paul A

2016-01-01

It is hypothesized that the grieving process of relatives of missing persons is complicated by having to deal with uncertainty about the fate of their loved one. We developed a cognitive behavioural therapy (CBT) with mindfulness that focuses on dealing with this uncertainty. In this article, we elucidate the rationale of a pilot randomised controlled trial (RCT) for testing the feasibility and potential effectiveness of this CBT for reducing symptoms of psychopathology in relatives of missing persons. A pilot RCT comparing participants of the CBT condition ( n  = 15) with waiting list controls ( n  = 15) will be executed. Individuals suffering from psychopathology related to the long-term disappearance of a loved one are eligible to participate. The treatment consists of eight individual sessions. Questionnaires tapping psychological constructs will be administered before, during, and after the treatment. The feasibility of the treatment will be evaluated using descriptive statistics (e.g., attrition rate). The primary analysis consists of a within-group analysis of changes in mean scores of persistent complex bereavement disorder from baseline to immediately post-treatment and follow-up (12 and 24 weeks post-treatment). A significant number of people experience the disappearance of a loved one. Surprisingly, an RCT to evaluate a treatment for psychopathology among relatives of missing persons has never been conducted. Knowledge about treatment effects is needed to improve treatment options for those in need of help. The strengths of this study are the development of a tailored treatment for relatives of missing persons and the use of a pilot design before exposing a large sample to a treatment that has yet to be evaluated. Future research could benefit from the results of this study. NTR4732 (The Netherlands National Trial Register (NTR)).

Accelerated Titration of Oxytocin in Nulliparous Women with Labour Dystocia: Results of the ACTION Pilot Randomized Controlled Trial.

PubMed

Dy, Jessica; Rainey, Jenna; Walker, Mark C; Fraser, William; Smith, Graeme N; White, Ruth Rennicks; Waddell, Patti; Janoudi, Ghayath; Corsi, Daniel J; Wei, Shu Qin

2018-06-01

The primary objective was to determine the feasibility of a large RCT assessing the effectiveness of an accelerated oxytocin titration (AOT) protocol compared with a standard gradual oxytocin titration (GOT) in reducing the risk of CS in nulliparous women diagnosed with dystocia in the first stage of labour. The secondary objective was to obtain preliminary data on the safety and efficacy of the foregoing AOT protocol. This was a multicentre, double-masked, parallel-group pilot RCT. This study was conducted in three Canadian birthing centres. A total of 79 term nulliparous women carrying a singleton pregnancy in spontaneous labour, with a diagnosis of labour dystocia, were randomized to receive either GOT (initial dose 2 mU/min with increments of 2 mU/min) or AOT (initial dose 4 mU/min with increments of 4 mU/min), in a 1:1 ratio. An intention-to-treat analysis was applied. A total of 252 women were screened and approached, 137 (54.4%) consented, and 79 (31.3%) were randomized. Overall protocol adherence was 76 of 79 (96.2%). Of the women randomized, 10 (25.6%) allocated to GOT had a CS compared with six (15.0%) allocated to AOT (Fisher exact test P = 0.27). This pilot study demonstrated that a large, multicentre RCT is not only feasible, but also necessary to assess the effectiveness and safety of an AOT protocol for labour augmentation with regard to CS rate and indicators of maternal and perinatal morbidities. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

Direct and indirect comparison meta-analysis of levetiracetam versus phenytoin or valproate for convulsive status epilepticus.

PubMed

Brigo, Francesco; Bragazzi, Nicola; Nardone, Raffaele; Trinka, Eugen

2016-11-01

The aim of this study was to conduct a meta-analysis of published studies to directly compare intravenous (IV) levetiracetam (LEV) with IV phenytoin (PHT) or IV valproate (VPA) as second-line treatment of status epilepticus (SE), to indirectly compare intravenous IV LEV with IV VPA using common reference-based indirect comparison meta-analysis, and to verify whether results of indirect comparisons are consistent with results of head-to-head randomized controlled trials (RCTs) directly comparing IV LEV with IV VPA. Random-effects Mantel-Haenszel meta-analyses to obtain odds ratios (ORs) for efficacy and safety of LEV versus VPA and LEV or VPA versus PHT were used. Adjusted indirect comparisons between LEV and VPA were used. Two RCTs comparing LEV with PHT (144 episodes of SE) and 3 RCTs comparing VPA with PHT (227 episodes of SE) were included. Direct comparisons showed no difference in clinical seizure cessation, neither between VPA and PHT (OR: 1.07; 95% CI: 0.57 to 2.03) nor between LEV and PHT (OR: 1.18; 95% CI: 0.50 to 2.79). Indirect comparisons showed no difference between LEV and VPA for clinical seizure cessation (OR: 1.16; 95% CI: 0.45 to 2.97). Results of indirect comparisons are consistent with results of a recent RCT directly comparing LEV with VPA. The absence of a statistically significant difference in direct and indirect comparisons is due to the lack of sufficient statistical power to detect a difference. Conducting a RCT that has not enough people to detect a clinically important difference or to estimate an effect with sufficient precision can be regarded a waste of time and resources and may raise several ethical concerns, especially in RCT on SE. Copyright © 2016 Elsevier Inc. All rights reserved.

Psychoeducational Psychotherapy and Omega-3 Supplementation Improve Co-Occurring Behavioral Problems in Youth with Depression: Results from a Pilot RCT.

PubMed

Young, Andrea S; Arnold, L Eugene; Wolfson, Hannah L; Fristad, Mary A

2017-07-01

This pilot randomized controlled trial (RCT) investigated benefits of omega-3 fatty acid supplementation and Individual-Family Psychoeducational Psychotherapy (PEP; a family-focused, cognitive-behavioral therapy) for behavior problems among youth with depression. Participants aged 7-14 with DSM-IV-TR depressive disorders (N = 72; 56.9 % male) were randomized to 1 of 4 treatment conditions: PEP + omega-3, PEP monotherapy (with pill placebo), omega-3 monotherapy, or placebo (without active intervention). At screen, baseline, and 2, 4, 6, 9, and 12 weeks post-baseline, parents completed the SNAP-IV, which assesses attention-deficit/hyperactivity disorder symptoms, oppositional defiant disorder symptoms, and overall behavior problems. At screen, baseline (randomization), 6 and 12 weeks, parents completed the Eyberg Child Behavior Inventory (ECBI), which includes Intensity and Problem scales for child behavior problems. Youth who had a completed SNAP-IV or ECBI for at least two assessments during treatment (n = 48 and 38, respectively) were included in analyses of the respective outcome. ClinicalTrials.gov.:NCT01341925. Linear mixed effects models indicated a significant effect of combined PEP + omega-3 on SNAP-IV Total (p = 0.022, d = 0.80) and Hyperactivity/Impulsivity trajectories (p = 0.008, d = 0.80), such that youth in the combined group saw greater behavioral improvement than those receiving only placebo. Similarly, youth in combined treatment had more favorable ECBI Intensity trajectories than youth who received no active treatment (p = 0.012, d = 1.07). Results from this pilot RCT suggest that combined PEP + omega-3 is a promising treatment for co-occurring behavior symptoms in youth with depression.

Lessons Learned From a Pilot RCT of Simultaneous Versus Delayed Initiation of Continuous Glucose Monitoring in Children and Adolescents With Type 1 Diabetes Starting Insulin Pump Therapy

PubMed Central

Olivier, Patricia; Huot, Celine; Richardson, Christine; Nakhla, Meranda; Romain, Judette

2014-01-01

Uncertainty remains about effectiveness of continuous glucose monitoring (CGM) in pediatric type 1 diabetes (T1D). Success with CGM is related to CGM adherence, which may relate to readiness to make the behavior changes required for effective use. We hypothesize that readiness for change will be greater at initiation of insulin pump therapy than in established pump users, and that this will predict CGM adherence. Our objective was to evaluate the feasibility of a randomized controlled trial (RCT) in children with established T1D comparing simultaneous pump and CGM initiation to standard pump therapy with delayed CGM initiation. We randomized participants to simultaneous pump and CGM initiation or to standard pump therapy with the option of adding CGM 4 months later. CGM adherence was tracked via web-based download and readiness for change assessed with the SOCRATES questionnaire. Of 41 eligible children, 20 agreed to participate; 15 subjects completed the study (7 males; baseline age 11.8 ± 4.0 years; T1D duration 2.7 ± 2.7 years; mean A1C 8.2 ± 0.8%). Six of 8 simultaneous group subjects used CGM > 60% of the time for 4 months compared to 1 of 7 delayed group subjects (P = .02). Using SOCRATES, we could assign 87-100% of subjects to a single motivation stage at baseline and 4 months. This pilot study demonstrates the feasibility of randomizing pump naïve children and adolescents with established T1D to simultaneous pump and CGM initiation versus standard pump therapy with delayed CGM initiation. Lessons from this pilot study were used to inform development of a full-scale multicenter RCT. PMID:24876616

A comparative pilot study of second-generation antipsychotics in children and adolescents with schizophrenia-spectrum disorders.

PubMed

Jensen, Jonathan B; Kumra, Sanjiv; Leitten, Willa; Oberstar, Joel; Anjum, Afshan; White, Tonya; Wozniak, Jeffrey; Lee, Susanne S; Schulz, S Charles

2008-08-01

There is a limited evidence base to guide treatment of children and adolescents with nonaffective psychoses because few comparative studies of first-line second-generation antipsychotics (SGAs) have been undertaken. To plan the design of a subsequent randomized controlled trial (RCT), the authors conducted this pilot study to demonstrate the feasibility of the treatment and measurement protocols. Thirty children and adolescents (20 males, 10 females), ages 10-18 years, who met unmodified Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for a schizophrenia-spectrum disorder (schizophrenia, schizoaffective, schizophreniform, psychotic disorder not otherwise specified) were randomized to receive 12 weeks of open-label, flexibly dosed treatment with either risperidone (mean [standard deviation, SD] dose = 3.4 mg [1.5]), olanzapine (mean [SD] dose = 14.0 mg [4.6]) or quetiapine (mean [SD] dose = 611 mg [253.4]). Twenty one (70%) of 30 subjects completed the study. There was no overall statistically significant difference with regard to reduction in Positive and Negative Syndrome Scale (PANSS) total scores in treatment efficacy observed (F((2,24)) = 3.13, p = 0.06). However, the possibility of a large differential treatment effect with regard to change in PANSS total scores favoring risperidone relative to quetiapine (risperidone vs. quetiapine, d = 1.10 [95% confidence interval, CI, 0.09-2.01]) was suggested by the point estimate. These preliminary data, viewed together with the extant literature, suggest that a future larger RCT with only two treatment arms may be warranted to establish whether there is a clinically significant differential treatment effect between risperidone and quetiapine for children and adolescents with nonaffective psychoses. Additional challenges and considerations for mounting a larger RCT are explored.

Promoting physical activity for children and adolescents in low- and middle-income countries: An umbrella systematic review: A review on promoting physical activity in LMIC.

PubMed

Barbosa Filho, Valter Cordeiro; Minatto, Giseli; Mota, Jorge; Silva, Kelly Samara; de Campos, Wagner; Lopes, Adair da Silva

2016-07-01

It is unknown how much previous reviews on promoting physical activity (PA) for children and adolescents (aged 6-18years) take into account studies from low- and middle-income countries (LMIC, based on the World Bank definition) and the level of evidence of the effect of PA interventions in this population. This study aims to answer such questions using an umbrella systematic review approach. We searched for peer-reviewed systematic reviews and original studies in eight electronic databases, screening of reference lists and expert contacts. Information in systematic reviews on PA interventions for children and adolescents from LMIC was discussed. Original studies on PA interventions (randomized-controlled trials [RCT], cluster-RCT and non-RCT) with children and adolescents from LMIC were eligible. We assessed the methodological quality in all studies, and the evidence level of effect on PA in intervention studies. Fifty systematic reviews (nine meta-analyses) and 25 original studies (20 different interventions) met eligibility criteria. Only 3.1% of mentioned studies in previous reviews were from LMIC. Strong and LMIC-specific evidence was found that school-based, multicomponent, and short-term (up to six months) interventions, focused on adolescents primarily (aged 13-18years), can promote PA in children and adolescents from LMIC. Other intervention characteristics had inconclusive evidence due to the low number of studies, low methodological quality, and/or small sample size. A minimal part of PA interventions mentioned in previous reviews are from LMIC. Our LMIC-specific analyses showed priorities of implementation and practical implication that can be used in public policies for PA promotion in LMIC. Copyright © 2016 Elsevier Inc. All rights reserved.

Personality and medication non-adherence among older adults enrolled in a six-year trial

PubMed Central

Jerant, Anthony; Chapman, Benjamin; Duberstein, Paul; Robbins, John; Franks, Peter

2011-01-01

Objectives Personality factors parsimoniously capture the variation in dispositional characteristics that affect behaviours, but their value in predicting medication non-adherence is unclear. We investigated the relationship between five-factor model personality factors (Conscientiousness, Neuroticism, Agreeableness, Extraversion, and Openness) and medication non-adherence among older participants during a six-year randomized placebo-controlled trial (RCT). Design Observational cohort data from 771 subjects aged ≥72 years enrolled in the Ginkgo Evaluation of Memory study, a RCT of Ginkgo biloba for prevention of dementia. Methods Random effects logistic regression analyses examined effects of NEO Five-Factor Inventory scores on medication non-adherence, determined via pill counts every 6 months (median follow-up 6.1 years) and defined as taking <80% of prescribed pills. Analyses adjusted for covariates linked with non-adherence in prior studies. Results Each 5 year increment in participant age was associated with a 6.7% greater probability of non-adherence (95% confidence interval, CI [2.4, 11.0]). Neuroticism was the only personality factor associated with non-adherence: a 1 SD increase was associated with a 3.8% increase in the probability of non-adherence (95% CI [0.4, 7.2]). Lower cognitive function was also associated with non-adherence: a 1 SD decrease in mental status exam score was associated with a 3.0% increase in the probability of non-adherence (95% CI [0.2, 5.9]). Conclusions Neuroticism was associated with medication non-adherence over 6 years of follow-up in a large sample of older RCT participants. Personality measurement in clinical and research settings might help to identify and guide interventions for older adults at risk for medication non-adherence. PMID:21226789

Rationale, design, and baseline characteristics of the Acetylcystein for Contrast-Induced nephropaThy (ACT) Trial: a pragmatic randomized controlled trial to evaluate the efficacy of acetylcysteine for the prevention of contrast-induced nephropathy

PubMed Central

2009-01-01

Background Aceltylcysteine has been evaluated in several small trials as a means of reducing the risk of contrast-induced nephropathy (CIN), however systematic reviews of these studies do not provide conclusive answers. Therefore, a large randomized controlled trial (RCT) is needed to provide a reliable answer as to whether acetylcysteine is effective in decreasing the risk of CIN in high-risk patients undergoing angiographic procedures. Methods ACT is a RCT of acetylcysteine versus placebo in 2,300 patients at-risk for CIN undergoing an intravascular angiographic procedure. The randomization list will be concealed. Participants, health care staff, investigators and outcome assessors will be blinded to whether patients receive acetylcysteine or placebo. All analysis will follow the intention-to-treat principle. The study drugs (acetylcysteine 1200 mg or placebo) will be administered orally twice daily for two doses before and two doses after the procedure. The primary outcome is the occurrence of CIN, defined as a 25% elevation of serum creatinine above baseline between 48 and 96 hours after angiography. Discussion The first patient entered the trial on September, 2008. Up to April 7, 2009, 810 patients had been included in 35 centers. The mean age was 69 (Standard deviation: 10), 18% had a baseline serum creatinine >1.5 mg/dL, 57% were diabetics and 13% had a history of heart failure. The ongoing ACT Trial is the largest multicentre RCT that will determine whether acetylcysteine is effective in decreasing the risk of CIN in patients at risk undergoing angiography. Trial registration Clinicaltrials.gov NCT00736866 PMID:19497091

Recruitment and enrollment of African Americans into health promoting programs: the effects of health promoting programs on cardiovascular disease risk study.

PubMed

Okhomina, Victoria I; Seals, Samantha R; Marshall, Gailen D

2018-04-03

Randomized controlled trials (RCT) often employ multiple recruitment methods to attract participants, however, special care must be taken to be inclusive of under-represented populations. We examine how recruiting from an existing observational study affected the recruitment of African Americans into a RCT that included yoga-based interventions. In particular, we report the recruitment success of The Effects of Health Promoting Programs (HPP) on Cardiovascular Disease Risk (NCT02019953), the first yoga-based clinical trial to focus only on African Americans. To recruit participants, a multifaceted recruitment strategy was implemented exclusively in the Jackson Heart Study (JHS) cohort. The HPP recruited from the JHS cohort using direct mailings, signs and flyers placed around JHS study facilities, and through JHS annual follow-up interviews. Enrollment into HPP was open to all active JHS participants that were eligible to return for the third clinic exam (n = 4644). The target sample size was 375 JHS participants over a 24 month recruitment and enrollment period. From the active members of the JHS cohort, 503 were pre-screened for eligibility in HPP. More than 90% of those pre-screened were provisionally eligible for the study. The enrollment goal of 375 was completed after a 16-month enrollment period with over 25% (n = 97) of the required sample size enrolling during the second month of recruitment. The findings show that participants in observational studies can be successfully recruited into RCT. Observational studies provide researchers with a well-defined population that may be of interest when designing clinical trials. This is particularly useful in the recruitment of a high-risk, traditionally underrepresented populations for non-pharmacological clinical trials where traditional recruitment methods may prolong enrollment periods and extend study budgets.

Methods for a Rapid Systematic Review and Metaanalysis in Evaluating Selective Serotonin Reuptake Inhibitors for Premature Ejaculation

ERIC Educational Resources Information Center

Martyn-St. James, Marrissa; Cooper, Katy; Kaltenthaler, Eva

2017-01-01

The aim of this study was to evaluate a rapid systematic review method in which randomised controlled trial (RCT) data was extracted from existing reviews and subsequent RCTs. The method enabled: identification of RCTs not included by existing reviews; cross-checking RCT data for consistency where there was more than one review; double data…

Thinking outside the Randomized Controlled Trials Experimental Box: Strategies for Enhancing Credibility and Social Justice

ERIC Educational Resources Information Center

Hesse-Biber, Sharlene

2013-01-01

Some evaluators employ randomized controlled trials (RCTs) as the gold standard of evidence-based practice (EBP). Critics of RCT designs argue that RCTs do not include the complexity of program participants' experiences or clinical expertise, and couple this with criticisms that it is difficult to transfer RCT findings from the laboratory to…

Statistical Theory for the "RCT-YES" Software: Design-Based Causal Inference for RCTs. NCEE 2015-4011

ERIC Educational Resources Information Center

Schochet, Peter Z.

2015-01-01

This report presents the statistical theory underlying the "RCT-YES" software that estimates and reports impacts for RCTs for a wide range of designs used in social policy research. The report discusses a unified, non-parametric design-based approach for impact estimation using the building blocks of the Neyman-Rubin-Holland causal…

Inhibition of PDGFR signaling prevents muscular fatty infiltration after rotator cuff tear in mice.

PubMed

Shirasawa, Hideyuki; Matsumura, Noboru; Shimoda, Masayuki; Oki, Satoshi; Yoda, Masaki; Tohmonda, Takahide; Kanai, Yae; Matsumoto, Morio; Nakamura, Masaya; Horiuchi, Keisuke

2017-01-31

Fatty infiltration in muscle is often observed in patients with sizable rotator cuff tear (RCT) and is thought to be an irreversible event that significantly compromises muscle plasticity and contraction strength. These changes in the mechanical properties of the affected muscle render surgical repair of RCT highly formidable. Therefore, it is important to learn more about the pathology of fatty infiltration to prevent this undesired condition. In the present study, we aimed to generate a mouse model that can reliably recapitulate some of the important characteristics of muscular fatty infiltration after RCT in humans. We found that fatty infiltration can be efficiently induced by a combination of the following procedures: denervation of the suprascapular nerve, transection of the rotator cuff tendon, and resection of the humeral head. Using this model, we found that platelet-derived growth factor receptor-α (PDGFRα)-positive mesenchymal stem cells are induced after this intervention and that inhibition of PDGFR signaling by imatinib treatment can significantly suppress fatty infiltration. Taken together, the present study presents a reliable fatty infiltration mouse model and suggests a key role for PDGFRα-positive mesenchymal stem cells in the process of fatty infiltration after RCT in humans.

Inhibition of PDGFR signaling prevents muscular fatty infiltration after rotator cuff tear in mice

PubMed Central

Shirasawa, Hideyuki; Matsumura, Noboru; Shimoda, Masayuki; Oki, Satoshi; Yoda, Masaki; Tohmonda, Takahide; Kanai, Yae; Matsumoto, Morio; Nakamura, Masaya; Horiuchi, Keisuke

2017-01-01

Fatty infiltration in muscle is often observed in patients with sizable rotator cuff tear (RCT) and is thought to be an irreversible event that significantly compromises muscle plasticity and contraction strength. These changes in the mechanical properties of the affected muscle render surgical repair of RCT highly formidable. Therefore, it is important to learn more about the pathology of fatty infiltration to prevent this undesired condition. In the present study, we aimed to generate a mouse model that can reliably recapitulate some of the important characteristics of muscular fatty infiltration after RCT in humans. We found that fatty infiltration can be efficiently induced by a combination of the following procedures: denervation of the suprascapular nerve, transection of the rotator cuff tendon, and resection of the humeral head. Using this model, we found that platelet-derived growth factor receptor-α (PDGFRα)-positive mesenchymal stem cells are induced after this intervention and that inhibition of PDGFR signaling by imatinib treatment can significantly suppress fatty infiltration. Taken together, the present study presents a reliable fatty infiltration mouse model and suggests a key role for PDGFRα-positive mesenchymal stem cells in the process of fatty infiltration after RCT in humans. PMID:28139720

Feasibility study of a single-blind randomised controlled trial of an occupational therapy intervention.

PubMed

Gantschnig, Brigitte E; Nilsson, Ingeborg; Fisher, Anne G; Künzle, Christoph; Page, Julie

2016-07-01

Several factors facilitate or hinder efficacy research in occupational therapy. Strategies are needed, therefore, to support the successful implementation of trials. To assess the feasibility of conducting a randomised controlled trial (RCT). The main feasibility objectives of this study were to assess the process, resources, management, and scientific basis of a trial RCT. A total of 10 occupational therapists, between the ages of 30 and 55 (M 43.4; SD 8.3) with seven to 26 years' (M 14.3; SD 6.1) experience, participated in this study. Qualitative data collected included minutes of meetings, reports, and field notes. The data were analysed based on the principles of content analysis, using feasibility objectives as the main categories. Data analysis revealed strengths in relation to retention and inclusion criteria of participants, the study protocol, study organisation, and the competence of researchers. Weaknesses were found related to recruitment, randomisation, data collection, time for training and communication, commitment, and design. The findings indicated that there are several factors which had a considerable impact on the implementation of an RCT in practice. However, it was useful to assess methods and procedures of the trial RCT as a basis to refine research plans.

Outcomes of online support and resources for cancer survivors: a systematic literature review.

PubMed

Hong, Yan; Peña-Purcell, Ninfa C; Ory, Marcia G

2012-03-01

This study aims to review systematically the available literature on health outcomes of online cancer support and resources. We searched major databases with the following selection criteria: (1) empirical study on use of online support or resources by cancer survivors, (2) reporting effects or outcomes of online support or resources, (3) focusing on adult cancer survivors, and (4) peer-reviewed articles published by 2010. A total of 24 studies (37 articles) were included in the review. Most studies were focused on breast cancer survivors and had small sample sizes. Fifteen studies employed a cross-sectional design including eight qualitative studies. Only five studies used pre-post design, and four employed RCT design. The outcome measures have focused on psychosocial effects; most studies reported positive effects, although none of the RCT studies reported significant outcomes. Existing studies of online cancer support and resources have demonstrated preliminary but inconclusive evidence for positive outcomes. We call for additional studies with rigorous study designs and the inclusion of more diverse participants and cancer conditions. Connecting diverse cancer survivors to culturally appropriate, evidence-based online support and resources is a strategy to enhance health outcomes. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Bayesian methods including nonrandomized study data increased the efficiency of postlaunch RCTs.

PubMed

Schmidt, Amand F; Klugkist, Irene; Klungel, Olaf H; Nielen, Mirjam; de Boer, Anthonius; Hoes, Arno W; Groenwold, Rolf H H

2015-04-01

Findings from nonrandomized studies on safety or efficacy of treatment in patient subgroups may trigger postlaunch randomized clinical trials (RCTs). In the analysis of such RCTs, results from nonrandomized studies are typically ignored. This study explores the trade-off between bias and power of Bayesian RCT analysis incorporating information from nonrandomized studies. A simulation study was conducted to compare frequentist with Bayesian analyses using noninformative and informative priors in their ability to detect interaction effects. In simulated subgroups, the effect of a hypothetical treatment differed between subgroups (odds ratio 1.00 vs. 2.33). Simulations varied in sample size, proportions of the subgroups, and specification of the priors. As expected, the results for the informative Bayesian analyses were more biased than those from the noninformative Bayesian analysis or frequentist analysis. However, because of a reduction in posterior variance, informative Bayesian analyses were generally more powerful to detect an effect. In scenarios where the informative priors were in the opposite direction of the RCT data, type 1 error rates could be 100% and power 0%. Bayesian methods incorporating data from nonrandomized studies can meaningfully increase power of interaction tests in postlaunch RCTs. Copyright © 2015 Elsevier Inc. All rights reserved.

The effectiveness of self-help mindfulness-based cognitive therapy in a student sample: a randomised controlled trial.

PubMed

Lever Taylor, Billie; Strauss, Clara; Cavanagh, Kate; Jones, Fergal

2014-12-01

Mindfulness-based cognitive therapy (MBCT) involves approximately twenty hours of therapist contact time and is not universally available. MBCT self-help (MBCT-SH) may widen access but little is known about its effectiveness. This paper presents a randomised controlled trial (RCT) of MBCT-SH for students. Eighty students were randomly assigned to an eight-week MBCT-SH condition or a wait-list control. ANOVAs showed significant group by time interactions in favour of MBCT-SH on measures of depression, anxiety, stress, satisfaction with life, mindfulness and self-compassion. Post-intervention between-group effect sizes ranged from Cohen's d = 0.22 to 1.07. Engagement with MBCT-SH was high: participants engaged in mindfulness practice a median of two to three times a week and 85% read at least half the intervention book. Only 5% of participants dropped out. This is the first published RCT of MBCT-SH and benefits were found relative to a control group. MBCT-SH has the potential to be a low-cost, readily available and highly acceptable intervention. Future research should include an active control condition and explore whether findings extend to clinical populations. Copyright © 2014 Elsevier Ltd. All rights reserved.

RCT of a Psychological Intervention for Patients with Cancer: I. Mechanisms of Change

ERIC Educational Resources Information Center

Andersen, Barbara L.; Shelby, Rebecca A.; Golden-Kreutz, Deanna M.

2007-01-01

Little is known about the therapeutic processes contributing to efficacy of psychological interventions for patients with cancer. Data from a randomized clinical trial yielding robust biobehavioral and health effects (B. L. Andersen et al., 2004, 2007) were used to examine associations between process variables, treatment utilization, and…

Secular Trends and Smoke-Free Policy Development in Rural Kentucky

ERIC Educational Resources Information Center

Fallin, Amanda; Parker, Lindsay; Lindgreen, Janine; Riker, Carol; Kercsmar, Sarah; Hahn, Ellen J.

2011-01-01

Secondhand smoke (SHS) exposure causes cardiovascular disease, lung cancer and pulmonary disorders. Smoke-free policies are the most effective way to prevent exposure to SHS. A 5-year community-based randomized control trial (RCT) is in progress to assess factors associated with smoke-free policy development in rural communities. Considering…

EEG Neurofeedback for ADHD: Double-Blind Sham-Controlled Randomized Pilot Feasibility Trial

ERIC Educational Resources Information Center

Arnold, L. Eugene; Lofthouse, Nicholas; Hersch, Sarah; Pan, Xueliang; Hurt, Elizabeth; Bates, Bethany; Kassouf, Kathleen; Moone, Stacey; Grantier, Cara

2013-01-01

Objective: Preparing for a definitive randomized clinical trial (RCT) of neurofeedback (NF) for ADHD, this pilot trial explored feasibility of a double-blind, sham-controlled design and adherence/palatability/relative effect of two versus three treatments/week. Method: Unmedicated 6- to 12-year-olds with "Diagnostic and Statistical Manual of…

Linking Implementation Fidelity to Impacts in an RCT

ERIC Educational Resources Information Center

Unlu, Fatih; Bozzi, Laurie; Layzer, Carolyn; Smith, Arthur; Price, Cristofer; Hurtig, Richard

2013-01-01

In experimental studies, researchers are often interested in secondary research questions that explore important aspects of main findings, such as whether or not program effects vary according to the level of fidelity in which the program has been implemented; or according to the dosage received by individuals participated in the program. In this…

Increasing Young Children's Contact with Print during Shared Reading: Longitudinal Effects on Literacy Achievement

ERIC Educational Resources Information Center

Piasta, Shayne B.; Justice, Laura M.; McGinty, Anita S.; Kaderavek, Joan N.

2012-01-01

Longitudinal results for a randomized-controlled trial (RCT) assessing the impact of increasing preschoolers' attention to print during reading are reported. Four-year-old children (N = 550) in 85 classrooms experienced a 30-week shared reading program implemented by their teachers. Children in experimental classrooms experienced shared-book…

Summary Protocol for a Multi-Centre Randomised Controlled Trial of Enteral Lactoferrin Supplementation in Newborn Very Preterm Infants (ELFIN).

PubMed

2018-06-11

In a multi-centre randomised controlled trial (RCT), we are assessing whether giving very preterm (i.e., born at < 32 weeks' gestation) infants prophylactic enteral bovine lactoferrin supplementation (150 mg/kg/day) from shortly after birth until 34 weeks' post-menstrual age reduces the incidence of late-onset invasive infection (primary outcome), all-cause mortality, bronchopulmonary dysplasia, necrotising enterocolitis, retinopathy of prematurity, and the duration of antibiotic exposure, intensive care, and hospital admission. The trial is recruiting 2,200 participants from 37 neonatal care centres in the UK over 4 years. We will undertake an economic evaluation within the RCT to evaluate cost-effectiveness and provide an estimate of incremental costs for differences in the pre-specified outcomes in primary and subgroup analyses. If a statistically significant and clinically important effect on the primary outcome is detected, we will seek further funding and approval to assess the impact of enteral lactoferrin supplementation on rates of adverse neuro-developmental outcomes in the participating infants when they are 5 years old. © 2018 S. Karger AG, Basel.

Game-based digital interventions for depression therapy: a systematic review and meta-analysis.

PubMed

Li, Jinhui; Theng, Yin-Leng; Foo, Schubert

2014-08-01

The aim of this study was to review the existing literature on game-based digital interventions for depression systematically and examine their effectiveness through a meta-analysis of randomized controlled trials (RCTs). Database searching was conducted using specific search terms and inclusion criteria. A standard meta-analysis was also conducted of available RCT studies with a random effects model. The standard mean difference (Cohen's d) was used to calculate the effect size of each study. Nineteen studies were included in the review, and 10 RCTs (eight studies) were included in the meta-analysis. Four types of game interventions-psycho-education and training, virtual reality exposure therapy, exercising, and entertainment-were identified, with various types of support delivered and populations targeted. The meta-analysis revealed a moderate effect size of the game interventions for depression therapy at posttreatment (d=-0.47 [95% CI -0.69 to -0.24]). A subgroup analysis showed that interventions based on psycho-education and training had a smaller effect than those based on the other forms, and that self-help interventions yielded better outcomes than supported interventions. A higher effect was achieved when a waiting list was used as the control. The review and meta-analysis support the effectiveness of game-based digital interventions for depression. More large-scale, high-quality RCT studies with sufficient long-term data for treatment evaluation are needed.

Game-Based Digital Interventions for Depression Therapy: A Systematic Review and Meta-Analysis

PubMed Central

Theng, Yin-Leng; Foo, Schubert

2014-01-01

Abstract The aim of this study was to review the existing literature on game-based digital interventions for depression systematically and examine their effectiveness through a meta-analysis of randomized controlled trials (RCTs). Database searching was conducted using specific search terms and inclusion criteria. A standard meta-analysis was also conducted of available RCT studies with a random effects model. The standard mean difference (Cohen's d) was used to calculate the effect size of each study. Nineteen studies were included in the review, and 10 RCTs (eight studies) were included in the meta-analysis. Four types of game interventions—psycho-education and training, virtual reality exposure therapy, exercising, and entertainment—were identified, with various types of support delivered and populations targeted. The meta-analysis revealed a moderate effect size of the game interventions for depression therapy at posttreatment (d=−0.47 [95% CI −0.69 to −0.24]). A subgroup analysis showed that interventions based on psycho-education and training had a smaller effect than those based on the other forms, and that self-help interventions yielded better outcomes than supported interventions. A higher effect was achieved when a waiting list was used as the control. The review and meta-analysis support the effectiveness of game-based digital interventions for depression. More large-scale, high-quality RCT studies with sufficient long-term data for treatment evaluation are needed. PMID:24810933

RCT: Module 2.04, Dosimetry, Course 8769

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

Hillmer, Kurt T.

This course will introduce the types of instruments used to measure external and internal radiation to people. Dosimetry is the quantitative assessment of radiation received by the human body. Several types of dosimeters are used worldwide. This information is valuable to all radiological control personnel because dosimeters are the only direct method to measure and document personnel radiation exposure and ensure regulatory compliance with applicable limits. This course will cover dosimetry terms, Department of Energy (DOE) limits, Los Alamos National Laboratory (LANL) administrative guidelines, thermoluminescent dosimeters (TLDs), LANL dosimetry, and bioassay assessment methods. This course will prepare the student withmore » the skills necessary for radiological control technician (RCT) qualification by passing quizzes, tests, and the RCT Comprehensive Phase 1, Unit 2 Examination (TEST 27566) and providing in-thefield skills.« less

A New Model of Reverse Cholesterol Transport: EnTICEing Strategies to Stimulate Intestinal Cholesterol Excretion

PubMed Central

Temel, Ryan E.; Brown, J. Mark

2015-01-01

Cardiovascular disease (CVD) remains the largest cause of mortality in most developed countries. Although recent failed clinical trials and Mendelian randomization studies have called into question the high density lipoprotein (HDL) hypothesis, it remains well accepted that stimulating the process of reverse cholesterol transport (RCT) can prevent or even regress atherosclerosis. The prevailing model for RCT is that cholesterol from the artery wall must be delivered to the liver where it is secreted into bile before leaving the body through fecal excretion. However, many studies have demonstrated that RCT can proceed through a non-biliary pathway known as transintestinal cholesterol excretion (TICE). The goal of this review is to discuss the current state of knowledge of the TICE pathway, with emphasis on points of therapeutic intervention. PMID:25930707

General physical health advice for people with serious mental illness.

PubMed

Tosh, Graeme; Clifton, Andrew; Bachner, Mick

2011-02-16

There is currently much focus on provision of general physical health advice to people with serious mental illness and there has been increasing pressure for services to take responsibility for providing this. To assess the effects of general physical health advice as a means of reducing morbidity, mortality and improving or maintaining quality of life in people with serious mental illness. We searched the Cochrane Schizophrenia Group Trials Register (November 2009) which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. All randomised clinical trials focusing on general physical health advice. We extracted data independently. For binary outcomes we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data we estimated mean difference (MD) between groups and its 95% CI. We employed a random-effects model for analyses. For the comparison of physical healthcare advice versus standard care we identified five studies (total n = 884) of limited quality. For measures of quality of life one trial found no difference (n = 54, 1 RCT, MD Lehman scale 0.00 CI -0.67 to 0.67) but another did (n = 407, 1 RCT, MD Quality of Life Medical Outcomes Scale - mental component 3.7 CI 1.7 to 5.6). There was no difference between groups for the outcome of death (n = 407, 1 RCT, RR 1.3 CI 0.3 to 6.0), for the outcome of uptake of ill-health prevention services, one study found percentages significantly greater in the advice group (n = 363, 1 RCT, MD 36.9 CI 33.1 to 40.7). Economic data were equivocal. Attrition was large (> 30%) but similar for both groups (n = 884, 5 RCTs, RR 1.18 CI 0.97 to 1.43). Comparisons of one type of physical healthcare advice with another were grossly underpowered and equivocal. General physical health could lead to people with serious mental illness accessing more health services which, in turn, could mean they see longer term benefits such as reduced mortality or morbidity. On the other hand it is possible clinicians are expending much effort, time and financial expenditure on giving ineffective advice. This is an important area for good research reporting outcome of interest to carers and people with serious illnesses as well as researchers and fundholders.