The importance of preservation of the ethical principle of equipoise in the design of clinical trials: relative impact of the methodological quality domains on the treatment effect in randomized controlled trials.

PubMed

Djulbegovic, Benjamin; Cantor, Alan; Clarke, Mike

2003-01-01

Previous research has identified methodological problems in the design and conduct of randomized trials that could, if left unaddressed, lead to biased results. In this report we discuss one such problem, inadequate control intervention, and argue that it can be by far the most important design characteristic of randomized trials in overestimating the effect of new treatments. Current guidelines for the design and reporting of randomized trials, such as the Consolidated Standards of Reporting Trials (CONSORT) statement, do not address the choice of the comparator intervention. We argue that an adequate control intervention can be selected if people designing a trial explicitly take into consideration the ethical principle of equipoise, also known as "the uncertainty principle."

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

PubMed Central

2010-01-01

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

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

PubMed Central

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

2007-01-01

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

Contribution of Transcranial Direct Current Stimulation on Inhibitory Control to Assess the Neurobiological Aspects of Attention Deficit Hyperactivity Disorder: Randomized Controlled Trial

PubMed Central

Baptista, Abrahão Fontes; de Sena, Eduardo Pondé

2015-01-01

Background The applicability of transcranial direct current stimulation (tDCS) in individuals with attention deficit hyperactivity disorder (ADHD) has not yet been investigated. This low-cost, non-invasive, and safe technique optimized to modulate the inhibitory response might be a useful treatment option for those affected by this condition. Objective The aim of this single center, parallel, randomized, double-blinded, sham-controlled trial is to investigate the efficacy of transcranial direct current stimulation over the prefrontal cortex on the modulation of inhibitory control in adults with attention deficit hyperactivity disorder. Methods A total of 60 individuals will be divided into 2 groups by block randomization to receive active or sham stimulation. Anodal stimulation over the left dorsolateral prefrontal cortex will be applied at 1 mA during a single 20-minute session. Before and after interventions, subjects will perform 2 go/no go tasks and the brain electrical activity will be recorded by electroencephalogram (EEG) with 32 channels, according to the 10-20 international EEG system. Results The trial began in May 2013 and we are currently performing the statistical analysis for the secondary outcomes. Conclusions The findings from this study will provide preliminary results about the role of prefrontal cortex activation through tDCS on ADHD patients. Trial Registration Clinicaltrials.gov NCT01968512; http://clinicaltrials.gov/ct2/show/NCT01968512 (Archived by WebCite at www.webcitation.org/6YMSW2tkD). PMID:25986784

Object-Based Control of Attention Is Sensitive to Recent Experience

ERIC Educational Resources Information Center

Lee, Hyunkyu; Mozer, Michael C.; Kramer, Arthur F.; Vecera, Shaun P.

2012-01-01

How is attention guided by past experience? In visual search, numerous studies have shown that recent trials influence responses to the current trial. Repeating features such as color, shape, or location of a target facilitates performance. Here we examine whether recent experience also modulates a more abstract dimension of attentional control,…

Protocol design and current status of CLIVIT: a randomized controlled multicenter relevance trial comparing clips versus ligatures in thyroid surgery

PubMed Central

Seiler, CM; Fröhlich, BE; Veit, JA; Gazyakan, E; Wente, MN; Wollermann, C; Deckert, A; Witte, S; Victor, N; Buchler, MW; Knaebel, HP

2006-01-01

Background Annually, more than 90000 surgical procedures of the thyroid gland are performed in Germany. Strategies aimed at reducing the duration of the surgical procedure are relevant to patients and the health care system especially in the context of reducing costs. However, new techniques for quick and safe hemostasis have to be tested in clinically relevance randomized controlled trials before a general recommendation can be given. The current standard for occlusion of blood vessels in thyroid surgery is ligatures. Vascular clips may be a safe alternative but have not been investigated in a large RCT. Methods/design CLIVIT (Clips versus Ligatures in Thyroid Surgery) is an investigator initiated, multicenter, patient-blinded, two-group parallel relevance randomized controlled trial designed by the Study Center of the German Surgical Society. Patients scheduled for elective resection of at least two third of the gland for benign thyroid disease are eligible for participation. After surgical exploration patients are randomized intraoperatively into either the conventional ligature group, or into the clip group. The primary objective is to test for a relevant reduction in operating time (at least 15 min) when using the clip technique. Since April 2004, 121 of the totally required 420 patients were randomized in five centers. Discussion As in all trials the different forms of bias have to be considered, and as in this case, a surgical trial, the role of surgical expertise plays a key role, and will be documented and analyzed separately. This is the first randomized controlled multicenter relevance trial to compare different vessel occlusion techniques in thyroid surgery with adequate power and other detailed information about the design as well as framework. If significant, the results might be generalized and may change the current surgical practice. PMID:16948853

Culturally-Tailored Smoking Cessation for American Indians: Study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Cigarette smoking is the number one cause of preventable death among American Indian and Alaska Natives, AI/ANs. Two out of every five AI/AN will die from tobacco-related diseases if the current smoking rates of AI/ANs (40.8%) persist. Currently, there is no proven, effective culturally-tailored smoking cessation program designed specifically for a heterogeneous population of AI. The primary aim of this group randomized clinical trial is to test the efficacy of "All Nations Breath of Life" (ANBL) program compared to a non-tailored "Current Best Practices" smoking cessation program among AI smokers. Methods We will randomize 56 groups (8 smokers per group) to the tailored program or non-tailored program for a total sample size of 448 American Indian smokers. All participants in the proposed study will be offered pharmacotherapy, regardless of group assignment. This study is the first controlled trial to examine the efficacy of a culturally-tailored smoking cessation program for American Indians. If the intervention is successful, the potential health impact is significant because the prevalence of smoking is the highest in this population. Trial Registration ClinicalTrials.gov: NCT01106456 PMID:21592347

The Dengue Vaccine Pipeline: Implications for the Future of Dengue Control

PubMed Central

Schwartz, Lauren M.; Halloran, M. Elizabeth; Durbin, Anna P.; Longini, Ira M.

2015-01-01

Dengue has become the most rapidly expanding mosquito-borne infectious disease on the planet, surpassing malaria and infecting at least 390 million people per year. There is no effective treatment for dengue illness other than supportive care, especially for severe cases. Symptoms can be mild or life-threatening as in dengue hemorrhagic fever and dengue shock syndrome. Vector control has been only partially successful in decreasing dengue transmission. The potential use of safe and effective tetravalent dengue vaccines is an attractive addition to prevent disease or minimize the possibility of epidemics. There are currently no licensed dengue vaccines. This review summarizes the current status of all dengue vaccine candidates in clinical evaluation. Currently five candidate vaccines are in human clinical trials. One has completed two Phase III trials, two are in Phase II trials, and three are in Phase I testing. PMID:25989449

Clinical trials bureaucracy: unintended consequences of well-intentioned policy.

PubMed

Califf, Robert M

2006-01-01

As randomized controlled trials have become the 'gold standard' for medical research, a complex regulatory structure for the conduct of clinical trials has emerged. However, this structure has not been adequately assessed to ensure that regulations governing human subjects research actually produce the desired effects. Our purpose is to identify some of the major shortcomings in the current regulatory system of human clinical trials oversight, and to propose some potential solutions to these problems. We discuss the evolution of the current US regulatory environment and its application in the context of several widely-used drug therapies. Despite numerous randomized controlled trials, performed within a structure of extensive documentation and data collection, serious shortcomings in a number of pharmaceutical therapies were not detected until after the drugs were approved and widely adopted by clinicians. The current system of regulatory bureaucracy in clinical trials has led to an extremely expensive research paradigm that, in spite of complex systems of oversight and exhaustive data collection, cannot be shown to adequately ensure the integrity of the research process and the protection of human research subjects. Some parts of the system, including Research Ethics Review Boards, may not be well-suited to carrying out their core mission of overseeing research conduct, and other aspects of clinical trials regulatory structure, such as monitoring/auditing review and adverse event reporting, may constitute a waste of money and resources. Misdirected data collection and adverse events reporting divert valuable resources and hamper development of large, simple clinical trials powered to definitively answer important research questions. Careful scrutiny of the utility of current or proposed regulatory schemes is required to ensure the integrity of human subjects research and to enhance the effectiveness of research dollars.

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

PubMed

Shimada, Tatsuo; Takayama, Hisako; Nakamura, Yoshiki

2010-07-01

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

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

PubMed

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

2017-03-01

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

Duloxetine in the treatment of binge eating disorder with depressive disorders: a placebo-controlled trial.

PubMed

Guerdjikova, Anna I; McElroy, Susan L; Winstanley, Erin L; Nelson, Eric B; Mori, Nicole; McCoy, Jessica; Keck, Paul E; Hudson, James I

2012-03-01

This study evaluated duloxetine in the treatment of binge eating disorder (BED) with comorbid current depressive disorders. In this 12-week, double-blind, placebo-controlled trial, 40 patients with Diagnostic and Statistical Manual of Mental Disorders-IV-TR BED and a comorbid current depressive disorder received duloxetine (N = 20) or placebo (N = 20). The primary outcome measure was weekly binge eating day frequency. In the primary analysis, duloxetine (mean 78.7 mg/day) was superior to placebo in reducing weekly frequency of binge eating days (p = .04), binge eating episodes (p = .02), weight (p = .04), and Clinical Global Impression-Severity of Illness ratings for binge eating (p = .02) and depressive disorders (p = .01). Changes in body mass index and measures of eating pathology, depression, and anxiety did not differ between the two groups. Duloxetine may be effective for reducing binge eating, weight, and global severity of illness in BED with a comorbid current depressive disorder, but this finding needs confirmation in larger, placebo-controlled trials. Copyright © 2011 Wiley Periodicals, Inc.

Transfusion and Treatment of severe anaemia in African children (TRACT): a study protocol for a randomised controlled trial.

PubMed

Mpoya, Ayub; Kiguli, Sarah; Olupot-Olupot, Peter; Opoka, Robert O; Engoru, Charles; Mallewa, Macpherson; Chimalizeni, Yami; Kennedy, Neil; Kyeyune, Dorothy; Wabwire, Benjamin; M'baya, Bridon; Bates, Imelda; Urban, Britta; von Hensbroek, Michael Boele; Heyderman, Robert; Thomason, Margaret J; Uyoga, Sophie; Williams, Thomas N; Gibb, Diana M; George, Elizabeth C; Walker, A Sarah; Maitland, Kathryn

2015-12-29

In sub-Saharan Africa, where infectious diseases and nutritional deficiencies are common, severe anaemia is a common cause of paediatric hospital admission, yet the evidence to support current treatment recommendations is limited. To avert overuse of blood products, the World Health Organisation advocates a conservative transfusion policy and recommends iron, folate and anti-helminthics at discharge. Outcomes are unsatisfactory with high rates of in-hospital mortality (9-10%), 6-month mortality and relapse (6%). A definitive trial to establish best transfusion and treatment strategies to prevent both early and delayed mortality and relapse is warranted. TRACT is a multicentre randomised controlled trial of 3954 children aged 2 months to 12 years admitted to hospital with severe anaemia (haemoglobin < 6 g/dl). Children will be enrolled over 2 years in 4 centres in Uganda and Malawi and followed for 6 months. The trial will simultaneously evaluate (in a factorial trial with a 3 x 2 x 2 design) 3 ways to reduce short-term and longer-term mortality and morbidity following admission to hospital with severe anaemia in African children. The trial will compare: (i) R1: liberal transfusion (30 ml/kg whole blood) versus conservative transfusion (20 ml/kg) versus no transfusion (control). The control is only for children with uncomplicated severe anaemia (haemoglobin 4-6 g/dl); (ii) R2: post-discharge multi-vitamin multi-mineral supplementation (including folate and iron) versus routine care (folate and iron) for 3 months; (iii) R3: post-discharge cotrimoxazole prophylaxis for 3 months versus no prophylaxis. All randomisations are open. Enrolment to the trial started September 2014 and is currently ongoing. Primary outcome is cumulative mortality to 4 weeks for the transfusion strategy comparisons, and to 6 months for the nutritional support/antibiotic prophylaxis comparisons. Secondary outcomes include mortality, morbidity (haematological correction, nutritional and infectious), safety and cost-effectiveness. If confirmed by the trial, a cheap and widely available 'bundle' of effective interventions, directed at immediate and downstream consequences of severe anaemia, could lead to substantial reductions in mortality in a substantial number of African children hospitalised with severe anaemia every year, if widely implemented. Current Controlled Trials ISRCTN84086586 , Approved 11 February 2013.

The YouthMood Project: A Cluster Randomized Controlled Trial of an Online Cognitive Behavioral Program with Adolescents

ERIC Educational Resources Information Center

Calear, Alison L.; Christensen, Helen; Mackinnon, Andrew; Griffiths, Kathleen M.; O'Kearney, Richard

2009-01-01

The aim in the current study was to investigate the effectiveness of an online, self-directed cognitive-behavioral therapy program (MoodGYM) in preventing and reducing the symptoms of anxiety and depression in an adolescent school-based population. A cluster randomized controlled trial was conducted with 30 schools (N = 1,477) from across…

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

ERIC Educational Resources Information Center

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

2011-01-01

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

Vibrating vaginal balls to improve pelvic floor muscle performance in women after childbirth: a protocol for a randomised controlled feasibility trial.

PubMed

Oblasser, Claudia; McCourt, Christine; Hanzal, Engelbert; Christie, Janice

2016-04-01

This paper presents a feasibility trial protocol the purpose of which is to prepare for a future randomised controlled trial to determine the effectiveness of vibrating vaginal pelvic floor training balls for postpartum pelvic floor muscle rehabilitation. Vibrating vaginal pelvic floor training balls are available in Austria to enhance women's pelvic floor muscles and thus prevent or treat urinary incontinence and other pelvic floor problems following childbirth. Nonetheless, there is currently little empirical knowledge to substantiate their use or assess their relative effectiveness in comparison to current standard care, which involves pelvic floor muscle exercises. Single blind, randomised controlled feasibility trial with two parallel groups. It is planned to recruit 56 postpartum women in Vienna, who will be randomised into one of two intervention groups to use either vibrating vaginal balls or a comparator pelvic floor muscle exercises for 12 weeks. As this is a feasibility study, study design features (recruitment, selection, randomisation, intervention concordance, data collection methods and tools) will be assessed and participants' views and experiences will be surveyed. Tested outcome measures, collected before and after the intervention, will be pelvic floor muscle performance as reported by participants and measured by perineometry. Descriptive and inferential statistics and content analysis will serve the preparation of the future trial. The results of this feasibility trial will inform the design and conduct of a full randomised controlled trial and provide insight into the experiences of women regarding the interventions and study participation. © 2015 John Wiley & Sons Ltd.

Hubble trial: time to stick to basics for treatment of haemorrhoids?

PubMed

Brown, S R

2017-01-01

The results of the Hubble trial, a randomised controlled trial comparing haemorrhoidal artery ligation with rubber band ligation for early-grade prolapsing haemorrhoids, are discussed. The difficulties in defining treatment success are debated along with the trial design highlighting the pitfalls of previous research. A finding that haemorrhoidal artery ligation is not necessarily superior to cheap alternatives has implications for current practice and future commissioning of surgeons.

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

PubMed

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

2015-12-17

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

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

PubMed

Andrews, Peter J D

2010-03-01

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

Effects of the carrier frequency of interferential current on pain modulation in patients with chronic nonspecific low back pain: a protocol of a randomised controlled trial.

PubMed

Corrêa, Juliana Barbosa; Costa, Leonardo Oliveira Pena; de Oliveira, Naiane Teixeira Bastos; Sluka, Kathleen A; Liebano, Richard Eloin

2013-06-27

Low back pain is an important public health problem that is associated with poor quality of life and disability. Among the electrophysical treatments, interferential current (IFC) has not been studied in patients with low back pain in a high-quality randomised controlled trial examining not only pain, but pain mechanisms and function. A three-arm randomised controlled trial with patient and assessor blinded to the group allocation. One hundred fifty patients with chronic, nonspecific low back pain from outpatient physical therapy clinics in Brazil. The patients will be randomly allocated into 3 groups (IFC 1 kHz, IFC 4 kHz or Placebo IFC). The interferential current will be applied three days per week (30 minutes per session) over four weeks. Pain intensity. The pressure pain threshold, global impression of recovery, disability, function, conditioned pain modulation and temporal summation of pain, discomfort caused by the current. All outcomes will be measured at 4 weeks and 4 months after randomisation. The between-group differences will be calculated by using linear mixed models and Tukey's post-hoc tests. The use of a placebo group and double-blinding assessor and patients strengthen this study. The present study is the first to compare different IFC carrier frequencies in patients with chronic low back pain. Brazilian Registry of Clinical Trials: http://RBR-8n4hg2.

Effectiveness of the palliative care ‘Availability, Current issues and Anticipation’ (ACA) communication training programme for general practitioners on patient outcomes: A controlled trial

PubMed Central

Blankenstein, Annette H; Schweitzer, Bart PM; Knol, Dirk L; van der Horst, Henriëtte E; Aaronson, Neil K; Deliens, Luc

2014-01-01

Background: Although communicating effectively with patients receiving palliative care can be difficult, it may contribute to maintaining or enhancing patients’ quality of life. Little is known about the effect of training general practitioners in palliative care–specific communication. We hypothesized that palliative care patients of general practitioners exposed to the ‘Availability, Current issues and Anticipation’ communication training programme would report better outcomes than patients of control general practitioners. Aim: To evaluate the effectiveness of the Availability, Current issues and Anticipation training programme for general practitioners on patient-reported outcomes. Design: In a controlled trial, general practitioners followed the Availability, Current issues and Anticipation programme or were part of the control group. Patients receiving palliative care of participating general practitioners completed the Palliative Care Outcome Scale, the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative, the Rest & Peace Scale, the Patient Satisfaction Questionnaire–III and the Availability, Current issues and Anticipation Scale, at baseline and 12 months follow-up. We analysed differences between groups using linear mixed models. Trial registration: ISRCTN56722368. Setting/participants: General practitioners who attended a 2-year Palliative Care Training Course in the Netherlands. Results: Questionnaire data were available for 145 patients (89 in intervention and 56 in control group). We found no significant differences over time between the intervention and control groups in any of the five outcome measures. Ceiling effects were observed for the Rest & Peace Scale, Patient Satisfaction Questionnaire–III and Availability, Current issues and Anticipation Scale. Conclusion: General practitioner participation in the Availability, Current issues and Anticipation training programme did not have a measurable effect on any of the outcomes investigated. Patients reported high levels of satisfaction with general practitioner care, regardless of group assignment. Future research might focus on general practitioners without special interest in palliative care. PMID:24951633

Efficacy of transcranial direct-current stimulation (tDCS) in women with provoked vestibulodynia: study protocol for a randomized controlled trial.

PubMed

Morin, Annie; Léonard, Guillaume; Gougeon, Véronique; Waddell, Guy; Bureau, Yves-André; Girard, Isabelle; Morin, Mélanie

2016-05-14

Provoked vestibulodynia is the most common form of vulvodynia. Despite its high prevalence and deleterious sexual, conjugal, and psychological repercussions, effective evidence-based interventions for provoked vestibulodynia remain limited. For a high proportion of women, significant pain persists despite the currently available treatments. Growing evidence suggests that the central nervous system (CNS) could play a key role in provoked vestibulodynia; thus, treatment targeting the CNS, rather than localized dysfunctions, may be beneficial for women suffering from provoked vestibulodynia. In this study, we aim to build on the promising results of a previous case report and evaluate whether transcranial direct-current stimulation, a non-invasive brain stimulation technique targeting the CNS, could be an effective treatment option for women with provoked vestibulodynia. This single-center, triple-blind, parallel group, randomized, controlled trial aims to compare the efficacy of transcranial direct-current stimulation with sham transcranial direct-current stimulation in women with provoked vestibulodynia. Forty women diagnosed with provoked vestibulodynia by a gynecologist, following a standardized treatment protocol, are randomized to either active transcranial direct-current stimulation treatment for ten sessions of 20 minutes at an intensity of 2 mA or sham transcranial direct-current stimulation over a 2-week period. Outcome measures are collected at baseline, 2 weeks after treatment and at 3-month follow-up. The primary outcome is pain during intercourse, assessed with a numerical rating scale. Secondary measurements focus on the sexual function, vestibular pain sensitivity, psychological distress, treatment satisfaction, and the patient's global impression of change. To our knowledge, this study is the first randomized controlled trial to examine the efficacy of transcranial direct-current stimulation in women with provoked vestibulodynia. Findings from this trial are expected to provide significant information about a promising intervention targeting the centralization of pain in women with provoked vestibulodynia. Clinicaltrials.gov, NCT02543593 . Registered on September 4, 2015.

The transvaginal hybrid NOTES versus conventionally assisted laparoscopic sigmoid resection for diverticular disease (TRANSVERSAL) trial: study protocol for a randomized controlled trial.

PubMed

Senft, Jonas D; Warschkow, Rene; Diener, Markus K; Tarantino, Ignazio; Steinemann, Daniel C; Lamm, Sebastian; Simon, Thomas; Zerz, Andreas; Müller-Stich, Beat P; Linke, Georg R

2014-11-20

Natural orifice transluminal endoscopic surgery (NOTES) is the consequence of further development of minimally invasive surgery to reduce abdominal incisions and surgical trauma. The potential benefits are expected to be less postoperative pain, faster convalescence, and reduced risk for incisional hernias and wound infections compared to conventional methods. Recent clinical studies have demonstrated the feasibility and safety of transvaginal NOTES, and transvaginal access is currently the most frequent clinically applied route for NOTES procedures. However, despite increasing clinical application, no firm clinical evidence is available for objective assessment of the potential benefits and risks of transvaginal NOTES compared to the current surgical standard. The TRANSVERSAL trial is designed as a randomized controlled trial to compare transvaginal hybrid NOTES and laparoscopic-assisted sigmoid resection. Female patients referred to elective sigmoid resection due to complicated or reoccurring diverticulitis of the sigmoid colon are considered eligible. The primary endpoint will be pain intensity during mobilization 24 hours postoperatively as measured by the blinded patient and blinded assessor on a visual analogue scale (VAS). Secondary outcomes include daily pain intensity and analgesic use, patient mobility, intraoperative complications, morbidity, length of stay, quality of life, and sexual function. Follow-up visits are scheduled 3, 12, and 36 months after surgery. A total sample size of 58 patients was determined for the analysis of the primary endpoint. The confirmatory analysis will be performed based on the intention-to-treat (ITT) principle. The TRANSVERSAL trial is the first study to compare transvaginal hybrid NOTES and conventionally assisted laparoscopic surgery for colonic resection in a randomized controlled setting. The results of the TRANSVERSAL trial will allow objective assessment of the potential benefits and risks of NOTES compared to the current surgical standard for sigmoid resection. The trial protocol was registered in the German Clinical Trials Register ( DRKS00005995) on March 27, 2014.

Protocol for the New Medicine Service Study: a randomized controlled trial and economic evaluation with qualitative appraisal comparing the effectiveness and cost effectiveness of the New Medicine Service in community pharmacies in England

PubMed Central

2013-01-01

Background Medication non-adherence is considered an important cause of morbidity and mortality in primary care. This study aims to determine the effectiveness, cost effectiveness and acceptability of a complex intervention delivered by community pharmacists, the New Medicine Service (NMS), compared with current practice in reducing non-adherence to, and problems with, newly prescribed medicines for chronic conditions. Methods/design Research subject group: patients aged 14 years and above presenting in a community pharmacy for a newly prescribed medicine for asthma/chronic obstructive pulmonary disease (COPD); hypertension; type 2 diabetes or anticoagulant/antiplatelet agents in two geographical regions in England. Design: parallel group patient-level pragmatic randomized controlled trial. Interventions: patients randomized to either: (i) current practice; or (ii) NMS intervention comprising pharmacist-delivered support for a newly prescribed medicine. Primary outcomes: proportion of adherent patients at six, ten and 26 weeks from the date of presenting their prescriptions at the pharmacy; cost effectiveness of the intervention versus current practice at 10 weeks and 26 weeks; in-depth qualitative understanding of the operationalization of NMS in pharmacies. Secondary outcomes: impact of NMS on: patients’ understanding of their medicines, pharmacovigilance, interprofessional and patient-professional relationships and experiences of service users and stakeholders. Economic analysis: Trial-based economic analysis (cost per extra adherent patient) and long-term modeling of costs and health effects (cost per quality-adjusted-life-year) will be conducted from the perspective of National Health Service (NHS) England, comparing NMS with current practice. Qualitative analysis: a qualitative study of NMS implementation in different community settings, how organizational influences affect NMS delivery, patterns of NMS consultations and experiences of professionals and patients participating in NMS, and patients receiving current practice. Sample size: 250 patients in each treatment arm would provide at least 80% power (two-tailed alpha of 0.05) to demonstrate a reduction in patient-reported non-adherence from 20% to 10% in the NMS arm compared with current practice, assuming a 20% drop-out rate. Discussion At the time of submission of this article, 58 community pharmacies have been recruited and the interventions are being delivered. Analysis has not yet been undertaken. Trial registration Current controlled trials: ISRCTN23560818 Clinical Trials US (clinicaltrials.gov): NCT01635361 PMID:24289059

Therapeutic touch for anxiety disorders.

PubMed

Robinson, J; Biley, F C; Dolk, H

2007-07-18

Anxiety disorders are a common occurrence in today's society. There is interest from the community in the use of complementary therapies for anxiety disorders. This review examined the currently available evidence supporting the use of therapeutic touch in treating anxiety disorders. To examine the efficacy and adverse effects of therapeutic touch for anxiety disorders. We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References) (search date 13/01/06), the Controlled Trials website and Dissertation Abstracts International. Searches of reference lists of retrieved papers were also carried out and experts in the field were contacted. Inclusion criteria included all published and unpublished randomised and quasi-randomised controlled trials comparing therapeutic touch with sham (mimic) TT, pharmacological therapy, psychological treatment, other treatment or no treatment /waiting list. The participants included adults with an anxiety disorder defined by the Diagnostic and Statistical Manual (DSM-IV),the International Classification of Diseases (ICD-10), validated diagnostic instruments, or other validated clinician or self-report instruments. Two review authors independently applied inclusion criteria. Further information was sought from trialists where papers contained insufficient information to make a decision about eligibility. No randomised or quasi-randomised controlled trials of therapeutic touch for anxiety disorders were identified. Given the high prevalence of anxiety disorders and the current paucity of evidence on therapeutic touch in this population, there is a need for well conducted randomised controlled trials to examine the effectiveness of therapeutic touch for anxiety disorders.

Intensive glycemic control and cardiovascular disease: an update.

PubMed

Brown, Aparna; Reynolds, L Raymond; Bruemmer, Dennis

2010-07-01

Cardiovascular complications constitute the major cause of morbidity and mortality in patients with diabetes. The Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) provided consistent evidence that intensive glycemic control prevents the development and progression of microvascular complications in patients with type 1 or type 2 diabetes. However, whether intensive glucose lowering also prevents macrovascular disease and major cardiovascular events remains unclear. Extended follow-up of participants in these studies demonstrated that intensive glycemic control reduced the long-term incidence of myocardial infarction and death from cardiovascular disease. By contrast, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, and Veterans Affairs Diabetes Trial (VADT) results suggested that intensive glycemic control to near normoglycemia had either no, or potentially even a detrimental, effect on cardiovascular outcomes. This article discusses the effects of intensive glycemic control on cardiovascular disease, and examines key differences in the design of these trials that might have contributed to their disparate findings. Recommendations from the current joint ADA, AHA, and ACCF position statement on intensive glycemic control and prevention of cardiovascular disease are highlighted.

Comparative Effectiveness of Medication versus Cognitive-Behavioral Therapy in a Randomized Controlled Trial of Low-Income Young Minority Women with Depression

ERIC Educational Resources Information Center

Siddique, Juned; Chung, Joyce Y.; Brown, C. Hendricks; Miranda, Jeanne

2012-01-01

Objective: To examine whether there are latent trajectory classes in response to treatment and whether they moderate the effects of medication versus psychotherapy. Method: Data come from a 1-year randomized controlled trial of 267 low-income, young (M = 29 years), minority (44% Black, 50% Latina, 6% White) women with current major depression…

Effects of a Web-Based Decision Aid Regarding Diagnostic Self-Testing. A Single-Blind Randomized Controlled Trial

ERIC Educational Resources Information Center

Ickenroth, Martine H. P.; Grispen, J. E. J.; de Vries, N. K.; Dinant, G. J.; Ronda, G.; van der Weijden, T.

2016-01-01

Currently, there are many diagnostic self-tests on body materials available to consumers. The aim of this study was to assess the effect of an online decision aid on diagnostic self-testing for cholesterol and diabetes on knowledge among consumers with an intention to take these tests. A randomized controlled trial was designed. A total of 1259…

Cross-Age Peer Tutoring and Fluency-Based Instruction to Achieve Fluency with Mathematics Computation Skills: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Greene, Irene; Mc Tiernan, Aoife; Holloway, Jennifer

2018-01-01

The current study employed a randomized controlled trial to evaluate the use of peer tutoring and fluency-based instruction to increase mathematics fluency with addition and subtraction computation skills. Forty-one elementary school students between the ages of eight and 12 years participated in the 8-week study using cross-age peer tutoring, Say…

Preschool Teachers Can Use a PBS KIDS Transmedia Curriculum Supplement to Support Young Children's Mathematics Learning: Results of a Randomized Controlled Trial

ERIC Educational Resources Information Center

Llorente, Carlin; Pasnik, Shelley; Moorthy, Savitha; Hupert, Naomi; Rosenfeld, Deborah; Gerard, Sarah

2015-01-01

The current study, a randomized controlled trial, explores how technology and educational transmedia resources can enhance prekindergarten math teaching and learning in preschools, especially those serving children who may be at risk for academic difficulties due to economic and social disadvantages. This research is part of a multi-year summative…

Rationale, design and methods of the Study of Work and Pain (SWAP): a cluster randomised controlled trial testing the addition of a vocational advice service to best current primary care for patients with musculoskeletal pain (ISRCTN 52269669)

PubMed Central

2014-01-01

Background Musculoskeletal pain is a major contributor to short and long term work absence. Patients seek care from their general practitioner (GP) and yet GPs often feel ill-equipped to deal with work issues. Providing a vocational case management service in primary care, to support patients with musculoskeletal problems to remain at or return to work, is one potential solution but requires robust evaluation to test clinical and cost-effectiveness. Methods/Design This protocol describes a cluster randomised controlled trial, with linked qualitative interviews, to investigate the effect of introducing a vocational advice service into general practice, to provide a structured approach to managing work related issues in primary care patients with musculoskeletal pain who are absent from work or struggling to remain in work. General practices (n = 6) will be randomised to offer best current care or best current care plus a vocational advice service. Adults of working age who are absent from or struggling to remain in work due to a musculoskeletal pain problem will be invited to participate and 330 participants will be recruited. Data collection will be through patient completed questionnaires at baseline, 4 and 12 months. The primary outcome is self-reported work absence at 4 months. Incremental cost-utility analysis will be undertaken to calculate the cost per additional QALY gained and incremental net benefits. A linked interview study will explore the experiences of the vocational advice service from the perspectives of GPs, nurse practitioners (NPs), patients and vocational advisors. Discussion This paper presents the rationale, design, and methods of the Study of Work And Pain (SWAP) trial. The results of this trial will provide evidence to inform primary care practice and guide the development of services to provide support for musculoskeletal pain patients with work-related issues. Trial registration Current Controlled Trials ISRCTN52269669. PMID:25012813

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

PubMed

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

2014-09-09

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

Challenges and Recommendations for Placebo Controls in Randomized Trials in Physical and Rehabilitation Medicine

PubMed Central

Fregni, Felipe; Imamura, Marta; Chien, Hsin Fen; Lew, Henry L.; Boggio, Paulo; Kaptchuk, Ted J; Riberto, Marcelo; Hsing, Wu Tu; Battistella, Linamara Rizzo; Furlan, Andrea

2010-01-01

Compared to other specialties, the field of Physical and Rehabilitation Medicine (PRM) has not received the deserved recognition from clinicians and researchers in the scientific community. One of the reasons is the lack of sound evidence to support the traditional PRM treatments. The best way to change this disadvantage is through well-conducted clinical research, such as the standard placebo or sham-controlled randomized clinical trials. Therefore, having placebo groups in clinical trials is essential to improve the level of evidence-based practice in PRM that ultimately translates in a better clinical care. To address the challenges for the use of placebo in PRM randomized clinical trials, and to create useful recommendations, we convened a working group during the inaugural International Symposium in Placebo (February 2009, in Sao Paulo, Brazil) in which the following topics were discussed: (1) current status of randomized clinical trials in PRM, (2) challenges for the use of placebo in PRM, (3) bioethical issues, (4) use of placebo in acupuncture trials and for the treatment of low-back pain, (5) mechanisms of placebo, and (6) insights from other specialties. The current article represents the consensus report from the working group. PMID:20090428

Impact of a cancer clinical trials web site on discussions about trial participation: a cluster randomized trial.

PubMed

Dear, R F; Barratt, A L; Askie, L M; Butow, P N; McGeechan, K; Crossing, S; Currow, D C; Tattersall, M H N

2012-07-01

Cancer patients want access to reliable information about currently recruiting clinical trials. Oncologists and their patients were randomly assigned to access a consumer-friendly cancer clinical trials web site [Australian Cancer Trials (ACT), www.australiancancertrials.gov.au] or to usual care in a cluster randomized controlled trial. The primary outcome, measured from audio recordings of oncologist-patient consultations, was the proportion of patients with whom participation in any clinical trial was discussed. Analysis was by intention-to-treat accounting for clustering and stratification. Thirty medical oncologists and 493 patients were recruited. Overall, 46% of consultations in the intervention group compared with 34% in the control group contained a discussion about clinical trials (P=0.08). The mean consultation length in both groups was 29 min (P=0.69). The proportion consenting to a trial was 10% in both groups (P=0.65). Patients' knowledge about randomized trials was lower in the intervention than the control group (mean score 3.0 versus 3.3, P=0.03) but decisional conflict scores were similar (mean score 42 versus 43, P=0.83). Good communication between patients and physicians is essential. Within this context, a web site such as Australian Cancer Trials may be an important tool to encourage discussion about clinical trial participation.

Prefrontal transcranial direct current stimulation (tDCS) as treatment for major depression: study design and methodology of a multicenter triple blind randomized placebo controlled trial (DepressionDC).

PubMed

Padberg, Frank; Kumpf, Ulrike; Mansmann, Ulrich; Palm, Ulrich; Plewnia, Christian; Langguth, Berthold; Zwanzger, Peter; Fallgatter, Andreas; Nolden, Jana; Burger, Max; Keeser, Daniel; Rupprecht, Rainer; Falkai, Peter; Hasan, Alkomiet; Egert, Silvia; Bajbouj, Malek

2017-12-01

Transcranial direct current stimulation (tDCS) has been proposed as novel treatment for major depressive disorder (MDD) based on clinical pilot studies as well as randomized controlled monocentric trials. The DepressionDC trial is a triple-blind (blinding of rater, operator and patient), randomized, placebo controlled multicenter trial investigating the efficacy and safety of prefrontal tDCS used as additive treatment in MDD patients who have not responded to selective serotonin reuptake inhibitors (SSRI). At 5 study sites, 152 patients with MDD receive a 6-weeks treatment with active tDCS (anode F3 and cathode F4, 2 mA intensity, 30 min/day) or sham tDCS add-on to a stable antidepressant medication with an SSRI. Follow-up visits are at 3 and 6 months after the last tDCS session. The primary outcome measure is the change of the Montgomery-Asberg Depression Rating Scale (MADRS) scores at week 6 post-randomisation compared to baseline. Secondary endpoints also cover other psychopathological domains, and a comprehensive safety assessment includes measures of cognition. Patients undergo optional investigations comprising genetic testing and functional magnetic resonance imaging (fMRI) of structural and functional connectivity. The study uses also an advanced tDCS technology including standard electrode positioning and recording of technical parameters (current, impedance, voltage) in every tDCS session. Aside reporting the study protocol here, we present a novel approach for monitoring technical parameters of tDCS which will allow quality control of stimulation and further analysis of the interaction between technical parameters and clinical outcome. The DepressionDC trial will hopefully answer the important clinical question whether prefrontal tDCS is a safe and effective antidepressant intervention in patients who have not sufficiently responded to SSRIs. ClinicalTrials.gov Identifier NCT0253016.

Smartphone application for multi-phasic interventional trials in psychiatry: Technical design of a smart server.

PubMed

Zhang, Melvyn W B; Ho, Roger C M

2017-01-01

Smartphones and their accompanying applications are currently widely utilized in various healthcare interventions. Prior to the deployment of these tools for healthcare intervention, typically, proof of concept feasibility studies, as well as randomized trials are conducted to determine that these tools are efficacious prior to their actual implementation. In the field of psychiatry, most of the current interventions seek to compare smartphone based intervention against conventional care. There remains a paucity of research evaluating different forms of interventions using a single smartphone application. In the field of nutrition, there has been recent pioneering research demonstrating how a multi-phasic randomized controlled trial could be conducted using a single smartphone application. Despite the innovativeness of the previous smartphone conceptualization, there remains a paucity of technical information underlying the conceptualization that would support a multi-phasic interventional trial. It is thus the aim of the current technical note to share insights into an innovative server design that would enable the delivery of multi-phasic trials.

Bayesian selective response-adaptive design using the historical control.

PubMed

Kim, Mi-Ok; Harun, Nusrat; Liu, Chunyan; Khoury, Jane C; Broderick, Joseph P

2018-06-13

High quality historical control data, if incorporated, may reduce sample size, trial cost, and duration. A too optimistic use of the data, however, may result in bias under prior-data conflict. Motivated by well-publicized two-arm comparative trials in stroke, we propose a Bayesian design that both adaptively incorporates historical control data and selectively adapt the treatment allocation ratios within an ongoing trial responsively to the relative treatment effects. The proposed design differs from existing designs that borrow from historical controls. As opposed to reducing the number of subjects assigned to the control arm blindly, this design does so adaptively to the relative treatment effects only if evaluation of cumulated current trial data combined with the historical control suggests the superiority of the intervention arm. We used the effective historical sample size approach to quantify borrowed information on the control arm and modified the treatment allocation rules of the doubly adaptive biased coin design to incorporate the quantity. The modified allocation rules were then implemented under the Bayesian framework with commensurate priors addressing prior-data conflict. Trials were also more frequently concluded earlier in line with the underlying truth, reducing trial cost, and duration and yielded parameter estimates with smaller standard errors. © 2018 The Authors. Statistics in Medicine Published by John Wiley & Sons, Ltd.

Prazosin for Prophylaxis of Chronic Post Traumatic Headaches in OEF/OIF/OND Service Members and Veterans with Mild TBI

DTIC Science & Technology

2017-10-01

does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2017 2. REPORT TYPE...comes from a large open-label case series in Iraq and Afghanistan Veterans with mTBI and posttraumatic headaches and data from a placebo- controlled trial...will be accomplished by conducting a randomized placebo- controlled double blind trial of prazosin vs placebo in 160 Iraq/Afghanistan active-duty

Searches for Randomized Controlled Trials of Drugs in MEDLINE and EMBASE Using Only Generic Drug Names Compared with Searches Applied in Current Practice in Systematic Reviews

ERIC Educational Resources Information Center

Waffenschmidt, Siw; Guddat, Charlotte

2015-01-01

Background: It is unclear which terms should be included in bibliographic searches for randomized controlled trials (RCTs) of drugs, and identifying relevant drug terms can be extremely laborious. The aim of our analysis was to determine whether a bibliographic search using only the generic drug name produces sufficient results for the generation…

Medical Students' and Tutors' Experiences of Directed and Self-Directed Learning Programs in Evidence-Based Medicine: A Qualitative Evaluation Accompanying a Randomized Controlled Trial

ERIC Educational Resources Information Center

Bradley, Peter; Oterholt, Christina; Nordheim, Lena; Bjorndal, Arild

2005-01-01

This qualitative study aims to interpret the results of a randomized controlled trial comparing two educational programs (directed learning and self-directed learning) in evidence-based medicine (EBM) for medical students at the University of Oslo from 2002 to 2003. There is currently very little comparative educational research in this field. In…

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

PubMed

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

2017-03-28

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

Orthodontic treatment in periodontitis‐susceptible subjects: a systematic literature review

PubMed Central

Lindsten, Rune; Slotte, Christer; Bjerklin, Krister

2016-01-01

Abstract The aim is to evaluate the literature for clinical scientific data on possible effects of orthodontic treatment on periodontal status in periodontitis‐susceptible subjects. A systematic literature review was performed on studies in English using PubMed, MEDLINE, and Cochrane Library central databases (1965‐2014). By manually searching reference lists of selected studies, we identified additional articles; then we searched these publications: Journal of Periodontology, Periodontology 2000, Journal of Clinical Periodontology, American Journal of Orthodontics and Dentofacial Orthopedics, Angle Orthodontist, International Journal of Periodontics & Restorative Dentistry, and European Journal of Orthodontics. Search terms included randomized clinical trials, controlled clinical trials, prospective and retrospective clinical studies, case series >5 patients, periodontitis, orthodontics, alveolar bone loss, tooth migration, tooth movement, orthodontic extrusion, and orthodontic intrusion. Only studies on orthodontic treatment in periodontally compromised dentitions were included. One randomized controlled clinical trial, one controlled clinical trial, and 12 clinical studies were included. No evidence currently exists from controlled studies and randomized controlled clinical trials, which shows that orthodontic treatment improves or aggravates the status of periodontally compromised dentitions. PMID:29744163

[Clinical safety data management in company non-sponsored trials].

PubMed

Saito, Akiko; Sakai, Junko; Kurihara, Masaaki; Kami, Masahiro; Kanda, Yoshinobu; Mori, Shin-ichiro; Takaue, Yoichi; Ohashi, Yasuo

2003-09-01

There is currently no harmonized way in Japan to manage safety data which are obtained during clinical trials supported by Government funds. There are two types of clinical trials, 'sponsored trials(sponsored by industrial companies)' and 'non-sponsored trials(funded by the Government, etc.)'. The Japanese Ministry of Health and Welfare has issued many of pharmaceutical laws(GCP, GPMSP etc.) for the regulation of sponsored trials, while none has ever established for non-sponsored trials, thus leaving the most important quality control/assurance unregulated. In this manuscript we discuss that the simple application of pharmaceutical laws to government-sponsored trials can not be a proper answer because of the different nature of the two types of trials.

Awareness, trial, and current use of electronic cigarettes in 10 countries: Findings from the ITC project.

PubMed

Gravely, Shannon; Fong, Geoffrey T; Cummings, K Michael; Yan, Mi; Quah, Anne C K; Borland, Ron; Yong, Hua-Hie; Hitchman, Sara C; McNeill, Ann; Hammond, David; Thrasher, James F; Willemsen, Marc C; Seo, Hong Gwan; Jiang, Yuan; Cavalcante, Tania; Perez, Cristina; Omar, Maizurah; Hummel, Karin

2014-11-13

In recent years, electronic cigarettes (e-cigarettes) have generated considerable interest and debate on the implications for tobacco control and public health. Although the rapid growth of e-cigarettes is global, at present, little is known about awareness and use. This paper presents self-reported awareness, trial and current use of e-cigarettes in 10 countries surveyed between 2009 and 2013; for six of these countries, we present the first data on e-cigarettes from probability samples of adult smokers. A cross-sectional analysis of probability samples of adult (≥ 18 years) current and former smokers participating in the International Tobacco Control (ITC) surveys from 10 countries. Surveys were administered either via phone, face-to-face interviews, or the web. Survey questions included sociodemographic and smoking-related variables, and questions about e-cigarette awareness, trial and current use. There was considerable cross-country variation by year of data collection and for awareness of e-cigarettes (Netherlands (2013: 88%), Republic of Korea (2010: 79%), United States (2010: 73%), Australia (2013: 66%), Malaysia (2011: 62%), United Kingdom (2010: 54%), Canada (2010: 40%), Brazil (2013: 37%), Mexico (2012: 34%), and China (2009: 31%)), in self-reports of ever having tried e-cigarettes (Australia, (20%), Malaysia (19%), Netherlands (18%), United States (15%), Republic of Korea (11%), United Kingdom (10%), Brazil (8%), Mexico (4%), Canada (4%), and China (2%)), and in current use (Malaysia (14%), Republic of Korea (7%), Australia (7%), United States (6%), United Kingdom (4%), Netherlands (3%), Canada (1%), and China (0.05%)) [corrected]. The cross-country variability in awareness, trial, and current use of e-cigarettes is likely due to a confluence of country-specific market factors, tobacco control policies and regulations (e.g., the legal status of e-cigarettes and nicotine), and the survey timing along the trajectory of e-cigarette awareness and trial/use in each country. These ITC results constitute an important snapshot of an early stage of what appears to be a rapid progression of global e-cigarette use.

Aromatherapy for pain management in labour.

PubMed

Smith, Caroline A; Collins, Carmel T; Crowther, Caroline A

2011-07-06

Many women would like to avoid pharmacological or invasive methods of pain management in labour and this may contribute towards the popularity of complementary methods of pain management. This review examined currently available evidence supporting the use of aromatherapy for pain management in labour. To examine the effects of aromatherapy for pain management in labour on maternal and perinatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2010), The Cochrane Complementary Medicine Field's Trials Register (October 2010), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 4), MEDLINE (1966 to 31 October 2010), CINAHL (1980 to 31 October 2010), the Australian and New Zealand Trials Registry (31 October 2010), Chinese Clinical Trial Register (31 October 2010), Current Controlled Trials (31 October 2010), ClinicalTrials.gov (31 October 2010), ISRCTN Register (31 October 2010), National Center for Complementary and Alternative Medicine (NCCAM) (31 October 2010) and the WHO International Clinical Trials Registry Platform (31 October 2010). Randomised controlled trials comparing aromatherapy with placebo, no treatment or other non-pharmacological forms of pain management in labour. Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We included two trials (535 women) in the review. The trials found no difference between groups for the primary outcomes of pain intensity, assisted vaginal birth (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.48 to 2.28, one trial, 513 women; RR 0.83, 95% CI 0.06 to 11.70, one trial, 22 women), and caesarean section (RR 0.98, 95% CI 0.49 to 1.94, one trial, 513 women; RR 2.54, 95% CI 0.11 to 56.25, one trial, 22 women); there were more babies admitted to neonatal intensive care in the control group of one trial (RR 0.08, 95% CI 0.00 to 1.42, one trial, 513 women) but this difference did not reach statistical significance. The trials found no differences between groups for the secondary outcomes of use of pharmacological pain relief (RR 0.35, 95% CI 0.04 to 3.32, one trial, 513 women; RR 2.50, 95% CI 0.31 to 20.45, one trial, 22 women), spontaneous vaginal delivery (RR 1.00, 95% CI 0.94 to 1.06, one trial, 513 women; RR 0.93, 95% CI 0.67 to 1.28, one trial, 22 women) or length of labour and augmentation (RR 1.14, 95% CI 0.90 to 1.45, one trial, 513 women). The risk of bias was low in the trials. There is a lack of studies evaluating the role of aromatherapy for pain management in labour. Further research is needed before recommendations can be made for clinical practice.

Treatment of primary Sjögren syndrome: a systematic review.

PubMed

Ramos-Casals, Manuel; Tzioufas, Athanasios G; Stone, John H; Sisó, Antoni; Bosch, Xavier

2010-07-28

A variety of topical and systemic drugs are available to treat primary Sjögren syndrome, although no evidence-based therapeutic guidelines are currently available. To summarize evidence on primary Sjögren syndrome drug therapy from randomized controlled trials. We searched MEDLINE and EMBASE for articles on drug therapy for primary Sjögren syndrome published between January 1, 1986, and April 30, 2010. Controlled trials of topical and systemic drugs including adult patients with primary Sjögren syndrome were selected as the primary information source. The search strategy yielded 37 trials. A placebo-controlled trial found significant improvement in the Schirmer and corneal staining scores, blurred vision, and artificial tear use in patients treated with topical ocular 0.05% cyclosporine. Three placebo-controlled trials found that pilocarpine was associated with improvements in dry mouth (61%-70% vs 24%-31% in the placebo group) and dry eye (42%-53% vs 26%). Two placebo-controlled trials found that cevimeline was associated with improvement in dry mouth (66%-76% vs 35%-37% in the placebo group) and dry eye (39%-72% vs 24%-30%). Small trials (<20 patients) found no significant improvement in sicca outcomes for oral prednisone or hydroxychloroquine and limited benefits for immunosuppressive agents (azathioprine and cyclosporine). A large trial found limited benefits for oral interferon alfa-2a. Two placebo-controlled trials of infliximab and etanercept did not achieve the primary outcome (a composite visual analog scale measuring joint pain, fatigue, and dryness); neither did 2 small trials (<30 patients) testing rituximab, although significant results were observed in some secondary outcomes and improvement compared with baseline. In primary Sjögren syndrome, evidence from controlled trials suggests benefits for pilocarpine and cevimeline for sicca features and topical cyclosporine for moderate or severe dry eye. Anti-tumor necrosis factor agents have not shown clinical efficacy, and larger controlled trials are needed to establish the efficacy of rituximab.

Contribution of transcranial direct current stimulation on inhibitory control to assess the neurobiological aspects of attention deficit hyperactivity disorder: randomized controlled trial.

PubMed

Cosmo, Camila; Baptista, Abrahão Fontes; de Sena, Eduardo Pondé

2015-05-18

The applicability of transcranial direct current stimulation (tDCS) in individuals with attention deficit hyperactivity disorder (ADHD) has not yet been investigated. This low-cost, non-invasive, and safe technique optimized to modulate the inhibitory response might be a useful treatment option for those affected by this condition. The aim of this single center, parallel, randomized, double-blinded, sham-controlled trial is to investigate the efficacy of transcranial direct current stimulation over the prefrontal cortex on the modulation of inhibitory control in adults with attention deficit hyperactivity disorder. A total of 60 individuals will be divided into 2 groups by block randomization to receive active or sham stimulation. Anodal stimulation over the left dorsolateral prefrontal cortex will be applied at 1 mA during a single 20-minute session. Before and after interventions, subjects will perform 2 go/no go tasks and the brain electrical activity will be recorded by electroencephalogram (EEG) with 32 channels, according to the 10-20 international EEG system. The trial began in May 2013 and we are currently performing the statistical analysis for the secondary outcomes. The findings from this study will provide preliminary results about the role of prefrontal cortex activation through tDCS on ADHD patients. Clinicaltrials.gov NCT01968512; http://clinicaltrials.gov/ct2/show/NCT01968512 (Archived by WebCite at www.webcitation.org/6YMSW2tkD).

Point-of-care cluster randomized trial in stroke secondary prevention using electronic health records.

PubMed

Dregan, Alex; van Staa, Tjeerd P; McDermott, Lisa; McCann, Gerard; Ashworth, Mark; Charlton, Judith; Wolfe, Charles D A; Rudd, Anthony; Yardley, Lucy; Gulliford, Martin C; Trial Steering Committee

2014-07-01

The aim of this study was to evaluate whether the remote introduction of electronic decision support tools into family practices improves risk factor control after first stroke. This study also aimed to develop methods to implement cluster randomized trials in stroke using electronic health records. Family practices were recruited from the UK Clinical Practice Research Datalink and allocated to intervention and control trial arms by minimization. Remotely installed, electronic decision support tools promoted intensified secondary prevention for 12 months with last measure of systolic blood pressure as the primary outcome. Outcome data from electronic health records were analyzed using marginal models. There were 106 Clinical Practice Research Datalink family practices allocated (intervention, 53; control, 53), with 11 391 (control, 5516; intervention, 5875) participants with acute stroke ever diagnosed. Participants at trial practices had similar characteristics as 47,887 patients with stroke at nontrial practices. During the intervention period, blood pressure values were recorded in the electronic health records for 90% and cholesterol values for 84% of participants. After intervention, the latest mean systolic blood pressure was 131.7 (SD, 16.8) mm Hg in the control trial arm and 131.4 (16.7) mm Hg in the intervention trial arm, and adjusted mean difference was -0.56 mm Hg (95% confidence interval, -1.38 to 0.26; P=0.183). The financial cost of the trial was approximately US $22 per participant, or US $2400 per family practice allocated. Large pragmatic intervention studies may be implemented at low cost by using electronic health records. The intervention used in this trial was not found to be effective, and further research is needed to develop more effective intervention strategies. http://www.controlled-trials.com. Current Controlled Trials identifier: ISRCTN35701810. © 2014 American Heart Association, Inc.

Corticosteroids for the common cold.

PubMed

Hayward, Gail; Thompson, Matthew J; Perera, Rafael; Del Mar, Chris B; Glasziou, Paul P; Heneghan, Carl J

2015-10-13

The common cold is a frequent illness, which, although benign and self limiting, results in many consultations to primary care and considerable loss of school or work days. Current symptomatic treatments have limited benefit. Corticosteroids are an effective treatment in other upper respiratory tract infections and their anti-inflammatory effects may also be beneficial in the common cold. This updated review has included one additional study. To compare corticosteroids versus usual care for the common cold on measures of symptom resolution and improvement in children and adults. We searched Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 4), which includes the Acute Respiratory Infections (ARI) Group's Specialised Register, the Database of Reviews of Effects (DARE) (2015, Issue 2), NHS Health Economics Database (2015, Issue 2), MEDLINE (1948 to May week 3, 2015) and EMBASE (January 2010 to May 2015). Randomised, double-blind, controlled trials comparing corticosteroids to placebo or to standard clinical management. Two review authors independently extracted data and assessed trial quality. We were unable to perform meta-analysis and instead present a narrative description of the available evidence. We included three trials (353 participants). Two trials compared intranasal corticosteroids to placebo and one trial compared intranasal corticosteroids to usual care; no trials studied oral corticosteroids. In the two placebo-controlled trials, no benefit of intranasal corticosteroids was demonstrated for duration or severity of symptoms. The risk of bias overall was low or unclear in these two trials. In a trial of 54 participants, the mean number of symptomatic days was 10.3 in the placebo group, compared to 10.7 in those using intranasal corticosteroids (P value = 0.72). A second trial of 199 participants reported no significant differences in the duration of symptoms. The single-blind trial in children aged two to 14 years, who were also receiving oral antibiotics, had inadequate reporting of outcome measures regarding symptom resolution. The overall risk of bias was high for this trial. Mean symptom severity scores were significantly lower in the group receiving intranasal steroids in addition to oral amoxicillin. One placebo-controlled trial reported the presence of rhinovirus in nasal aspirates and found no differences. Only one of the three trials reported on adverse events; no differences were found. Two trials reported secondary bacterial infections (one case of sinusitis, one case of acute otitis media; both in the corticosteroid groups). A lack of comparable outcome measures meant that we were unable to combine the data. Current evidence does not support the use of intranasal corticosteroids for symptomatic relief from the common cold. However, there were only three trials, one of which was very poor quality, and there was limited statistical power overall. Further large, randomised, double-blind, placebo-controlled trials in adults and children are required to answer this question.

A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection

PubMed Central

2016-01-01

BACKGROUND Data from studies in nonhuman primates suggest that the triple monoclonal antibody cocktail ZMapp is a promising immune-based treatment for Ebola virus disease (EVD). METHODS Beginning in March 2015, we conducted a randomized, controlled trial of ZMapp plus the current standard of care as compared with the current standard of care alone in patients with EVD that was diagnosed in West Africa by polymerase-chain-reaction (PCR) assay. Eligible patients of any age were randomly assigned in a 1:1 ratio to receive either the current standard of care or the current standard of care plus three intravenous infusions of ZMapp (50 mg per kilogram of body weight, administered every third day). Patients were stratified according to baseline PCR cycle-threshold value for the virus (≤22 vs. >22) and country of enrollment. Oral favipiravir was part of the current standard of care in Guinea. The primary end point was mortality at 28 days. RESULTS A total of 72 patients were enrolled at sites in Liberia, Sierra Leone, Guinea, and the United States. Of the 71 patients who could be evaluated, 21 died, representing an overall case fatality rate of 30%. Death occurred in 13 of 35 patients (37%) who received the current standard of care alone and in 8 of 36 patients (22%) who received the current standard of care plus ZMapp. The observed posterior probability that ZMapp plus the current standard of care was superior to the current standard of care alone was 91.2%, falling short of the prespecified threshold of 97.5%. Frequentist analyses yielded similar results (absolute difference in mortality with ZMapp, −15 percentage points; 95% confidence interval, −36 to 7). Baseline viral load was strongly predictive of both mortality and duration of hospitalization in all age groups. CONCLUSIONS In this randomized, controlled trial of a putative therapeutic agent for EVD, although the estimated effect of ZMapp appeared to be beneficial, the result did not meet the prespecified statistical threshold for efficacy. (Funded by the National Institute of Allergy and Infectious Diseases and others; PREVAIL II ClinicalTrials.gov number, NCT02363322.) PMID:27732819

Design of a cluster-randomized minority recruitment trial: RECRUIT.

PubMed

Tilley, Barbara C; Mainous, Arch G; Smith, Daniel W; McKee, M Diane; Amorrortu, Rossybelle P; Alvidrez, Jennifer; Diaz, Vanessa; Ford, Marvella E; Fernandez, Maria E; Hauser, Robert A; Singer, Carlos; Landa, Veronica; Trevino, Aron; DeSantis, Stacia M; Zhang, Yefei; Daniels, Elvan; Tabor, Derrick; Vernon, Sally W

2017-06-01

Racial/ethnic minority groups remain underrepresented in clinical trials. Many strategies to increase minority recruitment focus on minority communities and emphasize common diseases such as hypertension. Scant literature focuses on minority recruitment to trials of less common conditions, often conducted in specialty clinics and dependent on physician referrals. We identified trust/mistrust of specialist physician investigators and institutions conducting medical research and consequent participant reluctance to participate in clinical trials as key-shared barriers across racial/ethnic groups. We developed a trust-based continuous quality improvement intervention to build trust between specialist physician investigators and community minority-serving physicians and ultimately potential trial participants. To avoid the inherent biases of non-randomized studies, we evaluated the intervention in the national Randomized Recruitment Intervention Trial (RECRUIT). This report presents the design of RECRUIT. Specialty clinic follow-up continues through April 2017. We hypothesized that specialist physician investigators and coordinators trained in the trust-based continuous quality improvement intervention would enroll a greater proportion of minority participants in their specialty clinics than specialist physician investigators in control specialty clinics. Specialty clinic was the unit of randomization. Using continuous quality improvement, the specialist physician investigators and coordinators tailored recruitment approaches to their specialty clinic characteristics and populations. Primary analyses were adjusted for clustering by specialty clinic within parent trial and matching covariates. RECRUIT was implemented in four multi-site clinical trials (parent trials) supported by three National Institutes of Health institutes and included 50 associated specialty clinics from these parent trials. Using current data, we have 88% power or greater to detect a 0.15 or greater difference from the currently observed control proportion adjusting for clustering. We detected no differences in baseline matching criteria between intervention and control specialty clinics (all p values > 0.17). RECRUIT was the first multi-site randomized control trial to examine the effectiveness of a trust-based continuous quality improvement intervention to increase minority recruitment into clinical trials. RECRUIT's innovations included its focus on building trust between specialist investigators and minority-serving physicians, the use of continuous quality improvement to tailor the intervention to each specialty clinic's specific racial/ethnic populations and barriers to minority recruitment, and the use of specialty clinics from more than one parent multi-site trial to increase generalizability. The effectiveness of the RECRUIT intervention will be determined after the completion of trial data collection and planned analyses.

Irrelevant learned reward associations disrupt voluntary spatial attention.

PubMed

MacLean, Mary H; Diaz, Gisella K; Giesbrecht, Barry

2016-10-01

Attention can be guided involuntarily by physical salience and by non-salient, previously learned reward associations that are currently task-irrelevant. Attention can be guided voluntarily by current goals and expectations. The current study examined, in two experiments, whether irrelevant reward associations could disrupt current, goal-driven, voluntary attention. In a letter-search task, attention was directed voluntarily (i.e., cued) on half the trials by a cue stimulus indicating the hemifield in which the target letter would appear with 100 % accuracy. On the other half of the trials, a cue stimulus was presented, but it did not provide information about the target hemifield (i.e., uncued). On both cued and uncued trials, attention could be involuntarily captured by the presence of a task-irrelevant, and physically non-salient, color, either within the cued or the uncued hemifield. Importantly, one week prior to the letter search task, the irrelevant color had served as a target feature that was predictive of reward in a separate training task. Target identification accuracy was better on cued compared to uncued trials. However, this effect was reduced when the irrelevant, and physically non-salient, reward-associated feature was present in the uncued hemifield. This effect was not observed in a second, control experiment in which the irrelevant color was not predictive of reward during training. Our results indicate that involuntary, value-driven capture can disrupt the voluntary control of spatial attention.

Female but not male young heavy drinkers display altered performance monitoring.

PubMed

Smith, Janette L; Mattick, Richard P; Sufani, Christopher

2015-09-30

Difficulties in monitoring ongoing behaviour may be linked to real-life problematic drinking behaviours. Prior research suggests female heavy drinkers in particular display greater cognitive control deficits. Here, we examine trial-to-trial behavioural adaptations in a conflict monitoring task, relative to drinking behaviour and sex. Heavy drinkers (n=31, 16 male) and controls (n=35, 18 male) completed an Eriksen flanker task while brain electrical activity was recorded. For reaction time, error rates, and N2 and P3 amplitude of the event-related potential, trial-to-trial conflict adaptation was evidenced by a differential response to the current (congruent vs. incongruent) trials dependent on the identity of the previous trial. For the proportion of errors, heavy drinkers showed increased conflict adaptation compared to controls. Conflict adaptation for N2 (indexing monitoring) was larger for female heavy drinkers than controls, and the opposite was observed for males. There were no interactions involving group or sex for the P3 (indexing inhibition). The results suggest a compensatory response, such that heavy drinkers are required to increase performance monitoring in order to achieve the same behavioural outcome as controls. We also confirm the importance of sex as a factor in the relationship between behavioural control and heavy alcohol use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

New approaches to trials in glomerulonephritis.

PubMed

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

2017-01-01

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

The effects and costs of the universal parent group program – all children in focus: a study protocol for a randomized wait-list controlled trial

PubMed Central

2013-01-01

Background In recent decades, parents have been involved in programs that aim to improve parenting style and reduce child behavior problems. Research of preventive parenting programs has shown that these interventions generally have a positive influence on both parents and children. However, to our knowledge there is a gap in the scientific literature when it comes to randomized controlled trials of brief, manual-based structured programs which address general parenting among the population, and focus on promoting health. A four-session universal health promotion parent group program named All Children in Focus was developed. It aims at promoting parental competence and children’s positive development with the parent–child relationship as the target. There is currently no randomized controlled trial existing of the program. Methods/Design A prospective multicenter randomized wait-list controlled trial is being conducted. Approximately 600 parents with children ranging in age from 3–12 years have been recruited in eleven municipalities and city districts in the County of Stockholm, Sweden. Parents are randomized at baseline to an intervention group, which receives the program directly, or to a waiting-list control group, which participates in the program six months later. Changes in parenting and child health and development are assessed with measures immediately post-intervention and six months after the baseline. Observations of a minor group of parents and children are conducted to explore possible relations between parental reports and observed behaviors, as well as changes in the interaction between parent and child. Further, data collected within the evaluation will also be applied to evaluate the possible cost-effectiveness of the program. Discussion This paper describes a study protocol of a randomized controlled trial. Except for the quantitative outcome measures to evaluate the effectiveness of All Children in Focus, this protocol also describes health economic and qualitative analyses to deepen the knowledge of the program. We further discuss some issues regarding the implementation of the program in municipalities and city districts. Trial registration Current Controlled Trials ISRCTN70202532 PMID:23890316

Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer

DTIC Science & Technology

2017-10-01

Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704...penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR...TERMS Breast cancer, adjuvant treatment, aspirin, randomized controlled trial 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF

Computer-based cognitive training for ADHD: a review of current evidence.

PubMed

Sonuga-Barke, Edmund; Brandeis, Daniel; Holtmann, Martin; Cortese, Samuele

2014-10-01

There has been an increasing interest in and the use of computer-based cognitive training as a treatment of attention-deficit/hyperactivity disorder (ADHD). The authors' review of current evidence, based partly on a stringent meta-analysis of 6 randomized controlled trials (RCTs) published in 2013, and an overview of 8 recently published RCTs highlights the inconsistency of findings between trials and across blinded and nonblinded ADHD measures within trials. Based on this, they conclude that more evidence from well-blinded studies is required before cognitive training can be supported as a frontline treatment of core ADHD symptoms. Copyright © 2014 Elsevier Inc. All rights reserved.

The added value of mifepristone to non-surgical treatment regimens for uterine evacuation in case of early pregnancy failure: a systematic review of the literature.

PubMed

van den Berg, Joyce; Gordon, Bernardus B M; Snijders, Marcus P M L; Vandenbussche, Frank P H A; Coppus, Sjors F P J

2015-12-01

Early pregnancy failure (EPF) is a common complication of pregnancy. Surgical intervention carries a risk of complications and, therefore, medical treatment appears to be a safe alternative. Unfortunately, the current medical treatment with misoprostol alone has complete evacuation rates between 53% and 87%. Some reports suggest that sequential treatment with mifepristone and misoprostol leads to higher success rates than misoprostol alone. To evaluate the added value of mifepristone to current non-surgical treatment regimens in women with EPF we performed a systematic literature search. Electronic databases were searched: PubMed, Cochrane Library, Current Controlled Trials, and ClinicalTrials.gov. Clinical studies, both randomised and non-randomised trials, reporting on the added value of mifepristone to current non-surgical treatment regimens in women with EPF were included. Data of sixteen studies were extracted using a data extraction sheet (based on the Cochrane Consumers and Communication Review Group's data extraction template). The methodological quality was assessed using the Cochrane Collaboration Risk of Bias tool. In five randomised and eleven non-randomised trials, success rates of sequential treatment with mifepristone and misoprostol in case of EPF varied between 52% and 95%. Large heterogeneity existed in treatment regimens and comparators between studies. The existing evidence is insufficient to draw firm conclusions about the added value of mifepristone to misoprostol alone. A sufficiently powered randomised, double blinded placebo-controlled trial is urgently required to test whether, in EPF, the sequential combination of mifepristone with misoprostol is superior to misoprostol only. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Study protocol of the Diabetes and Depression Study (DAD): a multi-center randomized controlled trial to compare the efficacy of a diabetes-specific cognitive behavioral group therapy versus sertraline in patients with major depression and poorly controlled diabetes mellitus

PubMed Central

2013-01-01

Background Depression is common in diabetes and associated with hyperglycemia, diabetes related complications and mortality. No single intervention has been identified that consistently leads to simultaneous improvement of depression and glycemic control. Our aim is to analyze the efficacy of a diabetes-specific cognitive behavioral group therapy (CBT) compared to sertraline (SER) in adults with depression and poorly controlled diabetes. Methods/Design This study is a multi-center parallel arm randomized controlled trial currently in its data analysis phase. We included 251 patients in 70 secondary care centers across Germany. Key inclusion criteria were: type 1 or 2 diabetes, major depression (diagnosed with the Structured Clinical Interview for DSM-IV, SCID) and hemoglobin A1C >7.5% despite current insulin therapy. During the initial phase, patients received either 50–200 mg/d sertraline or 10 CBT sessions aiming at the remission of depression and enhanced adherence to diabetes treatment and coping with diabetes. Both groups received diabetes treatment as usual. After 12 weeks of this initial open-label therapy, only the treatment-responders (50% depression symptoms reduction, Hamilton Depression Rating Scale, 17-item version [HAMD]) were included in the subsequent one year study phase and represented the primary analysis population. CBT-responders received no further treatment, while SER-responders obtained a continuous, flexible-dose SER regimen as relapse prevention. Adherence to treatment was analyzed using therapeutic drug monitoring (measurement of sertraline and N-desmethylsertraline concentrations in blood serum) and by counting the numbers of CBT sessions received. Outcome assessments were conducted by trained psychologists blinded to group assignment. Group differences in HbA1c (primary outcome) and depression (HAMD, secondary outcome) between 1-year follow-up and baseline will be analyzed by ANCOVA controlling for baseline values. As primary hypothesis we expect that CBT leads to significantly greater improvement of glycemic control in the one year follow-up in treatment responders of the short term phase. Discussion The DAD study is the first randomized controlled trial comparing antidepressants to a psychological treatment in diabetes patients with depression. The study is investigator initiated and was supported by the ‘Förderprogramm Klinische Studien (Clinical Trials)’ and the ‘Competence Network for Diabetes mellitus’ funded by the Federal Ministry of Education and Research (FKZ 01KG0505). Trial registration Current controlled trials ISRCTN89333241. PMID:23915015

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

PubMed

Ghanizadeh, Ahmad

2015-05-01

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

Early vasopressor use following traumatic injury: a systematic review

PubMed Central

Hylands, Mathieu; Toma, Augustin; Beaudoin, Nicolas; Frenette, Anne Julie; D’Aragon, Frédérick; Belley-Côté, Émilie; Charbonney, Emmanuel; Møller, Morten Hylander; Laake, Jon Henrik; Vandvik, Per Olav; Siemieniuk, Reed Alexander; Rochwerg, Bram; Lauzier, François; Green, Robert S; Ball, Ian; Scales, Damon; Murthy, Srinivas; Kwong, Joey S W; Guyatt, Gordon; Rizoli, Sandro; Asfar, Pierre; Lamontagne, François

2017-01-01

Objectives Current guidelines suggest limiting the use of vasopressors following traumatic injury; however, wide variations in practice exist. Although excessive vasoconstriction may be harmful, these agents may help reduce administration of potentially harmful resuscitation fluids. This systematic review aims to compare early vasopressor use to standard resuscitation in adults with trauma-induced shock. Design Systematic review. Data sources We searched MEDLINE, EMBASE, ClinicalTrials.gov and the Central Register of Controlled Trials from inception until October 2016, as well as the proceedings of 10 relevant international conferences from 2005 to 2016. Eligibility criteria for selecting studies Randomised controlled trials and controlled observational studies that compared the early vasopressor use with standard resuscitation in adults with acute traumatic injury. Results Of 8001 citations, we retrieved 18 full-text articles and included 6 studies (1 randomised controlled trial and 5 observational studies), including 2 published exclusively in abstract form. Across observational studies, vasopressor use was associated with increased short-term mortality, with unadjusted risk ratios ranging from 2.31 to 7.39. However, the risk of bias was considered high in these observational studies because patients who received vasopressors were systematically sicker than patients treated without vasopressors. One clinical trial (n=78) was too imprecise to yield meaningful results. Two clinical trials are currently ongoing. No study measured long-term quality of life or cognitive function. Conclusions Existing data on the effects of vasopressors following traumatic injury are of very low quality according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. With emerging evidence of harm associated with aggressive fluid resuscitation and, in selected subgroups of patients, with permissive hypotension, the alternatives to vasopressor therapy are limited. Observational data showing that vasopressors are part of usual care would provide a strong justification for high-quality clinical trials of early vasopressor use during trauma resuscitation. Trial registration number CRD42016033437. PMID:29151048

Randomized Controlled Trials in Music Therapy: Guidelines for Design and Implementation.

PubMed

Bradt, Joke

2012-01-01

Evidence from randomized controlled trials (RCTs) plays a powerful role in today's healthcare industry. At the same time, it is important that multiple types of evidence contribute to music therapy's knowledge base and that the dialogue of clinical effectiveness in music therapy is not dominated by the biomedical hierarchical model of evidence-based practice. Whether or not one agrees with the hierarchical model of evidence in the current healthcare climate, RCTs can contribute important knowledge to our field. Therefore, it is important that music therapists are prepared to design trials that meet current methodological standards and, equally important, are able to respond appropriately to those design aspects that may not be feasible in music therapy research. To provide practical guidelines to music therapy researchers for the design and implementation of RCTs as well as to enable music therapists to be well-informed consumers of RCT evidence. This article reviews key design aspects of RCTs and discusses how to best implement these standards in music therapy trials. A systematic presentation of basic randomization methods, allocation concealment strategies, issues related to blinding in music therapy trials and strategies for implementation, the use of treatment manuals, types of control groups, outcome selection, and sample size computation is provided. Despite the challenges of meeting all key design demands typical of an RCT, it is possible to design rigorous music therapy RCTs that accurately estimate music therapy treatment benefits.

Effects of transcutaneous electrical nerve stimulation (TENS) and interferential currents (IFC) in patients with nonspecific chronic low back pain: randomized clinical trial.

PubMed

Facci, Ligia Maria; Nowotny, Jean Paulus; Tormem, Fabio; Trevisani, Virgínia Fernandes Moça

2011-01-01

Transcutaneous electrical nerve stimulation (TENS) and interferential current are the most used electrotherapy methods, although there is little scientific evidence to support their use. The aim of this study was to compare the effects of TENS and interferential current among patients with nonspecific chronic low back pain. Single-blind randomized controlled trial in the Department of Physiotherapy, Centro Universitário de Maringá. One hundred and fifty patients were randomly divided into three groups: TENS (group 1), interferential current (group 2) and controls (group 3). The patients designated for electrotherapy received ten 30-minute sessions, while the control group remained untreated. All patients and controls were evaluated before and after treatment using a visual analog scale and the McGill Pain and Roland Morris questionnaires, and regarding their use of additional medications. There was a mean reduction on the visual analog scale of 39.18 mm with TENS, 44.86 mm with interferential current and 8.53 mm among the controls. In the Roland Morris questionnaire, group 1 had a mean reduction of 6.59; group 2, 7.20; and group 3, 0.70 points. In group 1, 84% of the patients stopped using medications after the treatment; in group 2, 75%; and in group 3, 34%. There was no statistically significant difference between the TENS and interferential current groups (P > 0.05); a difference was only found between these groups and the controls (P < 0.0001). There was no difference between TENS and interferential current for chronic low back pain treatment. NCT01017913.

Protocol for the New Medicine Service Study: a randomized controlled trial and economic evaluation with qualitative appraisal comparing the effectiveness and cost effectiveness of the New Medicine Service in community pharmacies in England.

PubMed

Boyd, Matthew; Waring, Justin; Barber, Nick; Mehta, Rajnikant; Chuter, Antony; Avery, Anthony J; Salema, Nde-Eshimuni; Davies, James; Latif, Asam; Tanajewski, Lukasz; Elliott, Rachel A

2013-12-01

Medication non-adherence is considered an important cause of morbidity and mortality in primary care. This study aims to determine the effectiveness, cost effectiveness and acceptability of a complex intervention delivered by community pharmacists, the New Medicine Service (NMS), compared with current practice in reducing non-adherence to, and problems with, newly prescribed medicines for chronic conditions. Research subject group: patients aged 14 years and above presenting in a community pharmacy for a newly prescribed medicine for asthma/chronic obstructive pulmonary disease (COPD); hypertension; type 2 diabetes or anticoagulant/antiplatelet agents in two geographical regions in England. parallel group patient-level pragmatic randomized controlled trial. patients randomized to either: (i) current practice; or (ii) NMS intervention comprising pharmacist-delivered support for a newly prescribed medicine. proportion of adherent patients at six, ten and 26 weeks from the date of presenting their prescriptions at the pharmacy; cost effectiveness of the intervention versus current practice at 10 weeks and 26 weeks; in-depth qualitative understanding of the operationalization of NMS in pharmacies. impact of NMS on: patients' understanding of their medicines, pharmacovigilance, interprofessional and patient-professional relationships and experiences of service users and stakeholders.Economic analysis: Trial-based economic analysis (cost per extra adherent patient) and long-term modeling of costs and health effects (cost per quality-adjusted-life-year) will be conducted from the perspective of National Health Service (NHS) England, comparing NMS with current practice.Qualitative analysis: a qualitative study of NMS implementation in different community settings, how organizational influences affect NMS delivery, patterns of NMS consultations and experiences of professionals and patients participating in NMS, and patients receiving current practice. 250 patients in each treatment arm would provide at least 80% power (two-tailed alpha of 0.05) to demonstrate a reduction in patient-reported non-adherence from 20% to 10% in the NMS arm compared with current practice, assuming a 20% drop-out rate. At the time of submission of this article, 58 community pharmacies have been recruited and the interventions are being delivered. Analysis has not yet been undertaken. Current controlled trials: ISRCTN23560818. Clinical Trials US (clinicaltrials.gov): NCT01635361.

Rationale, design and methods of the Study of Work and Pain (SWAP): a cluster randomised controlled trial testing the addition of a vocational advice service to best current primary care for patients with musculoskeletal pain (ISRCTN 52269669).

PubMed

Bishop, Annette; Wynne-Jones, Gwenllian; Lawton, Sarah A; van der Windt, Danielle; Main, Chris; Sowden, Gail; Burton, A Kim; Lewis, Martyn; Jowett, Sue; Sanders, Tom; Hay, Elaine M; Foster, Nadine E

2014-07-10

Musculoskeletal pain is a major contributor to short and long term work absence. Patients seek care from their general practitioner (GP) and yet GPs often feel ill-equipped to deal with work issues. Providing a vocational case management service in primary care, to support patients with musculoskeletal problems to remain at or return to work, is one potential solution but requires robust evaluation to test clinical and cost-effectiveness. This protocol describes a cluster randomised controlled trial, with linked qualitative interviews, to investigate the effect of introducing a vocational advice service into general practice, to provide a structured approach to managing work related issues in primary care patients with musculoskeletal pain who are absent from work or struggling to remain in work. General practices (n = 6) will be randomised to offer best current care or best current care plus a vocational advice service. Adults of working age who are absent from or struggling to remain in work due to a musculoskeletal pain problem will be invited to participate and 330 participants will be recruited. Data collection will be through patient completed questionnaires at baseline, 4 and 12 months. The primary outcome is self-reported work absence at 4 months. Incremental cost-utility analysis will be undertaken to calculate the cost per additional QALY gained and incremental net benefits. A linked interview study will explore the experiences of the vocational advice service from the perspectives of GPs, nurse practitioners (NPs), patients and vocational advisors. This paper presents the rationale, design, and methods of the Study of Work And Pain (SWAP) trial. The results of this trial will provide evidence to inform primary care practice and guide the development of services to provide support for musculoskeletal pain patients with work-related issues. Current Controlled Trials ISRCTN52269669.

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

PubMed

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

2017-09-22

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

Early initiation of post-sternotomy cardiac rehabilitation exercise training (SCAR): study protocol for a randomised controlled trial and economic evaluation

PubMed Central

Lobley, Grace; Worrall, Sandra; Powell, Richard; Kimani, Peter K; Banerjee, Prithwish; Barker, Thomas

2018-01-01

Introduction Current guidelines recommend abstinence from supervised cardiac rehabilitation (CR) exercise training for 6 weeks post-sternotomy. This practice is not based on empirical evidence, thus imposing potentially unnecessary activity restrictions. Delayed participation in CR exercise training promotes muscle atrophy, reduces cardiovascular fitness and prolongs recovery. Limited data suggest no detrimental effect of beginning CR exercise training as early as 2 weeks post-surgery, but randomised controlled trials are yet to confirm this. The purpose of this trial is to compare CR exercise training commenced early (2 weeks post-surgery) with current usual care (6 weeks post-surgery) with a view to informing future CR guidelines for patients recovering from sternotomy. Methods and analysis In this assessor-blind randomised controlled trial, 140 cardiac surgery patients, recovering from sternotomy, will be assigned to 8 weeks of twice-weekly supervised CR exercise training commencing at either 2 weeks (early CR) or 6 weeks (usual care CR) post-surgery. Usual care exercise training will adhere to current UK recommendations. Participants in the early CR group will undertake a highly individualised 2–3 week programme of functional mobility, strength and cardiovascular exercise before progressing to a usual care CR programme. Outcomes will be assessed at baseline (inpatient), pre-CR (2 or 6 weeks post-surgery), post-CR (10 or 14 weeks post-surgery) and 12 months. The primary outcome will be change in 6 min walk distance. Secondary outcomes will include measures of functional fitness, quality of life and cost-effectiveness. Ethics and dissemination Recruitment commenced on July 2017 and will complete by December 2019. Results will be disseminated via national governing bodies, scientific meetings and peer-reviewed journals. Trial registration number NCT03223558; Pre-results. PMID:29574443

Efficacy and safety of haloperidol for in-hospital delirium prevention and treatment: A systematic review of current evidence.

PubMed

Schrijver, E J M; de Graaf, K; de Vries, O J; Maier, A B; Nanayakkara, P W B

2016-01-01

Haloperidol is generally considered the drug of choice for in-hospital delirium management. We conducted a systematic review to evaluate the evidence for the efficacy and safety of haloperidol for the prevention and treatment of delirium in hospitalized patients. PubMed, Embase, Cumulative Index to Nursing and Allied Health (CINAHL), PsycINFO, and the Cochrane Library were systematically searched up to April 21, 2015. We included English full-text randomized controlled trials using haloperidol for the prevention or treatment of delirium in adult hospitalized patients reporting on delirium incidence, duration, or severity as primary outcome. Quality of evidence was graded. Meta-analysis was not conducted because of between-study heterogeneity. Twelve studies met our inclusion criteria, four prevention and eight treatment trials. Methodological limitations decreased the graded quality of included studies. Results from placebo-controlled prevention studies suggest a haloperidol-induced protective effect for delirium in older patients scheduled for surgery: two studies reported a significant reduction in ICU delirium incidence and one study found a significant reduction in delirium severity and duration. Although placebo-controlled trials are missing, pharmacological treatment of established delirium reduced symptom severity. Haloperidol administration was not associated with treatment-limiting side-effects, but few studies used a systematic approach to identify adverse events. Although results on haloperidol for delirium management seem promising, current prevention trials lack external validity and treatment trials did not include a placebo arm on top of standard nonpharmacological care. We therefore conclude that the current use of haloperidol for in-hospital delirium is not based on robust and generalizable evidence. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Therapeutic Plasma Transfusion in Bleeding Patients: A Systematic Review.

PubMed

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

2017-04-01

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

A study protocol for a single-blind, randomized controlled trial of adjunctive transcranial direct current stimulation (tDCS) for chronic pain among patients receiving specialized, inpatient multimodal pain management.

PubMed

Janice Jimenez-Torres, G; Weinstein, Benjamin L; Walker, Cory R; Christopher Fowler, J; Ashford, Philippa; Borckardt, Jeffrey J; Madan, Alok

2017-03-01

Available treatments for chronic pain (CP) are modestly effective or associated with iatrogenic harm. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that may be an effective, adjunctive treatment to non-opioid therapies. In this randomized control trial (RCT), we compare adjunctive active versus sham tDCS among patients in a multimodal inpatient pain management program. The primary objectives of the RCT are to improve pain tolerance and subjective pain experience. Patients admitted to the Pain Management Program at The Menninger Clinic in Houston, Texas are eligible for this trial. Eighty-four participants will be randomized (1:1) into a single-blind, 2×12 (group×time) controlled trial. A battery-powered direct and constant current stimulator (Soterix Medical Inc. 2014) delivers anodal stimulation over the left dorsolateral prefrontal cortex (DLPFC) and cathodal stimulation over the right DLPFC. Active tDCS is applied by supplying a 2mA current for 20min/session over 10 sessions. Participants complete self-report and performance-based assessments on a weekly basis just prior to brain stimulation. Self-report assessments are collected via Chronic Pain Tracker version 3.6, an iPad interfaced application. The performance-based pain tolerance task is completed through the cold presser task. Interventions with cross-symptomatic therapeutic potential are absolutely essential in the context of CP, in which psychiatric comorbidity is the norm. Modalities that can be used in tandem with evidence-based, non-opioid therapies have the potential to have a synergistic effect, resulting in increased effectiveness of what have been modestly effective treatments to date. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2017-01-01

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

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

ERIC Educational Resources Information Center

Middleton, Kathryn R.; Perri, Michael G.

2014-01-01

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

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

PubMed Central

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

2017-01-01

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

An oral health intervention for people with serious mental illness (Three Shires Early Intervention Dental Trial): study protocol for a randomised controlled trial.

PubMed

Jones, Hannah F; Adams, Clive E; Clifton, Andrew; Simpson, Jayne; Tosh, Graeme; Liddle, Peter F; Callaghan, Patrick; Yang, Min; Guo, Boliang; Furtado, Vivek

2013-05-29

Oral health is an important part of general physical health and is essential for self-esteem, self-confidence and overall quality of life. There is a well-established link between mental illness and poor oral health. Oral health problems are not generally well recognized by mental health professionals and many patients experience barriers to treatment. This is the protocol for a pragmatic cluster randomised trial that has been designed to fit within standard care. Dental awareness training for care co-ordinators plus a dental checklist for service users in addition to standard care will be compared with standard care alone for people with mental illness. The checklist consists of questions about service users' current oral health routine and condition. Ten Early Intervention in Psychosis (EIP) teams in Nottinghamshire, Derbyshire and Lincolnshire will be cluster randomised (five to intervention and five to standard care) in blocks accounting for location and size of caseload. The oral health of the service users will be monitored for one year after randomisation. Current Controlled Trials ISRCTN63382258.

Clinical trial design for orthodontists.

PubMed

Pandis, Nikolaos; Cobourne, Martyn T

2013-06-01

High-quality research should form the basis of all clinical practice. Randomized controlled trials currently provide the gold standard for investigating the effectiveness of treatment interventions and these are increasingly being used in orthodontics. Here we discuss the reasons why this form of investigation provides the most useful evidence for assessing treatment outcome. The methods available to achieve true randomization, a fundamental component in the design of these trials, are also discussed. In addition, we focus on how to minimize bias in clinical research, not only during the design and management of a trial, but also when disseminating results. We focus on the importance of using control groups correctly and describe methods that are available to adequately power a trial. Finally, we emphasise the importance of accurate and transparent reporting, which facilitates correct communication and assessment of the evidence.

Statistical analysis plan for the Pneumatic CompREssion for PreVENting Venous Thromboembolism (PREVENT) trial: a study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen; Al-Hameed, Fahad; Burns, Karen E A; Mehta, Sangeeta; Alsolamy, Sami; Almaani, Mohammed; Mandourah, Yasser; Almekhlafi, Ghaleb A; Al Bshabshe, Ali; Finfer, Simon; Alshahrani, Mohammed; Khalid, Imran; Mehta, Yatin; Gaur, Atul; Hawa, Hassan; Buscher, Hergen; Arshad, Zia; Lababidi, Hani; Al Aithan, Abdulsalam; Jose, Jesna; Abdukahil, Sheryl Ann I; Afesh, Lara Y; Dbsawy, Maamoun; Al-Dawood, Abdulaziz

2018-03-15

The Pneumatic CompREssion for Preventing VENous Thromboembolism (PREVENT) trial evaluates the effect of adjunctive intermittent pneumatic compression (IPC) with pharmacologic thromboprophylaxis compared to pharmacologic thromboprophylaxis alone on venous thromboembolism (VTE) in critically ill adults. In this multicenter randomized trial, critically ill patients receiving pharmacologic thromboprophylaxis will be randomized to an IPC or a no IPC (control) group. The primary outcome is "incident" proximal lower-extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the lower-extremity ultrasonography will be blinded to intervention allocation, whereas the patients and treating team will be unblinded. The trial has 80% power to detect a 3% absolute risk reduction in the rate of proximal DVT from 7% to 4%. Consistent with international guidelines, we have developed a detailed plan to guide the analysis of the PREVENT trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes, and defines covariates for adjusted analyses a priori. Application of this statistical analysis plan to the PREVENT trial will facilitate unbiased analyses of clinical data. ClinicalTrials.gov , ID: NCT02040103 . Registered on 3 November 2013; Current controlled trials, ID: ISRCTN44653506 . Registered on 30 October 2013.

Ginger as an antiemetic modality for chemotherapy-induced nausea and vomiting: a systematic review and meta-analysis.

PubMed

Lee, Jiyeon; Oh, Heeyoung

2013-03-01

To evaluate the effect of ginger as an antiemetic modality for the control of chemotherapy-induced nausea and vomiting (CINV). Databases searched included MEDLINE® (PubMed), Embase, CINAHL®, Cochrane Central Register of Controlled Trials, Korean Studies Information Service System, Research Information Sharing Service by the Korean Education and Research Information Service, and Dissertation Central. A systematic review was conducted of five randomized, controlled trials involving 872 patients with cancer. Ginger was compared with placebo or metoclopramide. The participant characteristics, chemotherapy regimen and antiemetic control, ginger preparation and protocol, measurements, results of the studies, adherence to the treatment protocol, and side effects were reviewed systematically. The incidence and severity of acute and delayed CINV were subject to meta-analysis. The incidence of acute nausea (p = 0.67), incidence of acute vomiting (p = 0.37), and severity of acute nausea (p = 0.12) did not differ significantly between the ginger and control groups. Current evidence does not support the use of ginger for the control of CINV. Ginger did not contribute to control of the incidence of acute nausea and vomiting or of the severity of acute nausea. Ginger has long been regarded as a traditional antiemetic modality, but its effectiveness remains to be established. The findings of this study could be incorporated into clinical guidelines, such as the Oncology Nursing Society's Putting Evidence Into Practice resources. Current evidence supports the need for more methodologically rigorous studies in this area. Although ginger is known as a traditional antiemetic, current evidence does not support the effect of ginger in CINV control. The findings of this study inform healthcare providers that its effectiveness remains to be established from methodologically rigorous future trials.

Diarrhea and dengue control in rural primary schools in Colombia: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Diarrheal diseases and dengue fever are major global health problems. Where provision of clean water is inadequate, water storage is crucial. Fecal contamination of stored water is a common source of diarrheal illness, but stored water also provides breeding sites for dengue vector mosquitoes. Poor household water management and sanitation are therefore potential determinants of both diseases. Little is known of the role of stored water for the combined risk of diarrhea and dengue, yet a joint role would be important for developing integrated control and management efforts. Even less is known of the effect of integrating control of these diseases in school settings. The objective of this trial was to investigate whether interventions against diarrhea and dengue will significantly reduce diarrheal disease and dengue entomological risk factors in rural primary schools. Methods/design This is a 2×2 factorial cluster randomized controlled trial. Eligible schools were rural primary schools in La Mesa and Anapoima municipalities, Cundinamarca, Colombia. Eligible pupils were school children in grades 0 to 5. Schools were randomized to one of four study arms: diarrhea interventions (DIA); dengue interventions (DEN); combined diarrhea and dengue interventions (DIADEN); and control (C). Schools were allocated publicly in each municipality (strata) at the start of the trial, obviating the need for allocation concealment. The primary outcome for diarrhea is incidence rate of diarrhea in school children and for dengue it is density of adult female Aedes aegypti per school. Approximately 800 pupils from 34 schools were enrolled in the trial with eight schools in the DIA arm, nine in the DEN, eight in the DIADEN, and nine in the control arms. The trial status as of June 2012 was: completed baseline data collections; enrollment, randomization, and allocation of schools. The trial was funded by the Research Council of Norway and the Lazos de Calandaima Foundation. Discussion This is the first trial investigating the effect of a set of integrated interventions to control both dengue and diarrhea. This is also the first trial to study the combination of diarrhea-dengue disease control in school settings. Trial registration Current Controlled Trials ISRCTN40195031 PMID:23034084

Emerging Therapies for Diabetic Nephropathy Patients: Beyond Blockade of the Renin-Angiotensin System

PubMed Central

Tanios, Bassem Y.; Ziyadeh, Fuad N.

2012-01-01

Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. The mainstay of treatment has been glycemic control and blood pressure lowering using agents blocking the renin-angiotensin system. Clinical trials are currently under way using novel agents for the treatment of patients with diabetic nephropathy. Promising agents emerging from some of the completed trials include pirfenidone and bardoxolone methyl, which have been shown in two recent randomized controlled trials in patients with diabetic nephropathy to result in an improved estimated glomerular filtration rate compared to placebo. Also, paricalcitol has been shown to decrease the urinary albumin-to-creatinine ratio, whereas sulodexide failed to do so in a large randomized double-blind placebo-controlled trial. Of note, pyridoxamine has also shown promise in the treatment of diabetic nephropathy if started early in the disease course. These preliminary trials have shown significant promise for managing patients with diabetic nephropathy, sparking active research in this field and providing the rationale for further clinical testing in long-term, hard-outcomes trials. PMID:23599705

Transcranial direct current stimulation for depression in Alzheimer's disease: study protocol for a randomized controlled trial.

PubMed

Narita, Zui; Yokoi, Yuma

2017-06-19

Patients with Alzheimer's disease frequently elicit neuropsychiatric symptoms as well as cognitive deficits. Above all, depression is one of the most common neuropsychiatric symptoms in Alzheimer's disease but antidepressant drugs have not shown significant beneficial effects on it. Moreover, electroconvulsive therapy has not ensured its safety for potential severe adverse events although it does show beneficial clinical effect. Transcranial direct current stimulation can be the safe alternative of neuromodulation, which applies weak direct electrical current to the brain. Although transcranial direct current stimulation has plausible evidence for its effect on depression in young adult patients, no study has explored it in older subjects with depression in Alzheimer's disease. Therefore, we present a study protocol designed to evaluate the safety and clinical effect of transcranial direct current stimulation on depression in Alzheimer's disease in subjects aged over 65 years. This is a two-arm, parallel-design, randomized controlled trial, in which patients and assessors will be blinded. Subjects will be randomized to either an active or a sham transcranial direct current stimulation group. Participants in both groups will be evaluated at baseline, immediately, and 2 weeks after the intervention. This study investigates the safety and effect of transcranial direct current stimulation that may bring a significant impact on both depression and cognition in patients with Alzheimer's disease, and may be useful to enhance their quality of life. ClinicalTrials.gov, NCT02351388 . Registered on 27 January 2015. Last updated on 30 May 2016.

Are Randomized Controlled Trials the (G)old Standard? From Clinical Intelligence to Prescriptive Analytics.

PubMed

Van Poucke, Sven; Thomeer, Michiel; Heath, John; Vukicevic, Milan

2016-07-06

Despite the accelerating pace of scientific discovery, the current clinical research enterprise does not sufficiently address pressing clinical questions. Given the constraints on clinical trials, for a majority of clinical questions, the only relevant data available to aid in decision making are based on observation and experience. Our purpose here is 3-fold. First, we describe the classic context of medical research guided by Poppers' scientific epistemology of "falsificationism." Second, we discuss challenges and shortcomings of randomized controlled trials and present the potential of observational studies based on big data. Third, we cover several obstacles related to the use of observational (retrospective) data in clinical studies. We conclude that randomized controlled trials are not at risk for extinction, but innovations in statistics, machine learning, and big data analytics may generate a completely new ecosystem for exploration and validation.

Are Randomized Controlled Trials the (G)old Standard? From Clinical Intelligence to Prescriptive Analytics

PubMed Central

2016-01-01

Despite the accelerating pace of scientific discovery, the current clinical research enterprise does not sufficiently address pressing clinical questions. Given the constraints on clinical trials, for a majority of clinical questions, the only relevant data available to aid in decision making are based on observation and experience. Our purpose here is 3-fold. First, we describe the classic context of medical research guided by Poppers’ scientific epistemology of “falsificationism.” Second, we discuss challenges and shortcomings of randomized controlled trials and present the potential of observational studies based on big data. Third, we cover several obstacles related to the use of observational (retrospective) data in clinical studies. We conclude that randomized controlled trials are not at risk for extinction, but innovations in statistics, machine learning, and big data analytics may generate a completely new ecosystem for exploration and validation. PMID:27383622

Attentional adjustment to conflict strength: evidence from the effects of manipulating flanker-target SOA on response times and prestimulus pupil size.

PubMed

Wendt, Mike; Kiesel, Andrea; Geringswald, Franziska; Purmann, Sascha; Fischer, Rico

2014-01-01

Current models of cognitive control assume gradual adjustment of processing selectivity to the strength of conflict evoked by distractor stimuli. Using a flanker task, we varied conflict strength by manipulating target and distractor onset. Replicating previous findings, flanker interference effects were larger on trials associated with advance presentation of the flankers compared to simultaneous presentation. Controlling for stimulus and response sequence effects by excluding trials with feature repetitions from stimulus administration (Experiment 1) or from the statistical analyses (Experiment 2), we found a reduction of the flanker interference effect after high-conflict predecessor trials (i.e., trials associated with advance presentation of the flankers) but not after low-conflict predecessor trials (i.e., trials associated with simultaneous presentation of target and flankers). This result supports the assumption of conflict-strength-dependent adjustment of visual attention. The selective adaptation effect after high-conflict trials was associated with an increase in prestimulus pupil diameter, possibly reflecting increased cognitive effort of focusing attention.

Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 1—Psychometric Characteristics of 5 Paradigms

PubMed Central

Reddy, L. Felice; Horan, William P.; Barch, Deanna M.; Buchanan, Robert W.; Dunayevich, Eduardo; Gold, James M.; Lyons, Naomi; Marder, Stephen R.; Treadway, Michael T.; Wynn, Jonathan K.; Young, Jared W.; Green, Michael F.

2015-01-01

Impairments in willingness to exert effort contribute to the motivational deficits characteristic of the negative symptoms of schizophrenia. The current study evaluated the psychometric properties of 5 new or adapted paradigms to determine their suitability for use in clinical trials of schizophrenia. This study included 94 clinically stable participants with schizophrenia and 40 healthy controls. The effort-based decision-making battery was administered twice to the schizophrenia group (baseline, 4-week retest) and once to the control group. The 5 paradigms included 1 that assesses cognitive effort, 1 perceptual effort, and 3 that assess physical effort. Each paradigm was evaluated on (1) patient vs healthy control group differences, (2) test-retest reliability, (3) utility as a repeated measure (ie, practice effects), and (4) tolerability. The 5 paradigms showed varying psychometric strengths and weaknesses. The Effort Expenditure for Rewards Task showed the best reliability and utility as a repeated measure, while the Grip Effort Task had significant patient-control group differences, and superior tolerability and administration duration. The other paradigms showed weaker psychometric characteristics in their current forms. These findings highlight challenges in adapting effort and motivation paradigms for use in clinical trials. PMID:26142081

Modulation of cognitive control levels via manipulation of saccade trial-type probability assessed with event-related BOLD fMRI.

PubMed

Pierce, Jordan E; McDowell, Jennifer E

2016-02-01

Cognitive control supports flexible behavior adapted to meet current goals and can be modeled through investigation of saccade tasks with varying cognitive demands. Basic prosaccades (rapid glances toward a newly appearing stimulus) are supported by neural circuitry, including occipital and posterior parietal cortex, frontal and supplementary eye fields, and basal ganglia. These trials can be contrasted with complex antisaccades (glances toward the mirror image location of a stimulus), which are characterized by greater functional magnetic resonance imaging (MRI) blood oxygenation level-dependent (BOLD) signal in the aforementioned regions and recruitment of additional regions such as dorsolateral prefrontal cortex. The current study manipulated the cognitive demands of these saccade tasks by presenting three rapid event-related runs of mixed saccades with a varying probability of antisaccade vs. prosaccade trials (25, 50, or 75%). Behavioral results showed an effect of trial-type probability on reaction time, with slower responses in runs with a high antisaccade probability. Imaging results exhibited an effect of probability in bilateral pre- and postcentral gyrus, bilateral superior temporal gyrus, and medial frontal gyrus. Additionally, the interaction between saccade trial type and probability revealed a strong probability effect for prosaccade trials, showing a linear increase in activation parallel to antisaccade probability in bilateral temporal/occipital, posterior parietal, medial frontal, and lateral prefrontal cortex. In contrast, antisaccade trials showed elevated activation across all runs. Overall, this study demonstrated that improbable performance of a typically simple prosaccade task led to augmented BOLD signal to support changing cognitive control demands, resulting in activation levels similar to the more complex antisaccade task. Copyright © 2016 the American Physiological Society.

Massage, reflexology and other manual methods for pain management in labour.

PubMed

Smith, Caroline A; Levett, Kate M; Collins, Carmel T; Jones, Leanne

2012-02-15

Many women would like to avoid pharmacological or invasive methods of pain management in labour, and this may contribute towards the popularity of complementary methods of pain management. This review examined currently available evidence supporting the use of manual healing methods including massage and reflexology for pain management in labour. To examine the effects of manual healing methods including massage and reflexology for pain management in labour on maternal and perinatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2 of 4), MEDLINE (1966 to 30 June 2011), CINAHL (1980 to 30 June 2011), the Australian and New Zealand Clinical Trial Registry (30 June 2011), Chinese Clinical Trial Register (30 June 2011), Current Controlled Trials (30 June 2011), ClinicalTrials.gov, (30 June 2011) ISRCTN Register (30 June 2011), National Centre for Complementary and Alternative Medicine (NCCAM) (30 June 2011) and the WHO International Clinical Trials Registry Platform (30 June 2011). Randomised controlled trials comparing manual healing methods with standard care, no treatment, other non-pharmacological forms of pain management in labour or placebo. Two authors independently assessed trial quality and extracted data. We attempted to contact study authors for additional information. We included six trials, with data reporting on five trials and 326 women in the meta-analysis. We found trials for massage only. Less pain during labour was reported from massage compared with usual care during the first stage of labour (standardised mean difference (SMD) -0.82, 95% confidence interval (CI) -1.17 to -0.47), four trials, 225 women), and labour pain was reduced in one trial of massage compared with music (risk ratio (RR) 0.40, 95% CI 0.18 to 0.89, 101 women). One trial of massage compared with usual care found reduced anxiety during the first stage of labour (MD -16.27, 95% CI -27.03 to -5.51, 60 women). No trial was assessed as being at a low risk of bias for all quality domains. Massage may have a role in reducing pain, and improving women's emotional experience of labour. However, there is a need for further research.

A Randomized, Double-Blind, Sham-Controlled Trial of Transcranial Direct Current Stimulation in Attention-Deficit/Hyperactivity Disorder

PubMed Central

Cosmo, Camila; Baptista, Abrahão Fontes; de Araújo, Arão Nogueira; do Rosário, Raphael Silva; Miranda, José Garcia Vivas; Montoya, Pedro; de Sena, Eduardo Pondé

2015-01-01

Background Current standardized treatments for cognitive impairment in attention-deficit/hyperactivity disorder remain limited and their efficacy restricted. Transcranial direct current stimulation (tDCS) is a promising tool for enhancing cognitive performance in several neuropsychiatric disorders. Nevertheless, the effects of tDCS in reducing cognitive impairment in patients with attention-deficit/hyperactivity disorder (ADHD) have not yet been investigated. Methods A parallel, randomized, double-blind, sham-controlled trial was conducted to examine the efficacy of tDCS on the modulation of inhibitory control in adults with ADHD. Thirty patients were randomly allocated to each group and performed a go/no-go task before and after a single session of either anodal stimulation (1 mA) over the left dorsolateral prefrontal cortex or sham stimulation. Results A nonparametric two-sample Wilcoxon rank-sum (Mann-Whitney) test revealed no significant differences between the two groups of individuals with ADHD (tDCS vs. sham) in regard to behavioral performance in the go/no go tasks. Furthermore, the effect sizes of group differences after treatment for the primary outcome measures—correct responses, impulsivity and omission errors—were small. No adverse events resulting from stimulation were reported. Conclusion According to these findings, there is no evidence in support of the use of anodal stimulation over the left dorsolateral prefrontal cortex as an approach for improving inhibitory control in ADHD patients. To the best of our knowledge, this is the first clinical study to assess the cognitive effects of tDCS in individuals with ADHD. Further research is needed to assess the clinical efficacy of tDCS in this population. Trial Registration ClinicalTrials.gov NCT01968512 PMID:26267861

Methods of pushing during vaginal delivery and pelvic floor and perineal outcomes: a review.

PubMed

de Tayrac, Renaud; Letouzey, Vincent

2016-12-01

Over the past 20 years, several randomized studies have compared Valsalva and spontaneous pushing techniques during vaginal delivery. This review summarizes current medical knowledge concerning their maternal and fetal consequences, focusing on pelvic and perineal outcomes. We selected nine randomized controlled trials comparing Valsalva and spontaneous pushing, and a secondary analysis of a randomized controlled trial comparing different methods of perineal protection. Two trials showed that spontaneous pushing reduces the risk of perineal tears, but no firm conclusions can be drawn given the heterogeneity and inconsistent results of these studies. Conflicting results have been reported regarding the duration of the second stage of labor. Pushing technique does not seem to affect episiotomy, instrumental delivery or cesarean rates. Maternal satisfaction seems to be better after spontaneous pushing. Spontaneous pushing appears to have no adverse effects on neonatal well being, and one study showed a significant improvement in prenatal fetal parameters during the expulsive phase. Valsalva and spontaneous pushing techniques currently appear comparable in terms of duration, pelvic floor, perineal, and neonatal outcomes. In the absence of strong evidence in favor of either technique, the decision should be guided by patient preference and the clinical situation. Additional, well-designed randomized controlled trials are required.

Are Age-Related Differences Uniform Across Different Inhibitory Functions?

PubMed

Vadaga, Kiran K; Blair, Mervin; Li, Karen Z H

2016-07-01

In the current experiment, we examined the relative age-sensitivity of 3 inhibitory functions: access, deletion, and restraint by taking into consideration their underlying control processes: proactive and reactive control. The 3 inhibitory functions were measured using a sequential flanker task. Young (age: 18-35, n = 24) and older adults (age: 60-75, n = 25) first memorized a series of 8 animal words in a fixed order. In the test phase, these stimuli were presented randomly either singly or with flankers and participants responded "yes" or "no" based on the prelearned sequence. In the access trials, flankers were either ahead of the current target or unrelated. In the deletion trials, flankers were previous target items. In the restraint trials, the flanker cues (XXXX) prompted the participants to withhold responses occasionally. Unflanked trials served as the baseline condition. Age-related differences in the magnitude of inhibition effects were largest in restraint, followed by deletion. No age-related differences were observed in access. Our findings suggest that the magnitude of age-related differences in inhibitory functions is contingent on the degree of proactive control recruited by a given inhibitory function. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Reconciling the influence of task-set switching and motor inhibition processes on stop signal after-effects.

PubMed

Anguera, Joaquin A; Lyman, Kyle; Zanto, Theodore P; Bollinger, Jacob; Gazzaley, Adam

2013-01-01

Executive response functions can be affected by preceding events, even if they are no longer associated with the current task at hand. For example, studies utilizing the stop signal task have reported slower response times to "GO" stimuli when the preceding trial involved the presentation of a "STOP" signal. However, the neural mechanisms that underlie this behavioral after-effect are unclear. To address this, behavioral and electroencephalography (EEG) measures were examined in 18 young adults (18-30 years) on "GO" trials following a previously "Successful Inhibition" trial (pSI), a previously "Failed Inhibition" trial (pFI), and a previous "GO" trial (pGO). Like previous research, slower response times were observed during both pSI and pFI trials (i.e., "GO" trials that were preceded by a successful and unsuccessful inhibition trial, respectively) compared to pGO trials (i.e., "GO" trials that were preceded by another "GO" trial). Interestingly, response time slowing was greater during pSI trials compared to pFI trials, suggesting executive control is influenced by both task set switching and persisting motor inhibition processes. Follow-up behavioral analyses indicated that these effects resulted from between-trial control adjustments rather than repetition priming effects. Analyses of inter-electrode coherence (IEC) and inter-trial coherence (ITC) indicated that both pSI and pFI trials showed greater phase synchrony during the inter-trial interval compared to pGO trials. Unlike the IEC findings, differential ITC was present within the beta and alpha frequency bands in line with the observed behavior (pSI > pFI > pGO), suggestive of more consistent phase synchrony involving motor inhibition processes during the ITI at a regional level. These findings suggest that between-trial control adjustments involved with task-set switching and motor inhibition processes influence subsequent performance, providing new insights into the dynamic nature of executive control.

Renal denervation: unde venis et quo vadis?

PubMed

Nähle, C P; Düsing, R; Schild, H

2015-04-01

Renal denervation is a minimally invasive, catheter-based option for the treatment of refractory hypertension. Indications and contraindications for renal denervation have been defined in an interdisciplinary manner. The efficacy and safety of the procedure were evaluated. Currently, indication for renal denervation is limited to patients with primary hypertension and a systolic blood pressure of ≥ 160 mm Hg (or ≥ 150 mm Hg in diabetes type 2) despite optimal medical therapy with ≥ 3 different antihypertensive drugs. In this specific patient population, an average blood pressure reduction of 32/14 mmHg was observed in non-randomized/-controlled trials after renal denervation. These results were not confirmed in the first randomized controlled trial with a non-significantly superior blood pressure reduction of 14.1 ± 23.9 mm Hg compared to controls (-11.74 ± 25.94 mm Hg, difference -2.39 mm Hg p = 0.26 for superiority with a margin of 5 mm Hg) who underwent a sham procedure. The efficacy and long-term effects of renal denervation need to be re-evaluated in light of the HTN3 study results. To date, renal denervation should not be performed outside of clinical trials. Future trials should also assess if renal denervation can be performed with sufficient safety and efficacy in patients with hypertension-associated diseases. The use of renal denervation as an alternative therapy (e. g. in patients with drug intolerance) can currently not be advocated. The indication for renal denervation should be assessed in an interdisciplinary fashion and according to current guidelines with a special focus on ruling out secondary causes for arterial hypertension. 5 - 10 % of patients with hypertension suffer from refractory hypertension, but only about 1 % of patients meet the criteria for a renal denervation. Renal denervation leads to a significant decrease in office blood pressure; however, the impact on 24-hour blood pressure measurements remains unclear. In the first randomized controlled trial on renal denervation with a control group undergoing a sham procedure, blood pressure reduction failed to reach the anticipated level of superiority over best medical treatment. Periprocedural complications are rare, but long-term safety can currently not be appraised due to the limited data available. © Georg Thieme Verlag KG Stuttgart · New York.

A pragmatic, multicentre, randomised controlled trial comparing stapled haemorrhoidopexy to traditional excisional surgery for haemorrhoidal disease (eTHoS): study protocol for a randomised controlled trial.

PubMed

Watson, Angus J M; Bruhn, Hanne; MacLeod, Kathleen; McDonald, Alison; McPherson, Gladys; Kilonzo, Mary; Norrie, John; Loudon, Malcolm A; McCormack, Kirsty; Buckley, Brian; Brown, Steven; Curran, Finlay; Jayne, David; Rajagopal, Ramesh; Cook, Jonathan A

2014-11-11

Current interventions for haemorrhoidal disease include traditional haemorrhoidectomy (TH) and stapled haemorrhoidopexy (SH) surgery. However, uncertainty remains as to how they compare from a clinical, quality of life (QoL) and economic perspective. The study is therefore designed to determine whether SH is more effective and more cost-effective, compared with TH. eTHoS (either Traditional Haemorrhoidectomy or Stapled Haemorrhoidopexy for Haemorrhoidal Disease) is a pragmatic, multicentre, randomised controlled trial. Currently, 29 secondary care centres are open to recruitment. Patients, aged 18 year or older, with circumferential haemorrhoids grade II to IV, are eligible to take part. The primary clinical and economic outcomes are QoL profile (area under the curve derived from the EuroQol Group's 5 Dimension Health Status Questionnaire (EQ-5D) at all assessment points) and incremental cost per quality adjusted life year (QALY) based on the responses to the EQ-5D at 24 months. The secondary outcomes include a comparison of the SF-36 scores, pain and symptoms sub-domains, disease recurrence, complication rates and direct and indirect costs to the National Health Service (NHS). A sample size of n =338 per group has been calculated to provide 90% power to detect a difference in the mean area under the curve (AUC) of 0.25 standard deviations derived from EQ-5D score measurements, with a two-sided significance level of 5%. Allowing for non-response, 400 participants will be randomised per group. Randomisation will utilise a minimisation algorithm that incorporates centre, grade of haemorrhoidal disease, baseline EQ-5D score and gender. Blinding of participants and outcome assessors is not attempted. This is one of the largest trials of its kind. In the United Kingdom alone, 29,000 operations for haemorrhoidal disease are done annually. The trial is therefore designed to give robust evidence on which clinicians and health service managers can base management decisions and, more importantly, patients can make informed choices. Current Controlled Trials ISRCTN80061723 (assigned 8 March 2010).

Positive imagery cognitive bias modification (CBM) and internet-based cognitive behavioural therapy (iCBT) versus control CBM and iCBT for depression: study protocol for a parallel-group randomised controlled trial.

PubMed

Williams, Alishia D; Blackwell, Simon E; Holmes, Emily A; Andrews, Gavin

2013-10-29

The current randomised controlled trial will evaluate the efficacy of an internet-delivered positive imagery cognitive bias modification (CBM) intervention for depression when compared with an active control condition and help establish the additive benefit of positive imagery CBM when delivered in combination with internet cognitive behavioural therapy for depression. Patients meeting diagnostic criteria for a current major depressive episode will be recruited through the research arm of a not-for-profit clinical and research unit in Australia. The minimum sample size for each group (α set at 0.05, power at 0.80) was identified as 29, but at least 10% more will be recruited to hedge against expected attrition. We will measure the impact of CBM on primary measures of depressive symptoms (Beck Depression Inventory-second edition (BDI-II), Patient Health Questionnaire (PHQ9)) and interpretive bias (ambiguous scenarios test-depression), and on a secondary measure of psychological distress (Kessler-10 (K10)) following the 1-week CBM intervention. Secondary outcome measures of psychological distress (K10), as well as disability (WHO disability assessment schedule-II), repetitive negative thinking (repetitive thinking questionnaire), and anxiety (state trait anxiety inventory-trait version) will be evaluated following completion of the 11-week combined intervention, in addition to the BDI-II and PHQ9. Intent-to-treat marginal and mixed effect models using restricted maximum likelihood estimation will be used to evaluate the primary hypotheses. Clinically significant change will be defined as high-end state functioning (a BDI-II score <14) combined with a total score reduction greater than the reliable change index score. Maintenance of gains will be assessed at 3-month follow-up. The current trial protocol has been approved by the Human Research Ethics Committee of St Vincent's Hospital and the University of New South Wales, Sydney. Australian New Zealand Clinical Trials Registry: ACTRN12613000139774 and Clinicaltrials.gov: NCT01787513. This trial protocol is written in compliance with the Standard Protocol Items: recommendations for Interventional Trials (SPIRIT) guidelines.

Comparing high altitude treatment with current best care in Dutch children with moderate to severe atopic dermatitis (and asthma): study protocol for a pragmatic randomized controlled trial (DAVOS trial)

PubMed Central

2014-01-01

Background About 10 to 20% of children in West European countries have atopic dermatitis (AD), often as part of the atopic syndrome. The full atopic syndrome also consists of allergic asthma, allergic rhinitis and food allergy. Treatment approaches for atopic dermatitis and asthma include intermittent anti-inflammatory therapy with corticosteroids, health education and self-management training. However, symptoms persist in a subgroup of patients. Several observational studies have shown significant improvement in clinical symptoms in children and adults with atopic dermatitis or asthma after treatment at high altitude, but evidence on the efficacy when compared to treatment at sea level is still lacking. Methods/Design This study is a pragmatic randomized controlled trial for children with moderate to severe AD within the atopic syndrome. Patients are eligible for enrolment in the study if they are: diagnosed with moderate to severe AD within the atopic syndrome, aged between 8 and 18 years, fluent in the Dutch language, have internet access at home, able to use the digital patient system Digital Eczema Center Utrecht (DECU), willing and able to stay in Davos for a six week treatment period. All data are collected at the Wilhelmina Children’s Hospital and DECU. Patients are randomized over two groups. The first group receives multidisciplinary inpatient treatment during six weeks at the Dutch Asthma Center in Davos, Switzerland. The second group receives multidisciplinary treatment during six weeks at the outpatient clinic of the Wilhelmina Children’s Hospital, Utrecht, the Netherlands. The trial is not conducted as a blind trial. The trial is designed with three components: psychosocial, clinical and translational. Primary outcomes are coping with itch, quality of life and disease activity. Secondary outcomes include asthma control, medication use, parental quality of life, social and emotional wellbeing of the child and translational parameters. Discussion The results of this trial will provide evidence for the efficacy of high altitude treatment compared to treatment at sea level for children with moderate to severe AD. Trial Registration Current Controlled Trials ISRCTN88136485. PMID:24670079

Does Ureaplasma spp. cause chronic lung disease of prematurity: Ask the audience?

PubMed Central

Maxwell, Nicola C.; Nuttall, Diane; Kotecha, Sailesh

2009-01-01

Ureaplasma has long been implicated in the pathogenesis of both preterm labour and neonatal morbidity, particularly chronic lung disease of prematurity (CLD), but despite numerous studies, reviews and meta-analyses, its exact role remains unclear. Many papers call for a definitive randomised control trial to determine if eradication of pulmonary Ureaplasma decreases the rates of CLD but few address in detail the obstacles to an adequately powered clinical trial. We review the evidence for Ureaplasma as a causative agent in CLD, asking why a randomised control trial has not been performed. We surveyed the opinions of senior neonatologists in the UK on whether they felt that there was sufficient evidence for Ureaplasma either causing or not causing CLD and whether a definitive trial was needed, as well as their views on the design of such a trial. Additionally, we ascertained current practice with respect to Ureaplasma detection in preterm neonates in the UK. There is clear support for an adequately powered randomised controlled clinical trial by senior neonatologists in the UK. There are no reasons why a definitive trial cannot be conducted especially as the appropriate samples, and methods to culture or identify the organism by PCR are already available. PMID:19144476

Dissociable neural mechanisms underlying response-based and familiarity-based conflict in working memory.

PubMed

Nelson, James K; Reuter-Lorenz, Patricia A; Sylvester, Ching-Yune C; Jonides, John; Smith, Edward E

2003-09-16

Cognitive control requires the resolution of interference among competing and potentially conflicting representations. Such conflict can emerge at different points between stimulus input and response generation, with the net effect being that of compromising performance. The goal of this article was to dissociate the neural mechanisms underlying different sources of conflict to elucidate the architecture of the neural systems that implement cognitive control. By using functional magnetic resonance imaging and a verbal working memory task (item recognition), we examined brain activity related to two kinds of conflict with comparable behavioral consequences. In a trial of our item-recognition task, participants saw four letters, followed by a retention interval, and a probe letter that did or did not match one of the letters held in working memory (positive probe and negative probe, respectively). On some trials, conflict arose solely because of the current negative probe having a high familiarity, due to its membership in the immediately preceding trial's target set. On other trials, additional conflict arose because of the current negative probe having also been a positive probe on the immediately preceding trial, producing response-level conflict. Consistent with previous work, conflict due to high familiarity was associated with left prefrontal activation, but not with anterior cingulate activation. The response-conflict condition, when compared with high-familiarity conflict trials, was associated with anterior cingulate cortex activation, but with no additional left prefrontal activation. This double dissociation points to differing contributions of specific cortical areas to cognitive control, which are based on the source of conflict.

Trial-by-trial adjustments in control triggered by incidentally encoded semantic cues.

PubMed

Blais, Chris; Harris, Michael B; Sinanian, Michael H; Bunge, Silvia A

2015-01-01

Cognitive control mechanisms provide the flexibility to rapidly adapt to contextual demands. These contexts can be defined by top-down goals-but also by bottom-up perceptual factors, such as the location at which a visual stimulus appears. There are now several experiments reporting contextual control effects. Such experiments establish that contexts defined by low-level perceptual cues such as the location of a visual stimulus can lead to context-specific control, suggesting a relatively early focus for cognitive control. The current set of experiments involved a word-word interference task designed to assess whether a high-level cue, the semantic category to which a word belongs, can also facilitate contextual control. Indeed, participants exhibit a larger Flanker effect to items pertaining to a semantic category in which 75% of stimuli are incongruent than in response to items pertaining to a category in which 25% of stimuli are incongruent. Thus, both low-level and high-level stimulus features can affect the bottom-up engagement of cognitive control. The implications for current models of cognitive control are discussed.

Role of massage therapy on reduction of neonatal hyperbilirubinemia in term and preterm neonates: a review of clinical trials.

PubMed

Garg, Bhawan Deep; Kabra, Nandkishor S; Balasubramanian, Haribalakrishna

2017-09-13

Neonatal hyperbilirubinemia (NNH) is one of the leading causes of admissions in nursery throughout the world. It affects approximately 2.4-15% of neonates during the first 2 weeks of life. To evaluate the role of massage therapy for reduction of NNH in both term and preterm neonates. The literature search was done for various randomized control trials (RCTs) by searching the Cochrane Library, PubMed, and EMBASE. This review included total of 10 RCTs (two in preterm neonates and eight in term neonates) that fulfilled inclusion criteria. In most of the trials, Field massage was given. Six out of eight trials reported reduction in bilirubin levels in term neonates. However, only one trial (out of two) reported significant reduction in bilirubin levels in preterm neonates. Both trials in preterm neonates and most of the trials in term neonates (five trials) reported increased stool frequencies. Role of massage therapy in the management of NNH is supported by the current evidence. However, due to limitations of the trials, current evidences are not sufficient to use massage therapy for the management of NNH in routine practice.

Early vasopressor use following traumatic injury: a systematic review.

PubMed

Hylands, Mathieu; Toma, Augustin; Beaudoin, Nicolas; Frenette, Anne Julie; D'Aragon, Frédérick; Belley-Côté, Émilie; Charbonney, Emmanuel; Møller, Morten Hylander; Laake, Jon Henrik; Vandvik, Per Olav; Siemieniuk, Reed Alexander; Rochwerg, Bram; Lauzier, François; Green, Robert S; Ball, Ian; Scales, Damon; Murthy, Srinivas; Kwong, Joey S W; Guyatt, Gordon; Rizoli, Sandro; Asfar, Pierre; Lamontagne, François

2017-11-17

Current guidelines suggest limiting the use of vasopressors following traumatic injury; however, wide variations in practice exist. Although excessive vasoconstriction may be harmful, these agents may help reduce administration of potentially harmful resuscitation fluids. This systematic review aims to compare early vasopressor use to standard resuscitation in adults with trauma-induced shock. Systematic review. We searched MEDLINE, EMBASE, ClinicalTrials.gov and the Central Register of Controlled Trials from inception until October 2016, as well as the proceedings of 10 relevant international conferences from 2005 to 2016. Randomised controlled trials and controlled observational studies that compared the early vasopressor use with standard resuscitation in adults with acute traumatic injury. Of 8001 citations, we retrieved 18 full-text articles and included 6 studies (1 randomised controlled trial and 5 observational studies), including 2 published exclusively in abstract form. Across observational studies, vasopressor use was associated with increased short-term mortality, with unadjusted risk ratios ranging from 2.31 to 7.39. However, the risk of bias was considered high in these observational studies because patients who received vasopressors were systematically sicker than patients treated without vasopressors. One clinical trial (n=78) was too imprecise to yield meaningful results. Two clinical trials are currently ongoing. No study measured long-term quality of life or cognitive function. Existing data on the effects of vasopressors following traumatic injury are of very low quality according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. With emerging evidence of harm associated with aggressive fluid resuscitation and, in selected subgroups of patients, with permissive hypotension, the alternatives to vasopressor therapy are limited. Observational data showing that vasopressors are part of usual care would provide a strong justification for high-quality clinical trials of early vasopressor use during trauma resuscitation. CRD42016033437. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Reporting of interventions and "standard of care" control arms in pediatric clinical trials: a quantitative analysis.

PubMed

Yu, Ashley M; Balasubramanaiam, Bannuya; Offringa, Martin; Kelly, Lauren E

2018-06-13

In pediatric medicine, the usual treatment received by children ("standard of care") varies across centers. Evaluations of new treatments often compare to the existing "standard of care" to determine if a treatment is more effective, has a better safety profile, or costs less. The objective of our study was to evaluate intervention and "standard of care" control arms reported in published pediatric clinical trials. Pediatric clinical trials, published in 2014, reporting the use of a "standard of care" control arm were included. Duplicate assessment of reporting completeness was done using the 12-item TIDieR (Template for Intervention Description and Replication) checklist for both the "standard of care" control arms and intervention arms within the same published study. Following screening, 214 pediatric trials in diverse therapeutic areas were included. Several different terms were used to describe "standard of care." There was a significant difference between the mean reported TIDieR checklist items of "standard of care" control arms (5.81 (SD 2.13) and intervention arms (8.45 (SD 1.39, p < 0.0001). Reporting of intervention and "standard of care" control arms in pediatric clinical trials should be improved as current "standard of care" reporting deficiencies limit reproducibility of research and may ultimately contribute to research waste.

The effects and costs of the universal parent group program - all children in focus: a study protocol for a randomized wait-list controlled trial.

PubMed

Lindberg, Lene; Ulfsdotter, Malin; Jalling, Camilla; Skärstrand, Eva; Lalouni, Maria; Lönn Rhodin, Kajsa; Månsdotter, Anna; Enebrink, Pia

2013-07-29

In recent decades, parents have been involved in programs that aim to improve parenting style and reduce child behavior problems. Research of preventive parenting programs has shown that these interventions generally have a positive influence on both parents and children. However, to our knowledge there is a gap in the scientific literature when it comes to randomized controlled trials of brief, manual-based structured programs which address general parenting among the population, and focus on promoting health. A four-session universal health promotion parent group program named All Children in Focus was developed. It aims at promoting parental competence and children's positive development with the parent-child relationship as the target. There is currently no randomized controlled trial existing of the program. A prospective multicenter randomized wait-list controlled trial is being conducted. Approximately 600 parents with children ranging in age from 3-12 years have been recruited in eleven municipalities and city districts in the County of Stockholm, Sweden. Parents are randomized at baseline to an intervention group, which receives the program directly, or to a waiting-list control group, which participates in the program six months later. Changes in parenting and child health and development are assessed with measures immediately post-intervention and six months after the baseline. Observations of a minor group of parents and children are conducted to explore possible relations between parental reports and observed behaviors, as well as changes in the interaction between parent and child. Further, data collected within the evaluation will also be applied to evaluate the possible cost-effectiveness of the program. This paper describes a study protocol of a randomized controlled trial. Except for the quantitative outcome measures to evaluate the effectiveness of All Children in Focus, this protocol also describes health economic and qualitative analyses to deepen the knowledge of the program. We further discuss some issues regarding the implementation of the program in municipalities and city districts. Current Controlled Trials ISRCTN70202532.

Diarrhea and dengue control in rural primary schools in Colombia: study protocol for a randomized controlled trial.

PubMed

Overgaard, Hans J; Alexander, Neal; Mátiz, Maria Ines; Jaramillo, Juan Felipe; Olano, Victor Alberto; Vargas, Sandra; Sarmiento, Diana; Lenhart, Audrey; Seidu, Razak; Stenström, Thor Axel

2012-10-03

Diarrheal diseases and dengue fever are major global health problems. Where provision of clean water is inadequate, water storage is crucial. Fecal contamination of stored water is a common source of diarrheal illness, but stored water also provides breeding sites for dengue vector mosquitoes. Poor household water management and sanitation are therefore potential determinants of both diseases. Little is known of the role of stored water for the combined risk of diarrhea and dengue, yet a joint role would be important for developing integrated control and management efforts. Even less is known of the effect of integrating control of these diseases in school settings. The objective of this trial was to investigate whether interventions against diarrhea and dengue will significantly reduce diarrheal disease and dengue entomological risk factors in rural primary schools. This is a 2×2 factorial cluster randomized controlled trial. Eligible schools were rural primary schools in La Mesa and Anapoima municipalities, Cundinamarca, Colombia. Eligible pupils were school children in grades 0 to 5. Schools were randomized to one of four study arms: diarrhea interventions (DIA); dengue interventions (DEN); combined diarrhea and dengue interventions (DIADEN); and control (C). Schools were allocated publicly in each municipality (strata) at the start of the trial, obviating the need for allocation concealment. The primary outcome for diarrhea is incidence rate of diarrhea in school children and for dengue it is density of adult female Aedes aegypti per school. Approximately 800 pupils from 34 schools were enrolled in the trial with eight schools in the DIA arm, nine in the DEN, eight in the DIADEN, and nine in the control arms. The trial status as of June 2012 was: completed baseline data collections; enrollment, randomization, and allocation of schools. The trial was funded by the Research Council of Norway and the Lazos de Calandaima Foundation. This is the first trial investigating the effect of a set of integrated interventions to control both dengue and diarrhea. This is also the first trial to study the combination of diarrhea-dengue disease control in school settings. Current Controlled Trials ISRCTN40195031.

Bibliotherapy for Children with Anxiety Disorders Using Written Materials for Parents: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Rapee, Ronald M.; Abbott, Maree J.; Lyneham, Heidi J.

2006-01-01

The current trial examined the value of modifying empirically validated treatment for childhood anxiety for application via written materials for parents of anxious children. Two hundred sixty-seven clinically anxious children ages 6-12 years and their parents were randomly allocated to standard group treatment, wait list, or a bibliotherapy…

Emotion Regulation Enhancement of Cognitive Behavior Therapy for College Student Problem Drinkers: A Pilot Randomized Controlled Trial

ERIC Educational Resources Information Center

Ford, Julian D.; Grasso, Damion J.; Levine, Joan; Tennen, Howard

2018-01-01

This pilot randomized clinical trial tested an emotion regulation enhancement to cognitive behavior therapy (CBT) with 29 college student problem drinkers with histories of complex trauma and current clinically significant traumatic stress symptoms. Participants received eight face-to-face sessions of manualized Internet-supported CBT for problem…

Temperature-controlled laminar airflow in severe asthma for exacerbation reduction (The LASER Trial): study protocol for a randomised controlled trial.

PubMed

Storrar, Will; Fogg, Carole; Brown, Tom; Dennison, Paddy; Yu, Ly-Mee; Dewey, Ann; Luengo-Fernandez, Ramon; Dean, Tara; Rahman, Najib; Mansur, Adel; Howarth, Peter H; Bradding, Peter; Chauhan, Anoop J

2016-01-08

Asthma affects more than 5 million patients in the United Kingdom. Nearly 500,000 of these patients have severe asthma with severe symptoms and frequent exacerbations that are inadequately controlled with available treatments. The burden of severe asthma on the NHS is enormous, accounting for 80 % of the total asthma cost (£1 billion), with frequent exacerbations and expensive medications generating much of this cost. Of those patients with severe asthma, 70 % are sensitised to indoor aeroallergens, and the level of exposure to allergens determines the symptoms; patients exposed to high levels are therefore most at risk of exacerbations and hospital admissions. The LASER trial aims to assess whether a new treatment, temperature controlled laminar airflow (TLA) delivered by the Airsonett™ device, can reduce the frequency of exacerbations in patients with severe allergic asthma by reducing exposure to aeroallergens overnight. This multicentre study is a placebo-controlled, blinded, randomised controlled, parallel group trial. A total of 222 patients with a new or current diagnosis of severe allergic asthma will be assigned with a random element in a 1:1 ratio to receive either an active device for one year or a placebo device. The primary outcome is the frequency of severe asthma exacerbations occurring over a 12-month period, defined in accordance with the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. Secondary outcomes include changes in asthma control, lung function, asthma-specific and global quality of life for participants and their carers, adherence to intervention, healthcare resource use and costs, and cost-effectiveness. Qualitative interviews will be conducted to elicit participant's and their partner's perceptions of the treatment. Effective measures of allergen avoidance have, to date, proved elusive. The LASER trial aims to address this. The study will ascertain whether home-based nocturnal TLA usage over a 12-month period can reduce the frequency of exacerbations and improve asthma control and quality of life as compared to placebo, whilst being cost-effective and acceptable to adults with poorly controlled, severe allergic asthma. The results of this study will be widely applicable to the many patients with allergic asthma both in the UK and internationally. Current controlled trials ISRCTN46346208 (Date assigned 22 January 2014).

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

PubMed

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

2016-01-01

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

The Use of Cannabinoids in Treating Dementia.

PubMed

Weier, Megan; Hall, Wayne

2017-08-01

To review and summarise the current evidence on the safety and efficacy of using cannabinoids to treat behavioural and neuropsychiatric symptoms of dementia. Two randomised controlled trials testing a synthetic form of tetrahydrocannabinol have shown that while well tolerated, there was no significant therapeutic effect, based on changes to scores on the neuropsychiatric inventory (NPI). Case reports and open label trials have indicated that there may be some therapeutic benefit of adding synthetic cannabinoids as an adjunctive therapy to reduce agitation, aberrant motor behaviour and nighttime behaviour. More well-controlled clinical trials in older populations with varying severity of dementia are needed to evaluate the effectiveness of cannabinoids in treating behaviour symptoms of dementia. We provide suggestions for designing such trials and evaluating possible adverse effects of cannabinoids on cognitive and neuropsychiatric functioning.

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

PubMed Central

2014-01-01

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

Infection control strategies for preventing the transmission of meticillin-resistant Staphylococcus aureus (MRSA) in nursing homes for older people.

PubMed

Hughes, Carmel; Smith, Michael; Tunney, Michael; Bradley, Marie C

2011-12-07

Nursing homes for older people provide an environment likely to promote the acquisition and spread of meticillin-resistant Staphylococcus aureus (MRSA), putting residents at increased risk of colonisation and infection. It is recognised that infection prevention and control strategies are important in preventing and controlling MRSA transmission. To determine the effects of infection prevention and control strategies for preventing the transmission of MRSA in nursing homes for older people. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2011, Issue 2), the Cochrane Wounds Group Specialised Register (searched May 27th, 2011). We also searched Ovid MEDLINE (from 1950 to April Week 2 2011), OVID MEDLINE (In-process and Other Non-Indexed Citations, April 26th 2011) Ovid EMBASE (1980 to 2011 Week 16), EBSCO CINAHL (1982 to April 21st 2011), DARE (1992 to 2011, week 16), Web of Science (1981 to May 2011), and the Health Technology Assessment (HTA) website (1988 to May 2011). Research in progress was sought through Current Clinical Trials (www.controlled-trials.com), Medical Research Council Research portfolio, and HSRPRoj (current USA projects). All randomised and controlled clinical trials, controlled before and after studies and interrupted time series studies of infection prevention and control interventions in nursing homes for older people were eligible for inclusion. Two review authors independently reviewed the results of the searches. Another review author appraised identified papers and undertook data extraction which was checked by a second review author. For this second update only one study was identified, therefore it was not possible to undertake a meta-analysis. A cluster randomised controlled trial in 32 nursing homes evaluated the effect of an infection control education and training programme on MRSA prevalence. The primary outcome was MRSA prevalence in residents and staff, and a change in infection control audit scores which measured adherence to infection control standards. At the end of the 12 month study, there was no change in MRSA prevalence between intervention and control sites, while mean infection control audit scores were significantly higher in the intervention homes compared with control homes. There is a lack of research evaluating the effects on MRSA transmission of infection prevention and control strategies in nursing homes. Rigorous studies should be conducted in nursing homes, to test interventions that have been specifically designed for this unique environment.

Transcranial direct current stimulation (tDCS) for treatment of major depression during pregnancy: study protocol for a pilot randomized controlled trial.

PubMed

Vigod, Simone; Dennis, Cindy-Lee; Daskalakis, Zafiris; Murphy, Kellie; Ray, Joel; Oberlander, Tim; Somerton, Sarah; Hussain-Shamsy, Neesha; Blumberger, Daniel

2014-09-18

Women with depression in pregnancy are faced with difficult treatment decisions. Untreated, antenatal depression has serious negative implications for mothers and children. While antidepressant drug treatment is likely to improve depressive symptoms, it crosses the placenta and may pose risks to the unborn child. Transcranial direct current stimulation is a focal brain stimulation treatment that improves depressive symptoms within 3 weeks of treatment by inducing changes to brain areas involved in depression, without impacting any other brain areas, and without inducing changes to heart rate, blood pressure or core body temperature. The localized nature of transcranial direct current stimulation makes it an ideal therapeutic approach for treating depression during pregnancy, although it has never previously been evaluated in this population. We describe a pilot randomized controlled trial of transcranial direct current stimulation among women with depression in pregnancy to assess the feasibility of a larger, multicentre efficacy study. Women over 18 years of age and between 14 and 32 weeks gestation can be enrolled in the study provided they meet diagnostic criteria for a major depressive episode of at least moderate severity and have been offered but refused antidepressant medication. Participants are randomized to receive active transcranial direct current stimulation or a sham condition that is administered in 15 30-minute treatments over three weeks. Women sit upright during treatment and receive obstetrical monitoring prior to, during and after each treatment session. Depressive symptoms, treatment acceptability, and pregnancy outcomes are assessed at baseline (prior to randomization), at the end of each treatment week, every four weeks post-treatment until delivery, and at 4 and 12 weeks postpartum. Transcranial direct current stimulation is a novel therapeutic option for treating depression during pregnancy. This protocol allows for assessment of the feasibility of, acceptability of and adherence with a clinical trial protocol to administer this treatment to pregnant women with moderate to severe depression. Results from this pilot study will guide the development of a larger multicentre trial to definitively test the efficacy and safety of transcranial direct current stimulation for pregnant women with depression. Clinical Trials Gov NCT02116127.

To assess whether indoor residual spraying can provide additional protection against clinical malaria over current best practice of long-lasting insecticidal mosquito nets in The Gambia: study protocol for a two-armed cluster-randomised trial

PubMed Central

2011-01-01

Background Recently, there has been mounting interest in scaling-up vector control against malaria in Africa. It needs to be determined if indoor residual spraying (IRS with DDT) will provide significant marginal protection against malaria over current best practice of long-lasting insecticidal nets (LLINs) and prompt treatment in a controlled trial, given that DDT is currently the most persistent insecticide for IRS. Methods A 2 armed cluster-randomised controlled trial will be conducted to assess whether DDT IRS and LLINs combined provide better protection against clinical malaria in children than LLINs alone in rural Gambia. Each cluster will be a village, or a group of small adjacent villages; all clusters will receive LLINs and half will receive IRS in addition. Study children, aged 6 months to 13 years, will be enrolled from all clusters and followed for clinical malaria using passive case detection to estimate malaria incidence for 2 malaria transmission seasons in 2010 and 2011. This will be the primary endpoint. Exposure to malaria parasites will be assessed using light and exit traps followed by detection of Anopheles gambiae species and sporozoite infection. Study children will be surveyed at the end of each transmission season to estimate the prevalence of Plasmodium falciparum infection and the prevalence of anaemia. Discussion Practical issues concerning intervention implementation, as well as the potential benefits and risks of the study, are discussed. Trial Registration ISRCTN01738840 - Spraying And Nets Towards malaria Elimination (SANTE) PMID:21663656

[Systematic review about eccentric training in chronic achilles tendinopathy].

PubMed

Krämer, R; Lorenzen, J; Vogt, P M; Knobloch, K

2010-12-01

Throughout the recent decade, eccentric training has become a widely accepted therapy option in the conservative treatment of chronic Achilles tendinopathy. Nevertheless, current recommendations are missing regarding dosage and duration of eccentric training as well as standardized training protocols. Is eccentric training as a conservative treatment in chronic Achilles tendinopathy of beneficial effect versus other conservative treatments? According to the current scientific data, is it possible to recommend dosages and duration of training time of eccentric training? Systematic review of the current scientific literature on eccentric training as a conservative treatment in chronic Achilles tendinopathy according to the PRISMA-guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). National library of Medicine (NLM) between the years 1950 and 2010. Prospective randomised controlled trials (RCT). 8 RCTs included 416 subjects with a median number of 42 subjects and a range of 17 to 116 subjects per trial. Median follow-up duration was 12 weeks with a range from 12 to 54 weeks. 124 papers met the eligibility criteria in the NLM, whereas only eight randomised controlled trials were included in this review after screening titles, abstracts and full texts. All included trials demonstrated an improvement in pain after performing equivalent training protocols of eccentric training in chronic Achilles tendinopathy. A pooled statistical evaluation of the included trials could not be performed due to different study designs as well as limited documentation of subjects' compliance. In spite of different compliance, effects of eccentric training in conservative treatment of chronic mid-portion-Achilles tendinopathy are promising. Because of the heterogeneous outcome variables (ordinal scale, VAS, FAOS, AOFAS, VISA-A) and the methodological limitations of the trials, no definite recommendation can be published concerning dosage and duration of eccentric training in chronic Achilles tendinopathy. © Georg Thieme Verlag KG Stuttgart · New York.

Enhancing motivation within a rapid opioid substitution treatment feasibility RCT: a nested qualitative study.

PubMed

Ayres, Rachel; Ingram, Jenny; Rees, Avril; Neale, Jane; Beattie, Angela; Telfer, Maggie

2014-11-18

Opioid substitution treatment (OST) has multiple benefits for heroin injectors and is an evidence-based major component of international treatment. The current qualitative study sought to explore participants' attitudes to and reasons for participating in a feasibility randomised trial in primary care offering 'same day' OST (methadone) for injecting heroin users compared to usual care. Twenty injecting heroin users (8 intervention and 12 controls; 16 males and 4 females) were interviewed; purposive sampling was used to select a maximum variation sample from those who agreed; and analysis used thematic methods. Motivation to join the trial included the need to secure treatment set against some ambivalence due to previous negative experiences of trying to obtain OST. Positive effects of securing methadone via the trial, included self-reported improvements in health and self-care; reduction in crime, stress and drug use. Completing the baseline questionnaires at recruitment appeared to enhance motivation for treatment for all participants. For some control participants, this motivation seemed to increase a sense of self-efficacy and cognitive dissonance generated was resolved by seeking treatment from their GP. Self-determination theory suggests that behaviour change may have been initiated during the recruitment appointment, resulting in an increased determination to seek treatment amongst control participants. Taking part in the 'script in a day' trial enabled participants in the intervention arm to gain same-day access to methadone and reduce their drug use. For those in the control arm, completing the baseline questionnaires at recruitment appeared to create cognitive dissonance between their current health state and own aspirations, so increasing motivation for treatment. Over 50% obtained and were still in receipt of OST (methadone or buprenorphine) at the 3 month follow-up. We suggest that a regular 'health evaluation' for injecting heroin users not in treatment, paired with low-barrier access to treatment, may be a way of exploring this and encouraging more into obtaining OST more quickly and at the best time for them. This intervention should be delivered without pressure for change. This trial is registered with International Standard Randomised Controlled Trial Number Register: SCript In a Day for injecting drug users: feasibility trial: ISRCTN16846554.

Further characterisation of the functional neuroanatomy associated with prosodic emotion decoding.

PubMed

Mitchell, Rachel L C

2013-06-01

Current models of prosodic emotion comprehension propose a three stage cognition mediated by temporal lobe auditory regions through to inferior and orbitofrontal regions. Cumulative evidence suggests that its mediation may be more flexible though, with a facility to respond in a graded manner based on the need for executive control. The location of this fine-tuning system is unclear, as is its similarity to the cognitive control system. In the current study, need for executive control was manipulated in a block-design functional MRI study by systematically altering the proportion of incongruent trials across time, i.e., trials for which participants identified prosodic emotions in the face of conflicting lexico-semantic emotion cues. Resultant Blood Oxygenation Level Dependent contrast data were analysed according to standard procedures using Statistical Parametric Mapping v8 (Ashburner et al., 2009). In the parametric analyses, superior (medial) frontal gyrus activity increased linearly with increased need for executive control. In the separate analyses of each level of incongruity, results suggested that the baseline prosodic emotion comprehension system was sufficient to deal with low proportions of incongruent trials, whereas a more widespread frontal lobe network was required for higher proportions. These results suggest an executive control system for prosodic emotion comprehension exists which has the capability to recruit superior (medial) frontal gyrus in a graded manner and other frontal regions once demand exceeds a certain threshold. The need to revise current models of prosodic emotion comprehension and add a fourth processing stage are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Immaturities in Reward Processing and Its Influence on Inhibitory Control in Adolescence

PubMed Central

Terwilliger, R.; Teslovich, T.; Velanova, K.; Luna, B.

2010-01-01

The nature of immature reward processing and the influence of rewards on basic elements of cognitive control during adolescence are currently not well understood. Here, during functional magnetic resonance imaging, healthy adolescents and adults performed a modified antisaccade task in which trial-by-trial reward contingencies were manipulated. The use of a novel fast, event-related design enabled developmental differences in brain function underlying temporally distinct stages of reward processing and response inhibition to be assessed. Reward trials compared with neutral trials resulted in faster correct inhibitory responses across ages and in fewer inhibitory errors in adolescents. During reward trials, the blood oxygen level–dependent signal was attenuated in the ventral striatum in adolescents during cue assessment, then overactive during response preparation, suggesting limitations during adolescence in reward assessment and heightened reactivity in anticipation of reward compared with adults. Importantly, heightened activity in the frontal cortex along the precentral sulcus was also observed in adolescents during reward-trial response preparation, suggesting reward modulation of oculomotor control regions supporting correct inhibitory responding. Collectively, this work characterizes specific immaturities in adolescent brain systems that support reward processing and describes the influence of reward on inhibitory control. In sum, our findings suggest mechanisms that may underlie adolescents’ vulnerability to poor decision-making and risk-taking behavior. PMID:19875675

Pre-cue Fronto-Occipital Alpha Phase and Distributed Cortical Oscillations Predict Failures of Cognitive Control

PubMed Central

Hamm, Jordan P.; Dyckman, Kara A.; McDowell, Jennifer E.; Clementz, Brett A.

2012-01-01

Cognitive control is required for correct performance on antisaccade tasks, including the ability to inhibit an externally driven ocular motor repsonse (a saccade to a peripheral stimulus) in favor of an internally driven ocular motor goal (a saccade directed away from a peripheral stimulus). Healthy humans occasionally produce errors during antisaccade tasks, but the mechanisms associated with such failures of cognitive control are uncertain. Most research on cognitive control failures focuses on post-stimulus processing, although a growing body of literature highlights a role of intrinsic brain activity in perceptual and cognitive performance. The current investigation used dense array electroencephalography and distributed source analyses to examine brain oscillations across a wide frequency bandwidth in the period prior to antisaccade cue onset. Results highlight four important aspects of ongoing and preparatory brain activations that differentiate error from correct antisaccade trials: (i) ongoing oscillatory beta (20–30Hz) power in anterior cingulate prior to trial initiation (lower for error trials), (ii) instantaneous phase of ongoing alpha-theta (7Hz) in frontal and occipital cortices immediately before trial initiation (opposite between trial types), (iii) gamma power (35–60Hz) in posterior parietal cortex 100 ms prior to cue onset (greater for error trials), and (iv) phase locking of alpha (5–12Hz) in parietal and occipital cortices immediately prior to cue onset (lower for error trials). These findings extend recently reported effects of pre-trial alpha phase on perception to cognitive control processes, and help identify the cortical generators of such phase effects. PMID:22593071

The Neural Substrates of Cognitive Control Deficits in Autism Spectrum Disorders

PubMed Central

Solomon, Marjorie; Ozonoff, Sally; Ursu, Stefan; Ravizza, Susan; Cummings, Neil; Ly, Stanford; Carter, Cameron

2009-01-01

Executive functions deficits are among the most frequently reported symptoms of autism spectrum disorders (ASDs), however, there have been few functional magnetic resonance imaging (fMRI) studies that investigate the neural substrates of executive functions deficits in ASDs, and only one in adolescents. The current study examined cognitive control –the ability to maintain task context online to support adaptive functioning in the face of response competition—in 22 adolescents aged 12–18 with autism spectrum disorders and 23 age, gender, and IQ matched typically developing subjects. During the cue phase of the task, where subjects must maintain information online to overcome a prepotent response tendency, typically developing subjects recruited significantly more anterior frontal (BA 10), parietal (BA 7, 40), and occipital regions (BA 18) for high control trials (25% of trials) versus low control trials (75% of trials). Both groups showed similar activation for low control cues, however the ASD group exhibited significantly less activation for high control cues. Functional connectivity analysis using time series correlation, factor analysis, and beta series correlation methods provided convergent evidence that the ASD group exhibited lower levels of functional connectivity and less network integration between frontal, parietal, and occipital regions. In the typically developing group, fronto-parietal connectivity was related to lower error rates on high control trials. In the autism group, reduced fronto-parietal connectivity was related to attention deficit hyperactivity disorder symptoms. PMID:19410583

The effectiveness of a stratified care model for non-specific low back pain in Danish primary care compared to current practice: study protocol of a randomised controlled trial.

PubMed

Morso, Lars; Schiøttz-Christensen, Berit; Søndergaard, Jens; Andersen, Nils-Bo de Vos; Pedersen, Flemming; Olsen, Kim Rose; Jensen, Morten Sall; Hill, Jonathan; Christiansen, David Høyrup

2018-06-08

Prior studies indicate that stratified care for low back pain results in better clinical outcome and reduced costs in healthcare compared to current practice. Stratified care may be associated with clinical benefits for patients with low back pain at a lower cost, but evidence is sparse. Hence this study aims to evaluate the clinical effects and cost-effectiveness of stratified care in patients with non-specific low back pain compared to current practice. The study is a two-armed randomised controlled trial in primary care in the Regions of Southern and Central Denmark (2.5 million citizens). Patients with non-specific low back will be recruited by paticpating GPs. Patients are randomised to either (1) stratified care or (2) current practice at participating physiotherapy clinics. In the stratified care arm, the intervention is based on the patient's STarT Back Tool classification and trained accordingly, whereas physiotherapists in the current pratice arm are blinded to the STarT score. Primary outcomes in the trial will be group differences in time off work, improvement in LBP disability measured by the Roland Morris Disability Questionnaire (RMDQ) and patient-reported global change. Secondary measures will be pain intensity, patient satisfaction, data on patient healthcare resource utilisation and quality-adjusted life year based on the EQ-5D-5L. Stratified care that effectively targets treatment to relevant sub-groups of patients has potentially great impact on the treatment pathways of low back pain. Thus, if effective, this could result in better patient outcomes and at the same time reduce the costs for treatment of low back pain. ClinicalTrials.gov , NCT02612467 . Registered on 16 November 2015.

Monitoring the outcomes of interventions against Taenia solium: options and suggestions.

PubMed

Lightowlers, M W; Garcia, H H; Gauci, C G; Donadeu, M; Abela-Ridder, B

2016-03-01

There is an increasing interest in reducing the incidence of human neurocysticercosis, caused by infection with the larval stage of Taenia solium. Several intervention trials are currently assessing various options for control of T. solium transmission. A critical aspect of these trials will be the evaluation of whether the interventions have been successful. However, there is no consensus about the most appropriate or valuable methods that should be used. Here, we undertake a critical assessment of the diagnostic tests which are currently available for human T. solium taeniasis and human and porcine cysticercosis, as well as their suitability for evaluation of intervention trial outcomes. Suggestions are made about which of the measures that are available for evaluation of T. solium interventions would be most suitable, and which methodologies are the most appropriate given currently available technologies. Suggestions are also made in relation to the most urgent research needs in order to address deficiencies in current diagnostic methods. © 2015 The Authors. Parasite Immunology Published by John Wiley & Sons Ltd.

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

PubMed

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

2017-01-01

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

Physical therapy with drug treatment in Bell palsy: a focused review.

PubMed

Ferreira, Margarida; Marques, Elisa E; Duarte, José A; Santos, Paula C

2015-04-01

The physical therapy (PT) associated with standard drug treatment (SDT) in Bell palsy has never been investigated. Randomized controlled trials or quasirandomized controlled trials have compared facial PT (except treatments such as acupuncture and osteopathic) combined with SDT against a control group with SDT alone. Participants included those older than 15 yrs with a clinical diagnosis of Bell palsy, and the primary outcome measure was motor function recovery by the House-Brackmann scale. The methodologic quality of each study was also independently assessed by two reviewers using the PEDro scale. Four studies met the inclusion criteria. Three trials indicate that PT in association with SDT supports higher motor function recovery than SDT alone between 15 days and 1 yr of follow-up. On the other hand, one trial showed that electrical stimulation added to conventional PT with SDT did not influence treatment outcomes. The present review suggests that the current practice of Bell palsy treatment by PT associated with SDT seems to have a positive effect on grade and time recovery compared with SDT alone. However, there is very little quality evidence from randomized controlled trials, and such evidence is insufficient to decide whether combined treatment is beneficial in the management of Bell palsy.

Comparing high altitude treatment with current best care in Dutch children with moderate to severe atopic dermatitis (and asthma): study protocol for a pragmatic randomized controlled trial (DAVOS trial).

PubMed

Fieten, Karin B; Zijlstra, Wieneke T; van Os-Medendorp, Harmieke; Meijer, Yolanda; Venema, Monica Uniken; Rijssenbeek-Nouwens, Lous; l'Hoir, Monique P; Bruijnzeel-Koomen, Carla A; Pasmans, Suzanne G M A

2014-03-26

About 10 to 20% of children in West European countries have atopic dermatitis (AD), often as part of the atopic syndrome. The full atopic syndrome also consists of allergic asthma, allergic rhinitis and food allergy. Treatment approaches for atopic dermatitis and asthma include intermittent anti-inflammatory therapy with corticosteroids, health education and self-management training. However, symptoms persist in a subgroup of patients. Several observational studies have shown significant improvement in clinical symptoms in children and adults with atopic dermatitis or asthma after treatment at high altitude, but evidence on the efficacy when compared to treatment at sea level is still lacking. This study is a pragmatic randomized controlled trial for children with moderate to severe AD within the atopic syndrome. Patients are eligible for enrolment in the study if they are: diagnosed with moderate to severe AD within the atopic syndrome, aged between 8 and 18 years, fluent in the Dutch language, have internet access at home, able to use the digital patient system Digital Eczema Center Utrecht (DECU), willing and able to stay in Davos for a six week treatment period. All data are collected at the Wilhelmina Children's Hospital and DECU. Patients are randomized over two groups. The first group receives multidisciplinary inpatient treatment during six weeks at the Dutch Asthma Center in Davos, Switzerland. The second group receives multidisciplinary treatment during six weeks at the outpatient clinic of the Wilhelmina Children's Hospital, Utrecht, the Netherlands. The trial is not conducted as a blind trial. The trial is designed with three components: psychosocial, clinical and translational. Primary outcomes are coping with itch, quality of life and disease activity. Secondary outcomes include asthma control, medication use, parental quality of life, social and emotional wellbeing of the child and translational parameters. The results of this trial will provide evidence for the efficacy of high altitude treatment compared to treatment at sea level for children with moderate to severe AD. Current Controlled Trials ISRCTN88136485.

ShopSmart 4 Health – Protocol of a skills-based randomised controlled trial promoting fruit and vegetable consumption among socioeconomically disadvantaged women

PubMed Central

2013-01-01

Background There is a need for evidence on the most effective and cost-effective approaches for promoting healthy eating among groups that do not meet dietary recommendations for good health, such as those with low incomes or experiencing socioeconomic disadvantage. This paper describes the ShopSmart 4 Health study, a randomised controlled trial conducted by Deakin University, Coles Supermarkets and the Heart Foundation, to investigate the effectiveness and cost-effectiveness of a skill-building intervention for promoting increased purchasing and consumption of fruits and vegetables amongst women of low socioeconomic position (SEP). Methods/design ShopSmart 4 Health employed a randomised controlled trial design. Women aged 18–60 years, holding a Coles store loyalty card, who shopped at Coles stores within socioeconomically disadvantaged neighbourhoods and met low-income eligibility criteria were invited to participate. Consenting women completed a baseline survey assessing food shopping and eating habits and food-related behaviours and attitudes. On receipt of their completed survey, women were randomised to either a skill-building intervention or a wait-list control condition. Intervention effects will be evaluated via self-completion surveys and using supermarket transaction sales data, collected at pre- and post-intervention and 6-month follow-up. An economic evaluation from a societal perspective using a cost-consequences approach will compare the costs and outcomes between intervention and control groups. Process evaluation will be undertaken to identify perceived value and effects of intervention components. Discussion This study will provide data to address the currently limited evidence base regarding the effectiveness and cost-effectiveness of skill-building intervention strategies aimed at increasing fruit and vegetable consumption among socioeconomically disadvantaged women, a target group at high risk of poor diets. Trial registration Current Controlled Trials ISRCTN48771770 PMID:23668896

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

PubMed Central

2014-01-01

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

The effect of replacing saturated fat with mostly n-6 polyunsaturated fat on coronary heart disease: a meta-analysis of randomised controlled trials.

PubMed

Hamley, Steven

2017-05-19

A cornerstone of conventional dietary advice is the recommendation to replace saturated fatty acids (SFA) with mostly n-6 polyunsaturated fatty acids (PUFA) to reduce the risk of coronary heart disease (CHD). Many clinical trials aimed to test this advice and have had their results pooled in several meta-analyses. However, earlier meta-analyses did not sufficiently account for major confounding variables that were present in some of those trials. Therefore, the aim of the study was to account for the major confounding variables in the diet heart trials, and emphasise the results from those trials that most accurately test the effect of replacing SFA with mostly n-6 PUFA. Clinical trials were identified from earlier meta-analyses. Relevant trials were categorised as 'adequately controlled' or 'inadequately controlled' depending on whether there were substantial dietary or non-dietary differences between the experimental and control groups that were not related to SFA or mostly n-6 PUFA intake, then were subject to different subgroup analyses. When pooling results from only the adequately controlled trials there was no effect for major CHD events (RR = 1.06, CI = 0.86-1.31), total CHD events (RR = 1.02, CI = 0.84-1.23), CHD mortality (RR = 1.13, CI = 0.91-1.40) and total mortality (RR = 1.07, CI = 0.90-1.26). Whereas, the pooled results from all trials, including the inadequately controlled trials, suggested that replacing SFA with mostly n-6 PUFA would significantly reduce the risk of total CHD events (RR = 0.80, CI = 0.65-0.98, P = 0.03), but not major CHD events (RR = 0.87, CI = 0.70-1.07), CHD mortality (RR = 0.90, CI = 0.70-1.17) and total mortality (RR = 1.00, CI = 0.90-1.10). Available evidence from adequately controlled randomised controlled trials suggest replacing SFA with mostly n-6 PUFA is unlikely to reduce CHD events, CHD mortality or total mortality. The suggestion of benefits reported in earlier meta-analyses is due to the inclusion of inadequately controlled trials. These findings have implications for current dietary recommendations.

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

Transcranial Direct Current Stimulation Improves Audioverbal Memory in Stroke Patients

PubMed Central

Kazuta, Toshinari; Takeda, Kotaro; Osu, Rieko; Tanaka, Satoshi; Oishi, Ayako; Kondo, Kunitsugu; Liu, Meigen

2017-01-01

Objective The aim of this study was to investigate whether anodal transcranial direct current stimulation over the left temporoparietal area improved audioverbal memory performance in stroke patients. Design Twelve stroke patients with audioverbal memory impairment participated in a single-masked, crossover, and sham-controlled experiment. The anodal or sham transcranial direct current stimulation was applied during the Rey Auditory Verbal Learning Test, which evaluates the ability to recall a list of 15 heard words over five trials. The number of correctly recalled words was compared between the anodal and sham conditions and the influence of transcranial direct current stimulation on serial position effect of the 15 words was also examined. Results The increase in the number of correctly recalled words from the first to the fifth trial was significantly greater in the anodal condition than in the sham condition (P < 0.01). There was a significant difference (P < 0.01) between the anodal and sham conditions in the number of correctly recalled words within the first five words (primacy region) over the second to fifth trial trials, but not in the middle (next five words) or recency (last five words) regions. Conclusions Anodal transcranial direct current stimulation over the left temporoparietal area improved audioverbal memory performance and induced the primacy effect in stroke patients. PMID:28085735

Transcranial Direct Current Stimulation Improves Audioverbal Memory in Stroke Patients.

PubMed

Kazuta, Toshinari; Takeda, Kotaro; Osu, Rieko; Tanaka, Satoshi; Oishi, Ayako; Kondo, Kunitsugu; Liu, Meigen

2017-08-01

The aim of this study was to investigate whether anodal transcranial direct current stimulation over the left temporoparietal area improved audioverbal memory performance in stroke patients. Twelve stroke patients with audioverbal memory impairment participated in a single-masked, crossover, and sham-controlled experiment. The anodal or sham transcranial direct current stimulation was applied during the Rey Auditory Verbal Learning Test, which evaluates the ability to recall a list of 15 heard words over five trials. The number of correctly recalled words was compared between the anodal and sham conditions and the influence of transcranial direct current stimulation on serial position effect of the 15 words was also examined. The increase in the number of correctly recalled words from the first to the fifth trial was significantly greater in the anodal condition than in the sham condition (P < 0.01). There was a significant difference (P < 0.01) between the anodal and sham conditions in the number of correctly recalled words within the first five words (primacy region) over the second to fifth trial trials, but not in the middle (next five words) or recency (last five words) regions. Anodal transcranial direct current stimulation over the left temporoparietal area improved audioverbal memory performance and induced the primacy effect in stroke patients.

Meta-analysis: aerobic exercise for the treatment of anxiety disorders.

PubMed

Bartley, Christine A; Hay, Madeleine; Bloch, Michael H

2013-08-01

This meta-analysis investigates the efficacy of exercise as a treatment for DSM-IV diagnosed anxiety disorders. We searched PubMED and PsycINFO for randomized, controlled trials comparing the anxiolytic effects of aerobic exercise to other treatment conditions for DSM-IV defined anxiety disorders. Seven trials were included in the final analysis, totaling 407 subjects. The control conditions included non-aerobic exercise, waitlist/placebo, cognitive-behavioral therapy, psychoeducation and meditation. A fixed-effects model was used to calculate the standardized mean difference of change in anxiety rating scale scores of aerobic exercise compared to control conditions. Subgroup analyses were performed to examine the effects of (1) comparison condition; (2) whether comparison condition controlled for time spent exercising and (3) diagnostic indication. Aerobic exercise demonstrated no significant effect for the treatment of anxiety disorders (SMD=0.02 (95%CI: -0.20-0.24), z = 0.2, p = 0.85). There was significant heterogeneity between trials (χ(2) test for heterogeneity = 22.7, df = 6, p = 0.001). The reported effect size of aerobic exercise was highly influenced by the type of control condition. Trials utilizing waitlist/placebo controls and trials that did not control for exercise time reported large effects of aerobic exercise while other trials report no effect of aerobic exercise. Current evidence does not support the use of aerobic exercise as an effective treatment for anxiety disorders as compared to the control conditions. This remains true when controlling for length of exercise sessions and type of anxiety disorder. Future studies evaluating the efficacy of aerobic exercise should employ larger sample sizes and utilize comparison interventions that control for exercise time. Copyright © 2013. Published by Elsevier Inc.

A pivotal registration phase III, multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB) project.

PubMed

Merle, Corinne S C; Sismanidis, Charalambos; Sow, Oumou Bah; Gninafon, Martin; Horton, John; Lapujade, Olivier; Lo, Mame Bocar; Mitchinson, Denis A; Perronne, Christian; Portaels, Francoise; Odhiambo, Joseph; Olliaro, Piero; Rustomjee, Roxana; Lienhardt, Christian; Fielding, Katherine

2012-05-18

There have been no major advances in tuberculosis (TB) drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago. Since then, the landscape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection, the spread of resistant TB bacilli strains, recent advances in mycobacteriological capacity, and drug discovery. As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials. To highlight key issues discussed: Is a superiority, equivalence, or non-inferiority design most appropriate? What should be the primary efficacy outcome? How to consider re-infections in the definition of the outcome? What is the optimal length of patient follow-up? Is blinding appropriate when treatment duration in test arm is shorter? What are the appropriate assumptions for sample size calculation? Various drugs are currently in the development pipeline. We are presenting in this paper the design of the most recently completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen. It is a randomized, open-label, multicenter, controlled trial aiming to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen (trial registration: ClinicalTrial.gov database: NCT00216385). In the light of the recent scientific and regulatory discussions, we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices, in order to best answer the trial objectives, while at the same time satisfying regulatory authority requirements. When shortening TB treatment, we are advocating for a non-inferiority, non-blinded design, with a composite unfavorable endpoint assessed 12 months post treatment completion, and added trial procedures specifically aiming to: (1) minimize endpoint unavailability; and (2) distinguish between relapse and re-infection.

A pivotal registration phase III, multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB) project

PubMed Central

2012-01-01

Background There have been no major advances in tuberculosis (TB) drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago. Since then, the landscape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection, the spread of resistant TB bacilli strains, recent advances in mycobacteriological capacity, and drug discovery. As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials. To highlight key issues discussed: Is a superiority, equivalence, or non-inferiority design most appropriate? What should be the primary efficacy outcome? How to consider re-infections in the definition of the outcome? What is the optimal length of patient follow-up? Is blinding appropriate when treatment duration in test arm is shorter? What are the appropriate assumptions for sample size calculation? Methods Various drugs are currently in the development pipeline. We are presenting in this paper the design of the most recently completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen. It is a randomized, open-label, multicenter, controlled trial aiming to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen (trial registration: ClinicalTrial.gov database: NCT00216385). Results In the light of the recent scientific and regulatory discussions, we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices, in order to best answer the trial objectives, while at the same time satisfying regulatory authority requirements. Conclusion When shortening TB treatment, we are advocating for a non-inferiority, non-blinded design, with a composite unfavorable endpoint assessed 12 months post treatment completion, and added trial procedures specifically aiming to: (1) minimize endpoint unavailability; and (2) distinguish between relapse and re-infection. PMID:22607233

Cochrane review: behavioural and cognitive-behavioural group-based parenting programmes for early-onset conduct problems in children aged 3 to 12 years (Review).

PubMed

Furlong, Mairead; McGilloway, Sinead; Bywater, Tracey; Hutchings, Judy; Smith, Susan M; Donnelly, Michael

2013-03-07

Early-onset child conduct problems are common and costly. A large number of studies and some previous reviews have focused on behavioural and cognitive-behavioural group-based parenting interventions, but methodological limitations are commonplace and evidence for the effectiveness and cost-effectiveness of these programmes has been unclear. To assess the effectiveness and cost-effectiveness of behavioural and cognitive-behavioural group-based parenting programmes for improving child conduct problems, parental mental health and parenting skills. We searched the following databases between 23 and 31 January 2011: CENTRAL (2011, Issue 1), MEDLINE (1950 to current), EMBASE (1980 to current), CINAHL (1982 to current), PsycINFO (1872 to current), Social Science Citation Index (1956 to current), ASSIA (1987 to current), ERIC (1966 to current), Sociological Abstracts (1963 to current), Academic Search Premier (1970 to current), Econlit (1969 to current), PEDE (1980 to current), Dissertations and Theses Abstracts (1980 to present), NHS EED (searched 31 January 2011), HEED (searched 31 January 2011), DARE (searched 31 January 2011), HTA (searched 31 January 2011), mRCT (searched 29 January 2011). We searched the following parent training websites on 31 January 2011: Triple P Library, Incredible Years Library and Parent Management Training. We also searched the reference lists of studies and reviews. We included studies if: (1) they involved randomised controlled trials (RCTs) or quasi-randomised controlled trials of behavioural and cognitive-behavioural group-based parenting interventions for parents of children aged 3 to 12 years with conduct problems, and (2) incorporated an intervention group versus a waiting list, no treatment or standard treatment control group. We only included studies that used at least one standardised instrument to measure child conduct problems. Two authors independently assessed the risk of bias in the trials and the methodological quality of health economic studies. Two authors also independently extracted data. We contacted study authors for additional information. This review includes 13 trials (10 RCTs and three quasi-randomised trials), as well as two economic evaluations based on two of the trials. Overall, there were 1078 participants (646 in the intervention group; 432 in the control group). The results indicate that parent training produced a statistically significant reduction in child conduct problems, whether assessed by parents (standardised mean difference (SMD) -0.53; 95% confidence interval (CI) -0.72 to -0.34) or independently assessed (SMD -0.44; 95% CI -0.77 to -0.11). The intervention led to statistically significant improvements in parental mental health (SMD -0.36; 95% CI -0.52 to -0.20) and positive parenting skills, based on both parent reports (SMD -0.53; 95% CI -0.90 to -0.16) and independent reports (SMD -0.47; 95% CI -0.65 to -0.29). Parent training also produced a statistically significant reduction in negative or harsh parenting practices according to both parent reports (SMD -0.77; 95% CI -0.96 to -0.59) and independent assessments (SMD -0.42; 95% CI -0.67 to -0.16). Moreover, the intervention demonstrated evidence of cost-effectiveness. When compared to a waiting list control group, there was a cost of approximately $2500 (GBP 1712; EUR 2217) per family to bring the average child with clinical levels of conduct problems into the non-clinical range. These costs of programme delivery are modest when compared with the long-term health, social, educational and legal costs associated with childhood conduct problems. Behavioural and cognitive-behavioural group-based parenting interventions are effective and cost-effective for improving child conduct problems, parental mental health and parenting skills in the short term. The cost of programme delivery was modest when compared with the long-term health, social, educational and legal costs associated with childhood conduct problems. Further research is needed on the long-term assessment of outcomes. Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Behavioural and cognitive-behavioural group-based parenting programmes for early-onset conduct problems in children aged 3 to 12 years.

PubMed

Furlong, Mairead; McGilloway, Sinead; Bywater, Tracey; Hutchings, Judy; Smith, Susan M; Donnelly, Michael

2012-02-15

Early-onset child conduct problems are common and costly. A large number of studies and some previous reviews have focused on behavioural and cognitive-behavioural group-based parenting interventions, but methodological limitations are commonplace and evidence for the effectiveness and cost-effectiveness of these programmes has been unclear. To assess the effectiveness and cost-effectiveness of behavioural and cognitive-behavioural group-based parenting programmes for improving child conduct problems, parental mental health and parenting skills. We searched the following databases between 23 and 31 January 2011: CENTRAL (2011, Issue 1), MEDLINE (1950 to current), EMBASE (1980 to current), CINAHL (1982 to current), PsycINFO (1872 to current), Social Science Citation Index (1956 to current), ASSIA (1987 to current), ERIC (1966 to current), Sociological Abstracts (1963 to current), Academic Search Premier (1970 to current), Econlit (1969 to current), PEDE (1980 to current), Dissertations and Theses Abstracts (1980 to present), NHS EED (searched 31 January 2011), HEED (searched 31 January 2011), DARE (searched 31 January 2011), HTA (searched 31 January 2011), mRCT (searched 29 January 2011). We searched the following parent training websites on 31 January 2011: Triple P Library, Incredible Years Library and Parent Management Training. We also searched the reference lists of studies and reviews. We included studies if: (1) they involved randomised controlled trials (RCTs) or quasi-randomised controlled trials of behavioural and cognitive-behavioural group-based parenting interventions for parents of children aged 3 to 12 years with conduct problems, and (2) incorporated an intervention group versus a waiting list, no treatment or standard treatment control group. We only included studies that used at least one standardised instrument to measure child conduct problems. Two authors independently assessed the risk of bias in the trials and the methodological quality of health economic studies. Two authors also independently extracted data. We contacted study authors for additional information. This review includes 13 trials (10 RCTs and three quasi-randomised trials), as well as two economic evaluations based on two of the trials. Overall, there were 1078 participants (646 in the intervention group; 432 in the control group). The results indicate that parent training produced a statistically significant reduction in child conduct problems, whether assessed by parents (standardised mean difference (SMD) -0.53; 95% confidence interval (CI) -0.72 to -0.34) or independently assessed (SMD -0.44; 95% CI -0.77 to -0.11). The intervention led to statistically significant improvements in parental mental health (SMD -0.36; 95% CI -0.52 to -0.20) and positive parenting skills, based on both parent reports (SMD -0.53; 95% CI -0.90 to -0.16) and independent reports (SMD -0.47; 95% CI -0.65 to -0.29). Parent training also produced a statistically significant reduction in negative or harsh parenting practices according to both parent reports (SMD -0.77; 95% CI -0.96 to -0.59) and independent assessments (SMD -0.42; 95% CI -0.67 to -0.16). Moreover, the intervention demonstrated evidence of cost-effectiveness. When compared to a waiting list control group, there was a cost of approximately $2500 (GBP 1712; EUR 2217) per family to bring the average child with clinical levels of conduct problems into the non-clinical range. These costs of programme delivery are modest when compared with the long-term health, social, educational and legal costs associated with childhood conduct problems. Behavioural and cognitive-behavioural group-based parenting interventions are effective and cost-effective for improving child conduct problems, parental mental health and parenting skills in the short term. The cost of programme delivery was modest when compared with the long-term health, social, educational and legal costs associated with childhood conduct problems. Further research is needed on the long-term assessment of outcomes.

Performance Assessment of Model-Based Optimal Feedforward and Feedback Current Profile Control in NSTX-U using the TRANSP Code

NASA Astrophysics Data System (ADS)

Ilhan, Z.; Wehner, W. P.; Schuster, E.; Boyer, M. D.; Gates, D. A.; Gerhardt, S.; Menard, J.

2015-11-01

Active control of the toroidal current density profile is crucial to achieve and maintain high-performance, MHD-stable plasma operation in NSTX-U. A first-principles-driven, control-oriented model describing the temporal evolution of the current profile has been proposed earlier by combining the magnetic diffusion equation with empirical correlations obtained at NSTX-U for the electron density, electron temperature, and non-inductive current drives. A feedforward + feedback control scheme for the requlation of the current profile is constructed by embedding the proposed nonlinear, physics-based model into the control design process. Firstly, nonlinear optimization techniques are used to design feedforward actuator trajectories that steer the plasma to a desired operating state with the objective of supporting the traditional trial-and-error experimental process of advanced scenario planning. Secondly, a feedback control algorithm to track a desired current profile evolution is developed with the goal of adding robustness to the overall control scheme. The effectiveness of the combined feedforward + feedback control algorithm for current profile regulation is tested in predictive simulations carried out in TRANSP. Supported by PPPL.

Evaluating the importance of sham controlled trials in the investigation of medical devices in interventional cardiology.

PubMed

Byrne, Robert A; Capodanno, Davide; Mahfoud, Felix; Fajadet, Jean; Windecker, Stephan; Jüni, Peter; Baumbach, Andreas; Wijns, William; Haude, Michael

2018-05-22

Cardiovascular medicine is one of the specialties that has relied most heavily on evidence from randomized clinical trials in determining best practice for the management of common disease conditions. When comparing treatment approaches, trials incorporating random allocation are the most appropriate method for protecting against treatment allocation bias. In order to protect against performance and ascertainment bias, trial designs including placebo control are preferable where feasible. In contrast to testing of medicines, treatments based on procedures or use of medical devices are more challenging to assess, as sham procedures are necessary to facilitate blinding of participants. However, in many cases, ethical concerns exist, as individual patients allocated to sham procedure are exposed only to risk without potential for benefit. Accordingly, the potential benefits to the general patient population must be carefully weighed against the risks of the exposed individuals. For this reason, trial design and study conduct are critically important to ensure that the investigation has the best chance of answering the study question at hand. In the current manuscript, we aim to review issues relating to the conduct of sham-controlled trials and discuss a number of recent examples in the field of interventional cardiology.

The Trial Using Motivational Interviewing and Positive Affect and Self-Affirmation in African-Americans with Hypertension (TRIUMPH): From Theory to Clinical Trial Implementation

PubMed Central

Boutin-Foster, Carla; Scott, Ebony; Rodriguez, Anna; Ramos, Rosio; Kanna, Balavenkatesh; Michelen, Walid; Charlson, Mary; Gbenga, Ogedegbe

2014-01-01

This paper describes the application of a translational research model in developing The Trial Using Motivational Interviewing and Positive Affect and Self-Affirmation in African-Americans with Hypertension (TRIUMPH), a theoretically-based, randomized controlled trial. TRIUMPH targets blood pressure control among African-Americans with hypertension in a community health center and public hospital setting. TRIUMPH applies positive affect, self-affirmation, and motivational interviewing as strategies to increase medication adherence and blood pressure control. A total of 220 participants were recruited in TRIUMPH and are currently being followed. This paper provides a detailed description of the theoretical framework and study design of TRIUMPH and concludes with a critical reflection of the lessons learned in the process of implementing a health behavior intervention in a community-based setting. TRIUMPH provides a model for incorporating the translational science research paradigm to conducting pragmatic behavioral trials in a real-world setting in a vulnerable population. Lessons learned through interactions with our community partners reinforce the value of community engagement in research. PMID:23403073

ShopSmart 4 Health - protocol of a skills-based randomised controlled trial promoting fruit and vegetable consumption among socioeconomically disadvantaged women.

PubMed

Ball, Kylie; McNaughton, Sarah A; Le, Ha; Andrianopoulos, Nick; Inglis, Victoria; McNeilly, Briohny; Lichomets, Irene; Granados, Alba; Crawford, David

2013-05-14

There is a need for evidence on the most effective and cost-effective approaches for promoting healthy eating among groups that do not meet dietary recommendations for good health, such as those with low incomes or experiencing socioeconomic disadvantage. This paper describes the ShopSmart 4 Health study, a randomised controlled trial conducted by Deakin University, Coles Supermarkets and the Heart Foundation, to investigate the effectiveness and cost-effectiveness of a skill-building intervention for promoting increased purchasing and consumption of fruits and vegetables amongst women of low socioeconomic position (SEP). ShopSmart 4 Health employed a randomised controlled trial design. Women aged 18-60 years, holding a Coles store loyalty card, who shopped at Coles stores within socioeconomically disadvantaged neighbourhoods and met low-income eligibility criteria were invited to participate. Consenting women completed a baseline survey assessing food shopping and eating habits and food-related behaviours and attitudes. On receipt of their completed survey, women were randomised to either a skill-building intervention or a wait-list control condition. Intervention effects will be evaluated via self-completion surveys and using supermarket transaction sales data, collected at pre- and post-intervention and 6-month follow-up. An economic evaluation from a societal perspective using a cost-consequences approach will compare the costs and outcomes between intervention and control groups. Process evaluation will be undertaken to identify perceived value and effects of intervention components. This study will provide data to address the currently limited evidence base regarding the effectiveness and cost-effectiveness of skill-building intervention strategies aimed at increasing fruit and vegetable consumption among socioeconomically disadvantaged women, a target group at high risk of poor diets. Current Controlled Trials ISRCTN48771770.

Distinct cognitive control mechanisms as revealed by modality-specific conflict adaptation effects.

PubMed

Yang, Guochun; Nan, Weizhi; Zheng, Ya; Wu, Haiyan; Li, Qi; Liu, Xun

2017-04-01

Cognitive control is essential to resolve conflict in stimulus-response compatibility (SRC) tasks. The SRC effect in the current trial is reduced after an incongruent trial as compared with a congruent trial, a phenomenon being termed conflict adaptation (CA). The CA effect is found to be domain-specific , such that it occurs when adjacent trials contain the same type of conflict, but disappears when the conflicts are of different types. Similar patterns have been observed when tasks involve different modalities, but the modality-specific effect may have been confounded by task switching. In the current study, we investigated whether or not cognitive control could transfer across auditory and visual conflicts when task-switching was controlled. Participants were asked to respond to a visual or auditory (Experiments 1A/B) stimulus, with conflict coming from either the same or a different modality. CA effects showed modality-specific patterns. To account for potential confounding effects caused by differences in task-irrelevant properties, we specifically examined the influence of task-irrelevant properties on CA effects within the visual modality (Experiments 2A/B). Significant CA effects were observed across different conflicts from distinct task-irrelevant properties, ruling out that the lack of cross-modal CA effects in Experiments 1A/B resulted from differences in task-irrelevant information. Task-irrelevant properties were further matched in Experiments 3A/B to examine the pure effect of modality. Results replicated Experiments 1A/B showing robust modality-specific CA effects. Taken together, we provide supporting evidences that modality affects cognitive control in conflict resolution, which should be taken into account in theories of cognitive control. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Toxoplasma gondii and schizophrenia: a review of published RCTs.

PubMed

Chorlton, Sam D

2017-07-01

Over the last 60 years, accumulating evidence has suggested that acute, chronic, and maternal Toxoplasma gondii infections predispose to schizophrenia. More recent evidence suggests that chronically infected patients with schizophrenia present with more severe disease. After acute infection, parasites form walled cysts in the brain, leading to lifelong chronic infection and drug resistance to commonly used antiparasitics. Chronic infection is the most studied and closely linked with development and severity of schizophrenia. There are currently four published randomized controlled trials evaluating antiparasitic drugs, specifically azithromycin, trimethoprim, artemisinin, and artemether, in patients with schizophrenia. No trials have demonstrated a change in psychopathology with adjunctive treatment. Published trials have either selected drugs without evidence against chronic infection or used them at doses too low to reduce brain cyst burden. Furthermore, trials have failed to achieve sufficient power or account for confounders such as previous antipsychotic treatment, sex, age, or rhesus status on antiparasitic effect. There are currently no ongoing trials of anti-Toxoplasma therapy in schizophrenia despite ample evidence to justify further testing.

A novel comparative effectiveness study of Tai Chi versus aerobic exercise for fibromyalgia: study protocol for a randomized controlled trial.

PubMed

Wang, Chenchen; McAlindon, Timothy; Fielding, Roger A; Harvey, William F; Driban, Jeffrey B; Price, Lori Lyn; Kalish, Robert; Schmid, Anna; Scott, Tammy M; Schmid, Christopher H

2015-01-30

Fibromyalgia is a chronic musculoskeletal pain syndrome that causes substantial physical and psychological impairment and costs the US healthcare system over $25 billion annually. Current pharmacological therapies may cause serious adverse effects, are expensive, and fail to effectively improve pain and function. Finding new and effective non-pharmacological treatments for fibromyalgia patients is urgently needed. We are currently conducting the first comparative effectiveness randomized trial of Tai Chi versus aerobic exercise (a recommended component of the current standard of care) in a large fibromyalgia population. This article describes the design and conduct of this trial. A single-center, 52-week, randomized controlled trial of Tai Chi versus aerobic exercise is being conducted at an urban tertiary medical center in Boston, Massachusetts. We plan to recruit 216 patients with fibromyalgia. The study population consists of adults ≥21 years of age with fibromyalgia who meet American College of Rheumatology 1990 and 2010 diagnostic criteria. Participants are randomized to one of four Tai Chi intervention groups: 12 or 24 weeks of supervised Tai Chi held once or twice per week, or a supervised aerobic exercise control held twice per week for 24 weeks. The primary outcome is the change in Revised Fibromyalgia Impact Questionnaire total score from baseline to 24 weeks. Secondary outcomes include measures of widespread pain, symptom severity, functional performance, balance, muscle strength and power, psychological functioning, sleep quality, self-efficacy, durability effects, and health-related quality of life at 12, 24, and 52 week follow-up. This study is the first comparative effectiveness randomized trial of Tai Chi versus aerobic exercise in a large fibromyalgia population with long-term follow up. We present here a robust and well-designed trial to determine the optimal frequency and duration of a supervised Tai Chi intervention with regard to short- and long-term effectiveness. The trial also explores multiple outcomes to elucidate the potential mechanisms of Tai Chi and aerobic exercise and the generalizability of these interventions across instructors. Results of this study are expected to have important public health implications for patients with a major disabling disease that incurs substantial health burdens and economic costs. ClinicalTrials.gov identifier: NCT01420640 , registered 18 August 2011.

Implicit contextual learning in prodromal and early stage Huntington's disease patients.

PubMed

van Asselen, Marieke; Almeida, Inês; Júlio, Filipa; Januário, Cristina; Campos, Elzbieta Bobrowicz; Simões, Mário; Castelo-Branco, Miguel

2012-07-01

Huntington's disease (HD) is a genetic neurodegenerative disorder affecting the basal ganglia. These subcortical structures are particularly important for motor functions, response selection and implicit learning. In the current study, we have assessed prodromal and symptomatic HD participants with an implicit contextual learning task that is not based on motor learning, but on a purely visual implicit learning mechanism. We used an implicit contextual learning task in which subjects need to locate a target among several distractors. In half of the trials, the positions of the distractors and target stimuli were repeated. By memorizing this contextual information, attention can be guided faster to the target stimulus. Nine symptomatic HD participants, 16 prodromal HD participants and 22 control subjects were included. We found that the responses of the control subjects were faster for the repeated trials than for the new trials, indicating that their visual search was facilitated when repeated contextual information was present. In contrast, no difference in response times between the repeated and new trials was found for the symptomatic and prodromal HD participants. The results of the current study indicate that both prodromal and symptomatic HD participants are impaired on an implicit contextual learning task.

Early biliary decompression versus conservative treatment in acute biliary pancreatitis (APEC trial): study protocol for a randomized controlled trial.

PubMed

Schepers, Nicolien J; Bakker, Olaf J; Besselink, Marc G H; Bollen, Thomas L; Dijkgraaf, Marcel G W; van Eijck, Casper H J; Fockens, Paul; van Geenen, Erwin J M; van Grinsven, Janneke; Hallensleben, Nora D L; Hansen, Bettina E; van Santvoort, Hjalmar C; Timmer, Robin; Anten, Marie-Paule G F; Bolwerk, Clemens J M; van Delft, Foke; van Dullemen, Hendrik M; Erkelens, G Willemien; van Hooft, Jeanin E; Laheij, Robert; van der Hulst, René W M; Jansen, Jeroen M; Kubben, Frank J G M; Kuiken, Sjoerd D; Perk, Lars E; de Ridder, Rogier J J; Rijk, Marno C M; Römkens, Tessa E H; Schoon, Erik J; Schwartz, Matthijs P; Spanier, B W Marcel; Tan, Adriaan C I T L; Thijs, Willem J; Venneman, Niels G; Vleggaar, Frank P; van de Vrie, Wim; Witteman, Ben J; Gooszen, Hein G; Bruno, Marco J

2016-01-05

Acute pancreatitis is mostly caused by gallstones or sludge. Early decompression of the biliary tree by endoscopic retrograde cholangiography (ERC) with sphincterotomy may improve outcome in these patients. Whereas current guidelines recommend early ERC in patients with concomitant cholangitis, early ERC is not recommended in patients with mild biliary pancreatitis. Evidence on the role of routine early ERC with endoscopic sphincterotomy in patients without cholangitis but with biliary pancreatitis at high risk for complications is lacking. We hypothesize that early ERC with sphincterotomy improves outcome in these patients. The APEC trial is a randomized controlled, parallel group, superiority multicenter trial. Within 24 hours after presentation to the emergency department, patients with biliary pancreatitis without cholangitis and at high risk for complications, based on an Acute Physiology and Chronic Health Evaluation (APACHE-II) score of 8 or greater, Modified Glasgow score of 3 or greater, or serum C-reactive protein above 150 mg/L, will be randomized. In 27 hospitals of the Dutch Pancreatitis Study Group, 232 patients will be allocated to early ERC with sphincterotomy or to conservative treatment. The primary endpoint is a composite of major complications (that is, organ failure, pancreatic necrosis, pneumonia, bacteremia, cholangitis, pancreatic endocrine, or exocrine insufficiency) or death within 180 days after randomization. Secondary endpoints include ERC-related complications, infected necrotizing pancreatitis, length of hospital stay and an economical evaluation. The APEC trial investigates whether an early ERC with sphincterotomy reduces the composite endpoint of major complications or death compared with conservative treatment in patients with biliary pancreatitis at high risk of complications. Current Controlled Trials ISRCTN97372133 (date registration: 17-12-2012).

The effects of low-intensity pulsed ultrasound and pulsed electromagnetic fields bone growth stimulation in acute fractures: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Hannemann, P F W; Mommers, E H H; Schots, J P M; Brink, P R G; Poeze, M

2014-08-01

The aim of this systematic review and meta-analysis was to evaluate the best currently available evidence from randomized controlled trials comparing pulsed electromagnetic fields (PEMF) or low-intensity pulsed ultrasound (LIPUS) bone growth stimulation with placebo for acute fractures. We performed a systematic literature search of the medical literature from 1980 to 2013 for randomized clinical trials concerning acute fractures in adults treated with PEMF or LIPUS. Two reviewers independently determined the strength of the included studies by assessing the risk of bias according to the criteria in the Cochrane Handbook for Systematic Reviews of Interventions. Seven hundred and thirty-seven patients from 13 trials were included. Pooled results from 13 trials reporting proportion of nonunion showed no significant difference between PEMF or LIPUS and control. With regard to time to radiological union, we found heterogeneous results that significantly favoured PEMF or LIPUS bone growth stimulation only in non-operatively treated fractures or fractures of the upper limb. Furthermore, we found significant results that suggest that the use of PEMF or LIPUS in acute diaphyseal fractures may accelerate the time to clinical union. Current evidence from randomized trials is insufficient to conclude a benefit of PEMF or LIPUS bone growth stimulation in reducing the incidence of nonunions when used for treatment in acute fractures. However, our systematic review and meta-analysis suggest that PEMF or LIPUS can be beneficial in the treatment of acute fractures regarding time to radiological and clinical union. PEMF and LIPUS significantly shorten time to radiological union for acute fractures undergoing non-operative treatment and acute fractures of the upper limb. Furthermore, PEMF or LIPUS bone growth stimulation accelerates the time to clinical union for acute diaphyseal fractures.

Acute cholecystitis in high risk surgical patients: percutaneous cholecystostomy versus laparoscopic cholecystectomy (CHOCOLATE trial): Study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Laparoscopic cholecystectomy in acute calculous cholecystitis in high risk patients can lead to significant morbidity and mortality. Percutaneous cholecystostomy may be an alternative treatment option but the current literature does not provide the surgical community with evidence based advice. Methods/Design The CHOCOLATE trial is a randomised controlled, parallel-group, superiority multicenter trial. High risk patients, defined as APACHE-II score 7-14, with acute calculous cholecystitis will be randomised to laparoscopic cholecystectomy or percutaneous cholecystostomy. During a two year period 284 patients will be enrolled from 30 high volume teaching hospitals. The primary endpoint is a composite endpoint of major complications within three months following randomization and need for re-intervention and mortality during the follow-up period of one year. Secondary endpoints include all other complications, duration of hospital admission, difficulty of procedures and total costs. Discussion The CHOCOLATE trial is designed to provide the surgical community with an evidence based guideline in the treatment of acute calculous cholecystitis in high risk patients. Trial Registration Netherlands Trial Register (NTR): NTR2666 PMID:22236534

Monolingual or Bilingual Intervention for Primary Language Impairment? A Randomized Control Trial

ERIC Educational Resources Information Center

Thordardottir, Elin; Cloutier, Geneviève; Ménard, Suzanne; Pelland-Blais, Elaine; Rvachew, Susan

2015-01-01

Purpose: This study investigated the clinical effectiveness of monolingual versus bilingual language intervention, the latter involving speech-language pathologist-parent collaboration. The study focuses on methods that are currently being recommended and that are feasible within current clinical contexts. Method: Bilingual children with primary…

Should we treat fever in critically ill patients? A summary of the current evidence from three randomized controlled trials

PubMed Central

Serpa, Ary; Pereira, Victor Galvão Moura; Colombo, Giancarlo; Scarin, Farah Christina de la Cruz; Pessoa, Camila Menezes Souza; Rocha, Leonardo Lima

2014-01-01

Fever is a nonspecific response to various types of infectious or non-infectious insult and its significance in disease remains an enigma. Our aim was to summarize the current evidence for the use of antipyretic therapy in critically ill patients. We performed systematic review and meta-analysis of publications from 1966 to 2013. The MEDLINE and CENTRAL databases were searched for studies on antipyresis in critically ill patients. The meta-analysis was limited to: randomized controlled trials; adult human critically ill patients; treatment with antipyretics in one arm versus placebo or non-treatment in another arm; and report of mortality data. The outcomes assessed were overall intensive care unit mortality, changes in temperature, intensive care unit length of stay, and hospital length of stay. Three randomized controlled trials, covering 320 participants, were included. Patients treated with antipyretic agents showed similar intensive care unit mortality (risk ratio 0.91, with 95% confidence interval 0.65-1.28) when compared with controls. The only difference observed was a greater decrease in temperature after 24 hours in patients treated with antipyretics (-1.70±0.40 versus - 0.56±0.25ºC; p=0.014). There is no difference in treating or not the fever in critically ill patients. PMID:25628209

Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 1—Psychometric Characteristics of 5 Paradigms.

PubMed

Reddy, L Felice; Horan, William P; Barch, Deanna M; Buchanan, Robert W; Dunayevich, Eduardo; Gold, James M; Lyons, Naomi; Marder, Stephen R; Treadway, Michael T; Wynn, Jonathan K; Young, Jared W; Green, Michael F

2015-09-01

Impairments in willingness to exert effort contribute to the motivational deficits characteristic of the negative symptoms of schizophrenia. The current study evaluated the psychometric properties of 5 new or adapted paradigms to determine their suitability for use in clinical trials of schizophrenia. This study included 94 clinically stable participants with schizophrenia and 40 healthy controls. The effort-based decision-making battery was administered twice to the schizophrenia group (baseline, 4-week retest) and once to the control group. The 5 paradigms included 1 that assesses cognitive effort, 1 perceptual effort, and 3 that assess physical effort. Each paradigm was evaluated on (1) patient vs healthy control group differences, (2) test-retest reliability, (3) utility as a repeated measure (ie, practice effects), and (4) tolerability. The 5 paradigms showed varying psychometric strengths and weaknesses. The Effort Expenditure for Rewards Task showed the best reliability and utility as a repeated measure, while the Grip Effort Task had significant patient-control group differences, and superior tolerability and administration duration. The other paradigms showed weaker psychometric characteristics in their current forms. These findings highlight challenges in adapting effort and motivation paradigms for use in clinical trials. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2015.

A Phase II/III Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Ginger (Zingiber officinale) for Nausea Caused by Chemotherapy for Cancer: A Currently Accruing URCC CCOP Cancer Control Study.

PubMed

Hickok, Jane T; Roscoe, Joseph A; Morrow, Gary R; Ryan, Julie L

2007-09-01

Despite the widespread use of 5-HT3 receptor antagonist antiemetics such as ondansetron and granistron, up to 70% of patients with cancer receiving highly emetogenic chemotherapy agents experience postchemotherapy nausea and vomiting. Delayed postchemotherapy nausea (nausea that occurs >/= 24 hours after chemotherapy administration) and anticipatory nausea (nausea that develops before chemotherapy administration, in anticipation of it) are poorly controlled by currently available antiemetic agents. Scientific studies suggest that ginger (Zingiber officinale) might have beneficial effects on nausea and vomiting associated with motion sickness, surgery, and pregnancy. In 2 small studies of patients with cancer receiving chemotherapy, addition of ginger to standard antiemetic medication further reduced the severity of postchemotherapy nausea. This article describes a phase II/III randomized, dose-finding, placebo-controlled, double-blind clinical trial to assess the efficacy of ginger for nausea associated with chemotherapy for cancer. The study is currently being conducted by private practice oncology groups that are funded by the National Cancer Institute's Community Clinical Oncology Program and affiliated with the University of Rochester Cancer Center Community Clinical Oncology Program Research Base.

Effectiveness of the ACA (Availability, Current issues and Anticipation) training programme on GP-patient communication in palliative care; a controlled trial

PubMed Central

2013-01-01

Background Communicating effectively with palliative care patients has been acknowledged to be somewhat difficult, but little is known about the effect that training general practitioners (GPs) in specific elements of communication in palliative care might have. We hypothesized that GPs exposed to a new training programme in GP-patient communication in palliative care focusing on availability of the GP for the patient, current issues the GP should discuss with the patient and anticipation by the GP of various scenarios (ACA), would discuss more issues and become more skilled in their communication with palliative care patients. Methods In this controlled trial among GPs who attended a two-year Palliative Care Peer Group Training Course in the Netherlands only intervention GPs received the ACA training programme. To evaluate the effect of the programme a content analysis (Roter Interaction Analysis System) was performed of one videotaped 15-minute consultation of each GP with a simulated palliative care patient conducted at baseline, and one at 12 months follow-up. Both how the GP communicated with the patient (‘availability’) and the number of current and anticipated issues the GP discussed with the patient were measured quantitatively. We used linear mixed models and logistic regression models to evaluate between-group differences over time. Results Sixty-two GPs were assigned to the intervention and 64 to the control group. We found no effect of the ACA training programme on how the GPs communicated with the patient or on the number of issues discussed by GPs with the patient. The total number of issues discussed by the GPs was eight out of 13 before and after the training in both groups. Conclusion The ACA training programme did not influence how the GPs communicated with the simulated palliative care patient or the number of issues discussed by the GPs in this trial. Further research should evaluate whether this training programme is effective for GPs who do not have a special interest in palliative care and whether studies using outcomes at patient level can provide more insight into the effectiveness of the ACA training programme. Trial registration Current Controlled Trials ISRCTN56722368 PMID:23819723

Pushing typists back on the learning curve: Memory chunking in the hierarchical control of skilled typewriting.

PubMed

Yamaguchi, Motonori; Logan, Gordon D

2016-12-01

Hierarchical control of skilled performance depends on the ability of higher level control to process several lower level units as a single chunk. The present study investigated the development of hierarchical control of skilled typewriting, focusing on the process of memory chunking. In the first 3 experiments, skilled typists typed words or nonwords under concurrent memory load. Memory chunks developed and consolidated into long-term memory when the same typing materials were repeated in 6 consecutive trials, but chunks did not develop when repetitions were spaced. However, when concurrent memory load was removed during training, memory chunks developed more efficiently with longer lags between repetitions than shorter lags. From these results, it is proposed that memory chunking requires 2 representations of the same letter string to be maintained simultaneously in short-term memory: 1 representation from the current trial, and the other from an earlier trial that is either retained from the immediately preceding trial or retrieved from long-term memory (i.e., study state retrieval). (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Fever and therapeutic normothermia in severe brain injury: an update.

PubMed

Bohman, Leif-Erik; Levine, Joshua M

2014-04-01

Fever is common in the ICU among patients with severe brain injury. Fever has been consistently shown to exacerbate brain injuries in animal models and has been consistently associated with poor outcome in human studies. However, whether fever control improves outcome and the ideal means of fever control remain unknown. This review will address recent literature on the impact of fever on severe brain injury and on interventions to maintain normothermia. Current guidelines generally recommend maintenance of normothermia after brain injury but have scant recommendations on methods to do this. Observational trials have continued to demonstrate the association between fever and poor outcome after severe brain injury. Recent trials have shown the efficacy of more aggressive approaches to fever reduction, whereas a large randomized trial showed the relative ineffectiveness of acetaminophen alone for fever control. Several studies have also described the impact of fever and of fever control on brain physiology. The value of therapeutic normothermia in the neurocritical care unit (NCCU) is increasingly accepted, yet prospective trials that demonstrate a functional benefit to patients are lacking.

Chemotherapy and targeted therapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials.

PubMed

Eckel, Florian; Schmid, Roland M

2014-01-01

In biliary tract cancer, gemcitabine platinum (GP) doublet palliative chemotherapy is the current standard treatment. The aim of this study was to analyze recent trials, even those small and nonrandomized, and identify superior new regimens. Trials published in English between January 2000 and January 2014 were analyzed, as well as ASCO abstracts from 2010 to 2013. In total, 161 trials comprising 6,337 patients were analyzed. The pooled results of standard therapy GP (no fluoropyrimidine, F, or other drug) were as follows: the median response rate (RR), tumor control rate (TCR), time to tumor progression (TTP) and overall survival (OS) were 25.9 and 63.5%, and 5.3 and 9.5 months, respectively. GFP triplets as well as G-based chemotherapy plus targeted therapy were significantly superior to GP concerning tumor control (TCR, TTP) and OS, with no difference in RR. Triplet combinations of GFP as well as G-based chemotherapy with (predominantly EGFR) targeted therapy are most effective concerning tumor control and survival.

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

PubMed

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

2014-03-04

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

Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis.

PubMed

Thomas, Peter W; Thomas, Sarah; Kersten, Paula; Jones, Rosemary; Nock, Alison; Slingsby, Vicky; Green, Colin; Baker, Roger; Galvin, Kate; Hillier, Charles

2010-06-16

Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change. This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. Current Controlled Trials ISRCTN76517470.

Effect of the Mediterranean diet on blood pressure in the PREDIMED trial: results from a randomized controlled trial

PubMed Central

2013-01-01

Background Hypertension can be prevented by adopting healthy dietary patterns. Our aim was to assess the 4-year effect on blood pressure (BP) control of a randomized feeding trial promoting the traditional Mediterranean dietary pattern. Methods The PREDIMED primary prevention trial is a randomized, single-blinded, controlled trial conducted in Spanish primary healthcare centers. We recruited 7,447 men (aged 55 to 80 years) and women (aged 60 to 80 years) who had high risk for cardiovascular disease. Participants were assigned to a control group or to one of two Mediterranean diets. The control group received education on following a low-fat diet, while the groups on Mediterranean diets received nutritional education and also free foods; either extra virgin olive oil, or nuts. Trained personnel measured participants’ BP at baseline and once yearly during a 4-year follow-up. We used generalized estimating equations to assess the differences between groups during the follow-up. Results The percentage of participants with controlled BP increased in all three intervention groups (P-value for within-group changes: P<0.001). Participants allocated to either of the two Mediterranean diet groups had significantly lower diastolic BP than the participants in the control group (−1.53 mmHg (95% confidence interval (CI) −2.01 to −1.04) for the Mediterranean diet supplemented with extra virgin olive oil, and −0.65 mmHg (95% CI -1.15 to −0.15) mmHg for the Mediterranean diet supplemented with nuts). No between-group differences in changes of systolic BP were seen. Conclusions Both the traditional Mediterranean diet and a low-fat diet exerted beneficial effects on BP and could be part of advice to patients for controlling BP. However, we found lower values of diastolic BP in the two groups promoting the Mediterranean diet with extra virgin olive oil or with nuts than in the control group. Trial registration Current Controlled Trials ISRCTN35739639 PMID:24050803

Cognitive performance and electrophysiological indices of cognitive control: a validation study of conflict adaptation.

PubMed

Clayson, Peter E; Larson, Michael J

2012-05-01

Psychiatric and neurologic disorders are associated with deficits in the postconflict recruitment of cognitive control. The primary aim of this study was to validate the relationship between cognitive functioning and indices of conflict adaptation. Event-related potentials were obtained from 89 healthy individuals who completed an Eriksen flanker task. Neuropsychological domains tested included memory, verbal fluency, and attention/executive functioning. Behavioral measures and N2 amplitudes showed significant conflict adaptation (i.e., previous-trial congruencies influenced current-trial measures). Higher scores on the attention/executive functioning and verbal fluency domains were associated with larger incongruent-trial N2 conflict adaptation; measures of cognitive functioning were not related to behavioral indices. This study provides initial validation of N2 conflict adaptation effects as cognitive function-related aspects of cognitive control. Copyright © 2012 Society for Psychophysiological Research.

Stop feeling: inhibition of emotional interference following stop-signal trials.

PubMed

Kalanthroff, Eyal; Cohen, Noga; Henik, Avishai

2013-01-01

Although a great deal of literature has been dedicated to the mutual links between emotion and the selective attention component of executive control, there is very little data regarding the links between emotion and the inhibitory component of executive control. In the current study we employed an emotional stop-signal task in order to examine whether emotion modulates and is modulated by inhibitory control. Results replicated previous findings showing reduced inhibitory control [longer stop-signal reaction time (SSRT)] following negative, compared to neutral pictures. Most importantly, results show decreased emotional interference following stop-signal trials. These results show that the inhibitory control component of executive control can serve to decrease emotional effects. We suggest that inhibitory control and emotion have a two-way connection in which emotion disrupts inhibitory control and activation of inhibitory control disrupts emotion.

The design and methodology of premature ejaculation interventional studies

PubMed Central

2016-01-01

Large well-designed clinical efficacy and safety randomized clinical trials (RCTs) are required to achieve regulatory approval of new drug treatments. The objective of this article is to make recommendations for the criteria for defining and selecting the clinical trial study population, design and efficacy outcomes measures which comprise ideal premature ejaculation (PE) interventional trial methodology. Data on clinical trial design, epidemiology, definitions, dimensions and psychological impact of PE was reviewed, critiqued and incorporated into a series of recommendations for standardisation of PE clinical trial design, outcome measures and reporting using the principles of evidence based medicine. Data from PE interventional studies are only reliable, interpretable and capable of being generalised to patients with PE, when study populations are defined by the International Society for Sexual Medicine (ISSM) multivariate definition of PE. PE intervention trials should employ a double-blind RCT methodology and include placebo control, active standard drug control, and/or dose comparison trials. Ejaculatory latency time (ELT) and subject/partner outcome measures of control, personal/partner/relationship distress and other study-specific outcome measures should be used as outcome measures. There is currently no published literature which identifies a clinically significant threshold response to intervention. The ISSM definition of PE reflects the contemporary understanding of PE and represents the state-of-the-art multi-dimensional definition of PE and is recommended as the basis of diagnosis of PE for all PE clinical trials. PMID:27652224

Efficacy of transcranial direct current stimulation (tDCS) in reducing consumption in patients with alcohol use disorders: study protocol for a randomized controlled trial.

PubMed

Trojak, Benoit; Soudry-Faure, Agnès; Abello, Nicolas; Carpentier, Maud; Jonval, Lysiane; Allard, Coralie; Sabsevari, Foroogh; Blaise, Emilie; Ponavoy, Eddy; Bonin, Bernard; Meille, Vincent; Chauvet-Gelinier, Jean-Christophe

2016-05-17

Approximately 15 million persons in the European Union and 10 million persons in the USA are alcohol-dependent. The global burden of disease and injury attributable to alcohol is considerable: worldwide, approximately one in 25 deaths in 2004 was caused by alcohol. At the same time, alcohol use disorders remain seriously undertreated. In this context, alternative or adjunctive therapies such as brain stimulation may play a prominent role. The early results of studies using transcranial direct current stimulation found that stimulations delivered to the dorsolateral prefrontal cortex result in a significant reduction of craving and an improvement of the decision-making processes in various additive disorders. We, therefore, hypothesize that transcranial direct current stimulation can lead to a decrease in alcohol consumption in patients suffering from alcohol use disorders. We report the protocol of a randomized, double-blind, placebo-controlled, parallel-group trial, to evaluate the efficacy of transcranial direct current stimulation on alcohol reduction in patients with an alcohol use disorder. The study will be conducted in 14 centers in France and Monaco. Altogether, 340 subjects over 18 years of age and diagnosed with an alcohol use disorder will be randomized to receive five consecutive twice-daily sessions of either active or placebo transcranial direct current stimulation. One session consists in delivering a current flow continuously (anode F4; cathode F3) twice for 13 minutes, with treatments separated by a rest interval of 20 min. Efficacy will be evaluated using the change from baseline (alcohol consumption during the 4 weeks before randomization) to 24 weeks in the total alcohol consumption and number of heavy drinking days. Secondary outcome measures will include alcohol craving, clinical and biological improvements, and the effects on mood and quality of life, as well as cognitive and safety assessments, and, for smokers, an assessment of the effects of transcranial direct current stimulation on tobacco consumption. Several studies have reported a beneficial effect of transcranial direct current stimulation on substance use disorders by reducing craving, impulsivity, and risk-taking behavior, and suggest that transcranial direct current stimulation may be a promising treatment in addiction. However, to date, no studies have included sufficiently large samples and sufficient follow-up to confirm the hypothesis. Results from this large randomized controlled trial will give a better overview of the therapeutic potential of transcranial direct current stimulation in alcohol use disorders. Clinical Trials Gov, NCT02505126 (registration date: July 15 2015).

Pancreatitis, very early compared with normal start of enteral feeding (PYTHON trial): design and rationale of a randomised controlled multicenter trial

PubMed Central

2011-01-01

Background In predicted severe acute pancreatitis, infections have a negative effect on clinical outcome. A start of enteral nutrition (EN) within 24 hours of onset may reduce the number of infections as compared to the current practice of starting an oral diet and EN if necessary at 3-4 days after admission. Methods/Design The PYTHON trial is a randomised controlled, parallel-group, superiority multicenter trial. Patients with predicted severe acute pancreatitis (Imrie-score ≥ 3 or APACHE-II score ≥ 8 or CRP > 150 mg/L) will be randomised to EN within 24 hours or an oral diet and EN if necessary, after 72 hours after hospital admission. During a 3-year period, 208 patients will be enrolled from 20 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of mortality or infections (bacteraemia, infected pancreatic or peripancreatic necrosis, pneumonia) during hospital stay or within 6 months following randomisation. Secondary endpoints include other major morbidity (e.g. new onset organ failure, need for intervention), intolerance of enteral feeding and total costs from a societal perspective. Discussion The PYTHON trial is designed to show that a very early (< 24 h) start of EN reduces the combined endpoint of mortality or infections as compared to the current practice of an oral diet and EN if necessary at around 72 hours after admission for predicted severe acute pancreatitis. Trial Registration ISRCTN: ISRCTN18170985 PMID:21392395

Current evidence demonstrates similar effects of kilohertz-frequency and low-frequency current on quadriceps evoked torque and discomfort in healthy individuals: a systematic review with meta-analysis.

PubMed

da Silva, Vinicius Zacarias Maldaner; Durigan, João Luiz Quaglioti; Arena, Ross; de Noronha, Marcos; Gurney, Burke; Cipriano, Gerson

2015-01-01

Neuromuscular electrical stimulation (NMES) is widely utilized to enhance muscle performance. However, the optimal NMES waveform with respect to treatment effect has not been established. To investigate the effects of kilohertz-frequency alternating current (KFAC) and low-frequency pulsed current (PC) on quadriceps evoked torque and self-reported discomfort. PubMed, The Cochrane Library, EMBASE, MEDLINE, Physiotherapy Evidence Database (PEDro), SinoMed, ISI Web of Knowledge, and CINAHL were searched for randomized controlled trials (RCTs) and quasi-randomized controlled trials (QRCTs). Two reviewers independently selected potential studies according to the inclusion criteria, extracted data, and assessed methodological quality. Studies were eligible if they compared KFAC versus PC interventions. Studies that included outcome measures for percentage of maximal isometric voluntary contraction (%MIVC) torque and self-reported discomfort level were eligible for evaluation. Seven studies involving 127 individuals were included. The methodological quality of eligible trials was moderate, with a mean of 5 on the 10-point PEDro scale. Overall, PC was no better than KFAC in terms of evoked torque and there was no difference in self-reported discomfort level. KFAC and PC have similar effects on quadriceps evoked torque and self-reported discomfort level in healthy individuals. The small number and overall methodological quality of currently available studies included in this meta-analysis indicate that new RCTs are needed to better determine optimal NMES treatment parameters.

Synergistic effect of combined transcranial direct current stimulation/constraint-induced movement therapy in children and young adults with hemiparesis: study protocol.

PubMed

Gillick, Bernadette; Menk, Jeremiah; Mueller, Bryon; Meekins, Gregg; Krach, Linda E; Feyma, Timothy; Rudser, Kyle

2015-11-12

Perinatal stroke occurs in more than 1 in 2,500 live births and resultant congenital hemiparesis necessitates investigation into interventions which may improve long-term function and decreased burden of care beyond current therapies ( http://www.cdc.gov/ncbddd/cp/data.html ). Constraint-Induced Movement Therapy (CIMT) is recognized as an effective hemiparesis rehabilitation intervention. Transcranial direct current stimulation as an adjunct treatment to CIMT may potentiate neuroplastic responses and improve motor function. The methodology of a clinical trial in children designed as a placebo-controlled, serial -session, non-invasive brain stimulation trial incorporating CIMT is described here. The primary hypotheses are 1) that no serious adverse events will occur in children receiving non-invasive brain stimulation and 2) that children in the stimulation intervention group will show significant improvements in hand motor function compared to children in the placebo stimulation control group. A randomized, controlled, double-blinded clinical trial. Twenty children and/or young adults (ages 8-21) with congenital hemiparesis, will be enrolled. The intervention group will receive ten 2-hour sessions of transcranial direct current stimulation combined with constraint-induced movement therapy and the control group will receive sham stimulation with CIMT. The primary outcome measure is safety assessment of transcranial direct current stimulation by physician evaluation, vital sign monitoring and symptom reports. Additionally, hand function will be evaluated using the Assisting Hand Assessment, grip strength and assessment of goals using the Canadian Occupational Performance Measure. Neuroimaging will confirm diagnoses, corticospinal tract integrity and cortical activation. Motor cortical excitability will also be examined using transcranial magnetic stimulation techniques. Combining non-invasive brain stimulation and CIMT interventions has the potential to improve motor function in children with congenital hemiparesis beyond each intervention independently. Such a combined intervention has the potential to benefit an individual throughout their lifetime. Clinicaltrials.gov, NCT02250092 Registered 18 September 2014.

Increasing instructional efficiency by presenting additional stimuli in learning trials for children with autism spectrum disorders.

PubMed

Vladescu, Jason C; Kodak, Tiffany M

2013-12-01

The current study examined the effectiveness and efficiency of presenting secondary targets within learning trials for 4 children with an autism spectrum disorder. Specifically, we compared 4 instructional conditions using a progressive prompt delay. In 3 conditions, we presented secondary targets in the antecedent or consequence portion of learning trials, or in the absence of prompts and reinforcement. In the fourth condition (control), we did not include secondary targets in learning trials. Results replicate and extend previous research by demonstrating that the majority of participants acquired secondary targets presented in the antecedent and consequent events of learning trials. © Society for the Experimental Analysis of Behavior.

Study protocol of the Diabetes and Depression Study (DAD): a multi-center randomized controlled trial to compare the efficacy of a diabetes-specific cognitive behavioral group therapy versus sertraline in patients with major depression and poorly controlled diabetes mellitus.

PubMed

Petrak, Frank; Herpertz, Stephan; Albus, Christian; Hermanns, Norbert; Hiemke, Christoph; Hiller, Wolfgang; Kronfeld, Kai; Kruse, Johannes; Kulzer, Bernd; Ruckes, Christian; Müller, Matthias J

2013-08-06

Depression is common in diabetes and associated with hyperglycemia, diabetes related complications and mortality. No single intervention has been identified that consistently leads to simultaneous improvement of depression and glycemic control. Our aim is to analyze the efficacy of a diabetes-specific cognitive behavioral group therapy (CBT) compared to sertraline (SER) in adults with depression and poorly controlled diabetes. This study is a multi-center parallel arm randomized controlled trial currently in its data analysis phase. We included 251 patients in 70 secondary care centers across Germany. Key inclusion criteria were: type 1 or 2 diabetes, major depression (diagnosed with the Structured Clinical Interview for DSM-IV, SCID) and hemoglobin A1C >7.5% despite current insulin therapy. During the initial phase, patients received either 50-200 mg/d sertraline or 10 CBT sessions aiming at the remission of depression and enhanced adherence to diabetes treatment and coping with diabetes. Both groups received diabetes treatment as usual. After 12 weeks of this initial open-label therapy, only the treatment-responders (50% depression symptoms reduction, Hamilton Depression Rating Scale, 17-item version [HAMD]) were included in the subsequent one year study phase and represented the primary analysis population. CBT-responders received no further treatment, while SER-responders obtained a continuous, flexible-dose SER regimen as relapse prevention. Adherence to treatment was analyzed using therapeutic drug monitoring (measurement of sertraline and N-desmethylsertraline concentrations in blood serum) and by counting the numbers of CBT sessions received. Outcome assessments were conducted by trained psychologists blinded to group assignment. Group differences in HbA1c (primary outcome) and depression (HAMD, secondary outcome) between 1-year follow-up and baseline will be analyzed by ANCOVA controlling for baseline values. As primary hypothesis we expect that CBT leads to significantly greater improvement of glycemic control in the one year follow-up in treatment responders of the short term phase. The DAD study is the first randomized controlled trial comparing antidepressants to a psychological treatment in diabetes patients with depression. Current controlled trials ISRCTN89333241.

A pilot randomised controlled trial of negative pressure wound therapy to treat grade III/IV pressure ulcers [ISRCTN69032034

PubMed Central

2012-01-01

Background Negative pressure wound therapy (NPWT) is widely promoted as a treatment for full thickness wounds; however, there is a lack of high-quality research evidence regarding its clinical and cost effectiveness. A trial of NPWT for the treatment of grade III/IV pressure ulcers would be worthwhile but premature without assessing whether such a trial is feasible. The aim of this pilot randomised controlled trial was to assess the feasibility of conducting a future full trial of NPWT for the treatment of grade III and IV pressure ulcers and to pilot all aspects of the trial. Methods This was a two-centre (acute and community), pilot randomised controlled trial. Eligible participants were randomised to receive either NPWT or standard care (SC) (spun hydrocolloid, alginate or foam dressings). Outcome measures were time to healing of the reference pressure ulcer, recruitment rates, frequency of treatment visits, resources used and duration of follow-up. Results Three hundred and twelve patients were screened for eligibility into this trial over a 12-month recruitment period and 12/312 participants (3.8%) were randomised: 6 to NPWT and 6 to SC. Only one reference pressure ulcer healed (NPWT group) during follow-up (time to healing 79 days). The mean number of treatment visits per week was 3.1 (NPWT) and 5.7 (SC); 6/6 NPWT and 1/6 SC participants withdrew from their allocated trial treatment. The mean duration of follow-up was 3.8 (NPWT) and 5.0 (SC) months. Conclusions This pilot trial yielded vital information for the planning of a future full study including projected recruitment rate, required duration of follow-up and extent of research nurse support required. Data were also used to inform the cost-effectiveness and value of information analyses, which were conducted alongside the pilot trial. Trial registration Current Controlled Trials ISRCTN69032034. PMID:22839453

The Ontario printed educational message (OPEM) trial to narrow the evidence-practice gap with respect to prescribing practices of general and family physicians: a cluster randomized controlled trial, targeting the care of individuals with diabetes and hypertension in Ontario, Canada

PubMed Central

Zwarenstein, Merrick; Hux, Janet E; Kelsall, Diane; Paterson, Michael; Grimshaw, Jeremy; Davis, Dave; Laupacis, Andreas; Evans, Michael; Austin, Peter C; Slaughter, Pamela M; Shiller, Susan K; Croxford, Ruth; Tu, Karen

2007-01-01

Background There are gaps between what family practitioners do in clinical practice and the evidence-based ideal. The most commonly used strategy to narrow these gaps is the printed educational message (PEM); however, the attributes of successful printed educational messages and their overall effectiveness in changing physician practice are not clear. The current endeavor aims to determine whether such messages change prescribing quality in primary care practice, and whether these effects differ with the format of the message. Methods/design The design is a large, simple, factorial, unblinded cluster-randomized controlled trial. PEMs will be distributed with informed, a quarterly evidence-based synopsis of current clinical information produced by the Institute for Clinical Evaluative Sciences, Toronto, Canada, and will be sent to all eligible general and family practitioners in Ontario. There will be three replicates of the trial, with three different educational messages, each aimed at narrowing a specific evidence-practice gap as follows: 1) angiotensin-converting enzyme inhibitors, hypertension treatment, and cholesterol lowering agents for diabetes; 2) retinal screening for diabetes; and 3) diuretics for hypertension. For each of the three replicates there will be three intervention groups. The first group will receive informed with an attached postcard-sized, short, directive "outsert." The second intervention group will receive informed with a two-page explanatory "insert" on the same topic. The third intervention group will receive informed, with both the above-mentioned outsert and insert. The control group will receive informed only, without either an outsert or insert. Routinely collected physician billing, prescription, and hospital data found in Ontario's administrative databases will be used to monitor pre-defined prescribing changes relevant and specific to each replicate, following delivery of the educational messages. Multi-level modeling will be used to study patterns in physician-prescribing quality over four quarters, before and after each of the three interventions. Subgroup analyses will be performed to assess the association between the characteristics of the physician's place of practice and target behaviours. A further analysis of the immediate and delayed impacts of the PEMs will be performed using time-series analysis and interventional, auto-regressive, integrated moving average modeling. Trial registration number Current controlled trial ISRCTN72772651. PMID:18039361

A Randomized Control Trial of a Community Mental Health Intervention for Military Personnel

DTIC Science & Technology

2014-12-01

trial to detect intervention effects. 15. SUBJECT TERMS Mental health literacy , Mental Health First Aid (MHFA), curriculum adaptation 16. SECURITY...KEYWORDS: National Guard; Mental Health First Aid; Mental Health Literacy ; Pilot Study; Veterans; Mental Health; Prevention; Access; Stigma OVERALL...gatekeeper training by providing a mental health literacy component that is currently not addressed. Despite the promise of m-MHFA to have substantial

Clinical significance of tumor necrosis factor-α inhibitors in the treatment of sciatica: a systematic review and meta-analysis.

PubMed

Wang, Yun Fu; Chen, Ping You; Chang, Wei; Zhu, Fi Qi; Xu, Li Li; Wang, Song Lin; Chang, Li Ying; Luo, Jie; Liu, Guang Jian

2014-01-01

Currently, no satisfactory treatment is available for sciatica caused by herniated discs and/or spinal stenosis. The objective of this study is to assess the value of tumor necrosis factor (TNF)-α inhibitors in the treatment of sciatica. Without language restrictions, we searched PubMed, OVID, EMBASE, the Web of Science, the Clinical Trials Registers, the Cochrane Central Register of Controlled Trials and the China Academic Library and Information System. We then performed a systematic review and meta-analysis on the enrolled trials that met the inclusion criteria. Nine prospective randomized controlled trials (RCTs) and two before-after controlled trials involving 531 patients met our inclusion criteria and were included in this study. Our systematic assessment and meta-analysis demonstrated that in terms of the natural course of the disease, compared with the control condition, TNF-α inhibitors neither significantly relieved lower back and leg pain (both p > 0.05) nor enhanced the proportion of patients who felt overall satisfaction (global perceived effect (satisfaction)) or were able to return to work (return to work) (combined endpoint; p > 0.05) at the short-term, medium-term and long-term follow-ups. In addition, compared with the control condition, TNF-α inhibitors could reduce the risk ratio (RR) of discectomy or radicular block (combined endpoint; RR = 0.51, 95% CI 0.26 to 1.00, p = 0.049) at medium-term follow-up, but did not decrease RR at the short-term (RR = 0.64, 95% CI 0.17 to 2.40, p = 0.508) and long-term follow-ups (RR = 0.64, 95% CI 0.40 to 1.03, p = 0.065). The currently available evidence demonstrated that other than reducing the RR of discectomy or radicular block (combined endpoint) at medium-term follow-up, TNF-α inhibitors showed limited clinical value in the treatment of sciatica caused by herniated discs and/or spinal stenosis.

Randomised controlled trial of school-based humanistic counselling for emotional distress in young people: Feasibility study and preliminary indications of efficacy

PubMed Central

2010-01-01

Aims The purpose of this study was to test the feasibility of a randomised controlled trial comparing six weeks of humanistic school-based counselling versus waiting list in the reduction of emotional distress in young people, and to obtain initial indications of efficacy. Methods Following a screening procedure, young people (13 - 15 years old) who experienced emotional distress were randomised to either humanistic counselling or waiting list in this multi-site study. Outcomes were assessed using a range of self-report mental health measures, with the emotional symptoms subscale of the Strengths and Difficulties Questionnaire (SDQ) acting as the primary outcome indicator. Results Recruitment procedures were successful, with 32 young people consenting to participate in the trial and 27 completing endpoint measures. Trial procedures were acceptable to all involved in the research. No significant differences were found between the counselling and waiting list groups in reductions in levels of emotional symptoms (Hedges' g = 0.03), but clients allocated to counselling showed significantly greater improvement in prosocial behaviour (g = 0.89) with an average effect size (g) across the nine outcome measures of 0.25. Participants with higher levels of depressive symptoms showed significantly greater change. Conclusion This study suggested that a randomised controlled trial of counselling in schools is acceptable and feasible, although initial indications of efficacy are mixed. Trial registration Current Controlled Trials ISRCTN68290510. PMID:20412578

Improving Well-being and Health for People with Dementia (WHELD): study protocol for a randomised controlled trial

PubMed Central

2014-01-01

Background People with dementia living in care homes often have complex mental health problems, disabilities and social needs. Providing more comprehensive training for staff working in care home environments is a high national priority. It is important that this training is evidence based and delivers improvement for people with dementia residing in these environments. Well-being and Health for People with Dementia (WHELD) combines the most effective elements of existing approaches to develop a comprehensive but practical staff training intervention. This optimised intervention is based on a factorial study and qualitative evaluation, to combine: training on person-centred care, promoting person-centred activities and interactions, and providing care home staff and general practitioners with updated knowledge regarding the optimal use of psychotropic medications for persons with dementia in care homes. Design The trial will be a randomised controlled two-arm cluster single blind trial that will take place for nine months across 80 care homes in the United Kingdom. Discussion The overarching goal of this trial is to determine whether this optimised WHELD intervention is more effective in improving the quality of life and mental health than the usual care provided to people with dementia living in nursing homes. This study will be the largest and best powered randomised controlled trial (RCT) evaluating the benefits of an augmented person-centred care training intervention in care homes worldwide. Trial registration Current controlled trials ISRCTN62237498 Date registered: 5 September 2013 PMID:25016303

Effects and Safety of Gyejibongnyeong-Hwan on Dysmenorrhea Caused by Blood Stagnation: A Randomized Controlled Trial

PubMed Central

Park, Jeong-Su; Park, Sunju; Cheon, Chun-Hoo; Jo, Seong-Cheon; Cho, Han Baek; Lim, Eun-Mee; Lim, Hyung Ho; Shin, Yong-Cheol; Ko, Seong-Gyu

2013-01-01

Objective. This study was a multicenter, randomized, double-blind, and controlled trial with two parallel arms: the GJBNH group and the placebo group. This trial recruited 100 women aging 18 to 35 years with primary dysmenorrhea caused by blood stagnation. The investigational drugs, GJBNH or placebo, were administered for two menstrual periods (8 weeks) to the participants three times per day. The participants were followed up for two menstrual cycles after the administration. Results. The results were analyzed by the intention-to-treat (ITT) dataset and the per-protocol (PP) dataset. In the ITT dataset, the change of the average menstrual pain VAS score in the GJBNH group was statistically significantly lower than that in the control group. Significant difference was not observed in the SF-MPQ score change between the GJBNH group and the placebo group. No significant difference was observed in the PP analyses. In the follow-up phase, the VAS scores of the average menstrual pain and the maximum menstrual pain continually decreased in the placebo group, but they increased in the GJBNH group. Conclusion. GJBNH treatment for eight weeks improved the pain of the dysmenorrhea caused by blood stagnation, but it should be successively administered for more than two menstrual cycles. Trial Registration. This trial is registered with Current Controlled Trials no. ISRCTN30426947. PMID:24191165

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

PubMed

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

2012-07-01

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

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

PubMed

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

2014-01-01

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

Medial tibial stress syndrome: evidence-based prevention.

PubMed

Craig, Debbie I

2008-01-01

Thacker SB, Gilchrist J, Stroup DF, Kimsey CD. The prevention of shin splints in sports: a systematic review of literature. Med Sci Sports Exerc. 2002;34(1):32-40. Among physically active individuals, which medial tibial stress syndrome (MTSS) prevention methods are most effective to decrease injury rates? Studies were identified by searching MEDLINE (1966-2000), Current Contents (1996-2000), Biomedical Collection (1993-1999), and Dissertation Abstracts. Reference lists of identified studies were searched manually until no further studies were identified. Experts in the field were contacted, including first authors of randomized controlled trials addressing prevention of MTSS. The Cochrane Collaboration (early stage of Cochrane Database of Systematic Reviews) was contacted. Inclusion criteria included randomized controlled trials or clinical trials comparing different MTSS prevention methods with control groups. Excluded were studies that did not provide primary research data or that addressed treatment and rehabilitation rather than prevention of incident MTSS. A total of 199 citations were identified. Of these, 4 studies compared prevention methods for MTSS. Three reviewers independently scored the 4 studies. Reviewers were blinded to the authors' names and affiliations but not the results. Each study was evaluated independently for methodologic quality using a 100-point checklist. Final scores were averages of the 3 reviewers' scores. Prevention methods studied were shock-absorbent insoles, foam heel pads, Achilles tendon stretching, footwear, and graduated running programs. No statistically significant results were noted for any of the prevention methods. Median quality scores ranged from 29 to 47, revealing flaws in design, control for bias, and statistical methods. No current evidence supports any single prevention method for MTSS. The most promising outcomes support the use of shock-absorbing insoles. Well-designed and controlled trials are critically needed to decrease the incidence of this common injury.

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

Trial-to-trial Adaptation: Parsing out the Roles of Cerebellum and BG in Predictive Motor Timing.

PubMed

Lungu, Ovidiu V; Bares, Martin; Liu, Tao; Gomez, Christopher M; Cechova, Ivica; Ashe, James

2016-07-01

We previously demonstrated that predictive motor timing (i.e., timing requiring visuomotor coordination in anticipation of a future event, such as catching or batting a ball) is impaired in patients with spinocerebellar ataxia (SCA) types 6 and 8 relative to healthy controls. Specifically, SCA patients had difficulties postponing their motor response while estimating the target kinematics. This behavioral difference relied on the activation of both cerebellum and striatum in healthy controls, but not in cerebellar patients, despite both groups activating certain parts of cerebellum during the task. However, the role of these two key structures in the dynamic adaptation of the motor timing to target kinematic properties remained unexplored. In the current paper, we analyzed these data with the aim of characterizing the trial-by-trial changes in brain activation. We found that in healthy controls alone, and in comparison with SCA patients, the activation in bilateral striatum was exclusively associated with past successes and that in the left putamen, with maintaining a successful performance across successive trials. In healthy controls, relative to SCA patients, a larger network was involved in maintaining a successful trial-by-trial strategy; this included cerebellum and fronto-parieto-temporo-occipital regions that are typically part of attentional network and action monitoring. Cerebellum was also part of a network of regions activated when healthy participants postponed their motor response from one trial to the next; SCA patients showed reduced activation relative to healthy controls in both cerebellum and striatum in the same contrast. These findings support the idea that cerebellum and striatum play complementary roles in the trial-by-trial adaptation in predictive motor timing. In addition to expanding our knowledge of brain structures involved in time processing, our results have implications for the understanding of BG disorders, such as Parkinson disease where feedback processing or reward learning is affected.

Central pathology review for phase III clinical trials: the enabling effect of virtual microscopy.

PubMed

Mroz, Pawel; Parwani, Anil V; Kulesza, Piotr

2013-04-01

Central pathology review (CPR) was initially designed as a quality control measure. The potential of CPR in clinical trials was recognized as early as in the 1960s and quickly became embedded as an integral part of many clinical trials since. To review the current experience with CPR in clinical trials, to summarize current developments in virtual microscopy, and to discuss the potential advantages and disadvantages of this technology in the context of CPR. A PubMed (US National Library of Medicine) search for published studies was conducted, and the relevant articles were reviewed, accompanied by the authors' experience at their practicing institution. The review of the available literature strongly suggests the growing importance of CPR both in the clinical trial setting as well as in second opinion cases. However, the currently applied approach significantly impedes efficient transfer of slides and patient data. Recent advances in imaging, digital microscopy, and Internet technologies suggest that the CPR process may be dramatically streamlined in the foreseeable future to allow for better diagnosis and quality assurance than ever before. In particular, whole slide imaging may play an important role in this process and result in a substantial reduction of the overall turnaround time required for slide review at the central location. Above all, this new approach may benefit the large clinical trials organized by oncology cooperative groups, since most of those trials involve complicated logistics owing to enrollment of large number of patients at several remotely located participating institutions.

Effects of Midas® on Nematodes in Commercial Floriculture Production in Florida

USDA-ARS?s Scientific Manuscript database

Cut flower producers currently have limited options for nematode control. Four field trials were conducted in 2006 and 2007 to evaluate Midas® (iodomethane:chloropicrin 50:50) for control of root-knot nematodes (Meloidogyne arenaria) on Celosia argentea var. cristata in a commercial floriculture pr...

Prostate cancer chemoprevention agent development: the National Cancer Institute, Division of Cancer Prevention portfolio.

PubMed

Parnes, Howard L; House, Margaret G; Kagan, Jacob; Kausal, David J; Lieberman, Ronald

2004-02-01

We describe the current National Cancer Institute chemoprevention agent development program and provide a summary of the intermediate end points used. The National Cancer Institute is currently sponsoring a wide range of studies of promising chemoprevention agents in a variety of informative cohorts, eg high grade prostatic intraepithelial neoplasia, positive family history of cancer, increased prostate specific antigen with negative biopsies, prostate cancer followed expectantly, prostate cancer awaiting definitive therapy and the general population. The rationale for each agent under investigation is derived from epidemiological observations, prostate cancer treatment trials, secondary analyses of large cancer prevention studies, an understanding of cancer biology and prostate carcinogenesis, and/or experimental animal models. Carcinogenesis is a multistep process occurring over decades which is characterized by disruption of the normal regulatory pathways controlling cellular proliferation, programmed cell death and differentiation. Administration of agents to reverse, inhibit or slow this process of malignant transformation is known as chemoprevention. Chemoprevention represents a promising approach to reducing the morbidity and mortality of prostate cancer. A variety of agents are currently being studied in phase 2 clinical trials, some of which may warrant subsequent evaluation in phase 3 trials with definitive cancer end points. Two large phase 3 trials, the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial, which are ongoing, are also sponsored by the National Cancer Institute.

Reduced posterior mesofrontal cortex activation by risky rewards in substance-dependent patients.

PubMed

Bjork, James M; Momenan, Reza; Smith, Ashley R; Hommer, Daniel W

2008-05-01

Substance-dependent individuals show disadvantageous decision-making, as well as alterated frontocortical recruitment when performing experimental tasks. We investigated whether substance-dependent patients (SDP) would show blunted recruitment of posterior mesofrontal cortex (PMC) by a conflict between concurrently increasing reward and risk of penalty in a monetary game of "chicken." SDP and controls performed: motor control (no reward) trials, guaranteed reward trials in which reward was not at risk, and risky trials where subjects were required to terminate their reward accrual before a secret varying time limit or else "bust" and forfeit that trial's winnings (low penalty) or the current trial's winnings plus an equal amount of previous winnings (high penalty). Reward accrual duration at risk of "busting" correlated negatively with trait neuroticism. The contrast between winning guaranteed reward versus non-reward activated the caudate head bilaterally in SDP but not controls. Accumulation of money at risk of low- or high-penalty (contrasted with accumulating guaranteed money) activated the PMC in both groups, but with a greater magnitude and more anterior extent in controls. Pre-decision signal increase in a PMC volume of interest negatively correlated with risk-taking in low-penalty trials, and was blunted in SDP relative to controls under both penalty conditions after controlling for individual differences in actual risk-taking and the higher neuroticism of SDP. These data suggest that SDP are characterized by a combination of: (a) striatal hypersensitivity to reward, and (b) under-recruitment of the specialized conflict-monitoring circuitry of the PMC when reward entails potential penalties.

Early intervention to protect the mother-infant relationship following postnatal depression: study protocol for a randomised controlled trial.

PubMed

Milgrom, Jeannette; Holt, Charlene

2014-10-03

At least 13% of mothers experience depression in the first postnatal year, with accompanying feelings of despair and a range of debilitating symptoms. Serious sequelae include disturbances in the mother-infant relationship and poor long-term cognitive and behavioural outcomes for the child. Surprisingly, treatment of maternal symptoms of postnatal depression does not improve the mother-infant relationship for a majority of women. Targeted interventions to improve the mother-infant relationship following postnatal depression are scarce and, of those that exist, the majority are not evaluated in randomised controlled trials. This study aims to evaluate a brief targeted mother-infant intervention, to follow cognitive behavioural therapy treatment of postnatal depression, which has the potential to improve developmental outcomes of children of depressed mothers. The proposed study is a two-arm randomised controlled trial with follow-up to 6 months. One hundred participants will be recruited via referrals from health professionals including maternal and child health nurses and general practitioners, as well as self-referrals from women who have seen promotional materials for the study. Women who meet inclusion criteria (infant aged <12 months, women 18+ years of age) will complete the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-IV-TR Axis I Disorders. Those with a clinical diagnosis of current major or minor depressive disorder and who do not meet exclusion criteria (that is, currently receiving treatment for depression, significant difficulty with English, medium to high suicide risk, current self-harm, current substance abuse, current post-traumatic stress disorder, current manic/hypomanic episode or psychotic symptoms) will be randomised to receive either a 4-session mother-infant intervention (HUGS: Happiness Understanding Giving and Sharing) or a 4-session attention placebo playgroup (Playtime) following a 12-session postnatal depression group treatment programme. Primary outcome measures are the Parenting Stress Index (self-report measure) and the Parent-child Early Relational Assessment (observational measure coded by a blinded observer). Measurements are taken at baseline, after the postnatal depression programme, post-HUGS/Playtime, and at 6 months post-HUGS/Playtime. This research addresses the need for specific treatment for mother-infant interactional difficulties following postnatal depression. There is a need to investigate interventions in randomised trials to prevent detrimental effects on child development and make available evidence-based treatments. Australia and New Zealand Clinical Trials Register: ACTRN12612001110875. Date Registered: 17 October 2012.

The STRIPES trial--support to rural India's public education system.

PubMed

Eble, Alex; Mann, Vera; Bhakta, Preetha; Lakshminarayana, Rashmi; Frost, Chris; Elbourne, Diana; Boone, Peter

2010-02-01

Performance of primary school students in India lags far below government expectations, and major disparity exists between rural and urban areas. The Naandi Foundation has designed and implemented a programme using community members to deliver after-school academic support for children in over 1,100 schools in five Indian states. Assessments to date suggest that it might have a substantial effect. This trial aims to evaluate the impact of this programme in villages of rural Andhra Pradesh and will compare test scores for children in three arms: a control and two intervention arms. In both intervention arms additional after-school instruction and learning materials will be offered to all eligible children and in one arm girls will also receive an additional 'kit' with a uniform and clothes. The trial is a cluster-randomised controlled trial conducted in conjunction with the CHAMPION trial. In the CHAMPION trial 464 villages were randomised so that half receive health interventions aiming to reduce neonatal mortality. STRIPES will be introduced in those CHAMPION villages which have a public primary school attended by at least 15 students at the time of a baseline test in 2008. 214 villages of the 464 were found to fulfil above criteria, 107 belonging to the control and 107 to the intervention arm of the CHAMPION trial. These latter 107 villages will serve as control villages in the STRIPES trial. A further randomisation will be carried out within the 107 STRIPES intervention villages allocating half to receive an additional kit for girls on the top of the instruction and learning materials. The primary outcome of the trial is a composite maths and language test score. The study is designed to measure (i) whether the educational intervention affects the exam score of children compared to the control arm, (ii) if the exam scores of girls who receive the additional kit are different from those of girls living in the other STRIPES intervention arm. One of the goals of the STRIPES trial is to provide benefit to the controls of the CHAMPION trial. We will also conduct a cost-benefit analysis in which we calculate the programme cost for 0.1 standard deviation improvement for both intervention arms. Current controlled trials ISRCTN69951502.

Efficacy and safety of acupuncture for chronic dizziness: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Dizziness is one of the most challenging symptoms in medicine. No medication for dizziness in current use has well-established curative or prophylactic value or is suitable for long-term palliative use. Unconventional remedies, such as acupuncture, should be considered and scientifically evaluated. However, there has been relatively little evidence in randomized controlled clinical trials on acupuncture to treat chronic dizziness. The aim of our study is to evaluate the efficacy and safety of acupuncture in patients with dizziness. Methods/Design This trial is a randomized, single-blind, controlled study. A total of 80 participants will be randomly assigned to two treatment groups receiving acupuncture and sham acupuncture treatment, respectively, for 4 weeks. The primary outcome measures are the Dizziness Handicap Inventory (DHI) and the Vertigo Symptom Scale (VSS). Treatment will be conducted over a period of 4 weeks, at a frequency of two sessions per week. The assessment is at baseline (before treatment initiation), 4 weeks after the first acupuncture session, and 8 weeks after the first acupuncture session. Discussion The results from this study will provide clinical evidence on the efficacy and safety of acupuncture in patients with chronic dizziness. Trial registration International Standard Randomized Controlled Trial Number Register: ISRCTN52695239 PMID:24330810

Is excess calcium harmful to health?

PubMed

Daly, Robin M; Ebeling, Peter R

2010-05-01

Most current guidelines recommend that older adults and the elderly strive for a total calcium intake (diet and supplements) of 1,000 to 1,300 mg/day to prevent osteoporosis and fractures. Traditionally, calcium supplements have been considered safe, effective and well tolerated, but their safety has recently been questioned due to potential adverse effects on vascular disease which may increase mortality. For example, the findings from a meta-analysis of randomized controlled trials (currently published in abstract form only) revealed that the use of calcium supplements was associated with an ~30% increased risk of myocardial infarction. If high levels of calcium are harmful to health, this may alter current public health recommendations with regard to the use of calcium supplements for preventing osteoporosis. In this review, we provide an overview of the latest information from human observational and prospective studies, randomized controlled trials and meta-analyses related to the effects of calcium supplementation on vascular disease and related risk factors, including blood pressure, lipid and lipoprotein levels and vascular calcification.

Is Excess Calcium Harmful to Health?

PubMed Central

Daly, Robin M.; Ebeling, Peter R.

2010-01-01

Most current guidelines recommend that older adults and the elderly strive for a total calcium intake (diet and supplements) of 1,000 to 1,300 mg/day to prevent osteoporosis and fractures. Traditionally, calcium supplements have been considered safe, effective and well tolerated, but their safety has recently been questioned due to potential adverse effects on vascular disease which may increase mortality. For example, the findings from a meta-analysis of randomized controlled trials (currently published in abstract form only) revealed that the use of calcium supplements was associated with an ~30% increased risk of myocardial infarction. If high levels of calcium are harmful to health, this may alter current public health recommendations with regard to the use of calcium supplements for preventing osteoporosis. In this review, we provide an overview of the latest information from human observational and prospective studies, randomized controlled trials and meta-analyses related to the effects of calcium supplementation on vascular disease and related risk factors, including blood pressure, lipid and lipoprotein levels and vascular calcification. PMID:22254038

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

PubMed

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

2018-04-05

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

History and present status of pulmonary metastasectomy in colorectal cancer.

PubMed

Treasure, Tom; Milošević, Mišel; Fiorentino, Francesca; Pfannschmidt, Joachim

2014-10-28

Clinical practice with respect to metastatic colorectal cancer differs from the other two most common cancers, breast and lung, in that routine surveillance is recommended with the specific intent of detecting liver and lung metastases and undertaking liver and lung resections for their removal. We trace the history of this approach to colorectal cancer by reviewing evidence for effectiveness from the 1950s to the present day. Our sources included published citation network analyses, the documented proposal for randomised trials, large systematic reviews, and meta-analysis of observational studies. The present consensus position has been adopted on the basis of a large number of observational studies but the randomised trials proposed in the 1980s and 1990s were either not done, or having been done, were not reported. Clinical opinion is the mainstay of current practice but in the absence of randomised trials there remains a possibility of selection bias. Randomised controlled trials (RCTs) are now routine before adoption of a new practice but RCTs are harder to run in evaluation of already established practice. One such trial is recruiting and shows that controlled trial are possible.

Field Balancing of Magnetically Levitated Rotors without Trial Weights

PubMed Central

Fang, Jiancheng; Wang, Yingguang; Han, Bangcheng; Zheng, Shiqiang

2013-01-01

Unbalance in magnetically levitated rotor (MLR) can cause undesirable synchronous vibrations and lead to the saturation of the magnetic actuator. Dynamic balancing is an important way to solve these problems. However, the traditional balancing methods, using rotor displacement to estimate a rotor's unbalance, requiring several trial-runs, are neither precise nor efficient. This paper presents a new balancing method for an MLR without trial weights. In this method, the rotor is forced to rotate around its geometric axis. The coil currents of magnetic bearing, rather than rotor displacement, are employed to calculate the correction masses. This method provides two benefits when the MLR's rotation axis coincides with the geometric axis: one is that unbalanced centrifugal force/torque equals the synchronous magnetic force/torque, and the other is that the magnetic force is proportional to the control current. These make calculation of the correction masses by measuring coil current with only a single start-up precise. An unbalance compensation control (UCC) method, using a general band-pass filter (GPF) to make the MLR spin around its geometric axis is also discussed. Experimental results show that the novel balancing method can remove more than 92.7% of the rotor unbalance and a balancing accuracy of 0.024 g mm kg−1 is achieved.

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

PubMed

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

2009-01-30

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

[Clinical trials registry].

PubMed

Ryder, Elena

2004-12-01

Authors and journals are more enthusiastic about the publication of trials with positive results than those negative or inconclusive trials. The International Committee of Medical Journal Editors proposed comprehensive trials registration as a solution to the problem of selective awareness and announces that the ICMJE member journals will adopt a trial-registration policy to promote this goal. They establish as a condition of consideration for publication, registration in a public trials registry. They recommend registries that meet certain criteria as www.clinicaltrials.com. Among those criteria is that the registry must be supported by a non-profit organization. On the other hand, people from Current Controlled Trials Ltd. being a commercial company, but meeting all the other criteria established by the ICMJE, feel that is being put aside. We wonder if clinical trials in our country are being registered in some of these International Registries. If not, would it be time to do so?

Component processes in voluntary task switching.

PubMed

Demanet, Jelle; Liefooghe, Baptist

2014-05-01

The present study investigated the involvement of bottom-up and top-down control in task-switching situations in which tasks are selected on a voluntary basis. We tested for indices of both types of control in the reduction in switch cost that is observed when more time is available before executing a task. Participants had to indicate their task choice overtly prior to the actual task execution, and two time intervals were manipulated: the interval between the task-execution response of the previous trial and task-indication response of the current trial and the interval between task-indication response and task-execution response of a particular trial. In Experiment 1, the length of these intervals was manipulated orthogonally, and indices for top-down and bottom-up control were observed. Concerned with the validity of these results, Experiments 2-3 additionally discouraged participants from preparing the upcoming task before their task-indication response. Indices for bottom-up control remained, but not for top-down control. The characteristics of top-down and bottom-up control in voluntary task switching and task switching in general are discussed.

A Meta-Analysis of Depressive Symptom Outcomes in Randomized, Controlled Trials for PTSD.

PubMed

Ronconi, Julia McDougal; Shiner, Brian; Watts, Bradley V

2015-07-01

Posttraumatic stress disorder (PTSD) often co-occurs with depression. Current PTSD practice guidelines lack specific guidance for clinicians regarding the treatment of depressive symptoms. We conducted a meta-analysis of all randomized, placebo-controlled trials for PTSD therapies focusing on depression outcomes to inform clinicians about effective treatment options for depressive symptoms associated with PTSD. We searched literature databases for randomized, controlled clinical trials of any treatment for PTSD published between 1980 and 2013. We selected articles in which all subjects were adults with a diagnosis of PTSD based on the Diagnostic and Statistical Manual of Mental Disorders criteria, and valid PTSD and depressive symptom measures were reported. The sample consisted of 116 treatment comparisons drawn from 93 manuscripts. Evidence-based PTSD treatments are effective for comorbid depressive symptoms. Existing PTSD treatments work as well for comorbid depressive symptoms as they do for PTSD symptoms.

Evaluator-blinded trial evaluating nurse-led immunotherapy DEcision Coaching In persons with relapsing-remitting Multiple Sclerosis (DECIMS) and accompanying process evaluation: study protocol for a cluster randomised controlled trial.

PubMed

Rahn, Anne Christin; Köpke, Sascha; Kasper, Jürgen; Vettorazzi, Eik; Mühlhauser, Ingrid; Heesen, Christoph

2015-03-21

Multiple sclerosis is a chronic neurological condition usually starting in early adulthood and regularly leading to severe disability. Immunotherapy options are growing in number and complexity, while costs of treatments are high and adherence rates remain low. Therefore, treatment decision-making has become more complex for patients. Structured decision coaching, based on the principles of evidence-based patient information and shared decision-making, has the potential to facilitate participation of individuals in the decision-making process. This cluster randomised controlled trial follows the assumption that decision coaching by trained nurses, using evidence-based patient information and preference elicitation, will facilitate informed choices and induce higher decision quality, as well as better decisional adherence. The decision coaching programme will be evaluated through an evaluator-blinded superiority cluster randomised controlled trial, including 300 patients with suspected or definite relapsing-remitting multiple sclerosis, facing an immunotherapy decision. The clusters are 12 multiple sclerosis outpatient clinics in Germany. Further, the trial will be accompanied by a mixed-methods process evaluation and a cost-effectiveness study. Nurses in the intervention group will be trained in shared decision-making, coaching, and evidence-based patient information principles. Patients who meet the inclusion criteria will receive decision coaching (intervention group) with up to three face-to-face coaching sessions with a trained nurse (decision coach) or counselling as usual (control group). Patients in both groups will be given access to an evidence-based online information tool. The primary outcome is 'informed choice' after six months, assessed with the multi-dimensional measure of informed choice including the sub-dimensions risk knowledge (questionnaire), attitude concerning immunotherapy (questionnaire), and immunotherapy uptake (telephone survey). Secondary outcomes include decisional conflict, adherence to immunotherapy decisions, autonomy preference, planned behaviour, coping self-efficacy, and perceived involvement in coaching and decisional encounters. Safety outcomes are comprised of anxiety and depression and disease-specific quality of life. This trial will assess the effectiveness of a new model of patient decision support concerning MS-immunotherapy options. The delegation of treatment information provision from physicians to trained nurses bears the potential to change current doctor-focused practice in Germany. Current Controlled Trials (identifier: ISRCTN37929939 ), May 27, 2014.

Using a fingerprint recognition system in a vaccine trial to avoid misclassification

PubMed Central

2007-01-01

Abstract Problem The potential for misidentification of trial participants, leading to misclassification, is a threat to the integrity of randomized controlled trials. The correct identification of study subjects in large trials over prolonged periods is of vital importance to those conducting clinical trials. Currently used means of identifying study participants, such as identity cards and records of name, address, name of household head and demographic characteristics, require large numbers of well-trained personnel, and still leave room for uncertainty. Approach We used fingerprint recognition technology for the identification of trial participants. This technology is already widely used in security and commercial contexts but not so far in clinical trials. Local setting A phase 2 cholera vaccine trial in SonLa, Viet Nam. Relevant changes An optical sensor was used to scan fingerprints. The fingerprint template of each participant was used to verify his or her identity during each of eight follow-up visits. Lessons learned A system consisting of a laptop computer and sensor is small in size, requires minimal training and on average six seconds for scanning and recognition. All participants’ identities were verified in the trial. Fingerprint recognition should become the standard technology for identification of participants in field trials. Fears exist, however, regarding the potential for invasion of privacy. It will therefore be necessary to convince not only trial participants but also investigators that templates of fingerprints stored in databases are less likely to be subject to abuse than currently used information databases. PMID:17242760

Lifestyle Advice Combined with Personalized Estimates of Genetic or Phenotypic Risk of Type 2 Diabetes, and Objectively Measured Physical Activity: A Randomized Controlled Trial

PubMed Central

van Sluijs, Esther M. F.; Marteau, Theresa M.; Sutton, Stephen

2016-01-01

Background Information about genetic and phenotypic risk of type 2 diabetes is now widely available and is being incorporated into disease prevention programs. Whether such information motivates behavior change or has adverse effects is uncertain. We examined the effect of communicating an estimate of genetic or phenotypic risk of type 2 diabetes in a parallel group, open, randomized controlled trial. Methods and Findings We recruited 569 healthy middle-aged adults from the Fenland Study, an ongoing population-based, observational study in the east of England (Cambridgeshire, UK). We used a computer-generated random list to assign participants in blocks of six to receive either standard lifestyle advice alone (control group, n = 190) or in combination with a genetic (n = 189) or a phenotypic (n = 190) risk estimate for type 2 diabetes (intervention groups). After 8 wk, we measured the primary outcome, objectively measured physical activity (kJ/kg/day), and also measured several secondary outcomes (including self-reported diet, self-reported weight, worry, anxiety, and perceived risk). The study was powered to detect a between-group difference of 4.1 kJ/kg/d at follow-up. 557 (98%) participants completed the trial. There were no significant intervention effects on physical activity (difference in adjusted mean change from baseline: genetic risk group versus control group 0.85 kJ/kg/d (95% CI −2.07 to 3.77, p = 0.57); phenotypic risk group versus control group 1.32 (95% CI −1.61 to 4.25, p = 0.38); and genetic risk group versus phenotypic risk group −0.47 (95% CI −3.40 to 2.46, p = 0.75). No significant differences in self-reported diet, self-reported weight, worry, and anxiety were observed between trial groups. Estimates of perceived risk were significantly more accurate among those who received risk information than among those who did not. Key limitations include the recruitment of a sample that may not be representative of the UK population, use of self-reported secondary outcome measures, and a short follow-up period. Conclusions In this study, we did not observe short-term changes in behavior associated with the communication of an estimate of genetic or phenotypic risk of type 2 diabetes. We also did not observe changes in worry or anxiety in the study population. Additional research is needed to investigate the conditions under which risk information might enhance preventive strategies. (Current Controlled Trials ISRCTN09650496; Date applied: April 4, 2011; Date assigned: June 10, 2011). Trial Registration The trial is registered with Current Controlled Trials, ISRCTN09650496. PMID:27898672

Active versus passive maintenance of visual nonverbal memory.

PubMed

McKeown, Denis; Holt, Jessica; Delvenne, Jean-Francois; Smith, Amy; Griffiths, Benjamin

2014-08-01

Forgetting over the short term has challenged researchers for more than a century, largely because of the difficulty of controlling what goes on within the memory retention interval. But the "recent-negative-probe" procedure offers a valuable paradigm, by examining the influences of (presumably) unattended memoranda from prior trials. Here we used a recent-probe task to investigate forgetting for visual nonverbal short-term memory. The target stimuli (two visually presented abstract shapes) on a trial were followed after a retention interval by a probe, and participants indicated whether the probe matched one of the target items. Proactive interference, and hence memory for old trial probes, was observed, whereby participants were slowed in rejecting a nonmatching probe on the current trial that nevertheless matched a target item on the previous trial (a recent-negative probe). The attraction of the paradigm is that, by uncovering proactive influences of past-trial probe stimuli, it can be argued that active maintenance in memory of those probes is unlikely. In two experiments, we recorded such proactive interference of prior-trial items over a range of interstimulus (ISI) and intertrial (ITI) intervals (between 1 and 6 s, respectively). Consistent with a proposed two-process memory conception (the active-passive memory model, or APM), actively maintained memories on current trials decayed, but passively "maintained," or unattended, visual memories of stimuli on past trials did not.

Study of Tranexamic Acid During Air Medical Prehospital Transport (STAAMP) Trial

DTIC Science & Technology

2017-10-01

Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an...ABSTRACT Multi-center, prospective, randomized, blinded, controlled interventional trial focusing on patients with concern for bleeding who are ...retraining scenarios were provided and are currently being converted into a quiz for distribution to the pre-hospital crews). 4. KEY RESEARCH

The role of sensorimotor processes in social group contagion.

PubMed

Cracco, Emiel; Brass, Marcel

2018-06-01

Although it is well known that action observation triggers an imitative response, not much is known about how these responses develop as a function of group size. Research on social contagion suggests that imitative tendencies initially increase but then stabilize as groups become larger. However, these findings have mainly been explained in terms of interpretative processes. Across seven experiments (N = 322), the current study investigated the contribution of sensorimotor processes to social group contagion by looking at the relation between group size and automatic imitation in a task that involved minimal interpretation. The results of Experiments 1-2 revealed that automatic imitation increased with group size according to an asymptotic curve on congruent trials but a linear curve on incongruent trials. The results of Experiments 3-7 showed that the asymptote on congruent trials disappeared when no control was needed, namely in the absence of incongruent trials. This suggests that the asymptote in the relation between group size and automatic imitation can be explained in terms of strategic control mechanisms that aim to prevent unintended imitative responses. The findings of the current study are in close correspondence with previous research in the social domain and as such support the hypothesis that sensorimotor processes contribute to the relation between group size and social contagion. Copyright © 2018 Elsevier Inc. All rights reserved.

A Randomized Controlled Trial of a Novel Self-Help Technique for Impulse Control Disorders: A Study on Nail-Biting

ERIC Educational Resources Information Center

Moritz, Steffen; Treszl, Andras; Rufer, Michael

2011-01-01

Nail-biting is currently classified as an impulse control disorder not otherwise specified. Although seldom targeted as a primary symptom, nail-biting is often associated with somatic complications and decreased quality of life. The present study assessed the effectiveness of an innovative self-help technique, titled decoupling (DC). DC aims at…

A critical review of clinical trials in systemic lupus erythematosus

PubMed Central

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

2016-01-01

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

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

PubMed

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

2014-01-01

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

Cognitive Training and Transcranial Direct Current Stimulation for Mild Cognitive Impairment in Parkinson's Disease: A Randomized Controlled Trial

PubMed Central

Gasson, Natalie; Johnson, Andrew R.; Booth, Leon; Loftus, Andrea M.

2018-01-01

This study examined whether standard cognitive training, tailored cognitive training, transcranial direct current stimulation (tDCS), standard cognitive training + tDCS, or tailored cognitive training + tDCS improved cognitive function and functional outcomes in participants with PD and mild cognitive impairment (PD-MCI). Forty-two participants with PD-MCI were randomized to one of six groups: (1) standard cognitive training, (2) tailored cognitive training, (3) tDCS, (4) standard cognitive training + tDCS, (5) tailored cognitive training + tDCS, or (6) a control group. Interventions lasted 4 weeks, with cognitive and functional outcomes measured at baseline, post-intervention, and follow-up. The trial was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR: 12614001039673). While controlling for moderator variables, Generalized Linear Mixed Models (GLMMs) showed that when compared to the control group, the intervention groups demonstrated variable statistically significant improvements across executive function, attention/working memory, memory, language, activities of daily living (ADL), and quality of life (QOL; Hedge's g range = 0.01 to 1.75). More outcomes improved for the groups that received standard or tailored cognitive training combined with tDCS. Participants with PD-MCI receiving cognitive training (standard or tailored) or tDCS demonstrated significant improvements on cognitive and functional outcomes, and combining these interventions provided greater therapeutic effects. PMID:29780572

Intensified treatment with high dose Rifampicin and Levofloxacin compared to standard treatment for adult patients with Tuberculous Meningitis (TBM-IT): protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Tuberculous meningitis is the most severe form of tuberculosis. Mortality for untreated tuberculous meningitis is 100%. Despite the introduction of antibiotic treatment for tuberculosis the mortality rate for tuberculous meningitis remains high; approximately 25% for HIV-negative and 67% for HIV positive patients with most deaths occurring within one month of starting therapy. The high mortality rate in tuberculous meningitis reflects the severity of the condition but also the poor antibacterial activity of current treatment regimes and relatively poor penetration of these drugs into the central nervous system. Improving the antitubercular activity in the central nervous system of current therapy may help improve outcomes. Increasing the dose of rifampicin, a key drug with known poor cerebrospinal fluid penetration may lead to higher drug levels at the site of infection and may improve survival. Of the second generation fluoroquinolones, levofloxacin may have the optimal pharmacological features including cerebrospinal fluid penetration, with a ratio of Area Under the Curve (AUC) in cerebrospinal fluid to AUC in plasma of >75% and strong bactericidal activity against Mycobacterium tuberculosis. We propose a randomized controlled trial to assess the efficacy of an intensified anti-tubercular treatment regimen in tuberculous meningitis patients, comparing current standard tuberculous meningitis treatment regimens with standard treatment intensified with high-dose rifampicin and additional levofloxacin. Methods/Design A randomized, double blind, placebo-controlled trial with two parallel arms, comparing standard Vietnamese national guideline treatment for tuberculous meningitis with standard treatment plus an increased dose of rifampicin (to 15 mg/kg/day total) and additional levofloxacin. The study will include 750 patients (375 per treatment group) including a minimum of 350 HIV-positive patients. The calculation assumes an overall mortality of 40% vs. 30% in the two arms, respectively (corresponding to a target hazard ratio of 0.7), a power of 80% and a two-sided significance level of 5%. Randomization ratio is 1:1. The primary endpoint is overall survival, i.e. time from randomization to death during a follow-up period of 9 months. Secondary endpoints are: neurological disability at 9 months, time to new neurological event or death, time to new or recurrent AIDS-defining illness or death (in HIV-positive patients only), severe adverse events, and rate of treatment interruption for adverse events. Discussion Currently very few options are available for the treatment of TBM and the mortality rate remains unacceptably high with severe disabilities seen in many of the survivors. This trial is based on the hypothesis that current anti-mycobacterial treatment schedules for TBM are not potent enough and that outcomes will be improved by increasing the CSF penetrating power of this regimen by optimising dosage and using additional drugs with better CSF penetration. Trial registration International Standard Randomised Controlled Trial Number ISRCTN61649292 PMID:21288325

Response repetition biases in human perceptual decisions are explained by activity decay in competitive attractor models

PubMed Central

Bonaiuto, James J; de Berker, Archy; Bestmann, Sven

2016-01-01

Animals and humans have a tendency to repeat recent choices, a phenomenon known as choice hysteresis. The mechanism for this choice bias remains unclear. Using an established, biophysically informed model of a competitive attractor network for decision making, we found that decaying tail activity from the previous trial caused choice hysteresis, especially during difficult trials, and accurately predicted human perceptual choices. In the model, choice variability could be directionally altered through amplification or dampening of post-trial activity decay through simulated depolarizing or hyperpolarizing network stimulation. An analogous intervention using transcranial direct current stimulation (tDCS) over left dorsolateral prefrontal cortex (dlPFC) yielded a close match between model predictions and experimental results: net soma depolarizing currents increased choice hysteresis, while hyperpolarizing currents suppressed it. Residual activity in competitive attractor networks within dlPFC may thus give rise to biases in perceptual choices, which can be directionally controlled through non-invasive brain stimulation. DOI: http://dx.doi.org/10.7554/eLife.20047.001 PMID:28005007

Adipose-Derived Stem Cells in Aesthetic Surgery: A Mixed Methods Evaluation of the Current Clinical Trial, Intellectual Property, and Regulatory Landscape.

PubMed

Arshad, Zeeshaan; Halioua-Haubold, Celine-Lea; Roberts, Mackenna; Urso-Baiarda, Fulvio; Branford, Oliver A; Brindley, David A; Davies, Benjamin M; Pettitt, David

2018-02-17

Adipose tissue, which can be readily harvested via a number of liposuction techniques, offers an easily accessible and abundant source of adipose-derived stem cells (ASCs). Consequently, ASCs have become an increasingly popular reconstructive option and a novel means of aesthetic soft tissue augmentation. This paper examines recent advances in the aesthetic surgery field, extending beyond traditional review formats to incorporate a comprehensive analysis of current clinical trials, adoption status, and the commercialization pathway. Keyword searches were carried out on clinical trial databases to search for trials using ASCs for aesthetic indications. An intellectual property landscape was created using commercial software (Thomson Reuters Thomson Innovation, New York, NY). Analysis of who is claiming what in respect of ASC use in aesthetic surgery for commercial purposes was analyzed by reviewing the patent landscape in relation to these techniques. Key international regulatory guidelines were also summarized. Completed clinical trials lacked robust controls, employed small sample sizes, and lacked long-term follow-up data. Ongoing clinical trials still do not address such issues. In recent years, claims to intellectual property ownership have increased in the "aesthetic stem cell" domain, reflecting commercial interest in the area. However, significant translational barriers remain including regulatory challenges and ethical considerations. Further rigorous randomized controlled trials are required to delineate long-term clinical efficacy and safety. Providers should consider the introduction of patient reported outcome metrics to facilitate clinical adoption. Robust regulatory and ethical policies concerning stem cells and aesthetic surgery should be devised to discourage further growth of "stem cell tourism." © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

Effect of a facility-based multifaceted intervention on the quality of obstetrical care: a cluster randomized controlled trial in Mali and Senegal

PubMed Central

2013-01-01

Background Maternal mortality in referral hospitals in Mali and Senegal surpasses 1% of obstetrical admissions. Poor quality obstetrical care contributes to high maternal mortality; however, poor care is often linked to insufficient hospital resources. One promising method to improve obstetrical care is maternal death review. With a cluster randomized trial, we assessed whether an intervention, based on maternal death review, could improve obstetrical quality of care. Methods The trial began with a pre-intervention year (2007), followed by two years of intervention activities and a post-intervention year. We measured obstetrical quality of care in the post-intervention year using a criterion-based clinical audit (CBCA). We collected data from 32 of the 46 trial hospitals (16 in each trial arm) and included 658 patients admitted to the maternity unit with a trial of labour. The CBCA questionnaire measured 5 dimensions of care- patient history, clinical examination, laboratory examination, delivery care and postpartum monitoring. We used adjusted mixed models to evaluate differences in CBCA scores by trial arms and examined how levels of hospital human and material resources affect quality of care differences associated with the intervention. Results For all women, the mean percentage of care criteria met was 66.3 (SD 13.5). There were significantly greater mean CBCA scores in women treated at intervention hospitals (68.2) compared to control hospitals (64.5). After adjustment, women treated at intervention sites had 5 points’ greater scores than those at control sites. This difference was mostly attributable to greater clinical examination and post-partum monitoring scores. The association between the intervention and quality of care was the same, irrespective of the level of resources available to a hospital; however, as resources increased, so did quality of care scores in both arms of the trial. Trial registration The QUARITE trial is registered on the Current Controlled Trials website under ISRCTN46950658 PMID:23351269

Control of Visceral Leishmaniasis in Latin America—A Systematic Review

PubMed Central

Romero, Gustavo A. S.; Boelaert, Marleen

2010-01-01

Background While three countries in South Asia decided to eliminate anthroponotic visceral leishmaniasis (VL) by 2015, its control in other regions seems fraught with difficulties. Is there a scope for more effective VL control in the Americas where transmission is zoonotic? We reviewed the evidence on VL control strategies in Latin America—diagnosis, treatment, veterinary interventions, vector control—with respect to entomological and clinical outcomes. Methodology/Principal Findings We searched the electronic databases of MEDLINE, LILACS, and the Cochrane Central Register of Controlled Trials, from 1960 to November 2008 and references of selected articles. Intervention trials as well as observational studies that evaluated control strategies of VL in the Americas were included. While the use of rapid diagnostic tests for VL diagnosis seems well established, there is a striking lack of evidence from clinical trials for drug therapy and few well designed intervention studies for control of vectors or canine reservoirs. Conclusion Elimination of zoonotic VL in the Americas does not seem a realistic goal at this point given the lack of political commitment, gaps in scientific knowledge, and the weakness of case management and surveillance systems. Research priorities and current strategies should be reviewed with the aim of achieving better VL control. PMID:20098726

Evidence-Base Update of Psychosocial Treatments for Child and Adolescent Depression

PubMed Central

Weersing, V. Robin; Jeffreys, Megan; Do, Minh-Chau T.; Schwartz, Karen T. G.; Bolano, Carl

2017-01-01

Depression in youth is prevalent and disabling and tends to presage a chronic and recurrent course of illness and impairment in adulthood. Clinical trial research in youth depression has a 30 year history, and evidence-based treatment reviews appeared in 1998 and 2008. The current review of 42 randomized controlled trials (RCTs) updates these reviews to include RCTs published between 2008 and 2014 (N = 14) and re-evaluates previously reviewed literature. Given the growing maturity of the field, this review utilized a stringent set of methodological criteria for trial inclusion, most notable for excluding trials based in sub-clinical samples of youth that had been included in previous reviews (N = 12) and including well-designed RCTs with null and negative findings (N = 8). Findings from the current review suggest that evidence for child treatments is notably weaker than for adolescent interventions, with no child treatments achieving well-established status and the evidentiary basis of treatments downgraded from previous reports. Cognitive behavioral therapy (CBT) for clinically depressed children appears to be possibly efficacious, with mixed findings across trials. For depressed adolescents, both CBT and Interpersonal Psychotherapy (IPT) are well-established interventions, with evidence of efficacy in multiple trials by independent investigative teams. This positive conclusion is tempered by the small size of the IPT literature (N = 6) and concern that CBT effects may be attenuated in clinically complicated samples and when compared against active control conditions. In conclusion, data on predictors, moderators, and mediators are examined and priorities for future research discussed. PMID:27870579

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

PubMed

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

2009-10-23

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

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

PubMed

Nelson, Nicole L; Churilla, James R

2017-09-01

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

[Rethinking clinical research in surgical oncology. From comic opera to quality control].

PubMed

Evrard, Serge

2016-01-01

The evidence base for the effectiveness of surgical interventions is relatively poor and data from large, randomized prospective studies are rare with often a poor quality. Many efforts have been made to increase the number of high quality randomized trials in surgery and theoretical proposals have been put forward to improve the situation, but practical implementation of these proposals is seriously lacking. The consequences of this policy are not trivial; with very few patients included in surgical oncology trials, this represents wasted opportunity for advances in cancer treatment. In this review, we cover the difficulties inherent to clinical research in surgical oncology, such as quality control, equipoise, accrual, and funding and promote alternative designs to the randomized controlled trial. Although the classic randomized controlled trial has a valid but limited place in surgical oncology, other prospective designs need to be promoted as a new deal. This new deal not only implicates surgeons but also journal editors, tender jury, as well as regulatory bodies to cover legal gaps currently surrounding surgical innovation. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

How to Prevent Diabetes: MedlinePlus Health Topic

MedlinePlus

... to 10 percent of your current weight. For example, if you weigh 200 pounds, your goal would ... 2 diabetes mellitus: A... Article: Design of a comparative effectiveness randomized controlled trial testing a... Article: Effect ...

Skills Training to Avoid Inadvertent Plagiarism: Results from a Randomised Control Study

ERIC Educational Resources Information Center

Newton, Fiona J.; Wright, Jill D.; Newton, Joshua D.

2014-01-01

Plagiarism continues to be a concern within academic institutions. The current study utilised a randomised control trial of 137 new entry tertiary students to assess the efficacy of a scalable short training session on paraphrasing, patch writing and plagiarism. The results indicate that the training significantly enhanced students' overall…

Stereotactic radiosurgery (SRS) in the modern management of patients with brain metastases

PubMed Central

Soliman, Hany; Das, Sunit; Larson, David A.; Sahgal, Arjun

2016-01-01

Stereotactic radiosurgery (SRS) is an established non-invasive ablative therapy for brain metastases. Early clinical trials with SRS proved that tumor control rates are superior to whole brain radiotherapy (WBRT) alone. As a result, WBRT plus SRS was widely adopted for patients with a limited number of brain metastases (“limited number” customarily means 1-4). Subsequent trials focused on answering whether WBRT upfront was necessary at all. Based on current randomized controlled trials (RCTs) and meta-analyses comparing SRS alone to SRS plus WBRT, adjuvant WBRT results in better intracranial control; however, at the expense of neurocognitive functioning and quality of life. These adverse effects of WBRT may also negatively impact on survival in younger patients. Based on the results of these studies, treatment has shifted to SRS alone in patients with a limited number of metastases. Additionally, RCTs are evaluating the role of SRS alone in patients with >4 brain metastases. New developments in SRS include fractionated SRS for large tumors and the integration of SRS with targeted systemic therapies that cross the blood brain barrier and/or stimulate an immune response. We present in this review the current high level evidence and rationale supporting SRS as the standard of care for patients with limited brain metastases, and emerging applications of SRS. PMID:26848525

A manual-based individual therapy to improve metacognition in schizophrenia: protocol of a multi-center RCT

PubMed Central

2014-01-01

Background Metacognitive dysfunction has been widely recognized as a feature of schizophrenia. As it is linked with deficits in several aspects of daily life functioning, improvement of metacognition may lead to improvement in functioning. Individual psychotherapy might be a useful form of treatment to improve metacognition in patients with schizophrenia; multiple case reports and a pilot study show promising results. The present study aims to measure the effectiveness of an individual, manual-based therapy (Metacognitive Reflection and Insight Therapy, MERIT) in improving metacognition in patients with schizophrenia. We also want to examine if improvement in metacognitive abilities is correlated with improvements in aspects of daily life functioning namely social functioning, experience of symptoms, quality of life, depression, work readiness, insight and experience of stigma. Methods/Design MERIT is currently evaluated in a multicenter randomized controlled trial. Thirteen therapists in six mental health institutions in the Netherlands participate in this study. Patients are randomly assigned to either MERIT or the control condition: treatment as usual (TAU). Discussion If proven effective, MERIT can be a useful addition to the care for schizophrenia patients. The design brings along some methodological difficulties, these issues are addressed in the discussion of this paper. Trial registration Current Controlled Trials: ISRCTN16659871. PMID:24490942

A protocol for a systematic review of non-randomised evaluations of strategies to improve participant recruitment to randomised controlled trials.

PubMed

Gardner, Heidi R; Fraser, Cynthia; MacLennan, Graeme; Treweek, Shaun

2016-08-02

Randomised controlled trials guard against selection bias and therefore offer the fairest way of evaluating healthcare interventions such as medicinal products, devices and services. Recruitment to trials can be extremely difficult, and poor recruitment can lead to extensions to both time and budget and may result in an underpowered study which does not satisfactorily answer the original research question. In the worst cases, a trial may be abandoned, causing huge waste. The evidence to support the choice of recruitment interventions is currently weak. Non-randomised evaluations of recruitment interventions are currently rejected on grounds of poor methodological quality, but systematic evaluation and assessment of this substantial body of work (using Grading of Recommendations Assessment, Development and Evaluation (GRADE) where possible) may provide useful information to support and inform the recruitment decisions of trialists and the research priorities of methodology researchers. The following databases will be searched for relevant studies: Cochrane Methodology Register, MEDLINE, EMBASE, CINAHL and PsycINFO. Any non-randomised study that includes a comparison of two or more interventions to improve recruitment to randomised controlled trials will be included. We will not apply any restrictions on publication date, language or journal. The primary outcome will be the number of individuals or centres recruited into a randomised controlled trial. The secondary outcome will be cost per recruit. Two reviewers will independently screen abstracts for eligible studies, and then, full texts of potentially relevant records will be reviewed. Disagreements will be resolved through discussion. The methodological quality of studies will be assessed using the Cochrane risk of bias tool for non-randomised studies, and the GRADE system will be used if studies are pooled. This review aims to summarise the evidence on methods used to improve recruitment to randomised controlled trials. Carrying out a systematic review including only data from non-randomised studies is a novel approach, and one which some may argue is futile. However, we believe that the systematic evaluation of what is likely to be a substantial amount of research activity is necessary, worthwhile, and will yield valuable results for the clinical trials community regardless of whether the outcomes find in favour of one or more interventions. Should the results of this review suggest that non-randomised evaluations do have something to offer trialists planning their recruitment strategies, the review may be combined in the future with the Cochrane review of randomised evaluations to produce a full review of recruitment strategies encompassing both randomised and non-randomised evaluation methods. PROSPERO CRD42016037718.

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

PubMed

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

2018-06-21

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

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

PubMed

Julious, Steven A

2011-01-01

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

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

PubMed

Roux, Gemma; Sofronoff, Kate; Sanders, Matthew

2013-09-01

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

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

PubMed Central

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

2009-01-01

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

Theory of planned behaviour variables and objective walking behaviour do not show seasonal variation in a randomised controlled trial.

PubMed

Williams, Stefanie L; French, David P

2014-02-05

Longitudinal studies have shown that objectively measured walking behaviour is subject to seasonal variation, with people walking more in summer compared to winter. Seasonality therefore may have the potential to bias the results of randomised controlled trials if there are not adequate statistical or design controls. Despite this there are no studies that assess the impact of seasonality on walking behaviour in a randomised controlled trial, to quantify the extent of such bias. Further there have been no studies assessing how season impacts on the psychological predictors of walking behaviour to date. The aim of the present study was to assess seasonal differences in a) objective walking behaviour and b) Theory of Planned Behaviour (TPB) variables during a randomised controlled trial of an intervention to promote walking. 315 patients were recruited to a two-arm cluster randomised controlled trial of an intervention to promote walking in primary care. A series of repeated measures ANCOVAs were conducted to examine the effect of season on pedometer measures of walking behaviour and TPB measures, assessed immediately post-intervention and six months later. Hierarchical regression analyses were conducted to assess whether season moderated the prediction of intention and behaviour by TPB measures. There were no significant differences in time spent walking in spring/summer compared to autumn/winter. There was no significant seasonal variation in most TPB variables, although the belief that there will be good weather was significantly higher in spring/summer (F = 19.46, p < .001). Season did not significantly predict intention or objective walking behaviour, or moderate the effects of TPB variables on intention or behaviour. Seasonality does not influence objectively measured walking behaviour or psychological variables during a randomised controlled trial. Consequently physical activity behaviour outcomes in trials will not be biased by the season in which they are measured. Previous studies may have overestimated the extent of seasonality effects by selecting the most extreme summer and winter months to assess PA. In addition, participants recruited to behaviour change interventions might have higher levels of motivation to change and are less affected by seasonal barriers. Current Controlled Trials ISRCTN95932902.

The data management of a phase III efficacy trial of an 11-valent pneumococcal conjugate vaccine and related satellite studies conducted in the Philippines

PubMed Central

2012-01-01

Background A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted. Results We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently. Conclusions There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff. Trial registration Current Controlled Trials ISRCTN62323832 PMID:22676626

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

PubMed Central

2012-01-01

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

Exit interviews to reduce turnover amongst healthcare professionals.

PubMed

Flint, Anndrea; Webster, Joan

2013-03-28

Exit interviews are widely used in healthcare organisations to identify reasons for staff attrition, yet their usefulness in limiting turnover is unclear. To determine the effectiveness of various exit interview strategies in decreasing turnover rates amongst healthcare professionals. We searched the Cochrane EPOC Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL), Issue 11, 2012; MEDLINE, Ovid (1950- ); EMBASE, Ovid (1947- ); CINAHL, EbscoHost (1980- ), and PsycINFO, OVID (1806-) between October 31 and November 6, 2012. We also screened the reference lists of included studies and relevant reviews; and searched trial registries for planned and on-going trials. We did not restrict searches by language or publication date. Randomised controlled trials, controlled clinical trials, controlled before-after studies and interrupted time series studies comparing turnover rates between healthcare professionals who had undergone one form of exit interview with another form of exit interview or with no interview. Two review authors independently assessed trial quality and extracted data. The original search identified 1560 citations, of which we considered 19 potentially relevant. The two authors independently reviewed the abstracts of these studies and retrieved the full texts of eight studies. We excluded all eight following independent assessment; they were either interviews, commentaries on how to do an exit interview or descriptive studies about reasons for leaving. We found no trials that matched our inclusion criteria. For this first update, we screened 2220 citations and identified no new trials. Evidence about the effectiveness of exit interviews to reduce turnover is currently not available. However, exit interviews may provide useful information about the work environment which, in turn, may be useful in the development of interventions to reduce turnover.

Exit interviews to reduce turnover amongst healthcare professionals.

PubMed

Webster, Joan; Flint, Anndrea

2014-03-15

Exit interviews are widely used in healthcare organisations to identify reasons for staff attrition, yet their usefulness in limiting turnover is unclear. To determine the effectiveness of various exit interview strategies in decreasing turnover rates amongst healthcare professionals. We searched the Cochrane EPOC Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL), Issue 11, 2012; MEDLINE, Ovid (1950- ); EMBASE, Ovid (1947- ); CINAHL, EbscoHost (1980- ), and PsycINFO, OVID (1806-) between October 31 and November 6, 2012. We also screened the reference lists of included studies and relevant reviews; and searched trial registries for planned and on-going trials. We did not restrict searches by language or publication date. Randomised controlled trials, controlled clinical trials, controlled before-after studies and interrupted time series studies comparing turnover rates between healthcare professionals who had undergone one form of exit interview with another form of exit interview or with no interview. Two review authors independently assessed trial quality and extracted data. The original search identified 1560 citations, of which we considered 19 potentially relevant. The two authors independently reviewed the abstracts of these studies and retrieved the full texts of eight studies. We excluded all eight following independent assessment; they were either interviews, commentaries on how to do an exit interview or descriptive studies about reasons for leaving. We found no trials that matched our inclusion criteria. For this first update, we screened 2220 citations and identified no new trials. Evidence about the effectiveness of exit interviews to reduce turnover is currently not available. However, exit interviews may provide useful information about the work environment which, in turn, may be useful in the development of interventions to reduce turnover.

Hepatocellular carcinoma Early Detection Strategy study — EDRN Public Portal

Cancer.gov

Part 1: The first part of this study is to conduct follow-up for patients that were enrolled in the EDRN Phase 2 Validation Study called DCP (13). For this part of the study, four groups are defined as follows: a) Vanguard Controls are cirrhotic controls, from the Phase 2 trial that have not developed HCC and sign a new consent form for HEDS participation. These patients will be followed for a minimum of an additional 24 months and have biospecimens collected every 6 months. b) Vanguard Interval Controls are cirrhotic controls, from the Phase 2 trial that have not developed HCC and do not sign a new consent form for HEDS participation. This group will have outcome data abstracted from their medical records. c) Vanguard Interval Cases are cirrhotic controls from the Phase 2 trial that developed HCC after completion of the Phase 2 trial but prior to the current study. This group will have outcome data abstracted from their medical records. d) Vanguard Cases are HCC cases from the Phase 2 trial. This group will have outcome data abstracted from their medical records. Part 2: New Controls - The second part of this study is the new accrual of cirrhotic controls at the seven participating sites. These patients will be followed for a minimum of 24 months and have biospecimens collected every 6 months. Data will be collected every 6 months: ultrasound, AFP, liver function tests, complete blood counts, MELD scores and any changes in medical history, personal cancer history and family cancer history.

Acceptance and commitment therapy - Do we know enough? Cumulative and sequential meta-analyses of randomized controlled trials.

PubMed

Hacker, Thomas; Stone, Paul; MacBeth, Angus

2016-01-15

Acceptance and Commitment Therapy (ACT) has accrued a substantial evidence base. Recent systematic and meta-analytic reviews suggest that ACT is effective compared to control conditions. However, these reviews appraise the efficacy of ACT across a broad range of presenting problems, rather than addressing specific common mental health difficulties. Focussing on depression and anxiety we performed a meta-analysis of trials of ACT. We incorporated sequential meta-analysis (SMA) techniques to critically appraise the sufficiency of the existing evidence base. Findings suggest that ACT demonstrates at least moderate group and pre-post effects for symptom reductions for both anxiety and depression. However using SMA findings are more qualified. There is currently insufficient evidence to confidently conclude that ACT for anxiety is efficacious when compared to active control conditions or as primary treatment for anxiety. Similarly, using SMA, there is currently insufficient evidence to suggest a moderate efficacy of ACT for depression compared to active control conditions. To stimulate further research we offer specific estimates of additional numbers of participants required to reach sufficiency to help inform future studies. We also discuss the appropriate strategies for future research into ACT for anxiety given the current evidence suggests no differential efficacy of ACT in the treatment of anxiety compared to active control conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

A pilot effectiveness study of the Enhancing Parenting Skills (EPaS) 2014 programme for parents of children with behaviour problems: study protocol for a randomised controlled trial.

PubMed

Williams, Margiad Elen; Hutchings, Judy

2015-05-20

The Enhancing Parenting Skills (EPaS) 2014 programme is a home-based, health visitor-delivered parenting support programme for parents of children with identified behaviour problems. This trial aims to evaluate the effectiveness of the EPaS 2014 programme compared to a waiting-list treatment as usual control group. This is a pragmatic, multicentre randomised controlled trial. Sixty health visitors will each be asked to identify two families that have a child scoring above the clinical cut-off for behaviour problems using the Eyberg Child Behaviour Inventory (ECBI). Families recruited to the trial will be randomised in a 1:1 ratio into an intervention or waiting-list control group. Randomisation will occur within health visitor to ensure that each health visitor has one intervention family and one control family. The primary outcome is change in child behaviour problems as measured by the parent-reported ECBI. Secondary outcomes include other measures of child behaviour, parent behaviour, and parental depression as measured by parent-reports and an independent observation of parent and child behaviour. Follow-up measures will be collected 6-months after the collection of baseline measures. This is the first rigorous evaluation of the EPaS 2014 programme. The trial will provide important information on the effectiveness of a one-to-one home-based intervention, delivered by health visitors, for pre-school children with behaviour problems. It will also examine potential mediating (improved parent behaviour and/or improved parental depression) and moderating (single parent, teenage parent, poverty, low education level) factors. Current Controlled Trials ISRCTN06867279 (18 June 2014).

Veterinary homeopathy: systematic review of medical conditions studied by randomised trials controlled by other than placebo.

PubMed

Mathie, Robert T; Clausen, Jürgen

2015-09-15

No systematic review has previously been carried out on randomised controlled trials (RCTs) of veterinary homeopathy in which the control group was an intervention other than placebo (OTP). For eligible peer-reviewed RCTs, the objectives of this study were to assess the risk of bias (RoB) and to quantify the effect size of homeopathic intervention compared with an active comparator or with no treatment. Our systematic review approach complied fully with the PRISMA 2009 Checklist. Cochrane methods were applied to assess RoB and to derive effect size using standard meta-analysis methods. Based on a thorough and systematic literature search, the following key attributes of the published research were distinguished: individualised homeopathy (n = 1 RCT)/non-individualised homeopathy (n = 19); treatment (n = 14)/prophylaxis (n = 6); active controls (n = 18)/untreated controls (n = 2). The trials were highly diverse, representing 12 different medical conditions in 6 different species. No trial had sufficiently low RoB to be judged as reliable evidence: 16 of the 20 RCTs had high RoB; the remaining four had uncertain RoB in several domains of assessment. For three trials with uncertain RoB and without overt vested interest, it was inconclusive whether homeopathy combined with conventional intervention was more or was less effective than conventional intervention alone for modulation of immune response in calves, or in the prophylaxis of cattle tick or of diarrhoea in piglets. Due to the poor reliability of their data, OTP-controlled trials do not currently provide useful insight into the effectiveness of homeopathy in animals.

Ethical considerations of neuro-oncology trial design in the era of precision medicine.

PubMed

Gupta, Saksham; Smith, Timothy R; Broekman, Marike L

2017-08-01

The field of oncology is currently undergoing a paradigm shift. Advances in the understanding of tumor biology and in tumor sequencing technology have contributed to the shift towards precision medicine, the therapeutic framework of targeting the individual oncogenic changes each tumor harbors. The success of precision medicine therapies, such as targeted kinase inhibitors and immunotherapies, in other cancers have motivated studies in brain cancers. The high specificity and cost of these therapies also encourage a shift in clinical trial design away from randomized control trials towards smaller, more exclusive early phase clinical trials. While these new trials advance the clinical application of increasingly precise and individualized therapies, their design brings ethical challenges . We review the pertinent ethical considerations for clinical trials of precision medicine in neuro-oncology and discuss methods to protect patients in this new era of trial design.

A Randomized, Double-Blind, Sham-Controlled Trial of Transcranial Direct Current Stimulation in Attention-Deficit/Hyperactivity Disorder.

PubMed

Cosmo, Camila; Baptista, Abrahão Fontes; de Araújo, Arão Nogueira; do Rosário, Raphael Silva; Miranda, José Garcia Vivas; Montoya, Pedro; de Sena, Eduardo Pondé

2015-01-01

Current standardized treatments for cognitive impairment in attention-deficit/hyperactivity disorder remain limited and their efficacy restricted. Transcranial direct current stimulation (tDCS) is a promising tool for enhancing cognitive performance in several neuropsychiatric disorders. Nevertheless, the effects of tDCS in reducing cognitive impairment in patients with attention-deficit/hyperactivity disorder (ADHD) have not yet been investigated. A parallel, randomized, double-blind, sham-controlled trial was conducted to examine the efficacy of tDCS on the modulation of inhibitory control in adults with ADHD. Thirty patients were randomly allocated to each group and performed a go/no-go task before and after a single session of either anodal stimulation (1 mA) over the left dorsolateral prefrontal cortex or sham stimulation. A nonparametric two-sample Wilcoxon rank-sum (Mann-Whitney) test revealed no significant differences between the two groups of individuals with ADHD (tDCS vs. sham) in regard to behavioral performance in the go/no go tasks. Furthermore, the effect sizes of group differences after treatment for the primary outcome measures-correct responses, impulsivity and omission errors--were small. No adverse events resulting from stimulation were reported. According to these findings, there is no evidence in support of the use of anodal stimulation over the left dorsolateral prefrontal cortex as an approach for improving inhibitory control in ADHD patients. To the best of our knowledge, this is the first clinical study to assess the cognitive effects of tDCS in individuals with ADHD. Further research is needed to assess the clinical efficacy of tDCS in this population. ClinicalTrials.gov NCT01968512.

Psychological impact of screening for type 2 diabetes: controlled trial and comparative study embedded in the ADDITION (Cambridge) randomised controlled trial.

PubMed

Eborall, Helen C; Griffin, Simon J; Prevost, A Toby; Kinmonth, Ann-Louise; French, David P; Sutton, Stephen

2007-09-08

To quantify the psychological impact of primary care based stepwise screening for type 2 diabetes. Controlled trial and comparative study embedded in a randomised controlled trial. 15 practices (10 screening, five control) in the ADDITION (Cambridge) trial in the east of England. 7380 adults (aged 40-69) in the top fourth for risk of having undiagnosed type 2 diabetes (6416 invited for screening, 964 controls). Invited for screening for type 2 diabetes or not invited (controls), incorporating a comparative study of subgroups of screening attenders. Attenders completed questionnaires after a random blood glucose test and at 3-6 months and 12-15 months later. Controls were sent questionnaires at corresponding time points. Non-attenders were sent questionnaires at 3-6 months and 12-15 months. State anxiety (Spielberger state anxiety inventory), anxiety and depression (hospital anxiety and depression scale), worry about diabetes, and self rated health. No significant differences were found between the screening and control participants at any time-for example, difference in means (95% confidence intervals) for state anxiety after the initial blood glucose test was -0.53, -2.60 to 1.54, at 3-6 months was 1.51 (-0.17 to 3.20), and at 12-15 months was 0.57, -1.11 to 2.24. After the initial test, compared with participants who screened negative, those who screened positive reported significantly poorer general health (difference in means -0.19, -0.25 to -0.13), higher state anxiety (0.93, -0.02 to 1.88), higher depression (0.32, 0.08 to 0.56), and higher worry about diabetes (0.25, 0.09 to 0.41), although effect sizes were small. Small but significant trends were found for self rated health across the screening subgroups at 3-6 months (P=0.047) and for worry about diabetes across the screen negative groups at 3-6 months and 12-15 months (P=0.001). Screening for type 2 diabetes has limited psychological impact on patients. Implementing a national screening programme based on the stepwise screening procedure used in the ADDITION (Cambridge) trial is unlikely to have significant consequences for patients' psychological health. Current Controlled Trials ISRCTN99175498 [controlled-trials.com].

A smartphone application for treating depressive symptoms: study protocol for a randomised controlled trial.

PubMed

Deady, M; Johnston, D A; Glozier, N; Milne, D; Choi, I; Mackinnon, A; Mykletun, A; Calvo, R A; Gayed, A; Bryant, R; Christensen, H; Harvey, S B

2018-06-01

Depression is a commonly occurring disorder linked to diminished role functioning and quality of life. The development of treatments that overcome barriers to accessing treatment remains an important area of clinical research as most people delay or do not receive treatment at an appropriate time. The workplace is an ideal setting to roll-out an intervention, particularly given the substantial psychological benefits associated with remaining in the workforce. Mobile health (mhealth) interventions utilising smartphone applications (apps) offer novel solutions to disseminating evidence based programs, however few apps have undergone rigorous testing. The present study aims to evaluate the effectiveness of a smartphone app designed to treat depressive symptoms in workers. The present study is a multicentre randomised controlled trial (RCT), comparing the effectiveness of the intervention to that of an attention control. The primary outcome measured will be reduced depressive symptoms at 3 months. Secondary outcomes such as wellbeing and work performance will also be measured. Employees from a range of industries will be recruited via a mixture of targeted social media advertising and Industry partners. Participants will be included if they present with likely current depression at baseline. Following baseline assessment (administered within the app), participants will be randomised to receive one of two versions of the Headgear application: 1) Intervention (a 30-day mental health intervention focusing on behavioural activation and mindfulness), or 2) attention control app (mood monitoring for 30 days). Participants will be blinded to their allocation. Analyses will be conducted within an intention to treat framework using mixed modelling. The results of this trial will provide valuable information about the effectiveness of mhealth interventions in the treatment of depressive symptoms in a workplace context. The current trial is registered with the Australian and New Zealand Clinical Trials Registry ( ACTRN12617000547347 , Registration date: 19/04/2017).

The mPED randomized controlled clinical trial: applying mobile persuasive technologies to increase physical activity in sedentary women protocol

PubMed Central

2011-01-01

Background Despite the significant health benefits of regular physical activity, approximately half of American adults, particularly women and minorities, do not meet the current physical activity recommendations. Mobile phone technologies are readily available, easily accessible and may provide a potentially powerful tool for delivering physical activity interventions. However, we need to understand how to effectively apply these mobile technologies to increase and maintain physical activity in physically inactive women. The purpose of this paper is to describe the study design and protocol of the mPED (mobile phone based physical activity education) randomized controlled clinical trial that examines the efficacy of a 3-month mobile phone and pedometer based physical activity intervention and compares two different 6-month maintenance interventions. Methods A randomized controlled trial (RCT) with three arms; 1) PLUS (3-month mobile phone and pedometer based physical activity intervention and 6-month mobile phone diary maintenance intervention), 2) REGULAR (3-month mobile phone and pedometer based physical activity intervention and 6-month pedometer maintenance intervention), and 3) CONTROL (pedometer only, but no intervention will be conducted). A total of 192 physically inactive women who meet all inclusion criteria and successfully complete a 3-week run-in will be randomized into one of the three groups. The mobile phone serves as a means of delivering the physical activity intervention, setting individualized weekly physical activity goals, and providing self-monitoring (activity diary), immediate feedback and social support. The mobile phone also functions as a tool for communication and real-time data capture. The primary outcome is objectively measured physical activity. Discussion If efficacy of the intervention with a mobile phone is demonstrated, the results of this RCT will be able to provide new insights for current behavioral sciences and mHealth. Trial Registration ClinicalTrials.gov#:NCTO1280812 PMID:22168267

A qualitative feasibility study to inform a randomised controlled trial of fluid bolus therapy in septic shock

PubMed Central

O’Hara, Caitlin B; Canter, Ruth R; Mouncey, Paul R; Carter, Anjali; Jones, Nicola; Nadel, Simon; Peters, Mark J; Lyttle, Mark D; Harrison, David A; Rowan, Kathryn M; Inwald, David; Woolfall, Kerry

2018-01-01

Objective The Fluids in Shock (FiSh) Trial proposes to evaluate whether restrictive fluid bolus therapy (10 mL/kg) is more beneficial than current recommended practice (20 mL/kg) in the resuscitation of children with septic shock in the UK. This qualitative feasibility study aimed to explore acceptability of the FiSh Trial, including research without prior consent (RWPC), potential barriers to recruitment and participant information for a pilot trial. Design Qualitative interview study involving parents of children who had presented to a UK emergency department or been admitted to a paediatric intensive care unit with severe infection in the previous 3 years. Participants Twenty-one parents (seven bereaved) were interviewed 16 (median) months since their child’s hospital admission (range: 1–41). Results All parents said they would have provided consent for the use of their child’s data in the FiSh Trial. The majority were unfamiliar with RWPC, yet supported its use. Parents were initially concerned about the change from currently recommended treatment, yet were reassured by explanations of the current evidence base, fluid bolus therapy and monitoring procedures. Parents made recommendations about the timing of the research discussion and content of participant information. Bereaved parents stated that recruiters should not discuss research immediately after a child’s death, but supported a personalised postal ‘opt-out’ approach to consent. Conclusions Findings show that parents whose child has experienced severe infection supported the proposed FiSh Trial, including the use of RWPC. Parents’ views informed the development of the pilot trial protocol and site staff training. Trial registration number ISRCTN15244462—results. PMID:28847877

Internet-Based Cognitive Behavior Therapy for Procrastination: Study Protocol for a Randomized Controlled Trial

PubMed Central

Rozental, Alexander

2013-01-01

Background Procrastination, to voluntarily delay an intended course of action despite expecting to be worse-off for the delay, is a persistent behavior pattern that can cause major psychological suffering. Approximately half of the student population and 15%-20% of the adult population are presumed having substantial difficulties due to chronic and recurrent procrastination in their everyday life. However, preconceptions and a lack of knowledge restrict the availability of adequate care. Cognitive behavior therapy (CBT) is often considered treatment of choice, although no clinical trials have previously been carried out. Objective The aim of this study will be to test the effects of CBT for procrastination, and to investigate whether it can be delivered via the Internet. Methods Participants will be recruited through advertisements in newspapers, other media, and the Internet. Only people residing in Sweden with access to the Internet and suffering from procrastination will be included in the study. A randomized controlled trial with a sample size of 150 participants divided into three groups will be utilized. The treatment group will consist of 50 participants receiving a 10-week CBT intervention with weekly therapist contact. A second treatment group with 50 participants receiving the same treatment, but without therapist contact, will also be employed. The intervention being used for the current study is derived from a self-help book for procrastination written by one of the authors (AR). It includes several CBT techniques commonly used for the treatment of procrastination (eg, behavioral activation, behavioral experiments, stimulus control, and psychoeducation on motivation and different work methods). A control group consisting of 50 participants on a wait-list control will be used to evaluate the effects of the CBT intervention. For ethical reasons, the participants in the control group will gain access to the same intervention following the 10-week treatment period, albeit without therapist contact. Results The current study is believed to result in three important findings. First, a CBT intervention is assumed to be beneficial for people suffering from problems caused by procrastination. Second, the degree of therapist contact will have a positive effect on treatment outcome as procrastination can be partially explained as a self-regulatory failure. Third, an Internet based CBT intervention is presumed to be an effective way to administer treatment for procrastination, which is considered highly important, as the availability of adequate care is limited. The current study is therefore believed to render significant knowledge on the treatment of procrastination, as well as providing support for the use of Internet based CBT for difficulties due to delayed tasks and commitments. Conclusions To our knowledge, the current study is the first clinical trial to examine the effects of CBT for procrastination, and is assumed to render significant knowledge on the treatment of procrastination, as well as investigating whether it can be delivered via the Internet. Trial Registration ClinicalTrials.gov: NCT01842945; http://clinicaltrials.gov/show/NCT01842945 (Archived by WebCite at http://www.webcitation.org/6KSmaXewC). PMID:24220277

Response control networks are selectively modulated by attention to rare events and memory load regardless of the need for inhibition.

PubMed

Wijeakumar, Sobanawartiny; Magnotta, Vincent A; Buss, Aaron T; Ambrose, Joseph P; Wifall, Timothy A; Hazeltine, Eliot; Spencer, John P

2015-10-15

Recent evidence has sparked debate about the neural bases of response selection and inhibition. In the current study, we employed two reactive inhibition tasks, the Go/Nogo (GnG) and Simon tasks, to examine questions central to these debates. First, we investigated whether a fronto-cortical-striatal system was sensitive to the need for inhibition per se or the presentation of infrequent stimuli, by manipulating the proportion of trials that do not require inhibition (Go/Compatible trials) relative to trials that require inhibition (Nogo/Incompatible trials). A cortico-subcortical network composed of insula, putamen, and thalamus showed greater activation on salient and infrequent events, regardless of the need for inhibition. Thus, consistent with recent findings, key parts of the fronto-cortical-striatal system are engaged by salient events and do not appear to play a selective role in response inhibition. Second, we examined how the fronto-cortical-striatal system is modulated by working memory demands by varying the number of stimulus-response (SR) mappings. Right inferior parietal lobule showed decreasing activation as the number of SR mappings increased, suggesting that a form of associative memory - rather than working memory - might underlie performance in these tasks. A broad motor planning and control network showed similar trends that were also modulated by the number of motor responses required in each task. Finally, bilateral lingual gyri were more robustly engaged in the Simon task, consistent with the role of this area in shifts of visuo-spatial attention. The current study sheds light on how the fronto-cortical-striatal network is selectively engaged in reactive control tasks and how control is modulated by manipulations of attention and memory load. Copyright © 2015 Elsevier Inc. All rights reserved.

Motor/Prefrontal Transcranial Direct Current Stimulation (tDCS) Following Lumbar Surgery Reduces Postoperative Analgesia Use.

PubMed

Glaser, John; Reeves, Scott T; Stoll, William David; Epperson, Thomas I; Hilbert, Megan; Madan, Alok; George, Mark S; Borckardt, Jeffrey J

2016-05-01

Randomized, controlled pilot trial. The present study is the first randomized, double-blind, sham-controlled pilot clinical trial of transcranial direct current stimulation (tDCS) for pain and patient-controlled analgesia (PCA) opioid usage among patients receiving spine surgery. Lumbar spinal surgeries are common, and while pain is often a complaint that precedes surgical intervention, the procedures themselves are associated with considerable postoperative pain lasting days to weeks. Adequate postoperative pain control is an important factor in determining recovery and new analgesic strategies are needed that can be used adjunctively to existing strategies potentially to reduce reliance on opioid analgesia. Several novel brain stimulation technologies including tDCS are beginning to demonstrate promise as treatments for a variety of pain conditions. Twenty-seven patients undergoing lumbar spine procedures at Medical University of South Carolina were randomly assigned to receive four 20-minute sessions of real or sham tDCS during their postsurgical hospital stay. Patient-administered hydromorphone usage was tracked along with numeric rating scale pain ratings. The effect of tDCS on the slope of the cumulative PCA curve was significant (P < 0.001) and tDCS was associated with a 23% reduction in PCA usage. In the real tDCS group a 31% reduction was observed in pain-at-its-least ratings from admission to discharge (P = 0.027), but no other changes in numeric rating scale pain ratings were significant in either group. The present pilot trial is the first study to demonstrate an opioid sparing effect of tDCS after spine surgical procedures. Although this was a small pilot trial in a heterogeneous sample of spinal surgery patients, a moderate effect-size was observed for tDCS, suggesting that future work in this area is warranted. 2.

Immediate vs. delayed insertion of intrauterine contraception after second trimester abortion: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background We describe the rationale and protocol for a randomized controlled trial (RCT) to assess whether intrauterine contraception placed immediately after a second trimester abortion will result in fewer pregnancies than current recommended practice of intended placement at 4 weeks post-abortion. Decision analysis suggests the novel strategy could substantially reduce subsequent unintended pregnancies and abortions. This paper highlights considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion. Methods/Design Consenting women choosing to use intrauterine contraception after abortion for a pregnancy of 12 to 24 weeks will be randomized to insertion timing groups either immediately (experimental intervention) or four weeks (recommended care) post abortion. Primary outcome measure is pregnancy rate at one year. Secondary outcomes include: cumulative pregnancy rates over five year follow-up period, comprehensive health economic analyses comparing immediate and delayed insertion groups, and device retention rates, complication rates (infection, expulsion) and, contraceptive method satisfaction. Web-based Contraception Satisfaction Questionnaires, clinical records and British Columbia linked health databases will be used to assess primary and secondary outcomes. Enrolment at all clinics in the province performing second trimester abortions began in May 2010 and is expected to complete in late 2011. Data on one year outcomes will be available for analysis in 2014. Discussion The RCT design combined with access to clinical records at all provincial abortion clinics, and to information in provincial single-payer linked administrative health databases, birth registry and hospital records, offers a unique opportunity to evaluate such an approach by determining pregnancy rate at one through five years among enrolled women. We highlight considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion. Trial registration Current Controlled Trials ISRCTN19506752 PMID:21672213

The LIPPSMAck POP (Lung Infection Prevention Post Surgery - Major Abdominal - with Pre-Operative Physiotherapy) trial: study protocol for a multi-centre randomised controlled trial.

PubMed

Boden, Ianthe; Browning, Laura; Skinner, Elizabeth H; Reeve, Julie; El-Ansary, Doa; Robertson, Iain K; Denehy, Linda

2015-12-15

Post-operative pulmonary complications are a significant problem following open upper abdominal surgery. Preliminary evidence suggests that a single pre-operative physiotherapy education and preparatory lung expansion training session alone may prevent respiratory complications more effectively than supervised post-operative breathing and coughing exercises. However, the evidence is inconclusive due to methodological limitations. No well-designed, adequately powered, randomised controlled trial has investigated the effect of pre-operative education and training on post-operative respiratory complications, hospital length of stay, and health-related quality of life following upper abdominal surgery. The Lung Infection Prevention Post Surgery - Major Abdominal- with Pre-Operative Physiotherapy (LIPPSMAck POP) trial is a pragmatic, investigator-initiated, bi-national, multi-centre, patient- and assessor-blinded, parallel group, randomised controlled trial, powered for superiority. Four hundred and forty-one patients scheduled for elective open upper abdominal surgery at two Australian and one New Zealand hospital will be randomised using concealed allocation to receive either i) an information booklet or ii) an information booklet, plus one additional pre-operative physiotherapy education and training session. The primary outcome is respiratory complication incidence using standardised diagnostic criteria. Secondary outcomes include hospital length of stay and costs, pneumonia diagnosis, intensive care unit readmission and length of stay, days/h to mobilise >1 min and >10 min, and, at 6 weeks post-surgery, patient reported complications, health-related quality of life, and physical capacity. The LIPPSMAck POP trial is a multi-centre randomised controlled trial powered and designed to investigate whether a single pre-operative physiotherapy session prevents post-operative respiratory complications. This trial standardises post-operative assisted ambulation and physiotherapy, measures many known confounders, and includes a post-discharge follow-up of complication rates, functional capacity, and health-related quality of life. This trial is currently recruiting. Australian New Zealand Clinical Trials Registry number: ACTRN12613000664741 , 19 June 2013.

Psycho-education with problem solving (PEPS) therapy for adults with personality disorder: A pragmatic multi-site community-based randomised clinical trial

PubMed Central

2011-01-01

Background Impairment in social functioning is a key component of personality disorder. Therefore psycho-education and problem solving (PEPS) therapy may benefit people with this disorder. Psycho-education aims to educate, build rapport, and motivate people for problem solving therapy. Problem solving therapy aims to help clients solve interpersonal problems positively and rationally, thereby improving social functioning and reducing distress. PEPS therapy has been evaluated with community adults with personality disorder in an exploratory trial. At the end of treatment, compared to a wait-list control group, those treated with PEPS therapy showed better social functioning, as measured by the Social Functioning Questionnaire (SFQ). A definitive evaluation is now being conducted to determine whether PEPS therapy is a clinically and cost-effective treatment for people with personality disorder Methods This is a pragmatic, two-arm, multi-centre, parallel, randomised controlled clinical trial. The target population is community-dwelling adults with one or more personality disorder, as identified by the International Personality Disorder Examination (IPDE). Inclusion criteria are: Living in the community (including residential or supported care settings); presence of one or more personality disorder; aged 18 or over; proficiency in spoken English; capacity to provide informed consent. Exclusion criteria are: Primary diagnosis of a functional psychosis; insufficient degree of literacy, comprehension or attention to be able to engage in trial therapy and assessments; currently engaged in a specific programme of psychological treatment for personality disorder or likely to start such treatment during the trial period; currently enrolled in any other trial. Suitable participants are randomly allocated to PEPS therapy plus treatment as usual (TAU) or TAU only. We aim to recruit 340 men and women. The primary outcome is social functioning as measured by the SFQ. A reduction (i.e., an improvement) of 2 points or more on the SFQ at follow-up 72 weeks post-randomisation is our pre-specified index of clinically significant change. Secondary outcomes include a reduction of unscheduled service usage and an increase in scheduled service usage; improved quality of life; and a reduction in mental distress. Discussion PEPS therapy has potential as an economical, accessible, and acceptable intervention for people with personality disorder. The results from this randomised controlled trial will tell us if PEPS therapy is effective and cost-effective. If so, then it will be a useful treatment for inclusion in a broader menu of treatment options for this group of service users. Trial Registration International Standard Randomised Controlled Trial Number - ISRCTN70660936 PMID:21864370

Memory Flexibility training (MemFlex) to reduce depressive symptomatology in individuals with major depressive disorder: study protocol for a randomised controlled trial.

PubMed

Hitchcock, Caitlin; Hammond, Emily; Rees, Catrin; Panesar, Inderpal; Watson, Peter; Werner-Seidler, Aliza; Dalgleish, Tim

2015-11-03

Major depressive disorder (MDD) is associated with chronic biases in the allocation of attention and recollection of personal memories. Impaired flexibility in attention and autobiographical memory retrieval is seen to both maintain current symptoms and predict future depression. Development of innovative interventions to reduce maladaptive cognitive patterns and improve cognitive flexibility in the domain of memory may therefore advance current treatment approaches for depression. Memory specificity training and cognitive bias modification techniques have both shown some promise in improving cognitive flexibility. Here we outline plans for a trial of an innovative memory flexibility training programme, MemFlex, which advances current training techniques with the aim of improving flexibility of autobiographical memory retrieval. This trial seeks to estimate the efficacy of MemFlex, provide data on feasibility, and begin to explore mechanisms of change. We plan a single-blind, randomised, controlled, patient-level trial in which 50 individuals with MDD will complete either psychoeducation (n = 25) or MemFlex (n = 25). After completing pre-treatment measures and an orientation session, participants complete eight workbook-based sessions at home. Participants will then be assessed at post-treatment and at 3 month follow-up. The co-primary outcomes are depressive symptoms and diagnostic status at 3 month follow-up. The secondary outcomes are memory flexibility at post-treatment and number of depression free days at 3 month follow-up. Other process outcomes and mediators of any treatment effects will also be explored. This trial will establish the efficacy of MemFlex in improving memory flexibility, and reducing depressive symptoms. Any effects on process measures related to relapse may also indicate whether MemFlex may be helpful in reducing vulnerability to future depressive episodes. The low-intensity and workbook-based format of the programme may improve access to psychological therapies, and, if encouraging, the results of this study will provide a platform for later-phase trials. NCT02371291 (ClinicalTrials.gov), registered 9 February 2015.

Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.

PubMed

Martin, Naomi H; Ibrahim, Fowzia; Tom, Brian; Galloway, James; Wailoo, Allan; Tosh, Jonathan; Lempp, Heidi; Prothero, Louise; Georgopoulou, Sofia; Sturt, Jackie; Scott, David L

2017-12-08

Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen in patients with established rheumatoid arthritis who have moderately active disease. It will evaluate both the clinical and cost-effectiveness of intensive treatment. Current Controlled Trials, ID: ISRCTN70160382 . Registered on 16 January 2014.

Delivery strategies to optimize resource utilization and performance status for patients with advanced life-limiting illness: results from the "palliative care trial" [ISRCTN 81117481].

PubMed

Abernethy, Amy P; Currow, David C; Shelby-James, Tania; Rowett, Debra; May, Frank; Samsa, Gregory P; Hunt, Roger; Williams, Helena; Esterman, Adrian; Phillips, Paddy A

2013-03-01

Evidence-based approaches are needed to improve the delivery of specialized palliative care. The aim of this trial was to improve on current models of service provision. This 2×2×2 factorial cluster randomized controlled trial was conducted at an Australian community-based palliative care service, allowing three simultaneous comparative effectiveness studies. Participating patients were newly referred adults, experiencing pain, and who were expected to live >48 hours. Patients enrolled with their general practitioners (GPs) and were randomized three times: 1) individualized interdisciplinary case conference including their GP vs. control, 2) educational outreach visiting for GPs about pain management vs. control, and 3) structured educational visiting for patients/caregivers about pain management vs. control. The control condition was current palliative care. Outcomes included Australia-modified Karnofsky Performance Status (AKPS) and pain from 60 days after randomization and hospitalizations. There were 461 participants: mean age 71 years, 50% male, 91% with cancer, median survival 179 days, and median baseline AKPS 60. Only 47% of individuals randomized to the case conferencing intervention received it; based on a priori-defined analyses, 32% of participants were included in final analyses. Case conferencing reduced hospitalizations by 26% (least squares means hospitalizations per patient: case conference 1.26 [SE 0.10] vs. control 1.70 [SE 0.13], P=0.0069) and better maintained performance status (AKPS case conferences 57.3 [SE 1.5] vs. control 51.7 [SE 2.3], P=0.0368). Among patients with declining function (AKPS <70), case conferencing and patient/caregiver education better maintained performance status (AKPS case conferences 55.0 [SE 2.1] vs. control 46.5 [SE 2.9], P=0.0143; patient/caregiver education 54.7 [SE 2.8] vs. control 46.8 [SE 2.1], P=0.0206). Pain was unchanged. GP education did not change outcomes. A single case conference added to current specialized community-based palliative care reduced hospitalizations and better maintained performance status. Comparatively, patient/caregiver education was less effective; GP education was not effective. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

A licence to vape: Is it time to trial of a nicotine licensing scheme to allow Australian adults controlled access to electronic cigarettes devices and refill solutions containing nicotine?

PubMed

Gartner, Coral; Hall, Wayne

2015-06-01

Australia has some of the most restrictive laws concerning use of nicotine in e-cigarettes. The only current legal option for Australians to legally possess and use nicotine for vaping is with a medical prescription and domestic supply is limited to compounding pharmacies that prepare medicines for specific patients. An alternative regulatory option that could be implemented under current drugs and poisons regulations is a 'nicotine licensing' scheme utilising current provisions for 'dangerous poisons'. This commentary discusses how such a scheme could be used to trial access to nicotine solutions for vaping outside of a 'medicines framework' in Australia. Copyright © 2015 Elsevier B.V. All rights reserved.

Evidence-based pharmacological treatment of substance use disorders and pathological gambling.

PubMed

van den Brink, Wim

2012-03-01

This review summarizes our current knowledge of the pharmacological treatment of substance use disorders and pathological gambling using data mainly from randomized controlled trials and meta-analyses regarding these randomized controlled trials. The review is restricted to the selection of first and second line pharmacological treatments for smoking, alcohol dependence, opioid dependence, cocaine dependence, cannabis dependence and pathological gambling. It is concluded that great progress has been made in the last three decades and that currently evidence-based pharmacological treatments are available for smoking cessation, alcohol and opioid dependence and pathological gambling. At the same time a series of existing and new pharmacological compounds are being tested in cocaine and cannabis dependence. The review concludes with a summary of additional strategies to increase the effect size of already available pharmacological interventions, including polypharmacy, combining pharmacotherapy with psychotherapy and psychosocial support, and improved patient-treatment matching.

Some Non-FDA Approved Uses for Neuromodulation: A Review of the Evidence.

PubMed

Lee, Samuel; Abd-Elsayed, Alaa

2016-09-01

Neuromodulation, including spinal cord stimulation and peripheral nerve field stimulation, has been used with success in treating several painful conditions. The FDA approved the use of neuromodulation for a few indications. We review evidence for neuromodulation in treating some important painful conditions that are not currently FDA approved. This review included an online web search for only clinical trials testing the efficacy of neuromodulation in treating coronary artery disease, peripheral vascular disease (PVD), headache, and peripheral field stimulation. Our systematic literature search found 10, 6, and 3 controlled studies relating to coronary artery disease, PVD, and headache, respectively. Our review also included 5 noncontrolled studies relating to peripheral field stimulation, as no controlled studies had been completed. This review article shows compelling evidence based on clinical trials that neuromodulation can be of benefit for patients with serious painful conditions that are not currently approved by the FDA. © 2015 World Institute of Pain.

The neural correlates of impaired attentional control in social anxiety: an ERP study of inhibition and shifting.

PubMed

Judah, Matt R; Grant, DeMond M; Mills, Adam C; Lechner, William V

2013-12-01

Cognitive models of social anxiety disorder posit that maladaptive thought processes play an etiological role in symptoms. The current study tested whether socially anxious individuals (HSAs) demonstrated impaired processing efficiency at the neural and behavioral level, and whether this was exacerbated by self-focused attention. Thirty-two (16 socially anxious, 16 nonanxious controls) subjects completed a mixed-antisaccade task with an oddball instructional cue. To manipulate self-focus, participants were told that the oddball cue indicated elevated heart rate. The HSA group demonstrated delayed saccade onset compared with controls, but made fewer errors. HSAs also had lower P3b amplitude compared with controls, suggesting reduced availability of resources for discriminating cues, and later P3b latency during self-focus trials, suggesting delayed cue categorization. Additionally, HSAs had greater CNV negativity compared with controls, suggesting greater effort in response preparation, and this negativity was reduced during self-focus trials, supporting the hypothesis that self-focused attention preoccupies executive resources. The current study supports and expands cognitive theories by documenting impaired neural and behavioral functioning in social anxiety and the role of self-focused attention in these deficits.

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

PubMed

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

2017-07-03

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

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

PubMed

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

2014-09-20

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

Determining the efficacy of guppies and pyriproxyfen (Sumilarv® 2MR) combined with community engagement on dengue vectors in Cambodia: study protocol for a randomized controlled trial.

PubMed

Hustedt, John; Doum, Dyna; Keo, Vanney; Ly, Sokha; Sam, BunLeng; Chan, Vibol; Alexander, Neal; Bradley, John; Prasetyo, Didot Budi; Rachmat, Agus; Muhammad, Shafique; Lopes, Sergio; Leang, Rithea; Hii, Jeffrey

2017-08-04

Evidence on the effectiveness of low-cost, sustainable, biological vector-control tools for the Aedes mosquitoes is limited. Therefore, the purpose of this trial is to estimate the impact of guppy fish (guppies), in combination with the use of the larvicide pyriproxyfen (Sumilarv® 2MR), and Communication for Behavioral Impact (COMBI) activities to reduce entomological indices in Cambodia. In this cluster randomized controlled, superiority trial, 30 clusters comprising one or more villages each (with approximately 170 households) will be allocated, in a 1:1:1 ratio, to receive either (1) three interventions (guppies, Sumilarv® 2MR, and COMBI activities), (2) two interventions (guppies and COMBI activities), or (3) control (standard vector control). Households will be invited to participate, and entomology surveys among 40 randomly selected households per cluster will be carried out quarterly. The primary outcome will be the population density of adult female Aedes mosquitoes (i.e., number per house) trapped using adult resting collections. Secondary outcome measures will include the House Index, Container Index, Breteau Index, Pupae Per House, Pupae Per Person, mosquito infection rate, guppy fish coverage, Sumilarv® 2MR coverage, and percentage of respondents with knowledge about Aedes mosquitoes causing dengue. In the primary analysis, adult female Aedes density and mosquito infection rates will be aggregated over follow-up time points to give a single rate per cluster. This will be analyzed by negative binomial regression, yielding density ratios. This trial is expected to provide robust estimates of the intervention effect. A rigorous evaluation of these vector-control interventions is vital to developing an evidence-based dengue control strategy and to help direct government resources. Current Controlled Trials, ID: ISRCTN85307778 . Registered on 25 October 2015.

Facilitating large-scale clinical trials: in Asia.

PubMed

Choi, Han Yong; Ko, Jae-Wook

2010-01-01

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

Theory of planned behaviour variables and objective walking behaviour do not show seasonal variation in a randomised controlled trial

PubMed Central

2014-01-01

Background Longitudinal studies have shown that objectively measured walking behaviour is subject to seasonal variation, with people walking more in summer compared to winter. Seasonality therefore may have the potential to bias the results of randomised controlled trials if there are not adequate statistical or design controls. Despite this there are no studies that assess the impact of seasonality on walking behaviour in a randomised controlled trial, to quantify the extent of such bias. Further there have been no studies assessing how season impacts on the psychological predictors of walking behaviour to date. The aim of the present study was to assess seasonal differences in a) objective walking behaviour and b) Theory of Planned Behaviour (TPB) variables during a randomised controlled trial of an intervention to promote walking. Methods 315 patients were recruited to a two-arm cluster randomised controlled trial of an intervention to promote walking in primary care. A series of repeated measures ANCOVAs were conducted to examine the effect of season on pedometer measures of walking behaviour and TPB measures, assessed immediately post-intervention and six months later. Hierarchical regression analyses were conducted to assess whether season moderated the prediction of intention and behaviour by TPB measures. Results There were no significant differences in time spent walking in spring/summer compared to autumn/winter. There was no significant seasonal variation in most TPB variables, although the belief that there will be good weather was significantly higher in spring/summer (F = 19.46, p < .001). Season did not significantly predict intention or objective walking behaviour, or moderate the effects of TPB variables on intention or behaviour. Conclusion Seasonality does not influence objectively measured walking behaviour or psychological variables during a randomised controlled trial. Consequently physical activity behaviour outcomes in trials will not be biased by the season in which they are measured. Previous studies may have overestimated the extent of seasonality effects by selecting the most extreme summer and winter months to assess PA. In addition, participants recruited to behaviour change interventions might have higher levels of motivation to change and are less affected by seasonal barriers. Trial registration Current Controlled Trials ISRCTN95932902 PMID:24499405

Relaxation techniques for pain management in labour.

PubMed

Smith, Caroline A; Levett, Kate M; Collins, Carmel T; Crowther, Caroline A

2011-12-07

Many women would like to avoid pharmacological or invasive methods of pain management in labour and this may contribute towards the popularity of complementary methods of pain management. This review examined currently available evidence supporting the use of relaxation therapies for pain management in labour. To examine the effects of relaxation methods for pain management in labour on maternal and perinatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2010), The Cochrane Complementary Medicine Field's Trials Register (November 2011), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 4), MEDLINE (1966 to 30 November 2010), CINAHL (1980 to 30 November 2010), the Australian and New Zealand Clinical Trial Registry (30 November 2010), Chinese Clinical Trial Register (30 November 2010), Current Controlled Trials (30 November 2010), ClinicalTrials.gov, (30 November 2010) ISRCTN Register (30 November 2010), National Centre for Complementary and Alternative Medicine (NCCAM) (30 November 2010) and the WHO International Clinical Trials Registry Platform (30 November 2010). Randomised controlled trials comparing relaxation methods with standard care, no treatment, other non-pharmacological forms of pain management in labour or placebo. Three review authors independently assessed trials for inclusion and extracted data. Data were checked for accuracy. Two review authors independently assessed trial quality. We attempted to contact study authors for additional information. We included 11 studies (1374 women) in the review. Relaxation was associated with a reduction in pain intensity during the latent phase (mean difference (MD) -1.25, 95% confidence interval (CI) -1.97 to -0.53, one trial, 40 women) and active phase of labour (MD -2.48, 95% CI -3.13 to 0.83, two trials, 74 women). There was evidence of improved outcomes from relaxation instruction with increased satisfaction with pain relief (risk ratio (RR) 8.00, 95% CI 1.10 to 58.19, one trial, 40 women) and lower assisted vaginal delivery (RR 0.07, 95% CI 0.01 to 0.50, two trials, 86 women). Yoga was associated with reduced pain (mean difference (MD) -6.12, 95% CI -11.77 to -0.47), one trial, 66 women), increased satisfaction with pain relief (MD 7.88, 95% CI 1.51 to 14.25, one trial, 66 women), satisfaction with the childbirth experience (MD) 6.34, 95% CI 0.26 to 12.42, one trial, 66 women), and reduced length of labour when compared to usual care (MD -139.91, 95% CI -252.50 to -27.32, one trial, 66 women) and when compared with supine position (MD -191.34, 95% CI -243.72 to -138.96, one trial, 83 women). Trials evaluating music and audio analgesia found no difference between groups in the primary outcomes pain intensity, satisfaction with pain relief, and caesarean delivery. The risk of bias was unclear for the majority of trials. Relaxation and yoga may have a role with reducing pain, increasing satisfaction with pain relief and reducing the rate of assisted vaginal delivery. There was insufficient evidence for the role of music and audio-analgesia. However, there is a need for further research.

Wearable activity monitors in oncology trials: Current use of an emerging technology.

PubMed

Gresham, Gillian; Schrack, Jennifer; Gresham, Louise M; Shinde, Arvind M; Hendifar, Andrew E; Tuli, Richard; Rimel, B J; Figlin, Robert; Meinert, Curtis L; Piantadosi, Steven

2018-01-01

Physical activity is an important outcome in oncology trials. Physical activity is commonly assessed using self-reported questionnaires, which are limited by recall and response biases. Recent advancements in wearable technology have provided oncologists with new opportunities to obtain real-time, objective physical activity data. The purpose of this review was to describe current uses of wearable activity monitors in oncology trials. We searched Pubmed, Embase, and the Cochrane Central Register of Controlled Trials for oncology trials involving wearable activity monitors published between 2005 and 2016. We extracted details on study design, types of activity monitors used, and purpose for their use. We summarized activity monitor metrics including step counts, sleep and sedentary time, and time spent in moderate-to-vigorous activity. We identified 41 trials of which 26 (63%) involved cancer survivors (post-treatment) and 15 trials (37%) involved patients with active cancer. Most trials (65%) involved breast cancer patients. Wearable activity monitors were commonly used in exercise (54%) or behavioral (29%) trials. Cancer survivors take between 4660 and 11,000 steps/day and those undergoing treatment take 2885 to 8300steps/day. Wearable activity monitors are increasingly being used to obtain objective measures of physical activity in oncology trials. There is potential for their use to expand to evaluate and predict clinical outcomes such as survival, quality of life, and treatment tolerance in future studies. Currently, there remains a lack of standardization in the types of monitors being used and how their data are being collected, analyzed, and interpreted. Recent advancements in wearable activity monitor technology have provided oncologists with new opportunities to monitor their patients' daily activity in real-world settings. The integration of wearable activity monitors into cancer care will help increase our understanding of the associations between physical activity and the prevention and management of the disease, in addition to other important cancer outcomes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Targeted full energy and protein delivery in critically ill patients: a study protocol for a pilot randomised control trial (FEED Trial).

PubMed

Fetterplace, Kate; Deane, Adam M; Tierney, Audrey; Beach, Lisa; Knight, Laura D; Rechnitzer, Thomas; Forsyth, Adrienne; Mourtzakis, Marina; Presneill, Jeffrey; MacIsaac, Christopher

2018-01-01

Current guidelines for the provision of protein for critically ill patients are based on incomplete evidence, due to limited data from randomised controlled trials. The present pilot randomised controlled trial is part of a program of work to expand knowledge about the clinical effects of protein delivery to critically ill patients. The primary aim of this pilot study is to determine whether an enteral feeding protocol using a volume target, with additional protein supplementation, delivers a greater amount of protein and energy to mechanically ventilated critically ill patients than a standard nutrition protocol. The secondary aims are to evaluate the potential effects of this feeding strategy on muscle mass and other patient-centred outcomes. This prospective, single-centred, pilot, randomised control trial will include 60 participants who are mechanically ventilated and can be enterally fed. Following informed consent, the participants receiving enteral nutrition in the intensive care unit (ICU) will be allocated using a randomisation algorithm in a 1:1 ratio to the intervention (high-protein daily volume-based feeding protocol, providing 25 kcal/kg and 1.5 g/kg protein) or standard care (hourly rate-based feeding protocol providing 25 kcal/kg and 1 g/kg protein). The co-primary outcomes are the average daily protein and energy delivered to the end of day 15 following randomisation. The secondary outcomes include change in quadriceps muscle layer thickness (QMLT) from baseline (prior to randomisation) to ICU discharge and other nutritional and patient-centred outcomes. This trial aims to examine whether a volume-based feeding protocol with supplemental protein increases protein and energy delivery. The potential effect of such increases on muscle mass loss will be explored. These outcomes will assist in formulating larger randomised control trials to assess mortality and morbidity. Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN: 12615000876594 UTN: U1111-1172-8563.

Maintenance N-acetyl cysteine treatment for bipolar disorder: a double-blind randomized placebo controlled trial.

PubMed

Berk, Michael; Dean, Olivia M; Cotton, Sue M; Gama, Clarissa S; Kapczinski, Flavio; Fernandes, Brisa; Kohlmann, Kristy; Jeavons, Susan; Hewitt, Karen; Moss, Kirsteen; Allwang, Christine; Schapkaitz, Ian; Cobb, Heidi; Bush, Ashley I; Dodd, Seetal; Malhi, Gin S

2012-08-14

N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493).

A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831)

PubMed Central

Kean, James D.; Kaufman, Jordy; Lomas, Justine; Goh, Antionette; White, David; Simpson, David; Scholey, Andrew; Singh, Hemant; Sarris, Jerome; Zangara, Andrea; Stough, Con

2015-01-01

Clinical diagnoses of Attention Deficit Hyperactivity Disorder (ADHD) and the use of prescription medications for its treatment have increased in recent years. Current treatments may involve the administration of amphetamine-type substances, a treatment path many parents are apprehensive to take. Therefore, alternative pharmacological treatments are required. Few nutritional or pharmacological alternatives that reduce ADHD associated symptoms (hyperactivity and inattention) have been subjected to rigorous clinical trials. Bacopa monnieri is a perennial creeping herb. CDRI 08 is a special extract of Bacopa monnieri which has been subjected to hundreds of scientific studies and has been shown in human randomized controlled trials (RCTs) to improve memory, attention, and mood. It is hypothesised that chronic administration of CDRI 08 will improve attention, concentration and behaviour in children with high levels of hyperactivity and/or inattention. This paper reports the protocol for the first 16-week, randomized, placebo-controlled, double-blind, parallel groups trial examining the efficacy and safety of CDRI 08 in male children aged 6–14 years with high levels of inattention and hyperactivity. The primary outcome variable will be the level of hyperactivity and inattention measured by the Conners’ Parent Rating Scale (CPRS). Secondary outcome variables include cognition, mood, sleep, and EEG. Trial registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000827831. PMID:26633481

Cardiac Autonomic and Blood Pressure Responses to an Acute Foam Rolling Session.

PubMed

Lastova, Kevin; Nordvall, Michael; Walters-Edwards, Michelle; Allnutt, Amy; Wong, Alexei

2018-03-22

Foam Rolling (FR) is a self-myofascial release method that has become extremely popular among athletes and fitness enthusiasts for its ability to improve flexibility and range of motion and alleviate delayed onset muscle soreness. However, the cardiac autonomic modulation and blood pressure (BP) responses induced by an acute FR session are currently unknown. The present study evaluated the effects of an acute session of FR exercise on heart rate variability (HRV) and BP responses in healthy individuals. Fifteen (M=8, F=7) healthy subjects completed either a FR or non-exercise control trial in randomized order. HRV and BP measurements were collected at baseline, 10 and 30 min after each trial. There were significant increases (P < 0.01) in markers of vagal tone (nHF) for 30 min after the FR trial, while no changes from baseline were observed following control. There were also significant decreases (P < 0.05) in markers of sympathetic activity (nLF), sympathovagal balance (nLF/nHF), systolic BP and diastolic BP at 10 and 30 min after the trial KB trial while no changes from baseline were observed after the control trial. Our findings indicate that FR decreases sympathovagal balance for 30 min post-intervention which is concurrent with an important hypotensive effect. Further research is warranted to evaluate the potential cardiovascular protective effects of FR in diverse populations.

Estimating economic thresholds for site-specific weed control using manual weed counts and sensor technology: an example based on three winter wheat trials.

PubMed

Keller, Martina; Gutjahr, Christoph; Möhring, Jens; Weis, Martin; Sökefeld, Markus; Gerhards, Roland

2014-02-01

Precision experimental design uses the natural heterogeneity of agricultural fields and combines sensor technology with linear mixed models to estimate the effect of weeds, soil properties and herbicide on yield. These estimates can be used to derive economic thresholds. Three field trials are presented using the precision experimental design in winter wheat. Weed densities were determined by manual sampling and bi-spectral cameras, yield and soil properties were mapped. Galium aparine, other broad-leaved weeds and Alopecurus myosuroides reduced yield by 17.5, 1.2 and 12.4 kg ha(-1) plant(-1)  m(2) in one trial. The determined thresholds for site-specific weed control with independently applied herbicides were 4, 48 and 12 plants m(-2), respectively. Spring drought reduced yield effects of weeds considerably in one trial, since water became yield limiting. A negative herbicide effect on the crop was negligible, except in one trial, in which the herbicide mixture tended to reduce yield by 0.6 t ha(-1). Bi-spectral cameras for weed counting were of limited use and still need improvement. Nevertheless, large weed patches were correctly identified. The current paper presents a new approach to conducting field trials and deriving decision rules for weed control in farmers' fields. © 2013 Society of Chemical Industry.

Pivotal factors concerned in design of acupuncture clinical research: From two articles in JAMA.

PubMed

Wu, Jia-Ni; Qin, Zong-Shi; Liu, Zhi-Shun

2017-11-01

Two randomized controlled trials of acupuncture concerning polycystic ovary syndrome (PCOS) and stress urinary incontinence (SUI) were published simultaneously in the 24th issue, 2017 of The Journal of the American Medical Association (JAMA). A trial involving PCOS indicated that active acupuncture did not increase live birth compared with sham acupuncture; meanwhile, another trial referring to SUI showed that electroacupuncture resulted in less urine leakage compared with sham electroacupuncture. With an eye to the negative and positive results of acupuncture, three pivotal factors should be contemplated: (1) proper illness for acupuncture, that is, a problem need to be solved in current medical science, and acupuncture may really work for it; (2) proper pre-studied primary outcome, which is better be objective and repeatedly measurable to reveal the therapeutic effect of acupuncture truly and objectively; (3) proper sham control, which can blind the patients to the upmost extent with minimal biological effects. Through the publication of clinical trials of acupuncture in high-impact journals in recent years, researchers should have confidence in their clinical trials by pondering over these three pivotal factors.

Correcting for multiple-testing in multi-arm trials: is it necessary and is it done?

PubMed

Wason, James M S; Stecher, Lynne; Mander, Adrian P

2014-09-17

Multi-arm trials enable the evaluation of multiple treatments within a single trial. They provide a way of substantially increasing the efficiency of the clinical development process. However, since multi-arm trials test multiple hypotheses, some regulators require that a statistical correction be made to control the chance of making a type-1 error (false-positive). Several conflicting viewpoints are expressed in the literature regarding the circumstances in which a multiple-testing correction should be used. In this article we discuss these conflicting viewpoints and review the frequency with which correction methods are currently used in practice. We identified all multi-arm clinical trials published in 2012 by four major medical journals. Summary data on several aspects of the trial design were extracted, including whether the trial was exploratory or confirmatory, whether a multiple-testing correction was applied and, if one was used, what type it was. We found that almost half (49%) of published multi-arm trials report using a multiple-testing correction. The percentage that corrected was higher for trials in which the experimental arms included multiple doses or regimens of the same treatments (67%). The percentage that corrected was higher in exploratory than confirmatory trials, although this is explained by a greater proportion of exploratory trials testing multiple doses and regimens of the same treatment. A sizeable proportion of published multi-arm trials do not correct for multiple-testing. Clearer guidance about whether multiple-testing correction is needed for multi-arm trials that test separate treatments against a common control group is required.

Transabdominal amnioinfusion for improving fetal outcomes after oligohydramnios secondary to preterm prelabour rupture of membranes before 26 weeks.

PubMed

Van Teeffelen, Stijn; Pajkrt, Eva; Willekes, Christine; Van Kuijk, Sander M J; Mol, Ben Willem J

2013-08-03

Preterm prelabour rupture of membranes (PPROM) before 26 weeks can delay lung development and can cause pulmonary hypoplasia, as a result of oligohydramnios. Restoring the amniotic fluid volume by transabdominal amnioinfusion might prevent abnormal lung development and might have a protective effect for neurological complications, fetal deformities and neonatal sepsis. To assess the effectiveness of transabdominal amnioinfusion in improving perinatal outcome in women with oligohydramnios secondary to rupture of fetal membranes before 26 weeks. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013). All randomised controlled trials comparing transabdominal amnioinfusion with no transabdominal amnioinfusion. Cluster- or quasi-randomised trials were not eligible for inclusion. In cases where only an abstract was available, we attempted to find the full articles. Two review authors assessed trials for inclusion. No eligible trials were identified. There are no included studies. There is currently no evidence to evaluate the use of transabdominal amnioinfusion in women with oligohydramnios secondary to rupture of fetal membranes before 26 weeks for improving perinatal outcome. Further research examining the effects of this intervention is needed. Two randomised controlled trials are ongoing but final data have not yet been published.

Field Assessment of a Novel Household-Based Water Filtration Device: A Randomised, Placebo-Controlled Trial in the Democratic Republic of Congo

PubMed Central

Boisson, Sophie; Kiyombo, Mbela; Sthreshley, Larry; Tumba, Saturnin; Makambo, Jacques; Clasen, Thomas

2010-01-01

Background Household water treatment can improve the microbiological quality of drinking water and may prevent diarrheal diseases. However, current methods of treating water at home have certain shortcomings, and there is evidence of bias in the reported health impact of the intervention in open trial designs. Methods and Findings We undertook a randomised, double-blinded, placebo-controlled trial among 240 households (1,144 persons) in rural Democratic Republic of Congo to assess the field performance, use and effectiveness of a novel filtration device in preventing diarrhea. Households were followed up monthly for 12 months. Filters and placebos were monitored for longevity and for microbiological performance by comparing thermotolerant coliform (TTC) levels in influent and effluent water samples. Mean longitudinal prevalence of diarrhea was estimated among participants of all ages. Compliance was assessed through self-reported use and presence of water in the top vessel of the device at the time of visit. Over the 12-month follow-up period, data were collected for 11,236 person-weeks of observation (81.8% total possible). After adjusting for clustering within the household, the longitudinal prevalence ratio of diarrhoea was 0.85 (95% confidence interval: 0.61–1.20). The filters achieved a 2.98 log reduction in TTC levels while, for reasons that are unclear, the placebos achieved a 1.05 log reduction (p<0.0001). After 8 months, 68% of intervention households met the study's definition of current users, though most (73% of adults and 95% of children) also reported drinking untreated water the previous day. The filter maintained a constant flow rate over time, though 12.4% of filters were damaged during the course of the study. Conclusions While the filter was effective in improving water quality, our results provide little evidence that it was protective against diarrhea. The moderate reduction observed nevertheless supports the need for larger studies that measure impact against a neutral placebo. Trial Registration Current Controlled Trials ISRCTN03844341 PMID:20856584

Social Skills Training for Young Adults with High-Functioning Autism Spectrum Disorders: A Randomized Controlled Pilot Study

ERIC Educational Resources Information Center

Gantman, Alexander; Kapp, Steven K.; Orenski, Kaely; Laugeson, Elizabeth A.

2012-01-01

Despite the psychosocial difficulties common among young adults with autism spectrum disorders (ASD), little to no evidence-based social skills interventions exist for this population. Using a randomized controlled trial (RCT) design, the current study tested the effectiveness of an evidence-based, caregiver-assisted social skills intervention…

Silence is deadly: a cluster-randomised controlled trial of a mental health help-seeking intervention for young men.

PubMed

Calear, Alison L; Banfield, Michelle; Batterham, Philip J; Morse, Alyssa R; Forbes, Owen; Carron-Arthur, Bradley; Fisk, Martin

2017-10-23

Young men are consistently less likely to seek help for mental health problems than their female peers. This is particularly concerning given the high rates of suicide among male adolescents. The school system has been identified as an ideal setting for the implementation of prevention and early intervention programs for young people. The current trial aims to determine the effectiveness of the Silence is Deadly program in increasing positive help-seeking intentions for mental health problems and suicide among male secondary school students. This study is a two-arm, cluster-randomised, controlled trial that will compare the Silence is Deadly program to a wait-list control condition. Eight Australian high schools will be recruited to the trial, with male students in grades 11 and 12 (16 to 18 years of age) targeted for participation. The program is an innovative male-tailored suicide prevention intervention, comprising a presentation that emphasises role-modelling and legitimises help-seeking for personal and emotional problems, and a brief video that features celebrity athletes who counter existing male norms around help-seeking and encourage communication about personal and emotional issues. The program also includes a discussion of how to help a friend in distress and ends with a question and answer session. The primary outcome measure for the current study is help-seeking intentions. Secondary outcomes include help-seeking behaviour, help-seeking attitudes, help-seeking stigma, mental health symptoms, and suicidal ideation. Data will be collected pre-intervention, post-intervention, and at 3-month follow-up. Primary analyses will compare changes in help-seeking intentions for the intervention condition relative to the wait-list control condition using mixed-effects repeated-measures analyses that account for clustering within schools. If proven to be effective, this targeted help-seeking intervention for adolescent males, which is currently only delivered in one jurisdiction, could be more widely delivered in Australian high schools. The Silence is Deadly program has the potential to significantly contribute to the mental health of young men in Australia by improving help-seeking for suicidality and mental health problems, allowing this population to better access treatment and support sooner. Australian New Zealand Clinical Trials Registry, ACTRN12617000658314 . Registered on 8 May 2017.

Systematic review of the effect of aerobic and resistance exercise training on systemic brain natriuretic peptide (BNP) and N-terminal BNP expression in heart failure patients.

PubMed

Smart, N A; Steele, M

2010-04-30

BNP and the N-terminal portion (NT-pro-BNP) have emerged as powerful tools in the diagnosis and prognosis of heart failure on acute presentation. The aim of this work was to systematically review the effect of exercise training on BNP and NT-pro-BNP levels in patients with left ventricular dysfunction. A systematic search was conducted of Medline (Ovid) (1950-July 2008), Embase.com (1974-current), Cochrane Central Register of Controlled Trials, CINAHL (1981-current) and Web of Science (2000-current) to identify randomized controlled trials of aerobic and/or resistance exercise training in heart failure patients that measured BNP and/or pro-BNP. Primary outcome measures were changes in BNP and NT-pro-BNP. Secondary outcomes were changes in functional capacity and energy expenditure, measures of study quality were also recorded. Nine randomized controlled studies measuring BNP or NT-pro-BNP met our eligibility criteria. Exercise training had a favourable effect on BNP (mean difference -79 pg/ml 95% C.I. -141 to - 17 pg/ml, P=0.01) and NT-pro-BNP (mean difference -621 pg/ml, 95% C.I. -844 to -398 pg/ml, P=<0.00001). Moreover the trials that showed a significant change in NT-pro-BNP all had a weekly exercise energy expenditure of more than 400 Kcal. Data from nine published studies, suggest exercise training has a favorable effect on BNP and NT-pro-BNP in heart failure patients. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Effect of village-wide use of long-lasting insecticidal nets on visceral Leishmaniasis vectors in India and Nepal: a cluster randomized trial.

PubMed

Picado, Albert; Das, Murari L; Kumar, Vijay; Kesari, Shreekant; Dinesh, Diwakar S; Roy, Lalita; Rijal, Suman; Das, Pradeep; Rowland, Mark; Sundar, Shyam; Coosemans, Marc; Boelaert, Marleen; Davies, Clive R

2010-01-26

Visceral leishmaniasis (VL) control in the Indian subcontinent is currently based on case detection and treatment, and on vector control using indoor residual spraying (IRS). The use of long-lasting insecticidal nets (LN) has been postulated as an alternative or complement to IRS. Here we tested the impact of comprehensive distribution of LN on the density of Phlebotomus argentipes in VL-endemic villages. A cluster-randomized controlled trial with household P. argentipes density as outcome was designed. Twelve clusters from an ongoing LN clinical trial--three intervention and three control clusters in both India and Nepal--were selected on the basis of accessibility and VL incidence. Ten houses per cluster selected on the basis of high pre-intervention P. argentipes density were monitored monthly for 12 months after distribution of LN using CDC light traps (LT) and mouth aspiration methods. Ten cattle sheds per cluster were also monitored by aspiration. A random effect linear regression model showed that the cluster-wide distribution of LNs significantly reduced the P. argentipes density/house by 24.9% (95% CI 1.80%-42.5%) as measured by means of LTs. The ongoing clinical trial, designed to measure the impact of LNs on VL incidence, will confirm whether LNs should be adopted as a control strategy in the regional VL elimination programs. The entomological evidence described here provides some evidence that LNs could be usefully deployed as part of the VL control program. ClinicalTrials.gov CT-2005-015374.

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

PubMed

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

2016-01-01

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

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

PubMed

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

2014-10-24

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

Lifestyle Advice Combined with Personalized Estimates of Genetic or Phenotypic Risk of Type 2 Diabetes, and Objectively Measured Physical Activity: A Randomized Controlled Trial.

PubMed

Godino, Job G; van Sluijs, Esther M F; Marteau, Theresa M; Sutton, Stephen; Sharp, Stephen J; Griffin, Simon J

2016-11-01

Information about genetic and phenotypic risk of type 2 diabetes is now widely available and is being incorporated into disease prevention programs. Whether such information motivates behavior change or has adverse effects is uncertain. We examined the effect of communicating an estimate of genetic or phenotypic risk of type 2 diabetes in a parallel group, open, randomized controlled trial. We recruited 569 healthy middle-aged adults from the Fenland Study, an ongoing population-based, observational study in the east of England (Cambridgeshire, UK). We used a computer-generated random list to assign participants in blocks of six to receive either standard lifestyle advice alone (control group, n = 190) or in combination with a genetic (n = 189) or a phenotypic (n = 190) risk estimate for type 2 diabetes (intervention groups). After 8 wk, we measured the primary outcome, objectively measured physical activity (kJ/kg/day), and also measured several secondary outcomes (including self-reported diet, self-reported weight, worry, anxiety, and perceived risk). The study was powered to detect a between-group difference of 4.1 kJ/kg/d at follow-up. 557 (98%) participants completed the trial. There were no significant intervention effects on physical activity (difference in adjusted mean change from baseline: genetic risk group versus control group 0.85 kJ/kg/d (95% CI -2.07 to 3.77, p = 0.57); phenotypic risk group versus control group 1.32 (95% CI -1.61 to 4.25, p = 0.38); and genetic risk group versus phenotypic risk group -0.47 (95% CI -3.40 to 2.46, p = 0.75). No significant differences in self-reported diet, self-reported weight, worry, and anxiety were observed between trial groups. Estimates of perceived risk were significantly more accurate among those who received risk information than among those who did not. Key limitations include the recruitment of a sample that may not be representative of the UK population, use of self-reported secondary outcome measures, and a short follow-up period. In this study, we did not observe short-term changes in behavior associated with the communication of an estimate of genetic or phenotypic risk of type 2 diabetes. We also did not observe changes in worry or anxiety in the study population. Additional research is needed to investigate the conditions under which risk information might enhance preventive strategies. (Current Controlled Trials ISRCTN09650496; Date applied: April 4, 2011; Date assigned: June 10, 2011). The trial is registered with Current Controlled Trials, ISRCTN09650496.

Maintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomized placebo controlled trial

PubMed Central

2012-01-01

Background N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493). PMID:22891797

Cardiac Autonomic and Blood Pressure Responses to an Acute Bout of Kettlebell Exercise.

PubMed

Wong, Alexei; Nordvall, Michael; Walters-Edwards, Michelle; Lastova, Kevin; Francavillo, Gwendolyn; Summerfield, Liane; Sanchez-Gonzalez, Marcos

2017-10-07

Kettlebell (KB) training has become an extremely popular exercise program for improving both muscle strength and aerobic fitness. However, the cardiac autonomic modulation and blood pressure (BP) responses induced by an acute KB exercise session are currently unknown. Understanding the impact of this exercise modality on the post-exercise autonomic modulation and BP would facilitate appropriate exercise prescription in susceptible populations. The present study evaluated the effects of an acute session of KB exercise on heart rate variability (HRV) and BP responses in healthy individuals. Seventeen (M=10, F=7) healthy subjects completed either a KB or non-exercise control trial in randomized order. HRV and BP measurements were collected at baseline, 3, 10 and 30 min after each trial. There were significant increases (P < 0.01) in heart rate, markers of sympathetic activity (nLF) and sympathovagal balance (nLF/nHF) for 30 min after the trial KB trial, while no changes from baseline were observed after the control trial. There were also significant decreases (P < 0.01) in markers of vagal tone (RMMSD, nHF) for 30 min as well as (P < 0.01) systolic BP and diastolic BP at 10 and 30 min after the trial KB trial while no changes from baseline were observed after the control trial. Our findings indicate that KB exercise increases sympathovagal balance for 30 min post-intervention which is concurrent with an important hypotensive effect. Further research is warranted to evaluate the potential clinical application of KB training in populations that might benefit from post-exercise hypotension, such as hypertensives.

The data management of a phase III efficacy trial of an 11-valent pneumococcal conjugate vaccine and related satellite studies conducted in the Philippines.

PubMed

Sanvictores, Diozele Hazel M; Lucero, Marilla G; Nohynek, Hanna; Tallo, Veronica L; Tanskanen, Antti; Nillos, Leilani T; Williams, Gail

2012-06-07

A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted. We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently. There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff. Current Controlled Trials ISRCTN62323832.

Alternating current cranial electrotherapy stimulation (CES) for depression.

PubMed

Kavirajan, Harish C; Lueck, Kristin; Chuang, Kenneth

2014-07-08

Depression is a mood disorder with a prevalence of approximately 1% to 3% worldwide, representing the fourth leading cause of disease burden globally. The current standard treatments of psychological therapy and antidepressant medications are not effective for everyone, and psychotropic drugs may be associated with significant adverse effects. Cranial electrical stimulation (CES) treatment, in which a low intensity electrical current is administered through the use of a small, portable electrical device, has been reported to have efficacy in the treatment of depression with minimal adverse effects. This systematic review investigated the scientific evidence regarding the efficacy and safety of CES in treatment of acute depression compared to sham, or simulated, CES treatment. To assess the effectiveness and safety of alternating current cranial electrotherapy stimulation (CES) compared with sham CES for acute depression. We searched The Cochrane Collaboration Depression, Anxiety and Neurosis review group's specialized register (CCDANCTR-Studies and CCDANCTR-References) to February 24, 2014 This register contains relevant randomized controlled trials from: The Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). We examined reference lists of review papers and books on CES. We contacted authors, other experts in the field and CES manufacturing companies for knowledge of suitable published or unpublished trials. Randomized controlled trials of CES versus sham CES for the acute treatment of depressive disorder in adults aged 18 to 75 years. We planned to extract data from the original reports of included studies independently by two authors. The main outcomes to be assessed were:(1) the efficacy of CES in reducing symptoms of depression as reflected in change scores on standardized depression rating scales.(2) the tolerability of CES treatment to participants, as reflected in rates of discontinuation due to adverse effects.We planned to analyze data using Review Manager 5. No studies met the inclusion criteria for this review. There are insufficient methodologically rigorous studies of CES in treatment of acute depression. There is a need for double-blind randomized controlled trials of CES in the treatment of acute depression.

Effectiveness of a structured education reminiscence-based programme for staff on the quality of life of residents with dementia in long-stay units: a study protocol for a cluster randomised trial.

PubMed

O'Shea, Eamon; Devane, Declan; Murphy, Kathy; Cooney, Adeline; Casey, Dympna; Jordan, Fionnuala; Hunter, Andrew; Murphy, Edel

2011-02-14

Current projections indicate that there will be a significant increase in the number of people with dementia in Ireland, from approximately 40,000 at present to 100,000 by 2036. Psychosocial interventions, such as reminiscence, have the potential to improve the quality of life of people with dementia. However, while reminiscence is used widely in dementia care, its impact on the quality of life of people with dementia remains largely undocumented and there is a need for a robust and fair assessment of its overall effectiveness. The DementiA education programme incorporating REminiscence for Staff study will evaluate the effectiveness of a structured reminiscence-based education programme for care staff on the quality of life of residents with dementia in long-stay units. The study is a two-group, single-blind cluster randomised trial conducted in public and private long-stay residential settings in Ireland. Randomisation to control and intervention is at the level of the long-stay residential unit. Sample size calculations suggest that 18 residential units each containing 17 people with dementia are required for randomisation to control and intervention groups to achieve power of at least 80% with alpha levels of 0.05. Each resident in the intervention group is linked with a nurse and care assistant who have taken the structured reminiscence-based education programme. Participants in the control group will receive usual care. The primary outcome is quality of life of residents as measured by the Quality of Life-AD instrument. Secondary outcomes include agitation, depression and carer burden. Blinded outcome assessment is undertaken at baseline and at 18-22 weeks post-randomisation. Trials on reminiscence-based interventions for people with dementia have been scarce and the quality of the information arising from those that have been done has been undermined by methodological problems, particularly in relation to scale and scope. This trial is powered to deliver more credible and durable results. The trial may also convey process utility to a long-stay system in Ireland that has not been geared for education and training, especially in relation to dementia. The results of this trial are applicable to long-stay residential units in Ireland and internationally. Current Controlled Trials ISRCTN99651465.

A walking programme and a supervised exercise class versus usual physiotherapy for chronic low back pain: a single-blinded randomised controlled trial. (The Supervised Walking In comparison to Fitness Training for Back Pain (SWIFT) Trial)

PubMed Central

Hurley, Deirdre A; O'Donoghue, Grainne; Tully, Mark A; Moffett, Jennifer Klaber; van Mechelen, Willem; Daly, Leslie; Boreham, Colin AG; McDonough, Suzanne M

2009-01-01

Background Chronic low back pain (CLBP) is a persistent disabling condition with rising significant healthcare, social and economic costs. Current research supports the use of exercise-based treatment approaches that encourage people with CLBP to assume a physically active role in their recovery. While international clinical guidelines and systematic reviews for CLBP support supervised group exercise as an attractive first-line option for treating large numbers of CLBP patients at low cost, barriers to their delivery include space and time restrictions in healthcare settings and poor patient attendance. The European Clinical Guidelines have identified the need for research in the use of brief/minimal contact self-activation interventions that encourage participation in physical activity for CLBP. Walking may be an ideally suited form of individualized exercise prescription as it is easy to do, requires no special skills or facilities, and is achievable by virtually all ages with little risk of injury, but its effectiveness for LBP is unproven. Methods and design This study will be an assessor-blinded randomized controlled trial that will investigate the difference in clinical effectiveness and costs of an individualized walking programme and a supervised general exercise programme compared to usual physiotherapy, which will act as the control group, in people with chronic low back pain. A sample of 246 patients will be recruited in Dublin, Ireland through acute general hospital outpatient physiotherapy departments that provide treatment for people with CLBP. Patients will be randomly allocated to one of the three groups in a concealed manner. The main outcomes will be functional disability, pain, quality of life, fear avoidance, back beliefs, physical activity, satisfaction and costs, which will be evaluated at baseline, and 3, 6 and 12 months [follow-up by pre-paid postage]. Qualitative telephone interviews and focus groups will be embedded in the research design to obtain feedback about participants' experiences of the interventions and trial participation, and to inform interpretation of the quantitative data. Planned analysis will be by intention to treat (quantitative data) and thematic analysis (qualitative data) Discussion The trial will evaluate the effectiveness of a walking programme and a supervised general exercise programme compared to usual physiotherapy in people with CLBP. Trial registration Current controlled trial ISRCTN17592092 PMID:19573247

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH2O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure ≤30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method. Trial registration ClinicalTrials.gov Identifier: NCT01374022 PMID:22929542

Internet-based cognitive behavior therapy for procrastination: study protocol for a randomized controlled trial.

PubMed

Rozental, Alexander; Carlbring, Per

2013-11-12

Procrastination, to voluntarily delay an intended course of action despite expecting to be worse-off for the delay, is a persistent behavior pattern that can cause major psychological suffering. Approximately half of the student population and 15%-20% of the adult population are presumed having substantial difficulties due to chronic and recurrent procrastination in their everyday life. However, preconceptions and a lack of knowledge restrict the availability of adequate care. Cognitive behavior therapy (CBT) is often considered treatment of choice, although no clinical trials have previously been carried out. The aim of this study will be to test the effects of CBT for procrastination, and to investigate whether it can be delivered via the Internet. Participants will be recruited through advertisements in newspapers, other media, and the Internet. Only people residing in Sweden with access to the Internet and suffering from procrastination will be included in the study. A randomized controlled trial with a sample size of 150 participants divided into three groups will be utilized. The treatment group will consist of 50 participants receiving a 10-week CBT intervention with weekly therapist contact. A second treatment group with 50 participants receiving the same treatment, but without therapist contact, will also be employed. The intervention being used for the current study is derived from a self-help book for procrastination written by one of the authors (AR). It includes several CBT techniques commonly used for the treatment of procrastination (eg, behavioral activation, behavioral experiments, stimulus control, and psychoeducation on motivation and different work methods). A control group consisting of 50 participants on a wait-list control will be used to evaluate the effects of the CBT intervention. For ethical reasons, the participants in the control group will gain access to the same intervention following the 10-week treatment period, albeit without therapist contact. The current study is believed to result in three important findings. First, a CBT intervention is assumed to be beneficial for people suffering from problems caused by procrastination. Second, the degree of therapist contact will have a positive effect on treatment outcome as procrastination can be partially explained as a self-regulatory failure. Third, an Internet based CBT intervention is presumed to be an effective way to administer treatment for procrastination, which is considered highly important, as the availability of adequate care is limited. The current study is therefore believed to render significant knowledge on the treatment of procrastination, as well as providing support for the use of Internet based CBT for difficulties due to delayed tasks and commitments. To our knowledge, the current study is the first clinical trial to examine the effects of CBT for procrastination, and is assumed to render significant knowledge on the treatment of procrastination, as well as investigating whether it can be delivered via the Internet. ClinicalTrials.gov: NCT01842945; http://clinicaltrials.gov/show/NCT01842945 (Archived by WebCite at http://www.webcitation.org/6KSmaXewC).

Developing stepped care treatment for depression (STEPS): study protocol for a pilot randomised controlled trial.

PubMed

Hill, Jacqueline J; Kuyken, Willem; Richards, David A

2014-11-20

Stepped care is recommended and implemented as a means to organise depression treatment. Compared with alternative systems, it is assumed to achieve equivalent clinical effects and greater efficiency. However, no trials have examined these assumptions. A fully powered trial of stepped care compared with intensive psychological therapy is required but a number of methodological and procedural uncertainties associated with the conduct of a large trial need to be addressed first. STEPS (Developing stepped care treatment for depression) is a mixed methods study to address uncertainties associated with a large-scale evaluation of stepped care compared with high-intensity psychological therapy alone for the treatment of depression. We will conduct a pilot randomised controlled trial with an embedded process study. Quantitative trial data on recruitment, retention and the pathway of patients through treatment will be used to assess feasibility. Outcome data on the effects of stepped care compared with high-intensity therapy alone will inform a sample size calculation for a definitive trial. Qualitative interviews will be undertaken to explore what people think of our trial methods and procedures and the stepped care intervention. A minimum of 60 patients with Major Depressive Disorder will be recruited from an Improving Access to Psychological Therapies service and randomly allocated to receive stepped care or intensive psychological therapy alone. All treatments will be delivered at clinic facilities within the University of Exeter. Quantitative patient-related data on depressive symptoms, worry and anxiety and quality of life will be collected at baseline and 6 months. The pilot trial and interviews will be undertaken concurrently. Quantitative and qualitative data will be analysed separately and then integrated. The outcomes of this study will inform the design of a fully powered randomised controlled trial to evaluate the effectiveness and efficiency of stepped care. Qualitative data on stepped care will be of immediate interest to patients, clinicians, service managers, policy makers and guideline developers. A more informed understanding of the feasibility of a large trial will be obtained than would be possible from a purely quantitative (or qualitative) design. Current Controlled Trials ISRCTN66346646 registered on 2 July 2014.

Translational medicine in the field of ablative fractional laser (AFXL)-assisted drug delivery: A critical review from basics to current clinical status.

PubMed

Haedersdal, Merete; Erlendsson, Andrés M; Paasch, Uwe; Anderson, R Rox

2016-05-01

Ablative fractional lasers enhance uptake of topical therapeutics and the concept of fractional laser-assisted drug delivery has now been taken into clinical practice. We systematically reviewed preclinical data and clinical evidence for fractional lasers to enhance drug uptake and improve clinical efficacy. We searched PubMed and Embase databases; 34 articles met the inclusion criteria. Studies were categorized into experimental preclinical studies and clinical trials, the latter graded according to level of evidence. All preclinical trials (n = 16) documented enhanced topical drug uptake into skin after ablative fractional laser treatment. Clinical evidence encompassed 18 studies, of which 9 were randomized controlled trials and 2 were controlled trials, examining neoplastic lesions, photodamaged skin, scars, onychomycosis, and topical anesthetics. The highest level of evidence was reached for actinic keratoses treated with methylaminolevulinate for photodynamic therapy (level IB, 5 randomized controlled trials), substantiating superior and long-lasting efficacy versus conventional photodynamic therapy. No adverse events were reported, but ablative fractional laser-assisted drug delivery implies risks of systemic drug absorption, especially when performed over large skin areas. Fractional laser-assisted drug delivery is beneficial in enhancing preclinical and clinical outcomes for certain skin conditions. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

The effect of short-duration sprint interval exercise on plasma postprandial triacylglycerol levels in young men.

PubMed

Allen, Edward; Gray, Partick; Kollias-Pearson, Angeliki; Oag, Erlend; Pratt, Katrina; Henderson, Jennifer; Gray, Stuart Robert

2014-01-01

It is well established that regular exercise can reduce the risk of cardiovascular disease, although the most time-efficient exercise protocol to confer benefits has yet to be established. The aim of the current study was to determine the effects of short-duration sprint interval exercise on postprandial triacylglycerol. Fifteen healthy male participants completed two 2 day trials. On day 1, participants rested (control) or carried out twenty 6 s sprints, interspersed with 24 s recovery (sprint interval exercise--14 min for total exercise session). On day 2, participants consumed a high-fat meal for breakfast with blood samples collected at baseline, 2 h and 4 h. Gas exchange was also measured at these time points. On day 2 of control and sprint interval exercise trials, there were no differences (P < 0.05) between trials in plasma glucose, triacylglycerol, insulin or respiratory exchange ratio (RER). The area under the curve for plasma triacylglycerol was 7.67 ± 2.37 mmol · l(-1) x 4 h(-1) in the control trial and 7.26 ± 2.49 mmol · l(-1) x 4 h(-1) in the sprint interval exercise trial. Although the sprint exercise protocol employed had no significant effect on postprandial triacylglycerol, there was a clear variability in responses that warrants further investigation.

Impact of a social franchising program on uptake of oral rehydration solution plus zinc for childhood diarrhea in myanmar: a community-level randomized controlled trial.

PubMed

Aung, Tin; Montagu, Dominic; Su Su Khin, Hnin; Win, Zaw; San, Ang Kyaw; McFarland, Willi

2014-06-01

Diarrhea's impact on childhood morbidity can be reduced by administering oral rehydration solution (ORS) with zinc; challenges to wider use are changing health-seeking behavior and ensuring access. We conducted a randomized controlled trial to increase ORS plus zinc uptake in rural Myanmar. Village tracts, matched in 52 pairs, were randomized to standard ORS access vs. a social franchising program training community educators and supplying ORS plus zinc. Intervention and control communities were comparable on demographics, prevalence of diarrhea and previous use of ORS. One year after randomization, ORS plus zinc use was 13.7% in the most recent case of diarrhea in intervention households compared with 1.8% in control households (p < 0.001) (N = 3605). A significant increase in ORS plus zinc use was noted in the intervention (p = 0.044) but not in the control (p = 0.315) group. Social franchising increased optimal treatment of childhood diarrhea in rural Myanmar. Scale-up stands to reduce morbidity among children in similar settings. Current Controlled Trials ISRCTN73606238. © The Author [2014]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

B-cell-targeted therapies in systemic lupus erythematosus and ANCA-associated vasculitis: current progress.

PubMed

Md Yusof, Md Yuzaiful; Vital, Edward M J; Emery, Paul

2013-08-01

B cells play a central role in the pathogenesis of systemic lupus erythematosus and anti-neutrophil cytoplasmic antibody-associated vasculitis. There are various strategies for targeting B cells including depletion, inhibition of survival factors, activation and inhibition of co-stimulatory molecules. Controlled trials in systemic lupus erythematosus have shown positive results for belimumab, promising results for epratuzumab and negative results for rituximab. The failure of rituximab in controlled trials has been attributed to trial design, sample size and outcome measures rather than true inefficacy. In anti-neutrophil cytoplasmic antibody-associated vasculitis, rituximab is effective for remission induction and in relapsing disease. However, the optimal long-term re-treatment strategy remains to be determined. Over the next 5 years, evidence will be available regarding the clinical efficacy of these novel therapies, biomarkers and their long-term safety.

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

PubMed

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

2017-07-11

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

Impact of the ALMS and MAINTAIN trials on the management of lupus nephritis.

PubMed

Morris, Heather K; Canetta, Pietro A; Appel, Gerald B

2013-06-01

Current treatment of lupus nephritis consists of both induction and maintenance therapy, with the latter being designed to consolidate remissions and prevent relapses. Long-term maintenance treatment with intravenous cyclophosphamide was effective but associated with considerable toxicity. A small but well-designed controlled trial found that for post-induction maintenance therapy, both oral mycophenolate mofetil (MMF) and oral azathioprine were superior in efficacy and had reduced toxicity than a regimen of continued every third month intravenous cyclophosphamide. Although these oral agents were rapidly accepted and utilized as maintenance medications, their usage was based on scant evidence and there were no comparisons between the two. Recently, two relatively large, randomized, well-controlled, multicenter trials dealing with maintenance therapy for severe lupus nephritis have been completed. The Aspreva Lupus Management Study (ALMS) maintenance and MAINTAIN nephritis trials provide important information regarding the comparative efficacy and safety of MMF and azathioprine as maintenance therapies, as well as information on the effect of dosage and duration of treatment with these agents.

Heparin in acute ischemic stroke revisited.

PubMed

Chamorro, A

2008-10-01

The evidence gathered in clinical trials of low molecular weight heparins (LMWHs) or with unfractionated heparin (UH) given subcutaneously at low or medium doses to patients with acute stroke cannot be extrapolated to the insufficiently tested effects of intravenous, weight-adjusted UH. Recent small studies have provided encouraging results but are potentially confounded and deserve confirmation in larger randomized controlled trials. In accordance with the current understanding of the biology of acute ischemic stroke and the pharmacology of UH, the new randomized controlled trials on heparin should give appropriate credit to the importance of a short therapeutic window, adequate dose adjustment of the drug, intravenous administration, and close monitoring of biological effects. UH is an orphan drug and only an academic driven trial would be able to face such an enterprise. Meanwhile, recommendations against the value of "early" anticoagulation with full dose of weight adjusted UH in the setting of acute ischemic stroke are not based on direct evidence but on extrapolations.

Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) post-natal intervention: an update to the study protocol for a randomized controlled trial.

PubMed

Shih, Sophy T F; Davis-Lameloise, Nathalie; Janus, Edward D; Wildey, Carol; Versace, Vincent L; Hagger, Virginia; Asproloupos, Dino; O'Reilly, Sharleen L; Phillips, Paddy A; Ackland, Michael; Skinner, Timothy; Oats, Jeremy; Carter, Rob; Best, James D; Dunbar, James A

2014-06-30

The Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) is a randomized controlled trial (RCT) that aims to assess the effectiveness of a structured diabetes prevention intervention for women who had gestational diabetes. The original protocol was published in Trials (http://www.trialsjournal.com/content/14/1/339). This update reports on an additional exclusion criterion and change in first eligibility screening to provide greater clarity. The new exclusion criterion "surgical or medical intervention to treat obesity" has been added to the original protocol. The risks of developing diabetes will be affected by any medical or surgical intervention as its impact on obesity will alter the outcomes being assessed by MAGDA-DPP. The screening procedures have also been updated to reflect the current recruitment operation. The first eligibility screening is now taking place either during or after pregnancy, depending on recruitment strategy. Australian New Zealand Clinical Trials Registry ANZCTRN 12610000338066.

A multicentre non-blinded randomised controlled trial to assess the impact of regular early specialist symptom control treatment on quality of life in malignant mesothelioma (RESPECT-MESO): study protocol for a randomised controlled trial.

PubMed

Gunatilake, Samal; Brims, Fraser J H; Fogg, Carole; Lawrie, Iain; Maskell, Nick; Forbes, Karen; Rahman, Najib; Morris, Steve; Ogollah, Reuben; Gerry, Stephen; Peake, Mick; Darlison, Liz; Chauhan, Anoop J

2014-09-19

Malignant pleural mesothelioma is an incurable cancer caused by exposure to asbestos. The United Kingdom has the highest death rate from mesothelioma in the world and this figure is increasing. Median survival is 8 to 12 months, and most patients have symptoms at diagnosis. The fittest patients may be offered chemotherapy with palliative intent. For patients not fit for systemic anticancer treatment, best supportive care remains the mainstay of management. A study from the United States examining advanced lung cancer showed that early specialist palliative care input improved patient health related quality of life and depression symptoms 12 weeks after diagnosis. While mesothelioma and advanced lung cancer share many symptoms and have a poor prognosis, oncology and palliative care services in the United Kingdom, and many other countries, vary considerably compared to the United States. The aim of this trial is to assess whether regular early symptom control treatment provided by palliative care specialists can improve health related quality of life in patients newly diagnosed with mesothelioma. This multicentre study is an non-blinded, randomised controlled, parallel group trial. A total of 174 patients with a new diagnosis of malignant pleural mesothelioma will be minimised with a random element in a 1:1 ratio to receive either 4 weekly regular early specialist symptom control care, or standard care. The primary outcome is health related quality of life for patients at 12 weeks. Secondary outcomes include health related quality of life for patients at 24 weeks, carer health related quality of life at 12 and 24 weeks, patient and carer mood at 12 and 24 weeks, overall survival and analysis of healthcare utilisation and cost. Current practice in the United Kingdom is to involve specialist palliative care towards the final weeks or months of a life-limiting illness. This study aims to investigate whether early, regular specialist care input can result in significant health related quality of life gains for patients with mesothelioma and if this change in treatment model is cost-effective. The results will be widely applicable to many institutions and patients both in the United Kingdom and internationally. Current controlled trials ISRCTN18955704. Date ISRCTN assigned: 31 January 2014.

Insufficient evidence of benefit regarding mortality due to albumin substitution in HCC-free cirrhotic patients undergoing large volume paracentesis.

PubMed

Kütting, Fabian; Schubert, Jens; Franklin, Jeremy; Bowe, Andrea; Hoffmann, Vera; Demir, Muenevver; Pelc, Agnes; Nierhoff, Dirk; Töx, Ulrich; Steffen, Hans-Michael

2017-02-01

Current guidelines for clinical practice recommend the infusion of human albumin after large volume paracentesis. After inspecting the current evidence behind this recommendation, we decided to conduct a systematic review and meta-analysis in order to address the effect of albumin on mortality and morbidity in the context of large volume paracentesis. We performed a comprehensive search of large databases and abstract books of conference proceedings up to March 15th 2016 for randomized controlled trials, testing the infusion of human albumin against alternatives (vs no treatment, vs plasma expanders; vs vasoconstrictors) in HCC-free patients suffering from cirrhosis. We analyzed these trials with regard to mortality, changes in plasma renin activity (PRA), hyponatremia, renal impairment, recurrence of ascites with consequential re-admission into hospital and additional complications. We employed trial sequential analysis in order to calculate the number of patients required in controlled trials to be able to determine a statistically significant advantage of the administration of one agent over another with regard to mortality. We were able to include 21 trials totaling 1277 patients. While the administration of albumin prevents a rise in PRA as well as hyponatremia, no improvement in strong clinical endpoints such as mortality could be demonstrated. Trial sequential analysis showed that at least 1550 additional patients need to be recruited into RCTs and analyzed with regard to this question in order to detect or disprove a 25% mortality effect. There is insufficient evidence that the infusion of albumin after LVP significantly lowers mortality in HCC-free patients with advanced liver disease. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Evaluation of a standard provision versus an autonomy promotive exercise referral programme: rationale and study design

PubMed Central

Jolly, Kate; Duda, Joan L; Daley, Amanda; Eves, Frank F; Mutrie, Nanette; Ntoumanis, Nikos; Rouse, Peter C; Lodhia, Rekha; Williams, Geoffrey C

2009-01-01

Background The National Institute of Clinical Excellence in the UK has recommended that the effectiveness of ongoing exercise referral schemes to promote physical activity should be examined in research trials. Recent empirical evidence in health care and physical activity promotion contexts provides a foundation for testing the utility of a Self Determination Theory (SDT)-based exercise referral consultation. Methods/Design Design: An exploratory cluster randomised controlled trial comparing standard provision exercise on prescription with a Self Determination Theory-based (SDT) exercise on prescription intervention. Participants: 347 people referred to the Birmingham Exercise on Prescription scheme between November 2007 and July 2008. The 13 exercise on prescription sites in Birmingham were randomised to current practice (n = 7) or to the SDT-based intervention (n = 6). Outcomes measured at 3 and 6-months: Minutes of moderate or vigorous physical activity per week assessed using the 7-day Physical Activity Recall; physical health: blood pressure and weight; health status measured using the Dartmouth CO-OP charts; anxiety and depression measured by the Hospital Anxiety and Depression Scale and vitality measured by the subjective vitality score; motivation and processes of change: perceptions of autonomy support from the advisor, satisfaction of the needs for competence, autonomy, and relatedness via physical activity, and motivational regulations for exercise. Discussion This trial will determine whether an exercise referral programme based on Self Determination Theory increases physical activity and other health outcomes compared to a standard programme and will test the underlying SDT-based process model (perceived autonomy support, need satisfaction, motivation regulations, outcomes) via structural equation modelling. Trial registration The trial is registered as Current Controlled trials ISRCTN07682833. PMID:19505293

Hyperbaric oxygen therapy in the treatment of osteonecrosis of the femoral head: a review of the current literature.

PubMed

Uzun, Gunalp; Mutluoglu, Mesut; Ersen, Omer; Yildiz, Senol

2016-01-01

To review the current literature on the use of hyperbaric oxygen (HBO₂) therapy in the treatment of osteonecrosis of the femoral head (ONFH). We searched PubMed, Directory of Open Access Journals (DOAJ), EMBASE, Web of Science, Academic Search Complete, CINAHL and MEDLINE through April 2015. We hand-searched relevant textbooks, conference proceedings and the reference lists of review articles and clinical studies Randomized controlled trials (RCT) and observational studies (cohort study, case-control study, case series) that reported the outcome of patients who received HBO₂therapy for ONFH were included. Only English-language articles were included. Study quality was not used as an exclusion criterion. Two authors independently assessed trials for inclusion, extracted data and presented to other authors. Disagreements were resolved by consensus. We identified eight clinical studies; two randomized controlled trials (RCTs); one historically controlled study; and five case series. The majority of the studies were small-scale, heterogeneous and methodologically weak. In four of the studies HBO₂therapy was combined with other treatment modalities, making it impossible to draw firm conclusions on the specific effects of HBO₂therapy. Hip survivorship in studies wherein HBO₂therapy was used alone was 95.5% in Steinberg Stage I lesions, 89% in Steinberg Stage II lesions and 100% in Ficat Stage II lesions. There is a room for HBO₂therapy in the management ONFH. Further RCTs, however, are required to better elucidate the role of HBO₂therapy in the treatment of ONFH.

The treatment of systemic lupus proliferative nephritis.

PubMed

Punaro, Marilynn G

2013-11-01

Lupus nephritis is one of the most common and serious complications of systemic lupus erythematosus (SLE) in childhood affecting more than 80% of patients. Treatment of this complication has undergone significant evolution in recent years. A series of randomized controlled trials has clarified the role of a variety of immunomodulating regimens including some novel biologic medications. This review touches on the major trials that have influenced practice and shaped current thinking about the treatment of proliferative lupus glomerulonephritis.

Field assessment of a novel household-based water filtration device: a randomised, placebo-controlled trial in the Democratic Republic of Congo.

PubMed

Boisson, Sophie; Kiyombo, Mbela; Sthreshley, Larry; Tumba, Saturnin; Makambo, Jacques; Clasen, Thomas

2010-09-10

Household water treatment can improve the microbiological quality of drinking water and may prevent diarrheal diseases. However, current methods of treating water at home have certain shortcomings, and there is evidence of bias in the reported health impact of the intervention in open trial designs. We undertook a randomised, double-blinded, placebo-controlled trial among 240 households (1,144 persons) in rural Democratic Republic of Congo to assess the field performance, use and effectiveness of a novel filtration device in preventing diarrhea. Households were followed up monthly for 12 months. Filters and placebos were monitored for longevity and for microbiological performance by comparing thermotolerant coliform (TTC) levels in influent and effluent water samples. Mean longitudinal prevalence of diarrhea was estimated among participants of all ages. Compliance was assessed through self-reported use and presence of water in the top vessel of the device at the time of visit. Over the 12-month follow-up period, data were collected for 11,236 person-weeks of observation (81.8% total possible). After adjusting for clustering within the household, the longitudinal prevalence ratio of diarrhoea was 0.85 (95% confidence interval: 0.61-1.20). The filters achieved a 2.98 log reduction in TTC levels while, for reasons that are unclear, the placebos achieved a 1.05 log reduction (p<0.0001). After 8 months, 68% of intervention households met the study's definition of current users, though most (73% of adults and 95% of children) also reported drinking untreated water the previous day. The filter maintained a constant flow rate over time, though 12.4% of filters were damaged during the course of the study. While the filter was effective in improving water quality, our results provide little evidence that it was protective against diarrhea. The moderate reduction observed nevertheless supports the need for larger studies that measure impact against a neutral placebo. Current Controlled Trials ISRCTN03844341.

Online interventions for problem gamblers with and without co-occurring problem drinking: study protocol of a randomized controlled trial.

PubMed

Cunningham, John A; Hodgins, David C; Keough, Matthew; Hendershot, Christian S; Bennett, Kylie; Bennett, Anthony; Godinho, Alexandra

2018-05-25

The current randomized controlled trial seeks to evaluate whether providing access to an Internet intervention for problem drinking in addition to an Internet intervention for problem gambling is beneficial for participants with gambling problems who do or do not have co-occurring problem drinking. Potential participants will be recruited online via a comprehensive advertisement strategy, if they meet the criteria for problem gambling. As part of the baseline measures, problem drinking will also be assessed. Eligible participants (N = 280) who agree to partake in the study and to be followed up for 6 months will be randomized into one of two versions of an Internet intervention for gamblers: an intervention that targets only gambling issues (G-only) and one that combines a gambling intervention with an intervention for problem drinking (G + A). For problem gamblers who exhibit co-occurring problem drinking, it is predicted that participants who are provided access to the G + A intervention will demonstrate a significantly greater level of reduction in gambling outcomes at 6 months compared to those provided access to the G-only intervention. This trial will expand upon the current research on Internet interventions for addictions and inform the development of treatments for those with co-occurring problem drinking and gambling. ClinicalTrials.gov, NCT03323606 . Registered on 24 October 2017.

Design of a Randomized Placebo-Controlled Trial to Assess Dabigatran and Omeprazole in Patients with Myocardial Injury after Noncardiac Surgery (MANAGE).

PubMed

Duceppe, Emmanuelle; Yusuf, Salim; Tandon, Vikas; Rodseth, Reitze; Biccard, Bruce M; Xavier, Denis; Szczeklik, Wojciech; Meyhoff, Christian S; Franzosi, Maria Grazia; Vincent, Jessica; Srinathan, Sadeesh K; Parlow, Joel; Magloire, Patrick; Neary, John; Rao, Mangala; Chaudhry, Navneet K; Mayosi, Bongani; de Nadal, Miriam; Popova, Ekaterine; Villar, Juan Carlos; Botto, Fernando; Berwanger, Otavio; Guyatt, Gordon; Eikelboom, John W; Sessler, Daniel I; Kearon, Clive; Pettit, Shirley; Connolly, Stuart J; Sharma, Mukul; Bangdiwala, Shrikant I; Devereaux, P J

2018-03-01

Worldwide approximately 200 million adults undergo major surgery annually, of whom 8 million are estimated to suffer a myocardial injury after noncardiac surgery (MINS). There is currently no trial data informing the management of MINS. Antithrombotic agents such as direct oral anticoagulants might prevent major vascular complications in patients with MINS. The Management of Myocardial Injury After Noncardiac Surgery (MANAGE) trial is a large international blinded randomized controlled trial of dabigatran vs placebo in patients who suffered MINS. We used a partial factorial design to also determine the effect of omeprazole vs placebo in reducing upper gastrointestinal bleeding and complications. Both study drugs were initiated in eligible patients within 35 days of suffering MINS and continued for a maximum of 2 years. The primary outcome is a composite of major vascular complications for the dabigatran trial and a composite of upper gastrointestinal complications for the omeprazole trial. We present the rationale and design of the trial and baseline characteristics of enrolled patients. The trial randomized 1754 patients between January 2013 and July 2017. Patients' mean age was 69.9 years, 51.1% were male, 14.3% had a history of peripheral artery disease, 6.6% had a history of stroke or transient ischemic attack, 12.9% had a previous myocardial infarction, and 26.0% had diabetes. The diagnosis of MINS was on the basis of an isolated ischemic troponin elevation in 80.4% of participants. MANAGE is the first randomized controlled trial to evaluate a potential treatment of patients who suffered MINS. Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Randomized controlled trials in children's heart surgery in the 21st century: a systematic review.

PubMed

Drury, Nigel E; Patel, Akshay J; Oswald, Nicola K; Chong, Cher-Rin; Stickley, John; Barron, David J; Jones, Timothy J

2018-04-01

Randomized controlled trials are the gold standard for evaluating health care interventions, yet are uncommon in children's heart surgery. We conducted a systematic review of clinical trials in paediatric cardiac surgery to evaluate the scope and quality of the current international literature. We searched MEDLINE, CENTRAL and LILACS, and manually screened retrieved references and systematic reviews to identify all randomized controlled trials reporting the effect of any intervention on the conduct or outcomes of heart surgery in children published in any language since January 2000; secondary publications and those reporting inseparable adult data were excluded. Two reviewers independently screened studies for eligibility and extracted data; the Cochrane Risk of Bias tool was used to assess for potential biases. We identified 333 trials from 34 countries randomizing 23 902 children. Most were early phase (313, 94.0%), recruiting few patients (median 45, interquartile range 28-82), and only 11 (3.3%) directly evaluated a surgical intervention. One hundred and nine (32.7%) trials calculated a sample size, 52 (15.6%) reported a CONSORT diagram, 51 (15.3%) were publicly registered and 25 (7.5%) had a Data Monitoring Committee. The overall risk of bias was low in 22 (6.6%), high in 69 (20.7%) and unclear in 242 (72.7%). The recent literature in children's heart surgery contains few late-phase clinical trials. Most trials did not conform to the accepted standards of reporting, and the overall risk of bias was low in few studies. There is a need for high-quality, multicentre clinical trials to provide a robust evidence base for contemporary paediatric cardiac surgical practice.

Randomized controlled trials in children’s heart surgery in the 21st century: a systematic review

PubMed Central

Drury, Nigel E; Patel, Akshay J; Oswald, Nicola K; Chong, Cher-Rin; Stickley, John; Barron, David J; Jones, Timothy J

2018-01-01

Abstract OBJECTIVES Randomized controlled trials are the gold standard for evaluating health care interventions, yet are uncommon in children’s heart surgery. We conducted a systematic review of clinical trials in paediatric cardiac surgery to evaluate the scope and quality of the current international literature. METHODS We searched MEDLINE, CENTRAL and LILACS, and manually screened retrieved references and systematic reviews to identify all randomized controlled trials reporting the effect of any intervention on the conduct or outcomes of heart surgery in children published in any language since January 2000; secondary publications and those reporting inseparable adult data were excluded. Two reviewers independently screened studies for eligibility and extracted data; the Cochrane Risk of Bias tool was used to assess for potential biases. RESULTS We identified 333 trials from 34 countries randomizing 23 902 children. Most were early phase (313, 94.0%), recruiting few patients (median 45, interquartile range 28–82), and only 11 (3.3%) directly evaluated a surgical intervention. One hundred and nine (32.7%) trials calculated a sample size, 52 (15.6%) reported a CONSORT diagram, 51 (15.3%) were publicly registered and 25 (7.5%) had a Data Monitoring Committee. The overall risk of bias was low in 22 (6.6%), high in 69 (20.7%) and unclear in 242 (72.7%). CONCLUSIONS The recent literature in children’s heart surgery contains few late-phase clinical trials. Most trials did not conform to the accepted standards of reporting, and the overall risk of bias was low in few studies. There is a need for high-quality, multicentre clinical trials to provide a robust evidence base for contemporary paediatric cardiac surgical practice. PMID:29186478

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

PubMed

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

2015-07-01

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

The Hawthorne Effect: a randomised, controlled trial

PubMed Central

McCarney, Rob; Warner, James; Iliffe, Steve; van Haselen, Robbert; Griffin, Mark; Fisher, Peter

2007-01-01

Background The 'Hawthorne Effect' may be an important factor affecting the generalisability of clinical research to routine practice, but has been little studied. Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge, no attempt has been made to quantify them. Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia. Methods Participants in a dementia trial were randomised to intensive follow-up (with comprehensive assessment visits at baseline and two, four and six months post randomisation) or minimal follow-up (with an abbreviated assessment at baseline and a full assessment at six months). Our primary outcomes were cognitive functioning (ADAS-Cog) and participant and carer-rated quality of life (QOL-AD). Results We recruited 176 participants, mainly through general practices. The main analysis was based on Intention to treat (ITT), with available data. In the ANCOVA model with baseline score as a co-variate, follow-up group had a significant effect on outcome at six months on the ADAS-Cog score (n = 140; mean difference = -2.018; 95%CI -3.914, -0.121; p = 0.037 favouring the intensive follow-up group), and on participant-rated quality of life score (n = 142; mean difference = -1.382; 95%CI -2.642, -0.122; p = 0.032 favouring minimal follow-up group). There was no significant difference on carer quality of life. Conclusion We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia resulted in a better outcome than minimal follow-up, as measured by their cognitive functioning. Trial registration Current controlled trials: ISRCTN45577048 PMID:17608932

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

PubMed Central

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

2018-01-01

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

How effective are cognitive behavior therapies for major depression and anxiety disorders? A meta‐analytic update of the evidence

PubMed Central

Cuijpers, Pim; Cristea, Ioana A.; Karyotaki, Eirini; Reijnders, Mirjam; Huibers, Marcus J.H.

2016-01-01

We report the current best estimate of the effects of cognitive behavior therapy (CBT) in the treatment of major depression (MDD), generalized anxiety disorder (GAD), panic disorder (PAD) and social anxiety disorder (SAD), taking into account publication bias, the quality of trials, and the influence of waiting list control groups on the outcomes. In our meta‐analyses, we included randomized trials comparing CBT with a control condition (waiting list, care‐as‐usual or pill placebo) in the acute treatment of MDD, GAD, PAD or SAD, diagnosed on the basis of a structured interview. We found that the overall effects in the 144 included trials (184 comparisons) for all four disorders were large, ranging from g=0.75 for MDD to g=0.80 for GAD, g=0.81 for PAD, and g=0.88 for SAD. Publication bias mostly affected the outcomes of CBT in GAD (adjusted g=0.59) and MDD (adjusted g=0.65), but not those in PAD and SAD. Only 17.4% of the included trials were considered to be high‐quality, and this mostly affected the outcomes for PAD (g=0.61) and SAD (g=0.76). More than 80% of trials in anxiety disorders used waiting list control groups, and the few studies using other control groups pointed at much smaller effect sizes for CBT. We conclude that CBT is probably effective in the treatment of MDD, GAD, PAD and SAD; that the effects are large when the control condition is waiting list, but small to moderate when it is care‐as‐usual or pill placebo; and that, because of the small number of high‐quality trials, these effects are still uncertain and should be considered with caution. PMID:27717254

Tilt Table Therapies for Patients with Severe Disorders of Consciousness: A Randomized, Controlled Trial

PubMed Central

Krewer, Carmen; Luther, Marianne; Koenig, Eberhard; Müller, Friedemann

2015-01-01

One major aim of the neurological rehabilitation of patients with severe disorders of consciousness (DOC) is to enhance patients’ arousal and ability to communicate. Mobilization into a standing position by means of a tilt table has been shown to improve their arousal and awareness. However, due to the frequent occurrence of syncopes on a tilt table, it is easier to accomplish verticalization using a tilt table with an integrated stepping device. The objective of this randomized controlled clinical trial was to evaluate the effectiveness of a tilt table therapy with or without an integrated stepping device on the level of consciousness. A total of 50 participants in vegetative or minimally conscious states 4 weeks to 6 month after injury were treated with verticalization during this randomized controlled trial. Interventions involved ten 1-hour sessions of the specific treatment over a 3-week period. Blinded assessors made measurements before and after the intervention period, as well as after a 3-week follow-up period. The coma recovery scale-revised (CRS-R) showed an improvement by a median of 2 points for the group receiving tilt table with integrated stepping (Erigo). The rate of recovery of the group receiving the conventional tilt table therapy significantly increased by 5 points during treatment and by an additional 2 points during the 3-week follow-up period. Changes in spasticity did not significantly differ between the two intervention groups. Compared to the conventional tilt table, the tilt table with integrated stepping device failed to have any additional benefit for DOC patients. Verticalization itself seems to be beneficial though and should be administered to patients in DOC in early rehabilitation. Trial Registration: Current Controlled Trials Ltd (www.controlled-trials.com), identifier number ISRCTN72853718 PMID:26623651

Tilt Table Therapies for Patients with Severe Disorders of Consciousness: A Randomized, Controlled Trial.

PubMed

Krewer, Carmen; Luther, Marianne; Koenig, Eberhard; Müller, Friedemann

2015-01-01

One major aim of the neurological rehabilitation of patients with severe disorders of consciousness (DOC) is to enhance patients' arousal and ability to communicate. Mobilization into a standing position by means of a tilt table has been shown to improve their arousal and awareness. However, due to the frequent occurrence of syncopes on a tilt table, it is easier to accomplish verticalization using a tilt table with an integrated stepping device. The objective of this randomized controlled clinical trial was to evaluate the effectiveness of a tilt table therapy with or without an integrated stepping device on the level of consciousness. A total of 50 participants in vegetative or minimally conscious states 4 weeks to 6 month after injury were treated with verticalization during this randomized controlled trial. Interventions involved ten 1-hour sessions of the specific treatment over a 3-week period. Blinded assessors made measurements before and after the intervention period, as well as after a 3-week follow-up period. The coma recovery scale-revised (CRS-R) showed an improvement by a median of 2 points for the group receiving tilt table with integrated stepping (Erigo). The rate of recovery of the group receiving the conventional tilt table therapy significantly increased by 5 points during treatment and by an additional 2 points during the 3-week follow-up period. Changes in spasticity did not significantly differ between the two intervention groups. Compared to the conventional tilt table, the tilt table with integrated stepping device failed to have any additional benefit for DOC patients. Verticalization itself seems to be beneficial though and should be administered to patients in DOC in early rehabilitation. Trial Registration: Current Controlled Trials Ltd (www.controlled-trials.com), identifier number ISRCTN72853718.

Effectiveness of alcohol brief intervention delivered by community pharmacists: study protocol of a two-arm randomised controlled trial

PubMed Central

2013-01-01

Background There is strong evidence to support the effectiveness of Brief Intervention (BI) in reducing alcohol consumption in primary healthcare. Methods and design This study is a two-arm randomised controlled trial to determine the effectiveness of BI delivered by community pharmacists in their pharmacies. Eligible and consenting participants (aged 18 years or older) will be randomised in equal numbers to either a BI delivered by 17 community pharmacists or a non-intervention control condition. The intervention will be a brief motivational discussion to support a reduction in alcohol consumption and will take approximately 10 minutes to deliver. Participants randomised to the control arm will be given an alcohol information leaflet with no opportunity for discussion. Study pharmacists will be volunteers who respond to an invitation to participate, sent to all community pharmacists in the London borough of Hammersmith and Fulham. Participating pharmacists will receive 7 hours training on trial procedures and the delivery of BI. Pharmacy support staff will also receive training (4 hours) on how to approach and inform pharmacy customers about the study, with formal trial recruitment undertaken by the pharmacist in a consultation room. At three month follow up, alcohol consumption and related problems will be assessed with the Alcohol Use Disorders Identification Test (AUDIT) administered by telephone. Discussion The UK Department of Health’s stated aim is to involve community pharmacists in the delivery of BI to reduce alcohol harms. This will be the first RCT study to assess the effectiveness of BI delivered by community pharmacists. Given this policy context, it is pragmatic in design. Trial registration Current Controlled Trials ISRCTN95216873 PMID:23419053

Morita therapy for depression and anxiety (Morita Trial): study protocol for a pilot randomised controlled trial.

PubMed

Sugg, Holly Victoria Rose; Richards, David A; Frost, Julia

2016-03-24

Morita Therapy, a psychological therapy for common mental health problems, is in sharp contrast to established western psychotherapeutic approaches in teaching that undesired symptoms are natural features of human emotion rather than something to control or eliminate. The approach is widely practiced in Japan, but untested and little known in the UK. A clinical trial of Morita Therapy is required to establish the effectiveness of Morita Therapy for a UK population. However, a number of methodological, procedural and clinical uncertainties associated with such a trial first require addressing. The Morita Trial is a mixed methods study addressing the uncertainties associated with an evaluation of Morita Therapy compared with treatment as usual for depression and anxiety. We will undertake a pilot randomised controlled trial with embedded qualitative study. Sixty participants with major depressive disorder, with or without anxiety disorders, will be recruited predominantly from General Practice record searches and randomised to receive Morita Therapy plus treatment as usual or treatment as usual alone. Morita Therapy will be delivered by accredited psychological therapists. We will collect quantitative data on depressive symptoms, general anxiety, attitudes and quality of life at baseline and four month follow-up to inform future sample size calculations; and rates of recruitment, retention and treatment adherence to assess feasibility. We will undertake qualitative interviews in parallel with the trial, to explore people's views of Morita Therapy. We will conduct separate and integrated analyses on the quantitative and qualitative data. The outcomes of this study will prepare the ground for the design and conduct of a fully-powered evaluation of Morita Therapy plus treatment as usual versus treatment as usual alone, or inform a conclusion that such a trial is not feasible and/or appropriate. We will obtain a more comprehensive understanding of these issues than would be possible from either a quantitative or qualitative approach alone. Current Controlled Trials ISRCTN17544090 registered on 23 July 2015.

Ethics of clinical trials in Nigeria.

PubMed

Okonta, Patrick I

2014-05-01

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

Ethics of clinical trials in Nigeria

PubMed Central

Okonta, Patrick I.

2014-01-01

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

The feasibility and acceptability of conducting a trial of specialist medical care and the Lightning Process in children with chronic fatigue syndrome: feasibility randomized controlled trial (SMILE study)

PubMed Central

2013-01-01

Background Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is relatively common in children with limited evidence for treatment. The Phil Parker Lightning Process (LP) is a trademarked intervention, which >250 children use annually. There are no reported studies investigating the effectiveness or possible side effects of LP. Methods The trial population was drawn from the Bath and Bristol NHS specialist paediatric CFS or ME service. The study was designed as a pilot randomized trial with children (aged 12 to 18 years) comparing specialist medical care with specialist medical care plus the Lightning Process. Integrated qualitative methodology was used to explore the feasibility and acceptability of the recruitment, randomization and interventions. Results A total of 56 children were recruited from 156 eligible children (1 October 2010 to 16 June 2012). Recruitment, randomization and both interventions were feasible and acceptable. Participants suggested changes to improve feasibility and acceptability and we incorporated the following in the trial protocol: stopped collecting 6-week outcomes; introduced a second reminder letter; used phone calls to collect primary outcomes from nonresponders; informed participants about different approaches of each intervention and changed our recommendation for the primary outcome for the full study from school attendance to disability (SF-36 physical function subscale) and fatigue (Chalder Fatigue Scale). Conclusions Conducting randomized controlled trials (RCTs) to investigate an alternative treatment such as LP is feasible and acceptable for children with CFS or ME. Feasibility studies that incorporate qualitative methodology enable changes to be made to trial protocols to improve acceptability to participants. This is likely to improve recruitment rate and trial retention. Trial registration Feasibility study first randomization: 29 September 2010. Trial registration: Current Controlled Trials ISRCTN81456207 (31 July 2012). Full trial first randomization: 19 September 2012. PMID:24304689

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

PubMed Central

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

2015-01-01

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

Cumulative Evidence of Randomized Controlled and Observational Studies on Catheter-Related Infection Risk of Central Venous Catheter Insertion Site in ICU Patients: A Pairwise and Network Meta-Analysis.

PubMed

Arvaniti, Kostoula; Lathyris, Dimitrios; Blot, Stijn; Apostolidou-Kiouti, Fani; Koulenti, Despoina; Haidich, Anna-Bettina

2017-04-01

Selection of central venous catheter insertion site in ICU patients could help reduce catheter-related infections. Although subclavian was considered the most appropriate site, its preferential use in ICU patients is not generalized and questioned by contradicted meta-analysis results. In addition, conflicting data exist on alternative site selection whenever subclavian is contraindicated. To compare catheter-related bloodstream infection and colonization risk between the three sites (subclavian, internal jugular, and femoral) in adult ICU patients. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled trials, CINAHL, and ClinicalTrials.gov. Eligible studies were randomized controlled trials and observational ones. Extracted data were analyzed by pairwise and network meta-analysis. Twenty studies were included; 11 were observational, seven were randomized controlled trials for other outcomes, and two were randomized controlled trials for sites. We evaluated 18,554 central venous catheters: 9,331 from observational studies, 5,482 from randomized controlled trials for other outcomes, and 3,741 from randomized controlled trials for sites. Colonization risk was higher for internal jugular (relative risk, 2.25 [95% CI, 1.84-2.75]; I = 0%) and femoral (relative risk, 2.92 [95% CI, 2.11-4.04]; I = 24%), compared with subclavian. Catheter-related bloodstream infection risk was comparable for internal jugular and subclavian, higher for femoral than subclavian (relative risk, 2.44 [95% CI, 1.25-4.75]; I = 61%), and lower for internal jugular than femoral (relative risk, 0.55 [95% CI, 0.34-0.89]; I = 61%). When observational studies that did not control for baseline characteristics were excluded, catheter-related bloodstream infection risk was comparable between the sites. In ICU patients, internal jugular and subclavian may, similarly, decrease catheter-related bloodstream infection risk, when compared with femoral. Subclavian could be suggested as the most appropriate site, whenever colonization risk is considered and not, otherwise, contraindicated. Current evidence on catheter-related bloodstream infection femoral risk, compared with the other sites, is inconclusive.

Cerebellar transcranial direct current stimulation in patients with ataxia: A double-blind, randomized, sham-controlled study.

PubMed

Benussi, Alberto; Koch, Giacomo; Cotelli, Maria; Padovani, Alessandro; Borroni, Barbara

2015-10-01

Numerous studies have highlighted the possibility of modulating the excitability of cerebellar circuits using transcranial direct current stimulation. The present study investigated whether a single session of cerebellar anodal transcranial direct current stimulation could improve symptoms in patients with ataxia. Nineteen patients with ataxia underwent a clinical and functional evaluation pre- and post-double-blind, randomized, sham, or anodal transcranial direct current stimulation. There was a significant interaction between treatment and time on the Scale for the Assessment and Rating of Ataxia, on the International Cooperative Ataxia Rating Scale, on the 9-Hole Peg Test, and on the 8-Meter Walking Time (P < 0.001). At the end of the sessions, all performance scores were significantly different in the sham trial, compared to the intervention trial. A single session of anodal cerebellar transcranial direct current stimulation can transiently improve symptoms in patients with ataxia and might represent a promising tool for future rehabilitative approaches. © 2015 International Parkinson and Movement Disorder Society.

Short-term anomia training and electrical brain stimulation.

PubMed

Flöel, Agnes; Meinzer, Marcus; Kirstein, Robert; Nijhof, Sarah; Deppe, Michael; Knecht, Stefan; Breitenstein, Caterina

2011-07-01

Language training success in chronic aphasia remains only moderate. Electric brain stimulation may be a viable way to enhance treatment efficacy. In a randomized, double-blind, sham-controlled crossover trial, we assessed if anodal transcranial direct current stimulation compared to cathodal transcranial direct current stimulation and sham stimulation over the right temporo-parietal cortex would improve the success of short-term high-frequency anomia training. Twelve chronic poststroke aphasia patients were studied. Naming outcome was assessed after training and 2 weeks later. All training conditions led to a significant increase in naming ability, which was retained for at least 2 weeks after the end of the training. Application of anodal transcranial direct current stimulation significantly enhanced the overall training effect compared to sham stimulation. Baseline naming ability significantly predicted anodal transcranial direct current stimulation effects. Anodal transcranial direct current stimulation applied over the nonlanguage dominant hemisphere can enhance language training outcome in chronic aphasia. Clinical Trial Registration- URL: www.clinicaltrials.gov/. Unique identifier: NCT00822068.

Post-conflict slowing after incongruent stimuli: from general to conflict-specific.

PubMed

Rey-Mermet, Alodie; Meier, Beat

2017-05-01

Encountering a cognitive conflict not only slows current performance, but it can also affect subsequent performance, in particular when the conflict is induced with bivalent stimuli (i.e., stimuli with relevant features for two different tasks) or with incongruent trials (i.e., stimuli with relevant features for two response alternatives). The post-conflict slowing following bivalent stimuli, called "bivalency effect", affects all subsequent stimuli, irrespective of whether the subsequent stimuli share relevant features with the conflict stimuli. To date, it is unknown whether the conflict induced by incongruent stimuli results in a similar post-conflict slowing. To investigate this, we performed six experiments in which participants switched between two tasks. In one task, incongruent stimuli appeared occasionally; in the other task, stimuli shared no feature with the incongruent trials. The results showed an initial performance slowing that affected all tasks after incongruent trials. On further trials, however, the slowing only affected the task sharing features with the conflict stimuli. Therefore, the post-conflict slowing following incongruent stimuli is first general and then becomes conflict-specific across trials. These findings are discussed within current task switching and cognitive control accounts.

Household interventions for preventing domestic lead exposure in children.

PubMed

Yeoh, Berlinda; Woolfenden, Susan; Lanphear, Bruce; Ridley, Greta F; Livingstone, Nuala; Jorgensen, Emile

2014-12-15

Lead poisoning is associated with physical, cognitive and neurobehavioural impairment in children and trials have tested many household interventions to prevent lead exposure. This is an update of the original review by the same authors first published in 2008. To determine the effectiveness of household interventions in preventing or reducing lead exposure in children as measured by reductions in blood lead levels and/or improvements in cognitive development. We identified trials through electronic searches of CENTRAL (2012, Issue 1), MEDLINE (1948 to January Week 1 2012), EMBASE (1980 to Week 2 2012), CINAHL (1937 to January 2012), PsycINFO (1887 to January Week 2 2012), ERIC (1966 to January 2012), Sociological Abstracts (1952 to January 2012), Science Citation Index (1970 to 20 January 2012), ZETOC (20 January 2012), LILACS (20 January 2012), Dissertation Abstracts (late 1960s to January 2012), ClinicalTrials.gov (19 January 2012), Current Controlled Trials (19 January 2012), Australian New Zealand Clinical Trials Registry (19 January 2012) and the National Research Register Archive. We also contacted experts to find unpublished studies. Randomised and quasi-randomised controlled trials of household educational or environmental interventions to prevent lead exposure in children where at least one standardised outcome measure was reported. Two authors independently reviewed all eligible studies for inclusion, assessed risk of bias and extracted data. We contacted trialists to obtain missing information. We included 14 studies (involving 2656 children). All studies reported blood lead level outcomes and none reported on cognitive or neurobehavioural outcomes. We put studies into subgroups according to their intervention type. We performed meta-analysis of both continuous and dichotomous data for subgroups where appropriate. Educational interventions were not effective in reducing blood lead levels (continuous: mean difference (MD) 0.02, 95% confidence interval (CI) -0.09 to 0.12, I(2) = 0 (log transformed); dichotomous ≥ 10µg/dL (≥ 0.48 µmol/L): relative risk (RR) 1.02, 95% CI 0.79 to 1.30, I(2)=0; dichotomous ≥ 15µg/dL (≥ 0.72 µmol/L): RR 0.60, 95% CI 0.33 to 1.09, I(2) = 0). Meta-analysis for the dust control subgroup also found no evidence of effectiveness (continuous: MD -0.15, 95% CI -0.42 to 0.11, I(2) = 0.9 (log transformed); dichotomous ≥ 10µg/dL (≥ 0.48 µmol/L): RR 0.93, 95% CI 0.73 to 1.18, I(2) =0; dichotomous ≥ 15µg/dL (≥ 0.72 µmol/L): RR 0.86, 95% CI 0.35 to 2.07, I(2) = 0.56). When meta-analysis for the dust control subgroup was adjusted for clustering, no statistical significant benefit was incurred. The studies using soil abatement (removal and replacement) and combination intervention groups were not able to be meta-analysed due to substantial differences between studies. Based on current knowledge, household educational or dust control interventions are ineffective in reducing blood lead levels in children as a population health measure. There is currently insufficient evidence to draw conclusions about the effectiveness of soil abatement or combination interventions.Further trials are required to establish the most effective intervention for prevention of lead exposure. Key elements of these trials should include strategies to reduce multiple sources of lead exposure simultaneously using empirical dust clearance levels. It is also necessary for trials to be carried out in developing countries and in differing socioeconomic groups in developed countries.

Household interventions for preventing domestic lead exposure in children.

PubMed

Yeoh, Berlinda; Woolfenden, Susan; Lanphear, Bruce; Ridley, Greta F; Livingstone, Nuala

2012-04-18

Lead poisoning is associated with physical, cognitive and neurobehavioural impairment in children and trials have tested many household interventions to prevent lead exposure. This is an update of the original review by the same authors first published in 2008. To determine the effectiveness of household interventions in preventing or reducing lead exposure in children as measured by reductions in blood lead levels and/or improvements in cognitive development. We identified trials through electronic searches of CENTRAL (The Cochrane Library, 2010, Issue 2), MEDLINE (1948 to April Week 1 2012), EMBASE (1980 to 2012 Week 2), CINAHL (1937 to 20 Jan 2012), PsycINFO (1887 to Dec week 2 2011), ERIC (1966 to 17 Jan 2012), Sociological Abstracts (1952 to 20 January 2012), Science Citation Index (1970 to 20 Jan 2012), ZETOC (20 Jan 2012), LILACS (20 Jan 2012), Dissertation Abstracts (late 1960s to Jan 2012), ClinicalTrials.gov (20 Jan 2012), Current Controlled Trials (Jan 2012), Australian New Zealand Clinical Trials Registry (Jan 2012) and the National Research Register Archive. We also contacted experts to find unpublished studies. Randomised and quasi-randomised controlled trials of household educational or environmental interventions to prevent lead exposure in children where at least one standardised outcome measure was reported. Two authors independently reviewed all eligible studies for inclusion, assessed risk of bias and extracted data. We contacted trialists to obtain missing information. We included 14 studies (involving 2656 children). All studies reported blood lead level outcomes and none reported on cognitive or neurobehavioural outcomes. We put studies into subgroups according to their intervention type. We performed meta-analysis of both continuous and dichotomous data for subgroups where appropriate. Educational interventions were not effective in reducing blood lead levels (continuous: mean difference (MD) 0.02, 95% confidence interval (CI) -0.09 to 0.12, I(2) = 0 (log transformed); dichotomous ≥ 10µg/dL (≥ 0.48 µmol/L): relative risk (RR) 1.02, 95% CI 0.79 to 1.30, I(2)=0; dichotomous ≥ 15µg/dL (≥ 0.72 µmol/L): RR 0.60, 95% CI 0.33 to 1.09, I(2) = 0). Meta-analysis for the dust control subgroup also found no evidence of effectiveness (continuous: MD -0.15, 95% CI -0.42 to 0.11, I(2) = 0.9 (log transformed); dichotomous ≥ 10µg/dL (≥ 0.48 µmol/L): RR 0.93, 95% CI 0.73 to 1.18, I(2) =0; dichotomous ≥ 15µg/dL (≥ 0.72 µmol/L): RR 0.86, 95% CI 0.35 to 2.07, I(2) = 0.56). When meta-analysis for the dust control subgroup was adjusted for clustering, no statistical significant benefit was incurred. The studies using soil abatement (removal and replacement) and combination intervention groups were not able to be meta-analysed due to substantial differences between studies. Based on current knowledge, household educational or dust control interventions are ineffective in reducing blood lead levels in children as a population health measure. There is currently insufficient evidence to draw conclusions about the effectiveness of soil abatement or combination interventions.Further trials are required to establish the most effective intervention for prevention of lead exposure. Key elements of these trials should include strategies to reduce multiple sources of lead exposure simultaneously using empirical dust clearance levels. It is also necessary for trials to be carried out in developing countries and in differing socioeconomic groups in developed countries.

Limited accessibility to designs and results of Japanese large-scale clinical trials for cardiovascular diseases.

PubMed

Sawata, Hiroshi; Ueshima, Kenji; Tsutani, Kiichiro

2011-04-14

Clinical evidence is important for improving the treatment of patients by health care providers. In the study of cardiovascular diseases, large-scale clinical trials involving thousands of participants are required to evaluate the risks of cardiac events and/or death. The problems encountered in conducting the Japanese Acute Myocardial Infarction Prospective (JAMP) study highlighted the difficulties involved in obtaining the financial and infrastructural resources necessary for conducting large-scale clinical trials. The objectives of the current study were: 1) to clarify the current funding and infrastructural environment surrounding large-scale clinical trials in cardiovascular and metabolic diseases in Japan, and 2) to find ways to improve the environment surrounding clinical trials in Japan more generally. We examined clinical trials examining cardiovascular diseases that evaluated true endpoints and involved 300 or more participants using Pub-Med, Ichushi (by the Japan Medical Abstracts Society, a non-profit organization), websites of related medical societies, the University Hospital Medical Information Network (UMIN) Clinical Trials Registry, and clinicaltrials.gov at three points in time: 30 November, 2004, 25 February, 2007 and 25 July, 2009. We found a total of 152 trials that met our criteria for 'large-scale clinical trials' examining cardiovascular diseases in Japan. Of these, 72.4% were randomized controlled trials (RCTs). Of 152 trials, 9.2% of the trials examined more than 10,000 participants, and 42.8% examined between 1,000 and 10,000 participants. The number of large-scale clinical trials markedly increased from 2001 to 2004, but suddenly decreased in 2007, then began to increase again. Ischemic heart disease (39.5%) was the most common target disease. Most of the larger-scale trials were funded by private organizations such as pharmaceutical companies. The designs and results of 13 trials were not disclosed. To improve the quality of clinical trials, all sponsors should register trials and disclose the funding sources before the enrolment of participants, and publish their results after the completion of each study.

Neural differences in the processing of semantic relationships across cultures.

PubMed

Gutchess, Angela H; Hedden, Trey; Ketay, Sarah; Aron, Arthur; Gabrieli, John D E

2010-06-01

The current study employed functional MRI to investigate the contribution of domain-general (e.g. executive functions) and domain-specific (e.g. semantic knowledge) processes to differences in semantic judgments across cultures. Previous behavioral experiments have identified cross-cultural differences in categorization, with East Asians preferring strategies involving thematic or functional relationships (e.g. cow-grass) and Americans preferring categorical relationships (e.g. cow-chicken). East Asians and American participants underwent functional imaging while alternating between categorical or thematic strategies to sort triads of words, as well as matching words on control trials. Many similarities were observed. However, across both category and relationship trials compared to match (control) trials, East Asians activated a frontal-parietal network implicated in controlled executive processes, whereas Americans engaged regions of the temporal lobes and the cingulate, possibly in response to conflict in the semantic content of information. The results suggest that cultures differ in the strategies employed to resolve conflict between competing semantic judgments.

Differential Recruitment of Executive Control Regions during Phonological Competition in Monolinguals and Bilinguals

PubMed Central

Marian, Viorica; Chabal, Sarah; Bartolotti, James; Bradley, Kailyn; Hernandez, Arturo E.

2015-01-01

Behavioral research suggests that monolinguals and bilinguals differ in how they manage within-language phonological competition when listening to language. The current study explored whether bilingual experience might also change the neural resources recruited to control spoken-word competition. Seventeen Spanish-English bilinguals and eighteen English monolinguals completed an fMRI task in which they searched for a picture representing an aurally presented word (e.g., “candy”) from an array of four presented images. On competitor trials, one of the objects in the display shared initial phonological overlap with the target (e.g., candle). While both groups experienced competition and responded more slowly on competitor trials than on unrelated trials, fMRI data suggest that monolinguals, but not bilinguals, activated executive control regions (e.g., anterior cingulate, superior frontal gyrus) during within-language phonological competition. We conclude that differences in how monolinguals and bilinguals manage competition may result from bilinguals’ more efficient deployment of neural resources. PMID:25463821

Real-time, ultrasound-based control of a virtual hand by a trans-radial amputee.

PubMed

Baker, Clayton A; Akhlaghi, Nima; Rangwala, Huzefa; Kosecka, Jana; Sikdar, Siddhartha

2016-08-01

Advancements in multiarticulate upper-limb prosthetics have outpaced the development of intuitive, non-invasive control mechanisms for implementing them. Surface electromyography is currently the most popular non-invasive control method, but presents a number of drawbacks including poor deep-muscle specificity. Previous research established the viability of ultrasound imaging as an alternative means of decoding movement intent, and demonstrated the ability to distinguish between complex grasps in able-bodied subjects via imaging of the anterior forearm musculature. In order to translate this work to clinical viability, able-bodied testing is insufficient. Amputation-induced changes in muscular geometry, dynamics, and imaging characteristics are all likely to influence the effectiveness of our existing techniques. In this work, we conducted preliminary trials with a transradial amputee participant to assess these effects, and potentially elucidate necessary refinements to our approach. Two trials were performed, the first using a set of three motion types, and the second using four. After a brief training period in each trial, the participant was able to control a virtual prosthetic hand in real-time; attempted grasps were successfully classified with a rate of 77% in trial 1, and 71% in trial 2. While the results are sub-optimal compared to our previous able-bodied testing, they are a promising step forward. More importantly, the data collected during these trials can provide valuable information for refining our image processing methods, especially via comparison to previously acquired data from able-bodied individuals. Ultimately, further work with amputees is a necessity for translation towards clinical application.

The effectiveness of a Web-based personalized feedback and social norms alcohol intervention on United Kingdom university students: randomized controlled trial.

PubMed

Bewick, Bridgette M; West, Robert M; Barkham, Michael; Mulhern, Brendan; Marlow, Robert; Traviss, Gemma; Hill, Andrew J

2013-07-24

Alcohol consumption in the student population continues to be cause for concern. Building on the established evidence base for traditional brief interventions, interventions using the Internet as a mode of delivery are being developed. Published evidence of replication of initial findings and ongoing development and modification of Web-based personalized feedback interventions for student alcohol use is relatively rare. The current paper reports on the replication of the initial Unitcheck feasibility trial. To evaluate the effectiveness of Unitcheck, a Web-based intervention that provides instant personalized feedback on alcohol consumption. It was hypothesized that use of Unitcheck would be associated with a reduction in alcohol consumption. A randomized control trial with two arms (control=assessment only; intervention=fully automated personalized feedback delivered using a Web-based intervention). The intervention was available week 1 through to week 15. Students at a UK university who were completing a university-wide annual student union electronic survey were invited to participate in the current study. Participants (n=1618) were stratified by sex, age group, year of study, self-reported alcohol consumption, then randomly assigned to one of the two arms, and invited to participate in the current trial. Participants were not blind to allocation. In total, n=1478 (n=723 intervention, n=755 control) participants accepted the invitation. Of these, 70% were female, the age ranged from 17-50 years old, and 88% were white/white British. Data were collected electronically via two websites: one for each treatment arm. Participants completed assessments at weeks 1, 16, and 34. Assessment included CAGE, a 7-day retrospective drinking diary, and drinks consumed per drinking occasion. The regression model predicted a monitoring effect, with participants who completed assessments reducing alcohol consumption over the final week. Further reductions were predicted for those allocated to receive the intervention, and additional reductions were predicted as the number of visits to the intervention website increased. Unitcheck can reduce the amount of alcohol consumed, and the reduction can be sustained in the medium term (ie, 19 weeks after intervention was withdrawn). The findings suggest self-monitoring is an active ingredient to Web-based personalized feedback.

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

PubMed Central

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

2014-01-01

Background Facing frequent stigma and discrimination, many people with mental illness have to choose between secrecy and disclosure in different settings. Coming Out Proud (COP), a 3-week peer-led group intervention, offers support in this domain in order to reduce stigma’s negative impact. Aims To examine COP’s efficacy to reduce negative stigma-related outcomes and to promote adaptive coping styles (Current Controlled Trials number: ISRCTN43516734). Method In a pilot randomised controlled trial, 100 participants with mental illness were assigned to COP or a treatment-as-usual control condition. Outcomes included self-stigma, empowerment, stigma stress, secrecy and perceived benefits of disclosure. Results Intention-to-treat analyses found no effect of COP on self-stigma or empowerment, but positive effects on stigma stress, disclosure-related distress, secrecy and perceived benefits of disclosure. Some effects diminished during the 3-week follow-up period. Conclusions Coming Out Proud has immediate positive effects on disclosure- and stigma stress-related variables and may thus alleviate stigma’s negative impact. PMID:24434073

Tai Chi exercise in improving cardiorespiratory capacity.

PubMed

Thornton, Everard W

2008-01-01

To evaluate evidence relating to effects of Tai Chi on cardiovascular outcomes, with emphasis on randomised control designs. Studies reviewed in 2004 were re-examined, together with more recent controlled trials of Tai Chi relating to cardiovascular outcome. The analysis provided comment on problems associated with randomised control design, including sources of bias in such trials. With a single exception, data support reduction of baseline systolic/diastolic blood pressure (BP). While there may be positive bias in these studies, data are from diverse ethnic groups, different gender, age, and level of functional ability. There are no data relating to BP reactive change to subsequent stressors. Few studies consider potential mediating mechanisms through which Tai Chi may provide these benefits. Caution is advocated in using randomised controlled trials as the only effective type of study. Such designs are difficult to conduct and effective trials are more likely given a better understanding of the mediating mechanism(s) through which benefits may be derived. It is currently unclear how changes in BP are derived. Some data indicate a shift to increased vagal relative to sympathetic dominance and there may be other potential physiological mediators. No study has examined relationships between potential psychological gains such as self-efficacy and BP change, or individual differences in outcomes.

Hydrocortisone concentration influences time to clinically significant healing of acute inflammation of the ocular surface and adnexa - results from a double-blind randomized controlled trial.

PubMed

Sergiyenko, Nikolay; Sukhina, Ludmila; Bezdetko, Pavel; Kovalenko, Yuriy; Nikitin, Nikolai; Merzbacher, Matthias; Gross, Dorothea; Kohnen, Ralf

2014-05-10

The efficacy of topical ophthalmic corticosteroids depends upon small modifications in preparations, such as drug concentration.The aim of this study was to confirm that hydrocortisone acetate (HC-ac) ophthalmic ointments of 2.5% and 1% are more effective than a 0.5% eye ointment. In this randomized, double-blind, placebo-controlled, parallel-group clinical study, the change of signs and symptoms of acute inflammation of the ocular surface and adnexa was evaluated in 411 subjects. Median time to clinically relevant response as estimated by 50% reduction in clinical signs and symptoms (CSS) total score over the entire trial was similar for subjects treated with HC-ac 2.5% (73.5 h) and for subjects treated with HC-ac 1.0% (67.7 h) and was considerably and significantly longer for subjects treated with HC-ac 0.5% (111.8 h) [p < 0.001 for both dosages]. All trial medications were safe and well tolerated. Hydrocortisone acetate 2.5% and Hydrocortisone acetate 1% eye ointments are efficacious and safe treatments for acute inflammations of the ocular surface or adnexa, and showed significantly better efficacy than a control group treated with Hydrocortisone acetate 0.5% therapy. Current Controlled Trials ISRCTN15464650.

Immediate effect of couple relationship education on low-satisfaction couples: a randomized clinical trial plus an uncontrolled trial replication.

PubMed

Kim Halford, W; Pepping, Christopher A; Hilpert, Peter; Bodenmann, Guy; Wilson, Keithia L; Busby, Dean; Larson, Jeffry; Holman, Thomas

2015-05-01

Couple relationship education (RE) usually is conceived of as relationship enhancement for currently satisfied couples, with a goal of helping couples sustain satisfaction. However, RE also might be useful as a brief, accessible intervention for couples with low satisfaction. Two studies were conducted that tested whether couples with low relationship satisfaction show meaningful gains after RE. Study 1 was a three-condition randomized controlled trial in which 182 couples were randomly assigned to RELATE with Couple CARE (RCC), a flexible delivery education program for couples, or one of two control conditions. Couples with initially low satisfaction receiving RCC showed a moderate increase in relationship satisfaction (d=0.50) relative to the control. In contrast, couples initially high in satisfaction showed little change and there was no difference between RCC and the control conditions. Study 2 was an uncontrolled trial of the Couple Coping Enhancement Training (CCET) administered to 119 couples. Couples receiving CCET that had initially low satisfaction showed a moderate increase in satisfaction (g=.44), whereas initially highly satisfied couples showed no change. Brief relationship education can assist somewhat distressed couples to enhance satisfaction, and has potential as a cost-effective way of enhancing the reach of couple interventions. Copyright © 2015. Published by Elsevier Ltd.

Garlic intake lowers fasting blood glucose: meta-analysis of randomized controlled trials.

PubMed

Hou, Li-qiong; Liu, Yun-hui; Zhang, Yi-yi

2015-01-01

Garlic is a common spicy flavouring agent also used for certain therapeutic purposes. Garlic's effects on blood glucose have been the subject of many clinical and animal studies, however, studies reporting hypoglycemic effects of garlic in humans are conflicting. A comprehensive literature search was conducted to identify relevant trials of garlic or garlic extracts on markers of glycemic control [fasting blood glucose (FBG), postprandial glucose (PPG), glycosylated haemoglobin (HbA1c)]. A meta-analysis of the effect of garlic intake on human was done to assess garlic's effectiveness in lowering glucose levels. Two reviewers extracted data from each of the identified studies. Seven eligible randomized controlled trials with 513 subjects were identified. Pooled analyses showed that garlic intake results in a statistically significant lowering in FBG [SMD=-1.67; 95% CI (-2.80, -0.55), p=0.004]. Our pooled analyses did not include PPG control and HbA1c outcomes. Because only 1 study included in the meta-analysis reported PPG variables and only 2 studies reported HbA1c variables. In conclusion, the current meta-analysis showed that the administration of garlic resulted in a significant reduction in FBG concentrations. More trials are needed to investigate the effectiveness of garlic on HbA1c and PPG.

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.

Effects of a home-based physical rehabilitation program on physical disability after hip fracture: a randomized controlled trial.

PubMed

Edgren, Johanna; Salpakoski, Anu; Sihvonen, Sanna E; Portegijs, Erja; Kallinen, Mauri; Arkela, Marja; Jäntti, Pirkko; Vanhatalo, Jukka; Pekkonen, Mika; Rantanen, Taina; Heinonen, Ari; Sipilä, Sarianna

2015-04-01

Fewer than half of the patients with hip fracture will regain the prefracture level of physical functioning. This secondary analysis of a randomized controlled trial investigated the effects of a multicomponent home-based rehabilitation program (ProMo) on physical disability after hip fracture. Randomized, controlled, parallel-group trial. Rehabilitation in participants' homes; measurements in university-based laboratory and local hospital. Population-based clinical sample of community-dwelling people older than 60 years (n = 81) operated for hip fracture were randomized into intervention and control groups. The year-long intervention aimed at restoring mobility. It included evaluation and modification of environmental hazards, guidance for safe walking, pain management, home exercise, physical activity counseling, and standard care. Physical disability was assessed by a questionnaire at baseline, and 3, 6, and 12 months thereafter. Sum scores were computed for basic (ADLs) and instrumental activities of daily living (IADLs). A higher score indicated more difficulty. GEE models were constructed to analyze the effect of the intervention. In the intention-to-treat analysis, no intervention effect was observed for sum scores. For the single disability items, borderline significant positive effects were observed for preparing food and handling medication (interaction P = .061 and P = .061, respectively). In the per-protocol analysis, the mean differences between groups were -0.4 points (SE 0.5), -1.7 (0.7), and -1.2 (0.7) at 3, 6, and 12 months for ADLs and -1.0 (1.2), -3.2 (1.5), and -2.5 (1.4) for IADLs, correspondingly. The current analyses suggest that home-based rehabilitation may reduce disability among older people after hip fracture. The present results need to be confirmed in a study with larger sample size. Potentially a more task-oriented rehabilitation approach might gain more benefits. Current Controlled Trials (ISRCTN53680197). Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Medial Tibial Stress Syndrome: Evidence-Based Prevention

PubMed Central

Craig, Debbie I

2008-01-01

Reference: Thacker SB, Gilchrist J, Stroup DF, Kimsey CD. The prevention of shin splints in sports: a systematic review of literature. Med Sci Sports Exerc. 2002;34(1):32–40. Clinical Question: Among physically active individuals, which medial tibial stress syndrome (MTSS) prevention methods are most effective to decrease injury rates? Data Sources: Studies were identified by searching MEDLINE (1966–2000), Current Contents (1996–2000), Biomedical Collection (1993–1999), and Dissertation Abstracts. Reference lists of identified studies were searched manually until no further studies were identified. Experts in the field were contacted, including first authors of randomized controlled trials addressing prevention of MTSS. The Cochrane Collaboration (early stage of Cochrane Database of Systematic Reviews) was contacted. Study Selection: Inclusion criteria included randomized controlled trials or clinical trials comparing different MTSS prevention methods with control groups. Excluded were studies that did not provide primary research data or that addressed treatment and rehabilitation rather than prevention of incident MTSS. Data Extraction: A total of 199 citations were identified. Of these, 4 studies compared prevention methods for MTSS. Three reviewers independently scored the 4 studies. Reviewers were blinded to the authors' names and affiliations but not the results. Each study was evaluated independently for methodologic quality using a 100-point checklist. Final scores were averages of the 3 reviewers' scores. Main Results: Prevention methods studied were shock-absorbent insoles, foam heel pads, Achilles tendon stretching, footwear, and graduated running programs. No statistically significant results were noted for any of the prevention methods. Median quality scores ranged from 29 to 47, revealing flaws in design, control for bias, and statistical methods. Conclusions: No current evidence supports any single prevention method for MTSS. The most promising outcomes support the use of shock-absorbing insoles. Well-designed and controlled trials are critically needed to decrease the incidence of this common injury. PMID:18523568

Horizon 2020 in Diabetic Kidney Disease: The Clinical Trial Pipeline for Add-On Therapies on Top of Renin Angiotensin System Blockade

PubMed Central

Perez-Gomez, Maria Vanessa; Sanchez-Niño, Maria Dolores; Sanz, Ana Belen; Martín-Cleary, Catalina; Ruiz-Ortega, Marta; Egido, Jesus; Navarro-González, Juan F.; Ortiz, Alberto; Fernandez-Fernandez, Beatriz

2015-01-01

Diabetic kidney disease is the most frequent cause of end-stage renal disease. This implies failure of current therapeutic approaches based on renin-angiotensin system (RAS) blockade. Recent phase 3 clinical trials of paricalcitol in early diabetic kidney disease and bardoxolone methyl in advanced diabetic kidney disease failed to meet the primary endpoint or terminated on safety concerns, respectively. However, various novel strategies are undergoing phase 2 and 3 randomized controlled trials targeting inflammation, fibrosis and signaling pathways. Among agents currently undergoing trials that may modify the clinical practice on top of RAS blockade in a 5-year horizon, anti-inflammatory agents currently hold the most promise while anti-fibrotic agents have so far disappointed. Pentoxifylline, an anti-inflammatory agent already in clinical use, was recently reported to delay estimated glomerular filtration rate (eGFR) loss in chronic kidney disease (CKD) stage 3–4 diabetic kidney disease when associated with RAS blockade and promising phase 2 data are available for the pentoxifylline derivative CTP-499. Among agents targeting chemokines or chemokine receptors, the oral small molecule C-C chemokine receptor type 2 (CCR2) inhibitor CCX140 decreased albuminuria and eGFR loss in phase 2 trials. A dose-finding trial of the anti-IL-1β antibody gevokizumab in diabetic kidney disease will start in 2015. However, clinical development is most advanced for the endothelin receptor A blocker atrasentan, which is undergoing a phase 3 trial with a primary outcome of preserving eGFR. The potential for success of these approaches and other pipeline agents is discussed in detail. PMID:26239562

Accelerated partial breast irradiation: Past, present, and future

PubMed Central

Tann, Anne W; Hatch, Sandra S; Joyner, Melissa M; Wiederhold, Lee R; Swanson, Todd A

2016-01-01

Accelerated partial breast irradiation (APBI) focuses higher doses of radiation during a shorter interval to the lumpectomy cavity, in the setting of breast conserving therapy for early stage breast cancer. The utilization of APBI has increased in the past decade because of the shorter treatment schedule and a growing body of outcome data showing positive cosmetic outcomes and high local control rates in selected patients undergoing breast conserving therapy. Technological advances in various APBI modalities, including intracavitary and interstitial brachytherapy, intraoperative radiation therapy, and external beam radiation therapy, have made APBI more accessible in the community. Results of early APBI trials served as the basis for the current consensus guidelines, and multiple prospective randomized clinical trials are currently ongoing. The pending long term results of these trials will help us identify optimal candidates that can benefit from ABPI. Here we provide an overview of the clinical and cosmetic outcomes of various APBI techniques and review the current guidelines for selecting suitable breast cancer patients. We also discuss the impact of APBI on the economics of cancer care and patient reported quality of life. PMID:27777879

Narcolepsy: current treatment options and future approaches

PubMed Central

Billiard, Michel

2008-01-01

The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1) Two tendencies characterize the conventional treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine as the first-line treatment of excessive daytime sleepiness (EDS) and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafinil, but on no direct comparison of modafinil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2) The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3) A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy. PMID:18830438

[Cinnamon: not suitable for the treatment of diabetes mellitus].

PubMed

Kleefstra, N; Logtenberg, S J J; Houweling, S T; Verhoeven, S; Bilo, H J G

2007-12-22

To identify published studies evaluating the effects of cinnamon on glycaemic control. Literature search. The Medline database was searched using all possible combinations of the words and medical subject headings (MeSH) 'cinnamon', 'diabetes mellitus', 'HbA1C' and 'glucose'. All human or animal studies in which cinnamon was administered as intervention were included. Several animal studies and 5 randomized placebo-controlled trials in humans were found. Most of the animal studies described beneficial effects of cinnamon on glycaemic control. One placebo-controlled trial in patients with type 2 diabetes found that cinnamon intake was associated with favourable effects on fasting plasma glucose. None of the studies reported an improvement in HbA1C. A study in patients with type 1 diabetes found that cinnamon had no effect. Based on the currently available evidence, cinnamon should not be recommended for the improvement ofglycaemic control.

Psycho-education with problem solving (PEPS) therapy for adults with personality disorder: a pragmatic multi-site community-based randomised clinical trial.

PubMed

McMurran, Mary; Crawford, Mike J; Reilly, Joseph G; McCrone, Paul; Moran, Paul; Williams, Hywel; Adams, Clive E; Duggan, Conor; Delport, Juan; Whitham, Diane; Day, Florence

2011-08-24

Impairment in social functioning is a key component of personality disorder. Therefore psycho-education and problem solving (PEPS) therapy may benefit people with this disorder. Psycho-education aims to educate, build rapport, and motivate people for problem solving therapy. Problem solving therapy aims to help clients solve interpersonal problems positively and rationally, thereby improving social functioning and reducing distress. PEPS therapy has been evaluated with community adults with personality disorder in an exploratory trial. At the end of treatment, compared to a wait-list control group, those treated with PEPS therapy showed better social functioning, as measured by the Social Functioning Questionnaire (SFQ). A definitive evaluation is now being conducted to determine whether PEPS therapy is a clinically and cost-effective treatment for people with personality disorder This is a pragmatic, two-arm, multi-centre, parallel, randomised controlled clinical trial. The target population is community-dwelling adults with one or more personality disorder, as identified by the International Personality Disorder Examination (IPDE). Inclusion criteria are: Living in the community (including residential or supported care settings); presence of one or more personality disorder; aged 18 or over; proficiency in spoken English; capacity to provide informed consent. Exclusion criteria are: Primary diagnosis of a functional psychosis; insufficient degree of literacy, comprehension or attention to be able to engage in trial therapy and assessments; currently engaged in a specific programme of psychological treatment for personality disorder or likely to start such treatment during the trial period; currently enrolled in any other trial. Suitable participants are randomly allocated to PEPS therapy plus treatment as usual (TAU) or TAU only. We aim to recruit 340 men and women. The primary outcome is social functioning as measured by the SFQ. A reduction (i.e., an improvement) of 2 points or more on the SFQ at follow-up 72 weeks post-randomisation is our pre-specified index of clinically significant change. Secondary outcomes include a reduction of unscheduled service usage and an increase in scheduled service usage; improved quality of life; and a reduction in mental distress. PEPS therapy has potential as an economical, accessible, and acceptable intervention for people with personality disorder. The results from this randomised controlled trial will tell us if PEPS therapy is effective and cost-effective. If so, then it will be a useful treatment for inclusion in a broader menu of treatment options for this group of service users. International Standard Randomised Controlled Trial Number - ISRCTN70660936.

Clinical trials needed to evaluate compression therapy in breast cancer related lymphedema (BCRL). Proposals from an expert group.

PubMed

Partsch, H; Stout, N; Forner-Cordero, I; Flour, M; Moffatt, C; Szuba, A; Milic, D; Szolnoky, G; Brorson, H; Abel, M; Schuren, J; Schingale, F; Vignes, S; Piller, N; Döller, W

2010-10-01

A mainstay of lymphedema management involves the use of compression therapy. Compression therapy application is variable at different levels of disease severity. Evidence is scant to direct clinicians in best practice regarding compression therapy use. Further, compression clinical trials are fragmented and poorly extrapolable to the greater population. An ideal construct for conducting clinical trials in regards to compression therapy will promote parallel global initiatives based on a standard research agenda. The purpose of this article is to review current evidence in practice regarding compression therapy for BCRL management and based on this evidence, offer an expert consensus recommendation for a research agenda and prescriptive trials. Recommendations herein focus solely on compression interventions. This document represents the proceedings of a session organized by the International Compression Club (ICC) in June 2009 in Ponzano (Veneto, Italy). The purpose of the meeting was to enable a group of experts to discuss the existing evidence for compression treatment in breast cancer related lymphedema (BCRL) concentrating on areas where randomized controlled trials (RCTs) are lacking. The current body of research suggests efficacy of compression interventions in the treatment and management of lymphedema. However, studies to date have failed to adequately address various forms of compression therapy and their optimal application in BCRL. We offer recommendations for standardized compression research trials for prophylaxis of arm lymphedema and for the management of chronic BCRL. Suggestions are also made regarding; inclusion and exclusion criteria, measurement methodology and additional variables of interest for researchers to capture. This document should inform future research trials in compression therapy and serve as a guide to clinical researchers, industry researchers and lymphologists regarding the strengths, weaknesses and shortcomings of the current literature. By providing this construct for research trials, the authors aim to support evidence-based therapy interventions, promote a cohesive, standardized and informative body of literature to enhance clinical outcomes, improve the quality of future research trials, inform industry innovation and guide policy related to BCRL.

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

PubMed Central

2011-01-01

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

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

PubMed

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

2010-11-01

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

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

PubMed

Okereke, Olivia I; Singh, Ankura

2016-07-01

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

Evaluation of a standard provision versus an autonomy promotive exercise referral programme: rationale and study design.

PubMed

Jolly, Kate; Duda, Joan L; Daley, Amanda; Eves, Frank F; Mutrie, Nanette; Ntoumanis, Nikos; Rouse, Peter C; Lodhia, Rekha; Williams, Geoffrey C

2009-06-08

The National Institute of Clinical Excellence in the UK has recommended that the effectiveness of ongoing exercise referral schemes to promote physical activity should be examined in research trials. Recent empirical evidence in health care and physical activity promotion contexts provides a foundation for testing the utility of a Self Determination Theory (SDT)-based exercise referral consultation. An exploratory cluster randomised controlled trial comparing standard provision exercise on prescription with a Self Determination Theory-based (SDT) exercise on prescription intervention. 347 people referred to the Birmingham Exercise on Prescription scheme between November 2007 and July 2008. The 13 exercise on prescription sites in Birmingham were randomised to current practice (n = 7) or to the SDT-based intervention (n = 6).Outcomes measured at 3 and 6-months: Minutes of moderate or vigorous physical activity per week assessed using the 7-day Physical Activity Recall; physical health: blood pressure and weight; health status measured using the Dartmouth CO-OP charts; anxiety and depression measured by the Hospital Anxiety and Depression Scale and vitality measured by the subjective vitality score; motivation and processes of change: perceptions of autonomy support from the advisor, satisfaction of the needs for competence, autonomy, and relatedness via physical activity, and motivational regulations for exercise. This trial will determine whether an exercise referral programme based on Self Determination Theory increases physical activity and other health outcomes compared to a standard programme and will test the underlying SDT-based process model (perceived autonomy support, need satisfaction, motivation regulations, outcomes) via structural equation modelling. The trial is registered as Current Controlled trials ISRCTN07682833.

UK Dermatology Clinical Trials Network’s STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network’s STOP GAP Trial has been designed to address this lack of trial evidence. Methods The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and presence or absence of underlying systemic disease (for example, rheumatoid arthritis). Patients who require topical therapy are asked to enter a parallel observational study (case series). If topical therapy fails and systemic therapy is required, participants are then considered for inclusion in the randomised trial. Trial registration Current controlled trials: ISRCTN35898459. Eudract No.2008-008291-14. PMID:22540770

Exposure therapy changes dysfunctional evaluations of somatic symptoms in patients with hypochondriasis (health anxiety). A randomized controlled trial.

PubMed

Weck, Florian; Neng, Julia M B; Schwind, Julia; Höfling, Volkmar

2015-08-01

Dysfunctional evaluations of somatic symptoms are considered a central factor in maintaining hypochondriasis. The aim of the current study was to investigate whether exposure therapy (ET) without cognitive restructuring is sufficient to change dysfunctional evaluations of somatic symptoms. The current study was based on a randomized controlled trial and compared patients with hypochondriasis (N=73) receiving ET or cognitive therapy (CT) to a wait list (WL) control group. In both the ET and CT groups, dysfunctional symptom evaluations changed significantly compared with the WL group. No differences between the ET and CT groups emerged. The relationship between the treatment condition (active treatment vs. WL) and reductions in health anxiety was mediated by changes in somatic symptom evaluations only in a specific card sorting procedure. We conclude that addressing dysfunctional symptom evaluations is a necessary precondition for the effective treatment of hypochondriasis. However, the results indicate that ET and CT appear to change those processes to a similar degree. Copyright © 2015 Elsevier Ltd. All rights reserved.

Muscarinic agonists for the treatment of cognition in schizophrenia.

PubMed

Sellin, Angela K; Shad, Mujeeb; Tamminga, Carol

2008-11-01

It is widely accepted that cholinergic activity at muscarinic receptors is required to maintain cognitive functions, including learning and memory. Memory domains are especially impaired in schizophrenia, which may explain difficulties in psychosocial rehabilitation of individuals with this illness. However, little is known about the mechanism of this impairment. To understand our current knowledge, we reviewed the literature since 1990 via a PubMed search for the terms "muscarinic", "schizophrenia", "cognition", "memory", "learning", and "agonist" in combination. We found 89 basic science/laboratory studies, case reports/series, case-control studies, cross-sectional studies, standardized controlled animal trials, standardized controlled human trials, and reviews. Although further research is required to fully understand the neuropharmacology of the cholinergic system in cognitive function in schizophrenia, we have examined the data currently available. In general, these data suggest that agonist activity at acetylcholine muscarinic type 1 (M1) receptors would enhance memory and learning in schizophrenia. We present an overview of likely side effects of muscarinic agonists. We outline the anticholinergic activity of several available antipsychotics and review the available M1 muscarinic agonists.

Review of drug treatment of oral submucous fibrosis.

PubMed

Chole, Revant H; Gondivkar, Shailesh M; Gadbail, Amol R; Balsaraf, Swati; Chaudhary, Sudesh; Dhore, Snehal V; Ghonmode, Sumeet; Balwani, Satish; Mankar, Mugdha; Tiwari, Manish; Parikh, Rima V

2012-05-01

This study undertook a review of the literature on drug treatment of oral submucous fibrosis. An electronic search was carried out for articles published between January 1960 to November 2011. Studies with high level of evidence were included. The levels of evidence of the articles were classified after the guidelines of the Oxford Centre for Evidence-Based Medicine. The main outcome measures used were improvement in oral ulceration, burning sensation, blanching and trismus. Only 13 publications showed a high level of evidence (3 randomized controlled trials and 10 clinical trials/controlled clinical trials), with a total of 1157 patients. Drugs like steroids, hyaluronidase, human placenta extracts, chymotrypsin and collagenase, pentoxifylline, nylidrin hydrochloride, iron and multivitamin supplements including lycopene, have been used. Only systemic agents were associated with few adverse effects like gastritis, gastric irritation and peripheral flushing with pentoxifylline, and flushingly warm skin with nylidrin hydrochloride; all other side-effects were mild and mainly local. Few studies with high levels of evidence were found. The drug treatment that is currently available for oral submucous fibrosis is clearly inadequate. There is a need for high-quality randomized controlled trials with carefully selected and standardized outcome measures. Copyright © 2011 Elsevier Ltd. All rights reserved.

A pilot randomised controlled trial of community-led ANtipsychotic Drug REduction for Adults with Learning Disabilities.

PubMed Central

McNamara, Rachel; Randell, Elizabeth; Gillespie, David; Wood, Fiona; Felce, David; Romeo, Renee; Angel, Lianna; Espinasse, Aude; Hood, Kerry; Davies, Amy; Meek, Andrea; Addison, Katy; Jones, Glyn; Deslandes, Paul; Allen, David; Knapp, Martin; Thapar, Ajay; Kerr, Michael

2017-01-01

BACKGROUND Data suggest that approximately 50,000 adults with learning disabilities (LDs) in England and Wales are currently prescribed antipsychotic medication. Illness in this population is common, including significant rates of challenging behaviour and mental illness, but there is particular concern over the use of antipsychotics prescribed for reasons other than the treatment of psychosis. Control of challenging behaviour is the primary reason why such medications are prescribed despite the absence of good evidence for any therapeutic effect for this purpose. OBJECTIVES To assess the feasibility of recruitment and retention and to explore non-efficacy-based barriers to a blinded antipsychotic medication withdrawal programme for adults with LDs without psychosis compared with treatment as usual. A secondary objective was to compare trial arms regarding clinical outcomes. DESIGN A two-arm individually randomised double-blind placebo-controlled drug reduction trial. SETTING Recruitment was through community learning disability teams (CLDTs) in south Wales and south-west England. PARTICIPANTS Adults with LDs who are prescribed risperidone for treatment of challenging behaviour with no known current psychosis or previous recurrence of psychosis following prior drug reduction. INTERVENTION A double-blind drug reduction programme leading to full withdrawal within 6 months. Treatment in the intervention group was gradually reduced over a 6-month period and then maintained at the same level for a further 3 months, still under blind conditions. In the control group, the baseline level of medication was maintained throughout the 9-month period. The blind was broken at 9 months, following final data collection. MAIN OUTCOME MEASURES Feasibility outcomes were (1) the number and proportion of general practices/CLDTs that progressed from initial approach to recruitment of participants and (2) the number and proportion of recruited participants who progressed through the various stages of the study. Trial arms were also compared regarding clinical outcomes, the Modified Overt Aggression Scale, the Aberrant Behaviour Checklist, the Psychiatric Assessment Schedule for Adults with Developmental Disability checklist, the Antipsychotic Side-effect Checklist, the Dyskinesia Identification System Condensed User Scale, the Client Service Receipt Inventory, use of other interventions to manage challenging behaviour, use of as-required (pro re nata) medication and level of psychotropic medication use. RESULTS Of the 22 participants randomised (intervention, n = 11; control, n = 11), 13 (59%) achieved progression through all four stages of reduction. Follow-up data at 6 and 9 months were obtained for 17 participants (intervention, n = 10; and control, n = 7; 77% of those randomised). There were no clinically important changes in participants' levels of aggression or challenging behaviour at the end of the study. There were no expedited safety reports. Four adverse events and one serious adverse event were reported during the trial. LIMITATIONS Recruitment was challenging, which was largely a result of difficulty in identifying appropriate persons to consent and carer concerns regarding re-emergence of challenging behaviour. Reduced recruitment meant that the full trial became an exploratory pilot study. CONCLUSIONS The results indicate that drug reduction is possible and safe. However, concerns about taking part were probably exacerbated by limited availability of alternative (behavioural) interventions to manage behaviour; therefore, focused support and alternative interventions are required. The results of the qualitative study provide important insights into the experiences of people taking part in drug reduction studies that should influence future trial development. FUTURE WORK We recommend that further work focuses on support for practitioners, carers and patients in reducing antipsychotic medication. TRIAL REGISTRATION Current Controlled Trials ISRCTN38126962. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 47. See the NIHR Journals Library website for further project information. PMID:28857740

Effect of interferential current therapy on pain perception and disability level in subjects with chronic low back pain: a randomized controlled trial.

PubMed

Albornoz-Cabello, Manuel; Maya-Martín, Julián; Domínguez-Maldonado, Gabriel; Espejo-Antúnez, Luis; Heredia-Rizo, Alberto Marcos

2017-02-01

To assess the short-term efficacy of transregional interferential current therapy on pain perception and disability level in chronic non-specific low back pain. A randomized, single-blinded (the assessor collecting the outcome data was blinded), controlled trial. A private physiotherapy research clinic. A total of 64 individuals, 20 men and 44 women, mean (SD) age was 51 years (11.93), with low back pain of more than three months, with or without pain radiating to the lower extremities above the knee, were distributed into a control ( n = 20) or an experimental group ( n = 44). A 2:1 randomization ratio was used in favour of the latter. A transregional interferential current electrotherapy protocol was performed for participants in the experimental group, while the control group underwent a 'usual care' treatment (massage, mobilization and soft-tissue techniques). All subjects received up to 10 treatment sessions of 25 minutes over a two-week period, and completed the intervention and follow-up evaluations. Self-perceived pain was assessed with a Visual Analogue Scale. Secondary measure included the Oswestry Low Back Disability Index. Evaluations were collected at baseline and after the intervention protocol. Significant between-group differences were found for interferential current therapy on pain perception ( p = 0.032) and disability level ( p = 0.002). The observed differences in the between-group mean changes were of 11.34 mm (1.77/20.91) and 13.38 points (4.97/21.78), respectively. A two-week transregional interferential current treatment has shown significant short-term efficacy, when compared with a 'usual care' protocol, on self-perceived pain and functionality in subjects with chronic low back pain.

Trial application of reliability technology to emergency diesel generators at the Trojan Nuclear Power Plant

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

Wong, S.M.; Boccio, J.L.; Karimian, S.

1986-01-01

In this paper, a trial application of reliability technology to the emergency diesel generator system at the Trojan Nuclear Power Plant is presented. An approach for formulating a reliability program plan for this system is being developed. The trial application has shown that a reliability program process, using risk- and reliability-based techniques, can be interwoven into current plant operational activities to help in controlling, analyzing, and predicting faults that can challenge safety systems. With the cooperation of the utility, Portland General Electric Co., this reliability program can eventually be implemented at Trojan to track its effectiveness.

Alternatives to inpatient mental health care for children and young people

PubMed Central

Shepperd, Sasha; Doll, Helen; Gowers, Simon; James, Anthony; Fazel, Mina; Fitzpatrick, Ray; Pollock, Jon

2014-01-01

Background Current policy in the UK and elsewhere places emphasis on the provision of mental health services in the least restrictive setting, whilst also recognising that some children will require inpatient care. As a result, there are a range of mental health services to manage young people with serious mental health problems who are at risk of being admitted to an inpatient unit in community or outpatient settings. Objectives 1. To assess the effectiveness, acceptability and cost of mental health services that provide an alternative to inpatient care for children and young people. 2. To identify the range and prevalence of different models of service that seek to avoid inpatient care for children and young people. Search methods Our search included the Cochrane Effective Practice and Organisation of Care Group Specialised Register (2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, issue 4), MEDLINE (1966 to 2007), EMBASE (1982 to 2006), the British Nursing Index (1994 to 2006), RCN database (1985 to 1996), CINAHL (1982 to 2006) and PsycInfo (1972 to 2007). Selection criteria Randomised controlled trials of mental health services providing specialist care, beyond the scope of generic outpatient provision, as an alternative to inpatient mental health care, for children or adolescents aged from five to 18 years who have a serious mental health condition requiring specialist services beyond the capacity of generic outpatient provision. The control group received mental health services in an inpatient or equivalent setting. Data collection and analysis Two authors independently extracted data and assessed study quality. We grouped studies according to the intervention type but did not pool data because of differences in the interventions and measures of outcome. Where data were available we calculated confidence intervals (CIs) for differences between groups at follow up. We also calculated standardised mean differences (SMDs) and 95% CIs for each outcome in terms of mean change from baseline to follow up using the follow-up SDs. We calculated SMDs (taking into account the direction of change and the scoring of each instrument) so that negative SMDs indicate results that favour treatment and positive SMDs favour the control group. Main results We included seven randomised controlled trials (recruiting a total of 799 participants) evaluating four distinct models of care: multi-systemic therapy (MST) at home, specialist outpatient service, intensive home treatment and intensive home-based crisis intervention (‘Homebuilders’ model for crisis intervention). Young people receiving home-based MST experienced some improved functioning in terms of externalising symptoms and they spent fewer days out of school and out-of-home placement. At short term follow up the control group had a greater improvement in terms of adaptability and cohesion; this was not sustained at four months follow up. There were small, significant patient improvements reported in both groups in the trial evaluating the intensive home-based crisis intervention using the ‘Homebuilders’ model. No differences at follow up were reported in the two trials evaluating intensive home treatment, or in the trials evaluating specialist outpatient services. Authors’ conclusions The quality of the evidence base currently provides very little guidance for the development of services. If randomised controlled trials are not feasible then consideration should be given to alternative study designs, such as prospective systems of audit conducted across several centres, as this has the potential to improve the current level of evidence. These studies should include baseline measurement at admission along with demographic data, and outcomes measured using a few standardised robust instruments. PMID:19370634

Two parallel, pragmatic, UK multicentre, randomised controlled trials comparing surgical options for upper compartment (vault or uterine) pelvic organ prolapse (the VUE Study): study protocol for a randomised controlled trial.

PubMed

Glazener, Cathryn; Constable, Lynda; Hemming, Christine; Breeman, Suzanne; Elders, Andrew; Cooper, Kevin; Freeman, Robert; Smith, Anthony R B; Hagen, Suzanne; McDonald, Alison; McPherson, Gladys; Montgomery, Isobel; Kilonzo, Mary; Boyers, Dwayne; Goulao, Beatriz; Norrie, John

2016-09-08

One in three women who have a prolapse operation will go on to have another operation, though not necessarily in the same compartment. Surgery can result in greater impairment of quality of life than the original prolapse itself (such as the development of new-onset urinary incontinence, or prolapse at a different site). Anterior and posterior prolapse surgery is most common (90 % of operations), but around 43 % of women also have a uterine (34 %) or vault (9 %) procedure at the same time. There is not enough evidence from randomised controlled trials (RCTs) to guide management of vault or uterine prolapse. The Vault or Uterine prolapse surgery Evaluation (VUE) study aims to assess the surgical management of upper compartment pelvic organ prolapse (POP) in terms of clinical effectiveness, cost-effectiveness and adverse events. VUE is two parallel, pragmatic, UK multicentre, RCTs (Uterine Trial and Vault Trial). Eligible for inclusion are women with vault or uterine prolapse: requiring a surgical procedure, suitable for randomisation and willing to be randomised. Randomisation will be computer-allocated separately for each trial, minimised on: requiring concomitant anterior and/or posterior POP surgery or not, concomitant incontinence surgery or not, age (under 60 years or 60 years and older) and surgeon. Participants will be randomly assigned, with equal probability to intervention or control arms in either the Uterine Trial or the Vault Trial. Uterine Trial participants will receive either a vaginal hysterectomy or a uterine preservation procedure. Vault Trial participants will receive either a vaginal sacrospinous fixation or an abdominal sacrocolpopexy. Participants will be followed up by postal questionnaires (6 months post surgery and 12 months post randomisation) and also reviewed in clinic 12 months post surgery. The primary outcome is the participant-reported Pelvic Organ Prolapse Symptom Score (POP-SS) at 12 months post randomisation. Demonstrating the efficacy of vault and uterine prolapse surgeries is relevant not only to patients and clinicians but also to health care providers, both in the UK and globally. Current controlled trials ISRCTN86784244 (assigned 19 October 2012), and the first subject was randomly assigned on 1 May 2013.

Garlic for hypertension: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Xiong, X J; Wang, P Q; Li, S J; Li, X K; Zhang, Y Q; Wang, J

2015-03-15

In the past decade, garlic has become one of the most popular complementary therapies for blood pressure (BP) control used by hypertensive patients. Numerous clinical studies have focused on the BP-lowering effect of garlic, but results have been inconsistent. Overall, there is a dearth of information available to guide the clinical community on the efficacy of garlic in hypertensive patients. To systematically review the medical literature to investigate the current evidence of garlic for the treatment of hypertension. PubMed, the Cochrane Library and EMBASE were searched for appropriate articles from their respective inceptions until August 2014. Randomized, placebo-controlled trials comparing garlic vs. a placebo in patients with hypertension were considered. Papers were independently reviewed by two reviewers and were analyzed using Cochrane software Revman 5.2. A total of seven randomized, placebo-controlled trials were identified. Compared with the placebo, this meta-analysis revealed a significant lowering effect of garlic on both systolic BP (WMD: -6.71 mmHg; 95% CI: -12.44 to -0.99; P = 0.02) and diastolic BP (WMD: -4.79 mmHg; 95% CI: -6.60 to -2.99; P < 0.00001). No serious adverse events were reported in any of the trials. The present review suggests that garlic is an effective and safe approach for hypertension. However, more rigorously designed randomized controlled trials focusing on primary endpoints with long-term follow-up are still warranted before garlic can be recommended to treat hypertensive patients. Copyright © 2015 Elsevier GmbH. All rights reserved.

Partial Gland Ablation for Prostate Cancer: Report of a Food and Drug Administration, American Urological Association, and Society of Urologic Oncology Public Workshop.

PubMed

Jarow, Jonathan P; Ahmed, Hashim U; Choyke, Peter L; Taneja, Samir S; Scardino, Peter T

2016-02-01

To summarize the discussion that took place at a public workshop, co-sponsored by the U.S. Food and Drug Administration, the American Urological Association, and Society of Urologic Oncology reviewing the current state of the art for partial gland ablation (PGA) for the management of patients with prostate cancer. The purpose of this workshop was to discuss potential indications, current available evidence, and designs for future trials to provide the evidence needed by patients and providers to decide how and when to use PGA. A workshop evaluating PGA for prostate cancer was held in New Orleans, Louisiana, in May 2015. Invited experts representing all stakeholders and attendees discussed the regulatory development of medical products, technology available, potential indications, and designs of trials to evaluate this modality of therapy. The panel presented the current information on the technologies available to perform PGA, the potential indications, and results of prior consensus conferences. Use of magnetic resonance imaging for patient selection, guide therapy, and follow-up was discussed. Designs of trials to assess PGA outcomes were discussed. The general consensus was that currently available technologies are capable of selective ablation with reasonable accuracy, but that criteria for patient selection remain debatable, and long-term cancer control remains to be established in properly designed and well-performed prospective clinical trials. Concerns include the potential for excessive, unnecessary use in patients with low-risk cancer and, conversely, that current diagnostic techniques may underestimate the extent and aggressiveness of some cancers, leading to inadequate treatment. Published by Elsevier Inc.

Impact of improved recording of work-relatedness in primary care visits at occupational health services on sickness absences: study protocol for a randomised controlled trial.

PubMed

Atkins, Salla; Ojajärvi, Ulla; Talola, Nina; Viljamaa, Mervi; Nevalainen, Jaakko; Uitti, Jukka

2017-07-26

Employment protects and fosters health. Occupational health services, particularly in Finland, have a central role in protecting employee health and preventing work ability problems. However, primary care within occupational health services is currently underused in informing preventive activities. This study was designed to assess whether the recording of work ability problems and improvement of follow-up of work-related primary care visits can reduce sickness absences and work disability pensions after 1 year. A pragmatic trial will be conducted using patient electronic registers and registers of the central pensions agency in Finland. Twenty-two occupational health centres will be randomised to intervention and control groups. Intervention units will receive training to improve recording of work ability illnesses in the primary care setting and improved follow-up procedures. The intervention impact will be assessed through examining rates of sickness absence across intervention and control clinics as well as before and after the intervention. The trial will develop knowledge of the intervention potential of primary care for preventing work disability pensions and sickness absence. The use of routine patient registers and pensions registers to assess the outcomes of a randomised controlled trial will bring forward trial methodology, particularly when using register-based data. If successful, the intervention will improve the quality of occupational health care primary care and contribute to reducing work disability. ISRCTN Registry reference number ISRCTN45728263 . Registered on 18 April 2016.

Community involvement in dengue vector control: cluster randomised trial.

PubMed

Vanlerberghe, V; Toledo, M E; Rodríguez, M; Gómez, D; Baly, A; Benítez, J R; Van der Stuyft, P

2010-01-01

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

Intensified treatment with high dose rifampicin and levofloxacin compared to standard treatment for adult patients with tuberculous meningitis (TBM-IT): protocol for a randomized controlled trial.

PubMed

Heemskerk, Dorothee; Day, Jeremy; Chau, Tran Thi Hong; Dung, Nguyen Huy; Yen, Nguyen Thi Bich; Bang, Nguyen Duc; Merson, Laura; Olliaro, Piero; Pouplin, Thomas; Caws, Maxine; Wolbers, Marcel; Farrar, Jeremy

2011-02-02

Tuberculous meningitis is the most severe form of tuberculosis. Mortality for untreated tuberculous meningitis is 100%. Despite the introduction of antibiotic treatment for tuberculosis the mortality rate for tuberculous meningitis remains high; approximately 25% for HIV-negative and 67% for HIV positive patients with most deaths occurring within one month of starting therapy. The high mortality rate in tuberculous meningitis reflects the severity of the condition but also the poor antibacterial activity of current treatment regimes and relatively poor penetration of these drugs into the central nervous system. Improving the antitubercular activity in the central nervous system of current therapy may help improve outcomes. Increasing the dose of rifampicin, a key drug with known poor cerebrospinal fluid penetration may lead to higher drug levels at the site of infection and may improve survival. Of the second generation fluoroquinolones, levofloxacin may have the optimal pharmacological features including cerebrospinal fluid penetration, with a ratio of Area Under the Curve (AUC) in cerebrospinal fluid to AUC in plasma of >75% and strong bactericidal activity against Mycobacterium tuberculosis. We propose a randomized controlled trial to assess the efficacy of an intensified anti-tubercular treatment regimen in tuberculous meningitis patients, comparing current standard tuberculous meningitis treatment regimens with standard treatment intensified with high-dose rifampicin and additional levofloxacin. A randomized, double blind, placebo-controlled trial with two parallel arms, comparing standard Vietnamese national guideline treatment for tuberculous meningitis with standard treatment plus an increased dose of rifampicin (to 15 mg/kg/day total) and additional levofloxacin. The study will include 750 patients (375 per treatment group) including a minimum of 350 HIV-positive patients. The calculation assumes an overall mortality of 40% vs. 30% in the two arms, respectively (corresponding to a target hazard ratio of 0.7), a power of 80% and a two-sided significance level of 5%. Randomization ratio is 1:1. The primary endpoint is overall survival, i.e. time from randomization to death during a follow-up period of 9 months. Secondary endpoints are: neurological disability at 9 months, time to new neurological event or death, time to new or recurrent AIDS-defining illness or death (in HIV-positive patients only), severe adverse events, and rate of treatment interruption for adverse events. Currently very few options are available for the treatment of TBM and the mortality rate remains unacceptably high with severe disabilities seen in many of the survivors. This trial is based on the hypothesis that current anti-mycobacterial treatment schedules for TBM are not potent enough and that outcomes will be improved by increasing the CSF penetrating power of this regimen by optimising dosage and using additional drugs with better CSF penetration. International Standard Randomised Controlled Trial Number ISRCTN61649292.

Activity Increase Despite Arthritis (AIDA): design of a Phase II randomised controlled trial evaluating an active management booklet for hip and knee osteoarthritis [ISRCTN24554946].

PubMed

Williams, Nefyn H; Amoakwa, Elvis; Burton, Kim; Hendry, Maggie; Belcher, John; Lewis, Ruth; Hood, Kerenza; Jones, Jeremy; Bennett, Paul; Edwards, Rhiannon T; Neal, Richard D; Andrew, Glynne; Wilkinson, Clare

2009-09-04

Hip and knee osteoarthritis is a common cause of pain and disability, which can be improved by exercise interventions. However, regular exercise is uncommon in this group because the low physical activity level in the general population is probably reduced even further by pain related fear of movement. The best method of encouraging increased activity in this patient group is not known. A booklet has been developed for patients with hip or knee osteoarthritis. It focuses on changing disadvantageous beliefs and encouraging increased physical activity. This paper describes the design of a Phase II randomised controlled trial (RCT) to test the effectiveness of this new booklet for patients with hip and knee osteoarthritis in influencing illness and treatment beliefs, and to assess the feasibility of conducting a larger definitive RCT in terms of health status and exercise behaviour. A computerised search of four general medical practice patients' record databases will identify patients older than 50 years of age who have consulted with hip or knee pain in the previous twelve months. A random sample of 120 will be invited to participate in the RCT comparing the new booklet with a control booklet, and we expect 100 to return final questionnaires. This trial will assess the feasibility of recruitment and randomisation, the suitability of the control intervention and outcome measurement tools, and will provide an estimate of effect size. Outcomes will include beliefs about hip and knee pain, beliefs about exercise, fear avoidance, level of physical activity, health status and health service costs. They will be measured at baseline, one month and three months. We discuss the merits of testing effectiveness in a phase II trial, in terms of intermediate outcome measures, whilst testing the processes for a larger definitive trial. We also discuss the advantages and disadvantages of testing the psychometric properties of the primary outcome measures concurrently with the trial. Current Controlled Trials ISRCTN24554946.

The group-based social skills training SOSTA-FRA in children and adolescents with high functioning autism spectrum disorder - study protocol of the randomised, multi-centre controlled SOSTA - net trial

PubMed Central

2013-01-01

Background Group-based social skills training (SST) has repeatedly been recommended as treatment of choice in high-functioning autism spectrum disorder (HFASD). To date, no sufficiently powered randomised controlled trial has been performed to establish efficacy and safety of SST in children and adolescents with HFASD. In this randomised, multi-centre, controlled trial with 220 children and adolescents with HFASD it is hypothesized, that add-on group-based SST using the 12 weeks manualised SOSTA–FRA program will result in improved social responsiveness (measured by the parent rated social responsiveness scale, SRS) compared to treatment as usual (TAU). It is further expected, that parent and self reported anxiety and depressive symptoms will decline and pro-social behaviour will increase in the treatment group. A neurophysiological study in the Frankfurt HFASD subgroup will be performed pre- and post treatment to assess changes in neural function induced by SST versus TAU. Methods/design The SOSTA – net trial is designed as a prospective, randomised, multi-centre, controlled trial with two parallel groups. The primary outcome is change in SRS score directly after the intervention and at 3 months follow-up. Several secondary outcome measures are also obtained. The target sample consists of 220 individuals with ASD, included at the six study centres. Discussion This study is currently one of the largest trials on SST in children and adolescents with HFASD worldwide. Compared to recent randomised controlled studies, our study shows several advantages with regard to in- and exclusion criteria, study methods, and the therapeutic approach chosen, which can be easily implemented in non-university-based clinical settings. Trial registration ISRCTN94863788 – SOSTA – net: Group-based social skills training in children and adolescents with high functioning autism spectrum disorder. PMID:23289935

Interventions for oropharyngeal dysphagia in children with neurological impairment.

PubMed

Morgan, Angela T; Dodrill, Pamela; Ward, Elizabeth C

2012-10-17

Oropharyngeal dysphagia encompasses problems with the oral preparatory phase of swallowing (chewing and preparing the food), oral phase (moving the food or fluid posteriorly through the oral cavity with the tongue into the back of the throat) and pharyngeal phase (swallowing the food or fluid and moving it through the pharynx to the oesophagus). Populations of children with neurological impairment who commonly experience dysphagia include, but are not limited to, those with acquired brain impairment (for example, cerebral palsy, traumatic brain injury, stroke), genetic syndromes (for example, Down syndrome, Rett syndrome) and degenerative conditions (for example, myotonic dystrophy). To examine the effectiveness of interventions for oropharyngeal dysphagia in children with neurological impairment. We searched the following electronic databases in October 2011: CENTRAL 2011(3), MEDLINE (1948 to September Week 4 2011), EMBASE (1980 to 2011 Week 40)
, CINAHL (1937 to current)
, ERIC (1966 to current), PsycINFO (1806 to October Week 1 2011), Science Citation Index (1970 to 7 October 2011), Social Science Citation Index (1970 to 7 October 2011), Cochrane Database of Systematic Reviews, 2011(3), DARE 2011(3), Current Controlled Trials (ISRCTN Register) (15 October 2011), ClinicalTrials.gov (15 October 2011) and WHO ICTRP (15 October 2011). We searched for dissertations and theses using Networked Digital Library of Theses and Dissertations, Australasian Digital Theses Program and DART-Europe E-theses Portal (11 October 2011). Finally, additional references were also obtained from reference lists from articles. The review included randomised controlled trials and quasi-randomised controlled trials for children with oropharyngeal dysphagia and neurological impairment. All three review authors (AM, PD and EW) independently screened titles and abstracts for inclusion and discussed results. In cases of uncertainty over whether an abstract met inclusion criterion, review authors obtained the full-text article and independently evaluated each paper for inclusion. The data were categorised for comparisons depending on the nature of the control group (for example, oral sensorimotor treatment versus no treatment). Effectiveness of the oropharyngeal dysphagia intervention was assessed by considering primary outcomes of physiological functions of the oropharyngeal mechanism for swallowing (for example, lip seal maintenance), the presence of chest infection and pneumonia, and diet consistency a child is able to consume. Secondary outcomes were changes in growth, child's level of participation in the mealtime routine and the level of parent or carer stress associated with feeding. Three studies met the inclusion criteria for the review. Two studies were based on oral sensorimotor interventions for participants with cerebral palsy compared to standard care and a third study trialled lip strengthening exercises for children with myotonic dystrophy type 1 compared to no treatment (Sjogreen 2010). A meta-analysis combining results across the three studies was not possible because one of the studies had participants with a different condition, and the remaining two, although using oral sensorimotor treatments, used vastly different approaches with different intensities and durations. The decision not to combine these was in line with our protocol. In this review, we present the results from individual studies for four outcomes: physiological functions of the oropharyngeal mechanism for swallowing, the presence of chest infection and pneumonia, diet consistency, and changes in growth. However, it is not possible to reach definitive conclusions on the effectiveness of particular interventions for oropharyngeal dysphagia based on these studies. One study had a high risk of attrition bias owing to missing data, had statistically significant differences (in weight) across experimental and control groups at baseline, and did not describe other aspects of the trial sufficiently to enable assessment of other potential risks of bias. Another study was at high risk of detection bias as some outcomes were assessed by parents who knew whether their child was in the intervention or control group. The third study overall seemed to be at low risk of bias, but like the other two studies, suffered from a small sample size. The review demonstrates that there is currently insufficient high-quality evidence from randomised controlled trials or quasi-randomised controlled trials to provide conclusive results about the effectiveness of any particular type of oral-motor therapy for children with neurological impairment. There is an urgent need for larger-scale (appropriately statistically powered), randomised trials to evaluate the efficacy of interventions for oropharyngeal dysphagia.

Conflict adaptation in prefrontal cortex: now you see it, now you don't.

PubMed

Kim, Chobok; Johnson, Nathan F; Gold, Brian T

2014-01-01

Daily life requires people to monitor and resolve conflict arising from distracting information irrelevant to current goals. The highly influential conflict monitoring theory (CMT) holds that the anterior cingulate cortex (ACC) detects conflict and subsequently triggers the dorsolateral prefrontal cortex (DLPFC) to regulate that conflict. Multiple lines of evidence have provided support for CMT. For example, performance is faster on incongruent trials that follow other incongruent trials (iI), and is accompanied by reduced ACC and increased DLPFC activation (the conflict adaptation effect). In this fMRI study, we explored whether ACC-DLPFC conflict signaling can result in behavioral adjustments beyond on-line contexts. Participants completed a modified version of the Stroop conflict adaptation paradigm which tested for conflict adaptation effects on the current (N) trial associated with not only the immediately preceding (N - 1) trial, but also 2-back (N - 2) trials. Results demonstrated evidence for direct relationships between ACC activity on N - 2 trials and both N trial DLPFC activity and behavioral adjustment when intervening trials were congruent (i.e., icI). In contrast, when N - 1 trials were incongruent (i.e., iiI), ACC-DLPFC signaling failed and conflict adaptation was absent. These results provide new evidence demonstrating that the conflict monitor-controller maintains previously experienced conflict in the service of subsequent behavioral adjustment. However, the processing of multiple, temporally proximal conflict signals takes a toll on the working memory (WM) system, which appears to require resetting in order to adapt our behavior to frequently changing environmental demands. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sildenafil citrate for the management of antidepressant-associated erectile dysfunction.

PubMed

Nurnberg, H George; Hensley, Paula L

2003-01-01

Sexual side effects of serotonin reuptake inhibitors, such as antidepressant-associated erectile dysfunction, are common and negatively impact treatment compliance. Current management approaches have important limitations, and most lack clear and meaningful efficacy in double-blind, placebo-controlled trials. A MEDLINE search (English language, 1966-2003) was performed using the terms antidepressive agents, erectile dysfunction, and sildenafil. Emphasis was placed on studies that used specific sexual function measurements and were placebo controlled. Sildenafil citrate, a selective and competitive inhibitor of phosphodiesterase type 5, enhances the cyclic guanosine monophosphate-mediated relaxation of cavernosal smooth muscles in response to sexual stimulation, permitting vascular engorgement and penile erection. The efficacy and tolerability of sildenafil in the treatment of antidepressant-associated erectile dysfunction have been confirmed in double-blind, placebo-controlled trials.

THE ETHICS OF SHAM SURGERY IN PARKINSON'S DISEASE: BACK TO THE FUTURE?

PubMed Central

Swift, Teresa; Huxtable, Richard

2013-01-01

Despite intense academic debate in the recent past over the use of ‘sham surgery’ control groups in research, there has been a recent resurgence in their use in the field of neurodegenerative disease. Yet the primacy of ethical arguments in favour of sham surgery controls is not yet established. Preliminary empirical research shows an asymmetry between the views of neurosurgical researchers and patients on the subject, while different ethical guidelines and regulations support conflicting interpretations. Research ethics committees faced with a proposal involving sham surgery should be aware of its ethical complexities. An overview of recent and current placebo-controlled surgical trials in the field of Parkinson's Disease is provided here, followed by an analysis of the key ethical issues which such trials raise. PMID:22150772

Detecting and accounting for violations of the constancy assumption in non-inferiority clinical trials.

PubMed

Koopmeiners, Joseph S; Hobbs, Brian P

2018-05-01

Randomized, placebo-controlled clinical trials are the gold standard for evaluating a novel therapeutic agent. In some instances, it may not be considered ethical or desirable to complete a placebo-controlled clinical trial and, instead, the placebo is replaced by an active comparator with the objective of showing either superiority or non-inferiority to the active comparator. In a non-inferiority trial, the experimental treatment is considered non-inferior if it retains a pre-specified proportion of the effect of the active comparator as represented by the non-inferiority margin. A key assumption required for valid inference in the non-inferiority setting is the constancy assumption, which requires that the effect of the active comparator in the non-inferiority trial is consistent with the effect that was observed in previous trials. It has been shown that violations of the constancy assumption can result in a dramatic increase in the rate of incorrectly concluding non-inferiority in the presence of ineffective or even harmful treatment. In this paper, we illustrate how Bayesian hierarchical modeling can be used to facilitate multi-source smoothing of the data from the current trial with the data from historical studies, enabling direct probabilistic evaluation of the constancy assumption. We then show how this result can be used to adapt the non-inferiority margin when the constancy assumption is violated and present simulation results illustrating that our method controls the type-I error rate when the constancy assumption is violated, while retaining the power of the standard approach when the constancy assumption holds. We illustrate our adaptive procedure using a non-inferiority trial of raltegravir, an antiretroviral drug for the treatment of HIV.

Detecting and Accounting for Violations of the Constancy Assumption in Non-Inferiority Clinical Trials

PubMed Central

Koopmeiners, Joseph S.; Hobbs, Brian P.

2016-01-01

Randomized, placebo-controlled clinical trials are the gold standard for evaluating a novel therapeutic agent. In some instances, it may not be considered ethical or desirable to complete a placebo-controlled clinical trial and, instead, the placebo is replaced by an active comparator (AC) with the objective of showing either superiority or non-inferiority to the AC. In a non-inferiority trial, the experimental treatment is considered non-inferior if it retains a pre-specified proportion of the effect of the AC as represented by the non-inferiority margin. A key assumption required for valid inference in the non-inferiority setting is the constancy assumption, which requires that the effect of the AC in the non-inferiority trial is consistent with the effect that was observed in previous trials. It has been shown that violations of the constancy assumption can result in a dramatic increase in the rate of incorrectly concluding non-inferiority in the presence of ineffective or even harmful treatment. In this paper, we illustrate how Bayesian hierarchical modeling can be used to facilitate multi-source smoothing of the data from the current trial with the data from historical studies, enabling direct probabilistic evaluation of the constancy assumption. We then show how this result can be used to adapt the non-inferiority margin when the constancy assumption is violated and present simulation results illustrating that our method controls the type-I error rate when the constancy assumption is violated, while retaining the power of the standard approach when the constancy assumption holds. We illustrate our adaptive procedure using a non-inferiority trial of raltegravir, an antiretroviral drug for the treatment of HIV. PMID:27587591

A systematic review of randomised controlled trials in rheumatoid arthritis: the reporting and handling of missing data in composite outcomes.

PubMed

Ibrahim, Fowzia; Tom, Brian D M; Scott, David L; Prevost, Andrew Toby

2016-06-02

Most reported outcome measures in rheumatoid arthritis (RA) trials are composite, whose components comprise single measures that are combined into one outcome. The aims of this review were to assess the range of missing data rates in primary composite outcomes and to document the current practice for handling and reporting missing data in published RA trials compared to the Consolidated Standards of Reporting Trials (CONSORT) recommendations. A systematic search for randomised controlled trials was conducted for RA trials published between 2008 and 2013 in four rheumatology and four high impact general medical journals. A total of 51 trials with a composite primary outcome were identified, of which 38 (75 %) used the binary American College of Rheumatology responder index and 13 (25 %) used the Disease Activity Score for 28 joints (DAS28). Forty-four trials (86 %) reported on an intention-to-treat analysis population, while 7 trials (14 %) analysed according to a modified intention-to-treat population. Missing data rates for the primary composite outcome ranged from 2-53 % and were above 30 % in 9 trials, 20-30 % in 11 trials, 10-20 % in 18 trials and below 10 % in 13 trials. Thirty-eight trials (75 %) used non-responder imputation and 10 (20 %) used last observation carried forward to impute missing composite outcome data at the primary time point. The rate of dropout was on average 61 % times higher in the placebo group compared to the treatment group in the 34 placebo controlled trials (relative rate 1.61, 95 % CI: 1.29, 2.02). Thirty-seven trials (73 %) did not report the use of sensitivity analyses to assess the handling of missing data in the primary analysis as recommended by CONSORT guidelines. This review highlights an improvement in rheumatology trial practice since the revision of CONSORT guidelines, in terms of power calculation and participant's flow diagram. However, there is a need to improve the handling and reporting of missing composite outcome data and their components in RA trials. In particular, sensitivity analyses need to be more widely used in RA trials because imputation is widespread and generally uses single imputation methods, and in this area the missing data rates are commonly differentially higher in the placebo group.

Flexible trial design in practice - stopping arms for lack-of-benefit and adding research arms mid-trial in STAMPEDE: a multi-arm multi-stage randomized controlled trial

PubMed Central

2012-01-01

Background Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) is a randomized controlled trial that follows a novel multi-arm, multi-stage (MAMS) design. We describe methodological and practical issues arising with (1) stopping recruitment to research arms following a pre-planned intermediate analysis and (2) adding a new research arm during the trial. Methods STAMPEDE recruits men who have locally advanced or metastatic prostate cancer who are starting standard long-term hormone therapy. Originally there were five research and one control arms, each undergoing a pilot stage (focus: safety, feasibility), three intermediate ‘activity’ stages (focus: failure-free survival), and a final ‘efficacy’ stage (focus: overall survival). Lack-of-sufficient-activity guidelines support the pairwise interim comparisons of each research arm against the control arm; these pre-defined activity cut-off becomes increasingly stringent over the stages. Accrual of further patients continues to the control arm and to those research arms showing activity and an acceptable safety profile. The design facilitates adding new research arms should sufficiently interesting agents emerge. These new arms are compared only to contemporaneously recruited control arm patients using the same intermediate guidelines in a time-delayed manner. The addition of new research arms is subject to adequate recruitment rates to support the overall trial aims. Results (1) Stopping Existing Therapy: After the second intermediate activity analysis, recruitment was discontinued to two research arms for lack-of-sufficient activity. Detailed preparations meant that changes were implemented swiftly at 100 international centers and recruitment continued seamlessly into Activity Stage III with 3 remaining research arms and the control arm. Further regulatory and ethical approvals were not required because this was already included in the initial trial design. (2) Adding New Therapy: An application to add a new research arm was approved by the funder, (who also organized peer review), industrial partner and regulatory and ethical bodies. This was all done in advance of any decision to stop current therapies. Conclusions The STAMPEDE experience shows that recruitment to a MAMS trial and mid-flow changes its design are achievable with good planning. This benefits patients and the scientific community as research treatments are evaluated in a more efficient and cost-effective manner. Trial registration ISRCTN78818544, NCT00268476 First patient into trial: 17 October 2005 First patient into abiraterone comparison: 15 November 2011 PMID:22978443

Reappraising the phototoxicity of tretinoin: a report of four controlled clinical trials.

PubMed

Slade, Herbert B; Shroot, Braham; Feldman, Steven R; Cargill, D Innes; Stanfield, Joe

2009-06-01

Retinoids are photoreactive molecules found in skin and retinal tissue. The use of retinoids in pharmacologic doses, applied topically, raises the potential of phototoxicities. Recent review articles and current US drug labeling indicate that tretinoin is a phototoxin. In developing a new formulation of topical all-trans-retinoic acid (tretinoin), formal testing of dermal photoreactions was therefore undertaken. Four prospective, randomized, and controlled trials were carried out in healthy volunteers at two independent research facilities. Two trials examined phototoxicity following 24 h of drug exposure under occlusion (combined n=51), and two examined photoallergenicity following a 3-week, six dose induction phase (combined n=72) followed by challenge. No phototoxic or photoallergic reactions occurred with tretinoin 0.05% in a new gel formulation. The findings in these studies are consistent with previous studies of tretinoin in various formulations, and support the conclusion that tretinoin appears to be neither phototoxic nor photoallergenic in vivo.

Authoritative knowledge, evidence-based medicine, and behavioral pediatrics.

PubMed

Kennell, J H

1999-12-01

Evidence-based medicine is the conscientious and judicious use of current best knowledge in making decisions about the care of individual patients, often from well-designed, randomized, controlled trials. Authoritative medicine is the traditional approach to learning and practicing medicine, but no one authority has comprehensive scientific knowledge. Archie Cochrane proposed that every medical specialty should compile a list of all of the randomized, controlled trials within its field to be available for those who wish to know what treatments are effective. This was done first for obstetrics by a group collecting and critically analyzing all of the randomized trials and then indicating procedures every mother should have and those that no mother should have. Support during labor was used as an example. Similar groups are now active in almost all specialties, with information available on the Internet in the Cochrane Database of Systematic Reviews. Developmental-behavioral pediatrics should be part of this movement to evidence-based medicine.

Is there a role for e-cigarettes in smoking cessation?

PubMed

Leduc, Charlotte; Quoix, Elisabeth

2016-04-01

The use of e-cigarettes has dramatically increased over the past few years and their role in smoking cessation remains controversial. Several clinical studies have evaluated their efficacy in smoking cessation but most of them are prospective cohort studies. Only two randomized, controlled trials have compared e-cigarettes versus placebo or patches. A meta-analysis of these two randomized, controlled trials has been performed. Nicotine-containing e-cigarettes appear to help smokers unable to stop smoking altogether to reduce their cigarette consumption when compared with placebo. However, these results are rated 'low' by GRADE standards. Many cohort studies have been conducted, with contradictory results. For some, e-cigarettes could increase the risk of nonsmokers developing nicotine dependence and of current smokers maintaining their dependence. The debate remains open and more randomized trials are needed with long-term data about the efficacy and safety of e-cigarettes. © The Author(s), 2015.

UK Dermatology Clinical Trials Network's STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial.

PubMed

Craig, Fiona F; Thomas, Kim S; Mitchell, Eleanor J; Williams, Hywel C; Norrie, John; Mason, James M; Ormerod, Anthony D

2012-04-28

Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network's STOP GAP Trial has been designed to address this lack of trial evidence. The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and presence or absence of underlying systemic disease (for example, rheumatoid arthritis).Patients who require topical therapy are asked to enter a parallel observational study (case series). If topical therapy fails and systemic therapy is required, participants are then considered for inclusion in the randomised trial. Current controlled trials: ISRCTN35898459. Eudract No.2008-008291-14.

Effectiveness of a lifestyle exercise program for older people receiving a restorative home care service: study protocol for a pragmatic randomised controlled trial.

PubMed

Burton, Elissa; Lewin, Gill; Clemson, Lindy; Boldy, Duncan

2013-10-18

Restorative home care services help older people maximise their independence using a multi-dimensional approach. They usually include an exercise program designed to improve the older person's strength, balance and function. The types of programs currently offered require allocation of time during the day to complete specific exercises. This is not how the majority of home care clients prefer to be active and may be one of the reasons that few older people do the exercises regularly and continue the exercises post discharge.This paper describes the study protocol to test whether a Lifestyle Functional Exercise (LiFE) program: 1) is undertaken more often; 2) is more likely to be continued over the longer term; and, 3) will result in greater functional gains compared to a standard exercise program for older people receiving a restorative home care service. A pragmatic randomised controlled trial (RCT) design was employed with two study arms: LiFE program (intervention) and the current exercise program (control). Silver Chain, a health and community care organisation in Perth, Western Australia. One hundred and fifty restorative home care clients, aged 65 years and older. The primary outcome is a composite measure incorporating balance, strength and mobility. Other outcome measures include: physical functioning, falls efficacy, and levels of disability and functioning. If LiFE is more effective than the current exercise program, the evidence will be presented to the service management accompanied by the recommendation that it be adopted as the generic exercise program to be used within the restorative home care service. Australian and New Zealand Clinical Trials Registry ACTRN12611000788976.

Supported Telemonitoring and Glycemic Control in People with Type 2 Diabetes: The Telescot Diabetes Pragmatic Multicenter Randomized Controlled Trial

PubMed Central

Wild, Sarah H.; Hanley, Janet; Lewis, Stephanie C.; McKnight, John A.; Padfield, Paul L.; Parker, Richard A.; Pinnock, Hilary; Sheikh, Aziz; McKinstry, Brian

2016-01-01

Background Self-monitoring of blood glucose among people with type 2 diabetes not treated with insulin does not appear to be effective in improving glycemic control. We investigated whether health professional review of telemetrically transmitted self-monitored glucose results in improved glycemic control in people with poorly controlled type 2 diabetes. Methods and Findings We performed a randomized, parallel, investigator-blind controlled trial with centralized randomization in family practices in four regions of the United Kingdom among 321 people with type 2 diabetes and glycated hemoglobin (HbA1c) >58 mmol/mol. The supported telemonitoring intervention involved self-measurement and transmission to a secure website of twice-weekly morning and evening glucose for review by family practice clinicians who were not blinded to allocation group. The control group received usual care, with at least annual review and more frequent reviews for people with poor glycemic or blood pressure control. HbA1c assessed at 9 mo was the primary outcome. Intention-to-treat analyses were performed. 160 people were randomized to the intervention group and 161 to the usual care group between June 6, 2011, and July 19, 2013. HbA1c data at follow-up were available for 146 people in the intervention group and 139 people in the control group. The mean (SD) HbA1c at follow-up was 63.0 (15.5) mmol/mol in the intervention group and 67.8 (14.7) mmol/mol in the usual care group. For primary analysis, adjusted mean HbA1c was 5.60 mmol/mol / 0.51% lower (95% CI 2.38 to 8.81 mmol/mol/ 95% CI 0.22% to 0.81%, p = 0·0007). For secondary analyses, adjusted mean ambulatory systolic blood pressure was 3.06 mmHg lower (95% CI 0.56–5.56 mmHg, p = 0.017) and mean ambulatory diastolic blood pressure was 2.17 mmHg lower (95% CI 0.62–3.72, p = 0.006) among people in the intervention group when compared with usual care after adjustment for baseline differences and minimization strata. No significant differences were identified between groups in weight, treatment pattern, adherence to medication, or quality of life in secondary analyses. There were few adverse events and these were equally distributed between the intervention and control groups. In secondary analysis, there was a greater number of telephone calls between practice nurses and patients in the intervention compared with control group (rate ratio 7.50 (95% CI 4.45–12.65, p < 0.0001) but no other significant differences between groups in use of health services were identified between groups. Key limitations include potential lack of representativeness of trial participants, inability to blind participants and health professionals, and uncertainty about the mechanism, the duration of the effect, and the optimal length of the intervention. Conclusions Supported telemonitoring resulted in clinically important improvements in control of glycaemia in patients with type 2 diabetes in family practice. Current Controlled Trials, registration number ISRCTN71674628. Trial Registration Current Controlled Trials ISRCTN 71674628 PMID:27458809

Psychosocial consequences in the Danish randomised controlled lung cancer screening trial (DLCST).

PubMed

Rasmussen, Jakob F; Siersma, V; Pedersen, J H; Brodersen, J

2015-01-01

To measure the psychosocial consequences in the Danish lung cancer screening trial (DLCST) and compare those between the computed tomography (CT) group and the control group. This study was a single centre randomised controlled trial with five annual screening rounds. Healthy current or former heavy smokers aged 50-70 years (men and women) were randomised 1:1 to a CT group and a control group. Heavy smokers were defined by having smoked ≥20 pack years and former smokers by being abstinent ≤10 years. Both groups were invited annually to the screening clinic to complete the validated lung-cancer-specific questionnaire consequences of screening lung cancer (COS-LC). The CT group was also offered a low dose CT scan of the lungs. The COS-LC measures nine scales with psychosocial properties: Anxiety, Behaviour, Dejection, Negative impact on sleep, Self-blame, Focus on Airway Symptoms, Stigmatisation, Introvert, and Harm of Smoking. 4104 participants were randomised to the DLCST and the COS-LC completion rates for the CT group and the control group were 95.5% and 73.6%, respectively. There was a significant increase in negative psychosocial consequences from baseline through rounds 2-5 for both the CT group and the control group (mean increase >0, p<.0001 for 3 of 4 possible scales). During rounds 2-5 the control group experienced significantly more negative psychosocial consequences in seven of nine scales compared with the CT group (mean Δ score >0 and p<.033). Lung cancer CT-screening trials induced more negative psychosocial reactions in both the CT group and the control group compared with the baseline psychosocial profile. The CT group experienced less negative psychosocial consequences compared with the control group, which might be explained by reassurance among those with normal screening results. ClinicalTrials.gov: NCT00496977. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Expert Opinion Is Necessary: Delphi Panel Methodology Facilitates a Scientific Approach to Consensus.

PubMed

Hohmann, Erik; Brand, Jefferson C; Rossi, Michael J; Lubowitz, James H

2018-02-01

Our current trend and focus on evidence-based medicine is biased in favor of randomized controlled trials, which are ranked highest in the hierarchy of evidence while devaluing expert opinion, which is ranked lowest in the hierarchy. However, randomized controlled trials have weaknesses as well as strengths, and no research method is flawless. Moreover, stringent application of scientific research techniques, such as the Delphi Panel methodology, allows survey of experts in a high quality and scientific manner. Level V evidence (expert opinion) remains a necessary component in the armamentarium used to determine the answer to a clinical question. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

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

PubMed

Derosa, Giuseppe; Maffioli, Pamela

2012-06-01

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

Development and Evaluation of a Psychosocial Intervention for Children and Teenagers Experiencing Diabetes (DEPICTED): a protocol for a cluster randomised controlled trial of the effectiveness of a communication skills training programme for healthcare professionals working with young people with type 1 diabetes

PubMed Central

2010-01-01

Background Diabetes is the third most common chronic condition in childhood and poor glycaemic control leads to serious short-term and life-limiting long-term complications. In addition to optimal medical management, it is widely recognised that psychosocial and educational factors play a key role in improving outcomes for young people with diabetes. Recent systematic reviews of psycho-educational interventions recognise the need for new methods to be developed in consultation with key stakeholders including patients, their families and the multidisciplinary diabetes healthcare team. Methods/design Following a development phase involving key stakeholders, a psychosocial intervention for use by paediatric diabetes staff and not requiring input from trained psychologists has been developed, incorporating a communication skills training programme for health professionals and a shared agenda-setting tool. The effectiveness of the intervention will be evaluated in a cluster-randomised controlled trial (RCT). The primary outcome, to be measured in children aged 4-15 years diagnosed with type 1 diabetes for at least one year, is the effect on glycaemic control (HbA1c) during the year after training of the healthcare team is completed. Secondary outcomes include quality of life for patients and carers and cost-effectiveness. Patient and carer preferences for service delivery will also be assessed. Twenty-six paediatric diabetes teams are participating in the trial, recruiting a total of 700 patients for evaluation of outcome measures. Half the participating teams will be randomised to receive the intervention at the beginning of the trial and remaining centres offered the training package at the end of the one year trial period. Discussion The primary aim of the trial is to determine whether a communication skills training intervention for specialist paediatric diabetes teams will improve clinical and psychological outcomes for young people with type 1 diabetes. Previous research indicates the effectiveness of specialist psychological interventions in achieving sustained improvements in glycaemic control. This trial will evaluate an intervention which does not require the involvement of trained psychologists, maximising the potential feasibility of delivery in a wider NHS context. Trial registration Current Controlled Trials ISRCTN61568050. PMID:20144218

Beyond the Randomized Controlled Trial: A Review of Alternatives in mHealth Clinical Trial Methods

PubMed Central

Wiljer, David; Cafazzo, Joseph A

2016-01-01

Background Randomized controlled trials (RCTs) have long been considered the primary research study design capable of eliciting causal relationships between health interventions and consequent outcomes. However, with a prolonged duration from recruitment to publication, high-cost trial implementation, and a rigid trial protocol, RCTs are perceived as an impractical evaluation methodology for most mHealth apps. Objective Given the recent development of alternative evaluation methodologies and tools to automate mHealth research, we sought to determine the breadth of these methods and the extent that they were being used in clinical trials. Methods We conducted a review of the ClinicalTrials.gov registry to identify and examine current clinical trials involving mHealth apps and retrieved relevant trials registered between November 2014 and November 2015. Results Of the 137 trials identified, 71 were found to meet inclusion criteria. The majority used a randomized controlled trial design (80%, 57/71). Study designs included 36 two-group pretest-posttest control group comparisons (51%, 36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71), and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a qualitative component to their methodology (24%, 17/71). Complete trial data collection required 20 months on average to complete (mean 21, SD 12). For trials with a total duration of 2 years or more (31%, 22/71), the average time from recruitment to complete data collection (mean 35 months, SD 10) was 2 years longer than the average time required to collect primary data (mean 11, SD 8). Trials had a moderate sample size of 112 participants. Two trials were conducted online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite study implementation was heavily favored (97%, 69/71). Trials with four data collection points had a longer study duration than trials with two data collection points: F4,56=3.2, P=.021, η2=0.18. Single-blinded trials had a longer data collection period compared to open trials: F2,58=3.8, P=.028, η2=0.12. Academic sponsorship was the most common form of trial funding (73%, 52/71). Trials with academic sponsorship had a longer study duration compared to industry sponsorship: F2,61=3.7, P=.030, η2=0.11. Combined, data collection frequency, study masking, sample size, and study sponsorship accounted for 32.6% of the variance in study duration: F4,55=6.6, P<.01, adjusted r2=.33. Only 7 trials had been completed at the time this retrospective review was conducted (10%, 7/71). Conclusions mHealth evaluation methodology has not deviated from common methods, despite the need for more relevant and timely evaluations. There is a need for clinical evaluation to keep pace with the level of innovation of mHealth if it is to have meaningful impact in informing payers, providers, policy makers, and patients. PMID:27613084

Beyond the Randomized Controlled Trial: A Review of Alternatives in mHealth Clinical Trial Methods.

PubMed

Pham, Quynh; Wiljer, David; Cafazzo, Joseph A

2016-09-09

Randomized controlled trials (RCTs) have long been considered the primary research study design capable of eliciting causal relationships between health interventions and consequent outcomes. However, with a prolonged duration from recruitment to publication, high-cost trial implementation, and a rigid trial protocol, RCTs are perceived as an impractical evaluation methodology for most mHealth apps. Given the recent development of alternative evaluation methodologies and tools to automate mHealth research, we sought to determine the breadth of these methods and the extent that they were being used in clinical trials. We conducted a review of the ClinicalTrials.gov registry to identify and examine current clinical trials involving mHealth apps and retrieved relevant trials registered between November 2014 and November 2015. Of the 137 trials identified, 71 were found to meet inclusion criteria. The majority used a randomized controlled trial design (80%, 57/71). Study designs included 36 two-group pretest-posttest control group comparisons (51%, 36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71), and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a qualitative component to their methodology (24%, 17/71). Complete trial data collection required 20 months on average to complete (mean 21, SD 12). For trials with a total duration of 2 years or more (31%, 22/71), the average time from recruitment to complete data collection (mean 35 months, SD 10) was 2 years longer than the average time required to collect primary data (mean 11, SD 8). Trials had a moderate sample size of 112 participants. Two trials were conducted online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite study implementation was heavily favored (97%, 69/71). Trials with four data collection points had a longer study duration than trials with two data collection points: F4,56=3.2, P=.021, η(2)=0.18. Single-blinded trials had a longer data collection period compared to open trials: F2,58=3.8, P=.028, η(2)=0.12. Academic sponsorship was the most common form of trial funding (73%, 52/71). Trials with academic sponsorship had a longer study duration compared to industry sponsorship: F2,61=3.7, P=.030, η(2)=0.11. Combined, data collection frequency, study masking, sample size, and study sponsorship accounted for 32.6% of the variance in study duration: F4,55=6.6, P<.01, adjusted r(2)=.33. Only 7 trials had been completed at the time this retrospective review was conducted (10%, 7/71). mHealth evaluation methodology has not deviated from common methods, despite the need for more relevant and timely evaluations. There is a need for clinical evaluation to keep pace with the level of innovation of mHealth if it is to have meaningful impact in informing payers, providers, policy makers, and patients.

Single dental implant retained mandibular complete dentures – influence of the loading protocol: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Over the years, there has been a strong consensus in dentistry that at least two implants are required to retain a complete mandibular denture. It has been shown in several clinical trials that one single median implant can retain a mandibular overdenture sufficiently well for up to 5 years without implant failures, when delayed loading was used. However, other trials have reported conflicting results with in part considerable failure rates when immediate loading was applied. Therefore it is the purpose of the current randomized clinical trial to test the hypothesis that immediate loading of a single mandibular midline implant with an overdenture will result in a comparable clinical outcome as using the standard protocol of delayed loading. Methods/design This prospective nine-center randomized controlled clinical trial is still ongoing. The final patient will complete the trial in 2016. In total, 180 edentulous patients between 60 and 89 years with sufficient complete dentures will receive one median implant in the edentulous mandible, which will retain the existing complete denture using a ball attachment. Loading of the median implant is either immediately after implant placement (experimental group) or delayed by 3 months of submerged healing at second-stage surgery (control group). Follow-up of patients will be performed for 24 months after implant loading. The primary outcome measure is non-inferiority of implant success rate of the experimental group compared to the control group. The secondary outcome measures encompass clinical, technical and subjective variables. The study was funded by the Deutsche Forschungsgemeinschaft (German research foundation, KE 477/8-1). Discussion This multi-center clinical trial will give information on the ability of a single median implant to retain a complete mandibular denture when immediately loaded. If viable, this treatment option will strongly improve everyday dental practice. Trial registration The trial has been registered at Deutsches Register Klinischer Studien (German register of clinical trials) under DRKS-ID: DRKS00003730 since 23 August 2012. (http://www.germanctr.de). PMID:24884848

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

PubMed Central

2013-01-01

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

Addition of transcranial direct current stimulation to quadriceps strengthening exercise in knee osteoarthritis: A pilot randomised controlled trial

PubMed Central

Chang, Wei-Ju; Bennell, Kim L.; Hodges, Paul W.; Hinman, Rana S.; Young, Carolyn L.; Buscemi, Valentina; Liston, Matthew B.

2017-01-01

A randomised, assessor- and participant-blind, sham-controlled trial was conducted to assess the safety and feasibility of adding transcranial direct current stimulation (tDCS) to quadriceps strengthening exercise in knee osteoarthritis (OA), and provide data to inform a fully powered trial. Participants were randomised to receive active tDCS+exercise (AT+EX) or sham tDCS+exercise (ST+EX) twice weekly for 8 weeks whilst completing home exercises twice per week. Feasibility, safety, patient-perceived response, pain, function, pressure pain thresholds (PPTs) and conditioned pain modulation (CPM) were assessed before and after treatment. Fifty-seven people were screened for eligibility. Thirty (52%) entered randomisation and 25 (84%) completed the trial. One episode of headache in the AT+EX group was reported. Pain reduced in both groups following treatment (AT+EX: p<0.001, partial η2 = 0.55; ST+EX: p = 0.026, partial η2 = 0.18) but no between-group differences were observed (p = 0.18, partial η2 = 0.08). Function improved in the AT+EX (p = 0.01, partial η2 = 0.22), but not the ST+EX (p = 0.16, partial η2 = 0.08) group, between-group differences did not reach significance (p = 0.28, partial η2 = 0.052). AT+EX produced greater improvements in PPTs than ST+EX (p<0.05) (superolateral knee: partial η2 = 0.17; superior knee: partial η2 = 0.3; superomedial knee: partial η2 = 0.26). CPM only improved in the AT+EX group but no between-group difference was observed (p = 0.054, partial η2 = 0.158). This study provides the first feasibility and safety data for the addition of tDCS to quadriceps strengthening exercise in knee OA. Our data suggest AT+EX may improve pain, function and pain mechanisms beyond that of ST+EX, and provides support for progression to a fully powered randomised controlled trial. PMID:28665989

Short-term outcomes of extracorporeal shock wave therapy for the treatment of chronic non-calcific tendinopathy of the supraspinatus: a double-blind, randomized, placebo-controlled trial

PubMed Central

2012-01-01

Background There is evidence supporting the use of extracorporeal shock wave therapy (ESWT) in calcific tendinopathy of the rotator cuff, but the best current evidence does not support its use in non-calcifying tendinopathy. We conducted a randomized placebo-controlled trial to investigate the efficacy and safety of low energy ESWT for non-calcifying tendinopathy of the rotator cuff. Methods 20 patients with non-calcifying supraspinatus tendinopathy (NCST) were randomized to an active or a sham treatment group. Physical, blood, roentgenographic, and MRI examinations of the shoulder were conducted to verify that patients met the inclusion and exclusion criteria. These examinations were repeated six and twelve weeks after treatments. Effectiveness was determined by comparison of the mean improvement in the Constant and Murley score (CMS) between the treatment and the placebo groups at three months. Safety was assessed by analyzing the number and severity of adverse events. Results All the patients completed the investigation protocol. At the final follow-up, significant improvement in the total CMS score and most of the CMS subscales was observed in the ESWT group when compared to the baseline values. Significantly higher total CMS, and significantly higher scores for CMS pain and ROM were observed in the ESWT group when compared to the placebo. No serious adverse events were noted after ESWT. Conclusions Patients suffering from NCST may benefit from low energy ESWT, at least in short-term. The application protocol of ESWT is likely to play a key-role in a successful treatment. Future investigations should be undertaken on the long-term effects of this technique for the treatment of NCST. Trial registration Current Controlled Trials ISRCTN41236511 PMID:22672772

Topical Steroid Therapy for the Treatment of Eosinophilic Esophagitis (EoE): A Systematic Review and Meta-Analysis

PubMed Central

Chuang, Ming-yu (Anthony); Chinnaratha, Mohamed A; Hancock, David G; Woodman, Richard; Wong, Geoffrey R; Cock, Charles; Fraser, Robert JL

2015-01-01

OBJECTIVES: Current guidelines recommend topical steroids as first-line treatment for patients with eosinophilic esophagitis (EoE). However, the evidence for this approach has been inconsistent in earlier reports. This meta-analysis aimed to clarify the efficacy of topical steroid treatment in active EoE using updated evidence. METHODS: CENTRAL, MEDLINE and EMBASE databases were searched for randomized controlled trials (RCTs) published up to May 2014 that compared topical steroids with control treatments for active EoE. Study bias was assessed using the Cochrane Collaboration Tool, and outcomes were pooled using random effects models. The primary outcome was the mean change in eosinophil counts. Secondary outcomes were symptom responses and adverse events. RESULTS: In total, seven RCTs (226 patients) were included. Topical steroids were associated with a significant reduction in esophageal mucosal eosinophil counts compared with control therapy although substantial heterogeneity between studies was observed (weighted mean difference (WMD) −27.2, 95% confidence interval (CI) −45.3 to −9.1, I2=56.2%). Subgroup analysis indicated the reduction in eosinophil counts was only present in studies where a proton pump inhibitor (PPI) trial was used to exclude other diagnoses (WMD −46.3, 95% CI −61.3 to −31.4, I2=0.0%). Subdivision of studies on the use of a PPI trial also accounted for the majority of heterogeneity among RCTs. No clear trends in symptom resolution were observed. Eleven out of 127 patients who received topical steroids developed asymptomatic esophageal candidiasis. CONCLUSIONS: These data provide updated high-quality evidence that support current guidelines for first-line EoE treatment with topical steroids after an initial PPI trial to exclude non-EoE pathologies (PROSPERO ID: CRD42014008828). PMID:25809314

Internet-based cognitive bias modification for obsessive compulsive disorder: study protocol for a randomized controlled trial.

PubMed

Williams, Alishia D; Pajak, Rosanna; O'Moore, Kathleen; Andrews, Gavin; Grisham, Jessica R

2014-05-29

Cognitive bias modification (CBM) interventions have demonstrated efficacy in augmenting core biases implicated in psychopathology. The current randomized controlled trial (RCT) will evaluate the efficacy of an internet-delivered positive imagery cognitive bias modification intervention for obsessive compulsive disorder (OCD) when compared to a control condition. Patients meeting diagnostic criteria for a current or lifetime diagnosis of OCD will be recruited via the research arm of a not-for-profit clinical and research unit in Australia. The minimum sample size for each group (alpha set at 0.05, power at .80) was identified as 29, but increased to 35 to allow for 20% attrition. We will measure the impact of CBM on interpretations bias using the OC Bias Measure (The Ambiguous Scenarios Test for OCD ;AST-OCD) and OC-beliefs (The Obsessive Beliefs Questionnaire-TRIP; OBQ-TRIP). Secondary outcome measures include the Dimensional Obsessive-Compulsive Scale (DOCS), the Patient Health Questionnaire (PHQ-9), The Kessler Psychological Distress Scale (K10), and the Word Sentence Association Test for OCD (WSAO). Change in diagnostic status will be indexed using the OCD Mini International Neuropsychiatric Interview (M.I.N.I) Module at baseline and follow-up. Intent-to-treat (ITT) marginal and mixed-effect models using restricted maximum likelihood (REML) estimation will be used to evaluate the primary hypotheses. Stability of bias change will be assessed at 1-month follow-up. A limitation of the online nature of the study is the inability to include a behavioral outcome measure. The trial was registered on 10 October 2013 with the Australian New Zealand Clinical Trials Registry (ACTRN12613001130752).

Familias Unidas for high risk adolescents: Study design of a cultural adaptation and randomized controlled trial of a U.S. drug and sexual risk behavior intervention in Ecuador.

PubMed

Jacobs, Petra; Estrada, Yannine A; Tapia, Maria I; Quevedo Terán, Ana M; Condo Tamayo, Cecilia; Albán García, Mónica; Valenzuela Triviño, Gilda M; Pantin, Hilda; Velazquez, Maria R; Horigian, Viviana E; Alonso, Elizabeth; Prado, Guillermo

2016-03-01

Developing, testing and implementing evidence-based prevention interventions are important in decreasing substance use and sexual risk behavior among adolescents. This process requires research expertise, infrastructure, resources and decades of research testing, which might not always be feasible for low resource countries. Adapting and testing interventions proven to be efficacious in similar cultures might circumvent the time and costs of implementing evidence-based interventions in new settings. This paper describes the two-phase study, including training and development of the research infrastructure in the Ecuadorian university necessary to implement a randomized controlled trial. Familias Unidas is a multilevel parent-centered intervention designed in the U.S. to prevent drug use and sexual risk behaviors in Hispanic adolescents. The current study consisted of Phase 1 feasibility study (n=38) which adapted the intervention and study procedures within a single-site school setting in an area with a high prevalence of drug use and unprotected sexual behavior among adolescents in Ecuador, and Phase 2 randomized controlled trial of the adapted intervention in two public high schools with a target population of families with adolescents from 12 to 14 years old. The trial is currently in Phase 2. Study recruitment was completed with 239 parent-youth dyads enrolling. The intervention phase and the first follow-up assessment have been completed. The second and third follow-up assessments will be completed in 2016. This project has the potential of benefitting a large population of families in areas of Ecuador that are disproportionally affected by drug trafficking and its consequences. MSP-DIS-2015-0055-0, Ministry of Public Health (MSP), Quito, Ecuador. Copyright © 2016 Elsevier Inc. All rights reserved.

Critical Appraisal on Orbital Decompression for Thyroid Eye Disease: A Systematic Review and Literature Search.

PubMed

Boboridis, Konstadinos G; Uddin, Jimmy; Mikropoulos, Dimitrios G; Bunce, Catey; Mangouritsas, George; Voudouragkaki, Irini C; Konstas, Anastasios G P

2015-07-01

Orbital decompression is the indicated procedure for addressing exophthalmos and compressive optic neuropathy in thyroid eye disease. There are an abundance of techniques for removal of orbital bone, fat, or a combination published in the scientific literature. The relative efficacy and complications of these interventions in relation to the specific indications remain as yet undocumented. We performed a systematic review of the current published evidence for the effectiveness of orbital decompression, possible complications, and impact on quality of life. We searched the current databases for medical literature and controlled trials, oculoplastic textbooks, and conference proceedings to identify relevant data up to February 2015. We included randomized controlled trials (RCTs) comparing two or more interventions for orbital decompression. We identified only two eligible RCTs for inclusion in the review. As a result of the significant variability between studies on decompression, i.e., methodology and outcome measures, we did not perform a meta-analysis. One study suggests that the transantral approach and endonasal technique had similar effects in reducing exophthalmos but the latter is safer. The second study provides evidence that intravenous steroids may be superior to primary surgical decompression in the management of compressive optic neuropathy requiring less secondary surgical procedures. Most of the published literature on orbital decompression consists of retrospective, uncontrolled trials. There is evidence from those studies that removal of the medial and lateral wall (balanced) and the deep lateral wall decompression, with or without fat removal, may be the most effective surgical methods with only few complications. There is a clear unmet need for controlled trials evaluating the different techniques for orbital decompression. Ideally, future studies should address the effectiveness, possible complications, quality of life, and cost of each intervention.

Efficacy and Safety of Nitazoxanide, Albendazole, and Nitazoxanide-Albendazole against Trichuris trichiura Infection: A Randomized Controlled Trial

PubMed Central

Speich, Benjamin; Ame, Shaali M.; Ali, Said M.; Alles, Rainer; Hattendorf, Jan; Utzinger, Jürg; Albonico, Marco; Keiser, Jennifer

2012-01-01

Background The currently used anthelmintic drugs, in single oral application, have low efficacy against Trichuris trichiura infection, and hence novel anthelmintic drugs are needed. Nitazoxanide has been suggested as potential drug candidate. Methodology The efficacy and safety of a single oral dose of nitazoxanide (1,000 mg), or albendazole (400 mg), and a nitazoxanide-albendazole combination (1,000 mg–400 mg), with each drug administered separately on two consecutive days, were assessed in a double-blind, randomized, placebo-controlled trial in two schools on Pemba, Tanzania. Cure and egg reduction rates were calculated by per-protocol analysis and by available case analysis. Adverse events were assessed and graded before treatment and four times after treatment. Principal Findings Complete data for the per-protocol analysis were available from 533 T. trichiura-positive children. Cure rates against T. trichiura were low regardless of the treatment (nitazoxanide-albendazole, 16.0%; albendazole, 14.5%; and nitazoxanide, 6.6%). Egg reduction rates were 54.9% for the nitazoxanide-albendazole combination, 45.6% for single albendazole, and 13.4% for single nitazoxanide. Similar cure and egg reduction rates were calculated using the available case analysis. Children receiving nitazoxanide had significantly more adverse events compared to placebo recipients. Most of the adverse events were mild and had resolved within 24 hours posttreatment. Conclusions/Significance Nitazoxanide shows no effect on T. trichiura infection. The low efficacy of albendazole against T. trichiura in the current setting characterized by high anthelmintic drug pressure is confirmed. There is a pressing need to develop new anthelmintics against trichuriasis. Trial Registration Controlled-Trials.com ISRCTN08336605 PMID:22679525

Study design and methodology for a multicentre, randomised controlled trial of transcranial direct current stimulation as a treatment for unipolar and bipolar depression.

PubMed

Alonzo, Angelo; Aaronson, Scott; Bikson, Marom; Husain, Mustafa; Lisanby, Sarah; Martin, Donel; McClintock, Shawn M; McDonald, William M; O'Reardon, John; Esmailpoor, Zeinab; Loo, Colleen

2016-11-01

Transcranial Direct Current Stimulation (tDCS) is a new, non-invasive neuromodulation approach for treating depression that has shown promising efficacy. The aim of this trial was to conduct the first international, multicentre randomised controlled trial of tDCS as a treatment for unipolar and bipolar depression. The study recruited 120 participants across 6 sites in the USA and Australia. Participants received active or sham tDCS (2.5mA, 20 sessions of 30min duration over 4weeks), followed by a 4-week open label active treatment phase and a 4-week taper phase. Mood and neuropsychological outcomes were assessed with the primary antidepressant outcome measure being the Montgomery-Asberg Depression Rating Scale (MADRS). A neuropsychological battery was administered to assess safety and examine cognitive effects. The study also investigated the possible influence of genetic polymorphisms on outcomes. The trial was triple-blinded. Participants, tDCS treaters and study raters were blinded to each participant's tDCS group allocation in the sham-controlled phase. Specific aspects of tDCS administration, device operation and group allocation were designed to optimise the integrity of blinding. Outcome measures will be tested using a mixed effects repeated measures analysis with the primary factors being Time as a repeated measure, tDCS condition (sham or active) and Diagnosis (unipolar or bipolar). A restricted number of random and fixed factors will be included as required to account for extraneous differences. As a promising treatment, tDCS has excellent potential for translation into widespread clinical use, being cost effective, portable, easy to operate and well tolerated. Copyright © 2016 Elsevier Inc. All rights reserved.

Pediatric stroke and transcranial direct current stimulation: methods for rational individualized dose optimization

PubMed Central

Gillick, Bernadette T.; Kirton, Adam; Carmel, Jason B.; Minhas, Preet; Bikson, Marom

2014-01-01

Background: Transcranial direct current stimulation (tDCS) has been investigated mainly in adults and doses may not be appropriate in pediatric applications. In perinatal stroke where potential applications are promising, rational adaptation of dosage for children remains under investigation. Objective: Construct child-specific tDCS dosing parameters through case study within a perinatal stroke tDCS safety and feasibility trial. Methods: 10-year-old subject with a diagnosis of presumed perinatal ischemic stroke and hemiparesis was identified. T1 magnetic resonance imaging (MRI) scans used to derive computerized model for current flow and electrode positions. Workflow using modeling results and consideration of dosage in previous clinical trials was incorporated. Prior ad hoc adult montages vs. de novo optimized montages provided distinct risk benefit analysis. Approximating adult dose required consideration of changes in both peak brain current flow and distribution which further tradeoff between maximizing efficacy and adding safety factors. Electrode size, position, current intensity, compliance voltage, and duration were controlled independently in this process. Results: Brain electric fields modeled and compared to values previously predicted models (Datta et al., 2011; Minhas et al., 2012). Approximating conservative brain current flow patterns and intensities used in previous adult trials for comparable indications, the optimal current intensity established was 0.7 mA for 10 min with a tDCS C3/C4 montage. Specifically 0.7 mA produced comparable peak brain current intensity of an average adult receiving 1.0 mA. Electrode size of 5 × 7 cm2 with 1.0 mA and low-voltage tDCS was employed to maximize tolerability. Safety and feasibility confirmed with subject tolerating the session well and no serious adverse events. Conclusion: Rational approaches to dose customization, with steps informed by computational modeling, may improve guidance for pediatric stroke tDCS trials. PMID:25285077

Making a decision about trial participation: the feasibility of measuring deliberation during the informed consent process for clinical trials.

PubMed

Gillies, Katie; Elwyn, Glyn; Cook, Jonathan

2014-07-30

Informed consent of trial participants is both an ethical and a legal requirement. When facing a decision about trial participation, potential participants are provided with information about the trial and have the opportunity to have any questions answered before their degree of 'informed-ness' is assessed, usually subjectively, and before they are asked to sign a consent form. Currently, standardised methods for assessing informed consent have tended to be focused on aspects of understanding and associated outcomes, rather than on the process of consent and the steps associated with decision-making. Potential trial participants who were approached regarding participation in one of three randomised controlled trials were asked to complete a short questionnaire to measure their deliberation about trial participation. A total of 136 participants completed the 10-item questionnaire (DelibeRATE) before they made an explicit decision about trial participation (defined as signing the clinical trial consent form). Overall DelibeRATE scores were compared and investigated for differences between trial consenters and refusers. No differences in overall DelibeRATE scores were identified. In addition, there was no significant difference between overall score and the decision to participate, or not, in the parent trial. To our knowledge, this is the first study to prospectively measure the deliberation stage of the informed consent decision-making process of potential trial participants across different conditions and clinical areas. Although there were no differences detected in overall scores or scores of trial consenters and refusers, we did identify some interesting findings. These findings should be taken into consideration by those designing trials and others interested in developing and implementing measures of potential trial participants decision making during the informed consent process for research. International Standard Randomised Controlled Trial Number (ISRCTN) Register ISRCTN60695184 (date of registration: 13 May 2009), ISRCTN80061723 (date of registration: 8 March 2010), ISRCTN69423238 (date of registration: 18 November 2010).

Psychological treatments in intellectual disability: the challenges of building a good evidence base.

PubMed

Bhaumik, Sabyasachi; Gangadharan, Satheesh; Hiremath, Avinash; Russell, Paul Swamidhas Sudhakar

2011-06-01

Psychological treatments are widely used for the management of mental health and behavioural problems in people with intellectual disabilities. The evidence base, including the cost-effectiveness of such interventions, is limited. This editorial explores the current evidence base and analyses its strengths and limitations. The editorial also highlights current problems in conducting randomised controlled trials in this area and suggests a way forward.

Relationship between Added Sugars Consumption and Chronic Disease Risk Factors: Current Understanding.

PubMed

Rippe, James M; Angelopoulos, Theodore J

2016-11-04

Added sugars are a controversial and hotly debated topic. Consumption of added sugars has been implicated in increased risk of a variety of chronic diseases including obesity, cardiovascular disease, diabetes and non-alcoholic fatty liver disease (NAFLD) as well as cognitive decline and even some cancers. Support for these putative associations has been challenged, however, on a variety of fronts. The purpose of the current review is to summarize high impact evidence including systematic reviews, meta-analyses, and randomized controlled trials (RCTs), in an attempt to provide an overview of current evidence related to added sugars and health considerations. This paper is an extension of a symposium held at the Experimental Biology 2015 conference entitled "Sweeteners and Health: Current Understandings, Controversies, Recent Research Findings and Directions for Future Research". We conclude based on high quality evidence from randomized controlled trials (RCT), systematic reviews and meta-analyses of cohort studies that singling out added sugars as unique culprits for metabolically based diseases such as obesity, diabetes and cardiovascular disease appears inconsistent with modern, high quality evidence and is very unlikely to yield health benefits. While it is prudent to consume added sugars in moderation, the reduction of these components of the diet without other reductions of caloric sources seems unlikely to achieve any meaningful benefit.

Relationship between Added Sugars Consumption and Chronic Disease Risk Factors: Current Understanding

PubMed Central

Rippe, James M.; Angelopoulos, Theodore J.

2016-01-01

Added sugars are a controversial and hotly debated topic. Consumption of added sugars has been implicated in increased risk of a variety of chronic diseases including obesity, cardiovascular disease, diabetes and non-alcoholic fatty liver disease (NAFLD) as well as cognitive decline and even some cancers. Support for these putative associations has been challenged, however, on a variety of fronts. The purpose of the current review is to summarize high impact evidence including systematic reviews, meta-analyses, and randomized controlled trials (RCTs), in an attempt to provide an overview of current evidence related to added sugars and health considerations. This paper is an extension of a symposium held at the Experimental Biology 2015 conference entitled “Sweeteners and Health: Current Understandings, Controversies, Recent Research Findings and Directions for Future Research”. We conclude based on high quality evidence from randomized controlled trials (RCT), systematic reviews and meta-analyses of cohort studies that singling out added sugars as unique culprits for metabolically based diseases such as obesity, diabetes and cardiovascular disease appears inconsistent with modern, high quality evidence and is very unlikely to yield health benefits. While it is prudent to consume added sugars in moderation, the reduction of these components of the diet without other reductions of caloric sources seems unlikely to achieve any meaningful benefit. PMID:27827899

Promoting smoking cessation in Pakistani and Bangladeshi men in the UK: pilot cluster randomised controlled trial of trained community outreach workers

PubMed Central

2011-01-01

Background Smoking prevalence is high among Pakistani and Bangladeshi men in the UK, but there are few tailored smoking cessation programmes for Pakistani and Bangladeshi communities. The aim of this study was to pilot a cluster randomised controlled trial comparing the effectiveness of Pakistani and Bangladeshi smoking cessation outreach workers with standard care to improve access to and the success of English smoking cessation services. Methods A pilot cluster randomised controlled trial was conducted in Birmingham, UK. Geographical lower layer super output areas were used to identify natural communities where more than 10% of the population were of Pakistani and Bangladeshi origin. 16 agglomerations of super output areas were randomised to normal care controls vs. outreach intervention. The number of people setting quit dates using NHS services, validated abstinence from smoking at four weeks, and stated abstinence at three and six months were assessed. The impact of the intervention on choice and adherence to treatments, attendance at clinic appointments and patient satisfaction were also assessed. Results We were able to randomise geographical areas and deliver the outreach worker-based services. More Pakistani and Bangladeshi men made quit attempts with NHS services in intervention areas compared with control areas, rate ratio (RR) 1.32 (95%CI: 1.03-1.69). There was a small increase in the number of 4-week abstinent smokers in intervention areas (RR 1.30, 95%CI: 0.82-2.06). The proportion of service users attending weekly appointments was lower in intervention areas than control areas. No difference was found between intervention and control areas in choice and adherence to treatments or patient satisfaction with the service. The total cost of the intervention was £124,000; an estimated cost per quality-adjusted life year (QALY) gained of £8,500. Conclusions The intervention proved feasible and acceptable. Outreach workers expanded reach of smoking cessation services in diverse locations of relevance to Pakistani and Bangladeshi communities. The outreach worker model has the potential to increase community cessation rates and could prove cost-effective, but needs evaluating definitively in a larger, appropriately powered, randomised controlled trial. These future trials of outreach interventions need to be of sufficient duration to allow embedding of new models of service delivery. Trial registration Current Controlled Trials ISRCTN82127540 PMID:21854596

A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831).

PubMed

Kean, James D; Kaufman, Jordy; Lomas, Justine; Goh, Antionette; White, David; Simpson, David; Scholey, Andrew; Singh, Hemant; Sarris, Jerome; Zangara, Andrea; Stough, Con

2015-12-02

Clinical diagnoses of Attention Deficit Hyperactivity Disorder (ADHD) and the use of prescription medications for its treatment have increased in recent years. Current treatments may involve the administration of amphetamine-type substances, a treatment path many parents are apprehensive to take. Therefore, alternative pharmacological treatments are required. Few nutritional or pharmacological alternatives that reduce ADHD associated symptoms (hyperactivity and inattention) have been subjected to rigorous clinical trials. Bacopa monnieri is a perennial creeping herb. CDRI 08 is a special extract of Bacopa monnieri which has been subjected to hundreds of scientific studies and has been shown in human randomized controlled trials (RCTs) to improve memory, attention, and mood. It is hypothesised that chronic administration of CDRI 08 will improve attention, concentration and behaviour in children with high levels of hyperactivity and/or inattention. This paper reports the protocol for the first 16-week, randomized, placebo-controlled, double-blind, parallel groups trial examining the efficacy and safety of CDRI 08 in male children aged 6-14 years with high levels of inattention and hyperactivity. The primary outcome variable will be the level of hyperactivity and inattention measured by the Conners' Parent Rating Scale (CPRS). Secondary outcome variables include cognition, mood, sleep, and EEG. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000827831.

An Intervention to Optimize Coach Motivational Climates and Reduce Athlete Willingness to Dope (CoachMADE): Protocol for a Cross-Cultural Cluster Randomized Control Trial

PubMed Central

Ntoumanis, Nikos; Gucciardi, Daniel F.; Backhouse, Susan H.; Barkoukis, Vassilis; Quested, Eleanor; Patterson, Laurie; Smith, Brendan J.; Whitaker, Lisa; Pavlidis, George; Kaffe, Stela

2018-01-01

Field-based anti-doping interventions in sport are scarce and focus on athletes. However, coaches are recognized as one of the most significant source of influence in terms of athletes’ cognitions, affect, and behavior. In this paper, we present the protocol for a cluster randomized control trial which aims to contrast the relative effects of a ‘motivation and anti-doping’ intervention program for coaches against an information-based anti-doping control program. In developing the motivation content of our intervention, we drew from Self-Determination Theory. The project is currently ongoing in Australia and has recently started in the United Kingdom and Greece. We aim to recruit 120 coaches and approximately 1200 of their athletes across the three countries. Various assessments will be taken from both coaches and athletes prior to the intervention, immediately after the 12-week intervention and at a 2-month follow up. The intervention comprises face-to-face workshops and weekly activities which are supported by printed and online material. The project aims to identify communication strategies that coaches can use to support athletes’ motivation in sport and also to promote self-determined reasons for athletes to comply with doping regulations. Trial Registration: The trial is registered with the Australia and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12616001688471. PMID:29375428

The effectiveness of ICT-based neurocognitive and psychosocial rehabilitation programmes in people with mild dementia and mild cognitive impairment using GRADIOR and ehcoBUTLER: study protocol for a randomised controlled trial.

PubMed

Vanova, Martina; Irazoki, Eider; García-Casal, J Antonio; Martínez-Abad, Fernando; Botella, Cristina; Shiells, Kate R; Franco-Martín, Manuel A

2018-02-12

Cognitive rehabilitation is a highly individualised, non-pharmacological intervention for people with mild cognitive impairment (MCI) and dementia, which in recent years has also been developed for various IT platforms. In this study, we aim to evaluate the effectiveness of the cognitive rehabilitation software GRADIOR in a multi-centre, single-blinded randomised controlled trial with people with MCI and mild dementia. A total of 400 people with MCI and mild dementia will be randomly allocated to one of four groups. This trial will compare the cognitive rehabilitation treatment using the GRADIOR programme with a psychosocial stimulation intervention (PSS) using the ehcoBUTLER platform, with a combined treatment consisting of GRADIOR and ehcoBUTLER, and with a group receiving treatment as usual during a period of 1 year. The outcomes of this clinical trial will be to determine any relevant changes in cognition, mood, quality of life, activities of daily living and quality of patient-carer relationship after 4 months and 1 year of intervention in a cross-sectional group comparison. Participants will be followed-up for 1 year to investigate potential long-term effects of the conducted treatments. Current Controlled Trials ISRCTN, ID: 15742788 . Registered on 12 June 2017.

An Intervention to Optimize Coach Motivational Climates and Reduce Athlete Willingness to Dope (CoachMADE): Protocol for a Cross-Cultural Cluster Randomized Control Trial.

PubMed

Ntoumanis, Nikos; Gucciardi, Daniel F; Backhouse, Susan H; Barkoukis, Vassilis; Quested, Eleanor; Patterson, Laurie; Smith, Brendan J; Whitaker, Lisa; Pavlidis, George; Kaffe, Stela

2017-01-01

Field-based anti-doping interventions in sport are scarce and focus on athletes. However, coaches are recognized as one of the most significant source of influence in terms of athletes' cognitions, affect, and behavior. In this paper, we present the protocol for a cluster randomized control trial which aims to contrast the relative effects of a 'motivation and anti-doping' intervention program for coaches against an information-based anti-doping control program. In developing the motivation content of our intervention, we drew from Self-Determination Theory. The project is currently ongoing in Australia and has recently started in the United Kingdom and Greece. We aim to recruit 120 coaches and approximately 1200 of their athletes across the three countries. Various assessments will be taken from both coaches and athletes prior to the intervention, immediately after the 12-week intervention and at a 2-month follow up. The intervention comprises face-to-face workshops and weekly activities which are supported by printed and online material. The project aims to identify communication strategies that coaches can use to support athletes' motivation in sport and also to promote self-determined reasons for athletes to comply with doping regulations. Trial Registration: The trial is registered with the Australia and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12616001688471.

Registration status and methodological reporting of randomized controlled trials in obesity research: A review.

PubMed

Byrne, Jillian L S; Yee, Tamara; O'Connor, Kathleen; Dyson, Michele P; Ball, Geoff D C

2017-04-01

To assess registration and reporting details of randomized controlled trials (RCTs) published from 2011 to 2016 across four obesity journals. All issues from four leading obesity journals were searched systematically for RCTs from January 2011 to June 2016. Data on registration status were extracted from manuscripts, online trial registries, and a trial database; corresponding authors were contacted for registration details, when necessary. The methodological reporting of RCTs was assessed on specific criteria from the Consolidated Standards of Reporting Trials. A total of 223 RCTs were reviewed. Three-quarters (n = 170) were registered publicly; 94 (55.3%) reported registration details in the manuscript, and 82 (48.2%) were registered prospectively. Newer RCTs were more likely to be registered prospectively than older RCTs (2014-2016: 57.3% vs. 2011-2013: 39.2%; c 2  = 5.5, P = 0.02). Assessment on the Consolidated Standards of Reporting Trials demonstrated that less than half of all studies reported data collection dates (n = 108; 48.4%) or included "randomized trial" in the title (n = 89; 39.9%). The methodological reporting of RCTs published in obesity journals is suboptimal, despite current guidelines and policies. To complement existing standards, editorial boards should incorporate mandatory fields within the online manuscript submission process to enhance the quality, transparency, and comprehensiveness of reporting RCTs in obesity journals. © 2017 The Obesity Society.

Atrial fibrillation and stroke: the evolving role of rhythm control.

PubMed

Patel, Taral K; Passman, Rod S

2013-06-01

Atrial fibrillation (AF) remains a major risk factor for stroke. Unfortunately, clinical trials have failed to demonstrate that a strategy of rhythm control--therapy to maintain normal sinus rhythm (NSR)--reduces stroke risk. The apparent lack of benefit of rhythm control likely reflects the difficulty in maintaining NSR using currently available therapies. However, there are signals from several trials that the presence of NSR is indeed beneficial and associated with better outcomes related to stroke and mortality. Most electrophysiologists feel that as rhythm control strategies continue to improve, the crucial link between rhythm control and stroke reduction will finally be demonstrated. Therefore, AF specialists tend to be aggressive in their attempts to maintain NSR, especially in patients who have symptomatic AF. A step-wise approach from antiarrhythmic drugs to catheter ablation to cardiac surgery is generally used. In select patients, catheter ablation or cardiac surgery may supersede antiarrhythmic drugs. The choice depends on the type of AF, concurrent heart disease, drug toxicity profiles, procedural risks, and patient preferences. Regardless of strategy, given the limited effectiveness of currently available rhythm control therapies, oral anticoagulation is still recommended for stroke prophylaxis in AF patients with other stroke risk factors. Major challenges in atrial fibrillation management include selecting patients most likely to benefit from rhythm control, choosing specific antiarrhythmic drugs or procedures to achieve rhythm control, long-term monitoring to gauge the efficacy of rhythm control, and determining which (if any) patients may safely discontinue anticoagulation if long-term NSR is achieved.

Acupuncture for menopausal vasomotor symptoms: study protocol for a randomised controlled trial

PubMed Central

2014-01-01

Background Hot flushes and night sweats (vasomotor symptoms) are common menopausal symptoms, often causing distress, sleep deprivation and reduced quality of life. Although hormone replacement therapy is an effective treatment, there are concerns about serious adverse events. Non-hormonal pharmacological therapies are less effective and can also cause adverse effects. Complementary therapies, including acupuncture, are commonly used for menopausal vasomotor symptoms. While the evidence for the effectiveness of acupuncture in treating vasomotor symptoms is inconclusive, acupuncture has a low risk of adverse effects, and two small studies suggest it may be more effective than non-insertive sham acupuncture. Our objective is to assess the efficacy of needle acupuncture in improving hot flush severity and frequency in menopausal women. Our current study design is informed by methods tested in a pilot study. Methods/design This is a stratified, parallel, randomised sham-controlled trial with equal allocation of participants to two trial groups. We are recruiting 360 menopausal women experiencing a minimum average of seven moderate hot flushes a day over a seven-day period and who meet diagnostic criteria for the Traditional Chinese Medicine diagnosis of Kidney Yin deficiency. Exclusion criteria include breast cancer, surgical menopause, and current hormone replacement therapy use. Eligible women are randomised to receive either true needle acupuncture or sham acupuncture with non-insertive (blunt) needles for ten treatments over eight weeks. Participants are blinded to treatment allocation. Interventions are provided by Chinese medicine acupuncturists who have received specific training on trial procedures. The primary outcome measure is hot flush score, assessed using the validated Hot Flush Diary. Secondary outcome measures include health-related quality of life, anxiety and depression symptoms, credibility of the sham treatment, expectancy and beliefs about acupuncture, and adverse events. Participants will be analysed in the groups in which they were randomised using an intention-to-treat analysis strategy. Discussion Results from this trial will significantly add to the current body of evidence on the role of acupuncture for vasomotor symptoms. If found to be effective and safe, acupuncture will be a valuable additional treatment option for women who experience menopausal vasomotor symptoms. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12611000393954 11/02/2009. PMID:24925094

The process of developing and implementing a telephone-based peer support program for postpartum depression: evidence from two randomized controlled trials

PubMed Central

2014-01-01

Background A randomized controlled trial evaluated the effect of telephone-based peer support on preventing postpartum depression (PPD) among high-risk mothers. The results indicated that support provided by peer volunteers may be an effective preventative strategy. The purpose of this paper is to outline the process of developing, implementing, maintaining, and evaluating the peer support program that we used in this PPD prevention trial. Methods The peer support program had been used successfully in a pilot trial and a previous breastfeeding peer support trial. Based on our experience and lessons learned, we developed a 4-phase, 12-step approach so that the peer support model could be copied and used by different health providers in various settings. We will use the PPD prevention trial to demonstrate the suggested steps. Results The trial aim to prevent the onset of PPD was established. Peer volunteers who previously experienced and recovered from self-reported PPD were recruited and attended a four-hour training session. Volunteers were screened and those identified as appropriate to provide support to postpartum mothers were selected. Women who scored more than 9 on the Edinburgh Postnatal Depression Scale within the first two weeks after childbirth were recruited to participate in the trial and proactive, individualized, telephone-based peer support (mother-to-mother) was provided to those randomized to the intervention group. Peer volunteers maintained the intervention, supported other volunteers, and evaluated the telephone-based support program. Possible negative effects of the intervention were assessed. An in-depth assessment of maternal perspectives of the program at 12 weeks postpartum was performed. Conclusions The 4-phase, 12-step approach delineated in this paper provides clear and concise guidelines for health professionals to follow in creating and implementing community-based, peer-support interventions with the potential to prevent PPD. Trial registration Current Controlled Trials ISRCTN68337727. PMID:24742217

Effectiveness of a Peer Support Programme versus Usual Care in Disease Management of Diabetes Mellitus Type 2 regarding Improvement of Metabolic Control: A Cluster-Randomised Controlled Trial.

PubMed

Johansson, Tim; Keller, Sophie; Winkler, Henrike; Ostermann, Thomas; Weitgasser, Raimund; Sönnichsen, Andreas C

2016-01-01

Testing the effectiveness of peer support additionally to a disease management programme (DMP) for type 2 diabetes patients. Unblinded cluster-randomised controlled trial (RCT) involving 49 general practices, province of Salzburg, Austria. All patients enrolled in the DMP were eligible, n = 337 participated (intervention: 148 in 19 clusters; control: 189 in 20 clusters). The peer support intervention ran over 24 months and consisted of peer supporter recruitment and training, and group meetings weekly for physical exercise and monthly for discussion of diabetes related topics. At two-year follow-up, adjusted analysis revealed a nonsignificant difference in HbA1c change of 0.14% (21.97 mmol/mol) in favour of the intervention (95% CI -0.08 to 0.36%, p = 0.22). Baseline values were 7.02 ± 1.25% in the intervention and 7.08 ± 1.25 in the control group. None of the secondary outcome measures showed significant differences except for improved quality of life (EQ-5D-VAS) in controls (4.3 points on a scale of 100; 95% CI 0.08 to 8.53, p = 0.046) compared to the intervention group. Our peer support intervention as an additional DMP component showed no significant effect on HbA1c and secondary outcome measures. Further RTCs with a longer follow-up are needed to reveal whether peer support will have clinically relevant effects. This trial has been registered with Current Controlled Trials Ltd. (ISRCTN10291077).

Cholesterol: Top Five Foods to Lower Your Numbers

MedlinePlus

... 2015. Sikand G, et al. Impact of functional foods on prevention of cardiovascular disease and diabetes. Current Cardiology Reports. 2015;17:39. Whitehead A, et al. Cholesterol-lowering effects of oat b-glucan: A meta-analysis of randomized control trials. American Journal of Clinical ...

A Randomized Control Trial of a Community Mental Health Intervention for Military Personnel

DTIC Science & Technology

2013-10-01

reporting period. 15. SUBJECT TERMS Mental health literacy , Mental Health First Aid (MHFA), curriculum adaptation 16. SECURITY CLASSIFICATION OF...Stress First Aid and suicide prevention gatekeeper training by providing a mental health literacy component that is currently not addressed

Pilot randomised controlled trial of protective socks against usual care to reduce skin tears in high risk people "STOPCUTS": study protocol.

PubMed

Powell, Roy J; Hayward, Christopher J; Snelgrove, Caroline L; Polverino, Kathleen; Park, Linda; Chauhan, Rohan; Evans, Philip H; Byford, Rachel; Charman, Carolyn; Foy, Christopher J W; Kingsley, Andrew

2015-01-01

Skin tears are traumatic injuries occurring mostly on the extremities due to shearing and friction forces that separate the epidermis and the dermis from underlying tissues. They are common and occur mostly in older adults and those taking medications that compromise skin integrity. Pretibial skin tears can develop into leg ulcers, which require lengthy, expensive treatment to heal. Traumatic injuries are the second most common type of wounds after pressure ulcers in care homes and are the commonest reason for older adults to require the attention of a community nurse. Common causes of skin tear injuries are bumping into furniture and other obstacles, using mobility aids, transfer to/from wheelchairs, getting in and out of bed and falls. No effective preventative measures currently exist but knee-length, protective socks are now available that contain impact-resistant Kevlar fibres (of the type used in stab-proof vests) and cushioning layers underneath. In this pilot parallel group, randomised controlled trial, 90 people at risk of skin-tear injury will be randomised with equal allocation to receive the intervention or usual care. They will be recruited from care homes and from the community via general practices and a research volunteer database. Pilot outcomes include recruitment, eligibility, attrition, ascertainment of injuries and completion of outcome measures. Acceptability of the intervention and of study participation will be explored using semi-structured interviews. The proposed primary outcome for the future definitive trial is skin tear-free days. Secondary outcomes are skin tear severity, health status, specific skin-tears quality of life, capability and fear of falling, measured at baseline and the end of the study and in the event of a skin tear. The results of this study will be used to inform the development and design of a future randomised controlled trial to assess the effectiveness and cost-effectiveness of a unique and innovative approach to skin tear prevention. Approval was granted by the NRES - Cornwall and Plymouth Research Ethics Committee (13/SW/013). Dissemination will include publication of quantitative and qualitative findings, and experience of public involvement in peer-reviewed journals. Current Controlled Trials: ISRCTN96565376.

Powered robotic exoskeletons in post-stroke rehabilitation of gait: a scoping review.

PubMed

Louie, Dennis R; Eng, Janice J

2016-06-08

Powered robotic exoskeletons are a potential intervention for gait rehabilitation in stroke to enable repetitive walking practice to maximize neural recovery. As this is a relatively new technology for stroke, a scoping review can help guide current research and propose recommendations for advancing the research development. The aim of this scoping review was to map the current literature surrounding the use of robotic exoskeletons for gait rehabilitation in adults post-stroke. Five databases (Pubmed, OVID MEDLINE, CINAHL, Embase, Cochrane Central Register of Clinical Trials) were searched for articles from inception to October 2015. Reference lists of included articles were reviewed to identify additional studies. Articles were included if they utilized a robotic exoskeleton as a gait training intervention for adult stroke survivors and reported walking outcome measures. Of 441 records identified, 11 studies, all published within the last five years, involving 216 participants met the inclusion criteria. The study designs ranged from pre-post clinical studies (n = 7) to controlled trials (n = 4); five of the studies utilized a robotic exoskeleton device unilaterally, while six used a bilateral design. Participants ranged from sub-acute (<7 weeks) to chronic (>6 months) stroke. Training periods ranged from single-session to 8-week interventions. Main walking outcome measures were gait speed, Timed Up and Go, 6-min Walk Test, and the Functional Ambulation Category. Meaningful improvement with exoskeleton-based gait training was more apparent in sub-acute stroke compared to chronic stroke. Two of the four controlled trials showed no greater improvement in any walking outcomes compared to a control group in chronic stroke. In conclusion, clinical trials demonstrate that powered robotic exoskeletons can be used safely as a gait training intervention for stroke. Preliminary findings suggest that exoskeletal gait training is equivalent to traditional therapy for chronic stroke patients, while sub-acute patients may experience added benefit from exoskeletal gait training. Efforts should be invested in designing rigorous, appropriately powered controlled trials before powered exoskeletons can be translated into a clinical tool for gait rehabilitation post-stroke.

Single-Session Transcranial Direct Current Stimulation Temporarily Improves Symptoms, Mood, and Self-Regulatory Control in Bulimia Nervosa: A Randomised Controlled Trial.

PubMed

Kekic, Maria; McClelland, Jessica; Bartholdy, Savani; Boysen, Elena; Musiat, Peter; Dalton, Bethan; Tiza, Meyzi; David, Anthony S; Campbell, Iain C; Schmidt, Ulrike

2017-01-01

Evidence suggests that pathological eating behaviours in bulimia nervosa (BN) are underpinned by alterations in reward processing and self-regulatory control, and by functional changes in neurocircuitry encompassing the dorsolateral prefrontal cortex (DLPFC). Manipulation of this region with transcranial direct current stimulation (tDCS) may therefore alleviate symptoms of the disorder. This double-blind sham-controlled proof-of-principle trial investigated the effects of bilateral tDCS over the DLPFC in adults with BN. Thirty-nine participants (two males) received three sessions of tDCS in a randomised and counterbalanced order: anode right/cathode left (AR/CL), anode left/cathode right (AL/CR), and sham. A battery of psychological/neurocognitive measures was completed before and after each session and the frequency of bulimic behaviours during the following 24-hours was recorded. AR/CL tDCS reduced eating disorder cognitions (indexed by the Mizes Eating Disorder Cognitions Questionnaire-Revised) when compared to AL/CR and sham tDCS. Both active conditions suppressed the self-reported urge to binge-eat and increased self-regulatory control during a temporal discounting task. Compared to sham stimulation, mood (assessed with the Profile of Mood States) improved after AR/CL but not AL/CR tDCS. Lastly, the three tDCS sessions had comparable effects on the wanting/liking of food and on bulimic behaviours during the 24 hours post-stimulation. These data suggest that single-session tDCS transiently improves symptoms of BN. They also help to elucidate possible mechanisms of action and highlight the importance of selecting the optimal electrode montage. Multi-session trials are needed to determine whether tDCS has potential for development as a treatment for adult BN.

Single-Session Transcranial Direct Current Stimulation Temporarily Improves Symptoms, Mood, and Self-Regulatory Control in Bulimia Nervosa: A Randomised Controlled Trial

PubMed Central

Kekic, Maria; McClelland, Jessica; Bartholdy, Savani; Boysen, Elena; Musiat, Peter; Dalton, Bethan; Tiza, Meyzi; David, Anthony S.; Campbell, Iain C.; Schmidt, Ulrike

2017-01-01

Background Evidence suggests that pathological eating behaviours in bulimia nervosa (BN) are underpinned by alterations in reward processing and self-regulatory control, and by functional changes in neurocircuitry encompassing the dorsolateral prefrontal cortex (DLPFC). Manipulation of this region with transcranial direct current stimulation (tDCS) may therefore alleviate symptoms of the disorder. Objective This double-blind sham-controlled proof-of-principle trial investigated the effects of bilateral tDCS over the DLPFC in adults with BN. Methods Thirty-nine participants (two males) received three sessions of tDCS in a randomised and counterbalanced order: anode right/cathode left (AR/CL), anode left/cathode right (AL/CR), and sham. A battery of psychological/neurocognitive measures was completed before and after each session and the frequency of bulimic behaviours during the following 24-hours was recorded. Results AR/CL tDCS reduced eating disorder cognitions (indexed by the Mizes Eating Disorder Cognitions Questionnaire-Revised) when compared to AL/CR and sham tDCS. Both active conditions suppressed the self-reported urge to binge-eat and increased self-regulatory control during a temporal discounting task. Compared to sham stimulation, mood (assessed with the Profile of Mood States) improved after AR/CL but not AL/CR tDCS. Lastly, the three tDCS sessions had comparable effects on the wanting/liking of food and on bulimic behaviours during the 24 hours post-stimulation. Conclusions These data suggest that single-session tDCS transiently improves symptoms of BN. They also help to elucidate possible mechanisms of action and highlight the importance of selecting the optimal electrode montage. Multi-session trials are needed to determine whether tDCS has potential for development as a treatment for adult BN. PMID:28121991

Subterranean termite control examinations on current and former experimental forests and ranges

Treesearch

T. G. Shelton; T. L. Wagner; C. J Peterson; J. E. Mulrooney

2014-01-01

For more than 70 years, the USDA Forest Service’s Termite Team has engaged in research to extend the life of wood in service by studying chemical (and a few nonchemical) subterranean termite control products. These efficacy data are produced in distinct field trials on experimental forests across the USA, and are used by industry cooperators to register their products...

Theory of Mind Training in Children with Autism: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Begeer, Sander; Gevers, Carolien; Clifford, Pamela; Verhoeve, Manja; Kat, Kirstin; Hoddenbach, Elske; Boer, Frits

2011-01-01

Many children with Autism Spectrum Disorders (ASD) participate in social skills or Theory of Mind (ToM) treatments. However, few studies have shown evidence for their effectiveness. The current study used a randomized controlled design to test the effectiveness of a 16-week ToM treatment in 8-13 year old children with ASD and normal IQs (n = 40).…

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

PubMed

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

2015-12-16

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

[Treatment of asymptomatic carotid artery stenosis: improvement of evidence with new SPACE-2 design necessary].

PubMed

Reiff, T; Amiri, H; Ringleb, P A; Jansen, O; Hacke, W; Eckstein, H H; Fraedrich, G; Mudra, H; Mansmann, U

2013-12-01

Asymptomatic carotid artery stenosis may be treated with carotid endarterectomy (CEA), carotid artery stenting (CAS) or with best medical treatment (BMT) only. Definitive and evidence-based treatment recommendations for one of these options are currently not possible. Studies showing an advantage of CEA over BMT alone do not meet current standards from a pharmacological point of view. On the other hand, more recent data point to a further stroke risk reduction using BMT according to current standards. Studies on carotid artery stenting as a third alternative treatment are partially insufficient, especially when comparing CAS with BMT. Initiated in 2009, the randomized, controlled, multicenter SPACE-2 trial is intended to answer the question about the best treatment option of asymptomatic carotid artery stenosis; however, to increase recruitment rates as a condition for the successful completion of this important study, the trial design had to be modified.

Efficacy and safety of Suanzaoren decoction for primary insomnia: a systematic review of randomized controlled trials

PubMed Central

2013-01-01

Background Insomnia is a widespread human health problem, but there currently are the limitations of conventional therapies available. Suanzaoren decoction (SZRD) is a well known classic Chinese herbal prescription for insomnia and has been treating people’s insomnia for more than thousand years. The objective of this study was to evaluate the efficacy and safety of SZRD for insomnia. Methods A systematic literature search was performed for 6 databases up to July of 2012 to identify randomized control trials (RCTs) involving SZRD for insomniac patients. The methodological quality of RCTs was assessed independently using the Cochrane Handbook for Systematic Reviews of Interventions. Results Twelve RCTs with total of 1376 adult participants were identified. The methodological quality of all included trials are no more than 3/8 score. Majority of the RCTs concluded that SZRD was more significantly effective than benzodiazepines for treating insomnia. Despite these positive outcomes, there were many methodological shortcomings in the studies reviewed, including insufficient information about randomization generation and absence of allocation concealment, lack of blinding and no placebo control, absence of intention-to-treat analysis and lack of follow-ups, selective publishing and reporting, and small number of sample sizes. A number of clinical heterogeneity such as diagnosis, intervention, control, and outcome measures were also reviewed. Only 3 trials reported adverse events, whereas the other 9 trials did not provide the safety information. Conclusions Despite the apparent reported positive findings, there is insufficient evidence to support efficacy of SZRD for insomnia due to the poor methodological quality and the small number of trials of the included studies. SZRD seems generally safe, but is insufficient evidence to make conclusions on the safety because fewer studies reported the adverse events. Further large sample-size and well-designed RCTs are needed. PMID:23336848

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

PubMed

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

2016-06-01

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

Bisphosphonates for prevention of osteopenia in kidney-transplant recipients: a systematic review of randomized controlled trials.

PubMed

Wang, J; Yao, M; Xu, J-h; Shu, B; Wang, Y-j; Cui, X-j

2016-05-01

We conducted a systematic review of randomized controlled trials (RCTs) of bisphosphonates for the prevention of osteopenia in kidney-transplant recipients. Bisphosphonates improved bone mineral density at the lumbar spine and femoral neck after 12 months. However, additional well-designed RCTs are required to determine the optimal treatment strategy. Osteopenic-osteoporotic syndrome is a bone complication of renal transplantation. Bisphosphonates, calcitonin, and vitamin D analogs may be used to prevent or treat osteoporosis or bone loss after renal transplantation. However, there is currently no widely recognized strategy for the prevention of corticosteroid-induced osteoporosis. This study aims to assess the available evidence to guide the targeted use of bisphosphonates for reducing osteoporosis and bone loss in renal-transplant recipients. We searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE for randomized controlled trials of bisphosphonates for osteoporosis or bone loss after renal transplantation. A total of 352 abstracts were identified, of which 55 were considered for evaluation and 9 were included in the final analysis. The primary outcome measure was change in the bone mineral density (BMD) of the lumbar spine and femoral neck after 12 months. Data extraction was performed independently by two investigators. BMD at the lumbar spine was improved after treatment with bisphosphonates [9 trials; 418 patients; weighted mean difference (WMD), 0.61; 95 % confidence interval (CI), 0.16-1.06]. Eight trials (406 patients) that reported changes in BMD at the femoral neck also showed improved outcomes after treatment with bisphosphonates (WMD, 0.06; 95 % CI, 0.03-0.09). Bisphosphonates improve BMD at the lumbar spine and femoral neck after 12 months in renal-transplant recipients.

A protocol for a pragmatic randomized controlled trial evaluating outcomes of emergency nurse practitioner service.

PubMed

Jennings, Natasha; Gardner, Glenn; O'Reilly, Gerard

2014-09-01

To evaluate emergency nurse practitioner service effectiveness on outcomes related to quality of care and service responsiveness. Increasing service pressures in the emergency setting have resulted in the adoption of service innovation models; the most common and rapidly expanding of these is the emergency nurse practitioner. The delivery of high quality patient care in the emergency department is one of the most important service indicators to be measured in health services today. The rapid uptake of emergency nurse practitioner service in Australia has outpaced the capacity to evaluate this model in outcomes related to safety and quality of patient care. Pragmatic randomized controlled trial at one site with 260 participants. This protocol describes a definitive prospective randomized controlled trial, which will examine the impact of emergency nurse practitioner service on key patient care and service indicators. The study control will be standard emergency department care. The intervention will be emergency nurse practitioner service. The primary outcome measure is pain score reduction and time to analgesia. Secondary outcome measures are waiting time, number of patients who did not wait, length of stay in the emergency department and representations within 48 hours. Scant research enquiry evaluating emergency nurse practitioner service on patient effectiveness and service responsiveness exists currently. This study is a unique trial that will test the effectiveness of the emergency nurse practitioner service on patients who present to the emergency department with pain. The research will provide an opportunity to further evaluate emergency nurse practitioner models of care and build research capacity into the workforce. Trial registration details: Australian and New Zealand Clinical Trials Registry dated 18th August 2013, ACTRN12613000933752. © 2014 John Wiley & Sons Ltd.

Predictors of Study Attrition in a Randomized Controlled Trial Evaluating a Perinatal Home-Visiting Program with Mothers with Psychosocial Vulnerabilities

PubMed Central

Foulon, Stéphanie; Greacen, Tim; Pasquet, Blandine; Dugravier, Romain; Saïas, Thomas; Guedeney, Nicole; Guedeney, Antoine; Tubach, Florence

2015-01-01

Objective Randomised controlled trials evaluating perinatal home-visiting programs are frequently confronted with the problem of high attrition rates. The aim of the present study is to identify predictors of study attrition in a trial evaluating a perinatal home-visiting program in France. Materials and Methods CAPEDP is a French randomized trial comparing a perinatal home-visiting program using psychologists versus usual care (N = 440). The first assessment was at inclusion into the trial at the 27th week of pregnancy and the final assessment when the child reached the age of two. Attrition rates were calculated at 3 and 24 months postpartum. Stepwise logistic regression was used to identify predictors of early (between inclusion and 3 months postpartum) and later (between 3 and 24 months postpartum) attrition among social, psychological and parenting factors. Results Attrition rates were 17% and 63% at 3 and 24 months respectively. At 24 months, there was significantly more attrition in the control arm (70.6%) compared to the intervention arm (55.2%). Five independent predictors of early attrition were identified: having already had an abortion; having greater attachment insecurity as measured with the Vulnerable Attachment Style Questionnaire (VASQ); having lower global severity of psychiatric symptoms as assessed with the Symptom Check-List (SCL-90) at inclusion, being neither currently employed nor studying; and declaring no tobacco consumption during pregnancy. Being randomized into the control arm, having undergone early parental loss before age 11 and having lower global severity of psychiatric symptoms (SCL-90) at 3 months postpartum were the only variables associated with later attrition. Conclusion This study provides key information for identifying mothers who may require specific support to avoid study attrition in trials evaluating a home-visiting program. PMID:26554839

Care delivery and self-management strategies for children with epilepsy.

PubMed

Lindsay, Bruce; Bradley, Peter M

2010-12-08

Epilepsy care for children has been criticised for its lack of impact. Various service models and strategies have been developed in response to perceived inadequacies in care provision for children and their families. We set out to compare the effectiveness of specialist or dedicated teams or individuals in the care of children with epilepsy with usual care services. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library February issue, 2010), MEDLINE (1950 to March 2010), EMBASE (1988 to May 2006*), PsycINFO (1806 to March 2010) and CINAHL (1982 to March 2010).*Please note that as we currently do not have access to EMBASE, we have been unable to update this aspect of our searching. We included randomised controlled trials, controlled or matched trials, cohort studies or other prospective studies with a control group, or time series studies. Each review author independently selected studies, extracted data and assessed the quality of included studies. Four trials and five reports are included in this review. They report on four different education and counselling programmes for children, children and parents, or teenagers and parents. Each programme showed some benefits for the well-being of children with epilepsy, but each trial had methodological flaws and no single programme was evaluated by more than one study. While each of the programmes in this review showed some benefit to children with epilepsy their impacts were extremely variable. No programme showed benefits across the full range of outcomes. No study appears to have demonstrated any detrimental effects but the evidence in favour of any single programme is insufficient to make it possible to recommend one programme rather than another. More trials, carried out by independent research teams, are needed.

Mindfulness-Based Interventions for People Diagnosed with a Current Episode of an Anxiety or Depressive Disorder: A Meta-Analysis of Randomised Controlled Trials

PubMed Central

Strauss, Clara; Cavanagh, Kate; Oliver, Annie; Pettman, Danelle

2014-01-01

Objective Mindfulness-based interventions (MBIs) can reduce risk of depressive relapse for people with a history of recurrent depression who are currently well. However, the cognitive, affective and motivational features of depression and anxiety might render MBIs ineffective for people experiencing current symptoms. This paper presents a meta-analysis of randomised controlled trials (RCTs) of MBIs where participants met diagnostic criteria for a current episode of an anxiety or depressive disorder. Method Post-intervention between-group Hedges g effect sizes were calculated using a random effects model. Moderator analyses of primary diagnosis, intervention type and control condition were conducted and publication bias was assessed. Results Twelve studies met inclusion criteria (n = 578). There were significant post-intervention between-group benefits of MBIs relative to control conditions on primary symptom severity (Hedges g = −0.59, 95% CI = −0.12 to −1.06). Effects were demonstrated for depressive symptom severity (Hedges g = −0.73, 95% CI = −0.09 to −1.36), but not for anxiety symptom severity (Hedges g = −0.55, 95% CI = 0.09 to −1.18), for RCTs with an inactive control (Hedges g = −1.03, 95% CI = −0.40 to −1.66), but not where there was an active control (Hedges g = 0.03, 95% CI = 0.54 to −0.48) and effects were found for MBCT (Hedges g = −0.39, 95% CI = −0.15 to −0.63) but not for MBSR (Hedges g = −0.75, 95% CI = 0.31 to −1.81). Conclusions This is the first meta-analysis of RCTs of MBIs where all studies included only participants who were diagnosed with a current episode of a depressive or anxiety disorder. Effects of MBIs on primary symptom severity were found for people with a current depressive disorder and it is recommended that MBIs might be considered as an intervention for this population. PMID:24763812

Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia (ARREST): study protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Staphylococcus aureus bacteraemia is a common and serious infection, with an associated mortality of ~25%. Once in the blood, S. aureus can disseminate to infect almost any organ, but bones, joints and heart valves are most frequently affected. Despite the infection’s severity, the evidence guiding optimal antibiotic therapy is weak: fewer than 1,500 patients have been included in 16 randomised controlled trials investigating S. aureus bacteraemia treatment. It is uncertain which antibiotics are most effective, their route of administration and duration, and whether antibiotic combinations are better than single agents. We hypothesise that adjunctive rifampicin, given in combination with a standard first-line antibiotic, will enhance killing of S. aureus early in the treatment course, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. Our aim is to determine whether adjunctive rifampicin reduces all-cause mortality within 14 days and bacteriological failure or death within 12 weeks from randomisation. Methods We will perform a parallel group, randomised (1:1), blinded, placebo-controlled trial in NHS hospitals across the UK. Adults (≥18 years) with S. aureus (meticillin-susceptible or resistant) grown from at least one blood culture who have received ≤96 h of active antibiotic therapy for the current infection and do not have contraindications to the use of rifampicin will be eligible for inclusion. Participants will be randomised to adjunctive rifampicin (600-900mg/day; orally or intravenously) or placebo for the first 14 days of therapy in combination with standard single-agent antibiotic therapy. The co-primary outcome measures will be all-cause mortality up to 14 days from randomisation and bacteriological failure/death (all-cause) up to 12 weeks from randomisation. 940 patients will be recruited, providing >80% power to detect 45% and 30% reductions in the two co-primary endpoints of death by 14 days and bacteriological failure/death by 12 weeks respectively. Discussion This pragmatic trial addresses the long-standing hypothesis that adjunctive rifampicin improves outcome from S. aureus bacteraemia through enhanced early bacterial killing. If proven correct, it will provide a paradigm through which further improvements in outcome from S. aureus bacteraemia can be explored. Trial registration Current Controlled Trial ISRCTN 37666216 PMID:23249501

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): study protocol for a randomized controlled trial.

PubMed

2012-08-28

Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH2O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure ≤30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method. ClinicalTrials.gov Identifier: NCT01374022.

Concise Review: Stem Cell Interventions for People With Cerebral Palsy: Systematic Review With Meta-Analysis.

PubMed

Novak, Iona; Walker, Karen; Hunt, Rod W; Wallace, Euan M; Fahey, Michael; Badawi, Nadia

2016-08-01

: Evidence for stem cells as a potential intervention for cerebral palsy is emerging. Our objective was to determine the efficacy and safety of stem cells for improving motor and cognitive function of people with cerebral palsy. Searches were conducted in October 2015 in CENTRAL, EMBASE, MEDLINE, and Cochrane Libraries. Randomized controlled trials and controlled clinical trials of stem cells for cerebral palsy were included. Two authors independently decided upon included trials, extracted data, quality, and risk of bias. The primary outcome was gross motor function. Secondary outcomes were cognitive function and adverse events (AEs). Effects were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI), using a random-effects model. Five trials comprising 328 participants met inclusion criteria. Four cell types were studied: olfactory ensheathing, neural, neural progenitors, and allogeneic umbilical cord blood (UCBs). Transplantation procedures differed from central nervous system neurosurgical transplantation to intravenous/arterial infusion. Participants were followed short-term for only 6 months. Evidence of variable quality indicated a small statistically significant intervention effect from stem cells on gross motor skills (SMD 1.27; 95% CI 0.22, 2.33), with UCBs most effective. There were insufficient and heterogeneous data to compare cognitive effects. Serious AEs were rare (n = 4/135 [3%] stem cells; n = 3/139 [2%] controls). Stem cells appeared to induce short-term improvements in motor skills. Different types of stem cell interventions were compared, meaning the data were heterogeneous and are a study limitation. Further randomized controlled trials are warranted, using rigorous methodologies. Stem cells are emerging as a scientifically plausible treatment and possible cure for cerebral palsy, but are not yet proven. The lack of valid animal models has significantly hampered the scope of clinical trials. Despite the state of current treatment evidence, parents remain optimistic about the potential improvements from stem cell intervention and feel compelled to exhaust all therapeutic options, including stem cell tourism. Receiving unproven therapies from unvalidated sources is potentially dangerous. Thus it is essential that researchers and clinicians stay up to date. A systematic review and meta-analysis summarizing and aggregating current research data may provide more conclusive evidence to inform treatment decision making and help direct future research. ©AlphaMed Press.

Concise Review: Stem Cell Interventions for People With Cerebral Palsy: Systematic Review With Meta-Analysis

PubMed Central

Walker, Karen; Hunt, Rod W.; Wallace, Euan M.; Fahey, Michael; Badawi, Nadia

2016-01-01

Evidence for stem cells as a potential intervention for cerebral palsy is emerging. Our objective was to determine the efficacy and safety of stem cells for improving motor and cognitive function of people with cerebral palsy. Searches were conducted in October 2015 in CENTRAL, EMBASE, MEDLINE, and Cochrane Libraries. Randomized controlled trials and controlled clinical trials of stem cells for cerebral palsy were included. Two authors independently decided upon included trials, extracted data, quality, and risk of bias. The primary outcome was gross motor function. Secondary outcomes were cognitive function and adverse events (AEs). Effects were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI), using a random-effects model. Five trials comprising 328 participants met inclusion criteria. Four cell types were studied: olfactory ensheathing, neural, neural progenitors, and allogeneic umbilical cord blood (UCBs). Transplantation procedures differed from central nervous system neurosurgical transplantation to intravenous/arterial infusion. Participants were followed short-term for only 6 months. Evidence of variable quality indicated a small statistically significant intervention effect from stem cells on gross motor skills (SMD 1.27; 95% CI 0.22, 2.33), with UCBs most effective. There were insufficient and heterogeneous data to compare cognitive effects. Serious AEs were rare (n = 4/135 [3%] stem cells; n = 3/139 [2%] controls). Stem cells appeared to induce short-term improvements in motor skills. Different types of stem cell interventions were compared, meaning the data were heterogeneous and are a study limitation. Further randomized controlled trials are warranted, using rigorous methodologies. Significance Stem cells are emerging as a scientifically plausible treatment and possible cure for cerebral palsy, but are not yet proven. The lack of valid animal models has significantly hampered the scope of clinical trials. Despite the state of current treatment evidence, parents remain optimistic about the potential improvements from stem cell intervention and feel compelled to exhaust all therapeutic options, including stem cell tourism. Receiving unproven therapies from unvalidated sources is potentially dangerous. Thus it is essential that researchers and clinicians stay up to date. A systematic review and meta-analysis summarizing and aggregating current research data may provide more conclusive evidence to inform treatment decision making and help direct future research. PMID:27245364

A cluster-randomized controlled trial of strategies to increase adolescents’ physical activity and motivation during physical education lessons: the Motivating Active Learning in Physical Education (MALP) trial

PubMed Central

2012-01-01

Background The physical activity (PA) levels of many children and adolescents in Australia are currently insufficient to promote health benefits. Physical education (PE) programs aim to promote PA and reach nearly all school-aged children, but PA levels within PE lessons are often low. PE teachers may influence children’s motivation to be physically active in PE lessons, but little is known about teacher strategies that effectively motivate children to participate in PA, and few intervention studies have examined motivational strategies in PE. The purpose of this study was to compare the effect of three motivational strategies, each based on Self-Determination Theory (SDT), on PA levels, and their hypothesized antecedents, during year 8 PE lessons. Methods/design This study employed a cluster-randomized controlled trial design. Following a familiarization session, PA levels and hypothesized PA antecedents were measured during a baseline lesson and a post-intervention or control lesson. Teachers (n = 16) and their classes from five secondary schools in Sydney, Australia were randomly assigned into four blocks and instructed to provide one of four 20-min lesson teaching strategy conditions: (1) explaining the relevance of activities; (2) providing choice from PA options selected by the teacher; (3) providing equipment and free choice of activities; or (4) usual practice. The primary outcomes were lesson time spent in moderate-to-vigorous PA, and motivation towards the lesson. Secondary outcomes were perceptions of teacher behavior, psychological needs satisfaction, and lesson time spent in sedentary behavior. PA and sedentary behavior were measured during baseline and post-intervention lessons with waist-mounted Actigraph GT3X accelerometers. Teacher behavior, psychological needs satisfaction, and motivation were assessed via questionnaires at the end of each lesson. Linear mixed-model analyses will be run on all outcomes, with students nested within teachers as a random effect. Discussion Study findings will inform the development of effective SDT-based teaching strategy interventions to enhance students’ psychological needs satisfaction, motivation, and PA levels. More effective teaching strategies may be identified that are capable of improving adolescents’ PA levels, and thereby provide beneficial population health outcomes. Trial registration This trial is registered with Current Controlled Trials and is traceable as ISRCTN07038258. PMID:23025261

Estimating statistical power for open-enrollment group treatment trials.

PubMed

Morgan-Lopez, Antonio A; Saavedra, Lissette M; Hien, Denise A; Fals-Stewart, William

2011-01-01

Modeling turnover in group membership has been identified as a key barrier contributing to a disconnect between the manner in which behavioral treatment is conducted (open-enrollment groups) and the designs of substance abuse treatment trials (closed-enrollment groups, individual therapy). Latent class pattern mixture models (LCPMMs) are emerging tools for modeling data from open-enrollment groups with membership turnover in recently proposed treatment trials. The current article illustrates an approach to conducting power analyses for open-enrollment designs based on the Monte Carlo simulation of LCPMM models using parameters derived from published data from a randomized controlled trial comparing Seeking Safety to a Community Care condition for women presenting with comorbid posttraumatic stress disorder and substance use disorders. The example addresses discrepancies between the analysis framework assumed in power analyses of many recently proposed open-enrollment trials and the proposed use of LCPMM for data analysis. Copyright © 2011 Elsevier Inc. All rights reserved.

Emotions in Go/NoGo conflicts.

PubMed

Schacht, Annekathrin; Nigbur, Roland; Sommer, Werner

2009-11-01

On the basis of current emotion theories and functional and neurophysiological ties between the processing of conflicts and errors on the one hand and errors and emotions on the other hand we predicted that conflicts between prepotent Go responses and occasional NoGo trials in the Go/NoGo task would induce emotions. Skin conductance responses (SCRs), corrugator muscle activity, and startle blink responses were measured in three experiments requiring speeded Go responses intermixed with NoGo trials of different relative probability and in a choice reaction experiment serving as a control. NoGo trials affected several of these emotion-sensitive indicators as SCRs and startle blinks were reduced whereas corrugator activity was prolonged as compared to Go trials. From the pattern of findings we suggest that NoGo conflicts are not aversive. Instead, they appear to be appraised as obstructive for the response goal and as less action relevant than Go trials.

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

PubMed

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

2016-02-17

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

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

PubMed

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

2007-11-19

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

Examining Participant Engagement in an Information Technology-Based Physical Activity and Nutrition Intervention for Men: The Manup Randomized Controlled Trial

PubMed Central

Vandelanotte, Corneel; Dixon, Marcus W; Rosenkranz, Richard; Caperchione, Cristina; Hooker, Cindy; Karunanithi, Mohan; Kolt, Gregory S; Maeder, Anthony; Ding, Hang; Taylor, Pennie; Duncan, Mitch J

2014-01-01

Background Males experience a shorter life expectancy and higher rates of chronic diseases compared to their female counterparts. To improve health outcomes among males, interventions specifically developed for males that target their health behaviors are needed. Information technology (IT)-based interventions may be a promising intervention approach in this population group, however, little is known about how to maximize engagement and retention in Web-based programs. Objective The current study sought to explore attributes hypothesized to influence user engagement among a subsample of participants from the ManUp study, a randomized controlled trial testing the efficacy of an interactive Web-based intervention for promoting physical activity and nutrition among middle-aged males. Methods Semistructured interviews were conducted and audiotaped with 20 of the ManUp participants. Interview questions were based on a conceptual model of engagement and centered on why participants took part in the study, what they liked and did not like about the intervention they received, and how they think the intervention could be improved. Interview recordings were transcribed and coded into themes. Results There were five themes that were identified in the study. These themes were: (1) users’ motives, (2) users’ desired outcomes, (3) users’ positive experiences, (4) users’ negative emotions, and (5) attributes desired by user. Conclusions There is little research in the field that has explored user experiences in human-computer interactions and how such experiences may relate to engagement, especially among males. Although not conclusive, the current study provides some insight into what personal attributes of middle-aged males (such as their key motives and goals for participating) and attributes of the intervention materials (such as usability, control, and interactivity) may impact on user engagement in this group. These findings will be helpful for informing the design and implementation of future health behavior interventions for males. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN12611000081910; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12611000081910 (Archived by WebCite at http://www.webcitation.org/6M4lBlvCA). PMID:24389361

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.

Does telecare prolong community living in dementia? A study protocol for a pragmatic, randomised controlled trial

PubMed Central

2013-01-01

Background Assistive technology and telecare (ATT) are relatively new ways of delivering care and support to people with social care needs. It is claimed that ATT reduces the need for community care, prevents unnecessary hospital admission, and delays or prevents admission into residential or nursing care. The current economic situation in England has renewed interest in ATT instead of community care packages. However, at present, the evidence base to support claims about the impact and effectiveness of ATT is limited, despite its potential to mitigate the high financial cost of caring for people with dementia and the social and psychological cost to unpaid carers. Method/design ATTILA (Assistive Technology and Telecare to maintain Independent Living At Home for People with Dementia) is a pragmatic, multi-centre, randomised controlled trial over 104 weeks that compares outcomes for people with dementia who receive ATT and those who receive equivalent community services but not ATT. The study hypothesis is that fewer people in the ATT group will go into institutional care over the 4-year period for which the study is funded. The study aims to recruit 500 participants, living in community settings, with dementia or significant cognitive impairment, who have recently been referred to social services. Primary outcome measures are time in days from randomisation to institutionalisation and cost effectiveness. Secondary outcomes are caregiver burden, health-related quality of life in carers, number and severity of serious adverse events, and data on acceptability, applicability and reliability of ATT intervention packages. Assessments will be undertaken in weeks 0 (baseline), 12, 24, 52 and 104 or until institutionalisation or withdrawal of the participant from the trial. Discussion In a time of financial austerity, CASSRs in England are increasingly turning to ATT in the belief that it will deliver good outcomes for less money. There is an absence of robust evidence for the cost-effectiveness and benefit of using assistive technology and telecare. The ATTILA trial meets a pressing need for robust, generalisable evidence to either justify continuing investment or reappraise the appropriate scale of ATT use. Trial registration Current Controlled Trials ISRCTN86537017 PMID:24152600

Single dose treatment of malaria - current status and perspectives.

PubMed

Mischlinger, Johannes; Agnandji, Selidji T; Ramharter, Michael

2016-07-01

Despite increased international efforts for control and ultimate elimination, malaria remains a major health problem. Currently, artemisinin-based combination therapies are the treatment of choice for uncomplicated malaria exhibiting high efficacy in clinical trial settings in sub-Saharan Africa. However, their administration over a three-day period is associated with important problems of treatment adherence resulting in markedly reduced effectiveness of currently recommended antimalarials under real world settings. Antimalarial drug candidates and antimalarial drug combinations currently under advanced clinical development for the indication as single dose antimalarial therapy. Expert commentary: Several new drug candidates and combinations are currently undergoing pivotal proof-of-concept studies or clinical development programmes. The development of a single dose combination therapy would constitute a breakthrough in the control of malaria. Such an innovative treatment approach would simultaneously close the effectiveness gap of current three-day therapies and revolutionize population based interventions in the context of malaria elimination campaigns.

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

PubMed

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

2008-08-06

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

Evaluation of Post-Trial Reviews of Courts-Martial within the Department of the Navy

DTIC Science & Technology

2010-12-10

subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. 1. REPORT DATE...Moreno case in an effort to take control of a situation the Navy and Marine Corps would not address. Over the years, the appellate courts repeatedly...inexperienced, first-tour lieutenants. Consequently, having senior, experienced counsel in supervisory positions is essential to controlling quality

Lifestyle Triple P: a parenting intervention for childhood obesity

PubMed Central

2012-01-01

Background Reversing the obesity epidemic requires the development and evaluation of childhood obesity intervention programs. Lifestyle Triple P is a parent-focused group program that addresses three topics: nutrition, physical activity, and positive parenting. Australian research has established the efficacy of Lifestyle Triple P, which aims to prevent excessive weight gain in overweight and obese children. The aim of the current randomized controlled trial is to assess the effectiveness of the Lifestyle Triple P intervention when applied to Dutch parents of overweight and obese children aged 4–8 years. This effectiveness study is called GO4fit. Methods/Design Parents of overweight and obese children are being randomized to either the intervention or the control group. Those assigned to the intervention condition receive the 14-week Lifestyle Triple P intervention, in which they learn a range of nutritional, physical activity and positive parenting strategies. Parents in the control group receive two brochures, web-based tailored advice, and suggestions for exercises to increase active playing at home. Measurements are taken at baseline, directly after the intervention, and at one year follow-up. Primary outcome measure is the children’s body composition, operationalized as BMI z-score, waist circumference, and fat mass (biceps and triceps skinfolds). Secondary outcome measures are children’s dietary behavior and physical activity level, parenting practices, parental feeding style, parenting style, parental self-efficacy, and body composition of family members (parents and siblings). Discussion Our intervention is characterized by a focus on changing general parenting styles, in addition to focusing on changing specific parenting practices, as obesity interventions typically do. Strengths of the current study are the randomized design, the long-term follow-up, and the broad range of both self-reported and objectively measured outcomes. Trial Registration Current Controlled Trials NTR 2555 MEC AzM/UM NL 31988.068.10 / MEC 10-3-052 PMID:22471971

Comparing exercise interventions to increase persistence with physical exercise and sporting activity among people with hypertension or high normal blood pressure: study protocol for a randomised controlled trial.

PubMed

Fife-Schaw, Chris; de Lusignan, Simon; Wainwright, Joe; Sprake, Hannah; Laver, Suzannah; Heald, Victoria; Orton, Julian; Prescott, Matt; Carr, Helen; O'Neill, Mark

2014-08-28

Increasing physical activity is known to have health benefits for people with hypertension and related conditions. Current general practitioner referrals for gym-based exercise increase physical activity but meta-analyses show that while these are effective the absolute health risk reduction is small due to patients failing to maintain activity levels over time. This study assesses the effectiveness of two sports-oriented interventions that are intended to bridge the intention-behaviour gap and thus increase the likelihood of sustained increases in physical activity. Four-arm randomised controlled trial. The study tests two types of intervention that are intended to increase physical activity among currently inactive 18- to 74-year-old people with hypertension or high-normal blood pressure. This study will assess the effectiveness of a 12-week sports-oriented exercise programme, the efficacy of a web-delivered self-help tool to promote and support sports participation and healthy behaviour change and the effect of these interventions in combination. The control arm will be a standard care general practitioner referral for gym-based exercise. Participants will be allocated using block randomisation. The first author and primary analyst is blinded to participant allocation. The primary outcome measures will be time spent in physical activity assessed in metabolic equivalent minutes per week using the International Physical Activity Questionnaire 1 year after commencement of the intervention. Secondary outcomes include increased involvement in sporting activity and biomedical health outcomes including change in body mass index, and waist and hip measurement and reductions in blood pressure. If proven to be superior to general practitioner referrals for gym-based exercise, these sports-oriented interventions would constitute low-cost alternatives. The next stage would be a full economic evaluation of the interventions. Current Controlled Trials ISRCTN71952900 (7 June 2013).

Pharmacological interventions for pain in children and adolescents with life-limiting conditions.

PubMed

Beecham, Emma; Candy, Bridget; Howard, Richard; McCulloch, Renée; Laddie, Jo; Rees, Henrietta; Vickerstaff, Victoria; Bluebond-Langner, Myra; Jones, Louise

2015-03-13

Pain is one of the most common symptoms in children and young people (CYP) with life-limiting conditions (LLCs) which include a wide range of diagnoses including cancer. The current literature indicates that pain is not well managed, however the evidence base to guide clinicians is limited. There is a clear need for evidence from a systematic review to inform prescribing. To evaluate the evidence on the effectiveness of different pharmacological interventions used for pain in CYP with LLCs. The following electronic databases were searched up to December 2014: CENTRAL (in the Cochrane Library), MEDLINE, EMBASE, PsycINFO and CINAHL. In addition, we searched conference proceedings and reference lists of included studies. For completeness, we also contacted experts in the field. No language restrictions were applied. Randomised controlled trials (RCTs), quasi-randomised studies and other studies that included a clearly defined comparator group were included. The studies investigated pharmacological treatments for pain associated with LLCs in CYP. The treatment included those specifically developed to treat pain and those that acted as an adjuvant, where the treatment was not primarily developed to treat pain but has pain relieving properties. The LLC was identified by its inclusion in the Richard Hain Directory of LLCs. Citations were screened by five review authors. Data were extracted by one review author and checked by a second. Two review authors assessed the risk of bias of included studies. A sufficient number of studies using homogeneous outcomes was not identified so a meta-analysis was not possible. We identified 24,704 citations from our database search. Nine trials with 379 participants fulfilled our inclusion criteria. Participants had cerebral palsy (CP) in five of the studies and osteogenesis imperfecta (OI) in the other four. Participants across the trials ranged in age from 2 to 19 years. All studies, apart from one cross-over trial, were parallel designed RCTs. Three of the trials on CP evaluated intrathecal baclofen (ITB) and two botulinum toxin A (BoNT-A). All of the OI trials evaluated the use of bisphosphonates (two alendronate and one pamidronate). No trials were identified that evaluated a commonly used analgesic in this patient group. Pain was a secondary outcome in five of the eight identified studies. Overall the quality of the trials was mixed. Only one study involved over 100 participants.For the two ITB studies for pain in CP, in the same study population but assessed at different time points in their disease, both found an effect on pain favouring the intervention compared to the control group (standard care or placebo) (mean difference (MD) 4.20, 95% confidence interval (CI) 2.15 to 6.25; MD 26.60, 95% CI 2.61 to 50.59, respectively). In these studies most of the adverse events related to the procedure or device for administration rather than the drug, such as swelling at the pump site. In one trial there were also eight serious adverse effects; these included difficulty swallowing and an epileptic seizure. The trial did not state if these occurred in the intervention group. At follow-up in both BoNT-A trials there was no evidence of a difference in pain between the trial arms among CP participants. The adverse events in the BoNT-A trials mostly involved those who received the intervention drug and involved seizures. Gastrointestinal problems were the most frequent adverse event in those who received alendronate. The trial investigating pamidronate found no evidence of a difference in pain compared to the control group. No adverse events were reported in this trial. Published, controlled evidence on the pharmacological interventions for pain in CYP with LLCs is limited. The evidence that is currently available evaluated pain largely as a secondary outcome and the drugs used were all adjuvants and not always commonly used in general paediatric palliative care for pain. Based on current data this systematic review is unable to determine the effects of pharmacological interventions for pain for CYP with LLCs. Future trials with larger populations should examine the effects of the drugs commonly used as analgesics; with the rising prevalence of many LLCs this becomes more necessary.

Influence of price discounts and skill-building strategies on purchase and consumption of healthy food and beverages: outcomes of the Supermarket Healthy Eating for Life randomized controlled trial.

PubMed

Ball, Kylie; McNaughton, Sarah A; Le, Ha N D; Gold, Lisa; Ni Mhurchu, Cliona; Abbott, Gavin; Pollard, Christina; Crawford, David

2015-05-01

Fiscal strategies are increasingly considered upstream nutrition promotion measures. However, few trials have investigated the effectiveness or cost effectiveness of pricing manipulations on diet in real-world settings. We assessed the effects on fruit, vegetable, and beverage purchasing and consumption of a 20% price-reduction intervention, a tailored skills-based behavior-change intervention, and a combined intervention compared with a control condition. The Supermarket Healthy Eating for Life trial was a randomized controlled trial conducted over 3 mo [baseline (time 1) to postintervention (time 2) with a 6-mo follow-up (time 3)]. Female primary household shoppers in Melbourne, Australia, were randomly assigned to a 1) skill-building (n = 160), 2) price-reduction (n = 161), 3) combined skill-building and price-reduction (n = 160), or 4) control (n = 161) group. Supermarket transaction data and surveys were used to measure the following study outcomes: fruit, vegetable, and beverage purchases and self-reported fruit and vegetable consumption at each time point. At 3 mo (time 2), price reduction-alone participants purchased more total vegetables and frozen vegetables than did controls. Price reduction-alone and price reduction-plus-skill-building participants purchased more fruit than did controls. Relative to controls, in the price-reduction group, total vegetable consumption increased by 233 g/wk (3.1 servings or 15% more than at baseline), and fruit purchases increased by 364 g/wk (2.4 servings; 35% more than at baseline). Increases were not maintained 6 mo postintervention (time 3). Price reduction-alone participants showed a tendency for a slight increase in fruit consumption at time 2 (P = 0.09) that was maintained at time 3 (P = 0.014). No intervention improved purchases of bottled water or low-calorie beverages. A 20% price reduction in fruit and vegetables resulted in increased purchasing per household of 35% for fruit and 15% for vegetables over the price-reduction period. These findings show that price modifications can directly increase produce purchases. The Supermarket Healthy Eating for Life trial was registered at Current Controlled Trials Registration as ISRCTN39432901. © 2015 American Society for Nutrition.

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

PubMed

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

2014-05-24

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

A theory-based online health behaviour intervention for new university students (U@Uni:LifeGuide): results from a repeat randomized controlled trial.

PubMed

Cameron, David; Epton, Tracy; Norman, Paul; Sheeran, Paschal; Harris, Peter R; Webb, Thomas L; Julious, Steven A; Brennan, Alan; Thomas, Chloe; Petroczi, Andrea; Naughton, Declan; Shah, Iltaf

2015-12-07

This paper reports the results of a repeat trial assessing the effectiveness of an online theory-based intervention to promote healthy lifestyle behaviours in new university students. The original trial found that the intervention reduced the number of smokers at 6-month follow-up compared with the control condition, but had non-significant effects on the other targeted health behaviours. However, the original trial suffered from low levels of engagement, which the repeat trial sought to rectify. Three weeks before staring university, all incoming undergraduate students at a large university in the UK were sent an email inviting them to participate in the study. After completing a baseline questionnaire, participants were randomly allocated to intervention or control conditions. The intervention consisted of a self-affirmation manipulation, health messages based on the theory of planned behaviour and implementation intention tasks. Participants were followed-up 1 and 6 months after starting university. The primary outcome measures were portions of fruit and vegetables consumed, physical activity levels, units of alcohol consumed and smoking status at 6-month follow-up. The study recruited 2,621 students (intervention n=1346, control n=1275), of whom 1495 completed at least one follow-up (intervention n=696, control n=799). Intention-to-treat analyses indicated that the intervention had a non-significant effect on the primary outcomes, although the effect of the intervention on fruit and vegetable intake was significant in the per-protocol analyses. Secondary analyses revealed that the intervention had significant effects on having smoked at university (self-report) and on a biochemical marker of alcohol use. Despite successfully increasing levels of engagement, the intervention did not have a significant effect on the primary outcome measures. The relatively weak effects of the intervention, found in both the original and repeat trials, may be due to the focus on multiple versus single health behaviours. Future interventions targeting the health behaviour of new university students should therefore focus on single health behaviours. Current Controlled Trials ISRCTN07407344 .

Involving older people in a multi-centre randomised trial of a complex intervention in pre-hospital emergency care: implementation of a collaborative model.

PubMed

Koniotou, Marina; Evans, Bridie Angela; Chatters, Robin; Fothergill, Rachael; Garnsworthy, Christopher; Gaze, Sarah; Halter, Mary; Mason, Suzanne; Peconi, Julie; Porter, Alison; Siriwardena, A Niroshan; Toghill, Alun; Snooks, Helen

2015-07-10

Health services research is expected to involve service users as active partners in the research process, but few examples report how this has been achieved in practice in trials. We implemented a model to involve service users in a multi-centre randomised controlled trial in pre-hospital emergency care. We used the generic Standard Operating Procedure (SOP) from our Clinical Trials Unit (CTU) as the basis for creating a model to fit the context and population of the SAFER 2 trial. In our model, we planned to involve service users at all stages in the trial through decision-making forums at 3 levels: 1) strategic; 2) site (e.g. Wales; London; East Midlands); 3) local. We linked with charities and community groups to recruit people with experience of our study population. We collected notes of meetings alongside other documentary evidence such as attendance records and study documentation to track how we implemented our model. We involved service users at strategic, site and local level. We also added additional strategic level forums (Task and Finish Groups and Writing Days) where we included service users. Service user involvement varied in frequency and type across meetings, research stages and locations but stabilised and increased as the trial progressed. Involving service users in the SAFER 2 trial showed how it is feasible and achievable for patients, carers and potential patients sharing the demographic characteristics of our study population to collaborate in a multi-centre trial at the level which suited their health, location, skills and expertise. A standard model of involvement can be tailored by adopting a flexible approach to take account of the context and complexities of a multi-site trial. Current Controlled Trials ISRCTN60481756. Registered: 13 March 2009.

Theory based interventions for caries related sugar intake in adults: systematic review.

PubMed

Al Rawahi, Said Hartih; Asimakopoulou, Koula; Newton, Jonathon Timothy

2017-07-25

Theories of behavior change are essential in the design of effective behaviour change strategies. No studies have assessed the effectiveness of interventions based on psychological theories to reduce sugar intake related to dental caries. The study assessed the effect of interventions based on Social Congition Models (SCMs) on sugar intake in adults, when compared with educational interventions or no intervention. A range of papers were considered: Systematic review Systematic Reviews with or without Meta Analyses; Randomised Controlled Trials; Controlled Clinical Trials and Before and after studies, of interventions based on Social Cognition Models aimed at dietary intake of sugar in adults. The Cochrane database including: Oral Health Group's Trials Register (2015), MEDLINE (from 1966 to September 2015), EMBASE (from 1980 to September 2015), PsycINFO (from 1966 to September 2015) were searched. No article met the full eligibility criteria for the current systematic review so no articles were included. There is a need for more clinical trials to assess the effectiveness of interventions based on psychological theory in reducing dietary sugar intake among adults. PROSPERO: CRD42015026357 .

Improving the retention rate for residential treatment of substance abuse by sequential intervention for social anxiety

PubMed Central

2014-01-01

Background Residential drug rehabilitation is often seen as a treatment of last resort for people with severe substance abuse issues. These clients present with more severe symptoms, and frequent psychiatric comorbidities relative to outpatients. Given the complex nature of this client group, a high proportion of clients seeking treatment often do not enter treatment, and of those who do, many exit prematurely. Given the highly social nature of residential drug rehabilitation services, it has been argued that social anxieties might decrease the likelihood of an individual entering treatment, or increase the likelihood of them prematurely exiting treatment. The current paper reports on the protocol of a Randomised Control Trial which examined whether treatment of social anxiety prior to entry to treatment improves entry rates and retention in residential drug rehabilitation. Method/design A Randomised Control Trial comparing a social skills treatment with a treatment as usual control group was employed. The social skills training program was based on the principles of Cognitive Behaviour Therapy, and was adapted from Ron Rapee’s social skills training program. A permutated block randomisation procedure was utilised. Participants are followed up at the completion of the program (or baseline plus six weeks for controls) and at three months following entry into residential rehabilitation (or six months post-baseline for participants who do not enter treatment). Discussion The current study could potentially have implications for addressing social anxiety within residential drug treatment services in order to improve entry and retention in treatment. The results might suggest that the use of additional screening tools in intake assessments, a focus on coping with social anxieties in support groups for clients waiting to enter treatment, and greater awareness of social anxiety issues is warranted. Australian New Zealand clinical trials registry Australian New Zealand Clinical Trials Registry (ACTRN) registration number: ACTRN12611000579998 PMID:24533512

The mPED randomized controlled clinical trial: applying mobile persuasive technologies to increase physical activity in sedentary women protocol.

PubMed

Fukuoka, Yoshimi; Komatsu, Judith; Suarez, Larry; Vittinghoff, Eric; Haskell, William; Noorishad, Tina; Pham, Kristin

2011-12-14

Despite the significant health benefits of regular physical activity, approximately half of American adults, particularly women and minorities, do not meet the current physical activity recommendations. Mobile phone technologies are readily available, easily accessible and may provide a potentially powerful tool for delivering physical activity interventions. However, we need to understand how to effectively apply these mobile technologies to increase and maintain physical activity in physically inactive women. The purpose of this paper is to describe the study design and protocol of the mPED (mobile phone based physical activity education) randomized controlled clinical trial that examines the efficacy of a 3-month mobile phone and pedometer based physical activity intervention and compares two different 6-month maintenance interventions. A randomized controlled trial (RCT) with three arms; 1) PLUS (3-month mobile phone and pedometer based physical activity intervention and 6-month mobile phone diary maintenance intervention), 2) REGULAR (3-month mobile phone and pedometer based physical activity intervention and 6-month pedometer maintenance intervention), and 3) CONTROL (pedometer only, but no intervention will be conducted). A total of 192 physically inactive women who meet all inclusion criteria and successfully complete a 3-week run-in will be randomized into one of the three groups. The mobile phone serves as a means of delivering the physical activity intervention, setting individualized weekly physical activity goals, and providing self-monitoring (activity diary), immediate feedback and social support. The mobile phone also functions as a tool for communication and real-time data capture. The primary outcome is objectively measured physical activity. If efficacy of the intervention with a mobile phone is demonstrated, the results of this RCT will be able to provide new insights for current behavioral sciences and mHealth. ClinicalTrials.gov#:NCTO1280812.

Efficacy of a 3 month training program on the jump-landing technique in jump-landing sports. Design of a cluster randomized controlled trial

PubMed Central

2010-01-01

Background With the relatively high rate of injuries to the lower extremity due to jump-landing movement patterns and the accompanied high costs, there is need for determining potential preventive programs. A program on the intervention of jump-landing technique is possibly an important preventative measure since it appeared to reduce the incidence of lower extremity injuries. In real life situations, amateur sports lack the infrastructure and funds to have a sports physician or therapist permanently supervising such a program. Therefore the current prevention program is designed so that it could be implemented by coaches alone. Objective The objective of this randomized controlled trial is to evaluate the effect of a coach supervised intervention program targeting jump-landing technique on the incidence of lower extremity injuries. Methods Of the 110 Flemish teams of the elite division, 24 teams are included and equally randomized to two study groups. An equal selection of female and male teams with allocation to intervention and control group is obtained. The program is a modification of other prevention programs previously proven to be effective. All exercises in the current program are adjusted so that a more progressive development in the exercise is presented. Both the control and intervention group continue with their normal training routine, while the intervention group carries out the program on jump-landing technique. The full intervention program has a duration of three months and is performed 2 times a week during warm-up (5-10 min). Injuries are registered during the entire season. Discussion The results of this study can give valuable information on the effect of a coach supervised intervention program on jump-landing technique and injury occurrence. Results will become available in 2011. Trial registration Trial registration number: NTR2560 PMID:21144030

Selective internal radiotherapy (SIRT) versus transarterial chemoembolization (TACE) for the treatment of intrahepatic cholangiocellular carcinoma (CCC): study protocol for a randomized controlled trial.

PubMed

Kloeckner, Roman; Ruckes, Christian; Kronfeld, Kai; Wörns, Marcus Alexander; Weinmann, Arndt; Galle, Peter Robert; Lang, Hauke; Otto, Gerd; Eichhorn, Waltraud; Schreckenberger, Mathias; Dueber, Christoph; Pitton, Michael Bernhard

2014-08-06

Cholangiocellular carcinoma is the second most common primary liver cancer after hepatocellular carcinoma. Over the last 30 years, the incidence of intrahepatic cholangiocellular carcinoma has risen continuously worldwide. Meanwhile, the intrahepatic cholangiocellular carcinoma has become more common than the extrahepatic growth type and currently accounts for 10-15% of all primary hepatic malignancies. Intrahepatic cholangiocellular carcinoma is typically diagnosed in advanced stages due to late clinical symptoms and an absence of classic risk factors. A late diagnosis precludes curative surgical resection. There is evidence that transarterial chemoembolization leads to better local tumor control and prolongs survival compared to systemic chemotherapy. New data indicates that selective internal radiotherapy, also referred to as radioembolization, provides promising results for treating intrahepatic cholangiocellular carcinoma. This pilot study is a randomized, controlled, single center, phase II trial. Twenty-four patients with intrahepatic cholangiocellular carcinoma will be randomized in a 1:1 ratio to receive either chemoembolization or radioembolization. Randomization will be stratified according to tumor load. Progression-free survival is the primary endpoint; overall survival and time to progression are secondary endpoints. To evaluate treatment success, patients will receive contrast enhanced magnetic resonance imaging every 3 months. Currently, chemoembolization is routinely performed in many centers instead of systemic chemotherapy for treating intrahepatic cholangiocellular carcinoma confined to the liver. Recently, radioembolization has been increasingly applied to cholangiocellular carcinoma as second line therapy after TACE failure or even as an alternative first line therapy. Nonetheless, no randomized studies have compared radioembolization and chemoembolization. Considering all this background information, we recognized a strong need for a randomized controlled trial (RCT) to compare the two treatments. Therefore, the present protocol describes the design of a RCT that compares SIRT and TACE as the first line therapy for inoperable CCC confined to the liver. ClinicalTrials.gov, Identifier: NCT01798147, registered 16th of February 2013.

Variable versus conventional lung protective mechanical ventilation during open abdominal surgery: study protocol for a randomized controlled trial.

PubMed

Spieth, Peter M; Güldner, Andreas; Uhlig, Christopher; Bluth, Thomas; Kiss, Thomas; Schultz, Marcus J; Pelosi, Paolo; Koch, Thea; Gama de Abreu, Marcelo

2014-05-02

General anesthesia usually requires mechanical ventilation, which is traditionally accomplished with constant tidal volumes in volume- or pressure-controlled modes. Experimental studies suggest that the use of variable tidal volumes (variable ventilation) recruits lung tissue, improves pulmonary function and reduces systemic inflammatory response. However, it is currently not known whether patients undergoing open abdominal surgery might benefit from intraoperative variable ventilation. The PROtective VARiable ventilation trial ('PROVAR') is a single center, randomized controlled trial enrolling 50 patients who are planning for open abdominal surgery expected to last longer than 3 hours. PROVAR compares conventional (non-variable) lung protective ventilation (CV) with variable lung protective ventilation (VV) regarding pulmonary function and inflammatory response. The primary endpoint of the study is the forced vital capacity on the first postoperative day. Secondary endpoints include further lung function tests, plasma cytokine levels, spatial distribution of ventilation assessed by means of electrical impedance tomography and postoperative pulmonary complications. We hypothesize that VV improves lung function and reduces systemic inflammatory response compared to CV in patients receiving mechanical ventilation during general anesthesia for open abdominal surgery longer than 3 hours. PROVAR is the first randomized controlled trial aiming at intra- and postoperative effects of VV on lung function. This study may help to define the role of VV during general anesthesia requiring mechanical ventilation. Clinicaltrials.gov NCT01683578 (registered on September 3 3012).

Laparoscopic-Assisted Resection of Colorectal Malignancies

PubMed Central

Chapman, Andrew E.; Levitt, Michael D.; Hewett, Peter; Woods, Rodney; Sheiner, Harry; Maddern, Guy J.

2001-01-01

Objective To compare the safety and efficacy of laparoscopic-assisted resection of colorectal malignancies with open colectomy. Methods Two search strategies were devised to retrieve literature from the Medline, Current Contents, Embase, and Cochrane Library databases until July 1999. Inclusion of papers was determined using a predetermined protocol, independent assessments by two reviewers, and a final consensus decision. English language papers were selected. Acceptable study designs included randomized controlled trials, controlled clinical trials, case series, or case reports. Fifty-two papers met the inclusion criteria. They were tabulated and critically appraised in terms of methodology and design, outcomes, and the possible influence of bias, confounding, and chance. Results Little high-level evidence was available. Laparoscopic resection of colorectal malignancy was more expensive and time-consuming, but little evidence suggests high rates of port site recurrence. The new procedure’s advantages revolve around early recovery from surgery and reduced pain. Conclusions The evidence base for laparoscopic-assisted resection of colorectal malignancies is inadequate to determine the procedure’s safety and efficacy. Because of inadequate evidence detailing circumferential marginal clearance of tumors and the necessity of determining a precise incidence of cardiac and other major complications, along with wound and port site recurrence, it is recommended that a controlled clinical trial, ideally with random allocation to an intervention and control group, be conducted. Long-term survival rates need to be a primary aim of such a trial. PMID:11685021

A cluster randomized controlled trial on the effects and costs of advance care planning in elderly care: study protocol.

PubMed

Korfage, Ida J; Rietjens, Judith A C; Overbeek, Anouk; Jabbarian, Lea J; Billekens, Pascalle; Hammes, Bernard J; Hansen-van der Meer, Ellen; Polinder, Suzanne; Severijnen, Johan; Swart, Siebe J; Witkamp, Frederika E; van der Heide, Agnes

2015-07-22

Currently, health care and medical decision-making at the end of life for older people are often insufficiently patient-centred. In this trial we study the effects of Advance Care Planning (ACP), a formalised process of timely communication about care preferences at the end of life, for frail older people. We will conduct a cluster randomised controlled trial among older people residing in care homes or receiving home care in the Netherlands. The intervention group will receive the ACP program Respecting Choices® in addition to usual care. The control group will receive usual care only. Participants in both groups will fill out questionnaires at baseline and after 12 months. We hypothesize that ACP will lead to better patient activation in medical decision making and quality of life, while reducing the number of medical interventions and thus health care costs. Multivariate analysis will be used to compare differences between the intervention group and the control group at baseline and to compare differences in changes after 12 months following the inclusion. Our study can contribute to more understanding of the effects of ACP on patient activation and quality of life in frail older people. Further, we will gain insight in the costs and cost-effectiveness of ACP. This study will facilitate ACP policy for older people in the Netherlands. Nederlands Trial Register: NTR4454.

Current issues in allogeneic islet transplantation.

PubMed

Chang, Charles A; Lawrence, Michael C; Naziruddin, Bashoo

2017-10-01

Transplantation of allogenic pancreatic islets is a minimally invasive treatment option to control severe hypoglycemia and dependence on exogenous insulin among type 1 diabetes (T1D) patients. This overview summarizes the current issues and progress in islet transplantation outcomes and research. Several clinical trials from North America and other countries have documented the safety and efficacy of clinical islet transplantation for T1D patients with impaired hypoglycemia awareness. A recently completed phase 3 clinical trial allows centres in the United States to apply for a Food and Drug Administration Biologics License for the procedure. Introduction of anti-inflammatory drugs along with T-cell depleting induction therapy has significantly improved long-term function of transplanted islets. Research into islet biomarkers, immunosuppression, extrahepatic transplant sites and potential alternative beta cell sources is driving further progress. Allogeneic islet transplantation has vastly improved over the past two decades. Success in restoration of glycemic control and hypoglycemic awareness after islet transplantation has been further highlighted by clinical trials. However, lack of effective strategies to maintain long-term islet function and insufficient sources of donor tissue still impose limitations to the widespread use of islet transplantation. In the United States, wide adoption of this technology still awaits regulatory approval and, importantly, a financial mechanism to support the use of this technology.

Current outcomes of off-pump versus on-pump coronary artery bypass grafting: evidence from randomized controlled trials

PubMed Central

Benedetto, Umberto; Pecchinenda, Gustavo Guida; Chivasso, Pierpaolo; Bruno, Vito Domenico; Rapetto, Filippo; Bryan, Alan; Angelini, Gianni Davide

2016-01-01

Coronary artery bypass grafting remains the standard treatment for patients with extensive coronary artery disease. Coronary surgery without use of cardiopulmonary bypass avoids the deleterious systemic inflammatory effects of the extracorporeal circuit. However there is an ongoing debate surrounding the clinical outcomes after on-pump versus off-pump coronary artery bypass (ONCAB versus OPCAB) surgery. The current review is based on evidence from randomized controlled trials (RCTs) and meta-analyses of randomized studies. It focuses on operative mortality, mid- and long-term survival, graft patency, completeness of revascularisation, neurologic and neurophysiologic outcomes, perioperative complications and outcomes in the high risk groups. Early and late survival rates for both OPCAB and ONCAB grafting are similar. Some studies suggest early poorer vein graft patency with off-pump when compared with on-pump, comparable midterm arterial conduit patency with no difference in long term venous and arterial graft patency. A recent, pooled analysis of randomised trials shows a reduction in stroke rates with use off-pump techniques. Furthermore, OPCAB grafting seems to reduce postoperative renal dysfunction, bleeding, transfusion requirement and respiratory complications while perioperative myocardial infarction rates are similar to ONCAB grafting. The high risk patient groups seem to benefit from off-pump coronary surgery. PMID:27942394

Acupuncture for Functional Dyspepsia: What Strength Does It Have? A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Li, Jing; Li, Bo; Hu, Ya-Cai; Cai, Qiu-Han

2016-01-01

Background. Although the effectiveness of acupuncture therapy on functional dyspepsia (FD) has been systematically reviewed, the available reports are still contradictive and no robust evidence has been provided to date. Objective. To assess the current evidence of high quality on the effects of acupuncture for patients with FD. Methods. A comprehensive literature database search was conducted to identify randomized controlled trials (RCTs) comparing acupuncture therapies (including manual acupuncture and electroacupuncture) to sham acupuncture and medication use. A meta-analysis was performed following a strict methodology. Results. 16 RCTs involving 1436 participants were included. The majority of the trials were determined to be of low quality. Positive results were found for acupuncture in improving the Nepean Dyspepsia Index (NDI) and scores of the MOS 36-Item Short-Form Health Survey (SF-36), as well as in alleviating relevant symptoms (especially postprandial fullness and early satiation) of FD patients. Conclusion. Based on current available evidence, acupuncture therapy achieves statistically significant effect for FD in comparison with sham acupuncture and is superior to medication (prokinetic agents) in improving the symptoms and quality of life of FD patients. Nonetheless, despite stringent methodological analyses, the conclusion of our review still needs to be strengthened by additional RCTs of higher quality. PMID:28119758

Plain packaging of cigarettes and smoking behavior: study protocol for a randomized controlled study.

PubMed

Maynard, Olivia M; Leonards, Ute; Attwood, Angela S; Bauld, Linda; Hogarth, Lee; Munafò, Marcus R

2014-06-25

Previous research on the effects of plain packaging has largely relied on self-report measures. Here we describe the protocol of a randomized controlled trial investigating the effect of the plain packaging of cigarettes on smoking behavior in a real-world setting. In a parallel group randomization design, 128 daily cigarette smokers (50% male, 50% female) will attend an initial screening session and be assigned plain or branded packs of cigarettes to smoke for a full day. Plain packs will be those currently used in Australia where plain packaging has been introduced, while branded packs will be those currently used in the United Kingdom. Our primary study outcomes will be smoking behavior (self-reported number of cigarettes smoked and volume of smoke inhaled per cigarette as measured using a smoking topography device). Secondary outcomes measured pre- and post-intervention will be smoking urges, motivation to quit smoking, and perceived taste of the cigarettes. Secondary outcomes measured post-intervention only will be experience of smoking from the cigarette pack, overall experience of smoking, attributes of the cigarette pack, perceptions of the on-packet health warnings, behavior changes, views on plain packaging, and the rewarding value of smoking. Sex differences will be explored for all analyses. This study is novel in its approach to assessing the impact of plain packaging on actual smoking behavior. This research will help inform policymakers about the effectiveness of plain packaging as a tobacco control measure. Current Controlled Trials ISRCTN52982308 (registered 27 June 2013).

A Review of Clinical Data for Currently Approved Hysteroscopic Sterilization Procedures

PubMed Central

Basinski, Cindy M

2010-01-01

Two hysteroscopic permanent sterilization procedures are approved for use in the United States: Essure® Permanent Birth Control System (Conceptus Incorporated, Mountain View, CA) and Adiana® Permanent Contraception (Hologic, Inc., Bedford, MA). This review compares the clinical trial data for these procedures. A notable difference is the resultant clinical pregnancy risk. The clinical trials for the Essure procedure have reported no pregnancies in 643 relying women in the 9 years since initiation of the studies. The clinical trial for the Adiana procedure has reported 12 pregnancies in 570 relying women in nearly 5 years of collected data. Other clinical outcome parameters concerning Essure and Adiana are examined in this review. PMID:21364861

Evolutionary cognitive therapy versus standard cognitive therapy for depression: a protocol for a blinded, randomized, superiority clinical trial.

PubMed

Giosan, Cezar; Cobeanu, Oana; Mogoase, Cristina; Muresan, Vlad; Malta, Loretta S; Wyka, Katarzyna; Szentagotai, Aurora

2014-03-19

Depression is estimated to become the leading cause of disease burden globally by 2030. Despite existing efficacious treatments (both medical and psychotherapeutic), a large proportion of patients do not respond to therapy. Recent insights from evolutionary psychology suggest that, in addition to targeting the proximal causes of depression (for example, targeting dysfunctional beliefs by cognitive behavioral therapy), the distal or evolutionary causes (for example, inclusive fitness) should also be addressed. A randomized superiority trial is conducted to develop and test an evolutionary-driven cognitive therapy protocol for depression, and to compare its efficacy against standard cognitive therapy for depression. Romanian-speaking adults (18 years or older) with elevated Beck Depression Inventory (BDI) scores (>13), current diagnosis of major depressive disorder or major depressive episode (MDD or MDE), and MDD with comorbid dysthymia, as evaluated by the Structured Clinical Interview for DSM-IV (SCID), are included in the study. Participants are randomized to one of two conditions: 1) evolutionary-driven cognitive therapy (ED-CT) or 2) cognitive therapy (CT). Both groups undergo 12 psychotherapy sessions, and data are collected at baseline, mid-treatment, post-treatment, and the 3-month follow-up. Primary outcomes are depressive symptomatology and a categorical diagnosis of depression post-treatment. This randomized trial compares the newly proposed ED-CT with a classic CT protocol for depression. To our knowledge, this is the first attempt to integrate insights from evolutionary theories of depression into the treatment of this condition in a controlled manner. This study can thus add substantially to the body of knowledge on validated treatments for depression. Current Controlled Trials ISRCTN64664414The trial was registered in June 2013. The first participant was enrolled on October 3, 2012.

What determines patient preferences for treating low risk basal cell carcinoma when comparing surgery vs imiquimod? A discrete choice experiment survey from the SINS trial.

PubMed

Tinelli, Michela; Ozolins, Mara; Bath-Hextall, Fiona; Williams, Hywel C

2012-10-04

The SINS trial (Controlled Clinical Trials ISRCTN48755084; Eudract No. 2004-004506-24) is a randomised controlled trial evaluating long term success of excisional surgery vs. imiquimod 5% cream for low risk nodular and superficial basal cell carcinoma (BCC). The trial included a discrete choice experiment questionnaire to explore patient preferences of a cream versus surgery for the treatment of their skin cancer. The self-completed questionnaire was administered at baseline to 183 participants, measuring patients' strength of preferences when choosing either alternative 'surgery' or 'imiquimod cream' instead of a fixed 'current situation' option (of surgical excision as standard practice in UK). The treatments were described according to: cost, chance of complete clearance, side effects and appearance. Participants had to choose between various scenarios. Analysis was performed using a mixed logit model, which took into account the impact of previous BCC treatment and sample preference variability. The analysis showed that respondents preferred 'imiquimod cream' to their 'current situation' or 'surgery', regardless of previous experience of BCC symptoms and treatment. Respondents were more likely to be worried about their cosmetic outcomes and side effects they might experience over and above their chance of clearance and cost. Those with no experience of surgery (compared with experience) valued more the choice of 'imiquimod cream' (£1013 vs £781). All treatment characteristics were significant determinants of treatment choice, and there was significant variability in the population preferences for all of them. Patients with BCC valued more 'imiquimod cream' than alternative 'surgery' options, and all treatment characteristics were important for their choice of care. Understanding how people with a BCC value alternative interventions may better inform the development of health care interventions.

[Dengzhan Xixin injection as an adjuvant treatment for angina pectoris: a systematic review and Meta-analysis of randomized controlled trials].

PubMed

Wang, Feng-jiao; Xie, Yan-ming; Liao, Xing; Jia, Min

2015-08-01

The paper is to systematically evaluate the efficacy and safety of Deng Zhan Xi Xin injection ( DZXXI) as an adjuvant treatment for patients with angina pectoris. The Cochrane Library, Medline, EMbase, CBM, CNKI, VIP, and Wan fang Data base were searched. Randomized controlled trials (RCTs) of DZXXI combined with western medicine routine treatment versus western medicine routine treatment alone for angina pectoris patients were all included. All trials were assessed according to the Cochrane Reviewer' s Handbook 5.1 for Systematic Reviews of Intervention and Meta analyses were performed by RevMan 5. 2 Software. A total of 30RCTs (3 086 patients including 1 572 patients of treatment group and 1 514 patients of control group) were included. Meta-analysis of treatment group compared with control group showed superior effect over reducing cardiovascular events ( OR = 0.33; 95% CI: [0.16, 0.67], P = 0.002, improving effective rate of DZXXI as adjuvant treatment for angina pectoris patients (OR = 3.97; 95% CI: [3.15, 5.02]; P < 0.000 010 and electrocardiogram curative effect (OR = 2.21; 95% CI; [1.83, 2.68]; P < 0.000 010. Funnel figure seemed that there was publication bias. The current limited evidence showed that when compared with the control group, treatment group was superior in improving patients with angina pectoris. But based on the limitations of the study, rigorous design with long follow up clinical trials are necessary for further evidence.

Protocol for the ENCODE trial: evaluating a novel online depression intervention for persons with epilepsy.

PubMed

Meyer, Björn; Weiss, Mario; Holtkamp, Martin; Arnold, Stephan; Brückner, Katja; Schröder, Johanna; Scheibe, Franziska; Nestoriuc, Yvonne

2017-02-07

Depression is common among persons with epilepsy (PwE), affecting roughly one in three individuals, and its presence is associated with personal suffering, impaired quality of life, and worse prognosis. Despite the availability of effective treatments, depression is often overlooked and treated inadequately in PwE, in part because of assumed concerns over drug interactions or proconvulsant effects of antidepressants. Internet-administered psychological interventions might complement antidepressant medication or psychotherapy, and preliminary evidence suggests that they can be effective. However, no trial has yet examined whether an Internet intervention designed to meet the needs of PwE can achieve sustained reductions in depression and related symptoms, such as anxiety, when offered as adjunct to treatment as usual. This randomized controlled trial will include 200 participants with epilepsy and a current depressive disorder, along with currently at least moderately elevated depression (Patient Health Questionnaire (PHQ-9) sum score of at least 10). Patients will be recruited via epilepsy treatment centers and other sources, including Internet forums, newspaper articles, flyers, posters, and media articles or advertisements, in German-speaking countries. Main inclusion criteria are: self-reported diagnosis of epilepsy and a depressive disorder, as assessed with a phone-administered structured diagnostic interview, none or stable antidepressant medication, no current psychotherapy, no other major psychiatric disorder, no acute suicidality. Participants will be randomly assigned to either (1) a care-as-usual/waitlist (CAU/WL) control group, in which they receive CAU and are given access to the Internet intervention after 3 months (that is, a CAU/WL control group), or (2) a treatment group that may also use CAU and in addition immediately receives six-month access to the novel, Internet-administered intervention. The primary outcome measure is the PHQ-9, collected at three months post-baseline; secondary measures include self-reported anxiety, work and social adjustment, epilepsy symptoms (including seizure frequency and severity), medication adherence, potential negative treatment effects and health-related quality of life. Measurements are collected online at pre-treatment (T0), three months (T1), six months (T2), and nine months (T3). Results of this trial are expected to extend the body of knowledge with regard to effective and efficient treatment options for PwE who experience elevated depression and anxiety. ClinicalTrials.gov: NCT02791724 . Registered 01 June 2016.

Efficacy of rintatolimod in the treatment of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)

PubMed Central

Mitchell, William M

2016-01-01

ABSTRACT Chronic fatigue syndrome/ Myalgic encephalomyelitis (CFS/ME) is a poorly understood seriously debilitating disorder in which disabling fatigue is an universal symptom in combination with a variety of variable symptoms. The only drug in advanced clinical development is rintatolimod, a mismatched double stranded polymer of RNA (dsRNA). Rintatolimod is a restricted Toll-Like Receptor 3 (TLR3) agonist lacking activation of other primary cellular inducers of innate immunity (e.g.- cytosolic helicases). Rintatolimod also activates interferon induced proteins that require dsRNA for activity (e.g.- 2ʹ-5ʹ adenylate synthetase, protein kinase R). Rintatolimod has achieved statistically significant improvements in primary endpoints in Phase II and Phase III double-blind, randomized, placebo-controlled clinical trials with a generally well tolerated safety profile and supported by open-label trials in the United States and Europe. The chemistry, mechanism of action, clinical trial data, and current regulatory status of rintatolimod for CFS/ME including current evidence for etiology of the syndrome are reviewed. PMID:27045557

Concurrent transcranial direct current stimulation and progressive resistance training in Parkinson's disease: study protocol for a randomised controlled trial.

PubMed

Hendy, Ashlee M; Tillman, Alex; Rantalainen, Timo; Muthalib, Makii; Johnson, Liam; Kidgell, Dawson J; Wundersitz, Daniel; Enticott, Peter G; Teo, Wei-Peng

2016-07-19

Parkinson's disease (PD) results from a loss of dopamine in the brain, leading to movement dysfunctions such as bradykinesia, postural instability, resting tremor and muscle rigidity. Furthermore, dopamine deficiency in PD has been shown to result in maladaptive plasticity of the primary motor cortex (M1). Progressive resistance training (PRT) is a popular intervention in PD that improves muscular strength and results in clinically significant improvements on the Unified Parkinson's Disease Rating Scale (UPDRS). In separate studies, the application of anodal transcranial direct current stimulation (a-tDCS) to the M1 has been shown to improve motor function in PD; however, the combined use of tDCS and PRT has not been investigated. We propose a 6-week, double-blind randomised controlled trial combining M1 tDCS and PRT of the lower body in participants (n = 42) with moderate PD (Hoehn and Yahr scale score 2-4). Supervised lower body PRT combined with functional balance tasks will be performed three times per week with concurrent a-tDCS delivered at 2 mA for 20 minutes (a-tDCS group) or with sham tDCS (sham group). Control participants will receive standard care (control group). Outcome measures will include functional strength, gait speed and variability, balance, neurophysiological function at rest and during movement execution, and the UPDRS motor subscale, measured at baseline, 3 weeks (during), 6 weeks (post), and 9 weeks (retention). Ethical approval has been granted by the Deakin University Human Research Ethics Committee (project number 2015-014), and the trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615001241527). This will be the first randomised controlled trial to combine PRT and a-tDCS targeting balance and gait in people with PD. The study will elucidate the functional, clinical and neurophysiological outcomes of combined PRT and a-tDCS. It is hypothesised that combined PRT and a-tDCS will significantly improve lower limb strength, postural sway, gait speed and stride variability compared with PRT with sham tDCS. Further, we hypothesise that pre-frontal cortex activation during dual-task cognitive and gait/balance activities will be reduced, and that M1 excitability and inhibition will be augmented, following the combined PRT and a-tDCS intervention. Australian New Zealand Clinical Trials Registry ACTRN12615001241527 . Registered on 12 November 2015.

Flexible trial design in practice - stopping arms for lack-of-benefit and adding research arms mid-trial in STAMPEDE: a multi-arm multi-stage randomized controlled trial.

PubMed

Sydes, Matthew R; Parmar, Mahesh K B; Mason, Malcolm D; Clarke, Noel W; Amos, Claire; Anderson, John; de Bono, Johann; Dearnaley, David P; Dwyer, John; Green, Charlene; Jovic, Gordana; Ritchie, Alastair W S; Russell, J Martin; Sanders, Karen; Thalmann, George; James, Nicholas D

2012-09-15

Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) is a randomized controlled trial that follows a novel multi-arm, multi-stage (MAMS) design. We describe methodological and practical issues arising with (1) stopping recruitment to research arms following a pre-planned intermediate analysis and (2) adding a new research arm during the trial. STAMPEDE recruits men who have locally advanced or metastatic prostate cancer who are starting standard long-term hormone therapy. Originally there were five research and one control arms, each undergoing a pilot stage (focus: safety, feasibility), three intermediate 'activity' stages (focus: failure-free survival), and a final 'efficacy' stage (focus: overall survival). Lack-of-sufficient-activity guidelines support the pairwise interim comparisons of each research arm against the control arm; these pre-defined activity cut-off becomes increasingly stringent over the stages. Accrual of further patients continues to the control arm and to those research arms showing activity and an acceptable safety profile. The design facilitates adding new research arms should sufficiently interesting agents emerge. These new arms are compared only to contemporaneously recruited control arm patients using the same intermediate guidelines in a time-delayed manner. The addition of new research arms is subject to adequate recruitment rates to support the overall trial aims. (1) Stopping Existing Therapy: After the second intermediate activity analysis, recruitment was discontinued to two research arms for lack-of-sufficient activity. Detailed preparations meant that changes were implemented swiftly at 100 international centers and recruitment continued seamlessly into Activity Stage III with 3 remaining research arms and the control arm. Further regulatory and ethical approvals were not required because this was already included in the initial trial design.(2) Adding New Therapy: An application to add a new research arm was approved by the funder, (who also organized peer review), industrial partner and regulatory and ethical bodies. This was all done in advance of any decision to stop current therapies. The STAMPEDE experience shows that recruitment to a MAMS trial and mid-flow changes its design are achievable with good planning. This benefits patients and the scientific community as research treatments are evaluated in a more efficient and cost-effective manner. ISRCTN78818544, NCT00268476. First patient into trial: 17 October 2005. First patient into abiraterone comparison: 15 November 2011.

Regulation of Clinical Trials with Advanced Therapy Medicinal Products in Germany.

PubMed

Renner, Matthias; Anliker, Brigitte; Sanzenbacher, Ralf; Schuele, Silke

2015-01-01

In the European Union, clinical trials for Advanced Therapy Medicinal Products are regulated at the national level, in contrast to the situation for a Marketing Authorisation Application, in which a centralised procedure is foreseen for these medicinal products. Although based on a common understanding regarding the regulatory requirement to be fulfilled before conduct of a clinical trial with an Advanced Therapy Investigational Medicinal Product, the procedures and partly the scientific requirements for approval of a clinical trial application differ between the European Union Member States. This chapter will thus give an overview about the path to be followed for a clinical trial application and the subsequent approval process for an Advanced Therapy Investigational Medicinal Product in Germany and will describe the role of the stakeholders that are involved. In addition, important aspects of manufacturing, quality control and non-clinical testing of Advanced Therapy Medicinal Products in the clinical development phase are discussed. Finally, current and future approaches for harmonisation of clinical trial authorisation between European Union Member States are summarised.

Engaging participants in a complex intervention trial in Australian General Practice

PubMed Central

Perkins, David; Harris, Mark F; Tan, Jocelyn; Christl, Bettina; Taggart, Jane; Fanaian, Mahnaz

2008-01-01

Background The paper examines the key issues experienced in recruiting and retaining practice involvement in a large complex intervention trial in Australian General Practice. Methods Reflective notes made by research staff and telephone interviews with staff from general practices which expressed interest, took part or withdrew from a trial of a complex general practice intervention. Results Recruitment and retention difficulties were due to factors inherent in the demands and context of general practice, the degree of engagement of primary care organisations (Divisions of General Practice), perceived benefits by practices, the design of the trial and the timing and complexity of data collection. Conclusion There needs to be clearer articulation to practices of the benefits of the research to participants and streamlining of the design and processes of data collection and intervention to fit in with their work practices. Ultimately deeper engagement may require additional funding and ongoing participation through practice research networks. Trial Registration Current Controlled Trials ACTRN12605000788673 PMID:18700984

Variable sensory perception in autism.

PubMed

Haigh, Sarah M

2018-03-01

Autism is associated with sensory and cognitive abnormalities. Individuals with autism generally show normal or superior early sensory processing abilities compared to healthy controls, but deficits in complex sensory processing. In the current opinion paper, it will be argued that sensory abnormalities impact cognition by limiting the amount of signal that can be used to interpret and interact with environment. There is a growing body of literature showing that individuals with autism exhibit greater trial-to-trial variability in behavioural and cortical sensory responses. If multiple sensory signals that are highly variable are added together to process more complex sensory stimuli, then this might destabilise later perception and impair cognition. Methods to improve sensory processing have shown improvements in more general cognition. Studies that specifically investigate differences in sensory trial-to-trial variability in autism, and the potential changes in variability before and after treatment, could ascertain if trial-to-trial variability is a good mechanism to target for treatment in autism. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Function after spinal treatment, exercise and rehabilitation (FASTER): improving the functional outcome of spinal surgery

PubMed Central

2010-01-01

Background The life-time incidence of low back pain is high and diagnoses of spinal stenosis and disc prolapse are increasing. Consequently, there is a steady rise in surgical interventions for these conditions. Current evidence suggests that while the success of surgery is incomplete, it is superior to conservative interventions. A recent survey indicates that there are large differences in the type and intensity of rehabilitation, if any, provided after spinal surgery as well as in the restrictions and advice given to patients in the post-operative period. This trial will test the hypothesis that functional outcome following two common spinal operations can be improved by a programme of post-operative rehabilitation that combines professional support and advice with graded active exercise and/or an educational booklet based on evidence-based messages and advice. Methods/Design The study design is a multi-centre, factorial, randomised controlled trial with patients stratified by surgeon and operative procedure. The trial will compare the effectiveness and cost-effectiveness of a rehabilitation programme and an education booklet for the postoperative management of patients undergoing discectomy or lateral nerve root decompression, each compared with "usual care"using a 2 × 2 factorial design. The trial will create 4 sub-groups; rehabilitation-only, booklet-only, rehabilitation-plus-booklet, and usual care only. The trial aims to recruit 344 patients, which equates to 86 patients in each of the four sub-groups. All patients will be assessed for functional ability (through the Oswestry Disability Index - a disease specific functional questionnaire), pain (using visual analogue scales), and satisfaction pre-operatively and then at 6 weeks, 3, 6 and 9 months and 1 year post-operatively. This will be complemented by a formal analysis of cost-effectiveness. Discussion This trial will determine whether the outcome of spinal surgery can be enhanced by either a post-operative rehabilitation programme or an evidence-based advice booklet or a combination of the two and as such will contribute to our knowledge on how to manage spinal surgery patients in the post-operative period. Trial Registration Current controlled trials ISRCTN46782945 UK CRN ID: 2670 PMID:20102625

The effects of rhythm control strategies versus rate control strategies for atrial fibrillation and atrial flutter: A systematic review with meta-analysis and Trial Sequential Analysis

PubMed Central

Gluud, Christian; Jakobsen, Janus C.

2017-01-01

Background Atrial fibrillation and atrial flutter may be managed by either a rhythm control strategy or a rate control strategy but the evidence on the clinical effects of these two intervention strategies is unclear. Our objective was to assess the beneficial and harmful effects of rhythm control strategies versus rate control strategies for atrial fibrillation and atrial flutter. Methods We searched CENTRAL, MEDLINE, Embase, LILACS, Web of Science, BIOSIS, Google Scholar, clinicaltrials.gov, TRIP, EU-CTR, Chi-CTR, and ICTRP for eligible trials comparing any rhythm control strategy with any rate control strategy in patients with atrial fibrillation or atrial flutter published before November 2016. Our primary outcomes were all-cause mortality, serious adverse events, and quality of life. Our secondary outcomes were stroke and ejection fraction. We performed both random-effects and fixed-effect meta-analysis and chose the most conservative result as our primary result. We used Trial Sequential Analysis (TSA) to control for random errors. Statistical heterogeneity was assessed by visual inspection of forest plots and by calculating inconsistency (I2) for traditional meta-analyses and diversity (D2) for TSA. Sensitivity analyses and subgroup analyses were conducted to explore the reasons for substantial statistical heterogeneity. We assessed the risk of publication bias in meta-analyses consisting of 10 trials or more with tests for funnel plot asymmetry. We used GRADE to assess the quality of the body of evidence. Results 25 randomized clinical trials (n = 9354 participants) were included, all of which were at high risk of bias. Meta-analysis showed that rhythm control strategies versus rate control strategies significantly increased the risk of a serious adverse event (risk ratio (RR), 1.10; 95% confidence interval (CI), 1.02 to 1.18; P = 0.02; I2 = 12% (95% CI 0.00 to 0.32); 21 trials), but TSA did not confirm this result (TSA-adjusted CI 0.99 to 1.22). The increased risk of a serious adverse event did not seem to be caused by any single component of the composite outcome. Meta-analysis showed that rhythm control strategies versus rate control strategies were associated with better SF-36 physical component score (mean difference (MD), 6.93 points; 95% CI, 2.25 to 11.61; P = 0.004; I2 = 95% (95% CI 0.94 to 0.96); 8 trials) and ejection fraction (MD, 4.20%; 95% CI, 0.54 to 7.87; P = 0.02; I2 = 79% (95% CI 0.69 to 0.85); 7 trials), but TSA did not confirm these results. Both meta-analysis and TSA showed no significant differences on all-cause mortality, SF-36 mental component score, Minnesota Living with Heart Failure Questionnaire, and stroke. Conclusions Rhythm control strategies compared with rate control strategies seem to significantly increase the risk of a serious adverse event in patients with atrial fibrillation. Based on current evidence, it seems that most patients with atrial fibrillation should be treated with a rate control strategy unless there are specific reasons (e.g., patients with unbearable symptoms due to atrial fibrillation or patients who are hemodynamically unstable due to atrial fibrillation) justifying a rhythm control strategy. More randomized trials at low risk of bias and low risk of random errors are needed. Trial registration PROSPERO CRD42016051433 PMID:29073191

A randomized controlled trial of a commercially available weight loss program

USDA-ARS?s Scientific Manuscript database

The U.S. Preventive Services Task Force (USPSTF) recommends that clinicians refer obese adults for intensive, multi-component behavioral counseling, yet most obese Americans choose a self-help approach to lose weight. The current study examined weight loss between a community-based, intensive behavi...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-20

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

Practical Effects of Classwide Mathematics Intervention

ERIC Educational Resources Information Center

VanDerHeyden, Amanda M.; Codding, Robin S.

2015-01-01

The current article presents additional analyses of a classwide mathematics intervention, from a previously reported randomized controlled trial, to offer new information about the treatment and to demonstrate the utility of different types of effect sizes. Multilevel modeling was used to examine treatment effects by race, sex, socioeconomic…

Efficacy, tolerability and safety of cannabinoids in chronic pain associated with rheumatic diseases (fibromyalgia syndrome, back pain, osteoarthritis, rheumatoid arthritis): A systematic review of randomized controlled trials.

PubMed

Fitzcharles, M-A; Baerwald, C; Ablin, J; Häuser, W

2016-02-01

In the absence of an ideal treatment for chronic pain associated with rheumatic diseases, there is interest in the potential effects of cannabinoid molecules, particularly in the context of global interest in the legalization of herbal cannabis for medicinal use. A systematic search until April 2015 was conducted in Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, www.cannabis-med.org and clinicaltrials.gov for randomized controlled trials with a study duration of at least 2 weeks and at least ten patients per treatment arm with herbal cannabis or pharmaceutical cannabinoid products in fibromyalgia syndrome (FMS), osteoarthritis (OA), chronic spinal pain, and rheumatoid arthritis (RA) pain. Outcomes were reduction of pain, sleep problems, fatigue and limitations of quality of life for efficacy, dropout rates due to adverse events for tolerability, and serious adverse events for safety. The methodology quality of the randomized controlled trials (RCTs) was evaluated by the Cochrane Risk of Bias Tool. Two RCTs of 2 and 4 weeks duration respectively with nabilone, including 71 FMS patients, one 4-week trial with nabilone, including 30 spinal pain patients, and one 5-week study with tetrahydrocannbinol/cannabidiol, including 58 RA patients were included. One inclusion criterion was pain refractory to conventional treatment in three studies. No RCT with OA patients was found. The risk of bias was high for three studies. The findings of a superiority of cannabinoids over controls (placebo, amitriptyline) were not consistent. Cannabinoids were generally well tolerated despite some troublesome side effects and safe during the study duration. Currently, there is insufficient evidence for recommendation for any cannabinoid preparations for symptom management in patients with chronic pain associated with rheumatic diseases.

Study protocol: a randomized controlled trial investigating the effects of a psychosexual training program for adolescents with autism spectrum disorder.

PubMed

Visser, Kirsten; Greaves-Lord, Kirstin; Tick, Nouchka T; Verhulst, Frank C; Maras, Athanasios; van der Vegt, Esther J M

2015-08-28

Previous research shows that adolescents with autism spectrum disorder (ASD) run several risks in their psychosexual development and that these adolescents can have limited access to reliable information on puberty and sexuality, emphasizing the need for specific guidance of adolescents with ASD in their psychosexual development. Few studies have investigated the effects of psychosexual training programs for adolescents with ASD and to date no randomized controlled trials are available to study the effects of psychosexual interventions for this target group. The randomized controlled trial (RCT) described in this study protocol aims to investigate the effects of the Tackling Teenage Training (TTT) program on the psychosexual development of adolescents with ASD. This parallel clinical trial, conducted in the South-West of the Netherlands, has a simple equal randomization design with an intervention and a waiting-list control condition. Two hundred adolescents and their parents participate in this study. We assess the participants in both conditions using self-report as well as parent-report questionnaires at three time points during 1 year: at baseline (T1), post-treatment (T2), and for follow-up (T3). To our knowledge, the current study is the first that uses a randomized controlled design to study the effects of a psychosexual training program for adolescents with ASD. It has a number of methodological strengths, namely a large sample size, a wide range of functionally relevant outcome measures, the use of multiple informants, and a standardized research and intervention protocol. Also some limitations of the described study are identified, for instance not making a comparison between two treatment conditions, and no use of blinded observational measures to investigate the ecological validity of the research results. Dutch Trial Register NTR2860. Registered on 20 April 2011.

A multi-site randomised controlled trial of evidence-based supported employment for adults with severe and persistent mental illness.

PubMed

Waghorn, Geoffrey; Dias, Shannon; Gladman, Beverley; Harris, Meredith; Saha, Sukanta

2014-12-01

The Individual Placement and Support (IPS) approach is an evidence-based form of supported employment for people with severe and persistent mental illness. This approach is not yet widely available in Australia even though there is mounting evidence of its generalisability outside the USA. One previous Australian randomised controlled trial found that IPS is effective for young people with first episode psychosis. The aim of the current trial was to assess the effectiveness of evidence-based supported employment when implemented for Australian adult consumers of public mental health services by utilising existing service systems. A four-site randomised control trial design (n = 208) was conducted in Brisbane (two sites), Townsville and Cairns. The intervention consisted of an IPS supported employment service hosted by a community mental health team. The control condition was delivered at each site by mental health teams referring consumers to other disability employment services in the local area. At 12 months, those in the IPS condition had 2.4 times greater odds of commencing employment than those in the control condition (42.5% vs. 23.5%). The conditions did not differ on secondary employment outcomes including job duration, hours worked, or job diversity. Attrition was higher than expected in both conditions with 28.4% completing the baseline interview but taking no further part in the study. The results support previous international findings that IPS-supported employment is more effective than non-integrated supported employment. IPS can be successfully implemented this way in Australia, but with a loss of effect strength compared to previous USA trials. © 2014 Occupational Therapy Australia.

Habit Reversal versus Object Manipulation Training for Treating Nail Biting: A Randomized Controlled Clinical Trial

PubMed Central

Ghanizadeh, Ahmad; Bazrafshan, Amir; Dehbozorgi, Gholamreza

2013-01-01

Objective This is a parallel, three group, randomized, controlled clinical trial, with outcomes evaluated up to three months after randomization for children and adolescents with chronic nail biting. The current study investigates the efficacy of habit reversal training (HRT) and compares its effect with object manipulation training (OMT) considering the limitations of the current literature. Method Ninety one children and adolescents with nail biting were randomly allocated to one of the three groups. The three groups were HRT (n = 30), OMT (n = 30), and wait-list or control group (n = 31). The mean length of nail was considered as the main outcome. Results The mean length of the nails after one month in HRT and OMT groups increased compared to the waiting list group (P < 0.001, P < 0.001, respectively). In long term, both OMT and HRT increased the mean length of nails (P < 0.01), but HRT was more effective than OMT (P < 0.021). The parent-reported frequency of nail biting did show similar results as to the mean length of nails assessment in long term. The number of children who completely stopped nail biting in HRT and OMT groups during three months was 8 and 7, respectively. This number was zero during one month for the wait-list group. Conclusion This trial showed that HRT is more effective than wait-list and OMT in increasing the mean length of nails of children and adolescents in long terms. PMID:24130603

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

PubMed

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

2013-07-09

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

The influence of short-chain essential fatty acids on children with attention-deficit/hyperactivity disorder: a double-blind placebo-controlled study.

PubMed

Raz, Raanan; Carasso, Rafael L; Yehuda, Shlomo

2009-04-01

Essential fatty acids (EFA) are needed for normal sensory, cognitive, and motor function. The EFA blood profile seems to be different in children with attention-deficit/hyperactivity disorder (ADHD) as compared to matched controls. Previous open EFA supplementation trials were successful in demonstrating significant therapeutic effects in this population, whereas most of the randomized controlled trials failed to show any benefit over placebo. The current randomized, double-blind, placebo-controlled trial tested the influence of short-chain EFA supplementation on ADHD children, using parent and teacher questionnaires and a computerized continuous performance test. A total of 73 unmedicated children aged 7-13 years with a diagnosis of ADHD participated in the study; 63 children completed the study. The EFA supplement contained 480 mg of linoleic acid and 120 mg of alpha-linolenic acid, and the placebo contained 1000 mg of vitamin C (daily amounts); both were given for a 7-week supplementation period. Analysis of variance for repeated measures revealed that both treatments ameliorated some of the symptoms, but no significant differences were found between the groups in any of the treatment effects.

Evidence for the impact of quality improvement collaboratives: systematic review

PubMed Central

2008-01-01

Objective To evaluate the effectiveness of quality improvement collaboratives in improving the quality of care. Data sources Relevant studies through Medline, Embase, PsycINFO, CINAHL, and Cochrane databases. Study selection Two reviewers independently extracted data on topics, participants, setting, study design, and outcomes. Data synthesis Of 1104 articles identified, 72 were included in the study. Twelve reports representing nine studies (including two randomised controlled trials) used a controlled design to measure the effects of the quality improvement collaborative intervention on care processes or outcomes of care. Systematic review of these nine studies showed moderate positive results. Seven studies (including one randomised controlled trial) reported an effect on some of the selected outcome measures. Two studies (including one randomised controlled trial) did not show any significant effect. Conclusions The evidence underlying quality improvement collaboratives is positive but limited and the effects cannot be predicted with great certainty. Considering that quality improvement collaboratives seem to play a key part in current strategies focused on accelerating improvement, but may have only modest effects on outcomes at best, further knowledge of the basic components effectiveness, cost effectiveness, and success factors is crucial to determine the value of quality improvement collaboratives. PMID:18577559

Randomized Clinical Trial of the Effectiveness of a Home-Based Advanced Practice Psychiatric Nurse Intervention: Outcomes for Individuals with Serious Mental Illness and HIV

PubMed Central

Hanrahan, Nancy P.; Wu, Evan; Kelly, Deena; Aiken, Linda H.; Blank, Michael B.

2011-01-01

Individuals with serious mental illness have greater risk for contracting HIV, multiple morbidities, and die 25 years younger than the general population. This high need and high cost subgroup face unique barriers to accessing required health care in the current health care system. The effectiveness of an advanced practice nurse model of care management was assessed in a four-year random controlled trial. Results are reported in this paper. In a four-year random controlled trial, a total of 238 community-dwelling individuals with HIV and serious mental illness (SMI) were randomly assigned to an intervention group (n=128) or to a control group (n=110). Over 12 months, the intervention group received care management from advanced practice psychiatric nurse, and the control group received usual care. The intervention group showed significant improvement in depression (P=.012) and the physical component of health-related quality of life (P=.03) from baseline to 12 months. The advanced practice psychiatric nurse intervention is a model of care that holds promise for a higher quality of care and outcomes for this vulnerable population. PMID:21935499

The "Healthy Habits, Healthy Girls" randomized controlled trial for girls: study design, protocol, and baseline results.

PubMed

Leme, Ana Carolina Barco; Philippi, Sonia Tucunduva

2015-07-01

The purpose of this article is to describe the study design, protocol, and baseline results of the "Healthy Habits, Healthy Girls" program. The intervention is being evaluated through a randomized controlled trial in 10 public schools in the city of São Paulo, Brazil. Data on the following variables were collected and assessed at baseline and will be reevaluated at 7 and 12 months: body mass index, waist circumference, dietary intake, nutrition, physical activity, social cognitive mediators, physical activity level, sedentary behaviors, self-rated physical status, and overall self-esteem. According to the baseline results, 32.4% and 23.4% of girls were overweight in the intervention and control groups, respectively, and in both groups a higher percentage failed to meet daily recommendations for moderate and vigorous physical activity and maximum screen time (TV, computer, mobile devices). There were no significant differences between the groups for most of the variables, except age (p = 0.000) and waist circumference (p = 0.014). The study showed a gap in the Brazilian literature on protocols for randomized controlled trials to prevent obesity among youth. The current study may thus be an important initial contribution to the field.

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

PubMed Central

2011-01-01

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

Community involvement in dengue vector control: cluster randomised trial

PubMed Central

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

2009-01-01

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

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

PubMed

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

2018-06-01

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