Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. A multicentre, randomised controlled trial: design and methodology.

PubMed

Gazzard, Gus; Konstantakopoulou, Evgenia; Garway-Heath, David; Barton, Keith; Wormald, Richard; Morris, Stephen; Hunter, Rachael; Rubin, Gary; Buszewicz, Marta; Ambler, Gareth; Bunce, Catey

2018-05-01

The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open-angle glaucoma (POAG) or ocular hypertension (OHT). The LiGHT Trial is a prospective, unmasked, multicentre, pragmatic, randomised controlled trial. 718 previously untreated patients with POAG or OHT were recruited at six collaborating centres in the UK between 2012 and 2014. The trial comprises two treatment arms: initial SLT followed by conventional medical therapy as required, and medical therapy without laser therapy. Randomisation was provided online by a web-based randomisation service. Participants will be monitored for 3 years, according to routine clinical practice. The target intraocular pressure (IOP) was set at baseline according to an algorithm, based on disease severity and lifetime risk of loss of vision at recruitment, and subsequently adjusted on the basis of IOP control, optic disc and visual field. The primary outcome measure is health-related quality of life (HRQL) (EQ-5D five-level). Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index, Glaucoma Symptom Scale, Glaucoma Quality of Life, objective measures of pathway effectiveness, visual function and safety profiles and concordance. A single main analysis will be performed at the end of the trial on an intention-to-treat basis. The LiGHT Trial is a multicentre, pragmatic, randomised clinical trial that will provide valuable data on the relative HRQL, clinical effectiveness and cost-effectiveness of SLT and topical IOP-lowering medication. ISRCTN32038223, Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A feasibility study investigating the acceptability and design of a multicentre randomised controlled trial of needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren's contractures of the fingers (HAND-1): study protocol for a randomised controlled trial.

PubMed

Harrison, Eleanor; Tan, Wei; Mills, Nicola; Karantana, Alexia; Sprange, Kirsty; Duley, Lelia; Elliott, Daisy; Blazeby, Jane; Hollingworth, William; Montgomery, Alan A; Davis, Tim

2017-08-25

Dupuytren's contractures are fibrous cords under the skin of the palm of the hand. The contractures are painless but cause one or more fingers to curl into the palm, resulting in loss of function. Standard treatment within the NHS is surgery to remove (fasciectomy) or divide (fasciotomy) the contractures, and the treatment offered is frequently determined by surgeon preference. This study aims to determine the feasibility of conducting a large, multicentre randomised controlled trial to assess the clinical and cost-effectiveness of needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren's contracture. HAND-1 is a parallel, two-arm, multicentre, randomised feasibility trial. Eligible patients aged 18 years or over who have one or more fingers with a Dupuytren's contracture of more than 30° in the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joints, well-defined cord(s) causing contracture, and have not undergone previous surgery for Dupuytren's on the same hand will be randomised (1:1) to treatment with either needle fasciotomy or limited fasciectomy. Participants will be followed-up for up to 6 months post surgery. Feasibility outcomes include number of patients screened, consented and randomised, adherence with treatment, completion of follow-up and identification of an appropriate patient-reported outcome measure (PROM) to use as primary outcome for a main trial. Embedded qualitative research, incorporating a QuinteT Recruitment Intervention, will focus on understanding and optimising the recruitment process, and exploring patients' experiences of trial participation and the interventions. This study will assess whether a large multicentre trial comparing the clinical and cost-effectiveness of needle fasciotomy and limited fasciectomy for the treatment of Dupuytren's contractures is feasible, and if so will provide data to inform its design and successful conduct. International Standard Registered Clinical/soCial sTudy Number: ISRCTN11164292 . Registered on 28 August 2015.

Lack of effect of nitrates on exercise tolerance in patients with mild to moderate heart failure caused by coronary disease already treated with captopril.

PubMed

Wieshammer, S; Hetzel, M; Hetzel, J; Kochs, M; Hombach, V

1993-07-01

To test the hypothesis that the addition of nitrates improves exercise tolerance in patients with heart failure caused by coronary artery disease already treated with an angiotensin converting enzyme inhibitor and diuretics. Randomised, double blind, placebo controlled, 16 week treatment periods. Outpatient clinic at a university hospital. 54 patients with previous myocardial infarction, symptoms of mild to moderate heart failure, left ventricular ejection fraction below 40%, no exercise-induced angina or electrocardiographic signs of ischaemia. Four patients in the nitrate group (n = 24) and one patient of the placebo group (n = 25) were withdrawn from the study. After the patients had been on constant doses of captopril and diuretics for at least 2 weeks, they were randomised to receive a target dose of 40 mg isosorbide dinitrate twice daily or placebo in addition to the continuation of captopril and diuretics. Bicycle exercise tests with measurement of gas exchange were carried out before randomisation and after 1, 6, 12, and 16 weeks of the double blind treatment. The change in peak oxygen uptake from control to week 16 was prospectively defined as the main outcome measure. The increase in peak oxygen uptake from before randomisation tended to be greater in the placebo group (before randomisation 17.4 (3.4) ml/min/kg) than in the nitrate group (before randomisation 17.1 (3.5) ml/min/kg) after 12 weeks (mean increase 1.1 (2.7) v 0.0 (2.7) ml/min/kg, p < 0.12) and 16 weeks (1.7 (3.0) v 0.3 (2.6) ml/min/kg, p < 0.14) of treatment. The addition of nitrates to a baseline treatment consisting of captopril and diuretics did not improve exercise tolerance.

SMART: self-management of anticoagulation, a randomised trial [ISRCTN19313375].

PubMed

McCahon, Deborah; Fitzmaurice, David A; Murray, Ellen T; Fuller, Christopher J; Hobbs, Richard F D; Allan, Teresa F; Raftery, James P

2003-09-18

Oral anticoagulation monitoring has traditionally taken place in secondary care because of the need for a laboratory blood test, the international normalised ratio (INR). The development of reliable near patient testing (NPT) systems for INR estimation has facilitated devolution of testing to primary care. Patient self-management is a logical progression from the primary care model. This study will be the first to randomise non-selected patients in primary care, to either self-management or standard care. The study was a multi-centred randomised controlled trial with patients from 49 general practices recruited. Those suitable for inclusion were aged 18 or over, with a long term indication for oral anticoagulation, who had taken warfarin for at least six months. Patients randomised to the intervention arm attended at least two training sessions which were practice-based, 1 week apart. Each patient was assessed on their capability to undertake self management. If considered capable, they were given a near patient INR testing monitor, test strips and quality control material for home testing. Patients managed their own anticoagulation for a period of 12 months and performed their INR test every 2 weeks. Control patients continued with their pre-study care either attending hospital or practice based anticoagulant clinics. The methodology used in this trial will overcome concerns from previous trials of selection bias and relevance to the UK health service. The study will give a clearer understanding of the benefits of self-management in terms of clinical and cost effectiveness and patient preference.

Effect of a high-density foam seating wedge on back pain intensity when used by 14 to 16-year-old school students: a randomised controlled trial.

PubMed

Candy, Elizabeth A; Farewell, Daniel; Jerosch-Herold, Christina; Shepstone, Lee; Watts, Richard A; Stephenson, Richard C

2012-12-01

No previous randomised controlled trials had been undertaken investigating the effect of school seating on back pain in 14 to 16 year olds. This study was designed to test the effect of the use of a high-density foam wedge on normal school seating on the intensity of back pain. Randomised controlled trial. Suffolk, a predominantly rural county in eastern England. One hundred and eighty-five students with back pain were recruited from 12 schools. Randomisation was stratified by school. The control and intervention groups included 92 and 83 students, respectively. Following a 1-week baseline observation period, each student in the intervention group was given a wedge to use on their school chairs. The primary outcome measure was pain intensity (numerical rating scale, 0 to 10) recorded in pain diaries over 4 weeks. Random effects models were used to analyse the pain intensity data. Ninety-seven students (46 control group, 51 intervention group) completed the trial. For the intervention group, pain intensity was reduced significantly over the 3 weeks of wedge use. The average reduction in pain intensity was estimated to be 0.709 points (95% confidence interval 0.341 to 1.077), representing a 58% reduction in back pain for those in the intervention group. Use of a wedge reduced the intensity of back pain significantly, especially in the evenings. The results suggest that further research into the longer-term effect of seating on pain intensity in adolescents should be considered. Copyright © 2011 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Evaluation of a novel information resource for patients with bronchiectasis: study protocol for a randomised controlled trial.

PubMed

Hester, Katy L M; Newton, Julia; Rapley, Tim; De Soyza, Anthony

2016-04-23

There is currently little patient information on bronchiectasis, a chronic lung disease with rising prevalence. Previous work shows that patients and their families want more information, which could potentially improve their understanding and self-management. Using interviews and focus groups, we have co-developed a novel patient and carer information resource, aiming to meet their identified needs. The aims and objectives are: 1. To assess the potential impact of the information resource 2. To evaluate and refine the intervention 3. To establish the feasibility of carrying out a multi-centre randomised controlled trial to determine its effect on understanding, self-management and health outcomes This is a feasibility study, with a single-centre, randomised controlled trial design, comparing use of a novel patient information resource to usual care in bronchiectasis. Additionally, patients and carers will be invited to focus groups to discuss their views on both the intervention itself and the trial process. The study duration for each participant will be 3 months from the study entry date. A total of 70 patients will be recruited to the study, and a minimum of 30 will be randomised to each arm. Ten participants (and their carers if applicable) will be invited to attend focus groups on completion of the study visits. Participants will be adults with bronchiectasis diagnosed as per national bronchiectasis guidelines. Once consented, participants will be randomised to the intervention or control arm using random permuted blocks to ensure treatment group numbers are evenly balanced. Randomisation will be web-based. Those randomised to the intervention will receive the information resource (website and booklet) and instructions on its use. Outcome measures (resource satisfaction, resource use and alternative information seeking, quality of life questionnaires, unscheduled healthcare visits, exacerbation frequency, bronchiectasis knowledge questionnaire and lung function tests) will be recorded at baseline, 2 weeks and 3 months. All outcome measures will be used in assessing feasibility and acceptability of a future definitive trial. Feasibility outcomes include recruitment, retention and study scale form completion rates. Focus groups will strengthen qualitative data for resource refinement and to identify participant views on the trial process, which will also inform feasibility assessments. Questionnaires will also be used to evaluate and refine the resource. ISRCTN84229105.

Guided, internet-based, rumination-focused cognitive behavioural therapy (i-RFCBT) versus a no-intervention control to prevent depression in high-ruminating young adults, along with an adjunct assessment of the feasibility of unguided i-RFCBT, in the REducing Stress and Preventing Depression trial (RESPOND): study protocol for a phase III randomised controlled trial.

PubMed

Cook, Lorna; Watkins, Edward

2016-01-04

Depression is a global health challenge. Prevention is highlighted as a priority to reduce its prevalence. Although effective preventive interventions exist, the efficacy and coverage can be improved. One proposed means to increase efficacy is by using interventions to target specific risk factors, such as rumination. Rumination-focused CBT (RFCBT) was developed to specifically target depressive rumination and reduces acute depressive symptoms and relapse for patients with residual depression in a randomised controlled trial. Preliminary findings from a Dutch randomised prevention trial in 251 high-risk 15- to 22-year-old subjects selected with elevated worry and rumination found that both supported internet-RFBCT and group-delivered RFCBT equally reduced depressive symptoms and the onset of depressive cases over a period of 1 year, relative to the no-intervention control. A phase III randomised controlled trial following the Medical Research Council (MRC) Complex Interventions Framework will extend a Dutch trial to the United Kingdom, with the addition of diagnostic interviews, primarily to test whether guided internet-RFCBT reduces the onset of depression relative to a no-intervention control. High-risk young adults (aged 18 to 24 years), selected with elevated worry/rumination and recruited through university and internet advertisement, will be randomised to receive either guided internet-RFCBT, supported by clinical psychologists or mental health paraprofessionals, or a no-intervention control. As an adjunct arm, participants are also randomised to unguided internet-RFCBT self-help to provide an initial test of the feasibility and effect size of this intervention. While participants are also randomised to unguided internet-RFCBT, the trial was designed and powered as a phase III trial comparing guided internet-RFCBT versus a no-intervention control. In the comparison between these two arms, the primary outcomes are as follows: a) onset of major depressive episode over a 12-month period, assessed with a Structured Clinical Interview for Diagnosis at 3 months (post-intervention), 6 months and 15 months after randomisation. The following secondary outcomes will be recorded: the incidence of generalized anxiety disorder, symptoms of depression and anxiety, and levels of worry and rumination, measured at baseline and at the same follow-up intervals. In relation to the pilot investigation of unguided internet-RFCBT (the adjunct intervention arm), we will assess the feasibility and acceptability of the data-collection procedures, levels of attrition, effect size and acceptability of the unguided internet-RFCBT intervention. Widespread implementation is necessary for effective prevention, suggesting that the internet may be a valuable mode of delivery. Previous research suggests that guided internet-RFCBT reduces incidence rates relative to controls. We are also interested in developing and evaluating an unguided version to potentially increase the availability and reduce the costs. Current Controlled Trials ISRCTN12683436 . Date of registration: 27 October 2014.

The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial): study protocol

PubMed Central

2014-01-01

Background Insertion of a ventriculoperitoneal shunt (VPS) for the treatment of hydrocephalus is one of the most common neurosurgical procedures in the UK, but failures caused by infection occur in approximately 8% of primary cases. VPS infection is associated with considerable morbidity and mortality and its management results in substantial cost to the health service. Antibiotic-impregnated (rifampicin and clindamycin) and silver-impregnated VPS have been developed to reduce infection rates. Whilst there is some evidence showing that such devices may lead to a reduction in VPS infection, there are no randomised controlled trials (RCTs) to support their routine use. Methods/design Overall, 1,200 patients will be recruited from 17 regional neurosurgical units in the UK and Ireland. Patients of any age undergoing insertion of their first VPS are eligible. Patients with previous indwelling VPS, active and on-going cerebrospinal fluid (CSF) or peritoneal infection, multiloculated hydrocephalus requiring multiple VPS or neuroendoscopy, and ventriculoatrial or ventriculopleural shunt planned will be excluded. Patients will be randomised 1:1:1 to either standard silicone (comparator), antibiotic-impregnated, or silver-impregnated VPS. The primary outcome measure is time to VPS infection. Secondary outcome measures include time to VPS failure of any cause, reason for VPS failure (infection, mechanical failure, or patient failure), types of bacterial VPS infection (organism type and antibiotic resistance), and incremental cost per VPS failure averted. Discussion The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial) is the first multi-centre RCT designed to determine whether antibiotic or silver-impregnated VPS reduce early shunt infection compared to standard silicone VPS. The results of this study will be used to inform current neurosurgical practice and may potentially benefit patients undergoing shunt surgery in the future. Trial registration International Standard Randomised Controlled Trial Number: ISRCTN49474281. PMID:24383496

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.

The citation of relevant systematic reviews and randomised trials in published reports of trial protocols.

PubMed

Pandis, Nikolaos; Fleming, Padhraig S; Koletsi, Despina; Hopewell, Sally

2016-12-07

It is important that planned randomised trials are justified and placed in the context of the available evidence. The SPIRIT guidelines for reporting clinical trial protocols recommend that a recent and relevant systematic review should be included. The aim of this study was to assess the use of the existing evidence in order to justify trial conduct. Protocols of randomised trials published over a 1-month period (December 2015) indexed in PubMed were obtained. Data on trial characteristics relating to location, design, funding, conflict of interest and type of evidence included for trial justification was extracted in duplicate and independently by two investigators. The frequency of citation of previous research including relevant systematic reviews and randomised trials was assessed. Overall, 101 protocols for RCTs were identified. Most proposed trials were parallel-group (n = 74; 73.3%). Reference to an earlier systematic review with additional randomised trials was found in 9.9% (n = 10) of protocols and without additional trials in 30.7% (n = 31), while reference was made to randomised trials in isolation in 21.8% (n = 22). Explicit justification for the proposed randomised trial on the basis of being the first to address the research question was made in 17.8% (n = 18) of protocols. A randomised controlled trial was not cited in 10.9% (95% CI: 5.6, 18.7) (n = 11), while in 8.9% (95% CI: 4.2, 16.2) (n = 9) of the protocols a systematic review was cited but did not inform trial design. A relatively high percentage of protocols of randomised trials involves prior citation of randomised trials, systematic reviews or both. However, improvements are required to ensure that it is explicit that clinical trials are justified and shaped by contemporary best evidence.

Protocol for a randomised, placebo-controlled pilot study for assessing feasibility and efficacy of faecal microbiota transplantation in a paediatric ulcerative colitis population: PediFETCh trial

PubMed Central

Popov, Jelena

2017-01-01

Introduction Ulcerative colitis (UC) is a chronic, relapsing condition characterised by colonic inflammation. Increasing prevalence in early-age diagnosis provides opportunities for additional complications in later life as a result of prolonged exposure to inflammatory and therapeutic insults, necessitating novel avenues for therapeutics which may result in fewer side effects. Faecal microbiota transplantation (FMT) has previously demonstrated potential therapeutic benefit in an adult randomised-controlled trial and several recurrent Clostridium difficile infection studies. This phase Ib pilot will be the first randomised, single-blinded, placebo-controlled trial to assess feasibility and patient outcomes in a paediatric inflammatory bowel disease (IBD) population. Methods and analysis Fifty patients will be randomised 1:1 to receive normal saline control or active sample. Enema administrations will be performed two times per week for 6 weeks, followed at a 6-month follow-up period. Feasibility outcomes will include measures of patient eligibility, recruitment, willingness to participate, samples collections, hospitalizations and drop-out rate. Improvements in disease symptoms will determine the efficacy of treatment. Clinical disease scores will be taken throughout the study period using the Paediatric Ulcerative Colitis Activity Index (PUCAI). Monitoring of inflammatory markers in blood and stool will be performed at regular intervals. Microbiome analysis will be conducted on stool samples collected throughout the trials period. Imaging and endoscopic surveillance will be conducted if clinically necessary. Ethics and dissemination Ethics was obtained from local hospital research ethics boards across all three sites. Health Canada and FDA approval was obtained for the use of an Investigatory New Drug product. Results from this trial will be presented in international conferences and published in peer-review journals. Trial registration number Trial registration number: NCT02487238; preresults. PMID:28827258

Disc extrusions and bulges in nonspecific low back pain and sciatica: Exploratory randomised controlled trial comparing yoga therapy and normal medical treatment.

PubMed

Monro, Robin; Bhardwaj, Abhishek Kumar; Gupta, Ram Kumar; Telles, Shirley; Allen, Beth; Little, Paul

2015-01-01

Previous trials of yoga therapy for nonspecific low back pain (nsLBP) (without sciatica) showed beneficial effects. To test effects of yoga therapy on pain and disability associated with lumbar disc extrusions and bulges. Parallel-group, randomised, controlled trial. Sixty-one adults from rural population, aged 20-45, with nsLBP or sciatica, and disc extrusions or bulges. Randomised to yoga (n=30) and control (n=31). Yoga: 3-month yoga course of group classes and home practice, designed to ensure safety for disc extrusions. normal medical care. OUTCOME MEASURES (3-4 months) Primary: Roland Morris Disability Questionnaire (RMDQ); worst pain in past two weeks. Secondary: Aberdeen Low Back Pain Scale; straight leg raise test; structural changes. Disc projections per case ranged from one bulge or one extrusion to three bulges plus two extrusions. Sixty-two percent had sciatica. Intention-to-treat analysis of the RMDQ data, adjusted for age, sex and baseline RMDQ scores, gave a Yoga Group score 3.29 points lower than Control Group (0.98, 5.61; p=0.006) at 3 months. No other significant differences in the endpoints occurred. No adverse effects of yoga were reported. Yoga therapy can be safe and beneficial for patients with nsLBP or sciatica, accompanied by disc extrusions and bulges.

Effectiveness of Educational Poster on Knowledge of Emergency Management of Dental Trauma–Part 1. Cluster Randomised Controlled Trial for Primary and Secondary School Teachers

PubMed Central

Young, Cecilia; Wong, Kin Yau; Cheung, Lim K.

2013-01-01

Objective To investigate the effectiveness of educational posters in improving the knowledge level of primary and secondary school teachers regarding emergency management of dental trauma. Methods A cluster randomised controlled trial was conducted. 32 schools with a total of 515 teachers were randomised into intervention (poster) and control groups at the school level. Teachers’ baseline levels of knowledge about dental trauma were obtained by using a questionnaire. Posters containing information on dental trauma management were displayed in the school medical room, the common room used by staff, and on a notice board for 2 weeks in each school of the intervention group; in the control group, no posters were displayed. Teachers in both groups completed the questionnaire after 2 weeks. Results The teachers in the intervention schools (where posters were displayed for 2 weeks) showed statistically significant improvement in scores in cases where they had not previously learned about dental emergencies from sources other than first aid training, with an average score increase of 2.6656 (score range of questionnaire, −13 to 9; p-value <0.0001). Conclusion Educational posters on the management of dental trauma can significantly improve the level of knowledge of primary and secondary school teachers in Hong Kong. KClinicalTrials.com HKCTR-1307 ClinicalTrials.gov: NCT01707355 PMID:24147154

Is a controlled randomised trial the non-plus-ultra design? A contribution to discussion on comparative, controlled, non-randomised trials.

PubMed

Gaus, Wilhelm; Muche, Rainer

2013-05-01

Clinical studies provide formalised experience for evidence-based medicine (EBM). Many people consider a controlled randomised trial (CRT, identical to a randomised controlled trial RCT) to be the non-plus-ultra design. However, CRTs also have limitations. The problem is not randomisation itself but informed consent for randomisation and masking of therapies according to today's legal and ethical standards. We do not want to de-rate CRTs, but we would like to contribute to the discussion on clinical research methodology. Informed consent to a CRT and masking of therapies plainly select patients. The excellent internal validity of CRTs can be counterbalanced by poor external validity, because internal and external validity act as antagonists. In a CRT, patients may feel like guinea pigs, this can decrease compliance, cause protocol violations, reduce self-healing properties, suppress unspecific therapeutic effects and possibly even modify specific efficacy. A control group (comparative study) is most important for the degree of evidence achieved by a trial. Study control by detailed protocol and good clinical practice (controlled study) is second in importance and randomisation and masking is third (thus the sequence CRT instead of RCT). Controlled non-randomised trials are just as ambitious and detailed as CRTs. We recommend clinicians and biometricians to take high quality controlled non-randomised trials into consideration more often. They combine good internal and external validity, better suit daily medical practice, show better patient compliance and fewer protocol violations, deliver estimators unbiased by alienated patients, and perhaps provide a clearer explanation of the achieved success. Copyright © 2013 Elsevier Inc. All rights reserved.

Hematopoietic stem cell transplantation for people with ß-thalassaemia major.

PubMed

Jagannath, Vanitha A; Fedorowicz, Zbys; Al Hajeri, Amani; Sharma, Akshay

2016-11-30

Thalassemia is an inherited autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions. This results in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In ß-thalassaemia major there is an underproduction of ß-globin chains combined with excess of free α-globin chains. The excess free α-globin chains precipitate in red blood cells, leading to their destruction (haemolysis) and ineffective erythropoiesis. The conventional approach to treatment is based on the correction of haemoglobin status through regular blood transfusions and iron chelation therapy for iron overload. Although conventional treatment has the capacity to improve the quality of life of people with ß-thalassaemia major, allogeneic hematopoietic stem cell transplantation is the only currently available procedure which has the curative potential. This is an update of a previously published Cochrane Review. To evaluate the effectiveness and safety of different types of allogeneic hematopoietic stem cell transplantation, in people with severe transfusion-dependant ß-thalassaemia major, ß-thalassaemia intermedia or ß0/+- thalassaemia variants requiring chronic blood transfusion. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 18 August 2016. Randomised controlled trials and quasi-randomised controlled trials comparing allogeneic hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen). Two review authors independently screened studies and had planned to extract data and assess risk of bias using standard Cochrane methodologies but no studies were identified for inclusion. No relevant studies were retrieved after a comprehensive search of the literature. We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of allogeneic stem cell transplantation in people with severe transfusion-dependant ß-thalassaemia major or ß0/+- thalassaemia variants requiring chronic blood transfusion. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.

Effectiveness of multifaceted educational programme to reduce antibiotic dispensing in primary care: practice based randomised controlled trial

PubMed Central

Simpson, Sharon A; Dunstan, Frank; Rollnick, Stephen; Cohen, David; Gillespie, David; Evans, Meirion R; health, senior lecturer in epidemiology and public; Alam, M Fasihul; Bekkers, Marie-Jet; Evans, John; Moore, Laurence; Howe, Robin; Hayes, Jamie; Hare, Monika; Hood, Kerenza

2012-01-01

Objective To evaluate the effectiveness and costs of a multifaceted flexible educational programme aimed at reducing antibiotic dispensing at the practice level in primary care. Design Randomised controlled trial with general practices as the unit of randomisation and analysis. Clinicians and researchers were blinded to group allocation until after randomisation. Setting 68 general practices with about 480 000 patients in Wales, United Kingdom. Participants 34 practices were randomised to receive the educational programme and 34 practices to be controls. 139 clinicians from the intervention practices and 124 from control practices had agreed to participate before randomisation. Practice level data covering all the clinicians in the 68 practices were analysed. Interventions Intervention practices followed the Stemming the Tide of Antibiotic Resistance (STAR) educational programme, which included a practice based seminar reflecting on the practices’ own dispensing and resistance data, online educational elements, and practising consulting skills in routine care. Control practices provided usual care. Main outcome measures Total numbers of oral antibiotic items dispensed for all causes per 1000 practice patients in the year after the intervention, adjusted for the previous year’s dispensing. Secondary outcomes included reconsultations, admissions to hospital for selected causes, and costs. Results The rate of oral antibiotic dispensing (items per 1000 registered patients) decreased by 14.1 in the intervention group but increased by 12.1 in the control group, a net difference of 26.1. After adjustment for baseline dispensing rate, this amounted to a 4.2% (95% confidence interval 0.6% to 7.7%) reduction in total oral antibiotic dispensing for the year in the intervention group relative to the control group (P=0.02). Reductions were found for all classes of antibiotics other than penicillinase-resistant penicillins but were largest and significant individually for phenoxymethylpenicillins (penicillin V) (7.3%, 0.4% to 13.7%) and macrolides (7.7%, 1.1% to 13.8%). There were no significant differences between intervention and control practices in the number of admissions to hospital or in reconsultations for a respiratory tract infection within seven days of an index consultation. The mean cost of the programme was £2923 (€3491, $4572) per practice (SD £1187). There was a 5.5% reduction in the cost of dispensed antibiotics in the intervention group compared with the control group (−0.4% to 11.4%), equivalent to a reduction of about £830 a year for an average intervention practice. Conclusion The STAR educational programme led to reductions in all cause oral antibiotic dispensing over the subsequent year with no significant change in admissions to hospital, reconsultations, or costs. Trial registration ISRCT No 63355948. PMID:22302780

Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation.

PubMed

Miles, David; Cameron, David; Bondarenko, Igor; Manzyuk, Lyudmila; Alcedo, Juan Carlos; Lopez, Roberto Ivan; Im, Seock-Ah; Canon, Jean-Luc; Shparyk, Yaroslav; Yardley, Denise A; Masuda, Norikazu; Ro, Jungsil; Denduluri, Neelima; Hubeaux, Stanislas; Quah, Cheng; Bais, Carlos; O'Shaughnessy, Joyce

2017-01-01

MERiDiAN evaluated plasma vascular endothelial growth factor-A (pVEGF-A) prospectively as a predictive biomarker for bevacizumab efficacy in metastatic breast cancer (mBC). In this double-blind placebo-controlled randomised phase III trial, eligible patients had HER2-negative mBC previously untreated with chemotherapy. pVEGF-A was measured before randomisation to paclitaxel 90 mg/m 2 on days 1, 8 and 15 with either placebo or bevacizumab 10 mg/kg on days 1 and 15, repeated every 4 weeks until disease progression, unacceptable toxicity or consent withdrawal. Stratification factors were baseline pVEGF-A, prior adjuvant chemotherapy, hormone receptor status and geographic region. Co-primary end-points were investigator-assessed progression-free survival (PFS) in the intent-to-treat and pVEGF-A high populations. Of 481 patients randomised (242 placebo-paclitaxel; 239 bevacizumab-paclitaxel), 471 received study treatment. The stratified PFS hazard ratio was 0.68 (99% confidence interval, 0.51-0.91; log-rank p = 0.0007) in the intent-to-treat population (median 8.8 months with placebo-paclitaxel versus 11.0 months with bevacizumab-paclitaxel) and 0.64 (96% confidence interval, 0.47-0.88; log-rank p = 0.0038) in the pVEGF-A high subgroup. The PFS treatment-by-VEGF-A interaction p value (secondary end-point) was 0.4619. Bevacizumab was associated with increased incidences of bleeding (all grades: 45% versus 27% with placebo), neutropenia (all grades: 39% versus 29%; grade ≥3: 25% versus 13%) and hypertension (all grades: 31% versus 13%; grade ≥3: 11% versus 4%). The significant PFS improvement with bevacizumab is consistent with previous placebo-controlled first-line trials in mBC. Results do not support using baseline pVEGF-A to identify patients benefitting most from bevacizumab. ClinicalTrials.gov NCT01663727. Copyright © 2016. Published by Elsevier Ltd.

Do personalised e-mail invitations increase the response rates of breast cancer survivors invited to participate in a web-based behaviour change intervention? A quasi-randomised 2-arm controlled trial.

PubMed

Short, Camille E; Rebar, Amanda L; Vandelanotte, Corneel

2015-08-19

Previous research has shown that the personalisation of study invitations improves response rates in survey-based research. To examine if this finding extends to experimental studies, we examined the impact of personalised study invitation e-mails on the response rates of potentially eligible breast cancer survivors for participation in a 6 month randomised controlled trial testing the efficacy of a physical activity intervention. Potential participants (n = 344) were sent either a personalised email or a generic email. Those sent the personalised email were 1.5 times (95 % CI = 1.18-1.93) more likely to respond than those sent the generic email. These findings suggest that personalisation may be a useful and potentially powerful tool that can be utilised when recruiting participants into experimental studies in order to boost response rates.

Maternal fish oil supplementation in pregnancy: a 12 year follow-up of a randomised controlled trial.

PubMed

Meldrum, Suzanne; Dunstan, Janet A; Foster, Jonathan K; Simmer, Karen; Prescott, Susan L

2015-03-20

A number of trials have been undertaken to assess whether the intake of omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) during pregnancy can influence the neurological development of the offspring, yet no consensus from these trials has been reached. We aimed to investigate the long-term effects (12 years) of fish oil supplementation in pregnancy on neurodevelopment, including cognition, language and fine motor skills. In a follow up of a previously published randomised controlled trial of 98 pregnant women, their children were assessed at 12 years of age using a battery of neurodevelopmental assessments. Fifty participants were assessed at 12 years, with 25 participant's mothers receiving fish oil supplementation, and 25 receiving control capsules. There were no significant differences for any of the assessment measures completed. Our data indicate that fish oil supplementation during pregnancy does not influence the cognition, language or fine motor skills of children in late primary school (12 years of age).

Maternal Fish Oil Supplementation in Pregnancy: A 12 Year Follow-Up of a Randomised Controlled Trial

PubMed Central

Meldrum, Suzanne; Dunstan, Janet A.; Foster, Jonathan K.; Simmer, Karen; Prescott, Susan L.

2015-01-01

A number of trials have been undertaken to assess whether the intake of omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) during pregnancy can influence the neurological development of the offspring, yet no consensus from these trials has been reached. We aimed to investigate the long-term effects (12 years) of fish oil supplementation in pregnancy on neurodevelopment, including cognition, language and fine motor skills. In a follow up of a previously published randomised controlled trial of 98 pregnant women, their children were assessed at 12 years of age using a battery of neurodevelopmental assessments. Fifty participants were assessed at 12 years, with 25 participant’s mothers receiving fish oil supplementation, and 25 receiving control capsules. There were no significant differences for any of the assessment measures completed. Our data indicate that fish oil supplementation during pregnancy does not influence the cognition, language or fine motor skills of children in late primary school (12 years of age). PMID:25803546

Vaccine testing for emerging infections: the case for individual randomisation

PubMed Central

Eyal, Nir; Lipsitch, Marc

2017-01-01

During the 2014–2015 Ebola outbreak in Guinea, Liberia and Sierra Leone, many opposed the use of individually randomised controlled trials to test candidate Ebola vaccines. For a raging fatal disease, they explained, it is unethical to relegate some study participants to control arms. In Zika and future emerging infections, similar opposition may hinder urgent vaccine research, so it is best to address these questions now. This article lays out the ethical case for individually randomised control in testing vaccines against many emerging infections, including lethal infections in low-income countries, even when at no point in the trial do the controls receive the countermeasures being tested. When individual randomisation is feasible—and it often will be—it tends to save more lives than alternative designs would. And for emerging infections, individual randomisation also tends as such to improve care, access to the experimental vaccine and prospects for all participants relative to their opportunities absent the trial, and no less than alternative designs would. That obtains even under placebo control and without equipoise—requiring which would undermine individual randomisation and the alternative designs that opponents proffered. Our arguments expound four often-neglected factors: benefits to non-participants, benefits to participants once a trial is over including post-trial access to the study intervention, participants’ prospects before randomisation to arms and the near-inevitable disparity between arms in any randomised controlled trial. PMID:28396558

Developing and testing accelerated partner therapy for partner notification for people with genital Chlamydia trachomatis diagnosed in primary care: a pilot randomised controlled trial

PubMed Central

Estcourt, Claudia S; Sutcliffe, Lorna J; Copas, Andrew; Mercer, Catherine H; Roberts, Tracy E; Jackson, Louise J; Symonds, Merle; Tickle, Laura; Muniina, Pamela; Rait, Greta; Johnson, Anne M; Aderogba, Kazeem; Creighton, Sarah; Cassell, Jackie A

2015-01-01

Background Accelerated partner therapy (APT) is a promising partner notification (PN) intervention in specialist sexual health clinic attenders. To address its applicability in primary care, we undertook a pilot randomised controlled trial (RCT) of two APT models in community settings. Methods Three-arm pilot RCT of two adjunct APT interventions: APTHotline (telephone assessment of partner(s) plus standard PN) and APTPharmacy (community pharmacist assessment of partner(s) plus routine PN), versus standard PN alone (patient referral). Index patients were women diagnosed with genital chlamydia in 12 general practices and three community contraception and sexual health (CASH) services in London and south coast of England, randomised between 1 September 2011 and 31 July 2013. Results 199 women described 339 male partners, of whom 313 were reported by the index as contactable. The proportions of contactable partners considered treated within 6 weeks of index diagnosis were APTHotline 39/111 (35%), APTPharmacy 46/100 (46%), standard patient referral 46/102 (45%). Among treated partners, 8/39 (21%) in APTHotline arm were treated via hotline and 14/46 (30%) in APTPharmacy arm were treated via pharmacy. Conclusions The two novel primary care APT models were acceptable, feasible, compliant with regulations and capable of achieving acceptable outcomes within a pilot RCT but intervention uptake was low. Although addition of these interventions to standard PN did not result in a difference between arms, overall PN uptake was higher than previously reported in similar settings, probably as a result of introducing a formal evaluation. Recruitment to an individually randomised trial proved challenging and full evaluation will likely require service-level randomisation. Trial registration number Registered UK Clinical Research Network Study Portfolio id number 10123. PMID:26019232

Effect of peer support on prevention of postnatal depression among high risk women: multisite randomised controlled trial.

PubMed

Dennis, C-L; Hodnett, E; Kenton, L; Weston, J; Zupancic, J; Stewart, D E; Kiss, A

2009-01-15

To evaluate the effectiveness of telephone based peer support in the prevention of postnatal depression. Multisite randomised controlled trial. Seven health regions across Ontario, Canada. 701 women in the first two weeks postpartum identified as high risk for postnatal depression with the Edinburgh postnatal depression scale and randomised with an internet based randomisation service. Proactive individualised telephone based peer (mother to mother) support, initiated within 48-72 hours of randomisation, provided by a volunteer recruited from the community who had previously experienced and recovered from self reported postnatal depression and attended a four hour training session. Edinburgh postnatal depression scale, structured clinical interview-depression, state-trait anxiety inventory, UCLA loneliness scale, and use of health services. After web based screening of 21 470 women, 701 (72%) eligible mothers were recruited. A blinded research nurse followed up more than 85% by telephone, including 613 at 12 weeks and 600 at 24 weeks postpartum. At 12 weeks, 14% (40/297) of women in the intervention group and 25% (78/315) in the control group had an Edinburgh postnatal depression scale score >12 (chi(2)=12.5, P<0.001; number need to treat 8.8, 95% confidence interval 5.9 to 19.6; relative risk reduction 0.46, 95% confidence interval 0.24 to 0.62). There was a positive trend in favour of the intervention group for maternal anxiety but not loneliness or use of health services. For ethical reasons, participants identified with clinical depression at 12 weeks were referred for treatment, resulting in no differences between groups at 24 weeks. Of the 221 women in the intervention group who received and evaluated their experience of peer support, over 80% were satisfied and would recommend this support to a friend. Telephone based peer support can be effective in preventing postnatal depression among women at high risk. ISRCTN 68337727.

Brief Report: Mediation of Treatment Effect in a Communication Intervention for Pre-School Children with Autism

ERIC Educational Resources Information Center

Aldred, Catherine; Green, Jonathan; Emsley, Richard; McConachie, Helen

2012-01-01

Tests of mediation in treatment trials can illuminate processes of change and suggest causal influences in development. We conducted a mediation analysis of a previously published randomised controlled trial of parent-mediated communication-focused treatment for autism against ordinary care, with 28 children aged 2-5 years (Aldred et al. in J…

Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies.

PubMed

Li, Xue; Meng, Xiangrui; Timofeeva, Maria; Tzoulaki, Ioanna; Tsilidis, Konstantinos K; Ioannidis, John PA; Campbell, Harry; Theodoratou, Evropi

2017-06-07

Objective  To map the diverse health outcomes associated with serum uric acid (SUA) levels. Design  Umbrella review. Data sources  Medline, Embase, Cochrane Database of Systematic Reviews, and screening of citations and references. Eligibility criteria  Systematic reviews and meta-analyses of observational studies that examined associations between SUA level and health outcomes, meta-analyses of randomised controlled trials that investigated health outcomes related to SUA lowering treatment, and Mendelian randomisation studies that explored the causal associations of SUA level with health outcomes. Results  57 articles reporting 15 systematic reviews and144 meta-analyses of observational studies (76 unique outcomes), 8 articles reporting 31 meta-analyses of randomised controlled trials (20 unique outcomes), and 36 articles reporting 107 Mendelian randomisation studies (56 unique outcomes) met the eligibility criteria. Across all three study types, 136 unique health outcomes were reported. 16 unique outcomes in meta-analyses of observational studies had P<10 -6 , 8 unique outcomes in meta-analyses of randomised controlled trials had P<0.001, and 4 unique outcomes in Mendelian randomisation studies had P<0.01. Large between study heterogeneity was common (80% and 45% in meta-analyses of observational studies and of randomised controlled trials, respectively). 42 (55%) meta-analyses of observational studies and 7 (35%) meta-analyses of randomised controlled trials showed evidence of small study effects or excess significance bias. No associations from meta-analyses of observational studies were classified as convincing; five associations were classified as highly suggestive (increased risk of heart failure, hypertension, impaired fasting glucose or diabetes, chronic kidney disease, coronary heart disease mortality with high SUA levels). Only one outcome from randomised controlled trials (decreased risk of nephrolithiasis recurrence with SUA lowering treatment) had P<0.001, a 95% prediction interval excluding the null, and no large heterogeneity or bias. Only one outcome from Mendelian randomisation studies (increased risk of gout with high SUA levels) presented convincing evidence. Hypertension and chronic kidney disease showed concordant evidence in meta-analyses of observational studies, and in some (but not all) meta-analyses of randomised controlled trials with respective intermediate or surrogate outcomes, but they were not statistically significant in Mendelian randomisation studies. Conclusion  Despite a few hundred systematic reviews, meta-analyses, and Mendelian randomisation studies exploring 136 unique health outcomes, convincing evidence of a clear role of SUA level only exists for gout and nephrolithiasis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series.

PubMed

Taylor, M A; Reilly, D; Llewellyn-Jones, R H; McSharry, C; Aitchison, T C

To test the hypothesis that homoeopathy is a placebo by examining its effect in patients with allergic rhinitis and so contest the evidence from three previous trials in this series. Randomised, double blind, placebo controlled, parallel group, multicentre study. Four general practices and a hospital ear, nose, and throat outpatient department. 51 patients with perennial allergic rhinitis. Random assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo. Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after randomisation. Fifty patients completed the study. The homoeopathy group had a significant objective improvement in nasal airflow compared with the placebo group (mean difference 19.8 l/min, 95% confidence interval 10.4 to 29.1, P=0.0001). Both groups reported improvement in symptoms, with patients taking homoeopathy reporting more improvement in all but one of the centres, which had more patients with aggravations. On average no significant difference between the groups was seen on visual analogue scale scores. Initial aggravations of rhinitis symptoms were more common with homoeopathy than placebo (7 (30%) v 2 (7%), P=0.04). Addition of these results to those of three previous trials (n=253) showed a mean symptom reduction on visual analogue scores of 28% (10.9 mm) for homoeopathy compared with 3% (1.1 mm) for placebo (95% confidence interval 4.2 to 15.4, P=0.0007). The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo.

Supervised pelvic floor muscle training versus attention-control massage treatment in patients with faecal incontinence: Statistical analysis plan for a randomised controlled trial.

PubMed

Ussing, Anja; Dahn, Inge; Due, Ulla; Sørensen, Michael; Petersen, Janne; Bandholm, Thomas

2017-12-01

Faecal incontinence affects approximately 8-9% of the adult population. The condition is surrounded by taboo; it can have a devastating impact on quality of life and lead to major limitations in daily life. Pelvic floor muscle training in combination with information and fibre supplements is recommended as first-line treatment for faecal incontinence. Despite this, the effect of pelvic floor muscle training for faecal incontinence is unclear. No previous trials have investigated the efficacy of supervised pelvic floor muscle training in combination with conservative treatment and compared this to an attention-control massage treatment including conservative treatment. The aim of this trial is to investigate if 16 weeks of supervised pelvic floor muscle training in combination with conservative treatment is superior to attention-control massage treatment and conservative treatment in patients with faecal incontinence. Randomised, controlled, superiority trial with two parallel arms. 100 participants with faecal incontinence will be randomised to either (1) individually supervised pelvic floor muscle training and conservative treatment or (2) attention-control massage treatment and conservative treatment. The primary outcome is participants' rating of symptom changes after 16 weeks of treatment using the Patient Global Impression of Improvement Scale. Secondary outcomes are the Vaizey Incontinence Score, the Fecal Incontinence Severity Index, the Fecal Incontinence Quality of Life Scale, a 14-day bowel diary, anorectal manometry and rectal capacity measurements. Follow-up assessment at 36 months will be conducted. This paper describes and discusses the rationale, the methods and in particular the statistical analysis plan of this trial.

Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial.

PubMed

Goya, Maria; Pratcorona, Laia; Merced, Carme; Rodó, Carlota; Valle, Leonor; Romero, Azahar; Juan, Miquel; Rodríguez, Alberto; Muñoz, Begoña; Santacruz, Belén; Bello-Muñoz, Juan Carlos; Llurba, Elisa; Higueras, Teresa; Cabero, Luis; Carreras, Elena

2012-05-12

Most previous studies of the use of cervical pessaries were either retrospective or case controlled and their results showed that this intervention might be a preventive strategy for women at risk of preterm birth; no randomised controlled trials have been undertaken. We therefore undertook a randomised, controlled trial to investigate whether the insertion of a cervical pessary in women with a short cervix identified by use of routine transvaginal scanning at 20-23 weeks of gestation reduces the rate of early preterm delivery. The Pesario Cervical para Evitar Prematuridad (PECEP) trial was undertaken in five hospitals in Spain. Pregnant women (aged 18-43 years) with a cervical length of 25 mm or less were randomly assigned according to a computer-generated allocation sequence by use of central telephone in a 1:1 ratio to the cervical pessary or expectant management (without a cervical pessary) group. Because of the nature of the intervention, this study was not masked. The primary outcome was spontaneous delivery before 34 weeks of gestation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00706264. 385 pregnant women with a short cervix were assigned to the pessary (n=192) and expectant management groups (n=193), and 190 were analysed in each group. Spontaneous delivery before 34 weeks of gestation was significantly less frequent in the pessary group than in the expectant management group (12 [6%] vs 51 [27%], odds ratio 0·18, 95% CI 0·08-0·37; p<0·0001). No serious adverse effects associated with the use of a cervical pessary were reported. Cervical pessary use could prevent preterm birth in a population of appropriately selected at-risk women previously screened for cervical length assessment at the midtrimester scan. Instituto Carlos III. Copyright © 2012 Elsevier Ltd. All rights reserved.

Granulocyte-macrophage colony stimulating factor administered as prophylaxis for reduction of sepsis in extremely preterm, small for gestational age neonates (the PROGRAMS trial): a single-blind, multicentre, randomised controlled trial.

PubMed

Carr, Robert; Brocklehurst, Peter; Doré, Caroline J; Modi, Neena

2009-01-17

Systemic sepsis is a major cause of death in preterm neonates. There are compelling theoretical reasons why treatment with haemopoietic colony-stimulating factors might reduce sepsis and improve outcomes, and as a consequence these agents have entered into use in neonatal medicine without adequate evidence. We assessed whether granulocyte-macrophage colony stimulating factor (GM-CSF) administered as prophylaxis to preterm neonates at high risk of neutropenia would reduce sepsis, mortality, and morbidity. We undertook a single-blind, multicentre, randomised controlled trial in 26 centres between June, 2000, and June, 2006. 280 neonates of below or equal to 31 weeks' gestation and below the 10th centile for birthweight were randomised within 72 h of birth to receive GM-CSF 10 microg/kg per day subcutaneously for 5 days or standard management. From recruitment to day 28 a detailed daily clinical record form was completed by the treating clinicians. Primary outcome was sepsis-free survival to 14 days from trial entry. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN42553489. Neutrophil counts after trial entry rose significantly more rapidly in infants treated with GM-CSF than in control infants during the first 11 days (difference between neutrophil count slopes 0.34 x 10(9)/L/day; 95% CI 0.12-0.56). There was no significant difference in sepsis-free survival for all infants (93 of 139 treated infants, 105 of 141 control infants; difference -8%, 95% CI -18 to 3). A meta-analysis of this trial and previous published prophylactic trials showed no survival benefit. Early postnatal prophylactic GM-CSF corrects neutropenia but does not reduce sepsis or improve survival and short-term outcomes in extremely preterm neonates.

Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials

PubMed Central

Tzoulaki, Ioanna; Zgaga, Lina; Ioannidis, John P A

2014-01-01

Objective To evaluate the breadth, validity, and presence of biases of the associations of vitamin D with diverse outcomes. Design Umbrella review of the evidence across systematic reviews and meta-analyses of observational studies of plasma 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D concentrations and randomised controlled trials of vitamin D supplementation. Data sources Medline, Embase, and screening of citations and references. Eligibility criteria Three types of studies were eligible for the umbrella review: systematic reviews and meta-analyses that examined observational associations between circulating vitamin D concentrations and any clinical outcome; and meta-analyses of randomised controlled trials assessing supplementation with vitamin D or active compounds (both established and newer compounds of vitamin D). Results 107 systematic literature reviews and 74 meta-analyses of observational studies of plasma vitamin D concentrations and 87 meta-analyses of randomised controlled trials of vitamin D supplementation were identified. The relation between vitamin D and 137 outcomes has been explored, covering a wide range of skeletal, malignant, cardiovascular, autoimmune, infectious, metabolic, and other diseases. Ten outcomes were examined by both meta-analyses of observational studies and meta-analyses of randomised controlled trials, but the direction of the effect and level of statistical significance was concordant only for birth weight (maternal vitamin D status or supplementation). On the basis of the available evidence, an association between vitamin D concentrations and birth weight, dental caries in children, maternal vitamin D concentrations at term, and parathyroid hormone concentrations in patients with chronic kidney disease requiring dialysis is probable, but further studies and better designed trials are needed to draw firmer conclusions. In contrast to previous reports, evidence does not support the argument that vitamin D only supplementation increases bone mineral density or reduces the risk of fractures or falls in older people. Conclusions Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable. PMID:24690624

Results of a feasibility randomised controlled study of the guidelines for exercise in multiple sclerosis project.

PubMed

Learmonth, Yvonne C; Adamson, Brynn C; Kinnett-Hopkins, Dominique; Bohri, Maria; Motl, Robert W

2017-03-01

There is increasing recognition that exercise is an efficacious strategy for managing many consequences of multiple sclerosis (MS), yet persons with MS are not engaging in sufficient exercise for accruing health benefits. Poor exercise uptake might be associated with the design of previous research. We conducted a randomised controlled trial (RCT) for examining the feasibility of a 4-month home-based, exercise-training program designed based on recent physical activity guidelines for MS and supplemented by behavioural strategies for compliance. Feasibility was assessed in the domains of process (e.g., recruitment), resource (e.g., monetary costs), management (e.g., personnel time requirements) and scientific outcomes (e.g., treatment effect). We recruited persons with mild-to-moderate MS who were randomised into an intervention or wait-list control condition. Intervention participants received a pedometer, elastic resistance bands, DVD, training manual, calendars, log-book, video coaching calls and newsletters. Participants in both conditions completed home-based assessments before and after the 4-month period. Ninety-nine persons with MS were assessed for eligibility, and 57 were randomised. Fifty-one persons completed the study (90%). Total costs of the study were US $5331.03. Personnel time to conduct the study totaled 263h. Participants in the intervention group complied fully with 71% of all exercise sessions. There was a moderate increase in self-reported exercise behaviour of the intervention participants as measured by the Godin Leisure-Time Exercise Questionnaire (d≥0.5). The results support the feasibility and acceptability of a home-based exercise intervention based on physical activity guidelines and supplemented with behavioural strategies for adults with mild-to-moderate MS. Copyright © 2016 Elsevier Inc. All rights reserved.

Self-managed loaded exercise versus usual physiotherapy treatment for rotator cuff tendinopathy: a pilot randomised controlled trial.

PubMed

Littlewood, Chris; Malliaras, Peter; Mawson, Sue; May, Stephen; Walters, Stephen J

2014-03-01

Rotator cuff tendinopathy is a common source of shoulder pain characterised by persistent and/or recurrent problems for a proportion of sufferers. The aim of this study was to pilot the methods proposed to conduct a substantive study to evaluate the effectiveness of a self-managed loaded exercise programme versus usual physiotherapy treatment for rotator cuff tendinopathy. A single-centre pragmatic unblinded parallel group pilot randomised controlled trial. One private physiotherapy clinic, northern England. Twenty-four participants with rotator cuff tendinopathy. The intervention was a programme of self-managed loaded exercise. The control group received usual physiotherapy treatment. Baseline assessment comprised the Shoulder Pain and Disability Index (SPADI) and the Short-Form 36, repeated three months post randomisation. The recruitment target was met and the majority of participants (98%) were willing to be randomised. 100% retention was attained with all participants completing the SPADI at three months. Exercise adherence rates were excellent (90%). The mean change in SPADI score was -23.7 (95% CI -14.4 to -33.3) points for the self-managed exercise group and -19.0 (95% CI -6.0 to -31.9) points for the usual physiotherapy treatment group. The difference in three month SPADI scores was 0.1 (95% CI -16.6 to 16.9) points in favour of the usual physiotherapy treatment group. In keeping with previous research which indicates the need for further evaluation of self-managed loaded exercise for rotator cuff tendinopathy, these methods and the preliminary evaluation of outcome offer a foundation and stimulus to conduct a substantive study. Copyright © 2013 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications.

PubMed

Kasenda, Benjamin; Schandelmaier, Stefan; Sun, Xin; von Elm, Erik; You, John; Blümle, Anette; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J; Stegert, Mihaela; Olu, Kelechi K; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M; Mertz, Dominik; Akl, Elie A; Bassler, Dirk; Busse, Jason W; Ferreira-González, Ignacio; Lamontagne, Francois; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Rosenthal, Rachel; Ebrahim, Shanil; Vandvik, Per O; Johnston, Bradley C; Walter, Martin A; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G; Bucher, Heiner C; Guyatt, Gordon H; Briel, Matthias

2014-07-16

To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. Cohort of protocols of randomised controlled trial and subsequent full journal publications. Six research ethics committees in Switzerland, Germany, and Canada. 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials. © The DISCO study group 2014.

Vaccine testing for emerging infections: the case for individual randomisation.

PubMed

Eyal, Nir; Lipsitch, Marc

2017-09-01

During the 2014-2015 Ebola outbreak in Guinea, Liberia and Sierra Leone, many opposed the use of individually randomised controlled trials to test candidate Ebola vaccines. For a raging fatal disease, they explained, it is unethical to relegate some study participants to control arms. In Zika and future emerging infections, similar opposition may hinder urgent vaccine research, so it is best to address these questions now. This article lays out the ethical case for individually randomised control in testing vaccines against many emerging infections, including lethal infections in low-income countries, even when at no point in the trial do the controls receive the countermeasures being tested. When individual randomisation is feasible-and it often will be-it tends to save more lives than alternative designs would. And for emerging infections, individual randomisation also tends as such to improve care, access to the experimental vaccine and prospects for all participants relative to their opportunities absent the trial, and no less than alternative designs would. That obtains even under placebo control and without equipoise-requiring which would undermine individual randomisation and the alternative designs that opponents proffered. Our arguments expound four often-neglected factors: benefits to non-participants, benefits to participants once a trial is over including post-trial access to the study intervention, participants' prospects before randomisation to arms and the near-inevitable disparity between arms in any randomised controlled trial. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The effects of crisis plans for patients with psychotic and bipolar disorders: a randomised controlled trial.

PubMed

Ruchlewska, A; Mulder, C L; Smulders, R; Roosenschoon, B J; Koopmans, G; Wierdsma, A

2009-07-09

Crises and (involuntary) admissions have a strong impact on patients and their caregivers. In some countries, including the Netherlands, the number of crises and (involuntary) admissions have increased in the last years. There is also a lack of effective interventions to prevent their occurrence. Previous research has shown that a form of psychiatric advance statement - joint crisis plan - may prevent involuntary admissions, but another study showed no significant results for another form. The question remains which form of psychiatric advance statement may help to prevent crisis situations. This study examines the effects of two other psychiatric advance statements. The first is created by the patient with help from a patient's advocate (Patient Advocate Crisis Plan: PACP) and the second with the help of a clinician only (Clinician facilitated Crisis Plan: CCP). We investigate whether patients with a PACP or CCP show fewer emergency visits and (involuntary) admissions as compared to patients without a psychiatric advance statement. Furthermore, this study seeks to identify possible mechanisms responsible for the effects of a PACP or a CCP. This study is a randomised controlled trial with two intervention groups and one control condition. Both interventions consist of a crisis plan, facilitated through the patient's advocate or the clinician respectively.Outpatients with psychotic or bipolar disorders, who experienced at least one psychiatric crisis during the previous two years, are randomly allocated to one of the three groups. Primary outcomes are the number of emergency (after hour) visits, (involuntary) admissions and the length of stay in hospital. Secondary outcomes include psychosocial functioning and treatment satisfaction. The possible mediator variables of the effects of the crisis plans are investigated by assessing the patient's involvement in the creation of the crisis plan, working alliance, insight into illness, recovery style, social support, locus of control, service engagement and coping with crises situations. The interviews take place before randomisation, nine month later and finally eighteen months after randomisation. This study examines the effects of two types of crisis plans. In addition, the results offer an understanding of the way these advance statements work and whether it is more effective to include a patients' advocate in the process of creating a psychiatric advance statement. These statements may be an intervention to prevent crises and the use of compulsion in mental health care. The strength and limitations of this study are discussed. Current Controlled Trails NTR1166.

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.

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

PubMed Central

Dias, Sofia; Ades, A E

2014-01-01

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

Preventing academic difficulties in preterm children: a randomised controlled trial of an adaptive working memory training intervention - IMPRINT study.

PubMed

Pascoe, Leona; Roberts, Gehan; Doyle, Lex W; Lee, Katherine J; Thompson, Deanne K; Seal, Marc L; Josev, Elisha K; Nosarti, Chiara; Gathercole, Susan; Anderson, Peter J

2013-09-16

Very preterm children exhibit difficulties in working memory, a key cognitive ability vital to learning information and the development of academic skills. Previous research suggests that an adaptive working memory training intervention (Cogmed) may improve working memory and other cognitive and behavioural domains, although further randomised controlled trials employing long-term outcomes are needed, and with populations at risk for working memory deficits, such as children born preterm.In a cohort of extremely preterm (<28 weeks' gestation)/extremely low birthweight (<1000 g) 7-year-olds, we will assess the effectiveness of Cogmed in improving academic functioning 2 years' post-intervention. Secondary objectives are to assess the effectiveness of Cogmed in improving working memory and attention 2 weeks', 12 months' and 24 months' post-intervention, and to investigate training related neuroplasticity in working memory neural networks 2 weeks' post-intervention. This double-blind, placebo-controlled, randomised controlled trial aims to recruit 126 extremely preterm/extremely low birthweight 7-year-old children. Children attending mainstream school without major intellectual, sensory or physical impairments will be eligible. Participating children will undergo an extensive baseline cognitive assessment before being randomised to either an adaptive or placebo (non-adaptive) version of Cogmed. Cogmed is a computerised working memory training program consisting of 25 sessions completed over a 5 to 7 week period. Each training session takes approximately 35 minutes and will be completed in the child's home. Structural, diffusion and functional Magnetic Resonance Imaging, which is optional for participants, will be completed prior to and 2 weeks following the training period. Follow-up assessments focusing on academic skills (primary outcome), working memory and attention (secondary outcomes) will be conducted at 2 weeks', 12 months' and 24 months' post-intervention. To our knowledge, this study will be the first randomised controlled trial to (a) assess the effectiveness of Cogmed in school-aged extremely preterm/extremely low birthweight children, while incorporating advanced imaging techniques to investigate neural changes associated with adaptive working memory training, and (b) employ long-term follow-up to assess the potential benefit of improved working memory on academic functioning. If effective, Cogmed would serve as a valuable, available intervention for improving developmental outcomes for this population. Australian New Zealand Clinical Trials Registry ACTRN12612000124831.

Effect of exercise versus cognitive behavioural therapy or no intervention on anxiety, depression, fitness and quality of life in adults with previous methamphetamine dependency: a systematic review.

PubMed

Morris, Linzette; Stander, Jessica; Ebrahim, Wardah; Eksteen, Stephanie; Meaden, Orissa Anna; Ras, Ané; Wessels, Annemarie

2018-01-16

Methamphetamine (MA) is a highly addictive psychostimulant used by approximately 52 million people worldwide. Chronic MA abuse leads to detrimental physiological and neurological changes, as well as increases in anxiety and depression, and decreases in overall fitness and quality of life. Exercise has been reported to possibly reverse physiological and neurological damage caused by previous MA use, and to reduce anxiety and depression in this population. The aim of this systematic review was to identify, clinically appraise and synthesise the available evidence for the effectiveness of exercise, compared to cognitive behavioural therapy (CBT), standard care or no intervention, on decreasing anxiety and depression and improving fitness and quality of life in previous MA users. Seven computerised databases were searched from inception to May 2017, namely Scopus, Cochrane Library, PubMed/MEDLINE, PEDro, CINAHL, and ScienceDirect. Search terms included exercise, methamphetamine, fitness measures, depression, anxiety and quality of life. Randomised and non-randomised controlled- or clinical trials and pilot studies, published in English, were considered for inclusion. Methodological quality was critically appraised according to the PEDro scale. Heterogeneity across studies regarding control groups and assessment intervals rendered meta analyses inappropriate for this review and results were thus described narratively using text and tables. Two hundred and fifty-one titles were identified following the initial search, and 14 potentially-relevant titles were selected and the abstracts reviewed. Three studies (two randomised controlled trials and one quasi-experimental pilot) were included, with an average PEDro score of 6.66. Exercise resulted in significantly lower depression and anxiety scores versus CBT (p = 0.001). Balance also significantly improved following exercise versus standard care (p < 0.001); as did vital capacity, hand-grip and one-leg stand with eyes closed. There were significant changes in all subdivisions of the Quality of Life Scale Questionnaire (p < 0.05), except psychology (p = 0.227). Level II evidence suggests that exercise is effective in reducing anxiety and depression and improving fitness in previous MA users, and Level III-2 evidence suggests that exercise is beneficial for improving quality of life in this population. Overall recovery in previous MA dependents might be significantly enhanced by including exercise in the rehabilitation process. Further research is required to strengthen these conclusions and to inform policy and health systems effectively.

Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series

PubMed Central

Taylor, Morag A; Reilly, David; Llewellyn-Jones, Robert H; McSharry, Charles; Aitchison, Tom C

2000-01-01

Objective To test the hypothesis that homoeopathy is a placebo by examining its effect in patients with allergic rhinitis and so contest the evidence from three previous trials in this series. Design Randomised, double blind, placebo controlled, parallel group, multicentre study. Setting Four general practices and a hospital ear, nose, and throat outpatient department. Participants 51 patients with perennial allergic rhinitis. Intervention Random assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo. Main outcome measures Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after randomisation. Results Fifty patients completed the study. The homoeopathy group had a significant objective improvement in nasal airflow compared with the placebo group (mean difference 19.8 l/min, 95% confidence interval 10.4 to 29.1, P=0.0001). Both groups reported improvement in symptoms, with patients taking homoeopathy reporting more improvement in all but one of the centres, which had more patients with aggravations. On average no significant difference between the groups was seen on visual analogue scale scores. Initial aggravations of rhinitis symptoms were more common with homoeopathy than placebo (7 (30%) v 2 (7%), P=0.04). Addition of these results to those of three previous trials (n=253) showed a mean symptom reduction on visual analogue scores of 28% (10.9 mm) for homoeopathy compared with 3% (1.1 mm) for placebo (95% confidence interval 4.2 to 15.4, P=0.0007). Conclusion The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo. PMID:10948025

Parent-focused treatment for adolescent anorexia nervosa: a study protocol of a randomised controlled trial

PubMed Central

2014-01-01

Background Family-based treatment is an efficacious outpatient intervention for medically stable adolescents with anorexia nervosa. Previous research suggests family-based treatment may be more effective for some families when parents and adolescents attend separate therapy sessions compared to conjoint sessions. Our service developed a novel separated model of family-based treatment, parent-focused treatment, and is undertaking a randomised controlled trial to compare parent-focused treatment to conjoint family-based treatment. Methods/Design This randomised controlled trial will recruit 100 adolescents aged 12–18 years with DSM-IV anorexia nervosa or eating disorder not otherwise specified (anorexia nervosa type). The trial commenced in 2010 and is expected to be completed in 2015. Participants are recruited from the Royal Children’s Hospital Eating Disorders Program, Melbourne, Australia. Following a multidisciplinary intake assessment, eligible families who provide written informed consent are randomly allocated to either parent-focused treatment or conjoint family-based treatment. In parent-focused treatment, the adolescent sees a clinical nurse consultant and the parents see a trained mental health clinician. In conjoint family-based treatment, the whole family attends sessions with the mental health clinician. Both groups receive 18 treatment sessions over 6 months and regular medical monitoring by a paediatrician. The primary outcome is remission at end of treatment and 6 and 12 month follow up, with remission defined as being ≥ 95% expected body weight and having an eating disorder symptom score within one standard deviation of community norms. The secondary outcomes include partial remission and changes in eating pathology, depressive symptoms and self-esteem. Moderating and mediating factors will also be explored. Discussion This will be first randomised controlled trial of a parent-focused model of family-based treatment of adolescent anorexia nervosa. If found to be efficacious, parent-focused treatment will offer an alternative approach for clinicians who treat adolescents with anorexia nervosa. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12610000216011. PMID:24712855

Parent-focused treatment for adolescent anorexia nervosa: a study protocol of a randomised controlled trial.

PubMed

Hughes, Elizabeth K; Le Grange, Daniel; Court, Andrew; Yeo, Michele S M; Campbell, Stephanie; Allan, Erica; Crosby, Ross D; Loeb, Katharine L; Sawyer, Susan M

2014-04-08

Family-based treatment is an efficacious outpatient intervention for medically stable adolescents with anorexia nervosa. Previous research suggests family-based treatment may be more effective for some families when parents and adolescents attend separate therapy sessions compared to conjoint sessions. Our service developed a novel separated model of family-based treatment, parent-focused treatment, and is undertaking a randomised controlled trial to compare parent-focused treatment to conjoint family-based treatment. This randomised controlled trial will recruit 100 adolescents aged 12-18 years with DSM-IV anorexia nervosa or eating disorder not otherwise specified (anorexia nervosa type). The trial commenced in 2010 and is expected to be completed in 2015. Participants are recruited from the Royal Children's Hospital Eating Disorders Program, Melbourne, Australia. Following a multidisciplinary intake assessment, eligible families who provide written informed consent are randomly allocated to either parent-focused treatment or conjoint family-based treatment. In parent-focused treatment, the adolescent sees a clinical nurse consultant and the parents see a trained mental health clinician. In conjoint family-based treatment, the whole family attends sessions with the mental health clinician. Both groups receive 18 treatment sessions over 6 months and regular medical monitoring by a paediatrician. The primary outcome is remission at end of treatment and 6 and 12 month follow up, with remission defined as being ≥ 95% expected body weight and having an eating disorder symptom score within one standard deviation of community norms. The secondary outcomes include partial remission and changes in eating pathology, depressive symptoms and self-esteem. Moderating and mediating factors will also be explored. This will be first randomised controlled trial of a parent-focused model of family-based treatment of adolescent anorexia nervosa. If found to be efficacious, parent-focused treatment will offer an alternative approach for clinicians who treat adolescents with anorexia nervosa. Australian and New Zealand Clinical Trials Registry ACTRN12610000216011.

Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial.

PubMed

Diéras, Véronique; Miles, David; Verma, Sunil; Pegram, Mark; Welslau, Manfred; Baselga, José; Krop, Ian E; Blackwell, Kim; Hoersch, Silke; Xu, Jin; Green, Marjorie; Gianni, Luca

2017-06-01

The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial. EMILIA was a randomised, international, open-label, phase 3 study of men and women aged 18 years or older with HER2-positive unresectable, locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane. Enrolled patients were randomly assigned (1:1) via a hierarchical, dynamic randomisation scheme and an interactive voice response system to trastuzumab emtansine (3·6 mg/kg intravenously every 3 weeks) or control (capecitabine 1000 mg/m 2 self-administered orally twice daily on days 1-14 on each 21-day cycle, plus lapatinib 1250 mg orally once daily on days 1-21). Randomisation was stratified by world region (USA vs western Europe vs or other), number of previous chemotherapy regimens for unresectable, locally advanced, or metastatic disease (0 or 1 vs >1), and disease involvement (visceral vs non-visceral). The coprimary efficacy endpoints were progression-free survival (per independent review committee assessment) and overall survival. Efficacy was analysed in the intention-to-treat population; safety was analysed in all patients who received at least one dose of study treatment, with patients analysed according to the treatment actually received. On May 30, 2012, the study protocol was amended to allow crossover from control to trastuzumab emtansine after the second interim overall survival analysis crossed the prespecified overall survival efficacy boundary. This study is registered with ClinicalTrials.gov, number NCT00829166. Between Feb 23, 2009, and Oct 13, 2011, 991 eligible patients were enrolled and randomly assigned to either trastuzumab emtansine (n=495) or capecitabine and lapatinib (control; n=496). In this final descriptive analysis, median overall survival was longer with trastuzumab emtansine than with control (29·9 months [95% CI 26·3-34·1] vs 25·9 months [95% CI 22·7-28·3]; hazard ratio 0·75 [95% CI 0·64-0·88]). 136 (27%) of 496 patients crossed over from control to trastuzumab emtansine after the second interim overall survival analysis (median follow-up duration 24·1 months [IQR 19·5-26·1]). Of those patients originally randomly assigned to trastuzumab emtansine, 254 (51%) of 495 received capecitabine and 241 [49%] of 495 received lapatinib (separately or in combination) after study drug discontinuation. In the safety population (488 patients treated with capecitabine plus lapatinib, 490 patients treated with trastuzumab emtansine), fewer grade 3 or worse adverse events occurred with trastuzumab emtansine (233 [48%] of 490) than with capecitabine plus lapatinib control treatment (291 [60%] of 488). In the control group, the most frequently reported grade 3 or worse adverse events were diarrhoea (103 [21%] of 488 patients) followed by palmar-plantar erythrodysaesthesia syndrome (87 [18%]), and vomiting (24 [5%]). The safety profile of trastuzumab emtansine was similar to that reported previously; the most frequently reported grade 3 or worse adverse events in the trastuzumab emtansine group were thrombocytopenia (70 [14%] of 490), increased aspartate aminotransferase levels (22 [5%]), and anaemia (19 [4%]). Nine patients died from adverse events; five of these deaths were judged to be related to treatment (two in the control group [coronary artery disease and multiorgan failure] and three in the trastuzumab emtansine group [metabolic encephalopathy, neutropenic sepsis, and acute myeloid leukaemia]). This descriptive analysis of final overall survival in the EMILIA trial shows that trastuzumab emtansine improved overall survival in patients with previously treated HER2-positive metastatic breast cancer even in the presence of crossover treatment. The safety profile was similar to that reported in previous analyses, reaffirming trastuzumab emtansine as an efficacious and tolerable treatment in this patient population. F Hoffmann-La Roche/Genentech. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of timing of admission in labour and management of labour on method of birth: results from a randomised controlled trial of caseload midwifery (COSMOS trial).

PubMed

Davey, Mary-Ann; McLachlan, Helen L; Forster, Della; Flood, Margaret

2013-12-01

to explore the relationship between the degree to which labour is established on admission to hospital and method of birth. a recent randomised controlled trial found fewer caesarean sections (CS) in women allocated to caseload midwifery (19.4%) compared with standard care (24.9%). There is interest in exploring what specific aspects of the care might have resulted in this reduction. a large tertiary-level maternity service in Melbourne, Australia. English-speaking women with no previous caesarean section at low risk of complications in pregnancy were recruited to a randomised controlled trial. Trial participants whose management did not include a planned caesarean and who were admitted to hospital in spontaneous labour were included in this secondary analysis of trial data (n=1532). this secondary analysis included women admitted to hospital in spontaneous labour who were randomised to caseload midwifery compared with those randomised to standard care with regard to timing of admission in labour, augmentation of labour and use of epidural analgesia. In a further analysis randomised groups were pooled to examine predictors of caesarean section for first births only using multiple logistic regression. nulliparous women randomised to standard care were more likely to have labour augmented than those having caseload care (54.2% and 45.5% respectively, p=0.008), but were no more likely to use epidural analgesia. They were admitted earlier in labour, spending 1.1 hours longer than those in the caseload arm in hospital before the birth (p=0.003). Parous women allocated to standard care were more likely than those in the caseload arm to use epidural analgesia (10.0% and 5.3% respectively, p=0.047), but were no more likely to have labour augmented. They were also admitted earlier in labour, with a median cervical dilatation of 4 cm compared with 5 cm in the caseload arm (p=0.012). Pooling the two randomised groups of nulliparous women, and after adjusting for randomised group, maternal age and maternal body mass index, early admission to hospital was strongly associated with caesarean section. Admission before the cervix was 5 cm dilated increased the odds 2.4-fold (95%CI 1.4, 4.0; p=0.001). Augmentation of labour and use of epidural analgesia were each strongly associated with caesarean section (adjusted odds ratios 3.10 (95%CI 2.1, 4.5) and 5.77 (95%CI 4.0, 8.4) respectively. these findings that women allocated to caseload care were admitted to hospital later in labour, and that earlier admission was strongly associated with birth by caesarean section, suggest that remaining at home somewhat longer in labour may be one of the mechanisms by which caseload care was effective in reducing caesarean section in the COSMOS trial. Copyright © 2013 Elsevier Ltd. All rights reserved.

Association between bibliometric parameters, reporting and methodological quality of randomised controlled trials in vascular and endovascular surgery.

PubMed

Hajibandeh, Shahab; Hajibandeh, Shahin; Antoniou, George A; Green, Patrick A; Maden, Michelle; Torella, Francesco

2017-04-01

Purpose We aimed to investigate association between bibliometric parameters, reporting and methodological quality of vascular and endovascular surgery randomised controlled trials. Methods The most recent 75 and oldest 75 randomised controlled trials published in leading journals over a 10-year period were identified. The reporting quality was analysed using the CONSORT statement, and methodological quality with the Intercollegiate Guidelines Network checklist. We used exploratory univariate and multivariable linear regression analysis to investigate associations. Findings Bibliometric parameters such as type of journal, study design reported in title, number of pages; external funding, industry sponsoring and number of citations are associated with reporting quality. Moreover, parameters such as type of journal, subject area and study design reported in title are associated with methodological quality. Conclusions The bibliometric parameters of randomised controlled trials may be independent predictors for their reporting and methodological quality. Moreover, the reporting quality of randomised controlled trials is associated with their methodological quality and vice versa.

Fortuitous phenomena: on complexity, pragmatic randomised controlled trials, and knowledge for evidence-based practice.

PubMed

Thompson, Carl

2004-01-01

Many of the interventions that nurses develop and implement are in themselves complex and have to operate in situations of irreducible complexity and uncertainty. This article argues that the primary means of generating knowledge for the evidence-based deployment of complex interventions should be the pragmatic randomised controlled trial. Randomised controlled trials represent the only research design to adequately deal with that which we know and (far more importantly) that which we do not. Using the example of practice development as an exemplar for complexity, and drawing on the objections often voiced as a response to calls to make use of randomised controlled trials in nursing and nursing research, the article presents a developmental framework and some methodological solutions to problems often encountered. Randomised controlled trials, whilst undoubtedly methodologically and strategically challenging, offer the most robust basis for developing primary research knowledge on the effects of complex interventions in nursing and their active components.

Compliance with the CONSORT checklist in obstetric anaesthesia randomised controlled trials.

PubMed

Halpern, S H; Darani, R; Douglas, M J; Wight, W; Yee, J

2004-10-01

The Consolidated Standards for Reporting of Trials (CONSORT) checklist is an evidence-based approach to help improve the quality of reporting randomised controlled trials. The purpose of this study was to determine how closely randomised controlled trials in obstetric anaesthesia adhere to the CONSORT checklist. We retrieved all randomised controlled trials pertaining to the practice of obstetric anaesthesia and summarised in Obstetric Anesthesia Digest between March 2001 and December 2002 and compared the quality of reporting to the CONSORT checklist. The median number of correctly described CONSORT items was 65% (range 36% to 100%). Information pertaining to randomisation, blinding of the assessors, sample size calculation, reliability of measurements and reporting of the analysis were often omitted. It is difficult to determine the value and quality of many obstetric anaesthesia clinical trials because journal editors do not insist that this important information is made available to readers. Both clinicians and clinical researchers would benefit from uniform reporting of randomised trials in a manner that allows rapid data retrieval and easy assessment for relevance and quality.

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.

MIDSHIPS: multicentre intervention designed for self-harm using interpersonal problem-solving: protocol for a randomised controlled feasibility study.

PubMed

Collinson, Michelle; Owens, David; Blenkiron, Paul; Burton, Kayleigh; Graham, Liz; Hatcher, Simon; House, Allan; Martin, Katie; Pembroke, Louise; Protheroe, David; Tubeuf, Sandy; Farrin, Amanda

2014-05-10

Around 150,000 people each year attend hospitals in England due to self-harm, many of them more than once. Over 5,000 people die by suicide each year in the UK, a quarter of them having attended hospital in the previous year because of self-harm. Self-harm is a major identifiable risk factor for suicide. People receive variable care at hospital; many are not assessed for their psychological needs and little psychological therapy is offered. Despite its frequent occurrence, we have no clear research evidence about how to reduce the repetition of self-harm. Some people who have self-harmed show less active ways of solving problems, and brief problem-solving therapies are considered the most promising psychological treatments. This is a pragmatic, individually randomised, controlled, feasibility study comparing interpersonal problem-solving therapy plus treatment-as-usual with treatment-as-usual alone, for adults attending a general hospital following self-harm. A total of 60 participants will be randomised equally between the treatment arms, which will be balanced with respect to the type of most recent self-harm event, number of previous self-harm events, gender and age. Feasibility objectives are as follows: a) To establish and field test procedures for implementing the problem-solving intervention; b) To determine the feasibility and best method of participant recruitment and follow up; c) To assess therapeutic delivery; d) To assess the feasibility of obtaining the definitive trial's primary and secondary outcomes; e) To assess the perceived burden and acceptability of obtaining the trial's self-reported outcome data; f) To inform the sample size calculation for the definitive trial. The results of this feasibility study will be used to determine the appropriateness of proceeding to a definitive trial and will allow us to design an achievable trial of interpersonal problem-solving therapy for adults who self-harm. Current Controlled Trials (ISRCTN54036115).

Randomised Controlled Trial (RCT) of cannabinoid replacement therapy (Nabiximols) for the management of treatment-resistant cannabis dependent patients: a study protocol.

PubMed

Bhardwaj, Anjali K; Allsop, David J; Copeland, Jan; McGregor, Iain S; Dunlop, Adrian; Shanahan, Marian; Bruno, Raimondo; Phung, Nghi; Montebello, Mark; Sadler, Craig; Gugusheff, Jessica; Jackson, Melissa; Luksza, Jennifer; Lintzeris, Nicholas

2018-05-18

The cannabis extract nabiximols (Sativex®) effectively supresses withdrawal symptoms and cravings in treatment resistant cannabis dependent individuals, who have high relapse rates following conventional withdrawal treatments. This study examines the efficacy, safety and cost-effectiveness of longer-term nabiximols treatment for outpatient cannabis dependent patients who have not responded to previous conventional treatment approaches. A phase III multi-site outpatient, randomised, double-blinded, placebo controlled parallel design, comparing a 12-week course of nabiximols to placebo, with follow up at 24 weeks after enrolment. Four specialist drug and alcohol outpatient clinics in New South Wales, Australia. One hundred forty-two treatment seeking cannabis dependent adults, with no significant medical, psychiatric or other substance use disorders. Nabiximols is an oromucosal spray prescribed on a flexible dose regimen to a maximum daily dose of 32 sprays; 8 sprays (total 21.6 mg tetrahydrocannabinol (THC) and 20 mg cannabidiol (CBD)) four times a day, or matching placebo, dispensed weekly. All participants will receive six-sessions of individual cognitive behavioural therapy (CBT) and weekly clinical reviews. Primary endpoints are use of non-prescribed cannabis (self-reported cannabis use days, urine toxicology), safety measures (adverse events and abuse liability), and cost effectiveness (incremental cost effectiveness in achieving additional Quality Adjusted Life Years). Secondary outcomes include, improvement in physical and mental health parameters, substance use other than cannabis, cognitive functioning and patient satisfaction measures. This is the first outpatient community-based randomised controlled study of nabiximols as an agonist replacement medication for treating cannabis dependence, targeting individuals who have not previously responded to conventional treatment approaches. The study and treatment design is modelled upon an earlier study with this population and more generally on other agonist replacement treatments (e.g. nicotine, opioids). Australian and New Zealand Clinical Trial Registry: ACTRN12616000103460 (Registered 1st February 2016).

MIDSHIPS: Multicentre Intervention Designed for Self-Harm using Interpersonal Problem-Solving: protocol for a randomised controlled feasibility study

PubMed Central

2014-01-01

Background Around 150,000 people each year attend hospitals in England due to self-harm, many of them more than once. Over 5,000 people die by suicide each year in the UK, a quarter of them having attended hospital in the previous year because of self-harm. Self-harm is a major identifiable risk factor for suicide. People receive variable care at hospital; many are not assessed for their psychological needs and little psychological therapy is offered. Despite its frequent occurrence, we have no clear research evidence about how to reduce the repetition of self-harm. Some people who have self-harmed show less active ways of solving problems, and brief problem-solving therapies are considered the most promising psychological treatments. Methods/Design This is a pragmatic, individually randomised, controlled, feasibility study comparing interpersonal problem-solving therapy plus treatment-as-usual with treatment-as-usual alone, for adults attending a general hospital following self-harm. A total of 60 participants will be randomised equally between the treatment arms, which will be balanced with respect to the type of most recent self-harm event, number of previous self-harm events, gender and age. Feasibility objectives are as follows: a) To establish and field test procedures for implementing the problem-solving intervention; b) To determine the feasibility and best method of participant recruitment and follow up; c) To assess therapeutic delivery; d) To assess the feasibility of obtaining the definitive trial’s primary and secondary outcomes; e) To assess the perceived burden and acceptability of obtaining the trial’s self-reported outcome data; f) To inform the sample size calculation for the definitive trial. Discussion The results of this feasibility study will be used to determine the appropriateness of proceeding to a definitive trial and will allow us to design an achievable trial of interpersonal problem-solving therapy for adults who self-harm. Trial registration Current Controlled Trials (ISRCTN54036115) PMID:24886683

Information and Risk Modification Trial (INFORM): design of a randomised controlled trial of communicating different types of information about coronary heart disease risk, alongside lifestyle advice, to achieve change in health-related behaviour.

PubMed

Silarova, Barbora; Lucas, Joanne; Butterworth, Adam S; Di Angelantonio, Emanuele; Girling, Christine; Lawrence, Kathryn; Mackintosh, Stuart; Moore, Carmel; Payne, Rupert A; Sharp, Stephen J; Shefer, Guy; Tolkien, Zoe; Usher-Smith, Juliet; Walker, Matthew; Danesh, John; Griffin, Simon

2015-09-07

Cardiovascular disease (CVD) remains the leading cause of death globally. Primary prevention of CVD requires cost-effective strategies to identify individuals at high risk in order to help target preventive interventions. An integral part of this approach is the use of CVD risk scores. Limitations in previous studies have prevented reliable inference about the potential advantages and the potential harms of using CVD risk scores as part of preventive strategies. We aim to evaluate short-term effects of providing different types of information about coronary heart disease (CHD) risk, alongside lifestyle advice, on health-related behaviours. In a parallel-group, open randomised trial, we are allocating 932 male and female blood donors with no previous history of CVD aged 40-84 years in England to either no intervention (control group) or to one of three active intervention groups: i) lifestyle advice only; ii) lifestyle advice plus information on estimated 10-year CHD risk based on phenotypic characteristics; and iii) lifestyle advice plus information on estimated 10-year CHD risk based on phenotypic and genetic characteristics. The primary outcome is change in objectively measured physical activity. Secondary outcomes include: objectively measured dietary behaviours; cardiovascular risk factors; current medication and healthcare usage; perceived risk; cognitive evaluation of provision of CHD risk scores; and psychological outcomes. The follow-up assessment takes place 12 weeks after randomisation. The experiences, attitudes and concerns of a subset of participants will be also studied using individual interviews and focus groups. The INFORM study has been designed to provide robust findings about the short-term effects of providing different types of information on estimated 10-year CHD risk and lifestyle advice on health-related behaviours. Current Controlled Trials ISRCTN17721237 . Registered 12 January 2015.

Five years of specialised early intervention versus two years of specialised early intervention followed by three years of standard treatment for patients with a first episode psychosis: randomised, superiority, parallel group trial in Denmark (OPUS II).

PubMed

Albert, Nikolai; Melau, Marianne; Jensen, Heidi; Emborg, Charlotte; Jepsen, Jens Richardt Mollegaard; Fagerlund, Birgitte; Gluud, Christian; Mors, Ole; Hjorthøj, Carsten; Nordentoft, Merete

2017-01-12

To compare the effects of five years of specialised early intervention (SEI) treatment for first episode schizophrenia spectrum disorder with the standard two years of SEI plus three years of treatment as usual. Randomised, superiority, parallel group trial with blinded outcome assessment. Randomisation was centralised and computerised with concealed randomisation sequence carried out at an external site. Participants were recruited from six OPUS teams in Denmark between 2009 and 2012. OPUS teams provide SEI treatment to all patients diagnosed with a schizophrenia spectrum disorder in Denmark. 400 participants (51% women) with a mean age of 25.6 (standard deviation 4.3) were randomised to five years of SEI (experimental intervention; n=197) or to two years of SEI plus three years of treatment as usual (control; n=203). OPUS treatment consists of three core elements-modified assertive community treatment, family involvement, and social skill training-with a patient-case manager ratio of no more than 12:1. For participants randomised to five years of OPUS treatment, the treatment was largely unchanged. Participants randomised to the control group were mostly referred to community health centres after two years of SEI treatment. Follow-up assessments were conducted five years after start of OPUS treatment. Primary outcome was negative symptoms measured on the scale for assessment of negative symptoms (avolition-apathy, anhedonia, alogia, and affective blunting). Secondary outcomes were remission of both negative and psychotic symptoms, psychotic symptoms, suicidal ideation, substance abuse, compliance with medical treatment, adherence with treatment, client satisfaction, days in hospital care, and labour market affiliation. Levels of negative symptoms did not differ between the intervention group and control group (1.72 v 1.81 points; estimated mean difference -0.10 (95% confidence interval -0.33 to 0.13), P=0.39). Participants receiving five years of OPUS treatment were more likely to remain in contact with specialised mental health services (90.4% v 55.6%, P<0.001), had higher client satisfaction (estimated mean difference 2.57 points (95% confidence interval 1.36 to 3.79), P<0.001), and had a stronger working alliance (estimated mean difference 5.56 points (95% confidence interval 2.30 to 8.82), P=0.001) than the control group. This trial tests SEI treatment for up to five years for patients with first episode schizophrenia spectrum disorder; previous trials have found treatment effects for programmes lasting from one to three years. The prolonged SEI treatment had few effects, which could be due to the high level of treatment provided to control participants and the late start of specialised treatment.Trial registration Clinicaltrial.gov NCT00914238. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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

PubMed

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

2018-03-14

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

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.

Changing cluster composition in cluster randomised controlled trials: design and analysis considerations

PubMed Central

2014-01-01

Background There are many methodological challenges in the conduct and analysis of cluster randomised controlled trials, but one that has received little attention is that of post-randomisation changes to cluster composition. To illustrate this, we focus on the issue of cluster merging, considering the impact on the design, analysis and interpretation of trial outcomes. Methods We explored the effects of merging clusters on study power using standard methods of power calculation. We assessed the potential impacts on study findings of both homogeneous cluster merges (involving clusters randomised to the same arm of a trial) and heterogeneous merges (involving clusters randomised to different arms of a trial) by simulation. To determine the impact on bias and precision of treatment effect estimates, we applied standard methods of analysis to different populations under analysis. Results Cluster merging produced a systematic reduction in study power. This effect depended on the number of merges and was most pronounced when variability in cluster size was at its greatest. Simulations demonstrate that the impact on analysis was minimal when cluster merges were homogeneous, with impact on study power being balanced by a change in observed intracluster correlation coefficient (ICC). We found a decrease in study power when cluster merges were heterogeneous, and the estimate of treatment effect was attenuated. Conclusions Examples of cluster merges found in previously published reports of cluster randomised trials were typically homogeneous rather than heterogeneous. Simulations demonstrated that trial findings in such cases would be unbiased. However, simulations also showed that any heterogeneous cluster merges would introduce bias that would be hard to quantify, as well as having negative impacts on the precision of estimates obtained. Further methodological development is warranted to better determine how to analyse such trials appropriately. Interim recommendations include avoidance of cluster merges where possible, discontinuation of clusters following heterogeneous merges, allowance for potential loss of clusters and additional variability in cluster size in the original sample size calculation, and use of appropriate ICC estimates that reflect cluster size. PMID:24884591

Study protocol for a multi-institutional, randomised, double-blinded, placebo-controlled phase III trial investigating additive efficacy of duloxetine for neuropathic cancer pain refractory to opioids and gabapentinoids: the DIRECT study.

PubMed

Matsuoka, Hiromichi; Ishiki, Hiroto; Iwase, Satoru; Koyama, Atsuko; Kawaguchi, Takashi; Kizawa, Yoshiyuki; Morita, Tatsuya; Matsuda, Yoshinobu; Miyaji, Tempei; Ariyoshi, Keisuke; Yamaguchi, Takuhiro

2017-08-28

Management of patients with cancer suffering from neuropathic pain refractory to opioids and gabapentinoids remains an important challenge. Duloxetine is one of the choices after first-line treatment fails. The efficacy of duloxetine has been reported in patients with non-cancer disease and in chemotherapy-induced peripheral neuropathy, but no randomised clinical trials have examined its effects on neuropathic cancer pain refractory to first-line treatment. The objective of this study is to assess the analgesic efficacy of duloxetine in patients suffering from neuropathic cancer pain refractory to opioids and gabapentinoids. A multi-institutional, prospective, randomised, double-blind, placebo-controlled, two-parallel trial is planned. The inclusion criteria are adult patients with cancer suffering from neuropathic cancer pain refractory to opioids and gabapentinoids, patients with a Numerical Rating Scale (NRS) pain score of 4 or higher and patients with a total Hospital Anxiety and Depression Scale score of less than 20. Patients with chemotherapy-induced peripheral neuropathy are excluded. The study will take place at 14 sites across Japan. Participants will be randomised (1:1 allocation ratio) to a duloxetine intervention group or a placebo control group. Evaluations will be made at baseline (T0 randomisation), day 0 (T1), day 3 (T2) and day 10 (T3). The primary endpoint is defined as the difference in NRS score for pain intensity (average over the previous 24 hours) at T3 between the duloxetine and placebo groups. A sample size of 70 patients will be examined between July 2015 and March 2018. Ethics approval was obtained at all participating sites.The results of this study will be submitted for publication in international peer-reviewed journals and the key findings presented at international scientific conferences. UMIN000017647; Pre-results. 2.2, 26 April 2017. © 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.

Te Ira Tangata: a Zelen randomised controlled trial of a treatment package including problem solving therapy compared to treatment as usual in Maori who present to hospital after self harm.

PubMed

Hatcher, Simon; Coupe, Nicole; Durie, Mason; Elder, Hinemoa; Tapsell, Rees; Wikiriwhi, Karen; Parag, Varsha

2011-05-11

Maori, the indigenous people of New Zealand, who present to hospital after intentionally harming themselves, do so at a higher rate than non-Maori. There have been no previous treatment trials in Maori who self harm and previous reviews of interventions in other populations have been inconclusive as existing trials have been under powered and done on unrepresentative populations. These reviews have however indicated that problem solving therapy and sending regular postcards after the self harm attempt may be an effective treatment. There is also a small literature on sense of belonging in self harm and the importance of culture. This protocol describes a pragmatic trial of a package of measures which include problem solving therapy, postcards, patient support, cultural assessment, improved access to primary care and a risk management strategy in Maori who present to hospital after self harm using a novel design. We propose to use a double consent Zelen design where participants are randomised prior to giving consent to enrol a representative cohort of patients. The main outcome will be the number of Maori scoring below nine on the Beck Hopelessness Scale. Secondary outcomes will be hospital repetition at one year; self reported self harm; anxiety; depression; quality of life; social function; and hospital use at three months and one year. A strength of the study is that it is a pragmatic trial which aims to recruit Maori using a Maori clinical team and protocol. It does not exclude people if English is not their first language. A potential limitation is the analysis of the results which is complex and may underestimate any effect if a large number of people refuse their consent in the group randomised to problem solving therapy as they will effectively cross over to the treatment as usual group. This study is the first randomised control trial to explicitly use cultural assessment and management. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12609000952246.

Te Ira Tangata: A Zelen randomised controlled trial of a treatment package including problem solving therapy compared to treatment as usual in Maori who present to hospital after self harm

PubMed Central

2011-01-01

Background Maori, the indigenous people of New Zealand, who present to hospital after intentionally harming themselves, do so at a higher rate than non-Maori. There have been no previous treatment trials in Maori who self harm and previous reviews of interventions in other populations have been inconclusive as existing trials have been under powered and done on unrepresentative populations. These reviews have however indicated that problem solving therapy and sending regular postcards after the self harm attempt may be an effective treatment. There is also a small literature on sense of belonging in self harm and the importance of culture. This protocol describes a pragmatic trial of a package of measures which include problem solving therapy, postcards, patient support, cultural assessment, improved access to primary care and a risk management strategy in Maori who present to hospital after self harm using a novel design. Methods We propose to use a double consent Zelen design where participants are randomised prior to giving consent to enrol a representative cohort of patients. The main outcome will be the number of Maori scoring below nine on the Beck Hopelessness Scale. Secondary outcomes will be hospital repetition at one year; self reported self harm; anxiety; depression; quality of life; social function; and hospital use at three months and one year. Discussion A strength of the study is that it is a pragmatic trial which aims to recruit Maori using a Maori clinical team and protocol. It does not exclude people if English is not their first language. A potential limitation is the analysis of the results which is complex and may underestimate any effect if a large number of people refuse their consent in the group randomised to problem solving therapy as they will effectively cross over to the treatment as usual group. This study is the first randomised control trial to explicitly use cultural assessment and management. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12609000952246 PMID:21569300

Evaluating an audit and feedback intervention for reducing antibiotic prescribing behaviour in general dental practice (the RAPiD trial): a partial factorial cluster randomised trial protocol.

PubMed

Prior, Maria; Elouafkaoui, Paula; Elders, Andrew; Young, Linda; Duncan, Eilidh M; Newlands, Rumana; Clarkson, Jan E; Ramsay, Craig R

2014-04-24

Antibiotic prescribing in dentistry accounts for 9% of total antibiotic prescriptions in Scottish primary care. The Scottish Dental Clinical Effectiveness Programme (SDCEP) published guidance in April 2008 (2nd edition, August 2011) for Drug Prescribing in Dentistry, which aims to assist dentists to make evidence-based antibiotic prescribing decisions. However, wide variation in prescribing persists and the overall use of antibiotics is increasing. RAPiD is a 12-month partial factorial cluster randomised trial conducted in NHS General Dental Practices across Scotland. Its aim is to compare the effectiveness of individualised audit and feedback (A&F) strategies for the translation into practice of SDCEP recommendations on antibiotic prescribing. The trial uses routinely collected electronic healthcare data in five aspects of its design in order to: identify the study population; apply eligibility criteria; carry out stratified randomisation; generate the trial intervention; analyse trial outcomes. Eligibility was determined on contract status and a minimum level of recent NHS treatment provision. All eligible dental practices in Scotland were simultaneously randomised at baseline either to current audit practice or to an intervention group. Randomisation was stratified by single-handed/multi-handed practices. General dental practitioners (GDPs) working at intervention practices will receive individualised graphical representations of their antibiotic prescribing rate from the previous 14 months at baseline and an update at six months. GDPs could not be blinded to their practice allocation. Intervention practices were further randomised using a factorial design to receive feedback with or without: a health board comparator; a supplementary text-based intervention; additional feedback at nine months. The primary outcome is the total antibiotic prescribing rate per 100 courses of treatment over the year following delivery of the baseline intervention. A concurrent qualitative process evaluation will apply theory-based approaches using the Consolidated Framework for Implementation Research to explore the acceptability of the interventions and the Theoretical Domains Framework to identify barriers and enablers to evidence-based antibiotic prescribing behaviour by GDPs. RAPiD will provide a robust evaluation of A&F in dentistry in Scotland. It also demonstrates that linked administrative datasets have the potential to be used efficiently and effectively across all stages of an randomised controlled trial. Current Controlled Trials ISRCTN49204710.

Evaluating an audit and feedback intervention for reducing antibiotic prescribing behaviour in general dental practice (the RAPiD trial): a partial factorial cluster randomised trial protocol

PubMed Central

2014-01-01

Background Antibiotic prescribing in dentistry accounts for 9% of total antibiotic prescriptions in Scottish primary care. The Scottish Dental Clinical Effectiveness Programme (SDCEP) published guidance in April 2008 (2nd edition, August 2011) for Drug Prescribing in Dentistry, which aims to assist dentists to make evidence-based antibiotic prescribing decisions. However, wide variation in prescribing persists and the overall use of antibiotics is increasing. Methods RAPiD is a 12-month partial factorial cluster randomised trial conducted in NHS General Dental Practices across Scotland. Its aim is to compare the effectiveness of individualised audit and feedback (A&F) strategies for the translation into practice of SDCEP recommendations on antibiotic prescribing. The trial uses routinely collected electronic healthcare data in five aspects of its design in order to: identify the study population; apply eligibility criteria; carry out stratified randomisation; generate the trial intervention; analyse trial outcomes. Eligibility was determined on contract status and a minimum level of recent NHS treatment provision. All eligible dental practices in Scotland were simultaneously randomised at baseline either to current audit practice or to an intervention group. Randomisation was stratified by single-handed/multi-handed practices. General dental practitioners (GDPs) working at intervention practices will receive individualised graphical representations of their antibiotic prescribing rate from the previous 14 months at baseline and an update at six months. GDPs could not be blinded to their practice allocation. Intervention practices were further randomised using a factorial design to receive feedback with or without: a health board comparator; a supplementary text-based intervention; additional feedback at nine months. The primary outcome is the total antibiotic prescribing rate per 100 courses of treatment over the year following delivery of the baseline intervention. A concurrent qualitative process evaluation will apply theory-based approaches using the Consolidated Framework for Implementation Research to explore the acceptability of the interventions and the Theoretical Domains Framework to identify barriers and enablers to evidence-based antibiotic prescribing behaviour by GDPs. Discussion RAPiD will provide a robust evaluation of A&F in dentistry in Scotland. It also demonstrates that linked administrative datasets have the potential to be used efficiently and effectively across all stages of an randomised controlled trial. Trial registration Current Controlled Trials ISRCTN49204710 PMID:24758164

Randomised Controlled Trials in Education Research: A Case Study of an Individually Randomised Pragmatic Trial

ERIC Educational Resources Information Center

Torgerson, Carole J.

2009-01-01

The randomised controlled trial (RCT) is an evaluative method used by social scientists in order to establish whether or not an intervention is effective. This contribution discusses the fundamental aspects of good RCT design. These are illustrated through the use of a recently completed RCT which evaluated an information and communication…

Relation between burden of disease and randomised evidence in sub-Saharan Africa: survey of research.

PubMed

Isaakidis, Petros; Swingler, George H; Pienaar, Elizabeth; Volmink, Jimmy; Ioannidis, John P A

2002-03-23

To evaluate whether the amount of randomised clinical research on various medical conditions is related to the burden of disease and health needs of the local populations in sub-Saharan Africa. Construction and analysis of comprehensive database of randomised controlled trials in sub-Saharan Africa based on Medline, the Cochrane Controlled Trials Register, and several African databases. Sub-Saharan Africa. Number of trials and randomised subjects for each category of disease in the global burden of disease taxonomy; ratios of disability adjusted life years (DALYs) per amount of randomised evidence. 1179 eligible randomised controlled trials were identified. The number of trials published each year increased over time. Almost half of the trials (n=565) had been done in South Africa. There was relatively good correlation between the estimated burden of disease at year 2000 and the number of trials performed (r=0.53, P=0.024) and the number of participants randomised (r=0.68, P=0.002). However,some conditions-for example, injuries (over 20 000 DALYs per patient ever randomised)-were more neglected than others. Despite recent improvements, few clinical trials are done in sub-Saharan Africa. Clinical research in this part of the world should focus more evenly on the major contributors to burden of disease.

Kangaroo mother method: randomised controlled trial of an alternative method of care for stabilised low-birthweight infants. Maternidad Isidro Ayora Study Team.

PubMed

Sloan, N L; Camacho, L W; Rojas, E P; Stern, C

1994-09-17

Because resources for care of low-birthweight (LBW) infants in developing countries are scarce, the Kangaroo mother method (KMM) was developed. The infant is kept upright in skin-to-skin contact with the mother's breast. Previous studies reported several benefits with the KMM but interpretation of their findings is limited by small size and design weaknesses. We have done a longitudinal, randomised, controlled trial at the Isidro Ayora Maternity Hospital in Quito, Ecuador. Infants with LBW (< 2000 g) who satisfied out-of-risk criteria of tolerance of food and weight stabilisation were randomly assigned to KMM and control (standard incubator care) groups (n = 128 and 147, respectively). During 6 months of follow-up the KMM group had a significantly lower rate than the control group of serious illness (lower-respiratory-tract disorders, apnoea, aspiration, pneumonia, septicaemia, general infections; 7 [5%] vs 27 [18%], p < 0.002), although differences between the groups in less severe morbidity were not significant. There was no significant difference in growth or in the proportion of women breastfeeding, perhaps because the proportion breastfeeding was high in both groups owing to strong promotion. Mortality was the same in both groups; most deaths occurred during the stabilisation period before randomisation. KMM mothers made more unscheduled clinic visits than control mothers but their infants had fewer re-admissions and so the cost of care was lower with the KMM. Since the eligibility criteria excluded nearly 50% of LBW infants from the study, the KMM is not universally applicable to these infants. The benefits might be greater in populations where breastfeeding is not so common.

Targets and self-management for the control of blood pressure in stroke and at risk groups (TASMIN-SR): protocol for a randomised controlled trial.

PubMed

O'Brien, Claire; Bray, Emma P; Bryan, Stirling; Greenfield, Sheila M; Haque, M Sayeed; Hobbs, F D Richard; Jones, Miren I; Jowett, Sue; Kaambwa, Billingsley; Little, Paul; Mant, Jonathan; Penaloza, Cristina; Schwartz, Claire; Shackleford, Helen; Varghese, Jinu; Williams, Bryan; McManus, Richard J

2013-03-23

Self-monitoring of hypertension with self-titration of antihypertensives (self-management) results in lower systolic blood pressure for at least one year. However, few people in high risk groups have been evaluated to date and previous work suggests a smaller effect size in these groups. This trial therefore aims to assess the added value of self-management in high risk groups over and above usual care. The targets and self-management for the control of blood pressure in stroke and at risk groups (TASMIN-SR) trial will be a pragmatic primary care based, unblinded, randomised controlled trial of self-management of blood pressure (BP) compared to usual care. Eligible patients will have a history of stroke, coronary heart disease, diabetes or chronic kidney disease and will be recruited from primary care. Participants will be individually randomised to either usual care or self-management. The primary outcome of the trial will be difference in office SBP between intervention and control groups at 12 months adjusted for baseline SBP and covariates. 540 patients will be sufficient to detect a difference in SBP between self-management and usual care of 5 mmHg with 90% power. Secondary outcomes will include self-efficacy, lifestyle behaviours, health-related quality of life and adverse events. An economic analysis will consider both within trial costs and a model extrapolating the results thereafter. A qualitative analysis will gain insights into patients' views, experiences and decision making processes. The results of the trial will be directly applicable to primary care in the UK. If successful, self-management of blood pressure in people with stroke and other high risk conditions would be applicable to many hundreds of thousands of individuals in the UK and beyond. ISRCTN87171227.

Does transcutaneous electrical nerve stimulation (TENS) alleviate the pain experienced during bone marrow sampling in addition to standard techniques? A randomised, double-blinded, controlled trial.

PubMed

Tucker, David L; Rockett, Mark; Hasan, Mehedi; Poplar, Sarah; Rule, Simon A

2015-06-01

Bone marrow aspiration and trephine (BMAT) biopsies remain important tests in haematology. However, the procedures can be moderately to severely painful despite standard methods of pain relief. To test the efficacy of transcutaneous electrical nerve stimulation (TENS) in alleviating the pain from BMAT in addition to standard analgesia using a numerical pain rating scale (NRS). 70 patients requiring BMAT were randomised (1:1) in a double-blind, placebo-controlled trial. -35 patients received TENS impulses at a strong but comfortable amplitude (intervention group) and 35 patients received TENS impulses just above the sensory threshold (control group) (median pulse amplitude 20 and 7 mA, respectively). Patients and operators were blinded to group allocation. Pain assessments were made using a numerical pain scale completed after the procedure. No significant difference in NRS pain recalled after the procedure was detected (median pain score 5.7 (95% CI 4.8 to 6.6) in control vs 5.6 (95% CI 4.8 to 6.4) in the intervention group). However, 100% of patients who had previous experience of BMAT and >94% of participants overall felt they benefited from using TENS and would recommend it to others for this procedure. There were no side effects from the TENS device, and it was well tolerated. TENS is a safe, non-invasive adjunct to analgesia for reducing pain during bone marrow biopsy and provides a subjective benefit to most users; however, no objective difference in pain scores was detected when using TENS in this randomised controlled study. NCT02005354. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Developing and testing accelerated partner therapy for partner notification for people with genital Chlamydia trachomatis diagnosed in primary care: a pilot randomised controlled trial.

PubMed

Estcourt, Claudia S; Sutcliffe, Lorna J; Copas, Andrew; Mercer, Catherine H; Roberts, Tracy E; Jackson, Louise J; Symonds, Merle; Tickle, Laura; Muniina, Pamela; Rait, Greta; Johnson, Anne M; Aderogba, Kazeem; Creighton, Sarah; Cassell, Jackie A

2015-12-01

Accelerated partner therapy (APT) is a promising partner notification (PN) intervention in specialist sexual health clinic attenders. To address its applicability in primary care, we undertook a pilot randomised controlled trial (RCT) of two APT models in community settings. Three-arm pilot RCT of two adjunct APT interventions: APTHotline (telephone assessment of partner(s) plus standard PN) and APTPharmacy (community pharmacist assessment of partner(s) plus routine PN), versus standard PN alone (patient referral). Index patients were women diagnosed with genital chlamydia in 12 general practices and three community contraception and sexual health (CASH) services in London and south coast of England, randomised between 1 September 2011 and 31 July 2013. 199 women described 339 male partners, of whom 313 were reported by the index as contactable. The proportions of contactable partners considered treated within 6 weeks of index diagnosis were APTHotline 39/111 (35%), APTPharmacy 46/100 (46%), standard patient referral 46/102 (45%). Among treated partners, 8/39 (21%) in APTHotline arm were treated via hotline and 14/46 (30%) in APTPharmacy arm were treated via pharmacy. The two novel primary care APT models were acceptable, feasible, compliant with regulations and capable of achieving acceptable outcomes within a pilot RCT but intervention uptake was low. Although addition of these interventions to standard PN did not result in a difference between arms, overall PN uptake was higher than previously reported in similar settings, probably as a result of introducing a formal evaluation. Recruitment to an individually randomised trial proved challenging and full evaluation will likely require service-level randomisation. Registered UK Clinical Research Network Study Portfolio id number 10123. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A review of reporting of participant recruitment and retention in RCTs in six major journals

PubMed Central

Toerien, Merran; Brookes, Sara T; Metcalfe, Chris; de Salis, Isabel; Tomlin, Zelda; Peters, Tim J; Sterne, Jonathan; Donovan, Jenny L

2009-01-01

Background Poor recruitment and retention of participants in randomised controlled trials (RCTs) is problematic but common. Clear and detailed reporting of participant flow is essential to assess the generalisability and comparability of RCTs. Despite improved reporting since the implementation of the CONSORT statement, important problems remain. This paper aims: (i) to update and extend previous reviews evaluating reporting of participant recruitment and retention in RCTs; (ii) to quantify the level of participation throughout RCTs. Methods We reviewed all reports of RCTs of health care interventions and/or processes with individual randomisation, published July–December 2004 in six major journals. Short, secondary or interim reports, and Phase I/II trials were excluded. Data recorded were: general RCT details; inclusion of flow diagram; participant flow throughout trial; reasons for non-participation/withdrawal; target sample sizes. Results 133 reports were reviewed. Overall, 79% included a flow diagram, but over a third were incomplete. The majority reported the flow of participants at each stage of the trial after randomisation. However, 40% failed to report the numbers assessed for eligibility. Percentages of participants retained at each stage were high: for example, 90% of eligible individuals were randomised, and 93% of those randomised were outcome assessed. On average, trials met their sample size targets. However, there were some substantial shortfalls: for example 21% of trials reporting a sample size calculation failed to achieve adequate numbers at randomisation, and 48% at outcome assessment. Reporting of losses to follow up was variable and difficult to interpret. Conclusion The majority of RCTs reported the flow of participants well after randomisation, although only two-thirds included a complete flow chart and there was great variability over the definition of "lost to follow up". Reporting of participant eligibility was poor, making assessments of recruitment practice and external validity difficult. Reporting of participant flow throughout RCTs could be improved by small changes to the CONSORT chart. PMID:19591685

A review of reporting of participant recruitment and retention in RCTs in six major journals.

PubMed

Toerien, Merran; Brookes, Sara T; Metcalfe, Chris; de Salis, Isabel; Tomlin, Zelda; Peters, Tim J; Sterne, Jonathan; Donovan, Jenny L

2009-07-10

Poor recruitment and retention of participants in randomised controlled trials (RCTs) is problematic but common. Clear and detailed reporting of participant flow is essential to assess the generalisability and comparability of RCTs. Despite improved reporting since the implementation of the CONSORT statement, important problems remain. This paper aims: (i) to update and extend previous reviews evaluating reporting of participant recruitment and retention in RCTs; (ii) to quantify the level of participation throughout RCTs. We reviewed all reports of RCTs of health care interventions and/or processes with individual randomisation, published July-December 2004 in six major journals. Short, secondary or interim reports, and Phase I/II trials were excluded. Data recorded were: general RCT details; inclusion of flow diagram; participant flow throughout trial; reasons for non-participation/withdrawal; target sample sizes. 133 reports were reviewed. Overall, 79% included a flow diagram, but over a third were incomplete. The majority reported the flow of participants at each stage of the trial after randomisation. However, 40% failed to report the numbers assessed for eligibility. Percentages of participants retained at each stage were high: for example, 90% of eligible individuals were randomised, and 93% of those randomised were outcome assessed. On average, trials met their sample size targets. However, there were some substantial shortfalls: for example 21% of trials reporting a sample size calculation failed to achieve adequate numbers at randomisation, and 48% at outcome assessment. Reporting of losses to follow up was variable and difficult to interpret. The majority of RCTs reported the flow of participants well after randomisation, although only two-thirds included a complete flow chart and there was great variability over the definition of "lost to follow up". Reporting of participant eligibility was poor, making assessments of recruitment practice and external validity difficult. Reporting of participant flow throughout RCTs could be improved by small changes to the CONSORT chart.

Trial Protocol: Cognitive functional therapy compared with combined manual therapy and motor control exercise for people with non-specific chronic low back pain: protocol for a randomised, controlled trial.

PubMed

Belache, Fabiana Terra Cunha; Souza, Cíntia Pereira de; Fernandez, Jessica; Castro, Julia; Ferreira, Paula Dos Santos; Rosa, Elizana Rodrigues de Sousa; Araújo, Nathalia Cristina Gimenez de; Reis, Felipe José Jandre; Almeida, Renato Santos de; Nogueira, Leandro Alberto Calazans; Correia, Luís Cláudio Lemos; Meziat-Filho, Ney

2018-06-11

Chronic low back pain is a public health problem, and there is strong evidence that it is associated with a complex interaction of biopsychosocial factors. Cognitive functional therapy is an intervention that deals with potentially modifiable multidimensional aspects of pain (eg, provocative cognitive, movement and lifestyle behaviours). There is evidence (from a single randomised, controlled trial) that cognitive functional therapy is better than combined manual therapy and motor control exercise. However, this study had significant methodological shortcomings including the failure to carry out an intention-to-treat analysis and a considerable loss of follow-up of participants. It is important to replicate this study in another domain through a randomised clinical trial with similar objectives but correcting these methodological shortcomings. To investigate the efficacy of cognitive functional therapy compared to combined manual therapy and exercise on pain and disability at 3 months in patients with chronic non-specific low back pain. Two-group, randomised, multicentre controlled trial with blinded assessors. One hundred and forty-eight participants with chronic low back pain that has persisted for >3months and no specific spinal pathology will be recruited from the school clinic of the Centro Universitário Augusto Motta and a private clinic in the city of Rio de Janeiro, Brazil. Four to 10 sessions of cognitive functional therapy. The physiotherapists who will treat the participants in the cognitive functional therapy group have previously attended 2 workshops with two different tutors of the method. Such physiotherapists have completed 106 hours of training, including workshops and patient examinations, as well as conducting a pilot study under the supervision of another physiotherapist with>3 years of clinical experience in cognitive functional therapy. Four to 10 sessions of combined manual therapy and motor control exercises. Participants in the combined manual therapy and exercise group will be treated by two physiotherapists with an average of >10years of clinical experience in manual therapy and motor control exercises, including isolated contractions of the deep abdominal muscles. The primary outcome measures will be pain intensity and disability 3 months after randomisation. Secondary outcomes will be pain and disability assessed 6 and 12 months after randomisation, and both global perceived effect and patient satisfaction at 3, 6 and 12 months after randomisation. The potential outcome mediators will be assessed at 3 and 6 months after randomisation, with brief screening questions for anxiety, social isolation, catastrophisation, depression, fear of movement, stress and sleep. Non-specific predictors and moderators will include age, gender, duration of chronic low back pain, chronicity risk (Örebro and Start Back score), number of pain areas, stressful life event, MRI scan imaging, and family history. Intention-to-treat analysis will be performed. Linear mixed models will be used to compare the mean differences in pain intensity, disability and global perceived effect between the intervention arms. The analysis of the effect of potential mediators of the treatment will be performed using the causal mediation methods described by Imai and colleagues. The baseline variables will be evaluated as predictors and moderators of treatment, including terms and interaction models. A level of statistical significance of 5% will be used in the analysis. All the analyses will be performed using RStudio. This study will investigate whether the results of the first cognitive functional therapy randomised clinical trial are reproducible. The present study will have a sample size capable of detecting clinically relevant effects of the treatment with a low risk of bias. In pragmatic terms, this clinical trial is designed to reproduce the intervention as it would be performed in clinical practice by a trained physiotherapist who works with cognitive functional therapy, which increases the relevance of this study. The combined manual therapy and exercise group comprises an intervention strategy widely used by physiotherapists to treat low back pain. As evidence of efficacy is still limited, the results of a randomised, controlled clinical trial of high methodological quality will help physiotherapists in clinical decision-making. Copyright © 2018 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

[Pre-randomisation in study designs: getting past the taboo].

PubMed

Schellings, R; Kessels, A G; Sturmans, F

2008-09-20

In October 2006 the Dutch Ministry of Health, Welfare and Sport announced that the use of pre-randomisation in study designs is admissible and not in conflict with the Dutch Medical Research in Human Subjects Act. With pre-randomisation, the conventional sequence of obtaining informed consent followed by randomisation is reversed. According to the original pre-randomisation design (Zelen design), participants are randomised before they are asked to consent; after randomisation, only participants in the experimental group are asked to consent to treatment and effect measurement. In the past, pre-randomisation has seldom been used, and when it was, it was often under the wrong circumstances. Awareness regarding the ethical, legal and methodological objections to pre-randomisation is increasing. About a decade ago, we illustrated the applicability and acceptability of pre-randomisation by means of a fictitious heroin provision trial. In general, pre-randomisation is justified if valid evaluation of the effects of an intervention is impossible using a conventional randomised design, e.g., if knowledge of the intervention may lead to non-compliance or drop-out in the control group, or when the intervention is an educational programme. Other requirements for pre-randomisation include the following: the study has a clinically relevant objective, it is likely that the study will lead to important new insights, the informed consent procedure bears no potential harm to participants, at least standard care is offered to participants in the control group, and the approval of an independent research ethics committee is obtained.

Effect of Fee on Cervical Cancer Screening Attendance--ScreenFee, a Swedish Population-Based Randomised Trial.

PubMed

Alfonzo, Emilia; Andersson Ellström, Agneta; Nemes, Szilard; Strander, Björn

2016-01-01

Attendance in the cervical cancer screening programme is one of the most important factors to lower the risk of contracting the disease. Attendance rates are often low in areas with low socioeconomic status. Charging a fee for screening might possibly decrease attendance in this population. Screening programme coverage is low in low socio-economic status areas in Gothenburg, Sweden, but has increased slightly after multiple interventions in recent years. For many years, women in the region have paid a fee for screening. We studied the effect of abolishing this fee in a trial emanating from the regular cervical cancer screening programme. Individually randomised controlled trial. All 3 124 women in three low-resource areas in Gothenburg, due for screening during the study period, were randomised to receive an offer of a free test or the standard invitation stating the regular fee of 100 SEK (≈11 €). The study was conducted during the first six months of 2013. Attendance was defined as a registered Pap smear within 90 days from the date the invitation was sent out. Attendance did not differ significantly between women who were charged and those offered free screening (RR 0.93; CI 0.85-1.02). No differences were found within the districts or as an effect of age, attendance after the most recent previous invitation or previous experience of smear taking. Abolishment of a modest screening fee in socially disadvantaged urban districts with low coverage, after previous multiple systematic interventions, does not increase attendance in the short term. Other interventions might be more important for increasing attendance in low socio-economic status areas. ClinicalTrials.gov NCT02378324.

Effect of Fee on Cervical Cancer Screening Attendance—ScreenFee, a Swedish Population-Based Randomised Trial

PubMed Central

Alfonzo, Emilia; Andersson Ellström, Agneta; Nemes, Szilard; Strander, Björn

2016-01-01

Background Attendance in the cervical cancer screening programme is one of the most important factors to lower the risk of contracting the disease. Attendance rates are often low in areas with low socioeconomic status. Charging a fee for screening might possibly decrease attendance in this population. Screening programme coverage is low in low socio-economic status areas in Gothenburg, Sweden, but has increased slightly after multiple interventions in recent years. For many years, women in the region have paid a fee for screening. We studied the effect of abolishing this fee in a trial emanating from the regular cervical cancer screening programme. Method Individually randomised controlled trial. All 3 124 women in three low-resource areas in Gothenburg, due for screening during the study period, were randomised to receive an offer of a free test or the standard invitation stating the regular fee of 100 SEK (≈11 €). The study was conducted during the first six months of 2013. Attendance was defined as a registered Pap smear within 90 days from the date the invitation was sent out. Results Attendance did not differ significantly between women who were charged and those offered free screening (RR 0.93; CI 0.85–1.02). No differences were found within the districts or as an effect of age, attendance after the most recent previous invitation or previous experience of smear taking. Conclusion Abolishment of a modest screening fee in socially disadvantaged urban districts with low coverage, after previous multiple systematic interventions, does not increase attendance in the short term. Other interventions might be more important for increasing attendance in low socio-economic status areas. Trial Registration ClinicalTrials.gov NCT02378324 PMID:26986848

Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials.

PubMed

Cooper, Cindy L; Whitehead, Amy; Pottrill, Edward; Julious, Steven A; Walters, Stephen J

2018-04-01

External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland-Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was -4.4% with limits of agreement of -37.1% to 28.2%. Limits of agreement for randomisation rates were -47.8% to 77.5%. Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate.

Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials

PubMed Central

Whitehead, Amy; Pottrill, Edward; Julious, Steven A; Walters, Stephen J

2018-01-01

Background/aims: External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. Methods: Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland–Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. Results: Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was −4.4% with limits of agreement of −37.1% to 28.2%. Limits of agreement for randomisation rates were −47.8% to 77.5%. Conclusion: Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate. PMID:29361833

A causal model for longitudinal randomised trials with time-dependent non-compliance

PubMed Central

Becque, Taeko; White, Ian R; Haggard, Mark

2015-01-01

In the presence of non-compliance, conventional analysis by intention-to-treat provides an unbiased comparison of treatment policies but typically under-estimates treatment efficacy. With all-or-nothing compliance, efficacy may be specified as the complier-average causal effect (CACE), where compliers are those who receive intervention if and only if randomised to it. We extend the CACE approach to model longitudinal data with time-dependent non-compliance, focusing on the situation in which those randomised to control may receive treatment and allowing treatment effects to vary arbitrarily over time. Defining compliance type to be the time of surgical intervention if randomised to control, so that compliers are patients who would not have received treatment at all if they had been randomised to control, we construct a causal model for the multivariate outcome conditional on compliance type and randomised arm. This model is applied to the trial of alternative regimens for glue ear treatment evaluating surgical interventions in childhood ear disease, where outcomes are measured over five time points, and receipt of surgical intervention in the control arm may occur at any time. We fit the models using Markov chain Monte Carlo methods to obtain estimates of the CACE at successive times after receiving the intervention. In this trial, over a half of those randomised to control eventually receive intervention. We find that surgery is more beneficial than control at 6months, with a small but non-significant beneficial effect at 12months. © 2015 The Authors. Statistics in Medicine Published by JohnWiley & Sons Ltd. PMID:25778798

The Collaborative Randomised Amnioinfusion for Meconium Project (CRAMP): 1. South Africa.

PubMed

Hofmeyr, G J; Gülmezoğlu, A M; Buchmann, E; Howarth, G R; Shaw, A; Nikodem, V C; Cronje, H; de Jager, M; Mahomed, K

1998-03-01

To evaluate transcervical amnioinfusion for meconium stained amniotic fluid during labout. Multicentre randomised controlled trial. Four urban academic hospitals in South Africa. Obstetric surveillance included the use of electronic fetal heart rate monitoring in most cases. Women in labour at term with moderate or thick meconium staining of the amniotic fluid. Transcervical amnioinfusion of 800 mL saline at 15 mL per minute, followed by a maintenance infusion at 3 mL per minute. The control group received routine care. Blinding of the intervention was not possible. Caesarean section, meconium aspiration syndrome and perinatal mortality. Caesarean section rates were similar (amnioinfusion group 70/167 vs control group 68/159; RR 0.98, 95% CI 0.76-1.26). The incidence of meconium aspiration syndrome was lower than expected on the basis of previous studies (4/162 vs 6/163; RR 0.67, 95% CI 0.19-2.33). There were no perinatal deaths. There were no significant differences between any of the subsidiary outcomes. This study concurred with three previous trials which found no effect of amnioinfusion for meconium-stained amniotic fluid on caesarean section rate, though the pooled data from all identified trials to date show a significant reduction. The findings with respect to meconium aspiration syndrome were inconclusive in this study alone because of the small number of babies affected, but the point estimate of the relative risk was consistent with the finding of a significant reduction in previous studies and with the Zimbabwe arm (CRAMP 2) of this study. Pooled data clearly support the use of amnioinfusion for meconium stained amniotic fluid to reduce the incidence of meconium aspiration syndrome.

Acupuncture for Bell's palsy.

PubMed

Chen, Ning; Zhou, Muke; He, Li; Zhou, Dong; Li, N

2010-08-04

Bell's palsy or idiopathic facial palsy is an acute facial paralysis due to inflammation of the facial nerve. A number of studies published in China have suggested acupuncture is beneficial for facial palsy. The objective of this review was to examine the efficacy of acupuncture in hastening recovery and reducing long-term morbidity from Bell's palsy. We updated the searches of the Cochrane Neuromuscular Disease Group Trials Specialized Register (24 May 2010), The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2010), MEDLINE (January 1966 to May 2010), EMBASE (January 1980 to May 2010), AMED (January 1985 to May 2010), LILACS (from January 1982 to May 2010) and the Chinese Biomedical Retrieval System (January 1978 to May 2010) for randomised controlled trials using 'Bell's palsy' and its synonyms, 'idiopathic facial paralysis' or 'facial palsy' as well as search terms including 'acupuncture'. Chinese journals in which we thought we might find randomised controlled trials relevant to our study were handsearched. We reviewed the bibliographies of the randomised trials and contacted the authors and known experts in the field to identify additional published or unpublished data. We included all randomised controlled trials involving acupuncture by needle insertion in the treatment of Bell's palsy irrespective of any language restrictions. Two review authors identified potential articles from the literature search, extracted data and assessed quality of each trial independently. All disagreements were resolved by discussion between the review authors. The literature search and handsearching identified 49 potentially relevant articles. Of these, six RCTs were included involving 537 participants with Bell's palsy. Two more possible trials were identified in the update than the previous version of this systematic review, but both were excluded because they were not real RCTs. Of the six included trials, five used acupuncture while the other one used acupuncture combined with drugs. No trial reported on the outcomes specified for this review. Harmful side effects were not reported in any of the trials. Poor quality caused by flaws in study design or reporting (including uncertain method of randomisation, allocation concealment and blinding) and clinical differences between trials prevented reliable conclusions about the efficacy of acupuncture. The quality of the included trials was inadequate to allow any conclusion about the efficacy of acupuncture. More research with high quality trials is needed.

Ad libitum or demand/semi-demand feeding versus scheduled interval feeding for preterm infants.

PubMed

McCormick, Felicia M; Tosh, Karen; McGuire, William

2010-02-17

Scheduled interval feeding of prescribed enteral volumes is current standard practice for preterm infants. However, feeding preterm infants in response to their hunger and satiation cues (ad libitum or demand/semi demand) rather than at scheduled intervals might help in the establishment of independent oral feeding, increase nutrient intake and growth rates, and allow earlier hospital discharge. To assess the effect of a policy of feeding preterm infants on an ad libitum or demand/semi-demand basis versus feeding prescribed volumes at scheduled intervals on growth rates and the time to hospital discharge. We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2009), MEDLINE (1966 to Oct 2009), EMBASE (1980 to Oct 2009), CINAHL (1982 to Oct 2009), conference proceedings, and previous reviews. Randomised or quasi-randomised controlled trials (including cluster randomised trials) that compared a policy of feeding preterm infants on an ad libitum or demand/semi-demand basis versus feeding at scheduled intervals. We used the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors. We found eight randomised controlled trials that compared ad libitum or demand/semi-demand regimens with scheduled interval regimes in preterm infants in the transition phase from intragastric tube to oral feeding. The trials were generally small and of variable methodological quality. The duration of the intervention and the duration of data collection and follow-up in most of the trials was not likely to have allowed detection of measurable effects on growth. Three trials reported that feeding preterm infants using an ad libitum or demand/semi-demand feeding regimen allowed earlier discharge from hospital (by about two to four days) but other trials did not confirm this finding. Limited evidence exists that feeding preterm infants with ad libitum or demand/semi-demand regimens allows earlier attainment of full oral feeding and earlier hospital discharge. This finding should be interpreted cautiously because of methodological weaknesses in the included trials. A large randomised controlled trial is needed to confirm this finding and to determine if ad libitum of demand/semi-demand feeding of preterm infants affects other clinically important outcomes.

Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial.

PubMed

Holtzheimer, Paul E; Husain, Mustafa M; Lisanby, Sarah H; Taylor, Stephan F; Whitworth, Louis A; McClintock, Shawn; Slavin, Konstantin V; Berman, Joshua; McKhann, Guy M; Patil, Parag G; Rittberg, Barry R; Abosch, Aviva; Pandurangi, Ananda K; Holloway, Kathryn L; Lam, Raymond W; Honey, Christopher R; Neimat, Joseph S; Henderson, Jaimie M; DeBattista, Charles; Rothschild, Anthony J; Pilitsis, Julie G; Espinoza, Randall T; Petrides, Georgios; Mogilner, Alon Y; Matthews, Keith; Peichel, DeLea; Gross, Robert E; Hamani, Clement; Lozano, Andres M; Mayberg, Helen S

2017-11-01

Deep brain stimulation (DBS) of the subcallosal cingulate white matter has shown promise as an intervention for patients with chronic, unremitting depression. To test the safety and efficacy of DBS for treatment-resistant depression, a prospective, randomised, sham-controlled trial was conducted. Participants with treatment-resistant depression were implanted with a DBS system targeting bilateral subcallosal cingulate white matter and randomised to 6 months of active or sham DBS, followed by 6 months of open-label subcallosal cingulate DBS. Randomisation was computer generated with a block size of three at each site before the site started the study. The primary outcome was frequency of response (defined as a 40% or greater reduction in depression severity from baseline) averaged over months 4-6 of the double-blind phase. A futility analysis was performed when approximately half of the proposed sample received DBS implantation and completed the double-blind phase. At the conclusion of the 12-month study, a subset of patients were followed up for up to 24 months. The study is registered at ClinicalTrials.gov, number NCT00617162. Before the futility analysis, 90 participants were randomly assigned to active (n=60) or sham (n=30) stimulation between April 10, 2008, and Nov 21, 2012. Both groups showed improvement, but there was no statistically significant difference in response during the double-blind, sham-controlled phase (12 [20%] patients in the stimulation group vs five [17%] patients in the control group). 28 patients experienced 40 serious adverse events; eight of these (in seven patients) were deemed to be related to the study device or surgery. This study confirmed the safety and feasibility of subcallosal cingulate DBS as a treatment for treatment-resistant depression but did not show statistically significant antidepressant efficacy in a 6-month double-blind, sham-controlled trial. Future studies are needed to investigate factors such as clinical features or electrode placement that might improve efficacy. Abbott (previously St Jude Medical). Copyright © 2017 Elsevier Ltd. All rights reserved.

Prostate cancer - evidence of exercise and nutrition trial (PrEvENT): study protocol for a randomised controlled feasibility trial.

PubMed

Hackshaw-McGeagh, Lucy; Lane, J Athene; Persad, Raj; Gillatt, David; Holly, Jeff M P; Koupparis, Anthony; Rowe, Edward; Johnston, Lyndsey; Cloete, Jenny; Shiridzinomwa, Constance; Abrams, Paul; Penfold, Chris M; Bahl, Amit; Oxley, Jon; Perks, Claire M; Martin, Richard

2016-03-07

A growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The 'Prostate Cancer: Evidence of Exercise and Nutrition Trial' investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6 months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures. The trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6 months post-randomisation). The Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery. Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.

Two decision aids for mode of delivery among women with previous caesarean section: randomised controlled trial.

PubMed

Montgomery, Alan A; Emmett, Clare L; Fahey, Tom; Jones, Claire; Ricketts, Ian; Patel, Roshni R; Peters, Tim J; Murphy, Deirdre J

2007-06-23

To determine the effects of two computer based decision aids on decisional conflict and mode of delivery among pregnant women with a previous caesarean section. Randomised trial, conducted from May 2004 to August 2006. Four maternity units in south west England, and Scotland. 742 pregnant women with one previous lower segment caesarean section and delivery expected at >or=37 weeks. Non-English speakers were excluded. Usual care: standard care given by obstetric and midwifery staff. Information programme: women navigated through descriptions and probabilities of clinical outcomes for mother and baby associated with planned vaginal birth, elective caesarean section, and emergency caesarean section. Decision analysis: mode of delivery was recommended based on utility assessments performed by the woman combined with probabilities of clinical outcomes within a concealed decision tree. Both interventions were delivered via a laptop computer after brief instructions from a researcher. Total score on decisional conflict scale, and mode of delivery. Women in the information programme (adjusted difference -6.2, 95% confidence interval -8.7 to -3.7) and the decision analysis (-4.0, -6.5 to -1.5) groups had reduced decisional conflict compared with women in the usual care group. The rate of vaginal birth was higher for women in the decision analysis group compared with the usual care group (37% v 30%, adjusted odds ratio 1.42, 0.94 to 2.14), but the rates were similar in the information programme and usual care groups. Decision aids can help women who have had a previous caesarean section to decide on mode of delivery in a subsequent pregnancy. The decision analysis approach might substantially affect national rates of caesarean section. Trial Registration Current Controlled Trials ISRCTN84367722.

Randomised controlled trial of a mobile phone infant resuscitation guide.

PubMed

Hawkes, Gavin A; Murphy, Geraldine; Dempsey, Eugene M; Ryan, Anthony C

2015-11-01

The aim of this study was to develop a mobile phone resuscitation guide (MPRG) and to evaluate its use during simulated resuscitation of a mannequin. An MPRG was developed using EpiSurveyor. A randomised controlled trial was performed in school-going children aged 15-16 years. All subjects were taught infant CPR skills using the American Heart Association Infant CPR Anytime. Two weeks later, the students were randomised to use of MPRG or not, and their CPR skills were re-assessed. The assessment was conducted using previously validated checklists. Twenty-one students participated in this trial. The MPRG group performed notably better in the areas of calling emergency services (80% vs. 36.4%, P = 0.044), completing sufficient CPR cycles (90% vs. 45.5%, P = 0.047) and following the correct CPR sequence (60% vs. 9.1%, P = 0.013). No difference in resuscitation skills of participants was observed. We have shown that participants were more likely to call emergency services if they were using the MPRG. Further trials are needed to investigate the utility of mobile phone guides and whether or not they can reduce the time taken to contact emergency services as well as if they can sustain correct CPR sequence in an in-vivo setting. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

A randomised, controlled trial of circumpatellar electrocautery in total knee replacement without patellar resurfacing: a concise follow-up at a mean of 3.7 years.

PubMed

van Jonbergen, H P W; Scholtes, V A B; Poolman, R W

2014-04-01

In the absence of patellar resurfacing, we have previously shown that the use of electrocautery around the margin of the patella improved the one-year clinical outcome of total knee replacement (TKR). In this prospective randomised study we compared the mean 3.7 year (1.1 to 4.2) clinical outcomes of 300 TKRs performed with and without electrocautery of the patellar rim: this is an update of a previous report. The overall prevalence of anterior knee pain was 32% (95% confidence intervals [CI] 26 to 39), and 26% (95% CI 18 to 35) in the intervention group compared with 38% (95% CI 29 to 48) in the control group (chi-squared test; p = 0.06). The overall prevalence of anterior knee pain remained unchanged between the one-year and 3.7 year follow-up (chi-squared test; p = 0.12). The mean total Western Ontario McMasters Universities Osteoarthritis Indices and the American Knee Society knee and function scores at 3.7 years' follow-up were similar in the intervention and control groups (repeated measures analysis of variance p = 0.43, p = 0.09 and p = 0.59, respectively). There were no complications. A total of ten patients (intervention group three, control group seven) required secondary patellar resurfacing after the first year. Our study suggests that the improved clinical outcome with electrocautery denervation compared with no electrocautery is not maintained at a mean of 3.7 years' follow-up.

Effectiveness of strategies incorporating training and support of traditional birth attendants on perinatal and maternal mortality: meta-analysis

PubMed Central

Wilson, Amie; Gallos, Ioannis D; Plana, Nieves; Lissauer, David; Khan, Khalid S; Zamora, Javier; MacArthur, Christine

2011-01-01

Objective To assess the effectiveness of strategies incorporating training and support of traditional birth attendants on the outcomes of perinatal, neonatal, and maternal death in developing countries. Design Systematic review with meta-analysis. Data sources Medline, Embase, the Allied and Complementary Medicine database, British Nursing Index, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, BioMed Central, PsycINFO, Latin American and Caribbean Health Sciences Literature database, African Index Medicus, Web of Science, Reproductive Health Library, and Science Citation Index (from inception to April 2011), without language restrictions. Search terms were “birth attend*”, “traditional midwife”, “lay birth attendant”, “dais”, and “comadronas”. Review methods We selected randomised and non-randomised controlled studies with outcomes of perinatal, neonatal, and maternal mortality. Two independent reviewers undertook data extraction. We pooled relative risks separately for the randomised and non-randomised controlled studies, using a random effects model. Results We identified six cluster randomised controlled trials (n=138 549) and seven non-randomised controlled studies (n=72 225) that investigated strategies incorporating training and support of traditional birth attendants. All six randomised controlled trials found a reduction in adverse perinatal outcomes; our meta-analysis showed significant reductions in perinatal death (relative risk 0.76, 95% confidence interval 0.64 to 0.88, P<0.001; number needed to treat 35, 24 to 70) and neonatal death (0.79, 0.69 to 0.88, P<0.001; 98, 66 to 170). Meta-analysis of the non-randomised studies also showed a significant reduction in perinatal mortality (0.70, 0.57 to 0.84, p<0.001; 48, 32 to 96) and neonatal mortality (0.61, 0.48 to 0.75, P<0.001; 96, 65 to 168). Six studies reported on maternal mortality and our meta-analysis showed a non-significant reduction (three randomised trials, relative risk 0.79, 0.53 to 1.05, P=0.12; three non-randomised studies, 0.80, 0.44 to 1.15, P=0.26). Conclusion Perinatal and neonatal deaths are significantly reduced with strategies incorporating training and support of traditional birth attendants. PMID:22134967

Effectiveness of strategies incorporating training and support of traditional birth attendants on perinatal and maternal mortality: meta-analysis.

PubMed

Wilson, Amie; Gallos, Ioannis D; Plana, Nieves; Lissauer, David; Khan, Khalid S; Zamora, Javier; MacArthur, Christine; Coomarasamy, Arri

2011-12-01

To assess the effectiveness of strategies incorporating training and support of traditional birth attendants on the outcomes of perinatal, neonatal, and maternal death in developing countries. Systematic review with meta-analysis. Medline, Embase, the Allied and Complementary Medicine database, British Nursing Index, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, BioMed Central, PsycINFO, Latin American and Caribbean Health Sciences Literature database, African Index Medicus, Web of Science, Reproductive Health Library, and Science Citation Index (from inception to April 2011), without language restrictions. Search terms were "birth attend*", "traditional midwife", "lay birth attendant", "dais", and "comadronas". Review methods We selected randomised and non-randomised controlled studies with outcomes of perinatal, neonatal, and maternal mortality. Two independent reviewers undertook data extraction. We pooled relative risks separately for the randomised and non-randomised controlled studies, using a random effects model. We identified six cluster randomised controlled trials (n=138 549) and seven non-randomised controlled studies (n=72 225) that investigated strategies incorporating training and support of traditional birth attendants. All six randomised controlled trials found a reduction in adverse perinatal outcomes; our meta-analysis showed significant reductions in perinatal death (relative risk 0.76, 95% confidence interval 0.64 to 0.88, P<0.001; number needed to treat 35, 24 to 70) and neonatal death (0.79, 0.69 to 0.88, P<0.001; 98, 66 to 170). Meta-analysis of the non-randomised studies also showed a significant reduction in perinatal mortality (0.70, 0.57 to 0.84, p<0.001; 48, 32 to 96) and neonatal mortality (0.61, 0.48 to 0.75, P<0.001; 96, 65 to 168). Six studies reported on maternal mortality and our meta-analysis showed a non-significant reduction (three randomised trials, relative risk 0.79, 0.53 to 1.05, P=0.12; three non-randomised studies, 0.80, 0.44 to 1.15, P=0.26). Perinatal and neonatal deaths are significantly reduced with strategies incorporating training and support of traditional birth attendants.

Introduction of the Misgav Ladach caesarean section at an African tertiary centre: a randomised controlled trial.

PubMed

Björklund, K; Kimaro, M; Urassa, E; Lindmark, G

2000-02-01

To determine whether the Misgav Ladach caesarean section technique can offer benefits compared with conventional caesarean section technique in the prevailing conditions of a busy African tertiary centre. A randomised controlled trial. A tertiary African obstetric unit with 18,000 deliveries annually. Three hundred and thirty-nine women undergoing caesarean section. Eight residents and registrars were instructed in the Misgav Ladach technique for caesarean section during one week, after which the study commenced. The course participants instructed their colleagues; in total, 16 doctors participated. Women requiring caesarean section were randomised to Misgav Ladach or to the conventional lower midline incision procedure, excluding those with a previous scar. During 11 weeks 339 randomised procedures (328 of which were emergency procedures) were carried out. Mean operating time was 25 x 3 minutes for Misgav Ladach and 32 x 6 minutes for the lower midline incision procedure (95% CI -8 x 3; -6 x 3). Mean blood loss was 354 mL and 447 mL (-133; -53), and the number of sutures 3 x 1 and 6 x 1 (-3 x 1; -2 x 9), respectively. No significant difference was found in Apgar scores. Mobilisation was earlier with the Misgav Ladach procedure. No difference was found in overall post-operative infection rates i.e. wound infection or febrile illness, but the combination of wound infection and fever was more common in the Misgav Ladach group. The Misgav Ladach caesarean section confers benefits such as reduced blood loss, conservation of time and suture material, and rapid mobilisation, but more studies are needed to explore modifications aimed at reducing post-operative infections in settings with limited resources.

The Home-Based Older People's Exercise (HOPE) trial: study protocol for a randomised controlled trial

PubMed Central

2011-01-01

Background Frailty is common in older age, and is associated with important adverse health outcomes including increased risk of disability and admission to hospital or long-term care. Exercise interventions for frail older people have the potential to reduce the risk of these adverse outcomes by increasing muscle strength and improving mobility. Methods/Design The Home-Based Older People's Exercise (HOPE) trial is a two arm, assessor blind pilot randomised controlled trial (RCT) to assess the effectiveness of a 12 week exercise intervention (the HOPE programme) designed to improve the mobility and functional abilities of frail older people living at home, compared with usual care. The primary outcome is the timed-up-and-go test (TUGT), measured at baseline and 14 weeks post-randomisation. Secondary outcomes include the Barthel Index of activities of daily living (ADL), EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D) quality of life measure and the geriatric depression scale (GDS), measured at baseline and 14 weeks post-randomisation. We will record baseline frailty using the Edmonton Frail Scale (EFS), record falls and document muscle/joint pain. We will test the feasibility of collection of data to identify therapy resources required for delivery of the intervention. Discussion The HOPE trial will explore and evaluate a home-based exercise intervention for frail older people. Although previous RCTs have used operationalised, non-validated methods of measuring frailty, the HOPE trial is, to our knowledge, the first RCT of an exercise intervention for frail older people that includes a validated method of frailty assessment at baseline. Trial registration ISRCTN: ISRCTN57066881 PMID:21651805

How informed is declared altruism in clinical trials? A qualitative interview study of patient decision-making about the QUEST trials (Quality of Life after Mastectomy and Breast Reconstruction).

PubMed

Bidad, Natalie; MacDonald, Lindsay; Winters, Zoë E; Edwards, Sarah J L; Emson, Marie; Griffin, Clare L; Bliss, Judith; Horne, Rob

2016-09-02

Randomised controlled trials (RCTs) often fail to recruit sufficient participants, despite altruism being cited as their motivation. Previous investigations of factors influencing participation decisions have been methodologically limited. This study evaluated how women weigh up different motivations after initially expressing altruism, and explored their understanding of a trial and its alternatives. The trial was the 'Quality of Life after Mastectomy and Breast Reconstruction' (QUEST) trial. Thirty-nine women participated in qualitative interviews 1 month post-surgery. Twenty-seven women (10 trial decliners and 17 acceptors) who spontaneously mentioned 'altruism' were selected for thematic analysis. Verbatim transcripts were coded independently by two researchers. Participants' motivations to accept or decline randomisation were cross-referenced with their understanding of the QUEST trials and the process of randomisation. The seven emerging themes were: (1) altruism expressed by acceptors and decliners; (2) overriding personal needs in decliners; (3) pure altruism in acceptors; (4) 'hypothetical altruism' amongst acceptors; (5) weak altruism amongst acceptors; (6) conditional altruism amongst acceptors; and (7) sense of duty to participate. Poor understanding of the trial rationale and its implications was also evident. Altruism was a motivating factor for participation in the QUEST randomised controlled trials where the main outcomes comprised quality of life and allocated treatments comprised established surgical procedures. Women's decisions were influenced by their understanding of the trial. Both acceptors and decliners of the trial expressed 'altruism', but most acceptors lacked an obvious treatment preference, hoped for personal benefits regarding a treatment allocation, or did not articulate complete understanding of the trial. QUEST A, ISRCTN38846532 ; Date assigned 6 January 2010. QUEST B, ISRCTN92581226 ; Date assigned 6 January 2010.

Efficacy of communication skills training on colorectal cancer screening by GPs: a cluster randomised controlled trial.

PubMed

Aubin-Auger, I; Laouénan, C; Le Bel, J; Mercier, A; Baruch, D; Lebeau, J P; Youssefian, A; Le Trung, T; Peremans, L; Van Royen, P

2016-01-01

Colorectal cancer (CRC) mass screening has been implemented in France since 2008. Participation rates remain too low. The objective of this study was to test if the implementation of a training course focused on communication skills among general practitioners (GP) would increase the delivery of gaiac faecal occult blood test and CRC screening participation among the target population of each participating GP. A cluster randomised controlled trial was conducted with GP's practice as a cluster unit. GPs from practices in the control group were asked to continue their usual care. GPs of the intervention group received a 4-h educational training, built with previous qualitative data on CRC screening focusing on doctor-patient communication with a follow-up of 7 months for both groups. The primary outcome measure was the patients' participation rate in the target population for each GP. Seventeen GPs (16 practices) in intervention group and 28 GPs (19 practices) in control group participated. The patients' participation rate in the intervention group were 36.7% vs. 24.5% in the control group (P = 0.03). Doctor-patient communication should be developed and appear to be one of the possible targets of improvement patients adherence and participation rate in the target population for CRC mass screening. © 2015 John Wiley & Sons Ltd.

Prehospital fast track care for patients with hip fracture: Impact on time to surgery, hospital stay, post-operative complications and mortality a randomised, controlled trial.

PubMed

Larsson, Glenn; Strömberg, Rn Ulf; Rogmark, Cecilia; Nilsdotter, Anna

2016-04-01

Ambulance organisations in Sweden have introduced prehospital fast track care (PFTC) for patients with suspected hip fracture. This means that the ambulance nurse starts the pre-operative procedure otherwise implemented at the accident & emergency ward (A&E) and transports the patient directly to the radiology department instead of A&E. If the diagnosis is confirmed, the patient is transported directly to the orthopaedic ward. No previous randomised, controlled studies have analysed PFTC to describe its possible advantages. The aim of this study is to examine whether PFTC has any impact on outcomes such as time to surgery, length of stay, post-operative complications and mortality. The design of this study is a prehospital randomised, controlled study, powered to include 400 patients. The patients were randomised into PFTC or the traditional care pathway (A&E group). Time from arrival to start for X-ray was faster for PFTC (mean, 28 vs. 145 min; p<0.001), but the groups did not differ with regard to time from start of X-ray to start of surgery (mean 18.40 h in both groups). No significant differences between the groups were observed with regard to: time from arrival to start of surgery (p=0.07); proportion operated within 24h (79% PFTC, 75% A&E; p=0.34); length of stay (p=0.34); post-operative complications (p=0.75); and 4 month mortality (18% PFTC, 15% A&E p=0.58). PFTC improved time to X-ray and admission to a ward, as expected, but did not significantly affect time to start of surgery, length of stay, post-operative complications or mortality. These outcomes were probably affected by other factors at the hospital. Patients with either possible life-threatening conditions or life-threatening conditions prehospital were excluded. Copyright © 2016 Elsevier Ltd. All rights reserved.

Periodontal treatment during pregnancy and birth outcomes: a meta-analysis of randomised trials.

PubMed

George, Ajesh; Shamim, Simin; Johnson, Maree; Ajwani, Shilpi; Bhole, Sameer; Blinkhorn, Anthony; Ellis, Sharon; Andrews, Karen

2011-06-01

The objective of this review was to conduct a meta-analysis of all up-to-date randomised control trials to determine whether periodontal treatment during pregnancy has the potential of reducing preterm birth and low birth weight incidence. Bibliographic databases MEDLINE (1966-present), EMBASE (1980-present), CINAHL (1982-present) and the Cochrane library up to and including 2010 Issue 10 were searched. The reference list of included studies and reviews were also searched for additional literature. Eligible studies were, published and ongoing randomised control trials that compared pregnancy outcomes for pregnant women who received periodontal treatment during the prenatal period. Two of the investigators independently assessed the studies and then extracted and summarised data from eligible trials. Extracted data were entered into Review Manager software and analysed. A total of 5645 pregnant women participated in the 10 eligible trials. Meta-analysis found that periodontal treatment significantly lowered preterm birth (odd ratio 0.65; 95% confidence interval, 0.45-0.93; P = 0.02) and low birth weight (odd ratio 0.53; 95% confidence interval, 0.31-0.92; P = 0.02) rates while no significant difference was found for spontaneous abortion/stillbirth (odd ratio 0.71; 95% confidence interval, 0.43-1.16; P = 0.17). Moderate heterogeneity was observed among the studies for preterm birth and low birth weight. Subgroup analysis showed significant effect of periodontal treatment in pregnant women with low rate of previous preterm birth/low birth weight (odd ratio 0.35; 95% confidence interval, 017-0.70; P = 0.003) and less severe periodontal disease (odd ratio 0.49; confidence interval, 028-0.87; P = 0.01) as defined by probing depth. The cumulative evidence suggests that periodontal treatment during pregnancy may reduce preterm birth and low birth weight incidence. However, these findings need to be further validated through larger more targeted randomised control trials. © 2011 The Authors. International Journal of Evidence-Based Healthcare © 2011 The Joanna Briggs Institute.

Randomised controlled trial of rhinothermy for treatment of the common cold: a feasibility study

PubMed Central

van de Hei, Susanne; McKinstry, Steven; Bardsley, George; Weatherall, Mark; Beasley, Richard; Fingleton, James

2018-01-01

Objective To determine the feasibility of a randomised controlled trial (RCT) of rhinothermy for the common cold. Design Open label, randomised, controlled feasibility study. Setting Single-centre research institute in New Zealand recruiting participants from the community. Participants 30 adult participants with symptoms of a common cold, presenting within 48 hours of the onset of symptoms. Interventions Participants were randomly assigned 2:1 to receive either 35 L/min of 100% humidified air at 41°C via high flow nasal cannulae, 2 hours per day for up to 5 days (rhinothermy), or vitamin C 250 mg daily for 5 days (control). Primary and secondary outcome measures The primary outcome was the proportion of screened candidates who were randomised. Secondary outcomes included: proportion of randomised participants who completed the study; modified Jackson scores from randomisation to 10 days after initiation of randomised regimen; time until feeling ‘a lot better’ compared with study entry; time until resolution of symptoms or symptom score at 10 days postrandomisation; proportion of organisms identified by PCR analysis of nasal swabs taken at baseline; the patterns of use of the rhinothermy device; estimated adherence of the control group; and rhinothermy device tolerability. Results In all 30/79 (38%, 95% CI 27% to 50%) of potential participants screened for eligibility were randomised. Rhinothermy was well tolerated, and all randomised participants completed the study (100%, 95% CI 88% to 100%). The reduction from baseline in the modified Jackson score was greater with rhinothermy compared with control at days 2, 3, 4, 5 and 6, with the maximum difference at day 4 (−6.4, 95% CI −9.4 to −3.3). The substantial clinical benefit threshold for modified Jackson score was a 5-unit change. Conclusions This study shows that an RCT of rhinothermy compared with low-dose vitamin C in the treatment of the common cold is feasible. Trial registration number ACTRN12616000470493; Results. PMID:29593018

Is inertial flywheel resistance training superior to gravity-dependent resistance training in improving muscle strength? A systematic review with meta-analyses.

PubMed

Vicens-Bordas, J; Esteve, E; Fort-Vanmeerhaeghe, A; Bandholm, T; Thorborg, K

2018-01-01

The primary aim of this systematic review was to determine if inertial flywheel resistance training is superior to gravity-dependent resistance training in improving muscle strength. The secondary aim was to determine whether inertial flywheel resistance training is superior to gravity-dependent resistance training in improving other muscular adaptations. A systematic review with meta-analyses of randomised and non-randomised controlled trials. We searched MEDLINE, Scopus, SPORTDiscus, Web of Science and Cochrane Central Register of Controlled Trials with no publication date restrictions until November 2016. We performed meta-analyses on randomised and non-randomised controlled trials to determine the standardized mean difference between the effects of inertial flywheel and gravity-dependent resistance training on muscle strength. A total of 76 and 71 participants were included in the primary and secondary analyses, respectively. After systematic review, we included three randomised and four non-randomised controlled trials. In the primary analysis for the primary outcome muscle strength, the pooled results from randomised controlled trials showed no difference (SMD=-0.05; 95%CI -0.51 to 0.40; p=0.82; I 2 =0%). In the secondary analyses of the primary outcome, the pooled results from non-randomised controlled trials showed no difference (SMD=0.02; 95%CI -0.45 to 0.49; p=0.93; I 2 =0%; and SMD=0.03; 95%CI -0.43 to 0.50; p=0.88; I 2 =0%). Meta-analysis on secondary outcomes could not be performed. Based on the available data, inertial flywheel resistance training was not superior to gravity-dependent resistance training in enhancing muscle strength. Data for other strength variables and other muscular adaptations was insufficient to draw firm conclusions from. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial.

PubMed

Schöffski, Patrick; Chawla, Sant; Maki, Robert G; Italiano, Antoine; Gelderblom, Hans; Choy, Edwin; Grignani, Giovanni; Camargo, Veridiana; Bauer, Sebastian; Rha, Sun Young; Blay, Jean-Yves; Hohenberger, Peter; D'Adamo, David; Guo, Matthew; Chmielowski, Bartosz; Le Cesne, Axel; Demetri, George D; Patel, Shreyaskumar R

2016-04-16

A non-randomised, phase 2 study showed activity and tolerability of eribulin in advanced or metastatic soft-tissue sarcoma. In this phase 3 study, we aimed to compare overall survival in patients with advanced or metastatic soft-tissue sarcoma who received eribulin with that in patients who received dacarbazine (an active control). We did this randomised, open-label, phase 3 study across 110 study sites in 22 countries. We enrolled patients aged 18 years or older with intermediate-grade or high-grade advanced liposarcoma or leiomyosarcoma who had received at least two previous systemic regimens for advanced disease (including an anthracycline). Using an interactive voice and web response system, an independent statistician randomly assigned (1:1) patients to receive eribulin mesilate (1·4 mg/m(2) intravenously on days 1 and 8) or dacarbazine (850 mg/m(2), 1000 mg/m(2), or 1200 mg/m(2) [dose dependent on centre and clinician] intravenously on day 1) every 21 days until disease progression. Randomisation was stratified by disease type, geographical region, and number of previous regimens for advanced soft-tissue sarcoma and in blocks of six. Patients and investigators were not masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT01327885, and is closed to recruitment, but treatment and follow-up continue. Between March 10, 2011 and May 22, 2013, we randomly assigned patients to eribulin (n=228) or dacarbazine (n=224). Overall survival was significantly improved in patients assigned to eribulin compared with those assigned to dacarbazine (median 13·5 months [95% CI 10·9-15·6] vs 11·5 months [9·6-13·0]; hazard ratio 0·77 [95% CI 0·62-0·95]; p=0·0169). Treatment-emergent adverse events occurred in 224 (99%) of 226 patients who received eribulin and 218 (97%) of 224 who received dacarbazine. Grade 3 or higher adverse events were more common in patients who received eribulin (152 [67%]) than in those who received dacarbazine (126 [56%]), as were deaths (10 [4%] vs 3 [1%]); one death (in the eribulin group) was considered treatment-related by the investigators. Overall survival was improved in patients assigned to eribulin compared with those assigned to an active control, suggesting that eribulin could be a treatment option for advanced soft-tissue sarcoma. Eisai. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2015-01-01

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

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

Relationship of ZNF423 and CTSO with breast cancer risk in two randomised tamoxifen prevention trials.

PubMed

Brentnall, Adam R; Cuzick, Jack; Byers, Helen; Segal, Corrinne; Reuter, Caroline; Detre, Simone; Sestak, Ivana; Howell, Anthony; Powles, Trevor J; Newman, William G; Dowsett, Mitchell

2016-08-01

A case-control study from two randomised breast cancer prevention trials of tamoxifen and raloxifene (P-1 and P-2) identified single-nucleotide polymorphisms (SNPs) in or near genes ZNF423 and CTSO as factors which predict which women will derive most anti-cancer benefit from selective oestrogen receptor modulator (SERM) therapy. In this article, we further examine this question using blood samples from two randomised tamoxifen prevention trials: the International Breast Cancer Intervention Study I (IBIS-I) and the Royal Marsden trial (Marsden). A nested case-control study was designed with 2:1 matching in IBIS-I and 1:1 matching in Marsden. The OncoArray was used for genotyping and included two SNPs previously identified (rs8060157 in ZNF423 and rs10030044 near CTSO), and 102 further SNPs within the same regions. Overall, there were 369 cases and 662 controls, with 148 cases and 268 controls from the tamoxifen arms. Odds ratios were estimated by conditional logistic regression, with Wald 95 % confidence intervals. In the tamoxifen arms, the per-allele odds ratio for rs8060157 was 0.99 (95 %CI 0.73-1.34) and 1.00 (95 %CI 0.76-1.33) for rs10030044. In the placebo arm, the odds ratio was 1.10 (95 %CI 0.87-1.40) for rs8060157 and 1.01 (95 %CI 0.79-1.29) for rs10030044. There was no evidence to suggest that other SNPs in the surrounding regions of these SNPs might predict response to tamoxifen. Results from these two prevention trials do not support the earlier findings. rs8060157 in ZNF423 and rs10030044 near CTSO do not appear to predict response to tamoxifen.

Economic Evaluations of Pharmaceuticals Granted a Marketing Authorisation Without the Results of Randomised Trials: A Systematic Review and Taxonomy.

PubMed

Hatswell, Anthony J; Freemantle, Nick; Baio, Gianluca

2017-02-01

Pharmaceuticals are usually granted a marketing authorisation on the basis of randomised controlled trials (RCTs). Occasionally the efficacy of a treatment is assessed without a randomised comparator group (either active or placebo). To identify and develop a taxonomic account of economic modelling approaches for pharmaceuticals licensed without RCT data. We searched PubMed, the websites of UK health technology assessment bodies and the International Society for Pharmacoeconomics and Outcomes Research Scientific Presentations Database for assessments of treatments granted a marketing authorisation by the US Food and Drug Administration or European Medicines Agency from January 1999 to May 2014 without RCT data (74 indications). The outcome of interest was the approach to modelling efficacy data. Fifty-one unique models were identified in 29 peer-reviewed articles, 30 health technology appraisals, and 15 International Society for Pharmacoeconomics and Outcomes Research abstracts concerning 30 indications (44 indications had not been modelled). We noted the high rate of non-submission to health technology assessment agencies (28/98). The majority of models (43/51) were based on 'historical controls'-comparisons to previous meta-analysis or pooling of trials (5), individual trials (16), registries/case series (15), or expert opinion (7). Other approaches used the patient as their own control, performed threshold analysis, assumed time on treatment was added to overall survival, or performed cost-minimisation analysis. There is considerable variation in the quality and approach of models constructed for drugs granted a marketing authorisation without a RCT. The most common approach is of a naive comparison to historical data (using other trials/registry data as a control group), which has considerable scope for bias.

Golimumab in patients with active rheumatoid arthritis who have previous experience with tumour necrosis factor inhibitors: results of a long-term extension of the randomised, double-blind, placebo-controlled GO-AFTER study through week 160

PubMed Central

Smolen, Josef S; Kay, Jonathan; Landewé, Robert B M; Matteson, Eric L; Gaylis, Norman; Wollenhaupt, Jurgen; Murphy, Frederick T; Zhou, Yiying; Hsia, Elizabeth C; Doyle, Mittie K

2012-01-01

Objective The aim of this study was to assess long-term golimumab therapy in patients with rheumatoid arthritis (RA) who discontinued previous tumour necrosis factor alpha (TNFα) inhibitor(s) for any reason. Methods Results through week 24 of this multicentre, randomised, double-blind, placebo-controlled study of active RA (≥4 tender, ≥4 swollen joints) were previously reported. Patients received placebo (Group 1), 50 mg golimumab (Group 2) or 100 mg golimumab (Group 3) subcutaneous injections every 4 weeks. Patients from Groups 1 and 2 with <20% improvement in tender/swollen joints at week 16 early escaped to golimumab 50 mg and 100 mg, respectively. At week 24, Group 1 patients crossed over to golimumab 50 mg, Group 2 continued golimumab 50/100 mg per escape status and Group 3 maintained dosing. Data through week 160 are reported. Results 459 of the 461 randomised patients were treated; 236/459 (51%) continued treatment through week 160. From week 24 to week 100, ACR20 (≥20% improvement in American College of Rheumatology criteria) response and ≥0.25 unit HAQ (Health Assessment Questionnaire) improvement were sustained in 70–73% and 75–81% of responding patients, respectively. Overall at week 160, 63%, 67% and 57% of patients achieved ACR20 response and 59%, 65% and 64% had HAQ improvement ≥0.25 unit in Groups 1, 2 and 3, respectively. Adjusted for follow-up duration, adverse event incidences (95% CI) per 100 patient-years among patients treated with golimumab 50 mg and 100 mg were 4.70 (2.63 to 7.75) and 8.07 (6.02 to 10.58) for serious infection, 0.95 (0.20 to 2.77) and 2.04 (1.09 to 3.49) for malignancy and 0.00 (0.00 to 0.94) and 0.62 (0.17 to 1.59) for death, respectively. Conclusion In patients with active RA who discontinued previous TNF-antagonist treatment, golimumab 50 and 100 mg injections every 4 weeks yielded sustained improvements in signs/symptoms and physical function in ∼57–67% of patients who continued treatment. Golimumab safety was consistent with other anti-TNF agents, although definitive conclusions regarding long-term safety require further monitoring. PMID:22459542

Solar disinfection of drinking water protects against cholera in children under 6 years of age

PubMed Central

Conroy, R; Meegan, M; Joyce, T; McGuigan, K; Barnes, J

2001-01-01

BACKGROUND AND AIMS—We have previously reported a reduction in risk of diarrhoeal disease in children who used solar disinfected drinking water. A cholera epidemic, occurring in an area of Kenya in which a controlled trial of solar disinfection and diarrhoeal disease in children aged under 6 had recently finished, offered an opportunity to examine the protection offered by solar disinfection against cholera.
METHODS—In the original trial, all children aged under 6 in a Maasai community were randomised by household: in the solar disinfection arm, children drank water disinfected by leaving it on the roof in a clear plastic bottle, while controls drank water kept indoors. We revisited all households which had participated in the original trial.
RESULTS—There were 131 households in the trial area, of which 67 had been randomised to solar disinfection (a further 19 households had migrated as a result of severe drought). There was no significant difference in the risk of cholera in adults or in older children in households randomised to solar disinfection; however, there were only three cases of cholera in the 155 children aged under 6 years drinking solar disinfected water compared with 20 of 144controls.
CONCLUSIONS—Results confirm the usefulness of solar disinfection in reducing risk of water borne disease in children. Point of consumption solar disinfection can be done with minimal resources, which are readily available, and may be an important first line response to cholera outbreaks. Its potential in chorine resistant cholera merits further investigation.

 PMID:11567937

[Design of a multicenter study for assessing the effectiveness of extracorporeal shockwave therapy in epicondylitis humeri radialis].

PubMed

Haake, M; Jensen, K; Prinz, H; Willenberg, T

2000-01-01

Previously published studies concerning, extracorporeal shock-wave therapy (ESWT) in the treatment of lateral epicondylitis do not fulfil the biometric standards of modern clinical research. The objective of the trial is to show that ESWT is effective in the treatment of chronic LE. A prospective, randomized, placebo-controlled, single-blinded, multicenter trial with an independent blinded observer was designed. The effectiveness of ESWT is evaluated by comparison with a control group in which sham-ESWT is performed, both under local anaesthesia. Outcome is determined on the basis of the Roles/Maudsley-Score. Inclusion criteria are a history of at least 6 months of LE and failure of conventional treatment. The therapy includes 3 sessions of low energy ESWT with 2000 impulses (energy flux density 0.07-0.09 mJ/mm2). Sample size is 272 patients. Randomisation started in October 1998 and is planned over a period of two and a half years. Only a randomised clinical trial with adequate control of placebo effects and observer bias can provide the required evidence for the efficiency of ESWT in the treatment of lateral epicondylitis of the elbow.

Anticonvulsants for preventing seizures in patients with chronic subdural haematoma.

PubMed

Ratilal, Bernardo O; Pappamikail, Lia; Costa, João; Sampaio, Cristina

2013-06-06

Anticonvulsant therapy is sometimes used prophylactically in patients with chronic subdural haematoma, although the benefit is unclear. To assess the effects of prophylactic anticonvulsants in patients with chronic subdural haematoma, in both the pre- and post-operative periods. We searched the Cochrane Injuries Group's Specialised Register, CENTRAL (The Cochrane Library), MEDLINE (OvidSP), EMBASE (OvidSP), PubMed, LILACS, and the databases clinicaltrials.gov, the WHO International Clinical Trials Registry Platform, and Current Controlled Trials. The search was through 27th March 2013. Randomised controlled trials comparing any anticonvulsant versus placebo or no intervention. Three authors screened the search results to identify relevant studies. No studies met the inclusion criteria for the review. No randomised controlled trials were identified. No formal recommendations can be made about the use of prophylactic anticonvulsants in patients with chronic subdural haematoma based on the literature currently available. There are no randomised controlled trials on this topic, and non-controlled studies have conflicting results. There is an urgent need for well-designed randomised controlled trials.

Assessing sex-differences and the effect of timing of vaccination on immunogenicity, reactogenicity and efficacy of vaccines in young children: study protocol for an individual participant data meta-analysis of randomised controlled trials.

PubMed

Voysey, Merryn; Pollard, Andrew J; Perera, Rafael; Fanshawe, Thomas R

2016-07-29

Disease incidence differs between males and females for some infectious or inflammatory diseases. Sex-differences in immune responses to some vaccines have also been observed, mostly to viral vaccines in adults. Little evidence is available on whether sex-differences occur in response to immunisation in infancy even though this is the age group in which most vaccines are administered. Factors other than sex, such as timing or coadministration of other vaccines, can also influence the immune response to vaccination. Individual participant data meta-analysis of randomised controlled trials of vaccines in healthy infants and young children will be conducted. Fully anonymised data from ∼170 randomised controlled trials of vaccines for diphtheria, tetanus, Bordetella pertussis, polio, Haemophilus influenzae type B, hepatitis B, Streptococcus pneumoniae, Neisseria meningitidis, measles, mumps, rubella, varicella and rotavirus will be combined for analysis. Outcomes include measures of immunogenicity (immunoglobulins), reactogenicity, safety and disease-specific clinical efficacy. Data from trials of vaccines containing similar components will be combined in hierarchical models and the effect of sex and timing of vaccinations estimated for each outcome separately. Systematic reviews of published estimates of sex-differences cannot adequately answer questions in this field since such comparisons are never the main purpose of a clinical trial, thus a large degree of reporting bias exists in the published literature. Recent improvements in the widespread availability of individual participant data from randomised controlled trials makes it feasible to conduct extensive individual participant data meta-analyses which were previously impossible, thereby reducing the effect of publication or reporting bias on the understanding of the infant immune response.Preliminary results will be available in 2016 with final results available in 2019. No ethics review is required for secondary analyses of anonymised data. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Minimising impairment: Protocol for a multicentre randomised controlled trial of upper limb orthoses for children with cerebral palsy.

PubMed

Imms, Christine; Wallen, Margaret; Elliott, Catherine; Hoare, Brian; Randall, Melinda; Greaves, Susan; Adair, Brooke; Bradshaw, Elizabeth; Carter, Rob; Orsini, Francesca; Shih, Sophy T F; Reddihough, Dinah

2016-05-27

Upper limb orthoses are frequently prescribed for children with cerebral palsy (CP) who have muscle overactivity predominantly due to spasticity, with little evidence of long-term effectiveness. Clinical consensus is that orthoses help to preserve range of movement: nevertheless, they can be complex to construct, expensive, uncomfortable and require commitment from parents and children to wear. This protocol paper describes a randomised controlled trial to evaluate whether long-term use of rigid wrist/hand orthoses (WHO) in children with CP, combined with usual multidisciplinary care, can prevent or reduce musculoskeletal impairments, including muscle stiffness/tone and loss of movement range, compared to usual multidisciplinary care alone. This pragmatic, multicentre, assessor-blinded randomised controlled trial with economic analysis will recruit 194 children with CP, aged 5-15 years, who present with flexor muscle stiffness of the wrist and/or fingers/thumb (Modified Ashworth Scale score ≥1). Children, recruited from treatment centres in Victoria, New South Wales and Western Australia, will be randomised to groups (1:1 allocation) using concealed procedures. All children will receive care typically provided by their treating organisation. The treatment group will receive a custom-made serially adjustable rigid WHO, prescribed for 6 h nightly (or daily) to wear for 3 years. An application developed for mobile devices will monitor WHO wearing time and adverse events. The control group will not receive a WHO, and will cease wearing one if previously prescribed. Outcomes will be measured 6 monthly over a period of 3 years. The primary outcome is passive range of wrist extension, measured with fingers extended using a goniometer at 3 years. Secondary outcomes include muscle stiffness, spasticity, pain, grip strength and hand deformity. Activity, participation, quality of life, cost and cost-effectiveness will also be assessed. This study will provide evidence to inform clinicians, services, funding agencies and parents/carers of children with CP whether the provision of a rigid WHO to reduce upper limb impairment, in combination with usual multidisciplinary care, is worth the effort and costs. ANZ Clinical Trials Registry: U1111-1164-0572 .

Figure-of-eight bandage versus arm sling for treating middle-third clavicle fractures in adults: study protocol for a randomised controlled trial.

PubMed

Lenza, Mario; Taniguchi, Luiz Fabiano Presente; Ferretti, Mario

2016-05-04

Fracture of the clavicle is common, accounting for 2.6 to 4.0 % of all fractures, with an overall incidence of 36.5 to 64 per 100,000 per year. Around 80 % of clavicle fractures occur in the middle third of the clavicle. Randomised controlled trials comparing treatment interventions have failed to indicate the best therapeutic practices for these fractures. The objective of this study is to evaluate the effects (benefits and harms) of two commonly-used conservative interventions: the figure-of-eight bandage versus the arm sling as treatments of middle-third clavicle fractures. This project has been designed as a single-centre, two-arm randomised controlled trial that will compare two interventions: figure-of-eight bandage versus the arm sling. We propose to recruit 110 adults, aged 18 years or older, with an acute (less than 10 days since injury) middle-third clavicle fracture. The primary outcomes to be evaluated will be function and/or disability measured by the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire. In order to assess the secondary outcomes, the Modified University of California at Los Angeles (modified - UCLA) Shoulder Rating Scale will be used. The occurrence of pain (Visual Analogue Scale for pain (VAS)), treatment failure, adverse events and the ability to return to previous activities will also be recorded and evaluated as secondary outcomes. the primary outcome DASH score and the secondary outcomes - modified UCLA and VAS scores - will be analysed graphically. We will apply generalised mixed models with the intervention groups (two levels), and time-point assessments (seven levels) as fixed effects and patients as a random effect. According to the current literature there is very limited evidence from two small trials regarding the effectiveness of different methods of conservative interventions for treating clavicle fractures. This is the first randomised controlled trial comparing the figure-of-eight bandage versus the arm sling for treating clavicle fractures that follows the CONSORT Statement guidelines. ClinicalTrials.gov NCT02398006 .

A falls prevention programme to improve quality of life, physical function and falls efficacy in older people receiving home help services: study protocol for a randomised controlled trial.

PubMed

Bjerk, Maria; Brovold, Therese; Skelton, Dawn A; Bergland, Astrid

2017-08-14

Falls and fall-related injuries in older adults are associated with great burdens, both for the individuals, the health care system and the society. Previous research has shown evidence for the efficiency of exercise as falls prevention. An understudied group are older adults receiving home help services, and the effect of a falls prevention programme on health-related quality of life is unclear. The primary aim of this randomised controlled trial is to examine the effect of a falls prevention programme on quality of life, physical function and falls efficacy in older adults receiving home help services. A secondary aim is to explore the mediating factors between falls prevention and health-related quality of life. The study is a single-blinded randomised controlled trial. Participants are older adults, aged 67 or older, receiving home help services, who are able to walk with or without walking aids, who have experienced at least one fall during the last 12 months and who have a Mini Mental State Examination of 23 or above. The intervention group receives a programme, based on the Otago Exercise Programme, lasting 12 weeks including home visits and motivational telephone calls. The control group receives usual care. The primary outcome is health-related quality of life (SF-36). Secondary outcomes are leg strength, balance, walking speed, walking habits, activities of daily living, nutritional status and falls efficacy. All measurements are performed at baseline, following intervention at 3 months and at 6 months' follow-up. Sample size, based on the primary outcome, is set to 150 participants randomised into the two arms, including an estimated 15-20% drop out. Participants are recruited from six municipalities in Norway. This trial will generate new knowledge on the effects of an exercise falls prevention programme among older fallers receiving home help services. This knowledge will be useful for clinicians, for health managers in the primary health care service and for policy makers. ClinicalTrials.gov . NCT02374307 . First registration, 16/02/2015.

Intra-aortic balloon pump counterpulsation (IABP) for myocardial infarction complicated by cardiogenic shock.

PubMed

Unverzagt, Susanne; Buerke, Michael; de Waha, Antoinette; Haerting, Johannes; Pietzner, Diana; Seyfarth, Melchior; Thiele, Holger; Werdan, Karl; Zeymer, Uwe; Prondzinsky, Roland

2015-03-27

Intra-aortic balloon pump counterpulsation (IABP) is currently the most commonly used mechanical assist device for patients with cardiogenic shock due to acute myocardial infarction. Although there has been only limited evidence from randomised controlled trials, the previous guidelines of the American Heart Association/American College of Cardiology (AHA/ACC) and the European Society of Cardiology (ESC) strongly recommended the use of the IABP in patients with infarction-related cardiogenic shock on the basis of pathophysiological considerations, non-randomised trials and registry data. The recent guidelines downgraded the recommendation based on a meta-analysis which could only include non-randomised trials showing conflicting results. Up to now, there have been no guideline recommendations and no actual meta-analysis including the results of the large randomised multicentre IABP-SHOCK II Trial which showed no survival benefit with IABP support. This systematic review is an update of the review published in 2011. To evaluate, in terms of efficacy and safety, the effect of IABP versus non-IABP or other assist devices guideline compliant standard therapy on mortality and morbidity in patients with acute myocardial infarction complicated by cardiogenic shock. Searches of CENTRAL, MEDLINE (Ovid) and EMBASE (Ovid), LILACS, IndMed and KoreaMed, registers of ongoing trials and proceedings of conferences were updated in October 2013. Reference lists were scanned and experts in the field contacted to obtain further information. No language restrictions were applied. Randomised controlled trials on patients with acute myocardial infarction complicated by cardiogenic shock. Data collection and analysis were performed according to the published protocol. Individual patient data were provided for six trials and merged with aggregate data. Summary statistics for the primary endpoints were hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs). Seven eligible studies were identified from a total of 2314 references. One new study with 600 patients was added to the original review. Four trials compared IABP to standard treatment and three to other percutaneous left assist devices (LVAD). Data from a total of 790 patients with acute myocardial infarction and cardiogenic shock were included in the updated meta-analysis: 406 patients were treated with IABP and 384 patients served as controls; 339 patients were treated without assisting devices and 45 patients with other LVAD. The HR for all-cause 30-day mortality of 0.95 (95% CI 0.76 to 1.19) provided no evidence for a survival benefit. Different non-fatal cardiovascular events were reported in five trials. During hospitalisation, 11 and 4 out of 364 patients from the intervention groups suffered from reinfarction or stroke, respectively. Altogether 5 out of 363 patients from the control group suffered from reinfarction or stroke. Reocclusion was treated with subsequent re-revascularization in 6 out of 352 patients from the intervention group and 13 out of 353 patients of the control group. The high incidence of complications such as moderate and severe bleeding or infection in the control groups has to be attributed to interventions with other LVAD. Possible reasons for bias were more frequent in small studies with high cross-over rates, early stopping and the inclusion of patients with IABP at randomisation. Available evidence suggests that IABP may have a beneficial effect on some haemodynamic parameters. However, this did not result in survival benefits so there is no convincing randomised data to support the use of IABP in infarct-related cardiogenic shock.

Cost-effective recruitment methods for a large randomised trial in people with diabetes: A Study of Cardiovascular Events iN Diabetes (ASCEND).

PubMed

Aung, Theingi; Haynes, Richard; Barton, Jill; Cox, Jolyon; Murawska, Aleksandra; Murphy, Kevin; Lay, Michael; Armitage, Jane; Bowman, Louise

2016-06-13

Clinical trials require cost-effective methods for identifying, randomising, and following large numbers of people in order to generate reliable evidence. ASCEND (A Study of Cardiovascular Events iN Diabetes) is a randomised '2 × 2 factorial design' study of aspirin and omega-3 fatty acid supplements for the primary prevention of cardiovascular events in people with diabetes; this study used central disease registers and a mail-based approach to identify, randomise, and follow 15,000 people. In collaboration with UK consultants and general practitioners (GPs), researchers identified potentially eligible people with diabetes from centrally held registers (e.g. for retinopathy screening) and GP-held disease registers. Permission was obtained under section 251 of the National Health Service Act 2006 (previously section 60 of the NHS act 2001) to allow invitation letters to be generated centrally in the name of the holder of the register. In addition, with the collaboration of the National Institutes for Health Research (NIHR) Diabetes and Primary Care Research Networks (DRN and PCRN), general practices sent pre-assembled invitation packs to people with a diagnosis of diabetes. Invitation packs included a cover letter, screening questionnaire (with consent form), information leaflet, and a Freepost envelope. Eligible patients entered a 2-month, pre-randomisation, run-in phase on placebo tablets and were only randomised if they completed a randomisation form and remained willing and eligible at the end of the run-in. Follow-up is ongoing, using mail-based approaches that are being supplemented by central registry data. Information on approximately 600,000 people listed on 58 centrally held diabetes registers was obtained, and 300,188 potentially eligible patients were invited to join the study. In addition, 785 GP practices mailed invitations to 120,875 patients. A further 2,340 potential study participants were identified via other routes. In total, 423,403 people with diabetes were invited to take part; 26,462 entered the 2-month, pre-randomisation, run-in phase; and 15,480 were randomised. If sufficient numbers of potentially eligible patients can be identified centrally and the trial treatments do not require participants to attend clinics, the recruitment and follow-up of patients by mail is feasible and cost-effective. Wider use of these methods could allow more, large, randomised trials to be undertaken successfully and cost-effectively. Current Controlled Trials, ISRCTN60635500 , registered on 14 July 2005.

Bicycling to school improves the cardiometabolic risk factor profile: a randomised controlled trial

PubMed Central

Østergaard, Lars; Børrestad, Line A B; Tarp, Jakob; Andersen, Lars Bo

2012-01-01

Objectives To investigate whether bicycling to school improves cardiometabolic risk factor profile and cardiorespiratory fitness among children. Design Prospective, blinded, randomised controlled trial. Setting Single centre study in Odense, Denmark Participants 43 children previously not bicycling to school were randomly allocated to control group (n=20) (ie, no change in lifestyle) or intervention group (ie, bicycling to school) (n=23). Primary and secondary outcome measures Change in cardiometabolic risk factor score and change in cardiorespiratory fitness. Results All participants measured at baseline returned at follow-up. Based upon intention-to-treat (ITT) analyses, clustering of cardiometabolic risk factors was lowered by 0.58 SD (95% CI −1.03 to −0.14, p=0.012) in the bicycling group compared to the control group. Cardiorespiratory fitness (l O2/min) per se did not increase significantly more in the intervention than in the control group (β=0.0337, 95% CI −0.06 to 0.12, p=0.458). Conclusions Bicycling to school counteracted a clustering of cardiometabolic risk factors and should thus be recognised as potential prevention of type 2 diabetes mellitus and cardiovascular disease (CVD). The intervention did, however, not elicit a larger increase in cardiorespiratory fitness in the intervention group as compared with the control group. Trial registration Registered at http://www.clinicaltrials.gov (NCT01236222). PMID:23117560

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.

The People with Asperger syndrome and anxiety disorders (PAsSA) trial: a pilot multicentre, single-blind randomised trial of group cognitive-behavioural therapy.

PubMed

Langdon, Peter E; Murphy, Glynis H; Shepstone, Lee; Wilson, Edward C F; Fowler, David; Heavens, David; Malovic, Aida; Russell, Alexandra; Rose, Alice; Mullineaux, Louise

2016-03-01

There is a growing interest in using cognitive-behavioural therapy (CBT) with people who have Asperger syndrome and comorbid mental health problems. To examine whether modified group CBT for clinically significant anxiety in an Asperger syndrome population is feasible and likely to be efficacious. Using a randomised assessor-blind trial, 52 individuals with Asperger syndrome were randomised into a treatment arm or a waiting-list control arm. After 24 weeks, those in the waiting-list control arm received treatment, while those initially randomised to treatment were followed up for 24 weeks. The conversion rate for this trial was high (1.6:1), while attrition was 13%. After 24 weeks, there was no significant difference between those randomised to the treatment arm compared with those randomised to the waiting-list control arm on the primary outcome measure, the Hamilton Rating Scale for Anxiety. Trials of psychological therapies with this population are feasible. Larger definitive trials are now needed. None. © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) licence.

Gene therapy for sickle cell disease.

PubMed

Olowoyeye, Abiola; Okwundu, Charles I

2016-11-14

Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal hemoglobin polymerisation leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. This is an update of a previously published Cochrane Review. The objectives of this review are:to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 15 August 2016. All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting. No trials of gene therapy for sickle cell disease were found. No trials of gene therapy for sickle cell disease were reported. No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.

Patient-oriented randomisation: A new trial design applied in the Neuroleptic Strategy Study.

PubMed

Schulz, Constanze; Timm, Jürgen; Cordes, Joachim; Gründer, Gerhard; Mühlbauer, Bernd; Rüther, Eckart; Heinze, Martin

2016-06-01

The 'gold standard' for clinical studies is a randomised controlled trial usually comparing specific treatments. If the scientific study expands to strategy comparison with each strategy including various treatments, the research problems are increasingly complicated. The strategy debate in the psychiatric community is the starting point for the development of our new design. It is widely accepted that second-generation antipsychotics are the therapy of choice in the treatment of schizophrenia. However, their general superiority over first-generation antipsychotics could not be demonstrated in recent randomised controlled trials. Furthermore, we are becoming increasingly aware that the experimental conditions of randomised controlled trials, as in the European First Episode Schizophrenia Trial and Clinical Antipsychotic Trials of Intervention Effectiveness Phase 1 studies, may be inappropriate for psychiatric treatments. The high heterogeneity in the patient population produces discrepancies between daily clinical perception and randomised controlled trials results. The patient-oriented approach in the Cost Utility of the Latest Antipsychotic drugs in Schizophrenia Study reflects everyday clinical practice. The results, however, are highly dependent on the physicians' preferences. The goal of the design described here is to take an intermediate path between randomised controlled trials and clinical studies such as Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study, combining the advantages of both study types. The idea is to randomise two treatment pairs each consisting of one first-generation antipsychotic and one second-generation antipsychotic in a first step and subsequently, to involve the investigators in deciding for a pair most appropriate to the patients' needs and then to randomise the allocation to one drug (first-generation antipsychotic or second-generation antipsychotic) of that chosen pair. This idea was first implemented in the clinical trial, the Neuroleptic Strategy Study, with a randomised design comparing efficacy and safety of two different strategies: either to use first-generation antipsychotics (haloperidol and flupentixol) or second-generation antipsychotics (olanzapine, aripiprazole and quetiapine) in patients suffering from schizophrenia. In the course of the Neuroleptic Strategy Study, feasibility of this design was demonstrated. All aspects of the new design were implemented: randomisation process, documentation of responses from investigators as well as patients and drug logistic experience. In implementing the design, furthermore, we could investigate its theoretical properties. The physicians' preferences for specific drugs used for the respective patients were analysed. The idea of patient-oriented randomisation can be generalised. In light of the heterogeneity and complexity of patient-drug interaction, this design should prove particularly useful. © The Author(s) 2016.

Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis.

PubMed

Johansen, Helle Krogh; Gøtzsche, Peter C

2015-08-23

Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. This is an update of a previously published review. To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30 March 2015). We previously searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May 2013). Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis. The authors independently selected trials, assessed them and extracted data. Six trials were identified. Two trials were excluded since they were not randomised and one old, small trial because it was not possible to assess whether is was randomised. The three included trials comprised 483, 476 and 37 patients, respectively. No data have been published from one of the large trials, but the company stated in a press release that the trial failed to confirm the results from an earlier study and that further clinical development was suspended. In the other large trial, relative risk for chronic infection was 0.91 (95% confidence interval 0.55 to 1.49), and in the small trial, the risk was also close to one. In the large trial, one patient was reported to have died in the observation period. In that trial, 227 adverse events (4 severe) were registered in the vaccine group and 91 (1 severe) in the control group. In this large trial of a vaccine developed against flagella antigens, antibody titres against the epitopes contained in the vaccine were higher in the vaccine group compared to the placebo group (P < 0.0001). Vaccines against Pseudomonas aeruginosa cannot be recommended.

Randomised controlled trial of improvisational music therapy's effectiveness for children with autism spectrum disorders (TIME-A): study protocol.

PubMed

Geretsegger, Monika; Holck, Ulla; Gold, Christian

2012-01-05

Previous research has suggested that music therapy may facilitate skills in areas typically affected by autism spectrum disorders such as social interaction and communication. However, generalisability of previous findings has been restricted, as studies were limited in either methodological accuracy or the clinical relevance of their approach. The aim of this study is to determine effects of improvisational music therapy on social communication skills of children with autism spectrum disorders. An additional aim of the study is to examine if variation in dose of treatment (i.e., number of music therapy sessions per week) affects outcome of therapy, and to determine cost-effectiveness. Children aged between 4;0 and 6;11 years who are diagnosed with autism spectrum disorder will be randomly assigned to one of three conditions. Parents of all participants will receive three sessions of parent counselling (at 0, 2, and 5 months). In addition, children randomised to the two intervention groups will be offered individual, improvisational music therapy over a period of five months, either one session (low-intensity) or three sessions (high-intensity) per week. Generalised effects of music therapy will be measured using standardised scales completed by blinded assessors (Autism Diagnostic Observation Schedule, ADOS) and parents (Social Responsiveness Scale, SRS) before and 2, 5, and 12 months after randomisation. Cost effectiveness will be calculated as man years. A group sequential design with first interim look at N = 235 will ensure both power and efficiency. Responding to the need for more rigorously designed trials examining the effectiveness of music therapy in autism spectrum disorders, this pragmatic trial sets out to generate findings that will be well generalisable to clinical practice. Addressing the issue of dose variation, this study's results will also provide information on the relevance of session frequency for therapy outcome. Current Controlled Trials ISRCTN78923965.

Immunogenicity of a low-dose diphtheria, tetanus and acellular pertussis combination vaccine with either inactivated or oral polio vaccine compared to standard-dose diphtheria, tetanus, acellular pertussis when used as a pre-school booster in UK children: A 5-year follow-up of a randomised controlled study.

PubMed

John, T; Voysey, M; Yu, L M; McCarthy, N; Baudin, M; Richard, P; Fiquet, A; Kitchin, N; Pollard, A J

2015-08-26

This serological follow up study assessed the kinetics of antibody response in children who previously participated in a single centre, open-label, randomised controlled trial of low-dose compared to standard-dose diphtheria booster preschool vaccinations in the United Kingdom (UK). Children had previously been randomised to receive one of three combination vaccines: either a combined adsorbed tetanus, low-dose diphtheria, 5-component acellular pertussis and inactivated polio vaccine (IPV) (Tdap-IPV, Repevax(®); Sanofi Pasteur MSD); a combined adsorbed tetanus, low-dose diphtheria and 5-component acellular pertussis vaccine (Tdap, Covaxis(®); Sanofi Pasteur MSD) given concomitantly with oral polio vaccine (OPV); or a combined adsorbed standard-dose diphtheria, tetanus, 2-component acellular pertussis and IPV (DTap-IPV, Tetravac(®); Sanofi Pasteur MSD). Blood samples for the follow-up study were taken at 1, 3 and 5 years after participation in the original trial (median, 5.07 years of age at year 1), and antibody persistence to each vaccine antigen measured against defined serological thresholds of protection. All participants had evidence of immunity to diphtheria with antitoxin concentrations greater than 0.01IU/mL five years after booster vaccination and 75%, 67% and 79% of children who received Tdap-IPV, Tdap+OPV and DTap-IPV, respectively, had protective antitoxin levels greater than 0.1IU/mL. Long lasting protective immune responses to tetanus and polio antigens were also observed in all groups, though polio responses were lower in the sera of those who received OPV. Low-dose diphtheria vaccines provided comparable protection to the standard-dose vaccine and are suitable for use for pre-school booster vaccination. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Randomised controlled trial of improvisational music therapy's effectiveness for children with autism spectrum disorders (TIME-A): study protocol

PubMed Central

2012-01-01

Background Previous research has suggested that music therapy may facilitate skills in areas typically affected by autism spectrum disorders such as social interaction and communication. However, generalisability of previous findings has been restricted, as studies were limited in either methodological accuracy or the clinical relevance of their approach. The aim of this study is to determine effects of improvisational music therapy on social communication skills of children with autism spectrum disorders. An additional aim of the study is to examine if variation in dose of treatment (i.e., number of music therapy sessions per week) affects outcome of therapy, and to determine cost-effectiveness. Methods/Design Children aged between 4;0 and 6;11 years who are diagnosed with autism spectrum disorder will be randomly assigned to one of three conditions. Parents of all participants will receive three sessions of parent counselling (at 0, 2, and 5 months). In addition, children randomised to the two intervention groups will be offered individual, improvisational music therapy over a period of five months, either one session (low-intensity) or three sessions (high-intensity) per week. Generalised effects of music therapy will be measured using standardised scales completed by blinded assessors (Autism Diagnostic Observation Schedule, ADOS) and parents (Social Responsiveness Scale, SRS) before and 2, 5, and 12 months after randomisation. Cost effectiveness will be calculated as man years. A group sequential design with first interim look at N = 235 will ensure both power and efficiency. Discussion Responding to the need for more rigorously designed trials examining the effectiveness of music therapy in autism spectrum disorders, this pragmatic trial sets out to generate findings that will be well generalisable to clinical practice. Addressing the issue of dose variation, this study's results will also provide information on the relevance of session frequency for therapy outcome. Trial Registration Current Controlled Trials ISRCTN78923965. PMID:22221670

INfluence of Successful Periodontal Intervention in REnal Disease (INSPIRED): study protocol for a randomised controlled pilot clinical trial.

PubMed

Sharma, Praveen; Cockwell, Paul; Dietrich, Thomas; Ferro, Charles; Ives, Natalie; Chapple, Iain L C

2017-11-13

Patients with chronic kidney disease (CKD) exhibit increased morbidity and mortality which is associated with an increased systemic inflammatory burden. Identifying and managing comorbid diseases that contribute to this load may inform novel care pathways that could have a beneficial impact on the morbidity/mortality associated with CKD. Periodontitis, a highly prevalent, chronic inflammatory disease affecting the supporting structures of teeth, is associated with an increased systemic inflammatory and oxidative stress burden and the successful treatment of periodontitis has been shown to reduce both. This pilot study aims to gather data to inform a definitive study into the impact of successful periodontal treatment on the cardio-renal health of patients with CKD. This pilot study will employ a randomised, controlled, parallel-group design. Sixty adult patients, with CKD with a high risk of progression and with periodontitis, from the Queen Elizabeth Hospital, Birmingham, will be randomised to receive either immediate, intensive periodontal treatment (n = 30) or treatment at a delay of 12 months (n = 30). Patients will be excluded if they have reached end-stage renal disease or have received specialist periodontal treatment in the previous year. Periodontal treatment will be delivered under local anaesthetic, on an outpatient basis, over several visits by a qualified dental hygienist at the Birmingham Dental Hospital, UK. Patients in the delayed-treatment arm will continue to receive the standard community level of periodontal care for a period of 12 months followed by the intensive periodontal treatment. Randomization will occur using a centralised telephone randomisation service, following baseline assessments. The assessor of periodontal health will be blinded to the patients' treatment allocation. Patients in either arm will be followed up at 3-monthly intervals for 18 months. Aside from the pilot outcomes to inform the practicalities of a larger trial later, data on cardio-renal function, periodontal health and patient-reported outcomes will be collected at each time point. This pilot randomised controlled trial will investigate the viability of undertaking a larger-scale study investigating the effect of treating periodontitis and maintaining periodontal health on cardio-renal outcomes in patients with CKD. National Institute of Health Research (NIHR) Clinical Research Network (UKCRN ID: 18458), ID: ISRCTN10227738 . Registered retrospectively to both registers on 23 April 2015.

Rehabilitation of memory following brain injury (ReMemBrIn): study protocol for a randomised controlled trial.

PubMed

das Nair, Roshan; Lincoln, Nadina B; Ftizsimmons, Deborah; Brain, Nicola; Montgomery, Alan; Bradshaw, Lucy; Drummond, Avril; Sackley, Catherine; Newby, Gavin; Thornton, Jim; Stapleton, Sandip; Pink, Anthony

2015-01-06

Impairments of memory are commonly reported by people with traumatic brain injuries (TBI). Such deficits are persistent, debilitating, and can severely impact quality of life. Currently, many do not routinely receive follow-up appointments for residual memory problems following discharge. This is a multi-centre, randomised controlled trial investigating the clinical and cost-effectiveness of a group-based memory rehabilitation programme. Three hundred and twelve people with a traumatic brain injury will be randomised from four centres. Participants will be eligible if they had a traumatic brain injury more than 3 months prior to recruitment, have memory problems, are 18 to 69 years of age, are able to travel to one of our centres and attend group sessions, and are able to give informed consent. Participants will be randomised in clusters of 4 to 6 to the group rehabilitation intervention or to usual care. Intervention groups will receive 10 weekly sessions of a manualised memory rehabilitation programme, which has been developed in previous pilot studies. The intervention will include restitution strategies to retrain impaired memory functions and compensation strategies to enable participants to cope with their memory problems. All participants will receive a follow-up postal questionnaire and an assessment by a research assistant at 6 and 12 months post-randomisation. The primary outcome is the Everyday Memory Questionnaire at 6 months. Secondary outcomes include the Rivermead Behavioural Memory Test-3, General Health Questionnaire-30, health related quality of life, cost-effectiveness analysis determined by the EQ-5D and a service use questionnaire, individual goal attainment, European Brain Injury Questionnaire (patient and relative versions), and the Everyday Memory Questionnaire-relative version. The primary analysis will be based on intention to treat. A mixed-model regression analysis of the Everyday Memory Questionnaire at 6 months will be used to estimate the effect of the group memory rehabilitation programme. The study will hopefully provide robust evidence regarding the clinical and cost-effectiveness of a group-based memory rehabilitation intervention for civilians and military personnel following TBI. We discuss our decision-making regarding choice of outcome measures and control group, and the unique challenges to recruiting people with memory problems to trials. ISRCTN65792154; Date: 18 October 2012.

Evaluation of community-level interventions to increase early initiation of antenatal care in pregnancy: protocol for the Community REACH study, a cluster randomised controlled trial with integrated process and economic evaluations.

PubMed

Sawtell, Mary; Sweeney, Lorna; Wiggins, Meg; Salisbury, Cathryn; Eldridge, Sandra; Greenberg, Lauren; Hunter, Rachael; Kaur, Inderjeet; McCourt, Christine; Hatherall, Bethan; Findlay, Gail; Morris, Joanne; Reading, Sandra; Renton, Adrian; Adekoya, Ruth; Green, Belinda; Harvey, Belinda; Latham, Sarah; Patel, Kanta; Vanlessen, Logan; Harden, Angela

2018-03-05

The provision of high-quality maternity services is a priority for reducing inequalities in health outcomes for mothers and infants. Best practice includes women having their initial antenatal appointment within the first trimester of pregnancy in order to provide screening and support for healthy lifestyles, well-being and self-care in pregnancy. Previous research has identified inequalities in access to antenatal care, yet there is little evidence on interventions to improve early initiation of antenatal care. The Community REACH trial will assess the effectiveness and cost-effectiveness of engaging communities in the co-production and delivery of an intervention that addresses this issue. The study design is a matched cluster randomised controlled trial with integrated process and economic evaluations. The unit of randomisation is electoral ward. The intervention will be delivered in 10 wards; 10 comparator wards will have normal practice. The primary outcome is the proportion of pregnant women attending their antenatal booking appointment by the 12th completed week of pregnancy. This and a number of secondary outcomes will be assessed for cohorts of women (n = approximately 1450 per arm) who give birth 2-7 and 8-13 months after intervention delivery completion in the included wards, using routinely collected maternity data. Eight hospitals commissioned to provide maternity services in six NHS trusts in north and east London and Essex have been recruited to the study. These trusts will provide anonymised routine data for randomisation and outcomes analysis. The process evaluation will examine intervention implementation, acceptability, reach and possible causal pathways. The economic evaluation will use a cost-consequences analysis and decision model to evaluate the intervention. Targeted community engagement in the research process was a priority. Community REACH aims to increase early initiation of antenatal care using an intervention that is co-produced and delivered by local communities. This pragmatic cluster randomised controlled trial, with integrated process and economic evaluation, aims to rigorously assess the effectiveness of this public health intervention, which is particularly complex due to the required combination of standardisation with local flexibility. It will also answer questions about scalability and generalisability. ISRCTN registry: registration number 63066975 . Registered on 18 August 2015.

Improving Diabetes care through Examining, Advising, and prescribing (IDEA): protocol for a theory-based cluster randomised controlled trial of a multiple behaviour change intervention aimed at primary healthcare professionals

PubMed Central

2014-01-01

Background New clinical research findings may require clinicians to change their behaviour to provide high-quality care to people with type 2 diabetes, likely requiring them to change multiple different clinical behaviours. The present study builds on findings from a UK-wide study of theory-based behavioural and organisational factors associated with prescribing, advising, and examining consistent with high-quality diabetes care. Aim To develop and evaluate the effectiveness and cost of an intervention to improve multiple behaviours in clinicians involved in delivering high-quality care for type 2 diabetes. Design/methods We will conduct a two-armed cluster randomised controlled trial in 44 general practices in the North East of England to evaluate a theory-based behaviour change intervention. We will target improvement in six underperformed clinical behaviours highlighted in quality standards for type 2 diabetes: prescribing for hypertension; prescribing for glycaemic control; providing physical activity advice; providing nutrition advice; providing on-going education; and ensuring that feet have been examined. The primary outcome will be the proportion of patients appropriately prescribed and examined (using anonymised computer records), and advised (using anonymous patient surveys) at 12 months. We will use behaviour change techniques targeting motivational, volitional, and impulsive factors that we have previously demonstrated to be predictive of multiple health professional behaviours involved in high-quality type 2 diabetes care. We will also investigate whether the intervention was delivered as designed (fidelity) by coding audiotaped workshops and interventionist delivery reports, and operated as hypothesised (process evaluation) by analysing responses to theory-based postal questionnaires. In addition, we will conduct post-trial qualitative interviews with practice teams to further inform the process evaluation, and a post-trial economic analysis to estimate the costs of the intervention and cost of service use. Discussion Consistent with UK Medical Research Council guidance and building on previous development research, this pragmatic cluster randomised trial will evaluate the effectiveness of a theory-based complex intervention focusing on changing multiple clinical behaviours to improve quality of diabetes care. Trial registration ISRCTN66498413. PMID:24886606

Preventing anxiety problems in children with Cool Little Kids Online: study protocol for a randomised controlled trial.

PubMed

Morgan, Amy J; Rapee, Ronald M; Tamir, Elli; Goharpey, Nahal; Salim, Agus; McLellan, Lauren F; Bayer, Jordana K

2015-11-05

Anxiety disorders are the most common type of mental health problem and begin early in life. Early intervention to prevent anxiety problems in young children who are at risk has the potential for long-term impact. The 'Cool Little Kids' parenting group program was previously established to prevent anxiety disorders in young children at risk because of inhibited temperament. This group program was efficacious in two randomised controlled trials and has recently been adapted into an online format. 'Cool Little Kids Online' was developed to widen and facilitate access to the group program's preventive content. A pilot evaluation of the online program demonstrated its perceived utility and acceptability among parents. This study aims to evaluate the efficacy of Cool Little Kids Online in a large randomised controlled trial. Parents of young children who are 3-6 years old and who have an inhibited temperament will be recruited (n = 385) and randomly assigned to either immediate access to Cool Little Kids Online or delayed access after a waiting period of 24 weeks. The online program contains eight modules that help parents address key issues in the development of anxiety problems in inhibited children, including children's avoidant coping styles, overprotective parenting behaviours, and parents' own fears and worries. Intervention participants will be offered clinician support when requested. The primary outcome will be change in parent-reported child anxiety symptoms. Secondary outcomes will be child internalising symptoms, child and family life interference due to anxiety, over-involved/protective parenting, plus child anxiety diagnoses assessed by using a new online diagnostic tool. Assessments will take place at baseline and 12 and 24 weeks after baseline. This trial expands upon previous research on the Cool Little Kids parenting group program and will evaluate the efficacy of online delivery. Online delivery of the program could result in an easily accessible evidence-based resource to help families with young children at temperamental risk for anxiety disorders. Australian New Zealand Clinical Trials Registry 12615000217505 (registered 5 March 2015).

Further statistics in dentistry. Part 4: Clinical trials 2.

PubMed

Petrie, A; Bulman, J S; Osborn, J F

2002-11-23

The principles which underlie a well-designed clinical trial were introduced in a previous paper. The trial should be controlled (to ensure that the appropriate comparisons are made), randomised (to avoid allocation bias) and, preferably, blinded (to obviate assessment bias). However, taken in isolation, these concepts will not necessarily ensure that meaningful conclusions can be drawn from the study. It is essential that the sample size is large enough to enable the effects of interest to be estimated precisely, and to detect any real treatment differences.

The impact of a home-based walking programme on falls in older people: the Easy Steps randomised controlled trial.

PubMed

Voukelatos, Alexander; Merom, Dafna; Sherrington, Catherine; Rissel, Chris; Cumming, Robert G; Lord, Stephen R

2015-05-01

walking is the most popular form of exercise in older people but the impact of walking on falls is unclear. This study investigated the impact of a 48-week walking programme on falls in older people. three hundred and eighty-six physically inactive people aged 65+ years living in the community were randomised into an intervention or control group. The intervention group received a self-paced, 48-week walking programme that involved three mailed printed manuals and telephone coaching. Coinciding with the walking programme manual control group participants received health information unrelated to falls. Monthly falls calendars were used to monitor falls (primary outcome) over 48 weeks. Secondary outcomes were self-reported quality of life, falls efficacy, exercise and walking levels. Mobility, leg strength and choice stepping reaction time were measured in a sub-sample (n = 178) of participants. there was no difference in fall rates between the intervention and control groups in the follow-up period (IRR = 0.88, 95% CI: 0.60-1.29). By the end of the study, intervention group participants spent significantly more time exercising in general, and specifically walking for exercise (median 1.69 versus 0.75 h/week, P < 0.001). our finding that a walking programme is ineffective in preventing falls supports previous research and questions the suitability of recommending walking as a fall prevention strategy for older people. Walking, however, increases physical activity levels in previously inactive older people. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Occupational impact of internet-delivered cognitive behaviour therapy for depression and anxiety: reanalysis of data from five Australian randomised controlled trials.

PubMed

Mackenzie, Anna; Harvey, Samuel; Mewton, Louise; Andrews, Gavin

2014-10-06

To determine whether internet-delivered cognitive behaviour therapy (iCBT) for depression and anxiety reduces self-reported absenteeism in employed individuals. We reanalysed data from five randomised controlled trials of iCBT: two for depression (conducted from September 2008 to February 2009 and from June 2009 to January 2010), two for generalised anxiety disorder (conducted from March 2009 to June 2009 and from July 2009 to January 2010) and one for social phobia (conducted from May 2008 to July 2008). Participants across Australia were recruited via a website. The inclusion criteria were: (i) meets criteria for the disorder of interest; (ii) aged 18 years or over; (iii) no previous history of a psychotic disorder or drug or alcohol misuse; (iv) not actively suicidal. The iCBT courses each consisted of six online lessons (to be completed within 11 weeks), homework assignments, automatic emails and resource documents. The number of days absent (self-reported absenteeism) in the previous week. We included 284 participants in our analysis. When data for the three disorders were combined, participants who received iCBT had significant reductions in self-reported absenteeism compared with those in the control groups (who were on a waitlist) (P = 0.03). When data for the three disorders were analysed separately, reductions in self-reported absenteeism for participants who received iCBT were not significantly different to those for participants in the control groups. Using data from five RCTs, we showed that iCBT was associated with reductions in self-reported absenteeism. Future research should focus on replicating these findings in other contexts, such as other disorders and other iCBT courses.

MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.

PubMed

Tourbah, Ayman; Lebrun-Frenay, Christine; Edan, Gilles; Clanet, Michel; Papeix, Caroline; Vukusic, Sandra; De Sèze, Jerome; Debouverie, Marc; Gout, Olivier; Clavelou, Pierre; Defer, Gilles; Laplaud, David-Axel; Moreau, Thibault; Labauge, Pierre; Brochet, Bruno; Sedel, Frédéric; Pelletier, Jean

2016-11-01

Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study. To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study. Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits. A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo. MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated. © The Author(s), 2016.

Brief psychological intervention after self-harm: randomised controlled trial from Pakistan.

PubMed

Husain, Nusrat; Afsar, Salahuddin; Ara, Jamal; Fayyaz, Hina; Rahman, Raza Ur; Tomenson, Barbara; Hamirani, Munir; Chaudhry, Nasim; Fatima, Batool; Husain, Meher; Naeem, Farooq; Chaudhry, Imran B

2014-06-01

Self-harm is a major risk factor for completed suicide. To determine the efficacy of a brief psychological intervention - culturally adapted manual-assisted problem-solving training (C-MAP) - delivered following an episode of self-harm compared with treatment as usual (TAU). The study was a randomised controlled assessor-masked clinical trial (trial registration: ClinicalTrials.gov NCT01308151). All patients admitted after an episode of self-harm during the previous 7 days to the participating medical units of three university hospitals in Karachi, Pakistan, were included in the study. A total of 250 patients were screened and 221 were randomly allocated to C-MAP plus treatment as usual (TAU) or to TAU alone. All patients were assessed at baseline, at 3 months (end of intervention) and at 6 months after baseline. The primary outcome measure was reduction in suicidal ideation at 3 months. The secondary outcome measures included hopelessness, depression, coping resources and healthcare utilisation. A total of 108 patients were randomised to the C-MAP group and 113 to the TAU group. Patients in the C-MAP group showed statistically significant improvement on the Beck Scale for Suicide Ideation and Beck Hopelessness Inventory, which was sustained at 3 months after the completion of C-MAP. There was also a significant reduction in symptoms of depression compared with patients receiving TAU. The positive outcomes of this brief psychological intervention in patients attempting self-harm are promising and suggest that C-MAP may have a role in suicide prevention. Royal College of Psychiatrists.

The effect of perindopril on postural instability in older people with a history of falls-a randomised controlled trial.

PubMed

Sumukadas, Deepa; Price, Rosemary; McMurdo, Marion E T; Rauchhaus, Petra; Struthers, Allan; McSwiggan, Stephen; Arnold, Graham; Abboud, Rami; Witham, Miles

2018-01-01

double-blind, parallel group, placebo-controlled randomised trial. we recruited people aged >65 years with at least one fall in the previous year. Participants received 4 mg perindopril or placebo daily for 15 weeks. The primary outcome was the between-group difference in force-plate measured anteroposterior (AP) sway at 15 weeks. Secondary outcomes included other measures of postural sway, limits of stability during maximal forward, right and left leaning, blood pressure, muscle strength, 6-min walk distance and falls. The primary outcome was assessed using two-way ANOVA, adjusted for baseline factors. we randomised 80 participants. Mean age was 78.0 (SD 7.4) years; 60 (75%) were female. About 77/80 (96%) completed the trial. At 15 weeks there were no significant between-group differences in AP sway with eyes open (mean difference 0 mm, 95% CI -8 to 7 mm, P = 0.91) or eyes closed (mean difference 2 mm, 95% CI -7 to 12 mm, P = 0.59); no differences in other measures of postural stability, muscle strength or function. About 16/40 (42%) of patients in each group had orthostatic hypotension at follow-up. The median number (IQR) of falls was 1 (0,4) in the perindopril versus 1 (0,2) in the placebo group (P = 0.24). perindopril did not improve postural sway in older people at risk of falls. ISRCTN58995463. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.

Islet transplantation versus insulin therapy in patients with type 1 diabetes with severe hypoglycaemia or poorly controlled glycaemia after kidney transplantation (TRIMECO): a multicentre, randomised controlled trial.

PubMed

Lablanche, Sandrine; Vantyghem, Marie-Christine; Kessler, Laurence; Wojtusciszyn, Anne; Borot, Sophie; Thivolet, Charles; Girerd, Sophie; Bosco, Domenico; Bosson, Jean-Luc; Colin, Cyrille; Tetaz, Rachel; Logerot, Sophie; Kerr-Conte, Julie; Renard, Eric; Penfornis, Alfred; Morelon, Emmanuel; Buron, Fanny; Skaare, Kristina; Grguric, Gwen; Camillo-Brault, Coralie; Egelhofer, Harald; Benomar, Kanza; Badet, Lionel; Berney, Thierry; Pattou, François; Benhamou, Pierre-Yves

2018-05-15

Islet transplantation is indicated for patients with type 1 diabetes with severe hypoglycaemia or after kidney transplantation. We did a randomised trial to assess the efficacy and safety of islet transplantation compared with insulin therapy in these patients. In this multicentre, open-label, randomised controlled trial, we randomly assigned (1:1) patients with type 1 diabetes at 15 university hospitals to receive immediate islet transplantation or intensive insulin therapy (followed by delayed islet transplantation). Eligible patients were aged 18-65 years and had severe hypoglycaemia or hypoglycaemia unawareness, or kidney grafts with poor glycaemic control. We used computer-generated randomisation, stratified by centre and type of patient. Islet recipients were scheduled to receive 11 000 islet equivalents per kg bodyweight in one to three infusions. The primary outcome was proportion of patients with a modified β-score (in which an overall score of 0 was not allocated when stimulated C-peptide was negative) of 6 or higher at 6 months after first islet infusion in the immediate transplantation group or 6 months after randomisation in the insulin group. The primary analysis included all patients who received the allocated intervention; safety was assessed in all patients who received islet infusions. This trial is registered with ClinicalTrials.gov, number NCT01148680, and is completed. Between July 8, 2010, and July 29, 2013, 50 patients were randomly assigned to immediate islet transplantation (n=26) or insulin treatment (n=24), of whom three (one in the immediate islet transplantation group and two in the insulin therapy group) did not receive the allocated intervention. Median follow-up was 184 days (IQR 181-186) in the immediate transplantation group and 185 days (172-201) in the insulin therapy group. At 6 months, 16 (64% [95% CI 43-82]) of 25 patients in the immediate islet transplantation group had a modified β-score of 6 or higher versus none (0% [0-15]) of the 22 patients in the insulin group (p<0·0001). At 12 months after first infusion, bleeding complications had occurred in four (7% [2-18]) of 55 infusions, and a decrease in median glomerular filtration rate from 90·5 mL/min (IQR 76·6-94·0) to 71·8 mL/min (59·0-89·0) was observed in islet recipients who had not previously received a kidney graft and from 63·0 mL/min (55·0-71·0) to 57·0 mL/min (45·5-65·1) in islet recipients who had previously received a kidney graft. For the indications assessed in this study, islet transplantation effectively improves metabolic outcomes. Although studies with longer-term follow-up are needed, islet transplantation seems to be a valid option for patients with severe, unstable type 1 diabetes who are not responding to intensive medical treatments. However, immunosuppression can affect kidney function, necessitating careful selection of patients. Programme Hospitalier de Recherche Clinique grant from the French Government. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quantity, topics, methods and findings of randomised controlled trials published by German university departments of general practice - systematic review.

PubMed

Heinmüller, Stefan; Schneider, Antonius; Linde, Klaus

2016-04-23

Academic infrastructures and networks for clinical research in primary care receive little funding in Germany. We aimed to provide an overview of the quantity, topics, methods and findings of randomised controlled trials published by German university departments of general practice. We searched Scopus (last search done in April 2015), publication lists of institutes and references of included articles. We included randomised trials published between January 2000 and December 2014 with a first or last author affiliated with a German university department of general practice or family medicine. Risk of bias was assessed with the Cochrane tool, and study findings were quantified using standardised mean differences (SMDs). Thirty-three trials met the inclusion criteria. Seventeen were cluster-randomised trials, with a majority investigating interventions aimed at improving processes compared with usual care. Sample sizes varied between 6 and 606 clusters and 168 and 7807 participants. The most frequent methodological problem was risk of selection bias due to recruitment of individuals after randomisation of clusters. Effects of interventions over usual care were mostly small (SMD <0.3). Sixteen trials randomising individual participants addressed a variety of treatment and educational interventions. Sample sizes varied between 20 and 1620 participants. The methodological quality of the trials was highly variable. Again, effects of experimental interventions over controls were mostly small. Despite limited funding, German university institutes of general practice or family medicine are increasingly performing randomised trials. Cluster-randomised trials on practice improvement are a focus, but problems with allocation concealment are frequent.

Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomised trial.

PubMed

Rodger, Marc A; Hague, William M; Kingdom, John; Kahn, Susan R; Karovitch, Alan; Sermer, Mathew; Clement, Anne Marie; Coat, Suzette; Chan, Wee Shian; Said, Joanne; Rey, Evelyne; Robinson, Sue; Khurana, Rshmi; Demers, Christine; Kovacs, Michael J; Solymoss, Susan; Hinshaw, Kim; Dwyer, James; Smith, Graeme; McDonald, Sarah; Newstead-Angel, Jill; McLeod, Anne; Khandelwal, Meena; Silver, Robert M; Le Gal, Gregoire; Greer, Ian A; Keely, Erin; Rosene-Montella, Karen; Walker, Mark; Wells, Philip S

2014-11-08

Thrombophilias are common disorders that increase the risk of pregnancy-associated venous thromboembolism and pregnancy loss and can also increase the risk of placenta-mediated pregnancy complications (severe pre-eclampsia, small-for-gestational-age infants, and placental abruption). We postulated that antepartum dalteparin would reduce these complications in pregnant women with thrombophilia. In this open-label randomised trial undertaken in 36 tertiary care centres in five countries, we enrolled consenting pregnant women with thrombophilia at increased risk of venous thromboembolism or with previous placenta-mediated pregnancy complications. Eligible participants were randomly allocated in a 1:1 ratio to either antepartum prophylactic dose dalteparin (5000 international units once daily up to 20 weeks' gestation, and twice daily thereafter until at least 37 weeks' gestation) or to no antepartum dalteparin (control group). Randomisation was done by a web-based randomisation system, and was stratified by country and gestational age at randomisation day with a permuted block design (block sizes 4 and 8). At randomisation, site pharmacists (or delegates) received a randomisation number and treatment allocation (by fax and/or e-mail) from the central web randomisation system and then dispensed study drug to the local coordinator. Patients and study personnel were not masked to treatment assignment, but the outcome adjudicators were masked. The primary composite outcome was independently adjudicated severe or early-onset pre-eclampsia, small-for-gestational-age infant (birthweight <10th percentile), pregnancy loss, or venous thromboembolism. We did intention-to-treat and on-treatment analyses. This trial is registered with ClinicalTrials.gov, number NCT00967382, and with Current Controlled Trials, number ISRCTN87441504. Between Feb 28, 2000, and Sept 14, 2012, 292 women consented to participate and were randomly assigned to the two groups. Three women were excluded after randomisation because of ineligibility (two in the antepartum dalteparin group and one in the control group), leaving 146 women assigned to antepartum dalteparin and 143 assigned to no antepartum dalteparin. Some patients crossed over to the other group during treatment, and therefore for on-treatment and safety analysis there were 143 patients in the dalteparin group and 141 in the no dalteparin group. Dalteparin did not reduce the incidence of the primary composite outcome in both intention-to-treat analysis (dalteparin 25/146 [17·1%; 95% CI 11·4-24·2%] vs no dalteparin 27/143 [18·9%; 95% CI 12·8-26·3%]; risk difference -1·8% [95% CI -10·6% to 7·1%)) and on-treatment analysis (dalteparin 28/143 [19·6%] vs no dalteparin 24/141 [17·0%]; risk difference +2·6% [95% CI -6·4 to 11·6%]). In safety analysis, the occurrence of major bleeding did not differ between the two groups. However, minor bleeding was more common in the dalteparin group (28/143 [19·6%]) than in the no dalteparin group (13/141 [9·2%]; risk difference 10·4%, 95% CI 2·3-18·4; p=0·01). Antepartum prophylactic dalteparin does not reduce the occurrence of venous thromboembolism, pregnancy loss, or placenta-mediated pregnancy complications in pregnant women with thrombophilia at high risk of these complications and is associated with an increased risk of minor bleeding. Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and Pharmacia and UpJohn. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effectiveness and cost-effectiveness of a mindfulness training programme in schools compared with normal school provision (MYRIAD): study protocol for a randomised controlled trial.

PubMed

Kuyken, Willem; Nuthall, Elizabeth; Byford, Sarah; Crane, Catherine; Dalgleish, Tim; Ford, Tamsin; Greenberg, Mark T; Ukoumunne, Obioha C; Viner, Russell M; Williams, J Mark G

2017-04-26

Mindfulness-based approaches for adults are effective at enhancing mental health, but few controlled trials have evaluated their effectiveness or cost-effectiveness for young people. The primary aim of this trial is to evaluate the effectiveness and cost-effectiveness of a mindfulness training (MT) programme to enhance mental health, wellbeing and social-emotional behavioural functioning in adolescence. To address this aim, the design will be a superiority, cluster randomised controlled, parallel-group trial in which schools offering social and emotional provision in line with good practice (Formby et al., Personal, Social, Health and Economic (PSHE) Education: A mapping study of the prevalent models of delivery and their effectiveness, 2010; OFSTED, Not Yet Good Enough: Personal, Social, Health and Economic Education in schools, 2013) will be randomised to either continue this provision (control) or include MT in this provision (intervention). The study will recruit and randomise 76 schools (clusters) and 5700 school students aged 12 to 14 years, followed up for 2 years. The study will contribute to establishing if MT is an effective and cost-effective approach to promoting mental health in adolescence. International Standard Randomised Controlled Trials, identifier: ISRCTN86619085 . Registered on 3 June 2016.

Psychosocial consequences of allocation to lung cancer screening: a randomised controlled trial.

PubMed

Aggestrup, Louise Mosborg; Hestbech, Mie Sara; Siersma, Volkert; Pedersen, Jesper Holst; Brodersen, John

2012-01-01

To examine the psychosocial consequences of being allocated to the control group as compared with the screen group in a randomised lung cancer screening trial. The Danish Lung Cancer Screening Trial, a randomised controlled trial, ran from 2004 to 2010 with the purpose of investigating the benefits and harms of lung cancer screening. The participants in Danish Lung Cancer Screening Trial were randomised to either the control group or the screen group and were asked to complete the questionnaires Consequences Of Screening and Consequences Of Screening in Lung Cancer (COS-LC). The Consequences Of Screening and the COS-LC were used to examine the psychosocial consequences of participating in the study, by comparing the control and the screen groups' responses at the prevalence and at the incidence round. There was no statistically significant difference in socio-demographic characteristics or smoking habits between the two groups. Responses to the COS-LC collected before the incidence round were statistically significantly different on the scales 'anxiety', 'behaviour', 'dejection', 'self-blame', 'focus on airway symptoms' and 'introvert', with the control group reporting higher negative psychosocial consequences. Furthermore, the participants in both the control and the screen groups exhibited a mean increase in negative psychosocial consequences when their responses from the prevalence round were compared with their responses from the first incidence round. Participation in a randomised controlled trial on lung cancer screening has negative psychosocial consequences for the apparently healthy participants-both the participants in the screen group and the control group. This negative impact was greatest for the control group.

Comparison of anticipated and actual control group outcomes in randomised trials in paediatric oncology provides evidence that historically controlled studies are biased in favour of the novel treatment.

PubMed

Moroz, Veronica; Wilson, Jayne S; Kearns, Pamela; Wheatley, Keith

2014-12-10

Historically controlled studies are commonly undertaken in paediatric oncology, despite their potential biases. Our aim was to compare the outcome of the control group in randomised controlled trials (RCTs) in paediatric oncology with those anticipated in the sample size calculations in the protocols. Our rationale was that, had these RCTs been performed as historical control studies instead, the available outcome data used to calculate the sample size in the RCT would have been used as the historical control outcome data. A systematic search was undertaken for published paediatric oncology RCTs using the Cochrane Central Register of Controlled Trials (CENTRAL) database from its inception up to July 2013. Data on sample size assumptions and observed outcomes (timetoevent and proportions) were extracted to calculate differences between randomised and historical control outcomes, and a one-sample t-test was employed to assess whether the difference between anticipated and observed control groups differed from zero. Forty-eight randomised questions were included. The median year of publication was 2005, and the range was from 1976 to 2010. There were 31 superiority and 11 equivalence/noninferiority randomised questions with time-to-event outcomes. The median absolute difference between observed and anticipated control outcomes was 5.0% (range: -23 to +34), and the mean difference was 3.8% (95% CI: +0.57 to +7.0; P = 0.022). Because the observed control group (that is, standard treatment arm) in RCTs performed better than anticipated, we found that historically controlled studies that used similar assumptions for the standard treatment were likely to overestimate the benefit of new treatments, potentially leading to children with cancer being given ineffective therapy that may have additional toxicity.

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.

Food incentives to improve completion of tuberculosis treatment: randomised controlled trial in Dili, Timor-Leste

PubMed Central

Martins, Nelson; Morris, Peter

2009-01-01

Objective To determine the effectiveness of the provision of whole food to enhance completion of treatment for tuberculosis. Design Parallel group randomised controlled trial. Setting Three primary care clinics in Dili, Timor-Leste. Participants 270 adults aged ≥18 with previously untreated newly diagnosed pulmonary tuberculosis. Main outcome measures Completion of treatment (including cure). Secondary outcomes included adherence to treatment, weight gain, and clearance of sputum smears. Outcomes were assessed remotely, blinded to allocation status. Interventions Participants started standard tuberculosis treatment and were randomly assigned to intervention (nutritious, culturally appropriate daily meal (weeks 1-8) and food package (weeks 9-32) (n=137) or control (nutritional advice, n=133) groups. Randomisation sequence was computer generated with allocation concealment by sequentially numbered, opaque, sealed envelopes. Results Most patients with tuberculosis were poor, malnourished men living close to the clinics; 265/270 (98%) contributed to the analysis. The intervention had no significant beneficial or harmful impact on the outcome of treatment (76% v 78% completion, P=0.7) or adherence (93% for both groups, P=0.7) but did lead to improved weight gain at the end of treatment (10.1% v 7.5% improvement, P=0.04). Itch was more common in the intervention group (21% v 9%, P<0.01). In a subgroup analysis of patients with positive results on sputum smears, there were clinically important improvements in one month sputum clearance (85% v 67%, P=0.13) and completion of treatment (78% v 68%, P=0.3). Conclusion Provision of food did not improve outcomes with tuberculosis treatment in these patients in Timor-Leste. Further studies in different settings and measuring different outcomes are required. Trial registration Clinical Trials NCT0019256. PMID:19858174

Effects of exercise training on HbA1c and VO2peak in patients with type 2 diabetes and coronary artery disease: A randomised clinical trial.

PubMed

Byrkjeland, Rune; Njerve, Ida U; Anderssen, Sigmund; Arnesen, Harald; Seljeflot, Ingebjørg; Solheim, Svein

2015-09-01

Few exercise trials have focused on patients with both type 2 diabetes and coronary artery disease. We investigated the effects of 1 year of exercise training on HbA1c and VO(2peak) in these patients. Patients with type 2 diabetes and coronary artery disease (n = 137) were randomised to combined exercise training or control group. HbA(1c) was measured at the beginning and end of the study. Changes in VO(2peak), and also ventilatory threshold and time to exhaustion, were assessed by cardiopulmonary exercise testing. No differences in changes between the randomised groups were observed in HbA1c and VO(2peak), whereas ventilatory threshold and time to exhaustion increased significantly in the exercise group compared with the controls (p = 0.046 and p = 0.034). In patients without previous acute myocardial infarction and diabetes microvascular complications (n = 46), the exercise group did improve HbA1c and VO(2peak) compared with the controls (p = 0.052 and p = 0.035). No significant effects of exercise training on HbA(1c) or VO(2peak) were observed in patients with type 2 diabetes and coronary artery disease, although improvements were seen in patients without vascular complications beyond coronary artery disease, implying that the degree of vascular disease may influence exercise responses. Ventilatory threshold and time to exhaustion did increase significantly, indicating improved exercise performance despite the minor change in VO(2peak). © The Author(s) 2015.

Cost-benefit analysis of fall injuries prevented by a programme of home modifications: a cluster randomised controlled trial.

PubMed

Keall, Michael D; Pierse, Nevil; Howden-Chapman, Philippa; Guria, Jagadish; Cunningham, Chris W; Baker, Michael G

2017-02-01

Injuries due to falls in the home impose a huge social and economic cost on society. We have previously found important safety benefits of home modifications such as handrails for steps and stairs, grab rails for bathrooms, outside lighting, edging for outside steps and slip-resistant surfacing for outside areas such as decks. Here we assess the economic benefits of these modifications. Using a single-blinded cluster randomised controlled trial, we analysed insurance payments for medically treated home fall injuries as recorded by the national injury insurer. The benefits in terms of the value of disability adjusted life years (DALYs) averted and social costs of injuries saved were extrapolated to a national level and compared with the costs of the intervention. An intention-to-treat analysis was carried out. Injury costs per time exposed to the modified homes compared with the unmodified homes showed a reduction in the costs of home fall injuries of 33% (95% CI 5% to 49%). The social benefits of injuries prevented were estimated to be at least six times the costs of the intervention. The benefit-cost ratio can be at least doubled for older people and increased by 60% for those with a prior history of fall injuries. This is the first randomised controlled trial to examine the benefits of home modification for reducing fall injury costs in the general population. The results show a convincing economic justification for undertaking relatively low-cost home repairs and installing safety features to prevent falls. ACTRN12609000779279. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Randomised crossover trial of telemonitoring in chronic respiratory patients (TeleCRAFT trial)

PubMed Central

Chatwin, M; Hawkins, G; Panicchia, L; Woods, A; Hanak, A; Lucas, R; Baker, E; Ramhamdany, E; Mann, B; Riley, J; Cowie, M R; Simonds, A K

2016-01-01

Objective To assess the impact of home telemonitoring on health service use and quality of life in patients with severe chronic lung disease. Design Randomised crossover trial with 6 months of standard best practice clinical care (control group) and 6 months with the addition of telemonitoring. Participants 68 patients with chronic lung disease (38 with COPD; 30 with chronic respiratory failure due to other causes), who had a hospital admission for an exacerbation within 6 months of randomisation and either used long-term oxygen therapy or had an arterial oxygen saturation (SpO2) of <90% on air during the previous admission. Individuals received telemonitoring (second-generation system) via broadband link to a hospital-based care team. Outcome measures Primary outcome measure was time to first hospital admission for an acute exacerbation. Secondary outcome measures were hospital admissions, general practitioner (GP) consultations and home visits by nurses, quality of life measured by EuroQol-5D and hospital anxiety and depression (HAD) scale, and self-efficacy score (Stanford). Results Median (IQR) number of days to first admission showed no difference between the two groups—77 (114) telemonitoring, 77.5 (61) control (p=0.189). Hospital admission rate at 6 months increased (0.63 telemonitoring vs 0.32 control p=0.026). Home visits increased during telemonitoring; GP consultations were unchanged. Self-efficacy fell, while HAD depression score improved marginally during telemonitoring. Conclusions Telemonitoring added to standard care did not alter time to next acute hospital admission, increased hospital admissions and home visits overall, and did not improve quality of life in chronic respiratory patients. Trial registration number NCT02180919 (ClinicalTrials.gov). PMID:26962013

Glutamine supplementation to prevent morbidity and mortality in preterm infants.

PubMed

Moe-Byrne, Thirimon; Brown, Jennifer V E; McGuire, William

2016-01-12

Glutamine is a conditionally essential amino acid. Endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress. Evidence exists that glutamine supplementation improves clinical outcomes in critically ill adults. It has been suggested that glutamine supplementation may also benefit preterm infants. To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 12), MEDLINE, EMBASE and Maternity and Infant Care (to December 2015), conference proceedings and previous reviews. Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in preterm infants at any time from birth to discharge from hospital. We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors. We synthesised data using a fixed-effect model and reported typical relative risk, typical risk difference and weighted mean difference. We identified 12 randomised controlled trials in which a total of 2877 preterm infants participated. Six trials assessed enteral glutamine supplementation and six trials assessed parenteral glutamine supplementation. The trials were generally of good methodological quality. Meta-analysis did not find an effect of glutamine supplementation on mortality (typical relative risk 0.97, 95% confidence interval 0.80 to 1.17; risk difference 0.00, 95% confidence interval -0.03 to 0.02) or major neonatal morbidities including the incidence of invasive infection or necrotising enterocolitis. Three trials that assessed neurodevelopmental outcomes in children aged 18 to 24 months and beyond did not find any effects. The available trial data do not provide evidence that glutamine supplementation confers important benefits for preterm infants.

Glutamine supplementation to prevent morbidity and mortality in preterm infants.

PubMed

Moe-Byrne, Thirimon; Brown, Jennifer V E; McGuire, William

2016-04-18

Glutamine is a conditionally essential amino acid. Endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress. Evidence exists that glutamine supplementation improves clinical outcomes in critically ill adults. It has been suggested that glutamine supplementation may also benefit preterm infants. To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 12), MEDLINE, EMBASE and Maternity and Infant Care (to December 2015), conference proceedings and previous reviews. Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in preterm infants at any time from birth to discharge from hospital. We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors. We synthesised data using a fixed-effect model and reported typical relative risk, typical risk difference and weighted mean difference. We identified 12 randomised controlled trials in which a total of 2877 preterm infants participated. Six trials assessed enteral glutamine supplementation and six trials assessed parenteral glutamine supplementation. The trials were generally of good methodological quality. Meta-analysis did not find an effect of glutamine supplementation on mortality (typical relative risk 0.97, 95% confidence interval 0.80 to 1.17; risk difference 0.00, 95% confidence interval -0.03 to 0.02) or major neonatal morbidities including the incidence of invasive infection or necrotising enterocolitis. Three trials that assessed neurodevelopmental outcomes in children aged 18 to 24 months and beyond did not find any effects. The available trial data do not provide evidence that glutamine supplementation confers important benefits for preterm infants.

Randomised controlled trial of joint crisis plans to reduce compulsory treatment for people with psychosis: economic outcomes.

PubMed

Barrett, Barbara; Waheed, Waquas; Farrelly, Simone; Birchwood, Max; Dunn, Graham; Flach, Clare; Henderson, Claire; Leese, Morven; Lester, Helen; Marshall, Max; Rose, Diana; Sutherby, Kim; Szmukler, George; Thornicroft, Graham; Byford, Sarah

2013-01-01

Compulsory admission to psychiatric hospitals may be distressing, disruptive to patients and families, and associated with considerable cost to the health service. Improved patient experience and cost reductions could be realised by providing cost-effective crisis planning services. Economic evaluation within a multi-centre randomised controlled trial comparing Joint Crisis Plans (JCP) plus treatment as usual (TAU) to TAU alone for patients aged over 16, with at least one psychiatric hospital admission in the previous two years and on the Enhanced Care Programme Approach register. JCPs, containing the patient's treatment preferences for any future psychiatric emergency, are a form of crisis intervention that aim to mitigate the negative consequences of relapse, including hospital admission and use of coercion. Data were collected at baseline and 18-months after randomisation. The primary outcome was admission to hospital under the Mental Health Act. The economic evaluation took a service perspective (health, social care and criminal justice services) and a societal perspective (additionally including criminal activity and productivity losses). The addition of JCPs to TAU had no significant effect on compulsory admissions or total societal cost per participant over 18-months follow-up. From the service cost perspective, however, evidence suggests a higher probability (80%) of JCPs being the more cost-effective option. Exploration by ethnic group highlights distinct patterns of costs and effects. Whilst the evidence does not support the cost-effectiveness of JCPs for White or Asian ethnic groups, there is at least a 90% probability of the JCP intervention being the more cost-effective option in the Black ethnic group. The results by ethnic group are sufficiently striking to warrant further investigation into the potential for patient gain from JCPs among black patient groups. Current Controlled Trials ISRCTN11501328.

Food incentives to improve completion of tuberculosis treatment: randomised controlled trial in Dili, Timor-Leste.

PubMed

Martins, Nelson; Morris, Peter; Kelly, Paul M

2009-10-26

To determine the effectiveness of the provision of whole food to enhance completion of treatment for tuberculosis. Parallel group randomised controlled trial. Three primary care clinics in Dili, Timor-Leste. 270 adults aged >or=18 with previously untreated newly diagnosed pulmonary tuberculosis. Completion of treatment (including cure). Secondary outcomes included adherence to treatment, weight gain, and clearance of sputum smears. Outcomes were assessed remotely, blinded to allocation status. Interventions Participants started standard tuberculosis treatment and were randomly assigned to intervention (nutritious, culturally appropriate daily meal (weeks 1-8) and food package (weeks 9-32) (n=137) or control (nutritional advice, n=133) groups. Randomisation sequence was computer generated with allocation concealment by sequentially numbered, opaque, sealed envelopes. Most patients with tuberculosis were poor, malnourished men living close to the clinics; 265/270 (98%) contributed to the analysis. The intervention had no significant beneficial or harmful impact on the outcome of treatment (76% v 78% completion, P=0.7) or adherence (93% for both groups, P=0.7) but did lead to improved weight gain at the end of treatment (10.1% v 7.5% improvement, P=0.04). Itch was more common in the intervention group (21% v 9%, P<0.01). In a subgroup analysis of patients with positive results on sputum smears, there were clinically important improvements in one month sputum clearance (85% v 67%, P=0.13) and completion of treatment (78% v 68%, P=0.3). Provision of food did not improve outcomes with tuberculosis treatment in these patients in Timor-Leste. Further studies in different settings and measuring different outcomes are required. Clinical Trials NCT00192556.

An international randomised placebo-controlled trial of a four-component combination pill ("polypill") in people with raised cardiovascular risk.

PubMed

Rodgers, Anthony; Patel, Anushka; Berwanger, Otavio; Bots, Michiel; Grimm, Richard; Grobbee, Diederick E; Jackson, Rod; Neal, Bruce; Neaton, Jim; Poulter, Neil; Rafter, Natasha; Raju, P Krishnam; Reddy, Srinath; Thom, Simon; Vander Hoorn, Stephen; Webster, Ruth

2011-01-01

There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ('polypills') to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability. We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up. At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment. This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk. Australian New Zealand Clinical Trials Registry ACTRN12607000099426.

Individual music therapy for managing neuropsychiatric symptoms for people with dementia and their carers: a cluster randomised controlled feasibility study.

PubMed

Hsu, Ming Hung; Flowerdew, Rosamund; Parker, Michael; Fachner, Jörg; Odell-Miller, Helen

2015-07-18

Previous research highlights the importance of staff involvement in psychosocial interventions targeting neuropsychiatric symptoms of dementia. Music therapy has shown potential effects, but it is not clear how this intervention can be programmed to involve care staff within the delivery of patients' care. This study reports initial feasibility and outcomes from a five month music therapy programme including weekly individual active music therapy for people with dementia and weekly post-therapy video presentations for their carers in care homes. 17 care home residents and 10 care staff were randomised to the music therapy intervention group or standard care control group. The cluster randomised, controlled trial included baseline, 3-month, 5-month and post-intervention 7-month measures of residents' symptoms and well-being. Carer-resident interactions were also assessed. Feasibility was based on carers' feedback through semi-structured interviews, programme evaluations and track records of the study. The music therapy programme appeared to be a practicable and acceptable intervention for care home residents and staff in managing dementia symptoms. Recruitment and retention data indicated feasibility but also challenges. Preliminary outcomes indicated differences in symptoms (13.42, 95 % CI: [4.78 to 22.07; p = 0.006]) and in levels of wellbeing (-0.74, 95 % CI: [-1.15 to -0.33; p = 0.003]) between the two groups, indicating that residents receiving music therapy improved. Staff in the intervention group reported enhanced caregiving techniques as a result of the programme. The data supports the value of developing a music therapy programme involving weekly active individual music therapy sessions and music therapist-carer communication. The intervention is feasible with modifications in a more rigorous evaluation of a larger sample size. Clinicaltrials.gov, number NCT01744600.

Risk of bias assessment of randomised controlled trials in high-impact ophthalmology journals and general medical journals: a systematic review.

PubMed

Joksimovic, Lazar; Koucheki, Robert; Popovic, Marko; Ahmed, Yusuf; Schlenker, Matthew B; Ahmed, Iqbal Ike K

2017-10-01

Evidence-based treatments in ophthalmology are often based on the results of randomised controlled trials. Biased conclusions from randomised controlled trials may lead to inappropriate management recommendations. This systematic review investigates the prevalence of bias risk in randomised controlled trials published in high-impact ophthalmology journals and ophthalmology trials from general medical journals. Using Ovid MEDLINE, randomised controlled trials in the top 10 high-impact ophthalmology journals in 2015 were systematically identified and critically appraised for the prevalence of bias risk. Included randomised controlled trials were assessed in all domains of bias as defined by the Cochrane Collaboration. In addition, the prevalence of conflict of interest and industry sponsorship was investigated. A comparison with ophthalmology articles from high-impact general medical journals was performed. Of the 259 records that were screened from ophthalmology-specific journals, 119 trials met all inclusion criteria and were critically appraised. In total, 29.4% of domains had an unclear risk, 13.8% had a high risk and 56.8% had a low risk of bias. In comparison, ophthalmology articles from general medical journals had a lower prevalence of unclear risk (17.1%), higher prevalence of high risk (21.9%) and a higher prevalence of low risk domains (61.9%). Furthermore, 64.7% of critically appraised trials from ophthalmology-specific journals did not report any conflicts of interest, while 70.6% did not report an industry sponsor of their trial. In closing, it is essential that authors, peer reviewers and readers closely follow published risk of bias guidelines. © 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.

The People with Asperger syndrome and anxiety disorders (PAsSA) trial: a pilot multicentre, single-blind randomised trial of group cognitive–behavioural therapy

PubMed Central

Murphy, Glynis H.; Shepstone, Lee; Wilson, Edward C.F.; Fowler, David; Heavens, David; Malovic, Aida; Russell, Alexandra; Rose, Alice; Mullineaux, Louise

2016-01-01

Background There is a growing interest in using cognitive–behavioural therapy (CBT) with people who have Asperger syndrome and comorbid mental health problems. Aims To examine whether modified group CBT for clinically significant anxiety in an Asperger syndrome population is feasible and likely to be efficacious. Method Using a randomised assessor-blind trial, 52 individuals with Asperger syndrome were randomised into a treatment arm or a waiting-list control arm. After 24 weeks, those in the waiting-list control arm received treatment, while those initially randomised to treatment were followed up for 24 weeks. Results The conversion rate for this trial was high (1.6:1), while attrition was 13%. After 24 weeks, there was no significant difference between those randomised to the treatment arm compared with those randomised to the waiting-list control arm on the primary outcome measure, the Hamilton Rating Scale for Anxiety. Conclusions Trials of psychological therapies with this population are feasible. Larger definitive trials are now needed. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) licence. PMID:27703772

A perturbation-based balance training program for older adults: study protocol for a randomised controlled trial

PubMed Central

Mansfield, Avril; Peters, Amy L; Liu, Barbara A; Maki, Brian E

2007-01-01

Background Previous research investigating exercise as a means of falls prevention in older adults has shown mixed results. Lack of specificity of the intervention may be an important factor contributing to negative results. Change-in-support (CIS) balance reactions, which involve very rapid stepping or grasping movements of the limbs, play a critical role in preventing falls; hence, a training program that improves ability to execute effective CIS reactions could potentially have a profound effect in reducing risk of falling. This paper describes: 1) the development of a perturbation-based balance training program that targets specific previously-reported age-related impairments in CIS reactions, and 2) a study protocol to evaluate the efficacy of this new training program. Methods/Design The training program involves use of unpredictable, multi-directional moving-platform perturbations to evoke stepping and grasping reactions. Perturbation magnitude is gradually increased over the course of the 6-week program, and concurrent cognitive and movement tasks are included during later sessions. The program was developed in accordance with well-established principles of motor learning, such as individualisation, specificity, overload, adaptation-progression and variability. Specific goals are to reduce the frequency of multiple-step responses, reduce the frequency of collisions between the stepping foot and stance leg, and increase the speed of grasping reactions. A randomised control trial will be performed to evaluate the efficacy of the training program. A total of 30 community-dwelling older adults (age 64–80) with a recent history of instability or falling will be assigned to either the perturbation-based training or a control group (flexibility/relaxation training), using a stratified randomisation that controls for gender, age and baseline stepping/grasping performance. CIS reactions will be tested immediately before and after the six weeks of training, using platform perturbations as well as a distinctly different method of perturbation (waist pulls) in order to evaluate the generalisability of the training effects. Discussion This study will determine whether perturbation-based balance training can help to reverse specific age-related impairments in balance-recovery reactions. These results will help to guide the development of more effective falls prevention programs, which may ultimately lead to reduced health-care costs and enhanced mobility, independence and quality of life. PMID:17540020

Fluvoxamine versus other anti-depressive agents for depression

PubMed Central

Omori, Ichiro M; Watanabe, Norio; Nakagawa, Atsuo; Cipriani, Andrea; Barbui, Corrado; McGuire, Hugh; Churchill, Rachel; Furukawa, Toshi A

2014-01-01

Background Fluvoxamine, one of the oldest selective serotonin reuptake inhibitors (SSRIs), is prescribed to patients with major depression in many countries. Several studies have previously reviewed the efficacy and tolerability of fluvoxamine for the treatment of major depression. However, these reviews are now outdated. Objectives Our objective is to evaluate the effectiveness, tolerability and side effect profile of fluvoxamine for major depression in comparison with other anti-depressive agents, including tricyclics (TCAs), heterocyclics, other SSRIs, SNRIs, other newer agents and other conventional psychotropic drugs. Search methods We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register. Trial databases and ongoing trial registers in North America, Europe, Japan and Australia, were handsearched for randomised controlled trials. We checked reference lists of the articles included in the review, previous systematic reviews and major textbooks of affective disorder for published reports and citations of unpublished research. The date of last search was 31 August 2008. Selection criteria We included all randomised controlled trials, published in any language, that compared fluvoxamine with any other active antidepressants in the acute phase treatment of major depression. Data collection and analysis Two independent review authors inspected citations and abstracts, obtained papers, extracted data and assessed the risk of bias of included studies. We analysed dichotomous data using odds ratios (ORs) and continuous data using the standardised mean difference (SMD). A random effects model was used to combine studies. Main results A total of 54 randomised controlled trials (n = 5122) were included. No strong evidence was found to indicate that fluvoxamine was either superior or inferior to other antidepressants regarding response, remission and tolerability. However, differing side effect profiles were evident, especially with regard to gastrointestinal side effects of fluvoxamine when compared to other antidepressants. For example, fluvoxamine was generally associated with a higher incidence of vomiting/nausea (versus imipramine, OR 2.23, CI 1.59 to 3.14; versus clomipramine, OR 2.13, CI 1.06 to 4.27; versus amitriptyline, OR 2.86, CI 1.31 to 2.63). Authors’ conclusions We found no strong evidence that fluvoxamine was either superior or inferior to any other antidepressants in terms of efficacy and tolerability in the acute phase treatment of depression. However, differing side effect profiles were evident. Based on these findings, we conclude that clinicians should focus on practical or clinically relevant considerations, including these differences in side effect profiles. PMID:20238342

A perturbation-based balance training program for older adults: study protocol for a randomised controlled trial.

PubMed

Mansfield, Avril; Peters, Amy L; Liu, Barbara A; Maki, Brian E

2007-05-31

Previous research investigating exercise as a means of falls prevention in older adults has shown mixed results. Lack of specificity of the intervention may be an important factor contributing to negative results. Change-in-support (CIS) balance reactions, which involve very rapid stepping or grasping movements of the limbs, play a critical role in preventing falls; hence, a training program that improves ability to execute effective CIS reactions could potentially have a profound effect in reducing risk of falling. This paper describes: 1) the development of a perturbation-based balance training program that targets specific previously-reported age-related impairments in CIS reactions, and 2) a study protocol to evaluate the efficacy of this new training program. The training program involves use of unpredictable, multi-directional moving-platform perturbations to evoke stepping and grasping reactions. Perturbation magnitude is gradually increased over the course of the 6-week program, and concurrent cognitive and movement tasks are included during later sessions. The program was developed in accordance with well-established principles of motor learning, such as individualisation, specificity, overload, adaptation-progression and variability. Specific goals are to reduce the frequency of multiple-step responses, reduce the frequency of collisions between the stepping foot and stance leg, and increase the speed of grasping reactions. A randomised control trial will be performed to evaluate the efficacy of the training program. A total of 30 community-dwelling older adults (age 64-80) with a recent history of instability or falling will be assigned to either the perturbation-based training or a control group (flexibility/relaxation training), using a stratified randomisation that controls for gender, age and baseline stepping/grasping performance. CIS reactions will be tested immediately before and after the six weeks of training, using platform perturbations as well as a distinctly different method of perturbation (waist pulls) in order to evaluate the generalisability of the training effects. This study will determine whether perturbation-based balance training can help to reverse specific age-related impairments in balance-recovery reactions. These results will help to guide the development of more effective falls prevention programs, which may ultimately lead to reduced health-care costs and enhanced mobility, independence and quality of life.

A randomised controlled trial to assess the effectiveness of a nurse-led palliative care intervention for HIV positive patients on antiretroviral therapy: recruitment, refusal, randomisation and missing data.

PubMed

Lowther, Keira; Higginson, Irene J; Simms, Victoria; Gikaara, Nancy; Ahmed, Aabid; Ali, Zipporah; Afuande, Gaudencia; Kariuki, Hellen; Sherr, Lorraine; Jenkins, Rachel; Selman, Lucy; Harding, Richard

2014-09-03

Despite the life threatening nature of an HIV diagnosis and the multidimensional problems experienced by this patient population during antiretroviral therapy, the effectiveness of a palliative care approach for HIV positive patients on ART is as yet unknown. A randomised controlled trial (RCT) was conducted in a sample of 120 HIV positive patients on ART in an urban clinic in Mombasa, Kenya. The intervention was a minimum of seven sessions of multidimensional, person-centred care, given by HIV nurses trained in the palliative care approach over a period of 5 months. Rates of recruitment and refusal, the effectiveness of the randomisation procedure, trial follow-up and attrition and extent of missing data are reported.120 patients (60 randomised to control arm, 60 randomised to intervention arm) were recruited over 5.5 months, with a refusal rate of 55.7%. During the study period, three participants died from cancer, three withdrew (two moved away and one withdrew due to time constraints). All of these patients were in the intervention arm: details are reported. There were five additional missing monthly interviews in both the control and intervention study arm, bringing the total of missing data to 26 data points (4.3%). The quality and implications of these data are discussed extensively and openly, including the effect of full and ethical consent procedures, respondent burden, HIV stigma, accurate randomisation, patient safety and the impact of the intervention. Data on recruitment randomisation, attrition and missing data in clinical trials should be routinely reported, in conjunction with the now established practice of publishing study protocols to enhance research integrity, transparency and quality. Transparency is especially important in cross cultural settings, in which the sources of funding and trial design are often not based in the country of data collection. Findings reported can be used to inform future RCTs in this area. Clinicaltrials.gov NCT01608802.

Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial.

PubMed

Pickard, Robert; Starr, Kathryn; MacLennan, Graeme; Lam, Thomas; Thomas, Ruth; Burr, Jennifer; McPherson, Gladys; McDonald, Alison; Anson, Kenneth; N'Dow, James; Burgess, Neil; Clark, Terry; Kilonzo, Mary; Gillies, Katie; Shearer, Kirsty; Boachie, Charles; Cameron, Sarah; Norrie, John; McClinton, Samuel

2015-07-25

Meta-analyses of previous randomised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic, but emphasised the need for high-quality trials with wide inclusion criteria. We aimed to fulfil this need by testing effectiveness of these drugs in a standard clinical care setting. For this multicentre, randomised, placebo-controlled trial, we recruited adults (aged 18-65 years) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals. Participants were randomly assigned by a remote randomisation system to tamsulosin 400 μg, nifedipine 30 mg, or placebo taken daily for up to 4 weeks, using an algorithm with centre, stone size (≤5 mm or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation covariates. Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of randomisation, analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data. This trial is registered with the European Clinical Trials Database, EudraCT number 2010-019469-26, and as an International Standard Randomised Controlled Trial, number 69423238. Between Jan 11, 2011, and Dec 20, 2013, we randomly assigned 1167 participants, 1136 (97%) of whom were included in the primary analysis (17 were excluded because of ineligibility and 14 participants were lost to follow-up). 303 (80%) of 379 participants in the placebo group did not need further intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group (adjusted risk difference 1·3% [95% CI -5·7 to 8·3]; p=0·73) and 304 (80%) of 379 in the nifedipine group (0·5% [-5·6 to 6·5]; p=0·88). No difference was noted between active treatment and placebo (p=0·78), or between tamsulosin and nifedipine (p=0·77). Serious adverse events were reported in three participants in the nifedipine group (one had right loin pain, diarrhoea, and vomiting; one had malaise, headache, and chest pain; and one had severe chest pain, difficulty breathing, and left arm pain) and in one participant in the placebo group (headache, dizziness, lightheadedness, and chronic abdominal pain). Tamsulosin 400 μg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic. UK National Institute for Health Research Health Technology Assessment Programme. Copyright © 2015 Pickard et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Psychosocial consequences of allocation to lung cancer screening: a randomised controlled trial

PubMed Central

Aggestrup, Louise Mosborg; Hestbech, Mie Sara; Siersma, Volkert; Pedersen, Jesper Holst

2012-01-01

Objective To examine the psychosocial consequences of being allocated to the control group as compared with the screen group in a randomised lung cancer screening trial. Method The Danish Lung Cancer Screening Trial, a randomised controlled trial, ran from 2004 to 2010 with the purpose of investigating the benefits and harms of lung cancer screening. The participants in Danish Lung Cancer Screening Trial were randomised to either the control group or the screen group and were asked to complete the questionnaires Consequences Of Screening and Consequences Of Screening in Lung Cancer (COS-LC). The Consequences Of Screening and the COS-LC were used to examine the psychosocial consequences of participating in the study, by comparing the control and the screen groups' responses at the prevalence and at the incidence round. Results There was no statistically significant difference in socio-demographic characteristics or smoking habits between the two groups. Responses to the COS-LC collected before the incidence round were statistically significantly different on the scales ‘anxiety’, ‘behaviour’, ‘dejection’, ‘self-blame’, ‘focus on airway symptoms’ and ‘introvert’, with the control group reporting higher negative psychosocial consequences. Furthermore, the participants in both the control and the screen groups exhibited a mean increase in negative psychosocial consequences when their responses from the prevalence round were compared with their responses from the first incidence round. Conclusions Participation in a randomised controlled trial on lung cancer screening has negative psychosocial consequences for the apparently healthy participants—both the participants in the screen group and the control group. This negative impact was greatest for the control group. PMID:22382119

Effects of a physiotherapy and occupational therapy intervention on mobility and activity in care home residents: a cluster randomised controlled trial.

PubMed

Sackley, Catherine M; van den Berg, Maayken E; Lett, Karen; Patel, Smitaa; Hollands, Kristen; Wright, Christine C; Hoppitt, Thomas J

2009-09-01

To compare the clinical effectiveness of a programme of physiotherapy and occupational therapy with standard care in care home residents who have mobility limitations and are dependent in performing activities of daily living. Cluster randomised controlled trial, with random allocation at the level of care home. Care homes within the NHS South Birmingham primary care trust and the NHS Birmingham East and North primary care trust that had more than five beds and provided for people in the care categories "physical disability" and "older people." Care home residents with mobility limitations, limitations in activities of daily living (as screened by the Barthel index), and not receiving end of life care were eligible to take part in the study. A targeted three month occupational therapy and physiotherapy programme. Scores on the Barthel index and the Rivermead mobility index. 24 of 77 nursing and residential homes that catered for residents with mobility limitations and dependency for activities of daily living were selected for study: 12 were randomly allocated to the intervention arm (128 residents, mean age 86 years) and 12 to the control arm (121 residents, mean age 84 years). Participants were evaluated by independent assessors blind to study arm allocation before randomisation (0 months), three months after randomisation (at the end of the treatment period for patients who received the intervention), and again at six months after randomisation. After adjusting for home effect and baseline characteristics, no significant differences were found in mean Barthel index scores at six months post-randomisation between treatment arms (mean effect 0.08, 95% confidence interval -1.14 to 1.30; P=0.90), across assessments (-0.01, -0.63 to 0.60; P=0.96), or in the interaction between assessment and intervention (0.42, -0.48 to 1.32; P=0.36). Similarly, no significant differences were found in the mean Rivermead mobility index scores between treatment arms (0.62, -0.51 to 1.76; P=0.28), across assessments (-0.15, -0.65 to 0.35; P=0.55), or interaction (0.71, -0.02 to 1.44; P=0.06). The three month occupational therapy and physiotherapy programme had no significant effect on mobility and independence. On the other hand, the variation in residents' functional ability, the prevalence of cognitive impairment, and the prevalence of depression were considerably higher in this sample than expected on the basis of previous work. Further research to clarify the efficacy of occupational therapy and physiotherapy is required if access to therapy services is to be recommended in this population. ISRCTN79859980.

The effects of cognitive remediation on functional outcomes among people with schizophrenia: a randomised controlled study.

PubMed

Tan, Bhing-Leet; King, Robert

2013-11-01

Cognitive remediation is an intervention to overcome cognitive deficits through drills and use of strategies. Previous studies have reported positive effects for cognitive remediation on neurocognition, but researchers' allegiance effects are not always adequately controlled. Furthermore, its efficacy amongst the Asian population has not been established. Hence, this study aimed to determine if cognitive remediation would have positive effects on neurocognition and functioning within an English-speaking Asian population, when compared against the effects of a credible and balanced control provided by therapists blinded to the study hypothesis. A total of 70 participants with schizophrenia who attended vocational training or day rehabilitation programmes were randomised to receive a 60-hour programme of either cognitive remediation or physical exercise. Neurocognition and functional outcomes were measured at baseline, upon completion of treatment, 6 months after treatment and 1 year after treatment. Participants who received cognitive remediation had significantly greater improvement in all neurocognitive domains. Furthermore, the cognitive remediation group achieved greater attainment of vocational or independent living skills and better functional outcomes at post-intervention and at the end of the 1-year follow-up. When compared against a credible intervention such as physical exercise, cognitive remediation was able to show significant positive effects on both neurocognition and functional outcomes among the Asian population of schizophrenia patients.

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

PubMed

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

2018-02-22

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

Total knee replacement plus physical and medical therapy or treatment with physical and medical therapy alone: a randomised controlled trial in patients with knee osteoarthritis (the MEDIC-study).

PubMed

Skou, Soren T; Roos, Ewa M; Laursen, Mogens B; Rathleff, Michael S; Arendt-Nielsen, Lars; Simonsen, Ole H; Rasmussen, Sten

2012-05-09

There is a lack of high quality evidence concerning the efficacy of total knee arthroplasty (TKA). According to international evidence-based guidelines, treatment of knee osteoarthritis (KOA) should include patient education, exercise and weight loss. Insoles and pharmacological treatment can be included as supplementary treatments. If the combination of these non-surgical treatment modalities is ineffective, TKA may be indicated. The purpose of this randomised controlled trial is to examine whether TKA provides further improvement in pain, function and quality of life in addition to optimised non-surgical treatment in patients with KOA defined as definite radiographic OA and up to moderate pain. The study will be conducted in The North Denmark Region. 100 participants with radiographic KOA (K-L grade ≥2) and mean pain during the previous week of ≤ 60 mm (0-100, best to worst scale) who are considered eligible for TKA by an orthopaedic surgeon will be included. The treatment will consist of 12 weeks of optimised non-surgical treatment consisting of patient education, exercise, diet, insoles, analgesics and/or NSAIDs. Patients will be randomised to either receiving or not receiving a TKA in addition to the optimised non-surgical treatment. The primary outcome will be the change from baseline to 12 months on the Knee Injury and Osteoarthritis Outcome Score (KOOS)(4) defined as the average score for the subscale scores for pain, symptoms, activities of daily living, and quality of life. Secondary outcomes include the five individual KOOS subscale scores, EQ-5D, pain on a 100 mm Visual Analogue Scale, self-efficacy, pain pressure thresholds, and isometric knee flexion and knee extension strength. This is the first randomised controlled trial to investigate the efficacy of TKA as an adjunct treatment to optimised non-surgical treatment in patients with KOA. The results will significantly contribute to evidence-based recommendations for the treatment of patients with KOA. Clinicaltrials.gov reference: NCT01410409.

Total knee replacement plus physical and medical therapy or treatment with physical and medical therapy alone: a randomised controlled trial in patients with knee osteoarthritis (the MEDIC-study)

PubMed Central

2012-01-01

Background There is a lack of high quality evidence concerning the efficacy of total knee arthroplasty (TKA). According to international evidence-based guidelines, treatment of knee osteoarthritis (KOA) should include patient education, exercise and weight loss. Insoles and pharmacological treatment can be included as supplementary treatments. If the combination of these non-surgical treatment modalities is ineffective, TKA may be indicated. The purpose of this randomised controlled trial is to examine whether TKA provides further improvement in pain, function and quality of life in addition to optimised non-surgical treatment in patients with KOA defined as definite radiographic OA and up to moderate pain. Methods/Design The study will be conducted in The North Denmark Region. 100 participants with radiographic KOA (K-L grade ≥2) and mean pain during the previous week of ≤ 60 mm (0–100, best to worst scale) who are considered eligible for TKA by an orthopaedic surgeon will be included. The treatment will consist of 12 weeks of optimised non-surgical treatment consisting of patient education, exercise, diet, insoles, analgesics and/or NSAIDs. Patients will be randomised to either receiving or not receiving a TKA in addition to the optimised non-surgical treatment. The primary outcome will be the change from baseline to 12 months on the Knee Injury and Osteoarthritis Outcome Score (KOOS)4 defined as the average score for the subscale scores for pain, symptoms, activities of daily living, and quality of life. Secondary outcomes include the five individual KOOS subscale scores, EQ-5D, pain on a 100 mm Visual Analogue Scale, self-efficacy, pain pressure thresholds, and isometric knee flexion and knee extension strength. Discussion This is the first randomised controlled trial to investigate the efficacy of TKA as an adjunct treatment to optimised non-surgical treatment in patients with KOA. The results will significantly contribute to evidence-based recommendations for the treatment of patients with KOA. Trial registration Clinicaltrials.gov reference: NCT01410409 PMID:22571284

Automated Risk Assessment for Stroke in Atrial Fibrillation (AURAS-AF)--an automated software system to promote anticoagulation and reduce stroke risk: study protocol for a cluster randomised controlled trial.

PubMed

Holt, Tim A; Fitzmaurice, David A; Marshall, Tom; Fay, Matthew; Qureshi, Nadeem; Dalton, Andrew R H; Hobbs, F D Richard; Lasserson, Daniel S; Kearley, Karen; Hislop, Jenny; Jin, Jing

2013-11-13

Patients with atrial fibrillation (AF) are at significantly increased risk of stroke. Oral anticoagulants (OACs) substantially reduce this risk, with gains seen across the spectrum of baseline risk. Despite the benefit to patients, OAC prescribing remains suboptimal in the United Kingdom (UK). We will investigate whether an automated software system, operating within primary care electronic medical records, can improve the management of AF by identifying patients eligible for OAC therapy and increasing uptake of this treatment. We will conduct a cluster randomised controlled trial, involving general practices using the Egton Medical Information Systems (EMIS) Web clinical system. We will randomise practices to use an electronic software tool or to continue with usual care. The tool will a) produce (and continually refresh) a list of patients with AF who are eligible for OAC therapy--practices will invite these patients to discuss therapy at the start of the trial--and b) generate electronic screen reminders in the medical records of those eligible, appearing throughout the trial. The software will run for 6 months in 23 intervention practices. A total of 23 control practices will manage their AF register in line with the usual care offered. The primary outcome is change in proportion of eligible patients with AF who have been prescribed OAC therapy after six months. Secondary outcomes are incidence of stroke, transient ischaemic attack, other major thromboembolism, major haemorrhage and reports of inappropriate OAC prescribing in the data collection sample--those deemed eligible for OACs. We will conduct a process evaluation in parallel with the randomised trial. We will use qualitative methods to examine patient and practitioner views of the intervention and its impact on primary care practice, including its time implications. AURAS-AF will investigate whether a simple intervention, using electronic primary care records, can improve OAC uptake in a high risk group for stroke. Given previous concerns about safety, especially surrounding inappropriate prescribing, we will also examine whether electronic reminders safely impact care in this clinical area. http://ISRCTN 55722437.

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

PubMed

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

2015-08-01

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

Anti-inflammatory drugs and analgesics for managing symptoms in people with cystic fibrosis-related arthritis.

PubMed

Thornton, Judith; Rangaraj, Satyapal

2016-01-21

Arthritis remains a relatively infrequent complication of cystic fibrosis, but is a cause of significant morbidity when it does occur. Two distinct types of arthritis are described in cystic fibrosis: cystic fibrosis-related arthropathy (CFA) and hypertrophic pulmonary osteoarthropathy (HPO). Management of arthritis in people with cystic fibrosis is uncertain and complex because of the underlying disease and its intense treatment. This is an update of a previously published review. To review the effectiveness and safety of pharmacological agents for the symptomatic management of cystic fibrosis-related arthritis in adults and children with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.Date of most recent search: 19 January 2016. Randomised controlled studies which compared the efficacy and safety of anti-inflammatory and analgesic agents (e.g. non-steroidal anti-inflammatory agents, systemic corticosteroids, intra-articular corticosteroids) with each other, with no treatment or with placebo for CFA and HPO. No relevant studies were identified. No studies were included in this review. Although it is generally recognised that CFA may be episodic and resolve spontaneously, treatment with analgesics and anti-inflammatory agents may be needed. While this approach may be sufficient to manage symptoms, it is disappointing that no randomised controlled trials to rigorously evaluate these agents were found, nor could the authors identify any quasi-randomised. This systematic review has identified the need for a well-designed adequately-powered randomised controlled trial to assess the efficacy and safety of pharmacological agents for the symptomatic management of cystic fibrosis-related arthritis (CFA and HPO) in adults and children with cystic fibrosis. Studies should also better define the two conditions. A study has recently been conducted in CFA and may help fill this gap when analysed and published.There are no trials included in the review up to January 2016. We will continue to run searches to identify any potentially relevant studies; however, we do not plan to update other sections of the review until new studies are published.

The effect of using an interactive booklet on childhood respiratory tract infections in consultations: study protocol for a cluster randomised controlled trial in primary care.

PubMed

Francis, Nick A; Hood, Kerenza; Simpson, Sharon; Wood, Fiona; Nuttall, Jacqueline; Butler, Christopher C

2008-04-24

Respiratory tract infections in children result in more primary care consultations than any other acute condition, and are the most common reason for prescribing antibiotics (which are largely unnecessary). About a fifth of children consult again for the same illness episode. Providing parents with written information on respiratory tract infections may result in a reduction in re-consultation rates and antibiotic prescribing for these illnesses. Asking clinicians to provide and discuss the information during the consultation may enhance effectiveness. This paper outlines the protocol for a study designed to evaluate the use of a booklet on respiratory tract infections in children within primary care consultations. This will be a cluster randomised controlled trial. General practices will be randomised to provide parents consulting because their child has an acute respiratory tract infection with either an interactive booklet, or usual care. The booklet provides information on the expected duration of their child's illness, the likely benefits of various treatment options, signs and symptoms that should prompt re-consultation, and symptomatic treatment advice. It has been designed for use within the consultation and aims to enhance communication through the use of specific prompts. Clinicians randomised to using the interactive booklet will receive online training in its use. Outcomes will be assessed via a telephone interview with the parent two weeks after first consulting. The primary outcome will be the proportion of children who re-consult for the same illness episode. Secondary outcomes include: antibiotic use, parental satisfaction and enablement, and illness costs. Consultation rates for respiratory tract infections for the subsequent year will be assessed by a review of practice notes. Previous studies in adults and children have shown that educational interventions can result in reductions in re-consultation rates and use of antibiotics for respiratory tract infections. This will be the first study to determine whether providing parents with a booklet on respiratory tract infections in children, and discussing it with them during the consultation, reduces re-consultations and antibiotic use for the same illness without reducing satisfaction with care. Current Controlled Trials ISRCTN46104365.

Protocol for a randomised controlled trial of fetal scalp blood lactate measurement to reduce caesarean sections during labour: the Flamingo trial [ACTRN12611000172909].

PubMed

East, Christine E; Kane, Stefan C; Davey, Mary-Ann; Kamlin, C Omar; Brennecke, Shaun P

2015-11-03

The rate of caesarean sections around the world is rising each year, reaching epidemic proportions. Although many caesarean sections are performed for concerns about fetal welfare on the basis of abnormal cardiotocography, the majority of babies are shown to be well at birth, meaning that the operation, with its inherent short and long term risks, could have been avoided without compromising the baby's health. Previously, fetal scalp blood sampling for pH estimation was performed in the context of an abnormal cardiotocograph, to improve the identification of babies in need of expedited delivery. This test has largely been replaced by lactate measurement, although its validity is yet to be established through a randomised controlled trial. This study aims to test the hypothesis that the performance of fetal scalp blood lactate measurement for women in labour with an abnormal cardiotocograph will reduce the rate of birth by caesarean section from 38 % to 25 % (a 35 % relative reduction). Prospective unblinded randomised controlled trial conducted at a single tertiary perinatal centre. Women labouring with a singleton fetus in cephalic presentation at 37 or more weeks' gestation with ruptured membranes and with an abnormal cardiotocograph will be eligible. Participants will be randomised to one of two groups: fetal monitoring by cardiotocography alone, or cardiotocography augmented by fetal scalp blood lactate analysis. Decisions regarding the timing and mode of delivery will be made by the treating team, in accordance with hospital protocols. The primary study endpoint is caesarean section with secondary outcomes collected from maternal, fetal and neonatal clinical course and morbidities. A cost effectiveness analysis will also be performed. A sample size of 600 will provide 90 % power to detect the hypothesised difference in the proportion of women who give birth by caesarean section. This world-first trial is adequately powered to determine the impact of fetal scalp blood lactate measurement on rates of caesarean section. Preventing unnecessary caesarean sections will reduce the health and financial burdens associated with this operation, both in the index and any future pregnancies. Australian New Zealand Clinical Trials Registry ACTRN12611000172909.

The effects of continuous positive airway pressure therapy on Troponin-T and N-terminal pro B-type natriuretic peptide in patients with obstructive sleep apnoea: a randomised controlled trial.

PubMed

Chang, Ya-Shu; Yee, Brendon J; Hoyos, Camilla M; Wong, Keith K; Sullivan, David R; Grunstein, Ronald R; Phillips, Craig L

2017-11-01

Untreated obstructive sleep apnoea (OSA) is associated with increased risk of coronary artery disease (CAD) and heart failure. High-sensitivity cardiac troponin (hs Trop-T) and B-type natriuretic peptide (NT-pro-BNP) are sensitive biomarkers for myocardial injury and heart failure respectively. No randomised controlled trials have examined the treatment effect of continuous positive airway pressure (CPAP) in patients with OSA on these biomarkers. Patients >21 years old with apnoea-hypopnoea index (AHI) ≥25/h by overnight polysomnography were recruited. Main exclusion criteria were previous CPAP use and any significant comorbidities including CAD and heart failure. Eligible subjects were randomised to receive CPAP or sham CPAP for eight weeks each in a crossover design with a wash out period of one month between the treatments. Blood samples were collected at 8pm, 3am, and 8am during sleep studies conducted at the end of each eight-week treatment period. Of the 37 patients who were randomised, 28 patients had stored frozen samples available for analysis. In comparison to sham treatment, CPAP significantly lowered the NT-pro-BNP level by 0.91 pmol/L (p = 0.0002). The reduction of 0.235 ng/L in hs Trop-T on CPAP therapy was not statistically significant (p = 0.052). There were no overnight changes, across the three time points, in either biomarker with either treatment. Our study confirms CPAP therapy in patients with moderate-severe OSA reduces NT-pro-BNP, but we did not confirm a significant effect on hs Trop-T. Future larger studies of longer duration incorporating biomarkers and cardiac functional measures are needed to better establish the benefit of OSA treatment. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Efficacy and safety of the Shexiang Baoxin Pill for the treatment of coronary artery disease not amenable to revascularisation: study protocol for a randomised, placebo-controlled, double-blinded trial

PubMed Central

Tian, Pan-pan; Li, Jun; Gao, Jian; Li, Ying

2018-01-01

Introduction Coronary artery disease (CAD) not amenable to revascularisation indicates that the coronary arteries have severe diffuse lesions or calcifications, or that CAD is complicated with severe multiple-organ disease. Currently, Western medicines available for the treatment of CAD not amenable to revascularisation are limited. Shexiang Baoxin Pill (SBP), a type of Chinese patent medicine, has been widely used to treat CAD in China for many years. Previous studies have shown that long-term administration of SBP (1–2 pills three times daily, for at least 6 months) for treatment of CAD is effective and safe, with a significant, long-term effect. This study aims to evaluate the efficacy and safety of SBP in patients with CAD not amenable to revascularisation. Methods and analysis This is a multicentre, randomised, double-blinded, placebo-controlled clinical trial. A total of 440 participants will be randomly allocated to two groups: the intervention group and the placebo group. Based on conventional treatment with Western medicine, the intervention group will be treated with SBP and the placebo group will be treated with SBP placebo. The primary outcomes include major adverse cardiovascular events (including angina, acute myocardial infarction, pulmonary embolism and aortic dissection). The secondary outcomes include C reactive protein, B-type natriuretic peptide, ECG, echocardiographic parameters (ejection fraction percentage and the E/A ratio) and hospital readmission rates due to CAD. Assessments will be performed at baseline (before randomisation) and at 24 weeks after randomisation. Ethics and dissemination The protocol has been approved by the Research Ethics Committee of Guang’anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, China (reference: 2016-129-KY-01). The results of this study will be published in a peer-reviewed journal and will be used as a basis for a multisite trial. Trial registration number NCT03072121; Pre-results. PMID:29444778

Ultrasound imaging to tailor the treatment of acute shoulder pain: a randomised controlled trial in general practice.

PubMed

Ottenheijm, Ramon P G; Cals, Jochen W L; Winkens, Bjorn; Weijers, René E; de Bie, Rob A; Dinant, Geert-Jan

2016-11-21

To determine the clinical effectiveness of ultrasound tailored treatment in patients with acute subacromial disorders. Pragmatic randomised controlled trial. Dutch general practice. Patients aged 18-65 years with acute (duration <3 months) unilateral shoulder pain and no previous treatment, in whom the general practitioner suspected a subacromial disorder was enrolled. All patients underwent ultrasound imaging of the affected shoulder. Patients who were still symptomatic after a qualification period of 2 weeks with standard treatment were randomised to treatment tailored to ultrasound diagnosis (disclosure of the ultrasound diagnosis) or usual care (non-disclosure of the ultrasound diagnosis). Patient-perceived recovery using the Global Perceived Effect questionnaire at 1 year. 129 patients were included. 18 patients recovered during the 2-week qualification period, resulting in 111 randomised patients; 56 were allocated to ultrasound tailored treatment and 55 to usual care. After 1 year, no statistically significant differences in recovery were found between the ultrasound tailored treatment group (72.5% (37/51)) and the usual care group (60% (30/50), OR 2.24 (95% CI 0.72 to 6.89; p=0.16)). Also, healthcare use was similar. This study has shown no clinically significant difference in the primary outcome measure between the ultrasound tailored treatment and usual care groups. Furthermore, there was no overall difference in healthcare resources used between groups. Although no formal cost data are included, one can only assume that the ultrasound examinations are additional costs for the intervention group, which cannot be justified in routine practice based on this trial. Based on this study, no change in current pragmatic guidelines to incorporate early ultrasound imaging can be recommended. NTR2403; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Self-reported quality of life before and after aerobic exercise training in individuals with hypertension: a randomised-controlled trial.

PubMed

Maruf, Fatai A; Akinpelu, Aderonke O; Salako, Babatunde L

2013-07-01

The Effects of Aerobic Exercise Training (AET) on self-reported Quality of Life (QoL) in people with hypertension have been previously documented. However, data on black populations, especially from Africa, seem not to be available. This study investigated the effects of AET on QoL and exercise capacity in Nigerians on treatment for essential hypertension. This randomised-controlled trial involved newly diagnosed individuals, with mild-to-moderate essential hypertension randomly assigned to antihypertensive drugs (ADs) alone (control: n = 60) and AET+ADs (exercise: n = 60) groups. The study lasted for 12 weeks. QoL was measured using the World Health Organization QoL Short Form (WHOQoL-BREF) and exercise capacity was assessed using the Rockport Fitness Walk Test pre- and post-study. Physical health, psychological health, and social relationships domains of QoL improved significantly in the exercise and control groups post-intervention. The environment domain of QoL and exercise capacity improved significantly in only the exercise group. There were larger improvements in the physical health, psychological health, and environment domains of QoL, and exercise capacity in the exercise group. Aerobic exercise improves QoL and exercise capacity in individuals with essential hypertension. © 2013 The Authors. Applied Psychology: Health and Well-Being © 2013 The International Association of Applied Psychology.

Randomised controlled trial of routine individual feedback to improve rationality and reduce numbers of test requests.

PubMed

Winkens, R A; Pop, P; Bugter-Maessen, A M; Grol, R P; Kester, A D; Beusmans, G H; Knottnerus, J A

1995-02-25

Feedback can be described as a way to provide information on doctors' performance to enable changes in future behaviour. Feedback is used with the aim of changing test-ordering behaviour. It can lead to reductions in test usage and cost savings. It is not sufficiently clear, however, whether feedback leads to more appropriate test use. Since 1985, the Diagnostic Coordinating Center Maastricht has been giving feedback on diagnostic tests as a routine health care activity to all family doctors in its region. Both quantity and quality of requests are discussed. In a randomised, controlled trial over 2.5 years, discussion of tests not included previously was added to the existing routine feedback. One group of family doctors (n = 39) received feedback on test-group A (electrocardiography, endoscopy, cervical smears, and allergy tests), the other (n = 40) on test-group B (radiographic and ultrasonographic tests). Thus, each group of doctors acted as a control group for the other. Changes in volume and rationality of requests were analysed. The number of requests decreased during the trial (p = 0.036). Request numbers decreased particularly for test-group A (p = 0.04). The proportion of requests that were non-rational decreased more in the intervention than in the control groups (p = 0.009). Rationality improved predominantly for test-group B (p = 0.043). Thus, routine feedback can change the quantity and quality of requests.

Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial.

PubMed

Krug, Lee M; Kindler, Hedy L; Calvert, Hilary; Manegold, Christian; Tsao, Anne S; Fennell, Dean; Öhman, Ronny; Plummer, Ruth; Eberhardt, Wilfried E E; Fukuoka, Kazuya; Gaafar, Rabab M; Lafitte, Jean-Jacques; Hillerdal, Gunnar; Chu, Quincy; Buikhuisen, Wieneke A; Lubiniecki, Gregory M; Sun, Xing; Smith, Margaret; Baas, Paul

2015-04-01

Vorinostat is a histone deacetylase inhibitor that changes gene expression and protein activity. On the basis of the clinical benefit reported in patients with malignant pleural mesothelioma treated in a phase 1 study of vorinostat, we designed this phase 3 trial to investigate whether vorinostat given as a second-line or third-line therapy improved patients' overall survival. This double-blind, randomised, placebo-controlled trial was done in 90 international centres. Patients with measurable advanced malignant pleural mesothelioma and disease progression after one or two previous systemic regimens were eligible. After stratification for Karnofsky performance status, histology, and number of previous chemotherapy regimens, patients were randomly assigned (1:1) by use of an interactive voice response system with a block size of four to either treatment with vorinostat or placebo. Patients received oral vorinostat 300 mg (or matching placebo) twice daily on days 1, 2, 3, 8, 9, 10, 15, 16, and 17 of a 21-day cycle. The primary endpoints were overall survival and safety and tolerability of vorinostat. The primary efficacy comparison was done in the intention-to-treat population, and safety and tolerability was assessed in the treated population. This trial is registered with ClinicalTrials.gov, number NCT00128102. From July 12, 2005, to Feb 14, 2011, 661 patients were enrolled and randomly assigned to receive either vorinostat (n=329) or placebo (n=332) and included in the intention-to-treat analysis. Median overall survival for vorinostat was 30·7 weeks (95% CI 26·7-36·1) versus 27·1 weeks (23·1-31·9) for placebo (hazard ratio 0·98, 95% CI 0·83-1·17, p=0·86). The most common grade 3 or worse adverse events for patients treated with vorinostat were fatigue or malaise (51 [16%] patients in the vorinostat group vs 25 [8%] in the placebo group]) and dyspnoea (35 [11%] vs 45 [14%]). In this randomised trial, vorinostat given as a second-line or third-line therapy did not improve overall survival and cannot be recommended as a therapy for patients with advanced malignant pleural mesothelioma. Merck & Co. Copyright © 2015 Elsevier Ltd. All rights reserved.

Use of qualitative methods alongside randomised controlled trials of complex healthcare interventions: methodological study

PubMed Central

Glenton, Claire; Oxman, Andrew D

2009-01-01

Objective To examine the use of qualitative approaches alongside randomised trials of complex healthcare interventions. Design Review of randomised controlled trials of interventions to change professional practice or the organisation of care. Data sources Systematic sample of 100 trials published in English from the register of the Cochrane Effective Practice and Organisation of Care Review Group. Methods Published and unpublished qualitative studies linked to the randomised controlled trials were identified through database searches and contact with authors. Data were extracted from each study by two reviewers using a standard form. We extracted data describing the randomised controlled trials and qualitative studies, the quality of these studies, and how, if at all, the qualitative and quantitative findings were combined. A narrative synthesis of the findings was done. Results 30 of the 100 trials had associated qualitative work and 19 of these were published studies. 14 qualitative studies were done before the trial, nine during the trial, and four after the trial. 13 studies reported an explicit theoretical basis and 11 specified their methodological approach. Approaches to sampling and data analysis were poorly described. For most cases (n=20) we found no indication of integration of qualitative and quantitative findings at the level of either analysis or interpretation. The quality of the qualitative studies was highly variable. Conclusions Qualitative studies alongside randomised controlled trials remain uncommon, even where relatively complex interventions are being evaluated. Most of the qualitative studies were carried out before or during the trials with few studies used to explain trial results. The findings of the qualitative studies seemed to be poorly integrated with those of the trials and often had major methodological shortcomings. PMID:19744976

The value of a pilot study in breast-feeding research.

PubMed

Carfoot, Sue; Williamson, Paula R; Dickson, Rumona

2004-06-01

To test the integrity of a protocol for a randomised controlled trial (RCT) to examine the effectiveness of skin-to-skin care compared to routine care on the initiation and duration of breast feeding and to provide data to be used in the power calculation for a proposed trial. Randomised pilot study. Warrington Hospital, Cheshire, UK. Women at 36 weeks' gestation with healthy singleton pregnancies, who intended to breast feed, who had 'booked' for care at Warrington Hospital and had given informed consent to participate. Twenty-eight women were randomised in the pilot study. Women were randomly allocated to receive either routine or skin-to-skin care following birth. The first breast feed was assessed using the Breast-feeding Assessment Tool (BAT). Mothers were followed up at discharge from hospital and again at four months to provide details of duration of breast feeding. 66 women were approached to participate in the trial and 44 consented (67% consent rate). Twenty-eight women were randomised in the study and 26 breast feeds were observed (93%). The pilot study identified procedural changes that were required in the design of the main study, provided an estimate of recruitment rates and confirmed the previously calculated sample size. The pilot study demonstrated that a large RCT of skin-to-skin versus routine care was feasible. This is an example of how a pilot study has the ability to identify unforeseen challenges in the conduct of the trial as well as allowing necessary changes to be made to the design that will increase the quality of the subsequent research.

Non-pharmacological interventions for people with epilepsy and intellectual disabilities.

PubMed

Jackson, Cerian F; Makin, Selina M; Marson, Anthony G; Kerr, Michael

2015-09-10

Approximately 30% of patients with epilepsy remain refractory to drug treatment and continue to experience seizures whilst taking one or more antiepileptic drugs (AEDs). Several non-pharmacological interventions that may be used in conjunction with or as an alternative to AEDs are available for refractory patients. In view of the fact that seizures in people with intellectual disabilities are often complex and refractory to pharmacological interventions, it is evident that good quality randomised controlled trials (RCTs) are needed to assess the efficacy of alternatives or adjuncts to pharmacological interventions.This is an updated version of the original Cochrane review (Beavis 2007) published in The Cochrane Library (2007, Issue 4). To assess data derived from randomised controlled trials of non-pharmacological interventions for people with epilepsy and intellectual disabilities.Non-pharmacological interventions include, but are not limited to, the following.• Surgical procedures.• Specialised diets, for example, the ketogenic diet, or vitamin and folic acid supplementation.• Psychological interventions for patients or for patients and carers/parents, for example, cognitive-behavioural therapy (CBT), electroencephalographic (EEG) biofeedback and educational intervention.• Yoga.• Acupuncture.• Relaxation therapy (e.g. music therapy). For the latest update of this review, we searched the Cochrane Epilepsy Group Specialised Register (19 August 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) via CRSO (19 August 2014), MEDLINE (Ovid, 1946 to 19 August 2014) and PsycINFO (EBSCOhost, 1887 to 19 August 2014). Randomised controlled trials of non-pharmacological interventions for people with epilepsy and intellectual disabilities. Two review authors independently applied the inclusion criteria and extracted study data. One study is included in this review. When two surgical procedures were compared, results indicated that corpus callosotomy with anterior temporal lobectomy was more effective than anterior temporal lobectomy alone in improving quality of life and performance on IQ tests among people with epilepsy and intellectual disabilities. No evidence was found to support superior benefit in seizure control for either intervention. This is the only study of its kind and was rated as having an overall unclear risk of bias. The previous update (December 2010) identified one RCT in progress. The study authors have confirmed that they are aiming to publish by the end of 2015; therefore this study (Bjurulf 2008) has not been included in the current review. This review highlights the need for well-designed randomised controlled trials conducted to assess the effects of non-pharmacological interventions on seizure and behavioural outcomes in people with intellectual disabilities and epilepsy.

Effects of an antiatherogenic diet during pregnancy on markers of maternal and fetal endothelial activation and inflammation: the CARRDIP study

PubMed Central

Khoury, J; Henriksen, T; Seljeflot, I; Mørkrid, L; Frøslie, KF; Tonstad, S

2007-01-01

Objective To study the effect of an antiatherogenic diet on maternal and cord blood concentrations of systemic biomarkers of endothelial cell activation, haemostasis and inflammation. Design Single blinded randomised controlled clinical trial. Setting Obstetric outpatient clinic and maternity unit of a university hospital in Norway. Population Nonsmoking pregnant women aged 21–38 years carrying a single fetus and with no previous pregnancy-related complications. Methods Subjects (n = 290) were randomised to continue their usual diet or to adopt a diet low in saturated fat and cholesterol from gestational week 17–20 to birth. Soluble forms of cellular adhesion molecules, high-sensitivity C-reactive protein (CRP) and haemostatic markers were measured at 17–20 weeks of gestation (baseline) and subsequently up to week 36. All the above, except CRP, were also measured in cord blood. Main outcome measures Concentrations of maternal and fetal biomarkers and maternal CRP. Results All biomarkers except CRP levels increased significantly during the study period in both the intervention and control groups. None of the maternal or fetal biomarkers were influenced by the intervention (P > 0.05) except for a tendency to lower concentrations of cord blood tissue plasminogen activator antigen in the intervention group compared with the control group, median (interquartile range) 5.4 ng/ml (3.1–7.7) versus 5.8 ng/ml (3.5–11.8), P = 0.05. Conclusion An antiatherogenic diet in pregnancy did not significantly influence maternal or fetal blood concentrations of a range of biomarkers for inflammation. Thus, the previously reported effects of a cholesterol-lowering diet on maternal lipid profile and preterm delivery (<37 complete weeks of gestation) do not seem to involve changes in the systemic inflammatory responses of pregnancy. PMID:17217362

Effectiveness of conventional versus virtual reality based vestibular rehabilitation in the treatment of dizziness, gait and balance impairment in adults with unilateral peripheral vestibular loss: a randomised controlled trial.

PubMed

Meldrum, Dara; Herdman, Susan; Moloney, Roisin; Murray, Deirdre; Duffy, Douglas; Malone, Kareena; French, Helen; Hone, Stephen; Conroy, Ronan; McConn-Walsh, Rory

2012-03-26

Unilateral peripheral vestibular loss results in gait and balance impairment, dizziness and oscillopsia. Vestibular rehabilitation benefits patients but optimal treatment remains unknown. Virtual reality is an emerging tool in rehabilitation and provides opportunities to improve both outcomes and patient satisfaction with treatment. The Nintendo Wii Fit Plus® (NWFP) is a low cost virtual reality system that challenges balance and provides visual and auditory feedback. It may augment the motor learning that is required to improve balance and gait, but no trials to date have investigated efficacy. In a single (assessor) blind, two centre randomised controlled superiority trial, 80 patients with unilateral peripheral vestibular loss will be randomised to either conventional or virtual reality based (NWFP) vestibular rehabilitation for 6 weeks. The primary outcome measure is gait speed (measured with three dimensional gait analysis). Secondary outcomes include computerised posturography, dynamic visual acuity, and validated questionnaires on dizziness, confidence and anxiety/depression. Outcome will be assessed post treatment (8 weeks) and at 6 months. Advances in the gaming industry have allowed mass production of highly sophisticated low cost virtual reality systems that incorporate technology previously not accessible to most therapists and patients. Importantly, they are not confined to rehabilitation departments, can be used at home and provide an accurate record of adherence to exercise. The benefits of providing augmented feedback, increasing intensity of exercise and accurately measuring adherence may improve conventional vestibular rehabilitation but efficacy must first be demonstrated. Clinical trials.gov identifier: NCT01442623.

RESPIRE 1: a phase III placebo-controlled randomised trial of ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis.

PubMed

De Soyza, Anthony; Aksamit, Timothy; Bandel, Tiemo-Joerg; Criollo, Margarita; Elborn, J Stuart; Operschall, Elisabeth; Polverino, Eva; Roth, Katrin; Winthrop, Kevin L; Wilson, Robert

2018-01-01

We evaluated the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in patients with non-cystic fibrosis bronchiectasis, two or more exacerbations in the previous year and pre-defined bacteria in sputum.In this phase III, double-blind, placebo-controlled trial, patients were randomised 2:1 to twice-daily ciprofloxacin DPI 32.5 mg or placebo in two treatment regimens consisting of on/off treatment cycles of 14 or 28 days for 48 weeks. The primary end-points were time to first exacerbation and frequency of exacerbations.A total of 416 patients were randomised to the 14-day on/off regimen (ciprofloxacin DPI (n=137) and placebo (n=68)) or the 28-day on/off regimen (ciprofloxacin DPI (n=141) and placebo (n=70)). Ciprofloxacin DPI 14 days on/off significantly prolonged time to first exacerbation versus pooled placebo (median time >336 versus 186 days; hazard ratio 0.53, 97.5% CI 0.36-0.80; p=0.0005) and reduced the frequency of exacerbations compared with matching placebo by 39% (mean number of exacerbations 0.6 versus 1.0; incidence rate ratio 0.61, 97.5% CI 0.40-0.91; p=0.0061). Outcomes for ciprofloxacin DPI 28 days on/off were not statistically significantly different from placebo. The safety profile of ciprofloxacin DPI was favourable.Ciprofloxacin DPI was well tolerated and has the potential to be an effective treatment option in non-cystic fibrosis bronchiectasis. Copyright ©ERS 2018.

Modafinil combined with cognitive training is associated with improved learning in healthy volunteers--a randomised controlled trial.

PubMed

Gilleen, J; Michalopoulou, P G; Reichenberg, A; Drake, R; Wykes, T; Lewis, S W; Kapur, S

2014-04-01

Improving cognition in people with neuropsychiatric disorders remains a major clinical target. By themselves pharmacological and non-pharmacological approaches have shown only modest effects in improving cognition. In the present study we tested a recently-proposed methodology to combine CT with a 'cognitive-enhancing' drug to improve cognitive test scores and expanded on previous approaches by delivering combination drug and CT, over a long intervention of repeated sessions, and used multiple tasks to reveal the cognitive processes being enhanced. We also aimed to determine whether gains from this combination approach generalised to untrained tests. In this proof of principle randomised-controlled trial thirty-three healthy volunteers were randomised to receive either modafinil or placebo combined with daily cognitive training over two weeks. Volunteers were trained on tasks of new-language learning, working memory and verbal learning following 200 mg modafinil or placebo for ten days. Improvements in trained and untrained tasks were measured. Rate of new-language learning was significantly enhanced with modafinil, and effects were greatest over the first five sessions. Modafinil improved within-day learning rather than between-day retention. No enhancement of gains with modafinil was observed in working memory nor rate of verbal learning. Gains in all tasks were retained post drug-administration, but transfer effects to broad cognitive abilities were not seen. This study shows that combining CT with modafinil specifically elevates learning over early training sessions compared to CT with placebo and provides a proof of principle experimental paradigm for pharmacological enhancement of cognitive remediation. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Cross-sectional associations between dietary intake and carotid intima media thickness in type 2 diabetes: baseline data from a randomised trial

PubMed Central

Chiavaroli, Laura; Mirrahimi, Arash; Ireland, Christopher; Mitchell, Sandra; Sahye-Pudaruth, Sandhya; Coveney, Judy; Olowoyeye, Omodele; Patel, Darshna; de Souza, Russell J; Augustin, Livia S A; Bashyam, Balachandran; Pichika, Sathish Chandra; Blanco Mejia, Sonia; Nishi, Stephanie K; Leiter, Lawrence A; Josse, Robert G; McKeown-Eyssen, Gail E; Moody, Alan R; Kendall, Cyril W C; Sievenpiper, John L; Jenkins, David J A

2017-01-01

Objective To assess associations between dietary intake and carotid intima media thickness (CIMT) by carotid ultrasound (CUS), a surrogate marker of cardiovascular disease (CVD) risk, in those with type 2 diabetes. Design Cross-sectional analysis of baseline data from 325 participants from three randomised controlled trials collected in the same way. Setting Risk Factor Modification Centre, St. Michael's Hospital, Toronto, Canada. Participants 325 participants with type 2 diabetes, taking oral antidiabetic agents, with an HbA1c between 6.5% and 8.0% at screening, without a recent cardiovascular event. Main outcome measures CIMT by CUS and associations with dietary intake from 7-day food records, as well as anthropometric measures and fasting serum samples. Results CIMT was significantly inversely associated with dietary pulse intake (β=−0.019, p=0.009), available carbohydrate (β=−0.004, p=0.008), glycaemic load (β=−0.001, p=0.007) and starch (β=−0.126, p=0.010), and directly associated with total (β=0.004, p=0.028) and saturated (β=0.012, p=0.006) fat intake in multivariate regression models adjusted for age, smoking, previous CVD event, blood pressure medication, antidiabetic medication and ultrasonographer. Conclusions Lower CIMT was significantly associated with greater consumption of dietary pulses and carbohydrates and lower total and saturated fat intake, suggesting a potential role for diet in CVD risk management in type 2 diabetes. Randomised controlled trials are anticipated to explore these associations further. Trial registration number NCT01063374. PMID:28336747

Participant experiences from chronic administration of a multivitamin versus placebo on subjective health and wellbeing: a double-blind qualitative analysis of a randomised controlled trial

PubMed Central

2012-01-01

Background While many randomised controlled trials have been conducted on multivitamins, to our knowledge no qualitative research exploring the subjective experience of taking a multivitamin during a clinical trial has been reported. Methods Semi-structured and open-ended written questions were incorporated into a 16-week double-blind, randomised, placebo-controlled, parallel groups trial of once-daily multivitamin administration. At the final study visit (week 16), three open-ended questions were posed to elucidate any positive, negative or unusual experiences from taking either the multivitamin or matched placebo. Qualitative thematic analysis was undertaken by researchers who were blind as to treatment condition of participants, and triangulation (independent analysis from three researchers) was employed to ensure methodological rigour. Participant’s experiences were categorised as “positive” or “negative” and a Chi Square analysis was then applied to each of the experiential themes, to compare experiences between the multivitamin and placebo groups, (subdividing the groups by gender). Usual experiences were categorised and discussed separately. Results Of the 182 participants enrolled, 116 completed the study and qualitative data were available from 114 participants. Thematic analysis revealed significant effects in favour of the multivitamin over placebo for participants experiencing increased energy levels (p=.022) and enhanced mood (p=.027). The beneficial effect on energy levels was particularly evident among female participants. A trend was found for participants reporting better sleep in the multivitamin over placebo. The multivitamin and placebo groups did not significantly differ in perceived positive or negative effects in areas relating to other aspects of mental function or physical health. No significant negative effects were revealed, although there was a non-significant trend for more people in the multivitamin group having minor digestive complaints. Conclusion This represents the first documented qualitative investigation of participants’ experience of chronic administration of a multivitamin. Results uncovered a range of subjective beneficial effects that are consistent with quantitative data from previously published randomised controlled trials examining the effects of multivitamins and B vitamin complexes on mood and well-being. Trial registration Prior to commencement this trial was registered with the Australian New Zealand Clinical Trials Registry ( http://www.anzctr.org.au) ACTRN12611000092998 PMID:23241329

Feasibility of an online mindfulness-based program for patients with melanoma: study protocol for a randomised controlled trial.

PubMed

Russell, Lahiru; Ugalde, Anna; Milne, Donna; Krishnasamy, Meinir; O Seung Chul, Eric; Austin, David W; Chambers, Richard; Orellana, Liliana; Livingston, Patricia M

2018-04-13

People with a melanoma diagnosis are at risk of recurrence, developing a new primary or experiencing disease progression. Previous studies have suggested that fear of a cancer recurrence is clinically relevant in this group of patients and, if not addressed, can lead to distress. Mindfulness-based interventions have been shown to alleviate symptoms of anxiety and depression among various groups of cancer patients. Online mindfulness-based interventions have the potential to reach people unable to attend face-to-face interventions due to limitations such as cancer-related illness, transportation or time constraints. This study aims to (1) examine whether individuals with a melanoma diagnosis are willing to participate and adhere to a 6-week online mindfulness-based intervention and (2) explore potential benefits of the program on fear of cancer recurrence, worries, rumination, perceived stress and trait mindfulness to inform the design of a clinical trial. This is a single-site randomised controlled trial of a feasibility study. Seventy-five participants with stage 2c or 3 melanoma will be recruited from a melanoma outpatient clinic and randomised (2:1) either to an online mindfulness-based program (intervention) or to usual care (control). The intervention is a 6-week program specifically developed for this study. It consists of videos describing the concept of mindfulness, short daily guided meditation practices (5-10 min), automated meditation reminders and instructions for applying mindfulness in daily life to enhance wellbeing. All participants will complete questionnaires at baseline and at 6-week post-randomisation. Participants in the control group will be given access to the online program at the end of the study. Primary outcomes are overall recruitment; retention; extent of questionnaire completion; and usability and acceptability of, and adherence to, the program. The secondary outcomes are fear of cancer recurrence, worries, rumination, perceived stress and trait mindfulness measured using validated instruments. This feasibility study will evaluate participants' satisfaction with the program and identify barriers to recruitment and adherence. The recruitment and data collection process will highlight methodological aspects to address in the planning of a larger scale study assessing the impact of an online mindfulness-based intervention on fear of cancer recurrence and wellbeing. Australian New Zealand Clinical Trials Registry, ACTRN12617000081314 . Registered on 16 January 2017.

Time Regained: When People Stop a Physical Activity Program, How Does Their Time Use Change? A Randomised Controlled Trial

PubMed Central

Gomersall, Sjaan; Maher, Carol; English, Coralie; Rowlands, Alex; Olds, Tim

2015-01-01

The aim of this study was to investigate how previously inactive adults who had participated in a structured, partly supervised 6-week exercise program restructured their time budgets when the program ended. Using a randomised controlled trial design, 129 previously inactive adults were recruited and randomly allocated to one of three groups: a Moderate or Extensive six-week physical activity intervention (150 and 300 additional minutes of exercise per week, respectively) or a Control group. Additional physical activity was accumulated through both group and individual exercise sessions with a wide range of activities. Use of time and time spent in energy expenditure zones was measured using a computerised 24-h self-report recall instrument, the Multimedia Activity Recall for Children and Adults, and accelerometry at baseline, mid- and end-program and at 3- and 6-months follow up. At final follow up, all significant changes in time use domains had returned to within 20 minutes of baseline levels (Physical Activity 1-2 min/d, Active Transport 3-9 min/d, Self-Care 0-2 min/d, Television/Videogames 13-18 min/d in the Moderate and Extensive group, relative to Controls, respectively, p>0.05). Similarly, all significant changes in time spent in the moderate energy expenditure zone had returned to within 1-3 min/d baseline levels (p>0.05), however time spent in vigorous physical activity according to accelerometry estimates remained elevated, although the changes were small in magnitude (1 min/d in the Moderate and Extensive groups, relative to Controls, p=0.01). The results of this study demonstrate strong recidivist patterns in physical activity, but also in other aspects of time use. In designing and determining the effectiveness of exercise interventions, future studies would benefit from considering the whole profile of time use, rather than focusing on individual activities. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12610000248066 PMID:26023914

Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomised controlled trials.

PubMed

Goldie, Christina; Taylor, Allen J; Nguyen, Peter; McCoy, Cody; Zhao, Xue-Qiao; Preiss, David

2016-02-01

Previous studies have suggested that niacin treatment raises glucose levels in patients with diabetes and may increase the risk of developing diabetes. We undertook a meta-analysis of published and unpublished data from randomised trials to confirm whether an association exists between niacin and new-onset diabetes. We searched Medline, EMBASE and the Cochrane Central Register of Controlled Trials, from 1975 to 2014, for randomised controlled trials of niacin primarily designed to assess its effects on cardiovascular endpoints and cardiovascular surrogate markers. We included trials with ≥50 non-diabetic participants and average follow-up of ≥24 weeks. Published data were tabulated and unpublished data sought from investigators. We calculated risk ratios (RR) for new-onset diabetes with random-effects meta-analysis. Heterogeneity between trials was assessed using the I(2) statistic. In 11 trials with 26 340 non-diabetic participants, 1371 (725/13 121 assigned niacin; 646/13 219 assigned control) were diagnosed with diabetes during a weighted mean follow-up of 3.6 years. Niacin therapy was associated with a RR of 1.34 (95% CIs 1.21 to 1.49) for new-onset diabetes, with limited heterogeneity between trials (I(2)=0.0%, p=0.87). This equates to one additional case of diabetes per 43 (95% CI 30 to 70) initially non-diabetic individuals who are treated with niacin for 5 years. Results were consistent regardless of whether participants received background statin therapy (p for interaction=0.88) or combined therapy with laropiprant (p for interaction=0.52). Niacin therapy is associated with a moderately increased risk of developing diabetes regardless of background statin or combination laropiprant therapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The effects of an extensive exercise programme on the progression of Mild Cognitive Impairment (MCI): study protocol for a randomised controlled trial.

PubMed

Devenney, Kate E; Sanders, Marit L; Lawlor, Brian; Olde Rikkert, Marcel G M; Schneider, Stefan

2017-03-22

Exercise interventions to prevent dementia and delay cognitive decline have gained considerable attention in recent years. Human and animal studies have demonstrated that regular physical activity targets brain function by increasing cognitive reserve. There is also evidence of structural changes caused by exercise in preventing or delaying the genesis of neurodegeneration. Although initial studies indicate enhanced cognitive performance in patients with mild cognitive impairment (MCI) following an exercise intervention, little is known about the effect of an extensive, controlled and regular exercise regimen on the neuropathology of patients with MCI. This study aims to determine the effects of an extensive exercise programme on the progression of MCI. This randomised controlled clinical intervention study will take place across three European sites. Seventy-five previously sedentary patients with a clinical diagnosis of MCI will be recruited at each site. Participants will be randomised to one of three groups. One group will receive a standardised 1-year extensive aerobic exercise intervention (3 units of 45 min/week). The second group will complete stretching and toning (non-aerobic) exercise (3 units of 45 min/week) and the third group will act as the control group. Change in all outcomes will be measured at baseline (T0), after six months (T1) and after 12 months (T2). The primary outcome, cognitive performance, will be determined by a neuropsychological test battery (CogState battery, Trail Making Test and Verbal fluency). Secondary outcomes include Montreal Cognitive Assessment (MoCA), cardiovascular fitness, physical activity, structural changes of the brain, quality of life measures and measures of frailty. Furthermore, outcome variables will be related to genetic variations on genes related to neurogenesis and epigenetic changes in these genes caused by the exercise intervention programme. The results will add new insights into the prevailing notion that exercise may slow the rate of cognitive decline in MCI. ClinicalTrials.gov NCT02913053.

Structure and content components of self-management interventions that improve health-related quality of life in people with inflammatory bowel disease: a systematic review, meta-analysis and meta-regression.

PubMed

Tu, Wenjing; Xu, Guihua; Du, Shizheng

2015-10-01

The purpose of this review was to identify and categorise the components of the content and structure of effective self-management interventions for patients with inflammatory bowel disease. Inflammatory bowel diseases are chronic gastrointestinal disorders impacting health-related quality of life. Although the efficacy of self-management interventions has been demonstrated in previous studies, the most effective components of the content and structure of these interventions remain unknown. A systematic review, meta-analysis and meta-regression of randomised controlled trials was used. A systematic search of six electronic databases, including Pubmed, Embase, Cochrane central register of controlled trials, Web of Science, Cumulative Index of Nursing and Allied Health Literature and Chinese Biomedical Literature Database, was conducted. Content analysis was used to categorise the components of the content and structure of effective self-management interventions for inflammatory bowel disease. Clinically important and statistically significant beneficial effects on health-related quality of life were explored, by comparing the association between effect sizes and various components of self-management interventions such as the presence or absence of specific content and different delivery methods. Fifteen randomised controlled trials were included in this review. Distance or remote self-management interventions demonstrated a larger effect size. However, there is no evidence for a positive effect associated with specific content component of self-management interventions in adult patients with inflammatory bowel disease in general. The results showed that self-management interventions have positive effects on health-related quality of life in patients with inflammatory bowel disease, and distance or remote self-management programmes had better outcomes than other types of interventions. This review provides useful information to clinician and researchers when determining components of effective self-management programmes for patients with inflammatory bowel disease. More high-quality randomised controlled trials are needed to test the results. © 2015 John Wiley & Sons Ltd.

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

PubMed

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

2015-09-28

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

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.

Effectiveness and cost-effectiveness of an educational intervention for practice teams to deliver problem focused therapy for insomnia: rationale and design of a pilot cluster randomised trial

PubMed Central

Siriwardena, A Niroshan; Apekey, Tanefa; Tilling, Michelle; Harrison, Andrew; Dyas, Jane V; Middleton, Hugh C; Ørner, Roderick; Sach, Tracey; Dewey, Michael; Qureshi, Zubair M

2009-01-01

Background Sleep problems are common, affecting over a third of adults in the United Kingdom and leading to reduced productivity and impaired health-related quality of life. Many of those whose lives are affected seek medical help from primary care. Drug treatment is ineffective long term. Psychological methods for managing sleep problems, including cognitive behavioural therapy for insomnia (CBTi) have been shown to be effective and cost effective but have not been widely implemented or evaluated in a general practice setting where they are most likely to be needed and most appropriately delivered. This paper outlines the protocol for a pilot study designed to evaluate the effectiveness and cost-effectiveness of an educational intervention for general practitioners, primary care nurses and other members of the primary care team to deliver problem focused therapy to adult patients presenting with sleep problems due to lifestyle causes, pain or mild to moderate depression or anxiety. Methods and design This will be a pilot cluster randomised controlled trial of a complex intervention. General practices will be randomised to an educational intervention for problem focused therapy which includes a consultation approach comprising careful assessment (using assessment of secondary causes, sleep diaries and severity) and use of modified CBTi for insomnia in the consultation compared with usual care (general advice on sleep hygiene and pharmacotherapy with hypnotic drugs). Clinicians randomised to the intervention will receive an educational intervention (2 × 2 hours) to implement a complex intervention of problem focused therapy. Clinicians randomised to the control group will receive reinforcement of usual care with sleep hygiene advice. Outcomes will be assessed via self-completion questionnaires and telephone interviews of patients and staff as well as clinical records for interventions and prescribing. Discussion Previous studies in adults have shown that psychological treatments for insomnia administered by specialist nurses to groups of patients can be effective within a primary care setting. This will be a pilot study to determine whether an educational intervention aimed at primary care teams to deliver problem focused therapy for insomnia can improve sleep management and outcomes for individual adult patients presenting to general practice. The study will also test procedures and collect information in preparation for a larger definitive cluster-randomised trial. The study is funded by The Health Foundation. Trial Registration ClinicalTrials.gov ID ISRCTN55001433 – PMID:19171070

Facet joint injections for people with persistent non-specific low back pain (Facet Injection Study): a feasibility study for a randomised controlled trial.

PubMed

Ellard, David R; Underwood, Martin; Achana, Felix; Antrobus, James Hl; Balasubramanian, Shyam; Brown, Sally; Cairns, Melinda; Griffin, James; Griffiths, Frances; Haywood, Kirstie; Hutchinson, Charles; Lall, Ranjit; Petrou, Stavros; Stallard, Nigel; Tysall, Colin; Walsh, David A; Sandhu, Harbinder

2017-05-01

The National Institute for Health and Care Excellence (NICE) 2009 guidelines for persistent low back pain (LBP) do not recommend the injection of therapeutic substances into the back as a treatment for LBP because of the absence of evidence for their effectiveness. This feasibility study aimed to provide a stable platform that could be used to evaluate a randomised controlled trial (RCT) on the clinical effectiveness and cost-effectiveness of intra-articular facet joint injections (FJIs) when added to normal care. To explore the feasibility of running a RCT to test the hypothesis that, for people with suspected facet joint back pain, adding the option of intra-articular FJIs (local anaesthetic and corticosteroids) to best usual non-invasive care is clinically effective and cost-effective. The trial was a mixed design. The RCT pilot protocol development involved literature reviews and a consensus conference followed by a randomised pilot study with an embedded mixed-methods process evaluation. Five NHS acute trusts in England. Participants were patients aged ≥ 18 years with moderately troublesome LBP present (> 6 months), who had failed previous conservative treatment and who had suspected facet joint pain. The study aimed to recruit 150 participants (approximately 30 per site). Participants were randomised sequentially by a remote service to FJIs combined with 'best usual care' (BUC) or BUC alone. All participants were to receive six sessions of a bespoke BUC rehabilitation package. Those randomised into the intervention arm were, in addition, given FJIs with local anaesthetic and steroids (at up to six injection sites). Randomisation occurred at the end of the first BUC session. Process and clinical outcomes. Clinical outcomes included a measurement of level of pain on a scale from 0 to 10, which was collected daily and then weekly via text messaging (or through a written diary). Questionnaire follow-up was at 3 months. Fifty-two stakeholders attended the consensus meeting. Agreement informed several statistical questions and three design considerations: diagnosis, the process of FJI and the BUC package and informing the design for the randomised pilot study. Recruitment started on 26 June 2015 and was terminated by the funder (as a result of poor recruitment) on 11 December 2015. In total, 26 participants were randomised. Process data illuminate some of the reasons for recruitment problems but also show that trial processes after enrolment ran smoothly. No between-group analysis was carried out. All pain-related outcomes show the expected improvement between baseline and follow-up. The mean total cost of the overall treatment package (injection £419.22 and BUC £264.00) was estimated at £683.22 per participant. This is similar to a NHS tariff cost for a course of FJIs of £686.84. Poor recruitment was a limiting factor. This feasibility study achieved consensus on the main challenges in a trial of FJIs for people with persistent non-specific low back pain. Further work is needed to test recruitment from alternative clinical situations. EudraCT 2014-000682-50 and Current Controlled Trials ISRCTN93184143. 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. 30. See the NIHR Journals Library website for further project information.

Can exercise improve self esteem in children and young people? A systematic review of randomised controlled trials

PubMed Central

Ekeland, E; Heian, F; Hagen, K; Coren, E

2005-01-01

Twenty three randomised controlled trials were analysed. A synthesis of several small, low quality trials indicates that exercise may have short term beneficial effects on self esteem in children and adolescents. However, high quality research on defined populations with adequate follow up is needed. PMID:16244186

Implementing Randomised Control Trials in Open and Distance Learning: A Feasibility Study

ERIC Educational Resources Information Center

Herodotou, Christothea; Heiser, Sarah; Rienties, Bart

2017-01-01

Randomised control trials (RCTs) are an evidence-based research approach which has not yet been adopted and widely used in open and distance education to inform educational policy and practice. Despite the challenges entailed in their application, RCTs hold the power to robustly evaluate the effects of educational interventions in distance…

Reading and Language Intervention for Children at Risk of Dyslexia: A Randomised Controlled Trial

ERIC Educational Resources Information Center

Duff, Fiona J.; Hulme, Charles; Grainger, Katy; Hardwick, Samantha J.; Miles, Jeremy N. V.; Snowling, Margaret J.

2014-01-01

Background: Intervention studies for children at risk of dyslexia have typically been delivered preschool, and show short-term effects on letter knowledge and phoneme awareness, with little transfer to literacy. Methods: This randomised controlled trial evaluated the effectiveness of a reading and language intervention for 6-year-old children…

Elementary Science Teachers' Integration of Engineering Design into Science Instruction: Results from a Randomised Controlled Trial

ERIC Educational Resources Information Center

Maeng, Jennifer L.; Whitworth, Brooke A.; Gonczi, Amanda L.; Navy, Shannon L.; Wheeler, Lindsay B.

2017-01-01

This randomised controlled trial used a mixed-methods approach to investigate the frequency and how elementary teachers integrated engineering design (ED) principles into their science instruction following professional development (PD). The ED components of the PD were aligned with Cunningham and Carlsen's [(2014). "Teaching engineering…

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…

Refining cost-effectiveness analyses using the net benefit approach and econometric methods: an example from a trial of anti-depressant treatment.

PubMed

Sabes-Figuera, Ramon; McCrone, Paul; Kendricks, Antony

2013-04-01

Economic evaluation analyses can be enhanced by employing regression methods, allowing for the identification of important sub-groups and to adjust for imperfect randomisation in clinical trials or to analyse non-randomised data. To explore the benefits of combining regression techniques and the standard Bayesian approach to refine cost-effectiveness analyses using data from randomised clinical trials. Data from a randomised trial of anti-depressant treatment were analysed and a regression model was used to explore the factors that have an impact on the net benefit (NB) statistic with the aim of using these findings to adjust the cost-effectiveness acceptability curves. Exploratory sub-samples' analyses were carried out to explore possible differences in cost-effectiveness. Results The analysis found that having suffered a previous similar depression is strongly correlated with a lower NB, independent of the outcome measure or follow-up point. In patients with previous similar depression, adding an selective serotonin reuptake inhibitors (SSRI) to supportive care for mild-to-moderate depression is probably cost-effective at the level used by the English National Institute for Health and Clinical Excellence to make recommendations. This analysis highlights the need for incorporation of econometric methods into cost-effectiveness analyses using the NB approach.

A multicentre, randomised controlled, non-inferiority trial, comparing nasal high flow with nasal continuous positive airway pressure as primary support for newborn infants with early respiratory distress born in Australian non-tertiary special care nurseries (the HUNTER trial): study protocol

PubMed Central

Manley, Brett J; Roberts, Calum T; Arnolda, Gaston R B; Wright, Ian M R; Owen, Louise S; Dalziel, Kim M; Foster, Jann P; Davis, Peter G; Buckmaster, Adam G

2017-01-01

Introduction Nasal high-flow (nHF) therapy is a popular mode of respiratory support for newborn infants. Evidence for nHF use is predominantly from neonatal intensive care units (NICUs). There are no randomised trials of nHF use in non-tertiary special care nurseries (SCNs). We hypothesise that nHF is non-inferior to nasal continuous positive airway pressure (CPAP) as primary support for newborn infants with respiratory distress, in the population cared for in non-tertiary SCNs. Methods and analysis The HUNTER trial is an unblinded Australian multicentre, randomised, non-inferiority trial. Infants are eligible if born at a gestational age ≥31 weeks with birth weight ≥1200 g and admitted to a participating non-tertiary SCN, are <24 hours old at randomisation and require non-invasive respiratory support or supplemental oxygen for >1 hour. Infants are randomised to treatment with either nHF or CPAP. The primary outcome is treatment failure within 72 hours of randomisation, as determined by objective oxygenation, apnoea or blood gas criteria or by a clinical decision that urgent intubation and mechanical ventilation, or transfer to a tertiary NICU, is required. Secondary outcomes include incidence of pneumothorax requiring drainage, duration of respiratory support, supplemental oxygen and hospitalisation, costs associated with hospital care, cost-effectiveness, parental stress and satisfaction and nursing workload. Ethics and dissemination Multisite ethical approval for the study has been granted by The Royal Children’s Hospital, Melbourne, Australia (Trial Reference No. 34222), and by each participating site. The trial is currently recruiting in eight centres in Victoria and New South Wales, Australia, with one previous site no longer recruiting. The trial results will be published in a peer-reviewed journal and will be presented at national and international conferences. Trial registration number Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614001203640; pre-results. PMID:28645982

A multicentre, randomised controlled, non-inferiority trial, comparing nasal high flow with nasal continuous positive airway pressure as primary support for newborn infants with early respiratory distress born in Australian non-tertiary special care nurseries (the HUNTER trial): study protocol.

PubMed

Manley, Brett J; Roberts, Calum T; Arnolda, Gaston R B; Wright, Ian M R; Owen, Louise S; Dalziel, Kim M; Foster, Jann P; Davis, Peter G; Buckmaster, Adam G

2017-06-23

Nasal high-flow (nHF) therapy is a popular mode of respiratory support for newborn infants. Evidence for nHF use is predominantly from neonatal intensive care units (NICUs). There are no randomised trials of nHF use in non-tertiary special care nurseries (SCNs). We hypothesise that nHF is non-inferior to nasal continuous positive airway pressure (CPAP) as primary support for newborn infants with respiratory distress, in the population cared for in non-tertiary SCNs. The HUNTER trial is an unblinded Australian multicentre, randomised, non-inferiority trial. Infants are eligible if born at a gestational age ≥31 weeks with birth weight ≥1200 g and admitted to a participating non-tertiary SCN, are <24 hours old at randomisation and require non-invasive respiratory support or supplemental oxygen for >1 hour. Infants are randomised to treatment with either nHF or CPAP. The primary outcome is treatment failure within 72 hours of randomisation, as determined by objective oxygenation, apnoea or blood gas criteria or by a clinical decision that urgent intubation and mechanical ventilation, or transfer to a tertiary NICU, is required. Secondary outcomes include incidence of pneumothorax requiring drainage, duration of respiratory support, supplemental oxygen and hospitalisation, costs associated with hospital care, cost-effectiveness, parental stress and satisfaction and nursing workload. Multisite ethical approval for the study has been granted by The Royal Children's Hospital, Melbourne, Australia (Trial Reference No. 34222), and by each participating site. The trial is currently recruiting in eight centres in Victoria and New South Wales, Australia, with one previous site no longer recruiting. The trial results will be published in a peer-reviewed journal and will be presented at national and international conferences. Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614001203640; pre-results. © 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.

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.

Vitamin K for upper gastrointestinal bleeding in people with acute or chronic liver diseases.

PubMed

Martí-Carvajal, Arturo J; Solà, Ivan

2015-06-09

Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. Several treatments are used for upper gastrointestinal bleeding in people with liver diseases. One of them is vitamin K administration, but it is not known whether it benefits or harms people with acute or chronic liver disease and upper gastrointestinal bleeding. This is an update of this Cochrane review. To assess the beneficial and harmful effects of vitamin K for people with acute or chronic liver disease and upper gastrointestinal bleeding. We searched The Cochrane Hepato-Biliary Controlled Trials Register (February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2 of 12, 2015), MEDLINE (Ovid SP) (1946 to February 2015), EMBASE (Ovid SP) (1974 to February 2015), Science Citation Index EXPANDED (1900 to February 2015), and LILACS (1982 to 25 February 2015). We sought additional randomised trials from two registries of clinical trials: the World Health Organization Clinical Trials Search Portal and the metaRegister of Controlled Trials. We looked through the reference lists of the retrieved publications and review articles. Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. We considered observational studies for assessment of harms only. \\We aimed to summarise data from randomised clinical trials using Standard Cochrane methodology and assess them according to the GRADE approach. We found no randomised trials on vitamin K for upper gastrointestinal bleeding in people with liver diseases assessing benefits and harms of the intervention. We identified no quasi-randomised studies, historically controlled studies, or observational studies assessing harms. This updated review found no randomised clinical trials of vitamin K for upper gastrointestinal bleeding in people with liver diseases. The benefits and harms of vitamin K need to be tested in randomised clinical trials. Until randomised clinical trials are conducted to assess the trade-off between benefits and harms, we cannot recommend or refute the use of vitamin K for upper gastrointestinal bleeding in people with liver diseases.

The Efficacy and Mechanism Evaluation of Treating Idiopathic Pulmonary fibrosis with the Addition of Co-trimoxazole (EME-TIPAC): study protocol for a randomised controlled trial.

PubMed

Hammond, Matthew; Clark, Allan B; Cahn, Anthony P; Chilvers, Edwin R; Fraser, William Duncan; Livermore, David M; Maher, Toby M; Parfrey, Helen; Swart, Ann Marie; Stirling, Susan; Thickett, David; Whyte, Moira; Wilson, Andrew

2018-02-05

We hypothesise, based upon the findings from our previous trial, that the addition of co-trimoxazole to standard therapy is beneficial to patients with moderate to severe idiopathic pulmonary fibrosis (IPF). We aim to investigate this by assessing unplanned hospitalisation-free survival (defined as time from randomisation to first non-elective hospitalisation, lung transplant or death) and to determine whether any effect relates to changes in infection and/or markers of disease control and neutrophil activity. The EME-TIPAC trial is a double-blind, placebo-controlled, randomised, multicentre clinical trial. A total of 330 symptomatic patients, aged 40 years old or older, with IPF diagnosed by a multidisciplinary team (MDT) according to international guidelines and a FVC ≤ 75% predicted will be enrolled. Patients are randomised equally to receive either two tablets of co-trimoxazole 480 mg or two placebo tablets twice daily over a median treatment period of 27 (range 12-42) months. All patients receive folic acid 5 mg daily whilst on the trial IMP to reduce the risk of bone marrow depression. The primary outcome for the trial is a composite endpoint consisting of the time to death, transplant or first non-elective hospital admission and will be determined from adverse event reporting, hospital databases and the Office of National Statistics with active tracing of patients missing appointments. Secondary outcomes include the individual components of the primary outcome, (1) King's Brief Interstitial Lung Disease Questionnaire, (2) MRC Dyspnoea Score, (3) EQ5D, (4) spirometry, (5) total lung-diffusing capacity and (6) routine sputum microbiology. Blood will be taken for cell count, biochemistry and analysis of biomarkers including C-reactive protein and markers of disease. The trial will last for 4 years. Recruitment will take place in a network of approximately 40 sites throughout the UK (see Table 1 for a full list of participating sites). We expect recruitment for 30 months, follow-up for 12 months and trial analysis and reporting to take 4 months. The trial is designed to test the hypothesis that treating IPF patients with co-trimoxazole will increase the time to death (all causes), lung transplant or first non-elective hospital admission compared to standard care ( https://www.nice.org.uk/guidance/cg163 ), in patients with moderate to severe disease. The mechanistic aims are to investigate the effect on lung microbiota and other measures of infection, markers of epithelial injury and markers of neutrophil activity. International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 17464641 . Registered on 29 January 2015.

Ad libitum or demand/semi-demand feeding versus scheduled interval feeding for preterm infants.

PubMed

Tosh, K; McGuire, W

2006-07-19

Feeding preterm infants in response to their hunger and satiation cues (ad libitum or demand/semi demand) rather than at scheduled intervals might help in the establishment of independent oral feeding, increase nutrient intake and growth rates, and allow earlier hospital discharge. To assess the effect of a policy of feeding preterm infants on an ad libitum or demand/semi-demand basis versus feeding prescribed volumes at scheduled intervals on growth rates and the time to hospital discharge. We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966 - March 2006), EMBASE (1980 - March 2006), CINAHL (1982 - March 2006), conference proceedings, and previous reviews. Randomised or quasi-randomised controlled trials (including cluster randomised trials) that compared a policy of feeding preterm infants on an ad libitum or demand/semi-demand basis versus feeding at scheduled intervals. The standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors. The primary outcomes of interest were growth rates and age at hospital discharge. We found seven randomised controlled trials that compared ad libitum or demand/semi-demand regimes with scheduled interval regimes in preterm infants in the transition phase from intragastric tube to oral feeding. The trials were generally small and of variable methodological quality. The duration of the intervention and the duration of data collection and follow up in most of the trials is not likely to have allowed detection of measurable effects on growth. The single trial that assessed growth for longer than one week found that the rate of weight gain was lower in the ad libitum fed infants [mean difference -3.30 (95% confidence interval -6.2 to -0.4) grams per kilogram per day]. Two trials reported that feeding preterm infants using an ad libitum or demand/semi-demand feeding regime allowed earlier discharge from hospital, but the other trials did not confirm this finding. We were not able to undertake meta-analyses because of differences in study design and in the way the findings were reported. There are insufficient data at present to guide clinical practice. A large randomised controlled trial is needed to determine if ad libitum of demand/semi-demand feeding of preterm infants affects clinically important outcomes. This trial should focus on infants in the transition phase from intragastric tube to oral feeding and should be of sufficient duration to assess effects on growth and time to oral feeding and hospital discharge.

Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea.

PubMed

Szajewska, H; Kołodziej, M

2015-10-01

Antibiotic-associated diarrhoea is a common complication of antibiotic use, but it can be prevented with administration of probiotics. To update our 2005 meta-analysis on the effectiveness of Saccharomyces boulardii in preventing antibiotic-associated diarrhoea in children and adults. The Cochrane Library, MEDLINE, and EMBASE databases were searched up until May 2015, with no language restrictions, for randomised controlled trials; additional references were obtained from reviewed articles. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Twenty-one randomised controlled trials (4780 participants), among which 16 were new trials, met the inclusion criteria for this updated systematic review. Administration of S. boulardii compared with placebo or no treatment reduced the risk of antibiotic-associated diarrhoea (as defined by the study investigators) in patients treated with antibiotics from 18.7% to 8.5% (risk ratio, RR: 0.47; 95% CI: 0.38-0.57, number needed to treat, NNT: 10; 95% CI: 9-13). In children, S. boulardii reduced the risk from 20.9% to 8.8% (6 randomised controlled trials, n=1653, RR: 0.43, 95% CI: 0.3-0.6); in adults, from 17.4% to 8.2% (15 randomised controlled trials, n=3114, RR: 0.49, 95% CI: 0.38-0.63). Moreover, S. boulardii reduced the risk of Clostridium difficile-associated diarrhoea; however, this reduction was significant only in children (2 randomised controlled trials, n = 579, RR: 0.25; 95% CI: 0.08-0.73) and not in adults (9 randomised controlled trials, n = 1441, RR: 0.8, 95% CI: 0.47-1.34). This meta-analysis confirms that S. boulardii is effective in reducing the risk of antibiotic-associated diarrhoea in children and adults. © 2015 John Wiley & Sons Ltd.

Study protocol of a multicentre randomised controlled trial of self-help cognitive behaviour therapy for working women with menopausal symptoms (MENOS@Work).

PubMed

Hunter, Myra S; Hardy, Claire; Norton, Sam; Griffiths, Amanda

2016-10-01

Hot flushes and night sweats (HFNS) - the main symptoms of the menopause transition - can reduce quality of life and are particularly difficult to manage at work. A cognitive behaviour therapy (CBT) intervention has been developed specifically for HFNS that is theoretically based and shown to reduce significantly the impact of HFNS in several randomised controlled trials (RCTs). Self-help CBT has been found to be as effective as group CBT for these symptoms, but these interventions are not widely available in the workplace. This paper describes the protocol of an RCT aiming to assess the efficacy of CBT for menopausal symptoms implemented in the workplace, with a nested qualitative study to examine acceptability and feasibility. One hundred menopausal working women, aged 45-60 years, experiencing bothersome HFNS for two months will be recruited from several (2-10) large organisations into a multicentre randomised controlled trial. Women will be randomly assigned to either treatment (a self-help CBT intervention lasting 4 weeks) or to a no treatment-wait control condition (NTWC), following a screening interview, consent, and completion of a baseline questionnaire. All participants will complete follow-up questionnaires at 6 weeks and 20 weeks post-randomisation. The primary outcome is the rating of HFNS; secondary measures include HFNS frequency, mood, quality of life, attitudes to menopause, HFNS beliefs and behaviours, work absence and presenteeism, job satisfaction, job stress, job performance, disclosure to managers and turnover intention. Adherence, acceptability and feasibility will be assessed at 20 weeks post-randomisation in questionnaires and qualitative interviews. Upon trial completion, the control group will also be offered the intervention. This is the first randomised controlled trial of a self-management intervention tailored for working women who have troublesome menopausal symptoms. Clin.Gov NCT02623374. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

Diamorphine for pain relief in labour : a randomised controlled trial comparing intramuscular injection and patient-controlled analgesia.

PubMed

McInnes, Rhona J; Hillan, Edith; Clark, Diana; Gilmour, Harper

2004-10-01

To compare the efficacy of diamorphine administered by a patient-controlled pump (patient-controlled analgesia) with intramuscular administration for pain relief in labour. Randomised controlled trial. The South Glasgow University Hospitals NHS Trust. Primigravidae and multigravidae in labour at term (37-42 weeks). Women were randomised in labour to the study (patient-controlled analgesia) or control group (intramuscular). Randomisation was achieved through a random permuted block design stratified by parity. Study group women were given a loading dose of 1.2 mg diamorphine intravenously and then attached to the pump. Control group women received intramuscular diamorphine as per hospital protocol. Participants were also given 3 mg of buccal Stemetil. Data were collected throughout labour and at six postnatal weeks. Analgesia requirements during labour and women's satisfaction with the method of pain relief. Women in the study group (patient-controlled analgesia) used significantly less diamorphine than women in the control group (intramuscular) but were significantly more likely to state that they were very dissatisfied with their use of diamorphine and were significantly more likely to opt out of the trial before the birth of the baby. The majority of women in both groups used other analgesia concurrent with diamorphine such as Entonox, aromatherapy or TENS. Patient-controlled analgesia administration of diamorphine for the relief of pain in labour offers no significant advantages over intramuscular administration. The results also suggest that diamorphine is a poor analgesic for labour pain irrespective of the mode of administration.

Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials

PubMed Central

Ju, Woong; Oh, Seung-Won; Park, Sang Min; Koo, Bon-Kwon; Park, Byung-Joo

2013-01-01

Objective To assess the efficacy of vitamin and antioxidant supplements in the prevention of cardiovascular diseases. Design Meta-analysis of randomised controlled trials. Data sources and study selection PubMed, EMBASE, the Cochrane Library, Scopus, CINAHL, and ClinicalTrials.gov searched in June and November 2012. Two authors independently reviewed and selected eligible randomised controlled trials, based on predetermined selection criteria. Results Out of 2240 articles retrieved from databases and relevant bibliographies, 50 randomised controlled trials with 294 478 participants (156 663 in intervention groups and 137 815 in control groups) were included in the final analyses. In a fixed effect meta-analysis of the 50 trials, supplementation with vitamins and antioxidants was not associated with reductions in the risk of major cardiovascular events (relative risk 1.00, 95% confidence interval 0.98 to 1.02; I2=42%). Overall, there was no beneficial effect of these supplements in the subgroup meta-analyses by type of prevention, type of vitamins and antioxidants, type of cardiovascular outcomes, study design, methodological quality, duration of treatment, funding source, provider of supplements, type of control, number of participants in each trial, and supplements given singly or in combination with other supplements. Among the subgroup meta-analyses by type of cardiovascular outcomes, vitamin and antioxidant supplementation was associated with a marginally increased risk of angina pectoris, while low dose vitamin B6 supplementation was associated with a slightly decreased risk of major cardiovascular events. Those beneficial or harmful effects disappeared in subgroup meta-analysis of high quality randomised controlled trials within each category. Also, even though supplementation with vitamin B6 was associated with a decreased risk of cardiovascular death in high quality trials, and vitamin E supplementation with a decreased risk of myocardial infarction, those beneficial effects were seen only in randomised controlled trials in which the supplements were supplied by the pharmaceutical industry. Conclusion There is no evidence to support the use of vitamin and antioxidant supplements for prevention of cardiovascular diseases. PMID:23335472

Review of Randomised Controlled Trials of Internet Interventions for Mental Disorders and Related Conditions

ERIC Educational Resources Information Center

Griffiths, Kathleen M.; Christensen, Helen

2006-01-01

Self-help Internet interventions have the potential to enable consumers to play a central role in managing their own health. This paper contains a systematic review of 15 randomised controlled trials of the effectiveness of self-help Internet interventions for mental disorders and related conditions. Conditions addressed by the interventions…

Representation of People with Intellectual Disabilities in Randomised Controlled Trials on Antipsychotic Treatment for Behavioural Problems

ERIC Educational Resources Information Center

Scheifes, A.; Stolker, J. J.; Egberts, A. C. G.; Nijman, H. L. I.; Heerdink, E. R.

2011-01-01

Background: Behavioural problems are common in people with intellectual disability (ID) and are often treated with antipsychotics. Aim: To establish the frequency and characteristics of people with ID included in randomised controlled trials (RCTs) on antipsychotic treatment for behavioural problems, and to investigate the quality of these RCTs.…

Effect of a Universal Anxiety Prevention Programme (FRIENDS) on Children's Academic Performance: Results from a Randomised Controlled Trial

ERIC Educational Resources Information Center

Skryabina, Elena; Taylor, Gordon; Stallard, Paul

2016-01-01

Background: Evaluations of school-based anxiety prevention programmes have reported improvements in psychological functioning although little is known about their effect upon educational outcomes. Methods: One thousand three hundred and sixty-two children from 40 primary schools in England took part in the randomised controlled trial, Preventing…

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

ERIC Educational Resources Information Center

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

2006-01-01

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

The Effectiveness of Picture Exchange Communication System (PECS) Training for Teachers of Children with Autism: A Pragmatic, Group Randomised Controlled Trial

ERIC Educational Resources Information Center

Howlin, Patricia; Gordon, R. Kate; Pasco, Greg; Wade, Angie; Charman, Tony

2007-01-01

Objective: To assess the effectiveness of expert training and consultancy for teachers of children with autism spectrum disorder in the use of the Picture Exchange Communication System (PECS). Method: Design: Group randomised, controlled trial (3 groups: immediate treatment, delayed treatment, no treatment). Participants: 84 elementary school…

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

ERIC Educational Resources Information Center

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

2009-01-01

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

Stress in Fathers of Moderately and Late Preterm Infants: A Randomised Controlled Trial

ERIC Educational Resources Information Center

Ravn, Ingrid Helen; Lindemann, Rolf; Smeby, Nina Aarhus; Bunch, Eli Haugen; Sandvik, Leiv; Smith, Lars

2012-01-01

The atypical behaviour of preterm infants can elicit stress in fathers and influence their ability to perceive and interpret infants' cues. This study investigated whether fathers of moderately and late preterm infants were more stressed than fathers of term infants. In a randomised controlled trial, we also studied the effect of the Mother-Infant…

Can Healthcare Assistant Training (CHAT) improve the relational care of older people? Study protocol for a pilot cluster randomised controlled trial.

PubMed

Arthur, Antony; Maben, Jill; Wharrad, Heather; Aldus, Clare; Sarre, Sophie; Schneider, Justine; Nicholson, Caroline; Barton, Garry; Cox, Karen; Clark, Allan

2015-12-09

People aged 75 years and over account for 1 in 4 of all hospital admissions. There has been increasing recognition of problems in the care of older people, particularly in hospitals. Evidence suggests that older people judge the care they receive in terms of kindness, empathy, compassion, respectful communication and being seen as a person not just a patient. These are aspects of care to which we refer when we use the term 'relational care'. Healthcare assistants deliver an increasing proportion of direct care to older people, yet their training needs are often overlooked. This study will determine the acceptability and feasibility of a cluster randomised controlled trial of 'Older People's Shoes' a 2-day training intervention for healthcare assistants caring for older people in hospital. Within this pilot, 2-arm, parallel, cluster randomised controlled trial, healthcare assistants within acute hospital wards are randomised to either the 2-day training intervention or training as usual. Registered nurses deliver 'Older People's Shoes' over 2 days, approximately 1 week apart. It contains three components: experiential learning about ageing, exploration of older people's stories, and customer care. Outcomes will be measured at the level of patient (experience of emotional care and quality of life during their hospital stay), healthcare assistant (empathy and attitudes towards older people), and ward (quality of staff/patient interaction). Semi-structured interviews of a purposive sample of healthcare assistants receiving the intervention, and all trainers delivering the intervention, will be undertaken to gain insights into the experiences of both the intervention and the trial, and its perceived impact on practice. Few training interventions for care staff have been rigorously tested using randomised designs. This study will establish the viability of a definitive cluster randomised controlled trial of a new training intervention to improve the relational care proided by healthcare assistants working with older people in hospital. The study was registered as an International Standard Randomised Controlled Trial ( ISRCTN10385799 ) on 29 December 2014.

Cognitive Existential Couple Therapy for newly diagnosed prostate cancer patients and their partners: a descriptive pilot study.

PubMed

Collins, Anna L; Love, Anthony W; Bloch, Sidney; Street, Annette F; Duchesne, Gillian M; Dunai, Judy; Couper, Jeremy W

2013-02-01

This paper aims to describe 'Cognitive Existential Couple Therapy' (CECT), a novel couples-based intervention for men with early stage prostate cancer (PCa) and their partners, and to report preliminary findings from a pilot study that investigated the acceptability and feasibility of the intervention and the measures to be used in a subsequent randomised controlled trial. A manualised CECT programme was delivered to 12 couples facing a diagnosis of PCa within the previous 12 months by psychiatrists and clinical psychologists. Participants completed measures of psychological distress, marital function and coping pattern before and after CECT. Semi-structured interviews were conducted with nine couples shortly after the completion of CECT. The application of CECT was both feasible and acceptable as indicated by favourable participant compliance (10 of the 12 couples attended all six designated sessions), completion of measures before and after CECT and participation in semi-structured interviews by nine couples. Preliminary results included reduced levels of avoidance and hyperarousal after the programme, with this effect stronger in partners than in patients. Interviews demonstrated that couples valued the therapist's contribution to their overall care. Previous research suggests that a couple-focused psychological intervention is desirable in the context of early stage PCa. This pilot study has established that CECT is acceptable, feasible and valued by couples facing a recent PCa diagnosis and demonstrates a potential for reduced psychological distress following CECT. A randomised controlled trial is currently being undertaken to validate the efficacy of this novel approach. Copyright © 2011 John Wiley & Sons, Ltd.

Protocol for a multicentre, parallel-arm, 12-month, randomised, controlled trial of arthroscopic surgery versus conservative care for femoroacetabular impingement syndrome (FASHIoN).

PubMed

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

2016-08-31

Femoroacetabular impingement (FAI) syndrome is a recognised cause of young adult hip pain. There has been a large increase in the number of patients undergoing arthroscopic surgery for FAI; however, a recent Cochrane review highlighted that there are no randomised controlled trials (RCTs) evaluating treatment effectiveness. We aim to compare the clinical and cost-effectiveness of arthroscopic surgery versus best conservative care for patients with FAI syndrome. We will conduct a multicentre, pragmatic, assessor-blinded, two parallel arm, RCT comparing arthroscopic surgery to physiotherapy-led best conservative care. 24 hospitals treating NHS patients will recruit 344 patients over a 26-month recruitment period. Symptomatic adults with radiographic signs of FAI morphology who are considered suitable for arthroscopic surgery by their surgeon will be eligible. Patients will be excluded if they have radiographic evidence of osteoarthritis, previous significant hip pathology or previous shape changing surgery. Participants will be allocated in a ratio of 1:1 to receive arthroscopic surgery or conservative care. Recruitment will be monitored and supported by qualitative intervention to optimise informed consent and recruitment. The primary outcome will be pain and function assessed by the international hip outcome tool 33 (iHOT-33) measured 1-year following randomisation. Secondary outcomes include general health (short form 12), quality of life (EQ5D-5L) and patient satisfaction. The primary analysis will compare change in pain and function (iHOT-33) at 12 months between the treatment groups, on an intention-to-treat basis, presented as the mean difference between the trial groups with 95% CIs. The study is funded by the Health Technology Assessment Programme (13/103/02). Ethical approval is granted by the Edgbaston Research Ethics committee (14/WM/0124). The results will be disseminated through open access peer-reviewed publications, including Health Technology Assessment, and presented at relevant conferences. ISRCTN64081839; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Parenting Resilient Kids (PaRK), an online parenting program to prevent anxiety and depression problems in primary school-aged children: Study protocol for a randomised controlled trial.

PubMed

Fernando, Luwishennadige Madhawee N; Sim, Wan Hua; Jorm, Anthony F; Rapee, Ron; Lawrence, Katherine A; Yap, Marie B H

2018-04-19

Preventive efforts targeting childhood anxiety and depression symptoms have the potential to alter the developmental trajectory of depression and anxiety disorders across the lifespan. Substantial previous research suggests that modifiable parenting factors such as parental aversiveness and over-involvement are associated with childhood anxiety, depressive and internalising symptoms, indicating that parents can play a critical role in prevention. The Parenting Resilient Kids study is a new evidence-based online parenting program designed to prevent anxiety and depression problems in primary school-aged children by reducing family-based risk factors and enhancing protective factors through increased positive interactions between parent and child. The current study is a parallel group superiority randomised controlled trial with parent-child dyads randomised to the intervention or active-control group in a 1:1 ratio. The intervention group will receive the Parenting Resilient Kids program consisting of a feedback report on parenting behaviours and up to 12 interactive online modules personalised based on responses to the parent survey. The active-control group will receive a standardised package of online educational materials about child development and wellbeing. The trial website is programmed to run a stratified random allocation sequence (based on parent gender) to determine group membership. We aim to recruit 340 parent-child dyads (170 dyads per group). We hypothesise that the intervention group will show greater improvement in parenting risk and protective factors from baseline to 3-month follow-up (primary outcome), which will in turn mediate changes in child depressive and anxiety symptoms from baseline to 12 and 24 months (co-primary outcomes). We also hypothesise that the intervention group will show greater benefits from baseline to 3-, 12- and 24-month follow-up, with regard to: child depressive and anxiety symptoms (co-primary outcomes); and child and parent health-related quality of life, and overall family functioning (secondary outcomes). This randomised controlled trial will examine the efficacy of the Parenting Resilient Kids program as a preventive intervention for anxiety and depression symptoms in primary school-aged children, as well as changes in child and parent health-related quality of life. Findings from this study will examine design features that render web-based prevention programs effective and the extent to which parents can be engaged and motivated to change through a minimally guided parenting program. Australian New Zealand Clinical Trials Registry (ANZCTR): Trial ID ACTRN12616000621415 Registered on 13 May 2016. Updated on 3 March 2017.

Limiting weight gain in overweight and obese women during pregnancy to improve health outcomes: the LIMIT randomised controlled trial

PubMed Central

2011-01-01

Background Obesity is a significant global health problem, with the proportion of women entering pregnancy with a body mass index greater than or equal to 25 kg/m2 approaching 50%. Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant, however there is more limited information available regarding effective interventions to improve health outcomes. The aims of this randomised controlled trial are to assess whether the implementation of a package of dietary and lifestyle advice to overweight and obese women during pregnancy to limit gestational weight gain is effective in improving maternal, fetal and infant health outcomes. Methods/Design Design: Multicentred randomised, controlled trial. Inclusion Criteria: Women with a singleton, live gestation between 10+0-20+0 weeks who are obese or overweight (defined as body mass index greater than or equal to 25 kg/m2), at the first antenatal visit. Trial Entry & Randomisation: Eligible, consenting women will be randomised between 10+0 and 20+0 weeks gestation using a central telephone randomisation service, and randomisation schedule prepared by non-clinical research staff with balanced variable blocks. Stratification will be according to maternal BMI at trial entry, parity, and centre where planned to give birth. Treatment Schedules: Women randomised to the Dietary and Lifestyle Advice Group will receive a series of inputs from research assistants and research dietician to limit gestational weight gain, and will include a combination of dietary, exercise and behavioural strategies. Women randomised to the Standard Care Group will continue to receive their pregnancy care according to local hospital guidelines, which does not currently include routine provision of dietary, lifestyle and behavioural advice. Outcome assessors will be blinded to the allocated treatment group. Primary Study Outcome: infant large for gestational age (defined as infant birth weight ≥ 90th centile for gestational age). Sample Size: 2,180 women to detect a 30% reduction in large for gestational age infants from 14.40% (p = 0.05, 80% power, two-tailed). Discussion This is a protocol for a randomised trial. The findings will contribute to the development of evidence based clinical practice guidelines. Trial Registration Australian and New Zealand Clinical Trials Registry ACTRN12607000161426 PMID:22026403

Immediate chest X-ray for patients at risk of lung cancer presenting in primary care: randomised controlled feasibility trial

PubMed Central

Neal, Richard D; Barham, Allan; Bongard, Emily; Edwards, Rhiannon Tudor; Fitzgibbon, Jim; Griffiths, Gareth; Hamilton, Willie; Hood, Kerenza; Nelson, Annmarie; Parker, David; Porter, Cath; Prout, Hayley; Roberts, Kirsty; Rogers, Trevor; Thomas-Jones, Emma; Tod, Angela; Yeo, Seow Tien; Hurt, Chris N

2017-01-01

Background: Achieving earlier stage diagnosis is one option for improving lung cancer outcomes in the United Kingdom. Patients with lung cancer typically present with symptoms to general practitioners several times before referral or investigation. Methods: We undertook a mixed methods feasibility individually randomised controlled trial (the ELCID trial) to assess the feasibility and inform the design of a definitive, fully powered, UK-wide, Phase III trial of lowering the threshold for urgent investigation of suspected lung cancer. Patients over 60, with a smoking history, presenting with new chest symptoms to primary care, were eligible to be randomised to intervention (urgent chest X-ray) or usual care. Results: The trial design and materials were acceptable to GPs and patients. We randomised 255 patients from 22 practices, although the proportion of eligible patients who participated was lower than expected. Survey responses (89%), and the fidelity of the intervention (82% patients X-rayed within 3 weeks) were good. There was slightly higher anxiety and depression in the control arm in participants aged >75. Three patients (1.2%) were diagnosed with lung cancer. Conclusions: We have demonstrated the feasibility of individually randomising patients at higher risk of lung cancer, to a trial offering urgent investigation or usual care. PMID:28072761

Effectiveness of telemonitoring integrated into existing clinical services on hospital admission for exacerbation of chronic obstructive pulmonary disease: researcher blind, multicentre, randomised controlled trial

PubMed Central

Hanley, Janet; McCloughan, Lucy; Todd, Allison; Krishan, Ashma; Lewis, Stephanie; Stoddart, Andrew; van der Pol, Marjon; MacNee, William; Sheikh, Aziz; Pagliari, Claudia; McKinstry, Brian

2013-01-01

Objective To test the effectiveness of telemonitoring integrated into existing clinical services such that intervention and control groups have access to the same clinical care. Design Researcher blind, multicentre, randomised controlled trial. Setting UK primary care (Lothian, Scotland). Participants Adults with at least one admission for chronic obstructive pulmonary disease (COPD) in the year before randomisation. We excluded people who had other significant lung disease, who were unable to provide informed consent or complete the study, or who had other significant social or clinical problems. Interventions Participants were recruited between 21 May 2009 and 28 March 2011, and centrally randomised to receive telemonitoring or conventional self monitoring. Using a touch screen, telemonitoring participants recorded a daily questionnaire about symptoms and treatment use, and monitored oxygen saturation using linked instruments. Algorithms, based on the symptom score, generated alerts if readings were omitted or breached thresholds. Both groups received similar care from existing clinical services. Main outcome measures The primary outcome was time to hospital admission due to COPD exacerbation up to one year after randomisation. Other outcomes included number and duration of admissions, and validated questionnaire assessments of health related quality of life (using St George’s respiratory questionnaire (SGRQ)), anxiety or depression (or both), self efficacy, knowledge, and adherence to treatment. Analysis was intention to treat. Results Of 256 patients completing the study, 128 patients were randomised to telemonitoring and 128 to usual care; baseline characteristics of each group were similar. The number of days to admission did not differ significantly between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.66 to 1.44). Over one year, the mean number of COPD admissions was similar in both groups (telemonitoring 1.2 admissions per person (standard deviation 1.9) v control 1.1 (1.6); P=0.59). Mean duration of COPD admissions over one year was also similar between groups (9.5 days per person (standard deviation 19.1) v 8.8 days (15.9); P=0.88). The intervention had no significant effect on SGRQ scores between groups (68.2 (standard deviation 16.3) v 67.3 (17.3); adjusted mean difference 1.39 (95% confidence interval −1.57 to 4.35)), or on other questionnaire outcomes. Conclusions In participants with a history of admission for exacerbations of COPD, telemonitoring was not effective in postponing admissions and did not improve quality of life. The positive effect of telemonitoring seen in previous trials could be due to enhancement of the underpinning clinical service rather than the telemonitoring communication. Trial registration ISRCTN96634935. Funding: The trial was funded by an NHS applied research programme grant from the Chief Scientist Office of the Scottish government (ARPG/07/03). The funder had no role in study design and the collection, analysis, and interpretation of data and the writing of the article and the decision to submit it for publication. NHS Lothian supported the telemonitoring service and the clinical services. PMID:24136634

A feasibility randomised controlled trial of a motivational interviewing-based intervention for weight loss maintenance in adults.

PubMed

Simpson, Sharon A; McNamara, Rachel; Shaw, Christine; Kelson, Mark; Moriarty, Yvonne; Randell, Elizabeth; Cohen, David; Alam, M Fasihul; Copeland, Lauren; Duncan, Donna; Espinasse, Aude; Gillespie, David; Hill, Andy; Owen-Jones, Eleri; Tapper, Katy; Townson, Julia; Williams, Simon; Hood, Kerry

2015-07-01

Obesity has significant health and NHS cost implications. Relatively small reductions in weight have clinically important benefits, but long-term weight loss maintenance (WLM) is challenging. Behaviour change interventions have been identified as key for WLM. Motivation is crucial to supporting behaviour change, and motivational interviewing (MI) has been identified as a successful approach to changing health behaviours. The study was designed as an adequately powered, pragmatic randomised controlled trial (RCT); however, owing to recruitment issues, the study became a feasibility trial. To assess recruitment, retention, feasibility, acceptability, compliance and delivery of a 12-month intervention to support WLM. Secondary objectives were to assess the impact of the intervention on body mass index (BMI) and other secondary outcomes. Three-arm individually randomised controlled trial comprising an intensive arm, a less intensive arm and a control arm. Community setting in South Wales and the East Midlands. Individuals aged 18-70 years with a current or previous BMI of ≥ 30 kg/m(2) who could provide evidence of at least 5% weight loss during the previous 12 months. Participants received individually tailored MI, which included planning and self-monitoring. The intensive arm received six face-to-face sessions followed by nine telephone sessions. The less intensive arm received two face-to-face sessions followed by two telephone sessions. The control arm received a leaflet advising them on healthy lifestyle. Feasibility outcomes included numbers recruited, retention and adherence. The primary effectiveness outcome was BMI at 12 months post randomisation. Secondary outcomes included waist circumference, waist-to-hip ratio, physical activity, proportion maintaining weight loss, diet, quality of life, health service resource usage, binge eating and well-being. A process evaluation assessed intervention delivery, adherence, and participants' and practitioners' views. Economic analysis aimed to assess cost-effectiveness in terms of quality-adjusted life-years (QALYs). A total of 170 participants were randomised. Retention was good (84%) and adherence was excellent (intensive, 83%; less intensive, 91%). The between-group difference in mean BMI indicated the intensive arm had BMIs 1.0 kg/m(2) lower than the controls [95% confidence interval (CI) -2.2 kg/m(2) to 0.2 kg/m(2)]. Similarly, a potential difference was found in weight (average difference of 2.8 kg, 95% CI -6.1 kg to 0.5 kg). The intensive arm had odds of maintaining on average 43% [odds ratio(OR) 1.4, 95% CI 0.6 to 3.5] higher than controls. None of these findings were statistically significant. Further analyses controlling for level of adherence indicated that average BMI was 1.2 kg/m(2) lower in the intensive arm than the control arm (95% CI -2.5 kg/m(2) to 0.0 kg/m(2)). The intensive intervention led to a statistically significant difference in weight (mean -3.7 kg, 95% CI -7.1 kg to -0.3 kg). The other secondary outcomes showed limited evidence of differences between groups. The intervention was delivered as planned, and both practitioners and participants were positive about the intervention and its impact. Although not powered to assess cost-effectiveness, results of this feasibility study suggest that neither intervention as currently delivered is likely to be cost-effective in routine practice. This is the first trial of an intervention for WLM in the UK, the intervention is feasible and acceptable, and retention and adherence were high. The main effectiveness outcome showed a promising mean difference in the intensive arm. Owing to the small sample size, we are limited in the conclusions we can draw. However, findings suggest that the intensive intervention may facilitate long-term weight maintenance and, therefore, further testing in an effectiveness trial may be indicated. Research examining WLM is in its infancy, further research is needed to develop our understanding of WLM and to expand theory to inform the development of interventions to be tested in rigorously designed RCTs with cost-effectiveness assessed. Current Controlled Trials ISRCTN35774128. This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 50. See the NIHR Journals Library website for further project information.

Effects of a midwife psycho-education intervention to reduce childbirth fear on women's birth outcomes and postpartum psychological wellbeing.

PubMed

Fenwick, Jennifer; Toohill, Jocelyn; Gamble, Jenny; Creedy, Debra K; Buist, Anne; Turkstra, Erika; Sneddon, Anne; Scuffham, Paul A; Ryding, Elsa L

2015-10-30

High levels of childbirth fear impact birth preparation, obstetric outcomes and emotional wellbeing for around one in five women living in developed countries. Higher rates of obstetric intervention and caesarean section (CS) are experienced in fearful women. The efficacy of interventions to reduce childbirth fear is unclear, with no previous randomised controlled trials reporting birth outcomes or postnatal psychological wellbeing following a midwife led intervention. Between May 2012 and June 2013 women in their second trimester of pregnancy were recruited. Women with a fear score ≥ 66 on the Wijma Delivery Expectancy / Experience Questionnaire (W-DEQ) were randomised to receive telephone psycho-education by a midwife, or usual maternity care. A two armed non-blinded parallel (1:1) multi-site randomised controlled trial with participants allocated in blocks of ten and stratified by hospital site and parity using an electronic centralised computer service. The outcomes of the RCT on obstetric outcomes, maternal psychological well-being, parenting confidence, birth satisfaction, and future birth preference were analysed by intention to treat and reported here. 1410 women were screened for high childbirth fear (W-DEQ ≥66). Three hundred and thirty-nine (n = 339) women were randomised (intervention n = 170; controls n = 169). One hundred and eighty-four women (54 %) returned data for final analysis at 6 weeks postpartum (intervention n = 91; controls n = 93). Compared to controls the intervention group had a clinically meaningful but not statistically significant reduction in overall caesarean section (34 % vs 42 %, p = 0.27) and emergency CS rates (18 % vs 25 %, p = 0.23). Fewer women in the intervention group preferred caesarean section for a future pregnancy (18 % vs 30 %, p = 0.04). All other obstetric variables remained similar. There were no differences in postnatal depression symptoms scores, parenting confidence, or satisfaction with maternity care between groups, but a lower incidence of flashbacks about their birth in the intervention group compared to controls (14 % vs 26 %, p = 0.05). Postnatally women who received psycho-education reported that the 'decision aid' helped reduce their fear (53 % vs 37 %, p = 0.02). Following a brief antenatal midwife-led psycho-education intervention for childbirth fear women were less likely to experience distressing flashbacks of birth and preferred a normal birth in a future pregnancy. A reduction in overall CS rates was also found. Psycho-education for fearful women has clinical benefits for the current birth and expectations of future pregnancies. Australian New Zealand Controlled Trials Registry ACTRN12612000526875 , 17th May 2012.

Open urethroplasty versus endoscopic urethrotomy--clarifying the management of men with recurrent urethral stricture (the OPEN trial): study protocol for a randomised controlled trial.

PubMed

Stephenson, Rachel; Carnell, Sonya; Johnson, Nicola; Brown, Robbie; Wilkinson, Jennifer; Mundy, Anthony; Payne, Steven; Watkin, Nick; N'Dow, James; Sinclair, Andrew; Rees, Rowland; Barclay, Stewart; Cook, Jonathan A; Goulao, Beatriz; MacLennan, Graeme; McPherson, Gladys; Jackson, Matthew; Rapley, Tim; Shen, Jing; Vale, Luke; Norrie, John; McColl, Elaine; Pickard, Robert

2015-12-30

Urethral stricture is a common cause of difficulty passing urine in men with prevalence of 0.5 %; about 62,000 men in the UK. The stricture is usually sited in the bulbar part of the urethra causing symptoms such as reduced urine flow. Initial treatment is typically by endoscopic urethrotomy but recurrence occurs in about 60% of men within 2 years. The best treatment for men with recurrent bulbar stricture is uncertain. Repeat endoscopic urethrotomy opens the narrowing but it usually scars up again within 2 years requiring repeated procedures. The alternative of open urethroplasty involves surgically reconstructing the urethra, which may need an oral mucosal graft. It is a specialist procedure with a longer recovery period but may give lower risk of recurrence. In the absence of firm evidence as to which is best, individual men have to trade off the invasiveness and possible benefit of each option. Their preference will be influenced by individual social circumstances, availability of local expertise and clinician guidance. The open urethroplasty versus endoscopic urethrotomy (OPEN) trial aims to better guide the choice of treatment for men with recurrent urethral strictures by comparing benefit over 2 years in terms of symptom control and need for further treatment. OPEN is a pragmatic, UK multicentre, randomised trial. Men with recurrent bulbar urethral strictures (at least one previous treatment) will be randomised to undergo endoscopic urethrotomy or open urethroplasty. Participants will be followed for 24 months after randomisation, measuring symptoms, flow rate, the need for re-intervention, health-related quality of life, and costs. The primary clinical outcome is the difference in symptom control over 24 months measured by the area under the curve (AUC) of a validated score. The trial has been powered at 90% with a type I error rate of 5% to detect a 0.1 difference in AUC measured on a 0-1 scale. The analysis will be based on all participants as randomised (intention-to-treat). The primary economic outcome is the incremental cost per quality-adjusted life year. A qualitative study will assess willingness to be randomised and hence ability to recruit to the trial. The OPEN Trial seeks to clarify relative benefit of the current options for surgical treatment of recurrent bulbar urethral stricture which differ in their invasiveness and resources required. Our feasibility study identified that participation would be limited by patient preference and differing recruitment styles of general and specialist urologists. We formulated and implemented effective strategies to address these issues in particular by inviting participation as close as possible to diagnosis. In addition re-calculation of sample size as recruitment progressed allowed more efficient design given the limited target population and funding constraints. Recruitment is now to target. ISRCTN98009168 Date of registration: 29 November 2012.

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

PubMed

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

2015-07-01

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

Comprehension of confidence intervals - development and piloting of patient information materials for people with multiple sclerosis: qualitative study and pilot randomised controlled trial.

PubMed

Rahn, Anne C; Backhus, Imke; Fuest, Franz; Riemann-Lorenz, Karin; Köpke, Sascha; van de Roemer, Adrianus; Mühlhauser, Ingrid; Heesen, Christoph

2016-09-20

Presentation of confidence intervals alongside information about treatment effects can support informed treatment choices in people with multiple sclerosis. We aimed to develop and pilot-test different written patient information materials explaining confidence intervals in people with relapsing-remitting multiple sclerosis. Further, a questionnaire on comprehension of confidence intervals was developed and piloted. We developed different patient information versions aiming to explain confidence intervals. We used an illustrative example to test three different approaches: (1) short version, (2) "average weight" version and (3) "worm prophylaxis" version. Interviews were conducted using think-aloud and teach-back approaches to test feasibility and analysed using qualitative content analysis. To assess comprehension of confidence intervals, a six-item multiple choice questionnaire was developed and tested in a pilot randomised controlled trial using the online survey software UNIPARK. Here, the average weight version (intervention group) was tested against a standard patient information version on confidence intervals (control group). People with multiple sclerosis were invited to take part using existing mailing-lists of people with multiple sclerosis in Germany and were randomised using the UNIPARK algorithm. Participants were blinded towards group allocation. Primary endpoint was comprehension of confidence intervals, assessed with the six-item multiple choice questionnaire with six points representing perfect knowledge. Feasibility of the patient information versions was tested with 16 people with multiple sclerosis. For the pilot randomised controlled trial, 64 people with multiple sclerosis were randomised (intervention group: n = 36; control group: n = 28). More questions were answered correctly in the intervention group compared to the control group (mean 4.8 vs 3.8, mean difference 1.1 (95 % CI 0.42-1.69), p = 0.002). The questionnaire's internal consistency was moderate (Cronbach's alpha = 0.56). The pilot-phase shows promising results concerning acceptability and feasibility. Pilot randomised controlled trial results indicate that the patient information is well understood and that knowledge gain on confidence intervals can be assessed with a set of six questions. German Clinical Trials Register: DRKS00008561 . Registered 8th of June 2015.

Waste the waist: a pilot randomised controlled trial of a primary care based intervention to support lifestyle change in people with high cardiovascular risk.

PubMed

Greaves, Colin; Gillison, Fiona; Stathi, Afroditi; Bennett, Paul; Reddy, Prasuna; Dunbar, James; Perry, Rachel; Messom, Daniel; Chandler, Roger; Francis, Margaret; Davis, Mark; Green, Colin; Evans, Philip; Taylor, Gordon

2015-01-16

In the UK, thousands of people with high cardiovascular risk are being identified by a national risk-assessment programme (NHS Health Checks). Waste the Waist is an evidence-informed, theory-driven (modified Health Action Process Approach), group-based intervention designed to promote healthy eating and physical activity for people with high cardiovascular risk. This pilot randomised controlled trial aimed to assess the feasibility of delivering the Waste the Waist intervention in UK primary care and of conducting a full-scale randomised controlled trial. We also conducted exploratory analyses of changes in weight. Patients aged 40-74 with a Body Mass Index of 28 or more and high cardiovascular risk were identified from risk-assessment data or from practice database searches. Participants were randomised, using an online computerised randomisation algorithm, to receive usual care and standardised information on cardiovascular risk and lifestyle (Controls) or nine sessions of the Waste the Waist programme (Intervention). Group allocation was concealed until the point of randomisation. Thereafter, the statistician, but not participants or data collectors were blinded to group allocation. Weight, physical activity (accelerometry) and cardiovascular risk markers (blood tests) were measured at 0, 4 and 12 months. 108 participants (22% of those approached) were recruited (55 intervention, 53 controls) from 6 practices and 89% provided data at both 4 and 12 months. Participants had a mean age of 65 and 70% were male. Intervention participants attended 72% of group sessions. Based on last observations carried forward, the intervention group did not lose significantly more weight than controls at 12 months, although the difference was significant when co-interventions and co-morbidities that could affect weight were taken into account (Mean Diff 2.6Kg. 95%CI: -4.8 to -0.3, p = 0.025). No significant differences were found in physical activity. The Waste the Waist intervention is deliverable in UK primary care, has acceptable recruitment and retention rates and produces promising preliminary weight loss results. Subject to refinement of the physical activity component, it is now ready for evaluation in a full-scale trial. Current Controlled Trials ISRCTN10707899 .

Efficacy and safety of prophylaxis with once-weekly BAY 79-4980 compared with thrice-weekly rFVIII-FS in haemophilia A patients. A randomised, active-controlled, double-blind study.

PubMed

Powell, Jerry; Martinowitz, Uri; Windyga, Jerzy; Di Minno, Giovanni; Hellmann, Andrzej; Pabinger, Ingrid; Maas Enriquez, Monika; Schwartz, Lawrence; Ingerslev, Jørgen

2012-11-01

The benefits of prophylaxis of haemophilia A patients regarding joint health and quality-of-life are well established. However, adherence to an up to every-other-day infusion regimen is a barrier to widespread adoption of prophylaxis. BAY 79-4980 is an investigational drug consisting of rFVIII-FS (sucrose-formulated recombinant FVIII) reconstituted with liposome solvent. Previous clinical studies showed extended protection from bleeding after a single injection of BAY 79-4980 (13.3 ± 6.2 days) compared with rFVIII-FS (7.2 ± 1.7 days). The effect of once-a-week prophylaxis with BAY 79-4980 (35 IU/kg) compared with three times-per-week rFVIII-FS (25 IU/kg) in previously treated, severe haemophilia A patients was evaluated in a 52-week, double-blind, two-arm, randomised, controlled study. The primary and secondary endpoints were protection from total bleeds and joint bleeds, respectively. Short- and long-term safety and tolerability of BAY 79-4980 including effects on lipid levels were assessed. A total of 139 and 131 subjects were evaluable for safety and efficacy analyses, respectively. A large difference in efficacy between treatment groups was observed with 72.1% (49/68) in the rFVIII-FS control group demonstrating <9 bleeds/year compared with 38.1% (24/63) of BAY 79-4980-treated subjects. A similar difference was seen in annualised joint bleeds, with 43 subjects (63.2%) in the control group demonstrating <5 joint bleeds/year compared with 24 subjects (38.1%) treated with BAY 79-4980. The distribution of bleeds seven days post-prophylactic treatment with BAY 79-4980 showed that 61% of bleeds occurred after day 4 post dosing. There were no safety concerns identified. The investigational treatment arm was prematurely discontinued due to failure to achieve the primary endpoint.

A feasibility randomised controlled trial of pre-operative occupational therapy to optimise recovery for patients undergoing primary total hip replacement for osteoarthritis (PROOF-THR).

PubMed

Jepson, Paul; Sands, Gina; Beswick, Andrew D; Davis, Edward T; Blom, Ashley W; Sackley, Catherine M

2016-02-01

To assess the feasibility of a pre-operative occupational therapy intervention for patients undergoing primary total hip replacement. Single blinded feasibility randomised controlled trial, with data collection prior to the intervention, and at 4, 12, and 26 weeks following surgery. Recruitment from two NHS orthopaedic outpatient centres in the West Midlands, UK. Patients awaiting primary total hip replacement due to osteoarthritis were recruited. Following pre-operative assessment, patients were individually randomised to intervention or control by a computer-generated block randomisation algorithm stratified by age and centre. The intervention group received a pre-surgery home visit by an occupational therapist who discussed expectations, assessed home safety, and provided appropriate adaptive equipment. The control group received treatment as usual. The study assessed the feasibility of recruitment procedures, delivery of the intervention, appropriateness of outcome measures and data collection methods. Health related quality of life and resource use were recorded at 4, 12 and 26 weeks. Forty-four participants were recruited, 21 were randomised to the occupational therapy intervention and 23 to usual care. Analysis of 26 week data included 18 participants in the intervention group and 21 in the control. The intervention was delivered successfully with no withdrawals or crossovers; 5/44 were lost to follow-up with further missing data for participation and resource use. The feasibility study provided the information required to conduct a definitive trial. Burden of assessment would need to be addressed. A total of 219 patients would be required in an efficacy trial. © The Author(s) 2015.

Impact of a web-based tool (WebCONSORT) to improve the reporting of randomised trials: results of a randomised controlled trial.

PubMed

Hopewell, Sally; Boutron, Isabelle; Altman, Douglas G; Barbour, Ginny; Moher, David; Montori, Victor; Schriger, David; Cook, Jonathan; Gerry, Stephen; Omar, Omar; Dutton, Peter; Roberts, Corran; Frangou, Eleni; Clifton, Lei; Chiocchia, Virginia; Rombach, Ines; Wartolowska, Karolina; Ravaud, Philippe

2016-11-28

The CONSORT Statement is an evidence-informed guideline for reporting randomised controlled trials. A number of extensions have been developed that specify additional information to report for more complex trials. The aim of this study was to evaluate the impact of using a simple web-based tool (WebCONSORT, which incorporates a number of different CONSORT extensions) on the completeness of reporting of randomised trials published in biomedical publications. We conducted a parallel group randomised trial. Journals which endorsed the CONSORT Statement (i.e. referred to it in the Instruction to Authors) but do not actively implement it (i.e. require authors to submit a completed CONSORT checklist) were invited to participate. Authors of randomised trials were requested by the editor to use the web-based tool at the manuscript revision stage. Authors registering to use the tool were randomised (centralised computer generated) to WebCONSORT or control. In the WebCONSORT group, they had access to a tool allowing them to combine the different CONSORT extensions relevant to their trial and generate a customised checklist and flow diagram that they must submit to the editor. In the control group, authors had only access to a CONSORT flow diagram generator. Authors, journal editors, and outcome assessors were blinded to the allocation. The primary outcome was the proportion of CONSORT items (main and extensions) reported in each article post revision. A total of 46 journals actively recruited authors into the trial (25 March 2013 to 22 September 2015); 324 author manuscripts were randomised (WebCONSORT n = 166; control n = 158), of which 197 were reports of randomised trials (n = 94; n = 103). Over a third (39%; n = 127) of registered manuscripts were excluded from the analysis, mainly because the reported study was not a randomised trial. Of those included in the analysis, the most common CONSORT extensions selected were non-pharmacologic (n = 43; n = 50), pragmatic (n = 20; n = 16) and cluster (n = 10; n = 9). In a quarter of manuscripts, authors either wrongly selected an extension or failed to select the right extension when registering their manuscript on the WebCONSORT study site. Overall, there was no important difference in the overall mean score between WebCONSORT (mean score 0.51) and control (0.47) in the proportion of CONSORT and CONSORT extension items reported pertaining to a given study (mean difference, 0.04; 95% CI -0.02 to 0.10). This study failed to show a beneficial effect of a customised web-based CONSORT checklist to help authors prepare more complete trial reports. However, the exclusion of a large number of inappropriately registered manuscripts meant we had less precision than anticipated to detect a difference. Better education is needed, earlier in the publication process, for both authors and journal editorial staff on when and how to implement CONSORT and, in particular, CONSORT-related extensions. ClinicalTrials.gov: NCT01891448 [registered 24 May 2013].

Developing an Australian-first recovery model for parents in Victorian mental health and family services: a study protocol for a randomised controlled trial.

PubMed

Maybery, Darryl; Goodyear, Melinda; Reupert, Andrea; Sheen, Jade; Cann, Warren; Dalziel, Kim; Tchernagovski, Phillip; O'Hanlon, Brendan; von Doussa, Henry

2017-05-26

A considerable number of people with a mental illness are parents caring for dependent children. For those with a mental illness, parenting can provide a sense of competence, belonging, identity and hope and hence is well aligned to the concept of personal recovery. However, little research has focused on the recovery journey of those who are parents and have a mental illness. This randomised controlled trial aims to (i) evaluate the effectiveness of an intervention model of recovery for parents (Let's Talk about Children) in three different mental health service sectors and (ii) examine the economic value of a larger roll out (longer term) of the parent recovery model. A two arm parallel randomised controlled trial will be used with participants, who are being treated for their mental illness in adult mental health, non-government community mental health or family welfare services. The study will involve 192 parents, who are considered by their treating practitioner to be sufficiently well to provide informed consent and participate in an intervention (Let's Talk about Children) or control group (treatment as usual). Participant randomisation will occur at the level of the treating practitioner and will be based on whether the randomised practitioner is trained in the intervention. Outcomes are compared at pre, post intervention and six-month follow-up. Recovery, parenting and family functioning, and quality of life questionnaires will be used to measure parent wellbeing and the economic benefits of the intervention. This is the first randomised controlled trial to investigate the efficacy of a parenting intervention on recovery outcomes and the first to provide an economic evaluation of an intervention for parents with a mental illness. An implementation model is required to embed the intervention in different sectors. The trial was retrospectively registered: ACTRN12616000460404 on the 8/4/2016.

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

PubMed

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

2015-01-01

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

The Efficacy of Phonics-Based Instruction of English as a Second Language in an Italian High School: A Randomised Controlled Trial

ERIC Educational Resources Information Center

Coates, Robert Alexander Graham; Gorham, Judith; Nicholas, Richard

2017-01-01

Recent neurological breakthroughs in our understanding of the Critical Period Hypothesis and prosody may suggest strategies on how phonics instruction could improve L2 language learning and in particular phoneme/grapheme decoding. We therefore conducted a randomised controlled-trial on the application of prosody and phonics techniques, to improve…

Information and Choice of A-Level Subjects: A Cluster Randomised Controlled Trial with Linked Administrative Data

ERIC Educational Resources Information Center

Davies, Peter; Davies, Neil M.; Qiu, Tian

2017-01-01

We estimated the effects of an intervention which provided information about graduate wages to 5593 students in England, using a blinded cluster randomised controlled trial in 50 schools (registration: AEARCTR-0000468). Our primary outcome was students' choice of A-level subjects at age 16. We also recorded the students' expectations of future…

A New Social Communication Intervention for Children with Autism: Pilot Randomised Controlled Treatment Study Suggesting Effectiveness

ERIC Educational Resources Information Center

Aldred, Catherine; Green, Jonathan; Adams, Catherine

2004-01-01

Background: Psychosocial treatments are the mainstay of management of autism in the UK but there is a notable lack of a systematic evidence base for their effectiveness. Randomised controlled trial (RCT) studies in this area have been rare but are essential because of the developmental heterogeneity of the disorder. We aimed to test a new…

A Randomised Group Comparison Controlled Trial of "Preschoolers with Autism": A Parent Education and Skills Training Intervention for Young Children with Autistic Disorder

ERIC Educational Resources Information Center

Tonge, Bruce; Brereton, Avril; Kiomall, Melissa; Mackinnon, Andrew; Rinehart, Nicole J.

2014-01-01

Aim: To determine the effect of parent education on adaptive behaviour, autism symptoms and cognitive/language skills of young children with autistic disorder. Method: A randomised group comparison design involving a parent education and counselling intervention and a parent education and behaviour management intervention to control for parent…

Randomised Controlled Trial of a Parenting Intervention in the Voluntary Sector for Reducing Child Conduct Problems: Outcomes and Mechanisms of Change

ERIC Educational Resources Information Center

Gardner, Frances; Burton, Jennifer; Klimes, Ivana

2006-01-01

Background: To test effectiveness of a parenting intervention, delivered in a community-based voluntary-sector organisation, for reducing conduct problems in clinically-referred children. Methods: Randomised controlled trial, follow-up at 6, 18 months, assessors blind to treatment status. Participants--76 children referred for conduct problems,…

Are Prenatal Ultrasound Scans Associated with the Autism Phenotype? Follow-Up of a Randomised Controlled Trial

ERIC Educational Resources Information Center

Stoch, Yonit K.; Williams, Cori J.; Granich, Joanna; Hunt, Anna M.; Landau, Lou I.; Newnham, John P.; Whitehouse, Andrew J. O.

2012-01-01

An existing randomised controlled trial was used to investigate whether multiple ultrasound scans may be associated with the autism phenotype. From 2,834 single pregnancies, 1,415 were selected at random to receive ultrasound imaging and continuous wave Doppler flow studies at five points throughout pregnancy (Intensive) and 1,419 to receive a…

Reduced in-hospital mortality for heart failure with clinical pathways: the results of a cluster randomised controlled trial.

PubMed

Panella, M; Marchisio, S; Demarchi, M L; Manzoli, L; Di Stanislao, F

2009-10-01

Hospital treatment of heart failure (HF) frequently does not follow published guidelines, potentially contributing to HF high morbidity, mortality and economic cost. The Experimental Prospective Study on the Effectiveness and Efficiency of the Implementation of Clinical Pathways was undertaken to determine how clinical pathways (CP) for hospital treatment of HF affected care variability, guidelines adherence, in-hospital mortality and outcomes at discharge. Methods/ Two-arm, cluster-randomised trial. Fourteen community hospitals were randomised either to the experimental arm (CP: appropriate therapeutic guidelines use, new organisation and procedures, patient education) or to the control arm (usual care). The main outcome was in-hospital mortality; secondary outcomes were length and appropriateness of the stay, rate of unscheduled readmissions, customer satisfaction, usage of diagnostic and therapeutic procedures during hospital stay and quality indicators at discharge. All outcomes were measured using validated instruments available in literature. In-hospital mortality was 5.6% in the experimental arm (n = 12); 15.4% in controls (n = 33, p = 0.001). In CP and usual care groups, the mean rates of unscheduled readmissions were 7.9% and 13.9%, respectively. Adjusting for age, smoking, New York Heart Association score, hypertension and source of referral, patients in the CP group, as compared to controls, had a significantly lower risk of in-hospital death (OR 0.18; 95% CI 0.07 to 0.46) and unscheduled readmissions (OR 0.42; 95% CI 0.20 to 0.87). No differences were found between CP and control with respect to the appropriateness of the stay, costs and patient's satisfaction. Except for electrocardiography, all recommended diagnostic procedures were used more in the CP group. Similarly, pharmaceuticals use was significantly greater in CP, with the exception of diuretics and anti-platelets agents. The introduction of a specifically tailored CP for the hospital treatment of HF was effective in reducing in-hospital mortality and unscheduled readmissions. This study adds to previous knowledge indicating that CP should be used to improve the quality of hospital treatment of HF. NCT00519038.

Concordance and acceptability of electric stimulation therapy: a randomised controlled trial.

PubMed

Miller, C; McGuiness, W; Wilson, S; Cooper, K; Swanson, T; Rooney, D; Piller, N; Woodward, M

2017-08-02

A pilot single-blinded randomised controlled trial (RCT) was conducted to examine concordance with and acceptability of electric stimulation therapy (EST) in patients with venous leg ulcers (VLUs) who had not tolerated moderate to high compression. Participants were randomised to the intervention group (n=15) or a placebo control group (n=8) in which EST was used four times daily for 20 minutes per session. Participants were monitored for eight weeks during which time concordance with the treatment and perceptions of the treatment were assessed. Concordance with the total recommended treatment time was 71.4% for the intervention group and 82.9% for the control group; a difference that was not statistically significant. Participants rated EST as acceptable (84.6% intervention; 83.3% control), only two participants, both from the placebo control group, would not be willing to use EST again. The majority considered EST easier to use than compression (68.4%). EST was a practical and acceptable treatment among people who have been unable to tolerate moderate to high compression therapy.

Efficacy of methylphenidate in the rehabilitation of attention following traumatic brain injury: a randomised, crossover, double blind, placebo controlled inpatient trial.

PubMed

Willmott, C; Ponsford, J

2009-05-01

Most previous studies evaluating the use of methylphenidate following traumatic brain injury (TBI) have been conducted many years post-injury. This study evaluated the efficacy of methylphenidate in facilitating cognitive function in the inpatient rehabilitation phase. 40 participants with moderate-severe TBI (mean 68 days post-injury) were recruited into a randomised, crossover, double blind, placebo controlled trial. Methylphenidate was administered at a dose of 0.3 mg/kg twice daily and lactose in identical capsules served as placebo. Methylphenidate and placebo administration was randomised in a crossover design across six sessions over a 2 week period. Primary efficacy outcomes were neuropsychological tests of attention. No participants were withdrawn because of side effects or adverse events. Methylphenidate significantly increased speed of information processing on the Symbol Digit Modalities Test (95% CI 0.30 to 2.95, Cohen's d = 0.39, p = 0.02), Ruff 2 and 7 Test-Automatic Condition (95% CI 1.38 to 6.12, Cohen's d = 0.51, p = 0.003), Simple Selective Attention Task (95% CI -58.35 to -17.43, Cohen's d = 0.59, p = 0.001) and Dissimilar Compatible (95% CI -70.13 to -15.38, Cohen's d = 0.51, p = 0.003) and Similar Compatible (95% CI -74.82 to -19.06, Cohen's d = 0.55, p = 0.002) conditions of the Four Choice Reaction Time Task. Those with more severe injuries and slower baseline information processing speed demonstrated a greater drug response. Methylphenidate enhances information processing speed in the inpatient rehabilitation phase following TBI. This trial is registered with the Australian New Zealand Clinical Trials Registry (12607000503426).

Randomised controlled trial of video clips and interactive games to improve vision in children with amblyopia using the I-BiT system

PubMed Central

Herbison, Nicola; MacKeith, Daisy; Vivian, Anthony; Purdy, Jon; Fakis, Apostolos; Ash, Isabel M; Cobb, Sue V; Eastgate, Richard M; Haworth, Stephen M; Gregson, Richard M; Foss, Alexander JE

2016-01-01

Background Traditional treatment of amblyopia involves either wearing a patch or atropine penalisation of the better eye. A new treatment is being developed on the basis of virtual reality technology allowing either DVD footage or computer games which present a common background to both eyes and the foreground, containing the imagery of interest, only to the amblyopic eye. Methods A randomised control trial was performed on patients with amblyopia aged 4–8 years with three arms. All three arms had dichoptic stimulation using shutter glass technology. One arm had DVD footage shown to the amblyopic eye and common background to both, the second used a modified shooter game, Nux, with sprite and targets presented to the amblyopic eye (and background to both) while the third arm had both background and foreground presented to both eyes (non-interactive binocular treatment (non-I-BiT) games). Results Seventy-five patients were randomised; 67 were residual amblyopes and 70 had an associated strabismus. The visual acuity improved in all three arms by approximately 0.07 logMAR in the amblyopic eye at 6 weeks. There was no difference between I-BiT DVD and non-I-BiT games compared with I-BiT games (stated primary outcome) in terms of gain in vision. Conclusions There was a modest vision improvement in all three arms. Treatment was well tolerated and safe. There was no difference between the three treatments in terms of primary stated outcomes but treatment duration was short and the high proportion of previously treated amblyopia and strabismic amblyopia disadvantaged dichoptic stimulation treatment. Trial registration number NCT01702727, results. PMID:26951772

Protocol investigating the clinical outcomes and cost-effectiveness of cognitive–behavioural therapy delivered remotely for unscheduled care users with health anxiety: randomised controlled trial

PubMed Central

Patel, Shireen; Malins, Sam; Guo, Boliang; James, Marilyn; Kai, Joe; Kaylor-Hughes, Catherine; Rowley, Emma; Simpson, Jayne; Smart, David; Stubley, Michelle; Tyrer, Helen

2016-01-01

Background Health anxiety and medically unexplained symptoms cost the National Health Service (NHS) an estimated £3 billion per year in unnecessary costs with little evidence of patient benefit. Effective treatment is rarely taken up due to issues such as stigma or previous negative experiences with mental health services. An approach to overcome this might be to offer remotely delivered psychological therapy, which can be just as effective as face-to-face therapy and may be more accessible and suitable. Aims To investigate the clinical outcomes and cost-effectiveness of remotely delivered cognitive–behavioural therapy (CBT) to people with high health anxiety repeatedly accessing unscheduled care (trial registration: NCT02298036). Method A multicentre randomised controlled trial (RCT) will be undertaken in primary and secondary care providers of unscheduled care across the East Midlands. One hundred and forty-four eligible participants will be equally randomised to receive either remote CBT (6–12 sessions) or treatment as usual (TAU). Two doctoral research studies will investigate the barriers and facilitators to delivering the intervention and the factors contributing to the optimisation of therapeutic outcome. Results This trial will be the first to test the clinical outcomes and cost-effectiveness of remotely delivered CBT for the treatment of high health anxiety. Conclusions The findings will enable an understanding as to how this intervention might fit into a wider care pathway to enhance patient experience of care. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703758

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

Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial.

PubMed

Ederle, Jörg; Dobson, Joanna; Featherstone, Roland L; Bonati, Leo H; van der Worp, H Bart; de Borst, Gert J; Lo, T Hauw; Gaines, Peter; Dorman, Paul J; Macdonald, Sumaira; Lyrer, Philippe A; Hendriks, Johanna M; McCollum, Charles; Nederkoorn, Paul J; Brown, Martin M

2010-03-20

Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006). Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery. Medical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union. Copyright 2010 Elsevier Ltd. All rights reserved.

Exercise and mental health: a review.

PubMed

Glenister, D

1996-02-01

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

Medical abortion or vacuum aspiration? Two year follow up of a patient preference trial.

PubMed

Howie, F L; Henshaw, R C; Naji, S A; Russell, I T; Templeton, A A

1997-07-01

To describe and compare health outcomes two years after medical abortion or vacuum aspiration in women recruited into a patient preference trial during 1990 to 1991. Women recruited to the original, partially randomised study were contacted for assessment using a structured interview. Grampian region of Scotland, UK. One hundred and forty women who had participated in a partially randomised study of first trimester abortion two years previously. Vacuum aspiration or medical abortion using mifepristone and gemeprost. Long-term general, reproductive and psychological health; acceptability of procedure; perceived value of choice of method of termination. There were no significant differences between women who had undergone medical abortion or vacuum aspiration two years previously in general, reproductive or psychological health. Almost all women placed a high value on the provision of choice of method of termination. There was a significant difference in perception of long term procedure acceptability among women who had been randomised to a method of termination. Women should have the opportunity to choose the method of termination. This opportunity will result in high levels of acceptability, particularly at gestations under 50 days of amenorrhoea.

Foot orthoses in the treatment of symptomatic midfoot osteoarthritis using clinical and biomechanical outcomes: a randomised feasibility study.

PubMed

Halstead, Jill; Chapman, Graham J; Gray, Janine C; Grainger, Andrew J; Brown, Sarah; Wilkins, Richard A; Roddy, Edward; Helliwell, Philip S; Keenan, Anne-Maree; Redmond, Anthony C

2016-04-01

This randomised feasibility study aimed to examine the clinical and biomechanical effects of functional foot orthoses (FFOs) in the treatment of midfoot osteoarthritis (OA) and the feasibility of conducting a full randomised controlled trial. Participants with painful, radiographically confirmed midfoot OA were recruited and randomised to receive either FFOs or a sham control orthosis. Feasibility measures included recruitment and attrition rates, practicality of blinding and adherence rates. Clinical outcome measures were: change from baseline to 12 weeks for severity of pain (numerical rating scale), foot function (Manchester Foot Pain and Disability Index) and patient global impression of change scale. To investigate the biomechanical effect of foot orthoses, in-shoe foot kinematics and plantar pressures were evaluated at 12 weeks. Of the 119 participants screened, 37 were randomised and 33 completed the study (FFO = 18, sham = 15). Compliance with foot orthoses and blinding of the intervention was achieved in three quarters of the group. Both groups reported improvements in pain, function and global impression of change; the FFO group reporting greater improvements compared to the sham group. The biomechanical outcomes indicated the FFO group inverted the hindfoot and increased midfoot maximum plantar force compared to the sham group. The present findings suggest FFOs worn over 12 weeks may provide detectable clinical and biomechanical benefits compared to sham orthoses. This feasibility study provides useful clinical, biomechanical and statistical information for the design and implementation of a definitive randomised controlled trial to evaluate the effectiveness of FFOs in treating painful midfoot OA.

The ring vaccination trial: a novel cluster randomised controlled trial design to evaluate vaccine efficacy and effectiveness during outbreaks, with special reference to Ebola.

PubMed

2015-07-27

A World Health Organization expert meeting on Ebola vaccines proposed urgent safety and efficacy studies in response to the outbreak in West Africa. One approach to communicable disease control is ring vaccination of individuals at high risk of infection due to their social or geographical connection to a known case. This paper describes the protocol for a novel cluster randomised controlled trial design which uses ring vaccination.In the Ebola ça suffit ring vaccination trial, rings are randomised 1:1 to (a) immediate vaccination of eligible adults with single dose vaccination or (b) vaccination delayed by 21 days. Vaccine efficacy against disease is assessed in participants over equivalent periods from the day of randomisation. Secondary objectives include vaccine effectiveness at the level of the ring, and incidence of serious adverse events. Ring vaccination trials are adaptive, can be run until disease elimination, allow interim analysis, and can go dormant during inter-epidemic periods. © Ebola ça suffit ring vaccination trial consortium 2015.

Placebo effects in psychiatry: mediators and moderators

PubMed Central

Weimer, Katja; Colloca, Luana; Enck, Paul

2015-01-01

A strong placebo response in psychiatric disorders has been noted for the past 50 years and various attempts have been made to identify predictors of it, by use of meta-analyses of randomised controlled trials and laboratory studies. We reviewed 31 meta-analyses and systematic reviews of more than 500 randomised placebo-controlled trials across psychiatry (depression, schizophrenia, mania, attention-deficit hyperactivity disorder, autism, psychosis, binge-eating disorder, and addiction) for factors identified to be associated with increased placebo response. Of 20 factors discussed, only three were often linked to high placebo responses: low baseline severity of symptoms, more recent trials, and unbalanced randomisation (more patients randomly assigned to drug than placebo). Randomised controlled trials in non-drug therapy have not added further predictors, and laboratory studies with psychological, brain, and genetic approaches have not been successful in identifying predictors of placebo responses. This comprehensive Review suggests that predictors of the placebo response are still to be discovered, the response probably has more than one mediator, and that different and distinct moderators are probably what cause the placebo response within psychiatry and beyond. PMID:25815249

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

Four layer bandage compared with short stretch bandage for venous leg ulcers: systematic review and meta-analysis of randomised controlled trials with data from individual patients

PubMed Central

Tierney, Jayne; Cullum, Nicky; Bland, J Martin; Franks, Peter J; Mole, Trevor; Scriven, Mark

2009-01-01

Objective To compare the effectiveness of two types of compression treatment (four layer bandage and short stretch bandage) in people with venous leg ulceration. Design Systematic review and meta-analysis of patient level data. Data sources Electronic databases (the Cochrane Central Register of Controlled Trials, the Cochrane Wounds Group Specialised Register, Medline, Embase, CINAHL, and National Research Register) and reference lists of retrieved articles searched to identify relevant trials and primary investigators. Primary investigators of eligible trials were invited to contribute raw data for re-analysis. Review methods Randomised controlled trials of four layer bandage compared with short stretch bandage in people with venous leg ulceration were eligible for inclusion. The primary outcome for the meta-analysis was time to healing. Cox proportional hazards models were run to compare the methods in terms of time to healing with adjustment for independent predictors of healing. Secondary outcomes included incidence and number of adverse events per patient. Results Seven eligible trials were identified (887 patients), and patient level data were retrieved for five (797 patients, 90% of known randomised patients). The four layer bandage was associated with significantly shorter time to healing: hazard ratio (95% confidence interval) from multifactorial model based on five trials was 1.31 (1.09 to 1.58), P=0.005. Larger ulcer area at baseline, more chronic ulceration, and previous ulceration were all independent predictors of delayed healing. Data from two trials showed no evidence of a difference in adverse event profiles between the two bandage types. Conclusions Venous leg ulcers in patients treated with four layer bandages heal faster, on average, than those of people treated with the short stretch bandage. Benefits were consistent across patients with differing prognostic profiles. PMID:19376798

Targeted rehabilitation to improve outcome after total knee replacement (TRIO): study protocol for a randomised controlled trial.

PubMed

Simpson, A Hamish R W; Hamilton, David F; Beard, David J; Barker, Karen L; Wilton, Timothy; Hutchison, James D; Tuck, Chris; Stoddard, Andrew; Macfarlane, Gary J; Murray, Gordon D

2014-02-01

Approximately 20% of patients are not satisfied with the outcome of total knee replacement, great volumes of which are carried out yearly. Physiotherapy is often provided by the NHS to address dysfunction following knee replacement; however the efficacy of this is unknown. Although clinically it is accepted that therapy is useful, provision of physiotherapy to all patients post-operatively does not enhance outcomes at one year. No study has previously assessed the effect of targeting therapy to individuals struggling to recover in the early post-operative phase.The aim of the TRIO study is to determine whether stratifying care by targeting physiotherapy to those individuals performing poorly following knee replacement is effective in improving the one year outcomes. We are also investigating whether the structure of the physiotherapy provision itself influences outcomes. The study is a multi-centre prospective randomised controlled trial (RCT) of patients undergoing primary total knee replacement, with treatment targeted at those deemed most susceptible to gain from it. Use of the national PROMS programme for pre-operative data collection allows us to screen all patients at initial post-operative clinical review, and recruit only those deemed to be recovering slowly.We aim to recruit 440 patients through various NHS orthopaedic centres who will undergo six weeks of physiotherapy. The intervention will be either 'intensive' involving both hospital and home-based functional exercise rehabilitation, or 'standard of care' consisting of home exercises. Patients will be randomised to either group using a web-based system. Both groups will receive pre and post-intervention physiotherapy review. Patients will be followed-up to one year post-operation. The primary outcome measure is the Oxford Knee Score. Secondary outcomes are patient satisfaction, functional ability, pain scores and cost-effectiveness. Current Controlled Trials ISRCTN23357609. ClinicalTrials.gov NCT01849445.

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

PubMed Central

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

1999-01-01

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

COgnitive behavioural therapy vs standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES): a multicentre randomised controlled trial protocol.

PubMed

Goldstein, Laura H; Mellers, John D C; Landau, Sabine; Stone, Jon; Carson, Alan; Medford, Nick; Reuber, Markus; Richardson, Mark; McCrone, Paul; Murray, Joanna; Chalder, Trudie

2015-06-27

The evidence base for the effectiveness of psychological interventions for patients with dissociative non-epileptic seizures (DS) is currently extremely limited, although data from two small pilot randomised controlled trials (RCTs), including from our group, suggest that Cognitive Behavioural Therapy (CBT) may be effective in reducing DS occurrence and may improve aspects of psychological status and psychosocial functioning. The study is a multicentre, pragmatic parallel group RCT to evaluate the clinical and cost-effectiveness of specifically-tailored CBT plus standardised medical care (SMC) vs SMC alone in reducing DS frequency and improving psychological and health-related outcomes. In the initial screening phase, patients with DS will receive their diagnosis from a neurologist/epilepsy specialist. If patients are eligible and interested following the provision of study information and a booklet about DS, they will consent to provide demographic information and fortnightly data about their seizures, and agree to see a psychiatrist three months later. We aim to recruit ~500 patients to this screening stage. After a review three months later by a psychiatrist, those patients who have continued to have DS in the previous eight weeks and who meet further eligibility criteria will be told about the trial comparing CBT + SMC vs SMC alone. If they are interested in participating, they will be given a further booklet on DS and study information. A research worker will see them to obtain their informed consent to take part in the RCT. We aim to randomise 298 people (149 to each arm). In addition to a baseline assessment, data will be collected at 6 and 12 months post randomisation. Our primary outcome is monthly seizure frequency in the preceding month. Secondary outcomes include seizure severity, measures of seizure freedom and reduction, psychological distress and psychosocial functioning, quality of life, health service use, cost effectiveness and adverse events. We will include a nested qualitative study to evaluate participants' views of the intervention and factors that acted as facilitators and barriers to participation. This study will be the first adequately powered evaluation of CBT for this patient group and offers the potential to provide an evidence base for treating this patient group. Current Controlled Trials ISRCTN05681227 ClinicalTrials.gov NCT02325544.

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

PubMed

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

2018-03-02

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

Thalidomide and prednisolone versus prednisolone alone as consolidation therapy after autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the ALLG MM6 multicentre, open-label, randomised phase 3 study.

PubMed

Kalff, Anna; Kennedy, Nola; Smiley, Angela; Prince, H Miles; Roberts, Andrew W; Bradstock, Kenneth; De Abreu Lourenço, Richard; Frampton, Chris; Spencer, Andrew

2014-12-01

We previously showed that consolidation therapy with thalidomide and prednisolone improved progression-free and overall survival in patients with multiple myeloma who had undergone autologous stem-cell transplantation. We aimed to assess whether these survival advantages were durable at 5 years. The ALLG MM6 trial was a multicentre, open-label, randomised phase 3 trial done between Jan 13, 2002, and March 15, 2005, at 29 sites in Australia and New Zealand. Patients with newly diagnosed multiple myeloma were randomly assigned (1:1), via computer-generated randomisation charts, to receive indefinite prednisolone maintenance alone (control group) or in combination with 12 months of thalidomide consolidation (thalidomide group) after autologous stem-cell transplantation. Randomisation was stratified by treating centre and pre-transplantation concentrations of β2 microglobulin. Patients and treating physicians were not masked to treatment allocation. Primary endpoints were progression-free survival and overall survival. Analysis was by intention to treat. Secondary endpoints were overall response to salvage therapy, incidence of second primary malignancy incidence, and cost-effectiveness. This trial is registered with the Australian and New Zealand Clinical Trials Registry, number ACTRN12607000382471. We randomly assigned 269 patients to the thalidomide (n=114) or control group (n=129). After a median follow-up of 5·4 years (IQR 3·1-7·2), estimated 5-year progression-free survival was 27% (95% CI 23-32) in the thalidomide group and 15% (11-18) in the control group (hazard ratio [HR] 0·16, 95% CI 0·044-0·58; p=0·0054) and 5-year overall survival was 66% (95% CI 61-70) and 47% (42-51), respectively (HR 0·12, 95% CI 0·028-0·56; p=0·0072). There was no difference in overall response to salvage therapy, survival post-progression, or incidence of secondary malignancies between the two groups. Incremental cost-effectiveness ratio was AUS$26 996 per mean life-year gained. Consolidation therapy with thalidomide and prednisolone after autologous stem-cell transplantaion is an acceptable therapeutic approach when alternative drugs are not available. Pharmion Corporation, Novartis Pharmaceuticals, Amgen Australia, The Merrin Foundation, and Alfred Health. Copyright © 2014 Elsevier Ltd. All rights reserved.

Habit training versus habit training with direct visual biofeedback in adults with chronic constipation: study protocol for a randomised controlled trial.

PubMed

Norton, Christine; Emmanuel, Anton; Stevens, Natasha; Scott, S Mark; Grossi, Ugo; Bannister, Sybil; Eldridge, Sandra; Mason, James M; Knowles, Charles H

2017-03-24

Constipation affects up to 20% of adults. Chronic constipation (CC) affects 1-2% of adults. Patient dissatisfaction is high; nearly 80% feel that laxative therapy is unsatisfactory and symptoms have significant impact on quality of life. There is uncertainty about the value of specialist investigations and whether equipment-intensive therapies using biofeedback confer additional benefit when compared with specialist conservative advice. A three-arm, parallel-group, multicentre randomised controlled trial. to determine whether standardised specialist-led habit training plus pelvic floor retraining using computerised biofeedback is more clinically effective than standardised specialist-led habit training alone; to determine whether outcomes are improved by stratification based on prior investigation of anorectal and colonic pathophysiology. Primary outcome measure is response to treatment, defined as a 0.4-point (10% of scale) or greater reduction in Patient Assessment of Constipation-Quality of Life (PAC-QOL) score 6 months after the end of treatment. Other outcomes up to 12 months include symptoms, quality of life, health economics, psychological health and qualitative experience. (1) habit training (HT) with computer-assisted direct visual biofeedback (HTBF) results in an average reduction in PAC-QOL score of 0.4 points at 6 months compared to HT alone in unselected adults with CC, (2) stratification to either HT or HTBF informed by pathophysiological investigation (INVEST) results in an average 0.4-point reduction in PAC-QOL score at 6 months compared with treatment not directed by investigations (No-INVEST). Inclusion: chronic constipation in adults (aged 18-70 years) defined by self-reported symptom duration of more than 6 months; failure of previous laxatives or prokinetics and diet and lifestyle modifications. Consenting participants (n = 394) will be randomised to one of three arms in an allocation ratio of 3:3:2: [1] habit training, [2] habit training and biofeedback or [3] investigation-led allocation to one of these arms. Analysis will be on an intention-to-treat basis. This trial has the potential to answer some of the major outstanding questions in the management of chronic constipation, including whether costly invasive tests are warranted and whether computer-assisted direct visual biofeedback confers additional benefit to well-managed specialist advice alone. International Standard Randomised Controlled Trial Number: ISRCTN11791740. Registered on 16 July 2015.

A pragmatic randomised multi-centre trial of multifamily and single family therapy for adolescent anorexia nervosa.

PubMed

Eisler, Ivan; Simic, Mima; Hodsoll, John; Asen, Eia; Berelowitz, Mark; Connan, Frances; Ellis, Gladys; Hugo, Pippa; Schmidt, Ulrike; Treasure, Janet; Yi, Irene; Landau, Sabine

2016-11-24

Considerable progress has been made in recent years in developing effective treatments for child and adolescent anorexia nervosa, with a general consensus in the field that eating disorders focussed family therapy (often referred to as Maudsley Family Therapy or Family Based Treatment) currently offers the most promising outcomes. Nevertheless, a significant number do not respond well and additional treatment developments are needed to improve outcomes. Multifamily therapy is a promising treatment that has attracted considerable interest and we report the results of the first randomised controlled trial of multifamily therapy for adolescent anorexia nervosa. The study was a pragmatic multicentre randomised controlled superiority trial comparing two outpatient eating disorder focussed family interventions - multifamily therapy (MFT-AN) and single family therapy (FT-AN). A total of 169 adolescents with a DSM-IV diagnosis of anorexia nervosa or eating disorder not otherwise specified (restricting type) were randomised to the two treatments using computer generated blocks of random sizes to ensure balanced numbers in the trial arms. Independent assessors, blind to the allocation, completed evaluations at baseline, 3 months, 12 months (end of treatment) and 18 months. Both treatment groups showed clinically significant improvements with just under 60% achieving a good or intermediate outcome (on the Morgan-Russell scales) at the end of treatment in the FT-AN group and more than 75% in the MFT-AN group - a statistically significant benefit in favour of the multifamily intervention (OR = 2.55 95%; CI 1.17, 5.52; p = 0.019). At follow-up (18 months post baseline) there was relatively little change compared to end of treatment although the difference in primary outcome between the treatments was no longer statistically significant. Clinically significant gains in weight were accompanied by improvements in mood and eating disorder psychopathology. Approximately half the patients in FT-AN and nearly 60% of those in MFT-AN had started menstruating. This study confirms previous research findings demonstrating the effectiveness of eating disorder focused family therapy and highlights the additional benefits of bringing together groups of families that maximises the use of family resources and mutual support leading to improved outcomes. Current Controlled Trials ISRCTN11275465 ; Registered 29 January 2007 (retrospectively registered).

Recruitment of older adults to three preventative lifestyle improvement studies.

PubMed

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

2018-02-20

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

Moderators of remission with interpersonal counselling or drug treatment in primary care patients with depression: randomised controlled trial.

PubMed

Menchetti, Marco; Rucci, Paola; Bortolotti, Biancamaria; Bombi, Annarosa; Scocco, Paolo; Kraemer, Helena Chmura; Berardi, Domenico

2014-02-01

Despite depressive disorders being very common there has been little research to guide primary care physicians on the choice of treatment for patients with mild to moderate depression. To evaluate the efficacy of interpersonal counselling compared with selective serotonin reuptake inhibitors (SSRIs), in primary care attenders with major depression and to identify moderators of treatment outcome. A randomised controlled trial in nine centres (DEPICS, Australian New Zealand Clinical Trials Registry number: ACTRN12608000479303). The primary outcome was remission of the depressive episode (defined as a Hamilton Rating Scale for Depression score ≤7 at 2 months). Daily functioning was assessed using the Work and Social Adjustment Scale. Logistic regression models were used to identify moderators of treatment outcome. The percentage of patients who achieved remission at 2 months was significantly higher in the interpersonal counselling group compared with the SSRI group (58.7% v. 45.1%, P = 0.021). Five moderators of treatment outcome were found: depression severity, functional impairment, anxiety comorbidity, previous depressive episodes and smoking habit. We identified some patient characteristics predicting a differential outcome with pharmacological and psychological interventions. Should our results be confirmed in future studies, these characteristics will help clinicians to define criteria for first-line treatment of depression targeted to patients' characteristics.

Hypnosis antenatal training for childbirth: a randomised controlled trial.

PubMed

Cyna, A M; Crowther, C A; Robinson, J S; Andrew, M I; Antoniou, G; Baghurst, P

2013-09-01

To determine the use of pharmacologic analgesia during childbirth when antenatal hypnosis is added to standard care. Randomised controlled clinical trial, conducted from December 2005 to December 2010. The largest tertiary referral centre for maternity care in South Australia. A cohort of 448 women at >34 weeks of gestation, with a singleton pregnancy and cephalic presentation, planning a vaginal birth. Exclusions were: the need for an interpreter; pre-existing pain; psychiatric illness; younger than 18 years; and previous experience of hypnosis for childbirth. All participants received usual care. The group of women termed Hypnosis + CD (hypnotherapist guided) were offered three antenatal live hypnosis sessions plus each session's corresponding audio CD for further practise, as well as a final fourth CD to listen to during labour. The group of women termed CD only (nurse administered) were played the same antenatal hypnosis CDs as group 1, but did not receive live hypnosis training. The control group participants were given no additional intervention or CDs. Use of pharmacological analgesia during labour and childbirth. No difference in the use of pharmacological analgesia during labour and childbirth was found comparing hypnosis + CD with control (81.2 versus 76.2%; relative risk, RR 1.07; 95% confidence interval, 95% CI 0.95-1.20), or comparing CD only with control (76.9 versus 76.2%, RR 1.01, 95% CI 0.89-1.15). Antenatal group hypnosis using the Hypnosis Antenatal Training for Childbirth (HATCh) intervention in late pregnancy does not reduce the use of pharmacological analgesia during labour and childbirth. © 2013 RCOG.

Effect of virtual reality training on laparoscopic surgery: randomised controlled trial

PubMed Central

Soerensen, Jette L; Grantcharov, Teodor P; Dalsgaard, Torur; Schouenborg, Lars; Ottosen, Christian; Schroeder, Torben V; Ottesen, Bent S

2009-01-01

Objective To assess the effect of virtual reality training on an actual laparoscopic operation. Design Prospective randomised controlled and blinded trial. Setting Seven gynaecological departments in the Zeeland region of Denmark. Participants 24 first and second year registrars specialising in gynaecology and obstetrics. Interventions Proficiency based virtual reality simulator training in laparoscopic salpingectomy and standard clinical education (controls). Main outcome measure The main outcome measure was technical performance assessed by two independent observers blinded to trainee and training status using a previously validated general and task specific rating scale. The secondary outcome measure was operation time in minutes. Results The simulator trained group (n=11) reached a median total score of 33 points (interquartile range 32-36 points), equivalent to the experience gained after 20-50 laparoscopic procedures, whereas the control group (n=10) reached a median total score of 23 (22-27) points, equivalent to the experience gained from fewer than five procedures (P<0.001). The median total operation time in the simulator trained group was 12 minutes (interquartile range 10-14 minutes) and in the control group was 24 (20-29) minutes (P<0.001). The observers’ inter-rater agreement was 0.79. Conclusion Skills in laparoscopic surgery can be increased in a clinically relevant manner using proficiency based virtual reality simulator training. The performance level of novices was increased to that of intermediately experienced laparoscopists and operation time was halved. Simulator training should be considered before trainees carry out laparoscopic procedures. Trial registration ClinicalTrials.gov NCT00311792. PMID:19443914

The effect of valacyclovir on HIV and HSV-2 in HIV-infected persons on antiretroviral therapy with previously unrecognised HSV-2.

PubMed

Van Wagoner, Nicholas; Geisler, William M; Bachmann, Laura H; Hook, Edward W

2015-07-01

In the absence of antiretroviral therapy, valacyclovir may reduce HIV viral load and increase CD4+ T-lymphocyte count. We sought to evaluate the impact of valacyclovir on HIV and HSV-2 in co-infected patients receiving antiretroviral therapy with previously unrecognised HSV-2 infection. A prospective, randomised-controlled, 24-week trial of valacyclovir 1000 mg was performed. Mean CD4+ T-lymphocyte count at 24 weeks compared to baseline CD4+ T-lymphocyte count was the primary outcome. HIV viral load suppression, HSV-2 outbreaks and asymptomatic HSV-2 shedding were secondary outcomes. Participants were randomised to valacyclovir (N = 66) or placebo (N = 35). Study completion was 64%. There was no change in 24 weeks compared to baseline CD4+ T-lymphocyte count in either group (valacyclovir p = 0.91, placebo p = 0.59) or the proportion with HIV viral load suppression (valacyclovir p = 0.75, placebo p = 1.0). Genital HSV and asymptomatic HSV-2 shedding were rare. Valacyclovir had no effect on CD4+ T-lymphocyte count or HIV viral load in this population. Valacyclovir may reduce clinical outbreaks and asymptomatic HSV-2 shedding, but the rarity of these events, along with its lack of benefit on HIV, does not support its use in this clinical setting. © The Author(s) 2014.

Exploring the Effects of a Universal Classroom Management Training Programme on Teacher and Child Behaviour: A Group Randomised Controlled Trial and Cost Analysis

ERIC Educational Resources Information Center

Hickey, Grainne; McGilloway, Sinead; Hyland, Lynda; Leckey, Yvonne; Kelly, Paul; Bywater, Tracey; Comiskey, Catherine; Lodge, Anne; Donnelly, Michael; O'Neill, Donal

2017-01-01

Teachers frequently struggle to cope with conduct problems in the classroom. The aim of this study was to assess the effectiveness of the Incredible Years Teacher Classroom Management Training Programme for improving teacher competencies and child adjustment. The study involved a group randomised controlled trial which included 22 teachers and 217…

Educational Benefits of Using Game Consoles in a Primary Classroom: A Randomised Controlled Trial

ERIC Educational Resources Information Center

Miller, David J.; Robertson, Derek P.

2011-01-01

It is known that computer games are motivating for children, but there is limited direct evidence of their effects on classroom learning. The studies that are available tend to be limited in terms of output data reported, or small in scale, or both. The aim of this randomised controlled trial was to upscale a recent study by Miller and Robertson…

The Importance of Specifying and Studying Causal Mechanisms in School-Based Randomised Controlled Trials: Lessons from Two Studies of Cross-Age Peer Tutoring

ERIC Educational Resources Information Center

Morris, Stephen P.; Edovald, Triin; Lloyd, Cheryl; Kiss, Zsolt

2016-01-01

Based on the experience of evaluating 2 cross-age peer-tutoring interventions, we argue that researchers need to pay greater attention to causal mechanisms within the context of school-based randomised controlled trials. Without studying mechanisms, researchers are less able to explain the underlying causal processes that give rise to results from…

A Randomised Controlled Trial Using Mobile Advertising to Promote Safer Sex and Sun Safety to Young People

ERIC Educational Resources Information Center

Gold, J.; Aitken, C. K.; Dixon, H. G.; Lim, M. S. C.; Gouillou, M.; Spelman, T.; Wakefield, M.; Hellard, M. E.

2011-01-01

Mobile phone text messages (SMS) are a promising method of health promotion, but a simple and low cost way to obtain phone numbers is required to reach a wide population. We conducted a randomised controlled trial with simultaneous brief interventions to (i) evaluate effectiveness of messages related to safer sex and sun safety and (ii) pilot the…

A Pilot Randomised Controlled Trial of a School-Based Resilience Intervention to Prevent Depressive Symptoms for Young Adolescents with Autism Spectrum Disorder: A Mixed Methods Analysis

ERIC Educational Resources Information Center

Mackay, Bethany A.; Shochet, Ian M.; Orr, Jayne A.

2017-01-01

Despite increased depression in adolescents with Autism Spectrum Disorder (ASD), effective prevention approaches for this population are limited. A mixed methods pilot randomised controlled trial (N = 29) of the evidence-based Resourceful Adolescent Program-Autism Spectrum Disorder (RAP-A-ASD) designed to prevent depression was conducted in…

A systematic review of randomised controlled trials on the effectiveness of exercise programs on Lumbo Pelvic Pain among postnatal women.

PubMed

Tseng, Pei-Ching; Puthussery, Shuby; Pappas, Yannis; Gau, Meei-Ling

2015-11-26

A substantial number of women tend to be affected by Lumbo Pelvic Pain (LPP) following child birth. Physical exercise is indicated as a beneficial method to relieve LPP, but individual studies appear to suggest mixed findings about its effectiveness. This systematic review aimed to synthesise evidence from randomised controlled trials on the effectiveness of exercise on LPP among postnatal women to inform policy, practice and future research. A systematic review was conducted of all randomised controlled trials published between January 1990 and July 2014, identified through a comprehensive search of following databases: PubMed, PEDro, Embase, Cinahl, Medline, SPORTDiscus, Cochrane Pregnancy and Childbirth Group's Trials Register, and electronic libraries of authors'institutions. Randomised controlled trials were eligible for inclusion if the intervention comprised of postnatal exercise for women with LPP onset during pregnancy or within 3 months after delivery and the outcome measures included changes in LPP. Selected articles were assessed using the PEDro Scale for methodological quality and findings were synthesised narratively as meta-analysis was found to be inappropriate due to heterogeneity among included studies. Four randomised controlled trials were included, involving 251 postnatal women. Three trials were rated as of 'good' methodological quality. All trials, except one, were at low risk of bias. The trials included physical exercise programs with varying components, differing modes of delivery, follow up times and outcome measures. Intervention in one trial, involving physical therapy with specific stabilising exercises, proved to be effective in reducing LPP intensity. An improvement in gluteal pain on the right side was reported in another trial and a significant difference in pain frequency in another. Our review indicates that only few randomised controlled trials have evaluated the effectiveness of exercise on LPP among postnatal women. There is also a great amount of variability across existing trials in the components of exercise programs, modes of delivery, follow up times and outcome measures. While there is some evidence to indicate the effectiveness of exercise for relieving LPP, further good quality trials are needed to ascertain the most effective elements of postnatal exercise programs suited for LPP treatment.

Five-year follow-up of survival and relapse in patients who received cryotherapy during high-dose chemotherapy for stem cell transplantation shows no safety concerns.

PubMed

Svanberg, A; Ohrn, K; Birgegård, G

2012-11-01

We have previously published a randomised controlled study of the efficacy of cryotherapy in preventing acute oral mucositis after high-dose chemotherapy for stem cell transplantation. The present study is a 5-year follow-up safety study of survival in these patients. In the previously published study oral cryotherapy (cooling of the oral cavity) during high-dose chemotherapy significantly reduced mucositis grade and opiate use in the treated group. All patients were followed up for at least 5 years with regard to relapse and death rates. Baseline data, transplant complications and mucositis data were compared. Significantly more patients (25/39) who received oral cryotherapy were alive after 5 years compared to 15/39 in the control group (P= 0.025). Relapse rates were similar. The only baseline difference was a lower proportion of patients in complete remission at transplantation in the control group (6 vs. 13, P= 0.047). This 5-year follow-up study gave no support for safety concerns with cryotherapy. © 2012 Blackwell Publishing Ltd.

Short structured general mental health in service training programme in Kenya improves patient health and social outcomes but not detection of mental health problems - a pragmatic cluster randomised controlled trial

PubMed Central

2013-01-01

Trial design A pragmatic cluster randomised controlled trial. Methods Participants: Clusters were primary health care clinics on the Ministry of Health list. Clients were eligible if they were aged 18 and over. Interventions: Two members of staff from each intervention clinic received the training programme. Clients in both intervention and control clinics subsequently received normal routine care from their health workers. Objective: To examine the impact of a mental health inservice training on routine detection of mental disorder in the clinics and on client outcomes. Outcomes: The primary outcome was the rate of accurate routine clinic detection of mental disorder and the secondary outcome was client recovery over a twelve week follow up period. Randomisation: clinics were randomised to intervention and control groups using a table of random numbers. Blinding: researchers and clients were blind to group assignment. Results Numbers randomised: 49 and 50 clinics were assigned to intervention and control groups respectively. 12 GHQ positive clients per clinic were identified for follow up. Numbers analysed: 468 and 478 clients were followed up for three months in intervention and control groups respectively. Outcome: At twelve weeks after training of the intervention group, the rate of accurate routine clinic detection of mental disorder was greater than 0 in 5% versus 0% of the intervention and control groups respectively, in both the intention to treat analysis (p = 0.50) and the per protocol analysis (p =0.50). Standardised effect sizes for client improvement were 0.34 (95% CI = (0.01,0.68)) for the General Health Questionnaire, 0.39 ((95% CI = (0.22, 0.61)) for the EQ and 0.49 (95% CI = (0.11,0.87)) for WHODAS (using ITT analysis); and 0.43 (95% CI = (0.09,0.76)) for the GHQ, 0.44 (95% CI = (0.22,0.65)) for the EQ and 0.58 (95% CI = (0.18,0.97)) for WHODAS (using per protocol analysis). Harms: None identified. Conclusion The training programme did not result in significantly improved recorded diagnostic rates of mental disorders in the routine clinic consultation register, but did have significant effects on patient outcomes in routine clinical practice. Trial registration International Standard Randomised Controlled Trial Number Register ISRCTN53515024. PMID:24188964

A randomised controlled trial of three or one breathing technique training sessions for breathlessness in people with malignant lung disease.

PubMed

Johnson, Miriam J; Kanaan, Mona; Richardson, Gerry; Nabb, Samantha; Torgerson, David; English, Anne; Barton, Rachael; Booth, Sara

2015-09-07

About 90 % of patients with intra-thoracic malignancy experience breathlessness. Breathing training is helpful, but it is unknown whether repeated sessions are needed. The present study aims to test whether three sessions are better than one for breathlessness in this population. This is a multi-centre randomised controlled non-blinded parallel arm trial. Participants were allocated to three sessions or single (1:2 ratio) using central computer-generated block randomisation by an independent Trials Unit and stratified for centre. The setting was respiratory, oncology or palliative care clinics at eight UK centres. Inclusion criteria were people with intrathoracic cancer and refractory breathlessness, expected prognosis ≥3 months, and no prior experience of breathing training. The trial intervention was a complex breathlessness intervention (breathing training, anxiety management, relaxation, pacing, and prioritisation) delivered over three hour-long sessions at weekly intervals, or during a single hour-long session. The main primary outcome was worst breathlessness over the previous 24 hours ('worst'), by numerical rating scale (0 = none; 10 = worst imaginable). Our primary analysis was area under the curve (AUC) 'worst' from baseline to 4 weeks. All analyses were by intention to treat. Between April 2011 and October 2013, 156 consenting participants were randomised (52 three; 104 single). Overall, the 'worst' score reduced from 6.81 (SD, 1.89) to 5.84 (2.39). Primary analysis [n = 124 (79 %)], showed no between-arm difference in the AUC: three sessions 22.86 (7.12) vs single session 22.58 (7.10); P value = 0.83); mean difference 0.2, 95 % CIs (-2.31 to 2.97). Complete case analysis showed a non-significant reduction in QALYs with three sessions (mean difference -0.006, 95 % CIs -0.018 to 0.006). Sensitivity analyses found similar results. The probability of the single session being cost-effective (threshold value of £20,000 per QALY) was over 80 %. There was no evidence that three sessions conferred additional benefits, including cost-effectiveness, over one. A single session of breathing training seems appropriate and minimises patient burden. Registry: ISRCTN; ISRCTN49387307; http://www.isrctn.com/ISRCTN49387307 ; registration date: 25/01/2011.

Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial.

PubMed

Iijima, Kazumoto; Sako, Mayumi; Nozu, Kandai; Mori, Rintaro; Tuchida, Nao; Kamei, Koichi; Miura, Kenichiro; Aya, Kunihiko; Nakanishi, Koichi; Ohtomo, Yoshiyuki; Takahashi, Shori; Tanaka, Ryojiro; Kaito, Hiroshi; Nakamura, Hidefumi; Ishikura, Kenji; Ito, Shuichi; Ohashi, Yasuo

2014-10-04

Rituximab could be an effective treatment for childhood-onset, complicated, frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). We investigated the efficacy and safety of rituximab in patients with high disease activity. We did a multicentre, double-blind, randomised, placebo-controlled trial at nine centres in Japan. We screened patients aged 2 years or older experiencing a relapse of FRNS or SDNS, which had originally been diagnosed as nephrotic syndrome when aged 1-18 years. Patients with complicated FRNS or SDNS who met all other criteria were eligible for inclusion after remission of the relapse at screening. We used a computer-generated sequence to randomly assign patients (1:1) to receive rituximab (375 mg/m(2)) or placebo once weekly for 4 weeks, with age, institution, treatment history, and the intervals between the previous three relapses as adjustment factors. Patients, guardians, caregivers, physicians, and individuals assessing outcomes were masked to assignments. All patients received standard steroid treatment for the relapse at screening and stopped taking immunosuppressive agents by 169 days after randomisation. Patients were followed up for 1 year. The primary endpoint was the relapse-free period. Safety endpoints were frequency and severity of adverse events. Patients who received their assigned intervention were included in analyses. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000001405. Patients were centrally registered between Nov 13, 2008, and May 19, 2010. Of 52 patients who underwent randomisation, 48 received the assigned intervention (24 were given rituximab and 24 placebo). The median relapse-free period was significantly longer in the rituximab group (267 days, 95% CI 223-374) than in the placebo group (101 days, 70-155; hazard ratio: 0·27, 0·14-0·53; p<0·0001). Ten patients (42%) in the rituximab group and six (25%) in the placebo group had at least one serious adverse event (p=0·36). Rituximab is an effective and safe treatment for childhood-onset, complicated FRNS and SDNS. Japanese Ministry of Health, Labour and Welfare. Copyright © 2014 Elsevier Ltd. All rights reserved.

Implementation and effectiveness of 'care navigation', coordinated management for people with complex chronic illness: rationale and methods of a randomised controlled trial.

PubMed

Plant, Natalie; Mallitt, Kylie-Ann; Kelly, Patrick J; Usherwood, Tim; Gillespie, James; Boyages, Steven; Jan, Stephen; McNab, Justin; Essue, Beverley M; Gradidge, Kathy; Maranan, Nereus; Ralphs, David; Aspin, Clive; Leeder, Stephen

2013-05-03

Chronic illness is a significant driver of the global burden of disease and associated health care costs. People living with severe chronic illness are heavy users of acute hospital services; better coordination of their care could potentially improve health outcomes while reducing hospital use. The Care Navigation trial will evaluate an in-hospital coordinated care intervention on health service use and quality of life in chronically ill patients. A randomised controlled trial in 500 chronically ill patients presenting to the emergency department of a hospital in Western Sydney, Australia. Participants have three or more hospital admissions within a previous 12 month period and either aged ≥70 years; or aged ≥45 years and of Aboriginal or Torres Strait Islander descent; or aged ≥ 16 with a diagnosis of a respiratory or cardiology related illness. Patients are randomised to either the coordinated care program (Care Navigation), or to usual care. The Care Navigation program consists of dedicated nurses who conduct patient risk assessments, oversee patient nursing while in hospital, and guide development of a care plan for the management of chronic illness after being discharged from hospital. These nurses also book community appointments and liaise with general practitioners. The main outcome variables are the number of emergency department re-presentations and hospital readmissions, and quality of life during a 24 month follow-up. Secondary outcomes are length of hospital stay, mortality, time to first hospital re-admission, time to first emergency department re-presentation, patient satisfaction, adherence to prescribed medications, amount and type of in-hospital referrals made for consultations and diagnostic testing, and the number and type of community health referrals. A process evaluation and economic analysis will be conducted alongside the randomised trial. A trial of in-hospital care coordination may support recent evidence that engaging primary health services in care plans linked to multidisciplinary team support improves patient outcomes and reduces costs to the health system. This will inform local, national and international health policy. Australia New Zealand Clinical Trials Registry ACTRN12609000554268.

The Head Injury Retrieval Trial (HIRT): a single-centre randomised controlled trial of physician prehospital management of severe blunt head injury compared with management by paramedics only

PubMed Central

Garner, Alan A; Mann, Kristy P; Fearnside, Michael; Poynter, Elwyn; Gebski, Val

2015-01-01

Background Advanced prehospital interventions for severe brain injury remains controversial. No previous randomised trial has been conducted to evaluate additional physician intervention compared with paramedic only care. Methods Participants in this prospective, randomised controlled trial were adult patients with blunt trauma with either a scene GCS score <9 (original definition), or GCS<13 and an Abbreviated Injury Scale score for the head region ≥3 (modified definition). Patients were randomised to either standard ground paramedic treatment or standard treatment plus a physician arriving by helicopter. Patients were evaluated by 30-day mortality and 6-month Glasgow Outcome Scale (GOS) scores. Due to high non-compliance rates, both intention-to-treat and as-treated analyses were preplanned. Results 375 patients met the original definition, of which 197 was allocated to physician care. Differences in the 6-month GOS scores were not significant on intention-to-treat analysis (OR 1.11, 95% CI 0.74 to 1.66, p=0.62) nor was the 30-day mortality (OR 0.91, 95% CI 0.60 to 1.38, p=0.66). As-treated analysis showed a 16% reduction in 30-day mortality in those receiving additional physician care; 60/195 (29%) versus 81/180 (45%), p<0.01, Number needed to treat =6. 338 patients met the modified definition, of which 182 were allocated to physician care. The 6-month GOS scores were not significantly different on intention-to-treat analysis (OR 1.14, 95% CI 0.73 to 1.75, p=0.56) nor was the 30-day mortality (OR 1.05, 95% CI 0.66 to 1.66, p=0.84). As-treated analyses were also not significantly different. Conclusions This trial suggests a potential mortality reduction in patients with blunt trauma with GCS<9 receiving additional physician care (original definition only). Confirmatory studies which also address non-compliance issues are needed. Trial registration number NCT00112398. PMID:25795741

Aspirin for Venous Ulcers: Randomised Trial (AVURT): study protocol for a randomised controlled trial.

PubMed

Tilbrook, Helen; Forsythe, Rachael O; Rolfe, Debbie; Clark, Laura; Bland, Martin; Buckley, Hannah; Chetter, Ian; Cook, Liz; Dumville, Jo; Gabe, Rhian; Harding, Keith; Layton, Alison; Lindsay, Ellie; McDaid, Catriona; Moffatt, Christine; Phillips, Ceri; Stansby, Gerard; Vowden, Peter; Williams, Laurie; Torgerson, David; Hinchliffe, Robert J

2015-11-10

Venous leg ulcers (VLUs) are the commonest cause of leg ulceration, affecting 1 in 100 adults. There is a significant health burden associated with VLUs - it is estimated that the cost of treatment for 1 ulcer is up to £1300 per year in the NHS. The mainstay of treatment is with graduated compression bandaging; however, treatment is often prolonged and up to one quarter of venous leg ulcers do not heal despite standard care. Two previous trials have suggested that low-dose aspirin, as an adjunct to standard care, may hasten healing, but these trials were small and of poor quality. Aspirin is an inexpensive, widely used medication but its safety and efficacy in the treatment of VLUs remains to be established. AVURT is a phase II randomised double blind, parallel-group, placebo-controlled efficacy trial. The primary objective is to examine whether aspirin, in addition to standard care, is effective in patients with chronic VLUs (i.e. over 6 weeks in duration or a history of VLU). Secondary objectives include feasibility and safety of aspirin in this population. A target of 100 participants, identified from community leg ulcer clinics and hospital clinics, will be randomised to receive either 300 mg of aspirin once daily or placebo. All participants will receive standard care with compression therapy. The primary outcome will be time to healing of the reference ulcer. Follow-up will occur for a maximum of 27 weeks. The primary analysis will use a Cox proportional hazards model to compare time to healing using the principles of intention-to-treat. Secondary outcomes will include ulcer size, pain evaluation, compliance and adverse events. The AVURT trial will investigate the efficacy and safety of aspirin as a treatment for VLU and will inform on the feasibility of proceeding to a larger phase III study. This study will address the paucity of information currently available regarding aspirin therapy to treat VLU. The study is registered on a public database with clinicaltrials.gov ( NCT02333123 ; registered on 5 November 2014).

Arthroscopic decompression not recommended in the treatment of rotator cuff tendinopathy: a final review of a randomised controlled trial at a minimum follow-up of ten years.

PubMed

Ketola, S; Lehtinen, J T; Arnala, I

2017-06-01

Rotator cuff tendinopathy has a multifactorial origin. Rejecting the mechanistic theory has also led to abandoning operative treatment at initial presentation in the first line. Physiotherapy exercise programmes are the accepted first line treatment. The aim of this study was to assess the long-term additional benefits of subacromial decompression in the treatment of rotator cuff tendinopathy. This randomised controlled trial of 140 patients (52 men, 88 women, mean age 47.1 years; 18 to 60) with rotator cuff tendinopathy extended previous work up to a maximum of 13 years. The patients were randomised into two treatment groups: arthroscopic acromioplasty and a supervised exercise treatment and a similar supervised exercise treatment alone. Self-reported pain on a visual analogue scale (VAS) was the primary outcome measure. Secondary measures were disability, working ability, pain at night, Shoulder Disability Questionnaire score and the number of painful days during the three months preceding the final assessment. A total of 90 patients (64%) returned questionnaires at a mean 12 years after randomisation. On an intention-to-treat basis, both treatment groups reached statistically significant improvement compared with the initial VAS for pain, but there was no significant difference between groups. The same was true in the secondary outcome measures. Due to group changes, the results were also analysed per protocol: operated or not. No significant differences between the groups were found. The natural history of rotator cuff tendinopathy probably plays a significant role in the results in the long-term. Even though the patients who underwent operative treatment had a stronger belief in recovery, which is likely to be surgical and the effect of placebo, the exercise group obtained similar results. In the future, an optimum exercise regime should be searched for, as the most clinically and cost-effective conservative treatment for rotator cuff tendinopathy. Cite this article: Bone Joint J 2017;99-B:799-805. ©2017 The British Editorial Society of Bone & Joint Surgery.

Antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease.

PubMed

Martí-Carvajal, Arturo J; Solà, Ivan

2015-06-09

Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. People with liver disease frequently have haemostatic abnormalities such as hyperfibrinolysis. Therefore, antifibrinolytic amino acids have been proposed to be used as supplementary interventions alongside any of the primary treatments for upper gastrointestinal bleeding in people with liver diseases. This is an update of this Cochrane review. To assess the beneficial and harmful effects of antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease. We searched The Cochrane Hepato-Biliary Controlled Trials Register (February 2015), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2 of 12, 2015), MEDLINE (Ovid SP) (1946 to February 2015), EMBASE (Ovid SP) (1974 to February 2015), Science Citation Index EXPANDED (1900 to February 2015), LILACS (1982 to February 2015), World Health Organization Clinical Trials Search Portal (accessed 26 February 2015), and the metaRegister of Controlled Trials (accessed 26 February 2015). We scrutinised the reference lists of the retrieved publications. Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. Observational studies for assessment of harms. We planned to summarise data from randomised clinical trials using standard Cochrane methodologies and assessed according to the GRADE approach. We found no randomised clinical trials assessing antifibrinolytic amino acids for treating upper gastrointestinal bleeding in people with acute or chronic liver disease. We did not identify quasi-randomised, historically controlled, or observational studies in which we could assess harms. This updated Cochrane review identified no randomised clinical trials assessing the benefits and harms of antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease. The benefits and harms of antifibrinolytic amino acids need to be tested in randomised clinical trials. Unless randomised clinical trials are conducted to assess the trade-off between benefits and harms, we cannot recommend or refute antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver diseases.

A pragmatic multi-centre randomised controlled trial of fluid loading and level of dependency in high-risk surgical patients undergoing major elective surgery: trial protocol

PubMed Central

2010-01-01

Background Patients undergoing major elective or urgent surgery are at high risk of death or significant morbidity. Measures to reduce this morbidity and mortality include pre-operative optimisation and use of higher levels of dependency care after surgery. We propose a pragmatic multi-centre randomised controlled trial of level of dependency and pre-operative fluid therapy in high-risk surgical patients undergoing major elective surgery. Methods/Design A multi-centre randomised controlled trial with a 2 * 2 factorial design. The first randomisation is to pre-operative fluid therapy or standard regimen and the second randomisation is to routine intensive care versus high dependency care during the early post-operative period. We intend to recruit 204 patients undergoing major elective and urgent abdominal and thoraco-abdominal surgery who fulfil high-risk surgical criteria. The primary outcome for the comparison of level of care is cost-effectiveness at six months and for the comparison of fluid optimisation is the number of hospital days after surgery. Discussion We believe that the results of this study will be invaluable in determining the future care and clinical resource utilisation for this group of patients and thus will have a major impact on clinical practice. Trial Registration Trial registration number - ISRCTN32188676 PMID:20398378

Twelve month follow-up on a randomised controlled trial of relaxation training for post-stroke anxiety.

PubMed

Golding, Katherine; Fife-Schaw, Chris; Kneebone, Ian

2017-09-01

To follow up participants in a randomised controlled trial of relaxation training for anxiety after stroke at 12 months. Twelve month follow-up to a randomised controlled trial, in which the control group also received treatment. Community. Fifteen of twenty one original participants with post-stroke anxiety participated in a one year follow-up study. A self-help autogenic relaxation CD listened to five times a week for one month, immediately in the intervention group and after three months in the control group. Hospital Anxiety and Depression Scale-Anxiety subscale and the Telephone Interview of Cognitive Status for inclusion. Hospital Anxiety and Depression Scale-Anxiety subscale for outcome. All measures were administered by phone. Anxiety ratings reduced significantly between pre and post-intervention, and between pre-intervention and one year follow-up ( χ 2 (2) = 22.29, p < 0.001). Reductions in anxiety in stroke survivors who received a self-help autogenic relaxation CD appear to be maintained after one year.

The effects of 2 weeks of interval vs continuous walking training on glycaemic control and whole-body oxidative stress in individuals with type 2 diabetes: a controlled, randomised, crossover trial.

PubMed

Karstoft, Kristian; Clark, Margaret A; Jakobsen, Ida; Müller, Ida A; Pedersen, Bente K; Solomon, Thomas P J; Ried-Larsen, Mathias

2017-03-01

The aim of this study was to evaluate the effects of oxygen consumption-matched short-term interval walking training (IWT) vs continuous walking training (CWT) on glycaemic control, including glycaemic variability, in individuals with type 2 diabetes. We also assessed whether any training-induced improvements in glycaemic control were associated with systemic oxidative stress levels. Participants (n = 14) with type 2 diabetes completed a crossover trial using three interventions (control intervention [CON], CWT and IWT), each lasting 2 weeks. These were performed in a randomised order (computerised generated randomisation) and separated by washout periods of 4 or 8 weeks after CON or training interventions, respectively. Training included ten supervised treadmill sessions, lasting 60 min/session, and was performed at the research facility. CWT was performed at moderate walking speed (75.6% ± 2.5% of walking peak oxygen consumption [[Formula: see text

The effect of intensive glucose control on all-cause and cardiovascular mortality, myocardial infarction and stroke in persons with type 2 diabetes mellitus: a systematic review and meta-analysis.

PubMed

Marso, Steven P; Kennedy, Kevin F; House, John A; McGuire, Darren K

2010-04-01

We performed a meta-analysis of studies evaluating the effect of intensive glucose control on major adverse cardiovascular events in patients with type 2 diabetes from 1990 to 2009. A search of the published literature and the Cochran Central Register for Controlled Trials was performed using pre-specified inclusion criteria consisting of randomised controlled trials evaluating intensive glycaemic control and reporting the individual endpoints of all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke. Incident rate ratios for these endpoints were calculated using standard meta-analytic techniques of pooled data from eligible trials. Six reports from four randomised trials including 27,544 patients met the pre-specified inclusion criteria. Mean follow-up was 5.4 years; haemoglobin A(1C) at study end was 6.6% vs. 7.4% in patients randomised to intensive compared with conventional glucose control. Intensive glucose control did not affect the incident rate ratio for all-cause mortality (1.01, 95% confidence interval 0.86-1.18, p=0.54) or stroke (1.02, 95% confidence interval 0.88-1.20, p=0.62). However, there was a statistically significant 14% reduction in non-fatal myocardial infarction in patients randomised to intensive glucose control (0.86, 95% confidence interval 0.77-0.97, p=0.015). Although intensification of glucose control did not affect mortality or non-fatal stroke, the risk for non-fatal myocardial infarction was significantly reduced in patients with type 2 diabetes.

The challenge of recruiting people with schizophrenia to a health promotion trial

PubMed Central

Abbott, Margaret; Arthur, Antony; Walker, Liz; Doody, Gillian

2005-01-01

People with schizophrenia have an increased risk of coronary heart disease. This pilot study tested the feasibility of carrying out a randomised controlled trial to compare coronary heart disease prevention for this population through an enhanced occupational therapy support intervention versus a practice-based intervention. Difficulty in deciding whether to take part meant that 123 visits were made to 25 people with 12 ultimately providing informed consent. Participants' discussion at a subsequent focus group (n = 3) suggested a poor understanding of the study process. Distrust of randomisation suggests that randomised controlled trials may not be the best way to evaluate community-based interventions for people with schizophrenia. PMID:16105374

Acute pancreatitis: recent advances through randomised trials.

PubMed

van Dijk, Sven M; Hallensleben, Nora D L; van Santvoort, Hjalmar C; Fockens, Paul; van Goor, Harry; Bruno, Marco J; Besselink, Marc G

2017-11-01

Acute pancreatitis is one of the most common GI conditions requiring acute hospitalisation and has a rising incidence. In recent years, important insights on the management of acute pancreatitis have been obtained through numerous randomised controlled trials. Based on this evidence, the treatment of acute pancreatitis has gradually developed towards a tailored, multidisciplinary effort, with distinctive roles for gastroenterologists, radiologists and surgeons. This review summarises how to diagnose, classify and manage patients with acute pancreatitis, emphasising the evidence obtained through randomised controlled trials. © 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.

Interventions in the workplace to support breastfeeding for women in employment.

PubMed

Abdulwadud, Omar A; Snow, Mary Elizabeth

2012-10-17

In recent years there has been a rise in the participation rate of women in employment. Some may become pregnant while in employment and subsequently deliver their babies. Most may decide to return early to work after giving birth for various reasons. Unless these mothers get support from their employers and fellow employees, they might give up breastfeeding when they return to work. As a result, the duration and exclusivity of breastfeeding to the recommended age of the babies would be affected.Workplace environment can play a positive role to promote breastfeeding. For women going back to work, various types of workplace support interventions are available and this should not be ignored by employers. Notably, promoting breastfeeding in a workplace may have benefits for the women, the baby and also the employer. To assess the effectiveness of workplace interventions to support and promote breastfeeding among women returning to paid work after the birth of their children, and its impact on process outcomes pertinent to employees and employers. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (2 August 2012). Two authors independently assessed all identified studies for randomised controlled trials and quasi-randomised controlled trials that compared workplace interventions with no intervention or two or more workplace interventions against each other. Two authors planned to evaluate the methodological quality of the eligible trials and extract data. There were no randomised controlled trials or quasi-randomised controlled trials identified. No trials have evaluated the effectiveness of workplace interventions in promoting breastfeeding among women returning to paid work after the birth of their child. The impact of such intervention on process outcomes is also unknown. Randomised controlled trials are required to establish the benefits of various types of workplace interventions to support, encourage and promote breastfeeding among working mothers.

Antenatal peer support workers and initiation of breast feeding: cluster randomised controlled trial.

PubMed

MacArthur, Christine; Jolly, Kate; Ingram, Lucy; Freemantle, Nick; Dennis, Cindy-Lee; Hamburger, Ros; Brown, Julia; Chambers, Jackie; Khan, Khalid

2009-01-30

To assess the effectiveness of an antenatal service using community based breastfeeding peer support workers on initiation of breast feeding. Cluster randomised controlled trial. Community antenatal clinics in one primary care trust in a multiethnic, deprived population. 66 antenatal clinics with 2511 pregnant women: 33 clinics including 1140 women were randomised to receive the peer support worker service and 33 clinics including 1371 women were randomised to receive standard care. An antenatal peer support worker service planned to comprise a minimum of two contacts with women to provide advice, information, and support from approximately 24 weeks' gestation within the antenatal clinic or at home. The trained peer support workers were of similar ethnic and sociodemographic backgrounds to their clinic population. Initiation of breast feeding obtained from computerised maternity records of the hospitals where women from the primary care trust delivered. The sample was multiethnic, with only 9.4% of women being white British, and 70% were in the lowest 10th for deprivation. Most of the contacts with peer support workers took place in the antenatal clinics. Data on initiation of breast feeding were obtained for 2398 of 2511 (95.5%) women (1083/1140 intervention and 1315/1371 controls). The groups did not differ for initiation of breast feeding: 69.0% (747/1083) in the intervention group and 68.1% (896/1315) in the control groups; cluster adjusted odds ratio 1.11 (95% confidence interval 0.87 to 1.43). Ethnicity, parity, and mode of delivery independently predicted initiation of breast feeding, but randomisation to the peer support worker service did not. A universal service for initiation of breast feeding using peer support workers provided within antenatal clinics serving a multiethnic, deprived population was ineffective in increasing initiation rates. Current Controlled Trials ISRCTN16126175.

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

Intrauterine resuscitation during the second stage of term labour by maternal hyperoxygenation versus conventional care: study protocol for a randomised controlled trial (INTEREST O2).

PubMed

Bullens, Lauren M; Hulsenboom, Alexandra D J; Moors, Suzanne; Joshi, Rohan; van Runnard Heimel, Pieter J; van der Hout-van der Jagt, M Beatrijs; van den Heuvel, Edwin R; Guid Oei, S

2018-03-23

Perinatal asphyxia is, even in developed countries, one the major causes of neonatal morbidity and mortality. Therefore, if foetal distress during labour is suspected, one should try to restore foetal oxygen levels or aim for immediate delivery. However, studies on the effect of intrauterine resuscitation during labour are scarce. We designed a randomised controlled trial to investigate the effect of maternal hyperoxygenation on the foetal condition. In this study, maternal hyperoxygenation is induced for the treatment of foetal distress during the second stage of term labour. This study is a single-centre randomised controlled trial being performed in a tertiary hospital in The Netherlands. From among cases of a suboptimal or abnormal foetal heart rate pattern during the second stage of term labour, a total of 116 patients will be randomised to the control group, where normal care is provided, or to the intervention group, where before normal care 100% oxygen is supplied to the mother by a non-rebreathing mask until delivery. The primary outcome is change in foetal heart rate pattern. Secondary outcomes are Apgar score, mode of delivery, admission to the neonatal intensive care unit and maternal side effects. In addition, blood gas values and malondialdehyde are determined in umbilical cord blood. This study will be the first randomised controlled trial to investigate the effect of maternal hyperoxygenation for foetal distress during labour. This intervention should be recommended only as a treatment for intrapartum foetal distress, when improvement of the foetal condition is likely and outweighs maternal and neonatal side effects. EudraCT, 2015-001654-15; registered on 3 April 2015. Dutch Trial Register, NTR5461; registered on 20 October 2015.

Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial.

PubMed

Al-Lamee, Rasha; Thompson, David; Dehbi, Hakim-Moulay; Sen, Sayan; Tang, Kare; Davies, John; Keeble, Thomas; Mielewczik, Michael; Kaprielian, Raffi; Malik, Iqbal S; Nijjer, Sukhjinder S; Petraco, Ricardo; Cook, Christopher; Ahmad, Yousif; Howard, James; Baker, Christopher; Sharp, Andrew; Gerber, Robert; Talwar, Suneel; Assomull, Ravi; Mayet, Jamil; Wensel, Roland; Collier, David; Shun-Shin, Matthew; Thom, Simon A; Davies, Justin E; Francis, Darrel P

2018-01-06

Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy. ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593. ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI -8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group. In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy. NIHR Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, Philips Volcano, NIHR Barts Biomedical Research Centre. Copyright © 2018 Elsevier Ltd. All rights reserved.

Promoting Recruitment using Information Management Efficiently (PRIME): a stepped-wedge, cluster randomised trial of a complex recruitment intervention embedded within the REstart or Stop Antithrombotics Randomised Trial.

PubMed

Maxwell, Amy E; Parker, Richard A; Drever, Jonathan; Rudd, Anthony; Dennis, Martin S; Weir, Christopher J; Al-Shahi Salman, Rustam

2017-12-28

Few interventions are proven to increase recruitment in clinical trials. Recruitment to RESTART, a randomised controlled trial of secondary prevention after stroke due to intracerebral haemorrhage, has been slower than expected. Therefore, we sought to investigate an intervention to boost recruitment to RESTART. We conducted a stepped-wedge, cluster randomised trial of a complex intervention to increase recruitment, embedded within the RESTART trial. The primary objective was to investigate if the PRIME complex intervention (a recruitment co-ordinator who conducts a recruitment review, provides access to bespoke stroke audit data exports, and conducts a follow-up review after 6 months) increases the recruitment rate to RESTART. We included 72 hospital sites located in England, Wales, or Scotland that were active in RESTART in June 2015. All sites began in the control state and were allocated using block randomisation stratified by hospital location (Scotland versus England/Wales) to start the complex intervention in one of 12 different months. The primary outcome was the number of patients randomised into RESTART per month per site. We quantified the effect of the complex intervention on the primary outcome using a negative binomial, mixed model adjusting for site, December/January months, site location, and background time trends in recruitment rate. We recruited and randomised 72 sites and recorded their monthly recruitment to RESTART over 24 months (March 2015 to February 2017 inclusive), providing 1728 site-months of observations for the primary analysis. The adjusted rate ratio for the number of patients randomised per month after allocation to the PRIME complex intervention versus control time before allocation to the PRIME complex intervention was 1.06 (95% confidence interval 0.55 to 2.03, p = 0.87). Although two thirds of respondents to the 6-month follow-up questionnaire agreed that the audit reports were useful, only six patients were reported to have been randomised using the audit reports. Respondents frequently reported resource and time pressures as being key barriers to running the audit reports. The PRIME complex intervention did not significantly improve the recruitment rate to RESTART. Further research is needed to establish if PRIME might be beneficial at an earlier stage in a prevention trial or for prevention dilemmas that arise more often in clinical practice.

Specialist teams for neonatal transport to neonatal intensive care units for prevention of morbidity and mortality.

PubMed

Chang, Alvin S M; Berry, Andrew; Jones, Lisa J; Sivasangari, Subramaniam

2015-10-28

Maternal antenatal transfers provide better neonatal outcomes. However, there will inevitably be some infants who require acute transport to a neonatal intensive care unit (NICU). Because of this, many institutions develop services to provide neonatal transport by specially trained health personnel. However, few studies report on relevant clinical outcomes in infants requiring transport to NICU. To determine the effects of specialist transport teams compared with non-specialist transport teams on the risk of neonatal mortality and morbidity among high-risk newborn infants requiring transport to neonatal intensive care. We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), MEDLINE (1966 to 31 July 2015), EMBASE (1980 to 31 July 2015), CINAHL (1982 to 31 July 2015), conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. randomised, quasi-randomised or cluster randomised controlled trials. neonates requiring transport to a neonatal intensive care unit. transport by a specialist team compared to a non-specialist team. any of the following outcomes - death; adverse events during transport leading to respiratory compromise; and condition on admission to the neonatal intensive care unit. The methodological quality of the trials was assessed using the information provided in the studies and by personal communication with the author. Data on relevant outcomes were extracted and the effect size estimated and reported as risk ratio (RR), risk difference (RD), number needed to treat for an additional beneficial outcome (NNTB) or number needed to treat for an additional harmful outcome (NNTH) and mean difference (MD) for continuous outcomes. Data from cluster randomised trials were not combined for analysis. One trial met the inclusion criteria of this review but was considered ineligible owing to serious bias in the reporting of the results. There is no reliable evidence from randomised trials to support or refute the effects of specialist neonatal transport teams for neonatal retrieval on infant morbidity and mortality. Cluster randomised trial study designs may be best suited to provide us with answers on effectiveness and clinical outcomes.

Fostering Effective Early Learning (FEEL) through a professional development programme for early childhood educators to improve professional practice and child outcomes in the year before formal schooling: study protocol for a cluster randomised controlled trial.

PubMed

Melhuish, Edward; Howard, Steven J; Siraj, Iram; Neilsen-Hewett, Cathrine; Kingston, Denise; de Rosnay, Marc; Duursma, Elisabeth; Luu, Betty

2016-12-19

A substantial research base documents the benefits of attendance at high-quality early childhood education and care (ECEC) for positive behavioural and learning outcomes. Research has also found that the quality of many young children's experiences and opportunities in ECEC depends on the skills, dispositions and understandings of the early childhood adult educators. Increasingly, research has shown that the quality of children's interactions with educators and their peers, more than any other programme feature, influence what children learn and how they feel about learning. Hence, we sought to investigate the extent to which evidence-based professional development (PD) - focussed on promoting sustained shared thinking through quality interactions - could improve the quality of ECEC and, as a consequence, child outcomes. The Fostering Effective Early Learning (FEEL) study is a cluster randomised controlled trial for evaluating the benefits of a professional development (PD) programme for early childhood educators, compared with no extra PD. Ninety long-day care and preschool centres in New South Wales, Australia, will be selected to ensure representation across National Quality Standards (NQS) ratings, location, centre type and socioeconomic areas. Participating centres will be randomly allocated to one of two groups, stratified by centre type and NQS rating: (1) an intervention group (45 centres) receiving a PD intervention or (2) a control group (45 centres) that continues engaging in typical classroom practice. Randomisation to these groups will occur after the collection of baseline environmental quality ratings. Primary outcomes, at the child level, will be two measures of language development: verbal comprehension and expressive vocabulary. Secondary outcomes at the child level will be measures of early numeracy, social development and self-regulation. Secondary outcomes at the ECEC room level will be measures of environmental quality derived from full-day observations. In all cases, data collectors will be blinded to group allocation. This is the first randomised controlled trial of a new approach to PD, which is focussed on activities previously found to be influential in children's early language, numeracy, social and self-regulatory development. Results should inform practitioners, policy-makers and families of the value of specific professional development for early childhood educators. Australian New Zealand Clinical Trials Registry (ACTRN) identifier ACTRN12616000536460 . Registered on 27 April 2016. This trial was retrospectively registered, given the first participant (centre) had been enrolled at the time of registration.

The Basilar Artery International Cooperation Study (BASICS): study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Despite recent advances in acute stroke treatment, basilar artery occlusion (BAO) is associated with a death or disability rate of close to 70%. Randomised trials have shown the safety and efficacy of intravenous thrombolysis (IVT) given within 4.5 h and have shown promising results of intra-arterial thrombolysis given within 6 h of symptom onset of acute ischaemic stroke, but these results do not directly apply to patients with an acute BAO because only few, if any, of these patients were included in randomised acute stroke trials. Recently the results of the Basilar Artery International Cooperation Study (BASICS), a prospective registry of patients with acute symptomatic BAO challenged the often-held assumption that intra-arterial treatment (IAT) is superior to IVT. Our observations in the BASICS registry underscore that we continue to lack a proven treatment modality for patients with an acute BAO and that current clinical practice varies widely. Design BASICS is a randomised controlled, multicentre, open label, phase III intervention trial with blinded outcome assessment, investigating the efficacy and safety of additional IAT after IVT in patients with BAO. The trial targets to include 750 patients, aged 18 to 85 years, with CT angiography or MR angiography confirmed BAO treated with IVT. Patients will be randomised between additional IAT followed by optimal medical care versus optimal medical care alone. IVT has to be initiated within 4.5 h from estimated time of BAO and IAT within 6 h. The primary outcome parameter will be favourable outcome at day 90 defined as a modified Rankin Scale score of 0–3. Discussion The BASICS registry was observational and has all the limitations of a non-randomised study. As the IAT approach becomes increasingly available and frequently utilised an adequately powered randomised controlled phase III trial investigating the added value of this therapy in patients with an acute symptomatic BAO is needed (clinicaltrials.gov: NCT01717755). PMID:23835026

Appendectomy versus non-operative treatment for acute uncomplicated appendicitis in children: study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

PubMed Central

Eaton, Simon; Abbo, Olivier; Arnaud, Alexis P; Beaudin, Marianne; Brindle, Mary; Bütter, Andreana; Davies, Dafydd; Jancelewicz, Tim; Johnson, Kathy; Keijzer, Richard; Lapidus-Krol, Eveline; Offringa, Martin; Piché, Nelson; Rintala, Risto; Skarsgard, Erik; Svensson, Jan F; Ungar, Wendy J; Wester, Tomas; Willan, Andrew R; Zani, Augusto; St Peter, Shawn D; Pierro, Agostino

2017-01-01

Background Appendectomy is considered the gold standard treatment for acute appendicitis. Recently the need for surgery has been challenged in both adults and children. In children there is growing clinician, patient and parental interest in non-operative treatment of acute appendicitis with antibiotics as opposed to surgery. To date no multicentre randomised controlled trials that are appropriately powered to determine efficacy of non-operative treatment (antibiotics) for acute appendicitis in children compared with surgery (appendectomy) have been performed. Methods Multicentre, international, randomised controlled trial with a non-inferiority design. Children (age 5–16 years) with a clinical and/or radiological diagnosis of acute uncomplicated appendicitis will be randomised (1:1 ratio) to receive either laparoscopic appendectomy or treatment with intravenous (minimum 12 hours) followed by oral antibiotics (total course 10 days). Allocation to groups will be stratified by gender, duration of symptoms (> or <48 hours) and centre. Children in both treatment groups will follow a standardised treatment pathway. Primary outcome is treatment failure defined as additional intervention related to appendicitis requiring general anaesthesia within 1 year of randomisation (including recurrent appendicitis) or negative appendectomy. Important secondary outcomes will be reported and a cost-effectiveness analysis will be performed. The primary outcome will be analysed on a non-inferiority basis using a 20% non-inferiority margin. Planned sample size is 978 children. Discussion The APPY trial will be the first multicentre randomised trial comparing non-operative treatment with appendectomy for acute uncomplicated appendicitis in children. The results of this trial have the potential to revolutionise the treatment of this common gastrointestinal emergency. The randomised design will limit the effect of bias on outcomes seen in other studies. Trial registration number clinicaltrials.gov: NCT02687464. Registered on Jan 13th 2016. PMID:29637088

Prostate cancer mortality reduction by prostate-specific antigen-based screening adjusted for nonattendance and contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC).

PubMed

Roobol, Monique J; Kerkhof, Melissa; Schröder, Fritz H; Cuzick, Jack; Sasieni, Peter; Hakama, Matti; Stenman, Ulf Hakan; Ciatto, Stefano; Nelen, Vera; Kwiatkowski, Maciej; Lujan, Marcos; Lilja, Hans; Zappa, Marco; Denis, Louis; Recker, Franz; Berenguer, Antonio; Ruutu, Mirja; Kujala, Paula; Bangma, Chris H; Aus, Gunnar; Tammela, Teuvo L J; Villers, Arnauld; Rebillard, Xavier; Moss, Sue M; de Koning, Harry J; Hugosson, Jonas; Auvinen, Anssi

2009-10-01

Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm. To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination. We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162,243 men 55-69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent). Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam. Relative risks (RRs) with 95% confidence intervals (CIs) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose. In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68-0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58-0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51-0.92) to 0.71 (95% CI, 0.55-0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres. PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of overdiagnosis and overtreatment inherent in PCa screening.

Changing eating behaviours to treat childhood obesity in the community using Mandolean: the Community Mandolean randomised controlled trial (ComMando)--a pilot study.

PubMed

Hamilton-Shield, Julian; Goodred, Joanna; Powell, Lesley; Thorn, Joanna; Banks, Jon; Hollinghurst, Sandra; Montgomery, Alan; Turner, Katrina; Sharp, Debbie

2014-07-01

Around one in five children in England is obese when they leave primary school. Thus far, it has not been demonstrated that primary care interventions to manage childhood obesity can achieve significant weight reduction. Training obese children to eat more slowly as an adjunct to other healthy lifestyle behaviour change has been shown to increase weight reduction in a hospital setting. This pilot study aimed to test recruitment strategies, treatment adherence, clinic attendance and participants' experiences of using a device [Mandolean® (previously Mandometer®, Mikrodidakt AB, Lund, Sweden)] to slow down speed of eating as an adjunct to dietary and activity advice in treating obesity in primary school-aged children. A two-arm, parallel, randomised controlled trial with a qualitative study embedded within the pilot. Randomisation occurred after informed consent and baseline measures were collected. Participants were randomised by the Bristol Randomised Trials Collaboration randomisation service with allocation stratified by hub and minimised by age of the child, gender, and baseline body mass index (BMI) standard deviation score (BMI z-value) of the child, and by BMI of the study parent (obese/not obese). General practices across Bristol, North Somerset and South Gloucestershire primary care trusts. Children (BMI ≥ 95th percentile) aged 5-11 years and their families. Standard care comprised dietary and activity advice by trained practice nurses. Adjunctive Mandolean training (the intervention) educated participants to eat meals more slowly and to rate levels of fullness (satiety). Mandolean is a small computer device attached to a weighing scale that provides visual and oral feedback during meals while generating a visual representation of levels of satiety during the meal. Participants were encouraged to eat their main meal each day from the Mandolean. One parent was also given a Mandolean to use when eating with the child. Outcomes for the pilot were recruitment of 36 families to the trial in the 9-month pilot phase, that meals would be eaten at least five times a week off a Mandolean by 90% of patients randomised to the intervention arm, that 80% of patients in both arms would attend the weight management clinic appointment 3 months post randomisation and that > 60% of children using Mandolean would demonstrate a reduction in speed of eating from baseline within 3 months of randomisation. None of the criteria for progression to the main trial were reached. Despite numerous pathways being available for referral, only 21 (13 to standard care, eight to intervention arm; 58%) of the target 36 families were recruited in the pilot phase. Less than 20% of those randomised to Mandolean used the device at least five times a week. The > 60% target for slowing down of eating speed by 3 months was unmet. Attendance at the weight management clinic in general practice hubs for both arms of the study at 3 months was 44% against a target of 80%. This pilot trial failed to meet its objectives in terms of recruitment, treatment adherence, demonstration of a reduction in speed of eating in sufficient numbers of children, and attendance at follow-up appointments. Despite a high prevalence of childhood obesity in the geographical area and practices signing up for the trial, this study, like many others, demonstrates a failure of families to engage with and respond to primary care weight management interventions. We need to understand why the target population seems inured to the health message that childhood obesity is a significant health-care issue and identify the barriers to seeking help and then acting on positive health behaviour retraining. Only when we have fully understood the general public's perceptions of childhood obesity and have identified ways of engaging target populations can we hope to develop interventions that can work in a primary or community-based setting. Current Controlled Trials ISRCTN90561114. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 47. See the NIHR Journals Library website for further project information.

Supermarket Healthy Eating for Life (SHELf): protocol of a randomised controlled trial promoting healthy food and beverage consumption through price reduction and skill-building strategies

PubMed Central

2011-01-01

Background In the context of rising food prices, there is a need for evidence on the most effective approaches for promoting healthy eating. Individually-targeted behavioural interventions for increasing food-related skills show promise, but are unlikely to be effective in the absence of structural supports. Fiscal policies have been advocated as a means of promoting healthy eating and reducing obesity and nutrition-related disease, but there is little empirical evidence of their effectiveness. This paper describes the Supermarket Healthy Eating for LiFe (SHELf) study, a randomised controlled trial to investigate effectiveness and cost-effectiveness of a tailored skill-building intervention and a price reduction intervention, separately and in combination, against a control condition for promoting purchase and consumption of healthy foods and beverages in women from high and low socioeconomic groups. Methods/design SHELf comprises a randomised controlled trial design, with participants randomised to receive either (1) a skill-building intervention; (2) price reductions on fruits, vegetables and low-joule soft drink beverages and water; (3) a combination of skill-building and price reductions; or (4) a control condition. Five hundred women from high and low socioeconomic areas will be recruited through a store loyalty card program and local media. Randomisation will occur on receipt of informed consent and baseline questionnaire. An economic evaluation from a societal perspective using a cost-consequences approach will compare the costs and outcomes between intervention and control groups. Discussion This study will build on a pivotal partnership with a major national supermarket chain and the Heart Foundation to investigate the effectiveness of intervention strategies aimed at increasing women's purchasing and consumption of fruits and vegetables and decreased purchasing and consumption of sugar-sweetened beverages. It will be among the first internationally to examine the effects of two promising approaches - skill-building and price reductions - on diet amongst women. Trial Registration Current Controlled Trials ISRCTN39432901 PMID:21936957

Supermarket Healthy Eating for Life (SHELf): protocol of a randomised controlled trial promoting healthy food and beverage consumption through price reduction and skill-building strategies.

PubMed

Ball, Kylie; McNaughton, Sarah A; Mhurchu, Cliona Ni; Andrianopoulos, Nick; Inglis, Victoria; McNeilly, Briohny; Le, Ha N D; Leslie, Deborah; Pollard, Christina; Crawford, David

2011-09-22

In the context of rising food prices, there is a need for evidence on the most effective approaches for promoting healthy eating. Individually-targeted behavioural interventions for increasing food-related skills show promise, but are unlikely to be effective in the absence of structural supports. Fiscal policies have been advocated as a means of promoting healthy eating and reducing obesity and nutrition-related disease, but there is little empirical evidence of their effectiveness. This paper describes the Supermarket Healthy Eating for LiFe (SHELf) study, a randomised controlled trial to investigate effectiveness and cost-effectiveness of a tailored skill-building intervention and a price reduction intervention, separately and in combination, against a control condition for promoting purchase and consumption of healthy foods and beverages in women from high and low socioeconomic groups. SHELf comprises a randomised controlled trial design, with participants randomised to receive either (1) a skill-building intervention; (2) price reductions on fruits, vegetables and low-joule soft drink beverages and water; (3) a combination of skill-building and price reductions; or (4) a control condition. Five hundred women from high and low socioeconomic areas will be recruited through a store loyalty card program and local media. Randomisation will occur on receipt of informed consent and baseline questionnaire. An economic evaluation from a societal perspective using a cost-consequences approach will compare the costs and outcomes between intervention and control groups. This study will build on a pivotal partnership with a major national supermarket chain and the Heart Foundation to investigate the effectiveness of intervention strategies aimed at increasing women's purchasing and consumption of fruits and vegetables and decreased purchasing and consumption of sugar-sweetened beverages. It will be among the first internationally to examine the effects of two promising approaches - skill-building and price reductions - on diet amongst women. Current Controlled Trials ISRCTN39432901.

The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial.

PubMed

Neal, Elizabeth G; Chaffe, Hannah; Schwartz, Ruby H; Lawson, Margaret S; Edwards, Nicole; Fitzsimmons, Geogianna; Whitney, Andrea; Cross, J Helen

2008-06-01

The ketogenic diet has been widely and successfully used to treat children with drug-resistant epilepsy since the 1920s. The aim of this study was to test the efficacy of the ketogenic diet in a randomised controlled trial. 145 children aged between 2 and 16 years who had at least daily seizures (or more than seven seizures per week), had failed to respond to at least two antiepileptic drugs, and had not been treated previously with the ketogenic diet participated in a randomised controlled trial of its efficacy to control seizures. Enrolment for the trial ran between December, 2001, and July, 2006. Children were seen at one of two hospital centres or a residential centre for young people with epilepsy. Children were randomly assigned to receive a ketogenic diet, either immediately or after a 3-month delay, with no other changes to treatment (control group). Neither the family nor investigators were blinded to the group assignment. Early withdrawals were recorded, and seizure frequency on the diet was assessed after 3 months and compared with that of the controls. The primary endpoint was a reduction in seizures; analysis was intention to treat. Tolerability of the diet was assessed by questionnaire at 3 months. The trial is registered with ClinicalTrials.gov, number NCT00564915. 73 children were assigned to the ketogenic diet and 72 children to the control group. Data from 103 children were available for analysis: 54 on the ketogenic diet and 49 controls. Of those who did not complete the trial, 16 children did not receive their intervention, 16 did not provide adequate data, and ten withdrew from the treatment before the 3-month review, six because of intolerance. After 3 months, the mean percentage of baseline seizures was significantly lower in the diet group than in the controls (62.0%vs 136.9%, 75% decrease, 95% CI 42.4-107.4%; p<0.0001). 28 children (38%) in the diet group had greater than 50% seizure reduction compared with four (6%) controls (p<0.0001), and five children (7%) in the diet group had greater than 90% seizure reduction compared with no controls (p=0.0582). There was no significant difference in the efficacy of the treatment between symptomatic generalised or symptomatic focal syndromes. The most frequent side-effects reported at 3-month review were constipation, vomiting, lack of energy, and hunger. The results from this trial of the ketogenic diet support its use in children with treatment-intractable epilepsy. HSA Charitable Trust; Smiths Charity; Scientific Hospital Supplies; Milk Development Council.

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

PubMed

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

2009-09-10

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

Safety and efficacy of antibiotics compared with appendicectomy for treatment of uncomplicated acute appendicitis: meta-analysis of randomised controlled trials

PubMed Central

Varadhan, Krishna K; Neal, Keith R

2012-01-01

Objective To compare the safety and efficacy of antibiotic treatment versus appendicectomy for the primary treatment of uncomplicated acute appendicitis. Design Meta-analysis of randomised controlled trials. Population Randomised controlled trials of adult patients presenting with uncomplicated acute appendicitis, diagnosed by haematological and radiological investigations. Interventions Antibiotic treatment versus appendicectomy. Outcome measures The primary outcome measure was complications. The secondary outcome measures were efficacy of treatment, length of stay, and incidence of complicated appendicitis and readmissions. Results Four randomised controlled trials with a total of 900 patients (470 antibiotic treatment, 430 appendicectomy) met the inclusion criteria. Antibiotic treatment was associated with a 63% (277/438) success rate at one year. Meta-analysis of complications showed a relative risk reduction of 31% for antibiotic treatment compared with appendicectomy (risk ratio (Mantel-Haenszel, fixed) 0.69 (95% confidence interval 0.54 to 0.89); I2=0%; P=0.004). A secondary analysis, excluding the study with crossover of patients between the two interventions after randomisation, showed a significant relative risk reduction of 39% for antibiotic therapy (risk ratio 0.61 (0.40 to 0.92); I2=0%; P=0.02). Of the 65 (20%) patients who had appendicectomy after readmission, nine had perforated appendicitis and four had gangrenous appendicitis. No significant differences were seen for treatment efficacy, length of stay, or risk of developing complicated appendicitis. Conclusion Antibiotics are both effective and safe as primary treatment for patients with uncomplicated acute appendicitis. Initial antibiotic treatment merits consideration as a primary treatment option for early uncomplicated appendicitis. PMID:22491789

When is a randomised controlled trial health equity relevant? Development and validation of a conceptual framework

PubMed Central

Jull, J; Whitehead, M; Petticrew, M; Kristjansson, E; Gough, D; Petkovic, J; Volmink, J; Weijer, C; Taljaard, M; Edwards, S; Mbuagbaw, L; Cookson, R; McGowan, J; Lyddiatt, A; Boyer, Y; Cuervo, L G; Armstrong, R; White, H; Yoganathan, M; Pantoja, T; Shea, B; Pottie, K; Norheim, O; Baird, S; Robberstad, B; Sommerfelt, H; Asada, Y; Wells, G; Tugwell, P; Welch, V

2017-01-01

Background Randomised controlled trials can provide evidence relevant to assessing the equity impact of an intervention, but such information is often poorly reported. We describe a conceptual framework to identify health equity-relevant randomised trials with the aim of improving the design and reporting of such trials. Methods An interdisciplinary and international research team engaged in an iterative consensus building process to develop and refine the conceptual framework via face-to-face meetings, teleconferences and email correspondence, including findings from a validation exercise whereby two independent reviewers used the emerging framework to classify a sample of randomised trials. Results A randomised trial can usefully be classified as ‘health equity relevant’ if it assesses the effects of an intervention on the health or its determinants of either individuals or a population who experience ill health due to disadvantage defined across one or more social determinants of health. Health equity-relevant randomised trials can either exclusively focus on a single population or collect data potentially useful for assessing differential effects of the intervention across multiple populations experiencing different levels or types of social disadvantage. Trials that are not classified as ‘health equity relevant’ may nevertheless provide information that is indirectly relevant to assessing equity impact, including information about individual level variation unrelated to social disadvantage and potentially useful in secondary modelling studies. Conclusion The conceptual framework may be used to design and report randomised trials. The framework could also be used for other study designs to contribute to the evidence base for improved health equity. PMID:28951402

Interventions to improve water quality and supply, sanitation and hygiene practices, and their effects on the nutritional status of children.

PubMed

Dangour, Alan D; Watson, Louise; Cumming, Oliver; Boisson, Sophie; Che, Yan; Velleman, Yael; Cavill, Sue; Allen, Elizabeth; Uauy, Ricardo

2013-08-01

Water, sanitation and hygiene (WASH) interventions are frequently implemented to reduce infectious diseases, and may be linked to improved nutrition outcomes in children. To evaluate the effect of interventions to improve water quality and supply (adequate quantity to maintain hygiene practices), provide adequate sanitation and promote handwashing with soap, on the nutritional status of children under the age of 18 years and to identify current research gaps. We searched 10 English-language (including MEDLINE and CENTRAL) and three Chinese-language databases for published studies in June 2012. We searched grey literature databases, conference proceedings and websites, reviewed reference lists and contacted experts and authors. Randomised (including cluster-randomised), quasi-randomised and non-randomised controlled trials, controlled cohort or cross-sectional studies and historically controlled studies, comparing WASH interventions among children aged under 18 years. Two review authors independently sought and extracted data on childhood anthropometry, biochemical measures of micronutrient status, and adherence, attrition and costs either from published reports or through contact with study investigators. We calculated mean difference (MD) with 95% confidence intervals (CI). We conducted study-level and individual-level meta-analyses to estimate pooled measures of effect for randomised controlled trials only. Fourteen studies (five cluster-randomised controlled trials and nine non-randomised studies with comparison groups) from 10 low- and middle-income countries including 22,241 children at baseline and nutrition outcome data for 9,469 children provided relevant information. Study duration ranged from 6 to 60 months and all studies included children under five years of age at the time of the intervention. Studies included WASH interventions either singly or in combination. Measures of child anthropometry were collected in all 14 studies, and nine studies reported at least one of the following anthropometric indices: weight-for-height, weight-for-age or height-for-age. None of the included studies were of high methodological quality as none of the studies masked the nature of the intervention from participants.Weight-for-age, weight-for-height and height-for-age z-scores were available for five cluster-randomised controlled trials with a duration of between 9 and 12 months. Meta-analysis including 4,627 children identified no evidence of an effect of WASH interventions on weight-for-age z-score (MD 0.05; 95% CI -0.01 to 0.12). Meta-analysis including 4,622 children identified no evidence of an effect of WASH interventions on weight-for-height z-score (MD 0.02; 95% CI -0.07 to 0.11). Meta-analysis including 4,627 children identified a borderline statistically significant effect of WASH interventions on height-for-age z-score (MD 0.08; 95% CI 0.00 to 0.16). These findings were supported by individual participant data analysis including information on 5,375 to 5,386 children from five cluster-randomised controlled trials.No study reported adverse events. Adherence to study interventions was reported in only two studies (both cluster-randomised controlled trials) and ranged from low (< 35%) to high (> 90%). Study attrition was reported in seven studies and ranged from 4% to 16.5%. Intervention cost was reported in one study in which the total cost of the WASH interventions was USD 15/inhabitant. None of the studies reported differential impacts relevant to equity issues such as gender, socioeconomic status and religion. The available evidence from meta-analysis of data from cluster-randomised controlled trials with an intervention period of 9-12 months is suggestive of a small benefit of WASH interventions (specifically solar disinfection of water, provision of soap, and improvement of water quality) on length growth in children under five years of age. The duration of the intervention studies was relatively short and none of the included studies is of high methodological quality. Very few studies provided information on intervention adherence, attrition and costs. There are several ongoing trials in low-income country settings that may provide robust evidence to inform these findings.

Cognitive Behaviour Therapy versus a Counselling Intervention for Anxiety in Young People with High-Functioning Autism Spectrum Disorders: A Pilot Randomised Controlled Trial

ERIC Educational Resources Information Center

Murphy, Suzanne M.; Chowdhury, Uttom; White, Susan W.; Reynolds, Laura; Donald, Louisa; Gahan, Hilary; Iqbal, Zeinab; Kulkarni, Mahesh; Scrivener, Louise; Shaker-Naeeni, Hadi; Press, Dee A.

2017-01-01

The use of cognitive-behavioural therapy (CBT) as a treatment for children and adolescents with autism spectrum disorder (ASD) has been explored in a number of trials. Whilst CBT appears superior to no treatment or treatment as usual, few studies have assessed CBT against a control group receiving an alternative therapy. Our randomised controlled…

Pragmatic Pilot Cluster Randomised Control Trial of a School-Based Peer-Led Anti-Smoking Intervention for 13-14 Year Olds in Malaysia: Process Evaluation

ERIC Educational Resources Information Center

Melson, Elniee; Bridle, Christopher; Markham, Wolfgang

2017-01-01

Purpose: The purpose of this paper is to report the process evaluation of a pilot randomised control trial of an anti-smoking intervention for Malaysian 13-14-year olds, conducted in 2011/2012. It was hypothesised that trained peer supporters would promote non-smoking among classmates through informal conversations. Design/methodology/approach:…

Melatonin versus Placebo in Children with Autism Spectrum Conditions and Severe Sleep Problems Not Amenable to Behaviour Management Strategies: A Randomised Controlled Crossover Trial

ERIC Educational Resources Information Center

Wright, Barry; Sims, David; Smart, Siobhan; Alwazeer, Ahmed; Alderson-Day, Ben; Allgar, Victoria; Whitton, Clare; Tomlinson, Heather; Bennett, Sophie; Jardine, Jenni; McCaffrey, Nicola; Leyland, Charlotte; Jakeman, Christine; Miles, Jeremy

2011-01-01

Twenty-two children with autism spectrum disorders who had not responded to supported behaviour management strategies for severe dysomnias entered a double blind, randomised, controlled crossover trial involving 3 months of placebo versus 3 months of melatonin to a maximum dose of 10 mg. 17 children completed the study. There were no significant…

Social validity of randomised controlled trials in health services research and intellectual disabilities: a qualitative exploration of stakeholder views

PubMed Central

2011-01-01

Background Randomised controlled trials (RCTs) are the gold standard of evidence-based practice in medicine but they have had limited influence in the field of intellectual disabilities. Previous literature suggests that participants and professionals have limited tolerance for this type of research methodology. However, it is not known how well service users, carers and other health professionals understand and accept the need for RCTs, and why it is important for individuals with intellectual disabilities to be included in this kind of research. Methods We examined individual perceptions of RCTs in 51 participants (18 carers, 6 service users and 27 professionals) using semi-structured interviews. A framework approach was adopted in the analysis of data. Results We found that participants had concerns about capacity and resource allocation but held positive views towards this type of research methodology. Understanding of the principles behind RCTs was poor amongst service users and a minority of carers, but mediated by previous exposure to research for professionals. Conclusions The social validity of RCTs in intellectual disabilities may be compromised by lack of understanding of the design and the on-going concerns about obtaining informed consent especially in incapacitated adults. However, the overall finding that the need for this form of research was seen in a positive light suggests that there is a turning point in the perceptions of stakeholders working in intellectual disabilities services. We recommend that researchers include on-going education on RCT design during trials, tailoring it to all stakeholders with emphasis on strong service user and care involvement. This could be a pivotal element in improving acceptability of, and recruitment to RCTs. PMID:21658215

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

PubMed

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

2015-12-10

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

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.

Clinical and cost effectiveness of mobile phone supported self monitoring of asthma: multicentre randomised controlled trial.

PubMed

Ryan, Dermot; Price, David; Musgrave, Stan D; Malhotra, Shweta; Lee, Amanda J; Ayansina, Dolapo; Sheikh, Aziz; Tarassenko, Lionel; Pagliari, Claudia; Pinnock, Hilary

2012-03-23

To determine whether mobile phone based monitoring improves asthma control compared with standard paper based monitoring strategies. Multicentre randomised controlled trial with cost effectiveness analysis. UK primary care. 288 adolescents and adults with poorly controlled asthma (asthma control questionnaire (ACQ) score ≥ 1.5) from 32 practices. Participants were centrally randomised to twice daily recording and mobile phone based transmission of symptoms, drug use, and peak flow with immediate feedback prompting action according to an agreed plan or paper based monitoring. Changes in scores on asthma control questionnaire and self efficacy (knowledge, attitude, and self efficacy asthma questionnaire (KASE-AQ)) at six months after randomisation. Assessment of outcomes was blinded. Analysis was on an intention to treat basis. There was no significant difference in the change in asthma control or self efficacy between the two groups (ACQ: mean change 0.75 in mobile group v 0.73 in paper group, mean difference in change -0.02 (95% confidence interval -0.23 to 0.19); KASE-AQ score: mean change -4.4 v -2.4, mean difference 2.0 (-0.3 to 4.2)). The numbers of patients who had acute exacerbations, steroid courses, and unscheduled consultations were similar in both groups, with similar healthcare costs. Overall, the mobile phone service was more expensive because of the expenses of telemonitoring. Mobile technology does not improve asthma control or increase self efficacy compared with paper based monitoring when both groups received clinical care to guidelines standards. The mobile technology was not cost effective. Clinical Trials NCT00512837.

Analysis and interpretation of cost data in randomised controlled trials: review of published studies

PubMed Central

Barber, Julie A; Thompson, Simon G

1998-01-01

Objective To review critically the statistical methods used for health economic evaluations in randomised controlled trials where an estimate of cost is available for each patient in the study. Design Survey of published randomised trials including an economic evaluation with cost values suitable for statistical analysis; 45 such trials published in 1995 were identified from Medline. Main outcome measures The use of statistical methods for cost data was assessed in terms of the descriptive statistics reported, use of statistical inference, and whether the reported conclusions were justified. Results Although all 45 trials reviewed apparently had cost data for each patient, only 9 (20%) reported adequate measures of variability for these data and only 25 (56%) gave results of statistical tests or a measure of precision for the comparison of costs between the randomised groups. Only 16 (36%) of the articles gave conclusions which were justified on the basis of results presented in the paper. No paper reported sample size calculations for costs. Conclusions The analysis and interpretation of cost data from published trials reveal a lack of statistical awareness. Strong and potentially misleading conclusions about the relative costs of alternative therapies have often been reported in the absence of supporting statistical evidence. Improvements in the analysis and reporting of health economic assessments are urgently required. Health economic guidelines need to be revised to incorporate more detailed statistical advice. Key messagesHealth economic evaluations required for important healthcare policy decisions are often carried out in randomised controlled trialsA review of such published economic evaluations assessed whether statistical methods for cost outcomes have been appropriately used and interpretedFew publications presented adequate descriptive information for costs or performed appropriate statistical analysesIn at least two thirds of the papers, the main conclusions regarding costs were not justifiedThe analysis and reporting of health economic assessments within randomised controlled trials urgently need improving PMID:9794854

Hysteroscopic resection of a uterine caesarean scar defect (niche) in women with postmenstrual spotting: a randomised controlled trial.

PubMed

Vervoort, Ajmw; van der Voet, L F; Hehenkamp, Wjk; Thurkow, A L; van Kesteren, Pjm; Quartero, H; Kuchenbecker, W; Bongers, M; Geomini, P; de Vleeschouwer, Lhm; van Hooff, Mha; van Vliet, H; Veersema, S; Renes, W B; Oude Rengerink, K; Zwolsman, S E; Brölmann, Ham; Mol, Bwj; Huirne, Jaf

2018-02-01

To compare the effectiveness of a hysteroscopic niche resection versus no treatment in women with postmenstrual spotting and a uterine caesarean scar defect. Multicentre randomised controlled trial. Eleven hospitals collaborating in a consortium for women's health research in the Netherlands. Women reporting postmenstrual spotting after a caesarean section who had a niche with a residual myometrium of ≥3 mm, measured during sonohysterography. Women were randomly allocated to hysteroscopic niche resection or expectant management for 6 months. The primary outcome was the number of days of postmenstrual spotting 6 months after randomisation. Secondary outcomes were spotting at the end of menstruation, intermenstrual spotting, dysuria, sonographic niche measurements, surgical parameters, quality of life, women's satisfaction, sexual function, and additional therapy. Outcomes were measured at 3 months and, except for niche measurements, also at 6 months after randomisation. We randomised 52 women to hysteroscopic niche resection and 51 women to expectant management. The median number of days of postmenstrual spotting at baseline was 8 days in both groups. At 6 months after randomisation, the median number of days of postmenstrual spotting was 4 days (interquartile range, IQR 2-7 days) in the intervention group and 7 days (IQR 3-10 days) in the control group (P = 0.04); on a scale of 0-10, discomfort as a result of spotting had a median score of 2 (IQR 0-7) in the intervention group, compared with 7 (IQR 0-8) in the control group (P = 0.02). In women with a niche with a residual myometrium of ≥3 mm, hysteroscopic niche resection reduced postmenstrual spotting and spotting-related discomfort. A hysteroscopic niche resection is an effective treatment to reduce niche-related spotting. © 2017 The Authors. BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

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.

Effectiveness of mat Pilates or equipment-based Pilates in patients with chronic non-specific low back pain: a protocol of a randomised controlled trial

PubMed Central

2013-01-01

Background Chronic low back pain is an expensive and difficult condition to treat. One of the interventions widely used by physiotherapists in the treatment of chronic non-specific low back pain is exercise therapy based upon the Pilates principles. Pilates exercises can be performed with or without specific equipment. These two types of Pilates exercises have never been compared on a high-quality randomised controlled trial. Methods/design This randomised controlled trial with a blinded assessor will evaluate eighty six patients of both genders with chronic low back pain, aged between 18 and 60 years, from one Brazilian private physiotherapy clinic. The patients will be randomly allocated into two groups: Mat Group will perform the exercises on the ground while the Equipment-based Group will perform the Pilates method exercises on the following equipment: Cadillac, Reformer, Ladder Barrel, and Step Chair. The general and specific disability of the patient, kinesiophobia, pain intensity and global perceived effect will be evaluated by a blinded assessor before randomisation and at six weeks and six months after randomisation. In addition, the expectation of the participants and their confidence with the treatment will be evaluated before randomisation and after the first treatment session, respectively. Discussion This will be the first study aiming to compare the effectiveness of Mat and Equipment-based Pilates exercises in patients with chronic non-specific low back pain. The results may help health-care professionals in clinical decision-making and could potentially reduce the treatment costs of this condition. Trial registration Brazilian Registry of Clinical Trials RBR-7tyg5j PMID:23298183

Angioplasty and stenting for patients with symptomatic intracranial atherosclerosis: study protocol of a randomised controlled trial

PubMed Central

Cui, Xiao-Ping; Lin, Min; Mu, Jun-Shan; Ye, Jian-Xin; He, Wen-Qing; Fu, Mao-Lin; Li, Hua; Fang, Jia-Yang; Shen, Feng-Feng; Lin, Hang

2016-01-01

Introduction Whether adding percutaneous transluminal angioplasty and stenting (PTAS) to background medical treatment is effective for decreasing the incidence of stroke or death in patients with symptomatic intracranial atherosclerosis (ICAS) is still controversial. We perform a randomised controlled trial to examine the effectiveness and safety of an improved PTAS procedure for patients with ICAS. Methods and analysis A randomised controlled trial will be conducted in three hospitals in China. Eligible patients with ICAS will be randomly assigned to receive medication treatment (MT) plus PTAS or MT alone. The MT will be initiated immediately after randomisation, while the PTAS will be performed when patients report relief of alarm symptoms defined as sudden weakness or numbness. All patients will be followed up at 30 days, 3 and 12 months after randomisation. The primary end point will be the incidence of stroke or death at 30 days after randomisation. Secondary outcomes will be the incidence of ischaemic stroke in the territory of stenosis arteries, the incidence of in-stent restenosis, the Chinese version of the modified Rankin Scale and the Chinese version of the Stroke-Specific Quality of Life (CSQoL). Ethics and dissemination The study protocol is approved by institutional review boards in participating hospitals (reference number FZ20160003, 180PLA20160101 and 476PLA2016007). The results of this study will be disseminated to patients, physicians and policymakers through publication in a peer-reviewed journal or presentations in conferences. It is anticipated that the results of this study will improve the quality of the current PTAS procedure and guide clinical decision-making for patients with ICAS. Trial registration number NCT02689037 PMID:27852711

A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial.

PubMed

Ngandu, Tiia; Lehtisalo, Jenni; Solomon, Alina; Levälahti, Esko; Ahtiluoto, Satu; Antikainen, Riitta; Bäckman, Lars; Hänninen, Tuomo; Jula, Antti; Laatikainen, Tiina; Lindström, Jaana; Mangialasche, Francesca; Paajanen, Teemu; Pajala, Satu; Peltonen, Markku; Rauramaa, Rainer; Stigsdotter-Neely, Anna; Strandberg, Timo; Tuomilehto, Jaakko; Soininen, Hilkka; Kivipelto, Miia

2015-06-06

Modifiable vascular and lifestyle-related risk factors have been associated with dementia risk in observational studies. In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a proof-of-concept randomised controlled trial, we aimed to assess a multidomain approach to prevent cognitive decline in at-risk elderly people from the general population. In a double-blind randomised controlled trial we enrolled individuals aged 60-77 years recruited from previous national surveys. Inclusion criteria were CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age. We randomly assigned participants in a 1:1 ratio to a 2 year multidomain intervention (diet, exercise, cognitive training, vascular risk monitoring), or a control group (general health advice). Computer-generated allocation was done in blocks of four (two individuals randomly allocated to each group) at each site. Group allocation was not actively disclosed to participants and outcome assessors were masked to group allocation. The primary outcome was change in cognition as measured through comprehensive neuropsychological test battery (NTB) Z score. Analysis was by modified intention to treat (all participants with at least one post-baseline observation). This trial is registered at ClinicalTrials.gov, number NCT01041989. Between Sept 7, 2009, and Nov 24, 2011, we screened 2654 individuals and randomly assigned 1260 to the intervention group (n=631) or control group (n=629). 591 (94%) participants in the intervention group and 599 (95%) in the control group had at least one post-baseline assessment and were included in the modified intention-to-treat analysis. Estimated mean change in NTB total Z score at 2 years was 0·20 (SE 0·02, SD 0·51) in the intervention group and 0·16 (0·01, 0·51) in the control group. Between-group difference in the change of NTB total score per year was 0·022 (95% CI 0·002-0·042, p=0·030). 153 (12%) individuals dropped out overall. Adverse events occurred in 46 (7%) participants in the intervention group compared with six (1%) participants in the control group; the most common adverse event was musculoskeletal pain (32 [5%] individuals for intervention vs no individuals for control). Findings from this large, long-term, randomised controlled trial suggest that a multidomain intervention could improve or maintain cognitive functioning in at-risk elderly people from the general population. Academy of Finland, La Carita Foundation, Alzheimer Association, Alzheimer's Research and Prevention Foundation, Juho Vainio Foundation, Novo Nordisk Foundation, Finnish Social Insurance Institution, Ministry of Education and Culture, Salama bint Hamdan Al Nahyan Foundation, Axa Research Fund, EVO funding for University Hospitals of Kuopio, Oulu, and Turku and for Seinäjoki Central Hospital and Oulu City Hospital, Swedish Research Council, Swedish Research Council for Health, Working Life and Welfare, and af Jochnick Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Positive effect of removal of subchondral bone plate for cemented acetabular component fixation in total hip arthroplasty: a randomised RSA study with ten-year follow-up.

PubMed

Flivik, G; Kristiansson, I; Ryd, L

2015-01-01

We hypothesised that the removal of the subchondral bone plate (SCBP) for cemented acetabular component fixation in total hip arthroplasty (THA) offers advantages over retention by improving the cement-bone interface, without jeopardising implant stability. We have previously published two-year follow-up data of a randomised controlled trial (RCT), in which 50 patients with primary osteoarthritis were randomised to either retention or removal of the SCBP. The mean age of the retention group (n = 25, 13 males) was 70.0 years (sd 6.8). The mean age in the removal group (n = 25, 16 males) was 70.3 years (sd 7.9). Now we have followed up the patients at six (retention group, n = 21; removal group, n = 20) and ten years (retention group: n = 17, removal group: n = 18), administering clinical outcome questionnaires and radiostereometric analysis (RSA), and determining the presence of radiolucent lines (RLLs) on conventional radiographs. RSA demonstrated similar translation and rotation patterns up to six years. Between six and ten years, proximal acetabular component migration and changes of inclination were larger in the retention group, although the mean differences did not reach statistical significance. Differences in migration were driven by two patients in the SCBP retention group with extensive migration versus none in the SCBP removal group. The significant difference (p < 0.001) in the development of radiolucent lines in the retention group, previously observed at two years, increased even further during the course of follow-up (p < 0.001). While recognising SCBP removal is a more demanding technique, we conclude that, wherever possible, the SCBP should be removed to improve the cement-bone interface in order to maximise acetabular component stability and longevity. ©2015 The British Editorial Society of Bone & Joint Surgery.

No economic benefit of early knee reconstruction over optional delayed reconstruction for ACL tears: registry enriched randomised controlled trial data.

PubMed

Kiadaliri, Aliasghar A; Englund, Martin; Lohmander, L Stefan; Carlsson, Katarina Steen; Frobell, Richard B

2016-05-01

To analyse 5-year cost-effectiveness of early versus optional delayed acute anterior cruciate ligament (ACL) reconstruction. 121 young, active adults with acute ACL injury to a previously uninjured knee were randomised to early ACL reconstruction (n=62, within 10 weeks of injury) or optional delayed ACL reconstruction (n=59; 30 with ACL reconstruction within 6-55 months); all patients received similar structured rehabilitation. Real life data on health care utilisation and sick leave were obtained from regional and national registers. Costs and quality-adjusted life years (QALYs) were discounted at 3%. Full-analysis set (based on study randomisation) and as-treated analysis (according to actual treatment over 5 years) principles were applied. Mean cost of early ACL reconstruction was €4695 higher than optional delayed ACL reconstruction (p=0.19) and provided an additional 0.13 QALYs (p=0.11). Full-analysis set showed incremental net benefit of early versus optional delayed ACL reconstruction was not statistically significantly different from zero at any level. As-treated analysis showed that costs for rehabilitation alone were €13 650 less than early ACL reconstruction (p<0.001). Results were robust to sensitivity analyses. In young active adults with acute ACL injury, a strategy of early ACL reconstruction did not provide extra economic value over a strategy of optional delayed ACL reconstruction over a 5-year period. Results from this and previous reports of the KANON-trial imply that early identification of individuals who would benefit from either early ACL reconstruction or rehabilitation alone might reduce resource consumption and decrease risk of unnecessary overtreatment. ISRCTN84752559. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Long-term pain prevalence and health-related quality of life outcomes for patients enrolled in a ketamine versus morphine for prehospital traumatic pain randomised controlled trial.

PubMed

Jennings, Paul A; Cameron, Peter; Bernard, Stephen; Walker, Tony; Jolley, Damien; Fitzgerald, Mark; Masci, Kevin

2014-10-01

Improved early pain control may affect the longer-term prevalence of persistent pain. In a previous randomised, controlled trial, we found that the administration of ketamine on hospital arrival decreased pain scores to a greater extent than morphine alone in patients with prehospital traumatic pain. In this follow-up study, we sought to determine the prevalence of persistent pain and whether there were differences in patients who received ketamine or morphine. This study was a long-term follow-up study of the prehospital, prospective, randomised, controlled, open-label study comparing ketamine with morphine in patients with trauma and a verbal pain score of >5 after 5 mg intravenous morphine. Patients were followed-up by telephone 6-12 months after enrollment, and a questionnaire including the SF-36 (V.2) health-related quality of life survey and the Verbal Numerical Rating Scale for pain was administered. A total of 97/135 (72%) patients were able to be followed-up 6-12 months after enrollment between July 2008 and July 2010. Overall, 44/97 (45%) participants reported persistent pain related to their injury, with 3/97 (3%) reporting persistent severe pain. The prevalence of persistent pain was the same between study groups (22/50 (44%) for the ketamine group vs 22/47 (46%) for the morphine group). There was no difference in the SF-36 scores between study arms. There is a high incidence of persistent pain after traumatic injury, even in patients with relatively minor severity of injury. Although decreased pain scores at hospital arrival are achieved with ketamine compared with morphine, this difference does not affect the prevalence of persistent pain or health-related quality of life 6 months after injury. Further larger studies are required to confirm this finding. Australian and New Zealand Clinical Trials Registry (ACTRN12607000441415). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Study of the therapeutic effects of an advanced hippotherapy simulator in children with cerebral palsy: a randomised controlled trial.

PubMed

Herrero, Pablo; Asensio, Angel; García, Elena; Marco, Alvaro; Oliván, Barbara; Ibarz, Alejandro; Gómez-Trullén, Eva M; Casas, Roberto

2010-04-16

Although hippotherapy treatment has been demonstrated to have therapeutic effects on children with cerebral palsy, the samples used in research studies have been very small. In the case of hippotherapy simulators, there are no studies that either recommend or advise against their use in the treatment of children with cerebral palsy. The aim of this randomised clinical study is to analyse the therapeutic effects or the contraindications of the use of a commercial hippotherapy simulator on several important factors relating to children with cerebral palsy such as their motor development, balance control in the sitting posture, hip abduction range of motion and electromyographic activity of adductor musculature. The study is a randomised controlled trial. It will be carried out with a sample of 37 children with cerebral palsy divided into two treatment groups. Eligible participants will be randomly allocated to receive either (a) Treatment Group with hippotherapy simulator, maintaining sitting posture, with legs in abduction and rhythmic movement of the simulator or (b) Treatment Group maintaining sitting posture, with legs in abduction and without rhythmic movement of the simulator. all measurements will be carried out by a specially trained blind assessor. To ensure standardization quality of the assessors, an inter-examiner agreement will be worked out at the start of the study. The trial is funded by the Department of Research, Innovation and Development of the Regional Government of Aragon (Official Bulletin of Aragon 23 July 2007), project number PM059/2007. Interest in this project is due to the following factors: Clinical originality (there are no previous studies analysing the effect of simulators on the population group of children with CP, nor any studies using as many variables as this project); Clinical impact (infantile cerebral palsy is a chronic multisystemic condition that affects not only the patient but also the patient's family and their close circle of friends); Practical benefits (the development of an effective treatment is very important for introducing this element into the rehabilitation of these children). Current Controlled Trials ISRCTN03663478.

Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants.

PubMed

Morgan, Jessie; Young, Lauren; McGuire, William

2014-01-01

The introduction of enteral feeds for very preterm (less than 32 weeks' gestation) or very low birth weight (VLBW; less than 1500 g) infants is often delayed for several days or longer after birth due to concern that early introduction may not be tolerated and may increase the risk of necrotising enterocolitis (NEC). However, delaying enteral feeding could diminish the functional adaptation of the gastrointestinal tract and prolong the need for parenteral nutrition with its attendant infectious and metabolic risks. To determine the effect of delayed introduction of progressive enteral feeds on the incidence of NEC, mortality and other morbidities in very preterm or VLBW infants. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 8), MEDLINE (1966 to September 2014), EMBASE (1980 to September 2014), CINAHL (1982 to September 2014), conference proceedings and previous reviews. We included randomised or quasi-randomised controlled trials that assessed the effect of delayed (more than four days after birth) versus earlier introduction of progressive enteral feeds on the incidence of NEC, mortality and other morbidities in very preterm or VLBW infants. Two review authors independently assessed trial eligibility and risk of bias and undertook data extraction. We analysed the treatment effects in the individual trials and reported the risk ratio (RR) and risk difference for dichotomous data and mean difference for continuous data, with respective 95% confidence intervals (CI). We used a fixed-effect model in meta-analyses and explored the potential causes of heterogeneity in sensitivity analyses. We identified nine randomised controlled trials in which 1106 infants participated. Few participants were extremely preterm (less 28 weeks' gestation) or extremely low birth weight (less than 1000 g). The trials defined delayed introduction of progressive enteral feeds as later than four to seven days after birth and early introduction as four days or less after birth. Meta-analyses did not detect statistically significant effects on the risk of NEC (typical RR 0.93, 95% CI 0.64 to 1.34; 8 trials; 1092 infants) or all-cause mortality (typical RR 1.18, 95% CI 0.75 to 1.88; 7 trials; 967 infants). Four of the trials restricted participation to growth-restricted infants with Doppler ultrasound evidence of abnormal fetal circulatory distribution or flow. Planned subgroup analyses of these trials found no statistically significant effects on the risk of NEC or all-cause mortality. Infants who had delayed introduction of enteral feeds took longer to establish full enteral feeding (reported median differences two to four days). The evidence available from randomised controlled trials suggested that delaying the introduction of progressive enteral feeds beyond four days after birth did not reduce the risk of developing NEC in very preterm or VLBW infants, including growth-restricted infants. Delaying the introduction of progressive enteral feeds resulted in a few days' delay in establishing full enteral feeds but the clinical importance of this effect was unclear. The applicability of these findings to extremely preterm or extremely low birth weight was uncertain. Further randomised controlled trials in this population may be warranted.

Stepwise strategy to improve Cervical Cancer Screening Adherence (SCAN-CC): automated text messages, phone calls and face-to-face interviews: protocol of a population-based randomised controlled trial.

PubMed

Firmino-Machado, João; Mendes, Romeu; Moreira, Amélia; Lunet, Nuno

2017-10-05

Screening is highly effective for cervical cancer prevention and control. Population-based screening programmes are widely implemented in high-income countries, although adherence is often low. In Portugal, just over half of the women adhere to cervical cancer screening, contributing for greater mortality rates than in other European countries. The most effective adherence raising strategies are based on patient reminders, small/mass media and face-to-face educational programmes, but sequential interventions targeting the general population have seldom been evaluated. The aim of this study is to assess the effectiveness of a stepwise approach, with increasing complexity and cost, to improve adherence to organised cervical cancer screening: step 1a-customised text message invitation; step 1b-customised automated phone call invitation; step 2-secretary phone call; step 3-family health professional phone call and face-to-face appointment. A population-based randomised controlled trial will be implemented in Portuguese urban and rural areas. Women eligible for cervical cancer screening will be randomised (1:1) to intervention and control. In the intervention group, women will be invited for screening through text messages, automated phone calls, manual phone calls and health professional appointments, to be applied sequentially to participants remaining non-adherent after each step. Control will be the standard of care (written letter). The primary outcome is the proportion of women adherent to screening after step 1 or sequences of steps from 1 to 3. The secondary outcomes are: proportion of women screened after each step (1a, 2 and 3); proportion of text messages/phone calls delivered; proportion of women previously screened in a private health institution who change to organised screening. The intervention and control groups will be compared based on intention-to-treat and per-protocol analyses. The study was approved by the Ethics Committee of the Northern Health Region Administration and National Data Protection Committee. Results will be disseminated through communications in scientific meetings and peer-reviewed journals. NCT03122275. © 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.

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

Antibacterial agents in composite restorations for the prevention of dental caries.

PubMed

Pereira-Cenci, Tatiana; Cenci, Maximiliano S; Fedorowicz, Zbys; Azevedo, Marina

2013-12-17

Dental caries is a multifactorial disease in which the fermentation of food sugars by bacteria from the biofilm (dental plaque) leads to localised demineralisation of tooth surfaces, which may ultimately result in cavity formation. Resin composites are widely used in dentistry to restore teeth. These restorations can fail for a number of reasons, such as secondary caries, and restorative material fracture and other minor reasons. From these, secondary caries, which are caries lesions developed adjacent to restorations, is the main cause for restorations replacement. The presence of antibacterials in both the filling material and the bonding systems would theoretically be able to affect the initiation and progression of caries adjacent to restorations. This is an update of the Cochrane review published in 2009. To assess the effects of antibacterial agents incorporated into composite restorations for the prevention of dental caries. We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 23 July 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 6), MEDLINE via OVID (1946 to 23 July 2013) and EMBASE via OVID (1980 to 23 July 2013). We searched the US National Institutes of Health Trials Register (http://clinicaltrials.gov), the metaRegister of Controlled Trials (www.controlled-trials.com) and the World Health Organization International Clinical Trials Registry platform (www.who.int/trialsearch) for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. Randomised controlled trials comparing resin composite restorations containing antibacterial agents with composite restorations not containing antibacterial agents. Two review authors conducted screening of studies in duplicate and independently, and although no eligible trials were identified, the two authors had planned to extract data independently and assess trial quality using standard Cochrane Collaboration methodologies. We retrieved 308 references to studies, none of which matched the inclusion criteria for this review and all of which were excluded. We were unable to identify any randomised controlled trials on the effects of antibacterial agents incorporated into composite restorations for the prevention of dental caries. The absence of high level evidence for the effectiveness of this intervention emphasises the need for well designed, adequately powered, randomised controlled clinical trials. Thus, conclusions remain the same as the previously published review, with no included clinical trials.

Indexing of randomised controlled trials of physiotherapy interventions: a comparison of AMED, CENTRAL, CINAHL, EMBASE, hooked on evidence, PEDro, PsycINFO and PubMed.

PubMed

Moseley, Anne M; Sherrington, Catherine; Elkins, Mark R; Herbert, Robert D; Maher, Christopher G

2009-09-01

To compare the comprehensiveness of indexing the reports of randomised controlled trials of physiotherapy interventions by eight bibliographic databases (AMED, CENTRAL, CINAHL, EMBASE, Hooked on Evidence, PEDro, PsycINFO and PubMed). Audit of bibliographic databases. Two hundred and eighty-one reports of randomised controlled trials of physiotherapy interventions were identified by screening the reference lists of 30 relevant systematic reviews published in four consecutive issues of the Cochrane Database of Systematic Reviews (Issue 3, 2007 to Issue 2, 2008). AMED, CENTRAL, CINAHL, EMBASE, Hooked on Evidence, PEDro, PsycINFO and PubMed were used to search for the trial reports. The number of trial reports indexed in each database was calculated. PEDro indexed 99% of the trial reports, CENTRAL indexed 98%, PubMed indexed 91%, EMBASE indexed 82%, CINAHL indexed 61%, Hooked on Evidence indexed 40%, AMED indexed 36% and PsycINFO indexed 17%. Most trial reports (92%) were indexed on four or more of the databases. One trial report was indexed on a single database (PEDro). Of the eight bibliographic databases examined, PEDro and CENTRAL provide the most comprehensive indexing of reports of randomised trials of physiotherapy interventions.

Tropomyosin Receptor Antagonism in Cylindromatosis (TRAC), an early phase trial of a topical tropomyosin kinase inhibitor as a treatment for inherited CYLD defective skin tumours: study protocol for a randomised controlled trial.

PubMed

Cranston, Amy; Stocken, Deborah D; Stamp, Elaine; Roblin, David; Hamlin, Julia; Langtry, James; Plummer, Ruth; Ashworth, Alan; Burn, John; Rajan, Neil

2017-03-07

Patients with germline mutations in a tumour suppressor gene called CYLD develop multiple, disfiguring, hair follicle tumours on the head and neck. The prognosis is poor, with up to one in four mutation carriers requiring complete surgical removal of the scalp. There are no effective medical alternatives to treat this condition. Whole genome molecular profiling experiments led to the discovery of an attractive molecular target in these skin tumour cells, named tropomyosin receptor kinase (TRK), upon which these cells demonstrate an oncogenic dependency in preclinical studies. Recently, the development of an ointment containing a TRK inhibitor (pegcantratinib - previously CT327 - from Creabilis SA) allowed for the assessment of TRK inhibition in tumours from patients with inherited CYLD mutations. Tropomysin Receptor Antagonism in Cylindromatosis (TRAC) is a two-part, exploratory, early phase, single-centre trial. Cohort 1 is a phase 1b open-labelled trial, and cohort 2 is a phase 2a randomised double-blinded exploratory placebo-controlled trial. Cohort 1 will determine the safety and acceptability of applying pegcantratinib for 4 weeks to a single tumour on a CYLD mutation carrier that is scheduled for a routine lesion excision (n = 8 patients). Cohort 2 will investigate if CYLD defective tumours respond following 12 weeks of treatment with pegcantratinib. As patients have multiple tumours, we intend to treat 10 tumours in each patient, 5 with active treatment and 5 with placebo. Patients will be allocated both active and placebo treatments to be applied randomly to tumours on the left or right side. The target is to treat 150 tumours in a maximum of 20 patients. Tumour volume will be measured at baseline and at 4 and 12 weeks. The primary outcome measure is the proportion of tumours responding to treatment by 12 weeks, based on change in tumour volume, with secondary measures based on adverse event profile, treatment compliance and acceptability, changes in tumour volume and surface area, patient quality of life and pain. Interventions for rare genetic skin diseases are often difficult to assess in an unbiased way due to small patient numbers and the challenges of incorporating adequate controls into trial design. Here we present a single-centre, randomised, placebo-controlled trial design that leverages the multiplicity of tumours seen in an inherited skin tumour syndrome that may inform the design of other studies in similar genetic diseases. International Standard Randomised Controlled Trial Number Registry, ISRCTN75715723 . Registered on 22 October 2014.

Effectiveness of an experiential workshop for enhancing helping professionals' self-competence in death work in Hong Kong: a randomised controlled trial.

PubMed

Chan, Wallace Chi Ho; Tin, Agnes Fong; Wong, Karen Lok Yi

2017-05-01

Helping professionals require self-competence in coping with the existential and emotional challenges of death work. Previous training often focused on knowledge and skills rather than on this competence. This study aimed to examine the effectiveness of a 3-day workshop in Hong Kong to enhance helping professionals' self-competence in death work. A randomised controlled trial was conducted to examine the effects of the training between January and May 2014. Targeted participants were helping professionals who had been doing death work for at least 6 months. The 112 participants were openly recruited from hospitals and NGOs and were assigned to an intervention group or a waitlist control group. Data were collected at pre-intervention and post-intervention. Primary outcome was self-competence in death work. All participants were grouped for analysing the changes in outcomes at pre-intervention, post-intervention and 3-month follow-up. Participants in the intervention group experienced a significant increase in the total score of the Self-competence in Death Work Scale (SC-DWS) and in scores of the Existential and Emotional subscales of SC-DWS. The positive effects of training on self-competence in death work were maintained at the 3-month follow-up. This study provides evidence of the effectiveness of training in enhancing helping professionals' self-competence in death work. Further research is required to examine the long-term effects of training. © 2016 John Wiley & Sons Ltd.

Protocol for a systematic review of psychological interventions for cancer-related fatigue in post-treatment cancer survivors.

PubMed

Corbett, Teresa; Devane, Declan; Walsh, Jane C; Groarke, AnnMarie; McGuire, Brian E

2015-12-04

Fatigue is a common symptom in cancer patients that can persist beyond the curative treatment phase. Some evidence has been reported for interventions for fatigue during active treatment. However, to date, there is no systematic review on psychological interventions for fatigue after the completion of curative treatment for cancer. This is a protocol for a systematic review that aims to evaluate the effectiveness of psychological interventions for cancer-related fatigue in post-treatment cancer survivors. This systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) database. We will search the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library), PubMed, MEDLINE, EMBASE, CINAHL, PsycINFO, and relevant sources of grey literature. Randomised controlled trials (RCTs) which have evaluated psychological interventions in adult cancer patients after the completion of treatment, with fatigue as an outcome measure, will be included. Two review authors will independently extract data from the selected studies and assess the methodological quality using the Cochrane Collaboration Risk of Bias Tool. Most existing evidence on cancer-related fatigue is from those in active cancer treatment. This systematic review and meta-analysis will build upon previous evaluations of psychological interventions in people during and after cancer treatment. With the growing need for stage-specific research in cancer, this review seeks to highlight a gap in current practice and to strengthen the evidence base of randomised controlled trials in the area. PROSPERO CRD42014015219.

The impact of constructive feedback on training in gastrointestinal endoscopy using high-fidelity Virtual-Reality simulation: a randomised controlled trial.

PubMed

Kruglikova, Irina; Grantcharov, Teodor P; Drewes, Asbjorn M; Funch-Jensen, Peter

2010-02-01

Recently, virtual reality computer simulators have been used to enhance traditional endoscopy teaching. Previous studies have demonstrated construct validity of these systems and transfer of virtual skills to the operating room. However, to date no simulator-training curricula have been designed and there is very little evidence on the impact of external feedback on acquisition of endoscopic skills. The aim of the present study was to assess the impact of external feedback on the learning curves on a VR colonoscopy simulator using inexperienced trainees. 22 trainees, without colonoscopy experience were randomised to a group which received structured feedback provided by an experienced supervisor and a controlled group. All participants performed 15 repetitions of task 3 from the Introduction colonoscopy module of the Accu Touch Endoscopy simulator. Retention/transfer tests on simulator were performed 4-6 weeks after the last repetition. The proficiency levels were based on the performance of eight experienced colonoscopists. All subjects were able to complete the procedure on the simulator. There were no perforations in the feedback group versus seven in the non-feedback group. Subjects in the feedback group reached expert proficiency levels in percentage of mucosa visualised and time to reach the caecum significantly faster compared with the control group. None of the groups demonstrated significant degradation of performance in simulator retention/transfer tests. Concurrent feedback given by supervisor concur an advantage in acquisition of basic colonoscopy skills and achieving of proficiency level as compared to independent training.

Light room therapy effective in mild forms of seasonal affective disorder--a randomised controlled study.

PubMed

Rastad, C; Ulfberg, J; Lindberg, P

2008-06-01

The most common way to provide bright light therapy to Swedish patients with Seasonal Affective Disorder (SAD), is treatment in a light therapy room. Since few studies have evaluated treatment provided in this setting and few have evaluated the effect of bright light in sub-clinical SAD (S-SAD), such a study including a one-month follow-up was designed. Fifty adults recruited from a previous prevalence study and clinically assessed as having SAD or S-SAD, were randomised to treatment in a light room or to a three-week waiting-list control group. The Hamilton Depression Rating Scale-Seasonal Affective Disorders Self-rating 29-items Version (SIGH-SAD/SR) was used to measure depressive mood at baseline, directly following treatment and at the one-month follow-up. ANCOVA with adjustment for baseline depression score, showed a significant main effect for the light room therapy group (p<0.001). Fifty-four percent (n=13/24) improved > or = 50% while no such improvement was seen in the control condition (n=0/24). After merging the two groups, repeated measures ANOVA confirmed the experimental analysis (p<0.001). At the one-month follow-up, 83.0% (n=39/47) had improved > or = 50% and 63.8% (n=30/47) had normal depression scores, i.e. < or = 8. Light room therapy was effective in reducing depressive symptoms in subjects with winter depressive mood. Results were maintained over a period of one month.

Reading and language intervention for children at risk of dyslexia: a randomised controlled trial.

PubMed

Duff, Fiona J; Hulme, Charles; Grainger, Katy; Hardwick, Samantha J; Miles, Jeremy N V; Snowling, Margaret J

2014-11-01

Intervention studies for children at risk of dyslexia have typically been delivered preschool, and show short-term effects on letter knowledge and phoneme awareness, with little transfer to literacy. This randomised controlled trial evaluated the effectiveness of a reading and language intervention for 6-year-old children identified by research criteria as being at risk of dyslexia (n = 56), and their school-identified peers (n = 89). An Experimental group received two 9-week blocks of daily intervention delivered by trained teaching assistants; the Control group received 9 weeks of typical classroom instruction, followed by 9 weeks of intervention. Following mixed effects regression models and path analyses, small-to-moderate effects were shown on letter knowledge, phoneme awareness and taught vocabulary. However, these were fragile and short lived, and there was no reliable effect on the primary outcome of word-level reading. This new intervention was theoretically motivated and based on previous successful interventions, yet failed to show reliable effects on language and literacy measures following a rigorous evaluation. We suggest that the intervention may have been too short to yield improvements in oral language; and that literacy instruction in and beyond the classroom may have weakened training effects. We argue that reporting of null results makes an important contribution in terms of raising standards both of trial reporting and educational practice. © 2014 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

Text messaging reminders for influenza vaccine in primary care: a cluster randomised controlled trial (TXT4FLUJAB).

PubMed

Herrett, Emily; Williamson, Elizabeth; van Staa, Tjeerd; Ranopa, Michael; Free, Caroline; Chadborn, Tim; Goldacre, Ben; Smeeth, Liam

2016-02-19

(1) To develop methods for conducting cluster randomised trials of text messaging interventions utilising routine electronic health records at low cost; (2) to assess the effectiveness of text messaging influenza vaccine reminders in increasing vaccine uptake in patients with chronic conditions. Cluster randomised trial with general practices as clusters. English primary care. 156 general practices, who used text messaging software, who had not previously used text message influenza vaccination reminders. Eligible patients were aged 18-64 in 'at-risk' groups. Practices were randomly allocated to either an intervention or standard care arm in the 2013 influenza season (September to December). Practices in the intervention arm were asked to send a text message influenza vaccination reminder to their at-risk patients under 65. Practices in the standard care arm were asked to continue their influenza campaign as planned. Practices were not blinded. Analysis was performed blinded to practice allocation. Practice-level influenza vaccine uptake among at-risk patients aged 18-64 years. 77 practices were randomised to the intervention group (76 analysed, n at-risk patients=51,121), 79 to the standard care group (79 analysed, n at-risk patients=51,136). The text message increased absolute vaccine uptake by 2.62% (95% CI -0.09% to 5.33%), p=0.058, though this could have been due to chance. Within intervention clusters, a median 21.0% (IQR 10.2% to 47.0%) of eligible patients were sent a text message. The number needed to treat was 7.0 (95% CI -0.29 to 14.3). Patient follow-up using routine electronic health records is a low cost method of conducting cluster randomised trials. Text messaging reminders are likely to result in modest improvements in influenza vaccine uptake, but levels of patients being texted need to markedly increase if text messaging reminders are to have much effect. ISRCTN48840025. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Development and Evaluation of a Pedagogical Tool to Improve Understanding of a Quality Checklist: A Randomised Controlled Trial

PubMed Central

Fourcade, Lola; Boutron, Isabelle; Moher, David; Ronceray, Lucie; Baron, Gabriel; Ravaud, Philippe

2007-01-01

Objective: The aim of this study was to develop and evaluate a pedagogical tool to enhance the understanding of a checklist that evaluates reports of nonpharmacological trials (CLEAR NPT). Design: Paired randomised controlled trial. Participants: Clinicians and systematic reviewers. Interventions: We developed an Internet-based computer learning system (ICLS). This pedagogical tool used many examples from published randomised controlled trials to demonstrate the main coding difficulties encountered when using this checklist. Randomised participants received either a specific Web-based training with the ICLS (intervention group) or no specific training. Outcome measures: The primary outcome was the rate of correct answers compared to a criterion standard for coding a report of randomised controlled trials with the CLEAR NPT. Results: Between April and June 2006, 78 participants were randomly assigned to receive training with the ICLS (39) or no training (39). Participants trained by the ICLS did not differ from the control group in performance on the CLEAR NPT. The mean paired difference and corresponding 95% confidence interval was 0.5 (−5.1 to 6.1). The rate of correct answers did not differ between the two groups regardless of the CLEAR NPT item. Combining both groups, the rate of correct answers was high or items related to allocation sequence (79.5%), description of the intervention (82.0%), blinding of patients (79.5%), and follow-up schedule (83.3%). The rate of correct answers was low for items related to allocation concealment (46.1%), co-interventions (30.3%), blinding of outcome assessors (53.8%), specific measures to avoid ascertainment bias (28.6%), and intention-to-treat analysis (60.2%). Conclusions: Although we showed no difference in effect between the intervention and control groups, our results highlight the gap in knowledge and urgency for education on important aspects of trial conduct. PMID:17479163

Changes in body weight and food choice in those attempting smoking cessation: a cluster randomised controlled trial

PubMed Central

2012-01-01

Background Fear of weight gain is a barrier to smoking cessation and significant cause of relapse for many people. The provision of nutritional advice as part of a smoking cessation programme may assist some in smoking cessation and perhaps limit weight gain. The aim of this study was to determine the effect of a structured programme of dietary advice on weight change and food choice, in adults attempting smoking cessation. Methods Cluster randomised controlled design. Classes randomised to intervention commenced a 24-week intervention, focussed on improving food choice and minimising weight gain. Classes randomised to control received “usual care”. Results Twenty-seven classes in Greater Glasgow were randomised between January and August 2008. Analysis, including those who continued to smoke, showed that actual weight gain and percentage weight gain was similar in both groups. Examination of data for those successful at giving up smoking showed greater mean weight gain in intervention subjects (3.9 (SD 3.1) vs. 2.7 (SD 3.7) kg). Between group differences were not significant (p = 0.23, 95% CI −0.9 to 3.5). In comparison to baseline improved consumption of fruit and vegetables and breakfast cereal were reported in the intervention group. A higher percentage of control participants continued smoking (74% vs. 66%). Conclusions The intervention was not successful at minimising weight gain in comparison to control but was successful in facilitating some sustained improvements in the dietary habits of intervention participants. Improved quit rates in the intervention group suggest that continued contact with advisors may have reduced anxieties regarding weight gain and encouraged cessation despite weight gain. Research should continue in this area as evidence suggests that the negative effects of obesity could outweigh the health benefits achieved through reductions in smoking prevalence. Trial registration Current Controlled Trials ISRCTN73824458 PMID:22642755

Effect of a lateral glide mobilisation with movement of the hip on vibration threshold in healthy volunteers.

PubMed

Smith, Darren A; Saranga, Jacob; Pritchard, Andrew; Kommatas, Nikolaos A; Punnoose, Shinu Kovelal; Kale, Supriya Tukaram

2018-01-01

Mulligan's mobilisation-with-movement (MWM) techniques are proposed to achieve their clinical benefit via neurophysiological mechanisms. However, previous research has focussed on responses in the sympathetic nervous system only, and is not conclusive. An alternative measure of neurophysiological response to MWM is required to support or refute this mechanism of action. Recently, vibration threshold (VT) has been used to quantify changes in the sensory nervous system in patients experiencing musculoskeletal pain. To investigate the effect of a lateral glide MWM of the hip joint on vibration threshold compared to a placebo and control condition in asymptomatic volunteers. Fifteen asymptomatic volunteers participated in this single-blinded, randomised, within-subject, placebo, control design. Participants received each of three interventions in a randomised order; a lateral glide MWM of the hip joint into flexion, a placebo MWM, and a control intervention. Vibration threshold (VT) measures were taken at baseline and immediately after each intervention. Mean change in VT from baseline was calculated for each intervention and then analysed for between group differences using a one-way analysis of variance (ANOVA). A one-way ANOVA revealed no statistically significant differences between the three experimental conditions (P = 0.812). This small study found that a lateral glide MWM of the hip did not significantly change vibration threshold compared to a placebo and control intervention in an asymptomatic population. This study provides a method of using vibration threshold to investigate the potential neurophysiological effects of a manual therapy intervention that should be repeated in a larger, symptomatic population. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Randomised Controlled Trial of the Use of a Piece of Commercial Software for the Acquisition of Reading Skills

ERIC Educational Resources Information Center

Khan, Muhammad Ahmad; Gorard, Stephen

2012-01-01

We report here the overall results of a cluster randomised controlled trial of the use of computer-aided instruction with 672 Year 7 pupils in 23 secondary school classes in the north of England. A new piece of commercial software, claimed on the basis of publisher testing to be effective in improving reading after just six weeks of use in the…

Effectiveness of educational poster on knowledge of emergency management of dental trauma--part 2: cluster randomised controlled trial for secondary school students.

PubMed

Young, Cecilia; Wong, Kin Yau; Cheung, Lim K

2014-01-01

To investigate the effectiveness of educational poster on improving secondary school students' knowledge of emergency management of dental trauma. A cluster randomised controlled trial was conducted. 16 schools with total 671 secondary students who can read Chinese or English were randomised into intervention (poster, 8 schools, 364 students) and control groups (8 schools, 305 students) at the school level. Baseline knowledge of dental trauma was obtained by a questionnaire. Poster containing information of dental trauma management was displayed in a classroom for 2 weeks in each school in the intervention group whereas in the control group there was no display of such posters. Students of both groups completed the same questionnaire after 2 weeks. Two-week display of posters improved the knowledge score by 1.25 (p-value = 0.0407) on average. Educational poster on dental trauma management significantly improved the level of knowledge of secondary school students in Hong Kong. HKClinicalTrial.com HKCTR-1343 ClinicalTrials.gov NCT01809457.

Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

PubMed

Turner, E L; Metcalfe, C; Donovan, J L; Noble, S; Sterne, J A C; Lane, J A; Avery, K N; Down, L; Walsh, E; Davis, M; Ben-Shlomo, Y; Oliver, S E; Evans, S; Brindle, P; Williams, N J; Hughes, L J; Hill, E M; Davies, C; Ng, S Y; Neal, D E; Hamdy, F C; Martin, R M

2014-06-10

Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50-69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up. Among randomised practices, 271 (68%) in the intervention arm (198,114 men) and 302 (78%) in the control arm (221,929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices). The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening.

An intervention to promote physical activity and self-management in people with stable chronic heart failure The Home-Heart-Walk study: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Chronic heart failure (CHF) is a chronic debilitating condition with economic consequences, mostly because of frequent hospitalisations. Physical activity and adequate self-management capacity are important risk reduction strategies in the management of CHF. The Home-Heart-Walk is a self-monitoring intervention. This model of intervention has adapted the 6-minute walk test as a home-based activity that is self-administered and can be used for monitoring physical functional capacity in people with CHF. The aim of the Home-Heart-Walk program is to promote adherence to physical activity recommendations and improving self-management in people with CHF. Methods/Design A randomised controlled trial is being conducted in English speaking people with CHF in four hospitals in Sydney, Australia. Individuals diagnosed with CHF, in New York Heart Association Functional Class II or III, with a previous admission to hospital for CHF are eligible to participate. Based on a previous CHF study and a loss to follow-up of 10%, 166 participants are required to be able to detect a 12-point difference in the study primary endpoint (SF-36 physical function domain). All enrolled participant receive an information session with a cardiovascular nurse. This information session covers key self-management components of CHF: daily weight; diet (salt reduction); medication adherence; and physical activity. Participants are randomised to either intervention or control group through the study randomisation centre after baseline questionnaires and assessment are completed. For people in the intervention group, the research nurse also explains the weekly Home-Heart-Walk protocol. All participants receive monthly phone calls from a research coordinator for six months, and outcome measures are conducted at one, three and six months. The primary outcome of the trial is the physical functioning domain of quality of life, measured by the physical functioning subscale of the Medical Outcome Study Short Form -36. Secondary outcomes include physical functional capacity measured by the standard six minute walk test, self-management capacity, health related quality of life measured by Medical Outcome Study Short Form -36 and Minnesota Living With Heart Failure Questionnaire, self-efficacy and self-care behaviour. Discussion A self-monitoring intervention that can improve individual's exercise self-efficacy, self-management capacity could have potential significance in improving the management of people with chronic heart failure in community settings. Trial Registration Australian New Zealand Clinical Trial Registry 12609000437268 PMID:21366927

An intervention to promote physical activity and self-management in people with stable chronic heart failure The Home-Heart-Walk study: study protocol for a randomized controlled trial.

PubMed

Du, Hui Y; Newton, Phillip J; Zecchin, Robert; Denniss, Robert; Salamonson, Yenna; Everett, Bronwyn; Currow, David C; Macdonald, Peter S; Davidson, Patricia M

2011-03-02

Chronic heart failure (CHF) is a chronic debilitating condition with economic consequences, mostly because of frequent hospitalisations. Physical activity and adequate self-management capacity are important risk reduction strategies in the management of CHF. The Home-Heart-Walk is a self-monitoring intervention. This model of intervention has adapted the 6-minute walk test as a home-based activity that is self-administered and can be used for monitoring physical functional capacity in people with CHF. The aim of the Home-Heart-Walk program is to promote adherence to physical activity recommendations and improving self-management in people with CHF. A randomised controlled trial is being conducted in English speaking people with CHF in four hospitals in Sydney, Australia. Individuals diagnosed with CHF, in New York Heart Association Functional Class II or III, with a previous admission to hospital for CHF are eligible to participate. Based on a previous CHF study and a loss to follow-up of 10%, 166 participants are required to be able to detect a 12-point difference in the study primary endpoint (SF-36 physical function domain).All enrolled participant receive an information session with a cardiovascular nurse. This information session covers key self-management components of CHF: daily weight; diet (salt reduction); medication adherence; and physical activity. Participants are randomised to either intervention or control group through the study randomisation centre after baseline questionnaires and assessment are completed. For people in the intervention group, the research nurse also explains the weekly Home-Heart-Walk protocol. All participants receive monthly phone calls from a research coordinator for six months, and outcome measures are conducted at one, three and six months. The primary outcome of the trial is the physical functioning domain of quality of life, measured by the physical functioning subscale of the Medical Outcome Study Short Form -36. Secondary outcomes include physical functional capacity measured by the standard six minute walk test, self-management capacity, health related quality of life measured by Medical Outcome Study Short Form -36 and Minnesota Living With Heart Failure Questionnaire, self-efficacy and self-care behaviour. A self-monitoring intervention that can improve individual's exercise self-efficacy, self-management capacity could have potential significance in improving the management of people with chronic heart failure in community settings. Australian New Zealand Clinical Trial Registry 12609000437268.

Medical versus surgical treatment for refractory or recurrent peptic ulcer.

PubMed

Gurusamy, Kurinchi Selvan; Pallari, Elena

2016-03-29

Refractory peptic ulcers are ulcers in the stomach or duodenum that do not heal after eight to 12 weeks of medical treatment or those that are associated with complications despite medical treatment. Recurrent peptic ulcers are peptic ulcers that recur after healing of the ulcer. Given the number of deaths due to peptic ulcer-related complications and the long-term complications of medical treatment (increased incidence of fracture), it is unclear whether medical or surgical intervention is the better treatment option in people with recurrent or refractory peptic ulcers. To assess the benefits and harms of medical versus surgical treatment for people with recurrent or refractory peptic ulcer. We searched the specialised register of the Cochrane Upper GI and Pancreatic Diseases group, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and trials registers until September 2015 to identify randomised trials and non-randomised studies, using search strategies. We also searched the references of included studies to identify further studies. We considered randomised controlled trials and non-randomised studies comparing medical treatment with surgical treatment in people with refractory or recurrent peptic ulcer, irrespective of language, blinding, or publication status for inclusion in the review. Two review authors independently identified trials and extracted data. We planned to calculate the risk ratio, mean difference, standardised mean difference, or hazard ratio with 95% confidence intervals using both fixed-effect and random-effects models with Review Manager 5 based on intention-to-treat analysis. We included only one non-randomised study published 30 years ago in the review. This study included 77 participants who had gastric ulcer and in whom medical therapy (histamine H2 receptor blockers, antacids, and diet) had failed after an average duration of treatment of 29 months. The authors do not state whether these were recurrent or refractory ulcers. It appears that the participants did not have previous complications such as bleeding or perforation. Of the 77 included participants, 37 participants continued to have medical therapy while 40 participants received surgical therapy (antrectomy with or without vagotomy; subtotal gastrectomy with or without vagotomy; vagotomy; pyloroplasty and suture of the ulcer; suture or closure of ulcer without vagotomy or excision of the ulcer; proximal gastric or parietal cell vagotomy alone; suture or closure of the ulcer with proximal gastric or parietal cell vagotomy). Whether to use medical or surgical treatment was determined by participant's or treating physician's preference.The study authors reported that two participants in the medical treatment group (2 out of 37; 5.4%) had gastric cancer, which was identified by repeated biopsy. They did not report the proportion of participants who had gastric cancer in the surgical treatment group. They also did not report the implications of the delayed diagnosis of gastric cancer in the medical treatment group. They did not report any other outcomes of interest for this review (that is health-related quality of life (using any validated scale), adverse events and serious adverse events, peptic ulcer bleeding, peptic ulcer perforation, abdominal pain, and long-term mortality). We found no studies that provide the relative benefits and harms of medical versus surgical treatment for recurrent or refractory peptic ulcers. Studies that evaluate the natural history of recurrent and refractory peptic ulcers are urgently required to determine whether randomised controlled trials comparing medical versus surgical management in patients with recurrent or refractory peptic ulcers or both are necessary. Such studies will also provide information for the design of such randomised controlled trials. A minimum follow-up of two to three years will allow the calculation of the incidence of complications and gastric cancer (in gastric ulcers only) in recurrent and refractory peptic ulcers. In addition to complications related to treatment and disease, health-related quality of life and loss of productivity should also be measured.

Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial

PubMed Central

2010-01-01

Summary Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4·0%) events of disabling stroke or death in the stenting group compared with 27 (3·2%) events in the endarterectomy group (hazard ratio [HR] 1·28, 95% CI 0·77–2·11). The incidence of stroke, death, or procedural myocardial infarction was 8·5% in the stenting group compared with 5·2% in the endarterectomy group (72 vs 44 events; HR 1·69, 1·16–2·45, p=0·006). Risks of any stroke (65 vs 35 events; HR 1·92, 1·27–2·89) and all-cause death (19 vs seven events; HR 2·76, 1·16–6·56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0·0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery. Funding Medical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union. PMID:20189239

When is a randomised controlled trial health equity relevant? Development and validation of a conceptual framework.

PubMed

Jull, J; Whitehead, M; Petticrew, M; Kristjansson, E; Gough, D; Petkovic, J; Volmink, J; Weijer, C; Taljaard, M; Edwards, S; Mbuagbaw, L; Cookson, R; McGowan, J; Lyddiatt, A; Boyer, Y; Cuervo, L G; Armstrong, R; White, H; Yoganathan, M; Pantoja, T; Shea, B; Pottie, K; Norheim, O; Baird, S; Robberstad, B; Sommerfelt, H; Asada, Y; Wells, G; Tugwell, P; Welch, V

2017-09-25

Randomised controlled trials can provide evidence relevant to assessing the equity impact of an intervention, but such information is often poorly reported. We describe a conceptual framework to identify health equity-relevant randomised trials with the aim of improving the design and reporting of such trials. An interdisciplinary and international research team engaged in an iterative consensus building process to develop and refine the conceptual framework via face-to-face meetings, teleconferences and email correspondence, including findings from a validation exercise whereby two independent reviewers used the emerging framework to classify a sample of randomised trials. A randomised trial can usefully be classified as 'health equity relevant' if it assesses the effects of an intervention on the health or its determinants of either individuals or a population who experience ill health due to disadvantage defined across one or more social determinants of health. Health equity-relevant randomised trials can either exclusively focus on a single population or collect data potentially useful for assessing differential effects of the intervention across multiple populations experiencing different levels or types of social disadvantage. Trials that are not classified as 'health equity relevant' may nevertheless provide information that is indirectly relevant to assessing equity impact, including information about individual level variation unrelated to social disadvantage and potentially useful in secondary modelling studies. The conceptual framework may be used to design and report randomised trials. The framework could also be used for other study designs to contribute to the evidence base for improved health equity. © 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.

Lee Silverman Voice Treatment versus standard speech and language therapy versus control in Parkinson's disease: a pilot randomised controlled trial (PD COMM pilot).

PubMed

Sackley, Catherine M; Smith, Christina H; Rick, Caroline E; Brady, Marian C; Ives, Natalie; Patel, Smitaa; Woolley, Rebecca; Dowling, Francis; Patel, Ramilla; Roberts, Helen; Jowett, Sue; Wheatley, Keith; Kelly, Debbie; Sands, Gina; Clarke, Carl E

2018-01-01

Speech-related problems are common in Parkinson's disease (PD), but there is little evidence for the effectiveness of standard speech and language therapy (SLT) or Lee Silverman Voice Treatment (LSVT LOUD®). The PD COMM pilot was a three-arm, assessor-blinded, randomised controlled trial (RCT) of LSVT LOUD®, SLT and no intervention (1:1:1 ratio) to assess the feasibility and to inform the design of a full-scale RCT. Non-demented patients with idiopathic PD and speech problems and no SLT for speech problems in the past 2 years were eligible. LSVT LOUD® is a standardised regime (16 sessions over 4 weeks). SLT comprised individualised content per local practice (typically weekly sessions for 6-8 weeks). Outcomes included recruitment and retention, treatment adherence, and data completeness. Outcome data collected at baseline, 3, 6, and 12 months included patient-reported voice and quality of life measures, resource use, and assessor-rated speech recordings. Eighty-nine patients were randomised with 90% in the therapy groups and 100% in the control group completing the trial. The response rate for Voice Handicap Index (VHI) in each arm was ≥ 90% at all time-points. VHI was highly correlated with the other speech-related outcome measures. There was a trend to improvement in VHI with LSVT LOUD® (difference at 3 months compared with control: - 12.5 points; 95% CI - 26.2, 1.2) and SLT (difference at 3 months compared with control: - 9.8 points; 95% CI - 23.2, 3.7) which needs to be confirmed in an adequately powered trial. Randomisation to a three-arm trial of speech therapy including a no intervention control is feasible and acceptable. Compliance with both interventions was good. VHI and other patient-reported outcomes were relevant measures and provided data to inform the sample size for a substantive trial. International Standard Randomised Controlled Trial Number Register: ISRCTN75223808. registered 22 March 2012.

Does an intensive self-management structured education course improve outcomes for children and young people with type 1 diabetes? The Kids In Control OF Food (KICk-OFF) cluster-randomised controlled trial protocol

PubMed Central

Price, Katherine J; Wales, Jerry; Eiser, Christine; Knowles, Julie; Heller, Simon; Freeman, Jenny; Brennan, Alan; McPherson, Amy; Wellington, Jerry

2013-01-01

Introduction The Kids In Control OF Food (KICk-OFF) is a cluster-randomised controlled trial, which aims to determine the efficacy of a 5 day structured education course for 11-year-olds to 16-year-olds with type 1 diabetes (T1DM) when compared with standard care, and its cost effectiveness. Less than 15% of children and young people with T1DM in the UK meet the recommended glycaemic target. Self-management education programmes for adults with T1DM improve clinical and psychological outcomes, but none have been evaluated in the paediatric population. KICk-OFF is a 5-day structured education course for 11-year-olds to 16- year-olds with T1DM. It was developed with input from young people, parents, teachers and educationalists. Methods and analysis 36 paediatric diabetes centres across the UK randomised into intervention and control arms. Up to 560 participants were recruited prior to centre randomisation. KICk-OFF courses are delivered in the intervention centres, with standard care continued in the control arm. Primary outcomes are change in glycaemic control (HbA1c) and quality of life between baseline and 6 months postintervention, and the incidence of severe hypoglycaemia. Sustained change in self-management behaviour is assessed by follow-up at 12 and 24 months. Health economic analysis will be undertaken. Data will be reported according to the CONSORT statement for cluster-randomised clinical trials. All analyses will be by intention-to-treat with a two-sided p value of <0.05 being regarded as statistically significant. The study commenced in 2008. Data collection from participants is ongoing and the study will be completed in 2013. Ethics The study has been approved by the Sheffield Research Ethics Committee. Dissemination Results will be reported in peer reviewed journals and conferences. Trial registration Current Controlled Trials ISRCTN37042683. PMID:23355675

Randomised controlled trial of biofeedback training in persistent encopresis with anismus.

PubMed

Nolan, T; Catto-Smith, T; Coffey, C; Wells, J

1998-08-01

Paradoxical external anal sphincter contraction during attempted defecation (anismus) is thought to be an important contributor to chronic faecal retention and encopresis in children. Biofeedback training can be used to teach children to abolish this abnormal contraction. A randomised controlled trial in medical treatment resistant and/or treatment dependent children with anismus using surface electromyographic (EMG) biofeedback training to determine whether such training produces sustained faecal continence. Up to four sessions of biofeedback training were conducted at weekly intervals for each patient. Anorectal manometry was performed before randomisation and six months later. Parents of patients completed the "child behaviour checklist" (CBCL) before randomisation and at follow up. Sixty eight children underwent anorectal manometry and EMG. Of these, 29 had anismus (ages 4-14 years) and were randomised to either EMG biofeedback training and conventional medical treatment (BFT) (n = 14) or to conventional medical treatment alone (n = 15). All but one child were able to learn relaxation of the external anal sphincter on attempted defecation. At six months' follow up, laxative free remission had been sustained in two of 14 patients in the BFT group and in two of 15 controls (95% confidence interval (CI) on difference, -24% to 26%). Remission or improvement occurred in four of 14 patients in the BFT group and six of 15 controls (95% CI on difference, -46% to 23%). Of subjects available for repeat anorectal manometry and EMG at six months, six of 13 in the BFT group still demonstrated anismus v 11 of 13 controls (95% CI on difference, -75% to -1%). Of the four patients in full remission at six months, only one (in the BFT group) did not exhibit anismus. Rectal hyposensitivity was not associated with remission or improvement in either of the groups. Mean CBCL total behaviour problem scores were not significantly different between the BFT and control groups, but there was a significant improvement in CBCL school scale scores in the BFT group, and this improvement was significantly greater than that seen in the control group. The result of this study, together with those reported in other controlled trials, argues against using biofeedback training in children with encopresis.

Primary cervical cancer screening with HPV testing compared with liquid-based cytology: results of round 1 of a randomised controlled trial -- the HPV FOCAL Study.

PubMed

Ogilvie, G S; Krajden, M; van Niekerk, D J; Martin, R E; Ehlen, T G; Ceballos, K; Smith, L W; Kan, L; Cook, D A; Peacock, S; Stuart, G C E; Franco, E L; Coldman, A J

2012-12-04

Round 1 data of human papillomavirus (HPV) FOCAL, a three-arm, randomised trial, which aims to establish the efficacy of HPV DNA testing as a primary screen for cervical cancer, are presented. The three arms are: Control arm - liquid based cytology with atypical squamous cells of unknown significance (ASC-US) triage with hrHPV testing; Intervention Arm - hrHPV at entry with liquid-based cytology (LBC) triage of hrHPV positives, with exit screen at 4 years; Safety check arm - hrHPV at entry with LBC triage of hrHPV positives with exit screen at 2 years. A total of 6154 women were randomised to the control arm and 12 494 to the HPV arms (intervention and safety check). In the HPV arm, the baseline cervical intraepithelial neoplasia (CIN)2+ and CIN3+ rate was 9.2/1000 (95%CI; 7.4, 10.9) and 4.8/1000 (95%CI; 3.6, 6.1), which increased to 16.1/1000 (95%CI 13.2, 18.9) for CIN2+ and to 8.0/1000 (95%CI; 5.9, 10.0) for CIN3+ after subsequent screening of HPV-DNA-positive/cytology-negative women. Detection rate in the control arm remained unchanged after subsequent screening of ASC-US-positive/hrHPV DNA-negative women at 11.0/1000 for CIN2+ and 5.0/1000 for CIN3+. After subsequent screening of women who were either hrHPV positive/cytology negative or ASC-US positive/HPV negative, women randomised to the HPV arms had increased CIN2+ detection compared with women randomised to the cytology arm.

A randomised controlled trial of clinics in secondary schools for adolescents with asthma.

PubMed Central

Salisbury, Chris; Francis, Caia; Rogers, Chris; Parry, Kate; Thomas, Huw; Chadwick, Stephanie; Turton, Pat

2002-01-01

AIM: To compare a nurse-led clinic in schools versus care in general practice for adolescents with asthma. DESIGN OF STUDY: Randomised controlled trial in four schools; parallel observational study in two schools. SETTING: Six comprehensive schools. METHOD: In the randomised trial, pupils were invited to attend asthma review at a nurse-led clinic either in school, or in general practice. The parallel observational study compared pupils invited to practice care within and outside the randomised trial. Primary outcome measures were attendance for asthma review, symptom control, and quality of life. Secondary outcomes were knowledge, attitudes, inhaler technique, use of steroids, school absence, peak flow rate, preference for future care, health service utilisation, and costs. RESULTS: School clinic pupils were more likely to attend an asthma review than those randomised to practice care (90.8% versus 51.0% overall [P < 0.001, not consistent across schools]). No differences were observed in symptom control (P = 0.42) or quality of life (P = 0.63). Pupils attending school clinics had greater knowledge of asthma (difference = +0.38, 95% CI = 0.19 to 0.56), more positive attitudes (difference = +0.21, 95% CI = 0.05 to 0.36), and better inhaler technique (P < 0.001, not consistent across all schools). No differences were observed in school absence or peak flow rate. A majority (63%) of those who had received care at school preferred this model in future. Median costs of providing care at school and at the practice were 32.10 Pounds and 19.80 Pounds, respectively. No differences were observed between the groups in the observational comparison on any outcome. CONCLUSIONS: The schools asthma clinic increased uptake of asthma reviews. There were improvements in various process measures, but not in clinical outcomes. PMID:12528584

Managing Injuries of the Neck Trial (MINT): design of a randomised controlled trial of treatments for whiplash associated disorders

PubMed Central

Lamb, Sarah E; Gates, Simon; Underwood, Martin R; Cooke, Matthew W; Ashby, Deborah; Szczepura, Ala; Williams, Mark A; Williamson, Esther M; Withers, Emma J; Mt Isa, Shahrul; Gumber, Anil

2007-01-01

Background A substantial proportion of patients with whiplash injuries develop chronic symptoms. However, the best treatment of acute injuries to prevent long-term problems is uncertain. A stepped care treatment pathway has been proposed, in which patients are given advice and education at their initial visit to the emergency department (ED), followed by review at three weeks and physiotherapy for those with persisting symptoms. MINT is a two-stage randomised controlled trial to evaluate two components of such a pathway: 1. use of The Whiplash Book versus usual advice when patients first attend the emergency department; 2. referral to physiotherapy versus reinforcement of advice for patients with continuing symptoms at three weeks. Methods Evaluation of the Whiplash Book versus usual advice uses a cluster randomised design in emergency departments of eight NHS Trusts. Eligible patients are identified by clinicians in participating emergency departments and are sent a study questionnaire within a week of their ED attendance. Three thousand participants will be included. Patients with persisting symptoms three weeks after their ED attendance are eligible to join an individually randomised study of physiotherapy versus reinforcement of the advice given in ED. Six hundred participants will be randomised. Follow-up is at 4, 8 and 12 months after their ED attendance. Primary outcome is the Neck Disability Index (NDI), and secondary outcomes include quality of life and time to return to work and normal activities. An economic evaluation is being carried out. Conclusion This paper describes the protocol and operational aspects of a complex intervention trial based in NHS emergency and physiotherapy departments, evaluating two components of a stepped-care approach to the treatment of whiplash injuries. The trial uses two randomisations, with the first stage being cluster randomised and the second individually randomised. PMID:17257408

The effect of dietary counselling on food intakes in pregnant women at risk for gestational diabetes: a secondary analysis of a randomised controlled trial RADIEL.

PubMed

Valkama, A; Koivusalo, S; Lindström, J; Meinilä, J; Kautiainen, H; Stach-Lempinen, B; Rönö, K; Klemetti, M; Pöyhönen-Alho, M; Tiitinen, A; Huvinen, E; Laivuori, H; Andersson, S; Roine, R; Eriksson, J G

2016-08-01

The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide. GDM may be prevented by improving the diets of pregnant women. The objective of this study was to evaluate the effect of dietary counselling on the diets of pregnant women at GDM risk. This study was a secondary analysis of a randomised controlled trial the Finnish gestational diabetes prevention study (RADIEL) in which pre-pregnant and pregnant women with previous GDM or BMI ⩾30 kg/m(2) were allocated into two groups, namely the control and the intervention groups. The control group received standard antenatal dietary counselling according to the Finnish Nutrition Recommendations. The intervention group participated in one individual dietary counselling session and one group dietary counselling session in addition to the standard counselling. This study included women who were recruited during pregnancy. To assess changes in food intake, food-intake questionnaires were collected during the first and the second trimester of pregnancy. Bootstrap type analysis of covariance was used, and 242 participants were included in the final analysis to study changes in food intake. The intakes of low-fat cheese (baseline adjusted mean 0.09 times/day; 95% confidence interval (CI) 0.07, 0.24; P=0.040) and fish (baseline adjusted mean 0.28 times per week; 95% CI 0.08, 0.49; P=0.011) showed a significant increase in the intervention group compared with the control group. This study showed that dietary counselling in early pregnancy can lead to modest dietary improvements in pregnant women at GDM risk.

Diet and anthropometry at 2 years of age following an oral health promotion programme for Australian Aboriginal children and their carers: a randomised controlled trial.

PubMed

Smithers, Lisa G; Lynch, John; Hedges, Joanne; Jamieson, Lisa M

2017-12-01

There are marked disparities between indigenous and non-indigenous children's diets and oral health. Both diet and oral health are linked to longer-term health problems. We aimed to investigate whether a culturally appropriate multi-faceted oral health promotion intervention reduced Aboriginal children's intake of sugars from discretionary foods at 2 years of age. We conducted a single-blind, parallel-arm randomised controlled trial involving women who were pregnant or had given birth to an Aboriginal child in the previous 6 weeks. The treatment group received anticipatory guidance, Motivational Interviewing, health and dental care for mothers during pregnancy and children at 6, 12 and 18 months. The control group received usual care. The key dietary outcome was the percent energy intake from sugars in discretionary foods (%EI), collected from up to three 24-h dietary recalls by trained research officers who were blind to intervention group. Secondary outcomes included intake of macronutrients, food groups, anthropometric z scores (weight, height, BMI and mid-upper arm circumference) and blood pressure. We enrolled 224 children to the treatment group and 230 to the control group. Intention-to-treat analyses showed that the %EI of sugars in discretionary foods was 1·6 % lower in the treatment group compared with control (95 % CI -3·4, 0·2). This culturally appropriate intervention at four time-points from pregnancy to 18 months resulted in small changes to 2-year-old Aboriginal children's diets, which was insufficient to warrant broader implementation of the intervention. Further consultation with Aboriginal communities is necessary for understanding how to improve the diet and diet-related health outcomes of young Aboriginal children.

Minimal access surgery compared with medical management for gastro-oesophageal reflux disease: five year follow-up of a randomised controlled trial (REFLUX).

PubMed

Grant, A M; Cotton, S C; Boachie, C; Ramsay, C R; Krukowski, Z H; Heading, R C; Campbell, M K

2013-04-18

To determine the long term clinical effectiveness of laparoscopic fundoplication as an alternative to drug treatment for chronic gastro-oesophageal reflux disease (GORD). Five year follow-up of multicentre, pragmatic randomised trial (with parallel non-randomised preference groups). Initial recruitment in 21 UK hospitals. Responders to annual questionnaires among 810 original participants. At entry, all had had GORD for >12 months. The surgeon chose the type of fundoplication. Medical therapy was reviewed and optimised by a specialist. Subsequent management was at the discretion of the clinician responsible for care, usually in primary care. Primary outcome measure was self reported quality of life score on disease-specific REFLUX questionnaire. Other measures were health status (with SF-36 and EuroQol EQ-5D questionnaires), use of antireflux medication, and complications. By five years, 63% (112/178) of patients randomised to surgery and 13% (24/179) of those randomised to medical management had received a fundoplication (plus 85% (222/261) and 3% (6/192) of those who expressed a preference for surgery and for medical management). Among responders at 5 years, 44% (56/127) of those randomised to surgery were taking antireflux medication versus 82% (98/119) of those randomised to medical management. Differences in the REFLUX score significantly favoured the randomised surgery group (mean difference 8.5 (95% CI 3.9 to 13.1), P<0.001, at five years). SF-36 and EQ-5D scores also favoured surgery, but were not statistically significant at five years. After fundoplication, 3% (12/364) had surgical treatment for a complication and 4% (16) had subsequent reflux-related operations-most often revision of the wrap. Long term rates of dysphagia, flatulence, and inability to vomit were similar in the two randomised groups. After five years, laparoscopic fundoplication continued to provide better relief of GORD symptoms than medical management. Adverse effects of surgery were uncommon and generally observed soon after surgery. A small proportion had re-operations. There was no evidence of long term adverse symptoms caused by surgery. Current Controlled Trials ISRCTN15517081.

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

Can exercise improve self esteem in children and young people? A systematic review of randomised controlled trials.

PubMed

Ekeland, E; Heian, F; Hagen, K B

2005-11-01

A systematic review to determine if exercise alone or as part of a comprehensive intervention can improve self esteem in children and young people is described. Twenty three randomised controlled trials were analysed. A synthesis of several small, low quality trials indicates that exercise may have short term beneficial effects on self esteem in children and adolescents. However, high quality research on defined populations with adequate follow up is needed.

Ambulatory versus inpatient management of severe nausea and vomiting of pregnancy: a randomised control trial with patient preference arm

PubMed Central

Mitchell-Jones, Nicola; Farren, Jessica Alice; Tobias, Aurelio; Bourne, Tom; Bottomley, Cecilia

2017-01-01

Objective To determine whether ambulatory (outpatient (OP)) treatment of severe nausea and vomiting of pregnancy (NVP) is as effective as inpatient (IP) care. Design Non-blinded randomised control trial (RCT) with patient preference arm. Setting Two multicentre teaching hospitals in London. Participants Women less than 20 weeks’ pregnant with severe NVP and associated ketonuria (>1+). Methods Women who agreed to the RCT were randomised via web-based application to either ambulatory or IP treatment. Women who declined randomisation underwent the treatment of their choice in the patient preference trial (PPT) arm. Treatment protocols, data collection and follow-up were the same for all participants. Main outcome measures Primary outcome was reduction in Pregnancy Unique Quantification of Emesis (PUQE) score 48 hours after starting treatment. Secondary outcome measures were duration of treatment, improvement in symptom scores and ketonuria at 48 hours, reattendances within 7 days of discharge and comparison of symptoms at 7 days postdischarge. Results 152/174 eligible women agreed to participate with 77/152 (51%) recruited to the RCT and 75/152 (49%) to the PPT. Patients were initially compared in four groups (randomised IP, randomised OP, non-randomised IP and non-randomised OP). Comprehensive cohort analysis of participants in the randomised group (RCT) and non-randomised group (PPT) did not demonstrate any differences in patient demographics or baseline clinical characteristics. Pooled analysis of IP versus OP groups showed no difference in reduction in PUQE score at 48 hours (p=0.86). There was no difference in change in eating score (p=0.69), drinking score (p=0.77), well-being rating (p=0.64) or reduction in ketonuria (p=0.47) at 48 hours, with no difference in duration of index treatment episode (p=0.83) or reattendances within 7 days (p=0.52). Conclusions Ambulatory management is an effective direct alternative to IP management of severe NVP. The trial also demonstrated that many women requiring treatment for severe NVP have strong preferences regarding treatment setting, which may need to be considered by care providers, especially given the psychological impact of severe NVP. Trial registration number http://www.isrctn.com/ISRCTN24659467 (March 2014). PMID:29222135

Reducing the Social Gradient in Uptake of the NHS Colorectal Cancer Screening Programme Using a Narrative-Based Information Leaflet: A Cluster-Randomised Trial

PubMed Central

McGregor, Lesley M.; von Wagner, Christian; Atkin, Wendy; Kralj-Hans, Ines; Halloran, Stephen P.; Handley, Graham; Logan, Richard F.; Rainbow, Sandra; Smith, Steve; Snowball, Julia; Thomas, Mary C.; Smith, Samuel G.; Vart, Gemma; Howe, Rosemary; Counsell, Nicholas; Hackshaw, Allan; Morris, Stephen; Duffy, Stephen W.; Raine, Rosalind; Wardle, Jane

2016-01-01

Objective. To test the effectiveness of adding a narrative leaflet to the current information material delivered by the NHS English colorectal cancer (CRC) screening programme on reducing socioeconomic inequalities in uptake. Participants. 150,417 adults (59–74 years) routinely invited to complete the guaiac Faecal Occult Blood test (gFOBt) in March 2013. Design. A cluster randomised controlled trial (ISRCTN74121020) to compare uptake between two arms. The control arm received the standard NHS CRC screening information material (SI) and the intervention arm received the standard information plus a supplementary narrative leaflet, which had previously been shown to increase screening intentions (SI + N). Between group comparisons were made for uptake overall and across socioeconomic status (SES). Results. Uptake was 57.7% and did not differ significantly between the two trial arms (SI: 58.5%; SI + N: 56.7%; odds ratio = 0.93; 95% confidence interval: 0.81–1.06; p = 0.27). There was no interaction between group and SES quintile (p = 0.44). Conclusions. Adding a narrative leaflet to existing information materials does not reduce the SES gradient in uptake. Despite the benefits of using a pragmatic trial design, the need to add to, rather than replace, existing information may have limited the true value of an evidence-based intervention on behaviour. PMID:27069473

The Effect of Anthocyanin-Rich Foods or Extracts on Vascular Function in Adults: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

PubMed Central

Fairlie-Jones, Lucy; Davison, Kade; Fromentin, Emilie

2017-01-01

Anthocyanins are of interest due to their anti-oxidative and vasodilatory properties. Earlier reviews have shown that berries and other anthocyanin rich foods or extracts can improve vascular health, however the effect of anthocyanins on vascular function has not yet been reviewed. To address this gap in the literature, we conducted a systematic review and meta-analysis of randomised-controlled trials examining anthocyanin-rich foods or extracts on measures of vascular reactivity and/or stiffness in adults. Data from 24 studies were pooled as standardized mean difference (SMD) with 95% confidence intervals (CI). Anthocyanin consumption significantly improved flow-mediated dilation (FMD) following acute (SMD: 3.92%, 95% CI: 1.47, 6.38, p = 0.002; I2 = 91.8%) and chronic supplementation (SMD: 0.84%, 95% CI: 0.55, 1.12, p = 0.000; I2 = 62.5%). Pulse wave velocity was improved following acute supplementation only (SMD: −1.27 m/s, 95% CI: −1.96, −0.58, p = 0.000; I2 = 17.8%). These results support the findings of previous reviews that anthocyanin rich foods or extracts may indeed improve vascular health, particularly with respect to vascular reactivity measured by FMD. More research is required to determine the optimal dosage, and the long-term effects of consumption. PMID:28825651

Effectiveness of recombinant human bone morphogenetic protein-7 in the management of congenital pseudoarthrosis of the tibia: a randomised controlled trial.

PubMed

Das, Sakti Prasad; Ganesh, Shankar; Pradhan, Sudhakar; Singh, Deepak; Mohanty, Ram Narayan

2014-09-01

Despite the popularity and an increased use of bone morphogenetic protein to improve bone healing in patients with congenital pseudoarthrosis of the tibia (CPT), no previous study has compared its efficacy against any other procedure. We randomised 20 consecutive patients (mean age 4.1 years) with CPT (Crawford type IV) associated with neurofibromatosis type 1(NF1) and no previous history of surgery into two groups. Group 1 received recombinant human bone morphogenetic protein-7 (rhBMP-7) along with intramedullary Kirschner (K)-wire fixation and autologous bone grafting; group 2 received only K wire and grafting. Outcome measures were time to achieve union, Johnston grade, tibial length and the American Orthopaedic Foot and Ankle Society (AOFAS) score, which were evaluated preoperatively and at five year follow-up. Study results showed that patients in group 1 achieved primary bone union at a mean of 14.5 months [standard error (SE) 5.2], whereas group 2 took a mean of 17.11 months (SE 5.0). However, the log-rank test showed no difference in healing times between groups at all time points (P = 0.636). There was a statistically significant pre- to post operative improvement (P < 0.05) within groups for the other outcome measures. In a five year follow-up, these results suggest that rh-BMP-7 and autologous bone grafting is no better than autologous grafting alone.

Individual music therapy for depression: randomised controlled trial.

PubMed

Erkkilä, Jaakko; Punkanen, Marko; Fachner, Jörg; Ala-Ruona, Esa; Pöntiö, Inga; Tervaniemi, Mari; Vanhala, Mauno; Gold, Christian

2011-08-01

Music therapy has previously been found to be effective in the treatment of depression but the studies have been methodologically insufficient and lacking in clarity about the clinical model employed. Aims To determine the efficacy of music therapy added to standard care compared with standard care only in the treatment of depression among working-age people. Participants (n = 79) with an ICD-10 diagnosis of depression were randomised to receive individual music therapy plus standard care (20 bi-weekly sessions) or standard care only, and followed up at baseline, at 3 months (after intervention) and at 6 months. Clinical measures included depression, anxiety, general functioning, quality of life and alexithymia. ISRCTN84185937. Participants receiving music therapy plus standard care showed greater improvement than those receiving standard care only in depression symptoms (mean difference 4.65, 95% CI 0.59 to 8.70), anxiety symptoms (1.82, 95% CI 0.09 to 3.55) and general functioning (-4.58, 95% CI -8.93 to -0.24) at 3-month follow-up. The response rate was significantly higher for the music therapy plus standard care group than for the standard care only group (odds ratio 2.96, 95% CI 1.01 to 9.02). Individual music therapy combined with standard care is effective for depression among working-age people with depression. The results of this study along with the previous research indicate that music therapy with its specific qualities is a valuable enhancement to established treatment practices.

Learning motivational interviewing in a real-life setting: a randomised controlled trial in the Swedish Prison Service.

PubMed

Forsberg, Lars; Ernst, Denise; Farbring, Carl Åke

2011-07-01

Motivational interviewing (MI) is a client-centred, directive counselling style for helping people to explore and resolve ambivalence about behaviour change and shown to decrease drug and alcohol use. A five-session semi-structured MI intervention [Beteende, Samtal, Förändring (BSF; Behaviour, Counselling, Change)] was implemented in Swedish prisons. To examine whether, in a real-life implementation of semi-structured MI, staff receiving ongoing MI training, based on audio-recorded feedback in peer groups (BSF+), possess greater MI skill compared with staff receiving workshop-only MI training (BSF), and staff conducting usual prison planning interviews (UPI). Prisoners were randomised to one of the three interventions. The fi rst sessions between staff and prisoner with complete data were assessed with the Motivational Interviewing Treatment Integrity Code 3.0. Content analysis of 45 staff: prisoner sessions revealed that counsellors in the BSF+ group were significantly more competent in MI than those in the UPI group, but there was no difference in MI competency between the BSF and UPI groups. Overall, staff were rated as not having achieved beginning proficiency. Our findings suggest that staff delivering motivational interviewing programmes for substance-misusing prisoners in Sweden are not being given sufficient training for the task. Previous literature has suggested that staff need more than a basic 3- to 5-day workshop training, but our findings suggest that they may need longer-term continuing supervision and support than previously recognised.

The Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE): study protocol for a cluster randomised controlled trial.

PubMed

White, David; Waugh, Norman; Elliott, Jackie; Lawton, Julia; Barnard, Katharine; Campbell, Michael J; Dixon, Simon; Heller, Simon

2014-09-03

People with type 1 diabetes (T1DM) require insulin therapy to sustain life, and need optimal glycaemic control to prevent diabetic ketoacidosis and serious long-term complications. Insulin is generally administered using multiple daily injections but can also be delivered using an infusion pump (continuous subcutaneous insulin infusion), a more costly option with benefits for some patients. The UK National Institute for Health and Care Excellence (NICE) recommend the use of pumps for patients with the greatest need, citing insufficient evidence to approve extension to a wider population. Far fewer UK adults use pumps than in comparable countries. Previous trials of pump therapy have been small and of short duration and failed to control for training in insulin adjustment. This paper describes the protocol for a large randomised controlled trial comparing pump therapy with multiple daily injections, where both groups are provided with high-quality structured education. A multicentre, parallel group, cluster randomised controlled trial among 280 adults with T1DM. All participants attended the week-long dose adjustment for normal eating (DAFNE) structured education course, and receive either multiple daily injections or pump therapy for 2 years. The trial incorporates a detailed mixed-methods psychosocial evaluation and cost-effectiveness analysis. The primary outcome will be the change in glycosylated haemoglobin (HbA1c) at 24 months in those participants whose baseline HbA1c is at or above 7.5% (58 mmol/mol). The key secondary outcome will be the proportion of participants reaching the NICE target of an HbA1c of 7.5% (58 mmol/mol) or less at 24 months. The protocol was approved by the Research Ethics Committee North West, Liverpool East and received Medicines and Healthcare products Regulatory Agency (MHRA) clinical trials authorisation. Each participating centre gave National Health Service R&D approval. We shall disseminate study findings to study participants and through peer reviewed publications and conference presentations, including lay user groups. ISRCTN 61215213. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Internet-based cognitive behavioural therapy (iCBT) for posttraumatic stress disorder versus waitlist control: study protocol for a randomised controlled trial.

PubMed

Allen, Adrian R; Newby, Jill M; Smith, Jessica; Andrews, Gavin

2015-12-01

This randomised controlled trial (RCT) with two parallel arms will evaluate the efficacy of an internet-delivered six-lesson 10-week cognitive behavioural therapy (iCBT) intervention for posttraumatic stress disorder (PTSD). It will also investigate the association between changes in PTSD symptoms, intolerance of uncertainty (IU) and emotion regulation. Patients with PTSD will be recruited via the research arm of a not-for-profit clinical and research unit in Australia and randomised to a treatment group or waitlist control group. The minimum sample size for each group (alpha 0.05, power 0.80 for a g of 0.47) was identified as 72, but 10 % more will be recruited to hedge against expected attrition. PTSD diagnosis will be determined using the PTSD module from the Mini International Neuropsychiatric Interview version 5.0.0. The PTSD Checklist - Civilian version (PCL-C) will be used to measure PTSD symptoms (the primary outcome measure), with the Intolerance of Uncertainty Scale 12-item version (IUS-12) and the Emotion Regulation Questionnaire (ERQ) used to measure intolerance of uncertainty and emotion regulation, respectively. The PCL-C will be administered to the treatment group before each lesson of the PTSD program and at 3-month follow-up. The IUS-12 and ERQ will be administered before lessons 1 and 4, at post-treatment and at 3-month follow-up. The waitlist control group will complete these measures at week 1, week 5 and week 11 of the waitlist period. PTSD program efficacy will be determined using intent-to-treat mixed models. Maintenance of gains will be assessed at 3-month follow-up. Mediation analyses using PROCESS will be used to examine the association between change in PTSD symptoms over treatment and change in each of IU and emotion regulation ability in separate analyses. The current RCT seeks to replicate previous efficacy findings of iCBT for PTSD in a formally assessed PTSD sample from the general population. Findings may point to future lines of enquiry for the role of IU and emotion regulation in the mechanism of PTSD symptom change during CBT. Australian New Zealand Clinical Trials Registry: ACTRN12614001213639 , registered 18 November 2014. This trial protocol is written in compliance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines.

Interventions for promoting smoke alarm ownership and function.

PubMed

DiGuiseppi, C; Higgins, J P

2001-01-01

Residential fires caused at least 67 deaths and 2,500 non-fatal injuries to children aged 0-16 in the United Kingdom in 1998. Smoke alarm ownership is associated with a reduced risk of residential fire death. We evaluated interventions to promote residential smoke alarms, to assess their effect on smoke alarm ownership, smoke alarm function, fires and burns and other fire-related injuries. We searched the Cochrane Controlled Trials Register, Cochrane Injuries Group database, MEDLINE, EMBASE, PsycLIT, CINAHL, ERIC, Dissertation Abstracts, International Bibliography of Social Sciences, ISTP, FIREDOC and LRC. Conference proceedings, published case studies, and bibliographies were systematically searched, and investigators and relevant organisations were contacted, to identify trials. Randomised, quasi-randomised or nonrandomised controlled trials completed or published after 1969 evaluating an intervention to promote residential smoke alarms. Two reviewers independently extracted data and assessed trial quality. We identified 26 trials, of which 13 were randomised. Overall, counselling and educational interventions had only a modest effect on the likelihood of owning an alarm (OR=1.26; 95% CI: 0.87 to 1.82) or having a functional alarm (OR=1.19; 0.85 to 1.66). Counselling as part of primary care child health surveillance had greater effects on ownership (OR=1.96; 1.03 to 3.72) and function (OR=1.72; 0.78 to 3.80). Results were sensitive to trial quality, however, and effects on fire-related injuries were not reported. In two non randomised trials, direct provision of free alarms significantly increased functioning alarms and reduced fire-related injuries. Media and community education showed little benefit in non randomised trials. Counselling as part of child health surveillance may increase smoke alarm ownership and function, but its effects on injuries are unevaluated. Community smoke alarm give-away programmes apparently reduce fire-related injuries, but these trials were not randomised and results must be interpreted cautiously. Further efforts to promote smoke alarms in primary care or through give-away programmes should be evaluated by adequately designed randomised controlled trials measuring injury outcomes.

Supplemental parenteral nutrition in critically ill patients: a study protocol for a phase II randomised controlled trial.

PubMed

Ridley, Emma J; Davies, Andrew R; Parke, Rachael; Bailey, Michael; McArthur, Colin; Gillanders, Lyn; Cooper, David J; McGuinness, Shay

2015-12-24

Nutrition is one of the fundamentals of care provided to critically ill adults. The volume of enteral nutrition received, however, is often much less than prescribed due to multiple functional and process issues. To deliver the prescribed volume and correct the energy deficit associated with enteral nutrition alone, parenteral nutrition can be used in combination (termed "supplemental parenteral nutrition"), but benefits of this method have not been firmly established. A multi-centre, randomised, clinical trial is currently underway to determine if prescribed energy requirements can be provided to critically ill patients by using a supplemental parenteral nutrition strategy in the critically ill. This prospective, multi-centre, randomised, stratified, parallel-group, controlled, phase II trial aims to determine whether a supplemental parenteral nutrition strategy will reliably and safely increase energy intake when compared to usual care. The study will be conducted for 100 critically ill adults with at least one organ system failure and evidence of insufficient enteral intake from six intensive care units in Australia and New Zealand. Enrolled patients will be allocated to either a supplemental parenteral nutrition strategy for 7 days post randomisation or to usual care with enteral nutrition. The primary outcome will be the average energy amount delivered from nutrition therapy over the first 7 days of the study period. Secondary outcomes include protein delivery for 7 days post randomisation; total energy and protein delivery, antibiotic use and organ failure rates (up to 28 days); duration of ventilation, length of intensive care unit and hospital stay. At both intensive care unit and hospital discharge strength and health-related quality of life assessments will be undertaken. Study participants will be followed up for health-related quality of life, resource utilisation and survival at 90 and 180 days post randomisation (unless death occurs first). This trial aims to determine if provision of a supplemental parenteral nutrition strategy to critically ill adults will increase energy intake compared to usual care in Australia and New Zealand. Trial outcomes will guide development of a subsequent larger randomised controlled trial. NCT01847534 (First registered 5 February 2013, last updated 14 October 2015).

Needle aspiration versus intercostal tube drainage for pneumothorax in the newborn.

PubMed

Bruschettini, Matteo; Romantsik, Olga; Ramenghi, Luca Antonio; Zappettini, Simona; O'Donnell, Colm P F; Calevo, Maria Grazia

2016-01-11

Pneumothorax occurs more frequently in the neonatal period than at any other time of life and is associated with increased mortality and morbidity. It may be treated with either needle aspiration or insertion of a chest tube. The former consists of aspiration of air with a syringe through a needle or an angiocatheter, usually through the second or third intercostal space in the midclavicular line. The chest tube is usually placed in the anterior pleural space passing through the sixth intercostal space into the pleural opening, turned anteriorly and directed to the location of the pneumothorax, and then connected to a Heimlich valve or an underwater seal with continuous suction. To compare the efficacy and safety of needle aspiration and intercostal tube drainage in the management of neonatal pneumothorax. We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 11), MEDLINE via PubMed (1966 to 30 November 2015), EMBASE (1980 to 30 November 2015), and CINAHL (1982 to 30 November 2015). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised controlled trials, quasi-randomised controlled trials and cluster trials comparing needle aspiration (either with the needle or angiocatheter left in situ or removed immediately after aspiration) to intercostal tube drainage in newborn infants with pneumothorax. For each of the included trial, two authors independently extracted data (e.g. number of participants, birth weight, gestational age, kind of needle and chest tube, choice of intercostal space, pressure and device for drainage) and assessed the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). The primary outcomes considered in this review are mortality during the neonatal period and during hospitalisation. One randomised controlled trial (72 infants) met the inclusion criteria of this review. We found no differences in the rates of mortality (risk ratio (RR) 1.50, 95% confidence interval (CI) 0.27 to 8.45) or complications related to the procedure. After needle aspiration, the angiocatheter was left in situ (mean 27.1 hours) and not removed immediately after the aspiration. The angiocatheter was in place for a shorter duration than the intercostal tube (mean difference (MD) -11.20 hours, 95% CI -15.51 to -6.89). None of the 36 newborns treated with needle aspiration with the angiocatheter left in situ required the placement of an intercostal tube drainage. Overall, the quality of the evidence supporting this finding is low. At present there is insufficient evidence to determine the efficacy and safety of needle aspiration versus intercostal tube drainage in the management of neonatal pneumothorax. Randomised controlled trials comparing the two techniques are warranted.

Evaluating the effectiveness of a smartphone app to reduce excessive alcohol consumption: protocol for a factorial randomised control trial.

PubMed

Garnett, Claire; Crane, David; Michie, Susan; West, Robert; Brown, Jamie

2016-07-08

Excessive alcohol consumption is a leading cause of death and morbidity worldwide and interventions to help people reduce their consumption are needed. Interventions delivered by smartphone apps have the potential to help harmful and hazardous drinkers reduce their consumption of alcohol. However, there has been little evaluation of the effectiveness of existing smartphone interventions. A systematic review, amongst other methodologies, identified promising modular content that could be delivered by an app: self-monitoring and feedback; action planning; normative feedback; cognitive bias re-training; and identity change. This protocol reports a factorial randomised controlled trial to assess the comparative potential of these five intervention modules to reduce excessive alcohol consumption. A between-subject factorial randomised controlled trial. Hazardous and harmful drinkers aged 18 or over who are making a serious attempt to reduce their drinking will be randomised to one of 32 (2(5)) experimental conditions after downloading the 'Drink Less' app. Participants complete baseline measures on downloading the app and are contacted after 1-month with a follow-up questionnaire. The primary outcome measure is change in past week consumption of alcohol. Secondary outcome measures are change in AUDIT score, app usage data and usability ratings for the app. A factorial between-subjects ANOVA will be conducted to assess main and interactive effects of the five intervention modules for the primary and secondary outcome measures. This study will establish the extent to which the five intervention modules offered in this app can help reduce hazardous and harmful drinking. This is the first step in optimising and understanding what component parts of an app could help to reduce excessive alcohol consumption. The findings from this study will be used to inform the content of a future integrated treatment app and evaluated against a minimal control in a definitive randomised control trial with long-term outcomes. ISRCTN40104069 Date of registration: 10/2/2016.

An educational intervention to reduce pain and improve pain management for Malawian people living with HIV/AIDS and their family carers: study protocol for a randomised controlled trial.

PubMed

Nkhoma, Kennedy; Seymour, Jane; Arthur, Antony

2013-07-13

Many HIV/AIDS patients experience pain often due to advanced HIV/AIDS infection and side effects of treatment. In sub-Saharan Africa, pain management for people with HIV/AIDS is suboptimal. With survival extended as a direct consequence of improved access to antiretroviral therapy, the prevalence of HIV/AIDS related pain is increasing. As most care is provided at home, the management of pain requires patient and family involvement. Pain education is an important aspect in the management of pain in HIV/AIDS patients. Studies of the effectiveness of pain education interventions for people with HIV/AIDS have been conducted almost exclusively in western countries. A randomised controlled trial is being conducted at the HIV and palliative care clinics of two public hospitals in Malawi. To be eligible, patient participants must have a diagnosis of HIV/AIDS (stage III or IV). Carer participants must be the individual most involved in the patient's unpaid care. Eligible participants are randomised to either: (1) a 30-minute face-to-face educational intervention covering pain assessment and management, augmented by a leaflet and follow-up telephone call at two weeks; or (2) usual care. Those allocated to the usual care group receive the educational intervention after follow-up assessments have been conducted (wait-list control group). The primary outcome is pain severity measured by the Brief Pain Inventory. Secondary outcomes are pain interference, patient knowledge of pain management, patient quality of life, carer knowledge of pain management, caregiver motivation and carer quality of life. Follow-up assessments are conducted eight weeks after randomisation by palliative care nurses blind to allocation. This randomised controlled trial conducted in sub-Saharan Africa among people living with HIV/AIDS and their carers will assess whether a pain education intervention is effective in reducing pain and improving pain management, quality of life and carer motivation. Current Controlled Trials ISRCTN72861423.

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

Effects of treatment in women with gestational diabetes mellitus: systematic review and meta-analysis.

PubMed

Horvath, Karl; Koch, Klaus; Jeitler, Klaus; Matyas, Eva; Bender, Ralf; Bastian, Hilda; Lange, Stefan; Siebenhofer, Andrea

2010-04-01

To summarise the benefits and harms of treatments for women with gestational diabetes mellitus. Systematic review and meta-analysis of randomised controlled trials. Embase, Medline, AMED, BIOSIS, CCMed, CDMS, CDSR, CENTRAL, CINAHL, DARE, HTA, NHS EED, Heclinet, SciSearch, several publishers' databases, and reference lists of relevant secondary literature up to October 2009. Review methods Included studies were randomised controlled trials of specific treatment for gestational diabetes compared with usual care or "intensified" compared with "less intensified" specific treatment. Five randomised controlled trials matched the inclusion criteria for specific versus usual treatment. All studies used a two step approach with a 50 g glucose challenge test or screening for risk factors, or both, and a subsequent 75 g or 100 g oral glucose tolerance test. Meta-analyses did not show significant differences for most single end points judged to be of direct clinical importance. In women specifically treated for gestational diabetes, shoulder dystocia was significantly less common (odds ratio 0.40, 95% confidence interval 0.21 to 0.75), and one randomised controlled trial reported a significant reduction of pre-eclampsia (2.5 v 5.5%, P=0.02). For the surrogate end point of large for gestational age infants, the odds ratio was 0.48 (0.38 to 0.62). In the 13 randomised controlled trials of different intensities of specific treatments, meta-analysis showed a significant reduction of shoulder dystocia in women with more intensive treatment (0.31, 0.14 to 0.70). Treatment for gestational diabetes, consisting of treatment to lower blood glucose concentration alone or with special obstetric care, seems to lower the risk for some perinatal complications. Decisions regarding treatment should take into account that the evidence of benefit is derived from trials for which women were selected with a two step strategy (glucose challenge test/screening for risk factors and oral glucose tolerance test).

A Scoping Review of Economic Evaluations Alongside Randomised Controlled Trials of Home Monitoring in Chronic Disease Management.

PubMed

Kidholm, Kristian; Kristensen, Mie Borch Dahl

2018-04-01

Many countries have considered telemedicine and home monitoring of patients as a solution to the demographic challenges that health-care systems face. However, reviews of economic evaluations of telemedicine have identified methodological problems in many studies as they do not comply with guidelines. The aim of this study was to examine economic evaluations alongside randomised controlled trials of home monitoring in chronic disease management and hereby to explore the resources included in the programme costs, the types of health-care utilisation that change as a result of home monitoring and discuss the value of economic evaluation alongside randomised controlled trials of home monitoring on the basis of the studies identified. A scoping review of economic evaluations of home monitoring of patients with chronic disease based on randomised controlled trials and including information on the programme costs and the costs of equipment was carried out based on a Medline (PubMed) search. Nine studies met the inclusion criteria. All studies include both costs of equipment and use of staff, but there is large variation in the types of equipment and types of tasks for the staff included in the costs. Equipment costs constituted 16-73% of the total programme costs. In six of the nine studies, home monitoring resulted in a reduction in primary care or emergency contacts. However, in total, home monitoring resulted in increased average costs per patient in six studies and reduced costs in three of the nine studies. The review is limited by the small number of studies found and the restriction to randomised controlled trials, which can be problematic in this area due to lack of blinding of patients and healthcare professionals and the difficulty of implementing organisational changes in hospital departments for the limited period of a trial. Furthermore, our results may be based on assessments of older telemedicine interventions.

Desmopressin acetate (DDAVP) for preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders.

PubMed

Karanth, Laxminarayan; Barua, Ankur; Kanagasabai, Sachchithanantham; Nair, Sreekumar

2015-09-09

Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of desmopressin acetate in these groups of pregnant women should be evaluated.This is an update of a Cochrane review first published in 2013. To determine the efficacy of desmopressin acetate in preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched for any randomised controlled trials in a registry of ongoing trials and the reference lists of relevant articles and reviews.Date of most recent search: 18 June 2015. Randomised and quasi-randomised controlled trials investigating the efficacy of desmopressin acetate versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. The review did not identify any randomised controlled trials investigating the relative effectiveness of desmopressin acetate for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with desmopressin acetate.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using desmopressin acetate in this population are needed.

Desmopressin acetate (DDAVP) for preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders.

PubMed

Karanth, Laxminarayan; Barua, Ankur; Kanagasabai, Sachchithanantham; Nair, N S

2013-04-30

Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of desmopressin acetate in these groups of pregnant women should be evaluated. To determine the efficacy of desmopressin acetate in preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched for any randomised controlled trials in a registry of ongoing trials and the reference lists of relevant articles and reviews.Date of most recent search: 28 February 2013. Randomised and quasi-randomised controlled trials investigating the efficacy of desmopressin acetate versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. The review did not identify any randomised controlled trials investigating the relative effectiveness of desmopressin acetate for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with desmopressin acetate.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using desmopressin acetate in this population are needed.

Can a documentary increase help-seeking intentions in men? A randomised controlled trial.

PubMed

King, Kylie Elizabeth; Schlichthorst, Marisa; Spittal, Matthew J; Phelps, Andrea; Pirkis, Jane

2018-01-01

We investigated whether a public health intervention-a three-part documentary called Man Up which explored the relationship between masculinity and mental health, well-being and suicidality-could increase men's intentions to seek help for personal and emotional problems. We recruited men aged 18 years or over who were not at risk of suicide to participate in a double-blind randomised controlled trial. Participants were randomly assigned (1:1) via computer randomisation to view Man Up (the intervention) or a control documentary. We hypothesised that 4 weeks after viewing Man Up participants would report higher levels of intention to seek help than those who viewed the control documentary. Our primary outcome was assessed using the General Help Seeking Questionnaire, and was analysed for all participants. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616001169437, Universal Trial Number: U1111-1186-1459) and was funded by the Movember Foundation. Three hundred and fifty-four men were assessed for eligibility for the trial and randomised to view Man Up or the control documentary. Of these, 337 completed all stages (nine participants were lost to follow-up in the intervention group and eight in the control group). Linear regression analysis showed a significant increase in intentions to seek help in the intervention group, but not in the control group (coef.=2.06, 95% CI 0.48 to 3.63, P=0.01). Our trial demonstrates the potential for men's health outcomes to be positively impacted by novel, media-based public health interventions that focus on traditional masculinity. ACTRN12616001169437, Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Population screening for osteoporosis risk: a randomised control trial of medication use and fracture risk.

PubMed

Barr, R J; Stewart, A; Torgerson, D J; Reid, D M

2010-04-01

Randomised control trial of osteoporosis screening in 4,800 women aged 45-54 years was carried out. Screened group observed an increase of 7.9% in hormone replacement therapy (HRT) use (p < 0.001), 15% in other osteoporosis treatments (p < 0.001) and a 25.9% reduction in fracture risk compared with control. Screening for osteoporosis significantly increases treatment use and reduces fracture incidence. Population screening programmes can identify menopausal women with low bone mineral density (BMD) and elevated risk of future fracture but require to be proven effective by a randomised control trial. A total of 4,800 women, 45-54 years, were randomised in equal numbers to screening or no screening (control) groups. Following screening, those in the lowest quartile of BMD were advised to consider HRT. Nine years later, the effect of screening on the uptake of treatment and the incidence of fractures were assessed by postal questionnaire. Categorical differences were assessed using chi(2) test. Cox regression was used to assess hazard ratio (HR). Of the screened and the control groups, 52.4% vs 44.5%, respectively, reported taking HRT (p < 0.001). In addition, 36.6% of the screened vs 21.6% of the control groups reported the use of vitamin D, calcium, alendronate, etidronate or raloxifene (p < 0.001). In a per protocol analysis of verified incident fractures, a 25.9% reduction in risk of fractures (of any site) in the screened group was observed (HR = 0.741, 95% CI = 0.551-0.998 adjusted age, weight and height). Screening for osteoporosis as assessed by low bone density significantly increases the use of HRT and other treatments for osteoporosis and reduces fracture incidence.

Can a documentary increase help-seeking intentions in men? A randomised controlled trial

PubMed Central

Schlichthorst, Marisa; Spittal, Matthew J; Phelps, Andrea; Pirkis, Jane

2018-01-01

Background We investigated whether a public health intervention—a three-part documentary called Man Up which explored the relationship between masculinity and mental health, well-being and suicidality—could increase men’s intentions to seek help for personal and emotional problems. Methods We recruited men aged 18 years or over who were not at risk of suicide to participate in a double-blind randomised controlled trial. Participants were randomly assigned (1:1) via computer randomisation to view Man Up (the intervention) or a control documentary. We hypothesised that 4 weeks after viewing Man Up participants would report higher levels of intention to seek help than those who viewed the control documentary. Our primary outcome was assessed using the General Help Seeking Questionnaire, and was analysed for all participants. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616001169437, Universal Trial Number: U1111-1186-1459) and was funded by the Movember Foundation. Results Three hundred and fifty-four men were assessed for eligibility for the trial and randomised to view Man Up or the control documentary. Of these, 337 completed all stages (nine participants were lost to follow-up in the intervention group and eight in the control group). Linear regression analysis showed a significant increase in intentions to seek help in the intervention group, but not in the control group (coef.=2.06, 95% CI 0.48 to 3.63, P=0.01). Conclusions Our trial demonstrates the potential for men’s health outcomes to be positively impacted by novel, media-based public health interventions that focus on traditional masculinity. Trial registration number ACTRN12616001169437, Results. PMID:29101215

Cognitive behavioural therapy as an adjunct to pharmacotherapy for primary care based patients with treatment resistant depression: results of the CoBalT randomised controlled trial.

PubMed

Wiles, Nicola; Thomas, Laura; Abel, Anna; Ridgway, Nicola; Turner, Nicholas; Campbell, John; Garland, Anne; Hollinghurst, Sandra; Jerrom, Bill; Kessler, David; Kuyken, Willem; Morrison, Jill; Turner, Katrina; Williams, Chris; Peters, Tim; Lewis, Glyn

2013-02-02

Only a third of patients with depression respond fully to antidepressant medication but little evidence exists regarding the best next-step treatment for those whose symptoms are treatment resistant. The CoBalT trial aimed to examine the effectiveness of cognitive behavioural therapy (CBT) as an adjunct to usual care (including pharmacotherapy) for primary care patients with treatment resistant depression compared with usual care alone. This two parallel-group multicentre randomised controlled trial recruited 469 patients aged 18-75 years with treatment resistant depression (on antidepressants for ≥6 weeks, Beck depression inventory [BDI] score ≥14 and international classification of diseases [ICD]-10 criteria for depression) from 73 UK general practices. Participants were randomised, with a computer generated code (stratified by centre and minimised according to baseline BDI score, whether the general practice had a counsellor, previous treatment with antidepressants, and duration of present episode of depression) to one of two groups: usual care or CBT in addition to usual care, and were followed up for 12 months. Because of the nature of the intervention it was not possible to mask participants, general practitioners, CBT therapists, or researchers to the treatment allocation. Analyses were by intention to treat. The primary outcome was response, defined as at least 50% reduction in depressive symptoms (BDI score) at 6 months compared with baseline. This trial is registered, ISRCTN38231611. Between Nov 4, 2008, and Sept 30, 2010, we assigned 235 patients to usual care, and 234 to CBT plus usual care. 422 participants (90%) were followed up at 6 months and 396 (84%) at 12 months, finishing on Oct 31, 2011. 95 participants (46%) in the intervention group met criteria for response at 6 months compared with 46 (22%) in the usual care group (odds ratio 3·26, 95% CI 2·10-5·06, p<0·001). Before this study, no evidence from large-scale randomised controlled trials was available for the effectiveness of augmentation of antidepressant medication with CBT as a next-step for patients whose depression has not responded to pharmacotherapy. Our study has provided robust evidence that CBT as an adjunct to usual care that includes antidepressants is an effective treatment, reducing depressive symptoms in this population. National Institute for Health Research Health Technology Assessment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evaluation of the clinical benefit of an electromagnetic navigation system for CT-guided interventional radiology procedures in the thoraco-abdominal region compared with conventional CT guidance (CTNAV II): study protocol for a randomised controlled trial.

PubMed

Rouchy, R C; Moreau-Gaudry, A; Chipon, E; Aubry, S; Pazart, L; Lapuyade, B; Durand, M; Hajjam, M; Pottier, S; Renard, B; Logier, R; Orry, X; Cherifi, A; Quehen, E; Kervio, G; Favelle, O; Patat, F; De Kerviler, E; Hughes, C; Medici, M; Ghelfi, J; Mounier, A; Bricault, I

2017-07-06

Interventional radiology includes a range of minimally invasive image-guided diagnostic and therapeutic procedures that have become routine clinical practice. Each procedure involves a percutaneous needle insertion, often guided using computed tomography (CT) because of its availability and usability. However, procedures remain complicated, in particular when an obstacle must be avoided, meaning that an oblique trajectory is required. Navigation systems track the operator's instruments, meaning the position and progression of the instruments are visualised in real time on the patient's images. A novel electromagnetic navigation system for CT-guided interventional procedures (IMACTIS-CT®) has been developed, and a previous clinical trial demonstrated improved needle placement accuracy in navigation-assisted procedures. In the present trial, we are evaluating the clinical benefit of the navigation system during the needle insertion step of CT-guided procedures in the thoraco-abdominal region. This study is designed as an open, multicentre, prospective, randomised, controlled interventional clinical trial and is structured as a standard two-arm, parallel-design, individually randomised trial. A maximum of 500 patients will be enrolled. In the experimental arm (navigation system), the procedures are carried out using navigation assistance, and in the active comparator arm (CT), the procedures are carried out with conventional CT guidance. The randomisation is stratified by centre and by the expected difficulty of the procedure. The primary outcome of the trial is a combined criterion to assess the safety (number of serious adverse events), efficacy (number of targets reached) and performance (number of control scans acquired) of navigation-assisted, CT-guided procedures as evaluated by a blinded radiologist and confirmed by an expert committee in case of discordance. The secondary outcomes are (1) the duration of the procedure, (2) the satisfaction of the operator and (3) the irradiation dose delivered, with (4) subgroup analysis according to the expected difficulty of the procedure, as well as an evaluation of (5) the usability of the device. This trial addresses the lack of published high-level evidence studies in which navigation-assisted CT-guided interventional procedures are evaluated. This trial is important because it addresses the problems associated with conventional CT guidance and is particularly relevant because the number of interventional radiology procedures carried out in routine clinical practice is increasing. ClinicalTrials.gov identifier: NCT01896219 . Registered on 5 July 2013.

Methods to improve recruitment to randomised controlled trials: Cochrane systematic review and meta-analysis

PubMed Central

Treweek, Shaun; Lockhart, Pauline; Pitkethly, Marie; Cook, Jonathan A; Kjeldstrøm, Monica; Johansen, Marit; Taskila, Taina K; Sullivan, Frank M; Wilson, Sue; Jackson, Catherine; Jones, Ritu; Mitchell, Elizabeth D

2013-01-01

This review is an abridged version of a Cochrane Review previously published in the Cochrane Database of Systematic Reviews 2010, Issue 4, Art. No.: MR000013 DOI: 10.1002/14651858.MR000013.pub5 (see www.thecochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and Cochrane Database of Systematic Reviews should be consulted for the most recent version of the review. Objective To identify interventions designed to improve recruitment to randomised controlled trials, and to quantify their effect on trial participation. Design Systematic review. Data sources The Cochrane Methodology Review Group Specialised Register in the Cochrane Library, MEDLINE, EMBASE, ERIC, Science Citation Index, Social Sciences Citation Index, C2-SPECTR, the National Research Register and PubMed. Most searches were undertaken up to 2010; no language restrictions were applied. Study selection Randomised and quasi-randomised controlled trials, including those recruiting to hypothetical studies. Studies on retention strategies, examining ways to increase questionnaire response or evaluating the use of incentives for clinicians were excluded. The study population included any potential trial participant (eg, patient, clinician and member of the public), or individual or group of individuals responsible for trial recruitment (eg, clinicians, researchers and recruitment sites). Two authors independently screened identified studies for eligibility. Results 45 trials with over 43 000 participants were included. Some interventions were effective in increasing recruitment: telephone reminders to non-respondents (risk ratio (RR) 1.66, 95% CI 1.03 to 2.46; two studies, 1058 participants), use of opt-out rather than opt-in procedures for contacting potential participants (RR 1.39, 95% CI 1.06 to 1.84; one study, 152 participants) and open designs where participants know which treatment they are receiving in the trial (RR 1.22, 95% CI 1.09 to 1.36; two studies, 4833 participants). However, the effect of many other strategies is less clear, including the use of video to provide trial information and interventions aimed at recruiters. Conclusions There are promising strategies for increasing recruitment to trials, but some methods, such as open-trial designs and opt-out strategies, must be considered carefully as their use may also present methodological or ethical challenges. Questions remain as to the applicability of results originating from hypothetical trials, including those relating to the use of monetary incentives, and there is a clear knowledge gap with regard to effective strategies aimed at recruiters. PMID:23396504

Phase III randomised chemoprevention study with selenium on the recurrence of non-invasive urothelial carcinoma. The SELEnium and BLAdder cancer Trial.

PubMed

Goossens, Maria E; Zeegers, Maurice P; van Poppel, Hendrik; Joniau, Steven; Ackaert, Koen; Ameye, Filip; Billiet, Ignace; Braeckman, Johan; Breugelmans, Alex; Darras, Jochen; Dilen, Kurt; Goeman, Lieven; Tombal, Bertrand; Van Bruwaene, Siska; Van Cleyenbreugel, Ben; Van der Aa, Frank; Vekemans, Kris; Buntinx, Frank

2016-12-01

In Belgium, bladder cancer (BC) is the fifth most common cancer in men. The per-patient lifetime cost is high. Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of BC. We therefore hypothesised that selenium may be suitable for chemoprevention of recurrence of BC. The Selenium and Bladder Cancer Trial (SELEBLAT) was an academic phase III placebo-controlled, double-blind, randomised clinical trial designed to determine the effect of selenium on recurrence of non-invasive urothelial carcinoma conducted in 14 Belgian hospitals. Patients were randomly assigned by a computer program to oral selenium yeast 200 μg once a day or placebo for three years, in addition to standard care. All study personnel and participants were blinded to treatment assignment for the duration of the study. All randomised patients were included in the intention to treat (ITT) and safety analyses. Per protocol analyses (PPAs) included all patients in the study three months after start date. Between September 18, 2009 and April 18, 2013, 151 and 141 patients were randomised in the selenium and placebo group. Patients were followed until December 31, 2015. The ITT analysis resulted in 43 (28%; 95% CI, 0.21-0.35) and 45 (32%; 95% CI, 0.24-0.40) recurrences in the selenium and placebo group. The hazard ratio (HR) was 0.85 (95% CI, 0.56-1.29; p = 0.44) while the HR for the PPA resulted in 42 and 39 (28%; 95% CI, 0.20-0.35) recurrences in the selenium and placebo group (HR = 0.96 [95% CI, 0.62-1.48]; p = 0.93). Selenium supplementation does not lower the probability of recurrence in BC patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Randomised feasibility study of a novel experience-based internet intervention to support self-management in chronic asthma.

PubMed

Newhouse, Nikki; Martin, Angela; Jawad, Sena; Yu, Ly-Mee; Davoudianfar, Mina; Locock, Louise; Ziebland, Sue; Powell, John

2016-12-28

To determine the feasibility of a randomised controlled trial (RCT) assessing the effects of an experience-based website as a resource for the self-management of chronic asthma. Feasibility, single-blind RCT in 2 regions of England. Randomisation used computer-generated random number sequence in a 1:1 ratio, after baseline data collection, to website access for 2 weeks. Adults (age ≥18 years), with clinically diagnosed asthma as coded in their primary care electronic record, prescribed inhaled corticosteroids for at least 3 months in the previous year, were recruited from 9 general practices. The EXPERT asthma intervention is an interactive PC/laptop/tablet/smartphone compatible website designed with extensive input from adults with asthma. It provides experience-based information and aims to support subjective perception of self-efficacy, self-management and improve health status. Primary outcomes were consent/recruitment, website usage and completion of outcome measures. Secondary outcomes included Partners in Health (PIH) questionnaire, the Chronic Disease Self-Efficacy Scale, the SF36 and the E-Health Impact Questionnaire. Participant blinding postrandomisation was not possible. The analysis was blind to allocation. Recruitment target exceeded. 148 participants randomised (73 intervention group). Age range 19-84 years; 59% female. 121 of 148 (84%; 62 intervention group) followed up. The median number of logins was 2 (IQR 2-3, range 1-48). Minimal differences of change from baseline between groups; both showed improvement in health state or management of their condition with no significant differences between arms. No adverse events. Recruitment and retention confirmed feasibility. The trends towards improved outcomes suggest that further research on digital interventions based on exposure to others' personal experiences may be of value in the self-management of chronic asthma. ISRCTN29549695; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Enzyme potentiated desensitisation in treatment of seasonal allergic rhinitis: double blind randomised controlled study.

PubMed

Radcliffe, Michael J; Lewith, George T; Turner, Richard G; Prescott, Philip; Church, Martin K; Holgate, Stephen T

2003-08-02

To assess the efficacy of enzyme potentiated desensitisation in the treatment of severe summer hay fever poorly controlled by pharmacotherapy. Double blind randomised placebo controlled parallel group study. Hospital in Hampshire. 183 participants aged between 18 and 64 with a history of severe summer hay fever for at least two years; all were skin prick test positive to timothy grass pollen. 90 randomised to active treatment; 93 randomised to placebo. Active treatment: two injections of enzyme potentiated desensitisation, given between eight and 11 weeks apart, each comprising 200 Fishman units of beta glucuronidase, 50 pg 1,3-cyclohexanediol, 50 ng protamine sulphate, and a mixed inhaled allergen extract (pollen mixes for trees, grasses, and weeds; allergenic fungal spores; cat and dog danders; dust and storage mites) in a total volume of 0.05 ml of buffered saline. Placebo: two injections of 0.05 ml buffered saline solution. Proportion of problem-free days; global rhinoconjunctivitis quality of life scores assessed weekly during pollen season. The active treatment group and the placebo group did not differ in the proportion of problem-free days, quality of life scores, symptom severity scores, change in quantitative skin prick provocation threshold, or change in conjunctival provocation threshold. No clinically significant adverse reactions occurred. Enzyme potentiated desensitisation showed no treatment effect in this study.

Group Therapy for Anxiety in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

McConachie, Helen; McLaughlin, Eleanor; Grahame, Victoria; Taylor, Helen; Honey, Emma; Tavernor, Laura; Rodgers, Jacqui; Freeston, Mark; Hemm, Cahley; Steen, Nick; Le Couteur, Ann

2014-01-01

Aim: To investigate the acceptability and feasibility of adapted group therapy for anxiety in children with autism spectrum disorder in a pilot randomised controlled trial. Method: A total of 32 children aged 9-13 years were randomised to immediate or delayed therapy using the "Exploring Feelings" manual (Attwood, 2004). Child and parent…

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.

PATCH: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial.

PubMed

de Gans, Koen; de Haan, Rob J; Majoie, Charles B; Koopman, Maria M; Brand, Anneke; Dijkgraaf, Marcel G; Vermeulen, Marinus; Roos, Yvo B

2010-03-18

Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect. The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included. To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease.

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.

Can social dancing prevent falls in older adults? a protocol of the Dance, Aging, Cognition, Economics (DAnCE) fall prevention randomised controlled trial

PubMed Central

2013-01-01

Background Falls are one of the most common health problems among older people and pose a major economic burden on health care systems. Exercise is an accepted stand-alone fall prevention strategy particularly if it is balance training or regular participation in Tai chi. Dance shares the ‘holistic’ approach of practices such as Tai chi. It is a complex sensorimotor rhythmic activity integrating multiple physical, cognitive and social elements. Small-scale randomised controlled trials have indicated that diverse dance styles can improve measures of balance and mobility in older people, but none of these studies has examined the effect of dance on falls or cognition. This study aims to determine whether participation in social dancing: i) reduces the number of falls; and ii) improves cognitive functions associated with fall risk in older people. Methods/design A single-blind, cluster randomised controlled trial of 12 months duration will be conducted. Approximately 450 participants will be recruited from 24 self-care retirement villages that house at least 60 residents each in Sydney, Australia. Village residents without cognitive impairment and obtain medical clearance will be eligible. After comprehensive baseline measurements including physiological and cognitive tests and self-completed questionnaires, villages will be randomised to intervention sites (ballroom or folk dance) or to a wait-listed control using a computer randomisation method that minimises imbalances between villages based on two baseline fall risk measures. Main outcome measures are falls, prospectively measured, and the Trail Making cognitive function test. Cost-effectiveness and cost-utility analyses will be performed. Discussion This study offers a novel approach to balance training for older people. As a community-based approach to fall prevention, dance offers older people an opportunity for greater social engagement, thereby making a major contribution to healthy ageing. Providing diversity in exercise programs targeting seniors recognises the heterogeneity of multicultural populations and may further increase the number of taking part in exercise. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12612000889853 The trial is now in progress with 12 villages already have been randomised. PMID:23675705

Can social dancing prevent falls in older adults? a protocol of the Dance, Aging, Cognition, Economics (DAnCE) fall prevention randomised controlled trial.

PubMed

Merom, Dafna; Cumming, Robert; Mathieu, Erin; Anstey, Kaarin J; Rissel, Chris; Simpson, Judy M; Morton, Rachael L; Cerin, Ester; Sherrington, Catherine; Lord, Stephen R

2013-05-15

Falls are one of the most common health problems among older people and pose a major economic burden on health care systems. Exercise is an accepted stand-alone fall prevention strategy particularly if it is balance training or regular participation in Tai chi. Dance shares the 'holistic' approach of practices such as Tai chi. It is a complex sensorimotor rhythmic activity integrating multiple physical, cognitive and social elements. Small-scale randomised controlled trials have indicated that diverse dance styles can improve measures of balance and mobility in older people, but none of these studies has examined the effect of dance on falls or cognition. This study aims to determine whether participation in social dancing: i) reduces the number of falls; and ii) improves cognitive functions associated with fall risk in older people. A single-blind, cluster randomised controlled trial of 12 months duration will be conducted. Approximately 450 participants will be recruited from 24 self-care retirement villages that house at least 60 residents each in Sydney, Australia. Village residents without cognitive impairment and obtain medical clearance will be eligible. After comprehensive baseline measurements including physiological and cognitive tests and self-completed questionnaires, villages will be randomised to intervention sites (ballroom or folk dance) or to a wait-listed control using a computer randomisation method that minimises imbalances between villages based on two baseline fall risk measures. Main outcome measures are falls, prospectively measured, and the Trail Making cognitive function test. Cost-effectiveness and cost-utility analyses will be performed. This study offers a novel approach to balance training for older people. As a community-based approach to fall prevention, dance offers older people an opportunity for greater social engagement, thereby making a major contribution to healthy ageing. Providing diversity in exercise programs targeting seniors recognises the heterogeneity of multicultural populations and may further increase the number of taking part in exercise. Australian New Zealand Clinical Trials Registry ACTRN12612000889853The trial is now in progress with 12 villages already have been randomised.

Screening and brief interventions for hazardous and harmful alcohol use in probation services: a cluster randomised controlled trial protocol

PubMed Central

2009-01-01

Background A large number of randomised controlled trials in health settings have consistently reported positive effects of brief intervention in terms of reductions in alcohol use. However, although alcohol misuse is common amongst offenders, there is limited evidence of alcohol brief interventions in the criminal justice field. This factorial pragmatic cluster randomised controlled trial with Offender Managers (OMs) as the unit of randomisation will evaluate the effectiveness and cost-effectiveness of different models of screening to identify hazardous and harmful drinkers in probation and different intensities of brief intervention to reduce excessive drinking in probation clients. Methods and design Ninety-six OMs from 9 probation areas across 3 English regions (the North East Region (n = 4) and London and the South East Regions (n = 5)) will be recruited. OMs will be randomly allocated to one of three intervention conditions: a client information leaflet control condition (n = 32 OMs); 5-minute simple structured advice (n = 32 OMs) and 20-minute brief lifestyle counselling delivered by an Alcohol Health Worker (n = 32 OMs). Randomisation will be stratified by probation area. To test the relative effectiveness of different screening methods all OMs will be randomised to either the Modified Single Item Screening Questionnaire (M-SASQ) or the Fast Alcohol Screening Test (FAST). There will be a minimum of 480 clients recruited into the trial. There will be an intention to treat analysis of study outcomes at 6 and 12 months post intervention. Analysis will include client measures (screening result, weekly alcohol consumption, alcohol-related problems, re-offending, public service use and quality of life) and implementation measures from OMs (the extent of screening and brief intervention beyond the minimum recruitment threshold will provide data on acceptability and feasibility of different models of brief intervention). We will also examine the practitioner and organisational factors associated with successful implementation. Discussion The trial will evaluate the impact of screening and brief alcohol intervention in routine probation work and therefore its findings will be highly relevant to probation teams and thus the criminal justice system in the UK. Ethical approval was given by Northern & Yorkshire REC Trial Registration number ISRCTN 19160244 PMID:19922618

Screening and brief interventions for hazardous and harmful alcohol use in probation services: a cluster randomised controlled trial protocol.

PubMed

Newbury-Birch, Dorothy; Bland, Martin; Cassidy, Paul; Coulton, Simon; Deluca, Paolo; Drummond, Colin; Gilvarry, Eilish; Godfrey, Christine; Heather, Nick; Kaner, Eileen; Myles, Judy; Oyefeso, Adenekan; Parrott, Steve; Perryman, Katherine; Phillips, Tom; Shenker, Don; Shepherd, Jonathan

2009-11-18

A large number of randomised controlled trials in health settings have consistently reported positive effects of brief intervention in terms of reductions in alcohol use. However, although alcohol misuse is common amongst offenders, there is limited evidence of alcohol brief interventions in the criminal justice field. This factorial pragmatic cluster randomised controlled trial with Offender Managers (OMs) as the unit of randomisation will evaluate the effectiveness and cost-effectiveness of different models of screening to identify hazardous and harmful drinkers in probation and different intensities of brief intervention to reduce excessive drinking in probation clients. Ninety-six OMs from 9 probation areas across 3 English regions (the North East Region (n = 4) and London and the South East Regions (n = 5)) will be recruited. OMs will be randomly allocated to one of three intervention conditions: a client information leaflet control condition (n = 32 OMs); 5-minute simple structured advice (n = 32 OMs) and 20-minute brief lifestyle counselling delivered by an Alcohol Health Worker (n = 32 OMs). Randomisation will be stratified by probation area. To test the relative effectiveness of different screening methods all OMs will be randomised to either the Modified Single Item Screening Questionnaire (M-SASQ) or the Fast Alcohol Screening Test (FAST). There will be a minimum of 480 clients recruited into the trial. There will be an intention to treat analysis of study outcomes at 6 and 12 months post intervention. Analysis will include client measures (screening result, weekly alcohol consumption, alcohol-related problems, re-offending, public service use and quality of life) and implementation measures from OMs (the extent of screening and brief intervention beyond the minimum recruitment threshold will provide data on acceptability and feasibility of different models of brief intervention). We will also examine the practitioner and organisational factors associated with successful implementation. The trial will evaluate the impact of screening and brief alcohol intervention in routine probation work and therefore its findings will be highly relevant to probation teams and thus the criminal justice system in the UK.Ethical approval was given by Northern & Yorkshire REC. ISRCTN 19160244.

A pilot randomised double blind controlled trial of the efficacy of purified fatty acids for the treatment of women with endometriosis-associated pain (PurFECT): study protocol.

PubMed

Abokhrais, Ibtisam M; Saunders, Philippa T K; Denison, Fiona C; Doust, Ann; Williams, Linda; Horne, Andrew W

2018-01-01

Endometriosis affects 6-10% of women and is associated with debilitating pelvic pain. It costs the UK > £2.8 billion per year in loss of productivity. Endometriosis can be managed by surgical excision or medically by ovarian suppression. However, ~ 75% symptoms recur after surgery and available medical treatments have undesirable side effects and are contraceptive. Omega-3 purified fatty acids (PUFA) have been shown in animal models to reduce factors that are thought to lead to endometriosis-associated pain, have minimal side effects, and no effects on fertility. This paper presents a protocol for a two-arm, pilot parallel randomised controlled trial (RCT) which aims to inform the planning of a future multicentre trial to evaluate the efficacy of Omega-3 PUFA in the management of endometriosis-associated pain in women. The study will recruit women with endometriosis over a 12-month period in the National Health Service (NHS) Lothian, UK, and randomise them to 8 weeks of treatment with Omega-3 PUFA or comparator (olive oil). The primary objective is to assess recruitment and retention rates. The secondary objectives are to determine the effectiveness/acceptability to participants of the proposed methods of recruitment/randomisation/treatments/questionnaires, to inform the sample size calculation and to refine the research methodology for a future large randomised controlled trial. Response to treatment will be monitored by pain scores and questionnaires assessing physical and emotional function compared at baseline and 8 weeks. We recognise that there may be potential difficulties in mounting a large randomised controlled trial for endometriosis to assess Omega-3 PUFA because they are a dietary supplement readily available over the counter and already used by women with endometriosis. We have therefore designed this pilot study to assess practical feasibility and following the 'Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials' recommendations for the design of chronic pain trials. ISRCTN44202346.

Prevalence and reporting of recruitment, randomisation and treatment errors in clinical trials: A systematic review.

PubMed

Yelland, Lisa N; Kahan, Brennan C; Dent, Elsa; Lee, Katherine J; Voysey, Merryn; Forbes, Andrew B; Cook, Jonathan A

2018-06-01

Background/aims In clinical trials, it is not unusual for errors to occur during the process of recruiting, randomising and providing treatment to participants. For example, an ineligible participant may inadvertently be randomised, a participant may be randomised in the incorrect stratum, a participant may be randomised multiple times when only a single randomisation is permitted or the incorrect treatment may inadvertently be issued to a participant at randomisation. Such errors have the potential to introduce bias into treatment effect estimates and affect the validity of the trial, yet there is little motivation for researchers to report these errors and it is unclear how often they occur. The aim of this study is to assess the prevalence of recruitment, randomisation and treatment errors and review current approaches for reporting these errors in trials published in leading medical journals. Methods We conducted a systematic review of individually randomised, phase III, randomised controlled trials published in New England Journal of Medicine, Lancet, Journal of the American Medical Association, Annals of Internal Medicine and British Medical Journal from January to March 2015. The number and type of recruitment, randomisation and treatment errors that were reported and how they were handled were recorded. The corresponding authors were contacted for a random sample of trials included in the review and asked to provide details on unreported errors that occurred during their trial. Results We identified 241 potentially eligible articles, of which 82 met the inclusion criteria and were included in the review. These trials involved a median of 24 centres and 650 participants, and 87% involved two treatment arms. Recruitment, randomisation or treatment errors were reported in 32 in 82 trials (39%) that had a median of eight errors. The most commonly reported error was ineligible participants inadvertently being randomised. No mention of recruitment, randomisation or treatment errors was found in the remaining 50 of 82 trials (61%). Based on responses from 9 of the 15 corresponding authors who were contacted regarding recruitment, randomisation and treatment errors, between 1% and 100% of the errors that occurred in their trials were reported in the trial publications. Conclusion Recruitment, randomisation and treatment errors are common in individually randomised, phase III trials published in leading medical journals, but reporting practices are inadequate and reporting standards are needed. We recommend researchers report all such errors that occurred during the trial and describe how they were handled in trial publications to improve transparency in reporting of clinical trials.

Speech therapy for children with dysarthria acquired before three years of age.

PubMed

Pennington, Lindsay; Parker, Naomi K; Kelly, Helen; Miller, Nick

2016-07-18

Children with motor impairments often have the motor speech disorder dysarthria, a condition which effects the tone, strength and co-ordination of any or all of the muscles used for speech. Resulting speech difficulties can range from mild, with slightly slurred articulation and breathy voice, to profound, with an inability to produce any recognisable words. Children with dysarthria are often prescribed communication aids to supplement their natural forms of communication. However, there is variation in practice regarding the provision of therapy focusing on voice and speech production. Descriptive studies have suggested that therapy may improve speech, but its effectiveness has not been evaluated. To assess whether any speech and language therapy intervention aimed at improving the speech of children with dysarthria is more effective in increasing children's speech intelligibility or communicative participation than no intervention at all , and to compare the efficacy of individual types of speech language therapy in improving the speech intelligibility or communicative participation of children with dysarthria. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015 , Issue 7 ), MEDLINE, EMBASE, CINAHL , LLBA, ERIC, PsychInfo, Web of Science, Scopus, UK National Research Register and Dissertation Abstracts up to July 2015, handsearched relevant journals published between 1980 and July 2015, and searched proceedings of relevant conferences between 1996 to 2015. We placed no restrictions on the language or setting of the studies. A previous version of this review considered studies published up to April 2009. In this update we searched for studies published from April 2009 to July 2015. We considered randomised controlled trials and studies using quasi-experimental designs in which children were allocated to groups using non-random methods. One author (LP) conducted searches of all databases, journals and conference reports. All searches included a reliability check in which a second review author independently checked a random sample comprising 15% of all identified reports. We planned that two review authors would independently assess the quality and extract data from eligible studies. No randomised controlled trials or group studies were identified. This review found no evidence from randomised trials of the effectiveness of speech and language therapy interventions to improve the speech of children with early acquired dysarthria. Rigorous, fully powered randomised controlled trials are needed to investigate if the positive changes in children's speech observed in phase I and phase II studies are generalisable to the population of children with early acquired dysarthria served by speech and language therapy services. Research should examine change in children's speech production and intelligibility. It must also investigate children's participation in social and educational activities, and their quality of life, as well as the cost and acceptability of interventions.

A cost analysis of inpatient compared with outpatient prostaglandin E2 cervical priming for induction of labour: results from the OPRA trial.

PubMed

Adelson, Pamela L; Wedlock, Garry R; Wilkinson, Chris S; Howard, Kirsten; Bryce, Robert L; Turnbull, Deborah A

2013-09-01

To compare the costs of inpatient (usual care) with outpatient (intervention) care for cervical priming for induction of labour in women with healthy, low-risk pregnancies who are being induced for prolonged pregnancies or for social reasons. Data from a randomised controlled trial at two hospitals in South Australia were matched with hospital financial data. A cost analysis comparing women randomised to inpatient care with those randomised to outpatient care was performed, with an additional analysis focusing on those who received the intervention. Overall, 48% of women randomised into the trial did not receive the intervention. Women randomised to outpatient care had an overall cost saving of $319 per woman (95% CI -$104 to $742) as compared with women randomised to usual care. When restricted to women who actually received the intervention, in-hospital cost savings of $433 (95% CI -$282 to $1148) were demonstrated in the outpatient group. However, these savings were partially offset by the cost of an outpatient priming clinic, reducing the overall cost savings to $156 per woman. Overall cost savings were not statistically significant in women who were randomised to or received the intervention. However, the trend in cost savings favoured outpatient priming.

Mendelian randomisation in cardiovascular research: an introduction for clinicians

PubMed Central

Bennett, Derrick A; Holmes, Michael V

2017-01-01

Understanding the causal role of biomarkers in cardiovascular and other diseases is crucial in order to find effective approaches (including pharmacological therapies) for disease treatment and prevention. Classical observational studies provide naïve estimates of the likely role of biomarkers in disease development; however, such studies are prone to bias. This has direct relevance for drug development as if drug targets track to non-causal biomarkers, this can lead to expensive failure of these drugs in phase III randomised controlled trials. In an effort to provide a more reliable indication of the likely causal role of a biomarker in the development of disease, Mendelian randomisation studies are increasingly used, and this is facilitated by the availability of large-scale genetic data. We conducted a narrative review in order to provide a description of the utility of Mendelian randomisation for clinicians engaged in cardiovascular research. We describe the rationale and provide a basic description of the methods and potential limitations of Mendelian randomisation. We give examples from the literature where Mendelian randomisation has provided pivotal information for drug discovery including predicting efficacy, informing on target-mediated adverse effects and providing potential new evidence for drug repurposing. The variety of the examples presented illustrates the importance of Mendelian randomisation in order to prioritise drug targets for cardiovascular research. PMID:28596306

Impact of pharmaceutical care on knowledge, quality of life and satisfaction of postmenopausal women with osteoporosis.

PubMed

Lai, Pauline Siew Mei; Chua, Siew Siang; Chan, Siew Pheng

2013-08-01

This study describes the analysis of secondary outcomes from a previously published randomised controlled trial, which assessed the effects of pharmaceutical care on medication adherence, persistence and bone turnover markers. The main focus of this manuscript is the effect of the provision of pharmaceutical care on these secondary outcomes, and details on the design of the intervention provided, the osteoporosis care plan and materials used to deliver the intervention. To evaluate the effects of pharmaceutical care on knowledge, quality of life (QOL) and satisfaction of postmenopausal osteoporotic women prescribed bisphosphonates, and their associating factors. Randomised controlled trial, performed at an osteoporosis clinic of a tertiary hospital in Malaysia. Postmenopausal women diagnosed with osteoporosis (T-score ≤-2.5/lowtrauma fracture), just been prescribed weekly alendronate/risedronate were randomly allocated to receive intervention or standard care (controls). Intervention participants received a medication review, education on osteoporosis, risk factors, lifestyle modifications, goals of therapy, side effects and the importance of medication adherence at months 0, 3, 6 and 12. Knowledge, QOL and satisfaction. A total of 198 postmenopausal osteoporotic women were recruited: intervention = 100 and control = 98. Intervention participants reported significantly higher knowledge scores at months 3 (72.50 vs. 62.50 %), 6 (75.00 vs. 65.00 %) and 12 (78.75 vs. 68.75 %) compared to control participants. QOL scores were also lower (which indicates better QOL) at months 3 (29.33 vs. 38.41), 6 (27.50 vs. 36.56) and 12 (27.53 vs. 37.56) compared to control participants. Similarly, satisfaction score was higher in intervention participants (93.67 vs. 84.83 %). More educated women, with back pain, who were provided pharmaceutical care had better knowledge levels. Similarly, older, more educated women, with previous falls and back pain tend to have poorer QOL, whilst women who exercised more frequently and were provided pharmaceutical care had better QOL. Satisfaction also increased as QOL increases and when provided pharmaceutical care. The provision of pharmaceutical care improved knowledge, QOL and satisfaction in Malaysian postmenopausal osteoporotic women, showing that pharmacists have the potential to improve patients' overall bone health. Policymakers should consider placing a clinical pharmacist in the osteoporosis clinic to provide counselling to improve these outcomes.

A randomised controlled trial and cost-effectiveness evaluation of 'booster' interventions to sustain increases in physical activity in middle-aged adults in deprived urban neighbourhoods.

PubMed

Goyder, Elizabeth; Hind, Daniel; Breckon, Jeff; Dimairo, Munyaradzi; Minton, Jonathan; Everson-Hock, Emma; Read, Simon; Copeland, Robert; Crank, Helen; Horspool, Kimberly; Humphreys, Liam; Hutchison, Andrew; Kesterton, Sue; Latimer, Nicolas; Scott, Emma; Swaile, Peter; Walters, Stephen J; Wood, Rebecca; Collins, Karen; Cooper, Cindy

2014-02-01

More evidence is needed on the potential role of 'booster' interventions in the maintenance of increases in physical activity levels after a brief intervention in relatively sedentary populations. To determine whether objectively measured physical activity, 6 months after a brief intervention, is increased in those receiving physical activity 'booster' consultations delivered in a motivational interviewing (MI) style, either face to face or by telephone. Three-arm, parallel-group, pragmatic, superiority randomised controlled trial with nested qualitative research fidelity and geographical information systems and health economic substudies. Treatment allocation was carried out using a web-based simple randomisation procedure with equal allocation probabilities. Principal investigators and study statisticians were blinded to treatment allocation until after the final analysis only. Deprived areas of Sheffield, UK. Previously sedentary people, aged 40-64 years, living in deprived areas of Sheffield, UK, who had increased their physical activity levels after receiving a brief intervention. Participants were randomised to the control group (no further intervention) or to two sessions of MI, either face to face ('full booster') or by telephone ('mini booster'). Sessions were delivered 1 and 2 months post-randomisation. The primary outcome was total energy expenditure (TEE) per day in kcal from 7-day accelerometry, measured using an Actiheart device (CamNtech Ltd, Cambridge, UK). Independent evaluation of practitioner competence was carried out using the Motivational Interviewing Treatment Integrity assessment. An estimate of the per-participant intervention costs, resource use data collected by questionnaire and health-related quality of life data were analysed to produce a range of economic models from a short-term NHS perspective. An additional series of models were developed that used TEE values to estimate the long-term cost-effectiveness. In total, 282 people were randomised (control = 96; mini booster = 92, full booster = 94) of whom 160 had a minimum of 4 out of 7 days' accelerometry data at 3 months (control = 61, mini booster = 47, full booster = 52). The mean difference in TEE per day between baseline and 3 months favoured the control arm over the combined booster arm but this was not statistically significant (-39 kcal, 95% confidence interval -173 to 95, p = 0.57). The autonomy-enabled MI communication style was generally acceptable, although some participants wanted a more paternalistic approach and most expressed enthusiasm for monitoring and feedback components of the intervention and research. Full boosters were more popular than mini boosters. Practitioners achieved and maintained a consistent level of MI competence. Walking distance to the nearest municipal green space or leisure facilities was not associated with physical activity levels. Two alternative modelling approaches both suggested that neither intervention was likely to be cost-effective. Although some individuals do find a community-based, brief MI 'booster' intervention supportive, the low levels of recruitment and retention and the lack of impact on objectively measured physical activity levels in those with adequate outcome data suggest that it is unlikely to represent a clinically effective or cost-effective intervention for the maintenance of recently acquired physical activity increases in deprived middle-aged urban populations. Future research with middle-aged and relatively deprived populations should explore interventions to promote physical activity that require less proactive engagement from individuals, including environmental interventions. Current Controlled Trials ISRCTN56495859, ClinicalTrials.gov NCT00836459. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 13. See the NIHR Journals Library website for further project information.

Effectiveness of Educational Poster on Knowledge of Emergency Management of Dental Trauma - Part 2: Cluster Randomised Controlled Trial for Secondary School Students

PubMed Central

Young, Cecilia; Wong, Kin Yau; Cheung, Lim K.

2014-01-01

Objective To investigate the effectiveness of educational poster on improving secondary school students' knowledge of emergency management of dental trauma. Methods A cluster randomised controlled trial was conducted. 16 schools with total 671 secondary students who can read Chinese or English were randomised into intervention (poster, 8 schools, 364 students) and control groups (8 schools, 305 students) at the school level. Baseline knowledge of dental trauma was obtained by a questionnaire. Poster containing information of dental trauma management was displayed in a classroom for 2 weeks in each school in the intervention group whereas in the control group there was no display of such posters. Students of both groups completed the same questionnarie after 2 weeks. Results Two-week display of posters improved the knowledge score by 1.25 (p-value = 0.0407) on average. Conclusion Educational poster on dental trauma management significantly improved the level of knowledge of secondary school students in Hong Kong. Trial Registration HKClinicalTrial.com HKCTR-1343 ClinicalTrials.gov NCT01809457 PMID:25093728

Feasibility of high-intensity interval training and moderate-intensity continuous training in adults with inactive or mildly active Crohn's disease: study protocol for a randomised controlled trial.

PubMed

Tew, Garry A; Carpenter, Roger; Seed, Michael; Anderson, Simon; Langmead, Louise; Fairhurst, Caroline; Bottoms, Lindsay

2017-01-01

Structured exercise training has been proposed as a useful adjunctive therapy for Crohn's disease by improving immune function and psychological health, reducing fatigue and promoting gains in muscle and bone strength. However, the evidence for exercise in Crohn's disease is sparse, with only a handful of small prospective trials [1, 2], with methodological limitations, including the use of non-randomised and non-controlled study designs and small sample sizes. Here, we describe the protocol for a study that aims to assess the feasibility and acceptability of two common types of exercise training-high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT)-in adults with inactive or mildly active Crohn's disease (CD). This is a randomised, controlled, assessor-blinded, feasibility trial with three parallel groups. Forty-five adults with inactive or mildly active Crohn's disease will be randomly assigned 1:1:1 to HIIT, MICT or usual care control. Participants in the HIIT and MICT groups will be invited to undertake three sessions of supervised exercise each week for 12 consecutive weeks. HIIT sessions will consist of ten 1-min intervals of cycling exercise at 90% of peak power output separated by 1 min of active recovery. MICT sessions will involve 30 min of continuous cycling at 35% of peak power output. Participants will be assessed before randomisation and 13 and 26 weeks after randomisation. Feasibility outcomes include rates of recruitment, retention and adherence. Interviews with participants will explore the acceptability of the exercise programmes and study procedures. Clinical/health outcomes include cardiorespiratory fitness, body mass index, resting blood pressure, markers of disease activity (faecal calprotectin and Crohn's Disease Activity Index) and activated T cell cytokine profiles. Study questionnaires include the Inflammatory Bowel Disease Quality of Life Questionnaire, EQ-5D-5L, IBD Fatigue Scale, Hospital and Anxiety Depression Scale, and International Physical Activity Questionnaire. This study will provide useful information on the feasibility and acceptability of supervised exercise training in adults with inactive and mildly active Crohn's disease and will inform the design of a subsequent, adequately powered, multi-centre trial. The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN13021107). Date registration assigned was 02/12/2015.

Study protocol for the G-SPIRIT trial: a randomised, placebo-controlled, double-blinded phase III trial of granulocyte colony-stimulating factor-mediated neuroprotection for acute spinal cord injury

PubMed Central

Koda, Masao; Hanaoka, Hideki; Sato, Takatoshi; Fujii, Yasuhisa; Hanawa, Michiko; Takahashi, Sho; Furuya, Takeo; Ijima, Yasushi; Saito, Junya; Kitamura, Mitsuhiro; Ohtori, Seiji; Matsumoto, Yukei; Abe, Tetsuya; Watanabe, Kei; Hirano, Toru; Ohashi, Masayuki; Shoji, Hirokazu; Mizouchi, Tatsuki; Takahashi, Ikuko; Kawahara, Norio; Kawaguchi, Masahito; Orita, Yugo; Sasamoto, Takeshi; Yoshioka, Masahito; Fujii, Masafumi; Yonezawa, Katsutaka; Soma, Daisuke; Taneichi, Hiroshi; Takeuchi, Daisaku; Inami, Satoshi; Moridaira, Hiroshi; Ueda, Haruki; Asano, Futoshi; Shibao, Yosuke; Aita, Ikuo; Takeuchi, Yosuke; Mimura, Masaya; Shimbo, Jun; Someya, Yukio; Ikenoue, Sumio; Sameda, Hiroaki; Takase, Kan; Ikeda, Yoshikazu; Nakajima, Fumitake; Hashimoto, Mitsuhiro; Ozawa, Tomoyuki; Hasue, Fumio; Fujiyoshi, Takayuki; Kamiya, Koshiro; Watanabe, Masahiko; Katoh, Hiroyuki; Matsuyama, Yukihiro; Yamamoto, Yu; Togawa, Daisuke; Hasegawa, Tomohiko; Kobayashi, Sho; Yoshida, Go; Oe, Shin; Banno, Tomohiro; Arima, Hideyuki; Akeda, Koji; Kawamoto, Eiji; Imai, Hiroshi; Sakakibara, Toshihiko; Sudo, Akihiro; Ito, Yasuo; Kikuchi, Tsuyoshi; Osaki, Shuhei; Tanaka, Nobuhiro; Nakanishi, Kazuyoshi; Kamei, Naosuke; Kotaka, Shinji; Baba, Hideo; Okudaira, Tsuyoshi; Konishi, Hiroaki; Yamaguchi, Takayuki; Ito, Keigo; Katayama, Yoshito; Matsumoto, Taro; Matsumoto, Tomohiro; Idota, Masaru; Kanno, Haruo; Aizawa, Toshimi; Hashimoto, Ko; Eto, Toshimitsu; Sugaya, Takehiro; Matsuda, Michiharu; Fushimi, Kazunari; Nozawa, Satoshi; Iwai, Chizuo; Taguchi, Toshihiko; Kanchiku, Tsukasa; Suzuki, Hidenori; Nishida, Norihiro; Funaba, Masahiro; Yamazaki, Masashi

2018-01-01

Introduction Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial. Methods and analysis The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m2/day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients). Ethics and dissemination The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper. Trial registration number UMIN000018752. PMID:29730616

Protocol for the ProCare Trial: a phase II randomised controlled trial of shared care for follow-up of men with prostate cancer

PubMed Central

Emery, Jon; Doorey, Juanita; Jefford, Michael; King, Madeleine; Pirotta, Marie; Hayne, Dickon; Martin, Andrew; Trevena, Lyndal; Lim, Tee; Constable, Roger; Hawks, Cynthia; Hyatt, Amelia; Hamid, Akhlil; Violet, John; Gill, Suki; Frydenberg, Mark; Schofield, Penelope

2014-01-01

Introduction Men with prostate cancer require long-term follow-up to monitor disease progression and manage common adverse physical and psychosocial consequences of treatment. There is growing recognition of the potential role of primary care in cancer follow-up. This paper describes the protocol for a phase II multisite randomised controlled trial of a novel model of shared care for the follow-up of men after completing treatment for low-moderate risk prostate cancer. Methods and analysis The intervention is a shared care model of follow-up visits in the first 12 months after completing treatment for prostate cancer with the following specific components: a survivorship care plan, general practitioner (GP) management guidelines, register and recall systems, screening for distress and unmet needs and patient information resources. Eligible men will have completed surgery and/or radiotherapy for low-moderate risk prostate cancer within the previous 8 weeks and have a GP who consents to participate. Ninety men will be randomised to the intervention or current hospital follow-up care. Study outcome measures will be collected at baseline, 3, 6 and 12 months and include anxiety, depression, unmet needs, prostate cancer-specific quality of life and satisfaction with care. Clinical processes and healthcare resource usage will also be measured. The principal emphasis of the analysis will be on obtaining estimates of the treatment effect size and assessing feasibility in order to inform the design of a subsequent phase III trial. Ethics and dissemination Ethics approval has been granted by the University of Western Australia and from all hospital recruitment sites in Western Australia and Victoria. Results of this phase II trial will be reported in peer-reviewed publications and in conference presentations. Trial Registration Australian New Zealand Clinical Trial Registry ACTRN12610000938000 PMID:24604487

Randomised controlled trial of video clips and interactive games to improve vision in children with amblyopia using the I-BiT system.

PubMed

Herbison, Nicola; MacKeith, Daisy; Vivian, Anthony; Purdy, Jon; Fakis, Apostolos; Ash, Isabel M; Cobb, Sue V; Eastgate, Richard M; Haworth, Stephen M; Gregson, Richard M; Foss, Alexander Je

2016-11-01

Traditional treatment of amblyopia involves either wearing a patch or atropine penalisation of the better eye. A new treatment is being developed on the basis of virtual reality technology allowing either DVD footage or computer games which present a common background to both eyes and the foreground, containing the imagery of interest, only to the amblyopic eye. A randomised control trial was performed on patients with amblyopia aged 4-8 years with three arms. All three arms had dichoptic stimulation using shutter glass technology. One arm had DVD footage shown to the amblyopic eye and common background to both, the second used a modified shooter game, Nux, with sprite and targets presented to the amblyopic eye (and background to both) while the third arm had both background and foreground presented to both eyes (non-interactive binocular treatment (non-I-BiT) games). Seventy-five patients were randomised; 67 were residual amblyopes and 70 had an associated strabismus. The visual acuity improved in all three arms by approximately 0.07 logMAR in the amblyopic eye at 6 weeks. There was no difference between I-BiT DVD and non-I-BiT games compared with I-BiT games (stated primary outcome) in terms of gain in vision. There was a modest vision improvement in all three arms. Treatment was well tolerated and safe. There was no difference between the three treatments in terms of primary stated outcomes but treatment duration was short and the high proportion of previously treated amblyopia and strabismic amblyopia disadvantaged dichoptic stimulation treatment. NCT01702727, results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. A multicentre randomised controlled trial: baseline patient characteristics.

PubMed

Konstantakopoulou, Evgenia; Gazzard, Gus; Vickerstaff, Victoria; Jiang, Yuzhen; Nathwani, Neil; Hunter, Rachael; Ambler, Gareth; Bunce, Catey

2018-05-01

The laser in glaucoma and ocular hypertension (LiGHT) trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open angle glaucoma (POAG) or ocular hypertension (OHT). LiGHT is a prospective unmasked, multicentre, pragmatic, randomised controlled trial (RCT). 718 previously untreated patients with POAG or OHT were recruited at 6 UK centres between 2012 and 2014. Patients were randomised to initial SLT followed by medical therapy or medical therapy without laser. Participants will be monitored for 3 years, according to routine clinical practice. The primary outcome is EQ-5D-5L. Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index (GUI), Glaucoma Symptom Scale, Glaucoma Quality of Life (GQL), pathway effectiveness, visual function, safety and concordance. A total of 555 patients had POAG and 163 OHT; 518 patients had both eyes eligible. The mean age for patients with POAG was 64 years and for OHT 58 years. 70% of all participants were white. Median IOP for OHT eyes was 26 mm Hg and 23 mm Hg for POAG eyes. Median baseline visual field mean deviation was -0.81 dB for OHT eyes and -2.82 dB for POAG eyes. There was no difference between patients with POAG and patients with OHT on the EQ-5D-5DL; the difference between OHT and POAG on the GUI was -0.02 and 1.23 on the GQL. The LiGHT trial is the first RCT to compare the two treatment options in a real-world setting. The baseline characteristics of the LiGHT cohort compare well with other landmark glaucoma studies. ISRCTN32038223, Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

GAME (Goals - Activity - Motor Enrichment): protocol of a single blind randomised controlled trial of motor training, parent education and environmental enrichment for infants at high risk of cerebral palsy.

PubMed

Morgan, Catherine; Novak, Iona; Dale, Russell C; Guzzetta, Andrea; Badawi, Nadia

2014-10-07

Cerebral palsy is the most common physical disability of childhood and early detection is possible using evidence based assessments. Systematic reviews indicate early intervention trials rarely demonstrate efficacy for improving motor outcomes but environmental enrichment interventions appear promising. This study is built on a previous pilot study and has been designed to assess the effectiveness of a goal - oriented motor training and enrichment intervention programme, "GAME", on the motor outcomes of infants at very high risk of cerebral palsy (CP) compared with standard community based care. A two group, single blind randomised controlled trial (n = 30) will be conducted. Eligible infants are those diagnosed with CP or designated "at high risk of CP" on the basis of the General Movements Assessment and/or abnormal neuroimaging. A physiotherapist and occupational therapist will deliver home-based GAME intervention at least fortnightly until the infant's first birthday. The intervention aims to optimize motor function and engage parents in developmental activities aimed at enriching the home learning environment. Primary endpoint measures will be taken 16 weeks after intervention commences with the secondary endpoint at 12 months and 24 months corrected age. The primary outcome measure will be the Peabody Developmental Motor Scale second edition. Secondary outcomes measures include the Gross Motor Function Measure, Bayley Scales of Infant and Toddler Development, Affordances in the Home Environment for Motor Development - Infant Scale, and the Canadian Occupational Performance Measure. Parent well-being will be monitored using the Depression Anxiety and Stress Scale. This paper presents the background, design and intervention protocol of a randomised trial of a goal driven, motor learning approach with customised environmental interventions and parental education for young infants at high risk of cerebral palsy. This trial is registered on the Australian New Zealand Clinical Trial register: ACTRN12611000572965.

Cervical auscultation in the diagnosis of oropharyngeal aspiration in children: a study protocol for a randomised controlled trial.

PubMed

Frakking, Thuy T; Chang, Anne B; O'Grady, Kerry-Ann F; Walker-Smith, Katie; Weir, Kelly A

2013-11-07

Oropharyngeal aspiration (OPA) can lead to recurrent respiratory illnesses and chronic lung disease in children. Current clinical feeding evaluations performed by speech pathologists have poor reliability in detecting OPA when compared to radiological procedures such as the modified barium swallow (MBS). Improved ability to diagnose OPA accurately via clinical evaluation potentially reduces reliance on expensive, less readily available radiological procedures. Our study investigates the utility of adding cervical auscultation (CA), a technique of listening to swallowing sounds, in improving the diagnostic accuracy of a clinical evaluation for the detection of OPA. We plan an open, unblinded, randomised controlled trial at a paediatric tertiary teaching hospital. Two hundred and sixteen children fulfilling the inclusion criteria will be randomised to one of the two clinical assessment techniques for the clinical detection of OPA: (1) clinical feeding evaluation only (CFE) group or (2) clinical feeding evaluation with cervical auscultation (CFE + CA) group. All children will then undergo an MBS to determine radiologically assessed OPA. The primary outcome is the presence or absence of OPA, as determined on MBS using the Penetration-Aspiration Scale. Our main objective is to determine the sensitivity, specificity, negative and positive predictive values of 'CFE + CA' versus 'CFE' only compared to MBS-identified OPA. Early detection and appropriate management of OPA is important to prevent chronic pulmonary disease and poor growth in children. As the reliability of CFE to detect OPA is low, a technique that can improve the diagnostic accuracy of the CFE will help minimise consequences to the paediatric respiratory system. Cervical auscultation is a technique that has previously been documented as a clinical adjunct to the CFE; however, no published RCTs addressing the reliability of this technique in children exist. Our study will be the first to establish the utility of CA in assessing and diagnosing OPA risk in young children. Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12613000589785.

Cervical auscultation in the diagnosis of oropharyngeal aspiration in children: a study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Oropharyngeal aspiration (OPA) can lead to recurrent respiratory illnesses and chronic lung disease in children. Current clinical feeding evaluations performed by speech pathologists have poor reliability in detecting OPA when compared to radiological procedures such as the modified barium swallow (MBS). Improved ability to diagnose OPA accurately via clinical evaluation potentially reduces reliance on expensive, less readily available radiological procedures. Our study investigates the utility of adding cervical auscultation (CA), a technique of listening to swallowing sounds, in improving the diagnostic accuracy of a clinical evaluation for the detection of OPA. Methods We plan an open, unblinded, randomised controlled trial at a paediatric tertiary teaching hospital. Two hundred and sixteen children fulfilling the inclusion criteria will be randomised to one of the two clinical assessment techniques for the clinical detection of OPA: (1) clinical feeding evaluation only (CFE) group or (2) clinical feeding evaluation with cervical auscultation (CFE + CA) group. All children will then undergo an MBS to determine radiologically assessed OPA. The primary outcome is the presence or absence of OPA, as determined on MBS using the Penetration-Aspiration Scale. Our main objective is to determine the sensitivity, specificity, negative and positive predictive values of ‘CFE + CA’ versus ‘CFE’ only compared to MBS-identified OPA. Discussion Early detection and appropriate management of OPA is important to prevent chronic pulmonary disease and poor growth in children. As the reliability of CFE to detect OPA is low, a technique that can improve the diagnostic accuracy of the CFE will help minimise consequences to the paediatric respiratory system. Cervical auscultation is a technique that has previously been documented as a clinical adjunct to the CFE; however, no published RCTs addressing the reliability of this technique in children exist. Our study will be the first to establish the utility of CA in assessing and diagnosing OPA risk in young children. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12613000589785. PMID:24199872

Progressive high-load strength training compared with general low-load exercises in patients with rotator cuff tendinopathy: study protocol for a randomised controlled trial.

PubMed

Ingwersen, Kim G; Christensen, Robin; Sørensen, Lilli; Jørgensen, Hans Ri; Jensen, Steen Lund; Rasmussen, Sten; Søgaard, Karen; Juul-Kristensen, Birgit

2015-01-27

Shoulder pain is the third most common musculoskeletal disorder, often affecting people's daily living and work capacity. The most common shoulder disorder is the subacromial impingement syndrome (SIS) which, among other pathophysiological changes, is often characterised by rotator cuff tendinopathy. Exercise is often considered the primary treatment option for rotator cuff tendinopathy, but there is no consensus on which exercise strategy is the most effective. As eccentric and high-load strength training have been shown to have a positive effect on patella and Achilles tendinopathy, the aim of this trial is to compare the efficacy of progressive high-load exercises with traditional low-load exercises in patients with rotator cuff tendinopathy. The current study is a randomised, participant- and assessor-blinded, controlled multicentre trial. A total of 260 patients with rotator cuff tendinopathy will be recruited from three outpatient shoulder departments in Denmark, and randomised to either 12 weeks of progressive high-load strength training or to general low-load exercises. Patients will receive six individually guided exercise sessions with a physiotherapist and perform home-based exercises three times a week. The primary outcome measure will be change from baseline to 12 weeks in the patient-reported outcome Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. Previous studies of exercise treatment for SIS have not differentiated between subgroups of SIS and have often had methodological flaws, making it difficult to specifically design target treatment for patients diagnosed with SIS. Therefore, it was considered important to focus on a subgroup such as tendinopathy, with a specific tailored intervention strategy based on evidence from other regions of the body, and to clearly describe the intervention in a methodologically strong study. The trial was registered with Clinicaltrials.gov ( NCT01984203 ) on 31 October 2013.

Counselling parents on young children's healthy diet: A modified scoping review.

PubMed

Holmberg Fagerlund, Bettina; Helseth, Sølvi; Owe, Jenny; Glavin, Kari

2017-12-01

To map and describe key information in existing research about counselling of parents of children aged 0-2 years on the child's healthy diet in preventive healthcare settings, particularly in public health nursing. Many parents are likely to be concerned with their infant's food-related happiness "here and now," disregarding the child's long-term health and development related to feeding practices. Hence, a focus on counselling parents in considering young children's healthy diet is important. A modified scoping review with an inductive qualitative content analysis of selected empirical studies. Systematic searches in EMBASE (1996-2015 Week 46), Ovid Nursing Database (1946-2015 November Week 1), Ovid MEDLINE and Ovid OLDMEDLINE (2000-18 November 2015) and CINAHL (2000-22 December 2015), using search terms based on aims. Eight included studies, with participants per sample ranging from 19->500. Research designs were focus group discussions and/or interview study (n = 2), cluster-randomised trials (n = 2), randomised controlled trials (n = 2), a follow-up interview study (n = 1) to a previous randomised controlled trial and a cross-sectional electronic questionnaire study (n = 1). The studies included a total sample of 2,025 participants, 42 of them in interview studies. Findings indicate parents' perceptions of inconsistency, misconceptions and uncertainty related to the recommendations on child feeding from the authorities. Thus, adapted advice could impact healthier child diet. Maternal knowledge on child feeding and reduced use of food as a reward are mediators for improved diet quality in children. Counselling on young children's healthy diet should be anticipatory, consistent and adapted to the family. Due to inconsistent recommendations and omitted focus on anticipatory counselling on child feeding, parents might perceive pressure and uncertainty related to the child's diet. © 2017 John Wiley & Sons Ltd.

Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial.

PubMed

Topol, Eric J; Bousser, Marie-Germaine; Fox, Keith A A; Creager, Mark A; Despres, Jean-Pierre; Easton, J Donald; Hamm, Christian W; Montalescot, Gilles; Steg, P Gabriel; Pearson, Thomas A; Cohen, Eric; Gaudin, Christophe; Job, Bernard; Murphy, Judith H; Bhatt, Deepak L

2010-08-14

Blockade of the endocannabinoid receptor reduces obesity and improves metabolic abnormalities such as triglycerides, HDL cholesterol, and fasting blood glucose. We assessed whether rimonabant would improve major vascular event-free survival. This double-blind, placebo-controlled trial was undertaken in 974 hospitals in 42 countries. 18,695 patients with previously manifest or increased risk of vascular disease were randomly assigned to receive either rimonabant 20 mg (n=9381) or matching placebo (n=9314). Randomisation was stratified by centre, implemented with an independent interactive voice response system, and all study personnel and participants were masked to group assignment. The primary endpoint was the composite of cardiovascular death, myocardial infarction, or stroke, as determined via central adjudication. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00263042. At a mean follow-up of 13.8 months (95% CI 13.6-14.0), the trial was prematurely discontinued because of concerns by health regulatory authorities in three countries about suicide in individuals receiving rimonabant. All randomised participants were analysed. At the close of the trial (Nov 6, 2008), the composite primary endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 364 (3.9%) patients assigned to rimonabant and 375 (4.0%) assigned to placebo (hazard ratio 0.97, 95% CI 0.84-1.12, p=0.68). With rimonabant, gastrointestinal (3038 [33%] vs 2084 [22%]), neuropsychiatric (3028 [32%] vs 1989 [21%]), and serious psychiatric side-effects (232 [2.5%] vs 120 [1.3%]) were significantly increased compared with placebo. Four patients in the rimonabant group and one in the placebo group committed suicide. The premature termination of this trial has important lessons for drug development. A drug that was being marketed for weight loss, but being tested for improving cardiovascular outcomes, induced a level of serious neuropsychiatric effects that was deemed unacceptable by regulatory authorities, and both the drug and the trial were abruptly terminated. Sanofi-Aventis. Copyright 2010 Elsevier Ltd. All rights reserved.

Reduction of common cold symptoms by encapsulated juice powder concentrate of fruits and vegetables: a randomised, double-blind, placebo-controlled trial.

PubMed

Roll, Stephanie; Nocon, Marc; Willich, Stefan N

2011-01-01

Dietary supplements have been suggested in the prevention of the common cold, but previous investigations have been inconsistent. The present study was designed to determine the preventive effect of a dietary supplement from fruits and vegetables on common cold symptoms. In a randomised, double-blind, placebo-controlled trial, healthcare professionals (mainly nursing staff aged 18-65 years) from a university hospital in Berlin, Germany, were randomised to four capsules of dietary supplement (Juice Plus+®) or matching placebo daily for 8 months, including a 2-month run-in period. The number of days with moderate or severe common cold symptoms within 6 months (primary outcome) was assessed by diary self-reports. We determined means and 95 % CI, and differences between the two groups were analysed by ANOVA. A total of 529 subjects were included into the primary analysis (Juice Plus+®: 263, placebo: 266). The mean age of the participants was 39·9 (sd 10·3) years, and 80 % of the participants were female. The mean number of days with moderate or severe common cold symptoms was 7·6 (95 % CI 6·5, 8·8) in the Juice Plus+® group and 9·5 (8·4, 10·6) in the placebo group (P = 0·023). The mean number of total days with any common cold symptoms was similar in the Juice Plus+® and in the placebo groups (29·4 (25·8, 33·0) v. 30·7 (27·1, 34·3), P = 0·616). Intake of a dietary supplement from fruits and vegetables was associated with a 20 % reduction of moderate or severe common cold symptom days in healthcare professionals particularly exposed to patient contact.

Evaluating the Benefits of Aphasia Intervention Delivered in Virtual Reality: Results of a Quasi-Randomised Study.

PubMed

Marshall, Jane; Booth, Tracey; Devane, Niamh; Galliers, Julia; Greenwood, Helen; Hilari, Katerina; Talbot, Richard; Wilson, Stephanie; Woolf, Celia

2016-01-01

This study evaluated an intervention for people with aphasia delivered in a novel virtual reality platform called EVA Park. EVA Park contains a number of functional and fantastic locations and allows for interactive communication between multiple users. Twenty people with aphasia had 5 weeks' intervention, during which they received daily language stimulation sessions in EVA Park from a support worker. The study employed a quasi randomised design, which compared a group that received immediate intervention with a waitlist control group. Outcome measures explored the effects of intervention on communication and language skills, communicative confidence and feelings of social isolation. Compliance with the intervention was also explored through attrition and usage data. There was excellent compliance with the intervention, with no participants lost to follow up and most (18/20) receiving at least 88% of the intended treatment dose. Intervention brought about significant gains on a measure of functional communication. Gains were achieved by both groups of participants, once intervention was received, and were well maintained. Changes on the measures of communicative confidence and feelings of social isolation were not achieved. Results are discussed with reference to previous aphasia therapy findings.

Audiovisual preconditioning enhances the efficacy of an anatomical dissection course: A randomised study.

PubMed

Collins, Anne M; Quinlan, Christine S; Dolan, Roisin T; O'Neill, Shane P; Tierney, Paul; Cronin, Kevin J; Ridgway, Paul F

2015-07-01

The benefits of incorporating audiovisual materials into learning are well recognised. The outcome of integrating such a modality in to anatomical education has not been reported previously. The aim of this randomised study was to determine whether audiovisual preconditioning is a useful adjunct to learning at an upper limb dissection course. Prior to instruction participants completed a standardised pre course multiple-choice questionnaire (MCQ). The intervention group was subsequently shown a video with a pre-recorded commentary. Following initial dissection, both groups completed a second MCQ. The final MCQ was completed at the conclusion of the course. Statistical analysis confirmed a significant improvement in the performance in both groups over the duration of the three MCQs. The intervention group significantly outperformed their control group counterparts immediately following audiovisual preconditioning and in the post course MCQ. Audiovisual preconditioning is a practical and effective tool that should be incorporated in to future course curricula to optimise learning. Level of evidence This study appraises an intervention in medical education. Kirkpatrick Level 2b (modification of knowledge). Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Evaluating the Benefits of Aphasia Intervention Delivered in Virtual Reality: Results of a Quasi-Randomised Study

PubMed Central

Marshall, Jane; Booth, Tracey; Devane, Niamh; Galliers, Julia; Greenwood, Helen; Hilari, Katerina; Talbot, Richard; Wilson, Stephanie; Woolf, Celia

2016-01-01

Introduction This study evaluated an intervention for people with aphasia delivered in a novel virtual reality platform called EVA Park. EVA Park contains a number of functional and fantastic locations and allows for interactive communication between multiple users. Twenty people with aphasia had 5 weeks’ intervention, during which they received daily language stimulation sessions in EVA Park from a support worker. The study employed a quasi randomised design, which compared a group that received immediate intervention with a waitlist control group. Outcome measures explored the effects of intervention on communication and language skills, communicative confidence and feelings of social isolation. Compliance with the intervention was also explored through attrition and usage data. Results There was excellent compliance with the intervention, with no participants lost to follow up and most (18/20) receiving at least 88% of the intended treatment dose. Intervention brought about significant gains on a measure of functional communication. Gains were achieved by both groups of participants, once intervention was received, and were well maintained. Changes on the measures of communicative confidence and feelings of social isolation were not achieved. Results are discussed with reference to previous aphasia therapy findings. PMID:27518188

A cluster-randomised, controlled trial to assess the impact of a workplace osteoporosis prevention intervention on the dietary and physical activity behaviours of working women: study protocol.

PubMed

Tan, Ai May; Lamontagne, Anthony D; Sarmugam, Rani; Howard, Peter

2013-04-29

Osteoporosis is a debilitating disease and its risk can be reduced through adequate calcium consumption and physical activity. This protocol paper describes a workplace-based intervention targeting behaviour change in premenopausal women working in sedentary occupations. A cluster-randomised design was used, comparing the efficacy of a tailored intervention to standard care. Workplaces were the clusters and units of randomisation and intervention. Sample size calculations incorporated the cluster design. Final number of clusters was determined to be 16, based on a cluster size of 20 and calcium intake parameters (effect size 250 mg, ICC 0.5 and standard deviation 290 mg) as it required the highest number of clusters.Sixteen workplaces were recruited from a pool of 97 workplaces and randomly assigned to intervention and control arms (eight in each). Women meeting specified inclusion criteria were then recruited to participate. Workplaces in the intervention arm received three participatory workshops and organisation wide educational activities. Workplaces in the control/standard care arm received print resources. Intervention workshops were guided by self-efficacy theory and included participatory activities such as goal setting, problem solving, local food sampling, exercise trials, group discussion and behaviour feedback.Outcomes measures were calcium intake (milligrams/day) and physical activity level (duration: minutes/week), measured at baseline, four weeks and six months post intervention. This study addresses the current lack of evidence for behaviour change interventions focussing on osteoporosis prevention. It addresses missed opportunities of using workplaces as a platform to target high-risk individuals with sedentary occupations. The intervention was designed to modify behaviour levels to bring about risk reduction. It is the first to address dietary and physical activity components each with unique intervention strategies in the context of osteoporosis prevention. The intervention used locally relevant behavioural strategies previously shown to support good outcomes in other countries. The combination of these elements have not been incorporated in similar studies in the past, supporting the study hypothesis that the intervention will be more efficacious than standard practice in osteoporosis prevention through improvements in calcium intake and physical activity.

The 'Big Five'. Hypothesis generation: a multidisciplinary intervention package reduces disease-specific hospitalisations from long-term care: a post hoc analysis of the ARCHUS cluster-randomised controlled trial.

PubMed

Connolly, Martin J; Broad, Joanna B; Boyd, Michal; Zhang, Tony Xian; Kerse, Ngaire; Foster, Susan; Lumley, Thomas; Whitehead, Noeline

2016-05-01

long-term care (LTC) residents have higher hospitalisation rates than non-LTC residents. Rapid decline may follow hospitalisations, hence the importance of preventing unnecessary hospitalisations. Literature describes diagnosis-specific interventions (for cardiac failure, ischaemic heart disease, chronic obstructive pulmonary disease, stroke, pneumonia-termed 'big five' diagnoses), impacting on hospitalisations of older community-dwellers, but few RCTs show reductions in acute admissions from LTC. LTC facilities with higher than expected hospitalisations were recruited for a cluster-randomised controlled trial (RCT) of facility-based complex, non-disease-specific, 9-month intervention comprising gerontology nurse specialist (GNS)-led staff education, facility benchmarking, GNS resident review and multidisciplinary discussion of residents selected using standard criteria. In this post hoc exploratory analysis, the outcome was acute hospitalisations for 'big five' diagnoses. Re-randomisation analyses were used for end points during months 1-14. For end points during months 4-14, proportional hazards models are adjusted for within-facility clustering. we recruited 36 facilities with 1,998 residents (1,408 female; mean age 82.9 years); 1,924 were alive at 3 months. The intervention did not impact overall rates of acute hospitalisations or mortality (previously published), but resulted in fewer 'big five' admissions (RR = 0.73, 95% CI = 0.54-0.99; P = 0.043) with no significant difference in the rate of other acute admissions. When considering events occurring after 3 months (only), the intervention group were 34.7% (HR = 0.65; 95% CI = 0.49-0.88; P = 0.005) less likely to have a 'big five' acute admission than controls, with no differences in likelihood of acute admissions for other diagnoses (P = 0.96). this generic intervention may reduce admissions for common conditions which the literature shows are impacted by disease-specific admission reduction strategies. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A feasibility study of short message service text messaging as a surveillance tool for alcohol consumption and vehicle for interventions in university students

PubMed Central

2013-01-01

Background Practitioners who come into contact with the intoxicated, such as those in unscheduled care, often have limited resources to provide structured interventions. There is therefore a need for cost-effective alcohol interventions requiring minimal input. This study assesses the barriers, acceptability and validity of text messaging to collect daily alcohol consumption data and explores the feasibility of a text-delivered intervention in an exploratory randomised controlled trial. Methods Study I. Participants (n = 82) completed the initial online screening survey and those eligible were asked each day, for 157 days via text message, to reply with the number of alcohol units consumed the previous day. Analyses compared standard measures of hazardous consumption with self-report alcohol use. Attrition and sampling biases were examined. Study I included secondary exploratory analyses using data from 70 participants to determine associations between events (including Christmas and other celebratory occasions) and consumption. Study I further included the thematic analysis of semi-structured interview data and assessed the feasibility of and barriers to surveillance and interventions delivered through text messaging. Developing findings from Study I, Study II developed an exploratory randomised control trial that delivered a single message on monthly alcohol expenditure in order to assess effect size and test generalisability. Results Self-report alcohol consumption data was significantly associated with FAST and AUDIT scores. Attrition from the study was not associated with greater alcohol use. Greater alcohol use was observed on Fridays, Saturdays and Wednesdays as were notable celebratory events. Interview data indicated that text messaging was acceptable to participants and preferred over email and web-based methods. The exploratory randomised controlled trial suggested that a simple text delivered intervention might be effective in eliciting a reduction in alcohol consumption in a future trial. Conclusions The ubiquity of mobile telephones and the acceptability of text messaging suggests that this approach can be developed as a surveillance tool to collect high frequency consumption data to identify periods of vulnerability and that it can offer a platform through which targeted interventions can be delivered. PMID:24160674

Glutamine supplementation for young infants with severe gastrointestinal disease.

PubMed

Brown, Jennifer V E; Moe-Byrne, Thirimon; McGuire, William

2014-12-15

Endogenous glutamine biosynthesis may be insufficient to meet the needs of people with severe gastrointestinal disease. Results from studies using experimental animal models of gastrointestinal disease have suggested that glutamine supplementation improves clinical outcomes. This review examines evidence on the effect of glutamine supplementation in young infants with severe gastrointestinal disease. To assess the effect of supplemental glutamine on mortality and morbidity in young infants with severe gastrointestinal disease. We searcheed the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2014, Issue 8), MEDLINE, EMBASE, and CINAHL (from inception to September 2014), conference proceedings, and reference lists from previous reviews. Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in infants up to three months old (corrected for preterm birth if necessary) with severe gastrointestinal disease defined as a congenital or acquired gastrointestinal condition that is likely to necessitate providing parenteral nutrition for at least 24 hours. Two review authors assessed trial eligibility and risk of bias and undertook data extraction independently. We analysed the treatment effects in the individual trials and reported the risk ratio (RR) and risk difference (RD) for dichotomous data and mean difference for continuous data, with 95% confidence intervals (CI). We used a fixed-effect model in meta-analyses and explored the potential causes of heterogeneity in sensitivity analyses. We found three trials in which a total of 274 infants participated. The trials were of good methodological quality but were too small to detect clinically important effects of glutamine supplementation. Meta-analyses did not reveal a statistically significant difference in the risk of death before hospital discharge (typical RR 0.79, 95% CI 0.19 to 3.20; typical RD -0.01, 95% CI -0.05 to 0.03) or in the rate of invasive infection (typical RR 1.37, 95% CI 0.89 to 2.11; typical RD 0.08, 95% CI -0.03 to 0.18]). The available data from randomised controlled trials do not suggest that glutamine supplementation has any important benefits for young infants with severe gastrointestinal disease.

Randomised controlled trial of an automated, interactive telephone intervention to improve type 2 diabetes self-management (Telephone-Linked Care Diabetes Project): study protocol

PubMed Central

2010-01-01

Background An estimated 285 million people worldwide have diabetes and its prevalence is predicted to increase to 439 million by 2030. For the year 2010, it is estimated that 3.96 million excess deaths in the age group 20-79 years are attributable to diabetes around the world. Self-management is recognised as an integral part of diabetes care. This paper describes the protocol of a randomised controlled trial of an automated interactive telephone system aiming to improve the uptake and maintenance of essential diabetes self-management behaviours. Methods/Design A total of 340 individuals with type 2 diabetes will be randomised, either to the routine care arm, or to the intervention arm in which participants receive the Telephone-Linked Care (TLC) Diabetes program in addition to their routine care. The intervention requires the participants to telephone the TLC Diabetes phone system weekly for 6 months. They receive the study handbook and a glucose meter linked to a data uploading device. The TLC system consists of a computer with software designed to provide monitoring, tailored feedback and education on key aspects of diabetes self-management, based on answers voiced or entered during the current or previous conversations. Data collection is conducted at baseline (Time 1), 6-month follow-up (Time 2), and 12-month follow-up (Time 3). The primary outcomes are glycaemic control (HbA1c) and quality of life (Short Form-36 Health Survey version 2). Secondary outcomes include anthropometric measures, blood pressure, blood lipid profile, psychosocial measures as well as measures of diet, physical activity, blood glucose monitoring, foot care and medication taking. Information on utilisation of healthcare services including hospital admissions, medication use and costs is collected. An economic evaluation is also planned. Discussion Outcomes will provide evidence concerning the efficacy of a telephone-linked care intervention for self-management of diabetes. Furthermore, the study will provide insight into the potential for more widespread uptake of automated telehealth interventions, globally. Trial Registration Number ACTRN12607000594426 PMID:20937148

Individualised cognitive functional therapy compared with a combined exercise and pain education class for patients with non-specific chronic low back pain: study protocol for a multicentre randomised controlled trial

PubMed Central

O'Keeffe, Mary; Purtill, Helen; Kennedy, Norelee; O'Sullivan, Peter; Dankaerts, Wim; Tighe, Aidan; Allworthy, Lars; Dolan, Louise; Bargary, Norma; O'Sullivan, Kieran

2015-01-01

Introduction Non-specific chronic low back pain (NSCLBP) is a very common and costly musculoskeletal disorder associated with a complex interplay of biopsychosocial factors. Cognitive functional therapy (CFT) represents a novel, patient-centred intervention which directly challenges pain-related behaviours in a cognitively integrated, functionally specific and graduated manner. CFT aims to target all biopsychosocial factors that are deemed to be barriers to recovery for an individual patient with NSCLBP. A recent randomised controlled trial (RCT) demonstrated the superiority of individualised CFT for NSCLBP compared to manual therapy combined with exercise. However, several previous RCTs have suggested that class-based interventions are as effective as individualised interventions. Therefore, it is important to examine whether an individualised intervention, such as CFT, demonstrates clinical effectiveness compared to a relatively cheaper exercise and education class. The current study will compare the clinical effectiveness of individualised CFT with a combined exercise and pain education class in people with NSCLBP. Methods and analysis This study is a multicentre RCT. 214 participants, aged 18–75 years, with NSCLBP for at least 6 months will be randomised to one of two interventions across three sites. The experimental group will receive individualised CFT and the length of the intervention will be varied in a pragmatic manner based on the clinical progression of participants. The control group will attend six classes which will be provided over a period of 6–8 weeks. Participants will be assessed preintervention, postintervention and after 6 and12 months. The primary outcomes will be functional disability and pain intensity. Non-specific predictors, moderators and mediators of outcome will also be analysed. Ethics and dissemination Ethical approval has been obtained from the Mayo General Hospital Research Ethics Committee (MGH-14-UL). Outcomes will be disseminated through publication according to the SPIRIT statement and will be presented at scientific conferences. Trial registration number (ClinicalTrials.gov NCT02145728). PMID:26033941

Protocol for a pilot randomised controlled trial of an intervention to increase the use of traffic light food labelling in UK shoppers (the FLICC trial).

PubMed

Scarborough, Peter; Hodgkins, Charo; Raats, Monique M; Harrington, Richard A; Cowburn, Gill; Dean, Moira; Doherty, Aiden; Foster, Charlie; Juszczak, Edmund; Matthews, Anne; Mizdrak, Anja; Mhurchu, Cliona Ni; Shepherd, Richard; Tiomotijevic, Lada; Winstone, Naomi; Rayner, Mike

2015-01-01

Traffic light labelling of foods-a system that incorporates a colour-coded assessment of the level of total fat, saturated fat, sugar and salt on the front of packaged foods-has been recommended by the UK Government and is currently in use or being phased in by many UK manufacturers and retailers. This paper describes a protocol for a pilot randomised controlled trial of an intervention designed to increase the use of traffic light labelling during real-life food purchase decisions. The objectives of this two-arm randomised controlled pilot trial are to assess recruitment, retention and data completion rates, to generate potential effect size estimates to inform sample size calculations for the main trial and to assess the feasibility of conducting such a trial. Participants will be recruited by email from a loyalty card database of a UK supermarket chain. Eligible participants will be over 18 and regular shoppers who frequently purchase ready meals or pizzas. The intervention is informed by a review of previous interventions encouraging the use of nutrition labelling and the broader behaviour change literature. It is designed to impact on mechanisms affecting belief and behavioural intention formation as well as those associated with planning and goal setting and the adoption and maintenance of the behaviour of interest, namely traffic light label use during purchases of ready meals and pizzas. Data will be collected using electronic sales data via supermarket loyalty cards and web-based questionnaires and will be used to estimate the effect of the intervention on the nutrition profile of purchased ready meals and pizzas and the behavioural mechanisms associated with label use. Data collection will take place over 48 weeks. A process evaluation including semi-structured interviews and web analytics will be conducted to assess feasibility of a full trial. The design of the pilot trial allows for efficient recruitment and data collection. The intervention could be generalised to a wider population if shown to be feasible in the main trial. ISRCTN: ISRCTN19316955.

A cluster-randomised, controlled trial to assess the impact of a workplace osteoporosis prevention intervention on the dietary and physical activity behaviours of working women: study protocol

PubMed Central

2013-01-01

Background Osteoporosis is a debilitating disease and its risk can be reduced through adequate calcium consumption and physical activity. This protocol paper describes a workplace-based intervention targeting behaviour change in premenopausal women working in sedentary occupations. Method/Design A cluster-randomised design was used, comparing the efficacy of a tailored intervention to standard care. Workplaces were the clusters and units of randomisation and intervention. Sample size calculations incorporated the cluster design. Final number of clusters was determined to be 16, based on a cluster size of 20 and calcium intake parameters (effect size 250 mg, ICC 0.5 and standard deviation 290 mg) as it required the highest number of clusters. Sixteen workplaces were recruited from a pool of 97 workplaces and randomly assigned to intervention and control arms (eight in each). Women meeting specified inclusion criteria were then recruited to participate. Workplaces in the intervention arm received three participatory workshops and organisation wide educational activities. Workplaces in the control/standard care arm received print resources. Intervention workshops were guided by self-efficacy theory and included participatory activities such as goal setting, problem solving, local food sampling, exercise trials, group discussion and behaviour feedback. Outcomes measures were calcium intake (milligrams/day) and physical activity level (duration: minutes/week), measured at baseline, four weeks and six months post intervention. Discussion This study addresses the current lack of evidence for behaviour change interventions focussing on osteoporosis prevention. It addresses missed opportunities of using workplaces as a platform to target high-risk individuals with sedentary occupations. The intervention was designed to modify behaviour levels to bring about risk reduction. It is the first to address dietary and physical activity components each with unique intervention strategies in the context of osteoporosis prevention. The intervention used locally relevant behavioural strategies previously shown to support good outcomes in other countries. The combination of these elements have not been incorporated in similar studies in the past, supporting the study hypothesis that the intervention will be more efficacious than standard practice in osteoporosis prevention through improvements in calcium intake and physical activity. PMID:23627684

Early closure of temporary ileostomy—the EASY trial: protocol for a randomised controlled trial

PubMed Central

Correa-Marinez, Adiela; Angenete, Eva; Skullmann, Stefan; Haglind, Eva; Rosenberg, Jacob

2011-01-01

Objective The objective is to evaluate efficiency based on data on morbidity and mortality, health-related quality of life and healthcare-related costs after early reversal of temporary ileostomy after rectal resection for cancer compared with the standard procedure (late reversal). Background Reversal of a temporary ileostomy is generally associated with a low morbidity and mortality. However, ostomy reversal may cause complications requiring reoperation with subsequent major complications, in ranges from 0% to 7–9% and minor complications varying from 4–5% to 30%. Based on studies exploring and describing the time of closure in previous studies which are mostly of low quality, a recent review concluded that closing a temporary stoma within 2 weeks did not seem to be associated with an increase in morbidity and mortality. Design and methods Early closure of temporary ileostomy (EASY), a randomised controlled trial, is a prospective randomised controlled multicentre study which is performed within the framework of the Scandinavian Surgical Outcomes Research Group (http://www.ssorg.net/) and plans to include 200 patients from Danish and Swedish hospitals. The primary end-point of the study is the frequency of complications 0–12 months after surgery (the stoma creation operation). The secondary end-points of the study are (1) comparison of the total costs of the two groups at 6 and 12 months after surgery (stoma creation); (2) comparison of health-related quality of life in the two groups evaluated with the 36-item short-form and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CR29/CR30 at 3, 6 and 12 months after surgery (stoma creation); and (3) comparison of disease-specific quality of life in the two groups at 3, 6 and 12 months after surgery (stoma creation). Discussion The aim of the EASY trial is to evaluate the efficiency of early reversal of temporary ileostomy after surgery for rectal cancer versus late reversal. The EASY trial is expected to have a huge impact on patient safety as well as an improvement in patient-reported outcome. Clinical trials identifier NCT01287637. PMID:22021780

Prospective economic evaluation of an electronic discharge communication tool: analysis of a randomised controlled trial

PubMed Central

Sevick, Laura K; Santana, Maria-Jose; Ghali, William A; Clement, Fiona

2017-01-01

Objective To complete an economic evaluation within a randomised controlled trial (RCT) comparing the use of an electronic discharge communication tool (eDCT) compared with usual care. Setting Patients being discharged from a single tertiary care centre’s internal medicine Medical Teaching Units. Participants Between January 2012 and December 2013, 1399 patients were randomised to a discharge mechanism. Forty-five patients were excluded from the economic evaluation as they did not have data for the index hospitalisation cost; 1354 patients contributed to the economic evaluation. Intervention eDCT generated at discharge containing structured content on reason for admission, details of the hospital stay, treatments received and follow-up care required. The control group was discharged via traditional dictation methods. Primary and secondary outcome measures The primary economic outcome was the cost per quality-adjusted life year (QALY) gained. Secondary outcomes included the cost per death avoided and the cost per readmission avoided. Results The average transcription cost was $C22.28 per patient, whereas the estimated cost of the eDCT was $C13.33 per patient. The cost per QALY gained was $C239 933 in the eDCT arm compared with usual care due to the very small gains in effectiveness and approximately $C800difference in resource utilisation costs. The bootstrap analyses resulted in eDCT being more effective and more costly in 29.2% of samples, less costly and more effective in 29.2% of samples, less effective and more costly in 23.9% of samples and finally, less costly and less effective in 17.7% of samples. Conclusions The eDCT reduced per patient costs of the generation of discharge summaries. The bootstrap estimates demonstrate considerable uncertainty supporting the finding of neutrality reported in the clinical component of the RCT. The immediate transcription cost savings and previously documented provider and patient satisfaction may increase the impetus for organisations to invest in such systems, provided they have a foundation of eHealth infrastructure and readiness. Trial registration number NCT01402609. PMID:29247110

Previous exposure to dietary phytase reduces the endogenous energy losses from precision-fed chickens.

PubMed

Pirgozliev, V; Acamovic, T; Bedford, M R

2009-09-01

1. A precision feeding experiment was conducted with broiler chickens, which were previously fed on diets with or without phytase, to study the effects of previous exposure to dietary phytase supplementation on the excretions of endogenous energy, nitrogen, amino acids and minerals. 2. Female Ross 308 broiler chickens, which had previously received one of 4 experimental diets (low P maize/soy diets (control, D), D + 250 international units of phytase per kg diet (FTU), D + 500 FTU and D + 2500 FTU) were used in the study. All birds were starved and then given 50 ml of glucose solution at 44 d of age. The birds were allocated to individual metabolism cages in a randomised block design with 8 replicates of each of the 4 dietary treatments. 3. Chickens which had been previously fed on diets supplemented with phytase excreted 32% less energy and 28% less dry matter per kg metabolic body weight (W(075)) from endogenous sources, compared to birds fed the unsupplemented diet. 4. Birds previously given phytase supplemented diets excreted 60% less sodium than those given the control diet, but there was no effect on all other minerals investigated. There was no effect of diet on the excretion of endogenous N, sialic acid or amino acids. 5. The results showed that the effects of feeding chickens on diets with supplementary phytase may continue for a few days after the diets are withdrawn. This suggests that previous exposure to phytase may alter the nutritive value of follow-on diets, which may be a commercially important effect.

The use of pH adjusted lignocaine in controlling operative pain in the day surgery unit: a prospective, randomised trial.

PubMed

Fitton, A R; Ragbir, M; Milling, M A

1996-09-01

We report the results of a randomised, case matched, controlled, double blind study on 40 patients undergoing correction of their prominent ears, comparing efficacy of pH adjusted lignocaine to lignocaine alone in controlling operative pain. Each patient received commercial lignocaine in one ear and the same preparation reconstituted with 1 ml of 8.4% sodium bicarbonate in the other ear according to our randomisation protocol. 30 patients were studied to compare the difference between the buffered and commercial preparation infiltrated at room temperature. A further 10 patients were studied to assess the benefit the buffered preparation at room temperature had over commercial lignocaine warmed to body temperature. Linear analogue pain scores for discomfort at infiltration and during the operation itself were analysed. Buffered lignocaine imparts a significant reduction in pain on infiltration, compared to the commercial preparation at both room and body temperature. Both preparations were equally effective in obliterating pain during the operation itself.

Evaluation of multisystemic therapy pilot services in the Systemic Therapy for At Risk Teens (START) trial: study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background There is an urgent need for clinically effective and cost-effective methods to manage antisocial and criminal behaviour in adolescents. Youth conduct disorder is increasingly prevalent in the UK and is associated with a range of negative outcomes. Quantitative systematic reviews carried out for the National Institute for Health and Clinical Excellence have identified multisystemic therapy, an intensive, multimodal, home-based, family intervention for youth with serious antisocial behaviour, as one of the most promising interventions for reducing antisocial or offending behaviour and improving individual and family functioning. Previous international trials of multisystemic therapy have yielded mixed outcomes, and it is questionable to what extent positive US findings can be generalised to a wider UK mental health and juvenile justice context. This paper describes the protocol for the Systemic Therapy for At Risk Teens (START) trial, a multicentre UK-wide randomised controlled trial of multisystemic therapy in antisocial adolescents at high risk of out-of-home placement. Methods/Design The trial is being conducted at 10 sites across the UK. Seven hundred participants and their families will be recruited and randomised on a 1:1 basis to multisystemic therapy or management as usual. Treatments are offered over a period of 3 to 5 months, with follow-up to 18 months post-randomisation. The primary outcome is out-of-home placement at 18 months. Secondary outcomes include offending rates, total service and criminal justice sector costs, and participant well-being and educational outcomes. Data will be gathered from police computer records, the National Pupil Database, and interview and self-report measures administered to adolescents, parents and teachers. Outcomes will be analysed on an intention-to-treat basis, using a logistic regression with random effects for the primary outcome and Cox regressions and linear mixed-effects models for secondary outcomes depending on whether the outcome is time-to-event or continuous. Discussion The START trial is a pragmatic national trial of sufficient size to evaluate multisystemic therapy, to inform policymakers, service commissioners, professionals, service users and their families about its potential in the UK. It will also provide data on the clinical and cost-effectiveness of usual services provided to youth with serious antisocial behaviour problems. Trial registration ISRCTN77132214 PMID:23962220

Booster dose vaccination for preventing hepatitis B.

PubMed

Poorolajal, Jalal; Hooshmand, Elham

2016-06-07

Antibodies against hepatitis B surface antigen (HBsAg) wane over time following hepatitis B immunisation; hence, it is unclear whether people vaccinated in three-dose or four-dose schedules of the hepatitis B vaccine are still immune when the hepatitis B surface antibody (anti-HBs) level in their body is undetectable, or lower than the level usually considered protective. This question may potentially be answered indirectly by measuring the anamnestic immune response to a booster dose of vaccine. The term 'booster' (or revaccination) refers to an additional dose of hepatitis B vaccine (HBV) given some time post-primary vaccination to induce immune memory and improve protection against hepatitis B virus (HBV) infection. To assess the benefits and harms of booster dose hepatitis B vaccination, more than five years after the primary vaccination, for preventing HBV infection in healthy individuals previously vaccinated with the hepatitis B vaccine, and with hepatitis B surface antibody (anti-HBs) levels below 10 mIU/mL. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, conference databases, and reference lists of articles to January 2016. We also contacted authors of articles. In addition, we searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials (May 2016). Randomised clinical trials addressing anamnestic immune response to a booster dose of hepatitis B vaccine, more than five years after the primary vaccination, in apparently healthy participants, vaccinated in a three-dose or four-dose schedule of the hepatitis B vaccine during the primary vaccination, without receiving an additional dose or immunoglobulin. Both review authors decided if the identified studies met the inclusion criteria or not. Primary outcomes included the proportion of participants with anamnestic immune response in non-protected participants and signs of HBV infection. Secondary outcomes were the proportion of participants that developed local and systemic adverse events following a booster dose injection. We planned to report the weighted proportion with 95% confidence intervals (CIs). There were no eligible randomised clinical trials fulfilling the inclusion criteria of this review. We were unable to include any randomised clinical trials on the topic; only randomised clinical trials will be able to provide an answer as to whether a booster dose vaccination is able to protect against hepatitis B infection.

Protocol for a systematic review of reductions in therapy for children with low-risk febrile neutropenia

PubMed Central

2014-01-01

Background Febrile neutropenia is a common complication of therapy in children with cancer. Some patients are at low risk of complications, and research has considered reduction in therapy for these patients. A previous systematic review broadly considered whether outpatient treatment and oral antibiotics were safe in this context and concluded that this was likely to be the case. Since that review, there has been further research in this area. Therefore, we aim to provide a more robust answer to these questions and to additionally explore whether the exact timing of discharge, including entirely outpatient treatment, has an impact on outcomes. Methods/design The search will cover MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, CDSR, CENTRAL, LILACS, HTA and DARE. A full search strategy is provided. Key conference proceedings and reference lists of included papers will be hand searched. Prominent authors/clinicians in the field will be contacted. We will include randomised and quasi-randomised controlled trials along with prospective single-arm studies that examine the location of therapy and/or the route of administration of antibiotics in children or young adults (aged less than 18 years) who attend paediatric services with fever and neutropenia due to treatment for cancer and are assessed to be at low risk of medical complications. Studies will be screened and data extracted by one researcher and independently checked by a second. All studies will be critically appraised using tools appropriate to the study design. Data from randomised controlled trials (RCTs) will be combined to provide comparative estimates of treatment failure, safety and adequacy. Information from quasi-randomised trials and single-arm studies will provide further data on the safety and adequacy of regimes. Random effects meta-analysis will be used to combine studies. A detailed analysis plan, including assessment of heterogeneity and publication bias, is provided. Discussion This study will aim to specifically define the features of a low-risk strategy that will maintain levels of safety and adequacy equivalent to those of traditional treatments. This will both inform the development of services and provide patients and families with data to help them make an informed decision about care. Systematic review registration PROSPERO CRD42014005817 PMID:25336249

Evaluation of multisystemic therapy pilot services in the Systemic Therapy for At Risk Teens (START) trial: study protocol for a randomised controlled trial.

PubMed

Fonagy, Peter; Butler, Stephen; Goodyer, Ian; Cottrell, David; Scott, Stephen; Pilling, Stephen; Eisler, Ivan; Fuggle, Peter; Kraam, Abdullah; Byford, Sarah; Wason, James; Haley, Rachel

2013-08-20

There is an urgent need for clinically effective and cost-effective methods to manage antisocial and criminal behaviour in adolescents. Youth conduct disorder is increasingly prevalent in the UK and is associated with a range of negative outcomes. Quantitative systematic reviews carried out for the National Institute for Health and Clinical Excellence have identified multisystemic therapy, an intensive, multimodal, home-based, family intervention for youth with serious antisocial behaviour, as one of the most promising interventions for reducing antisocial or offending behaviour and improving individual and family functioning. Previous international trials of multisystemic therapy have yielded mixed outcomes, and it is questionable to what extent positive US findings can be generalised to a wider UK mental health and juvenile justice context. This paper describes the protocol for the Systemic Therapy for At Risk Teens (START) trial, a multicentre UK-wide randomised controlled trial of multisystemic therapy in antisocial adolescents at high risk of out-of-home placement. The trial is being conducted at 10 sites across the UK. Seven hundred participants and their families will be recruited and randomised on a 1:1 basis to multisystemic therapy or management as usual. Treatments are offered over a period of 3 to 5 months, with follow-up to 18 months post-randomisation. The primary outcome is out-of-home placement at 18 months. Secondary outcomes include offending rates, total service and criminal justice sector costs, and participant well-being and educational outcomes. Data will be gathered from police computer records, the National Pupil Database, and interview and self-report measures administered to adolescents, parents and teachers. Outcomes will be analysed on an intention-to-treat basis, using a logistic regression with random effects for the primary outcome and Cox regressions and linear mixed-effects models for secondary outcomes depending on whether the outcome is time-to-event or continuous. The START trial is a pragmatic national trial of sufficient size to evaluate multisystemic therapy, to inform policymakers, service commissioners, professionals, service users and their families about its potential in the UK. It will also provide data on the clinical and cost-effectiveness of usual services provided to youth with serious antisocial behaviour problems. ISRCTN77132214.

Antenatal small-class education versus auditorium-based lectures to promote positive transitioning to parenthood - A randomised trial.

PubMed

Koushede, Vibeke; Brixval, Carina Sjöberg; Thygesen, Lau Caspar; Axelsen, Solveig Forberg; Winkel, Per; Lindschou, Jane; Gluud, Christian; Due, Pernille

2017-01-01

Prospective parents widely use education to gain information about, e.g., labour and parenting skills. It is unknown if antenatal education in small classes is more beneficial for parenting stress and parenting alliance compared with other types of antenatal education. In the present randomised trial, we examined the effect of antenatal education in small classes versus auditorium-based lectures on perceived stress, parenting stress, and parenting alliance. A total of 1,766 pregnant women were randomised to receive: antenatal education in small classes three times in pregnancy and one time after delivery, each session lasted 2.5 hours, versus standard care consisting of two times two hours auditorium-based lectures. Previous analysis of the primary outcome showed no difference between intervention and control group. Here we conduct an exploratory analysis of three secondary outcomes. Effects of the interventions on parents' global feelings of stress at 37 weeks gestation and nine weeks and six months postpartum and parenting stress nine weeks and six months postpartum were examined using linear regression analyses and mixed models with repeated measurements. The effect on parenting alliance six months postpartum was examined using the non-parametric Wilcoxon rank-sum test. Antenatal education in small classes had a small beneficial main effect on global feelings of stress six months postpartum and a statistically significant interaction between time and group favoring antenatal education in small classes. The P values of intervention effects on parenting stress and parenting alliance were all larger than the threshold value (0.05).

GET.ON Mood Enhancer: efficacy of Internet-based guided self-help compared to psychoeducation for depression: an investigator-blinded randomised controlled trial

PubMed Central

2014-01-01

Background Major depressive disorder (MDD) imposes a considerable disease burden on individuals and societies. A large number of randomised controlled trials (RCTs) have shown the efficacy of Internet-based guided self-help interventions in reducing symptoms of depression. However, study quality varies considerably. The aim of this study is to evaluate the efficacy of a new Internet-based guided self-help intervention (GET.ON Mood Enhancer) compared to online-based psychoeducation in an investigator-blinded RCT. Methods/design A RCT will be conducted to compare the efficacy of GET.ON Mood Enhancer with an active control condition receiving online psychoeducation on depression (OPD). Both treatment groups will have full access to treatment as usual. Adults with MDD (n = 128) will be recruited and randomised to one of the two conditions. Primary outcome will be observer-rated depressive symptoms (HRSD-24) by independent assessors blind to treatment conditions. Secondary outcomes include changes in self-reported depressive symptom severity, anxiety and quality of life. Additionally, potential negative effects of the treatments will systematically be evaluated on several dimensions (for example, symptom deteriorations, attitudes toward seeking psychological help, relationships and stigmatisation). Assessments will take place at baseline, 6 and 12 weeks after randomisation. Discussion This study evaluates a new Internet-based guided self-help intervention for depression using an active control condition (psychoeducation-control) and an independent, blinded outcome evaluation. This study will further enhance the evidence for Internet-based guided self-help interventions for MDD. Trial registration German Clinical Trial Registration (DRKS): DRKS00005025 PMID:24476555

Effects of manual therapy on treatment duration and motor development in infants with severe nonsynostotic plagiocephaly: a randomised controlled pilot study.

PubMed

Cabrera-Martos, I; Valenza, M C; Valenza-Demet, G; Benítez-Feliponi, A; Robles-Vizcaíno, C; Ruiz-Extremera, A

2016-11-01

Despite growing evidence regarding nonsynostotic plagiocephaly and their repercussions on motor development, there is little evidence to support the use of manual therapy as an adjuvant option. The aim of this study was to evaluate the effects of a therapeutic approach based on manual therapy as an adjuvant option on treatment duration and motor development in infants with severe nonsynostotic plagiocephaly. This is a randomised controlled pilot study. The study was conducted at a university hospital. Forty-six infants with severe nonsynostotic plagiocephaly (types 4-5 of the Argenta scale) referred to the Early Care and Monitoring Unit were randomly allocated to a control group receiving standard treatment (repositioning and an orthotic helmet) or to an experimental group treated with manual therapy added to standard treatment. Infants were discharged when the correction of the asymmetry was optimal taken into account the previous clinical characteristics. The outcome measures were treatment duration and motor development assessed with the Alberta Infant Motor Scale (AIMS) at baseline and at discharge. Asymmetry after the treatment was minimal (type 0 or 1 according to the Argenta scale) in both groups. A comparative analysis showed that treatment duration was significantly shorter (p < 0.001) in the experimental group (109.84 ± 14.45 days) compared to the control group (148.65 ± 11.53 days). The motor behaviour was normal (scores above the 16th percentile of the AIMS) in all the infants after the treatment. Manual therapy added to standard treatment reduces the treatment duration in infants with severe nonsynostotic plagiocephaly.

Effectiveness of an online social support intervention for caregivers of people with dementia: the study protocol of a randomised controlled trial.

PubMed

Dam, Alieske E H; de Vugt, Marjolein E; van Boxtel, Martin P J; Verhey, Frans R J

2017-08-29

Caregivers of people with dementia (PwD) face burden, feelings of loneliness, and social isolation. Previous studies have shown promising effects of online e-health interventions. Using social media may facilitate support for dementia caregiver networks. In an iterative step-wise approach, a social support tool entitled "Inlife" was developed. This paper describes the design of a study evaluating the effects of Inlife and its process characteristics. A mixed-method, randomised controlled trial with 122 caregivers of PwD will be conducted. Participants will be assigned to either the Inlife social support intervention or a waiting-list control group. After 16 weeks, the control group will obtain access to the Inlife environment. Data will be collected at baseline (T 0 ) and at 8-week (T 1 ), 16-week (T 2 ) and 42-week follow up (T 3 ). The 16-week follow-up assessment (T 2 ) is the primary endpoint to evaluate the results on the primary and secondary outcomes, measured by self-reported questionnaires. The primary outcomes include feelings of caregiver competence and perceived social support. The secondary outcomes include received support, feelings of loneliness, psychological complaints (e.g., anxiety, stress), and quality of life. A process evaluation, including semi-structured interviews, will be conducted to examine the internal and external validity of the intervention. Using a mixed-method design, our study will provide valuable insights into the usability, effectiveness, and factors related to implementation of the Inlife intervention. Our study results will indicate whether Inlife could be a valuable social support resource in future routine dementia care. Dutch trial register, NTR6131 . Registered on 20 October 2016.

Impact of a Participatory Intervention with Women’s Groups on Psychological Distress among Mothers in Rural Bangladesh: Secondary Analysis of a Cluster-Randomised Controlled Trial

PubMed Central

Clarke, Kelly; Azad, Kishwar; Kuddus, Abdul; Shaha, Sanjit; Nahar, Tasmin; Aumon, Bedowra Haq; Hossen, Mohammed Munir; Beard, James; Costello, Anthony; Houweling, Tanja A. J.; Prost, Audrey; Fottrell, Edward

2014-01-01

Background Perinatal common mental disorders (PCMDs) are a major cause of disability among women and disproportionately affect lower income countries. Interventions to address PCMDs are urgently needed in these settings, and group-based and peer-led approaches are potential strategies to increase access to mental health interventions. Participatory women’s health groups led by local women previously reduced postpartum psychological distress in eastern India. We assessed the effect of a similar intervention on postpartum psychological distress in rural Bangladesh. Method We conducted a secondary analysis of data from a cluster-randomised controlled trial with 18 clusters and an estimated population of 532,996. Nine clusters received an intervention comprising monthly meetings during which women’s groups worked through a participatory learning and action cycle to develop strategies for improving women’s and children’s health. There was one group for every 309 individuals in the population, 810 groups in total. Mothers in nine control clusters had access to usual perinatal care. Postpartum psychological distress was measured with the 20-item Self Reporting Questionnaire (SRQ-20) between six and 52 weeks after delivery, during the months of January to April, in 2010 and 2011. Results We analysed outcomes for 6275 mothers. Although the cluster mean SRQ-20 score was lower in the intervention arm (mean 5.2, standard deviation 1.8) compared to control (5.3, 1.2), the difference was not significant (β 1.44, 95% CI 0.28, 3.08). Conclusions Despite promising results in India, participatory women’s groups focused on women’s and children’s health had no significant effect on postpartum psychological distress in rural Bangladesh. PMID:25329470

A randomised controlled trial of a computerised intervention for children with social communication difficulties to support peer collaboration.

PubMed

Murphy, Suzanne M; Faulkner, Dorothy M; Reynolds, Laura R

2014-11-01

An intervention aiming to support children with social communication difficulties was tested using a randomised controlled design. Children aged 5-6 years old (n=32) were tested and selected for participation on the basis of their scores on the Test of Pragmatic Skills (TPS) and were then randomly assigned to the intervention arm or to the delayed intervention control group. Following previous research which suggested that computer technology may be particularly useful for this group of children, the intervention included a collaborative computer game which the children played with an adult. Subsequently, children's performance as they played the game with a classmate was observed. Micro-analytic observational methods were used to analyse the audio-recorded interaction of the children as they played. Pre- and post-intervention measures comprised the Test of Pragmatic Skills, children's performance on the computer game and verbal communication measures that the children used during the game. This evaluation of the intervention shows promise. At post-test, the children who had received the intervention, by comparison to the control group who had not, showed significant gains in their scores on the Test of Pragmatic Skills (p=.009, effect size r=-.42), a significant improvement in their performance on the computer game (p=.03, r=-.32) and significantly greater use of high-quality questioning during collaboration (p<.001, r=-.60). Furthermore, the children who received the intervention made significantly more positive statements about the game and about their partners (p=.02, r=-.34) suggesting that the intervention increased their confidence and enjoyment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inhaled mannitol for non-cystic fibrosis bronchiectasis: a randomised, controlled trial.

PubMed

Bilton, Diana; Tino, Gregory; Barker, Alan F; Chambers, Daniel C; De Soyza, Anthony; Dupont, Lieven J A; O'Dochartaigh, Conor; van Haren, Eric H J; Vidal, Luis Otero; Welte, Tobias; Fox, Howard G; Wu, Jian; Charlton, Brett

2014-12-01

Bronchiectasis is characterised by excessive production of mucus and pulmonary exacerbations. Inhaled osmotic agents may enhance mucociliary clearance, but few long-term clinical trials have been conducted. To determine the impact of inhaled mannitol on exacerbation rates in patients with non-cystic fibrosis (CF) bronchiectasis. Secondary endpoints included time to first exacerbation, duration of exacerbations, antibiotic use for exacerbations and quality of life (QOL) (St George's Respiratory Questionnaire, SGRQ). Patients with non-CF bronchiectasis and a history of chronic excess production of sputum and ≥2 pulmonary exacerbations in the previous 12 months were randomised (1:1) to 52 weeks treatment with inhaled mannitol 400 mg or low-dose mannitol control twice a day. Patients were 18-85 years of age, baseline FEV1 ≥40% and ≤85% predicted and a baseline SGRQ score ≥30. 461 patients (233 in the mannitol and 228 in the control arm) were treated. Baseline demographics were similar in the two arms. The exacerbation rate was not significantly reduced on mannitol (rate ratio 0.92, p=0.31). However, time to first exacerbation was increased on mannitol (HR 0.78, p=0.022). SGRQ score was improved on mannitol compared with low-dose mannitol control (-2.4 units, p=0.046). Adverse events were similar between groups. Mannitol 400 mg inhaled twice daily for 12 months in patients with clinically significant bronchiectasis did not significantly reduce exacerbation rates. There were statistically significant improvements in time to first exacerbation and QOL. Mannitol therapy was safe and well tolerated. NCT00669331. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effectiveness and cost-effectiveness of admissions to women's crisis houses compared with traditional psychiatric wards: pilot patient-preference randomised controlled trial.

PubMed

Howard, L; Flach, C; Leese, M; Byford, S; Killaspy, H; Cole, L; Lawlor, C; Betts, J; Sharac, J; Cutting, P; McNicholas, S; Johnson, S

2010-08-01

Women's crisis houses have been developed in the UK as a less stigmatising and less institutional alternative to traditional psychiatric wards. To examine the effectiveness and cost-effectiveness of women's crisis houses by first examining the feasibility of a pilot patient-preference randomised controlled trial (PP-RCT) design (ISRCTN20804014). We used a PP-RCT study design to investigate women presenting in crisis needing informal admission. The four study arms were the patient preference arms of women's crisis house or hospital admission, and randomised arms of women's crisis house or hospital admission. Forty-one women entered the randomised arms of the trial (crisis house n = 19, wards n = 22) and 61 entered the patient-preference arms (crisis house n = 37, ward n = 24). There was no significant difference in outcomes (symptoms, functioning, perceived coercion, stigma, unmet needs or quality of life) or costs for any of the groups (randomised or preference arms), but women who obtained their preferred intervention were more satisfied with treatment. Although the sample sizes were too small to allow definite conclusions, the results suggest that when services are able to provide interventions preferred by patients, those patients are more likely to be satisfied with treatment. This pilot study provides some evidence that women's crisis houses are as effective as traditional psychiatric wards, and may be more cost-effective.

Evaluation of In Vitro Cross-Reactivity to Avian H5N1 and Pandemic H1N1 2009 Influenza Following Prime Boost Regimens of Seasonal Influenza Vaccination in Healthy Human Subjects: A Randomised Trial

DTIC Science & Technology

2013-03-26

virus (IIV) vaccine (dose 0.5 mL intramuscularly, purchased in Thailand from Sanofi Pasteur). Both vaccines contained the three strains for the 2009/10...H1N1 2009 Influenza Following Prime Boost Regimens of Seasonal Influenza Vaccination in Healthy Human Subjects: A Randomised Trial. 5a. CONTRACT NUMBER...reported by WHO since 2003 [1]. Current seasonal trivalent influenza vaccines rely on predicted antigens based on the previous season’s circulating

Children, parents, and pets exercising together (CPET) randomised controlled trial: study rationale, design, and methods.

PubMed

Yam, Philippa S; Morrison, Ryan; Penpraze, Viki; Westgarth, Carri; Ward, Dianne S; Mutrie, Nanette; Hutchison, Pippa; Young, David; Reilly, John J

2012-03-19

Objectively measured physical activity is low in British children, and declines as childhood progresses. Observational studies suggest that dog-walking might be a useful approach to physical activity promotion in children and adults, but there are no published public health interventions based on dog-walking with children. The Children, Parents, and Pets Exercising Together Study aims to develop and evaluate a theory driven, generalisable, family-based, dog walking intervention for 9-11 year olds. The Children, Parents, and Pets Exercising Together Study is an exploratory, assessor-blinded, randomised controlled trial as defined in the UK MRC Framework on the development and evaluation of complex interventions in public health. The trial will follow CONSORT guidance. Approximately 40 dog-owning families will be allocated randomly in a ratio of 1.5:1 to receive a simple behavioural intervention lasting for 10 weeks or to a 'waiting list' control group. The primary outcome is change in objectively measured child physical activity using Actigraph accelerometry. Secondary outcomes in the child, included in part to shape a future more definitive randomised controlled trial, are: total time spent sedentary and patterning of sedentary behaviour (Actigraph accelerometry); body composition and bone health from dual energy x-ray absorptiometry; body weight, height and BMI; and finally, health-related quality of life using the PedsQL. Secondary outcomes in parents and dogs are: changes in body weight; changes in Actigraph accelerometry measured physical activity and sedentary behaviour. Process evaluation will consist of assessment of simultaneous child, parent, and dog accelerometry data and brief interviews with participating families. The Children, Parents, and Pets Exercising Together trial should be the first randomised controlled study to establish and evaluate an intervention aimed at dog-based physical activity promotion in families. It should advance our understanding of whether and how to use pet dogs to promote physical activity and/or to reduce sedentary behaviour in children and adults. The trial is intended to lead to a subsequent more definitive randomised controlled trial, and the work should inform future dog-based public health interventions such as secondary prevention interventions in children or adults. ISRCTN85939423.

Children, parents, and pets exercising together (CPET) randomised controlled trial: study rationale, design, and methods

PubMed Central

2012-01-01

Background Objectively measured physical activity is low in British children, and declines as childhood progresses. Observational studies suggest that dog-walking might be a useful approach to physical activity promotion in children and adults, but there are no published public health interventions based on dog-walking with children. The Children, Parents, and Pets Exercising Together Study aims to develop and evaluate a theory driven, generalisable, family-based, dog walking intervention for 9-11 year olds. Methods/design The Children, Parents, and Pets Exercising Together Study is an exploratory, assessor-blinded, randomised controlled trial as defined in the UK MRC Framework on the development and evaluation of complex interventions in public health. The trial will follow CONSORT guidance. Approximately 40 dog-owning families will be allocated randomly in a ratio of 1.5:1 to receive a simple behavioural intervention lasting for 10 weeks or to a 'waiting list' control group. The primary outcome is change in objectively measured child physical activity using Actigraph accelerometry. Secondary outcomes in the child, included in part to shape a future more definitive randomised controlled trial, are: total time spent sedentary and patterning of sedentary behaviour (Actigraph accelerometry); body composition and bone health from dual energy x-ray absorptiometry; body weight, height and BMI; and finally, health-related quality of life using the PedsQL. Secondary outcomes in parents and dogs are: changes in body weight; changes in Actigraph accelerometry measured physical activity and sedentary behaviour. Process evaluation will consist of assessment of simultaneous child, parent, and dog accelerometry data and brief interviews with participating families. Discussion The Children, Parents, and Pets Exercising Together trial should be the first randomised controlled study to establish and evaluate an intervention aimed at dog-based physical activity promotion in families. It should advance our understanding of whether and how to use pet dogs to promote physical activity and/or to reduce sedentary behaviour in children and adults. The trial is intended to lead to a subsequent more definitive randomised controlled trial, and the work should inform future dog-based public health interventions such as secondary prevention interventions in children or adults. Trial registration number ISRCTN85939423 PMID:22429665

A pragmatic randomised controlled trial of the effectiveness and cost-effectiveness of screening older women for the prevention of fractures: rationale, design and methods for the SCOOP study.

PubMed

Shepstone, L; Fordham, R; Lenaghan, E; Harvey, I; Cooper, C; Gittoes, N; Heawood, A; Peters, T J; O'Neill, T; Torgerson, D; Holland, R; Howe, A; Marshall, T; Kanis, J A; McCloskey, E

2012-10-01

SCOOP is a UK seven-centre, pragmatic, randomised controlled trial with 5-year follow-up, including 11,580 women aged 70 to 85 years, to assess the effectiveness and cost-effectiveness of a community-based screening programme to reduce fractures. It utilises the FRAX algorithm and DXA to assess the 10-year probability of fracture. Introduction Osteoporotic, or low-trauma, fractures present a considerable burden to the National Health Service and have major adverse effects on quality of life, disability and mortality for the individual. Methods Given the availability of efficacious treatments and a risk assessment tool based upon clinical risk factors and bone mineral density, a case exists to undertake a community-based controlled evaluation of screening for subjects at high risk of fracture, under the hypothesis that such a screening programme would reduce fractures in this population. Results This study is a UK seven-centre, unblinded, pragmatic, randomised controlled trial with a 5-year follow-up period. A total of 11,580 women, aged 70 to 85 years and not on prescribed bone protective therapy will be consented to the trial by post via primary care providing 90% power to detect an 18% decrease in fractures. Conclusions Participants will be randomised to either a screening arm or control. Those undergoing screening will have a 10-year fracture probability computed from baseline risk factors together with bone mineral density measured by DXA in selected subjects. Individuals above an age-dependent threshold of fracture probability will be recommended for treatment for the duration of the trial. Subjects in the control arm will receive 'usual care'. Participants will be followed up 6 months after randomisation and annually by postal questionnaires with independent checking of hospital and primary care records. The primary outcome will be the proportion of individuals sustaining fractures in each group. An economic analysis will be carried out to assess cost-effectiveness of screening. A qualitative evaluation will be conducted to examine the acceptability of the process to participants.

A randomised controlled trial of the use of aromatherapy and hand massage to reduce disruptive behaviour in people with dementia.

PubMed

Fu, Chieh-Yu; Moyle, Wendy; Cooke, Marie

2013-07-10

Aromatherapy and hand massage therapies have been reported to have some benefit for people with dementia who display behavioural symptoms; however there are a number of limitations of reported studies. The aim is to investigate the effect of aromatherapy (3% lavender oil spray) with and without hand massage on disruptive behaviour in people with dementia living in long-term care. In a single blinded randomised controlled trial 67 people with a diagnosis of dementia and a history of disruptive behaviour, from three long-term care facilities were recruited and randomised using a random number table into three groups: (1) Combination (aromatherapy and hand massage) (n = 22), (2) Aromatherapy (n = 23), (3) Placebo control (water spray) (n = 22). The intervention was given twice daily for six weeks. Data on residents' behaviour (CMAI) and cognition (MMSE) were collected before, during and after the intervention. Despite a downward trend in behaviours displayed not one of the interventions significantly reduced disruptive behaviour. Further large-scale placebo controlled studies are required where antipsychotic medication is controlled and a comparison of the methods of application of aromatherapy are investigated. ACTRN12612000917831.

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.

A systematic review of randomised controlled trials assessing effectiveness of prosthetic and orthotic interventions

PubMed Central

Farmer, Sybil; Pandyan, Anand; Chockalingam, Nachiappan

2018-01-01

Background Assistive products are items which allow older people and people with disabilities to be able to live a healthy, productive and dignified life. It has been estimated that approximately 1.5% of the world’s population need a prosthesis or orthosis. Objective The objective of this study was to systematically identify and review the evidence from randomized controlled trials assessing effectiveness and cost-effectiveness of prosthetic and orthotic interventions. Methods Literature searches, completed in September 2015, were carried out in fourteen databases between years 1995 and 2015. The search results were independently screened by two reviewers. For the purpose of this manuscript, only randomized controlled trials which examined interventions using orthotic or prosthetic devices were selected for data extraction and synthesis. Results A total of 342 randomised controlled trials were identified (319 English language and 23 non-English language). Only 4 of these randomised controlled trials examined prosthetic interventions and the rest examined orthotic interventions. These orthotic interventions were categorised based on the medical conditions/injuries of the participants. From these studies, this review focused on the medical condition/injuries with the highest number of randomised controlled trials (osteoarthritis, fracture, stroke, carpal tunnel syndrome, plantar fasciitis, anterior cruciate ligament, diabetic foot, rheumatoid and juvenile idiopathic arthritis, ankle sprain, cerebral palsy, lateral epicondylitis and low back pain). The included articles were assessed for risk of bias using the Cochrane Risk of Bias tool. Details of the clinical population examined, the type of orthotic/prosthetic intervention, the comparator/s and the outcome measures were extracted. Effect sizes and odds ratios were calculated for all outcome measures, where possible. Conclusions At present, for prosthetic and orthotic interventions, the scientific literature does not provide sufficient high quality research to allow strong conclusions on their effectiveness and cost-effectiveness. PMID:29538382

Epidurals in Pancreatic Resection Outcomes (E-PRO) study: protocol for a randomised controlled trial

PubMed Central

Pak, Linda Ma; Haroutounian, Simon; Hawkins, William G; Worley, Lori; Kurtz, Monika; Frey, Karen; Karanikolas, Menelaos; Swarm, Robert A; Bottros, Michael M

2018-01-01

Introduction Epidural analgesia provides an important synergistic method of pain control. In addition to reducing perioperative opioid consumption, the deliverance of analgesia into the epidural space, effectively creating a sympathetic blockade, has a multitude of additional potential benefits, from decreasing the incidence of postoperative delirium to reducing the development of persistent postsurgical pain (PPSP). Prior studies have also identified a correlation between the use of epidural analgesia and improved oncological outcomes and survival. The aim of this study is to evaluate the effect of epidural analgesia in pancreatic operations on immediate postoperative outcomes, the development of PPSP and oncological outcomes in a prospective, single-blind, randomised controlled trial. Methods The Epidurals in Pancreatic Resection Outcomes (E-PRO) study is a prospective, single-centre, randomised controlled trial. 150 patients undergoing either pancreaticoduodenectomy or distal pancreatectomy will be randomised to receive an epidural bupivacaine infusion following anaesthetic induction followed by continued epidural bupivacaine infusion postoperatively in addition to the institutional standardised pain regimen of hydromorphone patient-controlled analgesia (PCA), acetaminophen and ketorolac (intervention group) or no epidural infusion and only the standardised postoperative pain regimen (control group). The primary outcome was the postoperative opioid consumption, measured in morphine or morphine-equivalents. Secondary outcomes include patient-reported postoperative pain numerical rating scores, trend and relative ratios of serum inflammatory markers (interleukin (IL)-1β, IL-6, tumour necrosis factor-α, IL-10), occurrence of postoperative delirium, development of PPSP as determined by quantitative sensory testing, and disease-free and overall survival. Ethics and dissemination The E-PRO trial has been approved by the institutional review board. Recruitment began in May 2016 and will continue until the end of May 2018. Dissemination plans include presentations at scientific conferences and scientific publications. Trial registration number NCT02681796. PMID:29374667

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).

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

Exercise programs may be effective in preventing a new episode of neck pain: a systematic review and meta-analysis.

PubMed

de Campos, Tarcisio F; Maher, Chris G; Steffens, Daniel; Fuller, Joel T; Hancock, Mark J

2018-06-13

What is the effectiveness of interventions that aim to prevent a new episode of neck pain? Systematic review and meta-analysis of randomised, controlled trials. People without neck pain at study entry. Any intervention aiming to prevent a future episode of neck pain. New episode of neck pain. Five trials including a total of 3852 individuals met the inclusion criteria. The pooled results from two randomised, controlled trials (500 participants) found moderate-quality evidence that exercise reduces the risk of a new episode of neck pain (OR 0.32, 95% CI 0.12 to 0.86). One of the meta-analysed trials included some co-interventions with the exercise. There was low-quality evidence from three randomised, controlled trials (3352 participants) that ergonomic programs do not reduce the risk of a new neck pain episode (OR 1.00, 95% CI 0.74 to 1.35). This review found moderate-quality evidence supporting the effectiveness of an exercise program for reducing the risk of a new episode of neck pain. There is a need for high-quality randomised, controlled trials evaluating interventions to prevent new episodes of neck pain. PROSPERO CRD42017055174. [de Campos TF, Maher CG, Steffens D, Fuller JT, Hancock MJ (2018) Exercise programs may be effective in preventing a new episode of neck pain: a systematic review. Journal of Physiotherapy XX: XX-XX]. Copyright © 2018 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Social Stories in mainstream schools for children with autism spectrum disorder: a feasibility randomised controlled trial.

PubMed

Marshall, David; Wright, Barry; Allgar, Victoria; Adamson, Joy; Williams, Christine; Ainsworth, Hannah; Cook, Liz; Varley, Danielle; Hackney, Lisa; Dempster, Paul; Ali, Shehzad; Trepel, Dominic; Collingridge Moore, Danielle; Littlewood, Elizabeth; McMillan, Dean

2016-08-11

To assess the feasibility of recruitment, retention, outcome measures and intervention training/delivery among teachers, parents and children. To calculate a sample size estimation for full trial. A single-centre, unblinded, cluster feasibility randomised controlled trial examining Social Stories delivered within a school environment compared with an attentional control. 37 primary schools in York, UK. 50 participants were recruited and a cluster randomisation approach by school was examined. Participants were randomised into the treatment group (n=23) or a waiting list control group (n=27). Acceptability and feasibility of the trial, intervention and of measurements required to assess outcomes in a definitive trial. An assessment of the questionnaire completion rates indicated teachers would be most appropriate to complete the primary outcome measure. 2 outcome measures: the Social Responsiveness Scale (SRS)-2 and a goal-based measure showed both the highest levels of completion rates (above 80%) at the primary follow-up point (6 weeks postintervention) and captured relevant social and behaviour outcomes. Power calculations were based on these 2 outcome measures leading to a total proposed sample size of 180 participant groups. Results suggest that a future trial would be feasible to conduct and could inform the policy and practice of using Social Stories in mainstream schools. ISRCTN96286707; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Preoperative education interventions to reduce anxiety and improve recovery among cardiac surgery patients: a review of randomised controlled trials.

PubMed

Guo, Ping

2015-01-01

To update evidence of the effectiveness of preoperative education among cardiac surgery patients. Patients awaiting cardiac surgery may experience high levels of anxiety and depression, which can adversely affect their existing disease and surgery and result in prolonged recovery. There is evidence that preoperative education interventions can lead to improved patient experiences and positive postoperative outcomes among a mix of general surgical patients. However, a previous review suggested limited evidence to support the positive impact of preoperative education on patients' recovery from cardiac surgery. Comprehensive review of the literature. The Cochrane Central Register of Controlled Trials from the Cochrane Library, MEDLINE, CINAHL, PsycINFO, EMBASE and Web of Science were searched for English-language articles published between 2000-2011. Original articles were included reporting randomised controlled trials of cardiac preoperative education interventions. Six trials were identified and have produced conflicting findings. Some trials have demonstrated the effects of preoperative education on improving physical and psychosocial recovery of cardiac patients, while others found no evidence that patients' anxiety is reduced or of any effect on pain or hospital stay. Evidence of the effectiveness of preoperative education interventions among cardiac surgery patients remains inconclusive. Further research is needed to evaluate cardiac preoperative education interventions for sustained effect and in non-Western countries. A nurse-coordinated multidisciplinary preoperative education approach may offer a way forward to provide a more effective and efficient service. Staff training in developing and delivering such interventions is a priority. © 2014 John Wiley & Sons Ltd.

Glycaemic control and hypoglycaemia with insulin glargine 300 U/mL compared with glargine 100 U/mL in Japanese adults with type 2 diabetes using basal insulin plus oral anti-hyperglycaemic drugs (EDITION JP 2 randomised 12-month trial including 6-month extension).

PubMed

Terauchi, Y; Koyama, M; Cheng, X; Sumi, M; Riddle, M C; Bolli, G B; Hirose, T

2017-10-01

To compare insulin glargine 300 U/mL (Gla-300) with glargine 100 U/mL (Gla-100) in Japanese adults with uncontrolled type 2 diabetes on basal insulin and oral anti-hyperglycaemic drugs over 12 months. EDITION JP 2 was a randomised, open-label, phase 3 study. Following a 6-month treatment period, participants continued receiving previously assigned once daily Gla-300 or Gla-100, plus oral anti-hyperglycaemic drugs, in a 6-month extension period. Glycaemic control, hypoglycaemia and adverse events were assessed. The 12-month completion rate was 88% for Gla-300 and 96% for Gla-100, with comparable reasons for discontinuation. Mean HbA 1c decrease from baseline to month 12 was 0.3% in both groups. Annualised rates of confirmed (≤3.9mmol/L [≤70mg/dL]) or severe hypoglycaemia were lower with Gla-300 than Gla-100 (nocturnal [00:00-05:59h]: rate ratio 0.41; 95% confidence interval: 0.18 to 0.92; anytime [24h]: rate ratio 0.64; 95% confidence interval: 0.44 to 0.94). Cumulative number of hypoglycaemic events was lower with Gla-300 than Gla-100. Adverse event profiles were comparable between treatments. Over 12 months, Gla-300-treated participants achieved sustained glycaemic control and experienced less hypoglycaemia, particularly at night, versus Gla-100, supporting 6-month results. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Hygiene and health: systematic review of handwashing practices worldwide and update of health effects.

PubMed

Freeman, Matthew C; Stocks, Meredith E; Cumming, Oliver; Jeandron, Aurelie; Higgins, Julian P T; Wolf, Jennyfer; Prüss-Ustün, Annette; Bonjour, Sophie; Hunter, Paul R; Fewtrell, Lorna; Curtis, Valerie

2014-08-01

To estimate the global prevalence of handwashing with soap and derive a pooled estimate of the effect of hygiene on diarrhoeal diseases, based on a systematic search of the literature. Studies with data on observed rates of handwashing with soap published between 1990 and August 2013 were identified from a systematic search of PubMed, Embase and ISI Web of Knowledge. A separate search was conducted for studies on the effect of hygiene on diarrhoeal disease that included randomised controlled trials, quasi-randomised trials with control group, observational studies using matching techniques and observational studies with a control group where the intervention was well defined. The search used Cochrane Library, Global Health, BIOSIS, PubMed, and Embase databases supplemented with reference lists from previously published systematic reviews to identify studies published between 1970 and August 2013. Results were combined using multilevel modelling for handwashing prevalence and meta-regression for risk estimates. From the 42 studies reporting handwashing prevalence we estimate that approximately 19% of the world population washes hands with soap after contact with excreta (i.e. use of a sanitation facility or contact with children's excreta). Meta-regression of risk estimates suggests that handwashing reduces the risk of diarrhoeal disease by 40% (risk ratio 0.60, 95% CI 0.53-0.68); however, when we included an adjustment for unblinded studies, the effect estimate was reduced to 23% (risk ratio 0.77, 95% CI 0.32-1.86). Our results show that handwashing after contact with excreta is poorly practiced globally, despite the likely positive health benefits. © 2014 John Wiley & Sons Ltd.

A mobile phone intervention to reduce binge drinking among disadvantaged men: study protocol for a randomised controlled cost-effectiveness trial.

PubMed

Crombie, Iain K; Irvine, Linda; Williams, Brian; Sniehotta, Falko F; Petrie, Dennis; Evans, Josie Mm; Emslie, Carol; Jones, Claire; Ricketts, Ian W; Humphris, Gerry; Norrie, John; Rice, Peter; Slane, Peter W

2014-12-19

Socially disadvantaged men are at a substantially higher risk of developing alcohol-related problems. The frequency of heavy drinking in a single session is high among disadvantaged men. Brief alcohol interventions were developed for, and are usually delivered in, healthcare settings. The group who binge drink most frequently, young to middle-aged disadvantaged men, have less contact with health services and there is a need for an alternative method of intervention delivery. Text messaging has been used successfully to modify other adverse health behaviours. This study will test whether text messages can reduce the frequency of binge drinking by disadvantaged men. Disadvantaged men aged 25 to 44 years who drank >8 units of alcohol at least twice in the preceding month will be recruited from the community. Two recruitment strategies will be used: contacting men listed in primary care registers, and a community outreach method (time-space sampling). The intended sample of 798 men will be randomised to intervention or control, stratifying by recruitment method. The intervention group will receive a series of text messages designed to reduce the frequency of binge drinking through the formation of specific action plans. The control group will receive behaviourally neutral text messages intended to promote retention in the study. The primary outcome measure is the proportion of men consuming >8 units on at least three occasions in the previous 30 days. Secondary outcomes include total alcohol consumption and the frequency of consuming more than 16 units of alcohol in one session in the previous month. Process measures, developed during a previous feasibility study, will monitor engagement with the key behaviour change components of the intervention. The study will incorporate an economic evaluation comparing the costs of recruitment and intervention delivery with the benefits of reduced alcohol-related harm. This study will assess the effectiveness of a brief intervention, delivered by text messages, aimed at reducing the frequency of binge drinking in disadvantaged men. The process measures will identify components of the intervention which contribute to effectiveness. The study will also determine whether any benefit of the intervention is justified by the costs of intervening. ISRCTN07695192. Date assigned: 14 August 2013.

A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3 Trial Intracranial Bleeding Mechanistic Sub-Study [CRASH-3 IBMS]).

PubMed

Mahmood, Abda; Roberts, Ian; Shakur, Haleema

2017-07-17

Tranexamic acid prevents blood clots from breaking down and reduces bleeding. However, it is uncertain whether tranexamic acid is effective in traumatic brain injury. The CRASH-3 trial is a randomised controlled trial that will examine the effect of tranexamic acid (versus placebo) on death and disability in 13,000 patients with traumatic brain injury. The CRASH-3 trial hypothesizes that tranexamic acid will reduce intracranial haemorrhage, which will reduce the risk of death. Although it is possible that tranexamic acid will reduce intracranial bleeding, there is also a potential for harm. In particular, tranexamic acid may increase the risk of cerebral thrombosis and ischaemia. The protocol detailed here is for a mechanistic sub-study nested within the CRASH-3 trial. This mechanistic sub-study aims to examine the effect of tranexamic acid (versus placebo) on intracranial bleeding and cerebral ischaemia. The CRASH-3 Intracranial Bleeding Mechanistic Sub-Study (CRASH-3 IBMS) is nested within a prospective, double-blind, multi-centre, parallel-arm randomised trial called the CRASH-3 trial. The CRASH-3 IBMS will be conducted in a cohort of approximately 1000 isolated traumatic brain injury patients enrolled in the CRASH-3 trial. In the CRASH-3 IBMS, brain scans acquired before and after randomisation are examined, using validated methods, for evidence of intracranial bleeding and cerebral ischaemia. The primary outcome is the total volume of intracranial bleeding measured on computed tomography after randomisation, adjusting for baseline bleeding volume. Secondary outcomes include progression of intracranial haemorrhage (from pre- to post-randomisation scans), new intracranial haemorrhage (seen on post- but not pre-randomisation scans), intracranial haemorrhage following neurosurgery, and new focal ischaemic lesions (seen on post-but not pre-randomisation scans). A linear regression model will examine whether receipt of the trial treatment can predict haemorrhage volume. Bleeding volumes and new ischaemic lesions will be compared across treatment groups using relative risks and 95% confidence intervals. The CRASH-3 IBMS will provide an insight into the mechanism of action of tranexamic acid in traumatic brain injury, as well as information about the risks and benefits. Evidence from this trial could inform the management of patients with traumatic brain injury. The CRASH-3 trial was prospectively registered and the CRASH-3 IBMS is an addition to the original protocol registered at the International Standard Randomised Controlled Trials registry ( ISRCTN15088122 ) 19 July 2011, and ClinicalTrials.gov on 25 July 2011 (NCT01402882).

Propofol versus thiopental sodium for the treatment of refractory status epilepticus.

PubMed

Prabhakar, Hemanshu; Bindra, Ashish; Singh, Gyaninder Pal; Kalaivani, Mani

2012-08-15

Failure to respond to antiepileptic drugs in uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome. To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (10 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library 2012), and MEDLINE (1946 to May week 1, 2012). We also searched (10 May 2012) ClinicalTrials.gov, The South Asian Database of Controlled Clinical Trials, and IndMED (a bibliographic database of Indian Medical Journals). All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol. Two review authors screened the search results and reviewed abstracts of relevant and eligible trials before retrieving the full text publications. One study was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE and receiving either propofol or thiopental sodium for the control of seizure activity (Rossetti 2011). This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. There was no evidence of a difference between the drugs with respect to the outcome measures such as control of seizure activity and functional outcome at three months. There is lack of robust and randomised controlled evidence that can clarify the efficacy of propofol and thiopental sodium over each other in the treatment of RSE. There is a need for large, randomised controlled trials for this serious condition.

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.

Targeting intensive versus conventional glycaemic control for type 1 diabetes mellitus: a systematic review with meta-analyses and trial sequential analyses of randomised clinical trials

PubMed Central

Kähler, Pernille; Grevstad, Berit; Almdal, Thomas; Gluud, Christian; Wetterslev, Jørn; Vaag, Allan; Hemmingsen, Bianca

2014-01-01

Objective To assess the benefits and harms of targeting intensive versus conventional glycaemic control in patients with type 1 diabetes mellitus. Design A systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. Data sources The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded and LILACS to January 2013. Study selection Randomised clinical trials that prespecified different targets of glycaemic control in participants at any age with type 1 diabetes mellitus were included. Data extraction Two authors independently assessed studies for inclusion and extracted data. Results 18 randomised clinical trials included 2254 participants with type 1 diabetes mellitus. All trials had high risk of bias. There was no statistically significant effect of targeting intensive glycaemic control on all-cause mortality (risk ratio 1.16, 95% CI 0.65 to 2.08) or cardiovascular mortality (0.49, 0.19 to 1.24). Targeting intensive glycaemic control reduced the relative risks for the composite macrovascular outcome (0.63, 0.41 to 0.96; p=0.03), and nephropathy (0.37, 0.27 to 0.50; p<0.00001. The effect estimates of retinopathy, ketoacidosis and retinal photocoagulation were not consistently statistically significant between random and fixed effects models. The risk of severe hypoglycaemia was significantly increased with intensive glycaemic targets (1.40, 1.01 to 1.94). Trial sequential analyses showed that the amount of data needed to demonstrate a relative risk reduction of 10% were, in general, inadequate. Conclusions There was no significant effect towards improved all-cause mortality when targeting intensive glycaemic control compared with conventional glycaemic control. However, there may be beneficial effects of targeting intensive glycaemic control on the composite macrovascular outcome and on nephropathy, and detrimental effects on severe hypoglycaemia. Notably, the data for retinopathy and ketoacidosis were inconsistent. There was a severe lack of reporting on patient relevant outcomes, and all trials had poor bias control. PMID:25138801

Clinical effectiveness of a patient decision aid to improve decision quality and glycaemic control in people with diabetes making treatment choices: a cluster randomised controlled trial (PANDAs) in general practice

PubMed Central

Mathers, Nigel; Ng, Chirk Jenn; Campbell, Michael Joseph; Colwell, Brigitte; Brown, Ian; Bradley, Alastair

2012-01-01

Objective To determine the effectiveness of a patient decision aid (PDA) to improve decision quality and glycaemic control in people with diabetes making treatment choices using a cluster randomised controlled trial (RCT). Design A cluster RCT. Setting 49 general practices in UK randomised into intervention (n=25) and control (n=24). Participants General practices Inclusion criteria: >4 medical partners; list size >7000; and a diabetes register with >1% of practice population. 191 practices assessed for eligibility, and 49 practices randomised and completed the study. Patients People with type 2 diabetes mellitus (T2DM) taking at least two oral glucose-lowering drugs with maximum tolerated dose with a glycosolated haemoglobin (HbA1c) greater than 7.4% (IFCC HbA1c >57 mmol/mol) or advised in the preceeding 6 months to add or consider changing to insulin therapy. Exclusion criteria: currently using insulin therapy; difficulty reading or understanding English; difficulty in understanding the purpose of the study; visual or cognitive impairment or mentally ill. A total of 182 assessed for eligibility, 175 randomised to 95 intervention and 80 controls, and 167 completion and analysis. Intervention Brief training of clinicians and use of PDA with patients in single consultation. Primary outcomes Decision quality (Decisional Conflict Scores, knowledge, realistic expectations and autonomy) and glycaemic control (glycosolated haemoglobin, HbA1c). Secondary outcomes Knowledge and realistic expectations of the risks and benefits of insulin therapy and diabetic complications. Results Intervention group: lower total Decisional Conflict Scores (17.4 vs 25.2, p<0.001); better knowledge (51.6% vs 28.8%, p<0.001); realistic expectations (risk of ‘hypo’, ‘weight gain’, ‘complications’; 81.0% vs 5.2%, 70.5% vs 5.3%, 26.3% vs 5.0% respectively, p<0.001); and were more autonomous in decision-making (64.1% vs 42.9%, p=0.012). No significant difference in the glycaemic control between the two groups. Conclusions Use of the PANDAs decision aid reduces decisional conflict, improves knowledge, promotes realistic expectations and autonomy in people with diabetes making treatment choices in general practice. ISRCTN Trials Register Number 14842077. PMID:23129571

Continuous versus intermittent endotracheal cuff pressure control for the prevention of ventilator-associated respiratory infections in Vietnam: study protocol for a randomised controlled trial.

PubMed

Dat, Vu Quoc; Geskus, Ronald B; Wolbers, Marcel; Loan, Huynh Thi; Yen, Lam Minh; Binh, Nguyen Thien; Chien, Le Thanh; Mai, Nguyen Thi Hoang; Phu, Nguyen Hoan; Lan, Nguyen Phu Huong; Hao, Nguyen Van; Long, Hoang Bao; Thuy, Tran Phuong; Kinh, Nguyen Van; Trung, Nguyen Vu; Phu, Vu Dinh; Cap, Nguyen Trung; Trinh, Dao Tuyet; Campbell, James; Kestelyn, Evelyne; Wertheim, Heiman F L; Wyncoll, Duncan; Thwaites, Guy Edward; van Doorn, H Rogier; Thwaites, C Louise; Nadjm, Behzad

2018-04-04

Ventilator-associated respiratory infection (VARI) comprises ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT). Although their diagnostic criteria vary, together these are the most common hospital-acquired infections in intensive care units (ICUs) worldwide, responsible for a large proportion of antibiotic use within ICUs. Evidence-based strategies for the prevention of VARI in resource-limited settings are lacking. Preventing the leakage of oropharyngeal secretions into the lung using continuous endotracheal cuff pressure control is a promising strategy. The aim of this study is to investigate the efficacy of automated, continuous endotracheal cuff pressure control in preventing the development of VARI and reducing antibiotic use in ICUs in Vietnam. This is an open-label randomised controlled multicentre trial. We will enrol 600 adult patients intubated for ≤ 24 h at the time of enrolment. Eligible patients will be stratified according to admission diagnosis (180 tetanus, 420 non-tetanus) and site and will be randomised in a 1:1 ratio to receive either (1) automated, continuous control of endotracheal cuff pressure or (2) intermittent measurement and control of endotracheal cuff pressure using a manual cuff pressure meter. The primary outcome is the occurrence of VARI, defined as either VAP or VAT during the ICU admission up to a maximum of 90 days after randomisation. Patients in both groups who are at risk for VARI will receive a standardised battery of investigations if their treating physician feels a new infection has occurred, the results of which will be used by an endpoint review committee, blinded to the allocated arm and independent of patient care, to determine the primary outcome. All enrolled patients will be followed for mortality and endotracheal tube cuff-related complications at 28 days and 90 days after randomisation. Other secondary outcomes include antibiotic use; days ventilated, in ICU and in hospital; inpatient mortality; costs of antibiotics in ICU; duration of ICU stay; and duration of hospital stay. This study will provide high-quality evidence concerning the use of continuous endotracheal cuff pressure control as a method to reduce VARI, antibiotic use and hospitalisation costs and to shorten stay. ClinicalTrials.gov, NCT02966392 . Registered on November 9, 2016. Protocol version: 2.0; issue date March 3, 2017.

Randomised controlled trial of biofeedback training in persistent encopresis with anismus

PubMed Central

Nolan, T.; Catto-Smith, T.; Coffey, C.; Wells, J.

1998-01-01

BACKGROUND—Paradoxical external anal sphincter contraction during attempted defecation (anismus) is thought to be an important contributor to chronic faecal retention and encopresis in children. Biofeedback training can be used to teach children to abolish this abnormal contraction.
METHODS—A randomised controlled trial in medical treatment resistant and/or treatment dependent children with anismus using surface electromyographic (EMG) biofeedback training to determine whether such training produces sustained faecal continence. Up to four sessions of biofeedback training were conducted at weekly intervals for each patient. Anorectal manometry was performed before randomisation and six months later. Parents of patients completed the "child behaviour checklist" (CBCL) before randomisation and at follow up.
RESULTS—Sixty eight children underwent anorectal manometry and EMG. Of these, 29 had anismus (ages 4-14 years) and were randomised to either EMG biofeedback training and conventional medical treatment (BFT) (n = 14) or to conventional medical treatment alone (n = 15). All but one child were able to learn relaxation of the external anal sphincter on attempted defecation. At six months' follow up, laxative free remission had been sustained in two of 14 patients in the BFT group and in two of 15 controls (95% confidence interval (CI) on difference, −24% to 26%). Remission or improvement occurred in four of 14 patients in the BFT group and six of 15 controls (95% CI on difference, −46% to 23%). Of subjects available for repeat anorectal manometry and EMG at six months, six of 13 in the BFT group still demonstrated anismus v 11 of 13 controls (95% CI on difference, −75% to −1%). Of the four patients in full remission at six months, only one (in the BFT group) did not exhibit anismus. Rectal hyposensitivity was not associated with remission or improvement in either of the groups. Mean CBCL total behaviour problem scores were not significantly different between the BFT and control groups, but there was a significant improvement in CBCL school scale scores in the BFT group, and this improvement was significantly greater than that seen in the control group.
CONCLUSIONS—The result of this study, together with those reported in other controlled trials, argues against using biofeedback training in children with encopresis.

 PMID:9797593

Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial.

PubMed

Ellis, Paul; Barrett-Lee, Peter; Johnson, Lindsay; Cameron, David; Wardley, Andrew; O'Reilly, Susan; Verrill, Mark; Smith, Ian; Yarnold, John; Coleman, Robert; Earl, Helena; Canney, Peter; Twelves, Chris; Poole, Christopher; Bloomfield, David; Hopwood, Penelope; Johnston, Stephen; Dowsett, Mitchell; Bartlett, John M S; Ellis, Ian; Peckitt, Clare; Hall, Emma; Bliss, Judith M

2009-05-16

Incorporation of a taxane as adjuvant treatment for early breast cancer offers potential for further improvement of anthracycline-based treatment. The UK TACT study (CRUK01/001) investigated whether sequential docetaxel after anthracycline chemotherapy would improve patient outcome compared with standard chemotherapy of similar duration. In this multicentre, open-label, phase III, randomised controlled trial, 4162 women (aged >18 years) with node-positive or high-risk node-negative operable early breast cancer were randomly assigned by computer-generated permuted block randomisation to receive FEC (fluorouracil 600 mg/m(2), epirubicin 60 mg/m(2), cyclophosphamide 600 mg/m(2) at 3-weekly intervals) for four cycles followed by docetaxel (100 mg/m(2) at 3-weekly intervals) for four cycles (n=2073) or control (n=2089). For the control regimen, centres chose either FEC for eight cycles (n=1265) or epirubicin (100 mg/m(2) at 3-weekly intervals) for four cycles followed by CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) at 4-weekly intervals) for four cycles (n=824). The primary endpoint was disease-free survival. Analysis was by intention to treat (ITT). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN79718493. All randomised patients were included in the ITT population. With a median follow-up of 62 months, disease-free survival events were seen in 517 of 2073 patients in the experimental group compared with 539 of 2089 controls (hazard ratio [HR] 0.95, 95% CI 0.85-1.08; p=0.44). 75.6% (95% CI 73.7-77.5) of patients in the experimental group and 74.3% (72.3-76.2) of controls were alive and disease-free at 5 years. The proportion of patients who reported any acute grade 3 or 4 adverse event was significantly greater in the experimental group than in the control group (p<0.0001); the most frequent events were neutropenia (937 events vs 797 events), leucopenia (507 vs 362), and lethargy (456 vs 272). This study did not show any overall gain from the addition of docetaxel to standard anthracycline chemotherapy. Exploration of predictive biomarker-defined subgroups might have the potential to better target the use of taxane-based therapy. Cancer Research UK (CRUK 01/001), Sanofi-Aventis, Pfizer, and Roche.

Sample size calculation for stepped wedge and other longitudinal cluster randomised trials.

PubMed

Hooper, Richard; Teerenstra, Steven; de Hoop, Esther; Eldridge, Sandra

2016-11-20

The sample size required for a cluster randomised trial is inflated compared with an individually randomised trial because outcomes of participants from the same cluster are correlated. Sample size calculations for longitudinal cluster randomised trials (including stepped wedge trials) need to take account of at least two levels of clustering: the clusters themselves and times within clusters. We derive formulae for sample size for repeated cross-section and closed cohort cluster randomised trials with normally distributed outcome measures, under a multilevel model allowing for variation between clusters and between times within clusters. Our formulae agree with those previously described for special cases such as crossover and analysis of covariance designs, although simulation suggests that the formulae could underestimate required sample size when the number of clusters is small. Whether using a formula or simulation, a sample size calculation requires estimates of nuisance parameters, which in our model include the intracluster correlation, cluster autocorrelation, and individual autocorrelation. A cluster autocorrelation less than 1 reflects a situation where individuals sampled from the same cluster at different times have less correlated outcomes than individuals sampled from the same cluster at the same time. Nuisance parameters could be estimated from time series obtained in similarly clustered settings with the same outcome measure, using analysis of variance to estimate variance components. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Timing of birth for women with a twin pregnancy at term: a randomised controlled trial

PubMed Central

2010-01-01

Background There is a well recognized risk of complications for both women and infants of a twin pregnancy, increasing beyond 37 weeks gestation. Preterm birth prior to 37 weeks gestation is a recognized complication of a twin pregnancy, however, up to 50% of twins will be born after this time. The aims of this randomised trial are to assess whether elective birth at 37 weeks gestation compared with standard care in women with a twin pregnancy affects the risk of perinatal death, and serious infant complications. Methods/Design Design: Multicentred randomised trial. Inclusion Criteria: women with a twin pregnancy at 366 weeks or more without contraindication to continuation of pregnancy. Trial Entry & Randomisation: Following written informed consent, eligible women will be randomised from 36+6 weeks gestation. The randomisation schedule uses balanced variable blocks, with stratification for centre of birth and planned mode of birth. Women will be randomised to either elective birth or standard care. Treatment Schedules: Women allocated to the elective birth group will be planned for elective birth from 37 weeks gestation. Where the plan is for vaginal birth, this will involve induction of labour. Where the plan is for caesarean birth, this will involve elective caesarean section. For women allocated to standard care, birth will be planned for 38 weeks gestation or later. Where the plan is for vaginal birth, this will involve either awaiting the spontaneous onset of labour, or induction of labour if required. Where the plan is for caesarean birth, this will involve elective caesarean section (after 38 and as close to 39 weeks as possible). Primary Study Outcome: A composite of perinatal mortality or serious neonatal morbidity. Sample Size: 460 women with a twin pregnancy to show a reduction in the composite outcome from 16.3% to 6.7% with adjustment for the clustering of twin infants within mothers (p = 0.05, 80% power). Discussion This is a protocol for a randomised trial, the findings of which will contribute information about the optimal time of birth for women with an uncomplicated multiple pregnancy at and beyond 37 weeks gestation. Clinical Trial Registration Current Controlled Trials ISRCTN15761056 PMID:20973989

Minimal access surgery compared with medical management for gastro-oesophageal reflux disease: five year follow-up of a randomised controlled trial (REFLUX)

PubMed Central

Cotton, S C; Boachie, C; Ramsay, C R; Krukowski, Z H; Heading, R C; Campbell, M K

2013-01-01

Objectives To determine the long term clinical effectiveness of laparoscopic fundoplication as an alternative to drug treatment for chronic gastro-oesophageal reflux disease (GORD). Design Five year follow-up of multicentre, pragmatic randomised trial (with parallel non-randomised preference groups). Setting Initial recruitment in 21 UK hospitals. Participants Responders to annual questionnaires among 810 original participants. At entry, all had had GORD for >12 months. Intervention The surgeon chose the type of fundoplication. Medical therapy was reviewed and optimised by a specialist. Subsequent management was at the discretion of the clinician responsible for care, usually in primary care. Main outcome measures Primary outcome measure was self reported quality of life score on disease-specific REFLUX questionnaire. Other measures were health status (with SF-36 and EuroQol EQ-5D questionnaires), use of antireflux medication, and complications. Results By five years, 63% (112/178) of patients randomised to surgery and 13% (24/179) of those randomised to medical management had received a fundoplication (plus 85% (222/261) and 3% (6/192) of those who expressed a preference for surgery and for medical management). Among responders at 5 years, 44% (56/127) of those randomised to surgery were taking antireflux medication versus 82% (98/119) of those randomised to medical management. Differences in the REFLUX score significantly favoured the randomised surgery group (mean difference 8.5 (95% CI 3.9 to 13.1), P<0.001, at five years). SF-36 and EQ-5D scores also favoured surgery, but were not statistically significant at five years. After fundoplication, 3% (12/364) had surgical treatment for a complication and 4% (16) had subsequent reflux-related operations—most often revision of the wrap. Long term rates of dysphagia, flatulence, and inability to vomit were similar in the two randomised groups. Conclusions After five years, laparoscopic fundoplication continued to provide better relief of GORD symptoms than medical management. Adverse effects of surgery were uncommon and generally observed soon after surgery. A small proportion had re-operations. There was no evidence of long term adverse symptoms caused by surgery. Trial registration Current Controlled Trials ISRCTN15517081. PMID:23599318

Development of a practical approach to expert elicitation for randomised controlled trials with missing health outcomes: Application to the IMPROVE trial.

PubMed

Mason, Alexina J; Gomes, Manuel; Grieve, Richard; Ulug, Pinar; Powell, Janet T; Carpenter, James

2017-08-01

The analyses of randomised controlled trials with missing data typically assume that, after conditioning on the observed data, the probability of missing data does not depend on the patient's outcome, and so the data are 'missing at random' . This assumption is usually implausible, for example, because patients in relatively poor health may be more likely to drop out. Methodological guidelines recommend that trials require sensitivity analysis, which is best informed by elicited expert opinion, to assess whether conclusions are robust to alternative assumptions about the missing data. A major barrier to implementing these methods in practice is the lack of relevant practical tools for eliciting expert opinion. We develop a new practical tool for eliciting expert opinion and demonstrate its use for randomised controlled trials with missing data. We develop and illustrate our approach for eliciting expert opinion with the IMPROVE trial (ISRCTN 48334791), an ongoing multi-centre randomised controlled trial which compares an emergency endovascular strategy versus open repair for patients with ruptured abdominal aortic aneurysm. In the IMPROVE trial at 3 months post-randomisation, 21% of surviving patients did not complete health-related quality of life questionnaires (assessed by EQ-5D-3L). We address this problem by developing a web-based tool that provides a practical approach for eliciting expert opinion about quality of life differences between patients with missing versus complete data. We show how this expert opinion can define informative priors within a fully Bayesian framework to perform sensitivity analyses that allow the missing data to depend upon unobserved patient characteristics. A total of 26 experts, of 46 asked to participate, completed the elicitation exercise. The elicited quality of life scores were lower on average for the patients with missing versus complete data, but there was considerable uncertainty in these elicited values. The missing at random analysis found that patients randomised to the emergency endovascular strategy versus open repair had higher average (95% credible interval) quality of life scores of 0.062 (-0.005 to 0.130). Our sensitivity analysis that used the elicited expert information as pooled priors found that the gain in average quality of life for the emergency endovascular strategy versus open repair was 0.076 (-0.054 to 0.198). We provide and exemplify a practical tool for eliciting the expert opinion required by recommended approaches to the sensitivity analyses of randomised controlled trials. We show how this approach allows the trial analysis to fully recognise the uncertainty that arises from making alternative, plausible assumptions about the reasons for missing data. This tool can be widely used in the design, analysis and interpretation of future trials, and to facilitate this, materials are available for download.

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

PubMed

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

2015-08-12

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

The Effectiveness of Disaster Risk Communication: A Systematic Review of Intervention Studies

PubMed Central

Bradley, Declan T; McFarland, Marie; Clarke, Mike

2014-01-01

Introduction: A disaster is a serious disruption to the functioning of a community that exceeds its capacity to cope within its own resources. Risk communication in disasters aims to prevent and mitigate harm from disasters, prepare the population before a disaster, disseminate information during disasters and aid subsequent recovery. The aim of this systematic review is to identify, appraise and synthesise the findings of studies of the effects of risk communication interventions during four stages of the disaster cycle. Methods: We searched the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, PsycInfo, Sociological Abstracts, Web of Science and grey literature sources for randomised trials, cluster randomised trials, controlled and uncontrolled before and after studies, interrupted time series studies and qualitative studies of any method of disaster risk communication to at-risk populations. Outcome criteria were disaster-related knowledge and behaviour, and health outcomes. Results: Searches yielded 5,224 unique articles, of which 100 were judged to be potentially relevant. Twenty-five studies met the inclusion criteria, and two additional studies were identified from other searching. The studies evaluated interventions in all four stages of the disaster cycle, included a variety of man-made, natural and infectious disease disasters, and were conducted in many disparate settings. Only one randomised trial and one cluster randomised trial were identified, with less robust designs used in the other studies. Several studies reported improvements in disaster-related knowledge and behaviour. Discussion: We identified and appraised intervention studies of disaster risk communication and present an overview of the contemporary literature. Most studies used non-randomised designs that make interpretation challenging. We do not make specific recommendations for practice but highlight the need for high-quality randomised trials and appropriately-analysed cluster randomised trials in the field of disaster risk communication where these can be conducted within an appropriate research ethics framework. PMID:25642365

Effect of antidepressant treatment on cognitive impairments associated with depression: a randomised longitudinal study.

PubMed

Shilyansky, Carrie; Williams, Leanne M; Gyurak, Anett; Harris, Anthony; Usherwood, Timothy; Etkin, Amit

2016-05-01

Antidepressant treatment failure is a common problem worldwide. In this study, we assess whether or not an important aspect of depression, cognitive impairment, is untreated by antidepressants by studying the effect of acute antidepressant treatment on a range of cognitive domains. In this randomised longitudinal study, which is part of the International Study to Predict Optimized Treatment in Depression (iSPOT-D) trial, we assessed the effects of acute antidepressant treatment in a large patient population, across clinical remission outcomes, on a range of cognitive domains: attention, response inhibition, executive function during visuospatial navigation, cognitive flexibility, verbal memory, working memory, decision speed, information processing speed, and psychomotor response speed. We enrolled patients from primary or specialty care clinics in a multicentre, international, open-label, randomised, prospective trial. Eligible patients (aged 18-65 years) were previously untreated or were willing to undergo a 1-week medication washout before the study start, and could not have had inadequate response to study medications in the past. We enrolled a large population of medication-free (ie, untreated) outpatients in a depressive episode and assessed them for cognitive function at enrolment (pre-treatment), and again after 8 weeks of treatment with one of three antidepressant drugs (escitalopram, sertraline, or venlafaxine extended-release). Patients were randomly assigned (1:1:1) to one of the three antidepressants using a blocked randomisation procedure (block size of 12). As a comparison group, we also simultaneously enrolled matched healthy participants. Healthy participants received no medication or intervention, but were assessed for change in cognitive and clinical measures during the same interval and testing protocol. Therefore, this group acts as a test-retest control for the primary outcome measure examined in this study, change in cognitive measures over 8 weeks of treatment in depressed patients. This study is registered with ClinicalTrials.gov, number NCT00693849. Between Dec 8, 2008, and Sept 30, 2011, we enrolled 1008 eligible people into the study. Impairment in five domains-attention, response inhibition, verbal memory, decision speed, and information processing-showed no relative improvement with acute treatment (controlling for time or repeated testing), irrespective of antidepressant treatment group, even in patients whose depression remitted acutely according to clinical measures. Broader cognitive impairment was associated with greater illness chronicity (earlier illness onset) but not with symptom severity or previous antidepressant failures. Depression is associated with impairments in higher-order cognitive functions and information processing, which persist independently of clinical symptom change with treatment. We recorded no difference between the three antidepressants tested, with none showing efficacy for these impairments. Although the 8-week treatment period limits interpretation to acute treatment effects, it does highlight cognitive impairment as an untargeted contributor to incomplete treatment success. Brain Resource Company Operations Pty Ltd and NIH. Copyright © 2016 Elsevier Ltd. All rights reserved.

Audiovisual biofeedback breathing guidance for lung cancer patients receiving radiotherapy: a multi-institutional phase II randomised clinical trial.

PubMed

Pollock, Sean; O'Brien, Ricky; Makhija, Kuldeep; Hegi-Johnson, Fiona; Ludbrook, Jane; Rezo, Angela; Tse, Regina; Eade, Thomas; Yeghiaian-Alvandi, Roland; Gebski, Val; Keall, Paul J

2015-07-18

There is a clear link between irregular breathing and errors in medical imaging and radiation treatment. The audiovisual biofeedback system is an advanced form of respiratory guidance that has previously demonstrated to facilitate regular patient breathing. The clinical benefits of audiovisual biofeedback will be investigated in an upcoming multi-institutional, randomised, and stratified clinical trial recruiting a total of 75 lung cancer patients undergoing radiation therapy. To comprehensively perform a clinical evaluation of the audiovisual biofeedback system, a multi-institutional study will be performed. Our methodological framework will be based on the widely used Technology Acceptance Model, which gives qualitative scales for two specific variables, perceived usefulness and perceived ease of use, which are fundamental determinants for user acceptance. A total of 75 lung cancer patients will be recruited across seven radiation oncology departments across Australia. Patients will be randomised in a 2:1 ratio, with 2/3 of the patients being recruited into the intervention arm and 1/3 in the control arm. 2:1 randomisation is appropriate as within the interventional arm there is a screening procedure where only patients whose breathing is more regular with audiovisual biofeedback will continue to use this system for their imaging and treatment procedures. Patients within the intervention arm whose free breathing is more regular than audiovisual biofeedback in the screen procedure will remain in the intervention arm of the study but their imaging and treatment procedures will be performed without audiovisual biofeedback. Patients will also be stratified by treating institution and for treatment intent (palliative vs. radical) to ensure similar balance in the arms across the sites. Patients and hospital staff operating the audiovisual biofeedback system will complete questionnaires to assess their experience with audiovisual biofeedback. The objectives of this clinical trial is to assess the impact of audiovisual biofeedback on breathing motion, the patient experience and clinical confidence in the system, clinical workflow, treatment margins, and toxicity outcomes. This clinical trial marks an important milestone in breathing guidance studies as it will be the first randomised, controlled trial providing the most comprehensive evaluation of the clinical impact of breathing guidance on cancer radiation therapy to date. This study is powered to determine the impact of AV biofeedback on breathing regularity and medical image quality. Objectives such as determining the indications and contra-indications for the use of AV biofeedback, evaluation of patient experience, radiation toxicity occurrence and severity, and clinician confidence will shed light on the design of future phase III clinical trials. This trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), its trial ID is ACTRN12613001177741 .

A systematic review of randomised controlled trials evaluating the effect of mother/baby skin-to-skin care on successful breast feeding.

PubMed

Carfoot, Sue; Williamson, Paula R; Dickson, Rumona

2003-06-01

to examine the effects of early skin-to-skin contact between mother and baby on the initiation and duration of breast feeding. electronic databases--the Cochrane Library, MEDLINE,CINAHL and EMBASE. References of studies were examined to identify additional trials and contact was made with researchers in the field. Study selection criteria: randomised or quasi-randomised controlled trials in any language in which skin-to-skin contact between mothers and their healthy full-term newborn babies was compared to routine contact. Primary outcomes were success of first breast feed and duration of breast feeding. Secondary outcomes included, baby temperature and behaviour. STUDY-QUALITY ASSESSMENT: validity of included studies was assessed using criteria defined by the Cochrane Collaboration. Application of inclusion criteria, validity assessment and data extraction were carried out independently by two reviewers with a third reviewer to resolve differences. seven randomised controlled trials were identified. Five studies assessed duration of breast feeding with mixed results. None of the studies assessed the success of the first breast-feeding experience. Study quality was variable with methods of randomisation and blinding of assessment unclear in four of the five studies providing relevant results. the findings of this systematic review fail to support the current initiatives to implement changes in clinical practice to include skin-to-skin contact. Methodological flaws within the included studies prohibit firm conclusions being reached with regard to the effect of skin-to-skin contact on the duration of breast feeding, timing of first breast feed or baby physiological factors. The review highlights the need for further primary research to assess the effect of skin-to-skin contact on the breast-feeding experience.

Total or Partial Knee Arthroplasty Trial - TOPKAT: study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background In the majority of patients with osteoarthritis of the knee the disease originates in the medial compartment. There are two fundamentally different approaches to knee replacement for patients with unicompartmental disease: some surgeons feel that it is always best to replace both the knee compartments with a total knee replacement (TKR); whereas others feel it is best to replace just the damaged component of the knee using a partial or unicompartment replacement (UKR). Both interventions are established and well-documented procedures. Little evidence exists to prove the clinical and cost-effectiveness of either management option. This provides an explanation for the high variation in treatment of choice by individual surgeons for the same knee pathology. The aim of the TOPKAT study will be to assess the clinical and cost effectiveness of TKRs compared to UKRs in patients with medial compartment osteoarthritis. Methods/Design The design of the study is a single layer multicentre superiority type randomised controlled trial of unilateral knee replacement patients. Blinding will not be possible as the surgical scars for each procedure differ. We aim to recruit 500 patients from approximately 28 secondary care orthopaedic units from across the UK including district general and teaching hospitals. Participants will be randomised to either UKR or TKR. Randomisation will occur using a web-based randomisation system. The study is pragmatic in terms of implant selection for the knee replacement operation. Participants will be followed up for 5 years. The primary outcome is the Oxford Knee Score, which will be collected via questionnaires at 2 months, 1 year and then annually to 5 years. Secondary outcomes will include cost-effectiveness, patient satisfaction and complications data. Trial registration Current Controlled Trials ISRCTN03013488; ClinicalTrials.gov Identifier: NCT01352247 PMID:24028414

Effect of training and lifting equipment for preventing back pain in lifting and handling: systematic review

PubMed Central

2008-01-01

Objectives To determine whether advice and training on working techniques and lifting equipment prevent back pain in jobs that involve heavy lifting. Data sources Medline, Embase, CENTRAL, Cochrane Back Group’s specialised register, CINAHL, Nioshtic, CISdoc, Science Citation Index, and PsychLIT were searched up to September-November 2005. Review methods The primary search focused on randomised controlled trials and the secondary search on cohort studies with a concurrent control group. Interventions aimed to modify techniques for lifting and handling heavy objects or patients and including measurements for back pain, consequent disability, or sick leave as the main outcome were considered for the review. Two authors independently assessed eligibility of the studies and methodological quality of those included. For data synthesis, we summarised the results of studies comparing similar interventions. We used odds ratios and effect sizes to combine the results in a meta-analysis. Finally, we compared the conclusions of the primary and secondary analyses. Results Six randomised trials and five cohort studies met the inclusion criteria. Two randomised trials and all cohort studies were labelled as high quality. Eight studies looked at lifting and moving patients, and three studies were conducted among baggage handlers or postal workers. Those in control groups received no intervention or minimal training, physical exercise, or use of back belts. None of the comparisons in randomised trials (17 720 participants) yielded significant differences. In the secondary analysis, none of the cohort studies (772 participants) had significant results, which supports the results of the randomised trials. Conclusions There is no evidence to support use of advice or training in working techniques with or without lifting equipment for preventing back pain or consequent disability. The findings challenge current widespread practice of advising workers on correct lifting technique. PMID:18244957

Metformin and dietary advice to improve insulin sensitivity and promote gestational restriction of weight among pregnant women who are overweight or obese: the GRoW Randomised Trial.

PubMed

Dodd, Jodie M; Grivell, Rosalie M; Deussen, Andrea R; Dekker, Gustaaf; Louise, Jennie; Hague, William

2016-11-21

Obesity is a significant global health problem, with approximately 50% of women entering pregnancy having a body mass index greater than or equal to 25 kg/m 2 . Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant. Currently available data from large scale randomised trials and systematic reviews highlight only modest effects of antenatal dietary and lifestyle interventions in limiting gestational weight gain, with little impact on clinically relevant pregnancy outcomes. Further information evaluating alternative strategies is required. The aims of this randomised controlled trial are to assess whether the use of metformin as an adjunct therapy to dietary and lifestyle advice for overweight and obese women during pregnancy is effective in improving maternal, fetal and infant health outcomes. Design: Multicentre randomised, controlled trial. Women with a singleton, live gestation between 10 +0 -20 +0 weeks who are obese or overweight (defined as body mass index greater than or equal to 25 kg/m 2 ), at the first antenatal visit. Trial Entry & Randomisation: Eligible, consenting women will be randomised between 10 +0 and 20 +0 weeks gestation using an online computer randomisation system, and randomisation schedule prepared by non-clinical research staff with balanced variable blocks. Stratification will be according to maternal BMI at trial entry, parity, and centre where planned to give birth. Treatment Schedules: Women randomised to the Metformin Group will receive a supply of 500 mg oral metformin tablets. Women randomised to the Placebo Group will receive a supply of identical appearing and tasting placebo tablets. Women will be instructed to commence taking one tablet daily for a period of one week, increasing to a maximum of two tablets twice daily over four weeks and then continuing until birth. Women, clinicians, researchers and outcome assessors will be blinded to the allocated treatment group. All women will receive three face-to-face sessions (two with a research dietitian and one with a trained research assistant), and three telephone calls over the course of their pregnancy, in which they will be provided with dietary and lifestyle advice, and encouraged to make change utilising a SMART goals approach. Primary Study Outcome: infant birth weight >4000 grams. 524 women to detect a difference from 15.5% to 7.35% reduction in infants with birth weight >4000 grams (p = 0.05, 80% power, two-tailed). This is a protocol for a randomised trial. The findings will contribute to the development of evidence based clinical practice guidelines. Australian and New Zealand Clinical Trials Registry ACTRN12612001277831 , prospectively registered 10 th of December, 2012.

Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial.

PubMed

Pujade-Lauraine, Eric; Ledermann, Jonathan A; Selle, Frédéric; Gebski, Val; Penson, Richard T; Oza, Amit M; Korach, Jacob; Huzarski, Tomasz; Poveda, Andrés; Pignata, Sandro; Friedlander, Michael; Colombo, Nicoletta; Harter, Philipp; Fujiwara, Keiichi; Ray-Coquard, Isabelle; Banerjee, Susana; Liu, Joyce; Lowe, Elizabeth S; Bloomfield, Ralph; Pautier, Patricia

2017-09-01

Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has previously shown efficacy in a phase 2 study when given in capsule formulation to all-comer patients with platinum-sensitive, relapsed high-grade serous ovarian cancer. We aimed to confirm these findings in patients with a BRCA1 or BRCA2 (BRCA1/2) mutation using a tablet formulation of olaparib. This international, multicentre, double-blind, randomised, placebo-controlled, phase 3 trial evaluated olaparib tablet maintenance treatment in platinum-sensitive, relapsed ovarian cancer patients with a BRCA1/2 mutation who had received at least two lines of previous chemotherapy. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status at baseline of 0-1 and histologically confirmed, relapsed, high-grade serous ovarian cancer or high-grade endometrioid cancer, including primary peritoneal or fallopian tube cancer. Patients were randomly assigned 2:1 to olaparib (300 mg in two 150 mg tablets, twice daily) or matching placebo tablets using an interactive voice and web response system. Randomisation was stratified by response to previous platinum chemotherapy (complete vs partial) and length of platinum-free interval (6-12 months vs ≥12 months) and treatment assignment was masked for patients, those giving the interventions, data collectors, and data analysers. The primary endpoint was investigator-assessed progression-free survival and we report the primary analysis from this ongoing study. The efficacy analyses were done on the intention-to-treat population; safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01874353, and is ongoing and no longer recruiting patients. Between Sept 3, 2013, and Nov 21, 2014, we enrolled 295 eligible patients who were randomly assigned to receive olaparib (n=196) or placebo (n=99). One patient in the olaparib group was randomised in error and did not receive study treatment. Investigator-assessed median progression-free survival was significantly longer with olaparib (19·1 months [95% CI 16·3-25·7]) than with placebo (5·5 months [5·2-5·8]; hazard ratio [HR] 0·30 [95% CI 0·22-0·41], p<0·0001). The most common adverse events of grade 3 or worse severity were anaemia (38 [19%] of 195 patients in the olaparib group vs two [2%] of 99 patients in the placebo group), fatigue or asthenia (eight [4%] vs two [2%]), and neutropenia (ten [5%] vs four [4%]). Serious adverse events were experienced by 35 (18%) patients in the olaparib group and eight (8%) patients in the placebo group. The most common in the olaparib group were anaemia (seven [4%] patients), abdominal pain (three [2%] patients), and intestinal obstruction (three [2%] patients). The most common in the placebo group were constipation (two [2%] patients) and intestinal obstruction (two [2%] patients). One (1%) patient in the olaparib group had a treatment-related adverse event (acute myeloid leukaemia) with an outcome of death. Olaparib tablet maintenance treatment provided a significant progression-free survival improvement with no detrimental effect on quality of life in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Apart from anaemia, toxicities with olaparib were low grade and manageable. AstraZeneca. Copyright © 2017 Elsevier Ltd. All rights reserved.

An evaluation of Croí MyAction community lifestyle modification programme compared to standard care to reduce progression to diabetes/pre-diabetes in women with prior gestational diabetes mellitus (GDM): study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Universal screening using the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria has identified a prevalence of gestational diabetes mellitus (GDM) of 12.4% in women living in Ireland. Women with prior GDM are at increased risk of developing type 2 diabetes later in life. A number of risk factors linked to the development of type 2 diabetes are potentially modifiable through lifestyle and behaviour changes, and medical management. No previous Irish studies have adequately investigated the efficacy of lifestyle intervention programmes in reducing these risk factors in women with prior GDM. Through a two-group, parallel randomised controlled trial (RCT), this study aims to assess the clinical impact, cost-effectiveness and psychological experience of the Croí MyAction intensive lifestyle modification programme for women with prior GDM. Methods/Design A total of 54 women with a history of GDM and persistent post-partum glucose dysfunction (impaired glucose tolerance (IGT) or impaired fasting glucose (IFG)), are randomly assigned to a control arm (n = 27) or to the Croí MyAction intervention group (n = 27). The control arm receives usual health care advice - written information on diet and lifestyle changes for reducing diabetes risks and visits with general practitioners as required. The intervention group receives usual health care as per the control group in addition to attending a 12-week intensive lifestyle modification programme known as Croí MyAction. Croí MyAction involves 2.5 hour sessions once per week (for 12 weeks) comprising a group exercise programme, group health promotion or education seminars, and one-to-one meetings with a multidisciplinary health care team to personalise risk factor reductions. Randomisation and allocation to the intervention arms is carried out by an independent researcher, ensuring that the allocation sequence is concealed from study researchers until the interventions are assigned. The primary analysis is based on glucose dysfunction, comparing a mean reduction in fasting plasma glucose (FPG) levels on a 75 gram oral glucose tolerance test (OGTT) in the two groups at a one-year, post-intervention follow-up. The trial is funded by the Irish Health Research Board (HRB). Ethics approval was obtained on 27 March 2012 from the Clinical Research Ethics Committee, Galway University Hospitals, Health Service Executive of Ireland (Ref: C.A.691). Trial registration Current Controlled Trials ISRCTN41202110. PMID:23782471

An evaluation of Croí MyAction community lifestyle modification programme compared to standard care to reduce progression to diabetes/pre-diabetes in women with prior gestational diabetes mellitus (GDM): study protocol for a randomised controlled trial.

PubMed

Infanti, Jennifer J; Dunne, Fidelma P; O'Dea, Angela; Gillespie, Paddy; Gibson, Irene; Glynn, Liam G; Noctor, Eoin; Newell, John; McGuire, Brian E

2013-05-02

Universal screening using the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria has identified a prevalence of gestational diabetes mellitus (GDM) of 12.4% in women living in Ireland. Women with prior GDM are at increased risk of developing type 2 diabetes later in life. A number of risk factors linked to the development of type 2 diabetes are potentially modifiable through lifestyle and behaviour changes, and medical management. No previous Irish studies have adequately investigated the efficacy of lifestyle intervention programmes in reducing these risk factors in women with prior GDM. Through a two-group, parallel randomised controlled trial (RCT), this study aims to assess the clinical impact, cost-effectiveness and psychological experience of the Croí MyAction intensive lifestyle modification programme for women with prior GDM. A total of 54 women with a history of GDM and persistent post-partum glucose dysfunction (impaired glucose tolerance (IGT) or impaired fasting glucose (IFG)), are randomly assigned to a control arm (n=27) or to the Croí MyAction intervention group (n=27). The control arm receives usual health care advice--written information on diet and lifestyle changes for reducing diabetes risks and visits with general practitioners as required. The intervention group receives usual health care as per the control group in addition to attending a 12-week intensive lifestyle modification programme known as Croí MyAction. Croí MyAction involves 2.5 hour sessions once per week (for 12 weeks) comprising a group exercise programme, group health promotion or education seminars, and one-to-one meetings with a multidisciplinary health care team to personalise risk factor reductions. Randomisation and allocation to the intervention arms is carried out by an independent researcher, ensuring that the allocation sequence is concealed from study researchers until the interventions are assigned. The primary analysis is based on glucose dysfunction, comparing a mean reduction in fasting plasma glucose (FPG) levels on a 75 gram oral glucose tolerance test (OGTT) in the two groups at a one-year, post-intervention follow-up. The trial is funded by the Irish Health Research Board (HRB). Ethics approval was obtained on 27 March 2012 from the Clinical Research Ethics Committee, Galway University Hospitals, Health Service Executive of Ireland (Ref: C.A.691). Current Controlled Trials ISRCTN41202110.

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.

Physical therapy for Bell s palsy (idiopathic facial paralysis).

PubMed

Teixeira, Lázaro Juliano; Soares, Bernardo Garcia de Oliveira; Vieira, Vanessa Pedrosa; Prado, Gilmar F

2008-07-16

Bell's palsy (idiopathic facial paralysis) is commonly treated by physical therapy services with various therapeutic strategies and devices. There are many questions about their efficacy and effectiveness. To evaluate the efficacy of physical therapies on the outcome of Bell's palsy. We searched the Cochrane Neuromuscular Disease Group Trials Register (February 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2007), MEDLINE (January 1966 to February 2008), EMBASE (January 1980 to February 2008), LILACS (January 1982 to February 2008), PEDro (from 1929 to February 2008), and CINAHL (January 1982 to February 2008). We selected randomised or quasi-randomised controlled trials involving any physical therapy. We included participants of any age with a diagnosis of Bell's palsy and all degrees of severity. The outcome measures were: incomplete recovery six months after randomisation, motor synkinesis, crocodile tears or facial spasm six months after onset, incomplete recovery after one year and adverse effects attributable to the intervention. Titles and abstracts identified from the register were scrutinized. The assessment of methodological quality took into account secure method of randomisation, allocation concealment, observer blinding, patient blinding, differences at baseline of the experimental groups, and completeness of follow-up. Data were extracted using a specially constructed data extraction form. Separate subgroup analyses of participants with more and less severe disability were undertaken. The search identified 45 potentially relevant articles. Six studies met the inclusion criteria. Three trials studied the efficacy of electrostimulation (294 participants) and three exercises (253 participants). Neither treatment produced significantly more improvement than the control treatment or no treatment. There was limited evidence that improvement began earlier in the exercise group. There is no evidence of significant benefit or harm from any physical therapy for idiopathic facial paralysis. The possibility that facial exercise reduces time to recover and sequelae needs confirming with good quality randomised controlled trials.

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 LeucoPatch® system in the management of hard-to-heal diabetic foot ulcers: study protocol for a randomised controlled trial.

PubMed

Game, Frances; Jeffcoate, William; Tarnow, Lise; Day, Florence; Fitzsimmons, Deborah; Jacobsen, Judith

2017-10-10

Diabetic foot ulcers are a common and severe complication of diabetes mellitus. Standard treatment includes debridement, offloading, management of infection and revascularisation where appropriate, although healing times may be long. The LeucoPatch® device is used to generate an autologous platelet-rich fibrin and leucocyte wound dressing produced from the patient's own venous blood by centrifugation, but without the addition of any reagents. The final product comprises a thin, circular patch composed predominantly of fibrin together with living platelets and leucocytes. Promising results have been obtained in non-controlled studies this system, but this now needs to be tested in a randomised controlled trial (RCT). If confirmed, the LeucoPatch® may become an important new tool in the armamentarium in the management of diabetic foot ulcers which are hard-to-heal. People with diabetes and hard-to-heal ulcers of the foot will receive either pre-specified good standard care or good standard care supplemented by the application of the LeucoPatch® device. The primary outcome will be the percentage of ulcers healed within 20 weeks. Healing will be defined as complete epithelialisation without discharge that is maintained for 4 weeks and is confirmed by an observer blind to randomisation group. Ulcers of the foot are a major source of morbidity to patients with diabetes and costs to health care economies. The study population is designed to be as inclusive as possible with the aim of maximising the external validity of any findings. The primary outcome measure is healing within 20 weeks of randomisation and the trial also includes a number of secondary outcome measures. Among these are rate of change in ulcer area as a predictor of the likelihood of eventual healing, minor and major amputation of the target limb, the incidence of infection and quality of life. International Standard Randomised Controlled Trial, ISRCTN27665670 . Registered on 5 July 2013.

Are we drawing the right conclusions from randomised placebo-controlled trials? A post-hoc analysis of data from a randomised controlled trial

PubMed Central

2009-01-01

Background Assumptions underlying placebo controlled trials include that the placebo effect impacts on all study arms equally, and that treatment effects are additional to the placebo effect. However, these assumptions have recently been challenged, and different mechanisms may potentially be operating in the placebo and treatment arms. The objective of the current study was to explore the nature of placebo versus pharmacological effects by comparing predictors of the placebo response with predictors of the treatment response in a randomised, placebo-controlled trial of a phytotherapeutic combination for the treatment of menopausal symptoms. A substantial placebo response was observed but no significant difference in efficacy between the two arms. Methods A post hoc analysis was conducted on data from 93 participants who completed this previously published study. Variables at baseline were investigated as potential predictors of the response on any of the endpoints of flushing, overall menopausal symptoms and depression. Focused tests were conducted using hierarchical linear regression analyses. Based on these findings, analyses were conducted for both groups separately. These findings are discussed in relation to existing literature on placebo effects. Results Distinct differences in predictors were observed between the placebo and active groups. A significant difference was found for study entry anxiety, and Greene Climacteric Scale (GCS) scores, on all three endpoints. Attitude to menopause was found to differ significantly between the two groups for GCS scores. Examination of the individual arms found anxiety at study entry to predict placebo response on all three outcome measures individually. In contrast, low anxiety was significantly associated with improvement in the active treatment group. None of the variables found to predict the placebo response was relevant to the treatment arm. Conclusion This study was a post hoc analysis of predictors of the placebo versus treatment response. Whilst this study does not explore neurobiological mechanisms, these observations are consistent with the hypotheses that 'drug' effects and placebo effects are not necessarily additive, and that mutually exclusive mechanisms may be operating in the two arms. The need for more research in the area of mechanisms and mediators of placebo versus active responses is supported. Trial Registration International Clinical Trials Registry ISRCTN98972974. PMID:19549306

Case Method in COPD education for primary care physicians: study protocol for a cluster randomised controlled trial.

PubMed

Sandelowsky, Hanna; Krakau, Ingvar; Modin, Sonja; Ställberg, Björn; Nager, Anna

2017-04-27

Chronic obstructive pulmonary disease (COPD) is a common cause of morbidity and mortality worldwide. It is often undiagnosed and insufficiently managed. Effective forms of continuing medical education (CME) for primary care physicians (PCPs) are necessary to ensure the implementation of guidelines in clinical practice and, thus, improve patients' health. In this study, we will measure the effects of CME by Case Method and compare them against those of traditional lectures and no CME at all through an unblinded, cluster randomised controlled trial (CRCT). Thirty-three primary health care centres (PHCCs) in Stockholm, Sweden, with a total of 180 PCPs will be involved. Twenty-two primary PHCCs, will be cluster-randomised into: an intervention group who will receive CME by Case Method (n = 11) and a control group who will receive traditional lectures (n = 11). The remaining PHCCs (n = 11) will be a reference group and will receive no CME. From the intervention and control groups, 460 randomly selected patients with COPD in GOLD stages 2 and 3 will participate, while no patients will be recruited from the reference group. For the patients, smoking status, actual treatment and urgent visits to a health provider due to airway problems will be registered. For the PCPs, professional competence (i.e. knowledge and management skills) in COPD, will be measured using a questionnaire based on current guidelines and guideline implementation problems in clinical practice which has previously been described by the authors. Data will be collected at baseline and at follow-up, which will be after 1.5 years for the patients, and 1 year for the PCPs. Statistical methods for individual-level and cluster-level analyses will be used. COPD is considered a particularly complex clinical challenge involving managing multimorbidity, symptom adaptation, and lifestyle problematisation. Case Method in CME for PCPs may contribute to a better understanding of the impact of COPD on patients' lives and, thus, improve their management of it. The present study is expected to contribute scientific knowledge about indicators for an effective CME in COPD that is tailor-made to primary care physicians. ClinicalTrials.gov, identifier: NCT02213809 . Registered on 10 August 2014. Protocol version: Issue date: May 2014.