The effect of pelvic physiotherapy on reduction of functional constipation in children: design of a multicentre randomised controlled trial.

PubMed

van Engelenburg-van Lonkhuyzen, Marieke L; Bols, Esther M J; Benninga, Marc A; Verwijs, Wim A; Bluijssen, Netty M W L; de Bie, Rob A

2013-08-02

Functional constipation is a common disorder worldwide and is found in all paediatric age groups. Functional constipation can be caused by delayed colonic transit or dysfunction of the pelvic floor muscles. Standard medical care in paediatric practice is often based on clinical experience and mainly consists of a behavioural approach and toilet training, along with the prescription of laxatives. Evidence to evaluate the effectiveness of pelvic physiotherapy for this complaint is lacking. A two-armed multicentre randomised controlled trial has been designed. We hypothesise that the combination of pelvic physiotherapy and standard medical care will be more effective than standard medical care alone for constipated children, aged 5 to 17 years. Children with functional constipation according to the Rome III will be included. Web-based baseline and follow-up measurements, scheduled at 3 and 6 months after inclusion, consist of the numeric rating scale in relation to the perceived severity of the problem, the Strength and Difficulties Questionnaire and subjective improvement post-intervention (global perceived effect). Examination of the pelvic floor muscle functions, including digital testing and biofeedback, will take place during baseline and follow-up measurements at the physiotherapist. The control group will only receive standard medical care, involving at least three contacts during five months, whereas the experimental group will receive standard medical care plus pelvic physiotherapy, with a maximum of six contacts. The physiotherapy intervention will include standard medical care, pelvic floor muscle training, attention to breathing, relaxation and awareness of body and posture. The study duration will be six months from randomisation, with a three-year recruitment period. The primary outcome is the absence of functional constipation according to the Rome III criteria. This section discusses the relevance of publishing the study design and the development of the presented physiotherapy protocol. It also addresses difficulties when interpreting the literature with regard to the effectiveness of biofeedback, potential confounding, and future research indications. To our knowledge, this article is the first to describe the design of a randomised controlled trial among children with constipation to assess the effect of pelvic physiotherapy as an add-on to standard medical care. Current Controlled Trials NL30551.068.09.

The effect of pelvic physiotherapy on reduction of functional constipation in children: design of a multicentre randomised controlled trial

PubMed Central

2013-01-01

Background Functional constipation is a common disorder worldwide and is found in all paediatric age groups. Functional constipation can be caused by delayed colonic transit or dysfunction of the pelvic floor muscles. Standard medical care in paediatric practice is often based on clinical experience and mainly consists of a behavioural approach and toilet training, along with the prescription of laxatives. Evidence to evaluate the effectiveness of pelvic physiotherapy for this complaint is lacking. Methods/design A two-armed multicentre randomised controlled trial has been designed. We hypothesise that the combination of pelvic physiotherapy and standard medical care will be more effective than standard medical care alone for constipated children, aged 5 to 17 years. Children with functional constipation according to the Rome III will be included. Web-based baseline and follow-up measurements, scheduled at 3 and 6 months after inclusion, consist of the numeric rating scale in relation to the perceived severity of the problem, the Strength and Difficulties Questionnaire and subjective improvement post-intervention (global perceived effect). Examination of the pelvic floor muscle functions, including digital testing and biofeedback, will take place during baseline and follow-up measurements at the physiotherapist. The control group will only receive standard medical care, involving at least three contacts during five months, whereas the experimental group will receive standard medical care plus pelvic physiotherapy, with a maximum of six contacts. The physiotherapy intervention will include standard medical care, pelvic floor muscle training, attention to breathing, relaxation and awareness of body and posture. The study duration will be six months from randomisation, with a three-year recruitment period. The primary outcome is the absence of functional constipation according to the Rome III criteria. Discussion This section discusses the relevance of publishing the study design and the development of the presented physiotherapy protocol. It also addresses difficulties when interpreting the literature with regard to the effectiveness of biofeedback, potential confounding, and future research indications. To our knowledge, this article is the first to describe the design of a randomised controlled trial among children with constipation to assess the effect of pelvic physiotherapy as an add-on to standard medical care. Trial registration Current Controlled Trials NL30551.068.09 PMID:23914827

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

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.

Ethical considerations in placebo-controlled randomised clinical trials.

PubMed

Kaufman, Kenneth R

2015-06-01

Ethical considerations in standard medical care and clinical research are underpinnings to quality medicine. Similarly, the placebo-controlled double-blind randomised clinical trial is the gold standard for medical research and fundamental to the development of evidence-based medicine. Researchers and clinicians are challenged by ethical concerns in the informed consent with a need to maximise understanding and minimise therapeutic misconception. This editorial expands on themes raised by Chen et al 's article 'Disclosing the Potential Impact of Placebo Controls in Antidepressant Trials' and serves as an invitation for further submissions to BJPsych Open on ethics, research design and informed consent. None. © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Frontal lesions predict response to prism adaptation treatment in spatial neglect: A randomised controlled study.

PubMed

Goedert, Kelly M; Chen, Peii; Foundas, Anne L; Barrett, A M

2018-03-20

Spatial neglect commonly follows right hemisphere stroke. It is defined as impaired contralesional stimulus detection, response, or action, causing functional disability. While prism adaptation treatment is highly promising to promote functional recovery of spatial neglect, not all individuals respond. Consistent with a primary effect of prism adaptation on spatial movements, we previously demonstrated that functional improvement after prism adaptation treatment is linked to frontal lobe lesions. However, that study was a treatment-only study with no randomised control group. The current study randomised individuals with spatial neglect to receive 10 days of prism adaptation treatment or to receive only standard care (control group). Replicating our earlier results, we found that the presence of frontal lesions moderated response to prism adaptation treatment: among prism-treated patients, only those with frontal lesions demonstrated functional improvements in their neglect symptoms. Conversely, among individuals in the standard care control group, the presence of frontal lesions did not modify recovery. These results suggest that further research is needed on how frontal lesions may predict response to prism adaptation treatment. Additionally, the results help elucidate the neural network involved in spatial movement and could be used to aid decisions about treatment.

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.

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.

Prevention and treatment of long-term social disability amongst young people with emerging severe mental illness with social recovery therapy (The PRODIGY Trial): study protocol for a randomised controlled trial.

PubMed

Fowler, David; French, Paul; Banerjee, Robin; Barton, Garry; Berry, Clio; Byrne, Rory; Clarke, Timothy; Fraser, Rick; Gee, Brioney; Greenwood, Kathryn; Notley, Caitlin; Parker, Sophie; Shepstone, Lee; Wilson, Jon; Yung, Alison R; Hodgekins, Joanne

2017-07-11

Young people who have social disability associated with severe and complex mental health problems are an important group in need of early intervention. Their problems often date back to childhood and become chronic at an early age. Without intervention, the long-term prognosis is often poor and the economic costs very large. There is a major gap in the provision of evidence-based interventions for this group, and therefore new approaches to detection and intervention are needed. This trial provides a definitive evaluation of a new approach to early intervention with young people with social disability and severe and complex mental health problems using social recovery therapy (SRT) over a period of 9 months to improve mental health and social recovery outcomes. This is a pragmatic, multi-centre, single blind, superiority randomised controlled trial. It is conducted in three sites in the UK: Sussex, Manchester and East Anglia. Participants are aged 16 to 25 and have both persistent and severe social disability (defined as engaged in less than 30 hours per week of structured activity) and severe and complex mental health problems. The target sample size is 270 participants, providing 135 participants in each trial arm. Participants are randomised 1:1 using a web-based randomisation system and allocated to either SRT plus optimised treatment as usual (enhanced standard care) or enhanced standard care alone. The primary outcome is time use, namely hours spent in structured activity per week at 15 months post-randomisation. Secondary outcomes assess typical mental health problems of the group, including subthreshold psychotic symptoms, negative symptoms, depression and anxiety. Time use, secondary outcomes and health economic measures are assessed at 9, 15 and 24 months post-randomisation. This definitive trial will be the first to evaluate a novel psychological treatment for social disability and mental health problems in young people presenting with social disability and severe and complex non-psychotic mental health problems. The results will have important implications for policy and practice in the detection and early intervention for this group in mental health services. Trial Registry: International Standard Randomised Controlled Trial Number (ISRCTN) Registry. ISRCTN47998710 (registered 29/11/2012).

The MATISSE study: a randomised trial of group art therapy for people with schizophrenia

PubMed Central

2010-01-01

Background Art Therapy has been promoted as a means of helping people who may find it difficult to express themselves verbally engage in psychological treatment. Group Art Therapy has been widely used as an adjunctive treatment for people with schizophrenia but there have been few attempts to examine its effects and cost effectiveness has not been examined. The MATISSE study aims to evaluate the clinical and cost effectiveness of group Art Therapy for people with schizophrenia. Method/Design The MATISSE study is a three-arm, parallel group, pragmatic, randomised, controlled trial of referral to group Art Therapy plus standard care, referral to an attention control 'activity' group plus standard care, or standard care alone. Study participants were recruited from inpatient and community-based mental health and social care services at four centres in England and Northern Ireland. Participants were aged over 18 years with a clinical diagnosis of schizophrenia, confirmed by an examination of case notes using operationalised criteria. Participants were then randomised via an independent and remote telephone randomisation service using permuted stacked blocks, stratified by site. Art Therapy and activity groups were made available to participants once a week for up to 12 months. Outcome measures were assessed by researchers masked to allocation status at 12 and 24 months after randomisation. Participants and care givers were aware which arm of the trial participants were allocated to. The primary outcomes for the study are global functioning (measured using the Global Assessment of Functioning scale) and mental health symptoms (measured using the Positive and Negative Syndrome Scale) assessed at 24 months. Secondary outcomes were assessed at 12 and 24 months and comprise levels of group attendance, social function, satisfaction with care, mental wellbeing, and costs. Discussion We believe that this is the first large scale pragmatic trial of Art Therapy for people with schizophrenia. Trial registration Current Controlled Trials ISRCTN46150447 PMID:20799930

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.

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/

Effects of continuity of care by a primary midwife (caseload midwifery) on caesarean section rates in women of low obstetric risk: the COSMOS randomised controlled trial.

PubMed

McLachlan, H L; Forster, D A; Davey, M A; Farrell, T; Gold, L; Biro, M A; Albers, L; Flood, M; Oats, J; Waldenström, U

2012-11-01

To determine whether primary midwife care (caseload midwifery) decreases the caesarean section rate compared with standard maternity care. Randomised controlled trial. Tertiary-care women's hospital in Melbourne, Australia. A total of 2314 low-risk pregnant women. Women randomised to caseload received antenatal, intrapartum and postpartum care from a primary midwife with some care by 'back-up' midwives. Women randomised to standard care received either midwifery or obstetric-trainee care with varying levels of continuity, or community-based general practitioner care. caesarean birth. Secondary outcomes included instrumental vaginal births, analgesia, perineal trauma, induction of labour, infant admission to special/neonatal intensive care, gestational age, Apgar scores and birthweight. In total 2314 women were randomised-1156 to caseload and 1158 to standard care. Women allocated to caseload were less likely to have a caesarean section (19.4% versus 24.9%; risk ratio [RR] 0.78; 95% CI 0.67-0.91; P = 0.001); more likely to have a spontaneous vaginal birth (63.0% versus 55.7%; RR 1.13; 95% CI 1.06-1.21; P < 0.001); less likely to have epidural analgesia (30.5% versus 34.6%; RR 0.88; 95% CI 0.79-0.996; P = 0.04) and less likely to have an episiotomy (23.1% versus 29.4%; RR 0.79; 95% CI 0.67-0.92; P = 0.003). Infants of women allocated to caseload were less likely to be admitted to special or neonatal intensive care (4.0% versus 6.4%; RR 0.63; 95% CI 0.44-0.90; P = 0.01). No infant outcomes favoured standard care. In settings with a relatively high baseline caesarean section rate, caseload midwifery for women at low obstetric risk in early pregnancy shows promise for reducing caesarean births. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

Protocol for a pilot randomised controlled clinical trial to compare the effectiveness of a graduated three layer straight tubular bandaging system when compared to a standard short stretch compression bandaging system in the management of people with venous ulceration: 3VSS2008

PubMed Central

2010-01-01

Background The incidence of venous ulceration is rising with the increasing age of the general population. Venous ulceration represents the most prevalent form of difficult to heal wounds and these problematic wounds require a significant amount of health care resources for treatment. Based on current knowledge multi-layer high compression system is described as the gold standard for treating venous ulcers. However, to date, despite our advances in venous ulcer therapy, no convincing low cost compression therapy studies have been conducted and there are no clear differences in the effectiveness of different types of high compression. Methods/Design The trial is designed as a pilot multicentre open label parallel group randomised trial. Male and female participants aged greater than 18 years with a venous ulcer confirmed by clinical assessment will be randomised to either the intervention compression bandage which consists of graduated lengths of 3 layers of elastic tubular compression bandage or to the short stretch inelastic compression bandage (control). The primary objective is to assess the percentage wound reduction from baseline compared to week 12 following randomisation. Randomisation will be allocated via a web based central independent randomisation service (nQuery v7) and stratified by study centre and wound size ≤ 10 cm2 or >10 cm2. Neither participants nor study staff will be blinded to treatment. Outcome assessments will be undertaken by an assessor who is blinded to the randomisation process. Discussion The aim of this study is to evaluate the efficacy and safety of two compression bandages; graduated three layer straight tubular bandaging (3L) when compared to standard short stretch (SS) compression bandaging in healing venous ulcers in patients with chronic venous ulceration. The trial investigates the differences in clinical outcomes of two currently accepted ways of treating people with venous ulcers. This study will help answer the question whether the 3L compression system or the SS compression system is associated with better outcomes. Trial Registration ACTRN12608000599370 PMID:20214822

Group art therapy as an adjunctive treatment for people with schizophrenia: multicentre pragmatic randomised trial

PubMed Central

Killaspy, Helen; Barnes, Thomas R E; Barrett, Barbara; Byford, Sarah; Clayton, Katie; Dinsmore, John; Floyd, Siobhan; Hoadley, Angela; Johnson, Tony; Kalaitzaki, Eleftheria; King, Michael; Leurent, Baptiste; Maratos, Anna; O’Neill, Francis A; Osborn, David P; Patterson, Sue; Soteriou, Tony; Tyrer, Peter; Waller, Diane

2012-01-01

Objectives To evaluate the clinical effectiveness of group art therapy for people with schizophrenia and to test whether any benefits exceed those of an active control treatment. Design Three arm, rater blinded, pragmatic, randomised controlled trial. Setting Secondary care services across 15 sites in the United Kingdom. Participants 417 people aged 18 or over, who had a diagnosis of schizophrenia and provided written informed consent to take part in the study. Interventions Participants, stratified by site, were randomised to 12 months of weekly group art therapy plus standard care, 12 months of weekly activity groups plus standard care, or standard care alone. Art therapy and activity groups had up to eight members and lasted for 90 minutes. In art therapy, members were given access to a range of art materials and encouraged to use these to express themselves freely. Members of activity groups were offered various activities that did not involve use of art or craft materials and were encouraged to collectively select those they wanted to pursue. Main outcome measures The primary outcomes were global functioning, measured using the global assessment of functioning scale, and mental health symptoms, measured using the positive and negative syndrome scale, 24 months after randomisation. Main secondary outcomes were levels of group attendance, social functioning, and satisfaction with care at 12 and 24 months. Results 417 participants were assigned to either art therapy (n=140), activity groups (n=140), or standard care alone (n=137). Primary outcomes between the three study arms did not differ. The adjusted mean difference between art therapy and standard care at 24 months on the global assessment of functioning scale was −0.9 (95% confidence interval −3.8 to 2.1), and on the positive and negative syndrome scale was 0.7 (−3.1 to 4.6). Secondary outcomes did not differ between those referred to art therapy or those referred to standard care at 12 or 24 months. Conclusions Referring people with established schizophrenia to group art therapy as delivered in this trial did not improve global functioning, mental health, or other health related outcomes. Trial registration Current Controlled Trials ISRCTN46150447. PMID:22374932

A phase III, multi-centre, double-masked randomised controlled trial of adjunctive intraocular and peri-ocular steroid (triamcinolone acetonide) versus standard treatment in eyes undergoing vitreoretinal surgery for open globe trauma (ASCOT): statistical analysis plan.

PubMed

Lo, Jessica W; Bunce, Catey; Charteris, David; Banerjee, Philip; Phillips, Rachel; Cornelius, Victoria R

2016-08-02

Open globe ocular trauma complicated by intraocular scarring (proliferative vitreoretinopathy) is a relatively rare, blinding, but potentially treatable condition for which, at present, surgery is often unsatisfactory and visual results frequently poor. To date, no pharmacological adjuncts to surgery have been proven to be effective. The aim of the Adjunctive Steroid Combination in Ocular Trauma (ASCOT) randomised controlled trial is to determine whether adjunctive steroid (triamcinolone acetonide), given at the time of surgery, can improve the outcome of vitreoretinal surgery in patients with open globe ocular trauma. This article presents the statistical analysis plan for the main publication as approved and signed off by the Trial Steering Committee prior to the first data extraction for the Data Monitoring Committee meeting report. ASCOT is a pragmatic, multi-centre, parallel-group, double-masked randomised controlled trial. The aim of the study is to recruit from 20-25 centres in the United Kingdom and randomise 300 eyes (from 300 patients) into two treatment arms. Both groups will receive standard surgical treatment and care; the intervention arm will additionally receive a pre-operative steroid combination (triamcinolone acetonide) into the vitreous cavity consisting of 4 mg/0.1 ml and 40 mg/1 ml sub-Tenon's. Participants will be followed for 6 months post-surgery. The primary outcome is the proportion of patients achieving a clinically meaning improvement in visual acuity in the study eye at 6 months after initial surgery, defined as a 10 letter score improvement in the ETDRS (the standard scale to test visual acuity). ISRCTN30012492 . Registered on 5 September 2014. EudraCT2014-002193-37 . Registered on 5 September 2014.

Streamlining cardiovascular clinical trials to improve efficiency and generalisability.

PubMed

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

2017-08-01

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

Low-dose intravenous immunoglobulin treatment for complex regional pain syndrome (LIPS): study protocol for a randomized controlled trial.

PubMed

Goebel, Andreas; Shenker, Nicholas; Padfield, Nick; Shoukrey, Karim; McCabe, Candida; Serpell, Mick; Sanders, Mark; Murphy, Caroline; Ejibe, Amaka; Milligan, Holly; Kelly, Joanna; Ambler, Gareth

2014-10-24

Longstanding complex regional pain syndrome (CRPS) is refractory to treatment with established analgesic drugs in most cases, and for many patients, alternative pain treatment approaches, such as with neuromodulation devices or rehabilitation methods, also do not work. The development of novel, effective treatment technologies is, therefore, important. There are preliminary data suggesting that low-dose immunoglobulin treatment may significantly reduce pain from longstanding CRPS. LIPS is a multicentre (United Kingdom), double-blind, randomised parallel group, placebo-controlled trial, designed to evaluate the efficacy, safety, and tolerability of intravenous immunoglobulin (IVIg) 0.5 g/kg plus standard treatment, versus matched placebo plus standard treatment in 108 patients with longstanding complex regional pain syndrome. Participants with moderate or severe CRPS of between 1 and 5 years duration will be randomly allocated to receive IVIg 0.5 g/kg (IntratectTM 50 g/l solution for infusion) or matching placebo administered day 1 and day 22 after randomisation, followed by two optional doses of open-label medication on day 43 after randomisation and on day 64 after randomisation. The primary outcome is the patients' pain intensity in the IVIG group compared with the placebo group, between 6 and 42 days after randomisation. The primary trial objective is to confirm the efficacy and confidently determine the effect size of the IVIG treatment technology in this group of patients. ISRCTN42179756 (Registered 28 June 13).

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

A randomised study of ilio-inguinal nerve blocks following inguinal hernia repair: a stopped randomised controlled trial.

PubMed

Walker, Stuart; Orlikowski, Chris

2008-02-01

Local anaesthetic use for post-operative pain control is widely used following open inguinal hernia repair but this is not without risk. The aim of this study was to compare ilio-inguinal nerve block and wound irrigation in patients undergoing open inguinal hernia repair under general anaesthetic in a randomised, double blind, placebo controlled trial. Adult patients admitted for unilateral primary open mesh repair of an inguinal hernia were recruited. The patients received a standard general anaesthetic. Prior to skin incision, an ilio-inguinal injection was performed by the anaesthetist with either ropivicaine or normal saline. Prior to closure of the wound, the wound was irrigated with either ropivicaine or normal saline. Post-operatively, all patients received fentynal patient controlled analgesia and regular oral analgesia. Pain scores and visual analogue scores were recorded until discharge. Patients were then contacted by telephone at 24h, 48h, 2weeks and 4weeks post-operatively and asked a standard series of questions, mainly related to post-operative pain. After 12 patients had been recruited the trial was stopped as 5 of the 8 patients who received an ilio-inguinal nerve block suffered a neurological complication. Ilio-inguinal nerve block with ropivicaine should be avoided.

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.

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

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.

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

BTS randomised feasibility study of active symptom control with or without chemotherapy in malignant pleural mesothelioma: ISRCTN 54469112.

PubMed

Muers, M F; Rudd, R M; O'Brien, M E R; Qian, W; Hodson, A; Parmar, M K B; Girling, D J

2004-02-01

The incidence of mesothelioma is rising rapidly in the UK. There is no generally accepted standard treatment. The BTS recommends active symptom control (ASC). It is not known whether chemotherapy in addition prolongs survival or provides worthwhile palliation with acceptable toxicity. Palliation as recorded by patients has been fully reported for only two regimens: mitomycin, vinblastine, and cisplatin (MVP), and vinorelbine (N). The BTS and collaborators planned to conduct a phase III randomised trial comparing ASC only, ASC+MVP, and ASC+N in 840 patients with survival as the primary outcome measure. The aim of the present study was to assess the acceptability of the trial design to patients and the suitability of two standard quality of life (QL) questionnaires for mesothelioma. Collaborating centres registered all new patients with mesothelioma. Those eligible and giving informed consent completed EORTC QLQ-C30+LC13 and FACT-L QL questionnaires and were randomised between all three or any two of (1) ASC only, (2) ASC+4 cycles of MVP, and (3) ASC+12 weekly doses of N. During 1 year, 242 patients were registered of whom 109 (45%) were randomised (55% of the 197 eligible patients). Fifty two patients from 20 centres were randomised to an option including ASC only. This translates into a rate of 312 per year from 60 centres interested in collaborating in the phase III trial. The EORTC QL questionnaire was superior to FACT-L in terms of completeness of data and patient preference. Clinically relevant palliation was achieved with ASC. The planned phase III trial is feasible.

Opportunistic salpingectomy in women undergoing hysterectomy: Results from the HYSTUB randomised controlled trial.

PubMed

Van Lieshout, L A M; Pijlman, B; Vos, M C; de Groot, M J M; Houterman, S; Coppus, S F P J; Harmsen, M G; Vandenput, I; Piek, J M J

2018-01-01

To evaluate whether opportunistic salpingectomy in premenopausal women undergoing hysterectomy for benign indications is both hormonally and surgically safe, compared with hysterectomy without salpingectomy. In this multicentre randomised controlled trial, women were randomised to undergo either hysterectomy with opportunistic bilateral salpingectomy (intervention group) or standard hysterectomy with preservation of the Fallopian tubes (control group). The primary outcome was the difference in serum anti-Müllerian hormone concentration (ΔAMH), measured pre-surgery and 6 months post-surgery. Secondary outcomes were surgical outcomes and duration of hospital stay. The sample size was powered at 50 participants per group (n=100) to compare ΔAMH after hysterectomy with salpingectomy to ΔAMH after standard hysterectomy. Between March 2013 and December 2016, 104 women, aged 30-55 years, were randomly allocated to hysterectomy with opportunistic bilateral salpingectomy (n=52) or standard hysterectomy (n=52). The baseline characteristics did not differ between the two groups. The median ΔAMH was -0.14pmol/L (IQR -1.47-0.95) in the intervention group and 0.00pmol/L (IQR -1.05-0.80) in the control group (p=0.49). The addition of salpingectomy did not impair surgical results and it did not affect duration of hospital stay. Addition of opportunistic bilateral salpingectomy during hysterectomy did not result in a larger effect on ovarian reserve when compared with hysterectomy alone, neither did it affect surgical outcomes. Therefore, opportunistic salpingectomy seems to be a safe procedure in premenopausal women undergoing hysterectomy for benign gynaecological conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Stroke rehabilitation at home before and after discharge reduced disability and improved quality of life: a randomised controlled trial.

PubMed

Rasmussen, Rune Skovgaard; Østergaard, Ann; Kjær, Pia; Skerris, Anja; Skou, Christina; Christoffersen, Jane; Seest, Line Skou; Poulsen, Mai Bang; Rønholt, Finn; Overgaard, Karsten

2016-03-01

To evaluate if home-based rehabilitation of inpatients improved outcome compared to standard care. Interventional, randomised, safety/efficacy open-label trial. University hospital stroke unit in collaboration with three municipalities. Seventy-one eligible stroke patients (41 women) with focal neurological deficits hospitalised in a stroke unit for more than three days and in need of rehabilitation. Thirty-eight patients were randomised to home-based rehabilitation during hospitalization and for up to four weeks after discharge to replace part of usual treatment and rehabilitation services. Thirty-three control patients received treatment and rehabilitation following usual guidelines for the treatment of stroke patients. Ninety days post-stroke the modified Rankin Scale score was the primary endpoint. Other outcome measures were the modified Barthel-100 Index, Motor Assessment Scale, CT-50 Cognitive Test, EuroQol-5D, Body Mass Index and treatment-associated economy. Thirty-one intervention and 30 control patients completed the study. Patients in the intervention group achieved better modified Rankin Scale score (Intervention median = 2, IQR = 2-3; Control median = 3, IQR = 2-4; P=0.04). EuroQol-5D quality of life median scores were improved in intervention patients (Intervention median = 0.77, IQR = 0.66-0.79; Control median = 0.66, IQR = 0.56 - 0.72; P=0.03). The total amount of home-based training in minutes highly correlated with mRS, Barthel, Motor Assessment Scale and EuroQol-5D™ scores (P-values ranging from P<0.00001 to P=0.01). Economical estimations of intervention costs were lower than total costs of standard treatment. Early home-based rehabilitation reduced disability and increased quality of life. Compared to standard care, home-based stroke rehabilitation was more cost-effective. © The Author(s) 2015.

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.

Pressure ulcer management in paraplegic patients with a novel negative pressure device: a randomised controlled trial.

PubMed

Dwivedi, M K; Srivastava, R N; Bhagat, A K; Agarwal, R; Baghel, K; Jain, A; Raj, S

2016-04-01

A randomised controlled trial to compare negative pressure wound therapy (NPWT) using our innovative negative pressure device (NPD) and the standard pressure ulcer (PU) wound dressing of in traumatic paraplegia patients. This study was conducted in the Department of Orthopaedic Surgery at King George's Medical University, Lucknow, India. Traumatic paraplegia patients with sacral pressure ulcers of stage 3 and 4 were randomised into two groups, receiving either standard wound dressings or NPWT with NPD. The outcomes monitored were length, width (surface area), depth of PU, exudates, discharge, tissue type (necrotic, slough and red granulating tissue), and cost-effectiveness during 0 to 9 weeks follow-up. Length and width were significantly (p<0.01) decreased in NPWT group as compared with standard care group at week 9. At weeks 1, 2 and 3, depth was significantly (p<0.05) higher in NPWT group, whereas at week 9 a significant reduction (p=0.01) was observed. Exudates were significantly (p=0.001) lower in NPWT group at weeks 4 and 9. Conversion of slough into red granulation tissue was significantly higher in NPWT group (p=0.001). Discharge became significantly (p=0.001) lower in NPWT at week 2 and no discharge was observed after week 6. In all parameters, decrease was larger in NPWT group compared with standard care, which was significant for exudates type (p=0.03) and tissue type (p=0.004). Our NPD is better than standard wound care procedures and cost-effective for management of PU.

Reassessing RCTs as the "Gold Standard": Synergy Not Separatism in Evaluation Designs

ERIC Educational Resources Information Center

Hanley, Pam; Chambers, Bette; Haslam, Jonathan

2016-01-01

Randomised controlled trials (RCTs) are increasingly used to evaluate educational interventions in the UK. However, RCTs remain controversial for some elements of the research community. This paper argues that the widespread use of the term "gold standard" to describe RCTs is problematic, as it implies that other research methods are…

Randomised controlled clinical trial of increased dose and frequency of albendazole and ivermectin on Wuchereria bancrofti microfilarial clearance in northern Malawi.

PubMed

Tafatatha, Terence T; Ngwira, Bagrey M; Taegtmeyer, Miriam; Phiri, Amos J; Wilson, Trevor P; Banda, Louis G; Piston, Wilson N; Koole, Olivier; Horton, John; French, Neil

2015-06-01

In Africa, albendazole and ivermectin are currently used in combination for annual mass drug administration (MDA) for lymphatic filariasis (LF) elimination. Rapid and sustained clearance is desirable for public health impact and elimination of LF. Increasing the dose and/or frequency of albendazole and ivermectin treatment may be more effective in clearing microfilariae than standard MDA. We conducted a randomised controlled open label trial in northern Malawi comparing three modified treatment groups to standard dosage of ivermectin and albendazole in adults with confirmed circulating LF antigen and microfilaria. Participants were followed-up every 6 months for 2 years for repeat microfilarial counts and safety assessments. A total of 1851 adults were screened and 70 with microfilarial counts >80 microfilariae/ml were randomised. All treatment groups achieved a significant reduction of microfilariae levels by 12- and 24-months of follow-up. Doubling the standard dose and administering it twice yearly showed a non-significant tendency towards faster and more complete clearance. There were no serious adverse reactions. In this small study, all regimens effectively cleared microfilaria. Standard treatment may be adequate in settings like Malawi but not in all endemic settings and larger studies are required to demonstrate benefit of higher dosages. [ClinicalTrials.gov identifier: NCT01213576]. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Venous leg ulcer healing with electric stimulation therapy: a pilot randomised controlled trial.

PubMed

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

2017-03-02

Compression therapy is a gold standard treatment to promote venous leg ulcer (VLU) healing. Concordance with compression therapy is, however, often sub-optimal. The aim of this study was to evaluate the effectiveness of electric stimulation therapy (EST) to facilitate healing of VLUs among people who do not use moderate-to-high levels of compression (>25 mmHg). A pilot multicentre, single-blinded randomised controlled trial was conducted. Participants were randomised (2:1) to the intervention group or a control group where EST or a sham device was used 4 times daily for 20 minutes per session. Participants were monitored fortnightly for eight weeks. The primary outcome measure was percentage of area (wound size) change. In the 23 patients recruited, an average redution in wound size of 23.15% (standard deviation [SD]: 61.23) was observed for the control group compared with 32.67 % (SD: 42.54) for the intervention. A moderate effect size favouring the intervention group was detected from univariate [F(1,18)=1.588, p=0.224, partial eta squared=0.081] and multivariate repeated measures [F(1,18)=2.053, p=0.169, partial eta squared=0.102] analyses. The pilot study was not powered to detect statistical significance, however, the difference in healing outcomes are encouraging. EST may be an effective adjunct treatment among patients who have experienced difficulty adhering to moderate-to-high levels of compression therapy.

Randomised social-skills training and parental training plus standard treatment versus standard treatment of children with attention deficit hyperactivity disorder - The SOSTRA trial protocol

PubMed Central

2011-01-01

Background Children with attention deficit hyperactivity disorder (ADHD) are hyperactive and impulsive, cannot maintain attention, and have difficulties with social interactions. Medical treatment may alleviate symptoms of ADHD, but seldom solves difficulties with social interactions. Social-skills training may benefit ADHD children in their social interactions. We want to examine the effects of social-skills training on difficulties related to the children's ADHD symptoms and social interactions. Methods/Design The design is randomised two-armed, parallel group, assessor-blinded trial. Children aged 8-12 years with a diagnosis of ADHD are randomised to social-skills training and parental training plus standard treatment versus standard treatment alone. A sample size calculation estimated that at least 52 children must be included to show a 4-point difference in the primary outcome on the Conners 3rd Edition subscale for 'hyperactivity-impulsivity' between the intervention group and the control group. The outcomes will be assessed 3 and 6 months after randomisation. The primary outcome measure is ADHD symptoms. The secondary outcome is social skills. Tertiary outcomes include the relationship between social skills and symptoms of ADHD, the ability to form attachment, and parents' ADHD symptoms. Discussion We hope that the results from this trial will show that the social-skills training together with medication may have a greater general effect on ADHD symptoms and social and emotional competencies than medication alone. Trial registration ClinicalTrials (NCT): NCT00937469 PMID:21255399

Competing with big business: a randomised experiment testing the effects of messages to promote alcohol and sugary drink control policy.

PubMed

Scully, Maree; Brennan, Emily; Durkin, Sarah; Dixon, Helen; Wakefield, Melanie; Barry, Colleen L; Niederdeppe, Jeff

2017-12-28

Evidence-based policies encouraging healthy behaviours are often strongly opposed by well-funded industry groups. As public support is crucial for policy change, public health advocates need to be equipped with strategies to offset the impact of anti-policy messages. In this study, we aimed to investigate the effectiveness of theory-based public health advocacy messages in generating public support for sugary drink/alcohol policies (increased taxes; sport sponsorship bans) and improving resistance to subsequent anti-policy messages typical of the sugary drink/alcohol industry. We conducted a two-wave randomised online experiment assigning Australian adults to one of four health policies (sugary drink tax; sugary drink industry sports sponsorship ban; alcohol tax; alcohol industry sports sponsorship ban). Within each health policy, we randomised participants to one of five message conditions: (i) non-advocacy based message about the size and seriousness of the relevant health issue (control); (ii) standard pro-policy arguments alone; (iii) standard pro-policy arguments combined with an inoculation message (forewarning and directly refuting anti-policy arguments from the opposition); (iv) standard pro-policy arguments combined with a narrative message (a short, personal story about an individual's experience of the health issue); or (v) standard pro-policy arguments combined with a composite inoculation and narrative message. At time 1, we exposed participants (n = 6000) to their randomly assigned message. Around two weeks later, we re-contacted participants (n = 3285) and exposed them to an anti-policy message described as being from a representative of the sugary drink/alcohol industry. Generalised linear models tested for differences between conditions in policy support and anti-industry beliefs at both time points. Only the standard argument plus narrative message increased policy support relative to control at time 1. The standard argument plus narrative and standard argument plus inoculation messages were effective at increasing resistance to the persuasive impact of anti-policy messages relative to control at time 2. Dissemination of advocacy messages using inoculation or narrative components can help strengthen public resistance to subsequent anti-policy messages from industry groups.

Effects of natural childbirth preparation versus standard antenatal education on epidural rates, experience of childbirth and parental stress in mothers and fathers: a randomised controlled multicentre trial.

PubMed

Bergström, M; Kieler, H; Waldenström, U

2009-08-01

To examine the effects of antenatal education focussing on natural childbirth preparation with psychoprophylactic training versus standard antenatal education on the use of epidural analgesia, experience of childbirth and parental stress in first-time mothers and fathers. Randomised controlled multicentre trial. Fifteen antenatal clinics in Sweden between January 2006 and May 2007. A total of 1087 nulliparous women and 1064 of their partners. Natural group: Antenatal education focussing on natural childbirth preparation with training in breathing and relaxation techniques (psychoprophylaxis). Standard care group: Standard antenatal education focussing on both childbirth and parenthood, without psychoprophylactic training. Both groups: Four 2-hour sessions in groups of 12 participants during third trimester of pregnancy and one follow-up after delivery. Epidural analgesia during labour, experience of childbirth as measured by the Wijma Delivery Experience Questionnaire (B), and parental stress measured by the Swedish Parenthood Stress Questionnaire. The epidural rate was 52% in both groups. There were no statistically significant differences in the experience of childbirth or parental stress between the randomised groups, either in women or men. Seventy percent of the women in the Natural group reported having used psychoprophylaxis during labour. A minority in the Standard care group (37%) had also used this method, but subgroup analysis where these women were excluded did not change the principal findings. Natural childbirth preparation including training in breathing and relaxation did not decrease the use of epidural analgesia during labour, nor did it improve the birth experience or affect parental stress in early parenthood in nulliparous women and men, compared with a standard form of antenatal education.

Effects of natural childbirth preparation versus standard antenatal education on epidural rates, experience of childbirth and parental stress in mothers and fathers: a randomised controlled multicentre trial

PubMed Central

Bergström, M; Kieler, H; Waldenström, U

2009-01-01

Objective To examine the effects of antenatal education focussing on natural childbirth preparation with psychoprophylactic training versus standard antenatal education on the use of epidural analgesia, experience of childbirth and parental stress in first-time mothers and fathers. Design Randomised controlled multicentre trial. Setting Fifteen antenatal clinics in Sweden between January 2006 and May 2007. Sample A total of 1087 nulliparous women and 1064 of their partners. Methods Natural group: Antenatal education focussing on natural childbirth preparation with training in breathing and relaxation techniques (psychoprophylaxis). Standard care group: Standard antenatal education focussing on both childbirth and parenthood, without psychoprophylactic training. Both groups: Four 2-hour sessions in groups of 12 participants during third trimester of pregnancy and one follow-up after delivery. Main outcome measures Epidural analgesia during labour, experience of childbirth as measured by the Wijma Delivery Experience Questionnaire (B), and parental stress measured by the Swedish Parenthood Stress Questionnaire. Results The epidural rate was 52% in both groups. There were no statistically significant differences in the experience of childbirth or parental stress between the randomised groups, either in women or men. Seventy percent of the women in the Natural group reported having used psychoprophylaxis during labour. A minority in the Standard care group (37%) had also used this method, but subgroup analysis where these women were excluded did not change the principal findings. Conclusion Natural childbirth preparation including training in breathing and relaxation did not decrease the use of epidural analgesia during labour, nor did it improve the birth experience or affect parental stress in early parenthood in nulliparous women and men, compared with a standard form of antenatal education. PMID:19538406

Impact of growth hormone therapy on adult height of children with idiopathic short stature: systematic review.

PubMed

Deodati, Annalisa; Cianfarani, Stefano

2011-03-11

To systematically determine the impact of growth hormone therapy on adult height of children with idiopathic short stature. Systematic review. Cochrane Central Register of Controlled Trials, Medline, and the bibliographic references from retrieved articles of randomised and non-randomised controlled trials from 1985 to April 2010. Height in adulthood (standard deviation score) and overall gain in height (SD score) from baseline measurement in childhood. Randomised and non-randomised controlled trials with height measurements for adults. Inclusion criteria were initial short stature (defined as height >2 SD score below the mean), peak growth hormone responses >10 μg/L, prepubertal stage, no previous growth hormone therapy, and no comorbid conditions that would impair growth. Adult height was considered achieved when growth rate was <1.5 cm/year or bone age was 15 years in females and 16 years in males. Three randomised controlled trials (115 children) met the inclusion criteria. The adult height of the growth hormone treated children exceeded that of the controls by 0.65 SD score (about 4 cm). The mean height gain in treated children was 1.2 SD score compared with 0.34 SD score in untreated children. A slight difference of about 1.2 cm in adult height was observed between the two growth hormone dose regimens. In the seven non-randomised controlled trials the adult height of the growth hormone treated group exceeded that of the controls by 0.45 SD score (about 3 cm). Growth hormone therapy in children with idiopathic short stature seems to be effective in partially reducing the deficit in height as adults, although the magnitude of effectiveness is on average less than that achieved in other conditions for which growth hormone is licensed. The individual response to therapy is highly variable, and additional studies are needed to identify the responders.

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.

Improving adherence to Standard Precautions for the control of health care-associated infections.

PubMed

Moralejo, Donna; El Dib, Regina; Prata, Rafaela A; Barretti, Pasqual; Corrêa, Ione

2018-02-26

'Standard Precautions' refers to a system of actions, such as using personal protective equipment or adhering to safe handling of needles, that healthcare workers take to reduce the spread of germs in healthcare settings such as hospitals and nursing homes. To assess the effectiveness of interventions that target healthcare workers to improve adherence to Standard Precautions in patient care. We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, two other databases, and two trials registers. We applied no language restrictions. The date of the most recent search was 14 February 2017. We included randomised trials of individuals, cluster-randomised trials, non-randomised trials, controlled before-after studies, and interrupted time-series studies that evaluated any intervention to improve adherence to Standard Precautions by any healthcare worker with responsibility for patient care in any hospital, long-term care or community setting, or artificial setting, such as a classroom or a learning laboratory. Two review authors independently screened search results, extracted data from eligible trials, and assessed risk of bias for each included study, using standard methodological procedures expected by Cochrane. Because of substantial heterogeneity among interventions and outcome measures, meta-analysis was not warranted. We used the GRADE approach to assess certainty of evidence and have presented results narratively in 'Summary of findings' tables. We included eight studies with a total of 673 participants; three studies were conducted in Asia, two in Europe, two in North America, and one in Australia. Five studies were randomised trials, two were cluster-randomised trials, and one was a non-randomised trial. Three studies compared different educational approaches versus no education, one study compared education with visualisation of respiratory particle dispersion versus education alone, two studies compared education with additional infection control support versus no intervention, one study compared peer evaluation versus no intervention, and one study evaluated use of a checklist and coloured cues. We considered all studies to be at high risk of bias with different risks. All eight studies used different measures to assess healthcare workers' adherence to Standard Precautions. Three studies also assessed healthcare workers' knowledge, and one measured rates of colonisation with methicillin-resistant Staphylococcus aureus (MRSA) among residents and staff of long-term care facilities. Because of heterogeneity in interventions and outcome measures, we did not conduct a meta-analysis.Education may slightly improve both healthcare workers' adherence to Standard Precautions (three studies; four centres) and their level of knowledge (two studies; three centres; low certainty of evidence for both outcomes).Education with visualisation of respiratory particle dispersion probably improves healthcare workers' use of facial protection but probably leads to little or no difference in knowledge (one study; 20 nurses; moderate certainty of evidence for both outcomes).Education with additional infection control support may slightly improve healthcare workers' adherence to Standard Precautions (two studies; 44 long-term care facilities; low certainty of evidence) but probably leads to little or no difference in rates of health care-associated colonisation with MRSA (one study; 32 long-term care facilities; moderate certainty of evidence).Peer evaluation probably improves healthcare workers' adherence to Standard Precautions (one study; one hospital; moderate certainty of evidence).Checklists and coloured cues probably improve healthcare workers' adherence to Standard Precautions (one study; one hospital; moderate certainty of evidence). Considerable variation in interventions and in outcome measures used, along with high risk of bias and variability in the certainty of evidence, makes it difficult to draw conclusions about effectiveness of the interventions. This review underlines the need to conduct more robust studies evaluating similar types of interventions and using similar outcome measures.

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.

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.

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

Comparing the effects of whole-body vibration to standard exercise in ambulatory people with Multiple Sclerosis: a randomised controlled feasibility study.

PubMed

Uszynski, Marcin Kacper; Purtill, Helen; Donnelly, Alan; Coote, Susan

2016-07-01

This study aimed firstly to investigate the feasibility of the study protocol and outcome measures, secondly to obtain data in order to inform the power calculations for a larger randomised controlled trial, and finally to investigate if whole-body vibration (WBV) is more effective than the same duration and intensity of standard exercises (EXE) in people with Multiple Sclerosis (PwMS). Randomised controlled feasibility study. Outpatient MS centre. Twenty seven PwMS (age mean (SD) 48.1 (11.2)) with minimal gait impairments. Twelve weeks of WBV or standard EXE, three times weekly. Participants were measured with isokinetic muscle strength, vibration threshold, Timed Up and Go test (TUG), Mini-BESTest (MBT), 6 Minute Walk test (6MWT), Multiple Sclerosis Impact Scale 29 (MSIS 29), Modified Fatigue Impact Scale (MFIS) and Verbal Analogue scale for sensation (VAS) pre and post 12 week intervention. WBV intervention was found feasible with low drop-out rate (11.1%) and high compliance (90%). Data suggest that a sample of 52 in each group would be sufficient to detect a moderate effect size, with 80% power and 5% significance for 6 minute walk test. Large effect sizes in favour of standard exercise were found for vibration threshold at 5th metatarsophalangeal joint and heel (P=0.014, r= 0.5 and P=0.005, r=0.56 respectively). No between group differences were found for muscle strength, balance or gait (P>0.05). Data suggest that the protocol is feasible, there were no adverse effects. A trial including 120 people would be needed to detect an effect on walking endurance. © The Author(s) 2015.

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.

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

PubMed

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

2014-10-15

Thalassemia is an inherited blood disorder, caused by mutations in regulatory genes and transmitted as an autosomal recessive disorder, which 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 damage the red blood cell membranes, leading to their destruction and a phenomenon termed 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 potential to definitively cure the disease. 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: 11 November 2013. 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 Collaboration 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.

Can Arthroplasty Stem INfluence Outcome? (CASINO): a randomized controlled equivalence trial of 125 mm versus 150 mm Exeter V40 stems in total hip arthroplasty.

PubMed

Hamilton, David F; Ohly, Nicholas E; Gaston, Paul

2018-04-16

The use of shorter length femoral stems during total hip arthroplasty has been suggested to accommodate wider patient femoral geometry and offer maximal bone preservation. However, cemented short-stem designs may increase the risk of varus stem malalignment and influence patient outcomes. CASINO is a multi-centre randomised equivalence trial that will recruit 220 patients undergoing total hip arthroplasty for osteoarthritis at two NHS hospitals in Scotland. Patients will be aged 45-80, undergoing unilateral primary hip arthroplasty, with no plan for contralateral procedure within the study timeframe, and able to comply with the protocol. Participants will be randomised to receive either a short (125 mm) or a standard (150 mm) Exeter V40 stem. The Contemporary acetabular component will be used in all cases. All implants will be cemented. Patient pain, function and satisfaction will be assessed using change from baseline measurement in Oxford Hip Score, Forgotten Joint Score, EQ-5D, pain numerical rating scores, and patient satisfaction questionnaire at baseline and at 1 and 2 years following surgery. Radiographic assessment will evaluate stem position and will be appraised by independent reviewers. Patients will be blind to implant allocation. Stem length may be associated with outcome; however, we can find no randomised trial in which researchers investigated the effect of stem length on patient outcome following cemented total hip arthroplasty. The aim of this trial is to determine if the use of short cemented stems offers equivalent patient outcomes to those achieved following surgery with standard length stems. International Standard Randomised Controlled Trial Number, ISRCTN13154542 , Registered on 30 June 2017.

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.

Does the addition of visceral manipulation improve outcomes for patients with low back pain? Rationale and study protocol.

PubMed

Panagopoulos, John; Hancock, Mark; Ferreira, Paulo

2013-07-01

There has been no randomised controlled trial conducted to investigate the effectiveness of visceral manipulation (VM) for the treatment of low back pain (LBP). The primary aim of this study would be to investigate whether the addition of VM, to a standard physiotherapy treatment regimen, improves pain 6 weeks post treatment commencement in people with LBP. Secondary aims would be to examine the effect of VM on disability and functional outcomes at 2, 6 and 52 weeks post-treatment commencement and pain at 2 and 52 weeks. This paper describes the rationale and design of a randomised controlled trial investigating the addition of VM to a standard physiotherapy treatment algorithm which includes manual therapy, specific exercise and functional exercise prescription. Analysis of data would be carried out by a statistician blinded to group allocation and by intention-to-treat. Copyright © 2013 Elsevier Ltd. All rights reserved.

Injury risk in runners using standard or motion control shoes: a randomised controlled trial with participant and assessor blinding

PubMed Central

Malisoux, Laurent; Chambon, Nicolas; Delattre, Nicolas; Gueguen, Nils; Urhausen, Axel; Theisen, Daniel

2016-01-01

Background/aim This randomised controlled trial investigated if the usage of running shoes with a motion control system modifies injury risk in regular leisure-time runners compared to standard shoes, and if this influence depends on foot morphology. Methods Recreational runners (n=372) were given either the motion control or the standard version of a regular running shoe model and were followed up for 6 months regarding running activity and injury. Foot morphology was analysed using the Foot Posture Index method. Cox regression analyses were used to compare injury risk between the two groups, based on HRs and their 95% CIs, controlling for potential confounders. Stratified analyses were conducted to evaluate the effect of motion control system in runners with supinated, neutral and pronated feet. Results The overall injury risk was lower among the participants who had received motion control shoes (HR=0.55; 95% CI 0.36 to 0.85) compared to those receiving standard shoes. This positive effect was only observed in the stratum of runners with pronated feet (n=94; HR=0.34; 95% CI 0.13 to 0.84); there was no difference in runners with neutral (n=218; HR=0.78; 95% CI 0.44 to 1.37) or supinated feet (n=60; HR=0.59; 95% CI 0.20 to 1.73). Runners with pronated feet using standard shoes had a higher injury risk compared to those with neutral feet (HR=1.80; 95% CI 1.01 to 3.22). Conclusions The overall injury risk was lower in participants who had received motion control shoes. Based on secondary analysis, those with pronated feet may benefit most from this shoe type. PMID:26746907

Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia (ARREST): study protocol for a randomised controlled trial.

PubMed

Thwaites, Guy; Auckland, Cressida; Barlow, Gavin; Cunningham, Richard; Davies, Gerry; Edgeworth, Jonathan; Greig, Julia; Hopkins, Susan; Jeyaratnam, Dakshika; Jenkins, Neil; Llewelyn, Martin; Meisner, Sarah; Nsutebu, Emmanuel; Planche, Tim; Read, Robert C; Scarborough, Matthew; Soares, Marta; Tilley, Robert; Török, M Estée; Williams, John; Wilson, Peter; Wyllie, Sarah; Walker, A Sarah

2012-12-18

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. 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 (600-900 mg/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. 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.

Clinical effectiveness and cost-effectiveness of surgical options for the management of anterior and/or posterior vaginal wall prolapse: two randomised controlled trials within a comprehensive cohort study - results from the PROSPECT Study.

PubMed

Glazener, Cathryn; Breeman, Suzanne; Elders, Andrew; Hemming, Christine; Cooper, Kevin; Freeman, Robert; Smith, Anthony; Hagen, Suzanne; Montgomery, Isobel; Kilonzo, Mary; Boyers, Dwayne; McDonald, Alison; McPherson, Gladys; MacLennan, Graeme; Norrie, John

2016-12-01

The use of mesh in prolapse surgery is controversial, leading to a number of enquiries into its safety and efficacy. To compare synthetic non-absorbable mesh inlay, biological graft and mesh kit with a standard repair in terms of clinical effectiveness, adverse effects, quality of life (QoL), costs and cost-effectiveness. Two randomised controlled trials within a comprehensive cohort (CC) study. Allocation was by a remote web-based randomisation system in a 1 :1 : 1 ratio (Primary trial) or 1 : 1 : 2 ratio (Secondary trial), and was minimised on age, type of prolapse repair planned, need for a concomitant continence procedure, need for a concomitant upper vaginal prolapse procedure and surgeon. Participants and outcome assessors were blinded to randomisation; participants were unblinded if they requested the information. Surgeons were not blinded to allocated procedure. Thirty-five UK hospitals. Primary study : 2474 women in the analysis (including 1348 randomised) having primary anterior or posterior prolapse surgery. Secondary study : 398 in the analysis (including 154 randomised) having repeat anterior or posterior prolapse surgery. CC3 : 215 women having either uterine or vault prolapse repair. Anterior or posterior repair alone, or with mesh inlay, biological graft or mesh kit. Prolapse symptoms [Pelvic Organ Prolapse Symptom Score (POP-SS)]; prolapse-specific QoL; cost-effectiveness [incremental cost per quality-adjusted life-year (QALY)]. Primary trials : adjusting for baseline and minimisation covariates, mean POP-SS was similar for each comparison {standard 5.4 [standard deviation (SD) 5.5] vs. mesh 5.5 (SD 5.1), mean difference (MD) 0.00, 95% confidence interval (CI) -0.70 to 0.71; standard 5.5 (SD 5.6) vs. graft 5.6 (SD 5.6), MD -0.15, 95% CI -0.93 to 0.63}. Serious non-mesh adverse effects rates were similar between the groups in year 1 [standard 7.2% vs. mesh 7.8%, risk ratio (RR) 1.08, 95% CI 0.68 to 1.72; standard 6.3% vs. graft 9.8%, RR 1.57, 95% CI 0.95 to 2.59]. There were no statistically significant differences between groups in any other outcome measure. The cumulative mesh complication rates over 2 years were 2 of 430 (0.5%) for standard repair (trial 1), 46 of 435 (10.6%) for mesh inlay and 2 of 368 (0.5%) for biological graft. The CC findings were comparable. Incremental costs were £363 (95% CI -£32 to £758) and £565 (95% CI £180 to £950) for mesh and graft vs. standard, respectively. Incremental QALYs were 0.071 (95% CI -0.004 to 0.145) and 0.039 (95% CI -0.041 to 0.120) for mesh and graft vs. standard, respectively. A Markov decision model extrapolating trial results over 5 years showed standard repair had the highest probability of cost-effectiveness, but results were surrounded by considerable uncertainty. Secondary trials : there were no statistically significant differences between the randomised groups in any outcome measure, but the sample size was too small to be conclusive. The cumulative mesh complication rates over 2 years were 7 of 52 (13.5%) for mesh inlay and 4 of 46 (8.7%) for mesh kit, with no mesh exposures for standard repair. In women who were having primary repairs, there was evidence of no benefit from the use of mesh inlay or biological graft compared with standard repair in terms of efficacy, QoL or adverse effects (other than mesh complications) in the short term. The Secondary trials were too small to provide conclusive results. Women in the Primary trials included some with a previous repair in another compartment. Follow-up is vital to identify any long-term potential benefits and serious adverse effects. Long-term follow-up to at least 6 years after surgery is ongoing to identify recurrence rates, need for further prolapse surgery, adverse effects and cost-effectiveness. Current Controlled Trials ISRCTN60695184. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 20, No. 95. See the NIHR Journals Library website for further project information.

Interconception care for women with a history of gestational diabetes for improving maternal and infant outcomes.

PubMed

Tieu, Joanna; Shepherd, Emily; Middleton, Philippa; Crowther, Caroline A

2017-08-24

Gestational diabetes mellitus (GDM) is associated with adverse health outcomes for mothers and their infants both perinatally and long term. Women with a history of GDM are at risk of recurrence in subsequent pregnancies and may benefit from intervention in the interconception period to improve maternal and infant health outcomes. To assess the effects of interconception care for women with a history of GDM on maternal and infant health outcomes. We searched Cochrane Pregnancy and Childbirth's Trials Register (7 April 2017) and reference lists of retrieved studies. Randomised controlled trials, including quasi-randomised controlled trials and cluster-randomised trials evaluating any protocol of interconception care with standard care or other forms of interconception care for women with a history of GDM on maternal and infant health outcomes. Two review authors independently assessed study eligibility. In future updates of this review, at least two review authors will extract data and assess the risk of bias of included studies; the quality of the evidence will be assessed using the GRADE approach. No eligible published trials were identified. We identified a completed randomised controlled trial that was designed to evaluate the effects of a diet and exercise intervention compared with standard care in women with a history of GDM, however to date, it has only published results on women who were pregnant at randomisation (and not women in the interconception period). We also identified an ongoing trial, in obese women with a history of GDM planning a subsequent pregnancy, which is assessing the effects of an intensive lifestyle intervention, supported with liraglutide treatment, compared with usual care. We also identified a trial that was designed to evaluate the effects of a weight loss and exercise intervention compared with lifestyle education also in obese women with a history of GDM planning a subsequent pregnancy, however it has not yet been published. These trials will be re-considered for inclusion in the next review update. The role of interconception care for women with a history of GDM remains unclear. Randomised controlled trials are required evaluating different forms and protocols of interconception care for these women on perinatal and long-term maternal and infant health outcomes, acceptability of such interventions and cost-effectiveness.

Practice nurse health checks for adults with intellectual disabilities: a cluster-design, randomised controlled trial.

PubMed

Cooper, Sally-Ann; Morrison, Jill; Allan, Linda M; McConnachie, Alex; Greenlaw, Nicola; Melville, Craig A; Baltzer, Marion C; McArthur, Laura A; Lammie, Claire; Martin, Gordon; Grieve, Eleanor A D; Fenwick, Elisabeth

2014-12-01

Adults with intellectual disabilities have substantial health inequalities and poor access to health care. We assessed whether practice nurse-delivered health checks could improve the health of adults with intellectual disabilities compared with standard care. In this cluster-design, single-blind, randomised controlled trial, we included general practices in Scotland, UK. From June to December, 2011, we randomly assigned (1:1) these general practices to either health checks plus standard care (health-checks group), or standard care only (control group), and we recruited the patients from these practices. Randomisation was done with stratification by number of GPs per practice and number of registered patients with intellectual disabilities (<20 or ≥20). Two research assistants were masked to allocation, and undertook the review of 9 month medical records and interviews. Participants and carers were not masked. The intervention was one health check designed especially for people with intellectual disabilities delivered by a practice nurse. The objective was improvement in health and health care 9 months after randomisation, and the primary outcome was the incidence of newly detected health needs being met by this timepoint. Whether needs were met was established by the investigators being masked to group allocation. The analysis was by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN43324841. Between June 26 and Dec 20, 2011, we recruited 38 practices. 85 participants (from 16 practices) were randomly assigned to intervention and 67 (from 17 practices) to standard care; five of the identified practices did not supply any participants. 83 intervention and 66 standard care participants completed the trial. More newly detected health needs were met in the intervention group than in the control standard care group (median 1 [range 0-8], 76·4% met [SD 36·5] vs 2 [0-11], 72·6% met [35·4]; odds ratio [OR] 1·73 [95% CI 0·93-3·22], p=0·085), although this difference was not significant. Significantly more health monitoring needs were met in the intervention group than standard care (median 2 [0-20], 69·9% [SD 34·2] vs 2 [0-22], 56·8% [29·4], OR 2·38 [95% CI 1·31-4·32, p=0·0053]). The probability that health checks are cost effective was between 0·6 and 0·8, irrespective of the cost-effectiveness threshold level. Costs per patient were -£71·48 for health checks and -£20·56 for standard care. The difference (-£50·92) was not significant [95% CI -434 to 362]. No adverse events were attributable to the intervention. Health checks given by practice nurses to adults with intellectual disabilities produced health-care improvements that were more conducive to longer-term health than standard care given to this population. The intervention dominated standard care, being both cheaper and more effective. Health-check programmes might therefore be indicated for adults with intellectual disabilities. Scottish Government Change Fund, NHS Greater Glasgow and Clyde Research and Development. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Impact of numerical information on risk knowledge regarding human papillomavirus (HPV) vaccination among schoolgirls: a randomised controlled trial.

PubMed

Steckelberg, Anke; Albrecht, Martina; Kezle, Anna; Kasper, Jürgen; Mühlhauser, Ingrid

2013-01-01

In Germany the implementation of human papillomavirus (HPV) vaccination for women aged 12-17 years was accompanied by various campaigns. Evidence-based information including numerical data was not provided. However, standard information leads to overestimation of cancer risk and effects of HPV vaccination. Confidence in children's ability to deal with numerical data is low, especially in disadvantaged pupils. The aim of the present study was to compare the effects of a standard leaflet with an information leaflet supplemented with numerical data on 'risk knowledge' regarding HPV vaccination among schoolgirls. Randomised-controlled short-term trial. All 108 schoolgirls of seven school classes were asked to participate and 105 agreed. Participants were vocational schoolgirls who were preparing for grade 10 graduation and who were members of the target group for HPV vaccination. The control group was asked to read a standard leaflet on HPV vaccination of the German Women's Health Network. The intervention group received the same leaflet, but it was supplemented with numerical information on cancer risk and assumed effects of the HPV vaccination on cancer prevention. As baseline characteristics we surveyed: age, vaccination status, attitude towards HPV vaccination and aspects regarding migration background. The primary end point was 'risk knowledge'. Questionnaire surveys were performed under experimental conditions. Individual randomisation, participants, and intention-to-treat data analyses were blinded. The study was approved by the Ministry of Education and Culture of Schleswig-Holstein and the ethics committee of the Hamburg Chamber of Physicians. We analysed 'risk knowledge' for all 105 randomised participants. Baseline characteristics of the two groups were comparable. Numerical risk information recipients were more likely to give correct answers compared to standard information recipients: Mean value of risk knowledge score (0-5 points): 4.6±1.0 vs. 2.6±1.2 (mean difference 2.0 (95% CI 1.6-2.4)); (P<0.001). Post hoc distractor analysis of single items was performed. Incorrect answers of control participants indicated that cervical cancer risk was highly overestimated whereas total cancer risk was mostly underestimated, and possible impact of HPV vaccination on cancer prevention was overestimated. Supplementing health information on HPV vaccination with numerical data improves 'risk knowledge' among schoolgirls.

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.

Cost-effectiveness of FENO-based and web-based monitoring in paediatric asthma management: a randomised controlled trial.

PubMed

Beerthuizen, Thijs; Voorend-van Bergen, Sandra; van den Hout, Wilbert B; Vaessen-Verberne, Anja A; Brackel, Hein J; Landstra, Anneke M; van den Berg, Norbert J; de Jongste, Johan C; Merkus, Peter J; Pijnenburg, Mariëlle W; Sont, Jacob K

2016-07-01

In children with asthma, web-based monitoring and inflammation-driven therapy may lead to improved asthma control and reduction in medications. However, the cost-effectiveness of these monitoring strategies is yet unknown. We assessed the cost-effectiveness of web-based monthly monitoring and of 4-monthly monitoring of FENO as compared with standard care. An economic evaluation was performed alongside a randomised controlled multicentre trial with a 1-year follow-up. Two hundred and seventy-two children with asthma, aged 4-18 years, were randomised to one of three strategies. In standard care, treatment was adapted according to Asthma Control Test (ACT) at 4-monthly visits, in the web-based strategy also according to web-ACT at 1 month intervals, and in the FENO-based strategy according to ACT and FENO at 4-monthly visits. Outcome measures were patient utilities, healthcare costs, societal costs and incremental cost per quality-adjusted life year (QALY) gained. No statistically significant differences were found in QALYs and costs between the three strategies. The web-based strategy had 77% chance of being most cost-effective from a healthcare perspective at a willingness to pay a generally accepted €40 000/QALY. The FENO-based strategy had 83% chance of being most cost-effective at €40 000/QALY from a societal perspective. Economically, web-based monitoring was preferred from a healthcare perspective, while the FENO-based strategy was preferred from a societal perspective, although in QALYs and costs no statistically significant changes were found as compared with standard care. As clinical outcomes also favoured the web-based and FENO-based strategies, these strategies may be useful additions to standard care. Netherlands Trial Register (NTR1995). 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/

Theory-based modifications of an advanced notification letter improves screening for bowel cancer in men: A randomised controlled trial.

PubMed

Zajac, Ian T; Duncan, Amy C; Flight, Ingrid; Wittert, Gary A; Cole, Stephen R; Young, Graeme P; Wilson, Carlene J; Turnbull, Deborah A

2016-09-01

Male participation in screening for bowel cancer is sub-optimal. Theory-based interventions provide a means of improving screening uptake. To test the efficacy of modifying consumer invitation material in line with continuum and stage theories of health behaviour on screening participation. N = 9216 Australian men aged 50-74 years were randomised to one of four trial arms in a 2 × 2 factorial design randomised controlled trial. Participants received either standard invitation material (control group), or combinations of modified advance-notification and invitation letters. A subsample completed baseline and endpoint behavioural surveys. Participants who received the modified advance notification letter were 12% more likely to screen than those who received the standard version (RR = 1.12, χ(2)(1) = 10.38, p = 0.001). The modified invitation letter did not impact screening uptake (RR = 0.97, χ(2)(1) = 0.63, p = 0.424). No significant changes in psychological variables due to the intervention were observed. Modifications to advance notification letters in line with health behaviour theories significantly improves screening uptake in men. Australian New Zealand Clinical Trials Registry: ACTRN12612001122842 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362688. Copyright © 2016 Elsevier Ltd. All rights reserved.

Patient and family satisfaction levels in the intensive care unit after elective cardiac surgery: study protocol for a randomised controlled trial of a preoperative patient education intervention

PubMed Central

Leung, Patricia; Chiu, Chun Hung; Ho, Ka Man; Gomersall, Charles David; Underwood, Malcolm John

2016-01-01

Introduction Patients and their families are understandably anxious about the risk of complications and unfamiliar experiences following cardiac surgery. Providing information about postoperative care in the intensive care unit (ICU) to patients and families may lead to lower anxiety levels, and increased satisfaction with healthcare. The objectives of this study are to evaluate the effectiveness of preoperative patient education provided for patients undergoing elective cardiac surgery. Methods and analysis 100 patients undergoing elective coronary artery bypass graft, with or without valve replacement surgery, will be recruited into a 2-group, parallel, superiority, double-blinded randomised controlled trial. Participants will be randomised to either preoperative patient education comprising of a video and ICU tour with standard care (intervention) or standard education (control). The primary outcome measures are the satisfaction levels of patients and family members with ICU care and decision-making in the ICU. The secondary outcome measures are patient anxiety and depression levels before and after surgery. Ethics and dissemination Ethical approval has been obtained from the Joint Chinese University of Hong Kong—New Territories East Cluster Clinical Research Ethics Committee (reference number CREC 2015.308). The findings will be presented at conferences and published in peer-reviewed journals. Study participants will receive a 1-page plain language summary of results. Trial registration number ChiCTR-IOR-15006971. PMID:27334883

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.

Impact of a Brief Group Intervention to Enhance Parenting and the Home Learning Environment for Children Aged 6-36 Months: a Cluster Randomised Controlled Trial.

PubMed

Hackworth, N J; Berthelsen, D; Matthews, J; Westrupp, E M; Cann, W; Ukoumunne, O C; Bennetts, S K; Phan, T; Scicluna, A; Trajanovska, M; Yu, M; Nicholson, J M

2017-04-01

This study evaluated the effectiveness of a group parenting intervention designed to strengthen the home learning environment of children from disadvantaged families. Two cluster randomised controlled superiority trials were conducted in parallel and delivered within existing services: a 6-week parenting group (51 locations randomised; 986 parents) for parents of infants (aged 6-12 months), and a 10-week facilitated playgroup (58 locations randomised; 1200 parents) for parents of toddlers (aged 12-36 months). Each trial had three conditions: intervention (smalltalk group-only); enhanced intervention with home coaching (smalltalk plus); and 'standard'/usual practice controls. Parent-report and observational measures were collected at baseline, 12 and 32 weeks follow-up. Primary outcomes were parent verbal responsivity and home learning activities at 32 weeks. In the infant trial, there were no differences by trial arm for the primary outcomes at 32 weeks. In the toddler trial at 32-weeks, participants in the smalltalk group-only trial showed improvement compared to the standard program for parent verbal responsivity (effect size (ES) = 0.16; 95% CI 0.01, 0.36) and home learning activities (ES = 0.17; 95% CI 0.01, 0.38) but smalltalk plus did not. For the secondary outcomes in the infant trial, several initial differences favouring smalltalk plus were evident at 12 weeks, but not maintained to 32 weeks. For the toddler trial, differences in secondary outcomes favouring smalltalk plus were evident at 12 weeks and maintained to 32 weeks. These trials provide some evidence of the benefits of a parenting intervention focused on the home learning environment for parents of toddlers but not infants. 8 September 2011; ACTRN12611000965909 .

Training, executive, attention and motor skills (TEAMS) training versus standard treatment for preschool children with attention deficit hyperactivity disorder: a randomised clinical trial.

PubMed

Vibholm, Helle Annette; Pedersen, Jesper; Faltinsen, Erlend; Marcussen, Michael H; Gluud, Christian; Storebø, Ole Jakob

2018-06-08

This study compared the effectiveness of manualised training, executive, attention, and motor skills (TEAMS) training versus standard treatment in preschool children with attention deficit hyperactivity disorder (ADHD). We conducted a randomised parallel group, single-blinded, superiority trial. The primary outcome was ADHD symptoms and the secondary outcome was functionality. Parents and primary school teachers assessed outcomes at pretreatment, posttreatment, and at one, three, and 6 months follow-up. In total, 67 children (aged 3-6 years) were randomised. In the TEAMS group, 32 out of 33 (97%) participants completed the total 8-week program, compared with only 7 out of 26 (27%) in the control group. The repeated-model analyses showed no significant change between the two interventions for ADHD symptoms and functionality levels over time. The mean difference in ADHD symptoms between TEAMS versus standard treatment at posttreatment was 2.18 points (95% confidence interval - 8.62 to 13.0; trial sequential analysis-adjusted confidence interval - 19.3 to 23.7). Trial registration Clinical Trials identifier: NCT01918436 (Retrospectively registered). Registered on 7 August 2013.

Surrogate endpoints for overall survival in metastatic melanoma: a meta-analysis of randomised controlled trials

PubMed Central

Flaherty, Keith T; Hennig, Michael; Lee, Sandra J; Ascierto, Paolo A; Dummer, Reinhard; Eggermont, Alexander M M; Hauschild, Axel; Kefford, Richard; Kirkwood, John M; Long, Georgina V; Lorigan, Paul; Mackensen, Andreas; McArthur, Grant; O'Day, Steven; Patel, Poulam M; Robert, Caroline; Schadendorf, Dirk

2015-01-01

Summary Background Recent phase 3 trials have shown an overall survival benefit in metastatic melanoma. We aimed to assess whether progression-free survival (PFS) could be regarded as a reliable surrogate for overall survival through a meta-analysis of randomised trials. Methods We systematically reviewed randomised trials comparing treatment regimens in metastatic melanoma that included dacarbazine as the control arm, and which reported both PFS and overall survival with a standard hazard ratio (HR). We correlated HRs for overall survival and PFS, weighted by sample size or by precision of the HR estimate, assuming fixed and random effects. We did sensitivity analyses according to presence of crossover, trial size, and dacarbazine dose. Findings After screening 1649 reports and meeting abstracts published before Sept 8, 2013, we identified 12 eligible randomised trials that enrolled 4416 patients with metastatic melanoma. Irrespective of weighting strategy, we noted a strong correlation between the treatment effects for PFS and overall survival, which seemed independent of treatment type. Pearson correlation coefficients were 0.71 (95% CI 0.29–0.90) with a random-effects assumption, 0.85 (0.59–0.95) with a fixed-effects assumption, and 0.89 (0.68–0.97) with sample-size weighting. For nine trials without crossover, the correlation coefficient was 0.96 (0.81–0.99), which decreased to 0.93 (0.74–0.98) when two additional trials with less than 50% crossover were included. Inclusion of mature follow-up data after at least 50% crossover (in vemurafenib and dabrafenib phase 3 trials) weakened the PFS to overall survival correlation (0.55, 0.03–0.84). Inclusion of trials with no or little crossover with the random-effects assumption yielded a conservative statement of the PFS to overall survival correlation of 0.85 (0.51–0.96). Interpretation PFS can be regarded as a robust surrogate for overall survival in dacarbazine-controlled randomised trials of metastatic melanoma; we postulate that this association will hold as treatment standards evolve and are adopted as the control arm in future trials. Funding None. PMID:24485879

Extra Physiotherapy in Critical Care (EPICC) Trial Protocol: a randomised controlled trial of intensive versus standard physical rehabilitation therapy in the critically ill.

PubMed

Thomas, Kirsty; Wright, Stephen E; Watson, Gillian; Baker, Catherine; Stafford, Victoria; Wade, Clare; Chadwick, Thomas J; Mansfield, Leigh; Wilkinson, Jennifer; Shen, Jing; Deverill, Mark; Bonner, Stephen; Hugill, Keith; Howard, Philip; Henderson, Andrea; Roy, Alistair; Furneval, Julie; Baudouin, Simon V

2015-05-25

Patients discharged from Critical Care suffer from excessive longer term morbidity and mortality. Physical and mental health measures of quality of life show a marked and immediate fall after admission to Critical Care with some recovery over time. However, physical function is still significantly reduced at 6 months. The National Institute for Health and Care Excellence clinical guideline on rehabilitation after critical illness, identified the need for high-quality randomised controlled trials to determine the most effective rehabilitation strategy for critically ill patients at risk of critical illness-associated physical morbidity. In response to this, we will conduct a randomised controlled trial, comparing physiotherapy aimed at early and intensive patient mobilisation with routine care. We hypothesise that this intervention will improve physical outcomes and the mental health and functional well-being of survivors of critical illness. 308 adult patients who have received more than 48 h of non-invasive or invasive ventilation in Critical Care will be recruited to a patient-randomised, parallel group, controlled trial, comparing two intensities of physiotherapy. Participants will be randomised to receive either standard or intensive physiotherapy for the duration of their Critical Care admission. Outcomes will be recorded on Critical Care discharge, at 3 and 6 months following initial recruitment to the study. The primary outcome measure is physical health at 6 months, as measured by the SF-36 Physical Component Summary. Secondary outcomes include assessment of mental health, activities of daily living, delirium and ventilator-free days. We will also include a health economic analysis. The trial has ethical approval from Newcastle and North Tyneside 2 Research Ethics Committee (11/NE/0206). There is a Trial Oversight Committee including an independent chair. The results of the study will be submitted for publication in peer-reviewed journals and presented at national and international scientific meetings. ISRCTN20436833. 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.

A repeated short educational intervention improves asthma control and quality of life.

PubMed

Plaza, Vicente; Peiró, Meritxell; Torrejón, Montserrat; Fletcher, Monica; López-Viña, Antolín; Ignacio, José María; Quintano, José Antonio; Bardagí, Santiago; Gich, Ignasi

2015-11-01

We assessed the effectiveness of an asthma educational programme based on a repeated short intervention (AEP-RSI) to improve asthma control (symptom control and future risk) and quality of life. A total of 230 adults with mild-to-moderate persistent uncontrolled asthma participated in a 1-year cluster randomised controlled multicentre study. The AEP-RSI was given in four face-to-face sessions at 3-month intervals, and included administration of a written personalised action plan and training on inhaler technique. Centres were randomised to the AEP-RSI (intervention) group or usual clinical practice group. Specialised centres using a standard educational programme were the gold standard group. A significant improvement in the Asthma Control Test score was observed in all three groups (p<0.001), but improvements were higher in the intervention and gold standard groups than in the usual clinical practice group (p=0.042), which also showed fewer exacerbations (mean±sd; 1.20±2.02 and 0.56±1.5 versus 2.04±2.72, respectively) and greater increases in the Mini Asthma Quality of Life Questionnaire scores (0.95±1.04 and 0.89±0.84 versus 0.52±0.97, respectively). The AEP-RSI was effective in improving asthma symptom control, future risk and quality of life. Copyright ©ERS 2015.

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.

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.

Vouchers versus Lotteries: What works best in promoting Chlamydia screening? A cluster randomised controlled trial

PubMed Central

Niza, Claudia; Rudisill, Caroline; Dolan, Paul

2014-01-01

In this cluster randomised trial (N=1060), we tested the impact of financial incentives (£5 voucher vs. £200 lottery) framed as a gain or loss to promote Chlamydia screening in students aged 18–24 years, mimicking the standard outreach approach to student in halls of residence. Compared to the control group (1.5%), the lottery increased screening to 2.8% and the voucher increased screening to 22.8%. Incentives framed as gains were marginally more effective (10.5%) that loss-framed incentives (7.1%). This work fundamentally contributes to the literature by testing the predictive validity of Prospect Theory to change health behaviour in the field. PMID:25061507

An embedded randomised controlled trial of a Teaser Campaign to optimise recruitment in primary care.

PubMed

Lee, Hopin; Hübscher, Markus; Moseley, G Lorimer; Kamper, Steven J; Traeger, Adrian C; Skinner, Ian W; Williams, Christopher M; McAuley, James H

2017-04-01

Marketing communication and brand identity is a fundamental principle of advertising and end-user engagement. Health researchers have begun to apply this principle to trial recruitment in primary care. The aim of this study was to evaluate whether a Teaser Campaign using a series of postcards in advance of a conventional mail-out increases the number of primary care clinics that engage with a clinical trial. Embedded randomised recruitment trial across primary care clinics (general practitioners and physiotherapists) in the Sydney metropolitan area. Clinics in the Teaser Campaign group received a series of branded promotional postcards in advance of a standard letter inviting them to participate in a clinical trial. Clinics in the Standard Mail group did not receive the postcards. From a total of 744 clinics that were sent an invitation letter, 46 clinics in the Teaser Campaign group and 40 clinics in the Standard Mail group responded (11.6% total response rate). There was no between-group difference in the odds of responding to the invitation letter (odds ratio = 1.18, 95% confidence interval = 0.75-1.85, p = 0.49). For physiotherapy clinics and general practice clinics, the odds ratios were 1.43 (confidence interval = 0.82-2.48, p = 0.21) and 0.77 (confidence interval = 0.34-1.75, p  = 0.54), respectively. A Teaser Campaign using a series of branded promotional postcards did not improve clinic engagement for a randomised controlled trial in primary care.

Silk garments plus standard care compared with standard care for treating eczema in children: A randomised, controlled, observer-blind, pragmatic trial (CLOTHES Trial).

PubMed

Thomas, Kim S; Bradshaw, Lucy E; Sach, Tracey H; Batchelor, Jonathan M; Lawton, Sandra; Harrison, Eleanor F; Haines, Rachel H; Ahmed, Amina; Williams, Hywel C; Dean, Taraneh; Burrows, Nigel P; Pollock, Ian; Llewellyn, Joanne; Crang, Clare; Grundy, Jane D; Guiness, Juliet; Gribbin, Andrew; Mitchell, Eleanor J; Cowdell, Fiona; Brown, Sara J; Montgomery, Alan A

2017-04-01

The role of clothing in the management of eczema (also called atopic dermatitis or atopic eczema) is poorly understood. This trial evaluated the effectiveness and cost-effectiveness of silk garments (in addition to standard care) for the management of eczema in children with moderate to severe disease. This was a parallel-group, randomised, controlled, observer-blind trial. Children aged 1 to 15 y with moderate to severe eczema were recruited from secondary care and the community at five UK medical centres. Participants were allocated using online randomisation (1:1) to standard care or to standard care plus silk garments, stratified by age and recruiting centre. Silk garments were worn for 6 mo. Primary outcome (eczema severity) was assessed at baseline, 2, 4, and 6 mo, by nurses blinded to treatment allocation, using the Eczema Area and Severity Index (EASI), which was log-transformed for analysis (intention-to-treat analysis). A safety outcome was number of skin infections. Three hundred children were randomised (26 November 2013 to 5 May 2015): 42% girls, 79% white, mean age 5 y. Primary analysis included 282/300 (94%) children (n = 141 in each group). The garments were worn more often at night than in the day (median of 81% of nights [25th to 75th centile 57% to 96%] and 34% of days [25th to 75th centile 10% to 76%]). Geometric mean EASI scores at baseline, 2, 4, and 6 mo were, respectively, 9.2, 6.4, 5.8, and 5.4 for silk clothing and 8.4, 6.6, 6.0, and 5.4 for standard care. There was no evidence of any difference between the groups in EASI score averaged over all follow-up visits adjusted for baseline EASI score, age, and centre: adjusted ratio of geometric means 0.95, 95% CI 0.85 to 1.07, (p = 0.43). This confidence interval is equivalent to a difference of -1.5 to 0.5 in the original EASI units, which is not clinically important. Skin infections occurred in 36/142 (25%) and 39/141 (28%) of children in the silk clothing and standard care groups, respectively. Even if the small observed treatment effect was genuine, the incremental cost per quality-adjusted life year was £56,811 in the base case analysis from a National Health Service perspective, suggesting that silk garments are unlikely to be cost-effective using currently accepted thresholds. The main limitation of the study is that use of an objective primary outcome, whilst minimising detection bias, may have underestimated treatment effects. Silk clothing is unlikely to provide additional benefit over standard care in children with moderate to severe eczema. Current Controlled Trials ISRCTN77261365.

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.

Safe household water treatment and storage using ceramic drip filters: a randomised controlled trial in Bolivia.

PubMed

Clasen, T; Brown, J; Suntura, O; Collin, S

2004-01-01

A randomised controlled field trial was conducted to evaluate the effectiveness of ceramic drip filters to improve the microbiological quality of drinking water in a low-income community in rural Bolivia. In four rounds of water sampling over five months, 100% of the samples were free of thermotolerant (faecal) coliforms (TTC) compared to an arithmetic mean TTC count of 1517, 406, 167 and 245 among control households which continued to use their customary sources of drinking water. The filter systems produced water that consistently met WHO drinking-water standards despite levels of turbidity that presented a challenge to other low-cost POU treatment methods. The filter systems also demonstrated an ability to maintain the high quality of the treated water against subsequent re-contamination in the home.

International multicentre randomised controlled trial of improvisational music therapy for children with autism spectrum disorder: TIME-A study.

PubMed

Crawford, Mike J; Gold, Christian; Odell-Miller, Helen; Thana, Lavanya; Faber, Sarah; Assmus, Jörg; Bieleninik, Łucja; Geretsegger, Monika; Grant, Claire; Maratos, Anna; Sandford, Stephan; Claringbold, Amy; McConachie, Helen; Maskey, Morag; Mössler, Karin Antonia; Ramchandani, Paul; Hassiotis, Angela

2017-10-01

Preliminary studies have indicated that music therapy may benefit children with autism spectrum disorders (ASD). To examine the effects of improvisational music therapy (IMT) on social affect and responsiveness of children with ASD. International, multicentre, three-arm, single-masked randomised controlled trial, including a National Institute for Health Research (NIHR)-funded centre that recruited in London and the east of England. Randomisation was via a remote service using permuted blocks, stratified by study site. Schools and private, voluntary and state-funded health-care services. Children aged between 4 and 7 years with a confirmed diagnosis of ASD and a parent or guardian who provided written informed consent. We excluded children with serious sensory disorder and those who had received music therapy within the past 12 months. All parents and children received enhanced standard care (ESC), which involved three 60-minute sessions of advice and support in addition to treatment as usual. In addition, they were randomised to either one (low-frequency) or three (high-frequency) sessions of IMT per week, or to ESC alone, over 5 months in a ratio of 1 : 1 : 2. The primary outcome was measured using the social affect score derived from the Autism Diagnostic Observation Schedule (ADOS) at 5 months: higher scores indicated greater impairment. Secondary outcomes included social affect at 12 months and parent-rated social responsiveness at 5 and 12 months (higher scores indicated greater impairment). A total of 364 participants were randomised between 2011 and 2015. A total of 182 children were allocated to IMT (90 to high-frequency sessions and 92 to low-frequency sessions), and 182 were allocated to ESC alone. A total of 314 (86.3%) of the total sample were followed up at 5 months [165 (90.7%) in the intervention group and 149 (81.9%) in the control group]. Among those randomised to IMT, 171 (94.0%) received it. From baseline to 5 months, mean scores of ADOS social affect decreased from 14.1 to 13.3 in music therapy and from 13.5 to 12.4 in standard care [mean difference: music therapy vs. standard care = 0.06, 95% confidence interval (CI) -0.70 to 0.81], with no significant difference in improvement. There were also no differences in the parent-rated social responsiveness score, which decreased from 96.0 to 89.2 in the music therapy group and from 96.1 to 93.3 in the standard care group over this period (mean difference: music therapy vs. standard care = -3.32, 95% CI -7.56 to 0.91). There were seven admissions to hospital that were unrelated to the study interventions in the two IMT arms compared with 10 unrelated admissions in the ESC group. Adding IMT to the treatment received by children with ASD did not improve social affect or parent-assessed social responsiveness. Other methods for delivering music-focused interventions for children with ASD should be explored. Current Controlled Trials ISRCTN78923965. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 59. See the NIHR Journals Library website for further project information.

Maternal note-taking and infant care: a pilot randomised controlled trial.

PubMed

Kistin, Caroline J; Barrero-Castillero, Alejandra; Lewis, Sheilajane; Hoch, Rachel; Philipp, Barbara L; Bauchner, Howard; Wang, C Jason

2012-10-01

A pilot randomised controlled trial was conducted with postpartum mothers to assess the feasibility and impact of note-taking during newborn teaching. Controls received standard teaching; the intervention group received pen and paper to take notes. Subjects were called 2 days post-discharge to assess infant sleep position, breastfeeding, car seat use, satisfaction and information recall. 126 mothers were randomised. There was a consistent trend that intervention subjects were more likely to report infant supine sleep position (88% vs 78%, relative risks (RR) 1.13; 95% CI 0.95 to 1.34), breastfeeding (96% vs 86%, RR 1.11; 95% CI 0.99 to 1.25) and correct car seat use (98% vs 87%, RR 1.12; 95% CI 1.00 to 1.25). Satisfaction and information recall did not differ. Among first-time mothers, intervention subjects were significantly more likely to report infant supine sleep position (95% vs 65%, RR 1.46; 95% CI 1.06 to 2.00). Maternal note-taking is feasible and potentially efficacious in promoting desirable infant care.

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

PubMed

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

2018-03-26

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

Effect of the patient education - Learning and Coping strategies - in cardiac rehabilitation on return to work at one year: a randomised controlled trial show (LC-REHAB).

PubMed

Bitsch, Birgitte Laier; Nielsen, Claus Vinther; Stapelfeldt, Christina Malmose; Lynggaard, Vibeke

2018-05-21

Personal resources are identified as important for the ability to return to work (RTW) for patients with ischaemic heart disease (IHD) or heart failure (HF) undergoing cardiac rehabilitation (CR). The patient education 'Learning and Coping' (LC) addresses personal resources through a pedagogical approach. This trial aimed to assess effect of adding LC strategies in CR compared to standard CR measured on RTW status at one-year follow-up after CR. In an open parallel randomised controlled trial, patients with IHD or HF were block-randomised in a 1:1 ratio to the LC arm (LC plus CR) or the control arm (CR alone) across three Danish hospital units. Eligible patients were aged 18 to ≤60 and had not left the labour market. The intervention was developed from an inductive pedagogical approach consisting of individual interviews and group based teaching by health professionals with experienced patients as co-educators. The control arm consisted of deductive teaching (standard CR). RTW status was derived from the Danish Register for Evaluation of Marginalisation (DREAM). Blinding was not possible. The effect was evaluated by logistic regression analysis and reported as crude and adjusted odds ratios (OR) with 95% confidence interval (CI). The population for the present analysis was N = 244 (LC arm: n = 119 versus control arm: n = 125). No difference in RTW status was found at one year across arms (LC arm: 64.7% versus control arm: 68.8%, adjusted odds ratio OR: 0.76, 95% CI: 0.43-1.31). Addition of LC strategies in CR showed no improvement in RTW at one year follow-up. www.clinicaltrials.gov identifier NCT01668394. First Posted: August 20, 2012.

Infant adiposity following a randomised controlled trial of a behavioural intervention in obese pregnancy

PubMed Central

Patel, Nashita; Godfrey, Keith M.; Pasupathy, Dharmintra; Levin, Julia; Flynn, Angela C; Hayes, Louise; Briley, Annette L; Bell, Ruth; Lawlor, Debbie A; Oteng-Ntim, Eugene; Nelson, Scott M.; Robson, Stephen C.; Sattar, Naveed; Singh, Claire; Wardle, Jane; White, Sara; Seed, Paul T; Poston, Lucilla

2017-01-01

Objective Randomised controlled trials are required to address causality in the reported associations between maternal influences and offspring adiposity. The aim of this study was to determine whether an antenatal lifestyle intervention in obese pregnant women associated with improved maternal diet and reduced gestational weight gain leads to a reduction in infant adiposity and sustained improvements in maternal lifestyle behaviours at 6 months postpartum. Subjects and Methods We conducted a planned postnatal follow up of a randomised controlled trial (UPBEAT) of a complex behavioural intervention targeting maternal diet (glycemic load and saturated fat intake) and physical activity in 1555 obese pregnant women. The main outcome measure was infant adiposity, assessed by subscapular and triceps skinfold thicknesses. Maternal diet and physical activity, indices of the familial lifestyle environment, were assessed by questionnaire. Results 698 (45.9%) infants (342 intervention, 356 standard antenatal care) were followed up at mean age 5.92 months. There was no difference in triceps skinfold thickness z-scores between the intervention vs. standard care arms (difference -0.14 SD, 95% CI -0.38 to 0.10, p=0.246), but subscapular skinfold thickness z-score was 0.26 SD (-0.49 to -0.02; p=0.03) lower in the intervention arm. Maternal dietary glycemic load (-35.34; -48.0 to -22.67; p<0.001) and saturated fat intake (-1.93% energy; -2.64 to -1.22; p<0.001) were reduced in the intervention arm at 6 months postpartum. Causal mediation analysis suggested that lower infant subscapular skinfold thickness was mediated by changes in antenatal maternal diet and gestational weight gain rather than postnatal diet. Conclusion This study provides evidence from follow-up of a randomised controlled trial that a maternal behavioural intervention in obese pregnant women has the potential to reduce infant adiposity and to produce a sustained improvement in maternal diet at 6 months postpartum. PMID:28216644

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

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

A randomised controlled trial of empowerment training for Chinese abused pregnant women in Hong Kong.

PubMed

Tiwari, A; Leung, W C; Leung, T W; Humphreys, J; Parker, B; Ho, P C

2005-09-01

To evaluate the effectiveness of an empowerment intervention in reducing intimate partner violence (IPV) and improving health status. Randomised controlled trial. Antenatal clinic in a public hospital in Hong Kong. One hundred and ten Chinese pregnant women with a history of abuse by their intimate partners. Women were randomised to the experimental or control group. Experimental group women received empowerment training specially designed for Chinese abused pregnant women while the control group women received standard care for abused women. Data were collected at study entry and six weeks postnatal. IPV [on the Conflict Tactics Scale (CTS)], health-related quality of life (SF-36) and postnatal depression [Edinburgh Postnatal Depression Scale (EPDS)]. Following the training, the experimental group had significantly higher physical functioning and had significantly improved role limitation due to physical problems and emotional problems. They also reported less psychological (but not sexual) abuse, minor (but not severe) physical violence and had significantly lower postnatal depression scores. However, they reported more bodily pain. An empowerment intervention specially designed for Chinese abused pregnant women was effective in reducing IPV and improving the health status of the women.

Does peer-assisted learning improve academic performance? A scoping review.

PubMed

Williams, Brett; Reddy, Priya

2016-07-01

Due to the diverse and ever-changing nature of the healthcare industry, teaching pedagogies such as peer-assisted learning (PAL) are being implemented to align with external competency standards. A scoping review was conducted in order to map the breadth of literature available on PAL and its impact on student performance. This review used Arksey and O'Malley's six stage scoping methodology. The databases searched included: Cinahl, Ovid Medline, Proquest and Embase as well as grey literature sites and dissertations. 22 articles were included in this review, 10 of which were mixed methods randomised controlled trials, one retrospective study, four controlled trials, two randomised cross over controlled trial, three prospective randomised controlled trials, one thesis and one comparative research design. Analysis of the included articles identified three major themes outlining student performance. Student teachers themselves showed the most significant improvement in objective outcomes. The predominant healthcare field addressed were medical students with very few studies being completed on other professions. The search indicated an overall positive response to PAL with the measurable outcome of student tutors being of most significance. Further research is required to determine the relevance for the wider healthcare community. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cognitive training for technical and non-technical skills in robotic surgery: a randomised controlled trial.

PubMed

Raison, Nicholas; Ahmed, Kamran; Abe, Takashige; Brunckhorst, Oliver; Novara, Giacomo; Buffi, Nicolò; McIlhenny, Craig; van der Poel, Henk; van Hemelrijck, Mieke; Gavazzi, Andrea; Dasgupta, Prokar

2018-05-07

To investigate the effectiveness of motor imagery (MI) for technical skill and non-technical skill (NTS) training in minimally invasive surgery (MIS). A single-blind, parallel-group randomised controlled trial was conducted at the Vattikuti Institute of Robotic Surgery, King's College London. Novice surgeons were recruited by open invitation in 2015. After basic robotic skills training, participants underwent simple randomisation to either MI training or standard training. All participants completed a robotic urethrovesical anastomosis task within a simulated operating room. In addition to the technical task, participants were required to manage three scripted NTS scenarios. Assessment was performed by five blinded expert surgeons and a NTS expert using validated tools for evaluating technical skills [Global Evaluative Assessment of Robotic Skills (GEARS)] and NTS [Non-Technical Skills for Surgeons (NOTSS)]. Quality of MI was assessed using a revised Movement Imagery Questionnaire (MIQ). In all, 33 participants underwent MI training and 29 underwent standard training. Interrater reliability was high, Krippendorff's α = 0.85. After MI training, the mean (sd) GEARS score was significantly higher than after standard training, at 13.1 (3.25) vs 11.4 (2.97) (P = 0.03). There was no difference in mean NOTSS scores, at 25.8 vs 26.4 (P = 0.77). MI training was successful with significantly higher imagery scores than standard training (mean MIQ score 5.1 vs 4.5, P = 0.04). Motor imagery is an effective training tool for improving technical skill in MIS even in novice participants. No beneficial effect for NTS was found. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

The costs and benefits of technology-enabled, home-based cardiac rehabilitation measured in a randomised controlled trial.

PubMed

Whittaker, Frank; Wade, Victoria

2014-10-01

We conducted a cost benefit analysis of a home telehealth-based cardiac rehabilitation programme compared to the standard hospital-based programme. A total of 120 participants were enrolled in a trial, with 60 randomised to the telehealth group and 60 randomised to usual care. Participants in the telehealth group received a mobile phone, Wellness Diary and a Wellness web portal, with daily text messaging. Participants in the usual care group received the standard 6-week hospital-based outpatient cardiac rehabilitation programme, including gym sessions. The cost of delivery by telehealth was slightly lower than for patients attending a rehabilitation service in person. From the provider's perspective, the telehealth intervention could be delivered for $1633 per patient, compared to $1845 for the usual care group. From the participant's perspective, patient travel costs for home rehabilitation were substantially less than for hospital attendance ($80 vs $400). Cardiac rehabilitation by telehealth offers obvious advantages and the option should be available to all patients who are eligible for cardiac rehabilitation. © The Author(s) 2014 Reprints and permissions:]br]sagepub.co.uk/journalsPermissions.nav.

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.

Protocol for a multicentre randomiSed controlled TRial of IntraVEnous immunoglobulin versus standard therapy for the treatment of transverse myelitis in adults and children (STRIVE)

PubMed Central

Absoud, M; Gadian, J; Hellier, J; Brex, P A; Ciccarelli, O; Giovannoni, G; Kelly, J; McCrone, P; Murphy, C; Palace, J; Pickles, A; Pike, M; Robertson, N; Jacob, A; Lim, M

2015-01-01

Introduction Transverse myelitis (TM) is an immune-mediated disorder of the spinal cord which causes motor and sensory disturbance and limited recovery in 50% of patients. Standard treatment is steroids, and patients with more severe disease appear to respond to plasma exchange (PLEX). Intravenous immunoglobulin (IVIG) has also been used as an adjunct to steroids, but evidence is lacking. We propose the first randomised control trial in adults and children, to determine the benefit of additional treatment with IVIG. Methods and analysis 170 adults and children aged over 1 year with acute first episode TM or neuromyelitis optica (with myelitis) will be recruited over a 2.5-year period and followed up for 12 months. Participants randomised to the control arm will receive standard therapy of intravenous methylprednisolone (IVMP). The intervention arm will receive the above standard therapy, plus additional IVIG. Primary outcome will be a 2-point improvement on the American Spinal Injury Association (ASIA) Impairment scale at 6 months postrandomisation by blinded assessors. Additional secondary and tertiary outcome measures will be collected: ASIA motor and sensory scales, Kurtzke expanded disability status scale, International Spinal Cord Injury (SCI) Bladder/Bowel Data Set, Client Services Receipt Index, Pediatric Quality of Life Inventory, EQ-5D, SCI Pain and SCI Quality of Life Data Sets. Biological samples will be biobanked for future studies. After 6-months' follow-up of the first 52 recruited patients futility analysis will be carried out. Health economics analysis will be performed to calculate cost-effectiveness. After 6 months’ recruitment futility analysis will be performed. Ethics and dissemination Research Ethics Committee Approval was obtained: 14/SC/1329. Current protocol: v3.0 (15/01/2015). Study findings will be published in peer-reviewed journals. Trial registration numbers This study is registered with EudraCT (REF: 2014-002335-34), Clinicaltrials.gov (REF: NCT02398994) and ISRCTN (REF: 12127581). PMID:26009577

Protocol, and practical challenges, for a randomised controlled trial comparing the impact of high intensity interval training against standard care before major abdominal surgery: study protocol for a randomised controlled trial.

PubMed

Woodfield, John; Zacharias, Matthew; Wilson, Genevieve; Munro, Fran; Thomas, Kate; Gray, Andrew; Baldi, James

2018-06-25

Risk factors, such as the number of pre-existing co-morbidities, the extent of the underlying pathology and the magnitude of the required operation, cannot be changed before surgery. It may, however, be possible to improve the cardiopulmonary fitness of the patient with an individualised exercise program. We are performing a randomised controlled trial (RCT) assessing the impact of High Intensity Interval Training (HIIT) on preoperative cardiopulmonary fitness and postoperative outcomes in patients undergoing major abdominal surgery. Consecutive eligible patients undergoing elective abdominal surgery are being randomised to HIIT or standard care in a 1:1 ratio. Participants allocated to HIIT will perform 14 exercise sessions on a stationary cycle ergometer, over a period of 4-6 weeks before surgery. The sessions, which are individualised, aim to start with ten repeated 1-min blocks of intense exercise with a target of reaching a heart rate exceeding 90% of the age predicted maximum, followed by 1 min of lower intensity cycling. As endurance improves, the duration of exercise is increased to achieve five 2-min intervals of high intensity exercise followed by 2 min of lower intensity cycling. Each training session lasts approximately 30 min. The primary endpoint, change in peak oxygen consumption (Peak VO 2 ) measured during cardiopulmonary exercise testing, is assessed at baseline and before surgery. Secondary endpoints include postoperative complications, length of hospital stay and three clinically validated scores: the surgical recovery scale; the postoperative morbidity survey; and the SF-36 quality of life score. The standard deviation for changes in Peak VO 2 will be assessed after the first 30 patients and will be used to calculate the required sample size. We want to assess if 14 sessions of HIIT is sufficient to improve Peak VO 2 by 2 mL/kg/min in patients undergoing major abdominal surgery and to explore the best clinical endpoint for a subsequent RCT designed to assess if improving Peak VO 2 will translate into improving clinical outcomes after surgery. Australian New Zealand Clinical Trials Registry, ACTRN12617000587303 . Registered on 26 April 2017.

Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic lateral sclerosis (LiCALS) [Eudract number: 2008-006891-31].

PubMed

Al-Chalabi, Ammar; Shaw, Pamela J; Young, Carolyn A; Morrison, Karen E; Murphy, Caroline; Thornhill, Marie; Kelly, Joanna; Steen, I Nicholas; Leigh, P Nigel

2011-09-21

Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, no patients had died (i.e., 100% survival) at the end of the study (15 months from entry), compared to 71% surviving in the riluzole-only group. Although the trial can be criticised on several grounds, there is a substantial rationale from other laboratory studies that lithium is worth investigating therapeutically in amyotrophic lateral sclerosis. LiCALS is a multi-centre double-blind randomised parallel group controlled trial of the efficacy, safety, and tolerability of lithium carbonate (LiCO3) at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L), plus standard treatment, versus matched placebo plus standard treatment, in patients with amyotrophic lateral sclerosis. The study will be based in the UK, in partnership with the MND Association and DeNDRoN (the Dementias and Neurodegnerative Diseases Clinical Research Network). 220 patients will be recruited. All patients will be on the standard treatment for ALS of riluzole 100 mg daily. The primary outcome measure will be death from any cause at 18 months defined from the date of randomisation. Secondary outcome measures will be changes in three functional rating scales, the ALS Functional Rating Scale-Revised, The EuroQOL (EQ-5D), and the Hospital Anxiety and Depression Scale.Eligible patients will have El Escorial Possible, Laboratory-supported Probable, Probable or Definite amyotrophic lateral sclerosis with disease duration between 6 months and 36 months (inclusive), vital capacity ≥ 60% of predicted within 1 month prior to randomisation and age at least18 years. Patient recruitment began in June 2009 and the last patient is expected to complete the trial protocol in November 2011. Current controlled trials ISRCTN83178718.

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

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.

Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone-sensitive prostate cancer: a systematic review and meta-analyses of aggregate data

PubMed Central

Vale, Claire L; Burdett, Sarah; Rydzewska, Larysa H M; Albiges, Laurence; Clarke, Noel W; Fisher, David; Fizazi, Karim; Gravis, Gwenaelle; James, Nicholas D; Mason, Malcolm D; Parmar, Mahesh K B; Sweeney, Christopher J; Sydes, Matthew R; Tombal, Bertrand; Tierney, Jayne F

2016-01-01

Summary Background Results from large randomised controlled trials combining docetaxel or bisphosphonates with standard of care in hormone-sensitive prostate cancer have emerged. In order to investigate the effects of these therapies and to respond to emerging evidence, we aimed to systematically review all relevant trials using a framework for adaptive meta-analysis. Methods For this systematic review and meta-analysis, we searched MEDLINE, Embase, LILACS, and the Cochrane Central Register of Controlled Trials, trial registers, conference proceedings, review articles, and reference lists of trial publications for all relevant randomised controlled trials (published, unpublished, and ongoing) comparing either standard of care with or without docetaxel or standard of care with or without bisphosphonates for men with high-risk localised or metastatic hormone-sensitive prostate cancer. For each trial, we extracted hazard ratios (HRs) of the effects of docetaxel or bisphosphonates on survival (time from randomisation until death from any cause) and failure-free survival (time from randomisation to biochemical or clinical failure or death from any cause) from published trial reports or presentations or obtained them directly from trial investigators. HRs were combined using the fixed-effect model (Mantel-Haenzsel). Findings We identified five eligible randomised controlled trials of docetaxel in men with metastatic (M1) disease. Results from three (CHAARTED, GETUG-15, STAMPEDE) of these trials (2992 [93%] of 3206 men randomised) showed that the addition of docetaxel to standard of care improved survival. The HR of 0·77 (95% CI 0·68–0·87; p<0·0001) translates to an absolute improvement in 4-year survival of 9% (95% CI 5–14). Docetaxel in addition to standard of care also improved failure-free survival, with the HR of 0·64 (0·58–0·70; p<0·0001) translating into a reduction in absolute 4-year failure rates of 16% (95% CI 12–19). We identified 11 trials of docetaxel for men with locally advanced disease (M0). Survival results from three (GETUG-12, RTOG 0521, STAMPEDE) of these trials (2121 [53%] of 3978 men) showed no evidence of a benefit from the addition of docetaxel (HR 0·87 [95% CI 0·69–1·09]; p=0·218), whereas failure-free survival data from four (GETUG-12, RTOG 0521, STAMPEDE, TAX 3501) of these trials (2348 [59%] of 3978 men) showed that docetaxel improved failure-free survival (0·70 [0·61–0·81]; p<0·0001), which translates into a reduced absolute 4-year failure rate of 8% (5–10). We identified seven eligible randomised controlled trials of bisphosphonates for men with M1 disease. Survival results from three of these trials (2740 [88%] of 3109 men) showed that addition of bisphosphonates improved survival (0·88 [0·79–0·98]; p=0·025), which translates to 5% (1–8) absolute improvement, but this result was influenced by the positive result of one trial of sodium clodronate, and we found no evidence of a benefit from the addition of zoledronic acid (0·94 [0·83–1·07]; p=0·323), which translates to an absolute improvement in survival of 2% (−3 to 7). Of 17 trials of bisphosphonates for men with M0 disease, survival results from four trials (4079 [66%] of 6220 men) showed no evidence of benefit from the addition of bisphosphonates (1·03 [0·89–1·18]; p=0·724) or zoledronic acid (0·98 [0·82–1·16]; p=0·782). Failure-free survival definitions were too inconsistent for formal meta-analyses for the bisphosphonate trials. Interpretation The addition of docetaxel to standard of care should be considered standard care for men with M1 hormone-sensitive prostate cancer who are starting treatment for the first time. More evidence on the effects of docetaxel on survival is needed in the M0 disease setting. No evidence exists to suggest that zoledronic acid improves survival in men with M1 or M0 disease, and any potential benefit is probably small. Funding Medical Research Council UK. PMID:26718929

A cluster randomised feasibility study of an adolescent incentive intervention to increase uptake of HPV vaccination

PubMed Central

Forster, Alice S; Cornelius, Victoria; Rockliffe, Lauren; Marlow, Laura AV; Bedford, Helen; Waller, Jo

2017-01-01

Background: Uptake of human papillomavirus (HPV) vaccination is suboptimal among some groups. We aimed to determine the feasibility of undertaking a cluster randomised controlled trial (RCT) of incentives to improve HPV vaccination uptake by increasing consent form return. Methods: An equal-allocation, two-arm cluster RCT design was used. We invited 60 London schools to participate. Those agreeing were randomised to either a standard invitation or incentive intervention arm, in which Year 8 girls had the chance to win a £50 shopping voucher if they returned a vaccination consent form, regardless of whether consent was provided. We collected data on school and parent participation rates and questionnaire response rates. Analyses were descriptive. Results: Six schools completed the trial and only 3% of parents opted out. The response rate was 70% for the girls’ questionnaire and 17% for the parents’. In the intervention arm, 87% of girls returned a consent form compared with 67% in the standard invitation arm. The proportion of girls whose parents gave consent for vaccination was higher in the intervention arm (76%) than the standard invitation arm (61%). Conclusions: An RCT of an incentive intervention is feasible. The intervention may improve vaccination uptake but a fully powered RCT is needed. PMID:28829766

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

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

Pilot randomised controlled trial of the ENGAGER collaborative care intervention for prisoners with common mental health problems, near to and after release.

PubMed

Lennox, Charlotte; Kirkpatrick, Tim; Taylor, Rod S; Todd, Roxanne; Greenwood, Clare; Haddad, Mark; Stevenson, Caroline; Stewart, Amy; Shenton, Deborah; Carroll, Lauren; Brand, Sarah L; Quinn, Cath; Anderson, Rob; Maguire, Mike; Harris, Tirril; Shaw, Jennifer; Byng, Richard

2018-01-01

Rates of common mental health problems are much higher in prison populations, but access to primary care mental health support falls short of community equivalence. Discontinuity of care on release is the norm and is further complicated by substance use and a range of social problems, e.g. homelessness. To address these problems, we worked with criminal justice, third sector social inclusion services, health services and people with lived experiences (peer researchers), to develop a complex collaborative care intervention aimed at supporting men with common mental health problems near to and following release from prison. This paper describes an external pilot trial to test the feasibility of a full randomised controlled trial. Eligible individuals with 4 to 16 weeks left to serve were screened to assess for common mental health problems. Participants were then randomised at a ratio of 2:1 allocation to ENGAGER plus standard care (intervention) or standard care alone (treatment as usual). Participants were followed up at 1 and 3 months' post release. Success criteria for this pilot trial were to meet the recruitment target sample size of 60 participants, to follow up at least 50% of participants at 3 months' post release from prison, and to deliver the ENGAGER intervention. Estimates of recruitment and retention rates and 95% confidence intervals (CIs) are reported. Descriptive analyses included summaries (percentages or means) for participant demographics, and baseline characteristics are reported. Recruitment target was met with 60 participants randomised in 9 months. The average retention rates were 73% at 1 month [95% CI 61 to 83] and 47% at 3 months follow-up [95% CI 35 to 59]. Ninety percent of participants allocated to the intervention successfully engaged with a practitioner before release and 70% engaged following release. This pilot confirms the feasibility of conducting a randomised trial for prison leavers with common mental health problems. Based on this pilot study and some minor changes to the trial design and intervention, a full two-centre randomised trial assessing the clinical and cost-effectiveness of the ENGAGER intervention is currently underway.

Retrograde ejaculation, painful ejaculation and hematospermia

PubMed Central

Parnham, Arie

2016-01-01

Although there has been an increased interest on premature ejaculation in the recent years, our understanding regarding the disorders of retrograde ejaculation, painful ejaculation and hematospermia remain limited. All three of these conditions require a keen clinical acumen and willingness to engage in thinking outside of the standard established treatment paradigm. The development of novel investigational techniques and treatments has led to progress in the management of these conditions symptoms; however, the literature almost uniformly is limited to small series and rare randomised trials. Further investigation and randomised controlled trials are needed for progress in these often challenging cases. PMID:27652230

Injury risk in runners using standard or motion control shoes: a randomised controlled trial with participant and assessor blinding.

PubMed

Malisoux, Laurent; Chambon, Nicolas; Delattre, Nicolas; Gueguen, Nils; Urhausen, Axel; Theisen, Daniel

2016-04-01

This randomised controlled trial investigated if the usage of running shoes with a motion control system modifies injury risk in regular leisure-time runners compared to standard shoes, and if this influence depends on foot morphology. Recreational runners (n=372) were given either the motion control or the standard version of a regular running shoe model and were followed up for 6 months regarding running activity and injury. Foot morphology was analysed using the Foot Posture Index method. Cox regression analyses were used to compare injury risk between the two groups, based on HRs and their 95% CIs, controlling for potential confounders. Stratified analyses were conducted to evaluate the effect of motion control system in runners with supinated, neutral and pronated feet. The overall injury risk was lower among the participants who had received motion control shoes (HR=0.55; 95% CI 0.36 to 0.85) compared to those receiving standard shoes. This positive effect was only observed in the stratum of runners with pronated feet (n=94; HR=0.34; 95% CI 0.13 to 0.84); there was no difference in runners with neutral (n=218; HR=0.78; 95% CI 0.44 to 1.37) or supinated feet (n=60; HR=0.59; 95% CI 0.20 to 1.73). Runners with pronated feet using standard shoes had a higher injury risk compared to those with neutral feet (HR=1.80; 95% CI 1.01 to 3.22). The overall injury risk was lower in participants who had received motion control shoes. Based on secondary analysis, those with pronated feet may benefit most from this shoe type. 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 motivation and capacity to go 'above and beyond': Qualitative analysis of free-text survey responses in the M@NGO randomised controlled trial of caseload midwifery.

PubMed

Allen, Jyai; Kildea, Sue; Hartz, Donna L; Tracy, Mark; Tracy, Sally

2017-07-01

to explore whether women allocated to caseload care characterise their midwife differently to those allocated to standard care. multi-site unblinded, randomised, controlled, parallel-group trial. the study was conducted in two metropolitan teaching hospitals across two Australian cities. women of all obstetric risk were eligible to participate. Inclusion criteria were: 18 years or older, less than 24 week's gestation with a singleton pregnancy. Women already booked with a care provider or planning to have an elective caesarean section were excluded. participants were randomised to caseload midwifery or standard care. The caseload model provided antenatal, intrapartum and postnatal care from a primary midwife or 'back-up' midwife; as well as consultation with obstetric or medical physicians as indicated by national guidelines. The standard model included care from a general practitioner and/or midwives and obstetric doctors. participants' responses to open-ended questions were collected through a 6-week postnatal survey and analysed thematically. A total of 1748 women were randomised between December 2008 - May 2011; 871 to caseload midwifery and 877 to standard care. The response rate to the 6-week survey including free text items was 52% (n=901). Respondents from both groups characterised midwives as Informative, Competent and Kind. Participants in the caseload group perceived midwives with additional qualities conceptualised as Empowering and 'Endorphic'. These concepts highlight some of the active ingredients that moderated or mediated the effects of the midwifery care within the M@NGO trial. caseload midwifery attracts, motivates and enables midwives to go Above and Beyond such that women feel empowered, nurtured and safe during pregnancy, labour and birth. the concept of an Endorphic midwife makes a useful contribution to midwifery theory as it enhances our understanding of how the complex intervention of caseload midwifery influences normal birth rates and experiences. Defining personal midwife attributes which are important for caseload models has potential implications for graduate attributes in degree programs leading to registration as a midwife and selection criteria for caseload midwife positions. Copyright © 2017 Elsevier Ltd. All rights reserved.

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial.

PubMed

van Tilborg, Theodora C; Eijkemans, Marinus J C; Laven, Joop S E; Koks, Carolien A M; de Bruin, Jan Peter; Scheffer, Gabrielle J; van Golde, Ron J T; Fleischer, Kathrin; Hoek, Annemieke; Nap, Annemiek W; Kuchenbecker, Walter K H; Manger, Petra A; Brinkhuis, Egbert A; van Heusden, Arne M; Sluijmer, Alexander V; Verhoeff, Arie; van Hooff, Marcel H A; Friederich, Jaap; Smeenk, Jesper M J; Kwee, Janet; Verhoeve, Harold R; Lambalk, Cornelis B; Helmerhorst, Frans M; van der Veen, Fulco; Mol, Ben Willem J; Torrance, Helen L; Broekmans, Frank J M

2012-09-18

Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT. The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines. NTR2657.

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).

Text messaging reminders for influenza vaccine in primary care: protocol for a cluster randomised controlled trial (TXT4FLUJAB).

PubMed

Herrett, Emily; van Staa, Tjeerd; Free, Caroline; Smeeth, Liam

2014-05-02

The UK government recommends that at least 75% of people aged under 64 with certain conditions receive an annual influenza vaccination. Primary care practices often fall short of this target and strategies to increase vaccine uptake are required. Text messaging reminders are already used in 30% of practices to remind patients about vaccination, but there has been no trial addressing their effectiveness in increasing influenza vaccine uptake in the UK. The aims of the study are (1) to develop the methodology for conducting cluster randomised trials of text messaging interventions utilising routine electronic health records and (2) to assess the effectiveness of using a text messaging influenza vaccine reminder in achieving an increase in influenza vaccine uptake in patients aged 18-64 with chronic conditions, compared with standard care. This cluster randomised trial will recruit general practices across three settings in English primary care (Clinical Practice Research Datalink, ResearchOne and London iPLATO text messaging software users) and randomise them to either standard care or a text messaging campaign to eligible patients. Flu vaccine uptake will be ascertained using routinely collected, anonymised electronic patient records. This protocol outlines the proposed study design and analysis methods. This study will determine the effectiveness of text messaging vaccine reminders in primary care in increasing influenza vaccine uptake, and will strengthen the methodology for using electronic health records in cluster randomised trials of text messaging interventions. This trial was approved by the Surrey Borders Ethics Committee (13/LO/0872). The trial results will be disseminated at national conferences and published in a peer-reviewed medical journal. The results will also be distributed to the Primary Care Research Network and to all participating general practices. This study is registered at controlled-trials.com ISRCTN48840025, July 2013.

A randomised controlled trial evaluating a rehabilitation complex intervention for patients following intensive care discharge: the RECOVER study

PubMed Central

Salisbury, Lisa G; Boyd, Julia; Ramsay, Pamela; Merriweather, Judith; Huby, Guro; Forbes, John; Rattray, Janice Z; Griffith, David M; Mackenzie, Simon J; Hull, Alastair; Lewis, Steff; Murray, Gordon D

2012-01-01

Introduction Patients who survive an intensive care unit admission frequently suffer physical and psychological morbidity for many months after discharge. Current rehabilitation pathways are often fragmented and little is known about the optimum method of promoting recovery. Many patients suffer reduced quality of life. Methods and analysis The authors plan a multicentre randomised parallel group complex intervention trial with concealment of group allocation from outcome assessors. Patients who required more than 48 h of mechanical ventilation and are deemed fit for intensive care unit discharge will be eligible. Patients with primary neurological diagnoses will be excluded. Participants will be randomised into one of the two groups: the intervention group will receive standard ward-based care delivered by the NHS service with additional treatment by a specifically trained generic rehabilitation assistant during ward stay and via telephone contact after hospital discharge and the control group will receive standard ward-based care delivered by the current NHS service. The intervention group will also receive additional information about their critical illness and access to a critical care physician. The total duration of the intervention will be from randomisation to 3 months postrandomisation. The total duration of follow-up will be 12 months from randomisation for both groups. The primary outcome will be the Rivermead Mobility Index at 3 months. Secondary outcomes will include measures of physical and psychological morbidity and function, quality of life and survival over a 12-month period. A health economic evaluation will also be undertaken. Groups will be compared in relation to primary and secondary outcomes; quantitative analyses will be supplemented by focus groups with patients, carers and healthcare workers. Ethics and dissemination Consent will be obtained from patients and relatives according to patient capacity. Data will be analysed according to a predefined analysis plan. Trial registration The trial is registered as ISRCTN09412438 and funded by the Chief Scientist Office, Scotland. PMID:22761291

Effectiveness of autologous fibrin tissue adhesive in reducing postoperative blood loss during total hip arthroplasty: a prospective randomised study of 100 cases.

PubMed

Mawatari, M; Higo, T; Tsutsumi, Y; Shigematsu, M; Hotokebuchi, T

2006-08-01

To evaluate the effectiveness of autologous fibrin tissue adhesive (auto-FTA) in reducing blood loss during cementless total hip arthroplasty (THA). From September 2000 to August 2001, 100 patients who predonated 400 ml of autologous blood were randomised to undergo either standard treatment with auto-FTA (auto-FTA group) or standard treatment alone (control group). The volume of postoperative blood loss and the decrease in haemoglobin level were measured. All patients were followed up for 3 years to evaluate the rate of bone ingrowth and heterotopic ossification. The mean postoperative blood loss was 580 ml (standard deviation [SD], 240 ml) in the auto-FTA group and 810 ml (SD, 341 ml) in the control group; the difference was significant (230 ml, p<0.001). The decrease in haemoglobin concentration was 17 g/l (SD, 11 g/l) in the auto-FTA group and 22 g/l (SD, 12 g/l) in the control group. The difference was significant (5 g/l, p=0.03). The percentage of total blood loss of >1200 ml in any single patient was significantly lower in the auto-FTA group (4%) than in the control group (20%) [p=0.01]. Auto-FTA is a safe and effective means of reducing perioperative blood loss in THA.

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

Reverse breech extraction versus the standard approach of pushing the impacted fetal head up through the vagina in caesarean section for obstructed labour: A randomised controlled trial.

PubMed

Nooh, Ahmed Mohamed; Abdeldayem, Hussein Mohammed; Ben-Affan, Othman

2017-05-01

The objective of this study was to assess effectiveness and safety of the reverse breech extraction approach in Caesarean section for obstructed labour, and compare it with the standard approach of pushing the fetal head up through the vagina. This randomised controlled trial included 192 women. In 96, the baby was delivered by the 'reverse breech extraction approach', and in the remaining 96, by the 'standard approach'. Extension of uterine incision occurred in 18 participants (18.8%) in the reverse breech extraction approach group, and 46 (47.9%) in the standard approach group (p = .0003). Two women (2.1%) in the reverse breech extraction approach group needed blood transfusion and 11 (11.5%) in the standard approach group (p = .012). Pyrexia developed in 3 participants (3.1%) in the reverse breech extraction approach group, and 19 (19.8%) in the standard approach group (p = .0006). Wound infection occurred in 2 women (2.1%) in the reverse breech extraction approach group, and 12 (12.5%) in the standard approach group (p = .007). Apgar score <7 at 5 minutes was noted in 8 babies (8.3%) in the reverse breech extraction approach group, and 21 (21.9%) in the standard approach group (p = .015). In conclusion, reverse breech extraction in Caesarean section for obstructed labour is an effective and safe alternative to the standard approach of pushing the fetal head up through the vagina.

Evaluating the effectiveness of using personal tailored risk information and taster sessions to increase the uptake of smoking cessation services: study protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Although government-funded specialist smoking cessation services in England offer advice and support to smokers motivated to quit, only a small proportion of smokers make use of this service. Evidence suggests that if smokers are proactively and personally invited to use services, use will be higher than with a standard referral made by health professionals. Computer-based systems generating personalised tailored communications also have the potential to engage with a larger proportion of the smoking population. In this study smokers are proactively invited to use the NHS Stop Smoking Service (SSS), with a personal computer-tailored letter and the offer of a no-commitment introductory session designed to give more information about the service. The primary objective is to assess the relative effectiveness on attendance at the NHS SSS, of proactive recruitment by a brief personal letter, tailored to individual characteristics, and invitation to a taster session, over a standard generic letter advertising the service. Method/design This randomised controlled trial will recruit smokers from general practice who are motivated to quit and have not recently attended the NHS SSS. Smokers aged 16 years and over, identified from medical records in participating practices, are sent a brief screening questionnaire and cover letter from their GP. Smokers giving consent are randomised to the Control group to receive a standard generic letter advertising the local service, or to the Intervention group to receive a brief personal, tailored letter with risk information and an invitation to attend a ‘Come and Try it’ taster session. The primary outcome, assessed 6 months after the date of randomisation, is the proportion of people attending the NHS SSS for at least one session. Planned recruitment is to secure 4,500 participants, from 18 regions in England served by an NHS SSS. Discussion Personal risk information generated by computer, with the addition of taster sessions, could be widely replicated and delivered cost effectively to a large proportion of the smoking population. The results of this trial will inform the potential of this method to increase referrals to specialised smoking cessation services and prompt more quit attempts. Trial registration Current Controlled Trials ISRCTN76561916 PMID:23078797

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.

Tight intra-operative blood pressure control versus standard care for patients undergoing hip fracture repair - Hip Fracture Intervention Study for Prevention of Hypotension (HIP-HOP) trial: study protocol for a randomised controlled trial.

PubMed

Moppett, Iain Keith; White, Stuart; Griffiths, Richard; Buggy, Donal

2017-07-25

Hypotension during anaesthesia for hip fracture surgery is common. Recent data suggest that there is an association between the lowest intra-operative blood pressure and mortality, even when adjusted for co-morbidities. This is consistent with data derived from the wider surgical population, where magnitude and duration of hypotension are associated with mortality and peri-operative complications. However, there are no trial to data to support more aggressive blood pressure control. We are conducting a three-centre, randomised, double-blinded pilot study in three hospitals in the United Kingdom. The sample size will be 75 patients (25 from each centre). Randomisation will be done using computer-generated concealed tables. Both participants and investigators will be blinded to group allocation. Participants will be aged >70 years, cognitively intact (Abbreviated Mental Test Score 7 or greater), able to give informed consent and admitted directly through the emergency department with a fractured neck of the femur requiring operative repair. Patients randomised to tight blood pressure control or avoidance of intra-operative hypotension will receive active treatment as required to maintain both of the following: systolic arterial blood pressure >80% of baseline pre-operative value and mean arterial pressure >75 mmHg throughout. All participants will receive standard hospital care, including spinal or general anaesthesia, at the discretion of the clinical team. The primary outcome is a composite of the presence or absence of defined cardiovascular, renal and delirium morbidity within 7 days of surgery (myocardial injury, stroke, acute kidney injury, delirium). Secondary endpoints will include the defined individual morbidities, mortality, early mobility and discharge to usual residence. This is a small-scale pilot study investigating the feasibility of a trial of tight intra-operative blood pressure control in a frail elderly patient group with known high morbidity and mortality. Positive findings will provide the basis for a larger-scale study. ISRCTN Registry identifier: ISRCTN89812075 . Registered on 30 August 2016.

Effect of paper quality on the response rate to a postal survey: A randomised controlled trial. [ISRCTN32032031

PubMed Central

Clark, T Justin; Khan, Khalid S; Gupta, Janesh K

2001-01-01

Background Response rates to surveys are declining and this threatens the validity and generalisability of their findings. We wanted to determine whether paper quality influences the response rate to postal surveys Methods A postal questionnaire was sent to all members of the British Society of Gynaecological Endoscopy (BSGE). Recipients were randomised to receiving the questionnaire printed on standard quality paper or high quality paper. Results The response rate for the recipients of high quality paper was 43/195 (22%) and 57/194 (29%) for standard quality paper (relative rate of response 0.75, 95% CI 0.33–1.05, p = 0.1 Conclusion The use of high quality paper did not increase response rates to a questionnaire survey of gynaecologists affiliated to an endoscopic society. PMID:11782286

Music therapy for depression.

PubMed

Maratos, A S; Gold, C; Wang, X; Crawford, M J

2008-01-23

Depression is a highly prevalent disorder associated with reduced social functioning, impaired quality of life, and increased mortality. Music therapy has been used in the treatment of a variety of mental disorders, but its impact on those with depression is unclear. To examine the efficacy of music therapy with standard care compared to standard care alone among people with depression and to compare the effects of music therapy for people with depression against other psychological or pharmacological therapies. CCDANCTR-Studies and CCDANCTR-References were searched on 7/11/2007, MEDLINE, PsycINFO, EMBASE, PsycLit, PSYindex, and other relevant sites were searched in November 2006. Reference lists of retrieved articles were hand searched, as well as specialist music and arts therapies journals. All randomised controlled trials comparing music therapy with standard care or other interventions for depression. Data on participants, interventions and outcomes were extracted and entered onto a database independently by two review authors. The methodological quality of each study was also assessed independently by two review authors. The primary outcome was reduction in symptoms of depression, based on a continuous scale. Five studies met the inclusion criteria of the review. Marked variations in the interventions offered and the populations studied meant that meta-analysis was not appropriate. Four of the five studies individually reported greater reduction in symptoms of depression among those randomised to music therapy than to those in standard care conditions. The fifth study, in which music therapy was used as an active control treatment, reported no significant change in mental state for music therapy compared with standard care. Dropout rates from music therapy conditions appeared to be low in all studies. Findings from individual randomised trials suggest that music therapy is accepted by people with depression and is associated with improvements in mood. However, the small number and low methodological quality of studies mean that it is not possible to be confident about its effectiveness. High quality trials evaluating the effects of music therapy on depression are required.

Gene therapy for haemophilia.

PubMed

Sharma, Akshay; Easow Mathew, Manu; Sriganesh, Vasumathi; Neely, Jessica A; Kalipatnapu, Sasank

2014-11-14

Haemophilia is a genetic disorder which is characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy has recently been prompted as a curative treatment modality. To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 06 November 2014. Eligible trials included randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. No trials of gene therapy for haemophilia were found. No trials of gene therapy for haemophilia were identified. No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the effects of gene therapy for haemophilia. Gene therapy for haemophilia is still in its nascent stages and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

Protocol for a single-centre, randomised controlled study of a preoperative rehabilitation bundle in the frail and elderly undergoing abdominal surgery

PubMed Central

Lien, Victoria Peixin; Ong, Hwee Kuan; Er, Pei Ling; Hao, Ying; Khan, Shariq Ali; Liu, Christopher Weiyang

2017-01-01

Introduction Frail patients have decreased physiological reserves and consequently, they are unable to recover as quickly from surgery. Frailty, as an entity, is a risk factor of increased morbidity and mortality. It is also associated with a longer time to discharge. This trial is undertaken to determine if a novel prehabilitation protocol (10-day bundle of interventions—physiotherapy, nutritional supplementation and cognitive training) can reduce the postoperative length of stay of frail patients who are undergoing elective abdominal surgery, compared with standard care. Methods and analysis This is a prospective, single-centre, randomised controlled trial with two parallel arms. 62 patients who are frail and undergoing elective abdominal surgery will be recruited and randomised to receive either a novel prehabilitation protocol or standard care. Participants will receive telephone reminders preoperatively to encourage protocol compliance. Data will be collected for up to 30 days postoperatively. The primary outcome of the trial will be the postoperative length of stay and the secondary outcomes are the postoperative complications and functional recovery during the hospital admission. Ethics and dissemination This study has been approved by the Singapore General Hospital Institutional Review Board (CIRB Ref: 2016/2584). The study is also listed on ClinicalTrials.gov (Trial number: NCT02921932). All participants will sign an informed consent form before randomisation and translators will be made available to non-English speaking patients. The results of this study will be published in peer-reviewed journals as well as national and international conferences. The data collected will also be made available in a public data repository. Trial registration number NCT02921932 (ClinicalTrials.gov) PMID:28778994

Advance care planning in patients with incurable cancer: study protocol for a randomised controlled trial

PubMed Central

Clayton, Josephine; Butow, Phyllis N; Silvester, William; Detering, Karen; Hall, Jane; Kiely, Belinda E; Cebon, Jonathon; Clarke, Stephen; Bell, Melanie L; Stockler, Martin; Beale, Phillip; Tattersall, Martin H N

2016-01-01

Introduction There is limited evidence documenting the effectiveness of Advance Care Planning (ACP) in cancer care. The present randomised trial is designed to evaluate whether the administration of formal ACP improves compliance with patients' end-of-life (EOL) wishes and patient and family satisfaction with care. Methods and analysis A randomised control trial in eight oncology centres across New South Wales and Victoria, Australia, is designed to assess the efficacy of a formal ACP intervention for patients with cancer. Patients with incurable cancer and an expected survival of 3–12 months, plus a nominated family member or friend will be randomised to receive either standard care or standard care plus a formal ACP intervention. The project sample size is 210 patient–family/friend dyads. The primary outcome measure is family/friend-reported: (1) discussion with the patient about their EOL wishes and (2) perception that the patient's EOL wishes were met. Secondary outcome measures include: documentation of and compliance with patient preferences for medical intervention at the EOL; the family/friend's perception of the quality of the patient's EOL care; the impact of death on surviving family; patient–family and patient–healthcare provider communication about EOL care; patient and family/friend satisfaction with care; quality of life of patient and family/friend subsequent to trial entry, the patient's strength of preferences for quality of life and length of life; the costs of care subsequent to trial entry and place of death. Ethics and dissemination Ethical approval was received from the Sydney Local Health District (RPA Zone) Human Research Ethical Committee, Australia (Protocol number X13-0064). Study results will be submitted for publication in peer-reviewed journals and presented at national and international conferences. Trial registration number Pre-results; ACTRN12613001288718. PMID:27909034

Protocol for a single-centre, randomised controlled study of a preoperative rehabilitation bundle in the frail and elderly undergoing abdominal surgery.

PubMed

Abdullah, Hairil Rizal; Lien, Victoria Peixin; Ong, Hwee Kuan; Er, Pei Ling; Hao, Ying; Khan, Shariq Ali; Liu, Christopher Weiyang

2017-08-04

Frail patients have decreased physiological reserves and consequently, they are unable to recover as quickly from surgery. Frailty, as an entity, is a risk factor of increased morbidity and mortality. It is also associated with a longer time to discharge. This trial is undertaken to determine if a novel prehabilitation protocol (10-day bundle of interventions-physiotherapy, nutritional supplementation and cognitive training) can reduce the postoperative length of stay of frail patients who are undergoing elective abdominal surgery, compared with standard care. This is a prospective, single-centre, randomised controlled trial with two parallel arms. 62 patients who are frail and undergoing elective abdominal surgery will be recruited and randomised to receive either a novel prehabilitation protocol or standard care. Participants will receive telephone reminders preoperatively to encourage protocol compliance. Data will be collected for up to 30 days postoperatively. The primary outcome of the trial will be the postoperative length of stay and the secondary outcomes are the postoperative complications and functional recovery during the hospital admission. This study has been approved by the Singapore General Hospital Institutional Review Board (CIRB Ref: 2016/2584). The study is also listed on ClinicalTrials.gov (Trial number: NCT02921932). All participants will sign an informed consent form before randomisation and translators will be made available to non-English speaking patients. The results of this study will be published in peer-reviewed journals as well as national and international conferences. The data collected will also be made available in a public data repository. NCT02921932 (ClinicalTrials.gov). © 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.

Silk garments plus standard care compared with standard care for treating eczema in children: A randomised, controlled, observer-blind, pragmatic trial (CLOTHES Trial)

PubMed Central

Thomas, Kim S.; Lawton, Sandra; Ahmed, Amina; Dean, Taraneh; Burrows, Nigel P.; Pollock, Ian; Grundy, Jane D.; Guiness, Juliet

2017-01-01

Background The role of clothing in the management of eczema (also called atopic dermatitis or atopic eczema) is poorly understood. This trial evaluated the effectiveness and cost-effectiveness of silk garments (in addition to standard care) for the management of eczema in children with moderate to severe disease. Methods and findings This was a parallel-group, randomised, controlled, observer-blind trial. Children aged 1 to 15 y with moderate to severe eczema were recruited from secondary care and the community at five UK medical centres. Participants were allocated using online randomisation (1:1) to standard care or to standard care plus silk garments, stratified by age and recruiting centre. Silk garments were worn for 6 mo. Primary outcome (eczema severity) was assessed at baseline, 2, 4, and 6 mo, by nurses blinded to treatment allocation, using the Eczema Area and Severity Index (EASI), which was log-transformed for analysis (intention-to-treat analysis). A safety outcome was number of skin infections. Three hundred children were randomised (26 November 2013 to 5 May 2015): 42% girls, 79% white, mean age 5 y. Primary analysis included 282/300 (94%) children (n = 141 in each group). The garments were worn more often at night than in the day (median of 81% of nights [25th to 75th centile 57% to 96%] and 34% of days [25th to 75th centile 10% to 76%]). Geometric mean EASI scores at baseline, 2, 4, and 6 mo were, respectively, 9.2, 6.4, 5.8, and 5.4 for silk clothing and 8.4, 6.6, 6.0, and 5.4 for standard care. There was no evidence of any difference between the groups in EASI score averaged over all follow-up visits adjusted for baseline EASI score, age, and centre: adjusted ratio of geometric means 0.95, 95% CI 0.85 to 1.07, (p = 0.43). This confidence interval is equivalent to a difference of −1.5 to 0.5 in the original EASI units, which is not clinically important. Skin infections occurred in 36/142 (25%) and 39/141 (28%) of children in the silk clothing and standard care groups, respectively. Even if the small observed treatment effect was genuine, the incremental cost per quality-adjusted life year was £56,811 in the base case analysis from a National Health Service perspective, suggesting that silk garments are unlikely to be cost-effective using currently accepted thresholds. The main limitation of the study is that use of an objective primary outcome, whilst minimising detection bias, may have underestimated treatment effects. Conclusions Silk clothing is unlikely to provide additional benefit over standard care in children with moderate to severe eczema. Trial registration Current Controlled Trials ISRCTN77261365 PMID:28399154

The Effects of Clinical Hypnosis versus Neurolinguistic Programming (NLP) before External Cephalic Version (ECV): A Prospective Off-Centre Randomised, Double-Blind, Controlled Trial

PubMed Central

Reinhard, Joscha; Peiffer, Swati; Sänger, Nicole; Herrmann, Eva; Yuan, Juping; Louwen, Frank

2012-01-01

Objective. To examine the effects of clinical hypnosis versus NLP intervention on the success rate of ECV procedures in comparison to a control group. Methods. A prospective off-centre randomised trial of a clinical hypnosis intervention against NLP of women with a singleton breech fetus at or after 370/7 (259 days) weeks of gestation and normal amniotic fluid index. All 80 participants heard a 20-minute recorded intervention via head phones. Main outcome assessed was success rate of ECV. The intervention groups were compared with a control group with standard medical care alone (n = 122). Results. A total of 42 women, who received a hypnosis intervention prior to ECV, had a 40.5% (n = 17), successful ECV, whereas 38 women, who received NLP, had a 44.7% (n = 17) successful ECV (P > 0.05). The control group had similar patient characteristics compared to the intervention groups (P > 0.05). In the control group (n = 122) 27.3% (n = 33) had a statistically significant lower successful ECV procedure than NLP (P = 0.05) and hypnosis and NLP (P = 0.03). Conclusions. These findings suggest that prior clinical hypnosis and NLP have similar success rates of ECV procedures and are both superior to standard medical care alone. PMID:22778774

The Effects of Clinical Hypnosis versus Neurolinguistic Programming (NLP) before External Cephalic Version (ECV): A Prospective Off-Centre Randomised, Double-Blind, Controlled Trial.

PubMed

Reinhard, Joscha; Peiffer, Swati; Sänger, Nicole; Herrmann, Eva; Yuan, Juping; Louwen, Frank

2012-01-01

Objective. To examine the effects of clinical hypnosis versus NLP intervention on the success rate of ECV procedures in comparison to a control group. Methods. A prospective off-centre randomised trial of a clinical hypnosis intervention against NLP of women with a singleton breech fetus at or after 37(0/7) (259 days) weeks of gestation and normal amniotic fluid index. All 80 participants heard a 20-minute recorded intervention via head phones. Main outcome assessed was success rate of ECV. The intervention groups were compared with a control group with standard medical care alone (n = 122). Results. A total of 42 women, who received a hypnosis intervention prior to ECV, had a 40.5% (n = 17), successful ECV, whereas 38 women, who received NLP, had a 44.7% (n = 17) successful ECV (P > 0.05). The control group had similar patient characteristics compared to the intervention groups (P > 0.05). In the control group (n = 122) 27.3% (n = 33) had a statistically significant lower successful ECV procedure than NLP (P = 0.05) and hypnosis and NLP (P = 0.03). Conclusions. These findings suggest that prior clinical hypnosis and NLP have similar success rates of ECV procedures and are both superior to standard medical care alone.

Evaluation of a decision aid for women with breech presentation at term: a randomised controlled trial [ISRCTN14570598

PubMed Central

Nassar, N; Roberts, CL; Raynes-Greenow, CH; Barratt, A; Peat, B

2007-01-01

Objectives To evaluate the effectiveness of a decision aid for women with a breech presentation compared with usual care. Design Randomised controlled trial. Setting Tertiary obstetric hospitals offering external cephalic version (ECV). Population Women with a singleton pregnancy were diagnosed antenatally with a breech presentation at term, and were clinically eligible for ECV. Methods Women were randomised to either receive a decision aid about the management options for breech presentation in addition to usual care or to receive usual care only with standard counselling from their usual pregnancy care provider. The decision aid comprised a 24-page booklet supplemented by a 30-minute audio-CD and worksheet that was designed for women to take home and review with a partner. Main outcome measures Decisional conflict (uncertainty), knowledge, anxiety and satisfaction with decision making, and were assessed using self-administered questionnaires. Results Compared with usual care, women reviewing the decision aid experienced significantly lower decisional conflict (mean difference −8.92; 95% CI −13.18, −4.66) and increased knowledge (mean difference 8.40; 95% CI 3.10, 13.71), were more likely to feel that they had enough information to make a decision (RR 1.30; 95% CI 1.14, 1.47), had no increase in anxiety and reported greater satisfaction with decision making and overall experience of pregnancy and childbirth. In contrast, 19% of women in the usual care group reported they would have made a different decision about their care. Conclusions A decision aid is an effective and acceptable tool for pregnant women that provides an important adjunct to standard counselling for the management of breech presentation. Please cite this paper as: Nassar N, Roberts C, Raynes-Greenow C, Barratt A, Peat B, on behalf of the Decision Aid for Breech Presentation Trial Collaborators. Evaluation of a decision aid for women with breech presentation at term: a randomised controlled trial [ISRCTN14570598]. BJOG 2007;114:325–333. PMID:17217360

A Pilot RCT of Psychodynamic Group Art Therapy for Patients in Acute Psychotic Episodes: Feasibility, Impact on Symptoms and Mentalising Capacity

PubMed Central

Montag, Christiane; Haase, Laura; Seidel, Dorothea; Bayerl, Martin; Gallinat, Jürgen; Herrmann, Uwe; Dannecker, Karin

2014-01-01

This pilot study aimed to evaluate the feasibility of an assessor-blind, randomised controlled trial of psychodynamic art therapy for the treatment of patients with schizophrenia, and to generate preliminary data on the efficacy of this intervention during acute psychotic episodes. Fifty-eight inpatients with DSM-diagnoses of schizophrenia were randomised to either 12 twice-weekly sessions of psychodynamic group art therapy plus treatment as usual or to standard treatment alone. Primary outcome criteria were positive and negative psychotic and depressive symptoms as well as global assessment of functioning. Secondary outcomes were mentalising function, estimated with the Reading the mind in the eyes test and the Levels of emotional awareness scale, self-efficacy, locus of control, quality of life and satisfaction with care. Assessments were made at baseline, at post-treatment and at 12 weeks' follow-up. At 12 weeks, 55% of patients randomised to art therapy, and 66% of patients receiving treatment as usual were examined. In the per-protocol sample, art therapy was associated with a significantly greater mean reduction of positive symptoms and improved psychosocial functioning at post-treatment and follow-up, and with a greater mean reduction of negative symptoms at follow-up compared to standard treatment. The significant reduction of positive symptoms at post-treatment was maintained in an attempted intention-to-treat analysis. There were no group differences regarding depressive symptoms. Of secondary outcome parameters, patients in the art therapy group showed a significant improvement in levels of emotional awareness, and particularly in their ability to reflect about others' emotional mental states. This is one of the first randomised controlled trials on psychodynamic group art therapy for patients with acute psychotic episodes receiving hospital treatment. Results prove the feasibility of trials on art therapy during acute psychotic episodes and justify further research to substantiate preliminary positive results regarding symptom reduction and the recovery of mentalising function. Trial Registration ClinicalTrials.gov NCT01622166 PMID:25393414

A pilot RCT of psychodynamic group art therapy for patients in acute psychotic episodes: feasibility, impact on symptoms and mentalising capacity.

PubMed

Montag, Christiane; Haase, Laura; Seidel, Dorothea; Bayerl, Martin; Gallinat, Jürgen; Herrmann, Uwe; Dannecker, Karin

2014-01-01

This pilot study aimed to evaluate the feasibility of an assessor-blind, randomised controlled trial of psychodynamic art therapy for the treatment of patients with schizophrenia, and to generate preliminary data on the efficacy of this intervention during acute psychotic episodes. Fifty-eight inpatients with DSM-diagnoses of schizophrenia were randomised to either 12 twice-weekly sessions of psychodynamic group art therapy plus treatment as usual or to standard treatment alone. Primary outcome criteria were positive and negative psychotic and depressive symptoms as well as global assessment of functioning. Secondary outcomes were mentalising function, estimated with the Reading the mind in the eyes test and the Levels of emotional awareness scale, self-efficacy, locus of control, quality of life and satisfaction with care. Assessments were made at baseline, at post-treatment and at 12 weeks' follow-up. At 12 weeks, 55% of patients randomised to art therapy, and 66% of patients receiving treatment as usual were examined. In the per-protocol sample, art therapy was associated with a significantly greater mean reduction of positive symptoms and improved psychosocial functioning at post-treatment and follow-up, and with a greater mean reduction of negative symptoms at follow-up compared to standard treatment. The significant reduction of positive symptoms at post-treatment was maintained in an attempted intention-to-treat analysis. There were no group differences regarding depressive symptoms. Of secondary outcome parameters, patients in the art therapy group showed a significant improvement in levels of emotional awareness, and particularly in their ability to reflect about others' emotional mental states. This is one of the first randomised controlled trials on psychodynamic group art therapy for patients with acute psychotic episodes receiving hospital treatment. Results prove the feasibility of trials on art therapy during acute psychotic episodes and justify further research to substantiate preliminary positive results regarding symptom reduction and the recovery of mentalising function. ClinicalTrials.gov NCT01622166.

StereoTactic radiotherapy for wet Age-Related macular degeneration (STAR): study protocol for a randomised controlled clinical trial.

PubMed

Neffendorf, James E; Desai, Riti; Wang, Yanzhong; Kelly, Joanna; Murphy, Caroline; Reeves, Barnaby C; Chakravarthy, Usha; Wordsworth, Sarah; Lewis, Cornelius; Peacock, Janet; Uddin, Shahir; O'Sullivan, Joe M; Jackson, Timothy L

2016-11-24

The standard of care for neovascular age-related macular degeneration (nAMD) involves ongoing intravitreal injections of anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF). The most commonly used anti-VEGF drugs are ranibizumab, bevacizumab and aflibercept. The main objective of the STAR trial is to determine if stereotactic radiotherapy can reduce the number of anti-VEGF injections that patients with nAMD require. STAR is a multicentre, double-masked, randomised, sham-controlled clinical trial. It evaluates a new device (manufactured by Oraya, Newark, CA, USA) designed to deliver stereotactic radiotherapy (SRT) to nAMD lesions. The trial enrols participants with chronic, active nAMD. Participants receive a single SRT treatment (16 Gy or sham) with a concomitant baseline intravitreal injection of 0.5 mg ranibizumab. Thereafter, they attend every month for 24 months, and ranibizumab is administered at the visit if retreatment criteria are met. The primary outcome is the number of pro re nata ranibizumab injections during the first 24 months. Secondary outcomes include visual acuity, lesion morphology, quality of life and safety. Additional visits occur at 36 and 48 months to inspect for radiation retinopathy. The target sample size of 411 participants (randomised 2:1 in favour of radiation) is designed to detect a reduction of 2.5 injections against ranibizumab monotherapy, at 90% power, and a significance level (alpha) of 0.025 (one-sided two-sample t test). This gives 97% power to detect non-inferiority of visual acuity at a five-letter margin. The primary analyses will be by intention to treat. The safety and efficacy outcomes will help determine the role of SRT in the management of chronic, active nAMD. International Standard Randomised Controlled Trial Number: ISRCTN12884465. Registered on 28 November 2014. ClinicalTrials.gov: NCT02243878 . Registered on 17 September 2014.

TELEMAM: a cluster randomised trial to assess the use of telemedicine in multi-disciplinary breast cancer decision making.

PubMed

Kunkler, I H; Prescott, R J; Lee, R J; Brebner, J A; Cairns, J A; Fielding, R G; Bowman, A; Neades, G; Walls, A D F; Chetty, U; Dixon, J M; Smith, M E; Gardner, T W; Macnab, M; Swann, S; Maclean, J R

2007-11-01

The TELEMAM trial aimed to assess the clinical effectiveness and costs of telemedicine in conducting breast cancer multi-disciplinary meetings (MDTs). Over 12 months 473 MDT patient discussions in two district general hospitals (DGHs) were cluster randomised (2:1) to the intervention of telemedicine linkage to breast specialists in a cancer centre or to the control group of 'in-person' meetings. Primary endpoints were clinical effectiveness and costs. Economic analysis was based on a cost-minimisation approach. Levels of agreement of MDT members on a scale from 1 to 5 were high and similar in both the telemedicine and standard meetings for decision sharing (4.04 versus 4.17), consensus (4.06 versus 4.20) and confidence in the decision (4.16 versus 4.07). The threshold at which the telemedicine meetings became cheaper than standard MDTs was approximately 40 meetings per year. Telemedicine delivered breast cancer multi-disciplinary meetings have similar clinical effectiveness to standard 'in-person' meetings.

pRotective vEntilation with veno-venouS lung assisT in respiratory failure: A protocol for a multicentre randomised controlled trial of extracorporeal carbon dioxide removal in patients with acute hypoxaemic respiratory failure.

PubMed

McNamee, J J; Gillies, M A; Barrett, N A; Agus, A M; Beale, R; Bentley, A; Bodenham, A; Brett, S J; Brodie, D; Finney, S J; Gordon, A J; Griffiths, M; Harrison, D; Jackson, C; McDowell, C; McNally, C; Perkins, G D; Tunnicliffe, W; Vuylsteke, A; Walsh, T S; Wise, M P; Young, D; McAuley, D F

2017-05-01

One of the few interventions to demonstrate improved outcomes for acute hypoxaemic respiratory failure is reducing tidal volumes when using mechanical ventilation, often termed lung protective ventilation. Veno-venous extracorporeal carbon dioxide removal (vv-ECCO 2 R) can facilitate reducing tidal volumes. pRotective vEntilation with veno-venouS lung assisT (REST) is a randomised, allocation concealed, controlled, open, multicentre pragmatic trial to determine the clinical and cost-effectiveness of lower tidal volume mechanical ventilation facilitated by vv-ECCO 2 R in patients with acute hypoxaemic respiratory failure. Patients requiring intubation and mechanical ventilation for acute hypoxaemic respiratory failure will be randomly allocated to receive either vv-ECCO 2 R and lower tidal volume mechanical ventilation or standard care with stratification by recruitment centre. There is a need for a large randomised controlled trial to establish whether vv-ECCO 2 R in acute hypoxaemic respiratory failure can allow the use of a more protective lung ventilation strategy and is associated with improved patient outcomes.

Deliberate self harm: systematic review of efficacy of psychosocial and pharmacological treatments in preventing repetition

PubMed Central

Hawton, Keith; Arensman, Ella; Townsend, Ellen; Bremner, Sandy; Feldman, Eleanor; Goldney, Robert; Gunnell, David; Hazell, Philip; van Heeringen, Kees; House, Allan; Owens, David; Sakinofsky, Isaac; Träskman-Bendz, Lil

1998-01-01

Objective: To identify and synthesise the findings from all randomised controlled trials that have examined the effectiveness of treatments of patients who have deliberately harmed themselves. Design: Systematic review of randomised controlled trials of psychosocial and physical treatments. Studies categorised according to type of treatment. When there was more than one investigation in a particular category a summary odds ratio was estimated with the Mantel-Haenszel method. Setting: Randomised trials available in electronic databases in 1996, in the Cochrane Controlled Trials Register in 1997, and from hand searching of journals to 1997. Subjects: Patients who had deliberately harmed themselves shortly before entry into the trials with information on repetition of behaviour. The included trials comprised 2452 randomised participants with outcome data. Main outcome measure: Repetition of self harm. Results: 20 trials reported repetition of self harm as an outcome variable, classified into 10 categories. Summary odds ratio (all for comparison with standard aftercare) indicated reduced repetition for problem solving therapy (0.73; 95% confidence interval 0.45 to 1.18) and for provision of an emergency contact card in addition to standard care (0.45; 0.19 to 1.07). The summary odds ratios were 0.83 (0.61 to 1.14) for trials of intensive aftercare plus outreach and 1.19 (0.53 to 2.67) for antidepressant treatment compared with placebo. Significantly reduced rates of further self harm were observed for depot flupenthixol versus placebo in multiple repeaters (0.09; 0.02 to 0.50) and for dialectical behaviour therapy versus standard aftercare (0.24; 0.06 to 0.93). Conclusion: There remains considerable uncertainty about which forms of psychosocial and physical treatments of patients who harm themselves are most effective. Further larger trials of treatments are needed. Key messages A systematic review of the effectiveness of psychosocial and drug treatments of patients who deliberately harm themselves identified 20 randomised controlled trials in which repetition of self harm was reported as an outcome Promising results were found for problem solving therapy, provision of a card to allow patients to make emergency contact with services, depot flupenthixol for recurrent self harm, and long term psychological therapy for female patients with borderline personality disorder and recurrent self harm Assertive outreach can help to keep patients in treatment Nearly all the trials included too few patients to detect clinically significant differences in repetition of self harm, and even synthesis of results by meta-analysis did not have the power to detect such differences There is an urgent need for large trials of promising therapies for this substantial clinical population PMID:9703526

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.

Cardiac rehabilitation using the Family-Centered Empowerment Model versus home-based cardiac rehabilitation in patients with myocardial infarction: a randomised controlled trial

PubMed Central

Vahedian-Azimi, Amir; Hajiesmaieli, Mohammadreza; Kangasniemi, Mari; Alhani, Fatemah; Jelvehmoghaddam, Hosseinali; Fathi, Mohammad; Farzanegan, Behrooz; Ardehali, Seyed H; Hatamian, Sevak; Gahremani, Mehdi; Mosavinasab, Seyed M M; Rostami, Zohreh; Madani, Seyed J; Izadi, Morteza

2016-01-01

Objective To determine if a hybrid cardiac rehabilitation (CR) programme using the Family-Centered Empowerment Model (FCEM) as compared with standard CR will improve patient quality of life, perceived stress and state anxiety of patients with myocardial infarction (MI). Methods We conducted a randomised controlled trial in which patients received either standard home CR or CR using the FCEM strategy. Patient empowerment was measured with FCEM questionnaires preintervention and postintervention for a total of 9 assessments. Quality of life, perceived stress, and state and trait anxiety were assessed using the 36-Item Short Form Health Survey (SF-36), the 14-item Perceived Stress, and the 20-item State and 20-item Trait Anxiety questionnaires, respectively. Results 70 patients were randomised. Baseline characteristics were similar. Ejection fraction was significantly higher in the intervention group at measurements 2 (p=0.01) and 3 (p=0.001). Exercise tolerance measured as walking distance was significantly improved in the intervention group throughout the study. The quality of life results in the FCEM group showed significant improvement both within the group over time (p<0.0001) and when compared with control (p<0.0001). Similarly, the perceived stress and state anxiety results showed significant improvement both within the FCEM group over time (p<0.0001) and when compared with control (p<0.0001). No significant difference was found either within or between groups for trait anxiety. Conclusions The family-centred empowerment model may be an effective hybrid cardiac rehabilitation method for improving the physical and mental health of patients post-MI; however, further study is needed to validate these findings. Clinical Trials.gov identifier NCT02402582. Trial registration number NCT02402582. PMID:27110376

Impact of a new cryotherapy device on early rehabilitation after primary total knee arthroplasty (TKA): a prospective randomised controlled trial.

PubMed

Sadoghi, Patrick; Hasenhütl, Sandro; Gruber, Gerald; Leitner, Lukas; Leithner, Andreas; Rumpold-Seitlinger, Gudrun; Kastner, Norbert; Poolman, Rudolf W; Glehr, Mathias

2018-06-01

The aim of this prospective, randomised and single blinded study was to evaluate the efficiency and safety of a new cryotherapy device in patients undergoing unilateral, primary total knee arthroplasty (TKA). Our hypothesis was that patients administered to the new cryotherapy device would perform better than patients receiving a conventional standard cold therapy regimen. Ninety-seven patients were randomised into two groups receiving either the cTreatment® (new cryotherapy device) or the standard cold therapy protocol (including cold pack application for six days after the surgical intervention). We evaluated the following endpoints consisting of range of motion (ROM), pain intensity, and knee girth on admission day and the second, fourth, and sixth post-operative day (POD). A statistically significant benefit of the new cryotherapy device was detected regarding the ROM on the sixth POD with an average gain of 7 degrees (p = 0.021). Pain in the numeric rating scale (NRS) score in motion was significantly lower in the cTreatment® group on the second POD (p = 0.034). There were no statistically significant differences between groups regarding the NRS in rest, patient controlled analgesia (PCA) consumption, and girth measurements. No adverse effects were observed in both study groups. The new computer-controlled cooling therapy device provides benefits in terms of early post-operative remobilisation with respect to ROM and pain, which might be attributed to a reduced inflammatory response, as well as reduced secretion and bleeding. The cTreatment® system appears to be a safe and efficient procedure.

Patient and family satisfaction levels in the intensive care unit after elective cardiac surgery: study protocol for a randomised controlled trial of a preoperative patient education intervention.

PubMed

Lai, Veronica Ka Wai; Lee, Anna; Leung, Patricia; Chiu, Chun Hung; Ho, Ka Man; Gomersall, Charles David; Underwood, Malcolm John; Joynt, Gavin Matthew

2016-06-22

Patients and their families are understandably anxious about the risk of complications and unfamiliar experiences following cardiac surgery. Providing information about postoperative care in the intensive care unit (ICU) to patients and families may lead to lower anxiety levels, and increased satisfaction with healthcare. The objectives of this study are to evaluate the effectiveness of preoperative patient education provided for patients undergoing elective cardiac surgery. 100 patients undergoing elective coronary artery bypass graft, with or without valve replacement surgery, will be recruited into a 2-group, parallel, superiority, double-blinded randomised controlled trial. Participants will be randomised to either preoperative patient education comprising of a video and ICU tour with standard care (intervention) or standard education (control). The primary outcome measures are the satisfaction levels of patients and family members with ICU care and decision-making in the ICU. The secondary outcome measures are patient anxiety and depression levels before and after surgery. Ethical approval has been obtained from the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (reference number CREC 2015.308). The findings will be presented at conferences and published in peer-reviewed journals. Study participants will receive a 1-page plain language summary of results. ChiCTR-IOR-15006971. 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/

Enoxaparin for the prevention of preeclampsia and intrauterine growth restriction in women with a prior history - an open-label randomised trial (the EPPI trial): study protocol.

PubMed

Groom, K M; McCowan, L M; Stone, P R; Chamley, L C; McLintock, C

2016-11-22

Preeclampsia and intrauterine fetal growth restriction (IUGR) are two of the most common causes of maternal and perinatal morbidity and mortality. Current methods of predicting those at most risk of these conditions remain relatively poor, and in clinical practice past obstetric history remains the most commonly used tool. Aspirin and, in women at risk of preeclampsia only, calcium have been demonstrated to have a modest effect on risk reduction. Several observational studies and randomised trials suggest that low molecular weight heparin (LMWH) therapy may confer some benefit. This is a multicentre open label randomised controlled trial to determine the effect of the LMWH, enoxaparin, on the prevention of recurrence of preeclampsia and/or IUGR in women at high risk due to their past obstetric history in addition to standard high risk care for all participants. A singleton pregnancy >6 +0 and <16 +0 weeks gestation with most recent prior pregnancy with duration >12 weeks having; (1) preeclampsia delivered <36 +0 weeks, (2) Small for gestational age (SGA) infant <10 th customised birthweight centile delivered <36 +0 weeks or, (3) SGA infant ≤3 rd customised birthweight centile delivered at any gestation. Randomisation is stratified for maternal thrombophilia status and women are randomly assigned to 'standard high risk care' or 'standard high risk care' plus enoxaparin 40 mg from recruitment until 36 +0 weeks or delivery, whichever occurs sooner. Standard high risk care includes the use of aspirin 100 mg daily and calcium 1000-1500 mg daily (unless only had previous SGA with no preeclampsia). The primary outcome is preeclampsia and/or SGA <5 th customised birthweight centile. Analysis will be by intention to treat. The EPPI trial has more focussed and clinically relevant inclusion criteria than other randomised trials with a more restricted composite primary outcome. The inclusion of standard use of aspirin (and calcium) for all participants will help to ensure that any differences observed in outcome are likely to be related to enoxaparin use. These data will make a significant contribution to future meta-analyses and systematic reviews on the use of LMWH for the prevention of placental mediated conditions. ACTRN12609000699268 Australian New Zealand Clinical Trials Registry. Date registered 13/Aug/2009 (prospective registration).

Evaluating the effect of metronidazole plus amoxicillin-clavulanate versus amoxicillin-clavulanate alone in canine haemorrhagic diarrhoea: a randomised controlled trial in primary care practice.

PubMed

Ortiz, V; Klein, L; Channell, S; Simpson, B; Wright, B; Edwards, C; Gilbert, R; Day, R; Caddy, S L

2018-06-07

To investigate the benefit of supplementing amoxicillin-clavulanic acid therapy with metronidazole in dogs presenting to a primary care veterinary practice with severe haemorrhagic diarrhoea. Prospective randomised blinded trial on dogs presenting with haemorrhagic diarrhoea of less than 3 days duration to a primary care veterinary hospital and also requiring intravenous fluid therapy. Cases were randomised to receive either metronidazole or saline, in addition to standard supportive therapy consisting of amoxicillin-clavulanic acid, intravenous fluid therapy, buprenorphine and omeprazole. Treatment efficacy was measured by duration of hospitalisation and daily scoring of disease severity. Thirty-four cases successfully completed the trial. There was no significant difference in hospitalisation time between treatment groups (mean for dogs receiving metronidazole was 29.6 hours and for controls was 26.3 hours) nor in daily clinical scores. This study strongly suggests that addition of metronidazole is not an essential addition to amoxicillin-clavulanic acid therapy for treatment of severe cases of haemorrhagic diarrhoea in dogs. © 2018 British Small Animal Veterinary Association.

Cancer-related fatigue management: evaluation of a patient education program with a large-scale randomised controlled trial, the PEPs fatigue study.

PubMed

Bourmaud, A; Anota, A; Moncharmont, C; Tinquaut, F; Oriol, M; Trillet-Lenoir, V; Bajard, A; Parnalland, S; Rotonda, C; Bonnetain, F; Pérol, D; Chauvin, F

2017-03-28

To assess the efficacy of a patient educational program built according to guidelines that aims at reducing cancer-related fatigue (CRF). Randomised controlled trial, multicentre, comparing a patient education program, vs the standard of care. Patients were adult cancer outpatients with any tumour site. The primary outcome was fatigue severity assessed with a visual analogical scale (VAS), between the day of randomisation and week 7. Secondary outcomes were fatigue assessed with other scales, health-related quality of life, anxiety and depression. The time to fatigue severity deterioration was assessed. Analyses were performed in a modified intent-to-treat way, that is, including all patients with at least one baseline and 1 week 7 score. A total of 212 patients were included. Fatigue severity assessment was made on 79 patients in the experimental group and 65 in the control group. Between randomisation and week 7, the fatigue (VAS) improved by 0.96 (2.85) points in the experimental group vs 1.63 (2.63) points in the control group (P=0.15). No differences with the secondary outcomes were highlighted between two groups. No other factors were found to be associated with fatigue severity deterioration. Despite rigorous methodology, this study failed to highlight the program efficacy in fatigue reduction for cancer patients. Other assessment tools should be developed to measure the effect of the program on CRF and behaviour. The implementation of the program should also be explored in order to identify its mechanisms and longer-term impact.

Evaluation of a complex intervention to improve activities of daily living of disabled cancer patients: protocol for a randomised controlled study and feasibility of recruitment and intervention

PubMed Central

2014-01-01

Background Many cancer patients have problems performing activities of daily living (ADL). A randomised controlled trial was designed to examine the effects of an ADL intervention in addition to standard treatment and care in a hospital setting. The objective of this article was to present the study and to analyse the feasibility of the recruitment process and the intervention. Methods Adult disabled cancer patients at Næstved Hospital in Denmark were enrolled between 1 March 2010 and 30 June 2011 and randomised into an ADL intervention or to a control group. The intervention was performed by occupational therapists. The feasibility of the recruitment was analysed with regard to success in achieving the estimated number of participants and identification of barriers, and feasibility of the intervention was based on calculations of patient attendance and patient acceptability. The primary outcome of the randomised controlled trial was patients’ health-related quality of life 2 and 8 weeks after baseline. Results A total of 118 disabled cancer patients were enrolled in the study over a time span of 16 months. Very few meetings between occupational therapist and patient were cancelled. Time spent on the intervention varied considerably, but for the majority of patients, time consumption was between 1–3 hours. Conclusions Despite difficulties with recruitment, participation was considered feasible and the intervention was accepted among patients. Missing data in the follow-up period were mostly due to death among participants. Very few participants declined to complete questionnaires during follow-up. PMID:24779438

WITHDRAWN: Systemic treatments for metastatic cutaneous melanoma.

PubMed

Crosby, Tom; Fish, Reg; Coles, Bernadette; Mason, Malcolm

2018-02-07

Systemic therapies for metastatic cutaneous melanoma, the most aggressive of all skin cancers, remain disappointing. Few lasting remissions are achieved and the therapeutic aim remains one of palliation.Many agents are used alone or in combination with varying degrees of toxicity and cost. It is unclear whether evidence exists to support these complex regimens over best supportive care / placebo. To review the benefits from the use of systemic therapies in metastatic cutaneous melanoma compared to best supportive care/placebo, and to establish whether a 'standard' therapy exists which is superior to other treatments. Randomised controlled trials were identified from the MEDLINE, EMBASE and CCTR/CENTRAL databases. References, conference proceedings, and Science Citation Index/Scisearch were also used to locate trials. Cancer registries and trialists were also contacted. Randomised controlled trials of adults with histologically proven metastatic cutaneous melanoma in which systemic anti-cancer therapy was compared with placebo or supportive care. Study selection was performed by two independent reviewers. Data extraction forms were used for studies which appeared to meet the selection criteria and, where appropriate, full text articles were retrieved and reviewed independently. No randomised controlled trials were found comparing a systemic therapy with placebo or best supportive care in metastatic cutaneous melanoma. There is no evidence from randomised controlled clinical trials to show superiority of systemic therapy over best supportive care / placebo in the treatment of malignant cutaneous melanoma.Given that patients with metastatic melanoma frequently receive systemic therapy, it is our pragmatic view that a future systematic review could compare any systemic treatment, or combination of treatments, to single agent dacarbazine.

Mobile phones as a health communication tool to improve skilled attendance at delivery in Zanzibar: a cluster-randomised controlled trial.

PubMed

Lund, S; Hemed, M; Nielsen, B B; Said, A; Said, K; Makungu, M H; Rasch, V

2012-09-01

To examine the association between a mobile phone intervention and skilled delivery attendance in a resource-limited setting. Pragmatic cluster-randomised controlled trial with primary healthcare facilities as the unit of randomisation. Primary healthcare facilities in Zanzibar. Two thousand, five hundred and fifty pregnant women (1311 interventions and 1239 controls) who attended antenatal care at one of the selected primary healthcare facilities were included at their first antenatal care visit and followed until 42 days after delivery. All pregnant women were eligible for study participation. Twenty-four primary healthcare facilities in six districts in Zanzibar were allocated by simple randomisation to either mobile phone intervention (n = 12) or standard care (n = 12). The intervention consisted of a short messaging service (SMS) and mobile phone voucher component. Skilled delivery attendance. The mobile phone intervention was associated with an increase in skilled delivery attendance: 60% of the women in the intervention group versus 47% in the control group delivered with skilled attendance. The intervention produced a significant increase in skilled delivery attendance amongst urban women (odds ratio, 5.73; 95% confidence interval, 1.51-21.81), but did not reach rural women. The mobile phone intervention significantly increased skilled delivery attendance amongst women of urban residence. Mobile phone solutions may contribute to the saving of lives of women and their newborns and the achievement of Millennium Development Goals 4 and 5, and should be considered by maternal and child health policy makers in developing countries. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

Cancer-related fatigue management: evaluation of a patient education program with a large-scale randomised controlled trial, the PEPs fatigue study

PubMed Central

Bourmaud, A; Anota, A; Moncharmont, C; Tinquaut, F; Oriol, M; Trillet-Lenoir, V; Bajard, A; Parnalland, S; Rotonda, C; Bonnetain, F; Pérol, D; Chauvin, F

2017-01-01

Background: To assess the efficacy of a patient educational program built according to guidelines that aims at reducing cancer-related fatigue (CRF). Methods: Randomised controlled trial, multicentre, comparing a patient education program, vs the standard of care. Patients were adult cancer outpatients with any tumour site. The primary outcome was fatigue severity assessed with a visual analogical scale (VAS), between the day of randomisation and week 7. Secondary outcomes were fatigue assessed with other scales, health-related quality of life, anxiety and depression. The time to fatigue severity deterioration was assessed. Analyses were performed in a modified intent-to-treat way, that is, including all patients with at least one baseline and 1 week 7 score. Results: A total of 212 patients were included. Fatigue severity assessment was made on 79 patients in the experimental group and 65 in the control group. Between randomisation and week 7, the fatigue (VAS) improved by 0.96 (2.85) points in the experimental group vs 1.63 (2.63) points in the control group (P=0.15). No differences with the secondary outcomes were highlighted between two groups. No other factors were found to be associated with fatigue severity deterioration. Conclusions: Despite rigorous methodology, this study failed to highlight the program efficacy in fatigue reduction for cancer patients. Other assessment tools should be developed to measure the effect of the program on CRF and behaviour. The implementation of the program should also be explored in order to identify its mechanisms and longer-term impact. PMID:28196066

Efficacy of infant simulator programmes to prevent teenage pregnancy: a school-based cluster randomised controlled trial in Western Australia.

PubMed

Brinkman, Sally A; Johnson, Sarah E; Codde, James P; Hart, Michael B; Straton, Judith A; Mittinty, Murthy N; Silburn, Sven R

2016-11-05

Infant simulator-based programmes, which aim to prevent teenage pregnancy, are used in high-income as well as low-income and middle-income countries but, despite growing popularity, no published evidence exists of their long-term effect. The aim of this trial was to investigate the effect of such a programme, the Virtual Infant Parenting (VIP) programme, on pregnancy outcomes of birth and induced abortion in Australia. In this school-based pragmatic cluster randomised controlled trial, eligible schools in Perth, Western Australia, were enrolled and randomised 1:1 to the intervention and control groups. Randomisation using a table of random numbers without blocking, stratification, or matching was done by a researcher who was masked to the identity of the schools. Between 2003 and 2006, the VIP programme was administered to girls aged 13-15 years in the intervention schools, while girls of the same age in the control schools received the standard health education curriculum. Participants were followed until they reached 20 years of age via data linkage to hospital medical and abortion clinic records. The primary endpoint was the occurrence of pregnancy during the teenage years. Binomial and Cox proportional hazards regression was used to test for differences in pregnancy rates between study groups. This study is registered as an international randomised controlled trial, number ISRCTN24952438. 57 (86%) of 66 eligible schools were enrolled into the trial and randomly assigned 1:1 to the intervention (28 schools) or the control group (29 schools). Then, between Feb 1, 2003, and May 31, 2006, 1267 girls in the intervention schools received the VIP programme while 1567 girls in the control schools received the standard health education curriculum. Compared with girls in the control group, a higher proportion of girls in the intervention group recorded at least one birth (97 [8%] of 1267 in the intervention group vs 67 [4%] of 1567 in the control group) or at least one abortion as the first pregnancy event (113 [9%] vs 101 [6%]). After adjustment for potential confounders, the intervention group had a higher overall pregnancy risk than the control group (relative risk 1·36 [95% CI 1·10-1·67], p=0·003). Similar results were obtained with the use of proportional hazard models (hazard ratio 1·35 [95% CI 1·10-1·67], p=0·016). The infant simulator-based VIP programme did not achieve its aim of reducing teenage pregnancy. Girls in the intervention group were more likely to experience a birth or an induced abortion than those in the control group before they reached 20 years of age. Western Australian Health Promotion Foundation (Healthway), Lotteries WA, the Western Australian Department of Education and Training, and the Western Australian Department of Health. Copyright © 2016 Elsevier Ltd. All rights reserved.

High-flow warm humidified oxygen versus standard low-flow nasal cannula oxygen for moderate bronchiolitis (HFWHO RCT): an open, phase 4, randomised controlled trial.

PubMed

Kepreotes, Elizabeth; Whitehead, Bruce; Attia, John; Oldmeadow, Christopher; Collison, Adam; Searles, Andrew; Goddard, Bernadette; Hilton, Jodi; Lee, Mark; Mattes, Joerg

2017-03-04

Bronchiolitis is the most common lung infection in infants and treatment focuses on management of respiratory distress and hypoxia. High-flow warm humidified oxygen (HFWHO) is increasingly used, but has not been rigorously studied in randomised trials. We aimed to examine whether HFWHO provided enhanced respiratory support, thereby shortening time to weaning off oxygen. In this open, phase 4, randomised controlled trial, we recruited children aged less than 24 months with moderate bronchiolitis attending the emergency department of the John Hunter Hospital or the medical unit of the John Hunter Children's Hospital in New South Wales, Australia. Patients were randomly allocated (1:1) via opaque sealed envelopes to HFWHO (maximum flow of 1 L/kg per min to a limit of 20 L/min using 1:1 air-oxygen ratio, resulting in a maximum FiO 2 of 0·6) or standard therapy (cold wall oxygen 100% via infant nasal cannulae at low flow to a maximum of 2 L/min) using a block size of four and stratifying for gestational age at birth. The primary outcome was time from randomisation to last use of oxygen therapy. All randomised children were included in the primary and secondary safety analyses. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12612000685819. From July 16, 2012, to May 1, 2015, we randomly assigned 202 children to either HFWHO (101 children) or standard therapy (101 children). Median time to weaning was 24 h (95% CI 18-28) for standard therapy and 20 h (95% CI 17-34) for HFWHO (hazard ratio [HR] for difference in survival distributions 0·9 [95% CI 0·7-1·2]; log rank p=0·61). Fewer children experienced treatment failure on HFWHO (14 [14%]) compared with standard therapy (33 [33%]; p=0·0016); of these children, those on HFWHO were supported for longer than were those on standard therapy before treatment failure (HR 0·3; 95% CI 0·2-0·6; p<0·0001). 20 (61%) of 33 children who experienced treatment failure on standard therapy were rescued with HFWHO. 12 (12%) of children on standard therapy required transfer to the intensive care unit compared with 14 (14%) of those on HFWHO (difference -1%; 95% CI -7 to 16; p=0·41). Four adverse events occurred (oxygen desaturation and condensation inhalation in the HFWHO group, and two incidences of oxygen tubing disconnection in the standard therapy group); none resulted in withdrawal from the trial. No oxygen-related serious adverse events occurred. Secondary effectiveness outcomes are reported in the Results section. HFWHO did not significantly reduce time on oxygen compared with standard therapy, suggesting that early use of HFWHO does not modify the underlying disease process in moderately severe bronchiolitis. HFWHO might have a role as a rescue therapy to reduce the proportion of children requiring high-cost intensive care. Hunter Children's Research Foundation, John Hunter Hospital Charitable Trust, and the University of Newcastle Priority Research Centre GrowUpWell. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

A pilot, randomised controlled trial of a rotational thromboelastometry-based algorithm to treat bleeding episodes in extracorporeal life support: the TEM Protocol in ECLS Study (TEMPEST).

PubMed

Buscher, Hergen; Zhang, David; Nair, Priya

2017-10-01

Minimal evidence to guide haemostatic therapy for bleeding in extracorporeal life support (ECLS) has resulted in wide variability in practice. We aimed to show that a goal-directed algorithm incorporating results from thromboelastometry (TEM) is feasible and safe for the timely management of bleeding episodes in adult patients receiving ECLS. A pilot randomised controlled trial involving 16 adult patients who underwent ECLS, randomised over 10 months. The intervention group was treated according to a goal-directed algorithm based on TEM results during bleeding episodes. Apart from the intervention, both groups received standard care including conventional laboratory coagulation tests. Need for blood product transfusion, haemorrhagic and thromboembolic complications and survival. There was a statistically non-significant trend towards reduction in the amount of blood products transfused, occurrence of bleeding, and thrombotic complications, when comparing the intervention arm with the control arm. Survival to hospital discharge was 69%. A significant correlation was found between fibrinogen levels and FIBTEM clot firmness at 10 minutes (R = 0.812; P < 0.001); activated partial thromboplastin time and clotting time HEPTEM/INTEM ratio (R = -0.719; P < 0.001); and platelet count and EXTEM clot firmness at 10 minutes (R = 0.783; P < 0.001). TEM allows assessment for coagulation status in a timely manner and its use for the treatment of bleeding episodes in adult patients receiving ECLS appears feasible and safe. Clinical benefit should be investigated in larger multicentre randomised trials.

Effectiveness of a community-based intervention for people with schizophrenia and their caregivers in India (COPSI): a randomised controlled trial.

PubMed

Chatterjee, Sudipto; Naik, Smita; John, Sujit; Dabholkar, Hamid; Balaji, Madhumitha; Koschorke, Mirja; Varghese, Mathew; Thara, Rangaswamy; Weiss, Helen A; Williams, Paul; McCrone, Paul; Patel, Vikram; Thornicroft, Graham

2014-04-19

Observational evidence suggests that community-based services for people with schizophrenia can be successfully provided by community health workers, when supervised by specialists, in low-income and middle-income countries. We did the COmmunity care for People with Schizophrenia in India (COPSI) trial to compare the effectiveness of a collaborative community-based care intervention with standard facility-based care. We did a multicentre, parallel-group, randomised controlled trial at three sites in India between Jan 1, 2009 and Dec 31, 2010. Patients aged 16-60 years with a primary diagnosis of schizophrenia according to the tenth edition of the International Classification of Diseases, Diagnostic Criteria for Research (ICD-10-DCR) were randomly assigned (2:1), via a computer-generated randomisation list with block sizes of three, six, or nine, to receive either collaborative community-based care plus facility-based care or facility-based care alone. Randomisation was stratified by study site. Outcome assessors were masked to group allocation. The primary outcome was a change in symptoms and disabilities over 12 months, as measured by the positive and negative syndrome scale (PANSS) and the Indian disability evaluation and assessment scale (IDEAS). Analysis was by modified intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 56877013. 187 participants were randomised to the collaborative community-based care plus facility-based care group and 95 were randomised to the facility-based care alone group; 253 (90%) participants completed follow-up to month 12. At 12 months, total PANSS and IDEAS scores were lower in patients in the intervention group than in those in the control group (PANSS adjusted mean difference -3.75, 95% CI -7.92 to 0.42; p=0.08; IDEAS -0.95, -1.68 to -0.23; p=0.01). However, no difference was shown in the proportion of participants who had a reduction of more than 20% in overall symptoms (PANSS 85 [51%] in the intervention group vs 44 [51%] in the control group; p=0.89; IDEAS 75 [48%] vs 28 [35%]). We noted a significant reduction in symptom and disability outcomes at the rural Tamil Nadu site (-9.29, -15.41 to -3.17; p=0.003). Two patients (one in each group) died by suicide during the study, and two patients died because of complications of a road traffic accident and pre-existing cardiac disease. 18 (73%) patients (17 in the intervention group) were admitted to hospital during the course of the trial, of whom seven were admitted because of physical health problems, such as acute gastritis and vomiting, road accident, high fever, or cardiovascular disease. The collaborative community-based care plus facility-based care intervention is modestly more effective than facility-based care, especially for reducing disability and symptoms of psychosis. Our results show that the study intervention is best implemented as an initial service in settings where services are scarce, for example in rural areas. Wellcome Trust. Copyright © 2014 Chatterjee et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by Elsevier Ltd. All rights reserved.

A randomised trial of the cool pad pillow topper versus standard care for sleep disturbance and hot flushes in women on endocrine therapy for breast cancer.

PubMed

Marshall-McKenna, R; Morrison, A; Stirling, L; Hutchison, C; Rice, A M; Hewitt, C; Paul, L; Rodger, M; Macpherson, I R; McCartney, E

2016-04-01

Quality of life in women receiving adjuvant endocrine therapy for breast cancer (BC) may be impaired by hot flushes and night sweats. The cool pad pillow topper (CPPT) is a commercial product, promoted to improve quality of sleep disrupted by hot flushes. This study aimed to identify if the CPPT reduces severity of sleep disturbance by minimising effects of hot flushes. This randomised phase II trial, recruited women with BC, on adjuvant endocrine therapy, experiencing hot flushes and insomnia. Participants were randomised (stratified by baseline sleep efficiency score (SES) and menopausal status) to the intervention arm (CPPT + standard care) or control arm (standard care). Participants completed Hospital Anxiety and Depression Scale and Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaires and fortnightly sleep/hot flush diaries (where responses were averaged over 2-week periods). The primary endpoint was change in average SES from -2 to 0 weeks to 2 to 4 weeks. Seventy-four pre- (68.9 %) and post-menopausal (31.1 %) women were recruited. Median age was 49.5 years. Endocrine therapies included tamoxifen (93.2 %). Median SES at weeks 2 to 4 improved in both arms but the increase on the intervention arm was almost twice that on the control arm (p = 0.024). There were significantly greater reductions in hot flushes and HADS depression in the intervention arm (p = 0.09 and p = 0.036, respectively). There were no significant differences in FACT-B or HADS anxiety. This study supports the use of the CPPT as an aid to reduce sleep disturbance and the frequency/severity of hot flushes.

A neuromuscular exercise programme versus standard care for patients with traumatic anterior shoulder instability: study protocol for a randomised controlled trial (the SINEX study).

PubMed

Eshoj, Henrik; Rasmussen, Sten; Frich, Lars Henrik; Hvass, Inge; Christensen, Robin; Jensen, Steen Lund; Søndergaard, Jens; Søgaard, Karen; Juul-Kristensen, Birgit

2017-02-28

Anterior shoulder dislocation is a common injury and may have considerable impact on shoulder-related quality of life (QoL). If not warranted for initial stabilising surgery, patients are mostly left with little to no post-traumatic rehabilitation. This may be due to lack of evidence-based exercise programmes. In similar, high-impact injuries (e.g. anterior cruciate ligament tears in the knee) neuromuscular exercise has shown large success in improving physical function and QoL. Thus, the objective of this trial is to compare a nonoperative neuromuscular exercise shoulder programme with standard care in patients with traumatic anterior shoulder dislocations (TASD). Randomised, assessor-blinded, controlled, multicentre trial. Eighty patients with a TASD will be recruited from three orthopaedic departments in Denmark. Patients with primary or recurrent anterior shoulder dislocations due to at least one traumatic event will be randomised to 12 weeks of either a standardised, individualised or physiotherapist-supervised neuromuscular shoulder exercise programme or standard care (self-managed shoulder exercise programme). Patients will be stratified according to injury status (primary or recurrent). Primary outcome will be change from baseline to 12 weeks in the patient-reported QoL outcome questionnaire, the Western Ontario Shoulder Instability Index (WOSI). This trial will be the first study to compare the efficacy and safety of two different nonoperative exercise treatment strategies for patients with TASD. Moreover, this is also the first study to investigate nonoperative treatment effects in patients with recurrent shoulder dislocations. Lastly, this study will add knowledge to the shared decision-making process of treatment strategies for clinical practice. ClinicalTrials.gov, identifier: NCT02371928 . Registered on 9 February 2015 at the National Institutes of Health Clinical Trials Protocol Registration System.

Symptoms and quality of life in patients with suspected angina undergoing CT coronary angiography: a randomised controlled trial

PubMed Central

Hunter, Amanda; Shah, Anoop; Assi, Valentina; Lewis, Stephanie; Mangion, Kenneth; Berry, Colin; Boon, Nicholas A; Clark, Elizabeth; Flather, Marcus; Forbes, John; McLean, Scott; Roditi, Giles; van Beek, Edwin JR; Timmis, Adam D; Newby, David E

2017-01-01

Background In patients with suspected angina pectoris, CT coronary angiography (CTCA) clarifies the diagnosis, directs appropriate investigations and therapies, and reduces clinical events. The effect on patient symptoms is currently unknown. Methods In a prospective open-label parallel group multicentre randomised controlled trial, 4146 patients with suspected angina due to coronary heart disease were randomised 1:1 to receive standard care or standard care plus CTCA. Symptoms and quality of life were assessed over 6 months using the Seattle Angina Questionnaire and Short Form 12. Results Baseline scores indicated mild physical limitation (74±0.4), moderate angina stability (44±0.4), modest angina frequency (68±0.4), excellent treatment satisfaction (92±0.2) and moderate impairment of quality of life (55±0.3). Compared with standard care alone, CTCA was associated with less marked improvements in physical limitation (difference −1.74 (95% CIs, −3.34 to −0.14), p=0.0329), angina frequency (difference −1.55 (−2.85 to −0.25), p=0.0198) and quality of life (difference −3.48 (−4.95 to −2.01), p<0.0001) at 6 months. For patients undergoing CTCA, improvements in symptoms were greatest in those diagnosed with normal coronary arteries or who had their preventative therapy discontinued, and least in those with moderate non-obstructive disease or had a new prescription of preventative therapy (p<0.001 for all). Conclusions While improving diagnosis, treatment and outcome, CTCA is associated with a small attenuation of the improvements in symptoms and quality of life due to the detection of moderate non-obstructive coronary artery disease. Trial registration number: NCT01149590. PMID:28246175

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 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 effects of antenatal dietary and lifestyle advice for women who are overweight or obese on maternal diet and physical activity: the LIMIT randomised trial.

PubMed

Dodd, Jodie M; Cramp, Courtney; Sui, Zhixian; Yelland, Lisa N; Deussen, Andrea R; Grivell, Rosalie M; Moran, Lisa J; Crowther, Caroline A; Turnbull, Deborah; McPhee, Andrew J; Wittert, Gary; Owens, Julie A; Robinson, Jeffrey S

2014-10-13

Overweight and obesity is a significant health concern during pregnancy. Our aim was to investigate the effect of providing antenatal dietary and lifestyle advice to women who are overweight or obese on components of maternal diet and physical activity. We conducted a randomised controlled trial, in which pregnant women with a body mass index≥25 kg/m2, and singleton gestation between 10(+0) to 20(+0) weeks were recruited and randomised to Lifestyle Advice (involving a comprehensive dietary and lifestyle intervention over their pregnancy) or Standard Care. Within the intervention group, we conducted a nested randomised trial in which a subgroup of women were further randomised to receive access to supervised group walking sessions in addition to the standard information presented during the intervention contacts (the Walking group) or standard information only. The outcome measures were maternal dietary intake, (including food groups, macronutrient and micronutrient intake, diet quality (using the Healthy Eating Index; HEI), dietary glycaemic load, and glycaemic index) and maternal physical activity. Women completed the Harvard Semi-Structured Food Frequency Questionnaire, and the Short Questionnaire to Assess Health-enhancing Physical Activity (SQUASH), at trial entry, 28 and 36 weeks' gestational age, and 4 months postpartum. Analyses were performed on an intention-to-treat basis, using linear mixed effects models with adjustment for the stratification variables. Women randomised to Lifestyle Advice demonstrated a statistically significant increase in the number of servings of fruit and vegetables consumed per day, as well as increased consumption of fibre, and reduced percentage energy intake from saturated fats (P<0.05 for all). Maternal HEI was significantly improved at both 28 (73.35±6.62 versus 71.86±7.01; adjusted difference in means 1.58; 95% CI 0.89 to 2.27; P<0.0001) and 36 (72.95±6.82 versus 71.17±7.69; adjusted difference in means 1.77; 95% CI 1.01 to 2.53; P<0.0001) weeks. There were no differences in dietary glycaemic index or glycaemic load. Women randomised to Lifestyle Advice also demonstrated greater total physical activity (adjusted difference in means 359.76 metabolic equivalent task units (MET) minutes/week; 95% CI 74.87 to 644.65; P=0.01) compared with women receiving Standard Care. The supervised walking group was poorly utilised. For women who are overweight or obese, antenatal lifestyle advice improves maternal diet and physical activity during pregnancy. Please see related articles: http://www.biomedcentral.com/1741-7015/12/163 and http://www.biomedcentral.com/1741-7015/12/201. Australian and New Zealand Clinical Trials Registry ( ACTRN12607000161426).

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

PubMed

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

2017-08-23

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

A Bayesian cost-effectiveness analysis of a telemedicine-based strategy for the management of sleep apnoea: a multicentre randomised controlled trial.

PubMed

Isetta, Valentina; Negrín, Miguel A; Monasterio, Carmen; Masa, Juan F; Feu, Nuria; Álvarez, Ainhoa; Campos-Rodriguez, Francisco; Ruiz, Concepción; Abad, Jorge; Vázquez-Polo, Francisco J; Farré, Ramon; Galdeano, Marina; Lloberes, Patricia; Embid, Cristina; de la Peña, Mónica; Puertas, Javier; Dalmases, Mireia; Salord, Neus; Corral, Jaime; Jurado, Bernabé; León, Carmen; Egea, Carlos; Muñoz, Aida; Parra, Olga; Cambrodi, Roser; Martel-Escobar, María; Arqué, Meritxell; Montserrat, Josep M

2015-11-01

Compliance with continuous positive airway pressure (CPAP) therapy is essential in patients with obstructive sleep apnoea (OSA), but adequate control is not always possible. This is clinically important because CPAP can reverse the morbidity and mortality associated with OSA. Telemedicine, with support provided via a web platform and video conferences, could represent a cost-effective alternative to standard care management. To assess the telemedicine impact on treatment compliance, cost-effectiveness and improvement in quality of life (QoL) when compared with traditional face-to-face follow-up. A randomised controlled trial was performed to compare a telemedicine-based CPAP follow-up strategy with standard face-to-face management. Consecutive OSA patients requiring CPAP treatment, with sufficient internet skills and who agreed to participate, were enrolled. They were followed-up at 1, 3 and 6 months and answered surveys about sleep, CPAP side effects and lifestyle. We compared CPAP compliance, cost-effectiveness and QoL between the beginning and the end of the study. A Bayesian cost-effectiveness analysis with non-informative priors was performed. We randomised 139 patients. At 6 months, we found similar levels of CPAP compliance, and improved daytime sleepiness, QoL, side effects and degree of satisfaction in both groups. Despite requiring more visits, the telemedicine group was more cost-effective: costs were lower and differences in effectiveness were not relevant. A telemedicine-based strategy for the follow-up of CPAP treatment in patients with OSA was as effective as standard hospital-based care in terms of CPAP compliance and symptom improvement, with comparable side effects and satisfaction rates. The telemedicine-based strategy had lower total costs due to savings on transport and less lost productivity (indirect costs). NCT01716676. 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.

Cost-effectiveness of an exercise program during pregnancy to prevent gestational diabetes: results of an economic evaluation alongside a randomised controlled trial.

PubMed

Oostdam, Nicolette; Bosmans, Judith; Wouters, Maurice G A J; Eekhoff, Elisabeth M W; van Mechelen, Willem; van Poppel, Mireille N M

2012-07-04

The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide. GDM and the risks associated with GDM lead to increased health care costs and losses in productivity. The objective of this study is to evaluate whether the FitFor2 exercise program during pregnancy is cost-effective from a societal perspective as compared to standard care. A randomised controlled trial (RCT) and simultaneous economic evaluation of the FitFor2 program were conducted. Pregnant women at risk for GDM were randomised to an exercise program to prevent high maternal blood glucose (n = 62) or to standard care (n = 59). The exercise program consisted of two sessions of aerobic and strengthening exercises per week. Clinical outcome measures were maternal fasting blood glucose levels, insulin sensitivity and infant birth weight. Quality of life was measured using the EuroQol 5-D and quality-adjusted life-years (QALYs) were calculated. Resource utilization and sick leave data were collected by questionnaires. Data were analysed according to the intention-to-treat principle. Missing data were imputed using multiple imputations. Bootstrapping techniques estimated the uncertainty surrounding the cost differences and incremental cost-effectiveness ratios. There were no statistically significant differences in any outcome measure. During pregnancy, total health care costs and costs of productivity losses were statistically non-significant (mean difference €1308; 95%CI €-229 - €3204). The cost-effectiveness analyses showed that the exercise program was not cost-effective in comparison to the control group for blood glucose levels, insulin sensitivity, infant birth weight or QALYs. The twice-weekly exercise program for pregnant women at risk for GDM evaluated in the present study was not cost-effective compared to standard care. Based on these results, implementation of this exercise program for the prevention of GDM cannot be recommended. NTR1139.

Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic Lateral Sclerosis (LiCALS) [Eudract number: 2008-006891-31

PubMed Central

2011-01-01

Background Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, no patients had died (i.e., 100% survival) at the end of the study (15 months from entry), compared to 71% surviving in the riluzole-only group. Although the trial can be criticised on several grounds, there is a substantial rationale from other laboratory studies that lithium is worth investigating therapeutically in amyotrophic lateral sclerosis. Methods/Design LiCALS is a multi-centre double-blind randomised parallel group controlled trial of the efficacy, safety, and tolerability of lithium carbonate (LiCO3) at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L), plus standard treatment, versus matched placebo plus standard treatment, in patients with amyotrophic lateral sclerosis. The study will be based in the UK, in partnership with the MND Association and DeNDRoN (the Dementias and Neurodegnerative Diseases Clinical Research Network). 220 patients will be recruited. All patients will be on the standard treatment for ALS of riluzole 100 mg daily. The primary outcome measure will be death from any cause at 18 months defined from the date of randomisation. Secondary outcome measures will be changes in three functional rating scales, the ALS Functional Rating Scale-Revised, The EuroQOL (EQ-5D), and the Hospital Anxiety and Depression Scale. Eligible patients will have El Escorial Possible, Laboratory-supported Probable, Probable or Definite amyotrophic lateral sclerosis with disease duration between 6 months and 36 months (inclusive), vital capacity ≥ 60% of predicted within 1 month prior to randomisation and age at least18 years. Discussion Patient recruitment began in June 2009 and the last patient is expected to complete the trial protocol in November 2011. Trial registration Current controlled trials ISRCTN83178718 PMID:21936930

No effect of the infiltration of local anaesthetic for total hip arthroplasty using an anterior approach: a randomised placebo controlled trial.

PubMed

den Hartog, Y M; Mathijssen, N M C; van Dasselaar, N T; Langendijk, P N J; Vehmeijer, S B W

2015-06-01

Only limited data are available regarding the infiltration of local anaesthetic for total hip arthroplasty (THA), and no studies were performed for THA using the anterior approach. In this prospective, randomised placebo-controlled study we investigated the effect of both standard and reverse infiltration of local anaesthetic in combination with the anterior approach for THA. The primary endpoint was the mean numeric rating score for pain four hours post-operatively. In addition, we recorded the length of hospital stay, the operating time, the destination of the patient at discharge, the use of pain medication, the occurrence of side effects and pain scores at various times post-operatively. Between November 2012 and January 2014, 75 patients were included in the study. They were randomised into three groups: standard infiltration of local anaesthetic, reversed infiltration of local anaesthetic, and placebo. There was no difference in mean numeric rating score for pain four hours post-operatively (p = 0.87). There were significantly more side effects at one and eight hours post-operatively in the placebo group (p = 0.02; p = 0.03), but this did not influence the mobilisation of the patients. There were no differences in all other outcomes between the groups. We found no clinically relevant effect when the infiltration of local anaesthetic with ropivacaine and epinephrine was used in a multimodal pain protocol for THA using the anterior approach. ©2015 The British Editorial Society of Bone & Joint Surgery.

Gene therapy for haemophilia.

PubMed

Sharma, Akshay; Easow Mathew, Manu; Sriganesh, Vasumathi; Reiss, Ulrike M

2016-12-20

Haemophilia is a genetic disorder characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy has recently been prompted as a curative treatment modality. This is an update of a published Cochrane Review. To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 18 August 2016. Eligible trials include randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation for individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. No trials of gene therapy for haemophilia were found. No trials of gene therapy for haemophilia were identified. No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the safety and efficacy of gene therapy for haemophilia. Gene therapy for haemophilia is still in its nascent stages and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

A randomised controlled trial to determine the clinical and cost effectiveness of thulium laser transurethral vaporesection of the prostate (ThuVARP) versus transurethral resection of the prostate (TURP) in the National Health Service (NHS) - the UNBLOCS trial: a study protocol for a randomised controlled trial.

PubMed

Worthington, Jo; Taylor, Hilary; Abrams, Paul; Brookes, Sara T; Cotterill, Nikki; Noble, Sian M; Page, Tobias; Swami, K Satchi; Lane, J Athene; Hashim, Hashim

2017-04-17

Transurethral resection of the prostate (TURP) has been the standard operation for benign prostatic obstruction (BPO) for 40 years, with approximately 25,000 procedures performed annually, and has remained largely unchanged. It is generally a successful operation, but has well-documented risks for the patient. Thulium laser transurethral vaporesection of the prostate (ThuVARP) vaporises and resects the prostate using a surgical technique similar to TURP. The small amount of study data currently available suggests that ThuVARP may have certain advantages over TURP, including reduced blood loss and shorter hospital stay, earlier return to normal activities, and shorter duration of catheterisation. A multicentre, pragmatic, randomised, controlled, parallel-group trial of ThuVARP versus standard TURP in men with BPO. Four hundred and ten men suitable for prostate surgery were randomised to receive either ThuVARP or TURP at four university teaching hospitals, and three district general hospitals. The key aim of the trial is to determine whether ThuVARP is equivalent to TURP judged on both the patient-reported International Prostate Symptom Score (IPSS) and the maximum urine flow rate (Qmax) at 12 months post-surgery. The general population has an increased life expectancy. As men get older their prostates enlarge, potentially causing BPO, which often requires surgery. Therefore, as the population ages, more prostate operations are needed to relieve obstruction. There is hence sustained interest in the condition and increasing need to find safer techniques than TURP. Various laser techniques have become available but none are widely used in the NHS because of lengthy training required for surgeons or inferior performance on clinical outcomes. Promising initial evidence from one RCT shows that ThuVARP has equivalent clinical effectiveness when compared to TURP, as well as other potential advantages. As ThuVARP uses a technique similar to that used in TURP, the learning curve is short, potentially making it also very quickly generalisable. This randomised study is designed to provide the high-quality evidence, in an NHS setting, with a range of patient-reported, clinical and cost-effectiveness outcomes, which will underpin and inform future NICE guidance. ISRCTN registry, ISRCTN00788389 . Registered on 20 September 2013.

Ergonomic positioning or equipment for treating carpal tunnel syndrome.

PubMed

O'Connor, Denise; Page, Matthew J; Marshall, Shawn C; Massy-Westropp, Nicola

2012-01-18

Non-surgical treatment, including ergonomic positioning or equipment, are sometimes offered to people experiencing mild to moderate symptoms from carpal tunnel syndrome (CTS). The effectiveness and duration of benefit from ergonomic positioning or equipment interventions for treating CTS are unknown. To assess the effects of ergonomic positioning or equipment compared with no treatment, a placebo or another non-surgical intervention in people with CTS. We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 June 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 2, in The Cochrane Library), MEDLINE (1966 to June 2011), EMBASE (1980 to June 2011), CINAHL Plus (1937 to June 2011), and AMED (1985 to June 2011). We also reviewed the reference lists of randomised or quasi-randomised trials identified from the electronic search. Randomised or quasi-randomised controlled trials comparing ergonomic positioning or equipment with no treatment, placebo or another non-surgical intervention in people with CTS. Two review authors independently selected trials for inclusion, extracted data and assessed risk of bias of included studies. We calculated risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for the primary and secondary outcomes. We pooled results of clinically and statistically homogeneous trials, where possible, to provide estimates of the effect of ergonomic positioning or equipment. We included two trials (105 participants) comparing ergonomic versus placebo keyboards. Neither trial assessed the primary outcome (short-term overall improvement) or adverse effects of interventions. In one small trial (25 participants) an ergonomic keyboard significantly reduced pain after 12 weeks (MD -2.40; 95% CI -4.45 to -0.35) but not six weeks (MD -0.20; 95% CI -1.51 to 1.11). In this same study, there was no difference between ergonomic and standard keyboards in hand function at six or 12 weeks or palm-wrist sensory latency at 12 weeks. The second trial (80 participants) reported no significant difference in pain severity after six months when using either of the three ergonomic keyboards versus a standard keyboard. No trials comparing (i) ergonomic positioning or equipment with no treatment, (ii) ergonomic positioning or equipment with another non-surgical treatment, or (iii) different ergonomic positioning or equipment regimes, were found. There is insufficient evidence from randomised controlled trials to determine whether ergonomic positioning or equipment is beneficial or harmful for treating carpal tunnel syndrome.

Cost-effectiveness of a pragmatic structured education intervention for the prevention of type 2 diabetes: economic evaluation of data from the Let's Prevent Diabetes cluster-randomised controlled trial

PubMed Central

Ahrabian, D; Davies, M J; Khunti, K; Yates, T; Gray, A M

2017-01-01

Objectives Prevention of type 2 diabetes mellitus (TD2M) is a priority for healthcare systems. We estimated the cost-effectiveness compared with standard care of a structured education programme (Let's Prevent) targeting lifestyle and behaviour change to prevent progression to T2DM in people with prediabetes. Design Cost-effectiveness analysis alongside randomised controlled trial. Setting 44 general practices in Leicestershire, England. Participants 880 participants with prediabetes randomised to receive either standard care or a 6-hour group structured education programme with follow-up sessions in a primary care setting. Main outcome measure Incremental cost utility from the UK National Health Service (NHS) perspective. Quality of life and resource use measured from baseline and during the 36 months follow-up using the EuroQoL EQ-5D and 15D instruments and an economic questionnaire. Outcomes measured using quality-adjusted life years (QALYs) and healthcare costs calculated in 2012–2013 prices. Results After accounting for clustering and missing data, the intervention group was found to have a net gain of 0.046 (95% CI −0.0171 to 0.109) QALYs over 3 years, adjusted for baseline utility, at an additional cost of £168 (95% CI −395 to 732) per patient compared with the standard care group. The incremental cost-effectiveness ratio is £3643/QALY with an 86% probability of being cost-effective at a willingness to pay threshold of £20 000/QALY. Conclusions The education programme had higher costs and higher quality of life compared with the standard care group. The Let's Prevent programme is very likely to be cost-effective at a willingness to pay threshold of £20 000/QALY gained. Trial registration number ISRCTN80605705. PMID:28069625

Cost-effectiveness of a pragmatic structured education intervention for the prevention of type 2 diabetes: economic evaluation of data from the Let's Prevent Diabetes cluster-randomised controlled trial.

PubMed

Leal, J; Ahrabian, D; Davies, M J; Gray, L J; Khunti, K; Yates, T; Gray, A M

2017-01-09

Prevention of type 2 diabetes mellitus (TD2M) is a priority for healthcare systems. We estimated the cost-effectiveness compared with standard care of a structured education programme (Let's Prevent) targeting lifestyle and behaviour change to prevent progression to T2DM in people with prediabetes. Cost-effectiveness analysis alongside randomised controlled trial. 44 general practices in Leicestershire, England. 880 participants with prediabetes randomised to receive either standard care or a 6-hour group structured education programme with follow-up sessions in a primary care setting. Incremental cost utility from the UK National Health Service (NHS) perspective. Quality of life and resource use measured from baseline and during the 36 months follow-up using the EuroQoL EQ-5D and 15D instruments and an economic questionnaire. Outcomes measured using quality-adjusted life years (QALYs) and healthcare costs calculated in 2012-2013 prices. After accounting for clustering and missing data, the intervention group was found to have a net gain of 0.046 (95% CI -0.0171 to 0.109) QALYs over 3 years, adjusted for baseline utility, at an additional cost of £168 (95% CI -395 to 732) per patient compared with the standard care group. The incremental cost-effectiveness ratio is £3643/QALY with an 86% probability of being cost-effective at a willingness to pay threshold of £20 000/QALY. The education programme had higher costs and higher quality of life compared with the standard care group. The Let's Prevent programme is very likely to be cost-effective at a willingness to pay threshold of £20 000/QALY gained. ISRCTN80605705. 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/.

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.

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.

Smartphone application for women with gestational diabetes mellitus: a study protocol for a multicentre randomised controlled trial.

PubMed

Borgen, Iren; Garnweidner-Holme, Lisa Maria; Jacobsen, Anne Flem; Bjerkan, Kirsti; Fayyad, Seraj; Joranger, Pål; Lilleengen, Anne Marie; Mosdøl, Annhild; Noll, Josef; Småstuen, Milada Cvancarova; Terragni, Laura; Torheim, Liv Elin; Lukasse, Mirjam

2017-03-27

The promotion of a healthy diet, physical activity and measurement of blood glucose levels are essential components in the care for women with gestational diabetes mellitus (GDM). Smartphones offer a new way to promote health behaviour. The main aim is to investigate if the use of the Pregnant+ app, in addition to standard care, results in better blood glucose levels compared with current standard care only, for women with GDM. This randomised controlled trial will include 230 pregnant women with GDM followed up at 5 outpatient departments (OPD) in the greater Oslo Region. Women with a 2-hour oral glucose tolerance test (OGTT) ≥9 mmol/L, who own a smartphone, understand Norwegian, Urdu or Somali and are <33 weeks pregnant, are invited. The intervention group receives the Pregnant+ app and standard care. The control group receives standard care only. Block randomisation is performed electronically. Data are collected using self-reported questionnaires and hospital records. Data will be analysed according to the intention-to-treat principle. Groups will be compared using linear regression for the main outcome and χ 2 test for categorical data and Student's t-test or Mann-Whitney-Wilcoxon test for skewed distribution. The main outcome is the glucose level measured at the 2-hour OGTT 3 months postpartum. Secondary outcomes are a change in health behaviour and knowledge about GDM, quality of life, birth weight, mode of delivery and complications for mother and child. The study is exempt from regional ethics review due to its nature of quality improvement in patient care. Our study has been approved by the Norwegian Social Science Data Services and the patient privacy protections boards governing over the recruitment sites. Findings will be presented in peer-reviewed journals and at conferences. NCT02588729, Post-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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

Cost-Effectiveness of a Specialist Geriatric Medical Intervention for Frail Older People Discharged from Acute Medical Units: Economic Evaluation in a Two-Centre Randomised Controlled Trial (AMIGOS).

PubMed

Tanajewski, Lukasz; Franklin, Matthew; Gkountouras, Georgios; Berdunov, Vladislav; Edmans, Judi; Conroy, Simon; Bradshaw, Lucy E; Gladman, John R F; Elliott, Rachel A

2015-01-01

Poor outcomes and high resource-use are observed for frail older people discharged from acute medical units. A specialist geriatric medical intervention, to facilitate Comprehensive Geriatric Assessment, was developed to reduce the incidence of adverse outcomes and associated high resource-use in this group in the post-discharge period. To examine the costs and cost-effectiveness of a specialist geriatric medical intervention for frail older people in the 90 days following discharge from an acute medical unit, compared with standard care. Economic evaluation was conducted alongside a two-centre randomised controlled trial (AMIGOS). 433 patients (aged 70 or over) at risk of future health problems, discharged from acute medical units within 72 hours of attending hospital, were recruited in two general hospitals in Nottingham and Leicester, UK. Participants were randomised to the intervention, comprising geriatrician assessment in acute units and further specialist management, or to control where patients received no additional intervention over and above standard care. Primary outcome was incremental cost per quality adjusted life year (QALY) gained. We undertook cost-effectiveness analysis for 417 patients (intervention: 205). The difference in mean adjusted QALYs gained between groups at 3 months was -0.001 (95% confidence interval [CI]: -0.009, 0.007). Total adjusted secondary and social care costs, including direct costs of the intervention, at 3 months were £4412 (€5624, $6878) and £4110 (€5239, $6408) for the intervention and standard care groups, the incremental cost was £302 (95% CI: 193, 410) [€385, $471]. The intervention was dominated by standard care with probability of 62%, and with 0% probability of cost-effectiveness (at £20,000/QALY threshold). The specialist geriatric medical intervention for frail older people discharged from acute medical unit was not cost-effective. Further research on designing effective and cost-effective specialist service for frail older people discharged from acute medical units is needed. ISRCTN registry ISRCTN21800480 http://www.isrctn.com/ISRCTN21800480.

Modified Pilates as an adjunct to standard physiotherapy care for urinary incontinence: a mixed methods pilot for a randomised controlled trial.

PubMed

Lausen, Adi; Marsland, Louise; Head, Samantha; Jackson, Joanna; Lausen, Berthold

2018-01-12

Urinary incontinence (UI) is a distressing condition affecting at least 5 million women in England and Wales. Traditionally, physiotherapy for UI comprises pelvic floor muscle training, but although evidence suggests this can be effective it is also recognised that benefits are often compromised by patient motivation and commitment. In addition, there is increasing recognition that physical symptoms alone are poor indicators of the impact of incontinence on individuals' lives. Consequently, more holistic approaches to the treatment of UI, such as Modified Pilates (MP) have been recommended. This study aimed to provide preliminary findings about the effectiveness of a 6-week course of MP classes as an adjunct to standard physiotherapy care for UI, and to test the feasibility of a randomised controlled trial (RCT) design. The study design was a single centre pilot RCT, plus qualitative interviews. 73 women referred to Women's Health Physiotherapy Services for UI at Colchester Hospital University NHS Foundation Trust were randomly assigned to two groups: a 6-week course of MP classes in addition to standard physiotherapy care (intervention) or standard physiotherapy care only (control). Main outcome measures were self-reported UI, quality of life and self-esteem at baseline (T1), completion of treatment (T2), and 5 months after randomisation (T3). Qualitative interviews were conducted with a subgroup at T2 and T3. Due to the nature of the intervention blinding of participants, physiotherapists and researchers was not feasible. Post-intervention data revealed a range of benefits for women who attended MP classes and who had lower symptom severity at baseline: improved self-esteem (p = 0.032), decreased social embarrassment (p = 0.026) and lower impact on normal daily activities (p = 0.025). In contrast, women with higher symptom severity showed improvement in their personal relationships (p = 0.017). Qualitative analysis supported these findings and also indicated that MP classes could positively influence attitudes to exercise, diet and wellbeing. A definitive RCT is feasible but will require a large sample size to inform clinical practice. ISRCTN74075972 Registered 12/12/12 (Retrospectively registered).

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.

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial

PubMed Central

2012-01-01

Background Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. Methods/Design Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT. Discussion The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines. Trial registration NTR2657 PMID:22989359

Effectiveness of personalised risk information and taster sessions to increase the uptake of smoking cessation services (Start2quit): a randomised controlled trial.

PubMed

Gilbert, Hazel; Sutton, Stephen; Morris, Richard; Petersen, Irene; Galton, Simon; Wu, Qi; Parrott, Steve; Nazareth, Irwin

2017-02-25

National Health Service Stop Smoking Services (SSSs) offer help to smokers motivated to quit; however, attendance rates are low and recent figures show a downward trend. We aimed to assess the effectiveness of a two-component personalised intervention on attendance at SSSs. We did this randomised controlled trial in 18 SSSs in England. Current smokers (aged ≥16 years) were identified from medical records in 99 general practices and invited to participate by their general practitioner. Individuals who gave consent, were motivated to quit, and had not attended the SSS within the past 12 months, were randomly assigned (3:2), via computer-generated randomisation with permuted blocks (block size of five), to receive either an individually tailored risk letter and invitation to attend a no-commitment introductory session run by the local SSS (intervention group) or a standard generic letter advertising the local SSS (control group). Randomisation was stratified by sex. Masking of participants to receipt of a personal letter and invitation to a taster session was not possible. The personal letter was generated by a research assistant, but the remainder of the research team were masked to group allocation. General practitioners, practice staff, and SSS advisers were unaware of their patients' allocation. The primary outcome was attendance at the first session of an SSS course within 6 months from randomisation. We did analysis by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN 76561916. Recruitment, collection of baseline data, delivery of the intervention, and follow up of participants took place between Jan 31, 2011, and July 12, 2014. We randomly assigned 4384 smokers to the intervention group (n=2636) or the control group (n=1748); 4383 participants comprised the intention-to-treat population. Attendance at the first session of an SSS course was significantly higher in the intervention group than in the control group (458 [17·4%] vs 158 [9·0%] participants; unadjusted odds ratio 2·12 [95% CI 1·75-2·57]; p<0·0001). Delivery of personalised risk information alongside an invitation to an introductory session more than doubled the odds of attending the SSS compared with a standard generic invitation to contact the service. This result suggests that a more proactive approach, combined with an opportunity to experience local services, can reduce patient barriers to receiving treatment and has high potential to increase uptake. National Institutes of Health Research Health Technology Assessment. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

The effects of vault drainage on postoperative morbidity after vaginal hysterectomy for benign gynaecological disease: a randomised controlled trial.

PubMed

Dua, A; Galimberti, A; Subramaniam, M; Popli, G; Radley, S

2012-02-01

To evaluate the efficacy of vault drainage in reducing the immediate postoperative morbidity associated with vaginal hysterectomy carried out for benign gynaecological conditions. Randomised controlled trial. A tertiary referral gynaecology centre in UK. A total of 272 women who underwent vaginal hysterectomy for benign conditions between March 2005 and June 2010. The 272 women were randomised to have a drain inserted or not inserted, 'drain' or 'no drain', respectively, before vault closure during vaginal hysterectomy, using a sealed envelope technique. The surgical procedures were performed using the surgeons' standard technique and postoperative care was delivered according to the unit's protocol. The primary outcome measure was reduction in postoperative febrile morbidity. Secondary outcome measures were hospital readmission rate, blood transfusion, change in postoperative haemoglobin and length of stay. In all, 135 women were randomised to have a drain and 137 to 'no drain'. There were no differences in the incidence of febrile morbidity, length of stay, change in haemoglobin or need for postoperative blood transfusion between the two groups. The routine use of vault drain at vaginal hysterectomy for benign disorders has no significant effect on postoperative morbidity. The use of vault drain in this context is not recommended. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

A randomised controlled trial to prevent smoking relapse among recently quit smokers enrolled in employer and health plan sponsored quitlines.

PubMed

McDaniel, Anna M; Vickerman, Katrina A; Stump, Timothy E; Monahan, Patrick O; Fellows, Jeffrey L; Weaver, Michael T; Carlini, Beatriz H; Champion, Victoria L; Zbikowski, Susan M

2015-06-29

To test adding an interactive voice response (IVR)-supported protocol to standard quitline treatment to prevent relapse among recently quit smokers. Parallel randomised controlled trial with three arms: standard quitline, standard plus technology enhanced quitline with 10 risk assessments (TEQ-10), standard plus 20 TEQ assessments (TEQ-20). Quit For Life (QFL) programme. 1785 QFL enrolees through 19 employers or health plans who were 24+ h quit. QFL is a 5-call telephone-based cessation programme including medications and web-based support. TEQ interventions included 10 or 20 IVR-delivered relapse risk assessments over 8 weeks with automated transfer to counselling for those at risk. Self-reported 7-day and 30-day abstinence assessed at 6-month and 12-month post-enrolment (response rates: 61% and 59%, respectively). Missing data were imputed. 1785 were randomised (standard n=592, TEQ-10 n=602, TEQ-20 n=591). Multiple imputation-derived, intent-to-treat 30-day quit rates (95% CI) at 6 months were 59.4% (53.7% to 63.8%) for standard, 62.3% (57.7% to 66.9%) for TEQ-10, 59.4% (53.7% to 65.1%) for TEQ-20 and 30-day quit rates at 12 months were 61.2% (55.6% to 66.8%) for standard, 60.6% (56.0% to 65.2%) for TEQ-10, 54.9% (49.0% to 60.9%) for TEQ-20. There were no significant differences in quit rates. 73.3% of TEQ participants were identified as at-risk by IVR assessments; on average, participants completed 0.41 IVR-transferred counselling calls. Positive risk assessments identified participants less likely (OR=0.56, 95% CI 0.42 to 0.76) to be abstinent at 6 months. Standard treatment was highly effective, with 61% remaining abstinent at 12 months using multiple imputation intent-to-treat (intent-to-treat missing=smoking quit rate: 38%). TEQ assessments identified quitters at risk for relapse. However, adding IVR-transferred counselling did not yield higher quit rates. Research is needed to determine if alternative designs can improve outcomes. NCT00888992. 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.

Intravenous iron isomaltoside 1000 administered by high single-dose infusions or standard medical care for the treatment of fatigue in women after postpartum haemorrhage: study protocol for a randomised controlled trial.

PubMed

Holm, Charlotte; Thomsen, Lars Lykke; Norgaard, Astrid; Langhoff-Roos, Jens

2015-01-14

Postpartum haemorrhage can lead to iron deficiency with and without anaemia, the clinical consequences of which include physical fatigue. Although oral iron is the standard treatment, it is often associated with gastrointestinal side effects and poor compliance. To date, no published randomised controlled studies have compared the clinical efficacy and safety of standard medical care with intravenous administration of iron supplementation after postpartum haemorrhage.The primary objective of this study is to compare the efficacy of an intravenous high single-dose of iron isomaltoside 1000 with standard medical care on physical fatigue in women with postpartum haemorrhage. In a single centre, open-labelled, randomised trial, women with postpartum haemorrhage exceeding 700 mL will be allocated to either a single dose of 1,200 mg of iron isomaltoside 1000 or standard medical care. Healthy parturients with a singleton pregnancy will be included within 48 hours after delivery.Participants will complete structured questionnaires that focus on several dimensions of fatigue and mental health (Multidimensional Fatigue Inventory, Edinburgh Postnatal Depression Scale and the Postpartum Questionnaire), at inclusion and at follow-up visits after three days, one week, three weeks, eight weeks, and 12 weeks postpartum. The primary endpoint is the aggregated change in physical fatigue score within 12 weeks postpartum, as measured by a subscale of the Multidimensional Fatigue Inventory. The primary objective will be considered to have been met if an intravenous high single dose of iron isomaltoside 1000 is shown to be superior to standard medical care in women after postpartum haemorrhage regarding physical fatigue.For claiming superiority, we set the minimal clinically relevant difference between the mean scores at 1.8, and the assumed standard deviation at 4.2. Hence, 87 participants per treatment group are needed in order to demonstrate superiority; to provide an extra margin for missing data and dropouts, 200 women will be included. The study will provide evidence on relevant clinical outcomes beyond biochemical parameters for intravenous iron isomaltoside 1000 compared to standard medical care in women after postpartum haemorrhage. This trial is registered with Clinicaltrials.gov (identifier: NCT01895218) on 26 June 2013.

Interactive web-based pulmonary rehabilitation programme: a randomised controlled feasibility trial

PubMed Central

Chaplin, Emma; Hewitt, Stacey; Apps, Lindsay; Bankart, John; Pulikottil-Jacob, Ruth; Boyce, Sally; Morgan, Mike; Williams, Johanna; Singh, Sally

2017-01-01

Objectives The aim of this study was to determine if an interactive web-based pulmonary rehabilitation (PR) programme is a feasible alternative to conventional PR. Design Randomised controlled feasibility trial. Setting Participants with a diagnosis of chronic obstructive pulmonary disease were recruited from PR assessments, primary care and community rehabilitation programmes. Patients randomised to conventional rehabilitation started the programme according to the standard care at their referred site on the next available date. Participants 103 patients were recruited to the study and randomised: 52 to conventional rehabilitation (mean (±SD) age 66 (±8) years, Medical Research Council (MRC) 3 (IQR2–4)); 51 to the web arm (mean (±SD) age 66 (±10) years, MRC 3 (IQR2–4)). Participants had to be willing to participate in either arm of the trial, have internet access and be web literate. Interventions Patients randomised to the web-based programme worked through the website, exercising and recording their progress as well as reading educational material. Conventional PR consisted of twice weekly, 2 hourly sessions (an hour for exercise training and an hour for education). Outcome measures Recruitment rates, eligibility, patient preference and dropout and completion rates for both programmes were collected. Standard outcomes for a PR assessment including measures of exercise capacity and quality of life questionnaires were also evaluated. Results A statistically significant improvement (p≤0.01) was observed within each group in the endurance shuttle walk test (WEB: mean change 189±211.1; PR classes: mean change 184.5±247.4 s) and Chronic Respiratory disease Questionnaire-Dyspnoea (CRQ-D; WEB: mean change 0.7±1.2; PR classes: mean change 0.8±1.0). However, there were no significant differences between the groups in any outcome. Dropout rates were higher in the web-based programme (57% vs 23%). Conclusions An interactive web-based PR programme is feasible and acceptable when compared with conventional PR. Future trials maybe around choice-based PR programmes for select patients enabling stratification of patient care. Trial registration number ISRCTN03142263; Results. PMID:28363923

Interactive web-based pulmonary rehabilitation programme: a randomised controlled feasibility trial.

PubMed

Chaplin, Emma; Hewitt, Stacey; Apps, Lindsay; Bankart, John; Pulikottil-Jacob, Ruth; Boyce, Sally; Morgan, Mike; Williams, Johanna; Singh, Sally

2017-03-31

The aim of this study was to determine if an interactive web-based pulmonary rehabilitation (PR) programme is a feasible alternative to conventional PR. Randomised controlled feasibility trial. Participants with a diagnosis of chronic obstructive pulmonary disease were recruited from PR assessments, primary care and community rehabilitation programmes. Patients randomised to conventional rehabilitation started the programme according to the standard care at their referred site on the next available date. 103 patients were recruited to the study and randomised: 52 to conventional rehabilitation (mean (±SD) age 66 (±8) years, Medical Research Council (MRC) 3 (IQR2-4)); 51 to the web arm (mean (±SD) age 66 (±10) years, MRC 3 (IQR2-4)). Participants had to be willing to participate in either arm of the trial, have internet access and be web literate. Patients randomised to the web-based programme worked through the website, exercising and recording their progress as well as reading educational material. Conventional PR consisted of twice weekly, 2 hourly sessions (an hour for exercise training and an hour for education). Recruitment rates, eligibility, patient preference and dropout and completion rates for both programmes were collected. Standard outcomes for a PR assessment including measures of exercise capacity and quality of life questionnaires were also evaluated. A statistically significant improvement (p≤0.01) was observed within each group in the endurance shuttle walk test (WEB: mean change 189±211.1; PR classes: mean change 184.5±247.4 s) and Chronic Respiratory disease Questionnaire-Dyspnoea (CRQ-D; WEB: mean change 0.7±1.2; PR classes: mean change 0.8±1.0). However, there were no significant differences between the groups in any outcome. Dropout rates were higher in the web-based programme (57% vs 23%). An interactive web-based PR programme is feasible and acceptable when compared with conventional PR. Future trials maybe around choice-based PR programmes for select patients enabling stratification of patient care. ISRCTN03142263; 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/.

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.

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

PubMed

Thwaites, Guy E; Scarborough, Matthew; Szubert, Alexander; Nsutebu, Emmanuel; Tilley, Robert; Greig, Julia; Wyllie, Sarah A; Wilson, Peter; Auckland, Cressida; Cairns, Janet; Ward, Denise; Lal, Pankaj; Guleri, Achyut; Jenkins, Neil; Sutton, Julian; Wiselka, Martin; Armando, Gonzalez-Ruiz; Graham, Clive; Chadwick, Paul R; Barlow, Gavin; Gordon, N Claire; Young, Bernadette; Meisner, Sarah; McWhinney, Paul; Price, David A; Harvey, David; Nayar, Deepa; Jeyaratnam, Dakshika; Planche, Tim; Minton, Jane; Hudson, Fleur; Hopkins, Susan; Williams, John; Török, M Estee; Llewelyn, Martin J; Edgeworth, Jonathan D; Walker, A Sarah

2018-02-17

Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. UK National Institute for Health Research Health Technology Assessment. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

The study protocol for 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.

PubMed

Garner, Alan A; Fearnside, Michael; Gebski, Val

2013-09-14

The utility of advanced prehospital interventions for severe blunt traumatic brain injury (BTI) remains controversial. Of all trauma patient subgroups it has been anticipated that this patient group would most benefit from advanced prehospital interventions as hypoxia and hypotension have been demonstrated to be associated with poor outcomes and these factors may be amenable to prehospital intervention. Supporting evidence is largely lacking however. In particular the efficacy of early anaesthesia/muscle relaxant assisted intubation has proved difficult to substantiate. This article describes the design and protocol of the Head Injury Retrieval Trial (HIRT) which is a randomised controlled single centre trial of physician prehospital care (delivering advanced interventions such as rapid sequence intubation and blood transfusion) in addition to paramedic care for severe blunt TBI compared with paramedic care alone. Primary endpoint is Glasgow Outcome Scale score at six months post injury. Issues with trial integrity resulting from drop ins from standard care to the treatment arm as the result of policy changes by the local ambulance system are discussed. This randomised controlled trial will contribute to the evaluation of the efficacy of advance prehospital interventions in severe blunt TBI. ClinicalTrials.gov: NCT00112398.

Navigating the fine line between benefit and risk in chronic atrial fibrillation: rationale and design of the Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY).

PubMed

Carrington, Melinda J; Ball, Jocasta; Horowitz, John D; Marwick, Thomas H; Mahadevan, Gnanadevan; Wong, Chiew; Abhayaratna, Walter P; Haluska, Brian; Thompson, David R; Scuffham, Paul A; Stewart, Simon

2013-06-20

Health outcomes associated with atrial fibrillation (AF) continue to be poor and standard management often does not provide clinical stability. The Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY) compares the efficacy of a post-discharge, nurse-led, multi-disciplinary programme to optimise AF management with usual care. SAFETY is a prospective, multi-centre, randomised controlled trial with blinded-endpoint adjudication. A target of 320 hospitalised patients with a chronic form of AF will be randomised (stratified by "rate" versus "rhythm" control) to usual post-discharge care or the SAFETY Intervention (SI). The SI involves home-based assessment, extensive clinical profiling and the application of optimal gold-standard pharmacology which is individually tailored according to a "traffic light" framework based on clinical stability, risk profile and therapeutic management. The primary endpoint is event-free survival from all-cause death or unplanned readmission during 18-36 months follow-up. Secondary endpoints include rate of recurrent hospital stay, treatment success (i.e. maintenance of rhythm or rate control and/or application of anti-thrombotic therapy without a bleeding event) and cost-efficacy. With study recruitment to be completed in early 2012, the results of this study will be available in early 2014. If positive, SAFETY will represent a potentially cost-effective and readily applicable strategy to improve health outcomes in high risk individuals discharged from hospital with chronic AF. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Ensuring respect for persons in COMPASS: a cluster randomised pragmatic clinical trial.

PubMed

Andrews, Joseph E; Moore, J Brian; Weinberg, Richard B; Sissine, Mysha; Gesell, Sabina; Halladay, Jacquie; Rosamond, Wayne; Bushnell, Cheryl; Jones, Sara; Means, Paula; King, Nancy M P; Omoyeni, Diana; Duncan, Pamela W

2018-05-02

Cluster randomised clinical trials present unique challenges in meeting ethical obligations to those who are treated at a randomised site. Obtaining informed consent for research within the context of clinical care is one such challenge. In order to solve this problem it is important that an informed consent process be effective and efficient, and that it does not impede the research or the healthcare. The innovative approach to informed consent employed in the COMPASS study demonstrates the feasibility of upholding ethical standards without imposing undue burden on clinical workflows, staff members or patients who may participate in the research by virtue of their presence in a cluster randomised facility. The COMPASS study included 40 randomised sites and compared the effectiveness of a postacute stroke intervention with standard care. Each site provided either the comprehensive postacute stroke intervention or standard care according to the randomisation assignment. Working together, the study team, institutional review board and members of the community designed an ethically appropriate and operationally reasonable consent process which was carried out successfully at all randomised sites. This achievement is noteworthy because it demonstrates how to effectively conduct appropriate informed consent in cluster randomised trials, and because it provides a model that can easily be adapted for other pragmatic studies. With this innovative approach to informed consent, patients have access to the information they need about research occurring where they are seeking care, and medical researchers can conduct their studies without ethical concerns or unreasonable logistical impediments. NCT02588664, recruiting. This article covers the development of consent process that is currentlty being employed in the study. © 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.

Using Environmental Print to Enhance Emergent Literacy and Print Motivation

ERIC Educational Resources Information Center

Neumann, Michelle M.; Hood, Michelle; Ford, Ruth M.

2013-01-01

Given the ubiquitous and salient nature of environmental print, it has the potential to scaffold emergent literacy in young children. This randomised control study evaluated the effects of using environmental print compared to standard print (the same labels in manuscript form) in an 8-week intervention (30 min per week) to foster 3- to…

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.

Effects of first exposure to plain cigarette packaging on smoking behaviour and attitudes: a randomised controlled study.

PubMed

Maynard, Olivia M; Leonards, Ute; Attwood, Angela S; Bauld, Linda; Hogarth, Lee; Munafò, Marcus R

2015-03-13

Plain packaging requires tobacco products to be sold in packs with a standard shape, method of opening and colour, leaving the brand name in a standard font and location. We ran a randomised controlled trial to investigate the impact of plain packaging on smoking behaviour and attitudes. In a parallel group randomised trial design, 128 daily smokers smoked cigarettes from their usual UK brand, or a plain Australian brand that was closely matched to their usual UK brand for 24 hours. Primary outcomes were number of cigarettes smoked and volume of smoke inhaled per cigarette. Secondary outcomes were self-reported ratings of motivation to quit, cigarette taste, experience of using the pack, experience of smoking, attributes of the pack, perceptions of the health warning, changes in smoking behaviour, and views on plain packaging. There was no evidence that pack type had an effect on either of the primary measures (ps > 0.279). However, smokers using plain cigarette packs rated the experience of using the pack more negatively (-0.52, 95% CI -0.82 to -0.22, p = 0.001), rated the pack attributes more negatively (-1.59, 95% CI -1.80 to -1.39, p < 0.001), and rated the health warning as more impactful (+0.51, 95% CI 0.24 to 0.78, p < 0.001). Plain cigarette packs reduce ratings of the experience of using the cigarette pack, and ratings of the pack attributes, and increase the self-perceived impact of the health warning, but do not change smoking behaviour, at least in the short term. Current Controlled Trials ISRCTN52982308. Registered 27 June 2013.

Method for appraising model validity of randomised controlled trials of homeopathic treatment: multi-rater concordance study

PubMed Central

2012-01-01

Background A method for assessing the model validity of randomised controlled trials of homeopathy is needed. To date, only conventional standards for assessing intrinsic bias (internal validity) of trials have been invoked, with little recognition of the special characteristics of homeopathy. We aimed to identify relevant judgmental domains to use in assessing the model validity of homeopathic treatment (MVHT). We define MVHT as the extent to which a homeopathic intervention and the main measure of its outcome, as implemented in a randomised controlled trial (RCT), reflect 'state-of-the-art' homeopathic practice. Methods Using an iterative process, an international group of experts developed a set of six judgmental domains, with associated descriptive criteria. The domains address: (I) the rationale for the choice of the particular homeopathic intervention; (II) the homeopathic principles reflected in the intervention; (III) the extent of homeopathic practitioner input; (IV) the nature of the main outcome measure; (V) the capability of the main outcome measure to detect change; (VI) the length of follow-up to the endpoint of the study. Six papers reporting RCTs of homeopathy of varying design were randomly selected from the literature. A standard form was used to record each assessor's independent response per domain, using the optional verdicts 'Yes', 'Unclear', 'No'. Concordance among the eight verdicts per domain, across all six papers, was evaluated using the kappa (κ) statistic. Results The six judgmental domains enabled MVHT to be assessed with 'fair' to 'almost perfect' concordance in each case. For the six RCTs examined, the method allowed MVHT to be classified overall as 'acceptable' in three, 'unclear' in two, and 'inadequate' in one. Conclusion Future systematic reviews of RCTs in homeopathy should adopt the MVHT method as part of a complete appraisal of trial validity. PMID:22510227

Rapid versus standard intravenous rehydration in paediatric gastroenteritis: pragmatic blinded randomised clinical trial

PubMed Central

Parkin, Patricia C; Willan, Andrew R; Schuh, Suzanne

2011-01-01

Objective To determine if rapid rather than standard intravenous rehydration results in improved hydration and clinical outcomes when administered to children with gastroenteritis. Design Single centre, two arm, parallel randomised pragmatic controlled trial. Blocked randomisation stratified by site. Participants, caregivers, outcome assessors, investigators, and statisticians were blinded to the treatment assignment. Setting Paediatric emergency department in a tertiary care centre in Toronto, Canada. Participants 226 children aged 3 months to 11 years; complete follow-up was obtained on 223 (99%). Eligible children were aged over 90 days, had a diagnosis of dehydration secondary to gastroenteritis, had not responded to oral rehydration, and had been prescribed intravenous rehydration. Children were excluded if they weighed less than 5 kg or more than 33 kg, required fluid restriction, had a suspected surgical condition, or had an insurmountable language barrier. Children were also excluded if they had a history of a chronic systemic disease, abdominal surgery, bilious or bloody vomit, hypotension, or hypoglycaemia or hyperglycaemia. Interventions Rapid (60 mL/kg) or standard (20 mL/kg) rehydration with 0.9% saline over an hour; subsequent fluids administered according to protocol. Main outcome measures Primary outcome: clinical rehydration, assessed with a validated scale, two hours after the start of treatment. Secondary outcomes: prolonged treatment, mean clinical dehydration scores over the four hour study period, time to discharge, repeat visits to emergency department, adequate oral intake, and physician’s comfort with discharge. Data from all randomised patients were included in an intention to treat analysis. Results 114 patients were randomised to rapid rehydration and 112 to standard. One child was withdrawn because of severe hyponatraemia at baseline. There was no evidence of a difference between the rapid and standard rehydration groups in the proportions of participants who were rehydrated at two hours (41/114 (36%) v 33/112 (30%); difference 6.5% (95% confidence interval −5.7% to 18.7%; P=0.32). The results did not change after adjustment for weight, baseline dehydration score, and baseline pH (odds ratio 1.8, 0.90 to 3.5; P=0.10). The rates of prolonged treatment were similar (52% rapid v 43% standard; difference 8.9%, 21% to −5%; P=0.19). Although dehydration scores were similar throughout the study period (P=0.96), the median time to discharge was longer in the rapid group (6.3 v 5.0 hours; P=0.03). Conclusions There are no relevant clinical benefits from the administration of rapid rather than standard intravenous rehydration to haemodynamically stable children deemed to require intravenous rehydration. Trail registration Clinical Trials NCT00392145. PMID:22094316

The protocol and design of a randomised controlled study on training of attention within the first year after acquired brain injury.

PubMed

Bartfai, Aniko; Markovic, Gabriela; Sargenius Landahl, Kristina; Schult, Marie-Louise

2014-05-08

To describe the design of the study aiming to examine intensive targeted cognitive rehabilitation of attention in the acute (<4 months) and subacute rehabilitation phases (4-12 months) after acquired brain injury and to evaluate the effects on function, activity and participation (return to work). Within a prospective, randomised, controlled study 120 consecutive patients with stroke or traumatic brain injury were randomised to 20 hours of intensive attention training by Attention Process Training or by standard, activity based training. Progress was evaluated by Statistical Process Control and by pre and post measurement of functional and activity levels. Return to work was also evaluated in the post-acute phase. Primary endpoints were the changes in the attention measure, Paced Auditory Serial Addition Test and changes in work ability. Secondary endpoints included measurement of cognitive functions, activity and work return. There were 3, 6 and 12-month follow ups focussing on health economics. The study will provide information on rehabilitation of attention in the early phases after ABI; effects on function, activity and return to work. Further, the application of Statistical Process Control might enable closer investigation of the cognitive changes after acquired brain injury and demonstrate the usefulness of process measures in rehabilitation. The study was registered at ClinicalTrials.gov Protocol. NCT02091453, registered: 19 March 2014.

Use of drains versus no drains after burr-hole evacuation of chronic subdural haematoma: a randomised controlled trial.

PubMed

Santarius, Thomas; Kirkpatrick, Peter J; Ganesan, Dharmendra; Chia, Hui Ling; Jalloh, Ibrahim; Smielewski, Peter; Richards, Hugh K; Marcus, Hani; Parker, Richard A; Price, Stephen J; Kirollos, Ramez W; Pickard, John D; Hutchinson, Peter J

2009-09-26

Chronic subdural haematoma causes serious morbidity and mortality. It recurs after surgical evacuation in 5-30% of patients. Drains might reduce recurrence but are not used routinely. Our aim was to investigate the effect of drains on recurrence rates and clinical outcomes. We did a randomised controlled trial at one UK centre between November, 2004, and November, 2007. 269 patients aged 18 years and older with a chronic subdural haematoma for burr-hole drainage were assessed for eligibility. 108 were randomly assigned by block randomisation to receive a drain inserted into the subdural space and 107 to no drain after evacuation. The primary endpoint was recurrence needing redrainage. The trial was stopped early because of a significant benefit in reduction of recurrence. Analyses were done on an intention-to-treat basis. This study is registered with the International Standard Randomised Controlled Trial Register (ISRCTN 97314294). Recurrence occurred in ten of 108 (9.3%) people with a drain, and 26 of 107 (24%) without (p=0.003; 95% CI 0.14-0.70). At 6 months mortality was nine of 105 (8.6%) and 19 of 105 (18.1%), respectively (p=0.042; 95% CI 0.1-0.99). Medical and surgical complications were much the same between the study groups. Use of a drain after burr-hole drainage of chronic subdural haematoma is safe and associated with reduced recurrence and mortality at 6 months. Academy of Medical Sciences, Health Foundation, and NIHR Biomedical Research Centre (Neurosciences Theme).

How standard is standard care? Exploring control group outcomes in behaviour change interventions for young people with type 1 diabetes.

PubMed

Ayling, K; Brierley, S; Johnson, B; Heller, S; Eiser, C

2015-01-01

Poor descriptions of standard care may compromise interpretation of results in randomised controlled trials (RCTs) of health interventions. We investigated quality of standard care in RCTs of behaviour change interventions for young people with type 1 diabetes and consider implications for evaluating trial outcomes. We conducted systematic searches for articles published between 1999 and 2012. We extracted standard care descriptions and contacted trial authors to complete a checklist of standard care activities. The relationship between standard care quality and outcomes was examined via subgroup meta-analyses and meta-regression. Standard care descriptions, standard care quality, and relationships between standard care quality with medical and psychological outcomes. We identified 20 RCTs described across 26 articles. Published descriptions of standard care were limited to service-level features. Author responses indicated standard care provision extended beyond published accounts. Subgroup analyses suggested control groups receiving higher standard care quality showed larger improvements in both medical and psychological outcomes, although standard care quality did not predict outcomes significantly. The quality of care delivered to control group participants can influence outcomes of RCTs. Inadequate reporting exacerbates this issue by masking variations between trials. We argue for increased clarity in reporting standard care in future trials.

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.

Active Treatment for Idiopathic Adolescent Scoliosis (ACTIvATeS): a feasibility study.

PubMed

Williams, Mark A; Heine, Peter J; Williamson, Esther M; Toye, Francine; Dritsaki, Melina; Petrou, Stavros; Crossman, Richard; Lall, Ranjit; Barker, Karen L; Fairbank, Jeremy; Harding, Ian; Gardner, Adrian; Slowther, Anne-Marie; Coulson, Neil; Lamb, Sarah E

2015-07-01

The feasibility of conducting a definitive randomised controlled trial (RCT) evaluating the clinical effectiveness and cost-effectiveness of scoliosis-specific exercises (SSEs) for adolescent idiopathic scoliosis (AIS) is uncertain. The aim of this study was to assess the feasibility of conducting a large, multicentre trial of SSE treatment for patients with AIS, in comparison with standard care, and to refine elements of the study design. The objectives were to (1) update a systematic review of controlled trials evaluating the efficacy of SSE in AIS; (2) survey UK orthopaedic surgeons and physiotherapists to determine current practice, patient populations and equipoise; (3) randomise 50 adolescents to a feasibility trial of either usual care or SSE interventions across a range of sites; (4) develop, document and assess acceptability and adherence of interventions; (5) assess and describe training requirements of physiotherapists; and (6) gain user input in all relevant stages of treatment and protocol design. Multicomponent feasibility study including UK clinician survey, systematic literature review and a randomised feasibility trial. The randomised feasibility study involved four secondary care NHS trusts providing specialist care for patients with AIS. The randomised feasibility study recruited people aged 10-16 years with mild AIS (Cobb angle of < 50°). The randomised study allocated participants to standard practice of advice and education or a physiotherapy SSE programme supported by a home exercise plan. Our choice of intervention was informed by a systematic review of exercise interventions for AIS. The main outcome was feasibility of recruitment to the randomised study. Other elements were to inform choice of outcomes for a definitive trial and included curve severity, quality of life, requirement for surgery/brace, adverse events, psychological symptoms, costs and health utilities. A UK survey of orthopaedic consultants and physiotherapists indicated a wide variation in current provision of exercise therapy through physiotherapy services. It also found that clinicians from at least 15 centres would be willing to have their patients involved in a full study. A systematic review update found five new studies that were generally of low quality but showed some promise of effectiveness of SSE. The randomised study recruited 58 patients from four NHS trusts over 11 months and exceeded the pre-specified target recruitment rate of 1.4 participants per centre per month, with acceptable 6-month follow-up (currently 73%). Adherence to treatment was variable (56% of participants completed treatment offered). The qualitative study found the exercise programme to be highly acceptable. We learnt important lessons from patient and public involvement during the study in terms of study and intervention presentation, as well as practical elements such as scheduling of intervention sessions. A definitive RCT evaluating clinical effectiveness and cost-effectiveness of SSE for idiopathic scoliosis is warranted and feasible. Such a RCT is a priority for future work in the area. There is a sufficiently large patient base, combined with willingness to be randomised within specialist UK centres. Interventions developed during the feasibility study were acceptable to patients, families and physiotherapists and can be given within the affordability envelope of current levels of physiotherapy commissioning. Current Controlled Trials ISRCTN90480705. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 55. See the NIHR Journals Library website for further project information.

Osteopathic manipulative treatment and pain in preterms: study protocol for a randomised controlled trial.

PubMed

Cerritelli, Francesco; Cicchitti, Luca; Martelli, Marta; Barlafante, Gina; Renzetti, Cinzia; Pizzolorusso, Gianfranco; Lupacchini, Mariacristina; D'Orazio, Marianna; Marinelli, Benedetta; Cozzolino, Vincenzo; Fusilli, Paola; D'Incecco, Carmine

2015-03-08

Recent evidence proved the necessity to improve health care and pain management in newborns. Osteopathic manipulative treatment (OMT) has been largely used to treat painful syndromes as well as term and preterm newborns. Recent studies have demonstrated positive results of osteopathy in reducing length of stay and costs. However, no trials were carried out on pain in newborns. The aim of the present clinical trial is to explore the effectiveness of osteopathic treatment in reducing pain in a sample of preterms. A three-armed single blinded placebo-control randomised controlled trial protocol has been designed to primarily evaluate the extent to which OMT is effective in reducing pain in preterms. One hundred and twenty newborns will be enrolled from one tertiary neonatal intensive care unit in central Italy and randomised in three groups: study, sham and control. The study group will be further prospectively randomised in two subgroups: experienced osteopaths and students. All preterms will receive standard medical care. Osteopathic treatment will be applied to the study group only whilst 'soft touch' will be administer to the sham group only. Newborns will undergo manual sessions once a week for the entire period of hospitalisation. Blinding will be assured for neonatal staff and outcome assessor. Primary outcome will be the mean difference in baseline score changes of PIPP questionnaire between discharge and entry among the three groups. Secondary outcomes will be: mean difference in length of stay and costs between groups. Statistical analyses will use per-protocol analysis method. Missing data will be handled using last observation carried forward imputation technique. The present single blinded randomised controlled trial has been designed to explore potential advantages of OMT in the management of newborns' pain. Currently, based on a patient-centred need-based approach, this research will be looking at the benefit of osteopathic care rather than the efficacy of a specific technique or a pre-determined protocol. The protocol has been registered on ClinicalTrials.gov ( NCT02146677 ) on 20 May 2014.

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.

A prospective, randomised, controlled, multi-centre comparative effectiveness study of healing using dehydrated human amnion/chorion membrane allograft, bioengineered skin substitute or standard of care for treatment of chronic lower extremity diabetic ulcers.

PubMed

Zelen, Charles M; Gould, Lisa; Serena, Thomas E; Carter, Marissa J; Keller, Jennifer; Li, William W

2015-12-01

A prospective, randomised, controlled, parallel group, multi-centre clinical trial was conducted at three sites to compare the healing effectiveness of treatment of chronic lower extremity diabetic ulcers with either weekly applications of Apligraf(®) (Organogenesis, Inc., Canton, MA), EpiFix(®) (MiMedx Group, Inc., Marietta, GA), or standard wound care with collagen-alginate dressing. The primary study outcome was the percent change in complete wound healing after 4 and 6 weeks of treatment. Secondary outcomes included percent change in wound area per week, velocity of wound closure and a calculation of the amount and cost of Apligraf or EpiFix used. A total of 65 subjects entered the 2-week run-in period and 60 were randomised (20 per group). The proportion of patients in the EpiFix group achieving complete wound closure within 4 and 6 weeks was 85% and 95%, significantly higher (all adjusted P-values ≤ 0·003) than for patients receiving Apligraf (35% and 45%), or standard care (30% and 35%). After 1 week, wounds treated with EpiFix had reduced in area by 83·5% compared with 53·1% for wounds treated with Apligraf. Median time to healing was significantly faster (all adjusted P-values ≤0·001) with EpiFix (13 days) compared to Apligraf (49 days) or standard care (49 days). The mean number of grafts used and the graft cost per patient were lower in the EpiFix group campared to the Apligraf group, at 2·15 grafts at a cost of $1669 versus 6·2 grafts at a cost of $9216, respectively. The results of this study demonstrate the clinical and resource utilisation superiority of EpiFix compared to Apligraf or standard of care, for the treatment of diabetic ulcers of the lower extremities. © 2014 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Evaluation of hospital palliative care teams: strengths and weaknesses of the before-after study design and strategies to improve it.

PubMed

Simon, S; Higginson, I J

2009-01-01

Hospital palliative care teams (HPCTs) are well established as multi-professional services to provide palliative care in an acute hospital setting and are increasing in number. However, there is still limited evaluation of them, in terms of efficacy and effectiveness. The gold standard method of evaluation is a randomised control trial, but because of methodological (e.g., randomisation), ethical and practical difficulties such trials are often not possible. HPCT is a complex intervention, and the specific situation in palliative care makes it challenging to evaluate (e.g., distress and cognitive impairment of patients). The quasi-experimental before-after study design has the advantage of enabling an experimental character without randomisation. But this has other weaknesses and is prone to bias, for example, temporal trends and selection bias. As for every study design, avoidance and minimisation of bias is important to improve validity. Therefore, strategies of selecting an appropriate control group or time series and applying valid outcomes and measurement tools help reducing bias and strengthen the methods. Special attention is needed to plan and define the design and applied method.

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/

Financial disincentives? A three-armed randomised controlled trial of the effect of financial Incentives  in Diabetic Eye Assessment  by Screening (IDEAS) trial.

PubMed

Judah, Gaby; Darzi, Ara; Vlaev, Ivo; Gunn, Laura; King, Derek; King, Dominic; Valabhji, Jonathan; Bicknell, Colin

2018-05-23

Conflicting evidence exists regarding the impact of financial incentives on encouraging attendance at medical screening appointments. The primary aim was to determine whether financial incentives increase attendance at diabetic eye screening in persistent non-attenders. A three-armed randomised controlled trial was conducted in London in 2015. 1051 participants aged over 16 years, who had not attended eye screening appointments for 2 years or more, were randomised (1.4:1:1 randomisation ratio) to receive the usual invitation letter (control), an offer of £10 cash for attending screening (fixed incentive) or a 1 in 100 chance of winning £1000 (lottery incentive) if they attend. The primary outcome was the proportion of invitees attending screening, and a comparative analysis was performed to assess group differences. Pairwise comparisons of attendance rates were performed, using a conservative Bonferroni correction for independent comparisons. 34/435 (7.8%) of control, 17/312 (5.5%) of fixed incentive and 10/304 (3.3%) of lottery incentive groups attended. Participants who received any incentive were significantly less likely to attend their appointment compared with controls (risk ratio (RR)=0.56; 95% CI 0.34 to 0.92). Those in the probabilistic incentive group (RR=0.42; 95% CI 0.18 to 0.98), but not the fixed incentive group (RR=1.66; 95% CI 0.65 to 4.21), were significantly less likely to attend than those in the control group. Financial incentives, particularly lottery-based incentives, attract fewer patients to diabetic eye screening than standard invites in this population. Financial incentives should not be used to promote screening unless tested in context, as they may negatively affect attendance rates. © 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.

Feasibility of personalised remote long-term follow-up of people with cochlear implants: a randomised controlled trial.

PubMed

Cullington, Helen; Kitterick, Padraig; Weal, Mark; Margol-Gromada, Magdalena

2018-04-20

Substantial resources are required to provide lifelong postoperative care to people with cochlear implants. Most patients visit the clinic annually. We introduced a person-centred remote follow-up pathway, giving patients telemedicine tools to use at home so they would only visit the centre when intervention was required. To assess the feasibility of comparing a remote care pathway with the standard pathway in adults using cochlear implants. Two-arm randomised controlled trial. Randomisation used a minimisation approach, controlling for potential confounding factors. Participant blinding was not possible, but baseline measures occurred before allocation. University of Southampton Auditory Implant Service: provider of National Health Service care. 60 adults who had used cochlear implants for at least 6 months. Control group (n=30) followed usual care pathway.Remote care group (n=30) received care remotely for 6 months incorporating: home hearing in noise test, online support tool and self-adjustment of device (only 10 had compatible equipment). Primary: change in patient activation; measured using the Patient Activation Measure.Secondary: change in hearing and quality of life; qualitative feedback from patients and clinicians. One participant in the remote care group dropped out. The remote care group showed a greater increase in patient activation than the control group. Changes in hearing differed between the groups. The remote care group improved on the Triple Digit Test hearing test; the control group perceived their hearing was worse on the Speech, Spatial and Qualities of Hearing Scale questionnaire. Quality of life remained unchanged in both groups. Patients and clinicians were generally positive about remote care tools and wanted to continue. Adults with cochlear implants were willing to be randomised and complied with the protocol. Personalised remote care for long-term follow-up is feasible and acceptable, leading to more empowered patients. ISRCTN14644286. © 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.

Feasibility of personalised remote long-term follow-up of people with cochlear implants: a randomised controlled trial

PubMed Central

Kitterick, Padraig; Weal, Mark; Margol-Gromada, Magdalena

2018-01-01

Introduction Substantial resources are required to provide lifelong postoperative care to people with cochlear implants. Most patients visit the clinic annually. We introduced a person-centred remote follow-up pathway, giving patients telemedicine tools to use at home so they would only visit the centre when intervention was required. Objectives To assess the feasibility of comparing a remote care pathway with the standard pathway in adults using cochlear implants. Design Two-arm randomised controlled trial. Randomisation used a minimisation approach, controlling for potential confounding factors. Participant blinding was not possible, but baseline measures occurred before allocation. Setting University of Southampton Auditory Implant Service: provider of National Health Service care. Participants 60 adults who had used cochlear implants for at least 6 months. Interventions Control group (n=30) followed usual care pathway. Remote care group (n=30) received care remotely for 6 months incorporating: home hearing in noise test, online support tool and self-adjustment of device (only 10 had compatible equipment). Main outcome measures Primary: change in patient activation; measured using the Patient Activation Measure. Secondary: change in hearing and quality of life; qualitative feedback from patients and clinicians. Results One participant in the remote care group dropped out. The remote care group showed a greater increase in patient activation than the control group. Changes in hearing differed between the groups. The remote care group improved on the Triple Digit Test hearing test; the control group perceived their hearing was worse on the Speech, Spatial and Qualities of Hearing Scale questionnaire. Quality of life remained unchanged in both groups. Patients and clinicians were generally positive about remote care tools and wanted to continue. Conclusions Adults with cochlear implants were willing to be randomised and complied with the protocol. Personalised remote care for long-term follow-up is feasible and acceptable, leading to more empowered patients. Trial registration number ISRCTN14644286. PMID:29678970

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.

Advance care planning in patients with incurable cancer: study protocol for a randomised controlled trial.

PubMed

Johnson, Stephanie; Clayton, Josephine; Butow, Phyllis N; Silvester, William; Detering, Karen; Hall, Jane; Kiely, Belinda E; Cebon, Jonathon; Clarke, Stephen; Bell, Melanie L; Stockler, Martin; Beale, Phillip; Tattersall, Martin H N

2016-12-01

There is limited evidence documenting the effectiveness of Advance Care Planning (ACP) in cancer care. The present randomised trial is designed to evaluate whether the administration of formal ACP improves compliance with patients' end-of-life (EOL) wishes and patient and family satisfaction with care. A randomised control trial in eight oncology centres across New South Wales and Victoria, Australia, is designed to assess the efficacy of a formal ACP intervention for patients with cancer. Patients with incurable cancer and an expected survival of 3-12 months, plus a nominated family member or friend will be randomised to receive either standard care or standard care plus a formal ACP intervention. The project sample size is 210 patient-family/friend dyads. The primary outcome measure is family/friend-reported: (1) discussion with the patient about their EOL wishes and (2) perception that the patient's EOL wishes were met. Secondary outcome measures include: documentation of and compliance with patient preferences for medical intervention at the EOL; the family/friend's perception of the quality of the patient's EOL care; the impact of death on surviving family; patient-family and patient-healthcare provider communication about EOL care; patient and family/friend satisfaction with care; quality of life of patient and family/friend subsequent to trial entry, the patient's strength of preferences for quality of life and length of life; the costs of care subsequent to trial entry and place of death. Ethical approval was received from the Sydney Local Health District (RPA Zone) Human Research Ethical Committee, Australia (Protocol number X13-0064). Study results will be submitted for publication in peer-reviewed journals and presented at national and international conferences. Pre-results; ACTRN12613001288718. 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/.

Pharmacist-led management of chronic pain in primary care: results from a randomised controlled exploratory trial

PubMed Central

Bruhn, Hanne; Bond, Christine M; Elliott, Alison M; Hannaford, Philip C; Lee, Amanda J; McNamee, Paul; Smith, Blair H; Watson, Margaret C; Holland, Richard; Wright, David

2013-01-01

Objectives To compare the effectiveness of pharmacist medication review, with or without pharmacist prescribing, with standard care, for patients with chronic pain. Design An exploratory randomised controlled trial. Setting Six general practices with prescribing pharmacists in Grampian (3) and East Anglia (3). Participants Patients on repeat prescribed pain medication (4815) were screened by general practitioners (GPs), and mailed invitations (1397). 196 were randomised and 180 (92%) completed. Exclusion criteria included: severe mental illness, terminally ill, cancer related pain, history of addiction. Randomisation and intervention Patients were randomised using a remote telephone service to: (1) pharmacist medication review with face-to-face pharmacist prescribing; (2) pharmacist medication review with feedback to GP and no planned patient contact or (3) treatment as usual (TAU). Blinding was not possible. Outcome measures Outcomes were the SF-12v2, the Chronic Pain Grade (CPG), the Health Utilities Index 3 and the Hospital Anxiety and Depression Scale (HADS). Outcomes were collected at 0, 3 and 6 months. Results In the prescribing arm (n=70) two patients were excluded/nine withdrew. In the review arm (n=63) one was excluded/three withdrew. In the TAU arm (n=63) four withdrew. Compared with baseline, patients had an improved CPG in the prescribing arm, 47.7% (21/44; p=0.003) and in the review arm, 38.6% (17/44; p=0.001), but not the TAU group, 31.3% (15/48; ns). The SF-12 Physical Component Score showed no effect in the prescribing or review arms but improvement in TAU (p=0.02). The SF-12 Mental Component Score showed no effect for the prescribing or review arms and deterioration in the TAU arm (p=0.002). HADS scores improved within the prescribing arm for depression (p=0.022) and anxiety (p=0.007), between groups (p=0.022 and p=0.045, respectively). Conclusions This is the first randomised controlled trial of pharmacist prescribing in the UK, and suggests that there may be a benefit for patients with chronic pain. A larger trial is required. Trial registration: www.isrctn.org/ISRCTN06131530. Medical Research Council funding. PMID:23562814

rpsftm: An R Package for Rank Preserving Structural Failure Time Models

PubMed Central

Allison, Annabel; White, Ian R; Bond, Simon

2018-01-01

Treatment switching in a randomised controlled trial occurs when participants change from their randomised treatment to the other trial treatment during the study. Failure to account for treatment switching in the analysis (i.e. by performing a standard intention-to-treat analysis) can lead to biased estimates of treatment efficacy. The rank preserving structural failure time model (RPSFTM) is a method used to adjust for treatment switching in trials with survival outcomes. The RPSFTM is due to Robins and Tsiatis (1991) and has been developed by White et al. (1997, 1999). The method is randomisation based and uses only the randomised treatment group, observed event times, and treatment history in order to estimate a causal treatment effect. The treatment effect, ψ, is estimated by balancing counter-factual event times (that would be observed if no treatment were received) between treatment groups. G-estimation is used to find the value of ψ such that a test statistic Z(ψ) = 0. This is usually the test statistic used in the intention-to-treat analysis, for example, the log rank test statistic. We present an R package that implements the method of rpsftm. PMID:29564164

rpsftm: An R Package for Rank Preserving Structural Failure Time Models.

PubMed

Allison, Annabel; White, Ian R; Bond, Simon

2017-12-04

Treatment switching in a randomised controlled trial occurs when participants change from their randomised treatment to the other trial treatment during the study. Failure to account for treatment switching in the analysis (i.e. by performing a standard intention-to-treat analysis) can lead to biased estimates of treatment efficacy. The rank preserving structural failure time model (RPSFTM) is a method used to adjust for treatment switching in trials with survival outcomes. The RPSFTM is due to Robins and Tsiatis (1991) and has been developed by White et al. (1997, 1999). The method is randomisation based and uses only the randomised treatment group, observed event times, and treatment history in order to estimate a causal treatment effect. The treatment effect, ψ , is estimated by balancing counter-factual event times (that would be observed if no treatment were received) between treatment groups. G-estimation is used to find the value of ψ such that a test statistic Z ( ψ ) = 0. This is usually the test statistic used in the intention-to-treat analysis, for example, the log rank test statistic. We present an R package that implements the method of rpsftm.

Acupuncture for treating acute ankle sprains in adults.

PubMed

Kim, Tae-Hun; Lee, Myeong Soo; Kim, Kun Hyung; Kang, Jung Won; Choi, Tae-Young; Ernst, Edzard

2014-06-23

An acute ankle sprain is a sudden-onset injury of one or more of the ankle ligaments. It is one of the most common musculoskeletal injuries in the general population as well as in athletes. In some countries, such as China and Korea, acupuncture is frequently used in the treatment of ankle sprains, either as a single treatment or a secondary intervention accompanied by standard medical treatment. To assess the effects (benefits and harms) of acupuncture for the treatment of ankle sprains in adults. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (May 2013), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 4), MEDLINE (1948 to May week 2 2013), EMBASE (1980 to May week 2 2013), China National Knowledge Infrastructure databases (1994 to August week 4 2013), the Cumulative Index to Nursing and Allied Health Literature (1937 to May 2013), the Allied and Complementary Medicine Database (1985 to May 2013), Science Links Japan (1996 to August week 4 2013), several Korean medical databases (August week 4 2013), the World Health Organization International Clinical Trials Registry Platform (August week 4 2013), the bibliographic references of included trials and conference proceedings. We included randomised and quasi-randomised controlled trials involving adults with acute ankle sprains. We included all types of acupuncture practices, such as needle acupuncture, electroacupuncture, laser acupuncture, pharmacoacupuncture, non-penetrating acupuncture point stimulation (e.g. acupressure and magnets) and moxibustion. Acupuncture could be compared with control (no treatment or placebo) or another standard non-surgical intervention. Two review authors independently screened the search results, assessed trial eligibility, assessed risk of bias and extracted data from the included trials. We calculated risk ratios (RRs) for dichotomous outcomes and mean differences for continuous outcomes. We conducted meta-analyses using the fixed-effect method or, where appropriate, the random-effects method, and used 95% confidence intervals (CI) throughout. We included a total of 20 heterogeneous studies (2012 participants with acute ankle sprains); three of which included more than one comparison. Seventeen trials were conducted in China. All of the studies had a high risk of bias due to lack of blinding. The results may also have been affected by selection bias, particularly as five studies were quasi-randomised controlled trials and 12 studies gave no information on their method of randomisation. Of our three prespecified primary outcomes, only cure rate was reported by the majority of studies. No study reported on patient-reported assessment of function and only one reported on adverse events (in which three participants receiving a control intervention experienced skin problems from over-the-counter Chinese herbal patches). The other 19 studies did not record or report on adverse events. We assessed the quality of evidence for cure rates as very low for all comparisons, which means we are very uncertain about the reliability of any of the estimates.The single study comparing acupuncture treatment with no treatment found acupuncture to be more effective with regard to cure rate at five days (31/31 versus 1/30; RR 20.34, 95% CI 4.27 to 96.68). Acupuncture plus another standard treatment versus that standard treatment alone was tested in eight studies; with cure rate data available for seven. Most of these studies reported higher cure rates in the acupuncture plus another standard treatment group than in the standard treatment alone group. However, while the results of an exploratory meta-analysis of cure rate data from eight trials testing acupuncture versus no acupuncture tended to favour acupuncture, the results were very inconsistent across the studies and the estimated effect was very imprecise (383/396 versus 272/355; RR 1.32, 95% CI 0.95 to 1.84; P value = 0.1; I(2) = 98%).Fourteen studies compared acupuncture with a variety of other non-surgical treatments, such as Chinese drug patches, hot and cold water, ice packs, oral Chinese herbal medicine and elastic bandage. Some studies found in favour of acupuncture, some in favour of the other treatment and some found a lack of evidence for a difference between the two interventions under test. The results of an exploratory meta-analysis of cure rate data from 11 trials testing acupuncture versus another non-surgical intervention tended to slightly favour acupuncture, but these were not statistically significant and the data were very heterogeneous (404/509 versus 416/497; RR 1.07, 95% CI 0.94 to 1.22; P value = 0.30; I(2) = 92%). The currently available evidence from a very heterogeneous group of randomised and quasi-randomised controlled trials evaluating the effects of acupuncture for the treatment of acute ankle sprains does not provide reliable support for either the effectiveness or safety of acupuncture treatments, alone or in combination with other non-surgical interventions; or in comparison with other non-surgical interventions. Future rigorous randomised clinical trials with larger sample sizes will be necessary to establish robust clinical evidence concerning the effectiveness and safety of acupuncture treatment for acute ankle sprains.

Cost-effectiveness of early intervention in first-episode psychosis: economic evaluation of a randomised controlled trial (the OPUS study).

PubMed

Hastrup, Lene Halling; Kronborg, Christian; Bertelsen, Mette; Jeppesen, Pia; Jorgensen, Per; Petersen, Lone; Thorup, Anne; Simonsen, Erik; Nordentoft, Merete

2013-01-01

Information about the cost-effectiveness of early intervention programmes for first-episode psychosis is limited. To evaluate the cost-effectiveness of an intensive early-intervention programme (called OPUS) (trial registration NCT00157313) consisting of enriched assertive community treatment, psychoeducational family treatment and social skills training for individuals with first-episode psychosis compared with standard treatment. An incremental cost-effectiveness analysis of a randomised controlled trial, adopting a public sector perspective was undertaken. The mean total costs of OPUS over 5 years (€123,683, s.e. = 8970) were not significantly different from that of standard treatment (€148,751, s.e. = 13073). At 2-year follow-up the mean Global Assessment of Functioning (GAF) score in the OPUS group (55.16, s.d. = 15.15) was significantly higher than in standard treatment group (51.13, s.d. = 15.92). However, the mean GAF did not differ significantly between the groups at 5-year follow-up (55.35 (s.d. = 18.28) and 54.16 (s.d. = 18.41), respectively). Cost-effectiveness planes based on non-parametric bootstrapping showed that OPUS was less costly and more effective in 70% of the replications. For a willingness-to-pay up to €50,000 the probability that OPUS was cost-effective was more than 80%. The incremental cost-effectiveness analysis showed that there was a high probability of OPUS being cost-effective compared with standard treatment.

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.

An assessment of early Child Life Therapy pain and anxiety management: A prospective randomised controlled trial.

PubMed

Hyland, Ela J; D'Cruz, Rachel; Harvey, John G; Moir, Jordyn; Parkinson, Christina; Holland, Andrew J A

2015-12-01

Burns remain extremely painful and distressing in young children. The consequences of poorly managed pain and anxiety can be life-long. Whilst Child Life Therapy (CLT) has been shown to be effective in many situations, few studies have looked at the effectiveness of CLT in regard to reducing pain and anxiety in children undergoing burn dressing changes. A prospective, randomised controlled trial was conducted, comparing CLT versus standard care in relation to pain and anxiety scores of children undergoing their initial burn dressing change. Pain and anxiety were assessed by an independent observer and questionnaires completed by the child, parent/caregiver and nursing staff. 50 subjects were recruited in each treatment group; median age 2.3 years (CLT) and 2.2 years (standard care). The median total body surface area (TBSA) burnt was 0.8% (CLT) and 0.5% (standard care). The majority were partial thickness dermal burns (88% CLT, 94% standard care). Rates of parent anxiety and pre-procedural child pain and anxiety were similar. Combined and scaled pain and anxiety scores in the CLT group were significantly less than in the standard treatment group (p=0.03). Whilst pain was significantly better in the CLT group (p=0.02), fear scores, wound outcomes and the need for skin grafting were not statistically different in either group. The presence of a Child Life Therapist, with their ability to adapt to the environment, the child and their family, significantly reduced the experience of pain during paediatric burn dressings. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial.

PubMed

Roberts, Ian; Yates, David; Sandercock, Peter; Farrell, Barbara; Wasserberg, Jonathan; Lomas, Gabrielle; Cottingham, Rowland; Svoboda, Petr; Brayley, Nigel; Mazairac, Guy; Laloë, Véronique; Muñoz-Sánchez, Angeles; Arango, Miguel; Hartzenberg, Bennie; Khamis, Hussein; Yutthakasemsunt, Surakrant; Komolafe, Edward; Olldashi, Fatos; Yadav, Yadram; Murillo-Cabezas, Francisco; Shakur, Haleema; Edwards, Phil

Corticosteroids have been used to treat head injuries for more than 30 years. In 1997, findings of a systematic review suggested that these drugs reduce risk of death by 1-2%. The CRASH trial--a multicentre international collaboration--aimed to confirm or refute such an effect by recruiting 20000 patients. In May, 2004, the data monitoring committee disclosed the unmasked results to the steering committee, which stopped recruitment. 10008 adults with head injury and a Glasgow coma score (GCS) of 14 or less within 8 h of injury were randomly allocated 48 h infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury and death or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation. Analysis was by intention to treat. Effects on outcomes within 2 weeks of randomisation are presented in this report. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN74459797. Compared with placebo, the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids (1052 [21.1%] vs 893 [17.9%] deaths; relative risk 1.18 [95% CI 1.09-1.27]; p=0.0001). The relative increase in deaths due to corticosteroids did not differ by injury severity (p=0.22) or time since injury (p=0.05). Our results show there is no reduction in mortality with methylprednisolone in the 2 weeks after head injury. The cause of the rise in risk of death within 2 weeks is unclear.

ADD-ASPIRIN: A phase III, double-blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours.

PubMed

Coyle, Christopher; Cafferty, Fay H; Rowley, Samuel; MacKenzie, Mairead; Berkman, Lindy; Gupta, Sudeep; Pramesh, C S; Gilbert, Duncan; Kynaston, Howard; Cameron, David; Wilson, Richard H; Ring, Alistair; Langley, Ruth E

2016-11-01

There is a considerable body of pre-clinical, epidemiological and randomised data to support the hypothesis that aspirin has the potential to be an effective adjuvant cancer therapy. Add-Aspirin is a phase III, multi-centre, double-blind, placebo-controlled randomised trial with four parallel cohorts. Patients who have undergone potentially curative treatment for breast (n=3100), colorectal (n=2600), gastro-oesophageal (n=2100) or prostate cancer (n=2120) are registered into four tumour specific cohorts. All cohorts recruit in the United Kingdom, with the breast and gastro-oesophageal cohort also recruiting in India. Eligible participants first undertake an active run-in period where 100mg aspirin is taken daily for approximately eight weeks. Participants who are able to adhere and tolerate aspirin then undergo a double-blind randomisation and are allocated in a 1:1:1 ratio to either 100mg aspirin, 300mg aspirin or a matched placebo to be taken daily for at least five years. Those participants ≥75years old are only randomised to 100mg aspirin or placebo due to increased toxicity risk. The primary outcome measures are invasive disease-free survival for the breast cohort, disease-free survival for the colorectal cohort, overall survival for the gastro-oesophageal cohort, and biochemical recurrence-free survival for the prostate cohort, with a co-primary outcome of overall survival across all cohorts. Secondary outcomes include adherence, toxicity including serious haemorrhage, cardiovascular events and some cohort specific measures. The Add-Aspirin trial investigates whether regular aspirin use after standard therapy prevents recurrence and prolongs survival in participants with four non-metastatic common solid tumours. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

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.

ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE): protocol for a multicentre randomised controlled trial

PubMed Central

Iro, M A; Sadarangani, M; Absoud, M; Chong, W K; Clark, C A; Easton, A; Gray, V; Kneen, R; Lim, M; Pike, M; Solomon, T; Vincent, A; Willis, L; Pollard, A J

2016-01-01

Introduction Infectious and immune-mediated encephalitides are important but under-recognised causes of morbidity and mortality in childhood, with a 7% death rate and up to 50% morbidity after prolonged follow-up. There is a theoretical basis for ameliorating the immune response with intravenous immunoglobulin (IVIG), which is supported by empirical evidence of a beneficial response following its use in the treatment of viral and autoimmune encephalitis. In immune-mediated encephalitis, IVIG is often used after a delay (by weeks in some cases), while diagnosis is confirmed. Wider use of IVIG in infectious encephalitis and earlier use in immune-mediated encephalitis could improve outcomes for these conditions. We describe the protocol for the first ever randomised control trial of IVIG treatment for children with all-cause encephalitis. Methods and analysis 308 children (6 months to 16 years) with a diagnosis of acute/subacute encephalitis will be recruited in ∼30 UK hospitals and randomised to receive 2 doses (1 g/kg/dose) of either IVIG or matching placebo, in addition to standard treatment. Recruitment will be over a 42-month period and follow-up of each participant will be for 12 months post randomisation. The primary outcome is ‘good recovery’ (score of 2 or lower on the Glasgow Outcome Score Extended—paediatric version), at 12 months after randomisation. Additional secondary neurological measures will be collected at 4–6 weeks after discharge from acute care and at 6 and 12 months after randomisation. Safety, radiological, other autoimmune and tertiary outcomes will also be assessed. Ethics and dissemination This trial has been approved by the UK National Research Ethics committee (South Central—Oxford A; REC 14/SC/1416). Current protocol: V4.0 (10/03/2016). The findings will be presented at national and international meetings and conferences and published in peer-reviewed journals. Trial registration numbers NCT02308982, EudraCT201400299735 and ISRCTN15791925; Pre-results. PMID:27810972

Moderating factors for the effectiveness of group art therapy for schizophrenia: secondary analysis of data from the MATISSE randomised controlled trial.

PubMed

Leurent, Baptiste; Killaspy, Helen; Osborn, David P; Crawford, Mike J; Hoadley, Angela; Waller, Diane; King, Michael

2014-11-01

Although some studies suggest that art therapy may be useful in the treatment of negative symptoms of schizophrenia, a recent large trial of group art therapy found no clinical advantage over standard care, but the study population was heterogeneous and uptake of the intervention was poor. This study aimed to investigate whether art therapy was more effective for specific subgroups of patients. Secondary analysis of data from a randomised controlled trial of group art therapy as an adjunctive treatment for schizophrenia (n = 140) versus standard care alone (n = 137). Positive and Negative Syndrome Scale scores at 12 months were compared between trial arms. Interaction between intervention effect and different subgroups, including those with more severe negative symptoms of schizophrenia, and those who expressed a preference for art therapy prior to randomisation, was tested using a linear mixed model. The clinical effectiveness of group art therapy did not significantly differ between participants with more or less severe negative symptoms [interaction for difference in PANSS = 1.7, 95 % CI (-8.6 to 12.1), P = 0.741], or between those who did and did not express a preference for art therapy [interaction = 3.9, 95 % CI (-6.7 to 14.5), P = 0.473]. None of the other exploratory subgroups suggested differences in intervention effect. There was no evidence of greater improvement in clinical symptoms of schizophrenia for those with more severe negative symptoms or those with a preference for art therapy. Identification of patients with schizophrenia who may benefit most from group art therapy remains elusive.

Methodological quality of randomised controlled trials in burns care. A systematic review.

PubMed

Danilla, Stefan; Wasiak, Jason; Searle, Susana; Arriagada, Cristian; Pedreros, Cesar; Cleland, Heather; Spinks, Anneliese

2009-11-01

To evaluate the methodological quality of published randomised controlled trials (RCTs) in burn care treatment and management. Using a predetermined search strategy we searched Ovid MEDLINE (1950 to January 2008) database to identify all English RCTs related to burn care. Full text studies identified were reviewed for key demographic and methodological characteristics. Methodological trial quality was assessed using the Jadad scale. A total of 257 studies involving 14,535 patients met the inclusion criteria. The median Jadad score was 2 (out of a best possible score of 5). Information was given in the introduction and discussion sections of most RCTs, although insufficient detail was provided on randomisation, allocation concealment, and blinding. The number of RCTs increased between 1950 and 2008 (Spearman's rho=0.6129, P<0.001), although the reporting quality did not improve over the same time period (P=0.1896) and was better in RCTs with larger sample sizes (median Jadad score, 4 vs. 2 points, P<0.0001). Methodological quality did not correlate with journal impact factor (P=0.2371). The reporting standards of RCTs are highly variable and less than optimal in most cases. The advent of evidence-based medicine heralds a new approach to burns care and systematic steps are needed to improve the quality of RCTs in this field. Identifying and reviewing the existing number of RCTs not only highlights the need for burn clinicians to conduct more trials, but may also encourage burn health clinicians to consider the importance of conducting trials that follow appropriate, evidence-based standards.

Coping with Unusual ExperienceS for 12-18 year olds (CUES+): a transdiagnostic randomised controlled trial of the effectiveness of cognitive therapy in reducing distress associated with unusual experiences in adolescent mental health services: study protocol for a randomised controlled trial.

PubMed

Jolley, Suzanne; Browning, Sophie; Corrigall, Richard; Laurens, Kristin R; Hirsch, Colette; Bracegirdle, Karen; Gin, Kimberley; Muccio, Francesca; Stewart, Catherine; Banerjea, Partha; Kuipers, Elizabeth; Garety, Philippa; Byrne, Majella; Onwumere, Juliana; Achilla, Evanthia; McCrone, Paul; Emsley, Richard

2017-12-04

Childhood 'unusual experiences' (such as hearing voices that others cannot, or suspicions of being followed) are common, but can become more distressing during adolescence, especially for young people in contact with Child and Adolescent Mental Health Services (CAMHS). Unusual experiences that are distressing or have adverse life impact (UEDs) are associated with a range of current and future emotional, behavioural and mental health difficulties. Recommendations for psychological intervention are based on evidence from adult studies, with some support from small, pilot, child-specific evaluations. Research is needed to ensure that the recommendations suit children as well as adults. The CUES+ study (Coping with Unusual ExperienceS for 12-18 year olds) aims to find out whether cognitive behaviour therapy for UEDs (CBT-UED) is a helpful and cost-effective addition to usual community care for 12-18 year olds presenting to United Kingdom National Health Service Child and Adolescent Mental Health Services in four London boroughs. The CUES+ study is a randomised controlled trial comparing CBT-UED plus routine care to routine care alone. CBT-UED comprises up to 16 sessions, including up to 12 individual and up to four family support meetings, each lasting around 45-60 min, delivered weekly. The primary outcome is emotional distress. Secondary outcomes are change in UEDs, risk events (self-harm, attendance at emergency services, other adverse events) and health economic outcomes. Participants will be randomised in a 1:1 ratio after baseline assessment. Randomisation will be stratified by borough and by severity of mental health presentation: 'severe' (an identified psychotic or bipolar disorder) or any 'other' condition. Outcomes will be assessed by a trained assessor blind to treatment condition at 0, 16 and 24 weeks. Recruitment began in February, 2015 and is ongoing until the end of March, 2017. The CUES+ study will contribute to the currently limited child-specific evidence base for psychological interventions for UEDs occurring in the context of psychosis or any other mental health presentation. International Standard Randomised Controlled Trials, ID: ISRCTN21802136 . Prospectively registered on 12 January 2015. Protocol V3 31 August 2015 with screening amended.

The 30-year experience-A meta-analysis of randomised and high-quality non-randomised studies of hyperthermic intraperitoneal chemotherapy in the treatment of gastric cancer.

PubMed

Desiderio, Jacopo; Chao, Joseph; Melstrom, Laleh; Warner, Susanne; Tozzi, Federico; Fong, Yuman; Parisi, Amilcare; Woo, Yanghee

2017-07-01

Hyperthermic intraperitoneal chemotherapy (HIPEC) has been used within various multimodality strategies for the prevention and treatment of gastric cancer peritoneal carcinomatosis. To systematically evaluate the role of HIPEC in gastric cancer and clarify its effectiveness at different stages of peritoneal disease progression. Medline and Embase databases between January 1, 1985 and June 1, 2016. Randomised control trials and high-quality non-randomised control trials selected on a validated tool (methodological index for non-randomised studies) comparing HIPEC and standard oncological management for the treatment of advanced stage gastric cancer with and without peritoneal carcinomatosis were considered. A random-effects network meta-analysis. The primary outcomes were overall survival and disease recurrence. Secondary outcomes were overall complications, type of complications, and sites of recurrence. A total of 11 RCTs and 21 non-randomised control trials (2520 patients) were included. For patients without the presence of peritoneal carcinomatosis (PC), the overall survival rates between the HIPEC and control groups at 3 or 5 years resulted in favour of the HIPEC group (risk ratio [RR] = 0.82, P = 0.01). No difference in the 3-year overall survival (RR = 0.99, P = 0.85) in but a prolonged median survival of 4 months in favour of the HIPEC group (WMD = 4.04, P < 0.001) was seen in patients with PC. HIPEC was associated with significantly higher risk of complications for both patients with PC (RR = 2.15, P < 0.01) and without (RR = 2.17, P < 0.01). This increased risk in the HIPEC group was related to systemic drugs toxicity. Anastomotic leakage rates were found to be similar between groups. Our study demonstrates a survival advantage of the use of HIPEC as a prophylactic strategy and suggests that patients whose disease burden is limited to positive cytology and limited nodal involvement may benefit the most from HIPEC. For patients with extensive carcinomatosis, the completeness of cytoreductive surgery is a critical prognostic factor for survival. Future RCTs should better define patient selection criteria. Copyright © 2017 Elsevier Ltd. All rights reserved.

Calorie and protein-enriched formula versus standard term formula for improving growth and development in preterm or low birth weight infants following hospital discharge.

PubMed

Henderson, G; Fahey, T; McGuire, W

2005-04-18

Preterm and low birth weight infants are often growth-restricted at hospital discharge. Feeding infants post-hospital discharge with calorie and protein-enriched formula milk might facilitate "catch-up" growth and improve development. To review the evidence from randomised controlled trials that feeding following hospital discharge with calorie and protein-enriched formula compared with standard term formula improves growth and development for preterm or low birth weight 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, The Cochrane Library, Issue 4, 2004), MEDLINE (1966 - December 2004), EMBASE (1980 - December 2004), CINAHL (1982 - December 2004), conference proceedings, and previous reviews. Randomised or quasi-randomised controlled trials that compared the effect of feeding preterm or low birth weight infants post-hospital discharge with calorie and protein-enriched formula compared with standard term formula. We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two authors, and synthesis of data using weighted mean difference and a fixed effects model for meta-analysis. We found six trials that were eligible for inclusion. These recruited a total of 424 infants and were generally of good methodological quality. These trials found little evidence that feeding with calorie and protein-enriched formula milk affected growth and development. Because of differences in the way individual trials measured and presented outcomes, data synthesis was limited. Meta-analysis of data from two trials found a statistically significant effect on crown-heel length at 18 months post-term (weighted mean difference 9.7 millimetres (95% confidence interval 3.2 to 16.2)), but not on weight or head circumference. Meta-analysis of data from the two trials that assessed neurodevelopment at 18 months post-term did not reveal a statistically significant difference in either Bayley Mental Development Index (weighted mean difference 0.23 (95% confidence interval -2.99 to 3.45)) or Psychomotor Development Index (weighted mean difference 0.56 (95% confidence interval -1.95 to 3.07)). There are not yet any data on growth or development through later childhood. The limited available data do not provide strong evidence that feeding preterm or low birth weight infants following hospital discharge with calorie and protein-enriched formula compared with standard term formula affects growth rates or development up to 18 months post-term.

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.

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).

A randomised controlled multicentre trial of women's and men's satisfaction with two models of antenatal education.

PubMed

Bergström, Malin; Kieler, Helle; Waldenström, Ulla

2011-12-01

To study women's and men's satisfaction with two models of antenatal education: natural childbirth preparation with psychoprophylaxis, and standard antenatal education including preparation for childbirth and parenthood but no psychoprophylaxis. Randomised controlled multicentre trial. 15 Antenatal clinics in Sweden between January 2006 and May 2007. 1087 Nulliparous women and 1064 of their partners. Both models had four two-hour sessions during pregnancy and one session post partum. The natural model was manual-based and focused on childbirth preparation, including psychoprophylaxis. In the standard care model, the group leader was free to choose her teaching approach, with an equal amount of time allocated to preparation for childbirth and for parenthood. Women's and men's evaluation of antenatal education at three months post partum. The proportion of women and men in each model that expressed satisfaction with the education were compared using χ(2) test. More women and men in the natural groups were satisfied with the education compared with the standard care groups: women 76% versus 68% (p = 0.03) and men 73% versus 65% (p = 0.03). The figures were similar for satisfaction with the childbirth preparation component: 78% and 62% in women (p < 0.001), and 79% and 67% in men (p < 0.001) in the natural and standard care groups, respectively. Fewer participants were satisfied with the parenthood preparation component, but the proportions were higher in the standard care groups: women 37% versus 32% (p < 0.001) and men 23% versus 20% (p < 0.001). A structured manual-based model of antenatal education which focuses on childbirth preparation with psychoprophylaxis may better meet expectant parents' expectations than standard antenatal education in Sweden. Copyright © 2010 Elsevier Ltd. All rights reserved.

A randomised controlled trial of cognitive behaviour therapy versus non-directive reflective listening for young people at ultra high risk of developing psychosis: The detection and evaluation of psychological therapy (DEPTh) trial.

PubMed

Stain, Helen J; Bucci, Sandra; Baker, Amanda L; Carr, Vaughan; Emsley, Richard; Halpin, Sean; Lewin, Terry; Schall, Ulrich; Clarke, Vanessa; Crittenden, Kylie; Startup, Mike

2016-10-01

Intervention trials for young people at ultra high risk (UHR) for psychosis have shown cognitive behaviour therapy (CBT) to have promising effects on treating psychotic symptoms but have not focused on functional outcomes. We hypothesized that compared to an active control, CBT would: (i) reduce the likelihood of, and/or delay, transition to psychosis; (ii) reduce symptom severity while improving social functioning and quality of life, whether or not transition occurred. This was a single-blind randomised controlled trial for young people at UHR for psychosis comparing CBT to an active control condition, Non Directive Reflective Listening (NDRL), both in addition to standard care, with a 6month treatment phase and 12months of follow-up. Statistical analysis is based on intention-to-treat and used random effect models to estimate treatment effects common to all time-points. Fifty-seven young people (mean age=16.5years) were randomised to CBT (n=30) or NDRL (n=27). Rate of transition to psychosis was 5%; the 3 transitions occurred in the CBT condition (baseline, 2months, 5months respectively). The NDRL condition resulted in a significantly greater reduction in distress associated with psychotic symptoms compared to CBT (treatment effect=36.71, standard error=16.84, p=0.029). There were no significant treatment effects on frequency and intensity of psychotic symptoms, global, social or role functioning. Our sample was higher functioning, younger and experiencing lower levels of psychotic like experiences than other trials. The significantly better treatment effect of NDRL on distress associated with psychotic symptoms supports the recommendations for a stepped-care model of service delivery. This treatment approach would accommodate the younger UHR population and facilitate timely intervention. ANZCTR 12606000101583. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of antenatal lifestyle advice for women who are overweight or obese on secondary measures of neonatal body composition: the LIMIT randomised trial

PubMed Central

Dodd, Jodie M; Deussen, Andrea R; Mohomad, Izyan; Rifas-Shiman, Sheryl L; Yelland, Lisa N; Louise, Jennie; McPhee, Andrew J; Grivell, Rosalie M; Owens, Julie A; Gillman, Matthew W; Robinson, Jeffrey S

2016-01-01

Objective To evaluate the effect of providing antenatal dietary and lifestyle advice on neonatal anthropometry, and to determine the inter-observer variability in obtaining anthropometric measurements. Design Randomised controlled trial Setting Public maternity hospitals across metropolitan Adelaide, South Australia Population Pregnant women with a singleton gestation between 10+0–20+0, and body mass index (BMI) ≥25kg/m2. Methods Women were randomised to either Lifestyle Advice (comprehensive dietary and lifestyle intervention over the course of pregnancy including dietary, exercise and behavioral strategies, delivered by a research dietician and research assistants) or continued Standard Care. Analyses were conducted using intention to treat principles. Main Outcome Measures Secondary outcome measures for the trial included assessment of infant body composition using body circumference and skinfold thickness measurements (SFTM), percentage body fat, and bio-impedance analysis of fat free mass. Results Anthropometric measurements were obtained from 970 neonates (488 Lifestyle Advice Group, and 482 Standard Care Group). In 394 of these neonates (215 Lifestyle Advice Group, and 179 Standard Care Group) bio-impedance analysis was also obtained. There were no statistically significant differences identified between those neonates born to women receiving Lifestyle Advice and those receiving Standard Care, in terms of body circumference measures, SFTM, percentage body fat, fat mass, or fat free mass. The intra-class correlation coefficient for SFTM was moderate to excellent (ICC 0.55 to 0.88). Conclusions Among neonates born to women who are overweight or obese, anthropometric measures of body composition were not modified by an antenatal dietary and lifestyle intervention. PMID:26841217

The impact of active stakeholder involvement on recruitment, retention and engagement of schools, children and their families in the cluster randomised controlled trial of the Healthy Lifestyles Programme (HeLP): a school-based intervention to prevent obesity.

PubMed

Lloyd, J; McHugh, C; Minton, J; Eke, H; Wyatt, K

2017-08-14

Recruitment and retention of participants is crucial for statistical power and internal and external validity and participant engagement is essential for behaviour change. However, many school-based interventions focus on programme content rather than the building of supportive relationships with all participants and tend to employ specific standalone strategies, such as incentives, to improve retention. We believe that actively involving stakeholders in both intervention and trial design improves recruitment and retention and increases the chances of creating an effective intervention. The Healthy Lifestyles Programme, HeLP (an obesity prevention programme for children 9-10 years old) was developed using intervention mapping and involved extensive stakeholder involvement in both the design of the trial and the intervention to ensure that: (i) delivery methods were suitably engaging, (ii) deliverers had the necessary skills and qualities to build relationships and (iii) the intervention dovetailed with the National Curriculum. HeLP was a year-long intervention consisting of 4 multi-component phases using a range of delivery methods. We recruited 1324 children from 32 schools from the South West of England to a cluster-randomised controlled trial to determine the effectiveness of HeLP in preventing obesity. The primary outcome was change in body mass index standard deviation score (BMI SDS) at 24 months post randomisation. Secondary outcomes included additional anthropometric and behavioural (physical activity and diet) measures at 18 and 24 months. Anthropometric and behavioural measures were taken in 99%, 96% and 94% of children at baseline, 18 and 24 months, respectively, with no differential follow up between the control and intervention groups at each time point. All children participated in the programme and 92% of children and 77% of parents across the socio-economic spectrum were considered to have actively engaged with HeLP. We attribute our excellent retention and engagement results to the high level of stakeholder involvement in both trial and intervention design, the building of relationships using appropriate personnel and creative delivery methods that are accessible to children and their families across the social spectrum. International Standard Randomised Controlled Trials Register, ISRCTN15811706 . Registered on 1 May 2012.

Mechanical ventilation for amyotrophic lateral sclerosis/motor neuron disease.

PubMed

Radunovic, Aleksandar; Annane, Djillali; Rafiq, Muhammad K; Mustfa, Naveed

2013-03-28

Amyotrophic lateral sclerosis, also known as motor neuron disease, is a fatal neurodegenerative disease. Neuromuscular respiratory failure is the commonest cause of death, usually within two to five years of the disease onset. Supporting respiratory function with mechanical ventilation may improve survival and quality of life. This is the first update of a review first published in 2009. The primary objective of the review is to examine the efficacy of mechanical ventilation (tracheostomy and non-invasive ventilation) in improving survival in ALS. The secondary objectives are to examine the effect of mechanical ventilation on functional measures of disease progression and quality of life in people with ALS; and assess adverse events related to the intervention. We searched The Cochrane Neuromuscular Disease Group Specialized Register (1 May 2012), CENTRAL (2012, Issue 4), MEDLINE (January 1966 to April 2012), EMBASE (January 1980 to April 2012), CINAHL Plus (January 1937 to April 2012), and AMED (January 1985 to April 2012). We also searched for ongoing studies on ClinicalTrials.gov. Randomised and quasi-randomised controlled trials involving non-invasive or tracheostomy assisted ventilation in participants with a clinical diagnosis of amyotrophic lateral sclerosis, independent of the reported outcomes. We planned to include comparisons with no intervention or the best standard care. For the original review, four authors independently selected studies for assessment and two authors reviewed searches for this update. All authors extracted data independently from the full text of selected studies and assessed the risk of bias in studies that met the inclusion criteria. We attempted to obtain missing data where possible. We planned to collect adverse event data from included studies. For the original Cochrane review, the review authors identified and included two randomised controlled trials involving 54 participants with ALS receiving non-invasive ventilation. There were no new randomised or quasi-randomised controlled trials at this first update.Incomplete data were published for one study and we contacted the trial authors who were not able to provide the missing data. Therefore, the results of the review were based on a single study of 41 participants that compared non-invasive ventilation with standard care. It was a well conducted study with low risk of bias.The study showed that the overall median survival was significantly different between the group treated with non-invasive ventilation and the standard care group. The median survival in the non-invasive ventilation group was 48 days longer (219 days compared to 171 days for the standard care group (estimated 95% CI 12 to 91 days, P = 0.0062)). This survival benefit was accompanied by an enhanced quality of life. On subgroup analysis, the survival and quality of life benefit was much more in the subgroup with normal to moderately impaired bulbar function (20 participants); median survival was 205 days longer (216 days in NIV group versus 11 days in the standard care group, P = 0.0059). Non-invasive ventilation did not prolong survival in participants with poor bulbar function (21 participants), although it showed significant improvement in the mean symptoms domain of the Sleep Apnoea Quality of Life Index but not in the Short Form-36 Health Survey Mental Component Summary score. Neither trial reported clinical data on intervention related adverse effects. Evidence from a single randomised trial of non-invasive ventilation in 41 participants suggests that it significantly prolongs survival and improves or maintains quality of life in people with ALS. Survival and some measures of quality of life were significantly improved in the subgroup of people with better bulbar function, but not in those with severe bulbar impairment. Future studies should examine the health economics of NIV and factors influencing access to NIV. We need to understand the factors, personal and socioeconomic, that determine access to NIV.

Mesh, graft, or standard repair for women having primary transvaginal anterior or posterior compartment prolapse surgery: two parallel-group, multicentre, randomised, controlled trials (PROSPECT).

PubMed

Glazener, Cathryn Ma; Breeman, Suzanne; Elders, Andrew; Hemming, Christine; Cooper, Kevin G; Freeman, Robert M; Smith, Anthony Rb; Reid, Fiona; Hagen, Suzanne; Montgomery, Isobel; Kilonzo, Mary; Boyers, Dwayne; McDonald, Alison; McPherson, Gladys; MacLennan, Graeme; Norrie, John

2017-01-28

The use of transvaginal mesh and biological graft material in prolapse surgery is controversial and has led to a number of enquiries into their safety and efficacy. Existing trials of these augmentations are individually too small to be conclusive. We aimed to compare the outcomes of prolapse repair involving either synthetic mesh inlays or biological grafts against standard repair in women. We did two pragmatic, parallel-group, multicentre, randomised controlled trials for our study (PROSPECT [PROlapse Surgery: Pragmatic Evaluation and randomised Controlled Trials]) in 35 centres (a mix of secondary and tertiary referral hospitals) in the UK. We recruited women undergoing primary transvaginal anterior or posterior compartment prolapse surgery by 65 gynaecological surgeons in these centres. We randomly assigned participants by a remote web-based randomisation system to one of the two trials: comparing standard (native tissue) repair alone with standard repair augmented with either synthetic mesh (the mesh trial) or biological graft (the graft trial). We assigned women (1:1:1 or 1:1) within three strata: assigned to one of the three treatment options, comparison of standard repair with mesh, and comparison of standard repair with graft. Participants, ward staff, and outcome assessors were masked to randomisation where possible; masking was obviously not possible for the surgeon. Follow-up was for 2 years after the surgery; the primary outcomes, measured at 1 year and 2 years, were participant-reported prolapse symptoms (i.e. the Pelvic Organ Prolapse Symptom Score [POP-SS]) and condition-specific (ie, prolapse-related) quality-of-life scores, analysed in the modified intention-to-treat population. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN60695184. Between Jan 8, 2010, and Aug 30, 2013, we randomly allocated 1352 women to treatment, of whom 1348 were included in the analysis. 865 women were included in the mesh trial (430 to standard repair alone, 435 to mesh augmentation) and 735 were included in the graft trial (367 to standard repair alone, 368 to graft augmentation). Because the analyses were carried out separately for each trial (mesh trial and graft trial) some women in the standard repair arm assigned to all treatment options were included in the standard repair group of both trials. 23 of these women did not receive any surgery (15 in the mesh trial, 13 in the graft trial; five were included in both trials) and were included in the baseline analyses only. Mean POP-SS at 1 year did not differ substantially between comparisons (standard 5·4 [SD 5·5] vs mesh 5·5 [5·1], mean difference 0·00, 95% CI -0·70 to 0·71; p=0·99; standard 5·5 [SD 5·6] vs graft 5·6 [5·6]; mean difference -0·15, -0·93 to 0·63; p=0·71). Mean prolapse-related quality-of-life scores also did not differ between groups at 1 year (standard 2·0 [SD 2·7] vs mesh 2·2 [2·7], mean difference 0·13, 95% CI -0·25 to 0·51; p=0·50; standard 2·2 [SD 2·8] vs graft 2·4 [2·9]; mean difference 0·13, -0·30 to 0·56; p=0·54). Mean POP-SS at 2 years were: standard 4·9 (SD 5·1) versus mesh 5·3 (5·1), mean difference 0·32, 95% CI -0·39 to 1·03; p=0·37; standard 4·9 (SD 5·1) versus graft 5·5 (5·7); mean difference 0·32, -0·48 to 1·12; p=0·43. Prolapse-related quality-of-life scores at 2 years were: standard 1·9 (SD 2·5) versus mesh 2·2 (2·6), mean difference 0·15, 95% CI -0·23 to 0·54; p=0·44; standard 2·0 (2·5) versus graft 2·2 (2·8); mean difference 0·10, -0·33 to 0·52; p=0·66. Serious adverse events such as infection, urinary retention, or dyspareunia or other pain, excluding mesh complications, occurred with similar frequency in the groups over 1 year (mesh trial: 31/430 [7%] with standard repair vs 34/435 [8%] with mesh, risk ratio [RR] 1·08, 95% CI 0·68 to 1·72; p=0·73; graft trial: 23/367 [6%] with standard repair vs 36/368 [10%] with graft, RR 1·57, 0·95 to 2·59; p=0·08). The cumulative number of women with a mesh complication over 2 years in women actually exposed to synthetic mesh was 51 (12%) of 434. Augmentation of a vaginal repair with mesh or graft material did not improve women's outcomes in terms of effectiveness, quality of life, adverse effects, or any other outcome in the short term, but more than one in ten women had a mesh complication. Therefore, follow-up is vital to identify any longer-term potential benefits and serious adverse effects of mesh or graft reinforcement in vaginal prolapse surgery. UK National Institute of Health Research. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Thrombus aspiration in non-ST-elevation myocardial infarction - 12-month clinical outcome of the randomised TATORT-NSTEMI trial.

PubMed

Meyer-Saraei, Roza; de Waha, Suzanne; Eitel, Ingo; Desch, Steffen; Scheller, Bruno; Böhm, Michael; Lauer, Bernward; Gawaz, Meinrad; Geisler, Tobias; Gunkel, Oliver; Bruch, Leonhard; Klein, Norbert; Pfeiffer, Dietrich; Schuler, Gerhard; Zeymer, Uwe; Thiele, Holger

2017-02-01

In the randomised TATORT-NSTEMI trial routine thrombus aspiration in comparison with standard percutaneous coronary intervention (PCI) did not reduce the primary endpoint of microvascular obstruction assessed by cardiac magnetic resonance imaging in patients with non-ST-elevation myocardial infarction (NSTEMI). So far, no data on long-term outcome of head-to-head comparisons between both treatment strategies in NSTEMI patients have been reported. The prospective, controlled, multicentre, randomised, open-label TATORT-NSTEMI trial assigned patients with NSTEMI and thrombus-containing lesions to aspiration thrombectomy plus PCI ( n=221) or standard PCI only ( n=219). The primary endpoint of the current analysis was the occurrence of major adverse cardiac events defined as the composite of death, myocardial reinfarction, target vessel revascularisation, and new congestive heart failure at 12-month follow-up. In addition, functional outcome and quality of life were assessed. At one year, major adverse cardiac events occurred in 19 patients in the thrombectomy arm and 29 patients in the standard PCI group (8.7% vs. 13.4%, relative risk 0.63, 95% confidence interval 0.35-1.12, p=0.11). The individual components of the combined endpoint such as death ( p=0.20), myocardial reinfarction ( p=0.73), target vessel revascularisation ( p=0.42), and congestive heart failure ( p=0.18) were similar in both groups. Functional outcome and quality of life did not differ significantly between both groups (Canadian Cardiovascular Society class: p=0.68, New York Heart Association class: p=0.70 and EuroQol5D score: p=0.96). Post-hoc analyses revealed consistent results with regard to the occurrence of major adverse cardiac events across a wide range of subgroups (all p>0.05). In this first randomised trial on thrombectomy in NSTEMI patients, routine thrombus aspiration before PCI did not improve clinical outcome at 12-month follow-up.

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

PubMed

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

2014-11-11

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

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

PubMed Central

2013-01-01

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

The study protocol for 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

PubMed Central

2013-01-01

Background The utility of advanced prehospital interventions for severe blunt traumatic brain injury (BTI) remains controversial. Of all trauma patient subgroups it has been anticipated that this patient group would most benefit from advanced prehospital interventions as hypoxia and hypotension have been demonstrated to be associated with poor outcomes and these factors may be amenable to prehospital intervention. Supporting evidence is largely lacking however. In particular the efficacy of early anaesthesia/muscle relaxant assisted intubation has proved difficult to substantiate. Methods This article describes the design and protocol of the Head Injury Retrieval Trial (HIRT) which is a randomised controlled single centre trial of physician prehospital care (delivering advanced interventions such as rapid sequence intubation and blood transfusion) in addition to paramedic care for severe blunt TBI compared with paramedic care alone. Results Primary endpoint is Glasgow Outcome Scale score at six months post injury. Issues with trial integrity resulting from drop ins from standard care to the treatment arm as the result of policy changes by the local ambulance system are discussed. Conclusion This randomised controlled trial will contribute to the evaluation of the efficacy of advance prehospital interventions in severe blunt TBI. Trial Registration ClinicalTrials.gov: NCT00112398 PMID:24034628

Evaluation of the Frails' Fall Efficacy by Comparing Treatments (EFFECT) on reducing fall and fear of fall in moderately frail older adults: study protocol for a randomised control trial.

PubMed

Kwok, Boon Chong; Mamun, Kaysar; Chandran, Manju; Wong, Chek Hooi

2011-06-18

Falls are common in frail older adults and often result in injuries and hospitalisation. The Nintendo® Wii™ is an easily available exercise modality in the community which has been shown to improve lower limb strength and balance. However, not much is known on the effectiveness of the Nintendo® Wii™ to improve fall efficacy and reduce falls in a moderately frail older adult. Fall efficacy is the measure of fear of falling in performing various daily activities. Fear contributes to avoidance of activities and functional decline. This randomised active-control trial is a comparison between the Nintendo WiiActive programme against standard gym-based rehabilitation of the older population. Eighty subjects aged above 60, fallers and non-fallers, will be recruited from the hospital outpatient clinic. The primary outcome measure is the Modified Falls Efficacy Scale and the secondary outcome measures are self-reported falls, quadriceps strength, walking agility, dynamic balance and quality of life assessments. The study is the first randomised control trial using the Nintendo Wii as a rehabilitation modality investigating a change in fall efficacy and self-reported falls. Longitudinally, the study will investigate if the interventions can successfully reduce falls and analyse the cost-effectiveness of the programme.

Medicoeconomic analysis of lobectomy using thoracoscopy versus thoracotomy for lung cancer: a study protocol for a multicentre randomised controlled trial (Lungsco01)

PubMed Central

Pagès, Pierre-Benoit; Abou Hanna, Halim; Bertaux, Anne-Claire; Serge Aho, Ludwig Serge; Magdaleinat, Pierre; Baste, Jean-Marc; Filaire, Marc; de Latour, Richard; Assouad, Jalal; Tronc, François; Jayle, Christophe; Mouroux, Jérome; Thomas, Pascal-Alexandre; Falcoz, Pierre-Emmanuel; Marty-Ané, Charles-Henri; Bernard, Alain

2017-01-01

Introduction In the last decade, video-assisted thoracoscopic surgery (VATS) lobectomy for non-small cell lung cancer (NSCLC) has had a major effect on thoracic surgery. Retrospective series have reported benefits of VATS when compared with open thoracotomy in terms of postoperative pain, postoperative complications and length of hospital stay. However, no large randomised control trial has been conducted to assess the reality of the potential benefits of VATS lobectomy or its medicoeconomic impact. Methods and analysis The French National Institute of Health funded Lungsco01 to determine whether VATS for lobectomy is superior to open thoracotomy for the treatment of NSCLC in terms of economic cost to society. This trial will also include an analysis of postoperative outcomes, the length of hospital stay, the quality of life, long-term survival and locoregional recurrence. The study design is a two-arm parallel randomised controlled trial comparing VATS lobectomy with lobectomy using thoracotomy for the treatment of NSCLC. Patients will be eligible if they have proven or suspected lung cancer which could be treated by lobectomy. Patients will be randomised via an independent service. All patients will be monitored according to standard thoracic surgical practices. All patients will be evaluated at day 1, day 30, month 3, month 6, month 12 and then every year for 2 years thereafter. The recruitment target is 600 patients. Ethics and dissemination The protocol has been approved by the French National Research Ethics Committee (CPP Est I: 09/06/2015) and the French Medicines Agency (09/06/2015). Results will be presented at national and international meetings and conferences and published in peer-reviewed journals. Trial registration number NCT02502318. PMID:28619764

Research ethics committee decision-making in relation to an efficient neonatal trial.

PubMed

Gale, C; Hyde, M J; Modi, N

2017-07-01

Randomised controlled trials, a gold-standard approach to reduce uncertainties in clinical practice, are growing in cost and are often slow to recruit. We determined whether methodological approaches to facilitate large, efficient clinical trials were acceptable to UK research ethics committees (RECs). We developed a protocol in collaboration with parents, for a comparative-effectiveness, randomised controlled trial comparing two widely used blood transfusion practices in preterm infants. We incorporated four approaches to improve recruitment and efficiency: (i) point-of-care design using electronic patient records for patient identification, randomisation and data acquisition, (ii) short two-page information sheet; (iii) explicit mention of possible inclusion benefit; (iv) opt-out consent with enrolment as the default. With the support of the UK Health Research Authority, we submitted an identical protocol to 12 UK REC. RECs in the UK. Number of REC granting favourable opinions. The use of electronic patient records was acceptable to all RECs; one REC raised concerns about the short parent information sheet, 10 about inclusion benefit and 9 about opt-out consent. Following responses to queries, nine RECs granted a favourable final opinion and three rejected the application because they considered the opt-out consent process invalid. A majority of RECs in this study consider the use of electronic patient record data, short information sheets, opt-out consent and mention of possible inclusion benefit to be acceptable in neonatal comparative-effectiveness research. We identified a need for guidance for RECs in relation to opt-out consent processes. These methods provide opportunity to facilitate large randomised controlled trials. 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 effect of pre-course e-learning prior to advanced life support training: a randomised controlled trial.

PubMed

Perkins, Gavin D; Fullerton, James N; Davis-Gomez, Nicole; Davies, Robin P; Baldock, Catherine; Stevens, Harry; Bullock, Ian; Lockey, Andrew S

2010-07-01

The role of e-learning in contemporary healthcare education is quickly developing. The aim of this study was to examine the relationship between the use of an e-learning simulation programme (Microsim, Laerdal, UK) prior to attending an Advanced Life Support (ALS) course and the subsequent relationship to candidate performance. An open label, multi-centre randomised controlled study was conducted. The control group received a course manual and pre-course MCQ four weeks prior to the face to face course. The intervention group in addition received the Microsim programme on a CD. The primary outcome was performance during a simulated cardiac arrest at the end of the course. Secondary outcomes were performance during multiple choice exams, resuscitation skills assessments and feedback to Microsim programme. 572 participants were randomised (287 Microsim, 285 control). There were no significant differences in the primary outcome (performance during a standard cardiac arrest simulation) or secondary outcomes. User evaluations were favorable. 79% would recommend it to colleagues. 9% stated Microsim could replace the entire ALS course, 25% parts. Over 70% of participants' perceived that Microsim improved their understanding of the key learning domains of the ALS course. Distributing Microsim to healthcare providers prior to attending an ALS courses did not improve either cognitive or psychomotor skills performance during cardiac arrest simulation testing. The challenge that lies ahead is to identify the optimal way to use e-learning as part of a blended approach to learning for this type of training programme.

Positioning In Macular hole Surgery (PIMS): statistical analysis plan for a randomised controlled trial.

PubMed

Bell, Lauren; Hooper, Richard; Bunce, Catey; Pasu, Saruban; Bainbridge, James

2017-06-13

The treatment of idiopathic full-thickness macular holes involves surgery to close the hole. Some surgeons advise patients to adopt a face-down position to increase the likelihood of successful macular hole closure. However, patients often find the face-down positioning arduous. There is a lack of conclusive evidence that face-down positioning improves the outcome. The 'Positioning In Macular hole Surgery' (PIMS) trial will assess whether advice to position face-down after surgery improves the surgical success rate for the closure of large (≥400 μm) macular holes. The PIMS trial is a multicentre, parallel-group, superiority clinical trial with 1:1 randomisation. Patients (n = 192) with macular holes (≥400 μm) will be randomised after surgery to either face-down positioning or face-forward positioning for at least 8 h (which can be either consecutive or nonconsecutive) a day, for 5 days following surgery. Inclusion criteria are: presence of an idiopathic full-thickness macular hole ≥400 μm in diameter, as measured by optical coherence tomography (OCT) scans, on either or both eyes; patients electing to have surgery for a macular hole, with or without simultaneous phacoemulsification and intraocular lens implant; ability and willingness to position face-down or in an inactive face-forward position; a history of visual loss suggesting a macular hole of 12 months' or less duration. The primary outcome is successful macular hole closure at 3 months post surgery. The treatment effect will be reported as an odds ratio with 95% confidence interval, adjusted for size of macular hole and phakic lens status at baseline. Secondary outcome measures at 3 months are: further surgery for macular holes performed or planned (of those with unsuccessful closure); patient-reported experience of positioning; whether patients report they would still have elected to have the operation given what they know at follow-up; best-corrected visual acuity (BCVA) measured using Snellen charts at a standard distance of 6 m; patient-reported health and quality of life assessed using the National Eye Institute Visual Function Questionnaire (VFQ-25). The PIMS trial is the first multicentre randomised control trial to investigate the value of face-down positioning following macular hole standardised surgery. International Standard Randomised Controlled Trials Number registry, ID: ISRCTN12410596. Registered on 11 February 2015. United Kingdom Clinical Research Network, ID: UKCRN17966 . Registered on 26 November 2014.

Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial.

PubMed

Lester, Richard T; Ritvo, Paul; Mills, Edward J; Kariri, Antony; Karanja, Sarah; Chung, Michael H; Jack, William; Habyarimana, James; Sadatsafavi, Mohsen; Najafzadeh, Mehdi; Marra, Carlo A; Estambale, Benson; Ngugi, Elizabeth; Ball, T Blake; Thabane, Lehana; Gelmon, Lawrence J; Kimani, Joshua; Ackers, Marta; Plummer, Francis A

2010-11-27

Mobile (cell) phone communication has been suggested as a method to improve delivery of health services. However, data on the effects of mobile health technology on patient outcomes in resource-limited settings are limited. We aimed to assess whether mobile phone communication between health-care workers and patients starting antiretroviral therapy in Kenya improved drug adherence and suppression of plasma HIV-1 RNA load. WelTel Kenya1 was a multisite randomised clinical trial of HIV-infected adults initiating antiretroviral therapy (ART) in three clinics in Kenya. Patients were randomised (1:1) by simple randomisation with a random number generating program to a mobile phone short message service (SMS) intervention or standard care. Patients in the intervention group received weekly SMS messages from a clinic nurse and were required to respond within 48 h. Randomisation, laboratory assays, and analyses were done by investigators masked to treatment allocation; however, study participants and clinic staff were not masked to treatment. Primary outcomes were self-reported ART adherence (>95% of prescribed doses in the past 30 days at both 6 and 12 month follow-up visits) and plasma HIV-1 viral RNA load suppression (<400 copies per mL) at 12 months. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00830622. Between May, 2007, and October, 2008, we randomly assigned 538 participants to the SMS intervention (n=273) or to standard care (n=265). Adherence to ART was reported in 168 of 273 patients receiving the SMS intervention compared with 132 of 265 in the control group (relative risk [RR] for non-adherence 0·81, 95% CI 0·69-0·94; p=0·006). Suppressed viral loads were reported in 156 of 273 patients in the SMS group and 128 of 265 in the control group, (RR for virologic failure 0·84, 95% CI 0·71-0·99; p=0·04). The number needed to treat (NNT) to achieve greater than 95% adherence was nine (95% CI 5·0-29·5) and the NNT to achieve viral load suppression was 11 (5·8-227·3). Patients who received SMS support had significantly improved ART adherence and rates of viral suppression compared with the control individuals. Mobile phones might be effective tools to improve patient outcome in resource-limited settings. US President's Emergency Plan for AIDS Relief. Copyright © 2010 Elsevier Ltd. All rights reserved.

Magnesium sulphate in acute severe asthma in children (MAGNETIC): a randomised, placebo-controlled trial.

PubMed

Powell, Colin; Kolamunnage-Dona, Ruwanthi; Lowe, John; Boland, Angela; Petrou, Stavros; Doull, Iolo; Hood, Kerenza; Williamson, Paula

2013-06-01

Little evidence is available for the effect of nebulised magnesium sulphate (MgSO(4)) in acute asthma in children. We assessed the effect of MgSO(4) treatment in children with severe acute asthma. In this randomised placebo-controlled, multi-centre, parallel trial, we enrolled children (aged 2-16 years) with severe acute asthma who did not respond to standard inhaled treatment from 30 hospitals in the UK. Children were randomly allocated (1:1) to receive nebulised salbutamol and ipratropium bromide with either 2·5 mL of isotonic MgSO(4) (250 mmol/L; 151 mg per dose; MgSO(4) group) or 2·5 mL of isotonic saline (placebo group) on three occasions at 20-min intervals. Randomisation was done with a computer-generated randomisation sequence, with random block sizes of two to four. Both patients and researchers were masked to treatment allocation. The primary outcome measure was the Yung Asthma Severity Score (ASS) at 60 min post-randomisation. We used a statistical significance level of p<0·05 for a between-group difference, but regarded a between-group difference in ASS of 0·5 as the minimal clinically significant treatment effect. Analysis was done by intention to treat. This trial is registered with controlled-trials.com, number ISRCTN81456894. Between Jan 3, 2009, and March 20, 2011, we recruited and randomly assigned 508 children to treatment: 252 to MgSO(4) and 256 to placebo. Mean ASS at 60 min was lower in the MgSO(4) group (4·72 [SD 1·37]) than it was in the placebo group (4·95 [SD 1·40]; adjusted difference -0·25, 95% CI -0·48 to -0·02; p=0·03). This difference, however, was not clinically significant. The clinical effect was larger in children with more severe asthma exacerbation (p=0·03) and those with symptoms present for less than 6 h (p=0·049). We detected no difference in the occurrence of adverse events between groups. Overall, nebulised isotonic MgSO(4), given as an adjuvant to standard treatment, did not show a clinically significant improvement in mean ASS in children with acute severe asthma. However, the greatest clinical response was seen in children with more severe attacks (SaO(2)<92%) at presentation and those with preceding symptoms lasting less than 6 h. National Institute for Health Research Health Technology Assessment Programme. Copyright © 2013 Elsevier Ltd. All rights reserved.

Combination of indoor residual spraying with long-lasting insecticide-treated nets for malaria control in Zambezia, Mozambique: a cluster randomised trial and cost-effectiveness study protocol

PubMed Central

Alonso, Sergi; Zulliger, Rose; Wagman, Joe; Saifodine, Abuchahama; Candrinho, Baltazar; Macete, Eusébio; Brew, Joe; Fornadel, Christen; Kassim, Hidayat; Loch, Lourdes; Sacoor, Charfudin; Varela, Kenyssony; Carty, Cara L; Robertson, Molly; Saute, Francisco

2018-01-01

Background Most of the reduction in malaria prevalence seen in Africa since 2000 has been attributed to vector control interventions. Yet increases in the distribution and intensity of insecticide resistance and higher costs of newer insecticides pose a challenge to sustaining these gains. Thus, endemic countries face challenging decisions regarding the choice of vector control interventions. Methods A cluster randomised trial is being carried out in Mopeia District in the Zambezia Province of Mozambique, where malaria prevalence in children under 5 is high (68% in 2015), despite continuous and campaign distribution of long-lasting insecticide-treated nets (LLINs). Study arm 1 will continue to use the standard, LLIN-based National Malaria Control Programme vector control strategy (LLINs only), while study arm 2 will receive indoor residual spraying (IRS) once a year for 2 years with a microencapsulated formulation of pirimiphos-methyl (Actellic 300 CS), in addition to the standard LLIN strategy (LLINs+IRS). Prior to the 2016 IRS implementation (the first of two IRS campaigns in this study), 146 clusters were defined and stratified per number of households. Clusters were then randomised 1:1 into the two study arms. The public health impact and cost-effectiveness of IRS intervention will be evaluated over 2 years using multiple methods: (1) monthly active malaria case detection in a cohort of 1548 total children aged 6–59 months; (2) enhanced passive surveillance at health facilities and with community health workers; (3) annual cross-sectional surveys; and (4) entomological surveillance. Prospective microcosting of the intervention and provider and societal costs will be conducted. Insecticide resistance status pattern and changes in local Anopheline populations will be included as important supportive outcomes. Discussion By evaluating the public health impact and cost-effectiveness of IRS with a non-pyrethroid insecticide in a high-transmission setting with high LLIN ownership, it is expected that this study will provide programmatic and policy-relevant data to guide national and global vector control strategies. Trial registration number NCT02910934. PMID:29564161

Combination of indoor residual spraying with long-lasting insecticide-treated nets for malaria control in Zambezia, Mozambique: a cluster randomised trial and cost-effectiveness study protocol.

PubMed

Chaccour, Carlos J; Alonso, Sergi; Zulliger, Rose; Wagman, Joe; Saifodine, Abuchahama; Candrinho, Baltazar; Macete, Eusébio; Brew, Joe; Fornadel, Christen; Kassim, Hidayat; Loch, Lourdes; Sacoor, Charfudin; Varela, Kenyssony; Carty, Cara L; Robertson, Molly; Saute, Francisco

2018-01-01

Most of the reduction in malaria prevalence seen in Africa since 2000 has been attributed to vector control interventions. Yet increases in the distribution and intensity of insecticide resistance and higher costs of newer insecticides pose a challenge to sustaining these gains. Thus, endemic countries face challenging decisions regarding the choice of vector control interventions. A cluster randomised trial is being carried out in Mopeia District in the Zambezia Province of Mozambique, where malaria prevalence in children under 5 is high (68% in 2015), despite continuous and campaign distribution of long-lasting insecticide-treated nets (LLINs). Study arm 1 will continue to use the standard, LLIN-based National Malaria Control Programme vector control strategy (LLINs only), while study arm 2 will receive indoor residual spraying (IRS) once a year for 2 years with a microencapsulated formulation of pirimiphos-methyl (Actellic 300 CS), in addition to the standard LLIN strategy (LLINs+IRS). Prior to the 2016 IRS implementation (the first of two IRS campaigns in this study), 146 clusters were defined and stratified per number of households. Clusters were then randomised 1:1 into the two study arms. The public health impact and cost-effectiveness of IRS intervention will be evaluated over 2 years using multiple methods: (1) monthly active malaria case detection in a cohort of 1548 total children aged 6-59 months; (2) enhanced passive surveillance at health facilities and with community health workers; (3) annual cross-sectional surveys; and (4) entomological surveillance. Prospective microcosting of the intervention and provider and societal costs will be conducted. Insecticide resistance status pattern and changes in local Anopheline populations will be included as important supportive outcomes. By evaluating the public health impact and cost-effectiveness of IRS with a non-pyrethroid insecticide in a high-transmission setting with high LLIN ownership, it is expected that this study will provide programmatic and policy-relevant data to guide national and global vector control strategies. NCT02910934.

A pragmatic randomised controlled trial assessing the non-inferiority of counselling for depression versus cognitive-behaviour therapy for patients in primary care meeting a diagnosis of moderate or severe depression (PRaCTICED): Study protocol for a randomised controlled trial.

PubMed

Saxon, David; Ashley, Kate; Bishop-Edwards, Lindsey; Connell, Janice; Harrison, Phillippa; Ohlsen, Sally; Hardy, Gillian E; Kellett, Stephen; Mukuria, Clara; Mank, Toni; Bower, Peter; Bradburn, Mike; Brazier, John; Elliott, Robert; Gabriel, Lynne; King, Michael; Pilling, Stephen; Shaw, Sue; Waller, Glenn; Barkham, Michael

2017-03-01

NICE guidelines state cognitive behavioural therapy (CBT) is a front-line psychological treatment for people presenting with depression in primary care. Counselling for Depression (CfD), a form of Person-Centred Experiential therapy, is also offered within Improving Access to Psychological Therapies (IAPT) services for moderate depression but its effectiveness for severe depression has not been investigated. A full-scale randomised controlled trial to determine the efficacy and cost-effectiveness of CfD is required. PRaCTICED is a two-arm, parallel group, non-inferiority randomised controlled trial comparing CfD against CBT. It is embedded within the local IAPT service using a stepped care service delivery model where CBT and CfD are routinely offered at step 3. Trial inclusion criteria comprise patients aged 18 years or over, wishing to work on their depression, judged to require a step 3 intervention, and meeting an ICD-10 diagnosis of moderate or severe depression. Patients are randomised using a centralised, web-based system to CfD or CBT with each treatment being delivered up to a maximum 20 sessions. Both interventions are manualised with treatment fidelity tested via supervision and random sampling of sessions using adherence/competency scales. The primary outcome measure is the Patient Health Questionnaire-9 collected at baseline, 6 and 12 months. Secondary outcome measures tap depression, generic psychological distress, anxiety, functioning and quality of life. Cost-effectiveness is determined by a patient service receipt questionnaire. Exit interviews are conducted with patients by research assessors blind to treatment allocation. The trial requires 500 patients (250 per arm) to test the non-inferiority hypothesis of -2 PHQ-9 points at the one-sided, 2.5% significance level with 90% power, assuming no underlying difference and a standard deviation of 6.9. The primary analysis will be undertaken on all patients randomised (intent to treat) alongside per-protocol and complier-average causal effect analyses as recommended by the extension to the CONSORT statement for non-inferiority trials. This large-scale trial utilises routinely collected outcome data as well as specific trial data to provide evidence of the comparative efficacy and cost-effectiveness of Counselling for Depression compared with Cognitive Behaviour Therapy as delivered within the UK government's Improving Access to Psychological Therapies initiative. Controlled Trials ISRCTN Registry, ISRCTN06461651 . Registered on 14 September 2014.

Immediate total-body CT scanning versus conventional imaging and selective CT scanning in patients with severe trauma (REACT-2): a randomised controlled trial.

PubMed

Sierink, Joanne C; Treskes, Kaij; Edwards, Michael J R; Beuker, Benn J A; den Hartog, Dennis; Hohmann, Joachim; Dijkgraaf, Marcel G W; Luitse, Jan S K; Beenen, Ludo F M; Hollmann, Markus W; Goslings, J Carel

2016-08-13

Published work suggests a survival benefit for patients with trauma who undergo total-body CT scanning during the initial trauma assessment; however, level 1 evidence is absent. We aimed to assess the effect of total-body CT scanning compared with the standard work-up on in-hospital mortality in patients with trauma. We undertook an international, multicentre, randomised controlled trial at four hospitals in the Netherlands and one in Switzerland. Patients aged 18 years or older with trauma with compromised vital parameters, clinical suspicion of life-threatening injuries, or severe injury were randomly assigned (1:1) by ALEA randomisation to immediate total-body CT scanning or to a standard work-up with conventional imaging supplemented with selective CT scanning. Neither doctors nor patients were masked to treatment allocation. The primary endpoint was in-hospital mortality, analysed in the intention-to-treat population and in subgroups of patients with polytrauma and those with traumatic brain injury. The χ(2) test was used to assess differences in mortality. This trial is registered with ClinicalTrials.gov, number NCT01523626. Between April 22, 2011, and Jan 1, 2014, 5475 patients were assessed for eligibility, 1403 of whom were randomly assigned: 702 to immediate total-body CT scanning and 701 to the standard work-up. 541 patients in the immediate total-body CT scanning group and 542 in the standard work-up group were included in the primary analysis. In-hospital mortality did not differ between groups (total-body CT 86 [16%] of 541 vs standard work-up 85 [16%] of 542; p=0.92). In-hospital mortality also did not differ between groups in subgroup analyses in patients with polytrauma (total-body CT 81 [22%] of 362 vs standard work-up 82 [25%] of 331; p=0.46) and traumatic brain injury (68 [38%] of 178 vs 66 [44%] of 151; p=0.31). Three serious adverse events were reported in patients in the total-body CT group (1%), one in the standard work-up group (<1%), and one in a patient who was excluded after random allocation. All five patients died. Diagnosing patients with an immediate total-body CT scan does not reduce in-hospital mortality compared with the standard radiological work-up. Because of the increased radiation dose, future research should focus on the selection of patients who will benefit from immediate total-body CT. ZonMw, the Netherlands Organisation for Health Research and Development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bath additives for the treatment of childhood eczema (BATHE): protocol for multicentre parallel group randomised trial.

PubMed

Santer, Miriam; Rumsby, Kate; Ridd, Matthew J; Francis, Nick A; Stuart, Beth; Chorozoglou, Maria; Wood, Wendy; Roberts, Amanda; Thomas, Kim S; Williams, Hywel C; Little, Paul

2015-11-01

Bath emollients are widely prescribed for childhood eczema, yet evidence of their benefits over direct application of emollients is lacking. Objectives To determine the clinical and cost-effectiveness of adding bath emollient to the standard management of eczema in children Pragmatic open 2-armed parallel group randomised controlled trial. General practitioner (GP) practices in England and Wales. Children aged over 12 months and less than 12 years with eczema, excluding inactive or very mild eczema (5 or less on Nottingham Eczema Severity Scale). Children will be randomised to either bath emollients plus standard eczema care or standard eczema care only. Primary outcome is long-term eczema severity, measured by the Patient-Oriented Eczema Measure (POEM) repeated weekly for 16 weeks. Secondary outcomes include: number of eczema exacerbations resulting in healthcare consultations over 1 year; eczema severity over 1 year; disease-specific and generic quality of life; medication use and healthcare resource use; cost-effectiveness. Aiming to detect a mean difference between groups of 2.0 (SD 7.0) in weekly POEM scores over 16 weeks (significance 0.05, power 0.9), allowing for 20% loss to follow-up, gives a total sample size of 423 children. We will use repeated measures analysis of covariance, or a mixed model, to analyse weekly POEM scores. We will control for possible confounders, including baseline eczema severity and child's age. Cost-effectiveness analysis will be carried out from a National Health Service (NHS) perspective. This protocol was approved by Newcastle and North Tyneside 1 NRES committee 14/NE/0098. Follow-up will be completed in 2017. Findings will be disseminated to participants and carers, the public, dermatology and primary care journals, guideline developers and decision-makers. ISRCTN84102309. 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/

Bath additives for the treatment of childhood eczema (BATHE): protocol for multicentre parallel group randomised trial

PubMed Central

Santer, Miriam; Rumsby, Kate; Ridd, Matthew J; Francis, Nick A; Stuart, Beth; Chorozoglou, Maria; Wood, Wendy; Roberts, Amanda; Thomas, Kim S; Williams, Hywel C; Little, Paul

2015-01-01

Introduction Bath emollients are widely prescribed for childhood eczema, yet evidence of their benefits over direct application of emollients is lacking. Objectives To determine the clinical and cost-effectiveness of adding bath emollient to the standard management of eczema in children Methods and analysis Design: Pragmatic open 2-armed parallel group randomised controlled trial. Setting: General practitioner (GP) practices in England and Wales. Participants: Children aged over 12 months and less than 12 years with eczema, excluding inactive or very mild eczema (5 or less on Nottingham Eczema Severity Scale). Interventions: Children will be randomised to either bath emollients plus standard eczema care or standard eczema care only. Outcome measures: Primary outcome is long-term eczema severity, measured by the Patient-Oriented Eczema Measure (POEM) repeated weekly for 16 weeks. Secondary outcomes include: number of eczema exacerbations resulting in healthcare consultations over 1 year; eczema severity over 1 year; disease-specific and generic quality of life; medication use and healthcare resource use; cost-effectiveness. Aiming to detect a mean difference between groups of 2.0 (SD 7.0) in weekly POEM scores over 16 weeks (significance 0.05, power 0.9), allowing for 20% loss to follow-up, gives a total sample size of 423 children. We will use repeated measures analysis of covariance, or a mixed model, to analyse weekly POEM scores. We will control for possible confounders, including baseline eczema severity and child's age. Cost-effectiveness analysis will be carried out from a National Health Service (NHS) perspective. Ethics and dissemination This protocol was approved by Newcastle and North Tyneside 1 NRES committee 14/NE/0098. Follow-up will be completed in 2017. Findings will be disseminated to participants and carers, the public, dermatology and primary care journals, guideline developers and decision-makers. Trial registration number ISRCTN84102309. PMID:26525422

Economic Evaluation of a General Hospital Unit for Older People with Delirium and Dementia (TEAM Randomised Controlled Trial).

PubMed

Tanajewski, Lukasz; Franklin, Matthew; Gkountouras, Georgios; Berdunov, Vladislav; Harwood, Rowan H; Goldberg, Sarah E; Bradshaw, Lucy E; Gladman, John R F; Elliott, Rachel A

2015-01-01

One in three hospital acute medical admissions is of an older person with cognitive impairment. Their outcomes are poor and the quality of their care in hospital has been criticised. A specialist unit to care for older people with delirium and dementia (the Medical and Mental Health Unit, MMHU) was developed and then tested in a randomised controlled trial where it delivered significantly higher quality of, and satisfaction with, care, but no significant benefits in terms of health status outcomes at three months. To examine the cost-effectiveness of the MMHU for older people with delirium and dementia in general hospitals, compared with standard care. Six hundred participants aged over 65 admitted for acute medical care, identified on admission as cognitively impaired, were randomised to the MMHU or to standard care on acute geriatric or general medical wards. Cost per quality adjusted life year (QALY) gained, at 3-month follow-up, was assessed in trial-based economic evaluation (599/600 participants, intervention: 309). Multiple imputation and complete-case sample analyses were employed to deal with missing QALY data (55%). The total adjusted health and social care costs, including direct costs of the intervention, at 3 months was £7714 and £7862 for MMHU and standard care groups, respectively (difference -£149 (95% confidence interval [CI]: -298, 4)). The difference in QALYs gained was 0.001 (95% CI: -0.006, 0.008). The probability that the intervention was dominant was 58%, and the probability that it was cost-saving with QALY loss was 39%. At £20,000/QALY threshold, the probability of cost-effectiveness was 94%, falling to 59% when cost-saving QALY loss cases were excluded. The MMHU was strongly cost-effective using usual criteria, although considerably less so when the less acceptable situation with QALY loss and cost savings were excluded. Nevertheless, this model of care is worthy of further evaluation. ClinicalTrials.gov NCT01136148.

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.

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.

Prescribed computer games in addition to occlusion versus standard occlusion treatment for childhood amblyopia: a pilot randomised controlled trial.

PubMed

Tailor, Vijay K; Glaze, Selina; Khandelwal, Payal; Davis, Alison; Adams, Gillian G W; Xing, Wen; Bunce, Catey; Dahlmann-Noor, Annegret

2015-01-01

Amblyopia ("lazy eye") is the commonest vision deficit in children. If not fully corrected by glasses, amblyopia is treated by patching or blurring the better-seeing eye. Compliance with patching is often poor. Computer-based activities are increasingly topical, both as an adjunct to standard treatment and as a platform for novel treatments. Acceptability by families has not been explored, and feasibility of a randomised controlled trial (RCT) using computer games in terms of recruitment and treatment acceptability is uncertain. We carried out a pilot RCT to test whether computer-based activities are acceptable and accessible to families and to test trial methods such as recruitment and retention rates, randomisation, trial-specific data collection tools and analysis. The trial had three arms: standard near activity advice, Eye Five, a package developed for children with amblyopia, and an off-the-shelf handheld games console with pre-installed games. We enrolled 60 children age 3-8 years with moderate or severe amblyopia after completion of optical treatment. This trial was registered as UKCRN-ID 11074. Pre-screening of 3600 medical notes identified 189 potentially eligible children, of whom 60 remained eligible after optical treatment, and were enrolled between April 2012 and March 2013. One participant was randomised twice and withdrawn from the study. Of the 58 remaining, 37 were boys. The mean (SD) age was 4.6 (1.7) years. Thirty-seven had moderate and 21 severe amblyopia. Three participants were withdrawn at week 6, and in total, four were lost to follow-up at week 12. Most children and parents/carers found the study procedures, i.e. occlusion treatment, usage of the allocated near activity and completion of a study diary, easy. The prescribed cumulative dose of near activity was 84 h at 12 weeks. Reported near activity usage numbers were close to prescribed numbers in moderate amblyopes (94 % of prescribed) but markedly less in severe amblyopes (64 %). Reported occlusion usage at 12 weeks was 90 % of prescribed dose for moderate and 33 % for severe amblyopes. Computer-based games and activities appear acceptable to families as part of their child's amblyopia treatment. Trial methods were appropriate and accepted by families.

Pilot cluster randomised controlled trial of flooring to reduce injuries from falls in wards for older people.

PubMed

Drahota, Amy Kim; Ward, Derek; Udell, Julie E; Soilemezi, Dia; Ogollah, Reuben; Higgins, Bernard; Dean, Taraneh P; Severs, Martin

2013-09-01

falls disproportionately affect older people, who are at increased risk of falls and injury. This pilot study investigates shock-absorbing flooring for fall-related injuries in wards for frail older people. we conducted a non-blinded cluster randomised trial in eight hospitals in England between April 2010 and August 2011. Each site allocated one bay as the 'study area', which was randomised via computer to intervention (8.3-mm thick Tarkett Omnisports EXCEL) or control (2-mm standard in situ flooring). Sites had an intervention period of 1 year. Anybody admitted to the study area was eligible. The primary outcome was the fall-related injury rate. Secondary outcomes were injury severity, fall rate and adverse events. during the intervention period, 226 participants were recruited to each group (219 and 223 were analysed in the intervention and control group, respectively). Of 35 falls (31 fallers) in the intervention group, 22.9% were injurious, compared with 42.4% of 33 falls (22 fallers) in the control group [injury incident rate ratio (IRR) = 0.58, 95% CI = 0.18-1.91]. There were no moderate or major injuries in the intervention group and six in the control group. The fall IRR was 1.07 (95% CI = 0.64-1.81). Staff at intervention sites raised concerns about pushing equipment, documenting one pulled back. future research should assess shock-absorbing flooring with better 'push/pull' properties and explore increased faller risk. We estimate a future trial will need 33,480-52,840 person bed-days per arm.

Self-sampling to increase participation in cervical cancer screening: an RCT comparing home mailing, distribution in pharmacies, and recall letter.

PubMed

Giorgi Rossi, P; Fortunato, C; Barbarino, P; Boveri, S; Caroli, S; Del Mistro, A; Ferro, A; Giammaria, C; Manfredi, M; Moretto, T; Pasquini, A; Sideri, M; Tufi, M C; Cogo, C; Altobelli, E

2015-02-17

We performed a multicentre randomised controlled trial to evaluate the effect on participation in organised screening programmes of a self-sampling device mailed home or picked up at a pharmacy compared with the standard recall letter. Women aged 30-64 non-responding to screening invitation were eligible. Response rate to first invitation ranged from 30% to 60% between centres. The control was the standard reminder letter to undergo the test used by the programme (Pap test in three centres and HPV DNA test in three other centres). Home mailing of the self-sampler was preceded by a letter with a leaflet about HPV. The analysis was intention-to-treat. In all, 14 041 women were randomised and recruited: 5012 in the control arm, 4516 to receive the self-sampler at home, and 4513 to pick up the self-sampler at a pharmacy. Participation was 11.9% in the control, 21.6% (relative participation: 1.75; 95% CI 1.60-1.93) in home, and 12.0% (relative participation: 0.96; 95% CI 0.86-1.07) in the pharmacy arms, respectively. The heterogeneity between centres was high (excess heterogeneity of that expected due to chance, i.e., I(2), 94.9% and 94.1% for home and pharmacy arm, respectively). The estimated impact on the overall coverage was +4.3% for home mail self-sampling compared with +2.2% for standard reminder. Home mailing of self-sampler proved to be an effective way to increase participation in screening programmes, even in those with HPV as primary testing. Picking up at pharmacies showed effects varying from centre to centre.

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.

SMART lunch box intervention to improve the food and nutrient content of children's packed lunches: UK wide cluster randomised controlled trial.

PubMed

Evans, C E L; Greenwood, D C; Thomas, J D; Cleghorn, C L; Kitchen, M S; Cade, J E

2010-11-01

Government standards are now in place for children's school meals but not for lunches prepared at home. The aim of this trial is to improve the content of children's packed lunches. A cluster randomised controlled trial in 89 primary schools across the UK involving 1291 children, age 8-9 years at baseline. Follow-up was 12 months after baseline. A "SMART" lunch box intervention programme consisted of food boxes, bag and supporting materials. The main outcome measures were weights of foods and proportion of children provided with sandwiches, fruit, vegetables, dairy food, savoury snacks and confectionery in each packed lunch. Levels of nutrients provided including energy, total fat, saturated fat, protein, non-milk extrinsic sugar, sodium, calcium, iron, folate, zinc, vitamin A and vitamin C. Moderately higher weights of fruit, vegetables, dairy and starchy food and lower weights of savoury snacks were provided to children in the intervention group. Children in the intervention group were provided with slightly higher levels of vitamin A and folate. 11% more children were provided with vegetables/salad in their packed lunch, and 13% fewer children were provided with savoury snacks (crisps). Children in the intervention group were more likely to be provided with packed lunches meeting the government school meal standards. The SMART lunch box intervention, targeting parents and children, led to small improvements in the food and nutrient content of children's packed lunches. Further interventions are required to bring packed lunches in line with the new government standards for school meals. Current controlled trials ISRCTN77710993.

An assessment of quality characteristics of randomised control trials published in dental journals.

PubMed

Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

2010-09-01

The purpose of this study was to investigate the quality of reporting of randomised clinical trials (RCTs) published in dental specialty journals. The journals possessing the highest impact factor (2008 data) in the six major dental specialties were included in the study. The contents of the 24 most recent issues of each journal were hand-searched and research articles identified as randomised controlled trials (RCTs) were selected. Quality evaluation was performed using the modified Consolidated Standards of Reporting Trials (CONSORT) statement checklist. The data were analysed using descriptive statistics followed by univariate and multivariate examination of statistical associations (alpha=0.05). Ninety-five RCTs were identified with generally suboptimal scores on quality reporting on key CONSORT areas. Significant differences were found among journals with the Journal of Clinical Periodontology achieving the highest score, followed by the American Journal of Orthodontics and Dentofacial Orthopedics. There was a positive association between quality score and number of authors, involvement of statistician/epidemiologist, and multicentre trials. The quality scores of RCTs in major dental journals are considered suboptimal in key CONSORT areas. This receives critical importance considering that improved quality of RCTs is a fundamental prerequisite for improved dental care. Copyright 2010 Elsevier Ltd. All rights reserved.

TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, randomised controlled trial

PubMed Central

Ware, Russell E.; Davis, Barry R.; Schultz, William H.; Brown, R. Clark; Aygun, Banu; Sarnaik, Sharada; Odame, Isaac; Fuh, Beng; George, Alex; Owen, William; Luchtman-Jones, Lori; Rogers, Zora R.; Hilliard, Lee; Gauger, Cynthia; Piccone, Connie; Lee, Margaret T.; Kwiatkowski, Janet L.; Jackson, Sherron; Miller, Scott T.; Roberts, Carla; Heeney, Matthew M.; Kalfa, Theodosia A.; Nelson, Stephen; Imran, Hamayun; Nottage, Kerri; Alvarez, Ofelia; Rhodes, Melissa; Thompson, Alexis A.; Rothman, Jennifer A.; Helton, Kathleen J.; Roberts, Donna; Coleman, Jamie; Bonner, Melanie J.; Kutlar, Abdullah; Patel, Niren; Wood, John; Piller, Linda; Wei, Peng; Luden, Judy; Mortier, Nicole A.; Stuber, Susan E.; Luban, Naomi L. C.; Cohen, Alan R.; Pressel, Sara; Adams, Robert J.

2017-01-01

Background For children with sickle cell anaemia and elevated transcranial Doppler (TCD) flow velocities, regular blood transfusions effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxyurea in this setting is unknown. Methods TWiTCH was a multicentre Phase III randomised open label, non-inferiority trial comparing standard treatment (transfusions) to alternative treatment (hydroxyurea) in children with abnormal TCD velocities but no severe vasculopathy. Iron overload was managed with chelation (Standard Arm) and serial phlebotomy (Alternative Arm). The primary study endpoint was the 24-month TCD velocity calculated from a general linear mixed model, with non-inferiority margin = 15 cm/sec. Findings Among 121 randomised participants (61 transfusions, 60 hydroxyurea), children on transfusions maintained <30% sickle haemoglobin, while those taking hydroxyurea (mean 27 mg/kg/day) averaged 25% fetal haemoglobin. The first scheduled interim analysis demonstrated non-inferiority, and the sponsor terminated the study. Final model-based TCD velocities (mean ± standard error) on Standard versus Alternative Arm were 143 ± 1.6 and 138 ± 1.6 cm/sec, respectively, with difference (95% CI) = 4.54 (0.10, 8.98), non-inferiority p=8.82 × 10−16 and post-hoc superiority p=0.023. Among 29 new neurological events adjudicated centrally by masked reviewers, no strokes occurred but there were 3 transient ischaemic attacks per arm. Exit brain MRI/MRA revealed no new cerebral infarcts in either arm, but worse vasculopathy in one participant (Standard Arm). Iron burden decreased more in the Alternative Arm, with ferritin difference −1047 ng/mL (−1524, −570), p<0.001 and liver iron difference −4.3 mg Fe/gm dry weight (−6.1, −2.5), p=0.001. Interpretation For high-risk children with sickle cell anaemia and abnormal TCD velocities, after four years of transfusions and without severe MRA vasculopathy, hydroxyurea therapy can substitute for chronic transfusions to maintain TCD velocities and help prevent primary stroke. PMID:26670617

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/.

Rapid reduction versus abrupt quitting for smokers who want to stop soon: a randomised controlled non-inferiority trial

PubMed Central

Lindson, Nicola; Aveyard, Paul; Ingram, Jackie T; Inglis, Jennie; Beach, Jane; West, Robert; Michie, Susan

2009-01-01

Background The standard way to stop smoking is to stop abruptly on a quit day with no prior reduction in consumption of cigarettes. Many smokers feel that reduction is natural and if reduction programmes were offered, many more might take up treatment. Few trials of reduction versus abrupt cessation have been completed. Most are small, do not use pharmacotherapy, and do not meet the standards necessary to obtain a marketing authorisation for a pharmacotherapy. Design/Methods We will conduct a non-inferiority randomised trial of rapid reduction versus standard abrupt cessation among smokers who want to stop smoking. In the reduction arm, participants will be advised to reduce smoking consumption by half in the first week and to 25% of baseline in the second, leading up to a quit day at which participants will stop smoking completely. This will be assisted by nicotine patches and an acute form of nicotine replacement therapy. In the abrupt arm participants will use nicotine patches only, whilst smoking as normal, for two weeks prior to a quit day, at which they will also stop smoking completely. Smokers in either arm will have standard withdrawal orientated behavioural support programme with a combination of nicotine patches and acute nicotine replacement therapy post-cessation. Outcomes/Follow-up The primary outcome of interest will be prolonged abstinence from smoking, with secondary trial outcomes of point prevalence, urges to smoke and withdrawal symptoms. Follow up will take place at 4 weeks, 8 weeks and 6 months post-quit day. Trial Registration Current Controlled Trials ISRCTN22526020 PMID:19682359

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

PubMed

MoghaddamHosseini, Vahideh; Nazarzadeh, Milad; Jahanfar, Shayesteh

2017-11-07

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

Randomised controlled trial of labouring in water compared with standard of augmentation for management of dystocia in first stage of labour

PubMed Central

Cluett, Elizabeth R; Pickering, Ruth M; Getliffe, Kathryn; Saunders, Nigel James St George

2004-01-01

Objectives To evaluate the impact of labouring in water during first stage of labour on rates of epidural analgesia and operative delivery in nulliparous women with dystocia. Design Randomised controlled trial. Setting University teaching hospital in southern England. Participants 99 nulliparous women with dystocia (cervical dilation rate < 1 cm/hour in active labour) at low risk of complications. Interventions Immersion in water in birth pool or standard augmentation for dystocia (amniotomy and intravenous oxytocin). Main outcome measures Primary: epidural analgesia and operative delivery rates. Secondary: augmentation rates with amniotomy and oxytocin, length of labour, maternal and neonatal morbidity including infections, maternal pain score, and maternal satisfaction with care. Results Women randomised to immersion in water had a lower rate of epidural analgesia than women allocated to augmentation (47% v 66%, relative risk 0.71 (95% confidence interval 0.49 to 1.01), number needed to treat for benefit (NNT) 5). They showed no difference in rates of operative delivery (49% v 50%, 0.98 (0.65 to 1.47), NNT 98), but significantly fewer received augmentation (71% v 96%, 0.74 (0.59 to 0.88), NNT 4) or any form of obstetric intervention (amniotomy, oxytocin, epidural, or operative delivery) (80% v 98%, 0.81 (0.67 to 0.92), NNT 5). More neonates of women in the water group were admitted to the neonatal unit (6 v 0, P = 0.013), but there was no difference in Apgar score, infection rates, or umbilical cord pH. Conclusions Labouring in water under midwifery care may be an option for slow progress in labour, reducing the need for obstetric intervention, and offering an alternative pain management strategy. PMID:14744822

Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study

PubMed Central

Katzenschlager, R; Evans, A; Manson, A; Patsalos, P; Ratnaraj, N; Watt, H; Timmermann, L; Van der Giessen, R; Lees, A

2004-01-01

Background: The seed powder of the leguminous plant, Mucuna pruriens has long been used in traditional Ayurvedic Indian medicine for diseases including parkinsonism. We have assessed the clinical effects and levodopa (L-dopa) pharmacokinetics following two different doses of mucuna preparation and compared them with standard L-dopa/carbidopa (LD/CD). Methods: Eight Parkinson's disease patients with a short duration L-dopa response and on period dyskinesias completed a randomised, controlled, double blind crossover trial. Patients were challenged with single doses of 200/50 mg LD/CD, and 15 and 30 g of mucuna preparation in randomised order at weekly intervals. L-Dopa pharmacokinetics were determined, and Unified Parkinson's Disease Rating Scale and tapping speed were obtained at baseline and repeatedly during the 4 h following drug ingestion. Dyskinesias were assessed using modified AIMS and Goetz scales. Results: Compared with standard LD/CD, the 30 g mucuna preparation led to a considerably faster onset of effect (34.6 v 68.5 min; p = 0.021), reflected in shorter latencies to peak L-dopa plasma concentrations. Mean on time was 21.9% (37 min) longer with 30 g mucuna than with LD/CD (p = 0.021); peak L-dopa plasma concentrations were 110% higher and the area under the plasma concentration v time curve (area under curve) was 165.3% larger (p = 0.012). No significant differences in dyskinesias or tolerability occurred. Conclusions: The rapid onset of action and longer on time without concomitant increase in dyskinesias on mucuna seed powder formulation suggest that this natural source of L-dopa might possess advantages over conventional L-dopa preparations in the long term management of PD. Assessment of long term efficacy and tolerability in a randomised, controlled study is warranted. PMID:15548480

Exploring the effect of space and place on response to exercise therapy for knee and hip pain—a protocol for a double-blind randomised controlled clinical trial: the CONEX trial

PubMed Central

Thorlund, Jonas Bloch; Ulrich, Roger S; Dieppe, Paul A; Roos, Ewa M

2015-01-01

Introduction Context effects are described as effects of a given treatment, not directly caused by the treatment itself, but rather caused by the context in which treatment is delivered. Exercise is a recommended core treatment in clinical guidelines for musculoskeletal disorders. Although moderately effective overall, variation is seen in size of response to exercise across randomised controlled trial (RCT) studies. Part of this variation may be related to the fact that exercise interventions are performed in different physical environments, which may affect participants differently. The study aims to investigate the effect of exercising in a contextually enhanced physical environment for 8 weeks in people with knee or hip pain. Methods and analysis The study is a double-blind RCT. Eligible participants are 35 years or older with persisting knee and/or hip pain for 3 months. Participants are randomised to one of three groups: (1) exercise in a contextually enhanced environment, (2) exercise in a standard environment and (3) waiting list. The contextually enhanced environment is located in a newly built facility, has large windows providing abundant daylight and overlooks a recreational park. The standard environment is in a basement, has artificial lighting and is marked by years of use; that is, resembling many clinical environments. The primary outcome is the participant's global perceived effect rated on a seven-point Likert scale after 8 weeks exercise. Patient-reported and objective secondary outcomes are included. Ethics and dissemination The Regional Scientific Ethical Committee for Southern Denmark has approved the study. Study findings will be disseminated in peer-reviewed publications and presented at national and international conferences. Trial registration number NCT02043613. PMID:25818278

Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study.

PubMed

Kitchener, H; Swart, A M C; Qian, Q; Amos, C; Parmar, M K B

2009-01-10

Hysterectomy and bilateral salpingo-oophorectomy (BSO) is the standard surgery for stage I endometrial cancer. Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterine disease and as a therapeutic procedure; however, randomised trials need to be done to assess therapeutic efficacy. The ASTEC surgical trial investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer. From 85 centres in four countries, 1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus were randomly allocated by a minimisation method to standard surgery (hysterectomy and BSO, peritoneal washings, and palpation of para-aortic nodes; n=704) or standard surgery plus lymphadenectomy (n=704). The primary outcome measure was overall survival. To control for postsurgical treatment, women with early-stage disease at intermediate or high risk of recurrence were randomised (independent of lymph-node status) into the ASTEC radiotherapy trial. Analysis was by intention to treat. This study is registered, number ISRCTN 16571884. After a median follow-up of 37 months (IQR 24-58), 191 women (88 standard surgery group, 103 lymphadenectomy group) had died, with a hazard ratio (HR) of 1.16 (95% CI 0.87-1.54; p=0.31) in favour of standard surgery and an absolute difference in 5-year overall survival of 1% (95% CI -4 to 6). 251 women died or had recurrent disease (107 standard surgery group, 144 lymphadenectomy group), with an HR of 1.35 (1.06-1.73; p=0.017) in favour of standard surgery and an absolute difference in 5-year recurrence-free survival of 6% (1-12). With adjustment for baseline characteristics and pathology details, the HR for overall survival was 1.04 (0.74-1.45; p=0.83) and for recurrence-free survival was 1.25 (0.93-1.66; p=0.14). Our results show no evidence of benefit in terms of overall or recurrence-free survival for pelvic lymphadenectomy in women with early endometrial cancer. Pelvic lymphadenectomy cannot be recommended as routine procedure for therapeutic purposes outside of clinical trials.

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

PubMed Central

James, Nicholas D; Sydes, Matthew R; Clarke, Noel W; Mason, Malcolm D; Dearnaley, David P; Spears, Melissa R; Ritchie, Alastair W S; Parker, Christopher C; Russell, J Martin; Attard, Gerhardt; de Bono, Johann; Cross, William; Jones, Rob J; Thalmann, George; Amos, Claire; Matheson, David; Millman, Robin; Alzouebi, Mymoona; Beesley, Sharon; Birtle, Alison J; Brock, Susannah; Cathomas, Richard; Chakraborti, Prabir; Chowdhury, Simon; Cook, Audrey; Elliott, Tony; Gale, Joanna; Gibbs, Stephanie; Graham, John D; Hetherington, John; Hughes, Robert; Laing, Robert; McKinna, Fiona; McLaren, Duncan B; O'Sullivan, Joe M; Parikh, Omi; Peedell, Clive; Protheroe, Andrew; Robinson, Angus J; Srihari, Narayanan; Srinivasan, Rajaguru; Staffurth, John; Sundar, Santhanam; Tolan, Shaun; Tsang, David; Wagstaff, John; Parmar, Mahesh K B

2016-01-01

Summary Background Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. Methods Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m2) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). Findings 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60–71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23–184). Median follow-up was 43 months (IQR 30–60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79–1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66–0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69–0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3–5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. Interpretation Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. Funding Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research. PMID:26719232

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial.

PubMed

James, Nicholas D; Sydes, Matthew R; Clarke, Noel W; Mason, Malcolm D; Dearnaley, David P; Spears, Melissa R; Ritchie, Alastair W S; Parker, Christopher C; Russell, J Martin; Attard, Gerhardt; de Bono, Johann; Cross, William; Jones, Rob J; Thalmann, George; Amos, Claire; Matheson, David; Millman, Robin; Alzouebi, Mymoona; Beesley, Sharon; Birtle, Alison J; Brock, Susannah; Cathomas, Richard; Chakraborti, Prabir; Chowdhury, Simon; Cook, Audrey; Elliott, Tony; Gale, Joanna; Gibbs, Stephanie; Graham, John D; Hetherington, John; Hughes, Robert; Laing, Robert; McKinna, Fiona; McLaren, Duncan B; O'Sullivan, Joe M; Parikh, Omi; Peedell, Clive; Protheroe, Andrew; Robinson, Angus J; Srihari, Narayanan; Srinivasan, Rajaguru; Staffurth, John; Sundar, Santhanam; Tolan, Shaun; Tsang, David; Wagstaff, John; Parmar, Mahesh K B

2016-03-19

Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research. Copyright © 2016 James et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

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.

Development and evaluation of an intervention aiming to reduce fatigue in airline pilots: design of a randomised controlled trial

PubMed Central

2013-01-01

Background A considerable percentage of flight crew reports to be fatigued regularly. This is partly caused by irregular and long working hours and the crossing of time zones. It has been shown that persistent fatigue can lead to health problems, impaired performance during work, and a decreased work-private life balance. It is hypothesized that an intervention consisting of tailored advice regarding exposure to daylight, optimising sleep, physical activity, and nutrition will lead to a reduction of fatigue in airline pilots compared to a control group, which receives a minimal intervention with standard available information. Methods/design The study population will consist of pilots of a large airline company. All pilots who posses a smartphone or tablet, and who are not on sick leave for more than four weeks at the moment of recruitment, will be eligible for participation. In a two-armed randomised controlled trial, participants will be allocated to an intervention group that will receive the tailored advice to optimise exposure to daylight, sleep, physical activity and nutrition, and a control group that will receive standard available information. The intervention will be applied using a smartphone application and a website, and will be tailored on flight- and participant-specific characteristics. The primary outcome of the study is perceived fatigue. Secondary outcomes are need for recovery, duration and quality of sleep, dietary and physical activity behaviours, work-private life balance, general health, and sickness absence. A process evaluation will be conducted as well. Outcomes will be measured at baseline and at three and six months after baseline. Discussion This paper describes the development of an intervention for airline pilots, consisting of tailored advice (on exposure to daylight and sleep-, physical activity, and nutrition) applied into a smartphone application. Further, the paper describes the design of the randomised controlled trial evaluating the effect of the intervention on fatigue, health and sickness absence. If proven effective, the intervention can be applied as a new and practical tool in fatigue management. Results are expected at the end of 2013. Trial registration Netherlands Trial Register: NTR2722 PMID:23971514

Placebo versus low-dose ketamine infusion in addition to remifentanil target-controlled infusion for conscious sedation during oocyte retrieval: A prospective, double-blinded, randomised controlled trial.

PubMed

Morue, Hélène I; Raj-Lawrence, Shalini; Saxena, Sarah; Delbaere, Anne; Engelman, Edgard; Barvais, Luc A

2018-04-30

Currently, there is no gold standard for monitored anaesthesia care during oocyte retrieval. In our institution, the standard is a conscious sedation technique using a target-controlled infusion (TCI) of remifentanil, titrated to maintain a visual analogue pain score less than 30 mm. This protocol is well accepted by patients but is associated with frequent episodes of respiratory depression. The main objective of this study was to evaluate whether the addition of a continuous intravenous infusion of ketamine could reduce these episodes. Controlled, randomised, prospective, double-blinded study. The current study was conducted in a tertiary-level hospital in Brussels (Belgium) from December 2013 to June 2014. Of the 132 women undergoing oocyte retrieval included, 121 completed the study. After randomisation, patients received either a ketamine infusion (40 μg kg min over 5 min followed by 2.5 μg kg min) or a 0.9% saline infusion in addition to the variable remifentanil TCI. The primary outcome was the number of respiratory depression episodes. Effect site target remifentanil concentrations, side effects, pain score, patient satisfaction and incidence of pregnancy were also recorded. No significant difference in the incidence of respiratory events was noted (pulse oximetry oxygen saturation < 95% was 49% in the ketamine group and 63% in the control group; P = 0.121). No patient required ventilatory support. In the ketamine group, visual analogue pain score and remifentanil concentrations were significantly reduced, but the latter remained above 2 ng ml. Postoperative nausea was less frequent in the ketamine group, 4 versus 15% (P = 0.038). The addition of ketamine did not influence length of stay nor patient satisfaction. The addition of low plasma levels of ketamine to a TCI remifentanil conscious sedation technique did not decrease the incidence nor the severity of respiratory depression. Continuous monitoring of capnography and oxygen saturation is always required. EUDRACT number 2013-003040-23.

Development and evaluation of an intervention aiming to reduce fatigue in airline pilots: design of a randomised controlled trial.

PubMed

van Drongelen, Alwin; van der Beek, Allard J; Hlobil, Hynek; Smid, Tjabe; Boot, Cécile R L

2013-08-26

A considerable percentage of flight crew reports to be fatigued regularly. This is partly caused by irregular and long working hours and the crossing of time zones. It has been shown that persistent fatigue can lead to health problems, impaired performance during work, and a decreased work-private life balance. It is hypothesized that an intervention consisting of tailored advice regarding exposure to daylight, optimising sleep, physical activity, and nutrition will lead to a reduction of fatigue in airline pilots compared to a control group, which receives a minimal intervention with standard available information. The study population will consist of pilots of a large airline company. All pilots who posses a smartphone or tablet, and who are not on sick leave for more than four weeks at the moment of recruitment, will be eligible for participation.In a two-armed randomised controlled trial, participants will be allocated to an intervention group that will receive the tailored advice to optimise exposure to daylight, sleep, physical activity and nutrition, and a control group that will receive standard available information. The intervention will be applied using a smartphone application and a website, and will be tailored on flight- and participant-specific characteristics. The primary outcome of the study is perceived fatigue. Secondary outcomes are need for recovery, duration and quality of sleep, dietary and physical activity behaviours, work-private life balance, general health, and sickness absence. A process evaluation will be conducted as well. Outcomes will be measured at baseline and at three and six months after baseline. This paper describes the development of an intervention for airline pilots, consisting of tailored advice (on exposure to daylight and sleep-, physical activity, and nutrition) applied into a smartphone application. Further, the paper describes the design of the randomised controlled trial evaluating the effect of the intervention on fatigue, health and sickness absence. If proven effective, the intervention can be applied as a new and practical tool in fatigue management. Results are expected at the end of 2013. Netherlands Trial Register: NTR2722.

Different systolic blood pressure targets for people with history of stroke or transient ischaemic attack: PAST-BP (Prevention After Stroke—Blood Pressure) randomised controlled trial

PubMed Central

McManus, Richard J; Roalfe, Andrea; Fletcher, Kate; Taylor, Clare J; Martin, Una; Virdee, Satnam; Greenfield, Sheila; Hobbs, F D Richard

2016-01-01

Objective To assess whether using intensive blood pressure targets leads to lower blood pressure in a community population of people with prevalent cerebrovascular disease. Design Open label randomised controlled trial. Setting 99 general practices in England, with participants recruited in 2009-11. Participants People with a history of stroke or transient ischaemic attack whose systolic blood pressure was 125 mm Hg or above. Interventions Intensive systolic blood pressure target (<130 mm Hg or 10 mm Hg reduction from baseline if this was <140 mm Hg) or standard target (<140 mm Hg). Apart from the different target, patients in both arms were actively managed in the same way with regular reviews by the primary care team. Main outcome measure Change in systolic blood pressure between baseline and 12 months. Results 529 patients (mean age 72) were enrolled, 266 to the intensive target arm and 263 to the standard target arm, of whom 379 were included in the primary analysis (182 (68%) intensive arm; 197 (75%) standard arm). 84 patients withdrew from the study during the follow-up period (52 intensive arm; 32 standard arm). Mean systolic blood pressure dropped by 16.1 mm Hg to 127.4 mm Hg in the intensive target arm and by 12.8 mm Hg to 129.4 mm Hg in the standard arm (difference between groups 2.9 (95% confidence interval 0.2 to 5.7) mm Hg; P=0.03). Conclusions Aiming for target below 130 mm Hg rather than 140 mm Hg for systolic blood pressure in people with cerebrovascular disease in primary care led to a small additional reduction in blood pressure. Active management of systolic blood pressure in this population using a <140 mm Hg target led to a clinically important reduction in blood pressure. Trial registration Current Controlled Trials ISRCTN29062286. PMID:26919870

Kangaroo mother care for the prevention of neonatal hypothermia: a randomised controlled trial in term neonates.

PubMed

Ramani, Manimaran; Choe, Eunjoo A; Major, Meggin; Newton, Rebecca; Mwenechanya, Musaku; Travers, Colm P; Chomba, Elwyn; Ambalavanan, Namasivayam; Carlo, Waldemar A

2018-05-01

To test the hypothesis that kangaroo mother care (KMC) initiated either at birth or at 1 hour after birth reduces moderate or severe hypothermia in term neonates at (A) 1 hour after birth and (B) at discharge when compared with standard thermoregulation care. Term neonates born at a tertiary delivery centre in Zambia were randomised in two phases (phase 1: birth to 1 hour, phase 2: 1 hour to discharge) to either as much KMC as possible in combination with standard thermoregulation care (KMC group) or to standard thermoregulation care (control group). The primary outcomes were moderate or severe hypothermia (axillary temperature <36.0°C) at (A) 1 hour after birth and (B) at discharge. The proportion of neonates with moderate or severe hypothermia did not differ between the KMC and control groups at 1 hour after birth (25% vs 27%, relative risk (RR)=0.93, 95% CI 0.59 to 1.4, P=0.78) or at discharge (7% vs 2%, RR=2.8, 95% CI 0.6 to 13.9, P=0.16). Hypothermia was not found among the infants who had KMC for at least 9 hours or 80% of the hospital stay. KMC practised as much as possible in combination with standard thermoregulation care initiated either at birth or at 1 hour after birth did not reduce moderate or severe hypothermia in term infants compared with standard thermoregulation care. The current study also shows that duration of KMC either for at least 80% of the time or at least 9 hours during the day of birth was effective in preventing hypothermia in term infants. NCT02189759. © 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.

Regular long-term red blood cell transfusions for managing chronic chest complications in sickle cell disease

PubMed Central

Estcourt, Lise J; Fortin, Patricia M; Hopewell, Sally; Trivella, Marialena; Hambleton, Ian R; Cho, Gavin

2016-01-01

Background Sickle cell disease is a genetic haemoglobin disorder, which can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Sickle cell disease is one of the most common severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. The two most common chronic chest complications due to sickle cell disease are pulmonary hypertension and chronic sickle lung disease. These complications can lead to morbidity (such as reduced exercise tolerance) and increased mortality. This is an update of a Cochrane review first published in 2011 and updated in 2014. Objectives We wanted to determine whether trials involving people with sickle cell disease that compare regular long-term blood transfusion regimens with standard care, hydroxycarbamide (hydroxyurea) any other drug treatment show differences in the following: mortality associated with chronic chest complications; severity of established chronic chest complications; development and progression of chronic chest complications; serious adverse events. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register. Date of the last search: 25 April 2016. We also searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 26 January 2016), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 26 January 2016. Selection criteria We included randomised controlled trials of people of any age with one of four common sickle cell disease genotypes, i.e. Hb SS, Sß0, SC, or Sß+ that compared regular red blood cell transfusion regimens (either simple or exchange transfusions) to hydroxycarbamide, any other drug treatment, or to standard care that were aimed at reducing the development or progression of chronic chest complications (chronic sickle lung and pulmonary hypertension). Data collection and analysis We used the standard methodological procedures expected by Cochrane. Main results No studies matching the selection criteria were found. Authors’ conclusions There is a need for randomised controlled trials looking at the role of long-term transfusion therapy in pulmonary hypertension and chronic sickle lung disease. Due to the chronic nature of the conditions, such trials should aim to use a combination of objective and subjective measures to assess participants repeatedly before and after the intervention. PMID:27198469

Push versus gravity for intermittent bolus gavage tube feeding of premature and low birth weight infants.

PubMed

Dawson, Jennifer A; Summan, Ravinder; Badawi, Nadia; Foster, Jann P

2012-11-14

Many small, sick and premature infants are unable to coordinate sucking, swallowing and breathing, and therefore, require gavage feeding. In gavage feeding, milk feeds are delivered through a tube passed via the nose or mouth into the stomach. Intermittent bolus milk feeds may be administered using a syringe to gently push milk into the infant's stomach (push feed). Alternatively, milk can be poured into a syringe attached to the tube and allowed to drip in by gravity (gravity feed). To determine whether the use of push compared with gravity gavage feeding results in a more rapid establishment of full gavage feeds without increasing adverse events in preterm or low birth weight, infants who require intermittent bolus gavage feeding. We searched the following electronic databases to locate randomised controlled or quasi-randomised trials: Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2012, Issue 5), MEDLINE (from 1966 to May 2012), EMBASE (from 1980 to May 2012), and CINAHL (from 1982 to May 2012). We used the standard search strategy of the Cochrane Neonatal Review Group. Randomised or quasi-randomised controlled trials comparing push versus gravity intermittent gavage tube feeding in premature or low birth weight, or both, infants. We assessed the methodology of trials regarding blinding of randomisation and outcome measurement. We evaluated treatment effect with a fixed-effect model using risk ratio (RR), relative risk reduction, risk difference (RD) and number needed to treat (NNT) for categorical data; and using mean, standard deviation and weighted mean difference (WMD) for continuous data. We analysed outcomes measured as count data, for example frequency of apnoea, bradycardia and episodes of pulse oximeter oxygen (SpO(2)) desaturation, by comparing rates of events and the rate ratio. We evaluated heterogeneity to help determine the suitability of pooling results. Only one small cross-over trial met the criteria for inclusion in this review and therefore meta-analysis for any of the treatment outcomes was not performed. Symon 1994 reported a trend towards a higher respiratory rate at 10 to 30 minutes following push gavage feeding and no statistical difference in the time taken to give the feeds regardless of the method used. There was one small cross-over study that was included in this review. There is insufficient evidence to recommend either method of gavage feeding. A randomised trial is needed to evaluate the benefits and harms of push versus gravity bolus tube feeding in preterm infants. Infants should be stratified by gestational age at birth (above and below 32 weeks) or birth weight (above and below 1500 grams) and respiratory support (ventilated versus non-ventilated) and the sample size should be of sufficient size to evaluate the primary outcomes outlined in this review (time to establish full tube feeds and feeding intolerance).

Standard cardiopulmonary resuscitation versus active compression-decompression cardiopulmonary resuscitation with augmentation of negative intrathoracic pressure for out-of-hospital cardiac arrest: a randomised trial.

PubMed

Aufderheide, Tom P; Frascone, Ralph J; Wayne, Marvin A; Mahoney, Brian D; Swor, Robert A; Domeier, Robert M; Olinger, Michael L; Holcomb, Richard G; Tupper, David E; Yannopoulos, Demetris; Lurie, Keith G

2011-01-22

Active compression-decompression cardiopulmonary resuscitation (CPR) with decreased intrathoracic pressure in the decompression phase can lead to improved haemodynamics compared with standard CPR. We aimed to assess effectiveness and safety of this intervention on survival with favourable neurological function after out-of-hospital cardiac arrest. In our randomised trial of 46 emergency medical service agencies (serving 2·3 million people) in urban, suburban, and rural areas of the USA, we assessed outcomes for patients with out-of-hospital cardiac arrest according to Utstein guidelines. We provisionally enrolled patients to receive standard CPR or active compression-decompression CPR with augmented negative intrathoracic pressure (via an impedance-threshold device) with a computer-generated block randomisation weekly schedule in a one-to-one ratio. Adults (presumed age or age ≥18 years) who had a non-traumatic arrest of presumed cardiac cause and met initial and final selection criteria received designated CPR and were included in the final analyses. The primary endpoint was survival to hospital discharge with favourable neurological function (modified Rankin scale score of ≤3). All investigators apart from initial rescuers were masked to treatment group assignment. This trial is registered with ClinicalTrials.gov, number NCT00189423. 2470 provisionally enrolled patients were randomly allocated to treatment groups. 813 (68%) of 1201 patients assigned to the standard CPR group (controls) and 840 (66%) of 1269 assigned to intervention CPR received designated CPR and were included in the final analyses. 47 (6%) of 813 controls survived to hospital discharge with favourable neurological function compared with 75 (9%) of 840 patients in the intervention group (odds ratio 1·58, 95% CI 1·07-2·36; p=0·019]. 74 (9%) of 840 patients survived to 1 year in the intervention group compared with 48 (6%) of 813 controls (p=0·03), with equivalent cognitive skills, disability ratings, and emotional-psychological statuses in both groups. The overall major adverse event rate did not differ between groups, but more patients had pulmonary oedema in the intervention group (94 [11%] of 840) than did controls (62 [7%] of 813; p=0·015). On the basis of our findings showing increased effectiveness and generalisability of the study intervention, active compression-decompression CPR with augmentation of negative intrathoracic pressure should be considered as an alternative to standard CPR to increase long-term survival after cardiac arrest. US National Institutes of Health grant R44-HL065851-03, Advanced Circulatory Systems. Copyright © 2011 Elsevier Ltd. All rights reserved.

Migration and head penetration of Vitamin-E diffused cemented polyethylene cup compared to standard cemented cup in total hip arthroplasty: study protocol for a randomised, double-blind, controlled trial (E1 HIP).

PubMed

Sköldenberg, Olof; Rysinska, Agata; Chammout, Ghazi; Salemyr, Mats; Muren, Olle; Bodén, Henrik; Eisler, Thomas

2016-07-07

In vitro, Vitamin-E-diffused, highly cross-linked polyethylene (PE) has been shown to have superior wear resistance and improved mechanical properties when compared to those of standard highly cross-linked PE liners used in total hip arthroplasty (THA). The aim of the study is to evaluate the safety of a new cemented acetabular cup with Vitamin-E-doped PE regarding migration, head penetration and clinical results. In this single-centre, double-blinded, randomised controlled trial, we will include 50 patients with primary hip osteoarthritis scheduled for THA and randomise them in a 1:1 ratio to a cemented cup with either argon gas-sterilised PE (control group) or Vitamin-E-diffused PE (vitamin-e group). All patients and the assessor of the primary outcome will be blinded and the same uncemented stem will be used for all participants. The primary end point will be proximal migration of the cup at 2 years after surgery measured with radiostereometry. Secondary end points include proximal migration at other follow-ups, total migration, femoral head penetration, clinical outcome scores and hip-related complications. Patients will be followed up at 3 months and at 1, 2, 5 and 10 years postoperatively. Results will be analysed using 95% CIs for the effect size. A regression model will also be used to adjust for stratification factors. The ethical committee at Karolinska Institutet has approved the study. The first results from the study will be disseminated to the medical community via presentations and publications in relevant medical journals when the last patient included has been followed up for 2 years. NCT02254980. 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/

Protocol for a randomised control trial of bisphosphonate (zoledronic acid) treatment in childhood femoral head avascular necrosis due to Perthes disease

PubMed Central

Zacharin, Margaret; Foster, Bruce; Donald, Geoffrey; Hassall, Timothy; Siafarikas, Aris; Johnson, Michael; Tham, Elaine; Whitewood, Colin; Gebski, Val; Cowell, Chris T; Little, David Graham; Munns, Craig Frank

2017-01-01

Introduction Perthes disease (PD) is an idiopathic disorder presenting with avascular necrosis to the femoral head, which frequently results in flattening. Long-term function is directly related to the subsequent femoral head sphericity. Current treatment includes mechanical modalities and surgical procedures, which are therapeutic but are not uniformly able to prevent collapse. The use of the nitrogen-containing bisphosphonate zoledronic acid (ZA) to inhibit osteoclastic bone resorption is aimed at preserving femoral head strength, reducing collapse and thus maintaining shape. The proposed multicentre, prospective, randomised controlled trial intends to evaluate the efficacy of ZA treatment in PD. Methods and analysis An open-label randomised control trial recruiting 100 children (50 each treatment arm) 5 to 16 years old with unilateral PD. Subjects are randomly assigned to either (a) ZA and standard care or (b) Standard care. The primary outcome measure is deformity index (DI), a radiographic parameter of femoral head roundness assessed at 24 months, following 12 months of ZA treatment (3-monthly doses of ZA 0.025 mg/kg at baseline, 3, 6, 9 and 12 months) plus 12 months observation (group A) or 24 months of observation (group B). Secondary outcome measures are femoral head subluxation, Faces Pain scale, Harris hip score and quality of life. Assessments are made at baseline, 3 monthly during the first year of follow-up and then 6 monthly, until the 24th month. Ethics and dissemination The study commenced following the written approval from the Human Research Ethics Committee. Safety considerations regarding the effects of ZA are monitored which include the subject’s symptomatology, mineral status, bone mass and turnover activity, and metaphyseal modelling. Data handling plan requires that all documents, clinical information, biological samples and investigation results will be held in strict confidence by study investigators to preserve its safety and confidentiality. Trial registration number Australian and New Zealand Clinical Trials ACTRN12610000407099, pre-results. PMID:29637122

A systematic review of randomised controlled trials of the effects of warmed irrigation fluid on core body temperature during endoscopic surgeries.

PubMed

Jin, Yinghui; Tian, Jinhui; Sun, Mei; Yang, Kehu

2011-02-01

The purpose of this systematic review was to establish whether warmed irrigation fluid temperature could decrease the drop of body temperature and incidence of shivering and hypothermia. Irrigation fluid, which is used in large quantities during endoscopic surgeries at room temperature, is considered to be associated with hypothermia and shivering. It remains controversial whether using warmed irrigation fluid to replace room-temperature irrigation fluid will decrease the drop of core body temperature and the occurrence of hypothermia. A comprehensive search (computerised database searches, footnote chasing, citation chasing) was undertaken to identify all the randomised controlled trials that explored temperature of irrigation fluid in endoscopic surgery. An approach involving meta-analysis was used. We searched PubMed, EMBASE, Cochrane Library, SCI, China academic journals full-text databases, Chinese Biomedical Literature Database, Chinese scientific journals databases and Chinese Medical Association Journals for trials that meet the inclusion criteria. Study quality was assessed using standards recommended by Cochrane Library Handbook 5.0.1. Disagreement was resolved by consensus. Thirteen randomised controlled trials including 686 patients were identified. The results showed that room-temperature irrigation fluid caused a greater drop of core body temperature in patients, compared to warmed irrigation fluid (p < 0.00001; I(2) = 85%). The occurrence of shivering [odds ratio (OR) 5.13, 95% CI: 2.95-10.19, p < 0.00001; I(2) = 0%] and hypothermia (OR 22.01, 95% CI: 2.03-197.08, p = 0.01; I(2) = 64%) in the groups having warmed irrigation fluid were lower than the group of studies having room-temperature fluid. In endoscopic surgeries, irrigation fluid is recommended to be warmed to decrease the drop of core body temperature and the risk of perioperative shivering and hypothermia. Warming irrigating fluid should be considered standard practice in all endoscopic surgeries. © 2011 Blackwell Publishing Ltd.

Migration and head penetration of Vitamin-E diffused cemented polyethylene cup compared to standard cemented cup in total hip arthroplasty: study protocol for a randomised, double-blind, controlled trial (E1 HIP)

PubMed Central

Sköldenberg, Olof; Rysinska, Agata; Chammout, Ghazi; Salemyr, Mats; Muren, Olle; Bodén, Henrik; Eisler, Thomas

2016-01-01

Introduction In vitro, Vitamin-E-diffused, highly cross-linked polyethylene (PE) has been shown to have superior wear resistance and improved mechanical properties when compared to those of standard highly cross-linked PE liners used in total hip arthroplasty (THA). The aim of the study is to evaluate the safety of a new cemented acetabular cup with Vitamin-E-doped PE regarding migration, head penetration and clinical results. Methods and analysis In this single-centre, double-blinded, randomised controlled trial, we will include 50 patients with primary hip osteoarthritis scheduled for THA and randomise them in a 1:1 ratio to a cemented cup with either argon gas-sterilised PE (control group) or Vitamin-E-diffused PE (vitamin-e group). All patients and the assessor of the primary outcome will be blinded and the same uncemented stem will be used for all participants. The primary end point will be proximal migration of the cup at 2 years after surgery measured with radiostereometry. Secondary end points include proximal migration at other follow-ups, total migration, femoral head penetration, clinical outcome scores and hip-related complications. Patients will be followed up at 3 months and at 1, 2, 5 and 10 years postoperatively. Results Results will be analysed using 95% CIs for the effect size. A regression model will also be used to adjust for stratification factors. Ethics and dissemination The ethical committee at Karolinska Institutet has approved the study. The first results from the study will be disseminated to the medical community via presentations and publications in relevant medical journals when the last patient included has been followed up for 2 years. Trial registration number NCT02254980. PMID:27388352

Safety and efficacy of antenatal milk expressing for women with diabetes in pregnancy: protocol for a randomised controlled trial

PubMed Central

Forster, Della A; Jacobs, Susan; Amir, Lisa H; Davis, Peter; Walker, Susan P; McEgan, Kerri; Opie, Gillian; Donath, Susan M; Moorhead, Anita M; Ford, Rachael; McNamara, Catharine; Aylward, Amanda; Gold, Lisa

2014-01-01

Introduction Many maternity providers recommend that women with diabetes in pregnancy express and store breast milk in late pregnancy so breast milk is available after birth, given (1) infants of these women are at increased risk of hypoglycaemia in the first 24 h of life; and (2) the delay in lactogenesis II compared with women without diabetes that increases their infant's risk of receiving infant formula. The Diabetes and Antenatal Milk Expressing (DAME) trial will establish whether advising women with diabetes in pregnancy (pre-existing or gestational) to express breast milk from 36 weeks gestation increases the proportion of infants who require admission to special or neonatal intensive care units (SCN/NICU) compared with infants of women receiving standard care. Secondary outcomes include birth gestation, breastfeeding outcomes and economic impact. Methods and analysis Women will be recruited from 34 weeks gestation to a multicentre, two arm, unblinded randomised controlled trial. The intervention starts at 36 weeks. Randomisation will be stratified by site, parity and diabetes type. Women allocated to the intervention will be taught expressing and encouraged to hand express twice daily for 10 min and keep an expressing diary. The sample size of 658 (329 per group) will detect a 10% difference in proportion of babies admitted to SCN/NICU (85% power, α 0.05). Data are collected at recruitment (structured questionnaire), after birth (abstracted from medical record blinded to group), and 2 and 12 weeks postpartum (telephone interview). Data analysis: the intervention group will be compared with the standard care group by intention to treat analysis, and the primary outcome compared using χ2 and ORs. Ethics and dissemination Research ethics approval will be obtained from participating sites. Results will be published in peer-reviewed journals and presented to clinicians, policymakers and study participants. Trial registration number Australian Controlled Trials Register ACTRN12611000217909. PMID:25358679

The RATPAC (Randomised Assessment of Treatment using Panel Assay of Cardiac markers) trial: a randomised controlled trial of point-of-care cardiac markers in the emergency department.

PubMed

Goodacre, S; Bradburn, M; Fitzgerald, P; Cross, E; Collinson, P; Gray, A; Hall, A S

2011-05-01

To evaluate the clinical effectiveness and cost-effectiveness of using a point-of-care cardiac marker panel in patients presenting to the emergency department (ED) with suspected but not proven acute myocardial infarction (AMI). Multicentre pragmatic open randomised controlled trial and economic evaluation. Six acute hospital EDs in the UK. Adults presenting to hospital with chest pain due to suspected but not proven myocardial infarction, and no other potentially serious alternative pathology or comorbidity. Participants were allocated using an online randomisation system to receive either (1) diagnostic assessment using the point-of-care biochemical marker panel or (2) conventional diagnostic assessment without the panel. All tests and treatments other than the panel were provided at the discretion of the clinician. The primary outcome was the proportion of patients successfully discharged home after ED assessment, defined as patients who had (1) either left the hospital or were awaiting transport home with a discharge decision having been made at 4 hours after initial presentation and (2) suffered no major adverse event (as defined below) during the following 3 months. Secondary outcomes included length of initial hospital stay and total inpatient days over 3 months, and major adverse events (death, non-fatal AMI, life-threatening arrhythmia, emergency revascularisation or hospitalisation for myocardial ischaemia). Economic analysis estimated mean costs and quality-adjusted life-years (QALYs), and then estimated the probability of cost-effectiveness assuming willingness to pay of £20,000 per QALY gained. We randomised 1132 participants to point of care and 1131 to standard care, and analysed 1125 and 1118, respectively [mean age 54.5 years, 1307/2243 (58%) male and 269/2243 (12%) with known coronary heart disease (CHD)]. In the point-of-care group 358/1125 (32%) were successfully discharged compared with 146/1118 (13%) in the standard-care group [odds ratio (OR) adjusted for age, gender and history of CHD 3.81; 95% confidence interval (CI) 3.01 to 4.82, p < 0.001]. Mean length of the initial hospital stay was 29.6 hours versus 31.8 hours (mean difference = 2.1 hours; 95% CI -3.7 to 8.0 hours, p = 0.462), while median length of initial hospital stay was 8.8 hours versus 14.2 hours (p < 0.001). More patients in the point-of-care group had no inpatient days recorded during follow-up (54% vs 40%, p < 0.001), but mean inpatient days did not differ between the two groups (1.8 vs 1.7, p = 0.815). More patients in the point-of-care group were managed on coronary care [50/1125 (4%) vs 31/1118 (3%), p = 0.041]. There were 36 (3%) patients with major adverse events in the point-of-care group and 26 (2%) in the standard-care group (adjusted OR 1.31; 95% CI 0.78 to 2.20, p = 0.313). Mean costs per patient were £1217 with point-of-care versus £1006 with standard care (p = 0.056), while mean QALYs were 0.158 versus 0.161 (p = 0.250). The probability of standard care being dominant (i.e. cheaper and more effective) was 0.888. Point-of-care testing increases the proportion of patients successfully discharged home and reduces the median (but not mean) length of hospital stay. It is more expensive than standard care and unlikely to be considered cost-effective. Current Controlled Trials ISRCTN37823923. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 23. See the HTA programme website for further project information.

Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial

PubMed Central

2013-01-01

Objective To investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza. Design Double blind randomised trial. Setting Thirteen hospitals in Indonesia, Singapore, Thailand, and Vietnam. Participants Patients aged ≥1 year admitted to hospital with confirmed severe influenza. Interventions Oral oseltamivir at double dose (150 mg twice a day/paediatric equivalent) versus standard dose (75 mg twice a day/paediatric equivalent). Main outcome measure Viral status according to reverse transcriptase polymerase chain reaction (RT-PCR) for influenza RNA in nasal and throat swabs on day five. Results Of 326 patients (including 246 (75.5%) children aged <15), 165 and 161 were randomised to double or standard dose oseltamivir, respectively. Of these, 260 (79.8%) were infected with influenza virus A (133 (40.8%) with A/H3N2, 72 (22.1%) with A/H1N1-pdm09, 38 (11.7%) with seasonal A/H1N1, 17 (5.2%) with A/H5N1) and 53 (16.2%) with influenza virus B. A further 3.9% (13) were false positive by rapid antigen test (negative by RT-PCR and no rise in convalescent haemagglutination inhibition titers). Similar proportions of patients were negative for RT-PCR on day five of treatment: 115/159 (72.3%, 95% confidence interval 64.9% to 78.7%) double dose recipients versus 105/154 (68.2%, 60.5% to 75.0%) standard dose recipients; difference 4.2% (−5.9 to 14.2); P=0.42. No differences were found in clearance of virus in subgroup analyses by virus type/subtype, age, and duration of illness before randomisation. Mortality was similar: 12/165 (7.3%, 4.2% to 12.3%) in double dose recipients versus 9/161 (5.6%, 3.0% to 10.3%) in standard dose recipients. No differences were found between double and standard dose arms in median days on supplemental oxygen (3 (interquartile range 2-5) v 3.5 (2-7)), in intensive care (4.5 (3-6) v 5 (2-11), and on mechanical ventilation (2.5 (1-16) v 8 (1-16)), respectively. No important differences in tolerability were found. Conclusions There were no virological or clinical advantages with double dose oseltamivir compared with standard dose in patients with severe influenza admitted to hospital. Registration Clinical Trials NCT00298233 PMID:23723457

Exercise improves glycaemic control in women diagnosed with gestational diabetes mellitus: a systematic review.

PubMed

Harrison, Anne L; Shields, Nora; Taylor, Nicholas F; Frawley, Helena C

2016-10-01

Does exercise improve postprandial glycaemic control in women diagnosed with gestational diabetes mellitus? A systematic review of randomised trials. Pregnant women diagnosed with gestational diabetes mellitus. Exercise, performed more than once a week, sufficient to achieve an aerobic effect or changes in muscle metabolism. Postprandial blood glucose, fasting blood glucose, glycated haemoglobin, requirement for insulin, adverse events and adherence. This systematic review identified eight randomised, controlled trials involving 588 participants; seven trials (544 participants) had data that were suitable for meta-analysis. Five trials scored ≥ 6 on the PEDro scale, indicating a relatively low risk of bias. Meta-analysis showed that exercise, as an adjunct to standard care, significantly improved postprandial glycaemic control (MD -0.33mmol/L, 95% CI -0.49 to -0.17) and lowered fasting blood glucose (MD -0.31 mmol/L, 95% CI -0.56 to -0.05) when compared with standard care alone, with no increase in adverse events. Effects of similar magnitude were found for aerobic and resistance exercise programs, if performed at a moderate intensity or greater, for 20 to 30minutes, three to four times per week. Meta-analysis did not show that exercise significantly reduced the requirement for insulin. All studies reported that complications or other adverse events were either similar or reduced with exercise. Aerobic or resistance exercise, performed at a moderate intensity at least three times per week, safely helps to control postprandial blood glucose levels and other measures of glycaemic control in women diagnosed with gestational diabetes mellitus. PROSPERO CRD42015019106. [Harrison AL, Shields N, Taylor NF, Frawley HC (2016) Exercise improves glycaemic control in women diagnosed with gestational diabetes mellitus: a systematic review.Journal of Physiotherapy62: 188-196]. Copyright © 2016 Australian Physiotherapy Association. Published by Elsevier B.V. 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.

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

PubMed Central

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

1996-01-01

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

Randomised controlled comparison of the Health Survey Short Form (SF-12) and the Graded Chronic Pain Scale (GCPS) in telephone interviews versus self-administered questionnaires. Are the results equivalent?

PubMed

Lungenhausen, Margitta; Lange, Stefan; Maier, Christoph; Schaub, Claudia; Trampisch, Hans J; Endres, Heinz G

2007-11-22

The most commonly used survey methods are self-administered questionnaires, telephone interviews, and a mixture of both. But until now evidence out of randomised controlled trials as to whether patient responses differ depending on the survey mode is lacking. Therefore this study assessed whether patient responses to surveys depend on the mode of survey administration. The comparison was between mailed, self-administered questionnaires and telephone interviews. A four-armed, randomised controlled two-period change-over design. Each patient responded to the same survey twice, once in written form and once by telephone interview, separated by at least a fortnight. The study was conducted in 2003/2004 in Germany. 1087 patients taking part in the German Acupuncture Trials (GERAC cohort study), who agreed to participate in a survey after completing acupuncture treatment from an acupuncture-certified family physician for headache, were randomised. Of these, 823 (664 women) from the ages of 18 to 83 (mean 51.7) completed both parts of the study. The main outcome measure was the comparison of the scores on the 12-Item Short-Form Health Survey (SF-12) and the Graded Chronic Pain Scale (GCPS) questionnaire for the two survey modes. Computer-aided telephone interviews (CATI) resulted in significantly fewer missing data (0.5%) than did mailed questionnaires (2.8%; p < 0.001). The analysis of equivalence revealed a difference between the survey modes only for the SF-12 mental scales. On average, reported mental status score was 3.5 score points (2.9 to 4.0) lower on the self-administered questionnaire compared to the telephone interview. The order of administration affected results. Patients who responded to the telephone interview first reported better mental health in the subsequent paper questionnaire (mean difference 2.8 score points) compared to those who responded to the paper questionnaire first (mean difference 4.1 score points). Despite the comparatively high cost of telephone interviews, they offer clear advantages over mailed self-administered questionnaires as regards completeness of data. Only items concerning mental status were dependent on the survey mode and sequence of administration. Items on physical status were not affected. Normative data for standardized telephone questionnaires could contribute to a better comparability with the results of the corresponding standardized paper questionnaires.

Randomised controlled comparison of the Health Survey Short Form (SF-12) and the Graded Chronic Pain Scale (GCPS) in telephone interviews versus self-administered questionnaires. Are the results equivalent?

PubMed Central

Lungenhausen, Margitta; Lange, Stefan; Maier, Christoph; Schaub, Claudia; Trampisch, Hans J; Endres, Heinz G

2007-01-01

Background The most commonly used survey methods are self-administered questionnaires, telephone interviews, and a mixture of both. But until now evidence out of randomised controlled trials as to whether patient responses differ depending on the survey mode is lacking. Therefore this study assessed whether patient responses to surveys depend on the mode of survey administration. The comparison was between mailed, self-administered questionnaires and telephone interviews. Methods A four-armed, randomised controlled two-period change-over design. Each patient responded to the same survey twice, once in written form and once by telephone interview, separated by at least a fortnight. The study was conducted in 2003/2004 in Germany. 1087 patients taking part in the German Acupuncture Trials (GERAC cohort study), who agreed to participate in a survey after completing acupuncture treatment from an acupuncture-certified family physician for headache, were randomised. Of these, 823 (664 women) from the ages of 18 to 83 (mean 51.7) completed both parts of the study. The main outcome measure was the comparison of the scores on the 12-Item Short-Form Health Survey (SF-12) and the Graded Chronic Pain Scale (GCPS) questionnaire for the two survey modes. Results Computer-aided telephone interviews (CATI) resulted in significantly fewer missing data (0.5%) than did mailed questionnaires (2.8%; p < 0.001). The analysis of equivalence revealed a difference between the survey modes only for the SF-12 mental scales. On average, reported mental status score was 3.5 score points (2.9 to 4.0) lower on the self-administered questionnaire compared to the telephone interview. The order of administration affected results. Patients who responded to the telephone interview first reported better mental health in the subsequent paper questionnaire (mean difference 2.8 score points) compared to those who responded to the paper questionnaire first (mean difference 4.1 score points). Conclusion Despite the comparatively high cost of telephone interviews, they offer clear advantages over mailed self-administered questionnaires as regards completeness of data. Only items concerning mental status were dependent on the survey mode and sequence of administration. Items on physical status were not affected. Normative data for standardized telephone questionnaires could contribute to a better comparability with the results of the corresponding standardized paper questionnaires. PMID:18034900

Effects of an interactive mHealth innovation for early detection of patient-reported symptom distress with focus on participatory care: protocol for a study based on prospective, randomised, controlled trials in patients with prostate and breast cancer.

PubMed

Langius-Eklöf, Ann; Crafoord, Marie-Therése; Christiansen, Mats; Fjell, Maria; Sundberg, Kay

2017-07-04

Cancer patients are predominantly treated as out-patients and as they often experience difficult symptoms and side effects it is important to facilitate and improve patient-clinician communication to support symptom management and self-care. Although the number of projects within supportive cancer care evaluating mobile health is increasing, few evidence-based interventions are described in the literature and thus there is a need for good quality clinical studies with a randomised design and sufficient power to guide future implementations. An interactive information and communications technology platform, including a smartphone/computer tablet app for reporting symptoms during cancer treatment was created in collaboration with a company specialising in health care management. The aim of this paper is to evaluate the effects of using the platform for patients with breast cancer during neo adjuvant chemotherapy treatment and patients with locally advanced prostate cancer during curative radiotherapy treatment. The main hypothesis is that the use of the platform will improve clinical management, reduce costs, and promote safe and participatory care. The study is a prospective, randomised, controlled trial for each patient group and it is based on repeated measurements. Patients are consecutively included and randomised. The intervention groups report symptoms via the app daily, during treatment and up to three weeks after end of treatment, as a complement to standard care. Patients in the control groups receive standard care alone. Outcomes targeted are symptom burden, quality of life, health literacy (capacity to understand and communicate health needs and promote healthy behaviours), disease progress and health care costs. Data will be collected before and after treatment by questionnaires, registers, medical records and biomarkers. Lastly, participants will be interviewed about participatory and meaningful care. Results will generate knowledge to enhance understanding about how to develop person-centred care using mobile technology. Supporting patients' involvement in their care to identify problems early, promotes more timely initiation of necessary treatment. This can benefit patients treated outside the hospital setting in regard to maintaining their safety. June 12 2015 NCT02477137 (Prostate cancer) and June 12 2015 NCT02479607 (Breast cancer).

The Sternal Management Accelerated Recovery Trial (S.M.A.R.T) - standard restrictive versus an intervention of modified sternal precautions following cardiac surgery via median sternotomy: study protocol for a randomised controlled trial.

PubMed

Katijjahbe, Md Ali; Denehy, Linda; Granger, Catherine L; Royse, Alistair; Royse, Colin; Bates, Rebecca; Logie, Sarah; Clarke, Sandy; El-Ansary, Doa

2017-06-23

The routine implementation of sternal precautions to prevent sternal complications that restrict the use of the upper limbs is currently worldwide practice following a median sternotomy. However, evidence is limited and drawn primarily from cadaver studies and orthopaedic research. Sternal precautions may delay recovery, prolong hospital discharge and be overly restrictive. Recent research has shown that upper limb exercise reduces post-operative sternal pain and results in minimal micromotion between the sternal edges as measured by ultrasound. The aims of this study are to evaluate the effects of modified sternal precautions on physical function, pain, recovery and health-related quality of life after cardiac surgery. This study is a phase II, double-blind, randomised controlled trial with concealed allocation, blinding of patients and assessors, and intention-to-treat analysis. Patients (n = 72) will be recruited following cardiac surgery via a median sternotomy. Sample size calculations were based on the minimal important difference (two points) for the primary outcome: Short Physical Performance Battery. Thirty-six participants are required per group to counter dropout (20%). All participants will be randomised to receive either standard or modified sternal precautions. The intervention group will receive guidelines encouraging the safe use of the upper limbs. Secondary outcomes are upper limb function, pain, kinesiophobia and health-related quality of life. Descriptive statistics will be used to summarise data. The primary hypothesis will be examined by repeated-measures analysis of variance to evaluate the changes from baseline to 4 weeks post-operatively in the intervention arm compared with the usual-care arm. In all tests to be conducted, a p value <0.05 (two-tailed) will be considered statistically significant, and confidence intervals will be reported. The Sternal Management Accelerated Recovery Trial (S.M.A.R.T.) is a two-centre randomised controlled trial powered and designed to investigate whether the effects of modifying sternal precautions to include the safe use of the upper limbs and trunk impact patients' physical function and recovery following cardiac surgery via median sternotomy. Australian and New Zealand Clinical Trials Registry identifier: ACTRN12615000968572 . Registered on 16 September 2015 (prospectively 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.

[Effects of a dance therapy programme on quality of life, sleep and blood pressure in middle-aged women: A randomised controlled trial].

PubMed

Serrano-Guzmán, María; Valenza-Peña, Carmen M; Serrano-Guzmán, Carmen; Aguilar-Ferrándiz, Encarnación; Valenza-Demet, Gerald; Villaverde-Gutiérrez, Carmen

2016-10-21

Evidence suggests that dance therapy may have positive effects in areas such as cardiovascular parameters and sleep. The aim of the present study is to explore whether a dance therapy programme improves sleep and blood pressure in a population of middle-aged pre-hypertensive and hypertensive women. A randomised controlled trial was conducted, in which participants were assigned to one of 2 groups: standard care (with usual activities and medication) or dance therapy (in which the participants followed a dance therapy programme, in addition to their medication). The intervention was an 8-week, 3-times-per-week, progressive and specific group dance-training programme. The dance steps were specifically designed to improve balance by shifting the body and relocating the centre of gravity. The main measures obtained were blood pressure, sleep quality and quality of life, measured by the Pittsburgh Sleep Quality Index and the European Quality of Life Questionnaire. Sixty-seven pre-hypertensive and hypertensive middle-aged women were randomised to either an intervention group (n=35) or a control group (n=32) after baseline testing. The intervention group reported a significant improvement in blood pressure values (P<.01), as well as in sleep quality (P<.05) and quality of life (P<.001), compared to the control group. The dance therapy programme improved blood pressure, sleep and quality of life in pre-hypertensive and hypertensive middle-aged women, and constitutes an interesting basis for larger-scale research. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Task shifting of frontline community health workers for cardiovascular risk reduction: design and rationale of a cluster randomised controlled trial (DISHA study) in India.

PubMed

Jeemon, Panniyammakal; Narayanan, Gitanjali; Kondal, Dimple; Kahol, Kashvi; Bharadwaj, Ashok; Purty, Anil; Negi, Prakash; Ladhani, Sulaiman; Sanghvi, Jyoti; Singh, Kuldeep; Kapoor, Deksha; Sobti, Nidhi; Lall, Dorothy; Manimunda, Sathyaprakash; Dwivedi, Supriya; Toteja, Gurudyal; Prabhakaran, Dorairaj

2016-03-15

Effective task-shifting interventions targeted at reducing the global cardiovascular disease (CVD) epidemic in low and middle-income countries (LMICs) are urgently needed. DISHA is a cluster randomised controlled trial conducted across 10 sites (5 in phase 1 and 5 in phase 2) in India in 120 clusters. At each site, 12 clusters were randomly selected from a district. A cluster is defined as a small village with 250-300 households and well defined geographical boundaries. They were then randomly allocated to intervention and control clusters in a 1:1 allocation sequence. If any of the intervention and control clusters were <10 km apart, one was dropped and replaced with another randomly selected cluster from the same district. The study included a representative baseline cross-sectional survey, development of a structured intervention model, delivery of intervention for a minimum period of 18 months by trained frontline health workers (mainly Anganwadi workers and ASHA workers) and a post intervention survey in a representative sample. The study staff had no information on intervention allocation until the completion of the baseline survey. In order to ensure comparability of data across sites, the DISHA study follows a common protocol and manual of operation with standardized measurement techniques. Our study is the largest community based cluster randomised trial in low and middle-income country settings designed to test the effectiveness of 'task shifting' interventions involving frontline health workers for cardiovascular risk reduction. CTRI/2013/10/004049 . Registered 7 October 2013.

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

PubMed

Viksveen, Petter; Relton, Clare; Nicholl, Jon

2017-07-06

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

Evaluation of the Frails' Fall Efficacy by Comparing Treatments (EFFECT) on reducing fall and fear of fall in moderately frail older adults: study protocol for a randomised control trial

PubMed Central

2011-01-01

Background Falls are common in frail older adults and often result in injuries and hospitalisation. The Nintendo® Wii™ is an easily available exercise modality in the community which has been shown to improve lower limb strength and balance. However, not much is known on the effectiveness of the Nintendo® Wii™ to improve fall efficacy and reduce falls in a moderately frail older adult. Fall efficacy is the measure of fear of falling in performing various daily activities. Fear contributes to avoidance of activities and functional decline. Methods This randomised active-control trial is a comparison between the Nintendo WiiActive programme against standard gym-based rehabilitation of the older population. Eighty subjects aged above 60, fallers and non-fallers, will be recruited from the hospital outpatient clinic. The primary outcome measure is the Modified Falls Efficacy Scale and the secondary outcome measures are self-reported falls, quadriceps strength, walking agility, dynamic balance and quality of life assessments. Discussions The study is the first randomised control trial using the Nintendo Wii as a rehabilitation modality investigating a change in fall efficacy and self-reported falls. Longitudinally, the study will investigate if the interventions can successfully reduce falls and analyse the cost-effectiveness of the programme. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000576022 PMID:21682909

Transabdominal amnioinfusion in preterm premature rupture of membranes: a randomised controlled trial.

PubMed

Tranquilli, Andrea Luigi; Giannubilo, Stefano Raffaele; Bezzeccheri, Valeria; Scagnoli, Caterina

2005-06-01

To evaluate the role of transabdominal amnioinfusion in improving the perinatal outcomes of pregnancies complicated by preterm premature rupture of membranes (pPROM). A randomised controlled trial. A teaching hospital in Italy, obstetric unit. Population Women with singleton pregnancies complicated by pPROM, between 24 + 0 and 32 + 6 weeks of gestation. Patients were randomised 24 hours after admission to our referral hospital, to expectant management with transabdominal amnioinfusion or expectant management only. The effects of transabdominal amnioinfusion on pPROM-delivery interval and on perinatal outcomes. Of the 65 women with pPROM 34 met the inclusion criteria. Seventeen women were assigned to amnioinfusion (the amnioinfusion group) and the other 17 to expectant management. Compared with the control group (median: 8 days; range: 3-14), the pPROM-delivery period was significantly longer in women who underwent amnioinfusion (median: 21 days; range: 15-29) (P < 0.05). Women with amnioinfusion were less likely to deliver within seven days since pPROM (RR: 0.18; range: 0.04-0.69 95% CI) or within two weeks (RR: 0.46; range: 0.21-1.02 95% CI). In the amnioinfusion group the neonatal survival was significantly higher at each gestational age (P < 0.01, Yates's correction for Log Rank Test) with a reduction in pulmonary hypoplasia. We demonstrated that compared with standard expectant management the treatment with transabdominal amnioinfusion after pPROM resulted in significant prolongation of pregnancy and better neonatal outcomes.

Fidelity considerations in translational research: Eating As Treatment - a stepped wedge, randomised controlled trial of a dietitian delivered behaviour change counselling intervention for head and neck cancer patients undergoing radiotherapy.

PubMed

Beck, Alison Kate; Baker, Amanda; Britton, Ben; Wratten, Chris; Bauer, Judith; Wolfenden, Luke; Carter, Gregory

2015-10-15

The confidence with which researchers can comment on intervention efficacy relies on evaluation and consideration of intervention fidelity. Accordingly, there have been calls to increase the transparency with which fidelity methodology is reported. Despite this, consideration and/or reporting of fidelity methods remains poor. We seek to address this gap by describing the methodology for promoting and facilitating the evaluation of intervention fidelity in The EAT (Eating As Treatment) project: a multi-site stepped wedge randomised controlled trial of a dietitian delivered behaviour change counselling intervention to improve nutrition (primary outcome) in head and neck cancer patients undergoing radiotherapy. In accordance with recommendations from the National Institutes of Health Behaviour Change Consortium Treatment Fidelity Workgroup, we sought to maximise fidelity in this stepped wedge randomised controlled trial via strategies implemented from study design through to provider training, intervention delivery and receipt. As the EAT intervention is designed to be incorporated into standard dietetic consultations, we also address unique challenges for translational research. We offer a strong model for improving the quality of translational findings via real world application of National Institutes of Health Behaviour Change Consortium recommendations. Greater transparency in the reporting of behaviour change research is an important step in improving the progress and quality of behaviour change research. ACTRN12613000320752 (Date of registration 21 March 2013).

Guidelines for patient selection and performance of carotid artery stenting.

PubMed

2009-12-01

The endovascular treatment of carotid atherosclerosis with carotid artery stenting (CAS) remains controversial. Carotid endarterectomy (CEA) remains the benchmark in terms of procedural mortality and morbidity. Consensus Australasian guidelines for the safe performance of CAS were developed using the modified Delphi consensus method of iterative consultation. Selection of patients suitable for CAS needs careful consideration of clinical and patho-anatomical criteria. Randomised controlled trials and pooled analyses have demonstrated that CAS is more hazardous than CEA. The CGSC therefore recommends that CAS should not be performed in the majority of patients requiring carotid revascularisation. There is currently no evidence to support CAS as a treatment for asymptomatic carotid stenosis. The use of distal protection devices during CAS remains controversial with increased risk of clinically silent stroke. The knowledge requirements for the safe performance of CAS include an understanding of the evidence base from randomised controlled trials, carotid and aortic arch anatomy and pathology, and recognition and management of periprocedural complications. It is critical that all patients being considered for a carotid intervention have adequate pre-procedural neuroimaging and peri-procedural, independent, neurological assessment. Maintenance of proficiency in CAS requires active involvement in surgical/endovascular audit and continuing medical education programmes. These standards should apply in the public and private health-care settings. These guidelines represent the consensus of an intercollegiate committee in order to direct appropriate patient selection to perform CAS. Advances in endovascular technologies and the results of randomised controlled trials will guide future revisions of this document.

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.

COBI (COntinuous hyperosmolar therapy for traumatic Brain-Injured patients) trial protocol: a multicentre randomised open-label trial with blinded adjudication of primary outcome.

PubMed

Roquilly, Antoine; Lasocki, Sigismond; Moyer, Jean Denis; Huet, Olivier; Perrigault, Pierre François; Dahyot-Fizelier, Claire; Seguin, Philippe; Sharshar, Tarek; Geeraerts, Thomas; Remerand, Francis; Feuillet, Fanny; Asehnoune, Karim

2017-09-24

Traumatic brain injury (TBI) is a major cause of death and severe prolonged disability. Intracranial hypertension (ICH) is a critical risk factor of bad outcomes after TBI. Continuous infusion of hyperosmolar therapy has been proposed for the prevention and the treatment of ICH. Whether an early administration of continuous hyperosmolar therapy improves long-term outcomes of patients with TBI is uncertain. The aim of the COBI study (number clinicaltrial.gov 03143751, pre-results stage) is to assess the efficiency and the safety of continuous hyperosmolar therapy in patients with TBI. The COBI (COntinuous hyperosmolar therapy in traumatic Brain-Injured patients) trial is a multicentre, randomised, controlled, open-label, two-arms study with blinded adjudication of primary outcome. Three hundred and seventy patients hospitalised in intensive care unit with a TBI (Glasgow Coma Scale ≤12 and abnormal brain CT scan) are randomised in the first 24 hours following trauma to standard care or continuous hyperosmolar therapy (20% NaCl) plus standard care. Continuous hyperosmolar therapy is maintained for at least 48 hours in the treatment group and continued for as long as is necessary to prevent ICH. The primary outcome is the score on the Extended Glasgow Outcome Scale at 6 months. The treatment effect is estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common OR. The COBI trial protocol has been approved by the ethics committee of Paris Ile de France VIII and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. The COBI trial is the first randomised controlled trial powered to investigate whether continuous hyperosmolar therapy in patients with TBI improve long-term recovery. Trial registration number is NCT03143751. © 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 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

ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE): protocol for a multicentre randomised controlled trial.

PubMed

Iro, M A; Sadarangani, M; Absoud, M; Chong, W K; Clark, C A; Easton, A; Gray, V; Kneen, R; Lim, M; Pike, M; Solomon, T; Vincent, A; Willis, L; Yu, L-M; Pollard, A J

2016-11-03

Infectious and immune-mediated encephalitides are important but under-recognised causes of morbidity and mortality in childhood, with a 7% death rate and up to 50% morbidity after prolonged follow-up. There is a theoretical basis for ameliorating the immune response with intravenous immunoglobulin (IVIG), which is supported by empirical evidence of a beneficial response following its use in the treatment of viral and autoimmune encephalitis. In immune-mediated encephalitis, IVIG is often used after a delay (by weeks in some cases), while diagnosis is confirmed. Wider use of IVIG in infectious encephalitis and earlier use in immune-mediated encephalitis could improve outcomes for these conditions. We describe the protocol for the first ever randomised control trial of IVIG treatment for children with all-cause encephalitis. 308 children (6 months to 16 years) with a diagnosis of acute/subacute encephalitis will be recruited in ∼30 UK hospitals and randomised to receive 2 doses (1 g/kg/dose) of either IVIG or matching placebo, in addition to standard treatment. Recruitment will be over a 42-month period and follow-up of each participant will be for 12 months post randomisation. The primary outcome is 'good recovery' (score of 2 or lower on the Glasgow Outcome Score Extended-paediatric version), at 12 months after randomisation. Additional secondary neurological measures will be collected at 4-6 weeks after discharge from acute care and at 6 and 12 months after randomisation. Safety, radiological, other autoimmune and tertiary outcomes will also be assessed. This trial has been approved by the UK National Research Ethics committee (South Central-Oxford A; REC 14/SC/1416). Current protocol: V4.0 (10/03/2016). The findings will be presented at national and international meetings and conferences and published in peer-reviewed journals. NCT02308982, EudraCT201400299735 and ISRCTN15791925; 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/.

Telemonitoring-based service redesign for the management of uncontrolled hypertension (HITS): cost and cost-effectiveness analysis of a randomised controlled trial

PubMed Central

Stoddart, Andrew; Hanley, Janet; Wild, Sarah; Pagliari, Claudia; Paterson, Mary; Lewis, Steff; Sheikh, Aziz; Krishan, Ashma; Padfield, Paul; McKinstry, Brian

2013-01-01

Objectives To compare the costs and cost-effectiveness of managing patients with uncontrolled blood pressure (BP) using telemonitoring versus usual care from the perspective of the National Health Service (NHS). Design Within trial post hoc economic evaluation of data from a pragmatic randomised controlled trial using an intention-to-treat approach. Setting 20 socioeconomically diverse general practices in Lothian, Scotland. Participants 401 primary care patients aged 29–95 with uncontrolled daytime ambulatory blood pressure (ABP) (≥135/85, but <210/135 mm Hg). Intervention Participants were centrally randomised to 6 months of a telemonitoring service comprising of self-monitoring of BP transmitted to a secure website for review by the attending nurse/doctor and patient, with optional automated patient decision-support by text/email (n=200) or usual care (n-201). Randomisation was undertaken with minimisation for age, sex, family practice, use of three or more hypertension drugs and self-monitoring history. Main outcome measures Mean difference in total NHS costs between trial arms and blinded assessment of mean cost per 1 mm Hg systolic BP point reduced. Results Home telemonitoring of BP costs significantly more than usual care (mean difference per patient £115.32 (95% CI £83.49 to £146.63; p<0.001)). Increased costs were due to telemonitoring service costs, patient training and additional general practitioner and nurse consultations. The mean cost of systolic BP reduction was £25.56/mm Hg (95% CI £16.06 to £46.89) per patient. Conclusions Over the 6-month trial period, supported telemonitoring was more effective at reducing BP than usual care but also more expensive. If clinical gains are maintained, these additional costs would be very likely to be compensated for by reductions in the cost of future cardiovascular events. Longer-term modelling of costs and outcomes is required to fully examine the cost-effectiveness implications. Trial registration International Standard Randomised Controlled Trials, number ISRCTN72614272. PMID:23793650

Camino Verde (The Green Way): evidence-based community mobilisation for dengue control in Nicaragua and Mexico: feasibility study and study protocol for a randomised controlled trial.

PubMed

Andersson, Neil; Arostegui, Jorge; Nava-Aguilera, Elizabeth; Harris, Eva; Ledogar, Robert J

2017-05-30

Since the Aedes aegypti mosquitoes that transmit dengue virus can breed in clean water, WHO-endorsed vector control strategies place sachets of organophosphate pesticide, temephos (Abate), in household water storage containers. These and other pesticide-dependent approaches have failed to curb the spread of dengue and multiple dengue virus serotypes continue to spread throughout tropical and subtropical regions worldwide. A feasibility study in Managua, Nicaragua, generated instruments, intervention protocols, training schedules and impact assessment tools for a cluster randomised controlled trial of community-based approaches to vector control comprising an alternative strategy for dengue prevention and control in Nicaragua and Mexico. The Camino Verde (Green Way) is a pragmatic parallel group trial of pesticide-free dengue vector control, adding effectiveness to the standard government dengue control. A random sample from the most recent census in three coastal regions of Guerrero state in Mexico will generate 90 study clusters and the equivalent sampling frame in Managua, Nicaragua will generate 60 clusters, making a total of 150 clusters each of 137-140 households. After a baseline study, computer-driven randomisation will allocate to intervention one half of the sites, stratified by country, evidence of recent dengue virus infection in children aged 3-9 years and, in Nicaragua, level of community organisation. Following a common evidence-based education protocol, each cluster will develop and implement its own collective interventions including house-to-house visits, school-based programmes and inter-community visits. After 18 months, a follow-up study will compare dengue history, serological evidence of recent dengue virus infection (via measurement of anti-dengue virus antibodies in saliva samples) and entomological indices between intervention and control sites. Our hypothesis is that informed community mobilisation adds effectiveness in controlling dengue. ISRCTN27581154 .

3-D bone models to improve treatment initiation among patients with osteoporosis: A randomised controlled pilot trial.

PubMed

Stephens, Melika H; Grey, Andrew; Fernandez, Justin; Kalluru, Ramanamma; Faasse, Kate; Horne, Anne; Petrie, Keith J

2016-01-01

To investigate the efficacy of 3-D printed bone models as a tool to facilitate initiation of bisphosphonate treatment among individuals who were newly diagnosed with osteoporosis. Fifty eight participants with estimated fracture risk above that at which guidelines recommend pharmacological intervention were randomised to receive either a standard physician interview or an interview augmented by the presentation of 3-D bone models. Participants' beliefs about osteoporosis and bisphosphonate treatment, initiation of bisphosphonate therapy assessed at two months using self-report and pharmacy dispensing data. Individuals in the 3-D bone model intervention condition were more emotionally affected by osteoporosis immediately after the interview (p = .04) and reported a greater understanding of osteoporosis at follow-up (p = .04), than the control group. While a greater proportion of the intervention group initiated an oral bisphosphonate regimen (alendronate) (52%) in comparison with the control group (21%), the overall initiation of medication for osteoporosis, including infusion (zoledronate), did not differ significantly (intervention group 62%, control group 45%, p = .19). The presentation of 3-D bone models during a medical consultation can modify cognitive and emotional representations relevant to treatment initiation among people with osteoporosis and might facilitate commencement of bisphosphonate treatment.

The mind-body connection in irritable bowel syndrome: A randomised controlled trial of hypnotherapy as a treatment.

PubMed

Phillips-Moore, Julie S; Talley, Nicholas J; Jones, Michael P

2015-01-01

Hypnotherapy has been reported as being beneficial in the treatment of irritable bowel syndrome (IBS). We aimed to test the hypothesis that patients with IBS treated 'holistically' by hypnosis (i.e. by combined psychological and physiological symptom imagery) would have greater improvement in their IBS symptoms than patients treated by hypnosis using standard 'gut-directed' hypnotherapy, and both would be superior to simple relaxation therapy. Patients ( n  = 51) with Rome II criteria were randomised to 'individualised' (holistic) hypnotherapy, standard 'gut-directed' hypnotherapy or relaxation therapy for a period of 11 weeks with two follow-up assessments at 2 weeks and at 3 months after the completion of the trial. The primary outcome was bowel symptom severity scale (BSSS). All the participants in this study improved their IBS symptoms (pain, bloating, constipation and diarrhoea) and physical functioning at the end of the treatment from baseline, but this was not significantly different across the treatment arms. Neither 'individualised' nor 'gut-directed' hypnotherapy is superior to relaxation therapy in IBS.

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.

Exercise-based cardiac rehabilitation increases daily physical activity of patients following myocardial infarction: subanalysis of two randomised controlled trials.

PubMed

Ribeiro, F; Oliveira, N L; Silva, G; Campos, L; Miranda, F; Teixeira, M; Alves, A J; Oliveira, J

2017-03-01

To assess the effects of an exercise-based cardiac rehabilitation programme on daily physical activity levels of patients following myocardial infarction. Subanalysis of two randomised, prospective controlled trials. Outpatient clinic of a secondary hospital. Fifty consecutive patients randomised to the exercise group {n=25; 23 males; mean age 54 [standard deviation (SD) 9] years} or the control group [n=25; 20 males; mean age 58 (SD 9) years]. The exercise group participated in an 8-week aerobic exercise programme plus usual medical care and follow-up. The control group received usual medical care and follow-up. The primary outcome measure was change in time spent undertaking moderate-to-vigorous physical activity per day, assessed by accelerometer over 7 consecutive days. Secondary outcome measures were cardiorespiratory fitness, body mass, and resting blood pressure and heart rate. Moderate-to-vigorous physical activity levels increased significantly in the exercise group [43.2 (SD 36.3) to 53.5 (SD 31.9) minutes/day, P=0.030], and remained unchanged in the control group [40.8 (SD 26.2) to 36.8 (SD 26.5) minutes/day, P=0.241] from baseline to the end of the programme. Cardiorespiratory fitness increased significantly in the exercise group (mean difference 2.8; 95% of the difference 1.3 to 4.4ml/kg/minute, P=0.001) after the 8-week programme. In patients under optimal medication following myocardial infarction, participation in an 8-week exercise-based cardiac rehabilitation programme was found to improve physical activity levels consistent with health-related benefits. Future studies are needed to determine whether the increase in physical activity is maintained in the long term. Copyright © 2015 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

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.

Music during interventional radiological procedures, effect on sedation, pain and anxiety: a randomised controlled trial

PubMed Central

Kulkarni, S; Johnson, P C D; Kettles, S; Kasthuri, R S

2012-01-01

Objective : To assess the effects of playing patient-selected music during interventional procedures on (1) the doses of sedation and analgesia and (2) anxiety levels. Methods : Patients undergoing interventional radiological procedures were randomised to either the intervention (music) or the control (no music) group. Patients in the intervention group had music of their choice played via headphones during the procedure. The primary outcomes were reductions in the doses of drugs for sedation (midazolam) and analgesia (fentanyl). Anxiety levels were assessed both before and after the procedure using the validated State Anxiety Inventory. Mean pulse rate and average of mean blood pressures were also recorded before and during the procedures as surrogate indicators of anxiety levels. Results : 100 patients were randomised in a 1:1 ratio. There were 58 males and 42 females, with a mean age of 58 years. Sedation was required in 21 (42%) patients in the music group compared with 30 (60%) patients in the control group (p=0.046). The mean [standard deviation (SD)] midazolam dose was 2.1 mg (2.3 mg) in the control group and 1.3 mg (2.2 mg) in the music group (p=0.027). The mean (SD) fentanyl dose was 29 mg (40 mg) in the control group and 18 mg (34 mg) in the music group (p=0.055). There was no significant effect of music on the change from baseline in anxiety levels (p=0.74), pulse rate (p=0.56) or blood pressure (p=0.34). Conclusion : Sedation requirements are significantly reduced by playing self-selected music to the patient during interventional radiology procedures. By lowering sedation during interventional radiology, music makes the procedure safer. It also contributes favourably to the overall patient experience. PMID:22422386

Trial of Optimal Personalised Care After Treatment for Gynaecological cancer (TOPCAT-G): a study protocol for a randomised feasibility trial.

PubMed

Pye, Kirstie; Totton, Nicola; Stuart, Nicholas; Whitaker, Rhiannon; Morrison, Val; Edwards, Rhiannon Tudor; Yeo, Seow Tien; Timmis, Laura J; Butterworth, Caryl; Hall, Liz; Rai, Tekendra; Hoare, Zoe; Neal, Richard D; Wilkinson, Clare; Leeson, Simon

2016-01-01

Gynaecological cancers are diagnosed in over 1000 women in Wales every year. We estimate that this is costing the National Health Service (NHS) in excess of £1 million per annum for routine follow-up appointments alone. Follow-up care is not evidence-based, and there are no definitive guidelines from The National Institute for Health and Care Excellence (NICE) for the type of follow-up that should be delivered. Standard care is to provide a regular medical review of the patient in a hospital-based outpatient clinic for a minimum of 5 years. This study is to evaluate the feasibility of a proposed alternative where the patients are delivered a specialist nurse-led telephone intervention known as Optimal Personalised Care After Treatment for Gynaecological cancer (OPCAT-G), which comprised of a protocol-based patient education, patient empowerment and structured needs assessment. The study will recruit female patients who have completed treatment for cervical, endometrial, epithelial ovarian or vulval cancer within the previous 3 months in Betsi Cadwaladr University Health Board (BCUHB) in North Wales. Following recruitment, participants will be randomised to one of two arms in the trial (standard care or OPCAT-G intervention). The primary outcomes for the trial are patient recruitment and attrition rates, and the secondary outcomes are quality of life, health status and capability, using the EORTC QLQ-C30, EQ-5D-3L and ICECAP-A measures. Additionally, a client service receipt inventory (CSRI) will be collected in order to pilot an economic evaluation. The results from this feasibility study will be used to inform a fully powered randomised controlled trial to evaluate the difference between standard care and the OPCAT-G intervention. ISRCTN45565436.

Uptake of community-based, self-collected HPV testing vs. visual inspection with acetic acid for cervical cancer screening in Kampala, Uganda: preliminary results of a randomised controlled trial.

PubMed

Moses, Erin; Pedersen, Heather N; Mitchell, Sheona M; Sekikubo, Musa; Mwesigwa, David; Singer, Joel; Biryabarema, Christine; Byamugisha, Josaphat K; Money, Deborah M; Ogilvie, Gina S

2015-10-01

To compare two cervical cancer screening methods: community-based self-collection of high-risk human papillomavirus (HR-HPV) testing and visual inspection with acetic acid (VIA). Pilot randomised controlled trial of 500 women aged 30-65 in the community of Kisenyi, Uganda. Women randomised to self-collection-based HR-HPV testing provided a cervico-vaginal swab for HR-HPV, and results were provided by phone after laboratory testing. Women who tested HPV positive were referred for VIA at the local health unit. Women randomised to VIA underwent screening at the local health unit, where women who tested positive with VIA were provided cryotherapy at time of screening, as per local standard of care. Women were referred for colposcopy when indicated. Outcome measures were uptake of screening, HR-HPV prevalence, VIA result and treatment rates. In the HR-HPV arm, 248 of 250 (p < 0.01) women provided samples, while in the VIA arm, 121 of 250 (48.4%) women attended screening. Among the 73 of 248 HR-HPV-positive women, 45.2% (N = 33) attended VIA screening for follow-up, 21.2% (N = 7) of whom screened positive; five received treatment and two were missing clinical follow-up records. Of the 121 women in the VIA arm who attended screening, 13.2% (N = 16) screened positive; seven received cryotherapy, three refused treatment, five were referred to colposcopy; and one woman had suspected cervical cancer and received treatment after confirmatory testing. This pilot study demonstrated trial feasibility and willingness of the women to participate and be randomised successfully into the two arms. Self-collection-based cervical cancer screening had a higher uptake than VIA. © 2015 John Wiley & Sons Ltd.

Randomised controlled trial of silk therapeutic garments for the management of atopic eczema in children: the CLOTHES trial.

PubMed

Thomas, Kim S; Bradshaw, Lucy E; Sach, Tracey H; Cowdell, Fiona; Batchelor, Jonathan M; Lawton, Sandra; Harrison, Eleanor F; Haines, Rachel H; Ahmed, Amina; Dean, Taraneh; Burrows, Nigel P; Pollock, Ian; Buckley, Hannah K; Williams, Hywel C; Llewellyn, Joanne; Crang, Clare; Grundy, Jane D; Guiness, Juliet; Gribbin, Andrew; Wake, Eileen V; Mitchell, Eleanor J; Brown, Sara J; Montgomery, Alan A

2017-04-01

Atopic eczema (AE) is a chronic, itchy, inflammatory skin condition that affects the quality of life of children and their families. The role of specialist clothing in the management of AE is poorly understood. To assess the effectiveness and cost-effectiveness of silk garments for the management of AE in children with moderate to severe disease. Parallel-group, observer-blind, randomised controlled trial of 6 months' duration, followed by a 2-month observational period. A nested qualitative study evaluated the beliefs of trial participants, health-care professionals and health-care commissioners about the use of silk garments for AE. Secondary care and the community in five UK centres. Children aged 1-15 years with moderate or severe AE. Participants were randomised (1 : 1 using online randomisation) to standard care or standard care plus 100% silk garments made from antimicrobially protected knitted sericin-free silk [DermaSilk TM (AlPreTec Srl, San Donà di Piave, Italy) or DreamSkin TM (DreamSkin Health Ltd, Hatfield, UK)]. Three sets of garments were supplied per participant, to be worn for up to 6 months (day and night). At 6 months the standard care group received the garments to use for the remaining 2-month observational period. Primary outcome - AE severity using the Eczema Area and Severity Index (EASI) assessed at 2, 4 and 6 months, by nurses blinded to treatment allocation. EASI scores were log-transformed for analysis. Secondary outcomes - patient-reported eczema symptoms (Patient Oriented Eczema Measure); global assessment of severity (Investigator Global Assessment); quality of life of the child (Atopic Dermatitis Quality of Life, Child Health Utility - 9 Dimensions), family (Dermatitis Family Impact Questionnaire) and main carer (EuroQoL-5 Dimensions-3 Levels); use of standard eczema treatments (e.g. emollients, topical corticosteroids); and cost-effectiveness. The acceptability and durability of the clothing, and adherence to wearing the garments, were assessed by parental/carer self-report. Safety outcomes - number of skin infections and hospitalisations for AE. A total of 300 children were randomised (26 November 2013 to 5 May 2015): 42% female, 79% white, mean age 5 years. The primary analysis included 282 out of 300 (94%) children ( n  = 141 in each group). Garments were worn for at least 50% of the time by 82% of participants. Geometric mean EASI scores at baseline, 2, 4 and 6 months were 8.4, 6.6, 6.0, 5.4 for standard care and 9.2, 6.4, 5.8, 5.4 for silk clothing, respectively. There was no evidence of difference between the groups in EASI score averaged over all follow-up visits adjusted for baseline EASI score, age and centre (ratio of geometric means 0.95, 95% confidence interval 0.85 to 1.07; p  = 0.43). This confidence interval is equivalent to a difference of -1.5 to 0.5 in the original EASI scale units. Skin infections occurred in 39 out of 141 (28%) and 36 out of 142 (25%) participants for standard care and silk clothing groups, respectively. The incremental cost per QALY of silk garments for children with moderate to severe eczema was £56,811 from a NHS perspective in the base case. Sensitivity analyses supported the finding that silk garments do not appear to be cost-effective within currently accepted thresholds. Knowledge of treatment allocation may have affected behaviour and outcome reporting for some of the patient-reported outcomes. The addition of silk garments to standard AE care is unlikely to improve AE severity, or to be cost-effective compared with standard care alone, for children with moderate or severe AE. This trial adds to the evidence base to guide clinical decision-making. Non-pharmacological interventions for the management of AE remain a research priority among patients. Current Controlled Trials ISRCTN77261365. 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. 16. See the NIHR Journals Library website for further project information.

Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes (ACCORD MIND): a randomised open-label substudy.

PubMed

Launer, Lenore J; Miller, Michael E; Williamson, Jeff D; Lazar, Ron M; Gerstein, Hertzel C; Murray, Anne M; Sullivan, Mark; Horowitz, Karen R; Ding, Jingzhong; Marcovina, Santica; Lovato, Laura C; Lovato, James; Margolis, Karen L; O'Connor, Patrick; Lipkin, Edward W; Hirsch, Joy; Coker, Laura; Maldjian, Joseph; Sunshine, Jeffrey L; Truwit, Charles; Davatzikos, Christos; Bryan, R Nick

2011-11-01

People with type 2 diabetes are at risk of cognitive impairment and brain atrophy. We aimed to compare the effects on cognitive function and brain volume of intensive versus standard glycaemic control. The Memory in Diabetes (MIND) study was done in 52 clinical sites in North America as part of Action to Control Cardiovascular Risk in Diabetes (ACCORD), a double two-by-two factorial parallel group randomised trial. Participants (aged 55-80 years) with type 2 diabetes, high glycated haemoglobin A(1c) (HbA(1c)) concentrations (>7·5%; >58 mmol/mol), and a high risk of cardiovascular events were randomly assigned to receive intensive glycaemic control targeting HbA(1c) to less than 6·0% (42 mmol/mol) or a standard strategy targeting HbA(1c) to 7·0-7·9% (53-63 mmol/mol). Randomisation was via a centralised web-based system and treatment allocation was not masked from clinic staff or participants. We assessed our cognitive primary outcome, the Digit Symbol Substitution Test (DSST) score, at baseline and at 20 and 40 months. We assessed total brain volume (TBV), our primary brain structure outcome, with MRI at baseline and 40 months in a subset of participants. We included all participants with follow-up data in our primary analyses. In February, 2008, raised mortality risk led to the end of the intensive treatment and transition of those participants to standard treatment. We tested our cognitive function hypotheses with a mixed-effects model that incorporated information from both the 20 and 40 month outcome measures. We tested our MRI hypotheses with an ANCOVA model that included intracranial volume and factors used to stratify randomisation. This study is registered with ClinicalTrials.gov, number NCT00182910. We consecutively enrolled 2977 patients (mean age 62·5 years; SD 5·8) who had been randomly assigned to treatment groups in the ACCORD study. Our primary cognitive analysis was of patients with a 20-month or 40-month DSST score: 1378 assigned to receive intensive treatment and 1416 assigned to receive standard treatment. Of the 614 patients with a baseline MRI, we included 230 assigned to receive intensive treatment and 273 assigned to receive standard treatment in our primary MRI analysis at 40 months. There was no significant treatment difference in mean 40-month DSST score (difference in mean 0·32, 95% CI -0·28 to 0·91; p=0·2997). The intensive-treatment group had a greater mean TBV than the standard-treatment group (4·62, 2·0 to 7·3; p=0·0007). Although significant differences in TBV favoured the intensive treatment, cognitive outcomes were not different. Combined with the non-significant effects on other ACCORD outcomes, and increased mortality in participants in the intensive treatment group, our findings do not support the use of intensive therapy to reduce the adverse effects of diabetes on the brain in patients with similar characteristics to those of our participants. US National Institute on Aging and US National Heart, Lung, and Blood Institute. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

Primary care referral to a commercial provider for weight loss treatment versus standard care: a randomised controlled trial.

PubMed

Jebb, Susan A; Ahern, Amy L; Olson, Ashley D; Aston, Louise M; Holzapfel, Christina; Stoll, Julia; Amann-Gassner, Ulrike; Simpson, Annie E; Fuller, Nicholas R; Pearson, Suzanne; Lau, Namson S; Mander, Adrian P; Hauner, Hans; Caterson, Ian D

2011-10-22

The increasing prevalence of overweight and obesity needs effective approaches for weight loss in primary care and community settings. We compared weight loss with standard treatment in primary care with that achieved after referral by the primary care team to a commercial provider in the community. In this parallel group, non-blinded, randomised controlled trial, 772 overweight and obese adults were recruited by primary care practices in Australia, Germany, and the UK. Participants were randomly assigned with a computer-generated simple randomisation sequence to receive either 12 months of standard care as defined by national treatment guidelines, or 12 months of free membership to a commercial programme (Weight Watchers), and followed up for 12 months. The primary outcome was weight change over 12 months. Analysis was by intention to treat (last observation carried forward [LOCF] and baseline observation carried forward [BOCF]) and in the population who completed the 12-month assessment. This trial is registered, number ISRCTN85485463. 377 participants were assigned to the commercial programme, of whom 230 (61%) completed the 12-month assessment; and 395 were assigned to standard care, of whom 214 (54%) completed the 12-month assessment. In all analyses, participants in the commercial programme group lost twice as much weight as did those in the standard care group. Mean weight change at 12 months was -5·06 kg (SE 0·31) for those in the commercial programme versus -2·25 kg (0·21) for those receiving standard care (adjusted difference -2·77 kg, 95% CI -3·50 to -2·03) with LOCF; -4·06 kg (0·31) versus -1·77 kg (0·19; adjusted difference -2·29 kg, -2·99 to -1·58) with BOCF; and -6·65 kg (0·43) versus -3·26 kg (0·33; adjusted difference -3·16 kg, -4·23 to -2·11) for those who completed the 12-month assessment. Participants reported no adverse events related to trial participation. Referral by a primary health-care professional to a commercial weight loss programme that provides regular weighing, advice about diet and physical activity, motivation, and group support can offer a clinically useful early intervention for weight management in overweight and obese people that can be delivered at large scale. Weight Watchers International, through a grant to the UK Medical Research Council. Copyright © 2011 Elsevier Ltd. All rights reserved.

Life skills programmes for chronic mental illnesses

PubMed Central

Tungpunkom, Patraporn; Maayan, Nicola; Soares-Weiser, Karla

2014-01-01

Background Most people with schizophrenia have a cyclical pattern of illness characterised by remission and relapses. The illness can reduce the ability of self-care and functioning and can lead to the illness becoming disabling. Life skills programmes, emphasising the needs associated with independent functioning, are often a part of the rehabilitation process. These programmes have been developed to enhance independent living and quality of life for people with schizophrenia. Objectives To review the effects of life skills programmes compared with standard care or other comparable therapies for people with chronic mental health problems. Search methods We searched the Cochrane Schizophrenia Group Trials Register (June 2010). We supplemented this process with handsearching and scrutiny of references. We inspected references of all included studies for further trials. Selection criteria We included all relevant randomised or quasi-randomised controlled trials for life skills programmes versus other comparable therapies or standard care involving people with serious mental illnesses. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a random-effects model. For continuous data, we calculated mean differences (MD), again based on a random-effects model. Main results We included seven randomised controlled trials with a total of 483 participants. These evaluated life skills programmes versus standard care, or support group. We found no significant difference in life skills performance between people given life skills training and standard care (1 RCT, n = 32, MD −1.10; 95% CI −7.82 to 5.62). Life skills training did not improve or worsen study retention (5 RCTs, n = 345, RR 1.16; 95% CI 0.40 to 3.36). We found no significant difference in PANSS positive, negative or total scores between life skills intervention and standard care. We found quality of life scores to be equivocal between participants given life skills training (1 RCT, n = 32, MD −0.02; 95% CI −0.07 to 0.03) and standard care. Life skills compared with support groups also did not reveal any significant differences in PANSS scores, quality of life, or social performance skills (1 RCT, n = 158, MD −0.90; 95% CI −3.39 to 1.59). Authors’ conclusions Currently there is no good evidence to suggest life skills programmes are effective for people with chronic mental illnesses. More robust data are needed from studies that are adequately powered to determine whether life skills training is beneficial for people with chronic mental health problems. PMID:22258941

Cost-effectiveness of high-dose versus standard-dose inactivated influenza vaccine in adults aged 65 years and older: an economic evaluation of data from a randomised controlled trial.

PubMed

Chit, Ayman; Becker, Debbie L; DiazGranados, Carlos A; Maschio, Michael; Yau, Eddy; Drummond, Michael

2015-12-01

Adults aged 65 years and older account for most seasonal influenza-related hospital admissions and deaths. Findings from the randomised controlled FIM12 study showed that high-dose inactivated influenza vaccine is more effective than standard-dose vaccine for prevention of laboratory-confirmed influenza in this age group. We aimed to assess the economic impact of high-dose versus standard-dose influenza vaccine in participants in the FIM12 study population. The FIM12 study was a head-to-head randomised controlled trial in which 31,989 participants aged 65 years and older were randomly assigned (1:1) to receive either high-dose or standard-dose trivalent inactivated influenza vaccine over two influenza seasons (2011-12 and 2012-13). Data for health-care resource consumption obtained in the FIM12 study were summarised across vaccine groups. Unit costs obtained from standard US cost sources were applied to each resource item, including to the vaccines (high dose US$31·82, standard dose $12·04). Clinical illness data were mapped to existing quality-of-life data. The time horizon was one influenza season; however, quality-adjusted life-years (QALYs) lost due to death during the study were calculated over a lifetime. We calculated incremental cost-effectiveness ratios (ICERs) for high-dose versus standard-dose vaccine and used QALYs as an outcome in the cost-utility analysis. We undertook a probabilistic sensitivity analysis using bootstrapping to explore the effect of statistical uncertainty on the study results. Mean per-participant medical costs were lower in the high-dose vaccine group ($1376·72 [SD 6857·59]) than in the standard-dose group ($1492·64 [7447·14]; difference -$115·92 [95% CI -264·18 to 35·48]). Mean societal costs were likewise lower in the high-dose versus the standard-dose group ($1506·48 [SD 7305·19] vs $1634·50 [7952·99]; difference -$128·02 [95% CI -286·89 to 33·30]). Hospital admissions contributed 95% of the total health-care-payer cost and 87% of the total societal costs. The mean per-participant number of hospital admissions was 0·0937 (SD 0·3644) in the high-dose group and 0·1017 (0·3708) in the standard-dose group (difference -0·0080, 95% CI -0·0160 to -0·0003). The high-dose vaccine provided a gain in QALYs (mean 8·1502 QALYs gained per participant [SD 0·5693]) compared with the standard-dose vaccine (8·1499 QALYs [0·5697]) and, due to cost savings, dominated standard-dose vaccine in the cost-utility analysis. The probabilistic sensitivity analysis showed that the high-dose vaccine is 93% likely to be cost saving. High-dose trivalent inactivated influenza vaccine is a less costly and more effective alternative to the standard-dose vaccine, driven by a reduction in the number of hospital admissions. These findings are relevant to US health-care beneficiaries, providers, payers, and recommending bodies, especially those seeking to improve outcomes while containing costs. Sanofi Pasteur. Copyright © 2015 Elsevier Ltd. All rights reserved.

Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials.

PubMed

Hills, Robert K; Castaigne, Sylvie; Appelbaum, Frederick R; Delaunay, Jacques; Petersdorf, Stephen; Othus, Megan; Estey, Elihu H; Dombret, Hervé; Chevret, Sylvie; Ifrah, Norbert; Cahn, Jean-Yves; Récher, Christian; Chilton, Lucy; Moorman, Anthony V; Burnett, Alan K

2014-08-01

Gemtuzumab ozogamicin was the first example of antibody-directed chemotherapy in cancer, and was developed for acute myeloid leukaemia. However, randomised trials in which it was combined with standard induction chemotherapy in adults have produced conflicting results. We did a meta-analysis of individual patient data to assess the efficacy of adding gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia. We searched PubMed for reports of randomised controlled trials published in any language up to May 1, 2013, that included an assessment of gemtuzumab ozogamicin given to adults (aged 15 years and older) in conjunction with the first course of intensive induction chemotherapy for acute myeloid leukaemia (excluding acute promyelocytic leukaemia) compared with chemotherapy alone. Published data were supplemented with additional data obtained by contacting individual trialists. The primary endpoint of interest was overall survival. We used standard meta-analytic techniques, with an assumption-free (or fixed-effect) method. We also did exploratory stratified analyses to investigate whether any baseline features predicted a greater or lesser benefit from gemtuzumab ozogamicin. We obtained data from five randomised controlled trials (3325 patients); all trials were centrally randomised and open label, with overall survival as the primary endpoint. The addition of gemtuzumab ozogamicin did not increase the proportion of patients achieving complete remission with or without complete peripheral count recovery (odds ratio [OR] 0·91, 95% CI 0·77-1·07; p=0·3). However, the addition of gemtuzumab ozogamicin significantly reduced the risk of relapse (OR 0·81, 0·73-0·90; p=0·0001), and improved overall survival at 5 years (OR 0·90, 0·82-0·98; p=0·01). At 6 years, the absolute survival benefit was especially apparent in patients with favourable cytogenetic characteristics (20·7%; OR 0·47, 0·31-0·73; p=0·0006), but was also seen in those with intermediate characteristics (5·7%; OR 0·84, 0·75-0·95; p=0·005). Patients with adverse cytogenetic characteristics did not benefit (2·2%; OR 0·99, 0·83-1·18; p=0·9). Doses of 3 mg/m(2) were associated with fewer early deaths than doses of 6 mg/m(2), with equal efficacy. Gemtuzumab ozogamicin can be safely added to conventional induction therapy and provides a significant survival benefit for patients without adverse cytogenetic characteristics. These data suggest that the use of gemtuzumab ozogamicin should be reassessed and its licence status might need to be reviewed. None. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of a hospital-based education programme on self-care behaviour, care dependency and quality of life in patients with heart failure--a randomised controlled trial.

PubMed

Köberich, Stefan; Lohrmann, Christa; Mittag, Oskar; Dassen, Theo

2015-06-01

To evaluate the effects of a nurse-led, hospital-based heart failure specific education session with a three-month telephone follow-up on self-care behaviour, care dependency and quality of life for patients with chronic heart failure. Patient education in patients with heart failure is able to promote heart failure-specific self-care, to reduce mortality, morbidity and rehospitalisation rates and to enhance quality of life, especially if heart failure education is embedded in a multidisciplinary approach. Evidence of the effect of a nurse-led self-care education, quality of life and care dependency in addition to standard medical treatment in Germany is lacking. Nonblinded, prospective, single-centre, randomised controlled trial. Sixty-four patients were allocated either to the intervention group or to the control group. Patients in the intervention group received education about heart failure self-care with a consecutive telephone follow-up over three months in addition to standard medical treatment. Patients in the control group received standard medical treatment only. Data of 110 patients (58 in the intervention group and 52 in the control group) with a mean age of 62 years and mean left ventricular ejection fraction of 28·2% could be analysed. Self-care education had a significant influence on overall heart failure self-care but not on quality of life and care dependency. A single education session with a consecutive telephone follow-up is able to improve overall self-care behaviours but not quality of life. Care dependency was not influenced by the education session. The easy to implement and short educational intervention has a positive effect on self-care behaviour for patients with heart failure. However, there was no effect on quality of life and care dependency. To improve quality of life and to influence care dependency, different measures have to be applied. © 2015 John Wiley & Sons Ltd.

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

Rituximab versus cyclophosphamide for the treatment of connective tissue disease-associated interstitial lung disease (RECITAL): study protocol for a randomised controlled trial.

PubMed

Saunders, Peter; Tsipouri, Vicky; Keir, Gregory J; Ashby, Deborah; Flather, Marcus D; Parfrey, Helen; Babalis, Daphne; Renzoni, Elisabetta A; Denton, Christopher P; Wells, Athol U; Maher, Toby M

2017-06-15

Interstitial lung disease (ILD) frequently complicates systemic autoimmune disorders resulting in considerable morbidity and mortality. The connective tissue diseases (CTDs) most frequently resulting in ILD include: systemic sclerosis, idiopathic inflammatory myositis (including dermatomyositis, polymyositis and anti-synthetase syndrome) and mixed connective tissue disease. Despite the development, over the last two decades, of a range of biological therapies which have resulted in significant improvements in the treatment of the systemic manifestations of CTD, the management of CTD-associated ILD has changed little. At present there are no approved therapies for CTD-ILD. Following trials in scleroderma-ILD, cyclophosphamide is the accepted standard of care for individuals with severe or progressive CTD-related ILD. Observational studies have suggested that the anti-CD20 monoclonal antibody, rituximab, is an effective rescue therapy in the treatment of refractory CTD-ILD. However, before now, there have been no randomised controlled trials assessing the efficacy of rituximab in this treatment population. RECITAL is a UK, multicentre, prospective, randomised, double-blind, double-dummy, controlled trial funded by the Efficacy and Mechanism Evaluation Programme of the Medical Research Council and National Institute for Health Research. The trial will compare rituximab 1 g given intravenously, twice at an interval of 2 weeks, with intravenously administered cyclophosphamide given monthly at a dose of 600 mg/m 2 body surface area in individuals with ILD due to systemic sclerosis, idiopathic inflammatory myositis (including anti-synthetase syndrome) or mixed connective tissue disease. A total of 116 individuals will be randomised 1:1 to each of the two treatment arms, with stratification based on underlying CTD, and will be followed for a total of 48 weeks from first dose. The primary endpoint for the study will be change in forced vital capacity (FVC) at 24 weeks. Key secondary endpoints include: safety, change in FVC at 48 weeks as well as survival, change in oxygen requirements, total 48-week corticosteroid exposure and utilisation of health care resources. This is the first randomised control trial to study the efficacy of rituximab as first-line treatment in CTD-associated ILD. The results generated should provide important information on the treatment of a life-threatening complication affecting a rare group of CTDs. ClinicalTrials.gov, NCT01862926. Registered on 22 May 2013.

GestationaL Obesity Weight management: Implementation of National Guidelines (GLOWING): a pilot cluster randomised controlled trial of a guideline implementation intervention for the management of maternal obesity by midwives.

PubMed

Heslehurst, Nicola; Rankin, Judith; McParlin, Catherine; Sniehotta, Falko F; Howel, Denise; Rice, Stephen; McColl, Elaine

2018-01-01

Weight management in pregnancy guidelines exist, although dissemination alone is an ineffective means of implementation. Midwives identify the need for support to overcome complex barriers to practice. An evaluation of an intervention to support midwives' guideline implementation would require a large-scale cluster randomised controlled trial. A pilot study is necessary to explore the feasibility of delivery and evaluation prior to a definitive trial. The GestationaL Obesity Weight management: Implementation of National Guidelines (GLOWING) trial aims to test whether it is feasible and acceptable to deliver a behaviour change intervention to support midwives' implementation of weight management guidelines. GLOWING is a multi-centre parallel group pilot cluster randomised controlled trial comparing the delivery of a behaviour change intervention for midwives versus usual practice. Four NHS Trusts (clusters) will be randomised to intervention and control arms, stratified by size of maternity services. The intervention uses social cognitive theory and consists of face-to-face midwifery training plus information resources for routine practice. The main outcomes are whether the intervention and trial procedures are feasible and acceptable to participants and the feasibility of recruitment and data collection for a definitive trial. Target recruitment involves all eligible midwives in the intervention arm recruited to receive the intervention, 30 midwives and pregnant women per arm for baseline and outcome questionnaire data collection and 20 midwives and women to provide qualitative data. All quantitative and qualitative analyses will be descriptive with the purpose of informing the development of the definitive trial. This pilot study has been developed to support community midwives' implementation of guidelines. Community midwives have been selected as they usually carry out the booking appointment which includes measuring and discussing maternal body mass index. A cluster design is the gold standard in implementation research as there would be a high risk of contamination if randomisation was at individual midwife level: community midwives usually work in locality-based teams, interact on a daily basis, and share care of pregnant women. The results of the pilot trial will be used to further develop and refine GLOWING prior to a definitive trial to evaluate effectiveness and cost-effectiveness. ISRCTN46869894; retrospectively registered 25th May 2016.

Deviation from intention to treat analysis in randomised trials and treatment effect estimates: meta-epidemiological study.

PubMed

Abraha, Iosief; Cherubini, Antonio; Cozzolino, Francesco; De Florio, Rita; Luchetta, Maria Laura; Rimland, Joseph M; Folletti, Ilenia; Marchesi, Mauro; Germani, Antonella; Orso, Massimiliano; Eusebi, Paolo; Montedori, Alessandro

2015-05-27

To examine whether deviation from the standard intention to treat analysis has an influence on treatment effect estimates of randomised trials. Meta-epidemiological study. Medline, via PubMed, searched between 2006 and 2010; 43 systematic reviews of interventions and 310 randomised trials were included. From each year searched, random selection of 5% of intervention reviews with a meta-analysis that included at least one trial that deviated from the standard intention to treat approach. Basic characteristics of the systematic reviews and randomised trials were extracted. Information on the reporting of intention to treat analysis, outcome data, risk of bias items, post-randomisation exclusions, and funding were extracted from each trial. Trials were classified as: ITT (reporting the standard intention to treat approach), mITT (reporting a deviation from the standard approach), and no ITT (reporting no approach). Within each meta-analysis, treatment effects were compared between mITT and ITT trials, and between mITT and no ITT trials. The ratio of odds ratios was calculated (value <1 indicated larger treatment effects in mITT trials than in other trial categories). 50 meta-analyses and 322 comparisons of randomised trials (from 84 ITT trials, 118 mITT trials, and 108 no ITT trials; 12 trials contributed twice to the analysis) were examined. Compared with ITT trials, mITT trials showed a larger intervention effect (pooled ratio of odds ratios 0.83 (95% confidence interval 0.71 to 0.96), P=0.01; between meta-analyses variance τ(2)=0.13). Adjustments for sample size, type of centre, funding, items of risk of bias, post-randomisation exclusions, and variance of log odds ratio yielded consistent results (0.80 (0.69 to 0.94), P=0.005; τ(2)=0.08). After exclusion of five influential studies, results remained consistent (0.85 (0.75 to 0.98); τ(2)=0.08). The comparison between mITT trials and no ITT trials showed no statistical difference between the two groups (adjusted ratio of odds ratios 0.92 (0.70 to 1.23); τ(2)=0.57). Trials that deviated from the intention to treat analysis showed larger intervention effects than trials that reported the standard approach. Where an intention to treat analysis is impossible to perform, authors should clearly report who is included in the analysis and attempt to perform multiple imputations. © Abraha et al 2015.

A multicentre randomiSed controlled TRial of IntraVEnous immunoglobulin compared with standard therapy for the treatment of transverse myelitis in adults and children (STRIVE).

PubMed

Absoud, Michael; Brex, Peter; Ciccarelli, Olga; Diribe, Onyinye; Giovannoni, Gavin; Hellier, Jennifer; Howe, Rosemary; Holland, Rachel; Kelly, Joanna; McCrone, Paul; Murphy, Caroline; Palace, Jackie; Pickles, Andrew; Pike, Michael; Robertson, Neil; Jacob, Anu; Lim, Ming

2017-05-01

Transverse myelitis (TM) is an immune-mediated disorder of the spinal cord that affects adults and children and that causes motor, sensory and autonomic dysfunction. There is a prolonged recovery phase, which may continue for many years. Neuromyelitis optica (NMO) is an uncommon relapsing inflammatory central nervous system condition in which TM can be the first presenting symptom. As TM and NMO affect many patients in the prime of their working life, the disorder can impose a significant demand on health resources. There are currently no robust controlled trials in children or adults to inform the optimal treatment of TM. However, treatment with intravenous immunoglobulin (IVIG) is being effectively used in the management of a range of neurological conditions. Although other interventions such as plasma exchange (PLEX) in addition to intravenous (IV) methylprednisolone therapy can be beneficial in TM, PLEX is costly and technically challenging to deliver in the acute setting. IVIG is more readily accessible and less costly. To evaluate whether additional and early treatment with IVIG is of extra benefit in TM compared with standard therapy with IV steroids. A multicentre, single-blind, parallel-group randomised controlled trial of IVIG compared with standard therapy for the treatment of TM in adults and children. Patients aged ≥ 1 year diagnosed with either acute first-onset TM or first presentation of NMO. Target recruitment was 170 participants (85 participants per arm). Participants were randomised 1 : 1 to treatment with IV methylprednisolone only or treatment with IV methylprednisolone plus 2 g/kg of IVIG in divided doses within 5 days of the first commencement of steroid therapy. Primary outcome measure - American Spinal Injury Association (ASIA) Impairment Scale at 6 months post randomisation, with a good outcome defined by a two-grade change. Secondary and tertiary outcome measures - ASIA motor and sensory scales, Expanded Disability Status Scale, health outcome, quality of life, Client Service Receipt Inventory and International Spinal Cord Injury Pain, Bladder and Bowel Basic Data Sets. In total, 26 participants were screened and two were randomised into the study. With the limited sample size, treatment effect could not be determined. However, we identified barriers to accrual that included strict inclusion criteria, the short enrolment window, challenges associated with the use of the ASIA Impairment Scale as an outcome measure and estimation of the incidence of TM. The study did not reach the end point and the effect of IVIG in TM/NMO could not be determined. Investigators should be aware of the potential challenges associated with carrying out a rare disease trial with a short enrolment window. The study question is one that still necessitates investigation. Preliminary work to ameliorate the effect of the barriers encountered in this study is vital. EudraCT 2014-002335-34, ClinicalTrials.gov NCT02398994 and Current Controlled Trials ISRCTN12127581. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 31. See the NIHR Journals Library website for further project information. Funding was also received from Biotest AG, Germany (supply of IVIG) and the Transverse Myelitis Society (excess research cost to facilitate study initiation).

A pilot cluster randomised controlled trial of a support and training intervention to improve the mental health of secondary school teachers and students - the WISE (Wellbeing in Secondary Education) study.

PubMed

Kidger, Judi; Stone, Tracey; Tilling, Kate; Brockman, Rowan; Campbell, Rona; Ford, Tamsin; Hollingworth, William; King, Michael; Araya, Ricardo; Gunnell, David

2016-10-06

Secondary school teachers are at heightened risk of psychological distress, which can lead to poor work performance, poor quality teacher-student relationships and mental illness. A pilot cluster randomised controlled trial (RCT) - the WISE study - evaluated the feasibility of a full-scale RCT of an intervention to support school staff's own mental health, and train them in supporting student mental health. Six schools were randomised to an intervention or control group. In the intervention schools i) 8-9 staff received Mental Health First Aid (MHFA) training and became staff peer supporters, and ii) youth MHFA training was offered to the wider staff body. Control schools continued with usual practice. We used thematic qualitative data analysis and regression modelling to ascertain the feasibility, acceptability and potential usefulness of the intervention. Thirteen training observations, 14 staff focus groups and 6 staff interviews were completed, and 438 staff (43.5 %) and 1,862 (56.3 %) students (years 8 and 9) completed questionnaires at baseline and one year later. MHFA training was considered relevant for schools, and trainees gained in knowledge, confidence in helping others, and awareness regarding their own mental health. Suggestions for reducing the length of the training and focusing on helping strategies were made. A peer support service was established in all intervention schools and was perceived to be helpful in supporting individuals in difficulty - for example through listening, and signposting to other services - and raising the profile of mental health at a whole school level. Barriers to use included lack of knowledge about the service, concerns about confidentiality and a preference for accessing support from pre-existing networks. The WISE intervention is feasible and acceptable to schools. Results support the development of a full-scale cluster RCT, if steps are taken to improve response rates and implement the suggested improvements to the intervention. International Standard Randomised Controlled Trial Number: ISRCTN13255300 retrospectively registered 28/09/16.

Prospective randomised controlled trial of nanocrystalline silver dressing versus plain gauze as the initial post-debridement management of military wounds on wound microbiology and healing.

PubMed

Fries, C A; Ayalew, Y; Penn-Barwell, J G; Porter, K; Jeffery, S L A; Midwinter, M J

2014-07-01

Recent conflicts have been characterised by the use of improvised explosive devices causing devastating injuries, including heavily contaminated wounds requiring meticulous surgical debridement. After being rendered surgical clean, these wounds are dressed and the patient transferred back to the UK for on-going treatment. A dressing that would prevent wounds from becoming colonised during transit would be desirable. The aim of this study was to establish whether using nanocrystalline silver dressings, as an adjunct to the initial debridement, would positively affect wound microbiology and wound healing compared to standard plain gauze dressings. Patients were prospectively randomised to receive either silver dressings, in a nanocrystalline preparation (Acticoat™), or standard of care dressings (plain gauze) following their initial debridement in the field hospital. On repatriation to the UK microbiological swabs were taken from the dressing and the wound, and an odour score recorded. Wounds were followed prospectively and time to wound healing was recorded. Additionally, patient demographic data were recorded, as well as the mechanism of injury and Injury Severity Score. 76 patients were recruited to the trial between February 2010 and February 2012. 39 received current dressings and 37 received the trial dressings. Eleven patients were not swabbed. There was no difference (p=0.1384, Fishers) in the primary outcome measure of wound colonisation between the treatment arm (14/33) and the control arm (20/32). Similarly time to wound healing was not statistically different (p=0.5009, Mann-Whitney). Wounds in the control group were scored as being significantly more malodorous (p=0.002, Mann-Whitney) than those in the treatment arm. This is the first randomised controlled trial to report results from an active theatre of war. Performing research under these conditions poses additional challenges to military clinicians. Meticulous debridement of wounds remains the critical determinant in wound healing and infection and this study did not demonstrate a benefit of nanocrystaline silver dressing in respect to preventing wound colonisation or promoting healing, these dressings do however seem to significantly reduce the unpleasant odour commonly associated with battlefield wounds. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Care in specialist medical and mental health unit compared with standard care for older people with cognitive impairment admitted to general hospital: randomised controlled trial (NIHR TEAM trial)

PubMed Central

Goldberg, Sarah E; Bradshaw, Lucy E; Kearney, Fiona C; Russell, Catherine; Whittamore, Kathy H; Foster, Pippa E R; Mamza, Jil; Gladman, John R F; Jones, Rob G; Lewis, Sarah A; Porock, Davina

2013-01-01

Objective To develop and evaluate a best practice model of general hospital acute medical care for older people with cognitive impairment. Design Randomised controlled trial, adapted to take account of constraints imposed by a busy acute medical admission system. Setting Large acute general hospital in the United Kingdom. Participants 600 patients aged over 65 admitted for acute medical care, identified as “confused” on admission. Interventions Participants were randomised to a specialist medical and mental health unit, designed to deliver best practice care for people with delirium or dementia, or to standard care (acute geriatric or general medical wards). Features of the specialist unit included joint staffing by medical and mental health professionals; enhanced staff training in delirium, dementia, and person centred dementia care; provision of organised purposeful activity; environmental modification to meet the needs of those with cognitive impairment; delirium prevention; and a proactive and inclusive approach to family carers. Main outcome measures Primary outcome: number of days spent at home over the 90 days after randomisation. Secondary outcomes: structured non-participant observations to ascertain patients’ experiences; satisfaction of family carers with hospital care. When possible, outcome assessment was blind to allocation. Results There was no significant difference in days spent at home between the specialist unit and standard care groups (median 51 v 45 days, 95% confidence interval for difference −12 to 24; P=0.3). Median index hospital stay was 11 versus 11 days, mortality 22% versus 25% (−9% to 4%), readmission 32% versus 35% (−10% to 5%), and new admission to care home 20% versus 28% (−16% to 0) for the specialist unit and standard care groups, respectively. Patients returning home spent a median of 70.5 versus 71.0 days at home (−6.0 to 6.5). Patients on the specialist unit spent significantly more time with positive mood or engagement (79% v 68%, 2% to 20%; P=0.03) and experienced more staff interactions that met emotional and psychological needs (median 4 v 1 per observation; P<0.001). More family carers were satisfied with care (overall 91% v 83%, 2% to 15%; P=0.004), and severe dissatisfaction was reduced (5% v 10%, −10% to 0%; P=0.05). Conclusions Specialist care for people with delirium and dementia improved the experience of patients and satisfaction of carers, but there were no convincing benefits in health status or service use. Patients’ experience and carers’ satisfaction might be more appropriate measures of success for frail older people approaching the end of life. Trial registration Clinical Trials NCT01136148 PMID:23819964

Holter-electrocardiogram-monitoring in patients with acute ischaemic stroke (Find-AFRANDOMISED): an open-label randomised controlled trial.

PubMed

Wachter, Rolf; Gröschel, Klaus; Gelbrich, Götz; Hamann, Gerhard F; Kermer, Pawel; Liman, Jan; Seegers, Joachim; Wasser, Katrin; Schulte, Anna; Jürries, Falko; Messerschmid, Anna; Behnke, Nico; Gröschel, Sonja; Uphaus, Timo; Grings, Anne; Ibis, Tugba; Klimpe, Sven; Wagner-Heck, Michaela; Arnold, Magdalena; Protsenko, Evgeny; Heuschmann, Peter U; Conen, David; Weber-Krüger, Mark

2017-04-01

Atrial fibrillation is a major risk factor for recurrent ischaemic stroke, but often remains undiagnosed in patients who have had an acute ischaemic stroke. Enhanced and prolonged Holter-electrocardiogram-monitoring might increase detection of atrial fibrillation. We therefore investigated whether enhanced and prolonged rhythm monitoring was better for detection of atrial fibrillation than standard care procedures in patients with acute ischaemic stroke. Find-AF randomised is an open-label randomised study done at four centres in Germany. We recruited patients with acute ischaemic stroke (symptoms for 7 days or less) aged 60 years or older presenting with sinus rhythm and without history of atrial fibrillation. Patients were included irrespective of the suspected cause of stroke, unless they had a severe ipsilateral carotid or intracranial artery stenosis, which were the exclusion criteria. We used a computer-generated allocation sequence to randomly assign patients in a 1:1 ratio with permuted block sizes of 2, 4, 6, and 8, stratified by centre, to enhanced and prolonged monitoring (ie, 10-day Holter-electrocardiogram [ECG]-monitoring at baseline, and at 3 months and 6 months of follow-up) or standard care procedures (ie, at least 24 h of rhythm monitoring). Participants and study physicians were not masked to group assignment, but the expert committees that adjudicated endpoints were. The primary endpoint was the occurrence of atrial fibrillation or atrial flutter (30 sec or longer) within 6 months after randomisation and before stroke recurrence. Because Holter ECG is a widely used procedure and not known to harm patients, we chose not to assess safety in detail. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01855035. Between May 8, 2013, and Aug 31, 2014, we recruited 398 patients. 200 patients were randomly assigned to the enhanced and prolonged monitoring group and 198 to the standard care group. After 6 months, we detected atrial fibrillation in 14% of 200 patients in the enhanced and prolonged monitoring group (27 patients) versus 5% in the control group (nine of 198 patients, absolute difference 9·0%; 95% CI 3·4-14·5, p=0·002; number needed to screen 11). Enhanced and prolonged monitoring initiated early in patients with acute ischaemic stroke aged 60 years or older was better than standard care for the detection of atrial fibrillation. These findings support the consideration of all patients aged 60 years or older with stroke for prolonged monitoring if the detection of atrial fibrillation would result in a change in medical management (eg, initiation of anticoagulation). Boehringer Ingelheim. Copyright © 2017 Elsevier Ltd. All rights reserved.

Examining the effects of enhanced provider-patient communication on postoperative tonsillectomy pain: protocol of a randomised controlled trial performed by nurses in daily clinical care.

PubMed

van Vliet, Liesbeth M; van Dulmen, Sandra; Thiel, Bram; van Deelen, Gerard W; Immerzeel, Stephanie; Godfried, Marc B; Bensing, Jozien M

2017-11-03

Placebo effects (true biopsychological effects not attributable to the active ingredients of medical technical interventions) can be attributed to several mechanisms, such as expectancy manipulation and empathy manipulation elicited by a provider's communication. So far, effects have primarily been shown in laboratory settings. The aim of this study is to determine the separate and combined effects of expectancy manipulation and empathy manipulation during preoperative and postoperative tonsillectomy analgesia care on clinical adult patients' outcomes. Using a two-by-two randomised controlled trial, 128 adult tonsillectomy patients will be randomly assigned to one out of four conditions differing in the level of expectancy manipulation (standard vs enhanced) and empathy manipulation (standard vs enhanced). Day care ward nurses are trained to deliver the intervention, while patients are treated via the standard analgesia protocol and hospital routines. The primary outcome, perceived pain, is measured via hospital routine by a Numeric Rating Scale, and additional prehospitalisation, perihospitalisation and posthospitalisation questionnaires are completed (until day 3, ie, 2 days after the operation). The manipulation is checked using audio recordings of nurse-patient interactions. Although communication is manipulated, the manipulations do not cross norms or values of acceptable behaviour. Standard medical care is provided. The ethical committee of the UMC Utrecht and the local OLVG hospital committee approved the study. Results will be published via (inter)national peer-reviewed journals and a lay publication. NTR5994; 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.

Modelling variable dropout in randomised controlled trials with longitudinal outcomes: application to the MAGNETIC study.

PubMed

Kolamunnage-Dona, Ruwanthi; Powell, Colin; Williamson, Paula Ruth

2016-04-28

Clinical trials with longitudinally measured outcomes are often plagued by missing data due to patients withdrawing or dropping out from the trial before completing the measurement schedule. The reasons for dropout are sometimes clearly known and recorded during the trial, but in many instances these reasons are unknown or unclear. Often such reasons for dropout are non-ignorable. However, the standard methods for analysing longitudinal outcome data assume that missingness is non-informative and ignore the reasons for dropout, which could result in a biased comparison between the treatment groups. In this article, as a post hoc analysis, we explore the impact of informative dropout due to competing reasons on the evaluation of treatment effect in the MAGNETIC trial, the largest randomised placebo-controlled study to date comparing the addition of nebulised magnesium sulphate to standard treatment in acute severe asthma in children. We jointly model longitudinal outcome and informative dropout process to incorporate the information regarding the reasons for dropout by treatment group. The effect of nebulised magnesium sulphate compared with standard treatment is evaluated more accurately using a joint longitudinal-competing risk model by taking account of such complexities. The corresponding estimates indicate that the rate of dropout due to good prognosis is about twice as high in the magnesium group compared with standard treatment. We emphasise the importance of identifying reasons for dropout and undertaking an appropriate statistical analysis accounting for such dropout. The joint modelling approach accounting for competing reasons for dropout is proposed as a general approach for evaluating the sensitivity of conclusions to assumptions regarding missing data in clinical trials with longitudinal outcomes. EudraCT number 2007-006227-12 . Registration date 18 Mar 2008.

Effect of local anaesthetic infiltration on chronic postsurgical pain after total hip and knee replacement: the APEX randomised controlled trials

PubMed Central

Wylde, Vikki; Lenguerrand, Erik; Gooberman-Hill, Rachael; Beswick, Andrew D.; Marques, Elsa; Noble, Sian; Horwood, Jeremy; Pyke, Mark; Dieppe, Paul; Blom, Ashley W.

2015-01-01

Abstract Total hip replacement (THR) and total knee replacement (TKR) are usually effective at relieving pain; however, 7% to 23% of patients experience chronic postsurgical pain. These trials aimed to investigate the effect of local anaesthetic wound infiltration on pain severity at 12 months after primary THR or TKR for osteoarthritis. Between November 2009 and February 2012, 322 patients listed for THR and 316 listed for TKR were recruited into a single-centre double-blind randomised controlled trial. Participants were randomly assigned (1:1) to receive local anaesthetic infiltration and standard care or standard care alone. Participants and outcomes assessors were masked to group allocation. The primary outcome was pain severity on the WOMAC Pain Scale at 12 months after surgery. Analyses were conducted using intention-to-treat and per-protocol approaches. In the hip trial, patients in the intervention group had significantly less pain at 12 months postoperative than patients in the standard care group (differences in means: 4.74; 95% confidence interval [CI]: 0.95-8.54; P = 0.015), although the difference was not clinically significant. Post hoc analysis found that patients in the intervention group were more likely to have none to moderate pain than severe pain at 12 months than those in the standard care group (odds ratio: 10.19; 95% CI: 2.10-49.55; P = 0.004). In the knee trial, there was no strong evidence that the intervention influenced pain severity at 12 months postoperative (difference in means: 3.83; 95% CI: −0.83 to 8.49; P = 0.107). In conclusion, routine use of infiltration could be beneficial in improving long-term pain relief for some patients after THR. PMID:25659070

The Sleep Or Mood Novel Adjunctive therapy (SOMNA) trial: a study protocol for a randomised controlled trial evaluating an internet-delivered cognitive behavioural therapy program for insomnia on outcomes of standard treatment for depression in men.

PubMed

Cockayne, Nicole L; Christensen, Helen M; Griffiths, Kathleen M; Naismith, Sharon L; Hickie, Ian B; Thorndike, Frances P; Ritterband, Lee M; Glozier, Nick S

2015-02-05

Insomnia is a significant risk factor for depression onset, can result in more disabling depressive illness, and is a common residual symptom following treatment cessation that can increase the risk of relapse. Internet-based cognitive behavioural therapy for insomnia has demonstrated efficacy and acceptability to men who are less likely than women to seek help in standard care. We aim to evaluate whether internet delivered cognitive behavioural therapy for insomnia as an adjunct to a standard depression therapeutic plan can lead to improved mood outcomes. Male participants aged 50 years or more, meeting Diagnostic and Statistical Manual of Mental Disorders criteria for current Major Depressive Episode and/or Dysthymia and self-reported insomnia symptoms, will be screened to participate in a single-centre double-blind randomised controlled trial with two parallel groups involving adjunctive internet-delivered cognitive behavioural therapy for insomnia and an internet-based control program. The trial will consist of a nine-week insomnia intervention period with a six-month follow-up period. During the insomnia intervention period participants will have their depression management coordinated by a psychiatrist using standard guideline-based depression treatments. The study will be conducted in urban New South Wales, Australia, where 80 participants from primary and secondary care and direct from the local community will be recruited. The primary outcome is change in the severity of depressive symptoms from baseline to week 12. This study will provide evidence on whether a widely accessible, evidence-based, internet-delivered cognitive behavioural therapy for insomnia intervention can lead to greater improvements than standard treatment for depression alone, in a group who traditionally do not readily access psychotherapy. The study is designed to establish effect size, feasibility and processes associated with implementing e-health solutions alongside standard clinical care, to warrant undertaking a larger more definitive clinical trial. Australian and New Zealand Clinical Trials Registry ACTRN12612000985886 .

Effect of a new insulin treatment regimen on glycaemic control and quality of life of Muslim patients with type 2 diabetes mellitus during Ramadan fast - an open label, controlled, multicentre, cluster randomised study.

PubMed

Shehadeh, N; Maor, Y

2015-11-01

We performed a non-inferiority trial comparing insulin detemir (Levemir) and biphasic insulin (NovoMix70) to standard care during Ramadan fast in insulin treated type 2 diabetes mellitus (T2DM) patients. This was an open label, controlled, multicentre, cluster randomised non-inferiority study. Insulin treated T2DM patients from 12 randomly selected primary clinics received Levemir and NovoMix 70 (intervention, n = 127) or standard care according to the American Diabetes Association recommendations (control, n = 118). Insulin dose (intervention) was 60% of the usual, of this 40% was dosed as Levemir at sunrise and 60% as NovoMix 70 before dinner. Insulin was titrated according to daily 4 point self-measured blood glucose (4P-SMBG) levels. The primary outcome was the difference in mean daily 4P-SMBG during days 23-30 of treatment. Mean age was 60.1 (SD 8.9) and 59.4 (SD 10.1) years in the intervention and control respectively. Mean HbA1c was 8.38% (68 mmol/mol) (SD 0.96) and 8.45% (69 mmol/mol) (SD 1.08). Mean BMI was 32.99 (SD 7.05) and 33.08 (SD 7.24), respectively. The intervention was non-inferior to standard care as assessed by mean 4P-SMBG during days 23-30 of treatment [155 (SD 30.76) mg% and 159 (SD 33.24) mg% respectively, p = 0.269]. Adverse event rate was significantly lower in the intervention group [0.04 (SD 0.06) vs. 0.07 (SD 0.11), p = 0.010]. In particular, hypoglycaemia event rate was lower in the intervention group [0.00 (SD 0.01) vs. 0.01 (SD 0.03), p ≤ 0.001]. To conclude, treatment with Levemir and NovoMix 70 was non-inferior to standard care in this heterogeneous group of patients and was associated with less adverse events. © 2015 John Wiley & Sons Ltd.

Pilot cluster randomised controlled trial of flooring to reduce injuries from falls in elderly care units: study protocol.

PubMed

Drahota, Amy; Gal, Diane; Windsor, Julie; Dixon, Simon; Udell, Julie; Ward, Derek; Soilemezi, Dia; Dean, Taraneh; Severs, Martin

2011-12-01

Falls are an issue disproportionately affecting older people who are at increased risk of falls and injury. This protocol describes a pilot study investigating shock-absorbing flooring for fall-related injuries in wards for older people. To inform future research by evaluating fall-related injuries on the intervention and existing flooring, assessing the sustainability of the flooring in ward environments, estimating the cost-effectiveness of the floor and assessing how the floor affects patients and other users. This study uses mixed methods a pilot cluster randomised controlled trial, observation via mechanical testing and interviews. Eight participating wards (clusters) are randomised using a computer-generated list. No blinding is incorporated into the study. Each site has a baseline period of approximately 6 months. Then, four sites receive the intervention floor, while four continue using standard floors. Sites are then followed up for approximately 1 year. Any person admitted to a bed in the 'study area' of a participating ward can be entered into the trial. Orientated patients, visitors and any hospital staff who use the floor in a study area are eligible for inclusion in an interview. An 8.3 mm thick vinyl floor covering with polyvinyl chloride foam backing (Tarkett Omnisports EXCEL). The primary outcome is fall-related injuries. Severity of injuries, falls, cost-effectiveness, user views and mechanical performance (shock absorbency and slip resistance) are also being assessed.

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

PubMed

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

2012-06-01

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

The TRACTISS Protocol: a randomised double blind placebo controlled clinical TRial of Anti-B-Cell Therapy In patients with primary Sjögren’s Syndrome

PubMed Central

2014-01-01

Background Primary Sjögren’s Syndrome (PSS) mainly affects women (9:1 female:male ratio) and is one of the commonest autoimmune diseases with a prevalence of 0.1 – 0.6% of adult women. For patients with PSS there is currently no effective therapy that can alter the progression of the disease. The aim of the TRACTISS study is to establish whether in patients with PSS, treatment with rituximab improves clinical outcomes. Methods/design TRACTISS is a UK multi-centre, double-blind, randomised, controlled, parallel group trial of 110 patients with PSS. Patients will be randomised on a 1:1 basis to receive two courses of either rituximab or placebo infusion in addition to standard therapy, and will be followed up for up to 48 weeks. The primary objective is to assess the extent to which rituximab improves symptoms of fatigue and oral dryness. Secondary outcomes include ocular dryness, salivary flow rates, lacrimal flow, patient quality of life, measures of disease damage and disease activity, serological and peripheral blood biomarkers, and glandular histology and composition. Discussion The TRACTISS trial will provide direct evidence as to whether rituximab in patients with PSS leads to an improvement in patient symptoms and a reduction in disease damage and activity. Trial registration UKCRN Portfolio ID: 9809 ISRCTN65360827. PMID:24438039

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.

Protocol for the "four steps to control your fatigue (4-STEPS)" randomised controlled trial: a self-regulation based physical activity intervention for patients with unexplained chronic fatigue

PubMed Central

2012-01-01

Background Unexplained Chronic Fatigue is a medical condition characterized by the presence of persistent, severe and debilitating medically unexplained fatigue, leading to impaired functioning and lower quality of life. Research suggests that physical activity can contribute to the reduction of fatigue and other somatic symptoms and can thus significantly improve physical functioning and quality of life in these patients. Based on the self-regulation (SR) theory of behaviour change, we developed a brief physical activity program for patients suffering from unexplained chronic fatigue which focuses on the training of self-regulation skills, the "4-STEPS to control your fatigue" program. Methods/Design This is a multi-centre, randomised controlled trial (RCT) that will be carried out in local primary care centres and at the Portuguese Fibromyalgia and Chronic Fatigue Syndrome Patients Association. Patients aged between 18 and 65 and fulfilling operationalized criteria for Idiopathic Chronic Fatigue (ICF) and Chronic Fatigue Syndrome (CFS) will be recruited and randomly allocated to standard care (SC) or standard care plus a self-regulation based physical activity program (4-STEPS). Patients will be assessed at baseline, after the intervention (3 months) and at 12 months follow-up. The primary outcome is fatigue severity. Discussion The results of the RCT will provide information about the effectiveness of a brief self-regulation intervention for promoting physical activity in patients with unexplained chronic fatigue. If the program proves to be effective, it may be considered as an adjunctive treatment for these patients. Trial Registration ISRCTN: ISRCTN70763996 PMID:22429404

Combination of a structured aerobic and resistance exercise improves glycaemic control in pregnant women diagnosed with gestational diabetes mellitus. A randomised controlled trial.

PubMed

Sklempe Kokic, Iva; Ivanisevic, Marina; Biolo, Gianni; Simunic, Bostjan; Kokic, Tomislav; Pisot, Rado

2017-10-18

Gestational diabetes mellitus, defined as any carbohydrate intolerance first diagnosed during pregnancy, is associated with a variety of adverse outcomes, both for the mother and her child. To investigate the impact of a structured exercise programme which consisted of aerobic and resistance exercises on the parameters of glycaemic control and other health-related outcomes in pregnant women diagnosed with gestational diabetes mellitus. Thirty-eight pregnant women diagnosed with gestational diabetes mellitus were randomised to two groups. Experimental group was treated with standard antenatal care for gestational diabetes mellitus, and regular supervised exercise programme plus daily brisk walks of at least 30min. Control group received only standard antenatal care for gestational diabetes mellitus. The exercise programme was started from the time of diagnosis of diabetes until birth. It was performed two times per week and sessions lasted 50-55min. The experimental group had lower postprandial glucose levels at the end of pregnancy (P<0.001). There was no significant difference between groups in the level of fasting glucose at the end of pregnancy. Also, there were no significant differences in the rate of complications during pregnancy and birth, need for pharmacological therapy, maternal body mass and body fat percentage gains during pregnancy, and neonatal Apgar scores, body mass and ponderal index. Neonatal body mass index was higher in the experimental group (P=0.035). The structured exercise programme had a beneficial effect on postprandial glucose levels at the end of pregnancy. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Caseload midwifery care versus standard maternity care for women of any risk: M@NGO, a randomised controlled trial.

PubMed

Tracy, Sally K; Hartz, Donna L; Tracy, Mark B; Allen, Jyai; Forti, Amanda; Hall, Bev; White, Jan; Lainchbury, Anne; Stapleton, Helen; Beckmann, Michael; Bisits, Andrew; Homer, Caroline; Foureur, Maralyn; Welsh, Alec; Kildea, Sue

2013-11-23

Women at low risk of pregnancy complications benefit from continuity of midwifery care, but no trial evidence exists for women with identified risk factors. We aimed to assess the clinical and cost outcomes of caseload midwifery care for women irrespective of risk factors. In this unblinded, randomised, controlled, parallel-group trial, pregnant women at two metropolitan teaching hospitals in Australia were randomly assigned to either caseload midwifery care or standard maternity care by a telephone-based computer randomisation service. Women aged 18 years and older were eligible if they were less than 24 weeks pregnant at the first booking visit. Those who booked with another care provider, had a multiple pregnancy, or planned to have an elective caesarean section were excluded. Women allocated to caseload care received antenatal, intrapartum, and postnatal care from a named caseload midwife (or back-up caseload midwife). Controls received standard care with rostered midwives in discrete wards or clinics. The participant and the clinician were not masked to assignment. The main primary outcome was the proportion of women who had a caesarean section. The other primary maternal outcomes were the proportions who had an instrumental or unassisted vaginal birth, and the proportion who had epidural analgesia during labour. Primary neonatal outcomes were Apgar scores, preterm birth, and admission to neonatal intensive care. We analysed all outcomes by intention to treat. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12609000349246. Publicly insured women were screened at the participating hospitals between Dec 8, 2008, and May 31, 2011. 1748 pregnant women were randomly assigned, 871 to caseload and 877 to standard care. The proportion of caesarean sections did not differ between the groups (183 [21%] in the caseload group vs 204 [23%] in the standard care group; odds ratio [OR] 0·88, 95% CI 0·70-1·10; p=0·26). The proportion of women who had elective caesarean sections (before onset of labour) differed significantly between caseload and standard care (69 [8%] vs 94 [11%]; OR 0·72, 95% CI 0·52-0·99; p=0·05). Proportions of instrumental birth were similar (172 [20%] vs 171 [19%]; p=0·90), as were the proportions of unassisted vaginal births (487 [56%] vs 454 [52%]; p=0·08) and epidural use (314 [36%] vs 304 [35%]; p=0·54). Neonatal outcomes did not differ between the groups. Total cost of care per woman was AUS$566·74 (95% 106·17-1027·30; p=0·02) less for caseload midwifery than for standard maternity care. Our results show that for women of any risk, caseload midwifery is safe and cost effective. National Health and Medical Research Council (Australia). Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of antenatal multiple micronutrient supplementation on anthropometry and blood pressure in mid-childhood in Nepal: follow-up of a double-blind randomised controlled trial

PubMed Central

Devakumar, Delan; Chaube, Shiva Shankar; Wells, Jonathan C K; Saville, Naomi M; Ayres, Jon G; Manandhar, Dharma S; Costello, Anthony; Osrin, David

2014-01-01

Summary Background In 2002–04, we did a randomised controlled trial in southern Nepal, and reported that children born to mothers taking multiple micronutrient supplements during pregnancy had a mean birthweight 77 g greater than children born to mothers taking iron and folic acid supplements. Children born to mothers in the study group were a mean 204 g heavier at 2·5 years of age and their systolic blood pressure was a mean 2·5 mm Hg lower than children born to mothers in the control group. We aimed to follow up the same children to mid-childhood (age 8·5 years) to investigate whether these differences would be sustained. Methods For this follow-up study, we identified children from the original trial and measured anthropometry, body composition with bioelectrical impedance (with population-specific isotope calibration), blood pressure, and renal dimensions by ultrasound. We documented socioeconomic status, household food security, and air pollution. Main outcomes of the follow-up at 8 years were Z scores for weight-for-age, height-for-age, and body-mass index (BMI)-for-age according to WHO Child Growth Standards for children aged 5–19 years, and blood pressure. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN88625934. Findings Between Sept 21, 2011, and Dec 7, 2012, we assessed 841 children (422 in the control group and 419 in the intervention group). Unadjusted differences (intervention minus control) in Z scores were 0·05 for weight-for-age (95% CI −0·09 to 0·19), 0·02 in height-for-age (−0·10 to 0·15), and 0·04 in BMI-for-age (−0·09 to 0·18). We recorded no difference in blood pressure. Adjusted differences were similar for all outcomes. Interpretation We recorded no differences in phenotype between children born to mothers who received antenatal multiple micronutrient or iron and folate supplements at age 8·5 years. Our findings did not extend to physiological differences or potential longer-term effects. Funding The Wellcome Trust. PMID:25442690

Neurofeedback ineffective in paediatric brain tumour survivors: Results of a double-blind randomised placebo-controlled trial.

PubMed

de Ruiter, Marieke Anna; Oosterlaan, Jaap; Schouten-van Meeteren, Antoinette Yvonne Narda; Maurice-Stam, Heleen; van Vuurden, Dannis Gilbert; Gidding, Corrie; Beek, Laura Rachel; Granzen, Bernd; Caron, Huib N; Grootenhuis, Martha Alexandra

2016-09-01

Many paediatric brain tumour survivors (PBTS) suffer from neurocognitive impairments. Promising effects of neurofeedback (NF) on neurocognitive functioning have been reported, however research into NF for PBTS has not been conducted. We investigated the effects of NF on neurocognitive functioning in PBTS using a double-blind randomised placebo-controlled trial with a parallel-group design (Pediatric Research on Improving Speed, Memory, and Attention; the PRISMA study). Eligible for inclusion were PBTS with neurocognitive complaints, aged 8-18 years, >2 years post-treatment. They were recruited from five medical centres in the Netherlands. A randomisation table assigned participants to 30 sessions (two per week) of either NF or placebo feedback (PF) (ratio 1:1). Participants, parents, trainers, and researchers handling the data were blinded to group assignment. Participants were assessed pre-, post- and 6 months post-training to determine whether NF training would lead to improved functioning as compared with PF training. Primary outcome measures were attention, processing speed, memory, executive functioning, visuomotor integration, and intelligence. Linear mixed models analyses were used to test differences between NF and PF training over time. A total of 82 children were enrolled (mean age 13.9 years, standard deviation = 3.2, 49% males); 80 participants were randomised (NF: n = 40, PF n = 40); 71 participants completed the training (NF: n = 34, PF: n = 37); 68 participants completed training and 6 months post-training assessment (NF: n = 33, PF: n = 35). Similar improvements were found over time for the two treatment groups on the primary outcomes (all p's > 0.15). Results indicated no specific treatment-effects of NF on neurocognitive functioning of PBTS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessment of the quality of harms reporting in non-randomised studies and randomised controlled studies of topiramate for the treatment of epilepsy using CONSORT criteria.

PubMed

Carmichael, Katie; Nolan, Sarah J; Weston, Jennifer; Tudur Smith, Catrin; Marson, Anthony G

2015-08-01

Treatment decisions should be informed by high quality evidence of both the potential benefit and harms of treatment alternatives. Randomised controlled trials (RCTs) provide the best evidence regarding benefits; however information relating to serious, rare and long-term harms is usually available only from non-randomised studies (NRSs). The aim of this study was to use a checklist based on the CONSORT (Consolidating Standards for Reporting Trials) extension for harms recommendations to assess the quality of reporting of harms data in both NRSs and RCTs of antiepileptic drugs, using studies of topiramate as an example. Seventy-eight studies were included from an online search of seven databases. Harms data was extracted from each study using a 25-point checklist. The mean number of items met was 11.5 (SD 2.96) per study. Commercially funded studies met on average 12.7 items and non-commercially funded studies met 10.08 (p value < 0.001). RCTs met on average 13.0 items and NRSs met 10.8 (p = 0.001). Multi-centre studies and commercially funded studies met significantly more items than single centre and non-commercially funded studies respectively. There was no significant difference in the mean number of items met by studies that had included adult vs. child participants, or studies published pre- vs. post-CONSORT extension for harms in 2004. Reporting of harms is significantly better in RCTs than in NRSs of TPM, but is suboptimal overall and has not improved since the publication of CONSORT extension for harms in 2004. There is a need to improve the reporting of harms in order to better inform treatment decisions. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2013-01-01

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

The Effect of Paracetamol on Core Body Temperature in Acute Traumatic Brain Injury: A Randomised, Controlled Clinical Trial.

PubMed

Saxena, Manoj K; Taylor, Colman; Billot, Laurent; Bompoint, Severine; Gowardman, John; Roberts, Jason A; Lipman, Jeffery; Myburgh, John

2015-01-01

Strategies to prevent pyrexia in patients with acute neurological injury may reduce secondary neuronal damage. The aim of this study was to determine the safety and efficacy of the routine administration of 6 grams/day of intravenous paracetamol in reducing body temperature following severe traumatic brain injury, compared to placebo. A multicentre, randomised, blind, placebo-controlled clinical trial in adult patients with traumatic brain injury (TBI). Patients were randomised to receive an intravenous infusion of either 1g of paracetamol or 0.9% sodium chloride (saline) every 4 hours for 72 hours. The primary outcome was the mean difference in core temperature during the study intervention period. Forty-one patients were included in this study: 21 were allocated to paracetamol and 20 to saline. The median (interquartile range) number of doses of study drug was 18 (17-18) in the paracetamol group and 18 (16-18) in the saline group (P = 0.85). From randomisation until 4 hours after the last dose of study treatment, there were 2798 temperature measurements (median 73 [67-76] per patient). The mean ± standard deviation temperature was 37.4±0.5°C in the paracetamol group and 37.7±0.4°C in the saline group (absolute difference -0.3°C; 95% confidence interval -0.6 to 0.0; P = 0.09). There were no significant differences in the use of physical cooling, or episodes of hypotension or hepatic abnormalities, between the two groups. The routine administration of 6g/day of intravenous paracetamol did not significantly reduce core body temperature in patients with TBI. Australian New Zealand Clinical Trials Registry ACTRN12609000444280.

Sexual health clinics for women led by specialist nurses or senior house officers in a central London GUM service: a randomised controlled trial.

PubMed

Miles, K; Penny, N; Mercey, D; Power, R

2002-04-01

To assess the care process and clinical outcomes for two different models of GUM clinic for women: one led by specialist nurses and the other by senior house officers (SHOs). An open randomised controlled trial was carried out in a central London genitourinary medicine (GUM) women's clinic. Of 1172 women telephoning for an appointment, 880 were randomised to provide 169 eligible patients in the specialist nurse arm and 178 in the SHO arm. Of the eligible patients a total of 224 attended their appointment. The clinical records of the randomised women were audited for adequacy of care according to local guidelines. 30 key variables were objectively assessed and recorded on a standard audit form. An overall unitary index score (%) was calculated for each patient. The main variables associated with the outcome of specialist nurse and SHO decision making (diagnostic test request, preliminary diagnosis, and treatment provided) were then analysed independently. The median documentation audit scores for specialist nurses (n=103) and SHOs (n=121) were 92% and 85% respectively (p<0.0001). The specialist nurses' documentation was significantly (p<0.05) more complete than the SHOs' for five variables: details of menstrual cycle, physical examination, medication instructions given to patients, health promotion discussion, and provision of condoms. Specialist nurses performed equally to the SHOs with regard to requesting the correct diagnostic tests, providing the correct preliminary diagnosis, and providing the correct treatment. A model of care using trained GUM nurses working within agreed protocols can provide comprehensive patient care for female patients that is equal to care provided by SHOs. Our results raise important issues regarding advanced GUM nursing education and training, protocol development, and accountability.

30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial.

PubMed

Ringleb, P A; Allenberg, J; Brückmann, H; Eckstein, H-H; Fraedrich, G; Hartmann, M; Hennerici, M; Jansen, O; Klein, G; Kunze, A; Marx, P; Niederkorn, K; Schmiedt, W; Solymosi, L; Stingele, R; Zeumer, H; Hacke, W

2006-10-07

Carotid endarterectomy is effective in stroke prevention for patients with severe symptomatic carotid-artery stenosis, and carotid-artery stenting has been widely used as alternative treatment. Since equivalence or superiority has not been convincingly shown for either treatment, we aimed to compare the two. 1200 patients with symptomatic carotid-artery stenosis were randomly assigned within 180 days of transient ischaemic attack or moderate stroke (modified Rankin scale score of < or =3) carotid-artery stenting (n=605) or carotid endarterectomy (n=595). The primary endpoint of this hospital-based study was ipsilateral ischaemic stroke or death from time of randomisation to 30 days after the procedure. The non-inferiority margin was defined as less than 2.5% on the basis of an expected event rate of 5%. Analyses were on an intention-to-treat basis. This trial is registered at Current Controlled Trials with the international standard randomised controlled trial number ISRCTN57874028. 1183 patients were included in the analysis. The rate of death or ipsilateral ischaemic stroke from randomisation to 30 days after the procedure was 6.84% with carotid-artery stenting and 6.34% with carotid endarterectomy (absolute difference 0.51%, 90% CI -1.89% to 2.91%). The one-sided p value for non-inferiority is 0.09. SPACE failed to prove non-inferiority of carotid-artery stenting compared with carotid endarterectomy for the periprocedural complication rate. The results of this trial do not justify the widespread use in the short-term of carotid-artery stenting for treatment of carotid-artery stenoses. Results at 6-24 months are awaited.

Gentamicin versus ceftriaxone for the treatment of gonorrhoea (G-TOG trial): study protocol for a randomised trial.

PubMed

Brittain, Clare; Childs, Margaret; Duley, Lelia; Harding, Jan; Hepburn, Trish; Meakin, Garry; Montgomery, Alan A; Tan, Wei; Ross, Jonathan D C

2016-11-24

Gonorrhoea is a common sexually transmitted infection which causes genital pain and discomfort; in women it can also lead to pelvic inflammatory disease and infertility, and in men to epididymo-orchitis. Current treatment is with ceftriaxone, but there is increasing evidence of antimicrobial resistance which is reducing its effectiveness against gonorrhoea. A small, but increasing, number of patients have already been found to have highly resistant strains of gonorrhoea which has been associated with clinical failure. This trial aims to determine whether gentamicin is not clinically worse than ceftriaxone in the treatment of gonorrhoea. This is a blinded, two-arm, multicentre, noninferiority randomised trial. Patients are eligible if they are aged 16-70 years with a diagnosis of genital, pharyngeal and/or rectal gonorrhoea. Exclusion criteria are: known concurrent sexually transmitted infection(s) (excluding chlamydia); bacterial vaginosis and/or Trichomonas vaginalis infection; contraindications or an allergy to gentamicin, ceftriaxone, azithromycin or lidocaine; pregnancy or breastfeeding; complicated gonorrhoeal infection; weight under 40 kg; use of ceftriaxone, gentamicin or azithromycin within the preceding 28 days. Randomisation is to receive a single intramuscular injection of either gentamicin or ceftriaxone, all participants receive 1 g oral azithromycin as standard treatment. The estimated sample size is 720 participants (noninferiority limit 5%). The primary outcome is clearance of Neisseria gonorrhoeae at all infected sites by a negative Nucleic Acid Amplification Test, 2 weeks post treatment. Secondary outcomes include clinical resolution of symptoms, frequency of adverse events, tolerability of therapy, relationship between clinical effectiveness and antibiotic minimum inhibitory concentration for N. gonorrhoeae, and cost-effectiveness. The options for future treatment of gonorrhoea are limited. Results from this randomised trial will demonstrate whether gentamicin is not clinically worse than ceftriaxone for the treatment of gonorrhoea. This will inform clinical practice and policy for the treatment of gonorrhoea when current therapy with cephalosporins is no longer effective, or is contraindicated. International Standard Randomised Controlled Trial Number - ISRCTN51783227 , Registered on 18 September 2014. Current protocol version 2.0 17 June 2015.

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.

Effect of antenatal education in small classes versus standard auditorium-based lectures on use of pain relief during labour and of obstetric interventions: results from the randomised NEWBORN trial.

PubMed

Brixval, Carina Sjöberg; Thygesen, Lau Caspar; Axelsen, Solveig Forberg; Gluud, Christian; Winkel, Per; Lindschou, Jane; Weber, Tom; Due, Pernille; Koushede, Vibeke

2016-06-10

To examine the effect of an antenatal education programme in small classes versus standard auditorium-based lectures. Randomised trial using random-generated web-based 1:1 allocation. The largest birth site in the Capital Region of Denmark, from August 2012 to May 2014. 1766 pregnant women. Inclusion criteria ≥18 years, pregnant with a single child, and able to speak and understand Danish. Women were enrolled in the trial from 10+0 to 20+0 weeks of gestation. The intervention programme consisted of three times 2.5 hours of antenatal education in small classes (n=6-8 women), and focused on improving information and problem-solving skills for expectant parents in order to ease birth and the transition to parenthood. The control group received standard auditorium-based lectures consisting of two times 2 hours in an auditorium with participation of ∼250 people. The primary trial outcome was use of epidural analgesia. Other types of pain relief and obstetric interventions were analysed as explorative outcomes. There was no statistically significant difference in use of epidural analgesia between participants in the intervention group (30.9%) versus the control group (29.1%), adjusted OR 1.10 (95% CI 0.87 to 1.34). Also, the two groups did not differ regarding other types of pain relief or obstetric interventions. Concomitant birth preparation was common in both groups and highest in the control group, but did not seem to influence our results noticeably. Antenatal education in small groups versus standard auditorium-based lectures did not differ regarding use of epidural analgesia, other pain relief, or obstetric interventions. NCT01672437; 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/

Haloperidol versus placebo for delirium prevention in acutely hospitalised older at risk patients: a multi-centre double-blind randomised controlled clinical trial.

PubMed

Schrijver, Edmée J M; de Vries, Oscar J; van de Ven, Peter M; Bet, Pierre M; Kamper, Ad M; Diepeveen, Sabine H A; van Marum, Rob J; van Strien, Astrid M; Anten, Sander; Lagaay, Anne M; Boelaarts, Leo; Bloemers, Frank W; Kramer, Mark H H; Nanayakkara, Prabath W B

2018-01-01

because the few randomised placebo-controlled trials investigating the potential role for prophylactic haloperidol in delirium prevention have focused on specific surgical populations, we investigated its efficacy and safety in acutely hospitalised older patients. this multi-centre, double-blind, stratified, block randomised, placebo-controlled trial was conducted at six Dutch hospitals. Patients age ≥70 years, acutely admitted through the emergency department for general medicine or surgical specialties and at risk for delirium were randomised (n = 245) to haloperidol or placebo 1 mg orally twice-daily (maximum of 14 doses) on top of standard nonpharmacological prevention strategies. The primary outcome was delirium incidence. Other endpoints included delirium severity and duration, drug safety and clinical outcomes. intention-to-treat analysis included 242 participants (calculated sample size n = 390, statistical power of current sample 59%) allocated to haloperidol (n = 118) or placebo (n = 124). In the haloperidol and placebo group, delirium incidence was 19.5 versus 14.5% (OR 1.43, 95% CI 0.72 to 2.78); median (IQR) delirium duration 4 (2, 5) versus 3 (1, 6) days (P = 0.366); maximum DRS-R-98 score 16 (9.8, 19.5) versus 10 (5.5, 22.5) (P = 0.549; 53.7% missing data); hospital LOS 7 (4, 10.3) versus 7 (5, 11.8) days (P = 0.343); 3-month mortality 9.9 versus 12.5% (OR 0.77, 95% CI 0.34 to 1.75), respectively. No treatment-limiting side effects were noted. prophylactic low-dose oral haloperidol did not reduce delirium incidence in acutely hospitalised older patients. Therefore, prophylactic use of haloperidol in this population is not recommended. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com

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

PubMed Central

2010-01-01

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

Medicoeconomic analysis of lobectomy using thoracoscopy versus thoracotomy for lung cancer: a study protocol for a multicentre randomised controlled trial (Lungsco01).

PubMed

Pagès, Pierre-Benoit; Abou Hanna, Halim; Bertaux, Anne-Claire; Serge Aho, Ludwig Serge; Magdaleinat, Pierre; Baste, Jean-Marc; Filaire, Marc; de Latour, Richard; Assouad, Jalal; Tronc, François; Jayle, Christophe; Mouroux, Jérome; Thomas, Pascal-Alexandre; Falcoz, Pierre-Emmanuel; Marty-Ané, Charles-Henri; Bernard, Alain

2017-06-15

In the last decade, video-assisted thoracoscopic surgery (VATS) lobectomy for non-small cell lung cancer (NSCLC) has had a major effect on thoracic surgery. Retrospective series have reported benefits of VATS when compared with open thoracotomy in terms of postoperative pain, postoperative complications and length of hospital stay. However, no large randomised control trial has been conducted to assess the reality of the potential benefits of VATS lobectomy or its medicoeconomic impact. The French National Institute of Health funded Lungsco01 to determine whether VATS for lobectomy is superior to open thoracotomy for the treatment of NSCLC in terms of economic cost to society. This trial will also include an analysis of postoperative outcomes, the length of hospital stay, the quality of life, long-term survival and locoregional recurrence. The study design is a two-arm parallel randomised controlled trial comparing VATS lobectomy with lobectomy using thoracotomy for the treatment of NSCLC. Patients will be eligible if they have proven or suspected lung cancer which could be treated by lobectomy. Patients will be randomised via an independent service. All patients will be monitored according to standard thoracic surgical practices. All patients will be evaluated at day 1, day 30, month 3, month 6, month 12 and then every year for 2 years thereafter. The recruitment target is 600 patients. The protocol has been approved by the French National Research Ethics Committee (CPP Est I: 09/06/2015) and the French Medicines Agency (09/06/2015). Results will be presented at national and international meetings and conferences and published in peer-reviewed journals. NCT02502318. © 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.

TOPPITS: Trial Of Proton Pump Inhibitors in Throat Symptoms. Study protocol for a randomised controlled trial.

PubMed

Watson, Gillian; O'Hara, James; Carding, Paul; Lecouturier, Jan; Stocken, Deborah; Fouweather, Tony; Wilson, Janet

2016-04-01

Persistent throat symptoms and Extra Oesophageal Reflux (EOR) are among the commonest reasons for attendance at a secondary care throat or voice clinic. There is a growing trend to treat throat symptom patients with proton pump inhibitors (PPIs) to suppress stomach acid, but most controlled studies fail to demonstrate a significant benefit of PPI over placebo. In addition, patient views on PPI use vary widely. A UK multi-centre, randomised, controlled trial for adults with persistent throat symptoms to compare the effectiveness of treatment with the proton pump inhibitor (PPI) lansoprazole versus placebo. The trial includes a six-month internal pilot, during which three sites will recruit 30 participants in total, to assess the practicality of the trial and assess the study procedures and willingness of the patient population to participate. If the pilot is successful, three additional sites will be opened to recruitment, and a further 302 participants recruited across the six main trial sites. Further trial sites may be opened, as necessary. The main trial will continue for a further 18 months. Participants will be followed up for 12 months from randomisation, throughout which both primary and secondary outcome data will be collected. The primary outcome is change in Reflux Symptom Index (RSI) score, the 'area standard' for this type of assessment, after 16 weeks (four months) of treatment. Secondary outcomes are RSI changes at 12 months after randomisation, Quality of Life assessment at four and 12 months, laryngeal mucosal changes, assessments of compliance and side effects, and patient-reported satisfaction. TOPPITS is designed to evaluate the relative effectiveness of treatment with a proton pump inhibitor versus placebo in patients with persistent throat symptoms. This will provide valuable information to clinicians and GPs regarding the treatment and management of care for these patients, on changes in symptoms, and in Quality of Life, over time. ISRCTN38578686 . Registered 17 April 2014.

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

PubMed

Treacy, Daniel; Schurr, Karl; Sherrington, Catherine

2013-07-20

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

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

PubMed

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

2010-10-21

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

Infant wellbeing at 2 years of age in the Growth Restriction Intervention Trial (GRIT): multicentred randomised controlled trial.

PubMed

Thornton, J G; Hornbuckle, J; Vail, A; Spiegelhalter, D J; Levene, M

Although delivery is widely used for preterm babies failing to thrive in utero, the effect of altering delivery timing has never been assessed in a randomised controlled trial. We aimed to compare the effect of delivering early with delaying birth for as long as possible. 548 pregnant women were recruited by 69 hospitals in 13 European countries. Participants had fetal compromise between 24 and 36 weeks, an umbilical-artery doppler waveform recorded, and clinical uncertainty about whether immediate delivery was indicated. Before birth, 588 babies were randomly assigned to immediate delivery (n=296) or delayed delivery until the obstetrician was no longer uncertain (n=292). The main outcome was death or disability at or beyond 2 years of age. Disability was defined as a Griffiths developmental quotient of 70 or less or the presence of motor or perceptual severe disability. Analysis was by intention-to-treat. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN41358726. Primary outcomes were available on 290 (98%) immediate and 283 (97%) deferred deliveries. Overall rate of death or severe disability at 2 years was 55 (19%) of 290 immediate births, and 44 (16%) of 283 delayed births. With adjustment for gestational age and umbilical-artery doppler category, the odds ratio (95% CrI) was 1.1 (0.7-1.8). Most of the observed difference was in disability in babies younger than 31 weeks of gestation at randomisation: 14 (13%) immediate versus five (5%) delayed deliveries. No important differences in the median Griffiths developmental quotient in survivors was seen. The lack of difference in mortality suggests that obstetricians are delivering sick preterm babies at about the correct moment to minimise mortality. However, they could be delivering too early to minimise brain damage. These results do not lend support to the idea that obstetricians can deliver before terminal hypoxaemia to improve brain development.

Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial.

PubMed

Ferreri, Andrés J M; Cwynarski, Kate; Pulczynski, Elisa; Ponzoni, Maurilio; Deckert, Martina; Politi, Letterio S; Torri, Valter; Fox, Christopher P; Rosée, Paul La; Schorb, Elisabeth; Ambrosetti, Achille; Roth, Alexander; Hemmaway, Claire; Ferrari, Angela; Linton, Kim M; Rudà, Roberta; Binder, Mascha; Pukrop, Tobias; Balzarotti, Monica; Fabbri, Alberto; Johnson, Peter; Gørløv, Jette Sønderskov; Hess, Georg; Panse, Jens; Pisani, Francesco; Tucci, Alessandra; Stilgenbauer, Stephan; Hertenstein, Bernd; Keller, Ulrich; Krause, Stefan W; Levis, Alessandro; Schmoll, Hans J; Cavalli, Franco; Finke, Jürgen; Reni, Michele; Zucca, Emanuele; Illerhaus, Gerald

2016-05-01

Standard treatment for patients with primary CNS lymphoma remains to be defined. Active therapies are often associated with increased risk of haematological or neurological toxicity. In this trial, we addressed the tolerability and efficacy of adding rituximab with or without thiotepa to methotrexate-cytarabine combination therapy (the MATRix regimen), followed by a second randomisation comparing consolidation with whole-brain radiotherapy or autologous stem cell transplantation in patients with primary CNS lymphoma. We report the results of the first randomisation in this Article. For the international randomised phase 2 International Extranodal Lymphoma Study Group-32 (IELSG32) trial, HIV-negative patients (aged 18-70 years) with newly diagnosed primary CNS lymphoma and measurable disease were enrolled from 53 cancer centres in five European countries (Denmark, Germany, Italy, Switzerland, and the UK) and randomly assigned (1:1:1) to receive four courses of methotrexate 3·5 g/m(2) on day 1 plus cytarabine 2 g/m(2) twice daily on days 2 and 3 (group A); or the same combination plus two doses of rituximab 375 mg/m(2) on days -5 and 0 (group B); or the same methotrexate-cytarabine-rituximab combination plus thiotepa 30 mg/m(2) on day 4 (group C), with the three groups repeating treatment every 3 weeks. Patients with responsive or stable disease after the first stage were then randomly allocated between whole-brain radiotherapy and autologous stem cell transplantation. A permuted blocks randomised design (block size four) was used for both randomisations, and a computer-generated randomisation list was used within each stratum to preserve allocation concealment. Randomisation was stratified by IELSG risk score (low vs intermediate vs high). No masking after assignment to intervention was used. The primary endpoint of the first randomisation was the complete remission rate, analysed by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01011920. Between Feb 19, 2010, and Aug 27, 2014, 227 eligible patients were recruited. 219 of these 227 enrolled patients were assessable. At median follow-up of 30 months (IQR 22-38), patients treated with rituximab and thiotepa had a complete remission rate of 49% (95% CI 38-60), compared with 23% (14-31) of those treated with methotrexate-cytarabine alone (hazard ratio 0·46, 95% CI 0·28-0·74) and 30% (21-42) of those treated with methotrexate-cytarabine plus rituximab (0·61, 0·40-0·94). Grade 4 haematological toxicity was more frequent in patients treated with methotrexate-cytarabine plus rituximab and thiotepa, but infective complications were similar in the three groups. The most common grade 3-4 adverse events in all three groups were neutropenia, thrombocytopenia, anaemia, and febrile neutropenia or infections. 13 (6%) patients died of toxicity. With the limitations of a randomised phase 2 study design, the IELSG32 trial provides a high level of evidence supporting the use of MATRix combination as the new standard chemoimmunotherapy for patients aged up to 70 years with newly diagnosed primary CNS lymphoma and as the control group for future randomised trials. Associazione Italiana del Farmaco, Cancer Research UK, Oncosuisse, and Swiss National Foundation. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Attention training for infants at familial risk of ADHD (INTERSTAARS): study protocol for a randomised controlled trial.

PubMed

Goodwin, Amy; Salomone, Simona; Bolton, Patrick; Charman, Tony; Jones, Emily J H; Pickles, Andrew; Robinson, Emily; Smith, Tim; Sonuga-Barke, Edmund J S; Wass, Sam; Johnson, Mark H

2016-12-28

Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder that can negatively impact on an individual's quality of life. It is pathophysiologically complex and heterogeneous with different neuropsychological processes being impaired in different individuals. Executive function deficits, including those affecting attention, working memory and inhibitory control, are common. Cognitive training has been promoted as a treatment option, based on the notion that by strengthening the neurocognitive networks underlying these executive processes, ADHD symptoms will also be reduced. However, if implemented in childhood or later, when the full disorder has become well-established, cognitive training has only limited value. INTERSTAARS is a trial designed to test a novel approach to intervention, in which cognitive training is implemented early in development, before the emergence of the disorder. The aim of INTERSTAARS is to train early executive skills, thereby increasing resilience and reducing later ADHD symptoms and associated impairment. Fifty 10-14-month-old infants at familial risk of ADHD will participate in INTERSTAARS. Infants will be randomised to an intervention or a control group. The intervention aims to train early attention skills by using novel eye-tracking technology and gaze-contingent training paradigms. Infants view animated games on a screen and different events take place contingent on where on the screen the infant is looking. Infants allocated to the intervention will receive nine weekly home-based attention training sessions. Control group infants will also receive nine weekly home visits, but instead of viewing the training games during these visits they will view non-gaze-contingent age-appropriate videos. At baseline and post treatment, infant attention control will be assessed using a range of eye-tracking, observational, parent-report and neurophysiological measures. The primary outcome will be a composite of eye-tracking tasks used to assess infant attention skills. Follow-up data will be collected on emerging ADHD symptoms when the infants are 2 and 3 years old. This is the first randomised controlled trial to assess the potential efficacy of cognitive training as a prevention measure for infants at familial risk of ADHD. If successful, INTERSTAARS could offer a promising new approach for developing early interventions for ADHD. International Standard Randomised Controlled Trial registry: ISRCTN37683928 . Registered on 22 June 2015.

Cell salvage and donor blood transfusion during cesarean section: A pragmatic, multicentre randomised controlled trial (SALVO)

PubMed Central

Khan, Khalid S.; Wilson, Matthew J.; Hooper, Richard; Allard, Shubha; Wrench, Ian; Geoghegan, James; Catling, Sue; Clark, Vicki A.; Ayuk, Paul; Robson, Stephen; Gao-Smith, Fang; Hogg, Matthew; Dodds, Julie

2017-01-01

Background Excessive haemorrhage at cesarean section requires donor (allogeneic) blood transfusion. Cell salvage may reduce this requirement. Methods and findings We conducted a pragmatic randomised controlled trial (at 26 obstetric units; participants recruited from 4 June 2013 to 17 April 2016) of routine cell salvage use (intervention) versus current standard of care without routine salvage use (control) in cesarean section among women at risk of haemorrhage. Randomisation was stratified, using random permuted blocks of variable sizes. In an intention-to-treat analysis, we used multivariable models, adjusting for stratification variables and prognostic factors identified a priori, to compare rates of donor blood transfusion (primary outcome) and fetomaternal haemorrhage ≥2 ml in RhD-negative women with RhD-positive babies (a secondary outcome) between groups. Among 3,028 women randomised (2,990 analysed), 95.6% of 1,498 assigned to intervention had cell salvage deployed (50.8% had salvaged blood returned; mean 259.9 ml) versus 3.9% of 1,492 assigned to control. Donor blood transfusion rate was 3.5% in the control group versus 2.5% in the intervention group (adjusted odds ratio [OR] 0.65, 95% confidence interval [CI] 0.42 to 1.01, p = 0.056; adjusted risk difference −1.03, 95% CI −2.13 to 0.06). In a planned subgroup analysis, the transfusion rate was 4.6% in women assigned to control versus 3.0% in the intervention group among emergency cesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 2.2% versus 1.8% among elective cesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46). No case of amniotic fluid embolism was observed. The rate of fetomaternal haemorrhage was higher with the intervention (10.5% in the control group versus 25.6% in the intervention group, adjusted OR 5.63, 95% CI 1.43 to 22.14, p = 0.013). We are unable to comment on long-term antibody sensitisation effects. Conclusions The overall reduction observed in donor blood transfusion associated with the routine use of cell salvage during cesarean section was not statistically significant. Trial registration This trial was prospectively registered on ISRCTN as trial number 66118656 and can be viewed on http://www.isrctn.com/ISRCTN66118656. PMID:29261655

Head-to-head comparison of intensive lifestyle intervention (U-TURN) versus conventional multifactorial care in patients with type 2 diabetes: protocol and rationale for an assessor-blinded, parallel group and randomised trial

PubMed Central

Ried-Larsen, Mathias; Hansen, Katrine B; Johansen, Mette Y; Pedersen, Maria; Zacho, Morten; Hansen, Louise S; Kofoed, Katja; Thomsen, Katja; Jensen, Mette S; Nielsen, Rasmus O; MacDonald, Chris; Langberg, Henning; Vaag, Allan A; Pedersen, Bente K; Karstoft, Kristian

2015-01-01

Introduction Current pharmacological therapies in patients with type 2 diabetes (T2D) are challenged by lack of sustainability and borderline firm evidence of real long-term health benefits. Accordingly, lifestyle intervention remains the corner stone in the management of T2D. However, there is a lack of knowledge regarding the optimal intervention programmes in T2D ensuring both compliance as well as long-term health outcomes. Our objective is to assess the effects of an intensive lifestyle intervention (the U-TURN intervention) on glycaemic control in patients with T2D. Our hypothesis is that intensive lifestyle changes are equally effective as standard diabetes care, including pharmacological treatment in maintaining glycaemic control (ie, glycated haemoglobin (HbA1c)) in patients with T2D. Furthermore, we expect that intensive lifestyle changes will decrease the need for antidiabetic medications. Methods and analysis The study is an assessor-blinded, parallel group and a 1-year randomised trial. The primary outcome is change in glycaemic control (HbA1c), with the key secondary outcome being reductions in antidiabetic medication. Participants will be patients with T2D (T2D duration <10 years) without complications who are randomised into an intensive lifestyle intervention (U-TURN) or a standard care intervention in a 2:1 fashion. Both groups will be exposed to the same standardised, blinded, target-driven pharmacological treatment and can thus maintain, increase, reduce or discontinue the pharmacological treatment. The decision is based on the standardised algorithm. The U-TURN intervention consists of increased training and basal physical activity level, and an antidiabetic diet including an intended weight loss. The standard care group as well as the U-TURN group is offered individual diabetes management counselling on top of the pharmacological treatment. Ethics and dissemination This study has been approved by the Scientific Ethical Committee at the Capital Region of Denmark (H-1–2014–114). Positive, negative or inconclusive findings will be disseminated in peer-reviewed journals, at national and international conferences. Trial registration number NCT02417012. PMID:26656025

Prophylactic antibiotics after acute stroke for reducing pneumonia in patients with dysphagia (STROKE-INF): a prospective, cluster-randomised, open-label, masked endpoint, controlled clinical trial.

PubMed

Kalra, Lalit; Irshad, Saddif; Hodsoll, John; Simpson, Matthew; Gulliford, Martin; Smithard, David; Patel, Anita; Rebollo-Mesa, Irene

2015-11-07

Post-stroke pneumonia is associated with increased mortality and poor functional outcomes. This study assessed the effectiveness of antibiotic prophylaxis for reducing pneumonia in patients with dysphagia after acute stroke. We did a prospective, multicentre, cluster-randomised, open-label controlled trial with masked endpoint assessment of patients older than 18 years with dysphagia after new stroke recruited from 48 stroke units in the UK, accredited and included in the UK National Stroke Audit. We excluded patients with contraindications to antibiotics, pre-existing dysphagia, or known infections, or who were not expected to survive beyond 14 days. We randomly assigned the units (1:1) by computer to give either prophylactic antibiotics for 7 days plus standard stroke unit care or standard stroke unit care only to patients clustered in the units within 48 h of stroke onset. We did the randomisation with minimisation to stratify for number of admissions and access to specialist care. Patient and staff who did the assessments and analyses were masked to stroke unit allocation. The primary outcome was post-stroke pneumonia in the first 14 days, assessed with both a criteria-based, hierarchical algorithm and by physician diagnosis in the intention-to-treat population. Safety was also analysed by intention to treat. This trial is closed to new participants and is registered with isrctn.com, number ISRCTN37118456. Between April 21, 2008, and May 17, 2014, we randomly assigned 48 stroke units (and 1224 patients clustered within the units) to the two treatment groups: 24 to antibiotics and 24 to standard care alone (control). 11 units and seven patients withdrew after randomisation before 14 days, leaving 1217 patients in 37 units for the intention-to-treat analysis (615 patients in the antibiotics group, 602 in control). Prophylactic antibiotics did not affect the incidence of algorithm-defined post-stroke pneumonia (71 [13%] of 564 patients in antibiotics group vs 52 [10%] of 524 in control group; marginal adjusted odds ratio [OR] 1·21 [95% CI 0·71-2·08], p=0·489, intraclass correlation coefficient [ICC] 0·06 [95% CI 0·02-0·17]. Algorithm-defined post-stroke pneumonia could not be established in 129 (10%) patients because of missing data. Additionally, we noted no differences in physician-diagnosed post-stroke pneumonia between groups (101 [16%] of 615 patients vs 91 [15%] of 602, adjusted OR 1·01 [95% CI 0·61-1·68], p=0·957, ICC 0·08 [95% CI 0·03-0·21]). The most common adverse events were infections unrelated to post-stroke pneumonia (mainly urinary tract infections), which were less frequent in the antibiotics group (22 [4%] of 615 vs 45 [7%] of 602; OR 0·55 [0·32-0·92], p=0·02). Diarrhoea positive for Clostridium difficile occurred in two patients (<1%) in the antibiotics group and four (<1%) in the control group, and meticillin-resistant Staphylococcus aureus colonisation occurred in 11 patients (2%) in the antibiotics group and 14 (2%) in the control group. Antibiotic prophylaxis cannot be recommended for prevention of post-stroke pneumonia in patients with dysphagia after stroke managed in stroke units. UK National Institute for Health Research. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Efficacy of cognitive behavioural therapy for sleep improvement in patients with persistent delusions and hallucinations (BEST): a prospective, assessor-blind, randomised controlled pilot trial

PubMed Central

Freeman, Daniel; Waite, Felicity; Startup, Helen; Myers, Elissa; Lister, Rachel; McInerney, Josephine; Harvey, Allison G; Geddes, John; Zaiwalla, Zenobia; Luengo-Fernandez, Ramon; Foster, Russell; Clifton, Lei; Yu, Ly-Mee

2015-01-01

Summary Background Sleep disturbance occurs in most patients with delusions or hallucinations and should be treated as a clinical problem in its own right. However, cognitive behavioural therapy (CBT)—the best evidence-based treatment for insomnia—has not been tested in this patient population. We aimed to pilot procedures for a randomised trial testing CBT for sleep problems in patients with current psychotic experiences, and to provide a preliminary assessment of potential benefit. Methods We did this prospective, assessor-blind, randomised controlled pilot trial (Better Sleep Trial [BEST]) at two mental health centres in the UK. Patients (aged 18–65 years) with persistent distressing delusions or hallucinations in the context of insomnia and a schizophrenia spectrum diagnosis were randomly assigned (1:1), via a web-based randomisation system with minimisation to balance for sex, insomnia severity, and psychotic experiences, to receive either eight sessions of CBT plus standard care (medication and contact with the local clinical team) or standard care alone. Research assessors were masked to group allocation. Assessment of outcome was done at weeks 0, 12 (post-treatment), and 24 (follow-up). The primary efficacy outcomes were insomnia assessed by the Insomnia Severity Index (ISI) and delusions and hallucinations assessed by the Psychotic Symptoms Rating Scale (PSYRATS) at week 12. We did analysis by intention to treat, with an aim to provide confidence interval estimation of treatment effects. This study is registered with ISRCTN, number 33695128. Findings Between Dec 14, 2012, and May 22, 2013, and Nov 7, 2013, and Aug 26, 2014, we randomly assigned 50 patients to receive CBT plus standard care (n=24) or standard care alone (n=26). The last assessments were completed on Feb 10, 2015. 48 (96%) patients provided follow-up data. 23 (96%) patients offered CBT took up the intervention. Compared with standard care, CBT led to reductions in insomnia in the large effect size range at week 12 (adjusted mean difference 6·1, 95% CI 3·0–9·2, effect size d=1·9). By week 12, nine (41%) of 22 patients receiving CBT and one (4%) of 25 patients receiving standard care alone no longer had insomnia, with ISI scores lower than the cutoff for insomnia. The treatment effect estimation for CBT covered a range from reducing but also increasing delusions (adjusted mean difference 0·3, 95% CI −2·0 to 2·6) and hallucinations (−1·9, −6·5 to 2·7). Three patients, all in the CBT group, had five adverse events, although none were regarded as related to study treatment. Interpretation Our findings show that CBT for insomnia might be highly effective for improving sleep in patients with persistent delusions or hallucinations. A larger, suitably powered phase 3 study is now needed to provide a precise estimate of the effects of CBT for sleep problems, both on sleep and psychotic experiences. Funding Research for Patient Benefit Programme, National Institute for Health Research. PMID:26363701

The London Exercise And Pregnant smokers (LEAP) trial: a randomised controlled trial of physical activity for smoking cessation in pregnancy with an economic evaluation.

PubMed

Ussher, Michael; Lewis, Sarah; Aveyard, Paul; Manyonda, Isaac; West, Robert; Lewis, Beth; Marcus, Bess; Riaz, Muhammad; Taylor, Adrian H; Barton, Pelham; Daley, Amanda; Essex, Holly; Esliger, Dale; Coleman, Tim

2015-10-01

Smoking during pregnancy is the main preventable cause of poor birth outcomes. Improved methods are needed to help women to stop smoking during pregnancy. Pregnancy provides a compelling rationale for physical activity (PA) interventions as cessation medication is contraindicated or ineffective, and an effective PA intervention could be highly cost-effective. To examine the effectiveness and cost-effectiveness of a PA intervention plus standard behavioural support for smoking cessation relative to behavioural support alone for achieving smoking cessation at the end of pregnancy. Multicentre, two-group, pragmatic randomised controlled trial and economic evaluation with follow-up at the end of pregnancy and 6 months postnatally. Randomisation was stratified by centre and a computer-generated sequence was used to allocate participants using a 1 : 1 ratio. 13 hospitals offering antenatal care in the UK. Women between 10 and 24 weeks' gestation smoking five or more cigarettes a day before pregnancy and one or more during pregnancy. Participants were randomised to behavioural support for smoking cessation (control) or behavioural support plus a PA intervention consisting of supervised treadmill exercise plus PA consultations. Neither participants nor researchers were blinded to treatment allocation. The primary outcome was self-reported, continuous smoking abstinence between a quit date and end of pregnancy, validated by expired carbon monoxide and/or salivary cotinine. Secondary outcomes were maternal weight, depression, birth outcomes, withdrawal symptoms and urges to smoke. The economic evaluation investigated the costs of the PA intervention compared with the control intervention. In total, 789 women were randomised (n = 394 PA, n = 395 control). Four were excluded post randomisation (two had been enrolled twice in sequential pregnancies and two were ineligible and randomised erroneously). The intention-to-treat analysis comprised 785 participants (n = 392 PA, n = 393 control). There was no significant difference in the rate of abstinence at the end of pregnancy between the PA group (7.7%) and the control group (6.4%) [odds ratio for PA group abstinence 1.21, 95% confidence interval (CI) 0.70 to 2.10]. For the PA group compared with the control group, there was a 33% (95% CI 14% to 56%), 28% (95% CI 7% to 52%) and 36% (95% CI 12% to 65%) significantly greater increase in self-reported minutes of moderate- and vigorous-intensity PA from baseline to 1 week, 4 weeks and 6 weeks respectively. Accelerometer data showed that there was no significant difference in PA levels between the groups. There were no significant differences between the groups for change in maternal weight, depression, withdrawal symptoms or urges to smoke. Adverse events and birth outcomes were similar between the groups except for there being significantly more caesarean births in the control group than in the PA group (28.7% vs. 21.3%; p < 0.023). The PA intervention was less costly than the control intervention by £35 per participant. This was mainly attributable to increased health-care usage in the control group. However, there was considerable statistical uncertainty around this estimate. During pregnancy, offering an intervention combining supervised exercise and PA counselling does not add to the effectiveness of behavioural support for smoking cessation. Only 10% of participants had PA levels accessed by accelerometer and it is, therefore, unclear whether or not the lack of an effect on the primary outcome is the result of insufficient increases in PA. Research is needed to identify the smoking populations most suitable for PA interventions and methods for increasing PA adherence. Current Controlled Trials ISRCTN48600346. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 84. See the NIHR Journals Library website for further project information.

Efficacy of Intravenous Haloperidol on the duration of Delirium and Coma in Critically Ill Patients (Hope-ICU): a Randomised, Placebo-Controlled Trial

PubMed Central

Page, Valerie J; Ely, E Wesley; Gates, Simon; Zhao, Xiao Bei; Alce, Timothy; Shintani, Ayumi; Jackson, Jim; Perkins, Gavin D; McAuley, Daniel F

2016-01-01

Background Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or in coma. Methods We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2·5mgs or 0·9% saline placebo intravenously every 8 h irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days treatment, which ever came first. Delirium was assessed using the confusion assessment method - for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14-day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. Findings 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0-10] vs 6 days [0-11] days; p= 0·53). The most common adverse events were oversedation (11 patients in the haloperidol group vs. six in the placebo) and QTc prolongation (seven in haloperidol group and six in the placebo group). No patient had a serious adverse event related to study drug. Interpretation These results do not support the hypothesis that haloperidol modifies duration of delirium in critically ill patients. Although haloperidol can be used safely in this population of patients, pending the results of trials in progress, the use of intravenous haloperidol should be reserved for the short-term management of acute agitation. Funding National Institute for Health Research PMID:24461612

Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial.

PubMed

Page, Valerie J; Ely, E Wesley; Gates, Simon; Zhao, Xiao Bei; Alce, Timothy; Shintani, Ayumi; Jackson, Jim; Perkins, Gavin D; McAuley, Daniel F

2013-09-01

Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or coma. We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2.5 mg or 0.9% saline placebo intravenously every 8 h, irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days of treatment, whichever came first. Delirium was assessed using the confusion assessment method for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14 day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0-10] vs 6 days [0-11] days; p=0.53). The most common adverse events were oversedation (11 patients in the haloperidol group vs six in the placebo group) and QTc prolongation (seven patients in the haloperidol group vs six in the placebo group). No patient had a serious adverse event related to the study drug. These results do not support the hypothesis that haloperidol modifies duration of delirium in critically ill patients. Although haloperidol can be used safely in this population of patients, pending the results of trials in progress, the use of intravenous haloperidol should be reserved for short-term management of acute agitation. National Institute for Health Research. Copyright © 2013 Elsevier Ltd. All rights reserved.

Economic Evaluation of a General Hospital Unit for Older People with Delirium and Dementia (TEAM Randomised Controlled Trial)

PubMed Central

Tanajewski, Lukasz; Franklin, Matthew; Gkountouras, Georgios; Berdunov, Vladislav; Harwood, Rowan H.; Goldberg, Sarah E.; Bradshaw, Lucy E.; Gladman, John R. F.; Elliott, Rachel A.

2015-01-01

Background One in three hospital acute medical admissions is of an older person with cognitive impairment. Their outcomes are poor and the quality of their care in hospital has been criticised. A specialist unit to care for older people with delirium and dementia (the Medical and Mental Health Unit, MMHU) was developed and then tested in a randomised controlled trial where it delivered significantly higher quality of, and satisfaction with, care, but no significant benefits in terms of health status outcomes at three months. Objective To examine the cost-effectiveness of the MMHU for older people with delirium and dementia in general hospitals, compared with standard care. Methods Six hundred participants aged over 65 admitted for acute medical care, identified on admission as cognitively impaired, were randomised to the MMHU or to standard care on acute geriatric or general medical wards. Cost per quality adjusted life year (QALY) gained, at 3-month follow-up, was assessed in trial-based economic evaluation (599/600 participants, intervention: 309). Multiple imputation and complete-case sample analyses were employed to deal with missing QALY data (55%). Results The total adjusted health and social care costs, including direct costs of the intervention, at 3 months was £7714 and £7862 for MMHU and standard care groups, respectively (difference -£149 (95% confidence interval [CI]: -298, 4)). The difference in QALYs gained was 0.001 (95% CI: -0.006, 0.008). The probability that the intervention was dominant was 58%, and the probability that it was cost-saving with QALY loss was 39%. At £20,000/QALY threshold, the probability of cost-effectiveness was 94%, falling to 59% when cost-saving QALY loss cases were excluded. Conclusions The MMHU was strongly cost-effective using usual criteria, although considerably less so when the less acceptable situation with QALY loss and cost savings were excluded. Nevertheless, this model of care is worthy of further evaluation. Trial Registration ClinicalTrials.gov NCT01136148 PMID:26684872

Supplementation of standard antibiotic therapy with oral probiotics for bacterial vaginosis and aerobic vaginitis: a randomised, double-blind, placebo-controlled trial.

PubMed

Heczko, Piotr B; Tomusiak, Anna; Adamski, Paweł; Jakimiuk, Artur J; Stefański, Grzegorz; Mikołajczyk-Cichońska, Aleksandra; Suda-Szczurek, Magdalena; Strus, Magdalena

2015-12-03

This multicentre, randomised, double-blind, placebo-controlled trial was performed to determine whether the use of oral probiotic preparation (prOVag®) containing three Lactobacillus strains together with standard metronidazole treatment and also targeted antibiotic treatment (following the failure of metronidazole therapy) could reduce the recurrence rates of bacterial vaginosis (BV) and aerobic vaginitis (AV). Patients at private gynaecological clinics in Poland with histories of recurrent BV/AV and current symptoms were randomly allocated to receive metronidazole and probiotic or placebo, and assessed monthly on visits II and III-V. The total number of study visits was 5-6 (I, II, II bis - if applicable, III, IV, V). One probiotic or placebo capsule was administered with metronidazole/targeted antibiotic twice daily for 10 days; during follow up, patients took one capsule daily for 10 days perimenstrually. Clinical examination and vaginal swabbing were performed at each visit. Primary outcomes were clinical or microbiological BV/AV recurrence and probiotic safety. Secondary outcomes were vaginal pH, Nugent score, and Lactobacillus counts in the vaginal microbiota. Safety analysis was performed in 578 (probiotic, n = 285; placebo, n = 293) 18-50-year-old women who were randomised. BV/AV was confirmed microbiologically in 241 (probiotic, n = 118; placebo, n = 123) participants, who continued the trial. Data from 154 (probiotic, n = 73; placebo, n = 81) participants who completed the study were analysed to determine the efficacy of prOVag. Additional analyses included 37 (probiotic, n = 22; placebo, n = 15) participants who received targeted antibiotics and probiotics or placebo. prOVag lengthened the time to clinical relapse of BV/AV symptoms up to 51 % (p < 0.05) compared with placebo; AV relapse was delayed by up to 76 % (p < 0.05). Probiotic use also reduced and maintained low vaginal pH and Nugent score, and increased vaginal Lactobacillus counts following standard treatment. This study demonstrated that oral probiotics lengthened remission in patients with recurrent BV/AV and improved clinical and microbiological parameters. NCT01993524 ; 20 November 2013.

Complementary therapies for labour and birth study: a randomised controlled trial of antenatal integrative medicine for pain management in labour

PubMed Central

Levett, Kate M; Smith, C A; Bensoussan, A; Dahlen, H G

2016-01-01

Objective To evaluate the effect of an antenatal integrative medicine education programme in addition to usual care for nulliparous women on intrapartum epidural use. Design Open-label, assessor blind, randomised controlled trial. Setting 2 public hospitals in Sydney, Australia. Population 176 nulliparous women with low-risk pregnancies, attending hospital-based antenatal clinics. Methods and intervention The Complementary Therapies for Labour and Birth protocol, based on the She Births and acupressure for labour and birth courses, incorporated 6 evidence-based complementary medicine techniques: acupressure, visualisation and relaxation, breathing, massage, yoga techniques, and facilitated partner support. Randomisation occurred at 24–36 weeks’ gestation, and participants attended a 2-day antenatal education programme plus standard care, or standard care alone. Main outcome measures Rate of analgesic epidural use. Secondary: onset of labour, augmentation, mode of birth, newborn outcomes. Results There was a significant difference in epidural use between the 2 groups: study group (23.9%) standard care (68.7%; risk ratio (RR) 0.37 (95% CI 0.25 to 0.55), p≤0.001). The study group participants reported a reduced rate of augmentation (RR=0.54 (95% CI 0.38 to 0.77), p<0.0001); caesarean section (RR=0.52 (95% CI 0.31 to 0.87), p=0.017); length of second stage (mean difference=−0.32 (95% CI −0.64 to 0.002), p=0.05); any perineal trauma (0.88 (95% CI 0.78 to 0.98), p=0.02) and resuscitation of the newborn (RR=0.47 (95% CI 0.25 to 0.87), p≤0.015). There were no statistically significant differences found in spontaneous onset of labour, pethidine use, rate of postpartum haemorrhage, major perineal trauma (third and fourth degree tears/episiotomy), or admission to special care nursery/neonatal intensive care unit (p=0.25). Conclusions The Complementary Therapies for Labour and Birth study protocol significantly reduced epidural use and caesarean section. This study provides evidence for integrative medicine as an effective adjunct to antenatal education, and contributes to the body of best practice evidence. Trial registration number ACTRN12611001126909. PMID:27406639

Protocol for a randomised controlled implementation trial of point-of-care viral load testing and task shifting: the Simplifying HIV TREAtment and Monitoring (STREAM) study

PubMed Central

Garrett, Nigel; Quame-Amaglo, Justice; Samsunder, Natasha; Ngobese, Hope; Ngomane, Noluthando; Moodley, Pravikrishnen; Mlisana, Koleka; Schaafsma, Torin; Donnell, Deborah; Barnabas, Ruanne; Naidoo, Kogieleum; Abdool Karim, Salim; Celum, Connie; Drain, Paul K

2017-01-01

Introduction Achieving the Joint United Nations Programme on HIV and AIDS 90-90-90 targets requires models of HIV care that expand antiretroviral therapy (ART) coverage without overburdening health systems. Point-of-care (POC) viral load (VL) testing has the potential to efficiently monitor ART treatment, while enrolled nurses may be able to provide safe and cost-effective chronic care for stable patients with HIV. This study aims to demonstrate whether POC VL testing combined with task shifting to enrolled nurses is non-inferior and cost-effective compared with laboratory-based VL monitoring and standard HIV care. Methods and analysis The STREAM (Simplifying HIV TREAtment and Monitoring) study is an open-label, non-inferiority, randomised controlled implementation trial. HIV-positive adults, clinically stable at 6 months after ART initiation, will be recruited in a large urban clinic in South Africa. Approximately 396 participants will be randomised 1:1 to receive POC HIV VL monitoring and potential task shifting to enrolled nurses, versus laboratory VL monitoring and standard South African HIV care. Initial clinic follow-up will be 2-monthly in both arms, with VL testing at enrolment, 6 months and 12 months. At 6 months (1 year after ART initiation), stable participants in both arms will qualify for a differentiated care model involving decentralised ART pickup at community-based pharmacies. The primary outcome is retention in care and virological suppression at 12 months from enrolment. Secondary outcomes include time to appropriate entry into the decentralised ART delivery programme, costs per virologically suppressed patient and cost-effectiveness of the intervention compared with standard care. Findings will inform the scale up of VL testing and differentiated care in HIV-endemic resource-limited settings. Ethics and dissemination Ethical approval has been granted by the University of KwaZulu-Natal Biomedical Research Ethics Committee (BFC296/16) and University of Washington Institutional Review Board (STUDY00001466). Results will be presented at international conferences and published in academic peer-reviewed journals. Trial registration NCT03066128; Pre-results. PMID:28963304

Interventions for recurrent corneal erosions.

PubMed

Watson, Stephanie L; Lee, Ming-Han H; Barker, Nigel H

2012-09-12

Recurrent corneal erosion is a common cause of disabling ocular symptoms and predisposes the cornea to infection. It may follow corneal trauma. Measures to prevent the development of recurrent corneal erosion following corneal trauma have not been firmly established. Once recurrent corneal erosion develops simple medical therapy (standard treatment) may lead to resolution of the episode. However, some patients continue to suffer when such therapy fails and once resolved further episodes of recurrent erosion may occur. A number of treatment and prophylactic options are then available but there is no agreement as to the best option. To assess the effectiveness and safety of prophylactic and treatment regimens for recurrent corneal erosion. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1946 to June 2012), EMBASE (January 1980 to June 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to June 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 June 2012. We also contacted researchers in the field. We included randomised and quasi-randomised trials that compared a prophylactic or treatment regimen with another prophylaxis/treatment or no prophylaxis/treatment for patients with recurrent corneal erosion. Two authors independently extracted data and assessed trial quality. We contacted study authors for additional information. Seven randomised and one quasi-randomised controlled trial were included in the review. The trials were heterogenous and of poor quality. Safety data presented were incomplete. For the treatment of recurrent corneal erosion, a single-centre trial in the UK with 30 participants showed that oral tetracycline 250 mg twice daily for 12 weeks or topical prednisolone 0.5% four times daily for one week, or both, in addition to standard treatment, accelerated healing rates and improved symptoms. A single-centre trial in Sweden with 56 participants showed that excimer laser ablation in addition to mechanical debridement may reduce the number of erosions and improve symptoms. Furthermore, in a single-centre trial in Germany with 100 participants, transepithelial technique for excimer laser ablation had the same efficacy as the traditional subepithelial excimer laser technique but caused less pain. In a small study of 24 participants in UK, therapeutic contact lens wear was inferior to lubricant drops and ointment in abolishing the symptoms of recurrent corneal erosion and had a high complication rate, although the contact lenses used were the older generation with low oxygen permeability. A recent study in Hong Kong with 48 participants found diamond burr polishing to reduce episodes of recurrent corneal erosion. For prophylaxis of further episodes of recurrent corneal erosion, there was no difference in the occurrence of objective signs of recurrent erosion between hypertonic saline ointment versus tetracycline ointment or lubricating ointment in a small Japanese study with 26 participants. Also, in a single-centre study in the UK with 117 participants, there was no difference in symptom improvement between hypertonic saline versus paraffin ointment when used for prophylaxis. In a UK study with 42 participants, lubricating ointment at night in addition to standard treatment to prevent recurrence following traumatic corneal abrasion (erosion) caused by fingernail injury led to increased symptoms of recurrent corneal erosion compared to standard therapy alone. Well-designed, masked, randomised controlled trials using standardised methods are needed to establish the benefits of new and existing prophylactic and treatment regimes for recurrent corneal erosion. International consensus is also needed to progress research efforts towards evaluation of the major effective treatments for recurrent corneal erosions.

Subdissociative intranasal ketamine plus standard pain therapy versus standard pain therapy in the treatment of paediatric sickle cell disease vaso-occlusive crises in resource-limited settings: study protocol for a randomised controlled trial.

PubMed

Young, James R; Sawe, Hendry Robert; Mfinanga, Juma A; Nshom, Ernest; Helm, Ethan; Moore, Charity G; Runyon, Michael S; Reynolds, Stacy L

2017-07-10

Pediatric sickle cell disease, highly prevalent in sub-Saharan Africa, carries great morbidity and mortality risk. Limited resources and monitoring make management of acute vaso-occlusive crises challenging. This study aims to evaluate the efficacy and safety of subdissociative intranasal ketamine as a cheap, readily available and easily administered adjunct to standard pain therapy. We hypothesise that subdissociative, intranasal ketamine may significantly augment current approaches to pain management in resource-limited settings in a safe and cost-effective manner. This is a multicentred, randomised, double-blind, placebo-controlled trial enrolling children 4-16 years of age with sickle cell disease and painful vaso-occlusive pain crises. Study sites include two sub-Saharan teaching and referral hospitals with acute intake areas. All patients receive standard analgesic therapy during evaluation. Patients randomised to the treatment arm receive 1 mg/kg intranasal ketamine at onset of therapy, while placebo arm participants receive volume-matched intranasal normal saline. All participants and clinical staff are blinded to the treatment allocation. Data will be analysed on an intention-to-treat basis. Primary endpoints are changes in self-report pain scales (Faces Pain Scale-Revised) at 30, 60 and 120 minutes and rates of adverse events. Secondary endpoints include hospital length of stay, total analgesia use and quality of life assessment 2-3 weeks postintervention. The research methods for this study have been approved by the Cameroon Baptist Convention Health Board Institutional Review Board (IRB2015-07), the Tanzanian National Institute for Medical Research (NIMR/HQ/R.8a/Vol. IX/2299), Muhimbili National Hospital IRB (MNH/IRB/I/2015/14) and the Tanzanian Food and Drugs Authority (TFDA0015/CTR/0015/9). Data reports will be provided to the Data and Safety Monitoring Board (DSMB) periodically throughout the study as well as all reports of adverse events. All protocol amendments will also be reviewed by the DSMB. Study results, regardless of direction or amplitude, will be submitted for publication in relevant peer-reviewed journals. ClinicalTrials.Gov, NCT02573714. Date of registration: 8 October 2015. 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.

Subdissociative intranasal ketamine plus standard pain therapy versus standard pain therapy in the treatment of paediatric sickle cell disease vaso-occlusive crises in resource-limited settings: study protocol for a randomised controlled trial

PubMed Central

Sawe, Hendry Robert; Mfinanga, Juma A; Nshom, Ernest; Helm, Ethan; Moore, Charity G; Runyon, Michael S; Reynolds, Stacy L

2017-01-01

Introduction Pediatric sickle cell disease, highly prevalent in sub-Saharan Africa, carries great morbidity and mortality risk. Limited resources and monitoring make management of acute vaso-occlusive crises challenging. This study aims to evaluate the efficacy and safety of subdissociative intranasal ketamine as a cheap, readily available and easily administered adjunct to standard pain therapy. We hypothesise that subdissociative, intranasal ketamine may significantly augment current approaches to pain management in resource-limited settings in a safe and cost-effective manner. Methods and analysis This is a multicentred, randomised, double-blind, placebo-controlled trial enrolling children 4–16 years of age with sickle cell disease and painful vaso-occlusive pain crises. Study sites include two sub-Saharan teaching and referral hospitals with acute intake areas. All patients receive standard analgesic therapy during evaluation. Patients randomised to the treatment arm receive 1 mg/kg intranasal ketamine at onset of therapy, while placebo arm participants receive volume-matched intranasal normal saline. All participants and clinical staff are blinded to the treatment allocation. Data will be analysed on an intention-to-treat basis. Primary endpoints are changes in self-report pain scales (Faces Pain Scale-Revised) at 30, 60 and 120 minutes and rates of adverse events. Secondary endpoints include hospital length of stay, total analgesia use and quality of life assessment 2–3 weeks postintervention. Ethics and dissemination The research methods for this study have been approved by the Cameroon Baptist Convention Health Board Institutional Review Board (IRB2015-07), the Tanzanian National Institute for Medical Research (NIMR/HQ/R.8a/Vol. IX/2299), Muhimbili National Hospital IRB (MNH/IRB/I/2015/14) and the Tanzanian Food and Drugs Authority (TFDA0015/CTR/0015/9). Data reports will be provided to the Data and Safety Monitoring Board (DSMB) periodically throughout the study as well as all reports of adverse events. All protocol amendments will also be reviewed by the DSMB. Study results, regardless of direction or amplitude, will be submitted for publication in relevant peer-reviewed journals. Trial registration ClinicalTrials.Gov, NCT02573714. Date of registration: 8 October 2015. Pre-results. PMID:28698351

COSMOS: COmparing Standard Maternity care with One-to-one midwifery Support: a randomised controlled trial

PubMed Central

McLachlan, Helen L; Forster, Della A; Davey, Mary-Ann; Lumley, Judith; Farrell, Tanya; Oats, Jeremy; Gold, Lisa; Waldenström, Ulla; Albers, Leah; Biro, Mary Anne

2008-01-01

Background In Australia and internationally, there is concern about the growing proportion of women giving birth by caesarean section. There is evidence of increased risk of placenta accreta and percreta in subsequent pregnancies as well as decreased fertility; and significant resource implications. Randomised controlled trials (RCTs) of continuity of midwifery care have reported reduced caesareans and other interventions in labour, as well as increased maternal satisfaction, with no statistically significant differences in perinatal morbidity or mortality. RCTs conducted in the UK and in Australia have largely measured the effect of teams of care providers (commonly 6–12 midwives) with very few testing caseload (one-to-one) midwifery care. This study aims to determine whether caseload (one-to-one) midwifery care for women at low risk of medical complications decreases the proportion of women delivering by caesarean section compared with women receiving 'standard' care. This paper presents the trial protocol in detail. Methods/design A two-arm RCT design will be used. Women who are identified at low medical risk will be recruited from the antenatal booking clinics of a tertiary women's hospital in Melbourne, Australia. Baseline data will be collected, then women randomised to caseload midwifery or standard low risk care. Women allocated to the caseload intervention will receive antenatal, intrapartum and postpartum care from a designated primary midwife with one or two antenatal visits conducted by a 'back-up' midwife. The midwives will collaborate with obstetricians and other health professionals as necessary. If the woman has an extended labour, or if the primary midwife is unavailable, care will be provided by the back-up midwife. For women allocated to standard care, options include midwifery-led care with varying levels of continuity, junior obstetric care and community based general medical practitioner care. Data will be collected at recruitment (self administered survey) and at 2 and 6 months postpartum by postal survey. Medical/obstetric outcomes will be abstracted from the medical record. The sample size of 2008 was calculated to identify a decrease in caesarean birth from 19 to 14% and detect a range of other significant clinical differences. Comprehensive process and economic evaluations will be conducted. Trial registration Australian New Zealand Clinical Trials Registry ACTRN012607000073404. PMID:18680606

Study design and rationale for Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective percutaneous coronary intervention patients (ONSIDE TEST): a prospective, open-label, randomised parallel-group multicentre trial (NCT01930773).

PubMed

Kołtowski, Łukasz; Aradi, Daniel; Huczek, Zenon; Tomaniak, Mariusz; Sibbing, Dirk; Filipiak, Krzysztof J; Kochman, Janusz; Balsam, Paweł; Opolski, Grzegorz

2016-01-01

High platelet reactivity (HPR) and presence of CYP2C19 loss-of-function alleles are associated with higher risk for periprocedural myocardial infarction in clopidogrel-treated patients undergoing percutaneous coronary intervention (PCI). It is unknown whether personalised treatment based on platelet function testing or genotyping can prevent such complications. The ONSIDE-TEST is a multicentre, prospective, open-label, randomised controlled clinical trial aiming to assess if optimisation of antiplatelet therapy based on either phenotyping or genotyping is superior to conventional care. Patients will be randomised into phenotyping, genotyping, or control arms. In the phenotyping group, patients will be tested with the VerifyNow P2Y12 assay before PCI, and patients with a platelet reactivity unit greater than 208 will be switched over to prasugrel, while others will continue on clopidogrel therapy. In the genotyping group, carriers of the *2 loss-of-function allele will receive prasugrel for PCI, while wild-type subjects will be treated with clopidogrel. Patients in the control arm will be treated with standard-dose clopidogrel. The primary endpoint of the study is the prevalence of periprocedural myocardial injury within 24 h after PCI in the controls as compared to the phenotyping and genotyping group. Secondary endpoints include cardiac death, myocardial infarction, definite or probable stent thrombosis, or urgent repeat revascularisation within 30 days of PCI. Primary safety outcome is Bleeding Academic Research Consortium (BARC) type 3 and 5 bleeding during 30 days of PCI. The ONSIDE TEST trial is expected to verify the clinical utility of an individualised antiplatelet strategy in preventing periprocedural myocardial injury by either phenotyping or genotyping. ClinicalTrials.gov: NCT01930773.

A randomised controlled trial of a web-based multi-modal therapy program to improve executive functioning in children and adolescents with acquired brain injury.

PubMed

Piovesana, Adina; Ross, Stephanie; Lloyd, Owen; Whittingham, Koa; Ziviani, Jenny; Ware, Robert S; McKinlay, Lynne; Boyd, Roslyn N

2017-10-01

To examine the efficacy of a multi-modal web-based therapy program, Move it to improve it (Mitii™) delivered at home to improve Executive Functioning (EF) in children with an acquired brain injury (ABI). Randomised Waitlist controlled trial. Home environment. Sixty children with an ABI were matched in pairs by age and intelligence quotient then randomised to either 20-weeks of Mitii™ training or 20 weeks of Care As Usual (waitlist control; n=30; 17 males; mean age=11y, 11m (±2y, 6m); Full Scale IQ=76.24±17.84). Fifty-eight children completed baseline assessments (32 males; mean age=11.87±2.47; Full Scale IQ=75.21±16.76). Executive functioning was assessed on four domains: attentional control, cognitive flexibility, goal setting, and information processing using subtests from the Wechsler Intelligence Scale for Children (WISC-IV), Delis-Kaplan Executive Functioning System (D-KEFS), Comprehensive Trail Making Test (CTMT), Tower of London (TOL), and Test of Everyday Attention for Children (Tea-Ch). Executive functioning performance in everyday life was assessed via parent questionnaire (Behaviour Rating Inventory of Executive Functioning; BRIEF). No differences were observed at baseline measures. Groups were compared at 20-weeks using linear regression with no significant differences found between groups on all measures of EF. Out of a potential total dose of 60 hours, children in the Mitii™ group completed a mean of 17 hours of Mitii™ intervention. Results indicate no additional benefit to receiving Mitii™ compared to standard care. Mitii™, in its current form, was not shown to improve EF in children with ABI.

Community-based InterVentions to prevent serIous Complications (CIVIC) following spinal cord injury in Bangladesh: protocol of a randomised controlled trial.

PubMed

Hossain, Mohammad S; Harvey, Lisa A; Rahman, Md Akhlasur; Muldoon, Stephen; Bowden, Jocelyn L; Islam, Md Shofiqul; Jan, Stephen; Taylor, Valerie; Cameron, Ian D; Chhabra, Harvinder Singh; Lindley, Richard I; Biering-Sørensen, Fin; Li, Qiang; Dhakshinamurthy, Murali; Herbert, Robert D

2016-01-07

In low-income and middle-income countries, people with spinal cord injury (SCI) are vulnerable to life-threatening complications after they are discharged from hospital. The aim of this trial is to determine the effectiveness and cost-effectiveness of an inexpensive and sustainable model of community-based care designed to prevent and manage complications in people with SCI in Bangladesh. A pragmatic randomised controlled trial will be undertaken. 410 wheelchair-dependent people with recent SCI will be randomised to Intervention and Control groups shortly after discharge from hospital. Participants in the Intervention group will receive regular telephone-based care and three home visits from a health professional over the 2 years after discharge. Participants in the Control group will receive standard care, which does not involve regular contact with health professionals. The primary outcome is all-cause mortality at 2 years. Recruitment started on 12 July 2015 and the trial is expected to take 5 years to complete. Ethical approval was obtained from the Institutional Ethics Committee at the site in Bangladesh and from the University of Sydney, Australia. The study will be conducted in compliance with all stipulations of its protocol, the conditions of ethics committee approval, the NHMRC National Statement on Ethical Conduct in Human Research (2007), the Note for Guidance on Good Clinical Practice (CPMP/ICH-135/95) and the Bangladesh Guidance on Clinical Trial Inspection (2011). The results of the trial will be disseminated through publications in peer-reviewed scientific journals and presentations at scientific conferences. ACTRN12615000630516, U1111-1171-1876. 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 systematic review of physical therapy interventions for patients with anorexia and bulemia nervosa.

PubMed

Vancampfort, Davy; Vanderlinden, Johan; De Hert, Marc; Soundy, Andrew; Adámkova, Milena; Skjaerven, Liv Helvik; Catalán-Matamoros, Daniel; Lundvik Gyllensten, Amanda; Gómez-Conesa, Antonia; Probst, Michel

2014-01-01

The purpose of this systematic review was to summarise the evidence from randomised controlled trials examining the effectiveness of physical therapy compared with care as usual or a wait-list condition on eating pathology and on physiological and psychological parameters in patients with anorexia and bulimia nervosa. EMBASE, PsycINFO, PubMed, Cumulative Index to Nursing and Allied Health Literature, Physiotherapy Evidence Database and The Cochrane Library were searched from their inception until February, 2013. Articles were eligible if they utilised a randomised controlled trial design, compared physical therapy with a placebo condition, control intervention, or standard care and included patients with anorexia and bulimia nervosa. The methodological quality was assessed with the Jadad scale. Eight randomised controlled trials involving 213 patients (age range: 16-36 years) met all selection criteria. Three of the 8 included studies were of strong methodological quality (Jadad score≥3). Major methodological weaknesses were attrition and selection bias. The main results demonstrate that aerobic and resistance training result in significantly increased muscle strength, body mass index and body fat percentage in anorexia patients. In addition, aerobic exercise, yoga, massage and basic body awareness therapy significantly lowered scores of eating pathology and depressive symptoms in both anorexia and bulimia nervosa patients. No adverse effects were reported. The paucity and heterogeneity of available studies limits overall conclusions and highlights the need for further research. Implications for Rehabilitation Supervised physical therapy might increase weight in anorexia nervosa patients. Aerobic exercise, massage, basic body awareness therapy and yoga might reduce eating pathology in patients with anorexia and bulimia nervosa. Aerobic exercise, yoga and basic body awareness therapy might improve mental and physical quality of life in patients with an eating disorder.

OA01.41. Selective ayurvedic therapy for the management of major depressive disorder: A randomised control trial

PubMed Central

Fulzele, Ashwini; Hudda, Nazmul

2012-01-01

Purpose: Mental health is the level of psychological well being and encompasses the abilities to develop emotionally, psychologically, intellectually, socially and spiritually. There is no health without mental health. Most common mental disorder is depression, anxiety & drug addiction. Major depressive disorder is a mental disorder characterised by an all encompassing low mood accompanied by low self esteem and loss of interest in normally enjoyable activities. Standard treatment for depression includes antidepressant medication which have unpleasant side effect and psychotherapy which is time consuming and expensive. Objective of the present study was to assess the effectiveness of a herbal preparation and shirodhara therapy for the treatment of major depressive disorder and to compare its effectiveness with a standard drug. Method: It was Open Randomised Controlled clinical Study. Study population was selected from OPD & IPD of Kaychikitsa department at NIA and OPD of Psychiatry, SMS Medical College & Hospital, Jaipur. Out of 42 screened patients, 30 patients fulfilling the DSM-IV criteria for diagnosis of depression were enrolled for the study and randomly divided into two groups. Group A was given standard drug fluoxetine 20mg orally BD for 42 days. Group B was given herbal preparation orally for 42 days with shirodhara by medicated plain Ashwagandha oil for 14 days. Observations were made on baseline day, 14thday, and 28thday and 42nd day of study. Result: Both the groups showed significant improvement, with no unpleasant side effect in Group B. Conclusion: Selected Herbal preparation and Shirodhara therapy can be used in mild & moderate condition of major depression with free of side effect.

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

PubMed

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

2009-06-08

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

Randomised controlled trial comparing the effectiveness of electroacupuncture and TENS for low back pain: a preliminary study for a pragmatic trial.

PubMed

Tsukayama, Hiroshi; Yamashita, Hitoshi; Amagai, Hitoshi; Tanno, Yasuo

2002-12-01

The objective of this study was to compare the effectiveness of electroacupuncture and TENS for low back pain when the electroacupuncture is applied in a clinically realistic manner. The study was designed as an evaluator-blinded randomised controlled trial (RCT). The study was performed at the Tsukuba College of Technology Clinic in Japan. Twenty subjects, who suffered from low back pain (LBP) without sciatica, were recruited, using leaflets in Tsukuba city. Subjects were allocated to either an electroacupuncture (EA) group (10 patients) or a transcutaneous electrical nerve stimulation (TENS) group (10 patients). The procedure for EA was in accordance with standard practice at our clinic. The main outcome measures were a pain relief scale (100 mm visual analogue scale: VAS) and a LBP score recommended by the Japanese Orthopaedic Association (JOA Score). Mean VAS value during the 2-weeks experimental period of the EA group was significantly smaller than that of the TENS group (65 mm vs 86 mm; 95% CI, 4.126 - 37.953). JOA Score in the EA group improved significantly while that in the TENS group showed no change. Although some placebo effect may be included, EA appeared more useful than TENS in the short-term effect on low back pain. We suggest that more realistic acupuncture interventions based on standard practice should be employed in pragmatic RCTs.

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

Effects of group prenatal care on psychosocial risk in pregnancy: Results from a randomised controlled trial

PubMed Central

Ickovics, Jeannette R.; Reed, Elizabeth; Magriples, Urania; Westdahl, Claire; Rising, Sharon Schindler; Kershaw, Trace S.

2012-01-01

Few interventions have succeeded in reducing psychosocial risk among pregnant women. The objective of this study was to determine whether an integrated group prenatal care intervention already shown to improve perinatal and sexual risk outcomes can also improve psychosocial outcomes compared to standard individual care. This randomised controlled trial included pregnant women ages 14–25 from two public hospitals (N = 1047) who were randomly assigned to standard individual care, group prenatal care or integrated group prenatal care intervention (CenteringPregnancy Plus, CP+). Timing and content of visits followed obstetrical guidelines, from 18-week gestation through birth. Each 2-h group prenatal care session included physical assessment, education/skills building and support via facilitated discussion. Using intention-to-treat models, there were no significant differences in psychosocial function; yet, women in the top tertile of psychosocial stress at study entry did benefit from integrated group care. High-stress women randomly assigned to CP+ reported significantly increased self-esteem, decreased stress and social conflict in the third trimester of pregnancy; social conflict and depression were significantly lower 1-year postpartum (all p-values <0.02). CP+ improved psychosocial outcomes for high-stress women. This ‘bundled’ intervention has promise for improving psychosocial outcomes, especially for young pregnant women who are traditionally more vulnerable and underserved. PMID:21318932

A prospective randomised comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers.

PubMed

Zelen, Charles M; Serena, Thomas E; Denoziere, Guilhem; Fetterolf, Donald E

2013-10-01

Our purpose was to compare healing characteristics of diabetic foot ulcers treated with dehydrated human amniotic membrane allografts (EpiFix®, MiMedx, Kennesaw, GA) versus standard of care. An IRB-approved, prospective, randomised, single-centre clinical trial was performed. Included were patients with a diabetic foot ulcer of at least 4-week duration without infection having adequate arterial perfusion. Patients were randomised to receive standard care alone or standard care with the addition of EpiFix. Wound size reduction and rates of complete healing after 4 and 6 weeks were evaluated. In the standard care group (n = 12) and the EpiFix group (n = 13) wounds reduced in size by a mean of 32.0% ± 47.3% versus 97.1% ± 7.0% (P < 0.001) after 4 weeks, whereas at 6 weeks wounds were reduced by -1.8% ± 70.3% versus 98.4% ± 5.8% (P < 0.001), standard care versus EpiFix, respectively. After 4 and 6 weeks of treatment the overall healing rate with application of EpiFix was shown to be 77% and 92%, respectively, whereas standard care healed 0% and 8% of the wounds (P < 0.001), respectively. Patients treated with EpiFix achieved superior healing rates over standard treatment alone. These results show that using EpiFix in addition to standard care is efficacious for wound healing. ©2013 The Authors. International Wound Journal published by John Wiley & Sons Ltd and Medicalhelplines.com Inc.

Personalised telehealth intervention for chronic disease management: A pilot randomised controlled trial.

PubMed

Bohingamu Mudiyanselage, Shalika; Stevens, Jo; Watts, Jennifer J; Toscano, Julian; Kotowicz, Mark A; Steinfort, Christopher L; Bell, Jennifer; Byrnes, Janette; Bruce, Stephanie; Carter, Sarah; Hunter, Claire; Barrand, Chris; Hayles, Robyn

2018-01-01

Introduction The aim of this study was to assess the impact of home-based telehealth monitoring on health outcomes, quality of life and costs over 12 months for patients with diabetes and/or chronic obstructive pulmonary disease (COPD) who were identified as being at high risk of readmission to hospital. Methods This pilot study was a randomised controlled trial combined with an economic analysis to examine the outcomes of standard care versus home-based telehealth for people with diabetes and/or COPD who were at risk of hospital readmission within one year. The primary outcomes were (i) hospital admission and length of stay (LOS); and (ii) health-related quality of life (HRQOL); and the secondary outcomes were (i) health-related clinical outcomes; (ii) anxiety and depression scores; and (iii) health literacy. The costs of the intervention and hospitalisations were included. Results A total of 86 and 85 participants were randomised to the intervention and control groups respectively. The difference between groups in hospital LOS was -3.89 (95% confidence interval (CI): -9.40, 1.62) days, and for HRQOL, 0.09 (95% CI: 0.05, 0.14) in favour of the telehealth monitoring group. There was a saving of AUD$6553 (95% CI: -12145, -961) in the cost of hospitalisation over 12 months, which offset the increased cost of tele-monitoring. The intervention group showed an improvement in anxiety, depression and health literacy at 12 months, and in the diabetes group, a reduction in microalbuminuria. Discussion The telehealth monitoring intervention improved patient's health outcomes and quality of life at no additional cost.

Comparing clinical quality indicators for asthma management in children with outcome measures used in randomised controlled trials: a protocol.

PubMed

Choong, Miew Keen; Tsafnat, Guy; Hibbert, Peter; Runciman, William B; Coiera, Enrico

2015-09-08

Clinical quality indicators are necessary to monitor the performance of healthcare services. The development of indicators should, wherever possible, be based on research evidence to minimise the risk of bias which may be introduced during their development, because of logistic, ethical or financial constraints alone. The development of automated methods to identify the evidence base for candidate indicators should improve the process of indicator development. The objective of this study is to explore the relationship between clinical quality indicators for asthma management in children with outcome and process measurements extracted from randomised controlled clinical trial reports. National-level indicators for asthma management in children will be extracted from the National Quality Measures Clearinghouse (NQMC) database and the National Institute for Health and Care Excellence (NICE) quality standards. Outcome measures will be extracted from published English language randomised controlled trial (RCT) reports for asthma management in children aged below 12 years. The two sets of measures will be compared to assess any overlap. The study will provide insights into the relationship between clinical quality indicators and measurements in RCTs. This study will also yield a list of measurements used in RCTs for asthma management in children, and will find RCT evidence for indicators used in practice. Ethical approval is not necessary because this study will not include patient data. Findings will be disseminated through peer-reviewed publications. 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.

Minimally invasive 'step-up approach' versus maximal necrosectomy in patients with acute necrotising pancreatitis (PANTER trial): design and rationale of a randomised controlled multicenter trial [ISRCTN13975868].

PubMed

Besselink, Marc G H; van Santvoort, Hjalmar C; Nieuwenhuijs, Vincent B; Boermeester, Marja A; Bollen, Thomas L; Buskens, Erik; Dejong, Cornelis H C; van Eijck, Casper H J; van Goor, Harry; Hofker, Sijbrand S; Lameris, Johan S; van Leeuwen, Maarten S; Ploeg, Rutger J; van Ramshorst, Bert; Schaapherder, Alexander F M; Cuesta, Miguel A; Consten, Esther C J; Gouma, Dirk J; van der Harst, Erwin; Hesselink, Eric J; Houdijk, Lex P J; Karsten, Tom M; van Laarhoven, Cees J H M; Pierie, Jean-Pierre E N; Rosman, Camiel; Bilgen, Ernst Jan Spillenaar; Timmer, Robin; van der Tweel, Ingeborg; de Wit, Ralph J; Witteman, Ben J M; Gooszen, Hein G

2006-04-11

The initial treatment of acute necrotizing pancreatitis is conservative. Intervention is indicated in patients with (suspected) infected necrotizing pancreatitis. In the Netherlands, the standard intervention is necrosectomy by laparotomy followed by continuous postoperative lavage (CPL). In recent years several minimally invasive strategies have been introduced. So far, these strategies have never been compared in a randomised controlled trial. The PANTER study (PAncreatitis, Necrosectomy versus sTEp up appRoach) was conceived to yield the evidence needed for a considered policy decision. 88 patients with (suspected) infected necrotizing pancreatitis will be randomly allocated to either group A) minimally invasive 'step-up approach' starting with drainage followed, if necessary, by videoscopic assisted retroperitoneal debridement (VARD) or group B) maximal necrosectomy by laparotomy. Both procedures are followed by CPL. Patients will be recruited from 20 hospitals, including all Dutch university medical centres, over a 3-year period. The primary endpoint is the proportion of patients suffering from postoperative major morbidity and mortality. Secondary endpoints are complications, new onset sepsis, length of hospital and intensive care stay, quality of life and total (direct and indirect) costs. To demonstrate that the 'step-up approach' can reduce the major morbidity and mortality rate from 45 to 16%, with 80% power at 5% alpha, a total sample size of 88 patients was calculated. The PANTER-study is a randomised controlled trial that will provide evidence on the merits of a minimally invasive 'step-up approach' in patients with (suspected) infected necrotizing pancreatitis.

Minimally invasive 'step-up approach' versus maximal necrosectomy in patients with acute necrotising pancreatitis (PANTER trial): design and rationale of a randomised controlled multicenter trial [ISRCTN38327949

PubMed Central

Besselink, Marc GH; van Santvoort, Hjalmar C; Nieuwenhuijs, Vincent B; Boermeester, Marja A; Bollen, Thomas L; Buskens, Erik; Dejong, Cornelis HC; van Eijck, Casper HJ; van Goor, Harry; Hofker, Sijbrand S; Lameris, Johan S; van Leeuwen, Maarten S; Ploeg, Rutger J; van Ramshorst, Bert; Schaapherder, Alexander FM; Cuesta, Miguel A; Consten, Esther CJ; Gouma, Dirk J; van der Harst, Erwin; Hesselink, Eric J; Houdijk, Lex PJ; Karsten, Tom M; van Laarhoven, Cees JHM; Pierie, Jean-Pierre EN; Rosman, Camiel; Bilgen, Ernst Jan Spillenaar; Timmer, Robin; van der Tweel, Ingeborg; de Wit, Ralph J; Witteman, Ben JM; Gooszen, Hein G

2006-01-01

Background The initial treatment of acute necrotizing pancreatitis is conservative. Intervention is indicated in patients with (suspected) infected necrotizing pancreatitis. In the Netherlands, the standard intervention is necrosectomy by laparotomy followed by continuous postoperative lavage (CPL). In recent years several minimally invasive strategies have been introduced. So far, these strategies have never been compared in a randomised controlled trial. The PANTER study (PAncreatitis, Necrosectomy versus sTEp up appRoach) was conceived to yield the evidence needed for a considered policy decision. Methods/design 88 patients with (suspected) infected necrotizing pancreatitis will be randomly allocated to either group A) minimally invasive 'step-up approach' starting with drainage followed, if necessary, by videoscopic assisted retroperitoneal debridement (VARD) or group B) maximal necrosectomy by laparotomy. Both procedures are followed by CPL. Patients will be recruited from 20 hospitals, including all Dutch university medical centres, over a 3-year period. The primary endpoint is the proportion of patients suffering from postoperative major morbidity and mortality. Secondary endpoints are complications, new onset sepsis, length of hospital and intensive care stay, quality of life and total (direct and indirect) costs. To demonstrate that the 'step-up approach' can reduce the major morbidity and mortality rate from 45 to 16%, with 80% power at 5% alpha, a total sample size of 88 patients was calculated. Discussion The PANTER-study is a randomised controlled trial that will provide evidence on the merits of a minimally invasive 'step-up approach' in patients with (suspected) infected necrotizing pancreatitis. PMID:16606471

Clinical and cost-effectiveness of cognitive behaviour therapy for health anxiety in medical patients: a multicentre randomised controlled trial.

PubMed

Tyrer, Peter; Cooper, Sylvia; Salkovskis, Paul; Tyrer, Helen; Crawford, Michael; Byford, Sarah; Dupont, Simon; Finnis, Sarah; Green, John; McLaren, Elenor; Murphy, David; Reid, Steven; Smith, Georgina; Wang, Duolao; Warwick, Hilary; Petkova, Hristina; Barrett, Barbara

2014-01-18

Health anxiety has been treated by therapists expert in cognitive behaviour therapy with some specific benefit in some patients referred to psychological services. Those in hospital care have been less often investigated. Following a pilot trial suggesting efficacy we carried out a randomised study in hospital medical clinics. We undertook a multicentre, randomised trial on health anxious patients attending cardiac, endocrine, gastroenterological, neurological, and respiratory medicine clinics in secondary care. We included those aged 16-75 years, who satisfied the criteria for excessive health anxiety, and were resident in the area covered by the hospital, were not under investigation for new pathology or too medically unwell to take part. We used a computer-generated random scheme to allocate eligible medical patients to an active treatment group of five-to-ten sessions of adapted cognitive behaviour therapy (CBT-HA group) delivered by hospital-based therapists or to standard care in the clinics. The primary outcome was change in health anxiety symptoms measured by the Health Anxiety Inventory at 1 year and the main secondary hypothesis was equivalence of total health and social care costs over 2 years, with an equivalence margin of £150. Analysis was by intention to treat. The study is registered with controlled-trials.com, ISRCTN14565822. Of 28,991 patients screened, 444 were randomly assigned to receive either adapted cognitive behaviour therapy (CBT-HA group, 219 participants) or standard care (standard care group, 225), with 205 participants in the CBT-HA group and 212 in the standard care group included in the analyses of the primary endpoints. At 1 year, improvement in health anxiety in the patients in the CBT-HA group was 2·98 points greater than in those in the standard care group (95% CI 1·64-4·33, p<0·0001), and twice as many patients receiving cognitive behaviour therapy achieved normal levels of health anxiety compared with those in the control group (13·9% vs 7·3%; odds ratio 2·15, 95% CI 1·09-4·23, p=0·0273). Similar differences were observed at 6 months and 2 years, and there were concomitant reductions in generalised anxiety and, to a lesser extent, depression. Of nine deaths, six were in the control group; all were due to pre-existing illness. Social functioning or health-related quality of life did not differ significantly between groups. Equivalence in total 2-year costs was not achieved, but the difference was not significant (adjusted mean difference £156, 95% CI -1446 to 1758, p=0·848). This form of adapted cognitive behaviour therapy for health anxiety led to sustained symptomatic benefit over 2 years, with no significant effect on total costs. It deserves wider application in medical care. National Institute for Health Research Health Technology Assessment Programme. Copyright © 2014 Elsevier Ltd. All rights reserved.

Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study

PubMed Central

2009-01-01

Summary Background Hysterectomy and bilateral salpingo-oophorectomy (BSO) is the standard surgery for stage I endometrial cancer. Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterine disease and as a therapeutic procedure; however, randomised trials need to be done to assess therapeutic efficacy. The ASTEC surgical trial investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer. Methods From 85 centres in four countries, 1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus were randomly allocated by a minimisation method to standard surgery (hysterectomy and BSO, peritoneal washings, and palpation of para-aortic nodes; n=704) or standard surgery plus lymphadenectomy (n=704). The primary outcome measure was overall survival. To control for postsurgical treatment, women with early-stage disease at intermediate or high risk of recurrence were randomised (independent of lymph-node status) into the ASTEC radiotherapy trial. Analysis was by intention to treat. This study is registered, number ISRCTN 16571884. Findings After a median follow-up of 37 months (IQR 24–58), 191 women (88 standard surgery group, 103 lymphadenectomy group) had died, with a hazard ratio (HR) of 1·16 (95% CI 0·87–1·54; p=0·31) in favour of standard surgery and an absolute difference in 5-year overall survival of 1% (95% CI −4 to 6). 251 women died or had recurrent disease (107 standard surgery group, 144 lymphadenectomy group), with an HR of 1·35 (1·06–1·73; p=0·017) in favour of standard surgery and an absolute difference in 5-year recurrence-free survival of 6% (1–12). With adjustment for baseline characteristics and pathology details, the HR for overall survival was 1·04 (0·74–1·45; p=0·83) and for recurrence-free survival was 1·25 (0·93–1·66; p=0·14). Interpretation Our results show no evidence of benefit in terms of overall or recurrence-free survival for pelvic lymphadenectomy in women with early endometrial cancer. Pelvic lymphadenectomy cannot be recommended as routine procedure for therapeutic purposes outside of clinical trials. Funding Medical Research Council and National Cancer Research Network. PMID:19070889

Evaluating the impact of a ‘virtual clinic’ on patient experience, personal and provider costs of care in urinary incontinence: A randomised controlled trial

PubMed Central

2018-01-01

Objective To evaluate the impact of using a ‘virtual clinic’ on patient experience and cost in the care of women with urinary incontinence. Materials and methods Women, aged > 18 years referred to a urogynaecology unit were randomised to either (1) A Standard Clinic or (2) A Virtual Clinic. Both groups completed a validated, web-based interactive, patient-reported outome measure (ePAQ-Pelvic Floor), in advance of their appointment followed by either a telephone consultation (Virtual Clinic) or face-to-face consultation (Standard Care). The primary outcome was the mean ‘short-term outcome scale’ score on the Patient Experience Questionnaire (PEQ). Secondary Outcome Measures included the other domains of the PEQ (Communications, Emotions and Barriers), Client Satisfaction Questionnaire (CSQ), Short-Form 12 (SF-12), personal, societal and NHS costs. Results 195 women were randomised: 98 received the intervention and 97 received standard care. The primary outcome showed a non-significant difference between the two study arms. No significant differences were also observed on the CSQ and SF-12. However, the intervention group showed significantly higher PEQ domain scores for Communications, Emotions and Barriers (including following adjustment for age and parity). Whilst standard care was overall more cost-effective, this was minimal (£38.04). The virtual clinic also significantly reduced consultation time (10.94 minutes, compared with a mean duration of 25.9 minutes respectively) and consultation costs compared to usual care (£31.75 versus £72.17 respectively), thus presenting potential cost-savings in out-patient management. Conclusions The virtual clinical had no impact on the short-term dimension of the PEQ and overall was not as cost-effective as standard care, due to greater clinic re-attendances in this group. In the virtual clinic group, consultation times were briefer, communication experience was enhanced and personal costs lower. For medical conditions of a sensitive or intimate nature, a virtual clinic has potential to support patients to communicate with health professionals about their condition. PMID:29346378

A randomised study of tailored toxicity-based dosage of fluorouracil-epirubicin-cyclophosphamide chemotherapy for early breast cancer (SBG 2000-1).

PubMed

Lindman, H; Andersson, M; Ahlgren, J; Balslev, E; Sverrisdottir, A; Holmberg, S B; Bengtsson, N O; Jacobsen, E H; Jensen, A B; Hansen, J; Tuxen, M K; Malmberg, L; Villman, K; Anderson, H; Ejlertsen, B; Bergh, J; Blomqvist, C

2018-05-01

Retrospective studies have demonstrated a worse outcome in breast cancer patients not developing leukopenia during adjuvant chemotherapy. The SBG 2000-1 is the first randomised trial designed to compare individually dosed chemotherapy without G-CSF support based on grade of toxicity to standard-dosed chemotherapy based on body surface area (BSA). Patients with early breast cancer were included and received the first cycle of standard FEC (fluorouracil 600 mg/m 2 , epirubicin 60 mg/m 2 , cyclophosphamide 600 mg/m 2 ). Patients with nadir leukopenia grade 0-2 after first cycle were randomised between either 6 additional courses of tailored FEC with increased doses (E 75-90 mg/m 2 , C 900-1200 mg/m 2 ) or fixed treatment with 6 standard FEC. Patients with grade 3-4 leukopenia were registered and treated with 6 standard FEC. Primary end-point was distant disease-free survival (DDFS). The study enrolled 1535 patients, of which 1052 patients were randomised to tailored FEC (N = 524) or standard FEC (N = 528), whereas 401 patients with leukopenia grade 3-4 continued standard FEC and formed the registered cohort. Dose escalation did not statistically significantly improve 10-year DDFS (79% and 77%, HR 0.87, CI 0.67-1.14, P = 0.32) or OS (82% and 78%, respectively, HR 0.89, CI 0.57-1.16, P = 0.38). Corresponding estimates for the registered group of patients were DDFS 79% and OS 82%, respectively. The SBG 2000-1 study failed to show a statistically significant improvement of escalated and tailored-dosed chemotherapy compared with standard BSA-based chemotherapy in patients with low haematological toxicity, although all efficacy parameters showed a numerical advantage for tailored treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

[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.

A randomised controlled trial of blended learning to improve the newborn examination skills of medical students.

PubMed

Stewart, Alice; Inglis, Garry; Jardine, Luke; Koorts, Pieter; Davies, Mark William

2013-03-01

To evaluate the hypotheses that a blended learning approach would improve the newborn examination skills of medical students and yield a higher level of satisfaction with learning newborn examination. Undergraduate medical students at a tertiary teaching hospital were individually randomised to receive either a standard neonatology teaching programme (control group), or additional online access to the PENSKE Baby Check Learning Module (blended learning group). The primary outcome was performance of newborn examination on standardised assessment by blinded investigators. The secondary outcomes were performance of all 'essential' items of the examination, and participant satisfaction. The recruitment rate was 88% (71/81). The blended learning group achieved a significantly higher mean score than the control group (p=0.02) for newborn examination. There was no difference for performance of essential items, or satisfaction with learning newborn examination. The blended learning group rated the module highly for effective use of learning time and ability to meet specific learning needs. A blended learning approach resulted in a higher level of performance of newborn examination on standardised assessment. This is consistent with published literature on blended learning and has implications for all neonatal clinicians including junior doctors, midwifes and nurse practitioners.

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.

Effectiveness of topiramate for tobacco dependence in patients with depression; a randomised, controlled trial

PubMed Central

Campayo, Javier García; Sobradiel, Natalia; Alda, Marta; Mas, Adoración; Andrés, Eva; Magallón, Rosa; Crucelaegui, Arantxa; Sanz, Beatriz

2008-01-01

Background Tobacco dependence management is a multi-component intervention that includes pharmacological treatments such as Nicotine Substitution Therapy (NST) or bupropion, and psychological therapy. There are some preliminary reports on topiramate efficacy for tobacco dependence. The aim of this study is to determine whether topiramate is as effective as the standard NST treatment for tobacco cessation at 1-year follow-up in patients with depression. Method/design Design: A randomised, controlled trial involving two groups, one of which is the control group consisting of patients on the standard pharmacological treatment for tobacco cessation (NST) and the other is the intervention group consisting of patients on topiramate as pharmacological treatment. Setting: 29 primary care health centres in the city of Zaragoza, Spain. Sample: 180 patients, aged 18–65 years, diagnosed with major depression, smoke more than 20 cigarettes/day, who have voluntarily asked for tobacco cessation therapy. Intervention: A multi-component programme for tobacco cessation is offered to all of the patients in the study. This programme is made up of pharmacological therapy + group cognitive-behavioural therapy. Pharmacological therapy consists of NST for the control group and topiramate (200 mg/day) for the intervention group. Psychological therapy is made up of 16 sessions of manualised group therapy. Measurements: Cessation will be assessed by patient self-declared abstinence, expired air carbon monoxide levels, and cotinine levels in saliva. Questionnaires on tobacco dependence, anxiety, depression, impulsiveness and self-efficacy will be administered. The interviewers will not know which group the patient belongs to (blind). The assessments will be carried out at baseline, D (cessation day) -1, D+1, weeks 1, 2, 3, 4, 6, 8, 10 and 13, and months 4, 5, 6, 8, 10 and 12. Main variables: Tobacco cessation rates and tobacco dependence. Analysis: The analysis will be per intent to treat. We will use the general linear models of the SPSS version 15 statistical package, to analyse the effect of the treatment on the result variable (tobacco cessation rate). Discussion It is necessary to develop new and more effective pharmacological treatments for tobacco cessation. This randomised clinical trial will determine whether topiramate is effective for tobacco cessation in patients with depression. Trial registration Current Controlled Trials ISRCTN93532081 PMID:18462502

Natural cycle in vitro fertilisation (IVF) for subfertile couples.

PubMed

Allersma, Thomas; Farquhar, Cindy; Cantineau, Astrid E P

2013-08-30

Subfertility affects 15% to 20% of couples trying to conceive. In vitro fertilisation (IVF) is one of the assisted reproduction techniques developed to improve chances of achieving pregnancy. In the standard IVF method with controlled ovarian hyperstimulation (COH), growth and development of multiple follicles are stimulated by using gonadotrophins, often combined with a gonadotrophin-releasing hormone (GnRH) agonist or antagonist. Although it is an established method of conception for subfertile couples, the treatment is expensive and has a high risk of adverse effects. Studies have shown that IVF in a natural cycle (NC) or a modified natural cycle (MNC) might be a promising low risk and low cost alternative to the standard stimulated IVF treatment since the available dominant follicle of each cycle is used. In this review, we included available randomised controlled studies comparing natural cycle IVF (NC and MNC) with standard IVF. To compare the efficacy and safety of natural cycle IVF (including both NC-IVF and MNC-IVF) with controlled ovarian hyperstimulation IVF (COH-IVF) in subfertile couples. An extended search including of the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ClinicalTrials.gov, conference abstracts in the Web of Knowledge, the World Health Organization International Trials Registry Platform search portal, LILACS database, PubMed and the OpenSIGLE database was conducted according to Cochrane guidelines. The last search was on 31st July 2013. All randomised controlled trials (RCTs) comparing either natural cycle IVF or modified natural cycle IVF versus standard IVF in subfertile couples were included. Data selection and extraction and risk of bias assessment were carried out independently by two authors (TA and AC). The primary outcome measures were live birth rate and ovarian hyperstimulation syndrome (OHSS) rate per randomised woman. We calculated Mantel-Haenszel odds ratios for each dichotomous outcome and either the mean difference or the standardised mean difference (SMD) for continuous outcomes, with 95% confidence intervals (CIs). A fixed effect model was used unless there was substantial heterogeneity, in which case a random effects model was used. Six randomised controlled trials with a total of 788 women were included. The largest of these trials included 396 women eligible for this review.No evidence of a statistically significant difference was found between natural cycle and standard IVF in live birth rates (OR 0.68, 95% CI 0.46 to 1.01, two studies, 425 women, I(2)= 0%, moderate quality evidence). The evidence suggests that for a woman with a 53% chance of live birth using standard IVF, the chance using natural cycle IVF would range from 34% to 53%. There was no evidence of a statistically significant difference between natural cycle and standard IVF in rates of OHSS (OR 0.19, 95% CI 0.01 to 4.06, one study, 60 women, very low quality evidence), clinical pregnancy (OR 0.52 95% CI 0.17 to 1.61, 4 studies, 351 women, I(2)=63%, low quality evidence), ongoing pregnancy (OR 0.72, 95% CI 0.50 to 1.05, three studies, 485 women, I(2)=0%, moderate quality evidence), multiple pregnancy (OR 0.76, 95% CI 0.25 to 2.31, 2 studies, 527 women, I(2)=0%, very low quality evidence), gestational abnormalities (OR 0.44 95% CI 0.03 to 5.93, 1 study, 18 women, very low quality evidence) or cycle cancellations (OR 8.98, 95% CI 0.20 to 393.66, 2 studies, 159 women, I(2)=83%, very low quality evidence). One trial reported that the oocyte retrieval rate was significantly lower in the natural cycle group (MD -4.40, 95% CI -7.87 to -0.93, 60 women, very low quality evidence). There were insufficient data to draw any conclusions about rates of treatment cancellation. Findings on treatment costs were inconsistent and more data are awaited. The evidence was limited by imprecision. Findings for pregnancy rate and for cycle cancellation were sensitive to the choice of statistical model: for these outcomes, use of a fixed effect model suggested a benefit for the standard IVF group. Moreover the largest trial has not yet completed follow up, though data have been reported for over 95% of women. Further evidence from well conducted large trials is awaited on natural cycle IVF treatment. Future trials should compare natural cycle IVF with standard IVF. Outcomes should include cumulative live birth and pregnancy rates, the number of treatment cycles necessary to reach live birth, treatment costs and adverse effects.

The Healthy Lifestyles Programme (HeLP), a novel school-based intervention to prevent obesity in school children: study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Over the last three decades there has been a substantial increase in the proportion of children who are overweight or obese. The Healthy Lifestyles Programme (HeLP) is a novel school-based intervention, using highly interactive and creative delivery methods to prevent obesity in children. Methods/Design We describe a cluster randomised controlled trial to evaluate the effectiveness and cost effectiveness of HeLP. The intervention has been developed using intervention mapping (involving extensive stakeholder involvement) and has been guided by the Information, Motivation, Behavioural Skills model. HeLP includes creating a receptive environment, drama activities, goal setting and reinforcement activities and runs over three school terms. Piloting showed that 9 to 10 year olds were the most receptive and participative. This study aims to recruit 1,300 children from 32 schools (over half of which will have ≥19% of pupils eligible for free school meals) from the southwest of England. Participating schools will be randomised to intervention or control groups with baseline measures taken prior to randomisation. The primary outcome is change in body mass index standard deviation score (BMI SDS) at 24 months post baseline. Secondary outcomes include, waist circumference and percent body fat SDS and proportion of children classified as overweight or obese at 18 and 24 months and objectively measured physical activity and food intake at 18 months. Between-group comparisons will be made using random effects regression analysis taking into account the hierarchical nature of the study design. An economic evaluation will estimate the incremental cost-effectiveness of HeLP, compared to control, from the perspective of the National Health Service (NHS)/third party payer. An in-depth process evaluation will provide insight into how HeLP works, and whether there is any differential uptake or engagement with the programme. Discussion The results of the trial will provide evidence on the effectiveness and cost effectiveness of the Healthy Lifestyles Programme in affecting the weight status of children. Trial registration ISRCTN15811706 PMID:23556434

Antenatal exercise in overweight and obese women and its effects on offspring and maternal health: design and rationale of the IMPROVE (Improving Maternal and Progeny Obesity Via Exercise) randomised controlled trial.

PubMed

Seneviratne, Sumudu N; Parry, Graham K; McCowan, Lesley Me; Ekeroma, Alec; Jiang, Yannan; Gusso, Silmara; Peres, Geovana; Rodrigues, Raquel O; Craigie, Susan; Cutfield, Wayne S; Hofman, Paul L

2014-04-26

Obesity during pregnancy is associated with adverse outcomes for the offspring and mother. Lifestyle interventions in pregnancy such as antenatal exercise, are proposed to improve both short- and long-term health of mother and child. We hypothesise that regular moderate-intensity exercise during the second half of pregnancy will result in improved maternal and offspring outcomes, including a reduction in birth weight and adiposity in the offspring, which may be protective against obesity in later life. The IMPROVE (Improving Maternal and Progeny Risks of Obesity Via Exercise) study is a two-arm parallel randomised controlled clinical trial being conducted in Auckland, New Zealand. Overweight and obese women (BMI ≥25 kg/m2) aged 18-40 years, with a singleton pregnancy of <20 weeks of gestation, from the Auckland region, are eligible for the trial. Exclusion criteria are ongoing smoking or medical contra-indications to antenatal exercise.Participants are randomised with 1:1 allocation ratio to either intervention or control group, using computer-generated randomisation sequences in variable block sizes, stratified on ethnicity and parity, after completion of baseline assessments. The intervention consists of a 16-week structured home-based moderate-intensity exercise programme utilising stationary cycles and heart rate monitors, commencing at 20 weeks of gestation. The control group do not receive any exercise intervention. Both groups undergo regular fetal ultrasonography and receive standard antenatal care. Due to the nature of the intervention, participants are un-blinded to group assignment during the trial.The primary outcome is offspring birth weight. Secondary offspring outcomes include fetal and neonatal body composition and anthropometry, neonatal complications and cord blood metabolic markers. Maternal outcomes include weight gain, pregnancy and delivery complications, aerobic fitness, quality of life, metabolic markers and post-partum body composition. The results of this trial will provide valuable insights on the effects of antenatal exercise on health outcomes in overweight and obese mothers and their offspring. Australian New Zealand Clinical Trials Registry ACTRN12612000932864.

Banked preterm versus banked term human milk to promote growth and development in very low birth weight infants.

PubMed

Dempsey, Eugene; Miletin, Jan

2010-06-16

Human milk banking has been available in many countries for the last three decades. The milk provided from milk banking is predominantly term breast milk, but some milk banks provide preterm breast milk. There are a number of differences between donor term and donor preterm human milk. To determine the effect of banked preterm milk compared with banked term milk regarding growth and developmental outcome in very low birth weight infants (infants weighing less than 1500 g). We used the standard methods of the Cochrane Neonatal Review Group, including a search of the Cochrane Neonatal Group specialized register and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, January 2010). We searched the computerised bibliographic databases MEDLINE (1966 to February 2010), EMBASE (1988 to February 2010) and Web of Science (1975 to February 2010). We searched reference lists of all selected articles, review articles and the Oxford Database of Perinatal Trials. We also searched abstracts from neonatal and pediatric meetings (PAS electronic version from 2000 to 2009, ESPR hand search from 2000 to 2009). We applied no language restrictions. Randomised and quasi-randomised trials comparing banked donor preterm milk with banked donor term milk regarding growth and developmental outcomes in very low birth weight infants We planned to perform assessment of methodology regarding blinding of randomisation, intervention and outcome measurements as well as completeness of follow-up. We planned to evaluate treatment effect using a fixed-effect model using relative risk (RR), relative risk reduction, risk difference (RD) and number needed to treat (NNT) for categorical data and using mean, standard deviation and weighted mean difference (WMD) for continuous data. We planned an evaluation of heterogeneity. No studies met the inclusion criteria. There are no randomised trials that compare preterm banked milk to banked term milk to promote growth and development in very low birth weight infants.

Enhanced performance feedback and patient participation to improve hand hygiene compliance of health-care workers in the setting of established multimodal promotion: a single-centre, cluster randomised controlled trial.

PubMed

Stewardson, Andrew James; Sax, Hugo; Gayet-Ageron, Angèle; Touveneau, Sylvie; Longtin, Yves; Zingg, Walter; Pittet, Didier

2016-12-01

Hand hygiene compliance of health-care workers remains suboptimal despite standard multimodal promotion, and evidence for the effectiveness of novel interventions is urgently needed. We aimed to assess the effect of enhanced performance feedback and patient participation on hand hygiene compliance in the setting of multimodal promotion. We did a single-centre, cluster randomised controlled trial at University of Geneva Hospitals (Geneva, Switzerland). All wards hosting adult, lucid patients, and all health-care workers and patients in these wards, were eligible. After a 15-month baseline period, eligible wards were assigned by computer-generated block randomisation (1:1:1), stratified by the type of ward, to one of three groups: control, enhanced performance feedback, or enhanced performance feedback plus patient participation. Standard multimodal hand hygiene promotion was done hospital-wide throughout the study. The primary outcome was hand hygiene compliance of health-care workers (according to the WHO Five Moments of Hand Hygiene) at the opportunity level, measured by direct observation (20-min sessions) by 12 validated infection control nurses, with each ward audited at least once every 3 months. This trial is registered with ISRCTN, number ISRCTN43599478. We randomly assigned 67 wards to the control group (n=21), enhanced performance feedback (n=24), or enhanced performance feedback plus patient participation (n=22) on May 19, 2010. One ward in the control group became a high-dependency unit and was excluded from analysis. During 1367 observation sessions, 12 579 hand hygiene opportunities were recorded. Between the baseline period (April 1, 2009, to June 30, 2010) and the intervention period (July 1, 2010, to June 30, 2012), mean hand hygiene compliance increased from 66% (95% CI 62-70) to 73% (70-77) in the control group (odds ratio [OR] 1·41, 95% CI 1·21-1·63), from 65% (62-69) to 75% (72-77) in the enhanced performance feedback group (1·61, 1·41-1·84), and from 66% (62-70) to 77% (74-80) in the enhanced performance feedback plus patient participation group (1·73, 1·51-1·98). The absolute difference in compliance attributable to interventions was 3 percentage points (95% CI 0-7; p=0·19) for the enhanced performance feedback group and 4 percentage points (1-8; p=0·048) for the enhanced performance feedback plus patient participation group. Hand hygiene compliance remained significantly higher than baseline in all three groups (OR 1·21 [1·00-1·47] vs 1·38 [1·19-1·60] vs 1·36 [1·18-1·57]) during the post-intervention follow-up (Jan 1, 2013, to Dec 31, 2014). Hand hygiene compliance improved in all study groups, and neither intervention had a clinically significant effect compared with control. Improvement in control wards might reflect cross-contamination, highlighting challenges with randomised trials of behaviour change. Swiss National Science Foundation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ketamine as the anaesthetic for electroconvulsive therapy: the KANECT randomised controlled trial

PubMed Central

Fernie, Gordon; Currie, James; Perrin, Jennifer S.; Stewart, Caroline A.; Anderson, Virginica; Bennett, Daniel M.; Hay, Steven; Reid, Ian C.

2017-01-01

Background Ketamine has recently become an agent of interest as an acute treatment for severe depression and as the anaesthetic for electroconvulsive therapy (ECT). Subanaesthetic doses result in an acute reduction in depression severity while evidence is equivocal for this antidepressant effect with anaesthetic or adjuvant doses. Recent systematic reviews call for high-quality evidence from further randomised controlled trials (RCTs). Aims To establish if ketamine as the anaesthetic for ECT results in fewer ECT treatments, improvements in depression severity ratings and less memory impairment than the standard anaesthetic. Method Double-blind, parallel-design, RCT of intravenous ketamine (up to 2 mg/kg) with an active comparator, intravenous propofol (up to 2.5 mg/kg), as the anaesthetic for ECT in patients receiving ECT for major depression on an informal basis. (Trial registration: European Clinical Trials Database (EudraCT): 2011-000396-14 and clinicalTrials.gov: NCT01306760.) Results No significant differences were found on any outcome measure during, at the end of or 1 month following the ECT course. Conclusions Ketamine as an anaesthetic does not enhance the efficacy of ECT. PMID:28254962

Integration of postpartum healthcare services for HIV-infected women and their infants in South Africa: A randomised controlled trial

PubMed Central

Zerbe, Allison; Hsiao, Nei-Yuan; Mellins, Claude A.; Abrams, Elaine J.

2018-01-01

Background As the number of HIV-infected women initiating lifelong antiretroviral therapy (ART) during pregnancy increases globally, concerns have emerged regarding low levels of retention in HIV services and suboptimal adherence to ART during the postpartum period. We examined the impact of integrating postpartum ART for HIV+ mothers alongside infant follow-up within maternal and child health (MCH) services in Cape Town, South Africa. Methods and findings We conducted a randomised trial among HIV+ postpartum women aged ≥18 years who initiated ART during pregnancy in the local antenatal care clinic and were breastfeeding when screened before 6 weeks postpartum. We compared an integrated postnatal service among mothers and their infants (the MCH-ART intervention) to the local standard of care (control)—immediate postnatal referral of HIV+ women on ART to general adult ART services and their infants to separate routine infant follow-up. Evaluation data were collected through medical records and trial measurement visits scheduled and located separately from healthcare services involved in either arm. The primary trial outcome was a composite endpoint of women’s retention in ART care and viral suppression (VS) (viral load < 50 copies/ml) at 12 months postpartum; secondary outcomes included duration of any and exclusive breastfeeding, mother-to-child HIV transmission, and infant mortality. Between 5 June 2013 and 10 December 2014, a total of 471 mother–infant pairs were enrolled and randomised (mean age, 28.6 years; 18% nulliparous; 57% newly diagnosed with HIV in pregnancy; median duration of ART use at randomisation, 18 weeks). Among 411 women (87%) with primary endpoint data available, 77% of women (n = 155) randomised to the MCH-ART intervention achieved the primary composite outcome of retention in ART services with VS at 12 months postpartum, compared to 56% of women (n = 117) randomised to the control arm (absolute risk difference, 0.21; 95% CI: 0.12–0.30; p < 0.001). The findings for improved retention in care and VS among women in the MCH-ART intervention arm were consistent across subgroups of participants according to demographic and clinical characteristics. The median durations of any breastfeeding and exclusive breastfeeding were longer in women randomised to the intervention versus control arm (6.9 versus 3.0 months, p = 0.006, and 3.0 versus 1.4 months, p < 0.001, respectively). For the infants, overall HIV-free survival through 12 months of age was 97%: mother-to-child HIV transmission was 1.2% overall (n = 4 and n = 1 transmissions in the intervention and control arms, respectively), and infant mortality was 1.9% (n = 6 and n = 3 deaths in the intervention and control arms, respectively), and these outcomes were similar by trial arm. Interpretation of these findings should be qualified by the location of this study in a single urban area as well as the self-reported nature of breastfeeding outcomes. Conclusions In this study, we found that integrating ART services into the MCH platform during the postnatal period was a simple and effective intervention, and this should be considered for improving maternal and child outcomes in the context of HIV. Trial registration ClinicalTrials.gov NCT01933477. PMID:29601570

Prevention of neonatal late-onset sepsis: a randomised controlled trial.

PubMed

Alcock, Gary; Liley, Helen G; Cooke, Lucy; Gray, Peter H

2017-04-04

Late-onset sepsis (LOS), defined as sepsis occurring after 48 h of age causes substantial mortality and morbidity in very low birth weight infants. Risk factors for LOS include immaturity, intravascular catheters, mechanical ventilation, and prolonged parenteral nutrition (PN). Little attention has been paid to studying the effects of PN administration methods. The aim of the study was to compare a bundle of measures for PN line management incorporating a strict aseptic technique with standard line management on LOS in very low birth weight infants. Infants <1500 g birth weight who required PN were randomised to either a bundle of a strict aseptic technique for line management together with single use intravascular catheter for PN or a standard technique. The primary outcome was the incidence of LOS in the first 28 days of life. Secondary outcomes were mortality, neonatal morbidities and developmental outcome at 12 months of age. There were 126 infants in the aseptic technique group and 123 in the standard technique group. Forty (31.8%) infants in the aseptic technique group and 36 (29.3%) in the standard technique group had an episode of sepsis (p = 0.77). This corresponds to incidences of 15.8 and 14.2 episodes of sepsis per 1000 patient days respectively. Subgroup analyses for infants <1000 g also revealed no difference in the rate of sepsis between the intervention and control groups. (p = 0.43). There were no significant differences in secondary outcomes and development between the groups. A bundle of measures including strict aseptic technique for parenteral nutrition line management did not result in a reduction in LOS when compared to a standard technique. There is no evidence to recommend this as routine practice. Interdisciplinary Maternal Perinatal Australasian Collaborative Trials (IMPACT) Network, TRN registration number: PT0363. Date: 06/03/2001; Australian New Zealand Clinical Trials Registry (ANZCTR), TRN registration number: ACTRN12617000455369 . Date: 28/03/2017 (retrospectively registered).

Comparative evaluation of terminalia chebula extract mouthwash and chlorhexidine mouthwash on plaque and gingival inflammation - 4-week randomised control trial.

PubMed

Gupta, Devanand; Gupta, Rajendra Kumar; Bhaskar, Dara John; Gupta, Vipul

2015-01-01

The present study was conducted to assess the effectiveness of Terminalia chebula on plaque and gingival inflammation and compare it with the gold standard chlorhexidine (CHX 0.2%) and distilled water as control (placebo). A double-blind randomised control trial was conducted among undergraduate students who volunteered. They were randomly allocated into three study groups: 1) Terminalia chebula mouthwash (n = 30); 2) chlorhexidine (active control) (n = 30); 3) distilled water (placebo) (n = 30). Assessment was carried out according to plaque score and gingival score. Statistical analysis was carried out to compare the effect of both mouthwashes. ANOVA and post-hoc LSD tests were performed using SPSS version 17 with p ≤ 0.05 considered statistically significant. Our result showed that Terminalia chebula mouthrinse is as effective as chlorhexidine in reducing dental plaque and gingival inflammation. The results demonstrated a significant reduction of gingival bleeding and plaque indices in both groups over a period of 15 and 30 days as compared to the placebo. The results of the present study indicate that Terminalia chebula may prove to be an effective mouthwash. Terminalia chebula extract mouthrinse can be used as an alternative to chlorhexidine mouthrinse as it has similar properties without the side-effects of the latter.

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

PubMed

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

2014-07-08

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

REFINE (REducing Falls in In-patieNt Elderly) using bed and bedside chair pressure sensors linked to radio-pagers in acute hospital care: a randomised controlled trial

PubMed Central

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

2014-01-01

Background: falls in hospitals are a major problem and contribute to substantial healthcare burden. Advances in sensor technology afford innovative approaches to reducing falls in acute hospital care. However, whether these are clinically effective and cost effective in the UK setting has not been evaluated. Methods: pragmatic, parallel-arm, individual randomised controlled trial of bed and bedside chair pressure sensors using radio-pagers (intervention group) compared with standard care (control group) in elderly patients admitted to acute, general medical wards, in a large UK teaching hospital. Primary outcome measure number of in-patient bedside falls per 1,000 bed days. Results: 1,839 participants were randomised (918 to the intervention group and 921 to the control group). There were 85 bedside falls (65 fallers) in the intervention group, falls rate 8.71 per 1,000 bed days compared with 83 bedside falls (64 fallers) in the control group, falls rate 9.84 per 1,000 bed days (adjusted incidence rate ratio, 0.90; 95% confidence interval [CI], 0.66–1.22; P = 0.51). There was no significant difference between the two groups with respect to time to first bedside fall (adjusted hazard ratio (HR), 0.95; 95% CI: 0.67–1.34; P= 0.12). The mean cost per patient in the intervention group was £7199 compared with £6400 in the control group, mean difference in QALYs per patient, 0.0001 (95% CI: −0.0006–0.0004, P= 0.67). Conclusions: bed and bedside chair pressure sensors as a single intervention strategy do not reduce in-patient bedside falls, time to first bedside fall and are not cost-effective in elderly patients in acute, general medical wards in the UK. Trial registration: isrctn.org identifier: ISRCTN44972300. PMID:24141253

Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial.

PubMed

Chabala, Chishala; Turkova, Anna; Thomason, Margaret J; Wobudeya, Eric; Hissar, Syed; Mave, Vidya; van der Zalm, Marieke; Palmer, Megan; Kapasa, Monica; Bhavani, Perumal K; Balaji, Sarath; Raichur, Priyanka A; Demers, Anne-Marie; Hoddinott, Graeme; Owen-Powell, Ellen; Kinikar, Aarti; Musoke, Philippa; Mulenga, Veronica; Aarnoutse, Rob; McIlleron, Helen; Hesseling, Anneke; Crook, Angela M; Cotton, Mark; Gibb, Diana M

2018-04-19

Tuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment in children is largely extrapolated from adult studies. Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries, making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible. The safety and efficacy of these higher drug doses has not been systematically assessed in large studies in children, and the pharmacokinetics across children representing the range of weights and ages should be confirmed. SHINE is a multicentre, open-label, parallel-group, non-inferiority, randomised controlled, two-arm trial comparing a 4-month vs the standard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses. We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB, with or without HIV infection. The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post randomisation and grade 3 or 4 adverse events. Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations, providing model-based predictions for optimal dosing, and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children. Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations. Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful, the question has never been addressed in children, who have mainly paucibacillary, non-severe smear-negative disease. SHINE should inform whether treatment-shortening of drug-susceptible TB in children, regardless of HIV status, is efficacious and safe. The trial will also fill existing gaps in knowledge on dosing and acceptability of new anti-tuberculosis formulations and commonly used HIV drugs in settings with a high burden of TB. A positive result from this trial could simplify and shorten treatment, improve adherence and be cost-saving for many children with TB. Recruitment to the SHINE trial begun in July 2016; results are expected in 2020. International Standard Randomised Controlled Trials Number: ISRCTN63579542 , 14 October 2014. Pan African Clinical Trials Registry Number: PACTR201505001141379 , 14 May 2015. Clinical Trial Registry-India, registration number: CTRI/2017/07/009119, 27 July 2017.

Protocol for extended antibiotic therapy after laparoscopic cholecystectomy for acute calculous cholecystitis (Cholecystectomy Antibiotic Randomised Trial, CHART).

PubMed

Pellegrini, Pablo; Campana, Juan Pablo; Dietrich, Agustín; Goransky, Jeremías; Glinka, Juan; Giunta, Diego; Barcan, Laura; Alvarez, Fernando; Mazza, Oscar; Sánchez Claria, Rodrigo; Palavecino, Martin; Arbues, Guillermo; Ardiles, Victoria; de Santibañes, Eduardo; Pekolj, Juan; de Santibañes, Martin

2015-11-18

Acute calculous cholecystitis represents one of the most common complications of cholelithiasis. While laparoscopic cholecystectomy is the standard treatment in mild and moderate forms, the need for antibiotic therapy after surgery remains undefined. The aim of the randomised controlled Cholecystectomy Antibiotic Randomised Trial (CHART) is therefore to assess if there are benefits in the use of postoperative antibiotics in patients with mild or moderate acute cholecystitis in whom a laparoscopic cholecystectomy is performed. A single-centre, double-blind, randomised trial. After screening for eligibility and informed consent, 300 patients admitted for acute calculus cholecystitis will be randomised into two groups of treatment, either receiving amoxicillin/clavulanic acid or placebo for 5 consecutive days. Postoperative evaluation will take place during the first 30 days. Postoperative infectious complications are the primary end point. Secondary end points are length of hospital stay, readmissions, need of reintervention (percutaneous or surgical reinterventions) and overall mortality. The results of this trial will provide strong evidence to either support or abandon the use of antibiotics after surgery, impacting directly in the incidence of adverse events associated with the use of antibiotics, the emergence of bacterial resistance and treatment costs. This study and informed consent sheets have been approved by the Research Projects Evaluating Committee (CEPI) of Hospital Italiano de Buenos Aires (protocol N° 2111). The results of the trial will be reported in a peer-reviewed publication. NCT02057679. 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 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.

Effect of a randomised exclusive breastfeeding counselling intervention nested into the MINIMat prenatal nutrition trial in Bangladesh.

PubMed

Khan, Ashraful Islam; Kabir, Iqbal; Eneroth, Hanna; El Arifeen, Shams; Ekström, Eva-Charlotte; Frongillo, Edward A; Persson, Lars Åke

2017-01-01

It is unknown whether maternal malnutrition reduces the effect of counselling on exclusive breastfeeding. This study evaluated the effect of breastfeeding counselling on the duration of exclusive breastfeeding, and whether the timing of prenatal food and different micronutrient supplements further prolonged this duration. Pregnant women in Matlab, Bangladesh, were randomised to receive daily food supplements of 600 kcal at nine weeks of gestation or at the standard 20 weeks. They also were allocated to either 30 mg of iron and 400 μg folic acid, or the standard programme 60 mg of iron and folic acid or multiple micronutrients. At 30 weeks of gestation, 3188 women were randomised to receive either eight breastfeeding counselling sessions or the usual health messages. The median duration of exclusive breastfeeding was 135 days in the counselling group and 75 days in the usual health message group (p < 0.001). Prenatal supplements did not modify the effects of counselling. Women in the usual health message group who were randomised to multiple micronutrients exclusively breastfed for 12 days longer than mothers receiving the standard iron-folate combination (p = 0.003). Breastfeeding counselling increased the duration of exclusive breastfeeding by 60 days. This duration was not influenced by the supplements. ©2016 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.

The mind–body connection in irritable bowel syndrome: A randomised controlled trial of hypnotherapy as a treatment

PubMed Central

Talley, Nicholas J; Jones, Michael P

2015-01-01

Background: Hypnotherapy has been reported as being beneficial in the treatment of irritable bowel syndrome (IBS). We aimed to test the hypothesis that patients with IBS treated ‘holistically’ by hypnosis (i.e. by combined psychological and physiological symptom imagery) would have greater improvement in their IBS symptoms than patients treated by hypnosis using standard ‘gut-directed’ hypnotherapy, and both would be superior to simple relaxation therapy. Methods: Patients (n = 51) with Rome II criteria were randomised to ‘individualised’ (holistic) hypnotherapy, standard ‘gut-directed’ hypnotherapy or relaxation therapy for a period of 11 weeks with two follow-up assessments at 2 weeks and at 3 months after the completion of the trial. The primary outcome was bowel symptom severity scale (BSSS). Results: All the participants in this study improved their IBS symptoms (pain, bloating, constipation and diarrhoea) and physical functioning at the end of the treatment from baseline, but this was not significantly different across the treatment arms. Conclusion: Neither ‘individualised’ nor ‘gut-directed’ hypnotherapy is superior to relaxation therapy in IBS. PMID:28070348

No socioeconomic inequalities in ovarian cancer survival within two randomised clinical trials

PubMed Central

Abdel-Rahman, M E; Butler, J; Sydes, M R; Parmar, M K B; Gordon, E; Harper, P; Williams, C; Crook, A; Sandercock, J; Swart, A M; Rachet, B; Coleman, M P

2014-01-01

Background: Ovarian cancer is the leading cause of death among cancers of the female genital tract, with poor outcomes despite chemotherapy. There was a persistent socioeconomic gradient in 1-year survival in England and Wales for more than 3 decades (1971–2001). Inequalities in 5-year survival persisted for more than 20 years but have been smaller for women diagnosed around 2000. We explored one possible explanation. Methods: We analysed data on 1406 women diagnosed with ovarian cancer during 1991–1998 and recruited to one of two randomised clinical trials. In the second International Collaborative Ovarian Neoplasm (ICON2) trial, women diagnosed between 1991 and 1996 were randomised to receive either the three-drug combination cyclophosphamide, doxorubicin and cisplatin (CAP) or single-agent carboplatin given at optimal dose. In the ICON3 trial, women diagnosed during 1995–1998 were randomised to receive either the same treatments as ICON2, or paclitaxel plus carboplatin. Relative survival at 1, 5 and 10 years was estimated for women in five categories of socioeconomic deprivation. The excess hazard of death over and above background mortality was estimated by fitting multivariable regression models with Poisson error structure and a dedicated link function in a generalised linear model framework, adjusting for the duration of follow-up and the confounding effects of age, Federation of Gynecology and Obstetrics (FIGO) stage and calendar period. Results: Unlike women with ovarian cancer in the general population, no statistically significant socioeconomic gradient was seen for women with ovarian cancer treated in the two randomised controlled trials. The deprivation gap in 1-year relative survival in the general population was statistically significant at −6.7% (95% CI (−8.1, −5.3)), compared with −3.6% (95% CI (−10.4, +3.2)) in the trial population. Conclusions: Although ovarian cancer survival is significantly lower among poor women than rich women in England and Wales, there was no evidence of an association between socioeconomic deprivation and survival among women with ovarian cancer who were treated and followed up consistently in two well-conducted randomised controlled trials. We conclude that the persistent socioeconomic gradient in survival among women with ovarian cancer, at least for 1-year survival, may be due to differences in access to treatment and standards of care. PMID:24918817

No socioeconomic inequalities in ovarian cancer survival within two randomised clinical trials.

PubMed

Abdel-Rahman, M E; Butler, J; Sydes, M R; Parmar, M K B; Gordon, E; Harper, P; Williams, C; Crook, A; Sandercock, J; Swart, A M; Rachet, B; Coleman, M P

2014-07-29

Ovarian cancer is the leading cause of death among cancers of the female genital tract, with poor outcomes despite chemotherapy. There was a persistent socioeconomic gradient in 1-year survival in England and Wales for more than 3 decades (1971-2001). Inequalities in 5-year survival persisted for more than 20 years but have been smaller for women diagnosed around 2000. We explored one possible explanation. We analysed data on 1406 women diagnosed with ovarian cancer during 1991-1998 and recruited to one of two randomised clinical trials. In the second International Collaborative Ovarian Neoplasm (ICON2) trial, women diagnosed between 1991 and 1996 were randomised to receive either the three-drug combination cyclophosphamide, doxorubicin and cisplatin (CAP) or single-agent carboplatin given at optimal dose. In the ICON3 trial, women diagnosed during 1995-1998 were randomised to receive either the same treatments as ICON2, or paclitaxel plus carboplatin.Relative survival at 1, 5 and 10 years was estimated for women in five categories of socioeconomic deprivation. The excess hazard of death over and above background mortality was estimated by fitting multivariable regression models with Poisson error structure and a dedicated link function in a generalised linear model framework, adjusting for the duration of follow-up and the confounding effects of age, Federation of Gynecology and Obstetrics (FIGO) stage and calendar period. Unlike women with ovarian cancer in the general population, no statistically significant socioeconomic gradient was seen for women with ovarian cancer treated in the two randomised controlled trials. The deprivation gap in 1-year relative survival in the general population was statistically significant at -6.7% (95% CI (-8.1, -5.3)), compared with -3.6% (95% CI (-10.4, +3.2)) in the trial population. Although ovarian cancer survival is significantly lower among poor women than rich women in England and Wales, there was no evidence of an association between socioeconomic deprivation and survival among women with ovarian cancer who were treated and followed up consistently in two well-conducted randomised controlled trials. We conclude that the persistent socioeconomic gradient in survival among women with ovarian cancer, at least for 1-year survival, may be due to differences in access to treatment and standards of care.

Preventing recurrence of endometriosis by means of long-acting progestogen therapy (PRE-EMPT): report of an internal pilot, multi-arm, randomised controlled trial incorporating flexible entry design and adaption of design based on feasibility of recruitment.

PubMed

Middleton, Lee J; Daniels, Jane P; Weckesser, Annalise; Bhattacharya, Siladitya

2017-03-11

Endometriosis is associated with the growth of endometrium in ectopic sites mainly within the pelvis. This results in inflammation and scarring, causing pain and impaired quality of life. Endometriotic lesions can be excised or ablated surgically, but the risk of recurrence is high. A Heath Technology Assessment commissioning call in 2011 sought applications for trials aimed at evaluating long-term effectiveness of postoperative, long-acting, reversible contraceptives (LARCs) in preventing recurrence of endometriosis. A survey of gynaecologists indicated that there was no consensus about which LARC (Levonorgestrel Intrauterine System (LNG-IUS) or depot medroxyprogesterone acetate injection (DMPA)) or comparator (combined oral contraceptive pill (COCP) or no treatment) should be evaluated. Hence, we designed a 'flexible-entry' internal pilot to assess whether a four-arm trial was feasible including a possible design adaption based on pilot findings. In this pilot, women could be randomised to two, three or four treatment options provided that one was a LARC and one was a non-LARC. An assessment of feasibility based on recruitment to these options and a revised substantive trial design was considered by an independent oversight committee. The study ran for 1 year from April 2014 and 77 women were randomised. Only 5 (6%) women accepted randomisation to all groups, with 63 (82%) having a LARC preference and 55 (71%) a non-LARC preference. Four-way and three-way designs were ruled out with a two-way LARC versus COCP design, stratified by prerandomisation choice of LARC and optional subrandomisation to LNG-IUS versus DMPA considered a feasible substantive study. Multi-arm studies are potentially efficient as they can answer multiple questions simultaneously but are difficult to recruit to if there are strong patient or clinician preferences. A flexible approach to randomisation in a pilot phase can be used to assess feasibility of such studies and modify a trial design based on chosen recruitment options, but trialists should consider carefully any practical arrangements should groups need to be dropped during a study. International Standard Randomised Controlled Trial Number, ISRCTN97865475 . Registered on 20 March 2014.

Postoperative shoulder pain after laparoscopic hysterectomy with deep neuromuscular blockade and low-pressure pneumoperitoneum: A randomised controlled trial.

PubMed

Madsen, Matias V; Istre, Olav; Staehr-Rye, Anne K; Springborg, Henrik H; Rosenberg, Jacob; Lund, Jørgen; Gätke, Mona R

2016-05-01

Postoperative shoulder pain remains a significant problem after laparoscopy. Pneumoperitoneum with insufflation of carbon dioxide (CO2) is thought to be the most important cause. Reduction of pneumoperitoneum pressure may, however, compromise surgical visualisation. Recent studies indicate that the use of deep neuromuscular blockade (NMB) improves surgical conditions during a low-pressure pneumoperitoneum (8 mmHg). The aim of this study was to investigate whether low-pressure pneumoperitoneum (8 mmHg) and deep NMB (posttetanic count 0 to 1) compared with standard-pressure pneumoperitoneum (12 mmHg) and moderate NMB (single bolus of rocuronium 0.3 mg kg with spontaneous recovery) would reduce the incidence of shoulder pain and improve recovery after laparoscopic hysterectomy. A randomised, controlled, double-blinded study. Private hospital in Denmark. Ninety-nine patients. Randomisation to either deep NMB and 8 mmHg pneumoperitoneum (Group 8-Deep) or moderate NMB and 12 mmHg pneumoperitoneum (Group 12-Mod). Pain was assessed on a visual analogue scale (VAS) for 14 postoperative days. The primary endpoint was the incidence of shoulder pain during 14 postoperative days. Secondary endpoints included area under curve VAS scores for shoulder, abdominal, incisional and overall pain during 4 and 14 postoperative days; opioid consumption; incidence of nausea and vomiting; antiemetic consumption; time to recovery of activities of daily living; length of hospital stay; and duration of surgery. Shoulder pain occurred in 14 of 49 patients (28.6%) in Group 8-Deep compared with 30 of 50 (60%) patients in Group 12-Mod. Absolute risk reduction was 0.31 (95% confidence interval 0.12 to 0.48; P = 0.002). There were no differences in any secondary endpoints including area under the curve for VAS scores. Deep NMB and low-pressure pneumoperitoneum (8 mmHg) reduced the incidence of shoulder pain after laparoscopic hysterectomy in comparison to moderate NMB and standard-pressure pneumoperitoneum (12 mmHg). Clinicaltrials.gov identifier: NCT01722097.

A randomised controlled non-inferiority trial of primary care-based facilitated access to an alcohol reduction website (EFAR Spain): the study protocol

PubMed Central

López-Pelayo, Hugo; Wallace, Paul; Segura, Lidia; Miquel, Laia; Díaz, Estela; Teixidó, Lidia; Baena, Begoña; Struzzo, Pierliugio; Palacio-Vieira, Jorge; Casajuana, Cristina; Colom, Joan; Gual, Antoni

2014-01-01

Introduction Early identification (EI) and brief interventions (BIs) for risky drinkers are effective tools in primary care. Lack of time in daily practice has been identified as one of the main barriers to implementation of BI. There is growing evidence that facilitated access by primary healthcare professionals (PHCPs) to a web-based BI can be a time-saving alternative to standard face-to-face BIs, but there is as yet no evidence about the effectiveness of this approach relative to conventional BI. The main aim of this study is to test non-inferiority of facilitation to a web-based BI for risky drinkers delivered by PHCP against face-to-face BI. Method and analysis A randomised controlled non-inferiority trial comparing both interventions will be performed in primary care health centres in Catalonia, Spain. Unselected adult patients attending participating centres will be given a leaflet inviting them to log on to a website to complete the Alcohol Use Disorders Identification Test (AUDIT-C) alcohol screening questionnaire. Participants with positive results will be requested online to complete a trial module including consent, baseline assessment and randomisation to either face-to-face BI by the practitioner or BI via the alcohol reduction website. Follow-up assessment of risky drinking will be undertaken online at 3 months and 1 year using the full AUDIT and D5-EQD5 scale. Proportions of risky drinkers in each group will be calculated and non-inferiority assessed against a specified margin of 10%. Assuming reduction of 30% of risky drinkers receiving standard intervention, 1000 patients will be required to give 90% power to reject the null hypothesis. Ethics and dissemination The protocol was approved by the Ethics Commmittee of IDIAP Jordi Gol i Gurina P14/028. The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations. Trial registration number ClinicalTrials.gov NCT02082990. PMID:25552616

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

PubMed

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

2017-10-05

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

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.

Exploring the feasibility and acceptability of couple-based psychosexual support following prostate cancer surgery: study protocol for a pilot randomised controlled trial

PubMed Central

2014-01-01

Background Men who undergo surgery for prostate cancer frequently experience significant side-effects including urinary and sexual dysfunction. These difficulties can lead to anxiety, depression and reduced quality of life. Many partners also experience psychological distress. An additional impact can be on the couple relationship, with changes to intimacy, and unmet psychosexual supportive needs in relation to sexual recovery and rehabilitation. The aim of this exploratory randomised controlled trial pilot study is to determine the feasibility and acceptability of a novel family-relational-psychosexual intervention to support intimacy and reduce distress among couples following prostate cancer surgery and to estimate the efficacy of this intervention. Methods/Design The intervention will comprise six sessions of psychosexual and relationship support delivered by experienced couple-support practitioners. Specialist training in delivering the intervention will be provided to practitioners and they will be guided by a detailed treatment manual based on systemic principles. Sixty-eight couples will be randomised to receive either the intervention or standard care (comprising usual follow-up hospital appointments). A pre-test, post-test design will be used to test the feasibility of the intervention (baseline, end of intervention and six-month follow-up) and its acceptability to couples and healthcare professionals (qualitative interviews). Both individual and relational outcome measures will assess sexual functioning, anxiety and depression, couple relationship, use of health services and erectile dysfunction medication/technologies. An economic analysis will estimate population costs of the intervention, compared to usual care, using simple modelling to evaluate the affordability of the intervention. Discussion Given the increasing incidence and survival of post-operative men with prostate cancer, it is timely and appropriate to determine the feasibility of a definitive trial through a pilot randomised controlled trial of a family-relational-psychosexual intervention for couples. The study will provide evidence about the components of a couple-based intervention, its acceptability to patients and healthcare professionals, and its influence on sexual and relational functioning. Data from this study will be used to calculate sample sizes required for any definitive trial. Trial registration ClinicalTrials.gov Identifier: NCT01842438. Registration date: 24 April 2013; Randomisation of first patient: 13 May 2013 PMID:24886676

United Kingdom Frozen Shoulder Trial (UK FROST), multi-centre, randomised, 12 month, parallel group, superiority study to compare the clinical and cost-effectiveness of Early Structured Physiotherapy versus manipulation under anaesthesia versus arthroscopic capsular release for patients referred to secondary care with a primary frozen shoulder: study protocol for a randomised controlled trial.

PubMed

Brealey, Stephen; Armstrong, Alison L; Brooksbank, Andrew; Carr, Andrew Jonathan; Charalambous, Charalambos P; Cooper, Cushla; Corbacho, Belen; Dias, Joseph; Donnelly, Iona; Goodchild, Lorna; Hewitt, Catherine; Keding, Ada; Kottam, Lucksy; Lamb, Sarah E; McDaid, Catriona; Northgraves, Matthew; Richardson, Gerry; Rodgers, Sara; Shah, Sarwat; Sharp, Emma; Spencer, Sally; Torgerson, David; Toye, Francine; Rangan, Amar

2017-12-22

Frozen shoulder (also known as adhesive capsulitis) occurs when the capsule, or the soft tissue envelope around the ball and socket shoulder joint, becomes scarred and contracted, making the shoulder tight, painful and stiff. It affects around 1 in 12 men and 1 in 10 women of working age. Although this condition can settle with time (typically taking 1 to 3 years), for some people it causes severe symptoms and needs referral to hospital. Our aim is to evaluate the clinical and cost-effectiveness of two invasive and costly surgical interventions that are commonly used in secondary care in the National Health Service (NHS) compared with a non-surgical comparator of Early Structured Physiotherapy. We will conduct a randomised controlled trial (RCT) of 500 adult patients with a clinical diagnosis of frozen shoulder, and who have radiographs that exclude other pathology. Early Structured Physiotherapy with an intra-articular steroid injection will be compared with manipulation under anaesthesia with a steroid injection or arthroscopic (keyhole) capsular release followed by manipulation. Both surgical interventions will be followed with a programme of post-procedural physiotherapy. These treatments will be undertaken in NHS hospitals across the United Kingdom. The primary outcome and endpoint will be the Oxford Shoulder Score (a patient self-reported assessment of shoulder function) at 12 months. This will also be measured at baseline, 3 and 6 months after randomisation; and on the day that treatment starts and 6 months later. Secondary outcomes include the Disabilities of Arm Shoulder and Hand (QuickDASH) score, the EQ-5D-5 L score, pain, extent of recovery and complications. We will explore the acceptability of the different treatments to patients and health care professionals using qualitative methods. The three treatments being compared are the most frequently used in secondary care in the NHS, but there is uncertainty about which one works best and at what cost. UK FROST is a rigorously designed and adequately powered study to inform clinical decisions for the treatment of this common condition in adults. International Standard Randomised Controlled Trial Register, ID: ISRCTN48804508 . Registered on 25 July 2014.

The effect of local anaesthetic wound infiltration on chronic pain after lower limb joint replacement: A protocol for a double-blind randomised controlled trial

PubMed Central

2011-01-01

Background For the majority of patients with osteoarthritis (OA), joint replacement is a successful intervention for relieving chronic joint pain. However, between 10-30% of patients continue to experience chronic pain after joint replacement. Evidence suggests that a risk factor for chronic pain after joint replacement is the severity of acute post-operative pain. The aim of this randomised controlled trial (RCT) is to determine if intra-operative local anaesthethic wound infiltration additional to a standard anaethesia regimen can reduce the severity of joint pain at 12-months after total knee replacement (TKR) and total hip replacement (THR) for OA. Methods 300 TKR patients and 300 THR patients are being recruited into this single-centre double-blind RCT. Participants are recruited before surgery and randomised to either the standard care group or the intervention group. Participants and outcome assessors are blind to treatment allocation throughout the study. The intervention consists of an intra-operative local anaesthetic wound infiltration, consisting of 60 mls of 0.25% bupivacaine with 1 in 200,000 adrenaline. Participants are assessed on the first 5 days post-operative, and then at 3-months, 6-months and 12-months. The primary outcome is the WOMAC Pain Scale, a validated measure of joint pain at 12-months. Secondary outcomes include pain severity during the in-patient stay, post-operative nausea and vomiting, satisfaction with pain relief, length of hospital stay, joint pain and disability, pain sensitivity, complications and cost-effectiveness. A nested qualitative study within the RCT will examine the acceptability and feasibility of the intervention for both patients and healthcare professionals. Discussion Large-scale RCTs assessing the effectiveness of a surgical intervention are uncommon, particulary in orthopaedics. The results from this trial will inform evidence-based recommendations for both short-term and long-term pain management after lower limb joint replacement. If a local anaesthetic wound infiltration is found to be an effective and cost-effective intervention, implementation into clinical practice could improve long-term pain outcomes for patients undergoing lower limb joint replacement. Trial registration Current Controlled Trials ISRCTN96095682 PMID:21352559

South Yorkshire Cohort: a 'cohort trials facility' study of health and weight - protocol for the recruitment phase.

PubMed

Relton, Clare; Bissell, Paul; Smith, Christine; Blackburn, Joanna; Cooper, Cindy L; Nicholl, Jon; Tod, Angela; Copeland, Rob; Loban, Amanda; Chater, Tim; Thomas, Kate; Young, Tracy; Weir, Carol; Harrison, Gill; Millbourn, Alison; Manners, Rachel

2011-08-11

Growing levels of both obesity and chronic disease in the general population pose a major public health problem. In the UK, an innovative 'health and weight' cohort trials facility, the 'South Yorkshire Cohort', is being built in order to provide robust evidence to inform policy, commissioning and clinical decisions in this field. This protocol reports the design of the facility and outlines the recruitment phase methods. The South Yorkshire Cohort health and weight study uses the cohort multiple randomised controlled trial design. This design recruits a large observational cohort of patients with the condition(s) of interest which then provides a facility for multiple randomised controlled trials (with large representative samples of participants, long term outcomes as standard, increased comparability between each trial conducted within the cohort and increased efficiency particularly for trials of expensive interventions) as well as ongoing information as to the natural history of the condition and treatment as usual.This study aims to recruit 20,000 participants to the population based South Yorkshire Cohort health and weight research trials facility. Participants are recruited by invitation letters from their General Practitioners. Data is collected using postal and/or online patient self completed Health Questionnaires. NHS numbers will be used to facilitate record linkage and access to routine data. Participants are eligible if they are: aged 16 - 85 years, registered with one of 40 practices in South Yorkshire, provide consent for further contact from the researchers and to have their information used to look at the benefit of health treatments. The first wave of data is being collected during 2010/12 and further waves are planned at 2 - 5 year intervals for the planned 20 year duration of the facility. The South Yorkshire Cohort combines the strengths of the standard observational, longitudinal cohort study design with a population based cohort facility for multiple randomised controlled trials in a range of long term health and weight related conditions (including obesity). This infrastructure will allow the rapid and cheap identification and recruitment of patients, and facilitate the provision of robust evidence to inform the management and self-management of health and weight.

South Yorkshire Cohort: a 'cohort trials facility' study of health and weight - Protocol for the recruitment phase

PubMed Central

2011-01-01

Background Growing levels of both obesity and chronic disease in the general population pose a major public health problem. In the UK, an innovative 'health and weight' cohort trials facility, the 'South Yorkshire Cohort', is being built in order to provide robust evidence to inform policy, commissioning and clinical decisions in this field. This protocol reports the design of the facility and outlines the recruitment phase methods. Method/Design The South Yorkshire Cohort health and weight study uses the cohort multiple randomised controlled trial design. This design recruits a large observational cohort of patients with the condition(s) of interest which then provides a facility for multiple randomised controlled trials (with large representative samples of participants, long term outcomes as standard, increased comparability between each trial conducted within the cohort and increased efficiency particularly for trials of expensive interventions) as well as ongoing information as to the natural history of the condition and treatment as usual. This study aims to recruit 20,000 participants to the population based South Yorkshire Cohort health and weight research trials facility. Participants are recruited by invitation letters from their General Practitioners. Data is collected using postal and/or online patient self completed Health Questionnaires. NHS numbers will be used to facilitate record linkage and access to routine data. Participants are eligible if they are: aged 16 - 85 years, registered with one of 40 practices in South Yorkshire, provide consent for further contact from the researchers and to have their information used to look at the benefit of health treatments. The first wave of data is being collected during 2010/12 and further waves are planned at 2 - 5 year intervals for the planned 20 year duration of the facility. Discussion The South Yorkshire Cohort combines the strengths of the standard observational, longitudinal cohort study design with a population based cohort facility for multiple randomised controlled trials in a range of long term health and weight related conditions (including obesity). This infrastructure will allow the rapid and cheap identification and recruitment of patients, and facilitate the provision of robust evidence to inform the management and self-management of health and weight. PMID:21834964

A single-arm trial indirect comparison investigation: a proof-of-concept method to predict venous leg ulcer healing time for a new acellular synthetic matrix matched to standard care control.

PubMed

Shannon, Ronald; Nelson, Andrea

2017-08-01

To compare data on time to healing from two separate cohorts: one treated with a new acellular synthetic matrix plus standard care (SC) and one matched from four large UK pragmatic, randomised controlled trials [venous leg ulcer (VLU) evidence network]. We introduce a new proof-of-concept strategy to a VLU clinical evidence network, propensity score matching and sensitivity analysis to predict the feasibility of the new acellular synthetic matrix plus SC for success in future randomised, controlled clinical trials. Prospective data on chronic VLUs from a safety and effectiveness study on an acellular synthetic matrix conducted in one wound centre in the UK (17 patients) and three wound centres in Australia (36 patients) were compared retrospectively to propensity score-matched data from patients with comparable leg ulcer disease aetiology, age, baseline ulcer area, ulcer duration, multi-layer compression bandaging and majority of care completed in specialist wound centres (average of 1 visit per week), with the outcome measures at comparable follow-up periods from patients enrolled in four prospective, multicentre, pragmatic, randomised studies of venous ulcers in the UK (the comparison group; VLU evidence network). Analysis using Kaplan-Meier survival curves showed a mean healing time of 73·1 days for ASM plus SC (ASM) treated ulcers in comparison with 83·5 days for comparison group ulcers treated with SC alone (Log rank test, χ 2 5·779, P = 0·016) within 12 weeks. Sensitivity analysis indicates that an unobserved covariate would have to change the odds of healing for SC by a factor of 1·1 to impact the baseline results. Results from this study predict a significant effect on healing time when using a new ASM as an adjunct to SC in the treatment of non-healing venous ulcers in the UK, but results are sensitive to unobserved covariates that may be important in healing time comparison. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Protocol for the melatools skin self-monitoring trial: a phase II randomised controlled trial of an intervention for primary care patients at higher risk of melanoma.

PubMed

Mills, Katie; Emery, Jon; Lantaff, Rebecca; Radford, Michael; Pannebakker, Merel; Hall, Per; Burrows, Nigel; Williams, Kate; Saunders, Catherine L; Murchie, Peter; Walter, Fiona M

2017-11-28

Melanoma is the fifth most common cancer in the UK. Incidence rates have quadrupled over the last 30 years and continue to rise, especially among younger people. As routine screening of the general population is not currently recommended in the UK, a focus on secondary prevention through early detection and prompt treatment in individuals at increased risk of melanoma could make an important contribution to improve melanoma outcomes. This paper describes the protocol for a phase II, multisite, randomised controlled trial, in the primary care setting, for patients at increased risk of melanoma. A skin self-monitoring (SSM) smartphone 'App' was used to improve symptom appraisal and encourage help seeking in primary care, thereby promoting early presentation with skin changes suspicious of melanoma. We aim to recruit 200 participants from general practice waiting rooms in the East of England. Eligible patients are those identified at higher melanoma risk (using a real-time risk assessment tool), without a personal history of melanoma, aged 18 to 75 years. Participants will be invited to a primary care nurse consultation, and randomised to the intervention group (standard written advice on skin cancer detection and sun protection, loading of an SSM 'App' onto the participant's smartphone and instructions on use including self-monitoring reminders) or control group (standard written advice alone). The primary outcomes are consultation rates for changes to a pigmented skin lesion, and the patient interval (time from first noticing a skin change to consultation). Secondary outcomes include patient sun protection behaviours, psychosocial outcomes, and measures of trial feasibility and acceptability. NHS ethical approval has been obtained from Cambridgeshire and Hertfordshire research ethics committee (REC reference 16/EE/0248). The findings from the MelaTools SSM Trial will be disseminated widely through peer-reviewed publications and scientific conferences. ISCTRN16061621. © 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 limitations in implementing and operating a rapid response system.

PubMed

Subramaniam, A; Botha, J; Tiruvoipati, R

2016-10-01

Despite the widespread introduction of rapid response systems (RRS)/medical emergency teams (MET), there is still controversy regarding how effective they are. While there are some observational studies showing improved outcomes with RRS, there are no data from randomised controlled trials to support the effectiveness. Nevertheless, the MET system has become a standard of care in many healthcare organisations. In this review, we present an overview of the limitations in implementing and operating a RRS in modern healthcare. © 2016 Royal Australasian College of Physicians.

Does oral carbohydrate supplementation improve labour outcome? A systematic review and individual patient data meta-analysis.

PubMed

Malin, G L; Bugg, G J; Thornton, J; Taylor, M A; Grauwen, N; Devlieger, R; Kardel, K R; Kubli, M; Tranmer, J E; Jones, N W

2016-03-01

Labour is a period of significant physical activity. The importance of carbohydrate intake to improve outcome has been recognised in sports medicine and general surgery. To assess the effect of oral carbohydrate supplementation on labour outcomes. MEDLINE (1966-2014), Embase, the Cochrane Library and clinical trial registries. Randomised controlled trials (RCT) of women randomised to receive oral carbohydrate in labour (<6 cm dilated), versus placebo or standard care. Authors were contacted to provide data. Individual patient data meta-analyses were performed to calculate pooled risk ratios (RR) and 95% confidence intervals (CI). Eight RCTs met the inclusion criteria. Six authors responded, four supplied data (n = 691). Three studies used isotonic drinks (one placebo-controlled, two compared with standard care), and one an advice booklet regarding carbohydrate intake. The mean difference in energy intake between the intervention and control groups was small [three studies, 195 kilocalories (kcal), 95% CI 118-273]. There was no difference in the risk of caesarean section (RR 1.15, 95% CI 0.83- 1.61), instrumental birth (RR 1.26, 95% CI 0.96-1.66) or syntocinon augmentation (RR 0.99, 95% CI 0.86-1.13). Length of labour was similar (mean difference -3.15 minutes, 95% CI -35.14 to 41.95). Restricting the analysis to primigravid women did not affect the result. Oral carbohydrates did not increase the risk of vomiting (RR 1.09, 95% CI 0.78-1.52) or 1-minute Apgar score <7 (RR 1.23, 95% CI 0.82-1.83). Oral carbohydrate supplements in small quantities did not alter labour outcome. Oral carbohydrate does not affect labour. But the difference between intervention and control equals 10 teaspoons sugar. © 2016 Royal College of Obstetricians and Gynaecologists.

The At Home/Chez Soi trial protocol: a pragmatic, multi-site, randomised controlled trial of a Housing First intervention for homeless individuals with mental illness in five Canadian cities

PubMed Central

Streiner, David L; Adair, Carol; Aubry, Tim; Barker, Jayne; Distasio, Jino; Hwang, Stephen W; Komaroff, Janina; Latimer, Eric; Somers, Julian; Zabkiewicz, Denise M

2011-01-01

Introduction Housing First is a complex housing and support intervention for homeless individuals with mental health problems. It has a sufficient knowledge base and interest to warrant a test of wide-scale implementation in various settings. This protocol describes the quantitative design of a Canadian five city, $110 million demonstration project and provides the rationale for key scientific decisions. Methods A pragmatic, mixed methods, multi-site field trial of the effectiveness of Housing First in Vancouver, Winnipeg, Toronto, Montreal and Moncton, is randomising approximately 2500 participants, stratified by high and moderate need levels, into intervention and treatment as usual groups. Quantitative outcome measures are being collected over a 2-year period and a qualitative process evaluation is being completed. Primary outcomes are housing stability, social functioning and, for the economic analyses, quality of life. Hierarchical linear modelling is the primary data analytic strategy. Ethics and dissemination Research ethics board approval has been obtained from 11 institutions and a safety and adverse events committee is in place. The results of the multi-site analyses of outcomes at 12 months and 2 years will be reported in a series of core scientific journal papers. Extensive knowledge exchange activities with non-academic audiences will occur throughout the duration of the project. Trial registration number This study has been registered with the International Standard Randomised Control Trial Number Register and assigned ISRCTN42520374. PMID:22102645

Comparing the effectiveness of video self-instruction versus traditional classroom instruction targeted at cardiopulmonary resuscitation skills for laypersons: a prospective randomised controlled trial.

PubMed

Chung, C H; Siu, Axel Y C; Po, Lucia L K; Lam, C Y; Wong, Peter C Y

2010-06-01

To determine whether in the local lay Hong Kong population, video self-instruction about cardiopulmonary resuscitation has comparable results to traditional classroom instructions. Prospective randomised single-blind controlled trial. A first-aid training organisation in Hong Kong. Cantonese applicants for cardiopulmonary resuscitation courses aged between 18 and 70 years were recruited into the study. They were randomised into two groups. Those selected for self-learning were given a kit (consisting of a mini-manikin, a video compact disc, and an instruction manual) and sent home. The other group underwent usual classroom training. Both groups were examined together; the examiners remained blinded to the background training of the subjects. Those who passed were asked to come back for re-examination after 1 year. The examination passing rates initially and after 1 year. During a 1-year period between 1 April 2007 to 31 March 2008, 256 subjects were recruited into this study, 124 for self-learning and 132 for classroom training. The age range was 18 to 62 (mean, 39; standard deviation, 10) years. There was no significant difference in passing rate between the two groups at the initial examination or at the re-examination after 1 year. Notably, 28 (23%) of the participants of the self-learning group taught cardiopulmonary resuscitation to relatives and friends. Video self-learning resulted in cardiopulmonary resuscitation performance as good as traditional classroom training.

A randomised study of perioperative esmolol infusion for haemodynamic stability during major vascular surgery; rationale and design of DECREASE-XIII.

PubMed

Bakker, E J; Ravensbergen, N J; Voute, M T; Hoeks, S E; Chonchol, M; Klimek, M; Poldermans, D

2011-09-01

This article describes the rationale and design of the DECREASE-XIII trial, which aims to evaluate the potential of esmolol infusion, an ultra-short-acting beta-blocker, during surgery as an add-on to chronic low-dose beta-blocker therapy to maintain perioperative haemodynamic stability during major vascular surgery. A double-blind, placebo-controlled, randomised trial. A total of 260 vascular surgery patients will be randomised to esmolol or placebo as an add-on to standard medical care, including chronic low-dose beta-blockers. Esmolol is titrated to maintain a heart rate within a target window of 60-80 beats per minute for 24 h from the induction of anaesthesia. Heart rate and ischaemia are assessed by continuous 12-lead electrocardiographic monitoring for 72 h, starting 1 day prior to surgery. The primary outcome measure is duration of heart rate outside the target window during infusion of the study drug. Secondary outcome measures will be the efficacy parameters of occurrence of cardiac ischaemia, troponin T release, myocardial infarction and cardiac death within 30 days after surgery and safety parameters such as the occurrence of stroke and hypotension. This study will provide data on the efficacy of esmolol titration in chronic beta-blocker users for tight heart-rate control and reduction of ischaemia in patients undergoing vascular surgery as well as data on safety parameters. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

STOP smoking and alcohol drinking before OPeration for bladder cancer (the STOP-OP study), perioperative smoking and alcohol cessation intervention in relation to radical cystectomy: study protocol for a randomised controlled trial.

PubMed

Lauridsen, Susanne Vahr; Thomsen, Thordis; Thind, Peter; Tønnesen, Hanne

2017-07-17

To evaluate the effect of a smoking-, alcohol- or combined-cessation intervention starting shortly before surgery and lasting 6 weeks on overall complications after radical cystectomy. Secondary objectives are to examine the effect on types and grades of complications, smoking cessation and alcohol cessation, length of hospital stay, health-related quality of life and return to work or habitual level of activity up to 12 months postoperatively. The study is a multi-institutional randomised clinical trial involving 110 patients with a risky alcohol intake and daily smoking who are scheduled for radical cystectomy. Patients will be randomised to the 6-week Gold Standard Programme (GSP) or treatment as usual (control). The GSP combines patient education and pharmacologic strategies. Smoking and alcohol intake is biochemically validated (blood, urine and breath tests) at the weekly meetings and at follow-up. Herein, we report the design of the STOP-OP study, objectives and accrual up-date. This study will provide new knowledge about how to prevent smoking and alcohol-related postoperative complications at the time of bladder cancer surgery. Till now 77 patients have been enrolled. Patient accrual is expected to be finalised before the end of 2017 and data will be published in 2018. ClinicalTrials.gov, ID: NCT02188446 . Registered on 28 May 2014.

A randomised controlled trial of exercise and hot water bottle in the management of dysmenorrhoea in school girls of Chandigarh, India.

PubMed

Chaudhuri, Aditi; Singh, Amarjeet; Dhaliwal, Lakhbir

2013-01-01

To estimate the prevalence of primary dysmenorrhoea among school girls and to compare the impact of exercise and hot water bottle on the occurrence and severity of primary dysmenorrhoea among the study population. A cross sectional study was done to estimate the prevalence of dysmenorrhoea in two schools of Chandigarh, India. For the Randomised Controlled Trial, group randomisation of the two schools was done into 2 intervention groups (exercise & hot water bottle groups). 53 girls in school 1 and 75 girls in school 2 participated in the intervention. Comparison of baseline Menstrual Distress Questionnaire (MDQ) scores & Visual Analogue Scale for Pain (VASP) scores were done with 1st, 2nd & 3rd month post intervention scores using mean, standard deviation, t-test. Prevalence of dysmenorrhoea was 60.7%. Median age of the school girls was 14 years. The mean VASP score decreased from 5.75 to 2.96 (P < 0.0001) and from 5.16 to 2.06 (P < 0.0001) at 3 months, in the exercise and hot water bottle group respectively. The mean MDQ score decreased from 14.53 to 7.85 (P < 0.0001) and from 14.92 to 8.16 (P < 0.0001) at 3 months, in the exercise and hot water bottle group respectively. Both exercise & hot water bottle can be used in dysmenorrhoeic girls in home setting to provide relief from pain and menstrual distress.

DiPALS: Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis - a randomised controlled trial.

PubMed

McDermott, Christopher J; Bradburn, Mike J; Maguire, Chin; Cooper, Cindy L; Baird, Wendy O; Baxter, Susan K; Cohen, Judith; Cantrill, Hannah; Dixon, Simon; Ackroyd, Roger; Baudouin, Simon; Bentley, Andrew; Berrisford, Richard; Bianchi, Stephen; Bourke, Stephen C; Darlison, Roy; Ealing, John; Elliott, Mark; Fitzgerald, Patrick; Galloway, Simon; Hamdalla, Hisham; Hanemann, C Oliver; Hughes, Philip; Imam, Ibrahim; Karat, Dayalan; Leek, Roger; Maynard, Nick; Orrell, Richard W; Sarela, Abeezar; Stradling, John; Talbot, Kevin; Taylor, Lyn; Turner, Martin; Simonds, Anita K; Williams, Tim; Wedzicha, Wisia; Young, Carolyn; Shaw, Pamela J

2016-06-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting in death, usually from respiratory failure, within 2-3 years of symptom onset. Non-invasive ventilation (NIV) is a treatment that when given to patients in respiratory failure leads to improved survival and quality of life. Diaphragm pacing (DP), using the NeuRx/4(®) diaphragm pacing system (DPS)™ (Synapse Biomedical, Oberlin, OH, USA), is a new technique that may offer additional or alternative benefits to patients with ALS who are in respiratory failure. The Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis (DiPALS) trial evaluated the effect of DP on survival over the study duration in patients with ALS with respiratory failure. The DiPALS trial was a multicentre, parallel-group, open-label, randomised controlled trial incorporating health economic analyses and a qualitative longitudinal substudy. Eligible participants had a diagnosis of ALS (ALS laboratory-supported probable, clinically probable or clinically definite according to the World Federation of Neurology revised El Escorial criteria), had been stabilised on riluzole for 30 days, were aged ≥ 18 years and were in respiratory failure. We planned to recruit 108 patients from seven UK-based specialist ALS or respiratory centres. Allocation was performed using 1 : 1 non-deterministic minimisation. Participants were randomised to either standard care (NIV alone) or standard care (NIV) plus DP using the NeuRX/4 DPS. The primary outcome was overall survival, defined as the time from randomisation to death from any cause. Secondary outcomes were patient quality of life [assessed by European Quality of Life-5 Dimensions, three levels (EQ-5D-3L), Short Form questionnaire-36 items and Sleep Apnoea Quality of Life Index questionnaire]; carer quality of life (EQ-5D-3L and Caregiver Burden Inventory); cost-utility analysis and health-care resource use; tolerability and adverse events. Acceptability and attitudes to DP were assessed in a qualitative substudy. In total, 74 participants were randomised into the trial and analysed, 37 participants to NIV plus pacing and 37 to standard care, before the Data Monitoring and Ethics Committee advised initial suspension of recruitment (December 2013) and subsequent discontinuation of pacing (on safety grounds) in all patients (June 2014). Follow-up assessments continued until the planned end of the study in December 2014. The median survival (interquartile range) was 22.5 months (lower quartile 11.8 months; upper quartile not reached) in the NIV arm and 11.0 months (6.7 to 17.0 months) in the NIV plus pacing arm, with an adjusted hazard ratio of 2.27 (95% confidence interval 1.22 to 4.25; p = 0.01). Diaphragmatic pacing should not be used as a routine treatment for patients with ALS in respiratory failure. It may be that certain population subgroups benefit from DP. We are unable to explain the mechanism behind the excess mortality in the pacing arm, something the small trial size cannot help address. Future research should investigate the mechanism by which harm or benefit occurs further. Current Controlled Trials ISRCTN53817913. 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. 20, No. 45. See the HTA programme website for further project information. Additional funding was provided by the Motor Neurone Disease Association of England, Wales and Northern Ireland.

Identifying additional studies for a systematic review of retention strategies in randomised controlled trials: making contact with trials units and trial methodologists.

PubMed

Brueton, Valerie; Tierney, Jayne F; Stenning, Sally; Rait, Greta

2017-08-22

Search strategies for systematic reviews aim to identify all evidence relevant to the research question posed. Reports of methodological research can be difficult to find leading to biased results in systematic reviews of research methodology. Evidence suggests that contact with investigators can help to identify unpublished research. To identify additional eligible randomised controlled trials (RCTs) for a Cochrane systematic review of strategies to improve retention in RCTs, we conducted a survey of UK clinical trials units (CTUs) and made contact with RCT methodologists. Key contacts for all UK CTUs were sent a personalised email with a short questionnaire and summary protocol of the Cochrane methodology review. The questionnaire asked whether a RCT evaluating strategies to improve retention embedded in a RCT had ever been conducted by the CTU. Questions about the stage of completion and publication of such RCTs were included. The summary protocol outlined the aims, eligibility criteria, examples of types of retention strategies, and the primary outcome for the systematic review. Personal communication with RCT methodologists and presentations of preliminary results of the review at conferences were also used to identify additional eligible RCTs. We checked the results of our standard searches to see if eligible studies identified through these additional methods were also found using our standard searches. We identified 14 of the 38 RCTs included in the Cochrane methodology review by contacting trials units and methodologists. Eleven of the 14 RCTs identified by these methods were either published in grey literature, in press or unpublished. Three remaining RCTs were fully published at the time. Six of the RCTs identified were not found through any other searches. The RCTs identified represented data for 6 of 14 RCTs of incentive strategies (52% of randomised participants included in the review), and 6 of 14 RCTs of communication strategies (52% of randomised participants included in the Cochrane review). Data were unavailable for two of the RCTs identified. Methodological evaluations embedded in RCTs may be unpublished, published in the grey literature or where published, poorly indexed in bibliographic databases. To identify such studies and minimise selection bias in systematic reviews of methodological evaluations, reviewers should consider contacting CTUs and trial methodologists.

'Complementary ENT': a systematic review of commonly used supplements.

PubMed

Karkos, P D; Leong, S C; Arya, A K; Papouliakos, S M; Apostolidou, M T; Issing, W J

2007-08-01

To assess the evidence surrounding the use of certain complementary supplements in otolaryngology. We specifically focussed on four commonly used supplements: spirulina, Ginkgo biloba, Vertigoheel and nutritional supplements (cod liver oil, multivitamins and pineapple enzyme). A systematic review of the English and foreign language literature. in vivo human studies. animal trials, in vitro studies and case reports. We also excluded other forms of 'alternative medicine' such as reflexology, acupuncture and other homeopathic remedies. Lack of common outcome measures prevented a formal meta-analysis. Three studies on the effects of spirulina in allergy, rhinitis and immunomodulation were found. One was a double-blind, placebo, randomised, controlled trial (RCT) of patients with allergic rhinitis, demonstrating positive effects in patients fed spirulina for 12 weeks. The other two studies, although non-randomised, also reported a positive role for spirulina in mucosal immunity. Regarding the use of Ginkgo biloba in tinnitus, a Cochrane review published in 2004 showed no evidence for this. The one double-blind, placebo-controlled trial that followed confirmed this finding. Regarding the use of Vertigoheel in vertigo, two double-blind RCTs and a meta-analysis were identified. The first RCT suggested that Vertigoheel was equally effective in reducing the severity, duration and frequency of vertigo compared with betahistine. The second RCT suggested that Vertigoheel was a suitable alternative to G. biloba in the treatment of atherosclerosis-related vertigo. A meta-analysis of only four clinical trials confirms that Vertigoheel was equally effective compared with betahistine, G. biloba and dimenhydrinate. Regarding multivitamins and sinusitis, two small paediatric pilot studies reported a positive response for chronic sinusitis and otitis media following a course of multivitamins and cod liver oil. Regarding bromelain (pineapple enzyme) and sinusitis, one randomised, multicentre trial including 116 children compared bromelain monotherapy to bromelain with standard therapy and standard therapy alone, for the treatment of acute sinusitis. The bromelain monotherapy group showed a faster recovery compared with the other groups. The positive effects of spirulina in allergic rhinitis and of Vertigoheel in vertigo are based on good levels of evidence, but larger trials are required. There is overwhelming evidence that G. biloba may play no role in tinnitus. There is limited evidence for the use of multivitamins in sinus symptoms, and larger randomised trials are required.

A prospective randomised comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers

PubMed Central

Zelen, Charles M; Serena, Thomas E; Denoziere, Guilhem; Fetterolf, Donald E

2013-01-01

Our purpose was to compare healing characteristics of diabetic foot ulcers treated with dehydrated human amniotic membrane allografts (EpiFix®, MiMedx, Kennesaw, GA) versus standard of care. An IRB-approved, prospective, randomised, single-centre clinical trial was performed. Included were patients with a diabetic foot ulcer of at least 4-week duration without infection having adequate arterial perfusion. Patients were randomised to receive standard care alone or standard care with the addition of EpiFix. Wound size reduction and rates of complete healing after 4 and 6 weeks were evaluated. In the standard care group (n = 12) and the EpiFix group (n = 13) wounds reduced in size by a mean of 32·0% ± 47·3% versus 97·1% ± 7·0% (P < 0·001) after 4 weeks, whereas at 6 weeks wounds were reduced by −1·8% ± 70·3% versus 98·4% ± 5·8% (P < 0·001), standard care versus EpiFix, respectively. After 4 and 6 weeks of treatment the overall healing rate with application of EpiFix was shown to be 77% and 92%, respectively, whereas standard care healed 0% and 8% of the wounds (P < 0·001), respectively. Patients treated with EpiFix achieved superior healing rates over standard treatment alone. These results show that using EpiFix in addition to standard care is efficacious for wound healing. PMID:23742102

Low-dose CT for the diagnosis of appendicitis in adolescents and young adults (LOCAT): a pragmatic, multicentre, randomised controlled non-inferiority trial.

PubMed

2017-11-01

CT radiation is arguably carcinogenic. Results from single-centre studies, mostly retrospective, have advocated lowering the CT radiation dose for the diagnosis of appendicitis. However, adoption of low-dose CT has been slow. We aimed to assess the effectiveness of low-dose CT compared with standard-dose CT in the diagnosis of appendicitis in adolescents and young adults. We did this pragmatic, multicentre, randomised controlled non-inferiority trial at 20 South Korean teaching hospitals with little experience with low-dose CT. Patients aged 15-44 years with suspected appendicitis were randomly assigned (1:1), via computer-generated random assignments (permuted block sizes of two, four, six, and eight) concealed in sequentially numbered envelopes, to receive low-dose CT (2 mSv) or standard-dose CT (≤8 mSv). Randomisation was stratified by site. Group allocation was concealed from patients, outcome assessors, and adverse event adjudicators; care providers, site pathologists, and data collectors were aware of allocation. The primary endpoint was the negative (unnecessary) appendectomy rate among all appendectomies, with a non-interiority margin of 4·5% for low-dose versus standard-dose CT. Primary analysis was by modified intention to treat, which included all patients who received an appendectomy in the group to which they were assigned. This trial is registered with ClinicalTrials.gov, number NCT01925014. Between Dec 4, 2013, and Aug 18, 2016, we assigned 1535 patients to the low-dose CT group and 1539 patients to the standard-dose CT group. 22 (3·9%) of 559 patients had a negative appendectomy in the low-dose group versus 16 (2·7%) of 601 patients in the standard-dose group (difference 1·3%, 95% CI -0·8 to 3·3; p=0·0022 for the non-inferiority test). We recorded 43 adverse events in 43 (2·8%) of 1535 patients in the low-dose group and 41 adverse events in 40 (2·6%) of 1539 patients in the standard-dose group. One life-threatening adverse event of anaphylaxis caused by an iodinated contrast material occurred in the low-dose group. Radiation dose of appendiceal CT for adolescents and young adults can be reduced to 2 mSv without impairing clinical outcomes. In view of the vast number of appendiceal CT examinations done worldwide, use of low-dose CT could prevent a sizeable number of radiation-associated cancers in the future. Korea Health Industry Development Institute, Seoul National University Bundang Hospital, Dasol Life Science, and Bracco Imaging Korea. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

McMurran, Mary; Crawford, Mike J; Reilly, Joseph G; McCrone, Paul; Moran, Paul; Williams, Hywel; Adams, Clive E; Duggan, Conor; Delport, Juan; Whitham, Diane; Day, Florence

2011-08-24

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

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

PubMed Central

2011-01-01

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

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.

CESAR: conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure.

PubMed

Peek, Giles J; Clemens, Felicity; Elbourne, Diana; Firmin, Richard; Hardy, Pollyanna; Hibbert, Clare; Killer, Hilliary; Mugford, Miranda; Thalanany, Mariamma; Tiruvoipati, Ravin; Truesdale, Ann; Wilson, Andrew

2006-12-23

An estimated 350 adults develop severe, but potentially reversible respiratory failure in the UK annually. Current management uses intermittent positive pressure ventilation, but barotrauma, volutrauma and oxygen toxicity can prevent lung recovery. An alternative treatment, extracorporeal membrane oxygenation, uses cardio-pulmonary bypass technology to temporarily provide gas exchange, allowing ventilator settings to be reduced. While extracorporeal membrane oxygenation is proven to result in improved outcome when compared to conventional ventilation in neonates with severe respiratory failure, there is currently no good evidence from randomised controlled trials to compare these managements for important clinical outcomes in adults, although evidence from case series is promising. The aim of the randomised controlled trial of Conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR) is to assess whether, for patients with severe, but potentially reversible, respiratory failure, extracorporeal membrane oxygenation will increase the rate of survival without severe disability ('confined to bed' and 'unable to wash or dress') by six months post-randomisation, and be cost effective from the viewpoints of the NHS and society, compared to conventional ventilatory support. Following assent from a relative, adults (18-65 years) with severe, but potentially reversible, respiratory failure (Murray score >/= 3.0 or hypercapnea with pH < 7.2) will be randomised for consideration of extracorporeal membrane oxygenation at Glenfield Hospital, Leicester or continuing conventional care in a centre providing a high standard of conventional treatment. The central randomisation service will minimise by type of conventional treatment centre, age, duration of high pressure ventilation, hypoxia/hypercapnea, diagnosis and number of organs failed, to ensure balance in key prognostic variables. Extracorporeal membrane oxygenation will not be available for patients meeting entry criteria outside the trial. 180 patients will be recruited to have 80% power to be able to detect a one third reduction in the primary outcome from 65% at 5% level of statistical significance (2-sided test). Secondary outcomes include patient morbidity and health status at 6 months. Analysis will be based on intention to treat. A concurrent economic evaluation will also be performed to compare the costs and outcomes of both treatments.

Social skills programmes for schizophrenia.

PubMed

Almerie, Muhammad Qutayba; Okba Al Marhi, Muhammad; Jawoosh, Muhammad; Alsabbagh, Mohamad; Matar, Hosam E; Maayan, Nicola; Bergman, Hanna

2015-06-09

Social skills programmes (SSP) are treatment strategies aimed at enhancing the social performance and reducing the distress and difficulty experienced by people with a diagnosis of schizophrenia and can be incorporated as part of the rehabilitation package for people with schizophrenia. The primary objective is to investigate the effects of social skills training programmes, compared to standard care, for people with schizophrenia. We searched the Cochrane Schizophrenia Group's Trials Register (November 2006 and December 2011) which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. We inspected references of all identified studies for further trials.A further search for studies has been conducted by the Cochrane Schizophrenia Group in 2015, 37 citations have been found and are currently being assessed by review authors. We included all relevant randomised controlled trials for social skills programmes versus standard care involving people with serious mental illnesses. We extracted data independently. For dichotomous data we calculated risk ratios (RRs) and their 95% confidence intervals (CI) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD) and 95% CIs. We included 13 randomised trials (975 participants). These evaluated social skills programmes versus standard care, or discussion group. We found evidence in favour of social skills programmes compared to standard care on all measures of social functioning. We also found that rates of relapse and rehospitalisation were lower for social skills compared to standard care (relapse: 2 RCTs, n = 263, RR 0.52 CI 0.34 to 0.79, very low quality evidence), (rehospitalisation: 1 RCT, n = 143, RR 0.53 CI 0.30 to 0.93, very low quality evidence) and participants' mental state results (1 RCT, n = 91, MD -4.01 CI -7.52 to -0.50, very low quality evidence) were better in the group receiving social skill programmes. Global state was measured in one trial by numbers not experiencing a clinical improvement, results favoured social skills (1 RCT, n = 67, RR 0.29 CI 0.12 to 0.68, very low quality evidence). Quality of life was also improved in the social skills programme compared to standard care (1 RCT, n = 112, MD -7.60 CI -12.18 to -3.02, very low quality evidence). However, when social skills programmes were compared to a discussion group control, we found no significant differences in the participants social functioning, relapse rates, mental state or quality of life, again the quality of evidence for these outcomes was very low. Compared to standard care, social skills training may improve the social skills of people with schizophrenia and reduce relapse rates, but at present, the evidence is very limited with data rated as very low quality. When social skills training was compared to discussion there was no difference on patients outcomes. Cultural differences might limit the applicability of the current results, as most reported studies were conducted in China. Whether social skills training can improve social functioning of people with schizophrenia in different settings remains unclear and should be investigated in a large multi-centre randomised controlled trial.

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.

The Community Navigator Study: a feasibility randomised controlled trial of an intervention to increase community connections and reduce loneliness for people with complex anxiety or depression.

PubMed

Lloyd-Evans, Brynmor; Bone, Jessica K; Pinfold, Vanessa; Lewis, Glyn; Billings, Jo; Frerichs, Johanna; Fullarton, Kate; Jones, Rebecca; Johnson, Sonia

2017-10-23

Loneliness is associated with poor health outcomes at all ages, including shorter life expectancy and greater risk of developing depression. People with mental health problems are particularly vulnerable to loneliness and, for those with anxiety or depression, loneliness is associated with poorer outcomes. Interventions which support people to utilise existing networks and access new social contact are advocated in policy but there is little evidence regarding their effectiveness. People with mental health problems have potential to benefit from interventions to reduce loneliness, but evidence is needed regarding their feasibility, acceptability and outcomes. An intervention to reduce loneliness for people with anxiety or depression treated in secondary mental health services was developed for this study, which will test the feasibility and acceptability of delivering and evaluating it through a randomised controlled trial. In this feasibility trial, 40 participants with anxiety or depression will be recruited through two secondary mental health services in London and randomised to an intervention (n = 30) or control group (n = 10). The control group will receive standard care and written information about local community resources. The coproduced intervention, developed in this study, includes up to ten sessions with a 'Community Navigator' over a 6-month period. Community Navigators will work with people individually to increase involvement in social activities, with the aim of reducing feelings of loneliness. Data will be collected at baseline and at 6-month follow-up - the end of the intervention period. The acceptability of the intervention and feasibility of participant recruitment and retention will be assessed. Potential primary and secondary outcomes for a future definitive trial will be completed to assess response and completeness, including measures of loneliness, depression and anxiety. Qualitative interviews with participants, staff and other stakeholders will explore experiences of Community Navigator support, the mechanisms by which it may have its effects and suggestions for improving the programme. Our trial will provide preliminary evidence of the feasibility and acceptability of Community Navigator support and of trial procedures for testing this. The results will inform a future definitive randomised controlled trial of this intervention. ISRCTN10771821 . Registered on 3 April 2017.

The effects of neoadjuvant chemoradiotherapy and an in-hospital exercise training programme on physical fitness and quality of life in locally advanced rectal cancer patients (The EMPOWER Trial): study protocol for a randomised controlled trial.

PubMed

Loughney, Lisa; West, Malcolm A; Kemp, Graham J; Rossiter, Harry B; Burke, Shaunna M; Cox, Trevor; Barben, Christopher P; Mythen, Michael G; Calverley, Peter; Palmer, Daniel H; Grocott, Michael P W; Jack, Sandy

2016-01-13

The standard treatment pathway for locally advanced rectal cancer is neoadjuvant chemoradiotherapy (CRT) followed by surgery. Neoadjuvant CRT has been shown to decrease physical fitness, and this decrease is associated with increased post-operative morbidity. Exercise training can stimulate skeletal muscle adaptations such as increased mitochondrial content and improved oxygen uptake capacity, both of which are contributors to physical fitness. The aims of the EMPOWER trial are to assess the effects of neoadjuvant CRT and an in-hospital exercise training programme on physical fitness, health-related quality of life (HRQoL), and physical activity levels, as well as post-operative morbidity and cancer staging. The EMPOWER Trial is a randomised controlled trial with a planned recruitment of 46 patients with locally advanced rectal cancer and who are undergoing neoadjuvant CRT and surgery. Following completion of the neoadjuvant CRT (week 0) prior to surgery, patients are randomised to an in-hospital exercise training programme (aerobic interval training for 6 to 9 weeks) or a usual care control group (usual care and no formal exercise training). The primary endpoint is oxygen uptake at lactate threshold ([Formula: see text] at [Formula: see text]) measured using cardiopulmonary exercise testing assessed over several time points throughout the study. Secondary endpoints include HRQoL, assessed using semi-structured interviews and questionnaires, and physical activity levels assessed using activity monitors. Exploratory endpoints include post-operative morbidity, assessed using the Post-Operative Morbidity Survey (POMS), and cancer staging, assessed by using magnetic resonance tumour regression grading. The EMPOWER trial is the first randomised controlled trial comparing an in-hospital exercise training group with a usual care control group in patients with locally advanced rectal cancer. This trial will allow us to determine whether exercise training following neoadjuvant CRT can improve physical fitness and activity levels, as well as other important clinical outcome measures such as HRQoL and post-operative morbidity. These results will aid the design of a large, multi-centre trial to determine whether an increase in physical fitness improves clinically relevant post-operative outcomes. ClinicalTrials.gov NCT01914068 (received: 7 June 2013). University Hospital Southampton NHS Foundation Trust.

Improving outcomes in adults with epilepsy and intellectual disability (EpAID) using a nurse-led intervention: study protocol for a cluster randomised controlled trial.

PubMed

Ring, Howard; Gilbert, Nakita; Hook, Roxanne; Platt, Adam; Smith, Christopher; Irvine, Fiona; Donaldson, Cam; Jones, Elizabeth; Kelly, Joanna; Mander, Adrian; Murphy, Caroline; Pennington, Mark; Pullen, Angela; Redley, Marcus; Rowe, Simon; Wason, James

2016-06-24

In adults with intellectual disability (ID) and epilepsy there are suggestions that improvements in management may follow introduction of epilepsy nurse-led care. However, this has not been tested in a definitive clinical trial and results cannot be generalised from general population studies as epilepsy tends to be more severe and to involve additional clinical comorbidities in adults with ID. This trial investigates whether nurses with expertise in epilepsy and ID, working proactively to a clinically defined role, can improve clinical and quality of life outcomes in the management of epilepsy within this population, compared to treatment as usual. The trial also aims to establish whether any perceived benefits represent good value for money. The EpAID clinical trial is a two-arm cluster randomised controlled trial of nurse-led epilepsy management versus treatment as usual. This trial aims to obtain follow-up data from 320 participants with ID and drug-resistant epilepsy. Participants are randomly assigned either to a 'treatment as usual' control or a 'defined epilepsy nurse role' active arm, according to the cluster site at which they are treated. The active intervention utilises the recently developed Learning Disability Epilepsy Specialist Nurse Competency Framework for adults with ID. Participants undergo 4 weeks of baseline data collection, followed by a minimum of 20 weeks intervention (novel treatment or treatment as usual), followed by 4 weeks of follow-up data collection. The primary outcome is seizure severity, including associated injuries and the level of distress manifest by the patient in the preceding 4 weeks. Secondary outcomes include cost-utility analysis, carer strain, seizure frequency and side effects. Descriptive measures include demographic and clinical descriptors of participants and clinical services in which they receive their epilepsy management. Qualitative study of clinical interactions and semi-structured interviews with clinicians and participants' carers are also undertaken. The EpAID clinical trial is the first cluster randomised controlled trial to test possible benefits of a nurse-led intervention in adults with epilepsy and ID. This research will have important implications for ID and epilepsy services. The challenges of undertaking such a trial in this population, and the approaches to meeting these are discussed. International Standard Randomised Controlled Trial Number: ISRCTN96895428 version 1.1. Registered on 26 March 2013.

Effects of postural specific sensorimotor training in patients with chronic low back pain: study protocol for randomised controlled trial.

PubMed

McCaskey, Michael A; Schuster-Amft, Corina; Wirth, Brigitte; de Bruin, Eling D

2015-12-15

Sensorimotor training (SMT) is popularly applied as a preventive or rehabilitative exercise method in various sports and rehabilitation settings. Yet, there is only low-quality evidence on its effect on pain and function. This randomised controlled trial will investigate the effects of a theory-based SMT in rehabilitation of chronic (>3 months) non-specific low back pain (CNLBP) patients. A pilot study with a parallel, single-blinded, randomised controlled design. Twenty adult patients referred to the clinic for CNLBP treatment will be included, randomised, and allocated to one of two groups. Each group will receive 9 x 30 minutes of standard physiotherapy (PT) treatment. The experimental group will receive an added 15 minutes of SMT. For SMT, proprioceptive postural exercises are performed on a labile platform with adjustable oscillation to provoke training effects on different entry levels. The active comparator group will perform 15 minutes of added sub-effective low-intensity endurance training. Outcomes are assessed on 4 time-points by a treatment blinded tester: eligibility assessment at baseline (BL) 2-4 days prior to intervention, pre-intervention assessment (T0), post-intervention assessment (T1), and at 4 weeks follow-up (FU). At BL, an additional healthy control group (n = 20) will be assessed to allow cross-sectional comparison with symptom-free participants. The main outcomes are self-reported pain (Visual Analogue Scale) and functional status (Oswestry Disability Index). For secondary analysis, postural control variables after an externally perturbed stance on a labile platform are analysed using a video-based marker tracking system and a pressure plate (sagittal joint-angle variability and centre of pressure confidence ellipse). Proprioception is measured as relative cervical joint repositioning error during a head-rotation task. Effect sizes and mixed-model MANOVA (2 groups × 4 measurements for 5 dependent variables) will be calculated. This is the first attempt to systematically investigate effects of a theory-based sensorimotor training in patients with CNLBP. It will provide analysis of several postural segments during a dynamic task for quantitative analysis of quality and change of the task performance in relation to changes in pain and functional status. Trial registry number on cliniclatrials.gov is NCT02304120 , first registered on 17 November 2014.

Aquatic therapy for children with Duchenne muscular dystrophy: a pilot feasibility randomised controlled trial and mixed-methods process evaluation.

PubMed

Hind, Daniel; Parkin, James; Whitworth, Victoria; Rex, Saleema; Young, Tracey; Hampson, Lisa; Sheehan, Jennie; Maguire, Chin; Cantrill, Hannah; Scott, Elaine; Epps, Heather; Main, Marion; Geary, Michelle; McMurchie, Heather; Pallant, Lindsey; Woods, Daniel; Freeman, Jennifer; Lee, Ellen; Eagle, Michelle; Willis, Tracey; Muntoni, Francesco; Baxter, Peter

2017-05-01

Duchenne muscular dystrophy (DMD) is a rare disease that causes the progressive loss of motor abilities such as walking. Standard treatment includes physiotherapy. No trial has evaluated whether or not adding aquatic therapy (AT) to land-based therapy (LBT) exercises helps to keep muscles strong and children independent. To assess the feasibility of recruiting boys with DMD to a randomised trial evaluating AT (primary objective) and to collect data from them; to assess how, and how well, the intervention and trial procedures work. Parallel-group, single-blind, randomised pilot trial with nested qualitative research. Six paediatric neuromuscular units. Children with DMD aged 7-16 years, established on corticosteroids, with a North Star Ambulatory Assessment (NSAA) score of 8-34 and able to complete a 10-m walk without aids/assistance. Exclusions: > 20% variation between baseline screens 4 weeks apart and contraindications. Participants were allocated on a 1 : 1 ratio to (1) optimised, manualised LBT (prescribed by specialist neuromuscular physiotherapists) or (2) the same plus manualised AT (30 minutes, twice weekly for 6 months: active assisted and/or passive stretching regime; simulated or real functional activities; submaximal exercise). Semistructured interviews with participants, parents ( n  = 8) and professionals ( n  = 8) were analysed using Framework analysis. An independent rater reviewed patient records to determine the extent to which treatment was optimised. A cost-impact analysis was performed. Quantitative and qualitative data were mixed using a triangulation exercise. Feasibility of recruiting 40 participants in 6 months, participant and therapist views on the acceptability of the intervention and research protocols, clinical outcomes including NSAA, independent assessment of treatment optimisation and intervention costs. Over 6 months, 348 children were screened - most lived too far from centres or were enrolled in other trials. Twelve (30% of target) were randomised to AT ( n  = 8) or control ( n  = 4). People in the AT ( n  = 8) and control ( n  = 2: attrition because of parental report) arms contributed outcome data. The mean change in NSAA score at 6 months was -5.5 [standard deviation (SD) 7.8] for LBT and -2.8 (SD 4.1) in the AT arm. One boy suffered pain and fatigue after AT, which resolved the same day. Physiotherapists and parents valued AT and believed that it should be delivered in community settings. The independent rater considered AT optimised for three out of eight children, with other children given programmes that were too extensive and insufficiently focused. The estimated NHS costs of 6-month service were between £1970 and £2734 per patient. The focus on delivery in hospitals limits generalisability. Neither a full-scale frequentist randomised controlled trial (RCT) recruiting in the UK alone nor a twice-weekly open-ended AT course delivered at tertiary centres is feasible. Further intervention development research is needed to identify how community-based pools can be accessed, and how families can link with each other and community physiotherapists to access tailored AT programmes guided by highly specialised physiotherapists. Bayesian RCTs may be feasible; otherwise, time series designs are recommended. Current Controlled Trials ISRCTN41002956. 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. 27. See the NIHR Journals Library website for further project information.

Hydroxyurea for reducing blood transfusion in non-transfusion dependent beta thalassaemias.

PubMed

Foong, Wai Cheng; Ho, Jacqueline J; Loh, C Khai; Viprakasit, Vip

2016-10-18

Non-transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non-transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non-transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews.Date of last search: 30 April 2016. Randomised or quasi-randomised controlled trials of hydroxyurea in people with non-transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks.Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference -2.39 (95% confidence interval - 2.8 to -1.98) and mean difference -1.5 (95% confidence interval -1.83 to -1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported.The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment. There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well-designed randomised controlled trials with sufficient duration of follow up are recommended.

Protocol for north of England and Scotland study of tonsillectomy and adeno-tonsillectomy in children (NESSTAC). A pragmatic randomised controlled trial comparing surgical intervention with conventional medical treatment in children with recurrent sore throats

PubMed Central

Bond, John; Wilson, Janet; Eccles, Martin; Vanoli, Alessandra; Steen, Nick; Clarke, Ray; Zarod, Andrew; Lock, Catherine; Brittain, Katie; Speed, Chris; Rousseau, Nikki

2006-01-01

Background Uncertainties surrounding the effectiveness and cost-effectiveness of childhood tonsillectomy for recurrent sore throat led the NHS Health Technology Assessment Programme to commission this research to evaluate the effectiveness and cost-effectiveness of tonsillectomy and adeno-tonsillectomy in comparison with standard non-surgical management in children aged under 16 with recurrent throat infections. The aim is to evaluate if tonsillectomy and adeno-tonsillectomy reduces the number of episodes of sore throats among children to a clinically significant extent. Methods/design A simple prospective pragmatic randomised controlled trial with economic analysis and prospective cohort study of non-trial participants comparing surgical intervention with conventional medical treatment. The treatment arm will receive tonsillectomy and adeno-tonsillectomy while in the control arm non-surgical conventional medical treatment only will be used. The primary outcome measure will be reported number of episodes of sore throat over two years with secondary outcomes measures of reported number of episodes of sore throat, otitis media and upper respiratory tract infection which invoke a GP consultation; reported number of symptom-free days; reported severity of sore throats and surgical and anaesthetic morbidity. The study will take place in five hospitals in the UK. The trial population will be 406 children aged 4–15 on their last birthday with recurrent sore throat referred by primary care to the 5 otolaryngology departments. The duration of the study is seven years (July 2001- July 2008). Discussion As with all pragmatic randomised controlled trials it is impossible to control the external environment in which the research is taking place. Since this trial began a number of factors have arisen which could affect the outcome including; a reduction in the incidence of respiratory tract infections, marked socio-economic differences in consultation rates, the results from the National Prospective Tonsillectomy Audit and the Government's waiting list initiatives. PMID:16899123

Protocol for north of England and Scotland study of tonsillectomy and adeno-tonsillectomy in children (NESSTAC). A pragmatic randomised controlled trial comparing surgical intervention with conventional medical treatment in children with recurrent sore throats.

PubMed

Bond, John; Wilson, Janet; Eccles, Martin; Vanoli, Alessandra; Steen, Nick; Clarke, Ray; Zarod, Andrew; Lock, Catherine; Brittain, Katie; Speed, Chris; Rousseau, Nikki

2006-08-09

Uncertainties surrounding the effectiveness and cost-effectiveness of childhood tonsillectomy for recurrent sore throat led the NHS Health Technology Assessment Programme to commission this research to evaluate the effectiveness and cost-effectiveness of tonsillectomy and adeno-tonsillectomy in comparison with standard non-surgical management in children aged under 16 with recurrent throat infections. The aim is to evaluate if tonsillectomy and adeno-tonsillectomy reduces the number of episodes of sore throats among children to a clinically significant extent. A simple prospective pragmatic randomised controlled trial with economic analysis and prospective cohort study of non-trial participants comparing surgical intervention with conventional medical treatment. The treatment arm will receive tonsillectomy and adeno-tonsillectomy while in the control arm non-surgical conventional medical treatment only will be used. The primary outcome measure will be reported number of episodes of sore throat over two years with secondary outcomes measures of reported number of episodes of sore throat, otitis media and upper respiratory tract infection which invoke a GP consultation; reported number of symptom-free days; reported severity of sore throats and surgical and anaesthetic morbidity. The study will take place in five hospitals in the UK. The trial population will be 406 children aged 4-15 on their last birthday with recurrent sore throat referred by primary care to the 5 otolaryngology departments. The duration of the study is seven years (July 2001-July 2008). As with all pragmatic randomised controlled trials it is impossible to control the external environment in which the research is taking place. Since this trial began a number of factors have arisen which could affect the outcome including; a reduction in the incidence of respiratory tract infections, marked socio-economic differences in consultation rates, the results from the National Prospective Tonsillectomy Audit and the Government's waiting list initiatives.

Protocol for: Sheffield Obesity Trial (SHOT): a randomised controlled trial of exercise therapy and mental health outcomes in obese adolescents [ISRCNT83888112].

PubMed

Daley, Amanda J; Copeland, Robert J; Wright, Neil P; Wales, Jerry K H

2005-10-31

While obesity is known to have many physiological consequences, the psychopathology of this condition has not featured prominently in the literature. Cross-sectional studies have indicated that obese children have increased odds of experiencing poor quality of life and mental health. However, very limited trial evidence has examined the efficacy of exercise therapy for enhancing mental health outcomes in obese children, and the Sheffield Obesity Trial (SHOT) will provide evidence of the efficacy of supervised exercise therapy in obese young people aged 11-16 years versus usual care and an attention-control intervention. SHOT is a randomised controlled trial where obese young people are randomised to receive; (1) exercise therapy, (2) attention-control intervention (involving body-conditioning exercises and games that do not involve aerobic activity), or (3) usual care. The exercise therapy and attention-control sessions will take place three times per week for eight weeks and a six-week home programme will follow this. Ninety adolescents aged between 11-16 years referred from a children's hospital for evaluation of obesity or via community advertisements will need to complete the study. Participants will be recruited according to the following criteria: (1) clinically obese and aged 11-16 years (Body Mass Index Centile > 98th UK standard) (2) no medical condition that would restrict ability to be active three times per week for eight weeks and (3) not diagnosed with insulin dependent diabetes or receiving oral steroids. Assessments of outcomes will take place at baseline, as well as four (intervention midpoint) and eight weeks (end of intervention) from baseline. Participants will be reassessed on outcome measures five and seven months from baseline. The primary endpoint is physical self-perceptions. Secondary outcomes include physical activity, self-perceptions, depression, affect, aerobic fitness and BMI.

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

PubMed

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

2007-04-01

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

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

PubMed Central

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

2009-01-01

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

Treatment outcomes in palliative care: the TOPCare study. A mixed methods phase III randomised controlled trial to assess the effectiveness of a nurse-led palliative care intervention for HIV positive patients on antiretroviral therapy

PubMed Central

2012-01-01

Background Patients with HIV/AIDS on Antiretroviral Therapy (ART) suffer from physical, psychological and spiritual problems. Despite international policy explicitly stating that a multidimensional approach such as palliative care should be delivered throughout the disease trajectory and alongside treatment, the effectiveness of this approach has not been tested in ART-experienced populations. Methods/design This mixed methods study uses a Randomised Controlled Trial (RCT) to test the null hypothesis that receipt of palliative care in addition to standard HIV care does not affect pain compared to standard care alone. An additional qualitative component will explore the mechanism of action and participant experience. The sample size is designed to detect a statistically significant decrease in reported pain, determined by a two tailed test and a p value of ≤0.05. Recruited patients will be adults on ART for more than one month, who report significant pain or symptoms which have lasted for more than two weeks (as measured by the African Palliative Care Association (APCA) African Palliative Outcome Scale (POS)). The intervention under trial is palliative care delivered by an existing HIV facility nurse trained to a set standard. Following an initial pilot the study will be delivered in two African countries, using two parallel independent Phase III clinical RCTs. Qualitative data will be collected from semi structured interviews and documentation from clinical encounters, to explore the experience of receiving palliative care in this context. Discussion The data provided by this study will provide evidence to inform the improvement of outcomes for people living with HIV and on ART in Africa. ClinicalTrials.gov Identifier: NCT01608802 PMID:23130740

Music therapy for end-of-life care: An updated systematic review.

PubMed

McConnell, Tracey; Scott, David; Porter, Sam

2016-10-01

Music therapy during palliative and end-of-life care is well established and positive benefits for patients have been reported. Assess the effectiveness of music therapy versus standard care alone or standard care in combination with other therapies for improving psychological, physiological and social outcomes among adult patients in any palliative care setting. In order to update an existing Cochrane systematic review, we searched MEDLINE, CINAHL, EMBASE, PsycINFO, CENTRAL, ClinicalTrials.gov register and Current Controlled Trials register to identify randomised or quasi-randomised controlled trials published between 2009 and April 2015. Nine electronic music therapy journals were searched from 2009 until April 2015, along with reference lists and contact was made with key experts in music therapy. Only studies published in English were eligible for inclusion. Two reviewers independently screened titles, abstracts, assessed relevant studies for eligibility, extracted data and judged risk of bias for included studies. Disagreements were resolved through discussion with a third reviewer. Data were synthesised in Revman using the random effects model. Heterogeneity was assessed using I(2). Three studies were included in the review. Findings suggest that music therapy may be effective for helping to reduce pain in palliative care patients (standard mean deviation = -0.42, 95% confidence interval = -0.68 to -0.17, p = 0.001). Available evidence did not support the use of music therapy to improve overall quality of life in palliative care. While this review suggests that music therapy may be effective for reducing pain, this is based on studies with a high risk of bias. Further high-quality research is required. © The Author(s) 2016.

Implementing an exercise-training programme to prevent lower-limb injuries: considerations for the development of a randomised controlled trial intervention delivery plan.

PubMed

Finch, Caroline F; White, Peta; Twomey, Dara; Ullah, Shahid

2011-08-01

To identify important considerations for the delivery of an exercise training intervention in a randomised controlled trial to maximise subsequent participation in that randomised controlled trial and intervention uptake. A cross-sectional survey, with a theoretical basis derived from the Health Belief Model (HBM) and the Reach, Efficacy/Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework. 374 male senior Australian Football players, aged 17-38 years. Beliefs about lower-limb injury causation/prevention, and the relative value of exercise training for performance and injury prevention. The data are interpreted within HBM constructs and implications for subsequent intervention implementation considered within the RE-AIM framework. Ordinal logistic regression compared belief scores across player characteristics. 74.4% of players agreed that doing specific exercises during training would reduce their risk of lower-limb injury and would be willing to undertake them. However, 64.1% agreed that training should focus more on improving game performance than injury prevention. Younger players (both in terms of age and playing experience) generally had more positive views. Players were most supportive of kicking (98.9%) and ball-handling (97.0%) skills for performance and warm-up runs and cool-downs (both 91.5%) for injury prevention. Fewer than three-quarters of all players believed that balance (69.2%), landing (71.3%) or cutting/stepping (72.8) training had injury-prevention benefits. Delivery of future exercise training programmes for injury prevention aimed at these players should be implemented as part of routine football activities and integrated with those as standard practice, as a means of associating them with training benefits for this sport.

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

Testing the feasibility of a mobile technology intervention promoting healthy gestational weight gain in pregnant women (txt4two) - study protocol for a randomised controlled trial.

PubMed

Willcox, Jane Catherine; Campbell, Karen Jane; McCarthy, Elizabeth Anne; Wilkinson, Shelley Ann; Lappas, Martha; Ball, Kylie; Fjeldsoe, Brianna; Griffiths, Anne; Whittaker, Robyn; Maddison, Ralph; Shub, Alexis; Pidd, Deborah; Fraser, Elise; Moshonas, Nelly; Crawford, David Andrew

2015-05-07

Overweight, obesity and excess gestational weight gain (GWG) are associated with negative health outcomes for mother and child in pregnancy and across the life course. Interventions promoting GWG within guidelines report mixed results. Most are time and cost intensive, which limits scalability. Mobile technologies (mHealth) offer low cost, ready access and individually-tailored support. We aim to test the feasibility of an mHealth intervention promoting healthy nutrition, physical activity and GWG in women who begin pregnancy overweight or obese. txt4two is a parallel randomised control trial pilot recruiting women with a singleton, live gestation between 10(+0) and 17(+6) weeks at the first hospital antenatal clinic visit. Inclusion criteria are pre-pregnancy BMI > 25 kg/m(2) and mobile phone ownership. One hundred consenting women will be randomised to intervention or control groups at a 1:1 ratio. All participants will receive standard antenatal care. In addition, the txt4two intervention will be delivered from baseline to 36 weeks gestation and consists of a tailored suite of theoretically-grounded, evidence-based intervention strategies focusing on healthy nutrition, physical activity and GWG. This includes: mobile phone interactive text messages promoting positive health behaviours, goal setting and self-monitoring; video messages; an information website; and a private moderated Facebook® chat forum. The primary outcome is the feasibility of the intervention. Secondary outcomes include GWG and participants' knowledge and behaviour regarding diet and physical activity during pregnancy. Findings will inform the development of larger-scale mHealth programmes to improve the delivery of healthy pregnancy nutrition, physical activity and GWG, that could be widely translated and disseminated. Australian New Zealand Clinical Trials Registry: ACTRNU111111544397 . Date of registration: 19 March 2014.

The BLISS cluster randomised controlled trial of the effect of 'active dissemination of information' on standards of care for premature babies in England (BEADI) study protocol [ISRCTN89683698].

PubMed

Acolet, Dominique; Jelphs, Kim; Davidson, Deborah; Peck, Edward; Clemens, Felicity; Houston, Rosie; Weindling, Michael; Lavis, John; Elbourne, Diana

2007-10-08

Gaps between research knowledge and practice have been consistently reported. Traditional ways of communicating information have limited impact on practice changes. Strategies to disseminate information need to be more interactive and based on techniques reported in systematic reviews of implementation of changes. There is a need for clarification as to which dissemination strategies work best to translate evidence into practice in neonatal units across England. The objective of this trial is to assess whether an innovative active strategy for the dissemination of neonatal research findings, recommendations, and national neonatal guidelines is more likely to lead to changes in policy and practice than the traditional (more passive) forms of dissemination in England. Cluster randomised controlled trial of all neonatal units in England (randomised by hospital, n = 182 and stratified by neonatal regional networks and neonatal units level of care) to assess the relative effectiveness of active dissemination strategies on changes in local policies and practices. Participants will be mainly consultant lead clinicians in each unit. The intervention will be multifaceted using: audit and feedback; educational meetings for local staff (evidence-based lectures on selected topics, interactive workshop to examine current practice and draw up plans for change); and quality improvement and organisational changes methods. Policies and practice outcomes for the babies involved will be collected before and after the intervention. Outcomes will assess all premature babies born in England during a three month period for timing of surfactant administration at birth, temperature control at birth, and resuscitation team (qualification and numbers) present at birth.

'The trial is owned by the team, not by an individual': a qualitative study exploring the role of teamwork in recruitment to randomised controlled trials in surgical oncology.

PubMed

Strong, Sean; Paramasivan, Sangeetha; Mills, Nicola; Wilson, Caroline; Donovan, Jenny L; Blazeby, Jane M

2016-04-26

Challenges exist in recruitment to trials involving interventions delivered by different clinical specialties. Collaboration is required between clinical specialty and research teams. The aim of this study was to explore how teamwork influences recruitment to a multicentre randomised controlled trial (RCT) involving interventions delivered by different clinical specialties. Semi-structured interviews were conducted in three centres with a purposeful sample of members of the surgical, oncology and research teams recruiting to a feasibility RCT comparing definitive chemoradiotherapy with chemoradiotherapy and surgery for oesophageal squamous cell carcinoma. Interviews explored factors known to influence healthcare team effectiveness and were audio-recorded and thematically analysed. Sampling, data collection and analysis were undertaken iteratively and concurrently. Twenty-one interviews were conducted. Factors that influenced how team working impacted upon trial recruitment were centred on: (1) the multidisciplinary team (MDT) meeting, (2) leadership of the trial, and (3) the recruitment process. The weekly MDT meeting was reported as central to successful recruitment and formed the focus for creating a 'study team', bringing together clinical and research teams. Shared study leadership positively influenced healthcare professionals' willingness to participate. Interviewees perceived their clinical colleagues to have strong treatment preferences which led to scepticism regarding whether the treatments were being described to patients in a balanced manner. This study has highlighted a number of aspects of team functioning that are important for recruitment to RCTs that span different clinical specialties. Understanding these issues will aid the production of guidance on team-relevant issues that should be considered in trial management and the development of interventions that will facilitate teamwork and improve recruitment to these challenging RCTs. International Standard Randomised Controlled Trial Number (ISRCTN): ISRCTN89052791 .

A cluster randomised controlled trial evaluating the effectiveness of eHealth-supported patient recruitment in primary care research: the TRANSFoRm study protocol.

PubMed

Mastellos, Nikolaos; Andreasson, Anna; Huckvale, Kit; Larsen, Mark; Curcin, Vasa; Car, Josip; Agreus, Lars; Delaney, Brendan

2015-02-03

Opportunistic recruitment is a highly laborious and time-consuming process that is currently performed manually, increasing the workload of already busy practitioners and resulting in many studies failing to achieve their recruitment targets. The Translational Medicine and Patient Safety in Europe (TRANSFoRm) platform enables automated recruitment, data collection and follow-up of patients, potentially improving the efficiency, time and costs of clinical research. This study aims to assess the effectiveness of TRANSFoRm in improving patient recruitment and follow-up in primary care trials. This multi-centre, parallel-arm cluster randomised controlled trial will compare TRANSFoRm-supported with standard opportunistic recruitment. Participants will be general practitioners and patients with gastro-oesophageal reflux disease from 40 primary care centres in five European countries. Randomisation will take place at the care centre level. The intervention arm will use the TRANSFoRm tools for recruitment, baseline data collection and follow-up. The control arm will use web-based case report forms and paper self-completed questionnaires. The primary outcome will be the proportion of eligible patients successfully recruited at the end of the 16-week recruitment period. Secondary outcomes will include the proportion of recruited patients with complete baseline and follow-up data and the proportion of participants withdrawn or lost to follow-up. The study will also include an economic evaluation and measures of technology acceptance and user experience. The study should shed light on the use of eHealth to improve the effectiveness of recruitment and follow-up in primary care research and provide an evidence base for future eHealth-supported recruitment initiatives. Reporting of results is expected in October 2015. EudraCT: 2014-001314-25.

Do patients diagnosed with Alzheimer's disease benefit from a psycho-educational programme for family caregivers? A randomised controlled study.

PubMed

de Rotrou, Jocelyne; Cantegreil, Inge; Faucounau, Véronique; Wenisch, Emilie; Chausson, Catherine; Jegou, David; Grabar, Sophie; Rigaud, Anne-Sophie

2011-08-01

The Aide dans la Maladie d'Alzheimer (AIDMA) study was conducted to determine whether a psycho-educational programme (PEP) for primary caregivers in addition to standard anti-dementia drugs for patients improves caregivers' psychological condition and patients' activities of daily life. Multicentre randomised controlled intervention trial. One hundred and sixty-seven dyads 'patient-caregiver' were recruited from 15 French memory clinics and randomised in two parallel groups. The intervention group was offered the PEP in 12 group sessions for 3 months. The control group had usual care. Patients in both groups with mild to moderate Alzheimer's disease (AD) were diagnosed and treated with pharmacotherapy. Patients' primary efficacy variable was functional status assessed with the Disability Assessment Scale for Dementia (DAD) scale. Alzheimer Disease Assessment Scale (ADAS-Cog) and Neuropsychiatric Inventory (NPI) were secondary criteria. Caregivers' first outcome measure was depressive symptoms assessed with the Montgomery and Asberg Depression Rating Scale (MADRS) scale. Zarit scale, Sense of Competence Questionnaire (SCQ) and Visual Analogue Scales (VAS) were secondary criteria. Assessment was done at baseline, 3 months (M3, end of intervention) and 6 months (M6). Patients' stabilisation was observed in both groups. In caregivers, significant improvement in disease understanding at M3 (p = 0.007) and M6 (p = 0.0001) and in ability to cope with care-recipients' disease at M6 (0.02) was evidenced. The PEP had no additional impact on patients but carers developed more effective disease understanding and ability of coping. Results support the idea that the PEP although improving caregivers' condition is not sufficient to improve patients' activities in daily life which requires additional individually tailored interventions provided by professionals. Copyright © 2010 John Wiley & Sons, Ltd.

Cognitive behaviour therapy (CBT) for anxiety and depression in adults with mild intellectual disabilities (ID): a pilot randomised controlled trial.

PubMed

Hassiotis, Angela; Serfaty, Marc; Azam, Kiran; Strydom, Andre; Martin, Sue; Parkes, Charles; Blizard, Robert; King, Michael

2011-04-14

Several studies have showed that people with intellectual disabilities (ID) have suitable skills to undergo cognitive behavioural therapy (CBT). Case studies have reported successful use of cognitive behavioural therapy techniques (with adaptations) in people with ID. Modified cognitive behavioural therapy may be a feasible and effective approach for the treatment of depression, anxiety, and other mood disorders in ID. To date, two studies have reported group-based manaulised cognitive behavioural treatment programs for depression in people with mild ID. However, there is no individual manualised programme for anxiety or depression in people with intellectual disabilities. The aims of the study are to determine the feasibility of conducting a randomised controlled trial for CBT in people with ID. The data will inform the power calculation and other aspects of carrying out a definitive randomised controlled trial. Thirty participants with mild ID will be allocated randomly to either CBT or treatment as usual (TAU). The CBT group will receive up to 20 hourly individual CBT over a period of 4 months. TAU is the standard treatment which is available to any adult with an intellectual disability who is referred to the intellectual disability service (including care management, community support, medical, nursing or social support). Beck Youth Inventories (Beck Anxiety Inventory & Beck Depression Inventory) will be administered at baseline; end of treatment (4 months) and at six months to evaluate the changes in depression and anxiety. Client satisfaction, quality of life and the health economics will be secondary outcomes. The broad outcome of the study will be to produce clear guidance for therapists to apply an established psychological intervention and identify how and whether it works with people with intellectual disabilities. ISRCTN: ISRCTN38099525.

The effect of group-based exercise on cognitive performance and mood in seniors residing in intermediate care and self-care retirement facilities: a randomised controlled trial.

PubMed

Brown, A K; Liu-Ambrose, T; Tate, R; Lord, S R

2009-08-01

To determine the effect of a general group-based exercise programme on cognitive performance and mood among seniors without dementia living in retirement villages. Randomised controlled trial. Four intermediate care and four self-care retirement village sites in Sydney, Australia. 154 seniors (19 men, 135 women; age range 62 to 95 years), who were residents of intermediate care and self-care retirement facilities. Participants were randomised to one of three experimental groups: (1) a general group-based exercise (GE) programme composed of resistance training and balance training exercises; (2) a flexibility exercise and relaxation technique (FR) programme; or (3) no-exercise control (NEC). The intervention groups (GE and FR) participated in 1-hour exercise classes twice a week for a total period of 6 months. Using standard neuropsychological tests, we assessed cognitive performance at baseline and at 6-month re-test in three domains: (1) fluid intelligence; (2) visual, verbal and working memory; and (3) executive functioning. We also assessed mood using the Geriatric Depression Scale (GDS) and the Positive and Negative Affect Schedule (PANAS). The GE programme significantly improved cognitive performance of fluid intelligence compared with FR or NEC. There were also significant improvements in the positive PANAS scale within both the GE and FR groups and an indication that the two exercise programmes reduced depression in those with initially high GDS scores. Our GE programme significantly improved cognitive performance of fluid intelligence in seniors residing in retirement villages compared with our FR programme and the NEC group. Furthermore, both group-based exercise programmes were beneficial for certain aspects of mood within the 6-month intervention period.

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.

Simulation in undergraduate paediatrics: a cluster-randomised trial.

PubMed

Morrissey, Benita; Jacob, Hannah; Harnik, Erika; Mackay, Kate; Moreiras, John

2016-10-01

Medical students lack confidence in recognising, assessing and managing unwell patients, particularly children. Our aim was to evaluate the impact of a 1-day novel paediatric simulation course on medical students' ability to recognise and assess sick children, and to evaluate medical students' views on the use of simulation in child health teaching. We conducted a cluster-randomised trial with a mixed-methods design. Students were cluster randomised into the intervention (simulation) group or control group (standard paediatric attachment). Students in the intervention group attended a 1-day simulation course during the last week of their attachment. The primary outcome measure was students' self-reported ability and confidence in recognising, assessing and managing sick children. There were 61 students in the study: 32 in the intervention group and 29 in the control group. Self-assessed confidence in recognising, assessing and managing a sick child was higher after the simulation course, compared with controls (p < 0.001). Six key themes were identified, including: increased confidence in emergency situations; the value of learning through participation in 'real-life' realistic scenarios in a safe environment; and an appreciation of the importance of human factors. Students found the simulation useful and wanted it offered to all undergraduates during child health attachments. A 1-day simulation course improves medical students' confidence in assessing and managing unwell children, and is highly valued by students. It could be used to complement undergraduate teaching on the management of sick children. Further studies are needed to evaluate its impact on real-life clinical performance and confidence over time. Students lack confidence in managing unwell patients, particularly children. © 2015 John Wiley & Sons Ltd.

Psychological treatments for depression in pre-adolescent children (12 years and younger): systematic review and meta-analysis of randomised controlled trials.

PubMed

Forti-Buratti, M Azul; Saikia, Rupalim; Wilkinson, Esther L; Ramchandani, Paul G

2016-10-01

The objective of this study was to evaluate the efficacy of psychological treatments for depression in pre-adolescent children, a disorder affecting 1-2 % of children in this age range. A systematic review of studies of psychological interventions to treat depressive disorder in pre-adolescent children (aged up to 12-years-old) was carried out. The primary outcome was level of depressive symptoms. Studies were found using Medline, PsycINFO, EMBASE and Web of Knowledge databases and selected on several criteria. Only randomised controlled trials were included. Where individual studies covered a broader age range (usually including adolescents up to age 18 years), authors of those studies were contacted and requested to provide individual patient level data for those aged 12 years and younger. 2822 abstracts were reviewed, and from these 124 full text articles were reviewed, yielding 7 studies for which we were able to access appropriate data for this review. 5 of these studies evaluated cognitive behaviour therapy (CBT). Combined results from these studies suggest that there is a lack of evidence that CBT is better than no treatment [standard mean difference -0.342 (95 % confidence interval -0.961, 0.278)], although the number of participants included in the trials was relatively small. The evidence for efficacy of family therapy and psychodynamic therapy is even more limited. The very limited number of participants in randomised controlled trials means that there is inconclusive evidence for the psychological treatment of depression in children aged 12 years and below. Given the prevalence and significant impact of this disorder, there is an urgent need to establish the effectiveness or otherwise of psychological intervention.

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

PubMed

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

2014-12-04

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

Randomised controlled trial of the clinical and cost effectiveness of a specialist team for managing refractory unipolar depressive disorder.

PubMed

Morriss, Richard; Marttunnen, Sarah; Garland, Anne; Nixon, Neil; McDonald, Ruth; Sweeney, Tim; Flambert, Heather; Fox, Richard; Kaylor-Hughes, Catherine; James, Marilyn; Yang, Min

2010-11-29

Around 40 per cent of patients with unipolar depressive disorder who are treated in secondary care mental health services do not respond to first or second line treatments for depression. Such patients have 20 times the suicide rate of the general population and treatment response becomes harder to achieve and sustain the longer they remain depressed. Despite this there are no randomised controlled trials of community based service delivery interventions delivering both algorithm based pharmacotherapy and psychotherapy for patients with chronic depressive disorder in secondary care mental health services who remain moderately or severely depressed after six months treatment. Without such trials evidence based guidelines on services for such patients cannot be derived. Single blind individually randomised controlled trial of a specialist depression disorder team (psychiatrist and psychotherapist jointly assessing and providing algorithm based drug and psychological treatment) versus usual secondary care treatment. We will recruit 174 patients with unipolar depressive disorder in secondary mental health services with a Hamilton Depression Rating Scale (HDRS) score ≥ 16 and global assessment of function (GAF) ≤ 60 after ≥ 6 months treatment. The primary outcome measures will be the HDRS and GAF supplemented by economic analysis including the EQ5 D and analysis of barriers to care, implementation and the process of care. Audits to benchmark both treatment arms against national standards of care will aid the interpretation of the results of the study. This trial will be the first to assess the effectiveness and implementation of a community based specialist depression disorder team. The study has been specially designed as part of the CLAHRC Nottinghamshire, Derbyshire and Lincolnshire joint collaboration between university, health and social care organisations to provide information of direct relevance to decisions on commissioning, service provision and implementation.

Tablet computers versus optical aids to support education and learning in children and young people with low vision: protocol for a pilot randomised controlled trial, CREATE (Children Reading with Electronic Assistance To Educate).

PubMed

Crossland, Michael D; Thomas, Rachel; Unwin, Hilary; Bharani, Seelam; Gothwal, Vijaya K; Quartilho, Ana; Bunce, Catey; Dahlmann-Noor, Annegret

2017-06-21

Low vision and blindness adversely affect education and independence of children and young people. New 'assistive' technologies such as tablet computers can display text in enlarged font, read text out to the user, allow speech input and conversion into typed text, offer document and spreadsheet processing and give access to wide sources of information such as the internet. Research on these devices in low vision has been limited to case series. We will carry out a pilot randomised controlled trial (RCT) to assess the feasibility of a full RCT of assistive technologies for children/young people with low vision. We will recruit 40 students age 10-18 years in India and the UK, whom we will randomise 1:1 into two parallel groups. The active intervention will be Apple iPads; the control arm will be the local standard low-vision aid care. Primary outcomes will be acceptance/usage, accessibility of the device and trial feasibility measures (time to recruit children, lost to follow-up). Exploratory outcomes will be validated measures of vision-related quality of life for children/young people as well as validated measures of reading and educational outcomes. In addition, we will carry out semistructured interviews with the participants and their teachers. NRES reference 15/NS/0068; dissemination is planned via healthcare and education sector conferences and publications, as well as via patient support organisations. NCT02798848; IRAS ID 179658, UCL reference 15/0570. © 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.

Improving coronary heart disease self-management using mobile technologies (Text4Heart): a randomised controlled trial protocol.

PubMed

Dale, Leila Pfaeffli; Whittaker, Robyn; Jiang, Yannan; Stewart, Ralph; Rolleston, Anna; Maddison, Ralph

2014-03-04

Cardiac rehabilitation (CR) is a secondary prevention program that offers education and support to assist patients with coronary heart disease (CHD) make lifestyle changes. Despite the benefits of CR, attendance at centre-based sessions remains low. Mobile technology (mHealth) has potential to reach more patients by delivering CR directly to mobile phones, thus providing an alternative to centre-based CR. The aim of this trial is to evaluate if a mHealth comprehensive CR program can improve adherence to healthy lifestyle behaviours (for example, physically active, fruit and vegetable intake, not smoking, low alcohol consumption) over and above usual CR services in New Zealand adults diagnosed with CHD. A two-arm, parallel, randomised controlled trial will be conducted at two Auckland hospitals in New Zealand. One hundred twenty participants will be randomised to receive a 24-week evidence- and theory-based personalised text message program and access to a supporting website in addition to usual CR care or usual CR care alone (control). The primary outcome is the proportion of participants adhering to healthy behaviours at 6 months, measured using a composite health behaviour score. Secondary outcomes include overall cardiovascular disease risk, body composition, illness perceptions, self-efficacy, hospital anxiety/depression and medication adherence. This study is one of the first to examine an mHealth-delivered comprehensive CR program. Strengths of the trial include quality research design and in-depth description of the intervention to aid replication. If effective, the trial has potential to augment standard CR practices and to be used as a model for other disease prevention or self-management programs. Australian New Zealand Clinical Trials Registry: ACTRN12613000901707.

Cognitive behaviour therapy (CBT) for anxiety and depression in adults with mild intellectual disabilities (ID): a pilot randomised controlled trial

PubMed Central

2011-01-01

Background Several studies have showed that people with intellectual disabilities (ID) have suitable skills to undergo cognitive behavioural therapy (CBT). Case studies have reported successful use of cognitive behavioural therapy techniques (with adaptations) in people with ID. Modified cognitive behavioural therapy may be a feasible and effective approach for the treatment of depression, anxiety, and other mood disorders in ID. To date, two studies have reported group-based manaulised cognitive behavioural treatment programs for depression in people with mild ID. However, there is no individual manualised programme for anxiety or depression in people with intellectual disabilities. The aims of the study are to determine the feasibility of conducting a randomised controlled trial for CBT in people with ID. The data will inform the power calculation and other aspects of carrying out a definitive randomised controlled trial. Methods Thirty participants with mild ID will be allocated randomly to either CBT or treatment as usual (TAU). The CBT group will receive up to 20 hourly individual CBT over a period of 4 months. TAU is the standard treatment which is available to any adult with an intellectual disability who is referred to the intellectual disability service (including care management, community support, medical, nursing or social support). Beck Youth Inventories (Beck Anxiety Inventory & Beck Depression Inventory) will be administered at baseline; end of treatment (4 months) and at six months to evaluate the changes in depression and anxiety. Client satisfaction, quality of life and the health economics will be secondary outcomes. Discussion The broad outcome of the study will be to produce clear guidance for therapists to apply an established psychological intervention and identify how and whether it works with people with intellectual disabilities. Trial registration ISRCTN: ISRCTN38099525 PMID:21492437

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.

Tablet computers versus optical aids to support education and learning in children and young people with low vision: protocol for a pilot randomised controlled trial, CREATE (Children Reading with Electronic Assistance To Educate)

PubMed Central

Crossland, Michael D; Thomas, Rachel; Unwin, Hilary; Bharani, Seelam; Gothwal, Vijaya K; Quartilho, Ana; Bunce, Catey

2017-01-01

Introduction Low vision and blindness adversely affect education and independence of children and young people. New ‘assistive’ technologies such as tablet computers can display text in enlarged font, read text out to the user, allow speech input and conversion into typed text, offer document and spreadsheet processing and give access to wide sources of information such as the internet. Research on these devices in low vision has been limited to case series. Methods and analysis We will carry out a pilot randomised controlled trial (RCT) to assess the feasibility of a full RCT of assistive technologies for children/young people with low vision. We will recruit 40 students age 10–18 years in India and the UK, whom we will randomise 1:1 into two parallel groups. The active intervention will be Apple iPads; the control arm will be the local standard low-vision aid care. Primary outcomes will be acceptance/usage, accessibility of the device and trial feasibility measures (time to recruit children, lost to follow-up). Exploratory outcomes will be validated measures of vision-related quality of life for children/young people as well as validated measures of reading and educational outcomes. In addition, we will carry out semistructured interviews with the participants and their teachers. Ethics and dissemination NRES reference 15/NS/0068; dissemination is planned via healthcare and education sector conferences and publications, as well as via patient support organisations. Trial registration number NCT02798848; IRAS ID 179658, UCL reference 15/0570. PMID:28637740

Drug treatment of bothersome lower urinary tract symptoms after ureteric JJ-stent insertion: A contemporary, comparative, prospective, randomised placebo-controlled study, single-centre experience.

PubMed

Hekal, Ihab A

2016-12-01

To provide a guide for medication to alleviate bothersome lower urinary tract symptoms (LUTS) in patients after JJ ureteric stenting. Between June 2011 and June 2015, a prospective randomised placebo-controlled study was conducted on 200 consecutive cases of ureteric stones that required JJ stents. All patients had signed informed consent and JJ-stent placement confirmed by X-ray. The patients were randomised into five groups: A, solifenacin 5 mg; B, trospium chloride 20 mg; C, antispasmodic; and E, α-blocker; and a placebo group (D). A standard model was created to lessen patient selection bias. Eligible patients were enrolled and assessed for side-effects and bothersome LUTS using the validated Ureteric Stent Symptoms Questionnaire. Appropriate statistical analysis was carried out. In all, 150 male patients in the five groups were compared. LUTS were less in groups A and B ( P  < 0.05), while dry mouth was significantly reported in Group A. Individual comparisons with the placebo group showed a non-significant difference with Group C, while Group E had significant nocturia improvement. Selective comparison of two best groups (A and B) showed less frequency in Group B, while the other LUTS were less in Group A with comparable side-effects. In symptomatic patients following JJ-stent insertion, anti-muscarinic medication, namely solifenacin 5 mg or trospium chloride 20 mg, was the best. The advantage of trospium over solifenacin is in the control of frequency rather than the other symptoms. Addition of an α-blocker (alfuzosin 10 mg) is valuable when nocturia is the predominant symptom.

Calcium and phosphorus supplementation of human milk for preterm infants.

PubMed

Harding, Jane E; Wilson, Jess; Brown, Julie

2017-02-26

Preterm infants are born with low skeletal stores of calcium and phosphorus. Preterm human milk provides insufficient calcium and phosphorus to meet the estimated needs of preterm infants for adequate growth. Supplementation of human milk with calcium and phosphorus may improve growth and development of preterm infants. To determine whether addition of calcium and phosphorus supplements to human milk leads to improved growth and bone metabolism of preterm infants without significant adverse effects. We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3), MEDLINE via PubMed (1966 to 14 April 2016), Embase (1980 to 14 April 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 14 April 2016). We also searched clinical trials databases (11 May 2016) and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised and quasi-randomised trials comparing supplementation of human milk with calcium and/or phosphorus versus no supplementation in hospitalised preterm infants were eligible for inclusion in this review. Two review authors (JB, JW) independently extracted data and assessed trial quality using standard methods of the Cochrane Neonatal Review Group. We reported dichotomous data as risk ratios (RRs) and continuous data as mean differences (MDs) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence. This is an update of a 2001 review that identified no eligible trials. One trial including 40 infants met the inclusion criteria for this review. Using GRADE criteria, we judged the quality of the evidence as low owing to risk of bias (inadequate reporting of methods of randomisation, allocation concealment and/or blinding) and imprecision (wide confidence intervals and data from a single small trial). We found no evidence of a difference between calcium and phosphorus supplementation versus no supplementation for neonatal growth outcomes (weight, length, head circumference) at any time point reported (two, four or six weeks postnatal age). At six weeks postnatal age, supplementation with calcium/phosphorus was associated with a decrease in serum alkaline phosphatase concentration (MD -56.85 IU/L, 95% CI -101.27 to -12.43; one randomised controlled trial (RCT); n = 40 infants). Investigators provided no data on growth at 12 to 18 months, neonatal fractures, feed intolerance, breastfeeding or any of the prespecified childhood outcomes for this review (fractures, growth, neurodevelopmental outcomes). We identified one small trial including only 40 infants that compared supplementation of human milk with calcium and phosphorus versus no supplementation in hospitalised preterm infants. We judged the evidence to be of low quality and found no evidence of differences between groups for clinically important outcomes including growth and fractures. Although serum alkaline phosphatase concentration was reduced in the group receiving supplementation at six weeks postnatal age, this difference is unlikely to be of clinical significance. We conclude that evidence is insufficient to determine whether benefit or harm ensues when human milk is supplemented with calcium and/or phosphorus for the hospitalised preterm infant. We see no advantage of conducting further trials of this intervention because with the advent of multi-component human milk fortifier, supplementation of human milk with calcium and/or phosphorus alone is no longer common practice. Future trials should consider assessing effects of multi-component fortifiers with different mineral compositions on clinically important outcomes during the neonatal period and in later childhood.

Exercise and self-management for people with chronic knee, hip or lower back pain: a cluster randomised controlled trial of clinical and cost-effectiveness. Study protocol.

PubMed

Walsh, Nicola; Cramp, Fiona; Palmer, Shea; Pollock, Jon; Hampson, Lisa; Gooberman-Hill, Rachael; Green, Colin; Jones, Louise; Phillips, Sonia; Johnson, Liz; Hurley, Mike

2013-12-01

Chronic musculoskeletal pain and osteoarthritis can significantly limit the functional independence of individuals, and given that 25% of the population experience these problems, the socioeconomic impact is immense. Exercise and self-management have proven benefits for these conditions, but most trials tailor interventions for specific joints. Epidemiological data demonstrates that many older people with degenerative joint problems experience pain and functional difficulty in other joints, seeking further healthcare input when these present. Managing multiple joint presentations simultaneously could potentially reduce the need for repeat visits to healthcare professionals as advice is frequently the same for differing site presentations. This single-blind cluster randomised controlled trial will determine the clinical and cost-effectiveness of an exercise and self-management intervention delivered to people over-50 with either hip, knee or lower back pain, compared to 'standard' GP care. A qualitative analysis will also establish the acceptability of the intervention. 352 people with chronic degenerative musculoskeletal pain of the hip, knee or lower back will be recruited from primary care. GP surgeries will be randomised to either the intervention or control arms. Participants in the intervention arm will receive a 6-week group exercise and self-management programme facilitated by a physiotherapist in primary care. Participants allocated to the control arm will continue under 'standard' GP care. The primary outcome measure is the Dysfunction Index of the Short Musculoskeletal Functional Assessment (SMFA). Individual patient responses will be modelled using a mixed effects linear regression, allowing for the clustering effects. Resource use and related intervention costs will be estimated and broader resource use data will be collected using a version of the Client Service Receipt Inventory adapted for musculoskeletal relevance. In addition, a cost-utility analysis will be undertaken to present an estimate of the incremental cost per QALY. A qualitative analysis investigating the acceptability of the intervention to participants and healthcare professionals will also be undertaken and thematically analysed. Ethical approval was received from South West 4 REC, identification number 11/SW/0053. Study findings will be disseminated via conference and journal presentation; via arthritis charitable organisations; and through local GP consortia. Copyright © 2012 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

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.