Homeopathic Arnica montana for post-tonsillectomy analgesia: a randomised placebo control trial.

PubMed

Robertson, A; Suryanarayanan, R; Banerjee, A

2007-01-01

To evaluate the efficacy of Homeopathic Arnica in reducing the morbidity following tonsillectomy. Randomised double blind, placebo controlled trial at a tertiary referral centre. 190 patients over the age of 18 undergoing tonsillectomy were randomised into intervention and control groups receiving either Arnica 30c or identical placebo, 2 tablets 6 times in the first post-operative day and then 2 tablets twice a day for the next 7 days. The primary outcome measure was the change in pain scores (visual analogue scale) recorded by the patient on a questionnaire over 14 days post-operatively; Secondary outcome measures were: analgesia consumption, visits to the GP or hospital, antibiotic usage, the day on which their swallowing returned to normal and the day on which they returned to work. 111 (58.4%) completed questionnaires were available for analysis. The Arnica group had a significantly larger drop in pain score from day 1 to day 14 (28.3) compared to the placebo group (23.8) with p < 0.05. The two groups did not differ significantly on analgesic consumption or any of the other secondary outcome measures (number of post-operative visits to GP, use of antibiotics and secondary haemorrhage readmissions). The results of this trial suggest that Arnica montana given after tonsillectomy provides a small, but statistically significant, decrease in pain scores compared to placebo.

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

Migraine with prolonged aura: phenotype and treatment.

PubMed

Viana, Michele; Afridi, Shazia

2018-01-01

We review the published literature on migraine with prolonged aura (PA), specifically with regards to the phenotype and treatment options. PA is not uncommon. A recent study found that about 17% of migraine auras are prolonged and that 26% of patients with migraine with aura have experienced at least one PA. The characteristics of PA are similar to most typical auras with the exception of a higher number of aura symptoms (in particular sensory and/or dysphasic). There are no well-established treatments at present which target the aura component of migraine. Other than case reports, there have been open-label studies of lamotrigine and greater occipital nerve blocks. The only randomised, blinded, controlled trial to date has been of nasal ketamine showing some reduction in aura severity but not duration. A small open-labelled pilot study of amiloride was also promising. Larger randomised, controlled trials are needed to establish whether any of the existing or novel compounds mentioned are significantly effective and safe.

Dark chocolate for children's blood pressure: randomised trial.

PubMed

Chan, Eunice K; Quach, Jon; Mensah, Fiona K; Sung, Valerie; Cheung, Michael; Wake, Melissa

2012-07-01

Higher adult blood pressure, even without hypertension, predicts cardiovascular outcomes, and is predicted by childhood blood pressure. Regular dark chocolate intake lowers blood pressure in adults, but effects in children are unknown. To examine the feasibility of school-based provision of dark chocolate and its short-term efficacy in reducing mean group blood pressure. 194 children (aged 10-12 years) were randomised by class to intervention (7 g dark chocolate daily for 7 weeks, n=124) or control (n=70) groups; 98% and 93% provided baseline and follow-up measurements, respectively. Intervention and control students had similar systolic (mean difference 1.7 mm Hg, 95% CI -0.6 to 4.1) and diastolic (-1.2 mm Hg, 95% CI -3.6 to 1.3) blood pressure, anthropometry and well-being at outcome. Results show that providing dark chocolate is feasible and acceptable in the school setting. For a definitive trial, the authors recommend a larger sample, endovascular function measures, and consideration of higher antioxidant 'dose' by virtue of duration and/or content.

Cognitive rehabiliation for Parkinson's disease demantia: a study protocol for a pilot randomised controlled trial.

PubMed

Hindle, John V; Watermeyer, Tamlyn J; Roberts, Julie; Martyr, Anthony; Lloyd-Williams, Huw; Brand, Andrew; Gutting, Petra; Hoare, Zoe; Edwards, Rhiannon Tudor; Clare, Linda

2016-03-22

There is growing interest in developing non-pharmacological treatments to address the cognitive deficits apparent in Parkinson's disease dementia and dementia with Lewy bodies. Cognitive rehabilitation is a goal-oriented behavioural intervention which focuses on improving everyday functioning through management of cognitive difficulties; it has been shown to be effective in Alzheimer's disease. To date, no studies have assessed its potential efficacy for addressing the impact of cognitive impairment in people with Parkinson's disease or dementia with Lewy bodies. Participants (n = 45) will be recruited from movement disorders, care for the elderly and memory clinics. Inclusion criteria include: a diagnosis of Parkinson's disease, Parkinson's disease dementia or dementia with Lewy bodies according to consensus criteria and an Addenbrooke's Cognitive Examination - III score of ≤ 82. Exclusion criteria include: a diagnosis of any other significant neurological condition; major psychiatric disorder, including depression, which is not related to the patient's Parkinson's disease and unstable medication use for their physical or cognitive symptoms. A single-blind pilot randomised controlled trial, with concurrent economic evaluation, will compare the relative efficacy of cognitive rehabilitation with that of two control conditions. Following a goal-setting interview, the participants will be randomised to one of the three study arms: cognitive rehabilitation (eight weekly sessions), relaxation therapy (eight weekly sessions) or treatment as usual. Randomisation and treatment group allocation will be carried out by a clinical trials unit using a dynamic adaptive sequential randomisation algorithm. The primary outcomes are patients' perceived goal attainment at a 2-months post-intervention assessment and a 6-months follow-up. Secondary outcomes include patients' objective cognitive performance (on tests of memory and executive function) and satisfaction with goal attainment, carers' perception of patients' goal attainment and patients' and carers' health status and psychosocial well-being, measured at the same time points. Cost-effectiveness will be examined to explore the design of a larger cost-effectiveness analysis alongside a full trial. This pilot study will evaluate the application of cognitive rehabilitation for the management of cognitive difficulties associated with Parkinson's disease dementia and dementia with Lewy bodies. The results of the study will inform the design of a fully powered randomised controlled trial. ISRCTN16584442 DOI 10.1186/ISRCTN16584442 13 April 2015.

A cluster randomised controlled trial evaluating an incentive-based outdoor physical activity programme to increase outdoor time and prevent myopia in children.

PubMed

Ngo, Cheryl S; Pan, Chen-Wei; Finkelstein, Eric A; Lee, Chun-Fan; Wong, Inez B; Ong, Julia; Ang, Marcus; Wong, Tien-Yin; Saw, Seang-Mei

2014-05-01

To evaluate an incentive-based intervention to increase time spent outdoors among children in a 9-month cluster randomised controlled trial. Two hundred and eighty-five children aged 6-12 years of age were randomised to the intervention (n = 147) or control arm (n = 138) in the Family incentive trial (FIT). The FIT intervention comprised of targeted education on myopia and good eye care habits, structured weekend outdoor activities and incentives for children to increase their daily steps via pedometers. The main outcome measure was outdoor time, measured by the WHO questionnaire and a 1-week diary. Interim analysis at 6 months showed a significant increase in mean outdoor time per week in the intervention arm (14.75 h week(-1) ) compared to the control arm (12.40 h week(-1) ) as measured by the questionnaire (p = 0.04). However, greater outdoor time was not statistically significant at the end of the trial (15.95 h week(-1) vs 14.34 h in the control group (p = 0.29). There was an increase in outdoor time for children in the incentive-based physical activity outdoor program after 6 months but not at the end of the trial. Further larger school trials with better compliance with the intervention and longer duration could be conducted to evaluate clinical outcomes such as myopic shifts. © 2014 The Authors Ophthalmic & Physiological Optics © 2014 The College of Optometrists.

Facilitating return to work through early specialist health-based interventions (FRESH): protocol for a feasibility randomised controlled trial.

PubMed

Radford, Kathryn A; Phillips, Julie; Jones, Trevor; Gibson, Ali; Sutton, Chris; Watkins, Caroline; Sach, Tracey; Duley, Lelia; Walker, Marion; Drummond, Avril; Hoffman, Karen; O'Connor, Rory; Forshaw, Denise; Shakespeare, David

2015-01-01

Over one million people sustain traumatic brain injury each year in the UK and more than 10 % of these are moderate or severe injuries, resulting in cognitive and psychological problems that affect the ability to work. Returning to work is a primary rehabilitation goal but fewer than half of traumatic brain injury survivors achieve this. Work is a recognised health service outcome, yet UK service provision varies widely and there is little robust evidence to inform rehabilitation practice. A single-centre cohort comparison suggested better work outcomes may be achieved through early occupational therapy targeted at job retention. This study aims to determine whether this intervention can be delivered in three new trauma centres and to conduct a feasibility, randomised controlled trial to determine whether its effects and cost effectiveness can be measured to inform a definitive trial. Mixed methods study, including feasibility randomised controlled trial, embedded qualitative studies and feasibility economic evaluation will recruit 102 people with traumatic brain injury and their nominated carers from three English UK National Health Service (NHS) trauma centres. Participants will be randomised to receive either usual NHS rehabilitation or usual rehabilitation plus early specialist traumatic brain injury vocational rehabilitation delivered by an occupational therapist. The primary objective is to assess the feasibility of conducting a definitive trial; secondary objectives include measurement of protocol integrity (inclusion/exclusion criteria, intervention adherence, reasons for non-adherence) recruitment rate, the proportion of eligible patients recruited, reasons for non-recruitment, spectrum of TBI severity, proportion of and reasons for loss to follow-up, completeness of data collection, gains in face-to-face V s postal data collection and the most appropriate methods of measuring primary outcomes (return to work, retention) to determine the sample size for a larger trial. To our knowledge, this is the first feasibility randomised controlled trial of a vocational rehabilitation health intervention specific to traumatic brain injury. The results will inform the design of a definitive trial. The trial is registered ISRCTN Number 38581822.

Podiatry intervention versus usual care to prevent falls in care homes: pilot randomised controlled trial (the PIRFECT study).

PubMed

Wylie, Gavin; Menz, Hylton B; McFarlane, Sarah; Ogston, Simon; Sullivan, Frank; Williams, Brian; Young, Zoe; Morris, Jacqui

2017-07-12

Common foot problems are independent risk factors for falls in older people. There is evidence that podiatry can prevent falls in community-dwelling populations. The feasibility of implementing a podiatry intervention and trial in the care home population is unknown. To inform a potential future definitive trial, we performed a pilot randomised controlled trial to assess: (i) the feasibility of a trial of a podiatry intervention to reduce care home falls, and (ii) the potential direction and magnitude of the effect of the intervention in terms of number of falls in care home residents. Informed by Medical Research Council guidance on developing and evaluating complex interventions, we conducted a single blind, pilot randomised controlled trial in six care homes in the East of Scotland. Participants were randomised to either: (i) a three month podiatry intervention comprising core podiatry care, foot and ankle exercises, orthoses and footwear provision or (ii) usual care. Falls-related outcomes (number of falls, time to first fall) and feasibility-related outcomes (recruitment, retention, adherence, data collection rates) were collected. Secondary outcomes included: generic health status, balance, mobility, falls efficacy, and ankle joint strength. 474 care home residents were screened. 43 (9.1%) participants were recruited: 23 to the intervention, 20 to control. Nine (21%) participants were lost to follow-up due to declining health or death. It was feasible to deliver the trial elements in the care home setting. 35% of participants completed the exercise programme. 48% reported using the orthoses 'all or most of the time'. Completion rates of the outcome measures were between 93% and 100%. No adverse events were reported. At the nine month follow-up period, the intervention group per-person fall rate was 0.77 falls vs. 0.83 falls in the control group. A podiatry intervention to reduce falls can be delivered to care home residents within a pilot randomised controlled trial of the intervention. Although not powered to determine effectiveness, these preliminary data provide justification for a larger trial, incorporating a full process evaluation, to determine whether this intervention can significantly reduce falls in this high-risk population. ClinicalTrials.gov identifier: NCT02178527 ; Date of registration: 17 June 2014.

Doxycycline in early CJD: a double-blinded randomised phase II and observational study.

PubMed

Varges, Daniela; Manthey, Henrike; Heinemann, Uta; Ponto, Claudia; Schmitz, Matthias; Schulz-Schaeffer, Walter J; Krasnianski, Anna; Breithaupt, Maren; Fincke, Fabian; Kramer, Katharina; Friede, Tim; Zerr, Inga

2017-02-01

The main objective of the present study is to study the therapeutic efficiency of doxycycline in a double-blinded randomised phase II study in a cohort of patients with sporadic Creutzfeldt-Jakob disease (sCJD). From the National Reference Center of TSE Surveillance in Germany, patients with probable or definite sCJD were recruited for a double-blinded randomised study with oral doxycycline (EudraCT 2006-003934-14). In addition, we analysed the data from patients with CJD who received compassionate treatment with doxycycline in a separate group. Potential factors which influence survival such as age at onset, gender, codon 129 polymorphism and cognitive functions were evaluated. The primary outcome measure was survival. Group 1: in the double-blinded randomised phase II study, 7 patients in the treatment group were compared with 5 controls. Group 2: 55 patients with sCJD treated with oral doxycycline were analysed and compared with 33 controls by a stratified propensity score applied to a Cox proportional hazard analysis. The results of both studies were combined by means of a random-effects meta-analysis. A slight increase in survival time in the doxycycline treatment group was observed (p=0.049, HR=0.63 (95% CI 0.402 to 0.999)). On the basis of our studies, a larger trial of doxycycline should be performed in persons in the earliest stages of CJD. EudraCT 2006-003934-14; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The effect of plant sterols on serum triglyceride concentrations is dependent on baseline concentrations: a pooled analysis of 12 randomised controlled trials.

PubMed

Demonty, Isabelle; Ras, Rouyanne T; van der Knaap, Henk C M; Meijer, Linsie; Zock, Peter L; Geleijnse, Johanna M; Trautwein, Elke A

2013-02-01

Plant sterols (PS) are well known for their low-density lipoprotein cholesterol-lowering effect. Until recently, they were believed to have little or no impact on blood triglycerides (TG). However, studies taken individually were possibly lacking statistical power to detect modest TG decreases. This study was performed to quantify the TG-lowering effect of PS by pooling individual subject data from 12 randomised controlled trials that investigated the effects of PS on blood lipids. The main outcome variable was the control-adjusted PS effect on relative (%) and absolute (mmol/L) changes in TG. The relative and absolute changes in high-density lipoprotein cholesterol (HDL-C) were also assessed. Differences in changes of serum lipid concentrations between PS and control treatments were estimated by an ANCOVA using a random effect model which included PS intake (active or control), study and predefined subject characteristics. The twelve randomised controlled trials included in total 935 hypercholesterolaemic subjects not preselected based on their baseline TG concentrations. In most studies, the PS dose ranged between 1.6 and 2.5 g/day. PS intake significantly lowered serum TG by 6.0% (95% CI: -10.7, -1.2) or 0.12 mmol/L (95% CI: -0.20, -0.04). No significant interaction was observed between PS intake and baseline TG concentrations on relative changes, but, on absolute changes, interaction was significant with larger TG decreases observed with higher TG concentrations at baseline. No effects were observed on HDL-C concentrations. These results show that PS exert a modest TG-lowering effect which is dependent on baseline concentrations.

Influenza vaccine efficacy in young children attending childcare: A randomised controlled trial.

PubMed

Li-Kim-Moy, Jean P; Yin, Jiehui K; Heron, Leon; Leask, Julie; Lambert, Stephen B; Nissen, Michael; Sloots, Theo; Booy, Robert

2017-01-01

Influenza causes a substantial burden in young children. Vaccine efficacy (VE) data are limited in this age group. We examined trivalent influenza vaccine (TIV) efficacy and safety in young children attending childcare. A double-blind, randomised controlled trial in children aged 6 to <48 months was conducted with recruitment from Sydney childcare centres in 2011. Children were randomised to receive two doses of TIV or control hepatitis A vaccine. Efficacy was evaluated against polymerase chain reaction-confirmed influenza using parent-collected nose/throat swabs during influenza-like-illness. Safety outcomes were assessed during 6 months of follow-up. Fifty-seven children were allocated to influenza vaccine and 67 to control; all completed the study. The influenza attack rate was 1.8 vs 13.4% in the TIV and control groups, respectively; VE 87% (95%CI: 0-98%). For children aged 24 to <48 months, 0 vs 8 (18.6%) influenza infections occurred in the TIV and control groups respectively, giving a VE of 100% (16-100%). Efficacy was not shown in children 6 to <24 months, probably due to insufficient power. Injection site and systemic adverse events were mostly mild to moderate with no significant differences, apart from more mild diarrhoea following dose 2 in TIV recipients (11.8 vs 0%). Influenza vaccine appeared efficacious in the subgroup of children aged 24 to <48 months, although caution is required due to the small number of participants. There were no serious adverse events and most parents would vaccinate again. Influenza vaccination in a childcare setting could be valuable and a larger confirmatory study would be helpful. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Psychoeducational support to post cardiac surgery heart failure patients and their partners--a randomised pilot study.

PubMed

Ågren, Susanna; Berg, Sören; Svedjeholm, Rolf; Strömberg, Anna

2015-02-01

Postoperative heart failure is a serious complication that changes the lives of both the person who is critically ill and family in many ways. The purpose of this study was to evaluate the effects of an intervention in postoperative heart failure patient-partner dyads regarding health, symptoms of depression and perceived control. Pilot study with a randomised controlled design evaluating psychosocial support and education from an interdisciplinary team. Patients with postoperative heart failure and their partners. SF-36, Beck Depression Inventory, Perceived Control at baseline, 3 and 12 months. A total of 42 patient-partner completed baseline assessment. Partners in the intervention group increased health in the role emotional and mental health dimensions and patients increased health in vitality, social function and mental health dimensions compared with the control group. Patients' perceived control improved significantly in the intervention group over time. Psychoeducational support to post cardiac surgery heart failure dyads improved health in both patients and partners at short term follow-up and improved patients' perceived control at both short and long-term follow-up. Psychoeducational support appears to be a promising intervention but the results need to be confirmed in larger studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

[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.

Amnioinfusion in preterm premature rupture of membranes (AMIPROM): a randomised controlled trial of amnioinfusion versus expectant management in very early preterm premature rupture of membranes--a pilot study.

PubMed

Roberts, Devender; Vause, Sarah; Martin, William; Green, Pauline; Walkinshaw, Stephen; Bricker, Leanne; Beardsmore, Caroline; Shaw, Ben N J; McKay, Andrew; Skotny, Gaynor; Williamson, Paula; Alfirevic, Zarko

2014-04-01

Fetal survival is severely compromised when the amniotic membrane ruptures between 16 and 24 weeks of pregnancy. Reduced amniotic fluid levels are associated with poor lung development, whereas adequate levels lead to better perinatal outcomes. Restoring amniotic fluid by means of ultrasound-guided amnioinfusion (AI) may be of benefit in improving perinatal and long-term outcomes in children of pregnancies with this condition. The AI in preterm premature rupture of membranes (AMIPROM) pilot study was conducted to assess the feasibility of recruitment, the methods for conduct and the retention through to long-term follow-up of participants with very early rupture of amniotic membranes (between 16 and 24 weeks of pregnancy). It was also performed to assess outcomes and collect data to inform a larger, more definitive, clinical trial. A prospective, non-blinded randomised controlled trial. A computer-generated random sequence using a 1 : 1 ratio was used. Randomisation was stratified for pregnancies in which the amniotic membrane ruptured between 16(+0) and 19(+6) weeks' gestation and 20(+0) and 24(+0) weeks' gestation. The randomisation sequence was generated in blocks of four. Telephone randomisation and intention-to-treat analysis were used. Four UK hospital-based fetal medicine units - Liverpool Women's NHS Trust, St. Mary's Hospital, Manchester, Birmingham Women's NHS Foundation Trust and Wirral University Hospitals Trust. Women with confirmed preterm prelabour rupture of membranes between 16(+0) and 24(+0) weeks' gestation. Women with multiple pregnancies, resultant fetal abnormalities or obstetric indication for immediate delivery were excluded. Participants were randomly allocated to either serial weekly transabdominal AI or expectant management (Exp) until 37 weeks of pregnancy, if the deepest pool of amniotic fluid was < 2 cm. Short-term maternal, pregnancy and neonatal outcomes and long-term outcomes for the child were studied. Long-term respiratory morbidity was assessed using validated respiratory questionnaires at 6, 12 and 18 months of age and infant lung function was assessed at approximately 12 months of age. Neurodevelopment was assessed using Bayley's Scale of Infant Development II at a corrected age of 2 years. Fifty-eight women were randomised and two were excluded from the analysis owing to termination of pregnancy for lethal anomaly, leaving 56 participants (28 serial AI, 28 Exp) recruited between 2002 and 2009, with annual recruitment rates varying between 2 and 14. Recruitment to the study improved significantly from 2007 with National Institute for Health Research (NIHR) funding. There was no significant difference in perinatal mortality [19/28 vs. 19/28; relative risk (RR) 1.0; 95% confidence interval (CI) 0.70 to 1.43], maternal morbidity or neonatal morbidity. The overall chance of surviving without long-term respiratory or neurodevelopmental disability is 4/56 (7.1%): 4/28 (14.3%) in the AI arm and 0/28 in the expectant arm (0%) (RR 9.0; 95% CI 0.51 to 159.70). This pilot study found no major differences in maternal, perinatal or pregnancy outcomes. The study was not designed to show a difference between the arms and the number of survivors was too small to draw any conclusions about long-term outcomes. It does signal, however, that a larger, definitive, study to evaluate AI for improvement in healthy survival is indicated. The results suggest that, with appropriate funding, such a study is feasible. A larger, definitive, study with full health economic analysis and patient perspective assessment is required to show whether AI can improve the healthy survivor rate.

A mixed method pilot study: the researchers' experiences.

PubMed

Secomb, Jacinta M; Smith, Colleen

2011-08-01

This paper reports on the outcomes of a small well designed pilot study. Pilot studies often disseminate limited or statistically meaningless results without adding to the body knowledge on the comparative research benefits. The design a pre-test post-test group parallel randomised control trial and inductive content analysis of focus group transcripts was tested specifically to increase outcomes in a proposed larger study. Strategies are now in place to overcome operational barriers and recruitment difficulties. Links between the qualitative and quantitative arms of the proposed larger study have been made; it is anticipated that this will add depth to the final report. More extensive reporting on the outcomes of pilot studies would assist researchers and increase the body of knowledge in this area.

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.

Metformin in cancer.

PubMed

Mallik, Ritwika; Chowdhury, Tahseen A

2018-05-26

Metformin is a lipophilic biguanide which inhibits hepatic gluconeogenesis and improves peripheral utilization of glucose. It is the first line pharmacotherapy for glucose control in patients with Type 2 diabetes due to its safety, efficacy and tolerability. Metformin exhibits pleotropic effects, which may have beneficial effects on a variety of tissues independent of glucose control. A potential anti-tumourigenic effect of metformin may be mediated by its role in activating AMP-kinase, which in turn inhibits mammalian target of rapamycin (mTOR). Non-AMPK dependent protective pathways may include reduction of insulin, insulin-like growth factor-1, leptin, inflammatory pathways and potentiation of adiponectin, all of which may have a role in tumourigenesis. A role in inhibiting cancer stem cells is also postulated. A number of large scale observational and cohort studies suggest metformin is associated with a reduced risk of a number of cancers, although the data is not conclusive. Recent randomised studies reporting use of metformin in treatment of cancer have revealed mixed results, and the results of much larger randomised trials of metformin as an adjuvant therapy in breast and colorectal cancers are awaited. Copyright © 2018 Elsevier B.V. All rights reserved.

'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.

Publishing interim results of randomised clinical trials in peer-reviewed journals.

PubMed

Counsell, Nicholas; Biri, Despina; Fraczek, Joanna; Hackshaw, Allan

2017-02-01

Interim analyses of randomised controlled trials are sometimes published before the final results are available. In several cases, the treatment effects were noticeably different after patient recruitment and follow-up completed. We therefore conducted a literature review of peer-reviewed journals to compare the reported treatment effects between interim and final publications and to examine the magnitude of the difference. We performed an electronic search of MEDLINE from 1990 to 2014 (keywords: 'clinical trial' OR 'clinical study' AND 'random*' AND 'interim' OR 'preliminary'), and we manually identified the corresponding final publication. Where the electronic search produced a final report in which the abstract cited interim results, we found the interim publication. We also manually searched every randomised controlled trial in eight journals, covering a range of impact factors and general medical and specialist publications (1996-2014). All paired articles were checked to ensure that the same comparison between interventions was available in both. In all, 63 studies are included in our review, and the same quantitative comparison was available in 58 of these. The final treatment effects were smaller than the interim ones in 39 (67%) trials and the same size or larger in 19 (33%). There was a marked reduction, defined as a ≥20% decrease in the size of the treatment effect from interim to final analysis, in 11 (19%) trials compared to a marked increase in 3 (5%), p = 0.057. The magnitude of percentage change was larger in trials where commercial support was reported, and increased as the proportion of final events at the interim report decreased in trials where commercial support was reported (interaction p = 0.023). There was no evidence of a difference between trials that stopped recruitment at the interim analysis where this was reported as being pre-specified versus those that were not pre-specified (interaction p = 0.87). Published interim trial results were more likely to be associated with larger treatment effects than those based on the final report. Publishing interim results should be discouraged, in order to have reliable estimates of treatment effects for clinical decision-making, regulatory authority reviews and health economic analyses. Our work should be expanded to include conference publications and manual searches of additional journal publications.

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.

Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study

PubMed Central

Miliku, Kozeta; Bauer, Anna; Engel, Stephanie M; Felix, Janine F; Jaddoe, Vincent W V; Lawlor, Debbie A; London, Stephanie J; McGinnis, Ralph; Nystad, Wenche; Page, Christian M; Rivadeneira, Fernando; Stene, Lars C; Tapia, German; Williams, Nicholas; Bonilla, Carolina; Fraser, Abigail

2018-01-01

Abstract Objective To use mendelian randomisation to investigate whether 25-hydroxyvitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia. Design One and two sample mendelian randomisation analyses. Setting Two European pregnancy cohorts (Avon Longitudinal Study of Parents and Children, and Generation R Study), and two case-control studies (subgroup nested within the Norwegian Mother and Child Cohort Study, and the UK Genetics of Pre-eclampsia Study). Participants 7389 women in a one sample mendelian randomisation analysis (751 with gestational hypertension and 135 with pre-eclampsia), and 3388 pre-eclampsia cases and 6059 controls in a two sample mendelian randomisation analysis. Exposures Single nucleotide polymorphisms in genes associated with vitamin D synthesis (rs10741657 and rs12785878) and metabolism (rs6013897 and rs2282679) were used as instrumental variables. Main outcome measures Gestational hypertension and pre-eclampsia defined according to the International Society for the Study of Hypertension in Pregnancy. Results In the conventional multivariable analysis, the relative risk for pre-eclampsia was 1.03 (95% confidence interval 1.00 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, and 2.04 (1.02 to 4.07) for 25-hydroxyvitamin D levels <25 nmol/L compared with ≥75 nmol/L. No association was found for gestational hypertension. The one sample mendelian randomisation analysis using the total genetic risk score as an instrument did not provide strong evidence of a linear effect of 25-hydroxyvitamin D on the risk of gestational hypertension or pre-eclampsia: odds ratio 0.90 (95% confidence interval 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. The two sample mendelian randomisation estimate gave an odds ratio for pre-eclampsia of 0.98 (0.89 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, an odds ratio of 0.96 (0.80 to 1.15) per unit increase in the log(odds) of 25-hydroxyvitamin D level <75 nmol/L, and an odds ratio of 0.93 (0.73 to 1.19) per unit increase in the log(odds) of 25-hydroxyvitamin D levels <50 nmol/L. Conclusions No strong evidence was found to support a causal effect of vitamin D status on gestational hypertension or pre-eclampsia. Future mendelian randomisation studies with a larger number of women with pre-eclampsia or more genetic instruments that would increase the proportion of 25-hydroxyvitamin D levels explained by the instrument are needed. PMID:29925546

Integrating culturally informed approaches into the physiotherapy assessment and treatment of chronic pain: protocol for a pilot randomised controlled trial

PubMed Central

Veljanova, Irena; Schabrun, Siobhan; Chipchase, Lucinda

2017-01-01

Introduction There is strong evidence that biopsychosocial approaches are efficacious in the management of chronic pain. However, implementation of these approaches in clinical practice is known not to account for the beliefs and values of culturally and linguistically diverse (CALD) patients. This limitation in translation of research contributes to the disparities in outcomes for CALD patients with chronic pain adding to the socioeconomic burden of this prevalent condition. Cultural adaptation of chronic pain assessment and management is urgently required. Thus, the aim of this pilot randomised controlled trial (RCT) is to determine the feasibility, participant acceptance with and clinical effectiveness of a culturally adapted physiotherapy assessment and treatment approach when contrasted with ‘usual evidence based physiotherapy care’ for three CALD communities. Methods and analysis Using a participant-blinded and assessor-blinded randomised controlled pilot design, patients with chronic pain who self-identify as Assyrian, Mandaean or Vietnamese will be randomised to either 'culturally adapted physiotherapy assessment and treatment' or ‘evidence informed usual physiotherapy care'. We will recruit 16 participants from each ethnocultural community that will give a total of 24 participants in each treatment arm. Both groups will receive physiotherapy treatment for up to 10 sessions over 3 months. Outcomes including feasibility data, acceptance with the culturally adapted intervention, functional and pain-related measures will be collected at baseline and 3 months by a blinded assessor. Analysis will be descriptive for feasibility outcomes, while measures for clinical effectiveness will be explored using independent samples t-tests and repeated measures analysis of variance. This analysis will inform sample size estimates while also allowing for identification of revisions in the protocol or intervention prior to a larger scale RCT. Ethics and dissemination This trial has full ethical approval (HREC/16/LPOOL/194). The results from this pilot RCT will be presented at scientific meetings and published in peer-reviewed journals. Trial registration number ACTRN12616000857404 PMID:28501812

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

PubMed

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

2011-06-01

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

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

PubMed Central

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

2012-01-01

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

Levobupivacaine-dextran mixture for transversus abdominis plane block and rectus sheath block in patients undergoing laparoscopic colectomy: a randomised controlled trial.

PubMed

Hamada, T; Tsuchiya, M; Mizutani, K; Takahashi, R; Muguruma, K; Maeda, K; Ueda, W; Nishikawa, K

2016-04-01

We performed a randomised controlled double-blinded study of patients having laparoscopic colectomy with bilateral transversus abdominis plane block plus rectus sheath block, comparing a control group receiving 80 ml levobupivacaine 0.2% in saline with a dextran group receiving 80 ml levobupivacaine 0.2% in 8% low-molecular weight dextran. Twenty-seven patients were studied in each group. The mean (SD) maximum plasma concentration of levobupivacaine in the control group (1410 (322) ng.ml(-1) ) was higher than the dextran group (1141 (287) ng.ml(-1) ; p = 0.004), and was reached more quickly (50.6 (30.2) min vs 73.2 (24.6) min; p = 0.006). The area under the plasma concentration-time curve from 0 min to 240 min in the control group (229,124 (87,254) ng.min.ml(-1) ) was larger than in the dextran group (172,484 (50,502) ng.min.ml(-1) ; p = 0.007). The median (IQR [range]) of the summated numerical pain rating score at rest during the first postoperative 24 h in the control group (16 (9-20 [3-31]) was higher than in the dextran group (8 (2-11 [0-18]); p = 0.0001). In this study, adding dextran to levobupivacaine decreased the risk of levobupivacaine toxicity while providing better analgesia. © 2016 The Association of Anaesthetists of Great Britain and Ireland.

Efficacy of adding a physiotherapy rehabilitation programme to arthroscopic management of femoroacetabular impingement syndrome: a randomised controlled trial (FAIR)

PubMed Central

Bennell, Kim L; Spiers, Libby; Takla, Amir; O’Donnell, John; Kasza, Jessica; Hunter, David J; Hinman, Rana S

2017-01-01

Objectives Although several rehabilitation programmes following hip arthroscopy for femoracetabular impingement (FAI) syndrome have been described, there are no clinical trials evaluating whether formal physiotherapy-prescribed rehabilitation improves recovery compared with self-directed rehabilitation. The objective of this study was to evaluate the efficacy of adding a physiotherapist-prescribed rehabilitation programme to arthroscopic surgery for FAI syndrome. Design Randomised controlled trial. Methods People aged ≥16 years with FAI syndrome scheduled for hip arthroscopy were recruited and randomly allocated to physiotherapy (PT) or control. The PT group received seven PT sessions (one preoperative and six postoperative) incorporating education, manual therapy and a progressive rehabilitation programme of home, aquatic and gym exercises while the control group did not undertake PT rehabilitation. Measurements were taken at baseline (2 weeks presurgery) and 14 and 24 weeks postsurgery. The primary outcomes were the International Hip Outcome Tool (iHOT-33) and the sport subscale of the Hip Outcome Score (HOS) at week 14. Results Due to slower than expected recruitment and funding constraints, recruitment was ceased after 23 months. Thirty participants (14 PT and 16 control) were randomised and 28 (14 PT and 14 control; 93%) and 22 (11 PT and 11 control; 73%) completed week 14 and 24 measurements, respectively. For the 14-week primary outcomes, the PT group showed significantly greater improvements on the iHOT-33 (mean difference 14.2 units; 95% CI 1.2 to 27.2) and sport subscale of the HOS (13.8 units; 95% CI 0.3 to 27.3). There were no significant between-group differences at week 24. Conclusions An individual PT treatment and rehabilitation programme may augment improvements in patient-reported outcomes following arthroscopy for FAI syndrome. However, given the small sample size, larger trials are needed to validate the findings. Trial registration number Trial registered with the Australian New Zealand Clinical Trials Registry :ACTRN12613000282785, Results. PMID:28645960

Effects of lipid emulsion particle size on satiety and energy intake: a randomised cross-over trial.

PubMed

Poppitt, Sally D; Budgett, Stephanie C; MacGibbon, Alastair K; Quek, Siew-Young; Kindleysides, Sophie; Wiessing, Katy R

2018-03-01

Emulsified lipids, with central lipid core surrounded by polar lipid 'protective coat', have been proposed to stimulate the ileal brake, alter appetite, food intake and aid weight control. In addition to lipid composition, emulsion particle size may contribute to efficacy with small droplets providing a larger surface area for gastrointestinal (GI) lipase action and larger droplets prolonging and delaying digestion in the GI tract. Tube feeding studies delivering emulsions directly into the small intestine show clear effects of smaller particle size on appetite and food intake, but evidence from oral feeding studies is sparse. The objective of this study was to determine the effects of lipid emulsion particle size on appetite response and food intake. In a three-arm randomised cross-over, high-phospholipid (PL) dairy lipid emulsions or matched control were consumed at breakfast within a yoghurt smoothie: (i) large-particle size emulsion, LPE (diameter 0.759 µm, 10 g lipid emulsion, 190 g yoghurt), (ii) small-particle size emulsion, SPE (diameter 0.290 µm, 10 g lipid emulsion, 190 g yoghurt), (iii) control non-emulsion, NE (10 g non-emulsion lipid, 190 g yoghurt). Twenty male participants completed the study, where postprandial appetite response was rated using visual analogue scales (VAS) and ad libitum energy intake at a lunch meal measured 3 h later. There was a trend for LPE to suppress hunger (P = 0.08) and enhance fullness (P = 0.24) relative to both SPE and NE but not statistically significant, and no significant effect of either emulsion on food intake at the lunch meal (P > 0.05). Altering particle size of a high-PL emulsion did not enhance satiety or alter eating behaviour in a group of lean men.

Treatment for Charcot-Marie-Tooth disease.

PubMed

Young, P; De Jonghe, P; Stögbauer, F; Butterfass-Bahloul, T

2008-01-23

Charcot-Marie-Tooth disease (CMT) comprises a large variety of different forms of motor and sensory neuropathies. The most frequent are demyelinating forms (CMT1) and axonal forms (CMT2). The molecular basis of several CMT forms has been clarified during the last 15 years. Since muscle wasting and sensory disturbance are the main features of these syndromes, treatments aim to improve motor impairment and sensory disturbances. Specific treatment trials are rare. The objective was to review systematically all randomised and quasi-randomised studies of any treatment for CMT. We searched the Cochrane Neuromuscular Disease Group Trials Register, MEDLINE (January 1966 to August 2007), EMBASE (January 1980 to August 2007), LILACS (January 1982 to August 2007) for randomised controlled trials of treatment for CMT. We included randomised and quasi-randomised trials of any treatment for people with CMT. Where a study aimed to evaluate the treatment of general neuromuscular symptoms of people with peripheral neuropathy including CMT, we included the study if we were able to identify the effect of treatment in the CMT group. Observational studies and case reports on the treatment of people with CMT were not included. Two review authors (PY and TBB) extracted the data, assessed study quality and performed data extraction independently. Only one trial with only eight participants met all the inclusion criteria and provided the primary outcome measure for this review. In this trial, four participants treated with neurotrophin-3 had more improvement after six months on the Neuropathy Impairment Score, mean difference -9.50 (95% CI -13.77 to -5.23), than those four treated with placebo. Small trials of exercise training, creatine monohydrate, orthoses and purified bovine brain ganglioside injections (Cronassial) showed no significant benefit in people with genetically undefined CMT1 or CMT2. Small trials of exercise, creatine, purified brain gangliosides, and orthoses have been performed. None showed significant benefit. A very small trial of neurotrophin-3 showed possible minor benefit which needs to be replicated in a larger trial. None of the two trials were large enough to detect moderate benefit or harm. Larger RCTs are needed for any form of pharmacological intervention as well as as for any form of physical intervention. Outcome measures should include a validated composite scale such as the Charcot-Marie-Tooth neuropathy scale.

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

PubMed

Gaus, Wilhelm; Muche, Rainer

2013-05-01

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

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.

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 randomised controlled trial of an SMS-based mobile epilepsy education system.

PubMed

Lua, Pei Lin; Neni, Widiasmoro Selamat

2013-01-01

We evaluated an epilepsy education programme based on text messaging (SMS). Epilepsy outpatients from three hospitals in Malaysia were randomised into two groups: intervention and control. Patients in the control group were supplied with printed epilepsy educational material while those in the intervention group also received text messages from the Mobile Epilepsy Educational System (MEES). A total of 136 patients completed the study (mean age 31 years; 91% Malay; 51% with an illness duration of more than 5 years). A between-group analysis showed that the awareness, knowledge and attitudes (AKA) about epilepsy did not significantly differ between the groups at baseline (P > 0.05). The intervention patients reported better AKA levels during follow-up compared to the control patients (P < 0.05). A within-group analysis showed that in intervention patients, there were significant improvements in all AKA domains with larger effect sizes (P < 0.01) while control patients also exhibited significant improvement in most domains except for Awareness but with smaller effect sizes. After controlling for possible confounding variables (age, gender, educational qualification, monthly income and baseline mean for each domain), the intervention group still reported significantly higher AKA than the control group particularly in Awareness (P < 0.001) and Total AKA (P = 0.003). There was also significantly better medication adherence and clinic attendance in the intervention group (P < 0.05). The results suggest that the addition of the MEES to conventional epilepsy education is effective in improving AKA.

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

Physical micro-environment interventions for healthier eating in the workplace: protocol for a stepped wedge randomised controlled pilot trial.

PubMed

Vasiljevic, Milica; Cartwright, Emma; Pechey, Rachel; Hollands, Gareth J; Couturier, Dominique-Laurent; Jebb, Susan A; Marteau, Theresa M

2017-01-01

An estimated one third of energy is consumed in the workplace. The workplace is therefore an important context in which to reduce energy consumption to tackle the high rates of overweight and obesity in the general population. Altering environmental cues for food selection and consumption-physical micro-environment or 'choice architecture' interventions-has the potential to reduce energy intake. The first aim of this pilot trial is to estimate the potential impact upon energy purchased of three such environmental cues (size of portions, packages and tableware; availability of healthier vs. less healthy options; and energy labelling) in workplace cafeterias. A second aim of this pilot trial is to examine the feasibility of recruiting eligible worksites, and identify barriers to the feasibility and acceptability of implementing the interventions in preparation for a larger trial. Eighteen worksite cafeterias in England will be assigned to one of three intervention groups to assess the impact on energy purchased of altering (a) portion, package and tableware size ( n  = 6); (b) availability of healthier options ( n  = 6); and (c) energy (calorie) labelling ( n  = 6). Using a stepped wedge design, sites will implement allocated interventions at different time periods, as randomised. This pilot trial will examine the feasibility of recruiting eligible worksites, and the feasibility and acceptability of implementing the interventions in preparation for a larger trial. In addition, a series of linear mixed models will be used to estimate the impact of each intervention on total energy (calories) purchased per time frame of analysis (daily or weekly) controlling for the total sales/transactions adjusted for calendar time and with random effects for worksite. These analyses will allow an estimate of an effect size of each of the three proposed interventions, which will form the basis of the sample size calculations necessary for a larger trial. ISRCTN52923504.

Multimedia information intervention and its benefits in partners of the head and neck cancer patients.

PubMed

D'Souza, V; Blouin, E; Zeitouni, A; Muller, K; Allison, P J

2017-07-01

We aimed to investigate the levels of anxiety, depression, satisfaction with information provision and cancer-related knowledge in partners of head and neck cancer (HNC) patients receiving a Multimode Comprehensive Tailored Information Package (MCTIP). A non-randomised, controlled trial was conducted with partners of HNC patients recruited at two academic hospitals in Montreal. The Test participants received the MCTIP, while the Control participants received information in an ad hoc manner. All participants were evaluated using the Hospital Anxiety and Depression Scale (HADS), Satisfaction with Cancer Information Profile and a cancer knowledge questionnaire at baseline, and 3 and 6 months later. Data were analysed using descriptive statistics, t-test and chi-square test, and mixed model analysis to test the impact of the intervention. A total of 31 partners of HNC patients participated in this study and completed all the evaluations. The partners in the Test group experienced significantly lower levels of anxiety (P = 0.001) and depression (P = 0.003) symptoms and were more satisfied (P = 0.002) with cancer information provided than partners in the Control group. Providing tailored information seems to have positive outcomes regarding anxiety, depression, and satisfaction in partners of HNC patients. Larger randomised studies are warranted to validate these effects. © 2016 John Wiley & Sons Ltd.

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.

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.

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.

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

PubMed

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

2009-10-23

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

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.

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.

Social marketing and community mobilisation to reduce underage alcohol consumption in Australia: A cluster randomised community trial.

PubMed

Rowland, Bosco Charles; Williams, Joanne; Smith, Rachel; Hall, Jessica Kate; Osborn, Amber; Kremer, Peter; Kelly, Adrian B; Leslie, Eva; Patton, George; Mohebbi, Mohammadreza; Toumbourou, John W

2018-08-01

In many countries adolescent alcohol use is a major health problem. To supplement national policies, it is important to trial community interventions as a potential strategy to prevent adolescent alcohol use. This study evaluated a multicomponent community intervention that included community mobilisation, social marketing, and the monitoring of alcohol sales to minors. Evaluation was a clustered randomised trial design with 14 intervention and 14 control communities. Prior to randomisation, communities were matched on socioeconomic status and location. Intervention communities were not blinded. 3545 Year 8 students (M = 12 years) were surveyed at baseline from 75 schools; 3377 students were surveyed post intervention in 2013 from 54 schools. It was hypothesised that the primary outcome, individual alcohol consumption in last 30 days, after the intervention would be 15% lower in intervention communities. Secondary outcomes were consumption in the past year and intention not to drink before age 18. The intervention communities showed larger relative reductions compared to the controls in last 30-day consumption and past year (10%), but not significantly different. A significantly lower proportion of participants in the intervention community (63%), compared to the controls (71%), reported intending to drink before 18 years old. Subgroup analysis identified regional and state differences for some secondary measures. Intervention assignment was associated with lower adolescent intention to drink before the age of 18. However, more intensive and longer-term intervention may be required to measure significant differences in behaviour change. ACTRN12612000384853. Rowland B, Toumbourou JW, Osborn A, et al. BMJ Open 2013;3:e002423. doi:10.1136/bmjopen-2012-002423. Copyright © 2018 Elsevier Inc. All rights reserved.

Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study.

PubMed

Magnus, Maria C; Miliku, Kozeta; Bauer, Anna; Engel, Stephanie M; Felix, Janine F; Jaddoe, Vincent W V; Lawlor, Debbie A; London, Stephanie J; Magnus, Per; McGinnis, Ralph; Nystad, Wenche; Page, Christian M; Rivadeneira, Fernando; Stene, Lars C; Tapia, German; Williams, Nicholas; Bonilla, Carolina; Fraser, Abigail

2018-06-20

To use mendelian randomisation to investigate whether 25-hydroxyvitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia. One and two sample mendelian randomisation analyses. Two European pregnancy cohorts (Avon Longitudinal Study of Parents and Children, and Generation R Study), and two case-control studies (subgroup nested within the Norwegian Mother and Child Cohort Study, and the UK Genetics of Pre-eclampsia Study). 7389 women in a one sample mendelian randomisation analysis (751 with gestational hypertension and 135 with pre-eclampsia), and 3388 pre-eclampsia cases and 6059 controls in a two sample mendelian randomisation analysis. Single nucleotide polymorphisms in genes associated with vitamin D synthesis (rs10741657 and rs12785878) and metabolism (rs6013897 and rs2282679) were used as instrumental variables. Gestational hypertension and pre-eclampsia defined according to the International Society for the Study of Hypertension in Pregnancy. In the conventional multivariable analysis, the relative risk for pre-eclampsia was 1.03 (95% confidence interval 1.00 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, and 2.04 (1.02 to 4.07) for 25-hydroxyvitamin D levels <25 nmol/L compared with ≥75 nmol/L. No association was found for gestational hypertension. The one sample mendelian randomisation analysis using the total genetic risk score as an instrument did not provide strong evidence of a linear effect of 25-hydroxyvitamin D on the risk of gestational hypertension or pre-eclampsia: odds ratio 0.90 (95% confidence interval 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. The two sample mendelian randomisation estimate gave an odds ratio for pre-eclampsia of 0.98 (0.89 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, an odds ratio of 0.96 (0.80 to 1.15) per unit increase in the log(odds) of 25-hydroxyvitamin D level <75 nmol/L, and an odds ratio of 0.93 (0.73 to 1.19) per unit increase in the log(odds) of 25-hydroxyvitamin D levels <50 nmol/L. No strong evidence was found to support a causal effect of vitamin D status on gestational hypertension or pre-eclampsia. Future mendelian randomisation studies with a larger number of women with pre-eclampsia or more genetic instruments that would increase the proportion of 25-hydroxyvitamin D levels explained by the instrument are needed. 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.

Insulin sensitivity and beta-cell function after carbohydrate oral loading in hip replacement surgery: a double-blind, randomised controlled clinical trial.

PubMed

Ljunggren, Stefan; Hahn, Robert G; Nyström, Thomas

2014-06-01

Surgery initiates a series of physiological stress processes in the body, inducing transient insulin resistance. Preoperative carbohydrate treatment can reduce the latter phenomenon. We investigated the effects of carbohydrate loading on insulin sensitivity and beta-cell function after elective hip replacement. Twenty-three nondiabetic patients (mean age of 68 years) who underwent elective hip replacement surgery participated in this double-blind controlled study. The patients were randomised to a nutrition group, which ingested a carbohydrate-rich fluid (50 kcal/100 ml) (Preop(®)), or a control group (tap water flavoured with lemon) 800 ml + 400 ml before the surgery. The insulin response (beta-cell function) and the insulin sensitivity were measured with an intravenous glucose tolerance test (IVGTT) and a hyperinsulinaemic euglycaemic glucose clamp, respectively, one day before and two days after the surgery. Insulin sensitivity decreased by 51% (median; 25-75th percentiles 35-61) after ingesting Preop(®) and by 39% (21-51) after ingesting in the control group (n.s.). The postoperative IVGTT in the nutrition group was followed by a significantly larger area under the curve (AUC) for plasma insulin (+54% versus the preoperative IVGTT) compared to the control group (+7%). This difference was already apparent during the first phase (0-10 min) of insulin secretion (+20 and -21%, respectively; P < 0.05). The patients randomised to the carbohydrate oral fluid or the water prior to the surgery demonstrated a significant but similar decrease in insulin sensitivity. The carbohydrates increased the beta-cell function as a compensatory response to the disposition index, resulting in a smaller reduction in surgery-induced insulin resistance compared to the tap water. The study was registered at http://www.clinicaltrials.gov (NCT01774084). Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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

PubMed

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

2013-07-01

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

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.

Amnioinfusion in preterm premature rupture of membranes (AMIPROM): a randomised controlled trial of amnioinfusion versus expectant management in very early preterm premature rupture of membranes--a pilot study.

PubMed Central

Roberts, Devender; Vause, Sarah; Martin, William; Green, Pauline; Walkinshaw, Stephen; Bricker, Leanne; Beardsmore, Caroline; Shaw, Ben N J; McKay, Andrew; Skotny, Gaynor; Williamson, Paula; Alfirevic, Zarko

2014-01-01

BACKGROUND Fetal survival is severely compromised when the amniotic membrane ruptures between 16 and 24 weeks of pregnancy. Reduced amniotic fluid levels are associated with poor lung development, whereas adequate levels lead to better perinatal outcomes. Restoring amniotic fluid by means of ultrasound-guided amnioinfusion (AI) may be of benefit in improving perinatal and long-term outcomes in children of pregnancies with this condition. OBJECTIVE The AI in preterm premature rupture of membranes (AMIPROM) pilot study was conducted to assess the feasibility of recruitment, the methods for conduct and the retention through to long-term follow-up of participants with very early rupture of amniotic membranes (between 16 and 24 weeks of pregnancy). It was also performed to assess outcomes and collect data to inform a larger, more definitive, clinical trial. DESIGN A prospective, non-blinded randomised controlled trial. A computer-generated random sequence using a 1 : 1 ratio was used. Randomisation was stratified for pregnancies in which the amniotic membrane ruptured between 16(+0) and 19(+6) weeks' gestation and 20(+0) and 24(+0) weeks' gestation. The randomisation sequence was generated in blocks of four. Telephone randomisation and intention-to-treat analysis were used. SETTING Four UK hospital-based fetal medicine units - Liverpool Women's NHS Trust, St. Mary's Hospital, Manchester, Birmingham Women's NHS Foundation Trust and Wirral University Hospitals Trust. PARTICIPANTS Women with confirmed preterm prelabour rupture of membranes between 16(+0) and 24(+0) weeks' gestation. Women with multiple pregnancies, resultant fetal abnormalities or obstetric indication for immediate delivery were excluded. INTERVENTIONS Participants were randomly allocated to either serial weekly transabdominal AI or expectant management (Exp) until 37 weeks of pregnancy, if the deepest pool of amniotic fluid was < 2 cm. MAIN OUTCOME MEASURE Short-term maternal, pregnancy and neonatal outcomes and long-term outcomes for the child were studied. Long-term respiratory morbidity was assessed using validated respiratory questionnaires at 6, 12 and 18 months of age and infant lung function was assessed at approximately 12 months of age. Neurodevelopment was assessed using Bayley's Scale of Infant Development II at a corrected age of 2 years. RESULTS Fifty-eight women were randomised and two were excluded from the analysis owing to termination of pregnancy for lethal anomaly, leaving 56 participants (28 serial AI, 28 Exp) recruited between 2002 and 2009, with annual recruitment rates varying between 2 and 14. Recruitment to the study improved significantly from 2007 with National Institute for Health Research (NIHR) funding. There was no significant difference in perinatal mortality [19/28 vs. 19/28; relative risk (RR) 1.0; 95% confidence interval (CI) 0.70 to 1.43], maternal morbidity or neonatal morbidity. The overall chance of surviving without long-term respiratory or neurodevelopmental disability is 4/56 (7.1%): 4/28 (14.3%) in the AI arm and 0/28 in the expectant arm (0%) (RR 9.0; 95% CI 0.51 to 159.70). CONCLUSIONS This pilot study found no major differences in maternal, perinatal or pregnancy outcomes. The study was not designed to show a difference between the arms and the number of survivors was too small to draw any conclusions about long-term outcomes. It does signal, however, that a larger, definitive, study to evaluate AI for improvement in healthy survival is indicated. The results suggest that, with appropriate funding, such a study is feasible. A larger, definitive, study with full health economic analysis and patient perspective assessment is required to show whether AI can improve the healthy survivor rate. PMID:24713309

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.

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.

A pilot randomised controlled trial to assess the utility of an e-learning package that trains users in adverse drug reaction causality.

PubMed

Conroy, Elizabeth J; Kirkham, Jamie J; Bellis, Jennifer R; Peak, Matthew; Smyth, Rosalind L; Williamson, Paula R; Pirmohamed, Munir

2015-12-01

Causality assessment of adverse drug reactions (ADRs) by healthcare professionals is often informal which can lead to inconsistencies in practice. The Liverpool Causality Assessment Tool (LCAT) offers a systematic approach. An interactive, web-based, e-learning package, the Liverpool ADR Causality Assessment e-learning Package (LACAeP), was designed to improve causality assessment using the LCAT. This study aimed to (1) get feedback on usability and usefulness on the LACAeP, identify areas for improvement and development, and generate data on effect size to inform a larger scale study; and (2) test the usability and usefulness of the LCAT. A pilot, single-blind, parallel-group, randomised controlled trial hosted by the University of Liverpool was undertaken. Participants were paediatric medical trainees at specialty training level 1+ within the Mersey and North-West England Deaneries. Participants were randomised (1 : 1) access to the LACAeP or no training. The primary efficacy outcome was score by correct classification, predefined by a multidisciplinary panel of experts. Following participation, feedback on both the LCAT and the LACAeP was obtained, via a built in survey, from participants. Of 57 randomised, 35 completed the study. Feedback was mainly positive although areas for improvement were identified. Seventy-four per cent of participants found the LCAT easy to use and 78% found the LACAeP training useful. Sixty-one per cent would be unlikely to recommend the training. Scores ranged from 4 to 13 out of 20. The LACAeP increased scores by 1.3, but this was not significant. Improving the LACAeP before testing it in an appropriately powered trial, informed by the differences observed, is required. Rigorous evaluation will enable a quality resource that will be of value in healthcare professional training. © 2015 The Authors. International Journal of Pharmacy Practice published by John Wiley & Sons Ltd on behalf of Royal Pharmaceutical Society.

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

PubMed

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

2017-11-01

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

Improving swallowing outcomes in patients with head and neck cancer using a theory-based pretreatment swallowing intervention package: protocol for a randomised feasibility study

PubMed Central

Smith, Christina H; Barratt, Helen; Taylor, Stuart A

2017-01-01

Introduction The incidence of head and neck cancer (HNC) in the UK is rising, with an average of 31 people diagnosed daily. Patients affected by HNC suffer significant short-term and long-term post-treatment morbidity as a result of dysphagia, which affects daily functioning and quality of life (QOL). Pretreatment swallowing exercises may provide additional benefit over standard rehabilitation in managing dysphagia after primary HNC treatments, but uncertainty about their effectiveness persists. This study was preceded by an intervention development phase to produce an optimised swallowing intervention package (SIP). The aim of the current study is to assess the feasibility of this new intervention and research processes within a National Health Service (NHS) setting. Method and analysis A two-arm non-blinded randomised controlled feasibility study will be carried out at one tertiary referral NHS centre providing specialist services in HNC. Patients newly diagnosed with stage III and IV disease undergoing planned surgery and/or chemoradiation treatments will be eligible. The SIP will be delivered pre treatment, and a range of swallowing-related and QOL measures will be collected at baseline, 1, 3 and 6 months post-treatment. Outcomes will test the feasibility of a future randomised controlled trial (RCT), detailing rate of recruitment and patient acceptance to participation and randomisation. Salient information relating to protocol implementation will be collated and study material such as the case report form will be tested. A range of candidate outcome measures will be examined for suitability in a larger RCT. Ethics and dissemination Ethical approval was obtained from an NHS Research Ethics Committee. Findings will be published open access in a peer-reviewed journal, and presented at relevant conferences and research meetings. Trial registration number ISRCTN40215425; Pre-results. PMID:28348190

Improving swallowing outcomes in patients with head and neck cancer using a theory-based pretreatment swallowing intervention package: protocol for a randomised feasibility study.

PubMed

Govender, Roganie; Smith, Christina H; Gardner, Benjamin; Barratt, Helen; Taylor, Stuart A

2017-03-27

The incidence of head and neck cancer (HNC) in the UK is rising, with an average of 31 people diagnosed daily. Patients affected by HNC suffer significant short-term and long-term post-treatment morbidity as a result of dysphagia, which affects daily functioning and quality of life (QOL). Pretreatment swallowing exercises may provide additional benefit over standard rehabilitation in managing dysphagia after primary HNC treatments, but uncertainty about their effectiveness persists. This study was preceded by an intervention development phase to produce an optimised swallowing intervention package (SIP). The aim of the current study is to assess the feasibility of this new intervention and research processes within a National Health Service (NHS) setting. A two-arm non-blinded randomised controlled feasibility study will be carried out at one tertiary referral NHS centre providing specialist services in HNC. Patients newly diagnosed with stage III and IV disease undergoing planned surgery and/or chemoradiation treatments will be eligible. The SIP will be delivered pre treatment, and a range of swallowing-related and QOL measures will be collected at baseline, 1, 3 and 6 months post-treatment. Outcomes will test the feasibility of a future randomised controlled trial (RCT), detailing rate of recruitment and patient acceptance to participation and randomisation. Salient information relating to protocol implementation will be collated and study material such as the case report form will be tested. A range of candidate outcome measures will be examined for suitability in a larger RCT. Ethical approval was obtained from an NHS Research Ethics Committee. Findings will be published open access in a peer-reviewed journal, and presented at relevant conferences and research meetings. ISRCTN40215425; 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/.

A pilot randomised controlled trial to assess the utility of an e‐learning package that trains users in adverse drug reaction causality

PubMed Central

Kirkham, Jamie J.; Bellis, Jennifer R.; Peak, Matthew; Smyth, Rosalind L.; Williamson, Paula R.; Pirmohamed, Munir

2015-01-01

Abstract Objectives Causality assessment of adverse drug reactions (ADRs) by healthcare professionals is often informal which can lead to inconsistencies in practice. The Liverpool Causality Assessment Tool (LCAT) offers a systematic approach. An interactive, web‐based, e‐learning package, the Liverpool ADR Causality Assessment e‐learning Package (LACAeP), was designed to improve causality assessment using the LCAT. This study aimed to (1) get feedback on usability and usefulness on the LACAeP, identify areas for improvement and development, and generate data on effect size to inform a larger scale study; and (2) test the usability and usefulness of the LCAT. Methods A pilot, single‐blind, parallel‐group, randomised controlled trial hosted by the University of Liverpool was undertaken. Participants were paediatric medical trainees at specialty training level 1+ within the Mersey and North‐West England Deaneries. Participants were randomised (1 : 1) access to the LACAeP or no training. The primary efficacy outcome was score by correct classification, predefined by a multidisciplinary panel of experts. Following participation, feedback on both the LCAT and the LACAeP was obtained, via a built in survey, from participants. Key findings Of 57 randomised, 35 completed the study. Feedback was mainly positive although areas for improvement were identified. Seventy‐four per cent of participants found the LCAT easy to use and 78% found the LACAeP training useful. Sixty‐one per cent would be unlikely to recommend the training. Scores ranged from 4 to 13 out of 20. The LACAeP increased scores by 1.3, but this was not significant. Conclusions Improving the LACAeP before testing it in an appropriately powered trial, informed by the differences observed, is required. Rigorous evaluation will enable a quality resource that will be of value in healthcare professional training. PMID:26032626

A pilot study to evaluate the efficacy of adding a structured home visiting intervention to improve outcomes for high-risk families attending the Incredible Years Parent Programme: study protocol for a randomised controlled trial.

PubMed

Lees, Dianne G; Fergusson, David M; Frampton, Christopher M; Merry, Sally N

2014-02-25

Antisocial behaviour and adult criminality often have their origins in childhood and are best addressed early in the child's life using evidence-based treatments such as the 'Incredible Years Parent Programme'. However, families with additional risk factors who are at highest risk for poor outcomes do not always make sufficient change while attending such programmes. Additional support to address barriers and improve implementation of positive parenting strategies while these families attend the Incredible Years Programme may improve overall outcomes.The study aims to evaluate the efficacy of adding a structured home visiting intervention (Home Parent Support) to improve outcomes in families most at risk of poor treatment response from the Incredible Years intervention. This study will inform the design of a larger prospective randomised controlled trial. A pilot single-blind, parallel, superiority, randomised controlled trial. Randomisation will be undertaken using a computer-generated sequence in a 1:1 ratio to the two treatments arranged in permuted blocks with stratification by age, sex, and ethnicity. One hundred and twenty six participants enrolled in the Incredible Years Parent Programme who meet the high-risk criteria will be randomly allocated to receive either Incredible Years Parent Programme and Home Parent Support, or the Incredible Years Parent Programme alone. The Home Parent Support is a 10-session structured home visiting intervention provided by a trained therapist, alongside the usual Incredible Years Parent Programme, to enhance the adoption of key parenting skills. The primary outcome is the change in child behaviour from baseline to post-intervention in parent reported Eyberg Child Behavior Inventory Problem Scale. This is the first formal evaluation of adding Home Parent Support alongside Incredible Years Parent Programme for families with risk factors who typically have poorer treatment outcomes. We anticipate that the intervention will help vulnerable families stay engaged, strengthen the adoption of effective parenting strategies, and improve outcomes for both the children and families. Australian New Zealand Clinical Trials Registry ACTRN12612000878875.

Health on the Web: Randomised Controlled Trial of Online Screening and Brief Alcohol Intervention Delivered in a Workplace Setting

PubMed Central

Khadjesari, Zarnie; Freemantle, Nick; Linke, Stuart; Hunter, Rachael; Murray, Elizabeth

2014-01-01

Background Alcohol misuse in England costs around £7.3 billion (US$12.2 billion) annually from lost productivity and absenteeism. Delivering brief alcohol interventions to employees as part of a health check may be acceptable, particularly with online delivery which can provide privacy for this stigmatised behaviour. Research to support this approach is limited and methodologically weak. The aim was to determine the effectiveness of online screening and personalised feedback on alcohol consumption, delivered in a workplace as part of a health check. Methods and Findings This two-group online individually randomised controlled trial recruited employees from a UK-based private sector organisation (approx. 100,000 employees). 3,375 employees completed the online health check in the three week recruitment period. Of these, 1,330 (39%) scored five or more on the AUDIT-C (indicating alcohol misuse) and were randomised to receive personalised feedback on their alcohol intake, alongside feedback on other health behaviours (n = 659), or to receive feedback on all health behaviours except alcohol intake (n = 671). Participants were mostly male (75%), with a median age of 48 years and half were in managerial positions (55%). Median Body Mass Index was 26, 12% were smokers, median time undertaking moderate/vigorous physical activity a week was 173 minutes and median fruit and vegetable consumption was three portions a day. Eighty percent (n = 1,066) of participants completed follow-up questionnaires at three months. An intention to treat analysis found no difference between experimental groups for past week drinking (primary outcome) (5.6% increase associated with the intervention (95% CI −4.7% to 16.9%; p = .30)), AUDIT (measure of alcohol-related harm) and health utility (EQ-5D). Conclusions There was no evidence to support the use of personalised feedback within an online health check for reducing alcohol consumption among employees in this organisation. Further research is needed on how to engage a larger proportion of employees in screening. Trial Registration International Standard Randomised Controlled Trial Number Register ISRCTN50658915 PMID:25409454

The Cognitive Remediation in Bipolar (CRiB) pilot study: study protocol for a randomised controlled trial.

PubMed

Strawbridge, Rebecca; Fish, Jessica; Halari, Rozmin; Hodsoll, John; Reeder, Clare; Macritchie, Karine; McCrone, Paul; Wykes, Til; Young, Allan H

2016-07-29

People with bipolar disorder often show difficulties with cognitive functioning, and though these difficulties are identified as important targets for intervention, few treatment options are available. Preliminary evidence suggests that cognitive remediation therapy (a psychological treatment proven beneficial for people diagnosed as having schizophrenia) is helpful for people with bipolar disorders. We are conducting a pilot trial to determine whether individual, computerised, cognitive remediation therapy (CRT) for people with bipolar disorder 1) increases cognitive function; 2) improves global functioning, goal attainment and mood symptoms; 3) is acceptable and feasible for participants; and 4) can be addressed in a comprehensive, larger, randomised, controlled trial. The study is designed as a two-arm, randomised, controlled trial comparing cognitive remediation therapy with treatment-as-usual (TAU) for euthymic bipolar patients. Participants are eligible to take part if aged between 18 and 65 with a diagnosis of bipolar disorder (type I) and currently in euthymic state, and no neurological, substance or personality disorder diagnoses. Sixty participants will be recruited (mainly through secondary and tertiary care) and will be block-randomised to receive either treatment-as-usual alone or in addition to a 12-week course of cognitive remediation therapy totalling 20-40 therapy hours. The intervention will comprise regular sessions with a therapist and computer-based training. Research assessments will take place before and after the intervention period and at a 12-week follow-up, and will include evaluation of neuropsychological, symptom-related, demographic and social factors, as well as collecting qualitative data regarding CRT expectations and satisfaction. Intention-to-treat analyses will examine the efficacy of cognitive remediation therapy primarily on cognition and additionally on functioning, quality of life and mood symptoms. Furthermore, we will examine the acceptability of CRT and undertake a preliminary health economics analysis to ascertain the cost of delivering the intervention. The results of this trial will provide valuable information about whether cognitive remediation therapy may be beneficial for people diagnosed with bipolar disorder in a euthymic state. ISRCTN registry, ISRCTN32290525 . Registered on 2 March 2016.

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/.

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

PubMed

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

2017-03-28

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

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

PubMed

Tu, Wenjing; Xu, Guihua; Du, Shizheng

2015-10-01

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

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

PubMed

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

2017-04-01

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

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

PubMed

Thompson, Carl

2004-01-01

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

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

PubMed

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

2004-10-01

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

[Efficacy of HRV-biofeedback as additional treatment of depression and PTSD].

PubMed

Blase, K L; van Dijke, A; Cluitmans, P J M; Vermetten, E

2016-01-01

Heartrate variability biofeedback (HRVB) is a non-invasive treatment in which patients are assumed to self-regulate a physiological dysregulated vagal nerve. Although the therapeutic approach of HRVB is promising in various stress-related disorders, it has only been offered on a regular basis in a few mental health treatment settings. To analyse the efficacy of HRV biofeedback as an additional psychophysiological treatment for depression and PTSD. Systematic review with search terms HRV, biofeedback, PTSD, depression, panic disorder and anxiety disorder. Our search of the literature yielded 789 studies. After critical appraisal using the GRADE method, we selected 6 randomised controlled trials (RCTs) and 4 relevant studies. The RCTs with control groups 'treatment as usual' and muscle relaxation training revealed significant clinical efficacy and better results than control conditions after 4 to 8 weeks training. Although this systematic review shows the popularity of HRV in literature, it does not indicate that HRVB really has been reviewed systematically. Significant outcomes of this limited number of randomised studies indicate there may be a clinical improvement when HRVB training is integrated into treatment of PTSD and depression, particularly when this integration procedure is combined with psychotherapy. More research needs to be done with larger groups and further efforts are needed to integrate HRVB into treatment of stress-related disorders in psychiatry. Future research also needs to focus on the psychophysiological mechanisms involved.

A small-scale randomised controlled trial of home telemonitoring in patients with severe chronic obstructive pulmonary disease.

PubMed

Shany, Tal; Hession, Michael; Pryce, David; Roberts, Mary; Basilakis, Jim; Redmond, Stephen; Lovell, Nigel; Schreier, Guenter

2017-08-01

Introduction This was a pilot study to examine the effects of home telemonitoring (TM) of patients with severe chronic obstructive pulmonary disease (COPD). Methods A randomised controlled 12-month trial of 42 patients with severe COPD was conducted. Home TM of oximetry, temperature, pulse, electrocardiogram, blood pressure, spirometry, and weight with telephone support and home visits was tested against a control group receiving only identical telephone support and home visits. Results The results suggest that TM had a reduction in COPD-related admissions, emergency department presentations, and hospital bed days. TM also seemed to increase the interval between COPD-related exacerbations requiring a hospital visit and prolonged the time to the first admission. The interval between hospital visits was significantly different between the study arms, while the other findings did not reach significance and only suggest a trend. There was a reduction in hospital admission costs. TM was adopted well by most patients and eventually, also by the nursing staff, though it did not seem to change patients' psychological well-being. Discussion Ability to draw firm conclusions is limited due to the small sample size. However the trends of reducing hospital visits warrant a larger study of a similar design. When designing such a trial, one should consider the potential impact of the high quality of care already made available to this patient cohort.

Counselling versus low-intensity cognitive behavioural therapy for persistent sub-threshold and mild depression (CLICD): a pilot/feasibility randomised controlled trial.

PubMed

Freire, Elizabeth; Williams, Christopher; Messow, Claudia-Martina; Cooper, Mick; Elliott, Robert; McConnachie, Alex; Walker, Andrew; Heard, Deborah; Morrison, Jill

2015-08-15

Persistent depressive symptoms below the threshold criteria for major depression represent a chronic condition with high risk of progression to a diagnosis of major depression. The evidence base for psychological treatments such as Person-Centred Counselling and Low-Intensity Cognitive Behavioural Therapy for sub-threshold depressive symptoms and mild depression is limited, particularly for longer-term outcomes. This study aimed to test the feasibility of delivering a randomised controlled trial into the clinical and cost effectiveness of Low-Intensity Cognitive Behavioural Therapy versus Person-Centred Counselling for patients with persistent sub-threshold depressive symptoms and mild depression. The primary outcome measures for this pilot/feasibility trial were recruitment, adherence and retention rates at six months from baseline. An important secondary outcome measure was recovery from, or prevention of, depression at six months assessed via a structured clinical interview by an independent assessor blind to the participant's treatment condition. Thirty-six patients were recruited in five general practices and were randomised to either eight weekly sessions of person-centred counselling each lasting up to an hour, or up to eight weeks of cognitive-behavioural self-help resources with guided telephone support sessions lasting 20-30 minutes each. Recruitment rate in relation to the number of patients approached at the general practices was 1.8 %. Patients attended an average of 5.5 sessions in both interventions. Retention rate for the 6-month follow-up assessments was 72.2 %. Of participants assessed at six months, 71.4 % of participants with a diagnosis of mild depression at baseline had recovered, while 66.7 % with a diagnosis of persistent subthreshold depression at baseline had not developed major depression. There were no significant differences between treatment groups for both recovery and prevention of depression at six months or on any of the outcome measures. It is feasible to recruit participants and successfully deliver both interventions in a primary care setting to patients with subthreshold and mild depression; however recruiting requires significant input at the general practices. The evidence from this study suggests that short-term Person-Centred Counselling and Low-Intensity Cognitive Behaviour Therapy are potentially effective and their effectiveness should be evaluated in a larger randomised controlled study which includes a health economic evaluation. Current Controlled Trials ISRCTN60972025 .

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

PubMed

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

2018-04-13

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

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

Advance care planning--a multi-centre cluster randomised clinical trial: the research protocol of the ACTION study.

PubMed

Rietjens, Judith A C; Korfage, Ida J; Dunleavy, Lesley; Preston, Nancy J; Jabbarian, Lea J; Christensen, Caroline Arnfeldt; de Brito, Maja; Bulli, Francesco; Caswell, Glenys; Červ, Branka; van Delden, Johannes; Deliens, Luc; Gorini, Giuseppe; Groenvold, Mogens; Houttekier, Dirk; Ingravallo, Francesca; Kars, Marijke C; Lunder, Urška; Miccinesi, Guido; Mimić, Alenka; Paci, Eugenio; Payne, Sheila; Polinder, Suzanne; Pollock, Kristian; Seymour, Jane; Simonič, Anja; Johnsen, Anna Thit; Verkissen, Mariëtte N; de Vries, Esther; Wilcock, Andrew; Zwakman, Marieke; van der Heide Pl, Agnes

2016-04-08

Awareness of preferences regarding medical care should be a central component of the care of patients with advanced cancer. Open communication can facilitate this but can occur in an ad hoc or variable manner. Advance care planning (ACP) is a formalized process of communication between patients, relatives and professional caregivers about patients' values and care preferences. It raises awareness of the need to anticipate possible future deterioration of health. ACP has the potential to improve current and future healthcare decision-making, provide patients with a sense of control, and improve their quality of life. We will study the effects of the ACP program Respecting Choices on the quality of life of patients with advanced lung or colorectal cancer. In a phase III multicenter cluster randomised controlled trial, 22 hospitals in 6 countries will be randomised. In the intervention sites, patients will be offered interviews with a trained facilitator. In the control sites, patients will receive care as usual. In total, 1360 patients will be included. All participating patients will be asked to complete questionnaires at inclusion, and again after 2.5 and 4.5 months. If a patient dies within a year after inclusion, a relative will be asked to complete a questionnaire on end-of-life care. Use of medical care will be assessed by checking medical files. The primary endpoint is patients' quality of life at 2.5 months post-inclusion. Secondary endpoints are the extent to which care as received is aligned with patients' preferences, patients' evaluation of decision-making processes, quality of end-of-life care and cost-effectiveness of the intervention. A complementary qualitative study will be carried out to explore the lived experience of engagement with the Respecting Choices program from the perspectives of patients, their Personal Representatives, healthcare providers and facilitators. Transferring the concept of ACP from care of the elderly to patients with advanced cancer, who on average are younger and retain their mental capacity for a larger part of their disease trajectory, is an important next step in an era of increased focus on patient centered healthcare and shared decision-making. International Standard Randomised Controlled Trial Number: ISRCTN63110516. Date of registration: 10/3/2014.

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.

The effect of funding sources on donepezil randomised controlled trial outcome: a meta-analysis.

PubMed

Killin, Lewis O J; Russ, Tom C; Starr, John M; Abrahams, Sharon; Della Sala, Sergio

2014-04-07

To investigate whether there is a difference in the treatment effect of donepezil on cognition in Alzheimer disease between industry-funded and independent randomised controlled trials. Fixed effects meta-analysis of standardised effects of donepezil on cognition as measured by the Mini Mental State Examination and the Alzheimer's Disease Assessment Scale-cognitive subscale. Studies included in the meta-analyses reported in the National Institute for Health and Care Excellence (NICE) technical appraisal 217 updated with new studies through a PubMed search. Inclusion criteria were double-blind, placebo-controlled trials of any length comparing patients diagnosed with probable Alzheimer disease (according to the NINCDS-ADRDA/DSM-III/IV criteria) taking any dosage of donepezil. Studies of combination therapies (eg, donepezil and memantine) were excluded, as were studies that enrolled patients with a diagnosis of Alzheimer disease associated with other disorders (eg, Parkinson's disease and Down's syndrome). Our search strategy identified 14 relevant trials (4 independent) with suitable data. Trials sponsored by pharmaceutical companies reported a larger effect of donepezil on standardised cognitive tests than trials published by independent research groups (standardised mean difference (SMD)=0.46, 95% CI 0.37 to 0.55 vs SMD=0.33, 95% CI 0.18 to 0.48, respectively). This difference remained when only data representing change up to 12 weeks from baseline were analysed (industry SMD=0.44, 95% CI 0.34 to 0.53 vs independent SMD=0.35, 95% CI 0.18 to 0.52). Analysis revealed that the effect of funding as a moderator variable of study heterogeneity was not statistically significant at either time point. The effect size of donepezil on cognition is larger in industry-funded than independent trials and this is not explained by the longer duration of industry-funded trials. The lack of a statistically significant moderator effect may indicate that the differences are due to chance, but may also result from lack of power.

Effectiveness of chronic care models for the management of type 2 diabetes mellitus in Europe: a systematic review and meta-analysis

PubMed Central

Bongaerts, Brenda W C; Müssig, Karsten; Wens, Johan; Lang, Caroline; Schwarz, Peter; Roden, Michael; Rathmann, Wolfgang

2017-01-01

Objectives We evaluated the effectiveness of European chronic care programmes for type 2 diabetes mellitus (characterised by integrative care and a multicomponent framework for enhancing healthcare delivery), compared with usual diabetes care. Design Systematic review and meta-analysis. Data sources MEDLINE, Embase, CENTRAL and CINAHL from January 2000 to July 2015. Eligibility criteria Randomised controlled trials focussing on (1) adults with type 2 diabetes, (2) multifaceted diabetes care interventions specifically designed for type 2 diabetes and delivered in primary or secondary care, targeting patient, physician and healthcare organisation and (3) usual diabetes care as the control intervention. Data extraction Study characteristics, characteristics of the intervention, data on baseline demographics and changes in patient outcomes. Data analysis Weighted mean differences in change in HbA1c and total cholesterol levels between intervention and control patients (95% CI) were estimated using a random-effects model. Results Eight cluster randomised controlled trials were identified for inclusion (9529 patients). One year of multifaceted care improved HbA1c levels in patients with screen-detected and newly diagnosed diabetes, but not in patients with prevalent diabetes, compared to usual diabetes care. Across all seven included trials, the weighted mean difference in HbA1c change was −0.07% (95% CI −0.10 to −0.04) (−0.8 mmol/mol (95% CI −1.1 to −0.4)); I2=21%. The findings for total cholesterol, LDL-cholesterol and blood pressure were similar to HbA1c, albeit statistical heterogeneity between studies was considerably larger. Compared to usual care, multifaceted care did not significantly change quality of life of the diabetes patient. Finally, measured for screen-detected diabetes only, the risk of macrovascular and mircovascular complications at follow-up was not significantly different between intervention and control patients. Conclusions Effects of European multifaceted diabetes care patient outcomes are only small. Improvements are somewhat larger for screen-detected and newly diagnosed diabetes patients than for patients with prevalent diabetes. PMID:28320788

Effectiveness of chronic care models for the management of type 2 diabetes mellitus in Europe: a systematic review and meta-analysis.

PubMed

Bongaerts, Brenda W C; Müssig, Karsten; Wens, Johan; Lang, Caroline; Schwarz, Peter; Roden, Michael; Rathmann, Wolfgang

2017-03-20

We evaluated the effectiveness of European chronic care programmes for type 2 diabetes mellitus (characterised by integrative care and a multicomponent framework for enhancing healthcare delivery), compared with usual diabetes care. Systematic review and meta-analysis. MEDLINE, Embase, CENTRAL and CINAHL from January 2000 to July 2015. Randomised controlled trials focussing on (1) adults with type 2 diabetes, (2) multifaceted diabetes care interventions specifically designed for type 2 diabetes and delivered in primary or secondary care, targeting patient, physician and healthcare organisation and (3) usual diabetes care as the control intervention. Study characteristics, characteristics of the intervention, data on baseline demographics and changes in patient outcomes. Weighted mean differences in change in HbA1c and total cholesterol levels between intervention and control patients (95% CI) were estimated using a random-effects model. Eight cluster randomised controlled trials were identified for inclusion (9529 patients). One year of multifaceted care improved HbA1c levels in patients with screen-detected and newly diagnosed diabetes, but not in patients with prevalent diabetes, compared to usual diabetes care. Across all seven included trials, the weighted mean difference in HbA1c change was -0.07% (95% CI -0.10 to -0.04) (-0.8 mmol/mol (95% CI -1.1 to -0.4)); I 2 =21%. The findings for total cholesterol, LDL-cholesterol and blood pressure were similar to HbA1c, albeit statistical heterogeneity between studies was considerably larger. Compared to usual care, multifaceted care did not significantly change quality of life of the diabetes patient. Finally, measured for screen-detected diabetes only, the risk of macrovascular and mircovascular complications at follow-up was not significantly different between intervention and control patients. Effects of European multifaceted diabetes care patient outcomes are only small. Improvements are somewhat larger for screen-detected and newly diagnosed diabetes patients than for patients with prevalent diabetes. 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/.

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

PubMed Central

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

2009-01-01

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

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.

Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial.

PubMed

Moll, Etelka; Bossuyt, Patrick M M; Korevaar, Johanna C; Lambalk, Cornelis B; van der Veen, Fulco

2006-06-24

To compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome. Randomised clinical trial. Multicentre trial in 20 Dutch hospitals. 228 women with polycystic ovary syndrome. Clomifene citrate plus metformin or clomifene citrate plus placebo. The primary outcome measure was ovulation. Secondary outcome measures were ongoing pregnancy, spontaneous abortion, and clomifene resistance. 111 women were allocated to clomifene citrate plus metformin (metformin group) and 114 women were allocated to clomifene citrate plus placebo (placebo group). The ovulation rate in the metformin group was 64% compared with 72% in the placebo group, a non-significant difference (risk difference - 8%, 95% confidence interval - 20% to 4%). There were no significant differences in either rate of ongoing pregnancy (40% v 46%; - 6%, - 20% to 7%) or rate of spontaneous abortion (12% v 11%; 1%, - 7% to 10%). A significantly larger proportion of women in the metformin group discontinued treatment because of side effects (16% v 5%; 11%, 5% to 16%). Metformin is not an effective addition to clomifene citrate as the primary method of inducing ovulation in women with polycystic ovary syndrome. Current Controlled Trials ISRCTN55906981 [controlled-trials.com].

Short-term effects of a peer co-led educational programme delivered before mental health treatment: A randomised controlled trial.

PubMed

Lara-Cabrera, M L; Gjerden, M; Gråwe, R W; Linaker, O M; Steinsbekk, A

2016-07-01

To investigate the 1-month effects of an educational programme co-led by peers delivered before treatment on treatment preferences, self-management knowledge and motivation in comparison to usual care. Adults referred to a community mental health centre were randomised to either a control group (n=48) or a peer co-led educational programme (intervention group, n=45). The programme consisted of an 8-hour group education session followed by an individual pretreatment planning session. The main topics of the educational programme were treatment options, patients' rights, self-management, the importance of patient activation and participation. At 1-month follow-up, a significantly larger proportion of the patients in the intervention group knew which type of treatment they preferred (76.7% vs. 32.5%, p<0.001). The intervention group had significantly higher self-management knowledge (p<0.001). There was no effect on treatment motivation (p=0.543). At 1-month following the delivery of a pretreatment educational programme, we found that participants' knowledge of treatment preferences and self-management had improved. Educational interventions co-led by peers can optimise the process of informing and educating outpatients, thereby helping patients to clarify their treatment preferences. Copyright © 2016 The Authors. Published by Elsevier Ireland 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.

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

PubMed

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

2008-09-20

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

Lack of efficacy of Lactobacillus GG in reducing pulmonary exacerbations and hospital admissions in children with cystic fibrosis: A randomised placebo controlled trial.

PubMed

Bruzzese, Eugenia; Raia, Valeria; Ruberto, Eliana; Scotto, Riccardo; Giannattasio, Antonietta; Bruzzese, Dario; Cavicchi, Maria Cristina; Francalanci, Michela; Colombo, Carla; Faelli, Nadia; Daccò, Valeria; Magazzù, Giuseppe; Costa, Stefano; Lucidi, Vincenzina; Majo, Fabio; Guarino, Alfredo

2017-11-08

Intestinal dysbiosis has been described in Cystic Fibrosis (CF) and probiotics have been proposed to restore microbial composition. Aim of the study was to investigate the effects of Lactobacillus rhamnosus GG (LGG) on clinical outcomes in children with cystic fibrosis (CF). A multicentre, randomised double-blind, clinical trial was conducted in children with CF. After 6months of baseline assessment, enrolled children (2 to 16years of age) received Lactobacillus GG (6×10 9 CFU/day) or placebo for 12months. Primary outcomes were proportion of subjects with at least one pulmonary exacerbation and hospitalisation over 12months. Secondary endpoints were total number of exacerbations and hospitalisations, pulmonary function, and nutritional status. Ninety-five patients were enrolled (51/95 female; median age of 103±50months). In a multivariate GEE logistic analysis, the odds of experiencing at least one exacerbation was not significantly different between the two groups, also after adjusting for the presence of different microbial organisms and for the number of pulmonary exacerbations within 6months before randomisation (OR 0.83; 95% CI 0.38 to 1.82, p=0.643). Similarly, LGG supplementation did not significantly affect the odds of hospitalisations (OR 1.67; 95% CI 0.75 to 3.72, p=0.211). No significant difference was found for body mass index and FEV1. LGG supplementation had no effect on respiratory and nutritional outcomes in this large study population of children with CF under stringent randomised clinical trial conditions. Whether earlier interventions, larger doses, or different strains of probiotics may be effective is unknown. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. 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

The effect of macronutrients on glycaemic control: a systematic review of dietary randomised controlled trials in overweight and obese adults with type 2 diabetes in which there was no difference in weight loss between treatment groups.

PubMed

Emadian, Amir; Andrews, Rob C; England, Clare Y; Wallace, Victoria; Thompson, Janice L

2015-11-28

Weight loss is crucial for treating type 2 diabetes mellitus (T2DM). It remains unclear which dietary intervention is best for optimising glycaemic control, or whether weight loss itself is the main reason behind observed improvements. The objective of this study was to assess the effects of various dietary interventions on glycaemic control in overweight and obese adults with T2DM when controlling for weight loss between dietary interventions. A systematic review of randomised controlled trials (RCT) was conducted. Electronic searches of Medline, Embase, Cinahl and Web of Science databases were conducted. Inclusion criteria included RCT with minimum 6 months duration, with participants having BMI≥25·0 kg/m2, a diagnosis of T2DM using HbA1c, and no statistically significant difference in mean weight loss at the end point of intervention between dietary arms. Results showed that eleven studies met the inclusion criteria. Only four RCT indicated the benefit of a particular dietary intervention over another in improving HbA1c levels, including the Mediterranean, vegan and low glycaemic index (GI) diets. However the findings from one of the four studies showing a significant benefit are questionable because of failure to control for diabetes medications and poor adherence to the prescribed diets. In conclusion there is currently insufficient evidence to suggest that any particular diet is superior in treating overweight and obese patients with T2DM. Although the Mediterranean, vegan and low-GI diets appear to be promising, further research that controls for weight loss and the effects of diabetes medications in larger samples is needed.

Effect of tailored on-road driving lessons on driving safety in older adults: A randomised controlled trial.

PubMed

Anstey, Kaarin J; Eramudugolla, Ranmalee; Kiely, Kim M; Price, Jasmine

2018-06-01

We evaluated the effectiveness of individually tailored driving lessons compared with a road rules refresher course for improving older driver safety. Two arm parallel randomised controlled trial, involving current drivers aged 65 and older (Mean age 72.0, 47.4% male) residing in Canberra, Australia. The intervention group (n = 28) received a two-hour class-based road rules refresher course, and two one-hour driving lessons tailored to improve poor driving skills and habits identified in a baseline on-road assessment. The control group (n = 29) received the road rules refresher course only. Tests of cognitive performance, and on-road driving were conducted at baseline and at 12-weeks. Main outcome measure was the Driver safety rating (DSR) on the on-road driving test. The number of Critical Errors made during the on-road was also recorded. 55 drivers completed the trial (intervention group: 27, control group: 28). Both groups showed reduction in dangerous/hazardous driver errors that required instructor intervention. From baseline to follow-up there was a greater reduction in the number of critical errors made by the intervention group relative to the control group (IRR = 0.53, SE = 0.1, p = .008). The intervention group improved on the DSR more than the control group (intervention mean change = 1.07 SD = 2.00, control group mean change = 0.32 SD = 1.61). The intervention group had 64% remediation of unsafe driving, where drivers who achieved a score of 'fail' at baseline, 'passed' at follow-up. The control group had 25% remediation. Tailored driving lessons reduced the critical driving errors made by older adults. Longer term follow-up and larger trials are required. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

Collaborative care for sick-listed workers with major depressive disorder: a randomised controlled trial from the Netherlands Depression Initiative aimed at return to work and depressive symptoms.

PubMed

Vlasveld, Moniek C; van der Feltz-Cornelis, Christina M; Adèr, Herman J; Anema, Johannes R; Hoedeman, Rob; van Mechelen, Willem; Beekman, Aartjan T F

2013-04-01

Major depressive disorder (MDD) is associated with absenteeism. In this study, the effectiveness of collaborative care, with a focus on return to work (RTW), was evaluated in its effect on depressive symptoms and the duration until RTW in sick-listed workers with MDD in the occupational health setting. In this randomised controlled trial, 126 sick-listed workers with MDD were randomised to usual care (N=61) or collaborative care (N=65). Collaborative care was applied by the occupational physician care manager, supported by a web-based tracking system and a consultant psychiatrist. Primary outcome measure was time to response. Secondary outcome measures were time to remission, depressive symptoms as continuous measure and the duration until full RTW. Collaborative care participants had a shorter time to response, with a difference of 2.8 months. However, no difference was found on time to remission or depressive symptoms as continuous measure. With a mean of 190 days in the collaborative care group, and 210 days in the usual care group, the groups did not differ significantly from each other in the duration until full RTW. Adherence to the collaborative care intervention was low. These results do not justify a widespread implementation of collaborative care in occupational healthcare, as it was operationalised in this study. However, since the study might have been underpowered for RTW and because treatment integrity was low, further research, with larger sample sizes, is needed to develop the best fitting (collaborative care) model for addressing RTW in depressed sick-listed workers. : ISRCTN78462860.

Rivastigmine in apathetic but dementia and depression-free patients with Parkinson's disease: a double-blind, placebo-controlled, randomised clinical trial.

PubMed

Devos, David; Moreau, Caroline; Maltête, David; Lefaucheur, Romain; Kreisler, Alexandre; Eusebio, Alexandre; Defer, Gilles; Ouk, Thavarak; Azulay, Jean-Philippe; Krystkowiak, Pierre; Witjas, Tatiana; Delliaux, Marie; Destée, Alain; Duhamel, Alain; Bordet, Régis; Defebvre, Luc; Dujardin, Kathy

2014-06-01

Even with optimal dopaminergic treatments, many patients with Parkinson's disease (PD) are frequently incapacitated by apathy prior to the development of dementia. We sought to establish whether rivastigmine's ability to inhibit acetyl- and butyrylcholinesterases could relieve the symptoms of apathy in dementia-free, non-depressed patients with advanced PD. We performed a multicentre, parallel, double-blind, placebo-controlled, randomised clinical trial (Protocol ID: 2008-002578-36; clinicaltrials.gov reference: NCT00767091) in patients with PD with moderate to severe apathy (despite optimised dopaminergic treatment) and without dementia. Patients from five French university hospitals were randomly assigned 1:1 to rivastigmine (transdermal patch of 9.5 mg/day) or placebo for 6 months. The primary efficacy criterion was the change over time in the Lille Apathy Rating Scale (LARS) score. 101 consecutive patients were screened, 31 were eligible and 16 and 14 participants were randomised into the rivastigmine and placebo groups, respectively. Compared with placebo, rivastigmine improved the LARS score (from -11.5 (-15/-7) at baseline to -20 (-25/-12) after treatment; F(1, 25)=5.2; p=0.031; adjusted size effect: -0.9). Rivastigmine also improved the caregiver burden and instrumental activities of daily living but failed to improve quality of life. No severe adverse events occurred in the rivastigmine group. Rivastigmine may represent a new therapeutic option for moderate to severe apathy in advanced PD patients with optimised dopaminergic treatment and without depression dementia. These findings require confirmation in a larger clinical trial. Our results also confirmed that the presence of apathy can herald a pre-dementia state in PD. Clinicaltrials.gov reference: NCT00767091.

A randomised controlled trial of an active telephone-based recruitment strategy to increase childcare-service staff attendance at a physical activity and nutrition training workshop.

PubMed

Yoong, Sze Lin; Wolfenden, Luke; Finch, Meghan; Williams, Amanda; Dodds, Pennie; Gillham, Karen; Wyse, Rebecca

2013-12-01

Centre-based childcare services represent a promising setting to target the prevention of excessive weight gain in preschool-aged children. Staff training is a key component of multi-strategy interventions to improve implementation of effective physical activity and nutrition promoting practices for obesity prevention in childcare services. This randomised controlled trial aimed to examine whether an active telephone-based strategy to invite childcare-service staff to attend a training workshop was effective in increasing the proportion of services with staff attending training, compared with a passive strategy. Services were randomised to an active telephone-based or a passive-recruitment strategy. Those in the active arm received an email invitation and one to three follow-up phone calls, whereas services in the passive arm were informed of the availability of training only via newsletters. The proportion of services with staff attending the training workshop was compared between the two arms. One hundred and twenty-eight services were included in this study. A significantly larger proportion (52%) of services in the active arm compared with those in the passive-strategy arm (3.1%) attended training (d.f.=1, χ2=34.3; P<0.001). An active, telephone-based recruitment strategy significantly increased the proportion of childcare services with staff attending training. Further strategies to improve staff attendance at training need to be identified and implemented. SO WHAT?: Active-recruitment strategies including follow-up telephone calls should be utilised to invite staff to participate in training, in order to maximise the use of training as an implementation strategy for obesity prevention in childcare services.

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

Compression stockings in the management of fractures of the ankle: a randomised controlled trial.

PubMed

Sultan, M J; Zhing, T; Morris, J; Kurdy, N; McCollum, C N

2014-08-01

In this randomised controlled trial, we evaluated the role of elastic compression using ankle injury stockings (AIS) in the management of fractures of the ankle. A total of 90 patients with a mean age of 47 years (16 to 79) were treated within 72 hours of presentation with a fracture of the ankle, 31 of whom were treated operatively and 59 conservatively, were randomised to be treated either with compression by AIS plus an Aircast boot or Tubigrip plus an Aircast boot. Male to female ratio was 36:54. The primary outcome measure was the functional Olerud-Molander ankle score (OMAS). The secondary outcome measures were; the American Orthopaedic Foot and Ankle Society score (AOFAS); the Short Form (SF)-12v2 Quality of Life score; and the frequency of deep vein thrombosis (DVT). Compression using AIS reduced swelling of the ankle at all time points and improved the mean OMAS score at six months to 98 (95% confidence interval (CI) 96 to 99) compared with a mean of 67 (95% CI 62 to 73) for the Tubigrip group (p < 0.001). The mean AOFAS and SF-12v2 scores at six months were also significantly improved by compression. Of 86 patients with duplex imaging at four weeks, five (12%) of 43 in the AIS group and ten (23%) of 43 in the Tubigrip group developed a DVT (p = 0.26). Compression improved functional outcome and quality of life following fracture of the ankle. DVTs were frequent, but a larger study would be needed to confirm that compression with AISs reduces the incidence of DVT. ©2014 The British Editorial Society of Bone & Joint Surgery.

Investigating the relationship between predictability and imbalance in minimisation: a simulation study

PubMed Central

2013-01-01

Background The use of restricted randomisation methods such as minimisation is increasing. This paper investigates under what conditions it is preferable to use restricted randomisation in order to achieve balance between treatment groups at baseline with regard to important prognostic factors and whether trialists should be concerned that minimisation may be considered deterministic. Methods Using minimisation as the randomisation algorithm, treatment allocation was simulated for hypothetical patients entering a theoretical study having values for prognostic factors randomly assigned with a stipulated probability. The number of times the allocation could have been determined with certainty and the imbalances which might occur following randomisation using minimisation were examined. Results Overall treatment balance is relatively unaffected by reducing the probability of allocation to optimal treatment group (P) but within-variable balance can be affected by any P <1. This effect is magnified by increased numbers of prognostic variables, the number of categories within them and the prevalence of these categories within the study population. Conclusions In general, for smaller trials, probability of treatment allocation to the treatment group with fewer numbers requires a larger value P to keep treatment and variable groups balanced. For larger trials probability of allocation values from P = 0.5 to P = 0.8 can be used while still maintaining balance. For one prognostic variable there is no significant benefit in terms of predictability in reducing the value of P. However, for more than one prognostic variable, significant reduction in levels of predictability can be achieved with the appropriate choice of P for the given trial design. PMID:23537389

Investigating the relationship between predictability and imbalance in minimisation: a simulation study.

PubMed

McPherson, Gladys C; Campbell, Marion K; Elbourne, Diana R

2013-03-27

The use of restricted randomisation methods such as minimisation is increasing. This paper investigates under what conditions it is preferable to use restricted randomisation in order to achieve balance between treatment groups at baseline with regard to important prognostic factors and whether trialists should be concerned that minimisation may be considered deterministic. Using minimisation as the randomisation algorithm, treatment allocation was simulated for hypothetical patients entering a theoretical study having values for prognostic factors randomly assigned with a stipulated probability. The number of times the allocation could have been determined with certainty and the imbalances which might occur following randomisation using minimisation were examined. Overall treatment balance is relatively unaffected by reducing the probability of allocation to optimal treatment group (P) but within-variable balance can be affected by any P <1. This effect is magnified by increased numbers of prognostic variables, the number of categories within them and the prevalence of these categories within the study population. In general, for smaller trials, probability of treatment allocation to the treatment group with fewer numbers requires a larger value P to keep treatment and variable groups balanced. For larger trials probability of allocation values from P = 0.5 to P = 0.8 can be used while still maintaining balance. For one prognostic variable there is no significant benefit in terms of predictability in reducing the value of P. However, for more than one prognostic variable, significant reduction in levels of predictability can be achieved with the appropriate choice of P for the given trial design.

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

Effectiveness of provider incentives for anaemia reduction in rural China: a cluster randomised trial

PubMed Central

Luo, Renfu; Zhang, Linxiu; Sylvia, Sean; Shi, Yaojiang; Foo, Patricia; Zhao, Qiran; Martorell, Reynaldo; Medina, Alexis; Rozelle, Scott

2012-01-01

Objectives To test the impact of provider performance pay for anaemia reduction in rural China. Design A cluster randomised trial of information, subsidies, and incentives for school principals to reduce anaemia among their students. Enumerators and study participants were not informed of study arm assignment. Setting 72 randomly selected rural primary schools across northwest China. Participants 3553 fourth and fifth grade students aged 9-11 years. All fourth and fifth grade students in sample schools participated in the study. Interventions Sample schools were randomly assigned to a control group, with no intervention, or one of three treatment arms: (a) an information arm, in which principals received information about anaemia; (b) a subsidy arm, in which principals received information and unconditional subsidies; and (c) an incentive arm, in which principals received information, subsidies, and financial incentives for reducing anaemia among students. Twenty seven schools were assigned to the control arm (1816 students at baseline, 1623 at end point), 15 were assigned to the information arm (659 students at baseline, 596 at end point), 15 to the subsidy arm (726 students at baseline, 667 at end point), and 15 to the incentive arm (743 students at baseline, 667 at end point). Main outcome measures Student haemoglobin concentrations. Results Mean student haemoglobin concentration rose by 1.5 g/L (95% CI –1.1 to 4.1) in information schools, 0.8 g/L (–1.8 to 3.3) in subsidy schools, and 2.4 g/L (0 to 4.9) in incentive schools compared with the control group. This increase in haemoglobin corresponded to a reduction in prevalence of anaemia (Hb <115 g/L) of 24% in incentive schools. Interactions with pre-existing incentives for principals to achieve good academic performance led to substantially larger gains in the information and incentive arms: when combined with incentives for good academic performance, associated effects on student haemoglobin concentration were 9.8 g/L (4.1 to 15.5) larger in information schools and 8.6 g/L (2.1 to 15.1) larger in incentive schools. Conclusions Financial incentives for health improvement were modestly effective. Understanding interactions with other motives and pre-existing incentives is critical. Trial registration number ISRCTN76158086. PMID:22842354

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

PubMed Central

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

2008-01-01

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

Safety and efficacy of the predictive low glucose management system in the prevention of hypoglycaemia: protocol for randomised controlled home trial to evaluate the Suspend before low function

PubMed Central

Abraham, M B; Nicholas, J A; Ly, T T; Roby, H C; Paramalingam, N; Fairchild, J; King, B R; Ambler, G R; Cameron, F; Davis, E A; Jones, T W

2016-01-01

Introduction Innovations with sensor-augmented pump therapy (SAPT) to reduce hypoglycaemia in patients with type 1 diabetes are an ongoing area of research. The predictive low glucose management (PLGM) system incorporates continuous glucose sensor data into an algorithm and suspends basal insulin before the occurrence of hypoglycaemia. The system was evaluated in in-clinic studies, and has informed the parameters of a larger home trial to study its efficacy and safety in real life. Methods and analysis The aim of this report is to describe the study design and outcome measures for the trial. This is a 6-month, multicentre, randomised controlled home trial to test the PLGM system in children and adolescents with type 1 diabetes. The system is available in the Medtronic MiniMed 640G pump as the ‘Suspend before low’ feature. Following a run-in period, participants are randomised to either the control arm with SAPT alone or the intervention arm with SAPT and Suspend before low. The primary aim of this study is to evaluate the time spent hypoglycaemic (sensor glucose <3.5 mmol/L) with and without the system. The secondary aims are to determine the number of hypoglycaemic events, the time spent hyperglycaemic, and to evaluate safety with ketosis and changes in glycated haemoglobin. The study also aims to assess the changes in counter-regulatory hormone responses to hypoglycaemia evaluated by a hyperinsulinaemic hypoglycaemic clamp in a subgroup of patients with impaired awareness. Validated questionnaires are used to measure the fear of hypoglycaemia and the impact on the quality of life to assess burden of the disease. Ethics and dissemination Ethics committee permissions were gained from respective Institutional Review boards. The findings of the study will provide high quality evidence of the ability of the system in the prevention of hypoglycaemia in real life. Trial registration number ACTRN12614000510640, Pre-results. PMID:27084290

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

PubMed Central

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

2009-01-01

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

Adherence therapy improves medication adherence and quality of life in people with Parkinson's disease: a randomised controlled trial.

PubMed

Daley, D J; Deane, K H O; Gray, R J; Clark, A B; Pfeil, M; Sabanathan, K; Worth, P F; Myint, P K

2014-08-01

Many factors are associated with medication non-adherence in Parkinson's disease (PD), including complex treatment regimens, mood disorders and impaired cognition. However, interventions to improve adherence which acknowledge such factors are lacking. A phase II randomised controlled trial was conducted investigating whether Adherence Therapy (AT) improves medication adherence and quality of life (QoL) compared with routine care (RC) in PD. Eligible PD patients and their spouse/carers were randomised to intervention (RC plus AT) or control (RC alone). Primary outcomes were change in adherence (Morisky Medication Adherence Scale) and QoL (Parkinson's Disease Questionnaire-39) from baseline to week-12 follow up. Secondary outcomes were MDS-UPDRS (part I, II, IV), Beliefs about Medication Questionnaire (BMQ), EuroQol (EQ-5D) and the Caregiving Distress Scale. Blinded data were analysed using logistic and linear regression models based on the intention-to-treat principle. Seventy-six patients and 46 spouse/carers completed the study (intervention: n = 38 patients, n = 24 spouse/carers). At week-12 AT significantly improved adherence compared with RC (OR 8.2; 95% CI: 2.8, 24.3). Numbers needed to treat (NNT) were 2.2 (CI: 1.6, 3.9). Compared with RC, AT significantly improved PDQ-39 (-9.0 CI: -12.2, -5.8), BMQ general harm (-1.0 CI: -1.9, -0.2) and MDS-UPDRS part II (-4.8 CI: -8.1, -1.4). No significant interaction was observed between the presence of a spouse/carer and the effect of AT. Adherence Therapy improved self-reported adherence and QoL in a PD sample. The small NNT suggests AT may be cost-effective. A larger pragmatic trial to test the efficacy and cost-effectiveness of AT by multiple therapists is required. © 2014 John Wiley & Sons Ltd.

Measuring skin necrosis in a randomised controlled feasibility trial of heat preconditioning on wound healing after reconstructive breast surgery: study protocol and statistical analysis plan for the PREHEAT trial.

PubMed

Cro, Suzie; Mehta, Saahil; Farhadi, Jian; Coomber, Billie; Cornelius, Victoria

2018-01-01

Essential strategies are needed to help reduce the number of post-operative complications and associated costs for breast cancer patients undergoing reconstructive breast surgery. Evidence suggests that local heat preconditioning could help improve the provision of this procedure by reducing skin necrosis. Before testing the effectiveness of heat preconditioning in a definitive randomised controlled trial (RCT), we must first establish the best way to measure skin necrosis and estimate the event rate using this definition. PREHEAT is a single-blind randomised controlled feasibility trial comparing local heat preconditioning, using a hot water bottle, against standard care on skin necrosis among breast cancer patients undergoing reconstructive breast surgery. The primary objective of this study is to determine the best way to measure skin necrosis and to estimate the event rate using this definition in each trial arm. Secondary feasibility objectives include estimating recruitment and 30 day follow-up retention rates, levels of compliance with the heating protocol, length of stay in hospital and the rates of surgical versus conservative management of skin necrosis. The information from these objectives will inform the design of a larger definitive effectiveness and cost-effectiveness RCT. This article describes the PREHEAT trial protocol and detailed statistical analysis plan, which includes the pre-specified criteria and process for establishing the best way to measure necrosis. This study will provide the evidence needed to establish the best way to measure skin necrosis, to use as the primary outcome in a future RCT to definitively test the effectiveness of local heat preconditioning. The pre-specified statistical analysis plan, developed prior to unblinded data extraction, sets out the analysis strategy and a comparative framework to support a committee evaluation of skin necrosis measurements. It will increase the transparency of the data analysis for the PREHEAT trial. ISRCTN ISRCTN15744669. Registered 25 February 2015.

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2018-01-01

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

Corticosteroids for Bell's palsy (idiopathic facial paralysis).

PubMed

Madhok, Vishnu B; Gagyor, Ildiko; Daly, Fergus; Somasundara, Dhruvashree; Sullivan, Michael; Gammie, Fiona; Sullivan, Frank

2016-07-18

Inflammation and oedema of the facial nerve are implicated in causing Bell's palsy. Corticosteroids have a potent anti-inflammatory action that should minimise nerve damage. This is an update of a review first published in 2002 and last updated in 2010. To determine the effectiveness and safety of corticosteroid therapy in people with Bell's palsy. On 4 March 2016, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS. We reviewed the bibliographies of the randomised trials and contacted known experts in the field to identify additional published or unpublished trials. We also searched clinical trials registries for ongoing trials. Randomised trials and quasi-randomised trials comparing different routes of administration and dosage schemes of corticosteroid or adrenocorticotrophic hormone therapy versus a control group receiving no therapy considered effective for this condition, unless the same therapy was given in a similar way to the experimental group. We used standard Cochrane methodology. The main outcome of interest was incomplete recovery of facial motor function (i.e. residual facial weakness). Secondary outcomes were cosmetically disabling persistent sequelae, development of motor synkinesis or autonomic dysfunction (i.e. hemifacial spasm, crocodile tears) and adverse effects of corticosteroid therapy manifested during follow-up. We identified seven trials, with 895 evaluable participants for this review. All provided data suitable for the primary outcome meta-analysis. One of the trials was new since the last version of this Cochrane systematic review. Risk of bias in the older, smaller studies included some unclear- or high-risk assessments, whereas we deemed the larger studies at low risk of bias. Overall, 79/452 (17%) participants allocated to corticosteroids had incomplete recovery of facial motor function six months or more after randomisation; significantly fewer than the 125/447 (28%) in the control group (risk ratio (RR) 0.63, 95% confidence interval (CI) 0.50 to 0.80, seven trials, n = 895). The number of people who need to be treated with corticosteroids to avoid one incomplete recovery was 10 (95% CI 6 to 20). The reduction in the proportion of participants with cosmetically disabling sequelae six months after randomisation was very similar in the corticosteroid and placebo groups (RR 0.96, 95% CI 0.40 to 2.29, two trials, n = 75, low-quality evidence). However, there was a significant reduction in motor synkinesis during follow-up in participants receiving corticosteroids (RR 0.64, 95% CI 0.45 to 0.91, three trials, n = 485, moderate-quality evidence). Three studies explicitly recorded the absence of adverse effects attributable to corticosteroids. One trial reported that three participants receiving prednisolone had temporary sleep disturbances and two trials gave a detailed account of adverse effects occurring in 93 participants, all non-serious; the combined analysis of data from these three trials found no significant difference in adverse effect rates between people receiving corticosteroids and people receiving placebo (RR 1.04, 95% CI 0.71 to 1.51, n = 715). The available moderate- to high-quality evidence from randomised controlled trials showed significant benefit from treating Bell's palsy with corticosteroids.

Effectiveness of routine antihelminthic treatment on anaemia in pregnancy in Rufiji District, Tanzania: a cluster randomised controlled trial.

PubMed

Urassa, David P; Nystrom, Lennarth; Carlsted, Anders

2011-09-01

The aim of this study was to estimate the effect of an antihelminthic drug, given at booking and at term to antenatal care visits, on the prevalence of anaemia at term and 4 months post-partum in Rufiji district, Tanzania, the area with high prevalence of intestinal parasites. A cluster randomised controlled trial was conducted on 3080 pregnant women. Out of these 1475 (study arm) received albendazole and 1605 (control arm) placebo. All women also received routine daily iron folate supplements (36 mg iron and 5 mg folate), and sulphadoxine pyramethamine (SP) to prevent malaria. Haemoglobin levels were assessed at booking, at term and 4 months post-partum. At term, median and mean haemoglobin level and the prevalence of severe (< 70 g/l) and moderate (70-104 g/l) anaemia did not differ. The reduction in the prevalence of anaemia from booking to term, was significantly larger in the study arm compared to control arm (26.1% vs. 18.8%; p < 0.001). At four months postpartum, mean haemoglobin was higher in the study arm compared to the control arm (118 vs. 113; p < 0.0001) while the reduction in proportion of women with anaemia (Hb <105 g/dl) was significantly lower (30.6 vs. 21.2; p < 0.0001) in the study arm compared to the control arm. These findings support WHO's recommendation for anthelmintic treatment during pregnancy. However benefits for deworming may be limited in areas with an antenatal iron supplementation programme or low intensity of hookworm infections and hence future research should be directed towards the cost-effectiveness of the de-worming compared to other interventions for reducing anaemia in pregnancy.

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).

Protocol for a feasibility trial for improving breast feeding initiation and continuation: assets-based infant feeding help before and after birth (ABA)

PubMed Central

Jolly, Kate; Ingram, Jenny; Clarke, Joanne; Johnson, Debbie; Trickey, Heather; Thomson, Gill; Dombrowski, Stephan U; Sitch, Alice; Dykes, Fiona; Feltham, Max G; Darwent, Kirsty; MacArthur, Christine; Roberts, Tracy

2018-01-01

Introduction Breast feeding improves the health of mothers and infants; the UK has low rates, with marked socioeconomic inequalities. While trials of peer support services have been effective in some settings, UK trials have not improved breast feeding rates. Qualitative research suggests that many women are alienated by the focus on breast feeding. We propose a change from breast feeding-focused interactions to respecting a woman’s feeding choices, inclusion of behaviour change theory and an increased intensity of contacts in the 2 weeks after birth when many women cease to breast feed. This will take place alongside an assets-based approach that focuses on the positive capability of individuals, their social networks and communities. We propose a feasibility study for a multicentre randomised controlled trial of the Assets feeding help Before and After birth (ABA) infant feeding service versus usual care. Methods and analysis A two-arm, non-blinded randomised feasibility study will be conducted in two UK localities. Women expecting their first baby will be eligible, regardless of feeding intention. The ABA infant feeding intervention will apply a proactive, assets-based, woman-centred, non-judgemental approach, delivered antenatally and postnatally tailored through face-to-face contacts, telephone and SMS texts. Outcomes will test the feasibility of delivering the intervention with recommended intensity and duration to disadvantaged women; acceptability to women, feeding helpers and professionals; and feasibility of a future randomised controlled trial (RCT), detailing recruitment rates, willingness to be randomised, follow-up rates at 3 days, 8 weeks and 6 months, and level of outcome completion. Outcomes of the proposed full trial will also be collected. Mixed methods will include qualitative interviews with women/partners, feeding helpers and health service staff; feeding helper logs; and review of audio-recorded helper–women interactions to assess intervention fidelity. Ethics and dissemination Study results will inform the design of a larger multicentre RCT. The National Research Ethics Service Committee approved the study protocol. Trial registration number ISRCTN14760978; Pre-results. PMID:29362263

A multifactorial intervention for frail older people is more than twice as effective among those who are compliant: complier average causal effect analysis of a randomised trial.

PubMed

Fairhall, Nicola; Sherrington, Catherine; Cameron, Ian D; Kurrle, Susan E; Lord, Stephen R; Lockwood, Keri; Herbert, Robert D

2017-01-01

What is the effect of a multifactorial intervention on frailty and mobility in frail older people who comply with their allocated treatment? Secondary analysis of a randomised, controlled trial to derive an estimate of complier average causal effect (CACE) of treatment. A total of 241 frail community-dwelling people aged ≥ 70 years. Intervention participants received a 12-month multidisciplinary intervention targeting frailty, with home exercise as an important component. Control participants received usual care. Primary outcomes were frailty, assessed using the Cardiovascular Health Study criteria (range 0 to 5 criteria), and mobility measured using the 12-point Short Physical Performance Battery. Outcomes were assessed 12 months after randomisation. The treating physiotherapist evaluated the amount of treatment received on a 5-point scale. 216 participants (90%) completed the study. The median amount of treatment received was 25 to 50% (range 0 to 100). The CACE (ie, the effect of treatment in participants compliant with allocation) was to reduce frailty by 1.0 frailty criterion (95% CI 0.4 to 1.5) and increase mobility by 3.2 points (95% CI 1.8 to 4.6) at 12 months. The mean CACE was substantially larger than the intention-to-treat effect, which was to reduce frailty by 0.4 frailty criteria (95% CI 0.1 to 0.7) and increase mobility by 1.4 points (95% CI 0.8 to 2.1) at 12 months. Overall, compliance was low in this group of frail people. The effect of the treatment on participants who comply with allocated treatment was substantially greater than the effect of allocation on all trial participants. Australian and New Zealand Trial Registry ANZCTRN12608000250336. [Fairhall N, Sherrington C, Cameron ID, Kurrle SE, Lord SR, Lockwood K, Herbert RD (2016) A multifactorial intervention for frail older people is more than twice as effective among those who are compliant: complier average causal effect analysis of a randomised trial.Journal of Physiotherapy63: 40-44]. Copyright © 2016 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Protocol for a feasibility trial for improving breast feeding initiation and continuation: assets-based infant feeding help before and after birth (ABA).

PubMed

Jolly, Kate; Ingram, Jenny; Clarke, Joanne; Johnson, Debbie; Trickey, Heather; Thomson, Gill; Dombrowski, Stephan U; Sitch, Alice; Dykes, Fiona; Feltham, Max G; Darwent, Kirsty; MacArthur, Christine; Roberts, Tracy; Hoddinott, Pat

2018-01-23

Breast feeding improves the health of mothers and infants; the UK has low rates, with marked socioeconomic inequalities. While trials of peer support services have been effective in some settings, UK trials have not improved breast feeding rates. Qualitative research suggests that many women are alienated by the focus on breast feeding. We propose a change from breast feeding-focused interactions to respecting a woman's feeding choices, inclusion of behaviour change theory and an increased intensity of contacts in the 2 weeks after birth when many women cease to breast feed. This will take place alongside an assets-based approach that focuses on the positive capability of individuals, their social networks and communities.We propose a feasibility study for a multicentre randomised controlled trial of the Assets feeding help Before and After birth (ABA) infant feeding service versus usual care. A two-arm, non-blinded randomised feasibility study will be conducted in two UK localities. Women expecting their first baby will be eligible, regardless of feeding intention. The ABA infant feeding intervention will apply a proactive, assets-based, woman-centred, non-judgemental approach, delivered antenatally and postnatally tailored through face-to-face contacts, telephone and SMS texts. Outcomes will test the feasibility of delivering the intervention with recommended intensity and duration to disadvantaged women; acceptability to women, feeding helpers and professionals; and feasibility of a future randomised controlled trial (RCT), detailing recruitment rates, willingness to be randomised, follow-up rates at 3 days, 8 weeks and 6 months, and level of outcome completion. Outcomes of the proposed full trial will also be collected. Mixed methods will include qualitative interviews with women/partners, feeding helpers and health service staff; feeding helper logs; and review of audio-recorded helper-women interactions to assess intervention fidelity. Study results will inform the design of a larger multicentre RCT. The National Research Ethics Service Committee approved the study protocol. ISRCTN14760978; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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.

Effect of a lateral glide mobilisation with movement of the hip on vibration threshold in healthy volunteers.

PubMed

Smith, Darren A; Saranga, Jacob; Pritchard, Andrew; Kommatas, Nikolaos A; Punnoose, Shinu Kovelal; Kale, Supriya Tukaram

2018-01-01

Mulligan's mobilisation-with-movement (MWM) techniques are proposed to achieve their clinical benefit via neurophysiological mechanisms. However, previous research has focussed on responses in the sympathetic nervous system only, and is not conclusive. An alternative measure of neurophysiological response to MWM is required to support or refute this mechanism of action. Recently, vibration threshold (VT) has been used to quantify changes in the sensory nervous system in patients experiencing musculoskeletal pain. To investigate the effect of a lateral glide MWM of the hip joint on vibration threshold compared to a placebo and control condition in asymptomatic volunteers. Fifteen asymptomatic volunteers participated in this single-blinded, randomised, within-subject, placebo, control design. Participants received each of three interventions in a randomised order; a lateral glide MWM of the hip joint into flexion, a placebo MWM, and a control intervention. Vibration threshold (VT) measures were taken at baseline and immediately after each intervention. Mean change in VT from baseline was calculated for each intervention and then analysed for between group differences using a one-way analysis of variance (ANOVA). A one-way ANOVA revealed no statistically significant differences between the three experimental conditions (P = 0.812). This small study found that a lateral glide MWM of the hip did not significantly change vibration threshold compared to a placebo and control intervention in an asymptomatic population. This study provides a method of using vibration threshold to investigate the potential neurophysiological effects of a manual therapy intervention that should be repeated in a larger, symptomatic population. Copyright © 2016 Elsevier Ltd. All rights reserved.

Increasing young adults' condom use intentions and behaviour through changing chlamydia risk and coping appraisals: study protocol for a cluster randomised controlled trial of efficacy.

PubMed

Newby, Katie V; French, David P; Brown, Katherine E; Lecky, Donna M

2013-05-30

Chlamydia is the most commonly diagnosed sexually transmitted infection (STI) in England and has serious public health consequences. Young people carry a disproportionate burden of infection. A number of social cognition models identify risk appraisal as a primary motivator of behaviour suggesting that changing risk appraisals for STIs may be an effective strategy in motivating protective behaviour. Meta-analytic evidence indicates that the relationship between risk appraisal and health behaviour is small, but studies examining this relationship have been criticised for their many conceptual and methodological weaknesses. The effect of risk appraisal on health behaviour may therefore be of larger size. The proposed study aims to examine the efficacy of an intervention to increase condom use intentions and behaviour amongst young people through changing chlamydia risk and coping appraisals. Coping appraisal is targeted to avoid the intervention being counterproductive amongst recipients who do not feel able to perform the behaviour required to reduce the threat. An experimental design with follow-up, a conditional measure of risk appraisal, and analysis which controls for past behaviour, enable the relationship between risk appraisal and protective behaviour to be accurately assessed. The proposed study is a two-arm cluster randomised controlled trial using a waiting-list control design to test the efficacy of the intervention compared to a control group. Participants will be school pupils aged 13-16 years old recruited from approximately ten secondary schools. Schools will be randomised into each arm. Participants will receive their usual teaching on STIs but those in the intervention condition will additionally receive a single-session sex education lesson on chlamydia. Measures will be taken at baseline, post-intervention and at follow-up three months later. The primary outcome measure is intention to use condoms with casual sexual partners. As far as the authors are aware, this is the first controlled trial testing the efficacy of an intervention to increase condom use intentions and behaviour through changing chlamydia risk appraisals. It is one of few experimental studies to accurately test the relationship between risk appraisal and precautionary sexual behaviour using a conditional measure of risk appraisal and controlling for past behaviour.

Long-term pain prevalence and health-related quality of life outcomes for patients enrolled in a ketamine versus morphine for prehospital traumatic pain randomised controlled trial.

PubMed

Jennings, Paul A; Cameron, Peter; Bernard, Stephen; Walker, Tony; Jolley, Damien; Fitzgerald, Mark; Masci, Kevin

2014-10-01

Improved early pain control may affect the longer-term prevalence of persistent pain. In a previous randomised, controlled trial, we found that the administration of ketamine on hospital arrival decreased pain scores to a greater extent than morphine alone in patients with prehospital traumatic pain. In this follow-up study, we sought to determine the prevalence of persistent pain and whether there were differences in patients who received ketamine or morphine. This study was a long-term follow-up study of the prehospital, prospective, randomised, controlled, open-label study comparing ketamine with morphine in patients with trauma and a verbal pain score of >5 after 5 mg intravenous morphine. Patients were followed-up by telephone 6-12 months after enrollment, and a questionnaire including the SF-36 (V.2) health-related quality of life survey and the Verbal Numerical Rating Scale for pain was administered. A total of 97/135 (72%) patients were able to be followed-up 6-12 months after enrollment between July 2008 and July 2010. Overall, 44/97 (45%) participants reported persistent pain related to their injury, with 3/97 (3%) reporting persistent severe pain. The prevalence of persistent pain was the same between study groups (22/50 (44%) for the ketamine group vs 22/47 (46%) for the morphine group). There was no difference in the SF-36 scores between study arms. There is a high incidence of persistent pain after traumatic injury, even in patients with relatively minor severity of injury. Although decreased pain scores at hospital arrival are achieved with ketamine compared with morphine, this difference does not affect the prevalence of persistent pain or health-related quality of life 6 months after injury. Further larger studies are required to confirm this finding. Australian and New Zealand Clinical Trials Registry (ACTRN12607000441415). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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.

Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial

PubMed Central

Moll, Etelka; Bossuyt, Patrick M M; Korevaar, Johanna C; Lambalk, Cornelis B; van der Veen, Fulco

2006-01-01

Objective To compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome. Design Randomised clinical trial. Setting Multicentre trial in 20 Dutch hospitals. Participants 228 women with polycystic ovary syndrome. Interventions Clomifene citrate plus metformin or clomifene citrate plus placebo. Main outcome measure The primary outcome measure was ovulation. Secondary outcome measures were ongoing pregnancy, spontaneous abortion, and clomifene resistance. Results 111 women were allocated to clomifene citrate plus metformin (metformin group) and 114 women were allocated to clomifene citrate plus placebo (placebo group). The ovulation rate in the metformin group was 64% compared with 72% in the placebo group, a non-significant difference (risk difference - 8%, 95% confidence interval - 20% to 4%). There were no significant differences in either rate of ongoing pregnancy (40% v 46%; - 6%, - 20% to 7%) or rate of spontaneous abortion (12% v 11%; 1%, - 7% to 10%). A significantly larger proportion of women in the metformin group discontinued treatment because of side effects (16% v 5%; 11%, 5% to 16%). Conclusion Metformin is not an effective addition to clomifene citrate as the primary method of inducing ovulation in women with polycystic ovary syndrome. Trial registration Current Controlled Trials ISRCTN55906981 [controlled-trials.com]. PMID:16769748

Antenatal perineal massage and subsequent perineal outcomes: a randomised controlled trial.

PubMed

Shipman, M K; Boniface, D R; Tefft, M E; McCloghry, F

1997-07-01

To study the effects of antenatal perineal massage on subsequent perineal outcomes at delivery. A randomised, single-blind prospective study. Department of Obstetrics and Gynaecology, Watford General Hospital. Eight hundred and sixty-one nulliparous women with singleton pregnancy and fulfilling criteria for entry to the trial between June 1994 and October 1995. Comparison of the group assigned to massage with the group assigned to no massage showed a reduction of 6.1% in second or third degree tears or episiotomies. This corresponded to tear rates of 75.1% in the no-massage group and 69.0% in the massage group (P = 0.073). There was a corresponding reduction in instrumental deliveries from 40.9% to 34.6% (P = 0.094). After adjustment for mother's age and infant's birthweight these reductions achieved statistical significance (P = 0.024 and P = 0.034, respectively). Analysis by mother's age showed a much larger benefit due to massage in those aged 30 and over and a smaller benefit in those under 30. Antenatal perineal massage appears to have some benefit in reducing second or third degree tears or episiotomies and instrumental deliveries. This effect was stronger in the age group 30 years and above.

Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment: Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia.

PubMed

Arai, Hidenori; Yamashita, Shizuya; Yokote, Koutaro; Araki, Eiichi; Suganami, Hideki; Ishibashi, Shun

2017-06-01

Substantial residual cardiovascular risks remain despite intensive statin treatment. Residual risks with high triglyceride and low high-density lipoprotein cholesterol are not the primary targets of statins. K-877 (pemafibrate) demonstrated robust efficacy on triglycerides and high-density lipoprotein cholesterol and a good safety profile as a monotherapy. The aim of these studies was to evaluate the efficacy and safety of K-877 add-on therapy to treat residual hypertriglyceridaemia during statin treatment. The objectives were investigated in two, multicentre, randomised, double-blind, placebo-controlled, parallel group comparison clinical trials: (A) K-877 0.1, 0.2, and 0.4 mg/day in combination with pitavastatin for 12 weeks in 188 patients, (B) K-877 0.2 (fixed dose) and 0.2 (0.4) (conditional up-titration) mg/day in combination with any statin for 24 weeks in 423 patients. In both studies, we found a robust reduction in fasting triglyceride levels by approximately 50% in all combination therapy groups, which was significant compared to the statin-monotherapy (placebo) groups (p < 0.001). High-performance liquid chromatography analysis for lipoprotein subfractions revealed that atherogenic lipoprotein profiles were ameliorated by K-877 add-on therapy, i.e. small low-density lipoproteins decreased whereas larger ones increased, and larger high-density lipoproteins decreased whereas smaller ones increased. The incidence rates of adverse events and adverse drug reactions in K-877 combination therapy groups were comparable to those in statin-monotherapy groups without any noteworthy event in both studies. These results strongly support the favourable benefit-to-risk ratio of K-877 add-on therapy in combination with statin treatment. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

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

PubMed

Heinmüller, Stefan; Schneider, Antonius; Linde, Klaus

2016-04-23

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

Vitamin D intervention in preschoolers with viral-induced asthma (DIVA): a pilot randomised controlled trial.

PubMed

Jensen, Megan E; Mailhot, Genevieve; Alos, Nathalie; Rousseau, Elizabeth; White, John H; Khamessan, Ali; Ducharme, Francine M

2016-07-26

Trials in school-aged children suggest vitamin D supplementation reduces asthma exacerbations. Primary aim: to examine whether vitamin D3 (100,000 IU) rapidly raises serum 25-hydroxyvitamin D (25OHD) ≥75 nmol/L in asthmatic preschoolers. In a double-blind, randomised, placebo-controlled trial, preschool-aged children with asthma received 100,000 IU vitamin D3 (intervention) or placebo (control), followed by 400 IU vitamin D3 daily for 6 months. Serum 25OHD was measured at baseline, 10 days, 3 and 6 months. Outcomes included the group difference in 25OHD change from baseline at 3 months (Δ25OHD); the proportion of children with 25OHD ≥75 nmol/L at 3 months; the pattern in serum vitamin D over 6 months; the proportion of children with hypercalciuria at any time point (safety); and group rates for oral corticosteroids. Continuous outcomes were analysed using generalised linear mixed models and group rate ratios of events per child were assessed using a Poisson distribution model. Twenty-two children were randomised (intervention:11; control:11) during winter. At 3 months, the group difference in Δ25OHD (7.2 nmol/L; 95 % CI: -13.7, 28.1) was not significant; yet, 100 % versus 54.5 % (intervention versus control) had serum 25OHD ≥75 nmol/L. There was a significant group difference in Δ25OHD at 10 days (110.3 nmol/L; 95 % CI: 64.0, 156.6). One child in each group had transient hypercalciuria at 10 days. Group oral corticosteroids rates were 0.82 and 1.18/child, intervention versus control (rate ratio = 0.68; 95 % CI: 0.30, 1.62; non-significant). Following 100,000 IU vitamin D3, all children reached serum 25OHD ≥75 nmol/L, compared with half who received placebo. Daily supplementation, sun exposure and insufficient power may explain the absence of a significant 3-month group difference in Δ25OHD. No clinically important alterations in bone metabolism biomarkers occurred. Group oral corticosteroid rates will inform sample size calculations for the larger trial. ( NCT01999907 , 25 November 2013).

Effect of characteristics of women on attendance in blind and non-blind randomised trials: analysis of recruitment data from the EPHT Trial.

PubMed

Veerus, Piret; Fischer, Krista; Hemminki, Elina; Hovi, Sirpa-Liisa; Hakama, Matti

2016-10-18

To analyse the effect of women's characteristics on their willingness to join a blind or a non-blind subtrial or to be excluded by physicians. Primary prevention trial of postmenopausal hormone therapy (HT). A 2×2, randomised design with a non-blind HT arm or control arm and a blind HT arm or placebo arm. 3 clinical centres in Estonia. Interest in joining the trial was asked in a questionnaire together with demographic and health status data. Interested and eligible women were invited to a health examination that also informed whether they belonged to a blind or to a non-blind subtrial; the arm was not revealed. Trial physicians made further exclusions when checking the women's eligibility. Thereafter, informed consent was asked as detailed in the flow chart. Comparisons were made between non-blind and blind subtrials. Analyses were carried out for each of the background variables. The proportion of willingness, eligibility and attendance. Women randomised to the non-blind subtrial were more willing to join (relative risk (RR) 1.17) and more likely to be found eligible by physicians (RR 1.10) than women in the blind subtrial, resulting in larger attendance (RR 1.29). Women with higher education were differentially more willing to join the non-blind trial (RR 1.29) than those with basic education (RR 1.08); the differential willingness of never-smokers (RR 1.20) was larger than that of current smokers (RR 1.07). The differential exclusion by physicians by education and smoking were small. Some subjective symptoms (eg, diarrhoea/constipation, stomach pain) had reverse differential effects on attendance in the non-blind subtrial in comparison to the blind subtrial. Menopausal symptoms did not affect the differential interest, eligibility or attendance. Blinding in RCT reduces attendance, due to decisions of the women and the trial physicians. Differential attendance by blinding may affect the generalisability of the results from trials. ISRCTN35338757. 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 effectiveness and cost-effectiveness of a mindfulness training programme in schools compared with normal school provision (MYRIAD): study protocol for a randomised controlled trial.

PubMed

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

2017-04-26

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

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

PubMed

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

2012-01-01

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

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

PubMed

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

2014-12-10

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

Preventive PCI versus culprit lesion stenting during primary PCI in acute STEMI: a systematic review and meta-analysis

PubMed Central

Pandit, Anil; Aryal, Madan Raj; Aryal Pandit, Aashrayata; Hakim, Fayaz Ahmad; Giri, Smith; Mainali, Naba Raj; Sharma, Prashant; Lee, Howard R; Fortuin, F David; Mookadam, Farouk

2014-01-01

Aim The benefit of preventive percutaneous coronary intervention (PCI) in ST elevation myocardial infarction (STEMI) has been shown in randomised trials. However, all the randomised trials are underpowered to detect benefit in cardiac death. We aim to systematically review evidence on the cardiac mortality benefit of preventive PCI in patients presenting with acute STEMI in randomised patient populations. Methods PubMed, Scopus, Cochrane and clinicaltrials.gov databases were searched for studies published until 30 September 2013. The studies were limited to randomised clinical trials. Independent observers abstracted the data on outcomes, characteristics and qualities of studies included. Fixed effect model was employed for meta-analysis. Heterogeneity of studies included was analysed using I2 statistics. Results In three randomised clinical trials published, involving 748 patients with acute STEMI and multivessel disease, 416 patients were randomised to preventive PCI and 332 to culprit-only PCI. Patients undergoing preventive PCI had significant lower risk of cardiovascular deaths (pooled OR 0.39, 95% CI 0.18 to 0.83, p=0.01, I2=0%), repeat revascularisation (pooled OR 0.28, 95% CI 0.18 to 0.44, p=0.00001, I2=0%) and non-fatal myocardial infarction (pooled OR 0.38, 95% CI 0.20 to 0.75, p=0.005, I2=0%) compared with culprit-only revascularisation. Conclusions In patients presenting with acute STEMI and significant multivessel coronary artery disease, based on our data, preventive PCI is associated with lower risk of cardiovascular mortality compared with primary PCI of only the culprit artery. This finding needs to be confirmed in larger adequately powered randomised clinical trials. PMID:25332779

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.

Clinical and economic evaluation of laparoscopic surgery compared with medical management for gastro-oesophageal reflux disease: 5-year follow-up of multicentre randomised trial (the REFLUX trial).

PubMed

Grant, A M; Boachie, C; Cotton, S C; Faria, R; Bojke, L; Epstein, D M; Ramsay, C R; Corbacho, B; Sculpher, M; Krukowski, Z H; Heading, R C; Campbell, M K

2013-06-01

Despite promising evidence that laparoscopic fundoplication provides better short-term relief of gastro-oesophageal reflux disease (GORD) than continued medical management, uncertainty remains about whether benefits are sustained and outweigh risks. To evaluate the long-term clinical effectiveness, cost-effectiveness and safety of laparoscopic surgery among people with GORD requiring long-term medication and suitable for both surgical and medical management. Five-year follow-up of a randomised trial (with parallel non-randomised preference groups) comparing a laparoscopic surgery-based policy with a continued medical management policy. Cost-effectiveness was assessed alongside the trial using a NHS perspective for costs and expressing health outcomes in terms of quality-adjusted life-years (QALYs). Follow-up was by annual postal questionnaire and selective hospital case notes review; initial recruitment in 21 UK hospitals. Questionnaire responders among the 810 original participants. At entry, all had documented evidence of GORD and symptoms for > 12 months. Questionnaire response rates (years 1-5) were from 89.5% to 68.9%. Three hundred and fifty-seven participants were recruited to the randomised comparison (178 randomised to surgical management and 179 randomised to continued medical management) and 453 to the preference groups (261 surgical management and 192 medical management). The surgeon chose the type of fundoplication. Primary: disease-specific outcome measure (the REFLUX questionnaire); secondary: Short Form questionnaire-36 items (SF-36), European Quality of Life-5 Dimensions (EQ-5D), NHS resource use, reflux medication, complications. The randomised groups were well balanced. By 5 years, 63% in the randomised surgical group and 13% in the randomised medical management group had received a total or partial wrap fundoplication (85% and 3% in the preference groups), with few perioperative complications and no associated deaths. At 1 year (and 5 years) after surgery, 36% (41%) in the randomised surgical group - 15% (26%) of those who had surgery - were taking proton pump inhibitor medication compared with 87% (82%) in the randomised medical group. At each year, differences in the REFLUX score significantly favoured the randomised surgical group (a third of a SD; p< 0.01 at 5 years). SF-36 and EQ-5D scores also favoured surgery, but differences attenuated over time and were generally not statistically significant at 5 years. The worse the symptoms at trial entry, the larger the benefit observed after surgery. Those randomised to medical management who subsequently had surgery had low baseline scores that markedly improved after surgery. Following fundoplication, 3% had surgical treatment for a complication and 4% had subsequent reflux-related operations - most often revision of the wrap. Dysphagia, flatulence and inability to vomit were similar in the two randomised groups. The economic analysis indicated that surgery was the more cost-effective option for this patient group. The incremental cost-effectiveness ratio for surgery in the base case was £7028 per additional QALY; these findings were robust to changes in approaches and assumptions. The probability of surgery being cost-effective at a threshold of £20,000 per additional QALY was > 0.80 for all analyses. After 5 years, laparoscopic fundoplication continues to provide better relief of GORD symptoms with associated improved health-related quality of life. Complications of surgery were uncommon. Despite being initially more costly, a surgical policy is highly likely to be cost-effective. Current Controlled Trials ISRCTN15517081. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 22. See the HTA programme website for further project information.

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

PubMed

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

2014-09-03

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

Protocol for a feasibility study and randomised pilot trial of a low-intensity psychological intervention for depression in adults with autism: the Autism Depression Trial (ADEPT)

PubMed Central

Russell, Ailsa; Cooper, Kate; Barton, Stephen; Ensum, Ian; Gaunt, Daisy; Horwood, Jeremy; Ingham, Barry; Kessler, David; Metcalfe, Chris; Parr, Jeremy; Rai, Dheeraj; Wiles, Nicola

2017-01-01

Introduction High rates of co-occurring depression are reported in autism spectrum disorder (ASD), a neurodevelopmental condition characterised by social communication impairments and repetitive behaviours. Cognitive-behavioural interventions adapted for ASD have been effective for anxiety problems. There have been evaluation studies of group cognitive-behavioural therapy for co-occurring depression, but no randomised trials investigating low-intensity psychological interventions as recommended in clinical guidelines for mild-moderate depression. Methods and analysis A feasibility study comprising a randomised controlled trial (RCT) and nested qualitative evaluation is under way as preparation for a definitive RCT. Participants (n=70) will be randomised to Guided Self-Help: a low-intensity psychological intervention based on behavioural activation adapted for ASD or treatment as usual. Outcomes including depression symptoms, anxiety, social function and service use will be measured at 10, 16 and 24 weeks postrandomisation and will be blind to group allocation for measures that are not self-administered. The analysis will aim to establish the rates of recruitment and retention for a larger-scale RCT as well as the most appropriate measure of depression to serve as primary outcome. The qualitative study will purposively sample up to 24 participants from each treatment group to consider the acceptability and feasibility of the intervention and the trial design. Ethics and dissemination Ethical approval has been received from WALES REC 3 (IRAS project ID: 191558) and the Health Research Authority with R&D approval from Avon and Wiltshire Mental Health Partnership and Northumberland, Tyne and Wear Foundation NHS Trusts. To our knowledge, this is the first study of a low-intensity intervention for depression in adults with autism. The results will inform the design of a definitive RCT. Dissemination will include peer-reviewed journal publications reporting the quantitative and qualitative research findings of the study and presentations at national and international conferences. Trial registration number ISRCTN54650760; Pre-results. PMID:29203509

Antenatal small-class education versus auditorium-based lectures to promote positive transitioning to parenthood - A randomised trial.

PubMed

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

2017-01-01

Prospective parents widely use education to gain information about, e.g., labour and parenting skills. It is unknown if antenatal education in small classes is more beneficial for parenting stress and parenting alliance compared with other types of antenatal education. In the present randomised trial, we examined the effect of antenatal education in small classes versus auditorium-based lectures on perceived stress, parenting stress, and parenting alliance. A total of 1,766 pregnant women were randomised to receive: antenatal education in small classes three times in pregnancy and one time after delivery, each session lasted 2.5 hours, versus standard care consisting of two times two hours auditorium-based lectures. Previous analysis of the primary outcome showed no difference between intervention and control group. Here we conduct an exploratory analysis of three secondary outcomes. Effects of the interventions on parents' global feelings of stress at 37 weeks gestation and nine weeks and six months postpartum and parenting stress nine weeks and six months postpartum were examined using linear regression analyses and mixed models with repeated measurements. The effect on parenting alliance six months postpartum was examined using the non-parametric Wilcoxon rank-sum test. Antenatal education in small classes had a small beneficial main effect on global feelings of stress six months postpartum and a statistically significant interaction between time and group favoring antenatal education in small classes. The P values of intervention effects on parenting stress and parenting alliance were all larger than the threshold value (0.05).

Can post-sternotomy mediastinitis be prevented by a closed incision management system?

PubMed Central

Dohmen, Pascal M.; Markou, Thanasie; Ingemansson, Richard; Rotering, Heinrich; Hartman, Jean M.; van Valen, René; Brunott, Maaike; Kramer, Axel; Segers, Patrique

2014-01-01

Post-sternotomy mediastinitis is a serious complication after cardiothoracic surgery and contribute significantly to post-operative morbidity, mortality, and healthcare costs. Negative pressure wound therapy is today’s golden standard for post-sternotomy mediastinitis treatment. A systematic literature search was conducted at PubMed until October 2012 to analyse whether vacuum-assisted closure technique prevents mediastinitis after clean surgical incisions closure. Today’s studies showed reduction of post-sternotomy mediastinitis including a beneficial socio-economic impact. Current studies, however included only high-risk patients, hence furthermore, larger randomised controlled trials are warranted to clarify the benefit for using surgical incision vacuum management systems in the general patient population undergoing sternotomy and clarify risk factor interaction. PMID:25285263

Use of an embedded, micro-randomised trial to investigate non-compliance in telehealth interventions.

PubMed

Law, Lisa M; Edirisinghe, Nuwani; Wason, James Ms

2016-08-01

Many types of telehealth interventions rely on activity from the patient in order to have a beneficial effect on their outcome. Remote monitoring systems require the patient to record regular measurements at home, for example, blood pressure, so clinicians can see whether the patient's health changes over time and intervene if necessary. A big problem in this type of intervention is non-compliance. Most telehealth trials report compliance rates, but they rarely compare compliance among various options of telehealth delivery, of which there may be many. Optimising telehealth delivery is vital for improving compliance and, therefore, clinical outcomes. We propose a trial design which investigates ways of improving compliance. For efficiency, this trial is embedded in a larger trial for evaluating clinical effectiveness. It employs a technique called micro-randomisation, where individual patients are randomised multiple times throughout the study. The aims of this article are (1) to verify whether the presence of an embedded secondary trial still allows valid analysis of the primary research and (2) to demonstrate the usefulness of the micro-randomisation technique for comparing compliance interventions. Simulation studies were used to simulate a large number of clinical trials, in which no embedded trial was used, a micro-randomised embedded trial was used, and a factorial embedded trial was used. Each simulation recorded the operating characteristics of the primary and secondary trials. We show that the type I error rate of the primary analysis was not affected by the presence of an embedded secondary trial. Furthermore, we show that micro-randomisation is superior to a factorial design as it reduces the variation caused by within-patient correlation. It therefore requires smaller sample sizes - our simulations showed a requirement of 128 patients for a micro-randomised trial versus 760 patients for a factorial design, in the presence of within-patient correlation. We believe that an embedded, micro-randomised trial is a feasible technique that can potentially be highly useful in telehealth trials. © The Author(s) 2016.

Cluster randomised controlled trial to examine medical mask use as source control for people with respiratory illness.

PubMed

MacIntyre, Chandini Raina; Zhang, Yi; Chughtai, Abrar Ahmad; Seale, Holly; Zhang, Daitao; Chu, Yanhui; Zhang, Haiyan; Rahman, Bayzidur; Wang, Quanyi

2016-12-30

Medical masks are commonly used by sick individuals with influenza-like illness (ILI) to prevent spread of infections to others, but clinical efficacy data are absent. Determine whether medical mask use by sick individuals with ILI protects well contacts from related respiratory infections. 6 major hospitals in 2 districts of Beijing, China. Cluster randomised controlled trial. 245 index cases with ILI. Index cases with ILI were randomly allocated to medical mask (n=123) and control arms (n=122). Since 43 index cases in the control arm also used a mask during the study period, an as-treated post hoc analysis was performed by comparing outcomes among household members of index cases who used a mask (mask group) with household members of index cases who did not use a mask (no-mask group). Primary outcomes measured in household members were clinical respiratory illness, ILI and laboratory-confirmed viral respiratory infection. In an intention-to-treat analysis, rates of clinical respiratory illness (relative risk (RR) 0.61, 95% CI 0.18 to 2.13), ILI (RR 0.32, 95% CI 0.03 to 3.13) and laboratory-confirmed viral infections (RR 0.97, 95% CI 0.06 to 15.54) were consistently lower in the mask arm compared with control, although not statistically significant. A post hoc comparison between the mask versus no-mask groups showed a protective effect against clinical respiratory illness, but not against ILI and laboratory-confirmed viral respiratory infections. The study indicates a potential benefit of medical masks for source control, but is limited by small sample size and low secondary attack rates. Larger trials are needed to confirm efficacy of medical masks as source control. ACTRN12613000852752; 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/.

Cluster randomised controlled trial to examine medical mask use as source control for people with respiratory illness

PubMed Central

MacIntyre, Chandini Raina; Zhang, Yi; Chughtai, Abrar Ahmad; Seale, Holly; Zhang, Daitao; Chu, Yanhui; Zhang, Haiyan; Rahman, Bayzidur; Wang, Quanyi

2016-01-01

Rationale Medical masks are commonly used by sick individuals with influenza-like illness (ILI) to prevent spread of infections to others, but clinical efficacy data are absent. Objective Determine whether medical mask use by sick individuals with ILI protects well contacts from related respiratory infections. Setting 6 major hospitals in 2 districts of Beijing, China. Design Cluster randomised controlled trial. Participants 245 index cases with ILI. Intervention Index cases with ILI were randomly allocated to medical mask (n=123) and control arms (n=122). Since 43 index cases in the control arm also used a mask during the study period, an as-treated post hoc analysis was performed by comparing outcomes among household members of index cases who used a mask (mask group) with household members of index cases who did not use a mask (no-mask group). Main outcome measure Primary outcomes measured in household members were clinical respiratory illness, ILI and laboratory-confirmed viral respiratory infection. Results In an intention-to-treat analysis, rates of clinical respiratory illness (relative risk (RR) 0.61, 95% CI 0.18 to 2.13), ILI (RR 0.32, 95% CI 0.03 to 3.13) and laboratory-confirmed viral infections (RR 0.97, 95% CI 0.06 to 15.54) were consistently lower in the mask arm compared with control, although not statistically significant. A post hoc comparison between the mask versus no-mask groups showed a protective effect against clinical respiratory illness, but not against ILI and laboratory-confirmed viral respiratory infections. Conclusions The study indicates a potential benefit of medical masks for source control, but is limited by small sample size and low secondary attack rates. Larger trials are needed to confirm efficacy of medical masks as source control. Trial registration number ACTRN12613000852752; Results. PMID:28039289

Patient-centred advice is effective in improving adherence to medicines.

PubMed

Clifford, Sarah; Barber, Nick; Elliott, Rachel; Hartley, Elaine; Horne, Rob

2006-06-01

To assess the effects of pharmacists giving advice to meet patients' needs after starting a new medicine for a chronic condition. A prospective health technology assessment including a randomised controlled trial of a pharmacist-delivered intervention to improve adherence using a centralised telephone service to patients at home in England. Patients were eligible for recruitment if they were receiving the first prescription for a newly prescribed medication for a chronic condition and were 75 or older or suffering from stroke, cardiovascular disease, asthma, diabetes or rheumatoid arthritis. Incidence of non-adherence, problems with the new medicine, beliefs about the new medicine, safety and usefulness of the interventions. Five hundred patients consented and were randomised. At 4-week follow-up, non-adherence was significantly lower in the intervention group compared to control (9% vs. 16%, P = 0.032). The number of patients reporting medicine-related problems was significantly lower in the intervention group compared to the control (23% vs. 34%, P = 0.021). Intervention group patients also had more positive beliefs about their new medicine, as shown by their higher score on the "necessity-concerns differential" (5.0 vs. 3.5, P = 0.007). The phone calls took a median of 12 min each. Most advice was judged by experts to be safe and helpful, and patients found it useful. Overall, these findings show benefits from pharmacists meeting patients' needs for information and advice on medicines, soon after starting treatment. While a substantially larger trial would be needed to confirm that the effect is real and sustained, these initial findings suggest the service may be safe and useful to patients.

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

PubMed Central

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

2012-01-01

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

The effect of communicating the genetic risk of cardiometabolic disorders on motivation and actual engagement in preventative lifestyle modification and clinical outcome: a systematic review and meta-analysis of randomised controlled trials.

PubMed

Li, Sherly X; Ye, Zheng; Whelan, Kevin; Truby, Helen

2016-09-01

Genetic risk prediction of chronic conditions including obesity, diabetes and CVD currently has limited predictive power but its potential to engage healthy behaviour change has been of immense research interest. We aimed to understand whether the latter is indeed true by conducting a systematic review and meta-analysis investigating whether genetic risk communication affects motivation and actual behaviour change towards preventative lifestyle modification. We included all randomised controlled trials (RCT) since 2003 investigating the impact of genetic risk communication on health behaviour to prevent cardiometabolic disease, without restrictions on age, duration of intervention or language. We conducted random-effects meta-analyses for perceived motivation for behaviour change and clinical changes (weight loss) and a narrative analysis for other outcomes. Within the thirteen studies reviewed, five were vignette studies (hypothetical RCT) and seven were clinical RCT. There was no consistent effect of genetic risk on actual motivation for weight loss, perceived motivation for dietary change (control v. genetic risk group standardised mean difference (smd) -0·15; 95 % CI -1·03, 0·73, P=0·74) or actual change in dietary behaviour. Similar results were observed for actual weight loss (control v. high genetic risk SMD 0·29 kg; 95 % CI -0·74, 1·31, P=0·58). This review found no clear or consistent evidence that genetic risk communication alone either raises motivation or translates into actual change in dietary intake or physical activity to reduce the risk of cardiometabolic disorders in adults. Of thirteen studies, eight were at high or unclear risk of bias. Additional larger-scale, high-quality clinical RCT are warranted.

The patient education - Learning and Coping Strategies - improves adherence in cardiac rehabilitation (LC-REHAB): A randomised controlled trial.

PubMed

Lynggaard, Vibeke; Nielsen, Claus Vinther; Zwisler, Ann-Dorthe; Taylor, Rod S; May, Ole

2017-06-01

Despite proven benefits of cardiac rehabilitation (CR), adherence to CR remains suboptimal. This trial aimed to assess the impact of the patient education 'Learning and Coping Strategies' (LC) on patient adherence to an eight-week CR program. 825 patients with ischaemic heart disease or heart failure were open label randomised to either the LC arm (LC plus CR) or the control arm (CR alone) across three hospital units in Denmark. Both arms received same amount of training and education hours. LC consisted of individual clarifying interviews, participation of experienced patients as co-educators, situational, reflective and inductive teaching. The control arm received structured deductive teaching. The primary outcomes were patient adherence to at least 75% of the exercise training or education sessions. We tested for subgroup effects on the primary outcomes using interaction terms. The primary outcomes were compared across arms using logistic regression. More patients in the LC arm adhered to at least 75% of the exercise training sessions than control (80% versus 73%, adjusted odds ratio (OR):1.48; 95% CI:1.07 to 2.05, P=0.018) and 75% of education sessions (79% versus 70%, adjusted OR:1.61, 1.17 to 2.22, P=0.003). Some evidence of larger effects of LC on adherence was seen for patients with heart failure, low education and household income. Addition of LC strategies improved adherence in rehabilitation both in terms of exercise training and education. Patients with heart failure, low levels of education and household income appear to benefit most from this adherence promoting intervention. www.clinicaltrials.gov identifier NCT01668394. Copyright © 2017 Elsevier B.V. All rights reserved.

The Boost study: design of a school- and community-based randomised trial to promote fruit and vegetable consumption among teenagers

PubMed Central

2012-01-01

Background The aim of the Boost study was to produce a persistent increase in fruit and vegetable consumption among 13-year-olds. This paper describes the development, implementation and evaluation of a school-and community-based, multi-component intervention guided by theory, evidence, and best practice. Methods/design We used the Intervention Mapping protocol to guide the development of the intervention. Programme activities combined environmental and educational strategies and focused on increasing access to fruit and vegetables in three settings: School: Daily provision of free fruit and vegetables; a pleasant eating environment; classroom curricular activities; individually computer tailored messages; one-day-workshop for teachers. Families: school meeting; guided child-parent activities; newsletters. Local community: guided visits in grocery stores and local area as part of classroom curriculum; information sheets to sports-and youth clubs. The Boost study employed a cluster-randomised controlled study design and applied simple two-stage cluster sampling: A random sample of 10 municipalities followed by a random sample of 4 schools within each municipality (N = 40 schools). Schools were randomised into a total of 20 intervention-and 20 control schools. We included all year 7 pupils except those from school classes with special needs. Timeline: Baseline survey: August 2010. Delivery of intervention: September 2010-May 2011. First follow-up survey: May/June 2011. Second follow-up survey: May/June 2012. Primary outcome measures: Daily mean intake of fruit and vegetables and habitual fruit and vegetable intake measured by validated 24-hour recall-and food frequency questionnaires. Secondary outcome measures: determinants of fruit and vegetable intake, positive side-effects and unintended adverse effects. Implementation was monitored by thorough process evaluation. Discussion The baseline data file included 2,156 adolescents (95%). There was baseline equivalence between intervention-and control groups for sociodemographics, primary outcomes, and availability at home, school and sports-and youth clubs. Significantly larger proportions of pupils in the control group had parents born in Denmark. The study will provide insights into effective strategies to increase fruit and vegetable intake among teenagers. The study will gain knowledge on implementation processes, intervention effects in population subgroups with low intake, and opportunities for including local communities in interventions. Trial registration Current Controlled Trials ISRCTN11666034. PMID:22413782

Psychosocial therapy for Parkinson's-related dementia: study protocol for the INVEST randomised controlled trial.

PubMed

McCormick, Sheree A; McDonald, Kathryn R; Vatter, Sabina; Orgeta, Vasiliki; Poliakoff, Ellen; Smith, Sarah; Silverdale, Monty A; Fu, Bo; Leroi, Iracema

2017-06-19

Parkinson's disease (PD) with mild cognitive impairment (MCI-PD) or dementia (PDD) and dementia with Lewy bodies (DLB) are characterised by motor and 'non-motor' symptoms which impact on quality of life. Treatment options are generally limited to pharmacological approaches. We developed a psychosocial intervention to improve cognition, quality of life and companion burden for people with MCI-PD, PDD or DLB. Here, we describe the protocol for a single-blind randomised controlled trial to assess feasibility, acceptability and tolerability of the intervention and to evaluate treatment implementation. The interaction among the intervention and selected outcome measures and the efficacy of this intervention in improving cognition for people with MCI-PD, PDD or DLB will also be explored. Dyads will be randomised into two treatment arms to receive either 'treatment as usual' (TAU) or cognitive stimulation therapy specifically adapted for Parkinson's-related dementias (CST-PD), involving 30 min sessions delivered at home by the study companion three times per week over 10 weeks. A mixed-methods approach will be used to collect data on the operational aspects of the trial and treatment implementation. This will involve diary keeping, telephone follow-ups, dyad checklists and researcher ratings. Analysis will include descriptive statistics summarising recruitment, acceptability and tolerance of the intervention, and treatment implementation. To pilot an outcome measure of efficacy, we will undertake an inferential analysis to test our hypothesis that compared with TAU, CST-PD improves cognition. Qualitative approaches using thematic analysis will also be applied. Our findings will inform a larger definitive trial. Ethical opinion was granted (REC reference: 15/YH/0531). Findings will be published in peer-reviewed journals and at conferences. We will prepare reports for dissemination by organisations involved with PD and dementia. ISRCTN (ISRCTN11455062). © 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.

Pain exposure physical therapy (PEPT) compared to conventional treatment in complex regional pain syndrome type 1: a randomised controlled trial

PubMed Central

Barnhoorn, Karlijn J; van de Meent, Henk; van Dongen, Robert T M; Klomp, Frank P; Groenewoud, Hans; Samwel, Han; Nijhuis-van der Sanden, Maria W G; Frölke, Jan Paul M; Staal, J Bart

2015-01-01

Objective To compare the effectiveness of pain exposure physical therapy (PEPT) with conventional treatment in patients with complex regional pain syndrome type 1 (CRPS-1) in a randomised controlled trial with a blinded assessor. Setting The study was conducted at a level 1 trauma centre in the Netherlands. Participants 56 adult patients with CRPS-1 participated. Three patients were lost to follow-up. Interventions Patients received either PEPT in a maximum of five treatment sessions, or conventional treatment following the Dutch multidisciplinary guideline. Measurements Outcomes were assessed at baseline and at 3, 6 and 9 months after randomisation. The primary outcome measure was the Impairment level Sum Score—Restricted Version (ISS-RV), consisting of visual analogue scale for pain (VAS-pain), McGill Pain Questionnaire, active range of motion (AROM) and skin temperature. Secondary outcome measures included Pain Disability Index (PDI); muscle strength; Short Form 36 (SF-36); disability of arm, shoulder and hand; Lower Limb Tasks Questionnaire (LLTQ); 10 m walk test; timed up-and-go test (TUG) and EuroQol-5D. Results The intention-to-treat analysis showed a clinically relevant decrease in ISS-RV (6.7 points for PEPT and 6.2 points for conventional treatment), but the between-group difference was not significant (0.96, 95% CI −1.56 to 3.48). Participants allocated to PEPT experienced a greater improvement in AROM (between-group difference 0.51, 95% CI 0.07 to 0.94; p=0.02). The per protocol analysis showed larger and significant between-group effects on ISS-RV, VAS-pain, AROM, PDI, SF-36, LLTQ and TUG. Conclusions We cannot conclude that PEPT is superior to conventional treatment for patients with CRPS-1. Further high-quality research on the effects of PEPT is warranted given the potential effects as indicated by the per protocol analysis. Trial registration numbers NCT00817128 and NTR 2090. PMID:26628523

Associations with health-related quality of life after intracerebral haemorrhage: pooled analysis of INTERACT studies.

PubMed

Delcourt, Candice; Zheng, Danni; Chen, Xiaoying; Hackett, Maree; Arima, Hisatomi; Hata, Jun; Heeley, Emma; Al-Shahi Salman, Rustam; Woodward, Mark; Huang, Yining; Robinson, Thompson; Lavados, Pablo M; Lindley, Richard I; Stapf, Christian; Davies, Leo; Chalmers, John; Anderson, Craig S; Sato, Shoichiro

2017-01-01

Limited data exist on health-related quality of life (HRQoL) after intracerebral haemorrhage (ICH). We aimed to determine baseline factors associated with HRQoL among participants of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT 1 and 2). The INTERACT studies were randomised controlled trials of early intensive blood pressure (BP) lowering in patients with ICH (<6 hours) and elevated systolic BP (150-220 mm Hg). HRQoL was determined using the European Quality of Life Scale (EQ-5D) at 90 days, completed by patients or proxy responders. Binary logistic regression analyses were performed to identify factors associated with poor overall HRQoL. 2756 patients were included. Demographic, clinical and radiological factors associated with lower EQ-5D utility score were age, randomisation outside of China, antithrombotic use, high baseline National Institutes of Health Stroke Scale (NIHSS) score, larger ICH, presence of intraventricular extension and use of proxy responders. High (≥14) NIHSS score, larger ICH and proxy responders were associated with low scores in all five dimensions of the EQ-5D. The NIHSS score had a strong association with poor HRQoL (p<0.001). Female gender and antithrombotic use were associated with decreased scores in dimensions of pain/discomfort and usual activity, respectively. Poor HRQoL was associated with age, comorbidities, proxy source of assessment, clinical severity and ICH characteristics. The strongest association was with initial clinical severity defined by high NIHSS score. NCT00226096 and NCT00716079; 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/.

Cost-effectiveness analysis alongside a pilot study of prophylactic negative pressure wound therapy.

PubMed

Heard, Christopher; Chaboyer, Wendy; Anderson, Vinah; Gillespie, Brigid M; Whitty, Jennifer A

2017-02-01

Negative pressure wound therapy (NPWT) is increasingly used prophylactically following surgery despite limited evidence of clinical or cost-effectiveness. To evaluate whether NPWT is cost-effective compared to standard care, for the prevention of surgical site infection (SSI) in obese women undergoing elective caesarean section, and inform development of a larger trial. An economic evaluation was conducted alongside a pilot randomised controlled trial at one Australian hospital, in which women were randomised to NPWT (n = 44) or standard care (n = 43). A public health care provider perspective and time horizon to four weeks post-discharge was adopted. Cost-effectiveness assessment was based on incremental cost per SSI prevented and per quality-adjusted life year (QALY) gained. Patients receiving NPWT each received health care costing AU$5887 (±1038) and reported 0.069 (±0.010) QALYs compared to AU$5754 (±1484) and 0.066 (±0.010) QALYs for patients receiving standard care. NPWT may be slightly more costly and more effective than standard care, with estimated incremental cost-effectiveness ratios (ICERs) of AU$1347 (95%CI dominant- $41,873) per SSI prevented and AU$42,340 (95%CI dominant- $884,019) per QALY gained. However, there was considerable uncertainty around these estimates. NPWT may be cost-effective in the prophylactic treatment of surgical wounds following elective caesarean section in obese women. Larger trials could clarify the cost-effectiveness of NPWT as a prophylactic treatment for SSI. Sensitive capture of QALYs and cost offsets will be important given the high level of uncertainty around the point estimate cost-effectiveness ratio which was close to conventional thresholds. ACTRN12612000171819. Copyright © 2016 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Does involvement in a cohort study improve health and affect health inequalities? A natural experiment.

PubMed

Quick, Annie; Böhnke, Jan R; Wright, John; Pickett, Kate E

2017-01-25

Evidence suggests that the process of taking part in health research can improve participants' health, independent of any intended intervention. However, no research has yet explored whether these effects differ across socioeconomic groups. If the effect of mere participation in health research also has a social gradient this could increase health inequalities and bias research results. This study used the Born in Bradford family cohort (BIB) to explore whether simply taking part in BIB had improved participants' health and, if so, whether this effect was mediated by socioeconomic status. Survey data on self-reported health behaviours were collected between 2007 and 2010 as part of BIB. These were augmented by clinical data on birth weight. Pregnant women on their second pregnancy, joining BIB for the first time formed the control group. Their health was compared to women on their second pregnancy who had both pregnancies within the study, who formed the exposed group. In order to limit the inherent bias in a non-randomised study, propensity score analysis was used, matching on age, ethnicity, education and date of questionnaire. The results were then compared according to mothers' education. Of six outcomes tested, only alcohol consumption showed a statistically significant reduction with exposure to BIB (OR: 0.35, 95% CIs 0.13, 0.92). Although effect estimates were larger for women with higher education compared to lower education, these effects were not statistically significant. Despite one significant finding, these results overall are insufficient to conclude that simply taking part in BIB affected participants' health. We recommend that socioeconomic status is considered in future studies testing effects of research participation, and that randomised studies with larger sample sizes are conducted.

Outcomes and Process in Reading Tutoring

ERIC Educational Resources Information Center

Topping, K. J.; Thurston, A.; McGavock, K.; Conlin, N.

2012-01-01

Background: Large-scale randomised controlled trials are relatively rare in education. The present study approximates to, but is not exactly, a randomised controlled trial. It was an attempt to scale up previous small peer tutoring projects, while investing only modestly in continuing professional development for teachers. Purpose: A two-year…

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

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.

Safety and efficacy of the predictive low glucose management system in the prevention of hypoglycaemia: protocol for randomised controlled home trial to evaluate the Suspend before low function.

PubMed

Abraham, M B; Nicholas, J A; Ly, T T; Roby, H C; Paramalingam, N; Fairchild, J; King, B R; Ambler, G R; Cameron, F; Davis, E A; Jones, T W

2016-04-15

Innovations with sensor-augmented pump therapy (SAPT) to reduce hypoglycaemia in patients with type 1 diabetes are an ongoing area of research. The predictive low glucose management (PLGM) system incorporates continuous glucose sensor data into an algorithm and suspends basal insulin before the occurrence of hypoglycaemia. The system was evaluated in in-clinic studies, and has informed the parameters of a larger home trial to study its efficacy and safety in real life. The aim of this report is to describe the study design and outcome measures for the trial. This is a 6-month, multicentre, randomised controlled home trial to test the PLGM system in children and adolescents with type 1 diabetes. The system is available in the Medtronic MiniMed 640G pump as the 'Suspend before low' feature. Following a run-in period, participants are randomised to either the control arm with SAPT alone or the intervention arm with SAPT and Suspend before low. The primary aim of this study is to evaluate the time spent hypoglycaemic (sensor glucose <3.5 mmol/L) with and without the system. The secondary aims are to determine the number of hypoglycaemic events, the time spent hyperglycaemic, and to evaluate safety with ketosis and changes in glycated haemoglobin. The study also aims to assess the changes in counter-regulatory hormone responses to hypoglycaemia evaluated by a hyperinsulinaemic hypoglycaemic clamp in a subgroup of patients with impaired awareness. Validated questionnaires are used to measure the fear of hypoglycaemia and the impact on the quality of life to assess burden of the disease. Ethics committee permissions were gained from respective Institutional Review boards. The findings of the study will provide high quality evidence of the ability of the system in the prevention of hypoglycaemia in real life. ACTRN12614000510640, 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/

A mobile technology intervention to reduce sedentary behaviour in 2- to 4-year-old children (Mini Movers): study protocol for a randomised controlled trial.

PubMed

Downing, Katherine L; Salmon, Jo; Hinkley, Trina; Hnatiuk, Jill A; Hesketh, Kylie D

2017-03-03

Sedentary behaviour (e.g. television viewing, sitting time) tracks over time and is associated with adverse health and developmental outcomes across the lifespan. Young children (5 years or younger) spend up to 12 h/day sedentary, of which around 2 h is spent in screen time (e.g. watching television). Interventions to reduce sedentary behaviour in early childhood report mixed results and many have limited potential for scalability. Mobile phones offer a wide-reaching, low-cost avenue for the delivery of health behaviour programmes to parents but their potential to reduce young children's sedentary behaviour has not been widely tested. This study aims to test the feasibility and efficacy of a parent-focused, predominantly mobile telephone-delivered intervention to support parents to minimise the amount of time their child spends using screens and in overall sitting time. Mini Movers is a pilot randomised controlled trial recruiting 100 parents and children. Inclusion criteria include having a child aged between 2 and 4 years, being able to speak, read and write English, and smartphone ownership. Participants will be randomised to the intervention or a wait-list control group at a 1:1 ratio. Intervention group parents will receive printed materials including a content booklet and goal-checking magnet and will participate in a one-on-one discussion with the interventionist to plan two goals to reduce their child's sedentary behaviour. Subsequently, the intervention will be delivered over 6 weeks via personalised and interactive text messages promoting positive health behaviours (strategies for decreasing screen time and overall sitting time), goal setting and self-monitoring. Outcomes to be assessed include intervention feasibility and children's screen time and objectively-assessed sitting time. Few studies have used mobile phone technology to deliver health behaviour programmes to parents of young children. Findings will inform the development of larger-scale interventions to reduce sedentary behaviour during early childhood. Australian New Zealand Clinical Trials registry, identifier: ACTRN12616000628448 . Prospectively registered on 16 May 2016.

Effectiveness of liaison psychiatric nursing in older medical inpatients with depression: a randomised controlled trial.

PubMed

Cullum, Sarah; Tucker, Sue; Todd, Chris; Brayne, Carol

2007-07-01

To compare liaison psychiatric nursing with usual medical care in the management of older medical inpatients who screen positive for depression. Pragmatic randomised controlled trial. Medical wards of UK district general hospital in rural East Anglia. One hundred and thirty-eight medical inpatients aged 65+ screened positive on the 15-item geriatric depression scale (GDS). One hundred and twenty-one out of 138 screen positives entered the trial (58/121 fulfilled criteria for depressive disorder at baseline). (i) A liaison psychiatric nurse assessed participants, formulated a care plan for treatment of their depression, ensured its implementation through liaison with appropriate agencies, and monitored participants' mood and response to treatment for up to 12 weeks. (ii) Usual treatment by hospital and primary care staff. ICD-10 depressive disorder, change in GDS-15 score, quality-adjusted life weeks (QALWs) and patient satisfaction rating. Eighty-six out of 121 participants completed the 16-week trial. Participants in the intervention group were more satisfied with their care, but no significant differences in depressive disorder, depression rating or QALWs gained were found between groups. However, there was a trend towards improvement in the intervention group and effect sizes were higher in the subgroup with depressive disorder. This study is the first RCT to evaluate liaison psychiatric nursing specifically for depression in older medical inpatients; the findings suggest improvement in mental health and quality of life, but a larger trial is required to provide convincing evidence.

The use of ketamine in ECT anaesthesia: A systematic review and critical commentary on efficacy, cognitive, safety and seizure outcomes.

PubMed

Gálvez, Verònica; McGuirk, Lucy; Loo, Colleen K

2017-09-01

This review will discuss ECT efficacy and cognitive outcomes when using ketamine as an ECT anaesthetic compared to other anaesthetics, taking into account important moderator variables that have often not been considered to date. It will also include information on safety and other ECT outcomes (seizure threshold and quality). A systematic search through MEDLINE, PubMed, PsychINFO, Cochrane Databases and reference lists from retrieved articles was performed. Search terms were: "ketamine" and "Electroconvulsive Therapy", from 1995 to September 2016. Meta-analyses, randomised controlled trials, open-label and retrospective studies published in English of depressed samples receiving ECT with ketamine anaesthesia were included (n = 24). Studies were heterogeneous in the clinical populations included and ECT treatment and anaesthetic methods. Frequently, studies did not report on ECT factors (i.e., pulse-width, treatment schedule). Findings regarding efficacy were mixed. Tolerance from repeated use may explain why several studies found that ketamine enhanced efficacy early in the ECT course but not at the end. The majority of studies did not comprehensively examine cognition and adverse effects were not systematically studied. Only a minority of the studies reported on seizure threshold and expression. The routine use of ketamine anaesthesia for ECT in clinical settings cannot yet be recommended based on published data. Larger randomised controlled trials, taking into account moderator variables, specifically reporting on ECT parameters and systematically assessing outcomes are encouraged.

Gait training assisted by multi-channel functional electrical stimulation early after stroke: study protocol for a randomized controlled trial.

PubMed

van Bloemendaal, Maijke; Bus, Sicco A; de Boer, Charlotte E; Nollet, Frans; Geurts, Alexander C H; Beelen, Anita

2016-10-01

Many stroke survivors suffer from paresis of lower limb muscles, resulting in compensatory gait patterns characterised by asymmetries in spatial and temporal parameters and reduced walking capacity. Functional electrical stimulation has been used to improve walking capacity, but evidence is mostly limited to the orthotic effects of peroneal functional electrical stimulation in the chronic phase after stroke. The aim of this study is to investigate the therapeutic effects of up to 10 weeks of multi-channel functional electrical stimulation (MFES)-assisted gait training on the restoration of spatiotemporal gait symmetry and walking capacity in subacute stroke patients. In a proof-of-principle study with a randomised controlled design, 40 adult patients with walking deficits who are admitted for inpatient rehabilitation within 31 days since the onset of stroke are randomised to either MFES-assisted gait training or conventional gait training. Gait training is delivered in 30-minute sessions each workday for up to 10 weeks. The step length symmetry ratio is the primary outcome. Blinded assessors conduct outcome assessments at baseline, every 2 weeks during the intervention period, immediately post intervention and at 3-month follow-up. This study aims to provide preliminary evidence for the feasibility and effectiveness of MFES-assisted gait rehabilitation early after stroke. Results will inform the design of a larger multi-centre trial. This trial is registered at the Netherlands Trial Register (number NTR4762 , registered 28 August 2014).

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

PubMed

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

2015-09-28

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

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

PubMed

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

2016-04-01

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

Pilot parallel randomised controlled trial of protective socks against usual care to reduce skin tears in high risk people: 'STOPCUTS'.

PubMed

Powell, Roy J; Hayward, Christopher J; Snelgrove, Caroline L; Polverino, Kathleen; Park, Linda; Chauhan, Rohan; Evans, Philip H; Byford, Rachel; Charman, Carolyn; Foy, Christopher J W; Pritchard, Colin; Kingsley, Andrew

2017-01-01

Skin tears are common in older adults and those taking steroids and warfarin. They are traumatic, often blunt injuries caused by oblique knocks to the extremities. The epidermis may separate from the dermis or both layers from underlying tissues leaving a skin flap or total loss of tissue, which is painful and prone to infection. 'Dermatuff™' knee-length socks containing Kevlar fibres (used in stab-proof vests and motorcyclists' clothing) aim to prevent skin tears. The acceptability of the socks and the feasibility of a randomised controlled trial (RCT) had not been explored. In this pilot parallel group RCT, 90 people at risk of skin-tear injury from Devon care homes and primary care were randomised to receive the socks or treatment as usual (TAU). The pilot aimed to estimate parameters to inform the design of a substantive trial and record professionals' views and participants' acceptability of the intervention and of study participation. Participants were randomised from July 2013 and followed up until February 2015. Community participants were easier to recruit than care homes residents but were 10 years younger on average and more active. To recruit 90 participants, 395 had to be approached overall as 77% were excluded or declined. Seventy-nine participants (88%) completed the trial and 27/44 (61%) wore the socks for 16 weeks. There were 31 skin tear injuries affecting 18 (20%) of the 90 participants. The TAU group received more injuries, more repeated episodes, and larger tears with greater severity. Common daily diary reasons for not wearing the socks included perceived warmth in hot weather or not being available (holiday, in hospital, bed rest). Resource use data were obtainable and indicated that sock wearing gave a reduction in treatment costs whilst well-completed questionnaires showed improvements in secondary outcomes. This pilot trial has successfully informed the design and conduct of a future definitive cost-effectiveness RCT. It would need to be conducted in primary care with 880 active at-risk, elderly patients (440 per arm). Skin tear incidence and quality of life (from EQ5D5L) over a 4-month period would be the primary and secondary outcomes respectively. ISRCTN, ISRCTN96565376.

Outcomes in a Randomised Controlled Trial of Mathematics Tutoring

ERIC Educational Resources Information Center

Topping, K. J.; Miller, D.; Murray, P.; Henderson, S.; Fortuna, C.; Conlin, N.

2011-01-01

Background: Large-scale randomised controlled trials (RCT) are relatively rare in education. The present study was an attempt to scale up previous small peer tutoring projects, while investing only modestly in continuing professional development for teachers. Purpose: A two-year RCT of peer tutoring in mathematics was undertaken in one local…

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

PubMed Central

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

2005-01-01

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

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

ERIC Educational Resources Information Center

Herodotou, Christothea; Heiser, Sarah; Rienties, Bart

2017-01-01

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

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

ERIC Educational Resources Information Center

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

2014-01-01

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

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

ERIC Educational Resources Information Center

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

2017-01-01

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

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

ERIC Educational Resources Information Center

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

2014-01-01

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

Therapeutic touch for anxiety disorders.

PubMed

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

2007-07-18

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

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

PubMed

Martí-Carvajal, Arturo J; Solà, Ivan

2015-06-09

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

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

PubMed

Szajewska, H; Kołodziej, M

2015-10-01

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

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

PubMed

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

2016-10-01

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

Two parallel, pragmatic, UK multicentre, randomised controlled trials comparing surgical options for upper compartment (vault or uterine) pelvic organ prolapse (the VUE Study): study protocol for a randomised controlled trial.

PubMed

Glazener, Cathryn; Constable, Lynda; Hemming, Christine; Breeman, Suzanne; Elders, Andrew; Cooper, Kevin; Freeman, Robert; Smith, Anthony R B; Hagen, Suzanne; McDonald, Alison; McPherson, Gladys; Montgomery, Isobel; Kilonzo, Mary; Boyers, Dwayne; Goulao, Beatriz; Norrie, John

2016-09-08

One in three women who have a prolapse operation will go on to have another operation, though not necessarily in the same compartment. Surgery can result in greater impairment of quality of life than the original prolapse itself (such as the development of new-onset urinary incontinence, or prolapse at a different site). Anterior and posterior prolapse surgery is most common (90 % of operations), but around 43 % of women also have a uterine (34 %) or vault (9 %) procedure at the same time. There is not enough evidence from randomised controlled trials (RCTs) to guide management of vault or uterine prolapse. The Vault or Uterine prolapse surgery Evaluation (VUE) study aims to assess the surgical management of upper compartment pelvic organ prolapse (POP) in terms of clinical effectiveness, cost-effectiveness and adverse events. VUE is two parallel, pragmatic, UK multicentre, RCTs (Uterine Trial and Vault Trial). Eligible for inclusion are women with vault or uterine prolapse: requiring a surgical procedure, suitable for randomisation and willing to be randomised. Randomisation will be computer-allocated separately for each trial, minimised on: requiring concomitant anterior and/or posterior POP surgery or not, concomitant incontinence surgery or not, age (under 60 years or 60 years and older) and surgeon. Participants will be randomly assigned, with equal probability to intervention or control arms in either the Uterine Trial or the Vault Trial. Uterine Trial participants will receive either a vaginal hysterectomy or a uterine preservation procedure. Vault Trial participants will receive either a vaginal sacrospinous fixation or an abdominal sacrocolpopexy. Participants will be followed up by postal questionnaires (6 months post surgery and 12 months post randomisation) and also reviewed in clinic 12 months post surgery. The primary outcome is the participant-reported Pelvic Organ Prolapse Symptom Score (POP-SS) at 12 months post randomisation. Demonstrating the efficacy of vault and uterine prolapse surgeries is relevant not only to patients and clinicians but also to health care providers, both in the UK and globally. Current controlled trials ISRCTN86784244 (assigned 19 October 2012), and the first subject was randomly assigned on 1 May 2013.

Effects of an exercise and manual therapy program on physical impairments, function and quality-of-life in people with osteoporotic vertebral fracture: a randomised, single-blind controlled pilot trial

PubMed Central

2010-01-01

Background This randomised, single-blind controlled pilot trial aimed to determine the effectiveness of a physiotherapy program, including exercise and manual therapy, in reducing impairments and improving physical function and health-related quality of life in people with a history of painful osteoporotic vertebral fracture. Methods 20 participants were randomly allocated to an intervention (n = 11) or control (n = 9) group. The intervention group attended individual sessions with an experienced clinician once a week for 10 weeks and performed daily home exercises with adherence monitored by a self-report diary. The control group received no treatment. Blinded assessment was conducted at baseline and 11 weeks. Questionnaires assessed self-reported changes in back pain, physical function, and health-related quality of life. Objective measures of thoracic kyphosis, back and shoulder muscle endurance (Timed Loaded Standing Test), and function (Timed Up and Go test) were also taken. Results Compared with the control group, the intervention group showed significant reductions in pain during movement (mean difference (95% CI) -1.8 (-3.5 to -0.1)) and at rest (-2.0 (-3.8 to -0.2)) and significantly greater improvements in Qualeffo physical function (-4.8 (-9.2 to -0.5)) and the Timed Loaded Standing test (46.7 (16.1 to 77.3) secs). For the perceived change in back pain over the 10 weeks, 9/11 (82%) participants in the intervention group rated their pain as 'much better' compared with only 1/9 (11%) participants in the control group. Conclusion Despite the modest sample size, these results support the benefits of exercise and manual therapy in the clinical management of patients with osteoporotic vertebral fractures, but need to be confirmed in a larger sample. Trail registration NCT00638768 PMID:20163739

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

PubMed

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

2004-10-01

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

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

PubMed

Williams, Stefanie L; French, David P

2014-02-05

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

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

PubMed Central

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

2013-01-01

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

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

PubMed Central

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

2015-01-01

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

Study protocol for the ‘HelpMeDoIt!’ randomised controlled feasibility trial: an app, web and social support-based weight loss intervention for adults with obesity

PubMed Central

Matthews, Lynsay; Pugmire, Juliana; Moore, Laurence; Kelson, Mark; McConnachie, Alex; McIntosh, Emma; Morgan-Trimmer, Sarah; Murphy, Simon; Hughes, Kathryn; Coulman, Elinor; Utkina-Macaskill, Olga; Simpson, Sharon Anne

2017-01-01

Introduction HelpMeDoIt! will test the feasibility of an innovative weight loss intervention using a smartphone app and website. Goal setting, self-monitoring and social support are three key facilitators of behaviour change. HelpMeDoIt! incorporates these features and encourages participants to invite ‘helpers’ from their social circle to help them achieve their goal(s). Aim To test the feasibility of the intervention in supporting adults with obesity to achieve weight loss goals. Methods and analysis 12-month feasibility randomised controlled trial and accompanying process evaluation. Participants (n=120) will be adults interested in losing weight, body mass index (BMI)≥30 kg/m2 and smartphone users. The intervention group will use the app/website for 12 months. Participants will nominate one or more helpers to support them. Helpers have access to the app/website. The control group will receive a leaflet on healthy lifestyle and will have access to HelpMeDoIt! after follow-up. The key outcome of the study is whether prespecified progression criteria have been met in order to progress to a larger randomised controlled effectiveness trial. Data will be collected at baseline, 6 and 12 months. Outcomes focus on exploring the feasibility of delivering the intervention and include: (i) assessing three primary outcomes (BMI, physical activity and diet); (ii) secondary outcomes of waist/hip circumference, health-related quality of life, social support, self-efficacy, motivation and mental health; (iii) recruitment and retention; (iv) National Health Service (NHS) resource use and participant borne costs; (v) usability and acceptability of the app/website; and (vi) qualitative interviews with up to 50 participants and 20 helpers on their experiences of the intervention. Statistical analyses will focus on feasibility outcomes and provide initial estimates of intervention effects. Thematic analysis of qualitative interviews will assess implementation, acceptability, mechanisms of effect and contextual factors influencing the intervention. Ethics and dissemination The protocol has been approved by the West of Scotland NHS Research Ethics Committee (Ref: 15/WS/0288) and the University of Glasgow MVLS College Ethics Committee (Ref: 200140108). Findings will be disseminated widely through peer-reviewed publication and conference presentations. Trial registration number ISRCTN85615983. PMID:29074513

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

ERIC Educational Resources Information Center

Griffiths, Kathleen M.; Christensen, Helen

2006-01-01

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

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

ERIC Educational Resources Information Center

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

2011-01-01

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

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

ERIC Educational Resources Information Center

Skryabina, Elena; Taylor, Gordon; Stallard, Paul

2016-01-01

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

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

ERIC Educational Resources Information Center

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

2006-01-01

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

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

ERIC Educational Resources Information Center

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

2007-01-01

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

"Every Child Counts": Testing Policy Effectiveness Using a Randomised Controlled Trial, Designed, Conducted and Reported to CONSORT Standards

ERIC Educational Resources Information Center

Torgerson, Carole; Wiggins, Andy; Torgerson, David; Ainsworth, Hannah; Hewitt, Catherine

2013-01-01

We report a randomised controlled trial evaluation of an intensive one-to-one numeracy programme--"Numbers Count"--which formed part of the previous government's numeracy policy intervention--"Every Child Counts." We rigorously designed and conducted the trial to CONSORT guidelines. We used a pragmatic waiting list design to…

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

ERIC Educational Resources Information Center

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

2009-01-01

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

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

ERIC Educational Resources Information Center

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

2012-01-01

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

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

PubMed

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

2015-12-09

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

Maternal adverse effects of different antenatal magnesium sulphate regimens for improving maternal and infant outcomes: a systematic review

PubMed Central

2013-01-01

Background Antenatal magnesium sulphate, widely used in obstetrics to improve maternal and infant outcomes, may be associated with adverse effects for the mother sufficient for treatment cessation. This systematic review aimed to quantify maternal adverse effects attributed to treatment, assess how adverse effects vary according to different regimens, and explore women’s experiences with this treatment. Methods Bibliographic databases were searched from their inceptions to July 2012 for studies of any design that reported on maternal adverse effects associated with antenatal magnesium sulphate given to improve maternal or infant outcomes. Primary outcomes were life-threatening adverse effects of treatment (death, cardiac arrest, respiratory arrest). For randomised controlled trials, data were meta-analysed, and risk ratios (RR) pooled using fixed-effects or random-effects models. For non-randomised studies, data were tabulated by design, and presented as RR, odds ratios or percentages, and summarised narratively. Results A total of 143 publications were included (21 randomised trials, 15 non-randomised comparative studies, 32 case series and 75 reports of individual cases), of mixed methodological quality. Compared with placebo or no treatment, magnesium sulphate was not associated with an increased risk of maternal death, cardiac arrest or respiratory arrest. Magnesium sulphate significantly increased the risk of 'any adverse effects’ overall (RR 4.62, 95% CI 2.42-8.83; 4 trials, 13,322 women), and treatment cessation due to adverse effects (RR 2.77; 95% CI 2.32-3.30; 5 trials, 13,666 women). Few subgroup differences were observed (between indications for use and treatment regimens). In one trial, a lower dose regimen (2 g/3 hours) compared with a higher dose regimen (5 g/4 hours) significantly reduced treatment cessation (RR 0.05; 95% CI 0.01-0.39, 126 women). Adverse effect estimates from studies of other designs largely supported data from randomised trials. Case reports supported an association between iatrogenic overdose of magnesium sulphate and life-threatening consequences. Conclusions Appropriate administration of antenatal magnesium sulphate was not shown to be associated with serious maternal adverse effects, though an increase in 'minor’ adverse effects and treatment cessation was shown. Larger trials are needed to determine optimal regimens, achieving maximal effectiveness with minimal adverse effects, for each antenatal indication for use. Vigilance in the use of magnesium sulphate is essential for women’s safety. PMID:24139447

Infant feeding bottle design, growth and behaviour: results from a randomised trial

PubMed Central

2012-01-01

Background Whether the design of an anti-vacuum infant feeding bottle influences infant milk intake, growth or behavior is unknown, and was the subject of this randomized trial. Methods Subjects 63 (36 male) healthy, exclusively formula-fed term infants. Intervention Randomisation to use Bottle A (n = 31), one-way air valve: Philips Avent) versus Bottle B (n = 32), internal venting system: Dr Browns). 74 breast-fed reference infants were recruited, with randomisation (n = 24) to bottle A (n = 11) or B (n = 13) if bottle-feeding was subsequently introduced. Randomisation stratified by gender and parity; computer-based telephone randomisation by independent clinical trials unit. Setting Infant home. Primary outcome measure infant weight gain to 4 weeks. Secondary outcomes (i) milk intake (ii) infant behaviour measured at 2 weeks (validated 3-day diary); (iii) risk of infection; (iv) continuation of breastfeeding following introduction of mixed feeding. Results Number analysed for primary outcome Bottle A n = 29, Bottle B n = 25. Primary outcome There was no significant difference in weight gain between randomised groups (0-4 weeks Bottle A 0.74 (SD 1.2) SDS versus bottle B 0.51 (0.39), mean difference 0.23 (95% CI -0.31 to 0.77). Secondary outcomes Infants using bottle A had significantly less reported fussing (mean 46 versus 74 minutes/day, p < 0.05) than those using bottle B. There was no significant difference in any other outcome measure. Breast-fed reference group There were no significant differences in primary or secondary outcomes between breast-fed and formula fed infants. The likelyhood of breastfeeding at 3 months was not significantly different in infants subsequently randomised to bottle A or B. Conclusion Bottle design may have short-term effects on infant behaviour which merit further investigation. No significant effects were seen on milk intake or growth; confidence in these findings is limited by the small sample size and this needs confirmation in a larger study. Trial registration Clinical Trials.gov NCT00325208. PMID:22424116

Gait retraining versus foot orthoses for patellofemoral pain: a pilot randomised clinical trial.

PubMed

Bonacci, Jason; Hall, Michelle; Saunders, Natalie; Vicenzino, Bill

2018-05-01

To determine the feasibility of a clinical trial that compares a 6-week, physiotherapist-guided gait retraining program with a foot orthoses intervention in runners with patellofemoral pain. Pilot randomised controlled trial. Runners aged 18-40 years with clinically diagnosed patellofemoral pain were randomly allocated to either a 6-week gait retraining intervention of increasing cadence and use of a minimalist shoe or prefabricated foot orthoses. Outcomes at baseline and 12-weeks included recruitment, retention, adherence, adverse events, global improvement, anterior knee pain scale, worst and average pain on a 100mm visual analogue scale. Of the 16 randomised participants, two withdrew prior to commencing treatment due to non-trial related matters (n=1 from each group) and 14 completed the pilot trial. Minor calf muscle soreness was reported by 3 participants in the gait retraining group while no adverse events were reported in the foot orthoses group. There were no deviations from the treatment protocols. There was a large between-group difference favouring gait retraining at 12-weeks in the anterior knee pain scale and the worst pain in the past week, which was reflected in the number needed-to-treat of 2. This study supports the feasibility of a trial comparing gait retraining with foot orthoses and provides point estimates of effect that informs the design and planning of a larger clinical trial. It appears that a 6-week gait retraining program has a clinically meaningful effect on runners with patellofemoral pain when compared to an evidence-based treatment of foot orthoses. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Telephone follow-up for cataract surgery: feasibility and patient satisfaction study.

PubMed

Hoffman, Jeremy J S L; Pelosini, Lucia

2016-05-09

Purpose - The purpose of this paper is to investigate the feasibility of telephone follow-up (TFU) after uncomplicated cataract surgery in low-risk patients and patient satisfaction with this alternative clinical pathway. Design/methodology/approach - Prospective, non-randomised cohort study. A ten-point subjective ophthalmic assessment questionnaire and a six-point patient satisfaction questionnaire were administered to patients following routine cataract surgery at two to three weeks post-procedure. All patients were offered a further clinic review if required. Exclusion criteria comprised ophthalmic co-morbidities, hearing/language impairment and high risk of post-operative complications. Patient notes were retrospectively reviewed over the study period to ensure no additional emergency attendances took place. Findings - Over three months, 50 eyes of 50 patients (mean age: 80; age range 60-91; 66 per cent second eye surgery) underwent uncomplicated phacoemulsification surgery received a TFU at 12-24 days (mean: 16 days) post-operatively. Subjective visual acuity was graded as good by 92 per cent of patients; 72 per cent patients reported no pain and 20 per cent reported mild occasional grittiness. Patient satisfaction was graded 8.9 out of 10; 81.6 per cent defined TFU as convenient and 75.5 per cent of patients preferred TFU to routine outpatient review. No additional visits were required. Research limitations/implications - Non-randomised with no control group; small sample size. One patient was unable to be contacted. Practical implications - Post-operative TFU can be suitably targeted to low-risk patients following uncomplicated cataract surgery. This study demonstrated a high patient satisfaction. A larger, randomised study is in progress to assess this further. Originality/value - This is the first study reporting TFU results and patient satisfaction to the usual alternative two-week outpatient review.

Antidepressant Controlled Trial For Negative Symptoms In Schizophrenia (ACTIONS): a double-blind, placebo-controlled, randomised clinical trial.

PubMed

Barnes, Thomas R E; Leeson, Verity C; Paton, Carol; Costelloe, Céire; Simon, Judit; Kiss, Noemi; Osborn, David; Killaspy, Helen; Craig, Tom K J; Lewis, Shôn; Keown, Patrick; Ismail, Shajahan; Crawford, Mike; Baldwin, David; Lewis, Glyn; Geddes, John; Kumar, Manoj; Pathak, Rudresh; Taylor, Simon

2016-04-01

Negative symptoms of schizophrenia represent deficiencies in emotional responsiveness, motivation, socialisation, speech and movement. When persistent, they are held to account for much of the poor functional outcomes associated with schizophrenia. There are currently no approved pharmacological treatments. While the available evidence suggests that a combination of antipsychotic and antidepressant medication may be effective in treating negative symptoms, it is too limited to allow any firm conclusions. To establish the clinical effectiveness and cost-effectiveness of augmentation of antipsychotic medication with the antidepressant citalopram for the management of negative symptoms in schizophrenia. A multicentre, double-blind, individually randomised, placebo-controlled trial with 12-month follow-up. Adult psychiatric services, treating people with schizophrenia. Inpatients or outpatients with schizophrenia, on continuing, stable antipsychotic medication, with persistent negative symptoms at a criterion level of severity. Eligible participants were randomised 1 : 1 to treatment with either placebo (one capsule) or 20 mg of citalopram per day for 48 weeks, with the clinical option at 4 weeks to increase the daily dosage to 40 mg of citalopram or two placebo capsules for the remainder of the study. The primary outcomes were quality of life measured at 12 and 48 weeks assessed using the Heinrich's Quality of Life Scale, and negative symptoms at 12 weeks measured on the negative symptom subscale of the Positive and Negative Syndrome Scale. No therapeutic benefit in terms of improvement in quality of life or negative symptoms was detected for citalopram over 12 weeks or at 48 weeks, but secondary analysis suggested modest improvement in the negative symptom domain, avolition/amotivation, at 12 weeks (mean difference -1.3, 95% confidence interval -2.5 to -0.09). There were no statistically significant differences between the two treatment arms over 48-week follow-up in either the health economics outcomes or costs, and no differences in the frequency or severity of adverse effects, including corrected QT interval prolongation. The trial under-recruited, partly because cardiac safety concerns about citalopram were raised, with the 62 participants recruited falling well short of the target recruitment of 358. Although this was the largest sample randomised to citalopram in a randomised controlled trial of antidepressant augmentation for negative symptoms of schizophrenia and had the longest follow-up, the power of statistical analysis to detect significant differences between the active and placebo groups was limited. Although adjunctive citalopram did not improve negative symptoms overall, there was evidence of some positive effect on avolition/amotivation, recognised as a critical barrier to psychosocial rehabilitation and achieving better social and community functional outcomes. Comprehensive assessment of side-effect burden did not identify any serious safety or tolerability issues. The addition of citalopram as a long-term prescribing strategy for the treatment of negative symptoms may merit further investigation in larger studies. Further studies of the viability of adjunctive antidepressant treatment for negative symptoms in schizophrenia should include appropriate safety monitoring and use rating scales that allow for evaluation of avolition/amotivation as a discrete negative symptom domain. Overcoming the barriers to recruiting an adequate sample size will remain a challenge. European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2009-009235-30 and Current Controlled Trials ISRCTN42305247. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 29. See the NIHR Journals Library website for further project information.

The optimal design of stepped wedge trials with equal allocation to sequences and a comparison to other trial designs.

PubMed

Thompson, Jennifer A; Fielding, Katherine; Hargreaves, James; Copas, Andrew

2017-12-01

Background/Aims We sought to optimise the design of stepped wedge trials with an equal allocation of clusters to sequences and explored sample size comparisons with alternative trial designs. Methods We developed a new expression for the design effect for a stepped wedge trial, assuming that observations are equally correlated within clusters and an equal number of observations in each period between sequences switching to the intervention. We minimised the design effect with respect to (1) the fraction of observations before the first and after the final sequence switches (the periods with all clusters in the control or intervention condition, respectively) and (2) the number of sequences. We compared the design effect of this optimised stepped wedge trial to the design effects of a parallel cluster-randomised trial, a cluster-randomised trial with baseline observations, and a hybrid trial design (a mixture of cluster-randomised trial and stepped wedge trial) with the same total cluster size for all designs. Results We found that a stepped wedge trial with an equal allocation to sequences is optimised by obtaining all observations after the first sequence switches and before the final sequence switches to the intervention; this means that the first sequence remains in the control condition and the last sequence remains in the intervention condition for the duration of the trial. With this design, the optimal number of sequences is [Formula: see text], where [Formula: see text] is the cluster-mean correlation, [Formula: see text] is the intracluster correlation coefficient, and m is the total cluster size. The optimal number of sequences is small when the intracluster correlation coefficient and cluster size are small and large when the intracluster correlation coefficient or cluster size is large. A cluster-randomised trial remains more efficient than the optimised stepped wedge trial when the intracluster correlation coefficient or cluster size is small. A cluster-randomised trial with baseline observations always requires a larger sample size than the optimised stepped wedge trial. The hybrid design can always give an equally or more efficient design, but will be at most 5% more efficient. We provide a strategy for selecting a design if the optimal number of sequences is unfeasible. For a non-optimal number of sequences, the sample size may be reduced by allowing a proportion of observations before the first or after the final sequence has switched. Conclusion The standard stepped wedge trial is inefficient. To reduce sample sizes when a hybrid design is unfeasible, stepped wedge trial designs should have no observations before the first sequence switches or after the final sequence switches.

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

PubMed Central

2011-01-01

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

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

PubMed Central

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

2017-01-01

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

Trimetazidine: a meta-analysis of randomised controlled trials in heart failure.

PubMed

Gao, Dengfeng; Ning, Ning; Niu, Xiaolin; Hao, Guanghua; Meng, Zhe

2011-02-01

To explore whether trimetazidine could improve symptoms, cardiac functions and clinical outcomes in patients with heart failure (HF). A systematic literature search was conducted to identify randomised controlled trials (RCT) of trimetazidine for HF between 1966 and May 2010 in Pubmed, the Cochrane Central Registry of Clinical Trials and EMBASE. Reports of trials were sought that compared trimetazidine with placebo control for chronic HF in adults, with outcomes including all-cause mortality, hospitalisation, cardiovascular events, changes in cardiac function parameters and exercise capacity. 17 trials with data for 955 patients were identified by the literature search. Trimetazidine therapy was associated with a significant improvement in left ventricular ejection fraction in patients with both ischaemic (weighted mean difference (WMD) with placebo 7.37%; 95% CI 6.05 to 8.70; p<0.01) and non-ischaemic HF (WMD 8.72%; 95% CI 5.51 to 11.92; p<0.01). With trimetazidine therapy, left ventricular end-systolic volume was significantly reduced (WMD 10.37 ml; 95% CI 15.46 to 5.29; p<0.01) and New York Heart Association classification was improved (WMD 0.41; 95% CI 0.51 to 0.31; p<0.01) as was exercise duration (WMD, 30.26 s; 95% CI 8.77 to 51.75; p<0.01). More importantly, trimetazidine had a significant protective effect for all-cause mortality (RR 0.29; 95% CI 0.17 to 0.49; p<0.00001) and cardiovascular events and hospitalisation (RR 0.42; 95% CI 0.30 to 0.58; p<0.00001). Trimetazidine might be an effective strategy for treating HF. More studies, especially larger multicentre RCT, are warranted to clarify the effect of trimetazidine on HF.

Physiotherapy education and training prior to upper abdominal surgery is memorable and has high treatment fidelity: a nested mixed-methods randomised-controlled study.

PubMed

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

2018-06-01

To (1) assess memorability and treatment fidelity of pre-operative physiotherapy education prior to elective upper abdominal surgery and, (2) to explore patient opinions on pre-operative education. Mixed-methods analysis of a convenience sample within a larger parallel-group, double-blinded, randomised controlled trial with concealed allocation and intention-to-treat analysis. Tertiary Australian hospital. Twenty-nine patients having upper abdominal surgery attending pre-admission clinic within six-weeks of surgery. The control group received an information booklet about preventing pulmonary complications with early ambulation and breathing exercises. The experimental group received an additional face-to-face 30-minute physiotherapy education and training session on pulmonary complications, early ambulation, and breathing exercises. Primary outcome was proportion of participants who remembered the taught breathing exercises following surgery. Secondary outcomes were recall of information sub-items and attainment of early ambulation goals. These were measured using standardised scoring of a semi-scripted digitally-recorded interview on the 5th postoperative day, and the attainment of early ambulation goals over the first two postoperative days. Experimental group participants were six-times more likely to remember the breathing exercises (95%CI 1.7 to 22) and 11-times more likely (95%CI 1.6 to 70) to report physiotherapy as the most memorable part of pre-admission clinic. Participants reported physiotherapy education content to be detailed, interesting, and of high value. Some participants reported not reading the booklet and professed a preference for face-to-face information delivery. Face-to-face pre-operative physiotherapy education and training prior to upper abdominal surgery is memorable and has high treatment fidelity. ACTRN-12613000664741. Copyright © 2017 Chartered Society of Physiotherapy. All rights reserved.

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

PubMed

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

2016-09-20

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

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

PubMed

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

2015-01-16

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

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

PubMed

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

2016-02-01

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

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

PubMed

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

2016-11-28

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

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

PubMed

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

2015-01-01

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

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

ERIC Educational Resources Information Center

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

2017-01-01

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

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

ERIC Educational Resources Information Center

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

2017-01-01

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

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

ERIC Educational Resources Information Center

Aldred, Catherine; Green, Jonathan; Adams, Catherine

2004-01-01

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

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

ERIC Educational Resources Information Center

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

2014-01-01

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

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

ERIC Educational Resources Information Center

Gardner, Frances; Burton, Jennifer; Klimes, Ivana

2006-01-01

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

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

ERIC Educational Resources Information Center

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

2012-01-01

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

Psychological effects of belonging to a Facebook weight management group in overweight and obese adults: Results of a randomised controlled trial.

PubMed

Jane, Monica; Foster, Jonathan; Hagger, Martin; Ho, Suleen; Kane, Robert; Pal, Sebely

2018-05-18

This study was conducted to test whether the weight outcomes in an online social networking group were mediated by changes to psychological outcome measures in overweight and obese individuals, following a weight management programme delivered via Facebook. The data analysed in this study were collected during a three-armed, randomised, controlled clinical weight management trial conducted with overweight and obese adults over 24 weeks. Two intervention groups were given the same weight management programme: one within a Facebook group, along with peer support from other group members (the Facebook Group); the other group received the same programme in a pamphlet (the Pamphlet Group). A Control Group was given standard care. The primary outcome was weight; secondary outcomes included the following domains from self-reported questionnaires: energy intake and expenditure; psychological health, social relationships, physical health, quality of life, depression, anxiety, stress, health anxiety, happiness, as well as Facebook Group participants' opinion of this group. The Facebook Group experienced a reduction in their baseline weight measurement by week 24, significantly compared to the Control Group (p = .016). The Facebook Group recorded a significant increase in the psychological health domain during the trial (at week 12) relative to their baseline measurement, and significant compared to the Control Group (p = .022). Mediation analysis indicated a statistical trend, but not statistical significance, for psychological health as a mediator to weight loss in the Facebook Group. While both intervention groups showed significant changes in psychological outcome measures, the Facebook Group was the only group to experience statistically significant weight loss by the end of the 24 weeks. Therefore, an examination of other psychological and/or behavioural outcome measures undertaken in larger studies in the future may help to identify significant mediators to improved weight loss outcomes in online social networking groups. © 2018 John Wiley & Sons Ltd.

Cluster randomised feasibility trial to improve the Control of Hypertension In Rural India (CHIRI): a study protocol

PubMed Central

Riddell, Michaela A; Joshi, Rohina; Oldenburg, Brian; Chow, Clara; Thankappan, K R; Mahal, Ajay; Thomas, Nihal; Srikanth, Velandai K; Evans, Roger G; Kalyanram, Kartik; Kartik, Kamakshi; Maulik, Pallab K; Arabshahi, Simin; Varma, R P; Guggilla, Rama K; Suresh, Oduru; Mini, G K; D'Esposito, Fabrizio; Sathish, Thirunavukkarasu; Alim, Mohammed

2016-01-01

Introduction Hypertension is emerging in rural populations of India. Barriers to diagnosis and treatment of hypertension may differ regionally according to economic development. Our main objectives are to estimate the prevalence, awareness, treatment and control of hypertension in 3 diverse regions of rural India; identify barriers to diagnosis and treatment in each setting and evaluate the feasibility of a community-based intervention to improve control of hypertension. Methods and analysis This study includes 4 main activities: (1) assessment of risk factors, quality of life, socioeconomic position and barriers to changes in lifestyle behaviours in ∼14 500 participants; (2) focus group discussions with individuals with hypertension and indepth interviews with healthcare providers, to identify barriers to control of hypertension; (3) use of a medicines-availability survey to determine the availability, affordability and accessibility of medicines and (4) trial of an intervention provided by Accredited Social Health Activists (ASHAs), comprising group-based education and support for individuals with hypertension to self-manage blood pressure. Wards/villages/hamlets of a larger Mandal are identified as the primary sampling unit (PSU). PSUs are then randomly selected for inclusion in the cross-sectional survey, with further randomisation to intervention or control. Changes in knowledge of hypertension and risk factors, and clinical and anthropometric measures, are assessed. Evaluation of the intervention by participants provides insight into perceptions of education and support of self-management delivered by the ASHAs. Ethics and dissemination Approval for the overall study was obtained from the Health Ministry's Screening Committee, Ministry of Health and Family Welfare (India), institutional review boards at each site and Monash University. In addition to publication in peer-reviewed articles, results will be shared with federal, state and local government health officers, local healthcare providers and communities. Trial registration number CTRI/2016/02/006678; Pre-results. PMID:27855099

Cluster randomised feasibility trial to improve the Control of Hypertension In Rural India (CHIRI): a study protocol.

PubMed

Riddell, Michaela A; Joshi, Rohina; Oldenburg, Brian; Chow, Clara; Thankappan, K R; Mahal, Ajay; Thomas, Nihal; Srikanth, Velandai K; Evans, Roger G; Kalyanram, Kartik; Kartik, Kamakshi; Maulik, Pallab K; Arabshahi, Simin; Varma, R P; Guggilla, Rama K; Suresh, Oduru; Mini, G K; D'Esposito, Fabrizio; Sathish, Thirunavukkarasu; Alim, Mohammed; Thrift, Amanda G

2016-10-08

Hypertension is emerging in rural populations of India. Barriers to diagnosis and treatment of hypertension may differ regionally according to economic development. Our main objectives are to estimate the prevalence, awareness, treatment and control of hypertension in 3 diverse regions of rural India; identify barriers to diagnosis and treatment in each setting and evaluate the feasibility of a community-based intervention to improve control of hypertension. This study includes 4 main activities: (1) assessment of risk factors, quality of life, socioeconomic position and barriers to changes in lifestyle behaviours in ∼14 500 participants; (2) focus group discussions with individuals with hypertension and indepth interviews with healthcare providers, to identify barriers to control of hypertension; (3) use of a medicines-availability survey to determine the availability, affordability and accessibility of medicines and (4) trial of an intervention provided by Accredited Social Health Activists (ASHAs), comprising group-based education and support for individuals with hypertension to self-manage blood pressure. Wards/villages/hamlets of a larger Mandal are identified as the primary sampling unit (PSU). PSUs are then randomly selected for inclusion in the cross-sectional survey, with further randomisation to intervention or control. Changes in knowledge of hypertension and risk factors, and clinical and anthropometric measures, are assessed. Evaluation of the intervention by participants provides insight into perceptions of education and support of self-management delivered by the ASHAs. Approval for the overall study was obtained from the Health Ministry's Screening Committee, Ministry of Health and Family Welfare (India), institutional review boards at each site and Monash University. In addition to publication in peer-reviewed articles, results will be shared with federal, state and local government health officers, local healthcare providers and communities. CTRI/2016/02/006678; 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/.

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

PubMed

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

2017-08-02

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

Exercise and mental health: a review.

PubMed

Glenister, D

1996-02-01

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

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

PubMed

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

2016-04-01

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

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

PubMed

2015-07-27

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

Placebo effects in psychiatry: mediators and moderators

PubMed Central

Weimer, Katja; Colloca, Luana; Enck, Paul

2015-01-01

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

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

PubMed Central

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

2007-01-01

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

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

PubMed

Cook, Lorna; Watkins, Edward

2016-01-04

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

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

PubMed Central

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

1999-01-01

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

Are Pain-Related Fears Mediators for Reducing Disability and Pain in Patients with Complex Regional Pain Syndrome Type 1? An Explorative Analysis on Pain Exposure Physical Therapy

PubMed Central

Barnhoorn, Karlijn J.; Staal, J. Bart; van Dongen, Robert T. M.; Frölke, Jan Paul M.; Klomp, Frank P.; van de Meent, Henk; Samwel, Han; Nijhuis-van der Sanden, Maria W. G.

2015-01-01

Objective To investigate whether pain-related fears are mediators for reducing disability and pain in patients with Complex Regional Pain Syndrome type 1 when treating with Pain Exposure Physical Therapy. Design An explorative secondary analysis of a randomised controlled trial. Participants Fifty-six patients with Complex Regional Pain Syndrome type 1. Interventions The experimental group received Pain Exposure Physical Therapy in a maximum of five treatment sessions; the control group received conventional treatment following the Dutch multidisciplinary guideline. Outcome measures Levels of disability, pain, and pain-related fears (fear-avoidance beliefs, pain catastrophizing, and kinesiophobia) were measured at baseline and after 3, 6, and 9 months follow-up. Results The experimental group had a significantly larger decrease in disability of 7.77 points (95% CI 1.09 to 14.45) and in pain of 1.83 points (95% CI 0.44 to 3.23) over nine months than the control group. The potential mediators pain-related fears decreased significantly in both groups, but there were no significant differences between groups, which indicated that there was no mediation. Conclusion The reduction of pain-related fears was comparable in both groups. We found no indication that pain-related fears mediate the larger reduction of disability and pain in patients with Complex Regional Pain Syndrome type 1 treated with Pain Exposure Physical Therapy compared to conventional treatment. Trial registration International Clinical Trials Registry NCT00817128 PMID:25919011

Achieving Good Outcomes for Asthma Living (GOAL): mixed methods feasibility and pilot cluster randomised controlled trial of a practical intervention for eliciting, setting and achieving goals for adults with asthma.

PubMed

Hoskins, Gaylor; Williams, Brian; Abhyankar, Purva; Donnan, Peter; Duncan, Edward; Pinnock, Hilary; van der Pol, Marjon; Rauchhaus, Petra; Taylor, Anne; Sheikh, Aziz

2016-12-08

Despite being a core component of self-management, goal setting is rarely used in routine care. We piloted a primary care, nurse-led intervention called Achieving Good Outcomes for Asthma Living (GOAL) for adults with asthma. Patients were invited to identify and prioritise their goals in preparation for discussing and negotiating an action/coping plan with the nurse at a routine asthma review. The 18-month mixed methods feasibility cluster pilot trial stratified and then randomised practices to deliver usual care (UC) or a goal-setting intervention (GOAL). Practice asthma nurses and adult patients with active asthma were invited to participate. The primary outcome was asthma-specific quality of life. Semi-structured interviews with a purposive patient sample (n = 14) and 10 participating nurses explored GOAL perception. The constructs of normalisation process theory (NPT) were used to analyse and interpret data. Ten practices participated (five in each arm), exceeding our target of eight. However, only 48 patients (target 80) were recruited (18 in GOAL practices). At 6 months post-intervention, the difference in mean asthma-related quality of life (mAQLQ) between intervention and control was 0.1 (GOAL 6.20: SD 0.76 (CI 5.76-6.65) versus UC 6.1: SD 0.81 (CI 5.63-6.57)), less than the minimal clinically important difference (MCID) of 0.5. However, change from baseline was stronger in the intervention group: at 6 months the change in the emotions sub-score was 0.8 for intervention versus 0.2 for control. Costs were higher in the intervention group by £22.17. Routine review with goal setting was considered more holistic, enhancing rapport and enabling patients to become active rather than passive participants in healthcare. However, time was a major barrier for nurses, who admitted to screening out patient goals they believed were unrelated to asthma. The difference in AQLQ score from baseline is larger in the intervention arm than the control, indicating the intervention may have impact if appropriately strengthened. The GOAL intervention changed the review dynamic and was well received by patients, but necessitated additional time, which was problematic in the confines of the traditional nurse appointment. Modification to recruitment methods and further development of the intervention are needed before proceeding to a definitive cluster randomised controlled trial. ISRCTN18912042 . Registered on 26 June 2012.

Protocol for a feasibility study and randomised pilot trial of a low-intensity psychological intervention for depression in adults with autism: the Autism Depression Trial (ADEPT).

PubMed

Russell, Ailsa; Cooper, Kate; Barton, Stephen; Ensum, Ian; Gaunt, Daisy; Horwood, Jeremy; Ingham, Barry; Kessler, David; Metcalfe, Chris; Parr, Jeremy; Rai, Dheeraj; Wiles, Nicola

2017-12-03

High rates of co-occurring depression are reported in autism spectrum disorder (ASD), a neurodevelopmental condition characterised by social communication impairments and repetitive behaviours. Cognitive-behavioural interventions adapted for ASD have been effective for anxiety problems. There have been evaluation studies of group cognitive-behavioural therapy for co-occurring depression, but no randomised trials investigating low-intensity psychological interventions as recommended in clinical guidelines for mild-moderate depression. A feasibility study comprising a randomised controlled trial (RCT) and nested qualitative evaluation is under way as preparation for a definitive RCT. Participants (n=70) will be randomised to Guided Self-Help: a low-intensity psychological intervention based on behavioural activation adapted for ASD or treatment as usual. Outcomes including depression symptoms, anxiety, social function and service use will be measured at 10, 16 and 24 weeks postrandomisation and will be blind to group allocation for measures that are not self-administered. The analysis will aim to establish the rates of recruitment and retention for a larger-scale RCT as well as the most appropriate measure of depression to serve as primary outcome. The qualitative study will purposively sample up to 24 participants from each treatment group to consider the acceptability and feasibility of the intervention and the trial design. Ethical approval has been received from WALES REC 3 (IRAS project ID: 191558) and the Health Research Authority with R&D approval from Avon and Wiltshire Mental Health Partnership and Northumberland, Tyne and Wear Foundation NHS Trusts. To our knowledge, this is the first study of a low-intensity intervention for depression in adults with autism. The results will inform the design of a definitive RCT. Dissemination will include peer-reviewed journal publications reporting the quantitative and qualitative research findings of the study and presentations at national and international conferences. ISRCTN54650760; 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.

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

ERIC Educational Resources Information Center

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

2017-01-01

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

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

ERIC Educational Resources Information Center

Miller, David J.; Robertson, Derek P.

2011-01-01

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

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

ERIC Educational Resources Information Center

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

2016-01-01

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

A Randomised Controlled Treatment Trial of Two Forms of Family Therapy in Adolescent Anorexia Nervosa: A Five-Year Follow-Up

ERIC Educational Resources Information Center

Eisler, Ivan; Simic, Mima; Russell, Gerald F. M.; Dare, Christopher

2007-01-01

Background: There is growing evidence that family therapy is an effective treatment for adolescent anorexia nervosa. This study aimed to ascertain the long-term impact of two forms of outpatient family intervention previously evaluated in a randomised controlled trial (RCT). Method: A five-year follow-up was conducted on a cohort of 40 patients…

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

ERIC Educational Resources Information Center

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

2011-01-01

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

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

ERIC Educational Resources Information Center

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

2017-01-01

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

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

PubMed

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

2015-11-26

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

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

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

PubMed Central

2014-01-01

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

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

PubMed

Martí-Carvajal, Arturo J; Solà, Ivan

2015-06-09

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

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

PubMed Central

2010-01-01

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

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

PubMed

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

2017-09-01

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

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

PubMed

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

2017-03-01

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

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

PubMed

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

2010-04-01

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

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

PubMed Central

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

2005-01-01

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

Acute pancreatitis: recent advances through randomised trials.

PubMed

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

2017-11-01

Acute pancreatitis is one of the most common GI conditions requiring acute hospitalisation and has a rising incidence. In recent years, important insights on the management of acute pancreatitis have been obtained through numerous randomised controlled trials. Based on this evidence, the treatment of acute pancreatitis has gradually developed towards a tailored, multidisciplinary effort, with distinctive roles for gastroenterologists, radiologists and surgeons. This review summarises how to diagnose, classify and manage patients with acute pancreatitis, emphasising the evidence obtained through randomised controlled trials. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

PubMed

Abdulwadud, Omar A; Snow, Mary Elizabeth

2012-10-17

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

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

PubMed

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

2009-01-30

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

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

PubMed Central

2014-01-01

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

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

PubMed

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

2018-03-23

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

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

PubMed

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

2018-01-06

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

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

PubMed

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

2017-12-28

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

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

PubMed

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

2015-10-28

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

A Systematic Review of Group Social Skills Interventions, and Meta-analysis of Outcomes, for Children with High Functioning ASD.

PubMed

Wolstencroft, J; Robinson, L; Srinivasan, R; Kerry, E; Mandy, W; Skuse, D

2018-07-01

Group social skills interventions (GSSIs) are a commonly offered treatment for children with high functioning ASD. We critically evaluated GSSI randomised controlled trials for those aged 6-25 years. Our meta-analysis of outcomes emphasised internal validity, thus was restricted to trials that used the parent-report social responsiveness scale (SRS) or the social skills rating system (SSRS). Large positive effect sizes were found for the SRS total score, plus the social communication and restricted interests and repetitive behaviours subscales. The SSRS social skills subscale improved with moderate effect size. Moderator analysis of the SRS showed that GSSIs that include parent-groups, and are of greater duration or intensity, obtained larger effect sizes. We recommend future trials distinguish gains in children's social knowledge from social performance.

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

PubMed Central

2013-01-01

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

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2009-10-01

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

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

PubMed Central

2011-01-01

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

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

PubMed

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

2011-09-22

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

24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial.

PubMed

Soininen, Hilkka; Solomon, Alina; Visser, Pieter Jelle; Hendrix, Suzanne B; Blennow, Kaj; Kivipelto, Miia; Hartmann, Tobias

2017-12-01

Nutrition is an important modifiable risk factor in Alzheimer's disease. Previous trials of the multinutrient Fortasyn Connect showed benefits in mild Alzheimer's disease dementia. LipiDiDiet investigated the effects of Fortasyn Connect on cognition and related measures in prodromal Alzheimer's disease. Here, we report the 24-month results of the trial. LipiDiDiet was a 24-month randomised, controlled, double-blind, parallel-group, multicentre trial (11 sites in Finland, Germany, the Netherlands, and Sweden), with optional 12-month double-blind extensions. The trial enrolled individuals with prodromal Alzheimer's disease, defined according to the International Working Group (IWG)-1 criteria. Participants were randomly assigned (1:1) to active product (125 mL once-a-day drink containing Fortasyn Connect) or control product. Randomisation was computer-generated centrally in blocks of four, stratified by site. All study personnel and participants were masked to treatment assignment. The primary endpoint was change in a neuropsychological test battery (NTB) score. Analysis was by modified intention to treat. Safety analyses included all participants who consumed at least one study product dose. This trial is registered with the Dutch Trial Register, number NTR1705. Between April 20, 2009, and July 3, 2013, 311 of 382 participants screened were randomly assigned to the active group (n=153) or control group (n=158). Mean change in NTB primary endpoint was -0·028 (SD 0·453) in the active group and -0·108 (0·528) in the control group; estimated mean treatment difference was 0·098 (95% CI -0·041 to 0·237; p=0·166). The decline in the control group was less than the prestudy estimate of -0·4 during 24 months. 66 (21%) participants dropped out of the study. Serious adverse events occurred in 34 (22%) participants in the active group and 30 (19%) in control group (p=0·487), none of which were regarded as related to the study intervention. The intervention had no significant effect on the NTB primary endpoint over 2 years in prodromal Alzheimer's disease. However, cognitive decline in this population was much lower than expected, rendering the primary endpoint inadequately powered. Group differences on secondary endpoints of disease progression measuring cognition and function and hippocampal atrophy were observed. Further study of nutritional approaches with larger sample sizes, longer duration, or a primary endpoint more sensitive in this pre-dementia population, is needed. European Commission 7th Framework Programme. Copyright © 2017 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.

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

PubMed

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

2009-09-10

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

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

PubMed Central

Varadhan, Krishna K; Neal, Keith R

2012-01-01

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

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

PubMed Central

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

2017-01-01

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

The use of everolimus in the treatment of neurocognitive problems in tuberous sclerosis (TRON): study protocol for a randomised controlled trial.

PubMed

Randell, Elizabeth; McNamara, Rachel; Davies, D Mark; Owen-Jones, Eleri; Kirby, Nigel; Angel, Lianna; Drew, Cheney; Cannings-John, Rebecca; Smalley, Michelle; Saxena, Anurag; McDermott, Emer; Stockwell, Laura; de Vries, Petrus J; Hood, Kerry; Sampson, Julian R

2016-08-11

Tuberous sclerosis complex (TSC) is a genetic disorder affecting about 1 in 6000 people and is characterised by the development of tumours in many organs, including the skin and kidneys, and by a range of neurological and neuropsychiatric manifestations. TSC-associated neuropsychiatric disorders (TAND) occur in the majority of those with TSC, and they have a significant impact on patients and their families, given the everyday impact of TAND on education, employment, family and social life. The potential benefits of better treatment for TAND therefore include reduction in health care demands and wider benefits for patients and their carers. We have planned a single-centre, two-arm, individually randomised, phase II, double-blind, placebo-controlled trial of everolimus versus placebo in the treatment of neurocognitive problems in patients with tuberous sclerosis. Everolimus is a licensed medicine in this patient group, but for a different target of effect. The present trial is a proof-of-principle study developed to provide effect size estimates which may be used to inform the design of subsequent trials. Forty-eight patients aged 16-60 years with tuberous sclerosis who have an IQ >60 and a significant deficit (at least -2 SD) in one or more primary outcome measures will be randomly allocated in a ratio of 2:1 to receive everolimus or placebo, respectively. Participants will be assessed for eligibility and then be started on study medication 4 weeks later. They will then be randomised and receive placebo or everolimus for 24 weeks. Neurocognitive and safety assessments will be carried out at baseline and weeks 4, 12, 24 and 36. This study is designed to determine the effect sizes of treatment with everolimus or placebo for 6 months on specific neurocognitive functions-recall memory (verbal and non-verbal) and executive function-in people affected by TSC who have significant deficits in these functions. These data will provide new evidence to determine whether larger-scale trials are indicated and to explore suitable outcome measures and analytical methods for neurocognitive trial design. ISRCTN09739757 . Registered on 28 Dec 2011.

Feasibility randomised controlled trial of Recovery-focused Cognitive Behavioural Therapy for Older Adults with bipolar disorder (RfCBT-OA): study protocol.

PubMed

Tyler, Elizabeth; Lobban, Fiona; Sutton, Chris; Depp, Colin; Johnson, Sheri; Laidlaw, Ken; Jones, Steven H

2016-03-03

Bipolar disorder is a severe and chronic mental health problem that persists into older adulthood. The number of people living with this condition is set to rise as the UK experiences a rapid ageing of its population. To date, there has been very little research or service development with respect to psychological therapies for this group of people. A parallel two-arm randomised controlled trial comparing a 14-session, 6-month Recovery-focused Cognitive-Behavioural Therapy for Older Adults with bipolar disorder (RfCBT-OA) plus treatment as usual (TAU) versus TAU alone. Participants will be recruited in the North-West of England via primary and secondary mental health services and through self-referral. The primary objective of the study is to evaluate the feasibility and acceptability of RfCBT-OA; therefore, a formal power calculation is not appropriate. It has been estimated that randomising 25 participants per group will be sufficient to be able to reliably determine the primary feasibility outcomes (eg, recruitment and retention rates), in line with recommendations for sample sizes for feasibility/pilot trials. Participants in both arms will complete assessments at baseline and then every 3 months, over the 12-month follow-up period. We will gain an estimate of the likely effect size of RfCBT-OA on a range of clinical outcomes and estimate parameters needed to determine the appropriate sample size for a definitive, larger trial to evaluate the effectiveness and cost-effectiveness of RfCBT-OA. Data analysis is discussed further in the Analysis section in the main paper. This protocol was approved by the UK National Health Service (NHS) Ethics Committee process (REC ref: 15/NW/0330). The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations and local, participating NHS trusts. ISRCTN13875321; 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/

Can we identify subfertile couples that benefit from immediate in vitro fertilisation over intrauterine insemination?

PubMed

Tjon-Kon-Fat, Raïssa I; Tajik, Parvin; Custers, Inge M; Bossuyt, Patrick M M; van der Veen, Fulco; van Wely, Madelon; Mol, Ben W; Zafarmand, Mohammad H

2016-07-01

Available treatment options in couples with unexplained or mild male subfertility are intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH) and in vitro fertilisation (IVF). IUI-COH is a less invasive treatment that is often used before proceeding with IVF. Yet as the IVF success rates might be higher and time to pregnancy shorter, expedited access to IVF might be the preferred option. To identify couples that could benefit from immediate IVF over IUI-COH, we assessed whether female age, duration of subfertility or prewash total motile count (TMC) can help to identify couples that would benefit from IVF over IUI-COH. We performed a secondary data-analysis of a multicentre open-label randomised controlled trial in three university and six teaching hospitals in the Netherlands. 116 couples with unexplained or mild male subfertility were randomised to one cycle of IVF with elective single embryo transfer with subsequent frozen-thawed embryo transfers or 3 cycles of IUI-COH. The primary outcome was an ongoing pregnancy within 4 months after randomisation. Our aim was to explore a possible differential effect of specific markers on the effectiveness of treatment. We chose to therefore assess female age, duration of subfertility and TMC as these have previously been identified as predictors. For each prognostic factor we developed a logistic regression model to predict ongoing pregnancy with that prognostic factor, treatment and a factor-by-treatment interaction term. Female age and duration of subfertility were not associated with better ongoing pregnancy chances after IVF compared to IUI-COH (p-value for interaction=0.65 and 0.26, respectively). Only when TMC was lower than 110 (×10(6)spermatozoa/mL), the probability of ongoing pregnancy was higher in women allocated to IVF (p-value for interaction=0.06). In couples with unexplained or mild male subfertility, a low TMC might lead to higher pregnancy rates after IVF than after IUI-COH. This finding needs to be validated in a larger trial before it can be applied in clinical practice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Impact of contact on adolescents' mental health literacy and stigma: the SchoolSpace cluster randomised controlled trial.

PubMed

Chisholm, Katharine; Patterson, Paul; Torgerson, Carole; Turner, Erin; Jenkinson, David; Birchwood, Max

2016-02-19

To investigate whether intergroup contact in addition to education is more effective than education alone in reducing stigma of mental illness in adolescents. A pragmatic cluster randomised controlled trial compared education alone with education plus contact. Blocking was used to randomly stratify classes within schools to condition. Random allocation was concealed, generated by a computer algorithm, and undertaken after pretest. Data was collected at pretest and 2-week follow-up. Analyses use an intention-to-treat basis. Secondary schools in Birmingham, UK. The parents and guardians of all students in year 8 (age 12-13 years) were approached to take part. A 1-day educational programme in each school led by mental health professional staff. Students in the 'contact' condition received an interactive session with a young person with lived experience of mental illness. The primary outcome was students' attitudinal stigma of mental illness. Secondary outcomes included knowledge-based stigma, mental health literacy, emotional well-being and resilience, and help-seeking attitudes. Participants were recruited between 1 May 2011 and 30 April 2012. 769 participants completed the pretest and were randomised to condition. 657 (85%) provided follow-up data. At 2-week follow-up, attitudinal stigma improved in both conditions with no significant effect of condition (95% CI -0.40 to 0.22, p=0.5, d=0.01). Significant improvements were found in the education-alone condition compared with the contact and education condition for the secondary outcomes of knowledge-based stigma, mental health literacy, emotional well-being and resilience, and help-seeking attitudes. Contact was found to reduce the impact of the intervention for a number of outcomes. Caution is advised before employing intergroup contact with younger student age groups. The education intervention appeared to be successful in reducing stigma, promoting mental health knowledge, and increasing mental health literacy, as well as improving emotional well-being and resilience. A larger trial is needed to confirm these results. ISRCTN07406026; 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/

Impact of contact on adolescents’ mental health literacy and stigma: the SchoolSpace cluster randomised controlled trial

PubMed Central

Chisholm, Katharine; Patterson, Paul; Torgerson, Carole; Turner, Erin; Jenkinson, David; Birchwood, Max

2016-01-01

Objectives To investigate whether intergroup contact in addition to education is more effective than education alone in reducing stigma of mental illness in adolescents. Design A pragmatic cluster randomised controlled trial compared education alone with education plus contact. Blocking was used to randomly stratify classes within schools to condition. Random allocation was concealed, generated by a computer algorithm, and undertaken after pretest. Data was collected at pretest and 2-week follow-up. Analyses use an intention-to-treat basis. Setting Secondary schools in Birmingham, UK. Participants The parents and guardians of all students in year 8 (age 12–13 years) were approached to take part. Interventions A 1-day educational programme in each school led by mental health professional staff. Students in the ‘contact’ condition received an interactive session with a young person with lived experience of mental illness. Outcomes The primary outcome was students’ attitudinal stigma of mental illness. Secondary outcomes included knowledge-based stigma, mental health literacy, emotional well-being and resilience, and help-seeking attitudes. Results Participants were recruited between 1 May 2011 and 30 April 2012. 769 participants completed the pretest and were randomised to condition. 657 (85%) provided follow-up data. At 2-week follow-up, attitudinal stigma improved in both conditions with no significant effect of condition (95% CI −0.40 to 0.22, p=0.5, d=0.01). Significant improvements were found in the education-alone condition compared with the contact and education condition for the secondary outcomes of knowledge-based stigma, mental health literacy, emotional well-being and resilience, and help-seeking attitudes. Conclusions Contact was found to reduce the impact of the intervention for a number of outcomes. Caution is advised before employing intergroup contact with younger student age groups. The education intervention appeared to be successful in reducing stigma, promoting mental health knowledge, and increasing mental health literacy, as well as improving emotional well-being and resilience. A larger trial is needed to confirm these results. Trial registration number ISRCTN07406026; Results. PMID:26895983

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

PubMed

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

2013-08-01

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

Cognitive Behaviour Therapy versus a Counselling Intervention for Anxiety in Young People with High-Functioning Autism Spectrum Disorders: A Pilot Randomised Controlled Trial

ERIC Educational Resources Information Center

Murphy, Suzanne M.; Chowdhury, Uttom; White, Susan W.; Reynolds, Laura; Donald, Louisa; Gahan, Hilary; Iqbal, Zeinab; Kulkarni, Mahesh; Scrivener, Louise; Shaker-Naeeni, Hadi; Press, Dee A.

2017-01-01

The use of cognitive-behavioural therapy (CBT) as a treatment for children and adolescents with autism spectrum disorder (ASD) has been explored in a number of trials. Whilst CBT appears superior to no treatment or treatment as usual, few studies have assessed CBT against a control group receiving an alternative therapy. Our randomised controlled…

Pragmatic Pilot Cluster Randomised Control Trial of a School-Based Peer-Led Anti-Smoking Intervention for 13-14 Year Olds in Malaysia: Process Evaluation

ERIC Educational Resources Information Center

Melson, Elniee; Bridle, Christopher; Markham, Wolfgang

2017-01-01

Purpose: The purpose of this paper is to report the process evaluation of a pilot randomised control trial of an anti-smoking intervention for Malaysian 13-14-year olds, conducted in 2011/2012. It was hypothesised that trained peer supporters would promote non-smoking among classmates through informal conversations. Design/methodology/approach:…

Melatonin versus Placebo in Children with Autism Spectrum Conditions and Severe Sleep Problems Not Amenable to Behaviour Management Strategies: A Randomised Controlled Crossover Trial

ERIC Educational Resources Information Center

Wright, Barry; Sims, David; Smart, Siobhan; Alwazeer, Ahmed; Alderson-Day, Ben; Allgar, Victoria; Whitton, Clare; Tomlinson, Heather; Bennett, Sophie; Jardine, Jenni; McCaffrey, Nicola; Leyland, Charlotte; Jakeman, Christine; Miles, Jeremy

2011-01-01

Twenty-two children with autism spectrum disorders who had not responded to supported behaviour management strategies for severe dysomnias entered a double blind, randomised, controlled crossover trial involving 3 months of placebo versus 3 months of melatonin to a maximum dose of 10 mg. 17 children completed the study. There were no significant…

Pharmacist-led management of chronic pain in primary care: costs and benefits in a pilot randomised controlled trial.

PubMed

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

2015-04-01

To explore differences in mean costs (from a UK National Health Service perspective) and effects of pharmacist-led management of chronic pain in primary care evaluated in a pilot randomised controlled trial (RCT), and to estimate optimal sample size for a definitive RCT. Regression analysis of costs and effects, using intention-to-treat and expected value of sample information analysis (EVSI). Six general practices: Grampian (3); East Anglia (3). 125 patients with complete resource use and short form-six-dimension questionnaire (SF-6D) data at baseline, 3 months and 6 months. Patients were randomised to either pharmacist medication review with face-to-face pharmacist prescribing or pharmacist medication review with feedback to general practitioner or treatment as usual (TAU). Differences in mean total costs and effects measured as quality-adjusted life years (QALYs) at 6 months and EVSI for sample size calculation. Unadjusted total mean costs per patient were £452 for prescribing (SD: £466), £570 for review (SD: £527) and £668 for TAU (SD: £1333). After controlling for baseline costs, the adjusted mean cost differences per patient relative to TAU were £77 for prescribing (95% CI -82 to 237) and £54 for review (95% CI -103 to 212). Unadjusted mean QALYs were 0.3213 for prescribing (SD: 0.0659), 0.3161 for review (SD: 0.0684) and 0.3079 for TAU (SD: 0.0606). Relative to TAU, the adjusted mean differences were 0.0069 for prescribing (95% CI -0.0091 to 0.0229) and 0.0097 for review (95% CI -0.0054 to 0.0248). The EVSI suggested the optimal future trial size was between 460 and 690, and between 540 and 780 patients per arm using a threshold of £30,000 and £20,000 per QALY gained, respectively. Compared with TAU, pharmacist-led interventions for chronic pain appear more costly and provide similar QALYs. However, these estimates are imprecise due to the small size of the pilot trial. The EVSI indicates that a larger trial is necessary to obtain more precise estimates of differences in mean effects and costs between treatment groups. ISRCTN06131530. 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.

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.

A feasibility study and pilot randomised trial of a tailored prevention program to reduce falls in older people with mild dementia.

PubMed

Wesson, Jacqueline; Clemson, Lindy; Brodaty, Henry; Lord, Stephen; Taylor, Morag; Gitlin, Laura; Close, Jacqueline

2013-09-03

People with dementia have a disproportionately high rate of falls and fractures and poorer outcomes, yet there is currently no evidence to guide falls prevention in this population. A randomised trial design was used to test feasibility of study components and acceptability of a home hazard reduction and balance and strength exercise fall prevention program. The program was tailored to participant's individual cognitive levels and implemented as a carer-supported intervention. Feasibility of recruitment, retention and implementation of intervention were recorded through observation and documented in field notes. Adherence, carer burden and use of task simplification strategies were also monitored. Outcome measures, collected at 12 weeks included physiological, fear of falling, cognitive and functional measures. Recruitment was achievable but may be more challenging in a multisite trial. Twenty two dyads of persons with mild dementia and their carers were randomised to intervention or usual care control group. Of 38 dyads referred to the study, there was a high rate of willingness to participate, with 6 (16%) declining and 10 (26%) not meeting inclusion criteria. The intervention was well received by participants and carers and adherence to both program components was very good. All participants implemented some home safety recommendations (range 19-80%) with half implementing 50% or more. At the end of 12 weeks, 72% of the intervention group were exercising. Both the rate of falling and the risk of a fall were lower in the intervention group but these findings were not significant (RR= 0.50 (95% CI 0.11-2.19). There were no differences in physiological outcome measures between the control and intervention groups. However results were influenced by the small study size and incomplete data primarily in the intervention group at follow up. The pilot study was feasible and acceptable to people with mild dementia and their carers. The lessons learnt included: recruitment for a larger trial will require multiple approaches; home safety recommendations should provide a greater emphasis on environmental use compared with behavioural change; strategies to ensure an adequate dosage of exercise should be further explored. We recommend that intervention delivery incorporate an integrated occupational therapy and physiotherapy approach and that carers be provided with an individualised session to enhance dementia-specific skills in management and communication. A refined intervention should be tested in a randomised trial with an adequately powered sample size. Australia and New Zealand Clinical Trials Registry 126100001049066.

A feasibility study and pilot randomised trial of a tailored prevention program to reduce falls in older people with mild dementia

PubMed Central

2013-01-01

Background People with dementia have a disproportionately high rate of falls and fractures and poorer outcomes, yet there is currently no evidence to guide falls prevention in this population. Methods A randomised trial design was used to test feasibility of study components and acceptability of a home hazard reduction and balance and strength exercise fall prevention program. The program was tailored to participant’s individual cognitive levels and implemented as a carer-supported intervention. Feasibility of recruitment, retention and implementation of intervention were recorded through observation and documented in field notes. Adherence, carer burden and use of task simplification strategies were also monitored. Outcome measures, collected at 12 weeks included physiological, fear of falling, cognitive and functional measures. Results Recruitment was achievable but may be more challenging in a multisite trial. Twenty two dyads of persons with mild dementia and their carers were randomised to intervention or usual care control group. Of 38 dyads referred to the study, there was a high rate of willingness to participate, with 6 (16%) declining and 10 (26%) not meeting inclusion criteria. The intervention was well received by participants and carers and adherence to both program components was very good. All participants implemented some home safety recommendations (range 19-80%) with half implementing 50% or more. At the end of 12 weeks, 72% of the intervention group were exercising. Both the rate of falling and the risk of a fall were lower in the intervention group but these findings were not significant (RR= 0.50 (95% CI 0.11-2.19). There were no differences in physiological outcome measures between the control and intervention groups. However results were influenced by the small study size and incomplete data primarily in the intervention group at follow up. Conclusions The pilot study was feasible and acceptable to people with mild dementia and their carers. The lessons learnt included: recruitment for a larger trial will require multiple approaches; home safety recommendations should provide a greater emphasis on environmental use compared with behavioural change; strategies to ensure an adequate dosage of exercise should be further explored. We recommend that intervention delivery incorporate an integrated occupational therapy and physiotherapy approach and that carers be provided with an individualised session to enhance dementia-specific skills in management and communication. A refined intervention should be tested in a randomised trial with an adequately powered sample size. Trial registration Australia and New Zealand Clinical Trials Registry 126100001049066 PMID:24004682

Safety and efficacy of eculizumab in Guillain-Barré syndrome: a multicentre, double-blind, randomised phase 2 trial.

PubMed

Misawa, Sonoko; Kuwabara, Satoshi; Sato, Yasunori; Yamaguchi, Nobuko; Nagashima, Kengo; Katayama, Kanako; Sekiguchi, Yukari; Iwai, Yuta; Amino, Hiroshi; Suichi, Tomoki; Yokota, Takanori; Nishida, Yoichiro; Kanouchi, Tadashi; Kohara, Nobuo; Kawamoto, Michi; Ishii, Junko; Kuwahara, Motoi; Suzuki, Hidekazu; Hirata, Koichi; Kokubun, Norito; Masuda, Ray; Kaneko, Juntaro; Yabe, Ichiro; Sasaki, Hidenao; Kaida, Ken-Ichi; Takazaki, Hiroshi; Suzuki, Norihiro; Suzuki, Shigeaki; Nodera, Hiroyuki; Matsui, Naoko; Tsuji, Shoji; Koike, Haruki; Yamasaki, Ryo; Kusunoki, Susumu

2018-06-01

Despite the introduction of plasmapheresis and immunoglobulin therapy, many patients with Guillain-Barré syndrome still have an incomplete recovery. Evidence from pathogenesis studies suggests the involvement of complement-mediated peripheral nerve damage. We aimed to investigate the safety and efficacy of eculizumab, a humanised monoclonal antibody against the complement protein C5, in patients with severe Guillain-Barré syndrome. This study was a 24 week, multicentre, double-blind, placebo-controlled, randomised phase 2 trial done at 13 hospitals in Japan. Eligible patients with Guillain-Barré syndrome were aged 18 years or older and could not walk independently (Guillain-Barré syndrome functional grade 3-5). Patients were randomly assigned (2:1) to receive 4 weeks of intravenous immunoglobulin plus either eculizumab (900 mg) or placebo; randomisation was done via a computer-generated process and web response system with minimisation for functional grade and age. The study had a parallel non-comparative single-arm outcome measure. The primary outcomes were efficacy (the proportion of patients with restored ability to walk independently [functional grade ≤2] at week 4) in the eculizumab group and safety in the full analysis set. For the efficacy endpoint, we predefined a response rate threshold of the lower 90% CI boundary exceeding 50%. This trial is registered with ClinicalTrials.gov, number, NCT02493725. Between Aug 10, 2015, and April 21, 2016, 34 patients were assigned to receive either eculizumab (n=23) or placebo (n=11). At week 4, the proportion of the patients able to walk independently (functional grade ≤2) was 61% (90% CI 42-78; n=14) in the eculizumab group, and 45% (20-73; n=5) in the placebo group. Adverse events occurred in all 34 patients. Three patients had serious adverse events: two in the eculizumab group (anaphylaxis in one patient and intracranial haemorrhage and abscess in another patient) and one in the placebo group (depression). The possibility that anaphylaxis and intracranial abscess were related to eculizumab could not be excluded. No deaths or meningococcal infections occurred. The primary outcome measure did not reach the predefined response rate. However, because this is a small study without statistical comparison with the placebo group, the efficacy and safety of eculizumab could be investigated in larger, randomised controlled trials. The Japan Agency for Medical Research and Development, Ministry of Health, Labor and Welfare, and Alexion Pharmaceuticals. Copyright © 2018 Elsevier Ltd. All rights reserved.

Clinical and cost effectiveness of mobile phone supported self monitoring of asthma: multicentre randomised controlled trial.

PubMed

Ryan, Dermot; Price, David; Musgrave, Stan D; Malhotra, Shweta; Lee, Amanda J; Ayansina, Dolapo; Sheikh, Aziz; Tarassenko, Lionel; Pagliari, Claudia; Pinnock, Hilary

2012-03-23

To determine whether mobile phone based monitoring improves asthma control compared with standard paper based monitoring strategies. Multicentre randomised controlled trial with cost effectiveness analysis. UK primary care. 288 adolescents and adults with poorly controlled asthma (asthma control questionnaire (ACQ) score ≥ 1.5) from 32 practices. Participants were centrally randomised to twice daily recording and mobile phone based transmission of symptoms, drug use, and peak flow with immediate feedback prompting action according to an agreed plan or paper based monitoring. Changes in scores on asthma control questionnaire and self efficacy (knowledge, attitude, and self efficacy asthma questionnaire (KASE-AQ)) at six months after randomisation. Assessment of outcomes was blinded. Analysis was on an intention to treat basis. There was no significant difference in the change in asthma control or self efficacy between the two groups (ACQ: mean change 0.75 in mobile group v 0.73 in paper group, mean difference in change -0.02 (95% confidence interval -0.23 to 0.19); KASE-AQ score: mean change -4.4 v -2.4, mean difference 2.0 (-0.3 to 4.2)). The numbers of patients who had acute exacerbations, steroid courses, and unscheduled consultations were similar in both groups, with similar healthcare costs. Overall, the mobile phone service was more expensive because of the expenses of telemonitoring. Mobile technology does not improve asthma control or increase self efficacy compared with paper based monitoring when both groups received clinical care to guidelines standards. The mobile technology was not cost effective. Clinical Trials NCT00512837.

Analysis and interpretation of cost data in randomised controlled trials: review of published studies

PubMed Central

Barber, Julie A; Thompson, Simon G

1998-01-01

Objective To review critically the statistical methods used for health economic evaluations in randomised controlled trials where an estimate of cost is available for each patient in the study. Design Survey of published randomised trials including an economic evaluation with cost values suitable for statistical analysis; 45 such trials published in 1995 were identified from Medline. Main outcome measures The use of statistical methods for cost data was assessed in terms of the descriptive statistics reported, use of statistical inference, and whether the reported conclusions were justified. Results Although all 45 trials reviewed apparently had cost data for each patient, only 9 (20%) reported adequate measures of variability for these data and only 25 (56%) gave results of statistical tests or a measure of precision for the comparison of costs between the randomised groups. Only 16 (36%) of the articles gave conclusions which were justified on the basis of results presented in the paper. No paper reported sample size calculations for costs. Conclusions The analysis and interpretation of cost data from published trials reveal a lack of statistical awareness. Strong and potentially misleading conclusions about the relative costs of alternative therapies have often been reported in the absence of supporting statistical evidence. Improvements in the analysis and reporting of health economic assessments are urgently required. Health economic guidelines need to be revised to incorporate more detailed statistical advice. Key messagesHealth economic evaluations required for important healthcare policy decisions are often carried out in randomised controlled trialsA review of such published economic evaluations assessed whether statistical methods for cost outcomes have been appropriately used and interpretedFew publications presented adequate descriptive information for costs or performed appropriate statistical analysesIn at least two thirds of the papers, the main conclusions regarding costs were not justifiedThe analysis and reporting of health economic assessments within randomised controlled trials urgently need improving PMID:9794854

Hysteroscopic resection of a uterine caesarean scar defect (niche) in women with postmenstrual spotting: a randomised controlled trial.

PubMed

Vervoort, Ajmw; van der Voet, L F; Hehenkamp, Wjk; Thurkow, A L; van Kesteren, Pjm; Quartero, H; Kuchenbecker, W; Bongers, M; Geomini, P; de Vleeschouwer, Lhm; van Hooff, Mha; van Vliet, H; Veersema, S; Renes, W B; Oude Rengerink, K; Zwolsman, S E; Brölmann, Ham; Mol, Bwj; Huirne, Jaf

2018-02-01

To compare the effectiveness of a hysteroscopic niche resection versus no treatment in women with postmenstrual spotting and a uterine caesarean scar defect. Multicentre randomised controlled trial. Eleven hospitals collaborating in a consortium for women's health research in the Netherlands. Women reporting postmenstrual spotting after a caesarean section who had a niche with a residual myometrium of ≥3 mm, measured during sonohysterography. Women were randomly allocated to hysteroscopic niche resection or expectant management for 6 months. The primary outcome was the number of days of postmenstrual spotting 6 months after randomisation. Secondary outcomes were spotting at the end of menstruation, intermenstrual spotting, dysuria, sonographic niche measurements, surgical parameters, quality of life, women's satisfaction, sexual function, and additional therapy. Outcomes were measured at 3 months and, except for niche measurements, also at 6 months after randomisation. We randomised 52 women to hysteroscopic niche resection and 51 women to expectant management. The median number of days of postmenstrual spotting at baseline was 8 days in both groups. At 6 months after randomisation, the median number of days of postmenstrual spotting was 4 days (interquartile range, IQR 2-7 days) in the intervention group and 7 days (IQR 3-10 days) in the control group (P = 0.04); on a scale of 0-10, discomfort as a result of spotting had a median score of 2 (IQR 0-7) in the intervention group, compared with 7 (IQR 0-8) in the control group (P = 0.02). In women with a niche with a residual myometrium of ≥3 mm, hysteroscopic niche resection reduced postmenstrual spotting and spotting-related discomfort. A hysteroscopic niche resection is an effective treatment to reduce niche-related spotting. © 2017 The Authors. BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

Effectiveness of mat Pilates or equipment-based Pilates in patients with chronic non-specific low back pain: a protocol of a randomised controlled trial

PubMed Central

2013-01-01

Background Chronic low back pain is an expensive and difficult condition to treat. One of the interventions widely used by physiotherapists in the treatment of chronic non-specific low back pain is exercise therapy based upon the Pilates principles. Pilates exercises can be performed with or without specific equipment. These two types of Pilates exercises have never been compared on a high-quality randomised controlled trial. Methods/design This randomised controlled trial with a blinded assessor will evaluate eighty six patients of both genders with chronic low back pain, aged between 18 and 60 years, from one Brazilian private physiotherapy clinic. The patients will be randomly allocated into two groups: Mat Group will perform the exercises on the ground while the Equipment-based Group will perform the Pilates method exercises on the following equipment: Cadillac, Reformer, Ladder Barrel, and Step Chair. The general and specific disability of the patient, kinesiophobia, pain intensity and global perceived effect will be evaluated by a blinded assessor before randomisation and at six weeks and six months after randomisation. In addition, the expectation of the participants and their confidence with the treatment will be evaluated before randomisation and after the first treatment session, respectively. Discussion This will be the first study aiming to compare the effectiveness of Mat and Equipment-based Pilates exercises in patients with chronic non-specific low back pain. The results may help health-care professionals in clinical decision-making and could potentially reduce the treatment costs of this condition. Trial registration Brazilian Registry of Clinical Trials RBR-7tyg5j PMID:23298183

Angioplasty and stenting for patients with symptomatic intracranial atherosclerosis: study protocol of a randomised controlled trial

PubMed Central

Cui, Xiao-Ping; Lin, Min; Mu, Jun-Shan; Ye, Jian-Xin; He, Wen-Qing; Fu, Mao-Lin; Li, Hua; Fang, Jia-Yang; Shen, Feng-Feng; Lin, Hang

2016-01-01

Introduction Whether adding percutaneous transluminal angioplasty and stenting (PTAS) to background medical treatment is effective for decreasing the incidence of stroke or death in patients with symptomatic intracranial atherosclerosis (ICAS) is still controversial. We perform a randomised controlled trial to examine the effectiveness and safety of an improved PTAS procedure for patients with ICAS. Methods and analysis A randomised controlled trial will be conducted in three hospitals in China. Eligible patients with ICAS will be randomly assigned to receive medication treatment (MT) plus PTAS or MT alone. The MT will be initiated immediately after randomisation, while the PTAS will be performed when patients report relief of alarm symptoms defined as sudden weakness or numbness. All patients will be followed up at 30 days, 3 and 12 months after randomisation. The primary end point will be the incidence of stroke or death at 30 days after randomisation. Secondary outcomes will be the incidence of ischaemic stroke in the territory of stenosis arteries, the incidence of in-stent restenosis, the Chinese version of the modified Rankin Scale and the Chinese version of the Stroke-Specific Quality of Life (CSQoL). Ethics and dissemination The study protocol is approved by institutional review boards in participating hospitals (reference number FZ20160003, 180PLA20160101 and 476PLA2016007). The results of this study will be disseminated to patients, physicians and policymakers through publication in a peer-reviewed journal or presentations in conferences. It is anticipated that the results of this study will improve the quality of the current PTAS procedure and guide clinical decision-making for patients with ICAS. Trial registration number NCT02689037 PMID:27852711

Motivational interviewing as a smoking cessation strategy with nurses: an exploratory randomised controlled trial.

PubMed

Mujika, Agurtzane; Forbes, Angus; Canga, Navidad; de Irala, Jokin; Serrano, Inmaculada; Gascó, Plácido; Edwards, Margaret

2014-08-01

Despite the important role that health professionals have in reducing tobacco use, many have a smoking habit themselves. The prevalence of smoking is particularly high among nurses. To test the efficacy, acceptability and feasibility of a motivational interviewing (MI) based smoking cessation intervention with nurses. Two group parallel experimental design with random allocation to groups. A large teaching hospital in the North of Spain. Nurses who smoked (n=30) were randomised into two groups: motivational interviewing based intervention (n=15) and usual care (n=15). Motivational interviewing based intervention consisted of four individual MI sessions. Usual care consisted of brief advice. Variables considered to assess efficacy were biochemically verified smoking cessation, mean cigarettes smoked, stages of change, self-efficacy and depression score. Variables to assess acceptability and feasibility included participant satisfaction, adherence to MI, and duration of sessions. Data were collected at: baseline, end of intervention and three months after the end of the intervention. At three month follow up, compared with the control group, more nurses in the intervention group had quit (absolute difference 33.3%; 95% confidence interval [CI] 2.6-58.2). In the nurses who did not quit, there was no significant difference between the intervention and control groups in the number of cigarettes smoked per day, although progress in the stages of change was greater in the intervention group compared to the control group. Measures of acceptability and feasibility indicated good satisfaction with the intervention, with high levels of attendance and completion. This study found a beneficial effect of motivational interviewing on nurses' smoking cessation. The intervention was acceptable for nurses and a number of aspects were identified that need to be considered prior to conducting a larger scale in order to optimise the intervention. Using MI might be a novel approach to the problem of health professionals who smoke. Copyright © 2013 Elsevier Ltd. All rights reserved.

Indexing of randomised controlled trials of physiotherapy interventions: a comparison of AMED, CENTRAL, CINAHL, EMBASE, hooked on evidence, PEDro, PsycINFO and PubMed.

PubMed

Moseley, Anne M; Sherrington, Catherine; Elkins, Mark R; Herbert, Robert D; Maher, Christopher G

2009-09-01

To compare the comprehensiveness of indexing the reports of randomised controlled trials of physiotherapy interventions by eight bibliographic databases (AMED, CENTRAL, CINAHL, EMBASE, Hooked on Evidence, PEDro, PsycINFO and PubMed). Audit of bibliographic databases. Two hundred and eighty-one reports of randomised controlled trials of physiotherapy interventions were identified by screening the reference lists of 30 relevant systematic reviews published in four consecutive issues of the Cochrane Database of Systematic Reviews (Issue 3, 2007 to Issue 2, 2008). AMED, CENTRAL, CINAHL, EMBASE, Hooked on Evidence, PEDro, PsycINFO and PubMed were used to search for the trial reports. The number of trial reports indexed in each database was calculated. PEDro indexed 99% of the trial reports, CENTRAL indexed 98%, PubMed indexed 91%, EMBASE indexed 82%, CINAHL indexed 61%, Hooked on Evidence indexed 40%, AMED indexed 36% and PsycINFO indexed 17%. Most trial reports (92%) were indexed on four or more of the databases. One trial report was indexed on a single database (PEDro). Of the eight bibliographic databases examined, PEDro and CENTRAL provide the most comprehensive indexing of reports of randomised trials of physiotherapy interventions.

Homeopathy for Perennial Asthma in Adolescents: Pilot Feasibility Study Testing a Randomised Withdrawal Design.

PubMed

Mitchiguian Hotta, Livia; Cardinalli Adler, Ubiratan; de Toledo Cesar, Amarilys; Martinez, Edson Zangiacomi; Demarzo, Marcelo Marcos Piva

2018-05-01

 Previous findings from a pragmatic trial suggest that usual care compared with usual care plus individualised homeopathy is not a feasible design to address homeopathic interventions for asthma.  The main purpose of this article was to investigate the feasibility of the randomised withdrawal design as a strategy to assess the effectiveness of a standardised clinical-pharmaceutical homeopathic protocol ( Organon.modus ) on perennial asthma in adolescents.  Randomised withdrawal, double-blind, parallel, placebo-controlled, 12-week study. 12 to 17 years old adolescents, with the diagnosis of perennial asthma, using inhalatory beclomethasone (plus fenoterol for wheezing episodes), who achieved 3 months of well-controlled asthma, after a variable period of individualised homeopathic treatment according to Organon.modus protocol. a secondary care medical specialist centre. continuation with the individualised homeopathic medicine or with indistinguishable placebo during 12 weeks of beclomethasone step-down. number of days of well-controlled asthma. Secondary measures: number of days of fenoterol use, number of visits to an emergency service (without hospitalisation) and percentage of patients excluded due to an exacerbation characterising a partly controlled asthma. Tolerability was assessed by Adverse Events, registered at every visit.  Nineteen patients were randomised to continue treatment with homeopathy and 21 with placebo. Effectiveness measures for the homeopathy and placebo groups respectively were median number of days of good clinical control: 84 versus 30 ( p  = 0.18); median number of days of fenoterol use per patient: 3 versus 5 ( p  = 0.41); visits to an emergency room: 1 versus 6 ( p  = 0.35); percentage of exclusion due to partly controlled asthma: 36.8% versus 71.4% ( p  = 0.05). Few Adverse Events were reported.  This pilot study supports the feasibility of the double-blind randomised withdrawal design in studies investigating homeopathy on teenage asthma, when performed by specialists following a standardised clinical-pharmaceutical homeopathic protocol.  RBR-6XTS8Z. The Faculty of Homeopathy.

Development and Evaluation of a Pedagogical Tool to Improve Understanding of a Quality Checklist: A Randomised Controlled Trial

PubMed Central

Fourcade, Lola; Boutron, Isabelle; Moher, David; Ronceray, Lucie; Baron, Gabriel; Ravaud, Philippe

2007-01-01

Objective: The aim of this study was to develop and evaluate a pedagogical tool to enhance the understanding of a checklist that evaluates reports of nonpharmacological trials (CLEAR NPT). Design: Paired randomised controlled trial. Participants: Clinicians and systematic reviewers. Interventions: We developed an Internet-based computer learning system (ICLS). This pedagogical tool used many examples from published randomised controlled trials to demonstrate the main coding difficulties encountered when using this checklist. Randomised participants received either a specific Web-based training with the ICLS (intervention group) or no specific training. Outcome measures: The primary outcome was the rate of correct answers compared to a criterion standard for coding a report of randomised controlled trials with the CLEAR NPT. Results: Between April and June 2006, 78 participants were randomly assigned to receive training with the ICLS (39) or no training (39). Participants trained by the ICLS did not differ from the control group in performance on the CLEAR NPT. The mean paired difference and corresponding 95% confidence interval was 0.5 (−5.1 to 6.1). The rate of correct answers did not differ between the two groups regardless of the CLEAR NPT item. Combining both groups, the rate of correct answers was high or items related to allocation sequence (79.5%), description of the intervention (82.0%), blinding of patients (79.5%), and follow-up schedule (83.3%). The rate of correct answers was low for items related to allocation concealment (46.1%), co-interventions (30.3%), blinding of outcome assessors (53.8%), specific measures to avoid ascertainment bias (28.6%), and intention-to-treat analysis (60.2%). Conclusions: Although we showed no difference in effect between the intervention and control groups, our results highlight the gap in knowledge and urgency for education on important aspects of trial conduct. PMID:17479163

Changes in body weight and food choice in those attempting smoking cessation: a cluster randomised controlled trial

PubMed Central

2012-01-01

Background Fear of weight gain is a barrier to smoking cessation and significant cause of relapse for many people. The provision of nutritional advice as part of a smoking cessation programme may assist some in smoking cessation and perhaps limit weight gain. The aim of this study was to determine the effect of a structured programme of dietary advice on weight change and food choice, in adults attempting smoking cessation. Methods Cluster randomised controlled design. Classes randomised to intervention commenced a 24-week intervention, focussed on improving food choice and minimising weight gain. Classes randomised to control received “usual care”. Results Twenty-seven classes in Greater Glasgow were randomised between January and August 2008. Analysis, including those who continued to smoke, showed that actual weight gain and percentage weight gain was similar in both groups. Examination of data for those successful at giving up smoking showed greater mean weight gain in intervention subjects (3.9 (SD 3.1) vs. 2.7 (SD 3.7) kg). Between group differences were not significant (p = 0.23, 95% CI −0.9 to 3.5). In comparison to baseline improved consumption of fruit and vegetables and breakfast cereal were reported in the intervention group. A higher percentage of control participants continued smoking (74% vs. 66%). Conclusions The intervention was not successful at minimising weight gain in comparison to control but was successful in facilitating some sustained improvements in the dietary habits of intervention participants. Improved quit rates in the intervention group suggest that continued contact with advisors may have reduced anxieties regarding weight gain and encouraged cessation despite weight gain. Research should continue in this area as evidence suggests that the negative effects of obesity could outweigh the health benefits achieved through reductions in smoking prevalence. Trial registration Current Controlled Trials ISRCTN73824458 PMID:22642755

How do you design randomised trials for smaller populations? A framework.

PubMed

Parmar, Mahesh K B; Sydes, Matthew R; Morris, Tim P

2016-11-25

How should we approach trial design when we can get some, but not all, of the way to the numbers required for a randomised phase III trial?We present an ordered framework for designing randomised trials to address the problem when the ideal sample size is considered larger than the number of participants that can be recruited in a reasonable time frame. Staying with the frequentist approach that is well accepted and understood in large trials, we propose a framework that includes small alterations to the design parameters. These aim to increase the numbers achievable and also potentially reduce the sample size target. The first step should always be to attempt to extend collaborations, consider broadening eligibility criteria and increase the accrual time or follow-up time. The second set of ordered considerations are the choice of research arm, outcome measures, power and target effect. If the revised design is still not feasible, in the third step we propose moving from two- to one-sided significance tests, changing the type I error rate, using covariate information at the design stage, re-randomising patients and borrowing external information.We discuss the benefits of some of these possible changes and warn against others. We illustrate, with a worked example based on the Euramos-1 trial, the application of this framework in designing a trial that is feasible, while still providing a good evidence base to evaluate a research treatment.This framework would allow appropriate evaluation of treatments when large-scale phase III trials are not possible, but where the need for high-quality randomised data is as pressing as it is for common diseases.

A Randomised Controlled Trial of the Use of a Piece of Commercial Software for the Acquisition of Reading Skills

ERIC Educational Resources Information Center

Khan, Muhammad Ahmad; Gorard, Stephen

2012-01-01

We report here the overall results of a cluster randomised controlled trial of the use of computer-aided instruction with 672 Year 7 pupils in 23 secondary school classes in the north of England. A new piece of commercial software, claimed on the basis of publisher testing to be effective in improving reading after just six weeks of use in the…

Effectiveness of educational poster on knowledge of emergency management of dental trauma--part 2: cluster randomised controlled trial for secondary school students.

PubMed

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

2014-01-01

To investigate the effectiveness of educational poster on improving secondary school students' knowledge of emergency management of dental trauma. A cluster randomised controlled trial was conducted. 16 schools with total 671 secondary students who can read Chinese or English were randomised into intervention (poster, 8 schools, 364 students) and control groups (8 schools, 305 students) at the school level. Baseline knowledge of dental trauma was obtained by a questionnaire. Poster containing information of dental trauma management was displayed in a classroom for 2 weeks in each school in the intervention group whereas in the control group there was no display of such posters. Students of both groups completed the same questionnaire after 2 weeks. Two-week display of posters improved the knowledge score by 1.25 (p-value = 0.0407) on average. Educational poster on dental trauma management significantly improved the level of knowledge of secondary school students in Hong Kong. HKClinicalTrial.com HKCTR-1343 ClinicalTrials.gov NCT01809457.

Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

PubMed

Turner, E L; Metcalfe, C; Donovan, J L; Noble, S; Sterne, J A C; Lane, J A; Avery, K N; Down, L; Walsh, E; Davis, M; Ben-Shlomo, Y; Oliver, S E; Evans, S; Brindle, P; Williams, N J; Hughes, L J; Hill, E M; Davies, C; Ng, S Y; Neal, D E; Hamdy, F C; Martin, R M

2014-06-10

Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50-69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up. Among randomised practices, 271 (68%) in the intervention arm (198,114 men) and 302 (78%) in the control arm (221,929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices). The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening.

Study protocol for the 'HelpMeDoIt!' randomised controlled feasibility trial: an app, web and social support-based weight loss intervention for adults with obesity.

PubMed

Matthews, Lynsay; Pugmire, Juliana; Moore, Laurence; Kelson, Mark; McConnachie, Alex; McIntosh, Emma; Morgan-Trimmer, Sarah; Murphy, Simon; Hughes, Kathryn; Coulman, Elinor; Utkina-Macaskill, Olga; Simpson, Sharon Anne

2017-10-25

HelpMeDoIt! will test the feasibility of an innovative weight loss intervention using a smartphone app and website. Goal setting, self-monitoring and social support are three key facilitators of behaviour change. HelpMeDoIt! incorporates these features and encourages participants to invite 'helpers' from their social circle to help them achieve their goal(s). To test the feasibility of the intervention in supporting adults with obesity to achieve weight loss goals. 12-month feasibility randomised controlled trial and accompanying process evaluation. Participants (n=120) will be adults interested in losing weight, body mass index (BMI) > 30 kg/m 2 and smartphone users. The intervention group will use the app/website for 12 months. Participants will nominate one or more helpers to support them. Helpers have access to the app/website. The control group will receive a leaflet on healthy lifestyle and will have access to HelpMeDoIt! after follow-up. The key outcome of the study is whether prespecified progression criteria have been met in order to progress to a larger randomised controlled effectiveness trial. Data will be collected at baseline, 6 and 12 months. Outcomes focus on exploring the feasibility of delivering the intervention and include: (i) assessing three primary outcomes (BMI, physical activity and diet); (ii) secondary outcomes of waist/hip circumference, health-related quality of life, social support, self-efficacy, motivation and mental health; (iii) recruitment and retention; (iv) National Health Service (NHS) resource use and participant borne costs; (v) usability and acceptability of the app/website; and (vi) qualitative interviews with up to 50 participants and 20 helpers on their experiences of the intervention. Statistical analyses will focus on feasibility outcomes and provide initial estimates of intervention effects. Thematic analysis of qualitative interviews will assess implementation, acceptability, mechanisms of effect and contextual factors influencing the intervention. The protocol has been approved by the West of Scotland NHS Research Ethics Committee (Ref: 15/WS/0288) and the University of Glasgow MVLS College Ethics Committee (Ref: 200140108). Findings will be disseminated widely through peer-reviewed publication and conference presentations. ISRCTN85615983. © 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.

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

PubMed

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

2017-09-25

Randomised controlled trials can provide evidence relevant to assessing the equity impact of an intervention, but such information is often poorly reported. We describe a conceptual framework to identify health equity-relevant randomised trials with the aim of improving the design and reporting of such trials. An interdisciplinary and international research team engaged in an iterative consensus building process to develop and refine the conceptual framework via face-to-face meetings, teleconferences and email correspondence, including findings from a validation exercise whereby two independent reviewers used the emerging framework to classify a sample of randomised trials. A randomised trial can usefully be classified as 'health equity relevant' if it assesses the effects of an intervention on the health or its determinants of either individuals or a population who experience ill health due to disadvantage defined across one or more social determinants of health. Health equity-relevant randomised trials can either exclusively focus on a single population or collect data potentially useful for assessing differential effects of the intervention across multiple populations experiencing different levels or types of social disadvantage. Trials that are not classified as 'health equity relevant' may nevertheless provide information that is indirectly relevant to assessing equity impact, including information about individual level variation unrelated to social disadvantage and potentially useful in secondary modelling studies. The conceptual framework may be used to design and report randomised trials. The framework could also be used for other study designs to contribute to the evidence base for improved health equity. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Lee Silverman Voice Treatment versus standard speech and language therapy versus control in Parkinson's disease: a pilot randomised controlled trial (PD COMM pilot).

PubMed

Sackley, Catherine M; Smith, Christina H; Rick, Caroline E; Brady, Marian C; Ives, Natalie; Patel, Smitaa; Woolley, Rebecca; Dowling, Francis; Patel, Ramilla; Roberts, Helen; Jowett, Sue; Wheatley, Keith; Kelly, Debbie; Sands, Gina; Clarke, Carl E

2018-01-01

Speech-related problems are common in Parkinson's disease (PD), but there is little evidence for the effectiveness of standard speech and language therapy (SLT) or Lee Silverman Voice Treatment (LSVT LOUD®). The PD COMM pilot was a three-arm, assessor-blinded, randomised controlled trial (RCT) of LSVT LOUD®, SLT and no intervention (1:1:1 ratio) to assess the feasibility and to inform the design of a full-scale RCT. Non-demented patients with idiopathic PD and speech problems and no SLT for speech problems in the past 2 years were eligible. LSVT LOUD® is a standardised regime (16 sessions over 4 weeks). SLT comprised individualised content per local practice (typically weekly sessions for 6-8 weeks). Outcomes included recruitment and retention, treatment adherence, and data completeness. Outcome data collected at baseline, 3, 6, and 12 months included patient-reported voice and quality of life measures, resource use, and assessor-rated speech recordings. Eighty-nine patients were randomised with 90% in the therapy groups and 100% in the control group completing the trial. The response rate for Voice Handicap Index (VHI) in each arm was ≥ 90% at all time-points. VHI was highly correlated with the other speech-related outcome measures. There was a trend to improvement in VHI with LSVT LOUD® (difference at 3 months compared with control: - 12.5 points; 95% CI - 26.2, 1.2) and SLT (difference at 3 months compared with control: - 9.8 points; 95% CI - 23.2, 3.7) which needs to be confirmed in an adequately powered trial. Randomisation to a three-arm trial of speech therapy including a no intervention control is feasible and acceptable. Compliance with both interventions was good. VHI and other patient-reported outcomes were relevant measures and provided data to inform the sample size for a substantive trial. International Standard Randomised Controlled Trial Number Register: ISRCTN75223808. registered 22 March 2012.

Does an intensive self-management structured education course improve outcomes for children and young people with type 1 diabetes? The Kids In Control OF Food (KICk-OFF) cluster-randomised controlled trial protocol

PubMed Central

Price, Katherine J; Wales, Jerry; Eiser, Christine; Knowles, Julie; Heller, Simon; Freeman, Jenny; Brennan, Alan; McPherson, Amy; Wellington, Jerry

2013-01-01

Introduction The Kids In Control OF Food (KICk-OFF) is a cluster-randomised controlled trial, which aims to determine the efficacy of a 5 day structured education course for 11-year-olds to 16-year-olds with type 1 diabetes (T1DM) when compared with standard care, and its cost effectiveness. Less than 15% of children and young people with T1DM in the UK meet the recommended glycaemic target. Self-management education programmes for adults with T1DM improve clinical and psychological outcomes, but none have been evaluated in the paediatric population. KICk-OFF is a 5-day structured education course for 11-year-olds to 16- year-olds with T1DM. It was developed with input from young people, parents, teachers and educationalists. Methods and analysis 36 paediatric diabetes centres across the UK randomised into intervention and control arms. Up to 560 participants were recruited prior to centre randomisation. KICk-OFF courses are delivered in the intervention centres, with standard care continued in the control arm. Primary outcomes are change in glycaemic control (HbA1c) and quality of life between baseline and 6 months postintervention, and the incidence of severe hypoglycaemia. Sustained change in self-management behaviour is assessed by follow-up at 12 and 24 months. Health economic analysis will be undertaken. Data will be reported according to the CONSORT statement for cluster-randomised clinical trials. All analyses will be by intention-to-treat with a two-sided p value of <0.05 being regarded as statistically significant. The study commenced in 2008. Data collection from participants is ongoing and the study will be completed in 2013. Ethics The study has been approved by the Sheffield Research Ethics Committee. Dissemination Results will be reported in peer reviewed journals and conferences. Trial registration Current Controlled Trials ISRCTN37042683. PMID:23355675

Randomised controlled trial of biofeedback training in persistent encopresis with anismus.

PubMed

Nolan, T; Catto-Smith, T; Coffey, C; Wells, J

1998-08-01

Paradoxical external anal sphincter contraction during attempted defecation (anismus) is thought to be an important contributor to chronic faecal retention and encopresis in children. Biofeedback training can be used to teach children to abolish this abnormal contraction. A randomised controlled trial in medical treatment resistant and/or treatment dependent children with anismus using surface electromyographic (EMG) biofeedback training to determine whether such training produces sustained faecal continence. Up to four sessions of biofeedback training were conducted at weekly intervals for each patient. Anorectal manometry was performed before randomisation and six months later. Parents of patients completed the "child behaviour checklist" (CBCL) before randomisation and at follow up. Sixty eight children underwent anorectal manometry and EMG. Of these, 29 had anismus (ages 4-14 years) and were randomised to either EMG biofeedback training and conventional medical treatment (BFT) (n = 14) or to conventional medical treatment alone (n = 15). All but one child were able to learn relaxation of the external anal sphincter on attempted defecation. At six months' follow up, laxative free remission had been sustained in two of 14 patients in the BFT group and in two of 15 controls (95% confidence interval (CI) on difference, -24% to 26%). Remission or improvement occurred in four of 14 patients in the BFT group and six of 15 controls (95% CI on difference, -46% to 23%). Of subjects available for repeat anorectal manometry and EMG at six months, six of 13 in the BFT group still demonstrated anismus v 11 of 13 controls (95% CI on difference, -75% to -1%). Of the four patients in full remission at six months, only one (in the BFT group) did not exhibit anismus. Rectal hyposensitivity was not associated with remission or improvement in either of the groups. Mean CBCL total behaviour problem scores were not significantly different between the BFT and control groups, but there was a significant improvement in CBCL school scale scores in the BFT group, and this improvement was significantly greater than that seen in the control group. The result of this study, together with those reported in other controlled trials, argues against using biofeedback training in children with encopresis.

Primary cervical cancer screening with HPV testing compared with liquid-based cytology: results of round 1 of a randomised controlled trial -- the HPV FOCAL Study.

PubMed

Ogilvie, G S; Krajden, M; van Niekerk, D J; Martin, R E; Ehlen, T G; Ceballos, K; Smith, L W; Kan, L; Cook, D A; Peacock, S; Stuart, G C E; Franco, E L; Coldman, A J

2012-12-04

Round 1 data of human papillomavirus (HPV) FOCAL, a three-arm, randomised trial, which aims to establish the efficacy of HPV DNA testing as a primary screen for cervical cancer, are presented. The three arms are: Control arm - liquid based cytology with atypical squamous cells of unknown significance (ASC-US) triage with hrHPV testing; Intervention Arm - hrHPV at entry with liquid-based cytology (LBC) triage of hrHPV positives, with exit screen at 4 years; Safety check arm - hrHPV at entry with LBC triage of hrHPV positives with exit screen at 2 years. A total of 6154 women were randomised to the control arm and 12 494 to the HPV arms (intervention and safety check). In the HPV arm, the baseline cervical intraepithelial neoplasia (CIN)2+ and CIN3+ rate was 9.2/1000 (95%CI; 7.4, 10.9) and 4.8/1000 (95%CI; 3.6, 6.1), which increased to 16.1/1000 (95%CI 13.2, 18.9) for CIN2+ and to 8.0/1000 (95%CI; 5.9, 10.0) for CIN3+ after subsequent screening of HPV-DNA-positive/cytology-negative women. Detection rate in the control arm remained unchanged after subsequent screening of ASC-US-positive/hrHPV DNA-negative women at 11.0/1000 for CIN2+ and 5.0/1000 for CIN3+. After subsequent screening of women who were either hrHPV positive/cytology negative or ASC-US positive/HPV negative, women randomised to the HPV arms had increased CIN2+ detection compared with women randomised to the cytology arm.

A randomised controlled trial of clinics in secondary schools for adolescents with asthma.

PubMed Central

Salisbury, Chris; Francis, Caia; Rogers, Chris; Parry, Kate; Thomas, Huw; Chadwick, Stephanie; Turton, Pat

2002-01-01

AIM: To compare a nurse-led clinic in schools versus care in general practice for adolescents with asthma. DESIGN OF STUDY: Randomised controlled trial in four schools; parallel observational study in two schools. SETTING: Six comprehensive schools. METHOD: In the randomised trial, pupils were invited to attend asthma review at a nurse-led clinic either in school, or in general practice. The parallel observational study compared pupils invited to practice care within and outside the randomised trial. Primary outcome measures were attendance for asthma review, symptom control, and quality of life. Secondary outcomes were knowledge, attitudes, inhaler technique, use of steroids, school absence, peak flow rate, preference for future care, health service utilisation, and costs. RESULTS: School clinic pupils were more likely to attend an asthma review than those randomised to practice care (90.8% versus 51.0% overall [P < 0.001, not consistent across schools]). No differences were observed in symptom control (P = 0.42) or quality of life (P = 0.63). Pupils attending school clinics had greater knowledge of asthma (difference = +0.38, 95% CI = 0.19 to 0.56), more positive attitudes (difference = +0.21, 95% CI = 0.05 to 0.36), and better inhaler technique (P < 0.001, not consistent across all schools). No differences were observed in school absence or peak flow rate. A majority (63%) of those who had received care at school preferred this model in future. Median costs of providing care at school and at the practice were 32.10 Pounds and 19.80 Pounds, respectively. No differences were observed between the groups in the observational comparison on any outcome. CONCLUSIONS: The schools asthma clinic increased uptake of asthma reviews. There were improvements in various process measures, but not in clinical outcomes. PMID:12528584

Managing Injuries of the Neck Trial (MINT): design of a randomised controlled trial of treatments for whiplash associated disorders

PubMed Central

Lamb, Sarah E; Gates, Simon; Underwood, Martin R; Cooke, Matthew W; Ashby, Deborah; Szczepura, Ala; Williams, Mark A; Williamson, Esther M; Withers, Emma J; Mt Isa, Shahrul; Gumber, Anil

2007-01-01

Background A substantial proportion of patients with whiplash injuries develop chronic symptoms. However, the best treatment of acute injuries to prevent long-term problems is uncertain. A stepped care treatment pathway has been proposed, in which patients are given advice and education at their initial visit to the emergency department (ED), followed by review at three weeks and physiotherapy for those with persisting symptoms. MINT is a two-stage randomised controlled trial to evaluate two components of such a pathway: 1. use of The Whiplash Book versus usual advice when patients first attend the emergency department; 2. referral to physiotherapy versus reinforcement of advice for patients with continuing symptoms at three weeks. Methods Evaluation of the Whiplash Book versus usual advice uses a cluster randomised design in emergency departments of eight NHS Trusts. Eligible patients are identified by clinicians in participating emergency departments and are sent a study questionnaire within a week of their ED attendance. Three thousand participants will be included. Patients with persisting symptoms three weeks after their ED attendance are eligible to join an individually randomised study of physiotherapy versus reinforcement of the advice given in ED. Six hundred participants will be randomised. Follow-up is at 4, 8 and 12 months after their ED attendance. Primary outcome is the Neck Disability Index (NDI), and secondary outcomes include quality of life and time to return to work and normal activities. An economic evaluation is being carried out. Conclusion This paper describes the protocol and operational aspects of a complex intervention trial based in NHS emergency and physiotherapy departments, evaluating two components of a stepped-care approach to the treatment of whiplash injuries. The trial uses two randomisations, with the first stage being cluster randomised and the second individually randomised. PMID:17257408

Randomised controlled trials of homeopathy in humans: characterising the research journal literature for systematic review.

PubMed

Mathie, Robert T; Hacke, Daniela; Clausen, Jürgen; Nicolai, Ton; Riley, David S; Fisher, Peter

2013-01-01

A new programme of systematic reviews of randomised controlled trials (RCTs) in homeopathy will distinguish important attributes of RCT records, including: placebo controlled versus other-than-placebo (OTP) controlled; individualised versus non-individualised homeopathy; peer-reviewed (PR) versus non peer-reviewed (NPR) sources. (a) To outline the methods used to search and categorise the RCT literature; (b) to report details of the records retrieved; (c) to compare our retrieved records with those reported in two previous systematic reviews (Linde et al., 1997; Shang et al., 2005). Ten major electronic databases were searched for records published up to the end of 2011. A record was accepted for subsequent systematic review if it was a substantive report of a clinical trial of homeopathic treatment or prophylaxis in humans, randomised and controlled, and published in a PR or NPR journal. 489 records were potentially eligible: 226 were rejected as non-journal, minor or repeat publications, or lacking randomisation and/or controls and/or a 'homeopathic' intervention; 263 (164 PR, 99 NPR) were acceptable for systematic review. The 263 accepted records comprised 217 (137 PR, 80 NPR) placebo-controlled RCTs, of which 121 were included by, 66 were published after, and 30 were potentially eligible for, but not listed by, Linde or Shang. The 137 PR records of placebo-controlled RCTs comprise 41 on individualised homeopathy and 96 on non-individualised homeopathy. Our findings clarify the RCT literature in homeopathy. The 263 accepted journal papers will be the basis for our forthcoming programme of systematic reviews. Copyright © 2012 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Difficulties in spinal needle use. Insertion characteristics and failure rates associated with 25-, 27- and 29-gauge Quincke-type spinal needles.

PubMed

Tarkkila, P; Huhtala, J; Salminen, U

1994-08-01

The effect of different size (25-, 27- and 29-gauge) Quincke-type spinal needles on the incidence of insertion difficulties and failure rates was investigated in a randomised, prospective study with 300 patients. The needle size was randomised but the insertion procedure was standardised. The time to achieve dural puncture was significantly longer with the 29-gauge spinal needle compared with the larger bore needles and was due to the greater flexibility of the thin needle. However, the difference was less than 1 min and cannot be considered clinically significant. There were no significant differences between groups in the number of insertion attempts or failures and the same sensory level of analgesia was reached with all the needle sizes studied. Postoperatively, no postdural puncture headaches occurred in the 29-gauge spinal needle group, whilst in the 25- and 27-gauge needle groups, the postdural puncture headache rates were 7.4% and 2.1% respectively. The incidence of backache was similar in all study groups. We conclude that dural puncture with a 29-gauge spinal needle is clinically as easy as with larger bore needles and its use is indicated in patients who have a high risk of postdural puncture headache.

One-stage or two-stage revision surgery for prosthetic hip joint infection--the INFORM trial: a study protocol for a randomised controlled trial.

PubMed

Strange, Simon; Whitehouse, Michael R; Beswick, Andrew D; Board, Tim; Burston, Amanda; Burston, Ben; Carroll, Fran E; Dieppe, Paul; Garfield, Kirsty; Gooberman-Hill, Rachael; Jones, Stephen; Kunutsor, Setor; Lane, Athene; Lenguerrand, Erik; MacGowan, Alasdair; Moore, Andrew; Noble, Sian; Simon, Joanne; Stockley, Ian; Taylor, Adrian H; Toms, Andrew; Webb, Jason; Whittaker, John-Paul; Wilson, Matthew; Wylde, Vikki; Blom, Ashley W

2016-02-17

Periprosthetic joint infection (PJI) affects approximately 1% of patients following total hip replacement (THR) and often results in severe physical and emotional suffering. Current surgical treatment options are debridement, antibiotics and implant retention; revision THR; excision of the joint and amputation. Revision surgery can be done as either a one-stage or two-stage operation. Both types of surgery are well-established practice in the NHS and result in similar rates of re-infection, but little is known about the impact of these treatments from the patient's perspective. The main aim of this randomised controlled trial is to determine whether there is a difference in patient-reported outcome measures 18 months after randomisation for one-stage or two-stage revision surgery. INFORM (INFection ORthopaedic Management) is an open, two-arm, multi-centre, randomised, superiority trial. We aim to randomise 148 patients with eligible PJI of the hip from approximately seven secondary care NHS orthopaedic units from across England and Wales. Patients will be randomised via a web-based system to receive either a one-stage revision or a two-stage revision THR. Blinding is not possible due to the nature of the intervention. All patients will be followed up for 18 months. The primary outcome is the WOMAC Index, which assesses hip pain, function and stiffness, collected by questionnaire at 18 months. Secondary outcomes include the following: cost-effectiveness, complications, re-infection rates, objective hip function assessment and quality of life. A nested qualitative study will explore patients' and surgeons' experiences, including their views about trial participation and randomisation. INFORM is the first ever randomised trial to compare two widely accepted surgical interventions for the treatment of PJI: one-stage and two-stage revision THR. The results of the trial will benefit patients in the future as the main focus is on patient-reported outcomes: pain, function and wellbeing in the long term. Patients state that these outcomes are more important than those that are clinically derived (such as re-infection) and have been commonly used in previous non-randomised studies. Results from the INFORM trial will also benefit clinicians and NHS managers by enabling the comparison of these key interventions in terms of patients' complication rates, health and social resource use and their overall cost-effectiveness. Current controlled trials ISRCTN10956306 (registered on 29 January 2015); UKCRN ID 18159.

Minimal access surgery compared with medical management for gastro-oesophageal reflux disease: five year follow-up of a randomised controlled trial (REFLUX).

PubMed

Grant, A M; Cotton, S C; Boachie, C; Ramsay, C R; Krukowski, Z H; Heading, R C; Campbell, M K

2013-04-18

To determine the long term clinical effectiveness of laparoscopic fundoplication as an alternative to drug treatment for chronic gastro-oesophageal reflux disease (GORD). Five year follow-up of multicentre, pragmatic randomised trial (with parallel non-randomised preference groups). Initial recruitment in 21 UK hospitals. Responders to annual questionnaires among 810 original participants. At entry, all had had GORD for >12 months. The surgeon chose the type of fundoplication. Medical therapy was reviewed and optimised by a specialist. Subsequent management was at the discretion of the clinician responsible for care, usually in primary care. Primary outcome measure was self reported quality of life score on disease-specific REFLUX questionnaire. Other measures were health status (with SF-36 and EuroQol EQ-5D questionnaires), use of antireflux medication, and complications. By five years, 63% (112/178) of patients randomised to surgery and 13% (24/179) of those randomised to medical management had received a fundoplication (plus 85% (222/261) and 3% (6/192) of those who expressed a preference for surgery and for medical management). Among responders at 5 years, 44% (56/127) of those randomised to surgery were taking antireflux medication versus 82% (98/119) of those randomised to medical management. Differences in the REFLUX score significantly favoured the randomised surgery group (mean difference 8.5 (95% CI 3.9 to 13.1), P<0.001, at five years). SF-36 and EQ-5D scores also favoured surgery, but were not statistically significant at five years. After fundoplication, 3% (12/364) had surgical treatment for a complication and 4% (16) had subsequent reflux-related operations-most often revision of the wrap. Long term rates of dysphagia, flatulence, and inability to vomit were similar in the two randomised groups. After five years, laparoscopic fundoplication continued to provide better relief of GORD symptoms than medical management. Adverse effects of surgery were uncommon and generally observed soon after surgery. A small proportion had re-operations. There was no evidence of long term adverse symptoms caused by surgery. Current Controlled Trials ISRCTN15517081.

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

PubMed Central

2012-01-01

Background Staphylococcus aureus bacteraemia is a common and serious infection, with an associated mortality of ~25%. Once in the blood, S. aureus can disseminate to infect almost any organ, but bones, joints and heart valves are most frequently affected. Despite the infection’s severity, the evidence guiding optimal antibiotic therapy is weak: fewer than 1,500 patients have been included in 16 randomised controlled trials investigating S. aureus bacteraemia treatment. It is uncertain which antibiotics are most effective, their route of administration and duration, and whether antibiotic combinations are better than single agents. We hypothesise that adjunctive rifampicin, given in combination with a standard first-line antibiotic, will enhance killing of S. aureus early in the treatment course, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. Our aim is to determine whether adjunctive rifampicin reduces all-cause mortality within 14 days and bacteriological failure or death within 12 weeks from randomisation. Methods We will perform a parallel group, randomised (1:1), blinded, placebo-controlled trial in NHS hospitals across the UK. Adults (≥18 years) with S. aureus (meticillin-susceptible or resistant) grown from at least one blood culture who have received ≤96 h of active antibiotic therapy for the current infection and do not have contraindications to the use of rifampicin will be eligible for inclusion. Participants will be randomised to adjunctive rifampicin (600-900mg/day; orally or intravenously) or placebo for the first 14 days of therapy in combination with standard single-agent antibiotic therapy. The co-primary outcome measures will be all-cause mortality up to 14 days from randomisation and bacteriological failure/death (all-cause) up to 12 weeks from randomisation. 940 patients will be recruited, providing >80% power to detect 45% and 30% reductions in the two co-primary endpoints of death by 14 days and bacteriological failure/death by 12 weeks respectively. Discussion This pragmatic trial addresses the long-standing hypothesis that adjunctive rifampicin improves outcome from S. aureus bacteraemia through enhanced early bacterial killing. If proven correct, it will provide a paradigm through which further improvements in outcome from S. aureus bacteraemia can be explored. Trial registration Current Controlled Trial ISRCTN 37666216 PMID:23249501

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

PubMed

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

2016-04-23

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

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

PubMed

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

2005-11-01

A systematic review to determine if exercise alone or as part of a comprehensive intervention can improve self esteem in children and young people is described. Twenty three randomised controlled trials were analysed. A synthesis of several small, low quality trials indicates that exercise may have short term beneficial effects on self esteem in children and adolescents. However, high quality research on defined populations with adequate follow up is needed.

The influence of industry sponsorship on the reporting of subgroup analyses within phase III randomised controlled trials in gastrointestinal oncology.

PubMed

Barton, Sarah; Peckitt, Clare; Sclafani, Francesco; Cunningham, David; Chau, Ian

2015-12-01

Correct interpretation of subgroup analyses (SGA) is important as it influences selection of therapeutic interventions for patient subsets. The primary aim of our study was to compare reporting of SGA between industry and non-industry sponsored trials. We performed a systematic literature review and extracted data from journal articles (JA) and conference abstracts (CA) published over a decade reporting SGA results of phase III randomised controlled gastrointestinal (GI) oncology trials with patient participants of ≥150. In JA, SGA was reported in 100/145 (69%) trials: 41/54 industry sponsored (76%; 95% confidence interval [CI]: 63-86%) and 59/91 non-industry sponsored (65%; 95% CI: 55-74%) trials (p = 0.16). In CA, SGA was reported in 86/204 (42%) trials: 43/83 industry sponsored (52%; 95% CI: 41-62%) and 43/121 non-industry sponsored (36%; 95% CI: 28-44%) trials (p = 0.02). Number of SGA performed per trial was significantly larger for industry compared to non-industry sponsored trials in both JA (median 6 versus 2, p = 0.003) and CA (median 1 versus 0, p = 0.023). Claims of subgroup effect were made in 52% of trials in JA and 50% in CA, with significant test of interaction evident in only 25% of JA and 16% of CA, with no difference between industry and non-industry trials. Industry sponsored trials with a significant primary end-point reported more SGA (p < 0.001 JA; p = 0.046 CA). Industry sponsored trials reported more SGA. Claimed subgroup effects were often not accompanied by significant interaction test; thus circumspection should be adopted when using SGA to deviate from standard therapeutic decision-making in GI oncology. Copyright © 2015 Elsevier Ltd. All rights reserved.

The experience of patients participating in a small randomised control trial that explored two different interventions to reduce anxiety prior to an MRI scan.

PubMed

Tugwell-Allsup, J; Pritchard, A W

2018-05-01

This paper reports qualitative findings from within a larger randomised control trial where a video clip or telephone conversation with a radiographer was compared to routine appointment letter and information sheet to help alleviate anxiety prior to their MRI scan. Questionnaires consisting of three free-text response questions were administered to all of the 74 patients recruited to the MRI anxiety clinical trial. The questionnaire was designed to establish patients' experiences of the intervention they had received. These questionnaires were administered post-scan. Two participants from each trial arm were also interviewed. A thematic approach was utilised for identifying recurrent categories emerging from the qualitative data which are supported by direct quotations. Participants in the interventional groups commented positively about the provision of pre-MRI scan information they received and this was contrastable with the relatively indifferent responses observed among those who received the standard information letter. Many important themes were identified including the patients needs for clear and simplified information, the experience of anticipation when waiting for the scan, and also the informally acquired information about having an MRI scan i.e. the shared experiences of friends and family. All themes highlighted the need for an inclusive and individually tailored approach to pre-scan information provision. Qualitative data collected throughout the trial is supportive of the statistical findings, where it is asserted that the use of a short video clip or a radiographer having a short conversation with patients before their scan reduces pre-scan anxiety. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Bridging the age gap in breast cancer: evaluation of decision support interventions for older women with operable breast cancer: protocol for a cluster randomised controlled trial.

PubMed

Collins, Karen; Reed, Malcolm; Lifford, Kate; Burton, Maria; Edwards, Adrian; Ring, Alistair; Brain, Katherine; Harder, Helena; Robinson, Thompson; Cheung, Kwok Leung; Morgan, Jenna; Audisio, Riccardo; Ward, Susan; Richards, Paul; Martin, Charlene; Chater, Tim; Pemberton, Kirsty; Nettleship, Anthony; Murray, Christopher; Walters, Stephen; Bortolami, Oscar; Armitage, Fiona; Leonard, Robert; Gath, Jacqui; Revell, Deirdre; Green, Tracy; Wyld, Lynda

2017-07-31

While breast cancer outcomes are improving steadily in younger women due to advances in screening and improved therapies, there has been little change in outcomes among the older age group. It is inevitable that comorbidities/frailty rates are higher, which may increase the risks of some breast cancer treatments such as surgery and chemotherapy, many older women are healthy and may benefit from their use. Adjusting treatment regimens appropriately for age/comorbidity/frailty is variable and largely non-evidence based, specifically with regard to rates of surgery for operable oestrogen receptor-positive disease and rates of chemotherapy for high-risk disease. This multicentre, parallel group, pragmatic cluster randomised controlled trial (RCT) (2015-18) reported here is nested within a larger ongoing 'Age Gap Cohort Study' (2012-18RP-PG-1209-10071), aims to evaluate the effectiveness of a complex intervention of decision support interventions to assist in the treatment decision making for early breast cancer in older women. The interventions include two patient decision aids (primary endocrine therapy vs surgery/antioestrogen therapy and chemotherapy vs no chemotherapy) and a clinical treatment outcomes algorithm for clinicians. National and local ethics committee approval was obtained for all UK participating sites. Results from the trial will be submitted for publication in international peer-reviewed scientific journals. 115550. European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2015-004220-61;Pre-results. Sponsor's Protocol Code Number Sheffield Teaching Hospitals STH17086. ISRCTN 32447*. © 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.

Effects of interventions on normalizing step width during self-paced dual-belt treadmill walking with virtual reality, a randomised controlled trial.

PubMed

Oude Lansink, I L B; van Kouwenhove, L; Dijkstra, P U; Postema, K; Hijmans, J M

2017-10-01

Step width is increased during dual-belt treadmill walking, in self-paced mode with virtual reality. Generally a familiarization period is thought to be necessary to normalize step width. The aim of this randomised study was to analyze the effects of two interventions on step width, to reduce the familiarization period. We used the GRAIL (Gait Real-time Analysis Interactive Lab), a dual-belt treadmill with virtual reality in the self-paced mode. Thirty healthy young adults were randomly allocated to three groups and asked to walk at their preferred speed for 5min. In the first session, the control-group received no intervention, the 'walk-on-the-line'-group was instructed to walk on a line, projected on the between-belt gap of the treadmill and the feedback-group received feedback about their current step width and were asked to reduce it. Interventions started after 1min and lasted 1min. During the second session, 7-10days later, no interventions were given. Linear mixed modeling showed that interventions did not have an effect on step width after the intervention period in session 1. Initial step width (second 30s) of session 1 was larger than initial step width of session 2. Step width normalized after 2min and variation in step width stabilized after 1min. Interventions do not reduce step width after intervention period. A 2-min familiarization period is sufficient to normalize and stabilize step width, in healthy young adults, regardless of interventions. A standardized intervention to normalize step width is not necessary. Copyright © 2017 Elsevier B.V. All rights reserved.

An intervention for pulmonary rehabilitators to develop a social identity for patients attending exercise rehabilitation: a feasibility and pilot randomised control trial protocol.

PubMed

Levy, Andrew R; Matata, Bashir; Pilsworth, Sam; Mcgonigle, Adrian; Wigelsworth, Lyndsey; Jones, Linda; Pott, Nicola; Bettany, Max; Midgley, Adrian W

2018-01-01

Chronic obstructive pulmonary disease (COPD) is a degenerative condition that can impair health-related quality of life (HRQoL). A number of self-management interventions, employing a variety of behavioural change techniques (BCTs), have been adopted to improve HRQoL for COPD patients. However, a lack of attention has been given to group management interventions with an emphasis on incorporating BCTs into rehabilitators' practice. This study aims to pilot and feasibly explore a social identity group management intervention, delivered by COPD rehabilitation staff to patients attending exercise pulmonary rehabilitation. Doing so will help inform the plausibility of the intervention before conducting a full trial to evaluate its effectiveness to improve HRQoL. This is a two-centre, randomised cross-over controlled trial. Two pulmonary rehabilitation centres based in the UK will be randomly allocated to two treatment arms (standard care and intervention). Outcome measurements relating to HRQoL and social identity will be completed pre- and post-exercise rehabilitation. Focus group interviews will be conducted at the end of exercise rehabilitation to capture participants' contextualised experiences of the intervention. COPD rehabilitators will undertake semi-structured interviews at the end of the trial to garner their holistic perspectives of intervention fidelity and implementation. This is the first study to adopt a social identity approach to develop a rehabilitator-led, group management intervention for COPD patients attending exercise pulmonary rehabilitation. The results of this study will provide evidence for the feasibility and sample size requirements to inform a larger study, which can ascertain the intervention's effectiveness for improving HRQoL for COPD patients. ClinicalTrials.gov NCT02288039. Date 31 October 2014.

A developmental approach to the treatment of bipolar disorder: IPSRT with an adolescent.

PubMed

Crowe, Marie; Inder, Maree; Joyce, Peter; Moor, Stephanie; Carter, Janet; Luty, Sue

2009-01-01

This case study explains how a psychotherapy previously used with adults can be used with adolescents by focusing on the specific developmental issues associated with adolescence. Bipolar disorder is a damaging disorder to experience during the developmental phase of adolescence. Interpersonal social rhythm psychotherapy has been developed as an adjunct to medication for managing bipolar disorder and shows some promising outcomes in adults. This is a single case study design drawn from a larger randomised control trial of two psychotherapies for bipolar disorder. The case study addressed the question: How can Interpersonal social rhythm therapy be applied with adolescents who have bipolar disorder? This study used a purposeful sampling process by selecting the youngest adolescent participating in the randomised control trial. All the subject's sessions of Interpersonal social rhythm therapy were taped, transcribed and analysed. The analysis involved describing the process of psychotherapy as it occurred over time, mapping the process as a trajectory across the three phases of psychotherapy experience and focusing the analysis around the impact of bipolar disorder and IPSRT on adolescent developmental issues, specifically the issue of identity development. Interpersonal social rhythm therapy allowed the therapist to address developmental issues within its framework. As a result of participation in the psychotherapy the adolescent was able to manage her mood symptoms and develop a sense of identity that was age-appropriate. Interpersonal social rhythm therapy provided the adolescent in the case study the opportunity to consider what it meant to have bipolar disorder and to integrate this meaning into her sense of self. Bipolar disorder is a chronic and recurring disorder that can have a serious impact on development and functioning. Interpersonal social rhythm therapy provides an approach to nursing care that enables adolescents to improve social functioning.

Minocycline as an adjunct for treatment-resistant depressive symptoms: A pilot randomised placebo-controlled trial.

PubMed

Husain, Muhammad I; Chaudhry, Imran B; Husain, Nusrat; Khoso, Ameer B; Rahman, Raza R; Hamirani, Munir M; Hodsoll, John; Qurashi, Inti; Deakin, John Fw; Young, Allan H

2017-09-01

Evidence suggests that anti-inflammatory medication may be effective in the treatment of depressive symptoms. In this study, we aimed to investigate whether minocycline added to treatment as usual (TAU) for 3 months in patients with treatment-resistant depression will lead to an improvement in depressive symptoms. Multi-site, 12-week, double-blind, placebo-controlled, pilot trial of minocycline added to TAU for patients suffering from DSM-5 major depressive disorder, whose current episode has failed to respond to at least two antidepressants. The primary outcome measure was mean change in Hamilton Depression Rating Scale (HAMD-17) scores from baseline to week 12. Secondary measures were the Clinical Global Impression scale (CGI), Patient Health Questionnaire-9 (PHQ-9), the Generalised Anxiety Disorder scale (GAD-7) and EuroQoL (EQ-5D) quality-of-life questionnaire. Side-effect checklists were also used. Minocycline was started at 100 mg once daily (OD) and increased to 200 mg after 2 weeks. A total of 41 participants were randomised, with 21 in the minocycline group and 20 in the placebo group. A large decrease in HAMD scores was observed in the minocycline group compared to the placebo group (standardised effect size (ES) -1.21, p < 0.001). CGI scores in the minocycline group also showed a large improvement compared with placebo (odds ratio (OR): 17.6, p < 0.001). PHQ-9, GAD-7 and EQ-5D total showed more moderate improvements (ES ~ 0.4-0.5). The findings indicate that adjunctive minocycline leads to improvement in symptoms of treatment-resistant depression. However, our findings require replication in a larger sample. ClinicalTrials.gov identifier: NCT02263872, registered October 2014.

Bridging the age gap in breast cancer: evaluation of decision support interventions for older women with operable breast cancer: protocol for a cluster randomised controlled trial

PubMed Central

Collins, Karen; Reed, Malcolm; Lifford, Kate; Burton, Maria; Edwards, Adrian; Ring, Alistair; Brain, Katherine; Harder, Helena; Robinson, Thompson; Cheung, Kwok Leung; Morgan, Jenna; Audisio, Riccardo; Ward, Susan; Richards, Paul; Martin, Charlene; Chater, Tim; Pemberton, Kirsty; Nettleship, Anthony; Murray, Christopher; Walters, Stephen; Bortolami, Oscar; Armitage, Fiona; Leonard, Robert; Gath, Jacqui; Revell, Deirdre; Green, Tracy; Wyld, Lynda

2017-01-01

Introduction While breast cancer outcomes are improving steadily in younger women due to advances in screening and improved therapies, there has been little change in outcomes among the older age group. It is inevitable that comorbidities/frailty rates are higher, which may increase the risks of some breast cancer treatments such as surgery and chemotherapy, many older women are healthy and may benefit from their use. Adjusting treatment regimens appropriately for age/comorbidity/frailty is variable and largely non-evidence based, specifically with regard to rates of surgery for operable oestrogen receptor-positive disease and rates of chemotherapy for high-risk disease. Methods and analysis This multicentre, parallel group, pragmatic cluster randomised controlled trial (RCT) (2015-18) reported here is nested within a larger ongoing ‘Age Gap Cohort Study’ (2012-18RP-PG-1209-10071), aims to evaluate the effectiveness of a complex intervention of decision support interventions to assist in the treatment decision making for early breast cancer in older women. The interventions include two patient decision aids (primary endocrine therapy vs surgery/antioestrogen therapy and chemotherapy vs no chemotherapy) and a clinical treatment outcomes algorithm for clinicians. Ethics and dissemination National and local ethics committee approval was obtained for all UK participating sites. Results from the trial will be submitted for publication in international peer-reviewed scientific journals. IRAS reference 115550. Trial registration number European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2015-004220-61;Pre-results. Sponsor's Protocol Code Number Sheffield Teaching Hospitals STH17086. ISRCTN 32447*. PMID:28760787

Ambulatory versus inpatient management of severe nausea and vomiting of pregnancy: a randomised control trial with patient preference arm

PubMed Central

Mitchell-Jones, Nicola; Farren, Jessica Alice; Tobias, Aurelio; Bourne, Tom; Bottomley, Cecilia

2017-01-01

Objective To determine whether ambulatory (outpatient (OP)) treatment of severe nausea and vomiting of pregnancy (NVP) is as effective as inpatient (IP) care. Design Non-blinded randomised control trial (RCT) with patient preference arm. Setting Two multicentre teaching hospitals in London. Participants Women less than 20 weeks’ pregnant with severe NVP and associated ketonuria (>1+). Methods Women who agreed to the RCT were randomised via web-based application to either ambulatory or IP treatment. Women who declined randomisation underwent the treatment of their choice in the patient preference trial (PPT) arm. Treatment protocols, data collection and follow-up were the same for all participants. Main outcome measures Primary outcome was reduction in Pregnancy Unique Quantification of Emesis (PUQE) score 48 hours after starting treatment. Secondary outcome measures were duration of treatment, improvement in symptom scores and ketonuria at 48 hours, reattendances within 7 days of discharge and comparison of symptoms at 7 days postdischarge. Results 152/174 eligible women agreed to participate with 77/152 (51%) recruited to the RCT and 75/152 (49%) to the PPT. Patients were initially compared in four groups (randomised IP, randomised OP, non-randomised IP and non-randomised OP). Comprehensive cohort analysis of participants in the randomised group (RCT) and non-randomised group (PPT) did not demonstrate any differences in patient demographics or baseline clinical characteristics. Pooled analysis of IP versus OP groups showed no difference in reduction in PUQE score at 48 hours (p=0.86). There was no difference in change in eating score (p=0.69), drinking score (p=0.77), well-being rating (p=0.64) or reduction in ketonuria (p=0.47) at 48 hours, with no difference in duration of index treatment episode (p=0.83) or reattendances within 7 days (p=0.52). Conclusions Ambulatory management is an effective direct alternative to IP management of severe NVP. The trial also demonstrated that many women requiring treatment for severe NVP have strong preferences regarding treatment setting, which may need to be considered by care providers, especially given the psychological impact of severe NVP. Trial registration number http://www.isrctn.com/ISRCTN24659467 (March 2014). PMID:29222135

The management of the painful bipartite patella: a systematic review.

PubMed

McMahon, Samuel E; LeRoux, Johannes A; Smith, Toby O; Hing, Caroline B

2016-09-01

This study aimed to identify the most effective method for the treatment of the symptomatic bipartite patella. A systematic review of the literature was completed, and all studies assessing the management of a bipartite patella were included. Owing to the paucity of randomised controlled trials, a narrative review of 22 studies was completed. A range of treatments were assessed: conservative measures, open and arthroscopic fixation or excision and soft tissue release and excision. All of the methods provided results ranging from good to excellent, with acceptable complication rates. This is a poorly answered treatment question. No firm guidance can be given as to the most appropriate method of treating the symptomatic bipartite patella. This study suggests that there are a number of effective treatments with acceptable complication rates and it may be that treatments that conserve the patella are more appropriate for larger fragments. IV.

Interventions for promoting smoke alarm ownership and function.

PubMed

DiGuiseppi, C; Higgins, J P

2001-01-01

Residential fires caused at least 67 deaths and 2,500 non-fatal injuries to children aged 0-16 in the United Kingdom in 1998. Smoke alarm ownership is associated with a reduced risk of residential fire death. We evaluated interventions to promote residential smoke alarms, to assess their effect on smoke alarm ownership, smoke alarm function, fires and burns and other fire-related injuries. We searched the Cochrane Controlled Trials Register, Cochrane Injuries Group database, MEDLINE, EMBASE, PsycLIT, CINAHL, ERIC, Dissertation Abstracts, International Bibliography of Social Sciences, ISTP, FIREDOC and LRC. Conference proceedings, published case studies, and bibliographies were systematically searched, and investigators and relevant organisations were contacted, to identify trials. Randomised, quasi-randomised or nonrandomised controlled trials completed or published after 1969 evaluating an intervention to promote residential smoke alarms. Two reviewers independently extracted data and assessed trial quality. We identified 26 trials, of which 13 were randomised. Overall, counselling and educational interventions had only a modest effect on the likelihood of owning an alarm (OR=1.26; 95% CI: 0.87 to 1.82) or having a functional alarm (OR=1.19; 0.85 to 1.66). Counselling as part of primary care child health surveillance had greater effects on ownership (OR=1.96; 1.03 to 3.72) and function (OR=1.72; 0.78 to 3.80). Results were sensitive to trial quality, however, and effects on fire-related injuries were not reported. In two non randomised trials, direct provision of free alarms significantly increased functioning alarms and reduced fire-related injuries. Media and community education showed little benefit in non randomised trials. Counselling as part of child health surveillance may increase smoke alarm ownership and function, but its effects on injuries are unevaluated. Community smoke alarm give-away programmes apparently reduce fire-related injuries, but these trials were not randomised and results must be interpreted cautiously. Further efforts to promote smoke alarms in primary care or through give-away programmes should be evaluated by adequately designed randomised controlled trials measuring injury outcomes.

Needle aspiration versus intercostal tube drainage for pneumothorax in the newborn.

PubMed

Bruschettini, Matteo; Romantsik, Olga; Ramenghi, Luca Antonio; Zappettini, Simona; O'Donnell, Colm P F; Calevo, Maria Grazia

2016-01-11

Pneumothorax occurs more frequently in the neonatal period than at any other time of life and is associated with increased mortality and morbidity. It may be treated with either needle aspiration or insertion of a chest tube. The former consists of aspiration of air with a syringe through a needle or an angiocatheter, usually through the second or third intercostal space in the midclavicular line. The chest tube is usually placed in the anterior pleural space passing through the sixth intercostal space into the pleural opening, turned anteriorly and directed to the location of the pneumothorax, and then connected to a Heimlich valve or an underwater seal with continuous suction. To compare the efficacy and safety of needle aspiration and intercostal tube drainage in the management of neonatal pneumothorax. We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 11), MEDLINE via PubMed (1966 to 30 November 2015), EMBASE (1980 to 30 November 2015), and CINAHL (1982 to 30 November 2015). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised controlled trials, quasi-randomised controlled trials and cluster trials comparing needle aspiration (either with the needle or angiocatheter left in situ or removed immediately after aspiration) to intercostal tube drainage in newborn infants with pneumothorax. For each of the included trial, two authors independently extracted data (e.g. number of participants, birth weight, gestational age, kind of needle and chest tube, choice of intercostal space, pressure and device for drainage) and assessed the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). The primary outcomes considered in this review are mortality during the neonatal period and during hospitalisation. One randomised controlled trial (72 infants) met the inclusion criteria of this review. We found no differences in the rates of mortality (risk ratio (RR) 1.50, 95% confidence interval (CI) 0.27 to 8.45) or complications related to the procedure. After needle aspiration, the angiocatheter was left in situ (mean 27.1 hours) and not removed immediately after the aspiration. The angiocatheter was in place for a shorter duration than the intercostal tube (mean difference (MD) -11.20 hours, 95% CI -15.51 to -6.89). None of the 36 newborns treated with needle aspiration with the angiocatheter left in situ required the placement of an intercostal tube drainage. Overall, the quality of the evidence supporting this finding is low. At present there is insufficient evidence to determine the efficacy and safety of needle aspiration versus intercostal tube drainage in the management of neonatal pneumothorax. Randomised controlled trials comparing the two techniques are warranted.

Evaluating the effectiveness of a smartphone app to reduce excessive alcohol consumption: protocol for a factorial randomised control trial.

PubMed

Garnett, Claire; Crane, David; Michie, Susan; West, Robert; Brown, Jamie

2016-07-08

Excessive alcohol consumption is a leading cause of death and morbidity worldwide and interventions to help people reduce their consumption are needed. Interventions delivered by smartphone apps have the potential to help harmful and hazardous drinkers reduce their consumption of alcohol. However, there has been little evaluation of the effectiveness of existing smartphone interventions. A systematic review, amongst other methodologies, identified promising modular content that could be delivered by an app: self-monitoring and feedback; action planning; normative feedback; cognitive bias re-training; and identity change. This protocol reports a factorial randomised controlled trial to assess the comparative potential of these five intervention modules to reduce excessive alcohol consumption. A between-subject factorial randomised controlled trial. Hazardous and harmful drinkers aged 18 or over who are making a serious attempt to reduce their drinking will be randomised to one of 32 (2(5)) experimental conditions after downloading the 'Drink Less' app. Participants complete baseline measures on downloading the app and are contacted after 1-month with a follow-up questionnaire. The primary outcome measure is change in past week consumption of alcohol. Secondary outcome measures are change in AUDIT score, app usage data and usability ratings for the app. A factorial between-subjects ANOVA will be conducted to assess main and interactive effects of the five intervention modules for the primary and secondary outcome measures. This study will establish the extent to which the five intervention modules offered in this app can help reduce hazardous and harmful drinking. This is the first step in optimising and understanding what component parts of an app could help to reduce excessive alcohol consumption. The findings from this study will be used to inform the content of a future integrated treatment app and evaluated against a minimal control in a definitive randomised control trial with long-term outcomes. ISRCTN40104069 Date of registration: 10/2/2016.

Electroacupuncture as a complement to usual care for patients with non-acute pain after back surgery: a study protocol for a pilot randomised controlled trial.

PubMed

Hwang, Man-Suk; Heo, Kwang-Ho; Cho, Hyun-Woo; Shin, Byung-Cheul; Lee, Hyeon-Yeop; Heo, In; Kim, Nam-Kwen; Choi, Byung-Kwan; Son, Dong-Wuk; Hwang, Eui-Hyoung

2015-02-04

Recurrent or persistent low back pain is common after back surgery but is typically not well controlled. Previous randomised controlled trials on non-acute pain after back surgery were flawed. In this article, the design and protocol of a randomised controlled trial to treat pain and improve function after back surgery are described. This study is a pilot randomised, active-controlled, assessor-blinded trial. Patients with recurring or persistent low back pain after back surgery, defined as a visual analogue scale value of ≥50 mm, with or without leg pain, will be randomly assigned to an electroacupuncture-plus-usual-care group or to a usual-care-only group. Patients assigned to both groups will have usual care management, including physical therapy and patient education, twice a week during a 4-week treatment period that would begin at randomisation. Patients assigned to the electroacupuncture-plus-usual-care group will also have electroacupuncture twice a week during the 4-week treatment period. The primary outcome will be measured with the 100 mm pain visual analogue scale of low back pain by a blinded evaluator. Secondary outcomes will be measured with the EuroQol 5-Dimension and the Oswestry Disability Index. The primary and secondary outcomes will be measured at 4 and 8 weeks after treatment. Written informed consent will be obtained from all participants. This study was approved by the Institutional Review Board (IRB) of Pusan National University Korean Hospital in September 2013 (IRB approval number 2013012). The study findings will be published in peer-reviewed journals and presented at national and international conferences. This trial was registered with the US National Institutes of Health Clinical Trials Registry: NCT01966250. 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.

An educational intervention to reduce pain and improve pain management for Malawian people living with HIV/AIDS and their family carers: study protocol for a randomised controlled trial.

PubMed

Nkhoma, Kennedy; Seymour, Jane; Arthur, Antony

2013-07-13

Many HIV/AIDS patients experience pain often due to advanced HIV/AIDS infection and side effects of treatment. In sub-Saharan Africa, pain management for people with HIV/AIDS is suboptimal. With survival extended as a direct consequence of improved access to antiretroviral therapy, the prevalence of HIV/AIDS related pain is increasing. As most care is provided at home, the management of pain requires patient and family involvement. Pain education is an important aspect in the management of pain in HIV/AIDS patients. Studies of the effectiveness of pain education interventions for people with HIV/AIDS have been conducted almost exclusively in western countries. A randomised controlled trial is being conducted at the HIV and palliative care clinics of two public hospitals in Malawi. To be eligible, patient participants must have a diagnosis of HIV/AIDS (stage III or IV). Carer participants must be the individual most involved in the patient's unpaid care. Eligible participants are randomised to either: (1) a 30-minute face-to-face educational intervention covering pain assessment and management, augmented by a leaflet and follow-up telephone call at two weeks; or (2) usual care. Those allocated to the usual care group receive the educational intervention after follow-up assessments have been conducted (wait-list control group). The primary outcome is pain severity measured by the Brief Pain Inventory. Secondary outcomes are pain interference, patient knowledge of pain management, patient quality of life, carer knowledge of pain management, caregiver motivation and carer quality of life. Follow-up assessments are conducted eight weeks after randomisation by palliative care nurses blind to allocation. This randomised controlled trial conducted in sub-Saharan Africa among people living with HIV/AIDS and their carers will assess whether a pain education intervention is effective in reducing pain and improving pain management, quality of life and carer motivation. Current Controlled Trials ISRCTN72861423.

The group-based social skills training SOSTA-FRA in children and adolescents with high functioning autism spectrum disorder - study protocol of the randomised, multi-centre controlled SOSTA - net trial

PubMed Central

2013-01-01

Background Group-based social skills training (SST) has repeatedly been recommended as treatment of choice in high-functioning autism spectrum disorder (HFASD). To date, no sufficiently powered randomised controlled trial has been performed to establish efficacy and safety of SST in children and adolescents with HFASD. In this randomised, multi-centre, controlled trial with 220 children and adolescents with HFASD it is hypothesized, that add-on group-based SST using the 12 weeks manualised SOSTA–FRA program will result in improved social responsiveness (measured by the parent rated social responsiveness scale, SRS) compared to treatment as usual (TAU). It is further expected, that parent and self reported anxiety and depressive symptoms will decline and pro-social behaviour will increase in the treatment group. A neurophysiological study in the Frankfurt HFASD subgroup will be performed pre- and post treatment to assess changes in neural function induced by SST versus TAU. Methods/design The SOSTA – net trial is designed as a prospective, randomised, multi-centre, controlled trial with two parallel groups. The primary outcome is change in SRS score directly after the intervention and at 3 months follow-up. Several secondary outcome measures are also obtained. The target sample consists of 220 individuals with ASD, included at the six study centres. Discussion This study is currently one of the largest trials on SST in children and adolescents with HFASD worldwide. Compared to recent randomised controlled studies, our study shows several advantages with regard to in- and exclusion criteria, study methods, and the therapeutic approach chosen, which can be easily implemented in non-university-based clinical settings. Trial registration ISRCTN94863788 – SOSTA – net: Group-based social skills training in children and adolescents with high functioning autism spectrum disorder. PMID:23289935

Effects of treatment in women with gestational diabetes mellitus: systematic review and meta-analysis.

PubMed

Horvath, Karl; Koch, Klaus; Jeitler, Klaus; Matyas, Eva; Bender, Ralf; Bastian, Hilda; Lange, Stefan; Siebenhofer, Andrea

2010-04-01

To summarise the benefits and harms of treatments for women with gestational diabetes mellitus. Systematic review and meta-analysis of randomised controlled trials. Embase, Medline, AMED, BIOSIS, CCMed, CDMS, CDSR, CENTRAL, CINAHL, DARE, HTA, NHS EED, Heclinet, SciSearch, several publishers' databases, and reference lists of relevant secondary literature up to October 2009. Review methods Included studies were randomised controlled trials of specific treatment for gestational diabetes compared with usual care or "intensified" compared with "less intensified" specific treatment. Five randomised controlled trials matched the inclusion criteria for specific versus usual treatment. All studies used a two step approach with a 50 g glucose challenge test or screening for risk factors, or both, and a subsequent 75 g or 100 g oral glucose tolerance test. Meta-analyses did not show significant differences for most single end points judged to be of direct clinical importance. In women specifically treated for gestational diabetes, shoulder dystocia was significantly less common (odds ratio 0.40, 95% confidence interval 0.21 to 0.75), and one randomised controlled trial reported a significant reduction of pre-eclampsia (2.5 v 5.5%, P=0.02). For the surrogate end point of large for gestational age infants, the odds ratio was 0.48 (0.38 to 0.62). In the 13 randomised controlled trials of different intensities of specific treatments, meta-analysis showed a significant reduction of shoulder dystocia in women with more intensive treatment (0.31, 0.14 to 0.70). Treatment for gestational diabetes, consisting of treatment to lower blood glucose concentration alone or with special obstetric care, seems to lower the risk for some perinatal complications. Decisions regarding treatment should take into account that the evidence of benefit is derived from trials for which women were selected with a two step strategy (glucose challenge test/screening for risk factors and oral glucose tolerance test).

A Scoping Review of Economic Evaluations Alongside Randomised Controlled Trials of Home Monitoring in Chronic Disease Management.

PubMed

Kidholm, Kristian; Kristensen, Mie Borch Dahl

2018-04-01

Many countries have considered telemedicine and home monitoring of patients as a solution to the demographic challenges that health-care systems face. However, reviews of economic evaluations of telemedicine have identified methodological problems in many studies as they do not comply with guidelines. The aim of this study was to examine economic evaluations alongside randomised controlled trials of home monitoring in chronic disease management and hereby to explore the resources included in the programme costs, the types of health-care utilisation that change as a result of home monitoring and discuss the value of economic evaluation alongside randomised controlled trials of home monitoring on the basis of the studies identified. A scoping review of economic evaluations of home monitoring of patients with chronic disease based on randomised controlled trials and including information on the programme costs and the costs of equipment was carried out based on a Medline (PubMed) search. Nine studies met the inclusion criteria. All studies include both costs of equipment and use of staff, but there is large variation in the types of equipment and types of tasks for the staff included in the costs. Equipment costs constituted 16-73% of the total programme costs. In six of the nine studies, home monitoring resulted in a reduction in primary care or emergency contacts. However, in total, home monitoring resulted in increased average costs per patient in six studies and reduced costs in three of the nine studies. The review is limited by the small number of studies found and the restriction to randomised controlled trials, which can be problematic in this area due to lack of blinding of patients and healthcare professionals and the difficulty of implementing organisational changes in hospital departments for the limited period of a trial. Furthermore, our results may be based on assessments of older telemedicine interventions.

Desmopressin acetate (DDAVP) for preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders.

PubMed

Karanth, Laxminarayan; Barua, Ankur; Kanagasabai, Sachchithanantham; Nair, Sreekumar

2015-09-09

Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of desmopressin acetate in these groups of pregnant women should be evaluated.This is an update of a Cochrane review first published in 2013. To determine the efficacy of desmopressin acetate in preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched for any randomised controlled trials in a registry of ongoing trials and the reference lists of relevant articles and reviews.Date of most recent search: 18 June 2015. Randomised and quasi-randomised controlled trials investigating the efficacy of desmopressin acetate versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. The review did not identify any randomised controlled trials investigating the relative effectiveness of desmopressin acetate for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with desmopressin acetate.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using desmopressin acetate in this population are needed.

Desmopressin acetate (DDAVP) for preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders.

PubMed

Karanth, Laxminarayan; Barua, Ankur; Kanagasabai, Sachchithanantham; Nair, N S

2013-04-30

Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of desmopressin acetate in these groups of pregnant women should be evaluated. To determine the efficacy of desmopressin acetate in preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched for any randomised controlled trials in a registry of ongoing trials and the reference lists of relevant articles and reviews.Date of most recent search: 28 February 2013. Randomised and quasi-randomised controlled trials investigating the efficacy of desmopressin acetate versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. The review did not identify any randomised controlled trials investigating the relative effectiveness of desmopressin acetate for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with desmopressin acetate.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using desmopressin acetate in this population are needed.

Can a documentary increase help-seeking intentions in men? A randomised controlled trial.

PubMed

King, Kylie Elizabeth; Schlichthorst, Marisa; Spittal, Matthew J; Phelps, Andrea; Pirkis, Jane

2018-01-01

We investigated whether a public health intervention-a three-part documentary called Man Up which explored the relationship between masculinity and mental health, well-being and suicidality-could increase men's intentions to seek help for personal and emotional problems. We recruited men aged 18 years or over who were not at risk of suicide to participate in a double-blind randomised controlled trial. Participants were randomly assigned (1:1) via computer randomisation to view Man Up (the intervention) or a control documentary. We hypothesised that 4 weeks after viewing Man Up participants would report higher levels of intention to seek help than those who viewed the control documentary. Our primary outcome was assessed using the General Help Seeking Questionnaire, and was analysed for all participants. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616001169437, Universal Trial Number: U1111-1186-1459) and was funded by the Movember Foundation. Three hundred and fifty-four men were assessed for eligibility for the trial and randomised to view Man Up or the control documentary. Of these, 337 completed all stages (nine participants were lost to follow-up in the intervention group and eight in the control group). Linear regression analysis showed a significant increase in intentions to seek help in the intervention group, but not in the control group (coef.=2.06, 95% CI 0.48 to 3.63, P=0.01). Our trial demonstrates the potential for men's health outcomes to be positively impacted by novel, media-based public health interventions that focus on traditional masculinity. ACTRN12616001169437, Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Population screening for osteoporosis risk: a randomised control trial of medication use and fracture risk.

PubMed

Barr, R J; Stewart, A; Torgerson, D J; Reid, D M

2010-04-01

Randomised control trial of osteoporosis screening in 4,800 women aged 45-54 years was carried out. Screened group observed an increase of 7.9% in hormone replacement therapy (HRT) use (p < 0.001), 15% in other osteoporosis treatments (p < 0.001) and a 25.9% reduction in fracture risk compared with control. Screening for osteoporosis significantly increases treatment use and reduces fracture incidence. Population screening programmes can identify menopausal women with low bone mineral density (BMD) and elevated risk of future fracture but require to be proven effective by a randomised control trial. A total of 4,800 women, 45-54 years, were randomised in equal numbers to screening or no screening (control) groups. Following screening, those in the lowest quartile of BMD were advised to consider HRT. Nine years later, the effect of screening on the uptake of treatment and the incidence of fractures were assessed by postal questionnaire. Categorical differences were assessed using chi(2) test. Cox regression was used to assess hazard ratio (HR). Of the screened and the control groups, 52.4% vs 44.5%, respectively, reported taking HRT (p < 0.001). In addition, 36.6% of the screened vs 21.6% of the control groups reported the use of vitamin D, calcium, alendronate, etidronate or raloxifene (p < 0.001). In a per protocol analysis of verified incident fractures, a 25.9% reduction in risk of fractures (of any site) in the screened group was observed (HR = 0.741, 95% CI = 0.551-0.998 adjusted age, weight and height). Screening for osteoporosis as assessed by low bone density significantly increases the use of HRT and other treatments for osteoporosis and reduces fracture incidence.

Can a documentary increase help-seeking intentions in men? A randomised controlled trial

PubMed Central

Schlichthorst, Marisa; Spittal, Matthew J; Phelps, Andrea; Pirkis, Jane

2018-01-01

Background We investigated whether a public health intervention—a three-part documentary called Man Up which explored the relationship between masculinity and mental health, well-being and suicidality—could increase men’s intentions to seek help for personal and emotional problems. Methods We recruited men aged 18 years or over who were not at risk of suicide to participate in a double-blind randomised controlled trial. Participants were randomly assigned (1:1) via computer randomisation to view Man Up (the intervention) or a control documentary. We hypothesised that 4 weeks after viewing Man Up participants would report higher levels of intention to seek help than those who viewed the control documentary. Our primary outcome was assessed using the General Help Seeking Questionnaire, and was analysed for all participants. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616001169437, Universal Trial Number: U1111-1186-1459) and was funded by the Movember Foundation. Results Three hundred and fifty-four men were assessed for eligibility for the trial and randomised to view Man Up or the control documentary. Of these, 337 completed all stages (nine participants were lost to follow-up in the intervention group and eight in the control group). Linear regression analysis showed a significant increase in intentions to seek help in the intervention group, but not in the control group (coef.=2.06, 95% CI 0.48 to 3.63, P=0.01). Conclusions Our trial demonstrates the potential for men’s health outcomes to be positively impacted by novel, media-based public health interventions that focus on traditional masculinity. Trial registration number ACTRN12616001169437, Results. PMID:29101215

Positive effect of removal of subchondral bone plate for cemented acetabular component fixation in total hip arthroplasty: a randomised RSA study with ten-year follow-up.

PubMed

Flivik, G; Kristiansson, I; Ryd, L

2015-01-01

We hypothesised that the removal of the subchondral bone plate (SCBP) for cemented acetabular component fixation in total hip arthroplasty (THA) offers advantages over retention by improving the cement-bone interface, without jeopardising implant stability. We have previously published two-year follow-up data of a randomised controlled trial (RCT), in which 50 patients with primary osteoarthritis were randomised to either retention or removal of the SCBP. The mean age of the retention group (n = 25, 13 males) was 70.0 years (sd 6.8). The mean age in the removal group (n = 25, 16 males) was 70.3 years (sd 7.9). Now we have followed up the patients at six (retention group, n = 21; removal group, n = 20) and ten years (retention group: n = 17, removal group: n = 18), administering clinical outcome questionnaires and radiostereometric analysis (RSA), and determining the presence of radiolucent lines (RLLs) on conventional radiographs. RSA demonstrated similar translation and rotation patterns up to six years. Between six and ten years, proximal acetabular component migration and changes of inclination were larger in the retention group, although the mean differences did not reach statistical significance. Differences in migration were driven by two patients in the SCBP retention group with extensive migration versus none in the SCBP removal group. The significant difference (p < 0.001) in the development of radiolucent lines in the retention group, previously observed at two years, increased even further during the course of follow-up (p < 0.001). While recognising SCBP removal is a more demanding technique, we conclude that, wherever possible, the SCBP should be removed to improve the cement-bone interface in order to maximise acetabular component stability and longevity. ©2015 The British Editorial Society of Bone & Joint Surgery.

Enzyme potentiated desensitisation in treatment of seasonal allergic rhinitis: double blind randomised controlled study.

PubMed

Radcliffe, Michael J; Lewith, George T; Turner, Richard G; Prescott, Philip; Church, Martin K; Holgate, Stephen T

2003-08-02

To assess the efficacy of enzyme potentiated desensitisation in the treatment of severe summer hay fever poorly controlled by pharmacotherapy. Double blind randomised placebo controlled parallel group study. Hospital in Hampshire. 183 participants aged between 18 and 64 with a history of severe summer hay fever for at least two years; all were skin prick test positive to timothy grass pollen. 90 randomised to active treatment; 93 randomised to placebo. Active treatment: two injections of enzyme potentiated desensitisation, given between eight and 11 weeks apart, each comprising 200 Fishman units of beta glucuronidase, 50 pg 1,3-cyclohexanediol, 50 ng protamine sulphate, and a mixed inhaled allergen extract (pollen mixes for trees, grasses, and weeds; allergenic fungal spores; cat and dog danders; dust and storage mites) in a total volume of 0.05 ml of buffered saline. Placebo: two injections of 0.05 ml buffered saline solution. Proportion of problem-free days; global rhinoconjunctivitis quality of life scores assessed weekly during pollen season. The active treatment group and the placebo group did not differ in the proportion of problem-free days, quality of life scores, symptom severity scores, change in quantitative skin prick provocation threshold, or change in conjunctival provocation threshold. No clinically significant adverse reactions occurred. Enzyme potentiated desensitisation showed no treatment effect in this study.

Group Therapy for Anxiety in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

McConachie, Helen; McLaughlin, Eleanor; Grahame, Victoria; Taylor, Helen; Honey, Emma; Tavernor, Laura; Rodgers, Jacqui; Freeston, Mark; Hemm, Cahley; Steen, Nick; Le Couteur, Ann

2014-01-01

Aim: To investigate the acceptability and feasibility of adapted group therapy for anxiety in children with autism spectrum disorder in a pilot randomised controlled trial. Method: A total of 32 children aged 9-13 years were randomised to immediate or delayed therapy using the "Exploring Feelings" manual (Attwood, 2004). Child and parent…

History and present status of pulmonary metastasectomy in colorectal cancer.

PubMed

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

2014-10-28

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

PATCH: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial.

PubMed

de Gans, Koen; de Haan, Rob J; Majoie, Charles B; Koopman, Maria M; Brand, Anneke; Dijkgraaf, Marcel G; Vermeulen, Marinus; Roos, Yvo B

2010-03-18

Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect. The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included. To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease.

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

PubMed

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

2013-05-29

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

Can social dancing prevent falls in older adults? a protocol of the Dance, Aging, Cognition, Economics (DAnCE) fall prevention randomised controlled trial

PubMed Central

2013-01-01

Background Falls are one of the most common health problems among older people and pose a major economic burden on health care systems. Exercise is an accepted stand-alone fall prevention strategy particularly if it is balance training or regular participation in Tai chi. Dance shares the ‘holistic’ approach of practices such as Tai chi. It is a complex sensorimotor rhythmic activity integrating multiple physical, cognitive and social elements. Small-scale randomised controlled trials have indicated that diverse dance styles can improve measures of balance and mobility in older people, but none of these studies has examined the effect of dance on falls or cognition. This study aims to determine whether participation in social dancing: i) reduces the number of falls; and ii) improves cognitive functions associated with fall risk in older people. Methods/design A single-blind, cluster randomised controlled trial of 12 months duration will be conducted. Approximately 450 participants will be recruited from 24 self-care retirement villages that house at least 60 residents each in Sydney, Australia. Village residents without cognitive impairment and obtain medical clearance will be eligible. After comprehensive baseline measurements including physiological and cognitive tests and self-completed questionnaires, villages will be randomised to intervention sites (ballroom or folk dance) or to a wait-listed control using a computer randomisation method that minimises imbalances between villages based on two baseline fall risk measures. Main outcome measures are falls, prospectively measured, and the Trail Making cognitive function test. Cost-effectiveness and cost-utility analyses will be performed. Discussion This study offers a novel approach to balance training for older people. As a community-based approach to fall prevention, dance offers older people an opportunity for greater social engagement, thereby making a major contribution to healthy ageing. Providing diversity in exercise programs targeting seniors recognises the heterogeneity of multicultural populations and may further increase the number of taking part in exercise. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12612000889853 The trial is now in progress with 12 villages already have been randomised. PMID:23675705

Can social dancing prevent falls in older adults? a protocol of the Dance, Aging, Cognition, Economics (DAnCE) fall prevention randomised controlled trial.

PubMed

Merom, Dafna; Cumming, Robert; Mathieu, Erin; Anstey, Kaarin J; Rissel, Chris; Simpson, Judy M; Morton, Rachael L; Cerin, Ester; Sherrington, Catherine; Lord, Stephen R

2013-05-15

Falls are one of the most common health problems among older people and pose a major economic burden on health care systems. Exercise is an accepted stand-alone fall prevention strategy particularly if it is balance training or regular participation in Tai chi. Dance shares the 'holistic' approach of practices such as Tai chi. It is a complex sensorimotor rhythmic activity integrating multiple physical, cognitive and social elements. Small-scale randomised controlled trials have indicated that diverse dance styles can improve measures of balance and mobility in older people, but none of these studies has examined the effect of dance on falls or cognition. This study aims to determine whether participation in social dancing: i) reduces the number of falls; and ii) improves cognitive functions associated with fall risk in older people. A single-blind, cluster randomised controlled trial of 12 months duration will be conducted. Approximately 450 participants will be recruited from 24 self-care retirement villages that house at least 60 residents each in Sydney, Australia. Village residents without cognitive impairment and obtain medical clearance will be eligible. After comprehensive baseline measurements including physiological and cognitive tests and self-completed questionnaires, villages will be randomised to intervention sites (ballroom or folk dance) or to a wait-listed control using a computer randomisation method that minimises imbalances between villages based on two baseline fall risk measures. Main outcome measures are falls, prospectively measured, and the Trail Making cognitive function test. Cost-effectiveness and cost-utility analyses will be performed. This study offers a novel approach to balance training for older people. As a community-based approach to fall prevention, dance offers older people an opportunity for greater social engagement, thereby making a major contribution to healthy ageing. Providing diversity in exercise programs targeting seniors recognises the heterogeneity of multicultural populations and may further increase the number of taking part in exercise. Australian New Zealand Clinical Trials Registry ACTRN12612000889853The trial is now in progress with 12 villages already have been randomised.

Screening and brief interventions for hazardous and harmful alcohol use in probation services: a cluster randomised controlled trial protocol

PubMed Central

2009-01-01

Background A large number of randomised controlled trials in health settings have consistently reported positive effects of brief intervention in terms of reductions in alcohol use. However, although alcohol misuse is common amongst offenders, there is limited evidence of alcohol brief interventions in the criminal justice field. This factorial pragmatic cluster randomised controlled trial with Offender Managers (OMs) as the unit of randomisation will evaluate the effectiveness and cost-effectiveness of different models of screening to identify hazardous and harmful drinkers in probation and different intensities of brief intervention to reduce excessive drinking in probation clients. Methods and design Ninety-six OMs from 9 probation areas across 3 English regions (the North East Region (n = 4) and London and the South East Regions (n = 5)) will be recruited. OMs will be randomly allocated to one of three intervention conditions: a client information leaflet control condition (n = 32 OMs); 5-minute simple structured advice (n = 32 OMs) and 20-minute brief lifestyle counselling delivered by an Alcohol Health Worker (n = 32 OMs). Randomisation will be stratified by probation area. To test the relative effectiveness of different screening methods all OMs will be randomised to either the Modified Single Item Screening Questionnaire (M-SASQ) or the Fast Alcohol Screening Test (FAST). There will be a minimum of 480 clients recruited into the trial. There will be an intention to treat analysis of study outcomes at 6 and 12 months post intervention. Analysis will include client measures (screening result, weekly alcohol consumption, alcohol-related problems, re-offending, public service use and quality of life) and implementation measures from OMs (the extent of screening and brief intervention beyond the minimum recruitment threshold will provide data on acceptability and feasibility of different models of brief intervention). We will also examine the practitioner and organisational factors associated with successful implementation. Discussion The trial will evaluate the impact of screening and brief alcohol intervention in routine probation work and therefore its findings will be highly relevant to probation teams and thus the criminal justice system in the UK. Ethical approval was given by Northern & Yorkshire REC Trial Registration number ISRCTN 19160244 PMID:19922618

Screening and brief interventions for hazardous and harmful alcohol use in probation services: a cluster randomised controlled trial protocol.

PubMed

Newbury-Birch, Dorothy; Bland, Martin; Cassidy, Paul; Coulton, Simon; Deluca, Paolo; Drummond, Colin; Gilvarry, Eilish; Godfrey, Christine; Heather, Nick; Kaner, Eileen; Myles, Judy; Oyefeso, Adenekan; Parrott, Steve; Perryman, Katherine; Phillips, Tom; Shenker, Don; Shepherd, Jonathan

2009-11-18

A large number of randomised controlled trials in health settings have consistently reported positive effects of brief intervention in terms of reductions in alcohol use. However, although alcohol misuse is common amongst offenders, there is limited evidence of alcohol brief interventions in the criminal justice field. This factorial pragmatic cluster randomised controlled trial with Offender Managers (OMs) as the unit of randomisation will evaluate the effectiveness and cost-effectiveness of different models of screening to identify hazardous and harmful drinkers in probation and different intensities of brief intervention to reduce excessive drinking in probation clients. Ninety-six OMs from 9 probation areas across 3 English regions (the North East Region (n = 4) and London and the South East Regions (n = 5)) will be recruited. OMs will be randomly allocated to one of three intervention conditions: a client information leaflet control condition (n = 32 OMs); 5-minute simple structured advice (n = 32 OMs) and 20-minute brief lifestyle counselling delivered by an Alcohol Health Worker (n = 32 OMs). Randomisation will be stratified by probation area. To test the relative effectiveness of different screening methods all OMs will be randomised to either the Modified Single Item Screening Questionnaire (M-SASQ) or the Fast Alcohol Screening Test (FAST). There will be a minimum of 480 clients recruited into the trial. There will be an intention to treat analysis of study outcomes at 6 and 12 months post intervention. Analysis will include client measures (screening result, weekly alcohol consumption, alcohol-related problems, re-offending, public service use and quality of life) and implementation measures from OMs (the extent of screening and brief intervention beyond the minimum recruitment threshold will provide data on acceptability and feasibility of different models of brief intervention). We will also examine the practitioner and organisational factors associated with successful implementation. The trial will evaluate the impact of screening and brief alcohol intervention in routine probation work and therefore its findings will be highly relevant to probation teams and thus the criminal justice system in the UK.Ethical approval was given by Northern & Yorkshire REC. ISRCTN 19160244.

A pilot randomised double blind controlled trial of the efficacy of purified fatty acids for the treatment of women with endometriosis-associated pain (PurFECT): study protocol.

PubMed

Abokhrais, Ibtisam M; Saunders, Philippa T K; Denison, Fiona C; Doust, Ann; Williams, Linda; Horne, Andrew W

2018-01-01

Endometriosis affects 6-10% of women and is associated with debilitating pelvic pain. It costs the UK > £2.8 billion per year in loss of productivity. Endometriosis can be managed by surgical excision or medically by ovarian suppression. However, ~ 75% symptoms recur after surgery and available medical treatments have undesirable side effects and are contraceptive. Omega-3 purified fatty acids (PUFA) have been shown in animal models to reduce factors that are thought to lead to endometriosis-associated pain, have minimal side effects, and no effects on fertility. This paper presents a protocol for a two-arm, pilot parallel randomised controlled trial (RCT) which aims to inform the planning of a future multicentre trial to evaluate the efficacy of Omega-3 PUFA in the management of endometriosis-associated pain in women. The study will recruit women with endometriosis over a 12-month period in the National Health Service (NHS) Lothian, UK, and randomise them to 8 weeks of treatment with Omega-3 PUFA or comparator (olive oil). The primary objective is to assess recruitment and retention rates. The secondary objectives are to determine the effectiveness/acceptability to participants of the proposed methods of recruitment/randomisation/treatments/questionnaires, to inform the sample size calculation and to refine the research methodology for a future large randomised controlled trial. Response to treatment will be monitored by pain scores and questionnaires assessing physical and emotional function compared at baseline and 8 weeks. We recognise that there may be potential difficulties in mounting a large randomised controlled trial for endometriosis to assess Omega-3 PUFA because they are a dietary supplement readily available over the counter and already used by women with endometriosis. We have therefore designed this pilot study to assess practical feasibility and following the 'Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials' recommendations for the design of chronic pain trials. ISRCTN44202346.

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

PubMed Central

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

2012-01-01

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

How should COPD patients exercise during respiratory rehabilitation? Comparison of exercise modalities and intensities to treat skeletal muscle dysfunction

PubMed Central

Puhan, M; Schunemann, H; Frey, M; Scharplatz, M; Bachmann, L

2005-01-01

Background: Physical exercise is an important component of respiratory rehabilitation because it reverses skeletal muscle dysfunction, a clinically important manifestation of COPD associated with reduced health-related quality of life (HRQL) and survival. However, there is controversy regarding the components of the optimal exercise protocol. A study was undertaken to systematically evaluate and summarise randomised controlled trials (RCTs) comparing different exercise protocols for COPD patients. Methods: Six electronic databases, congress proceedings and bibliographies of included studies were searched without imposing language restrictions. Two reviewers independently screened all records and extracted data on study samples, interventions and methodological characteristics of included studies. Results: The methodological quality of the 15 included RCTs was low to moderate. Strength exercise led to larger improvements of HRQL than endurance exercise (weighted mean difference for Chronic Respiratory Questionnaire 0.27, 95% CI 0.02 to 0.52). Interval exercise seems to be of similar effectiveness as continuous exercise, but there are few data on clinically relevant outcomes. One small RCT which included patients with mild COPD compared the effect of high and low intensity exercise (at 80% and 40% of the maximum exercise capacity, respectively) and found larger physiological training effects from high intensity exercise. Conclusions: Strength exercise should be routinely incorporated in respiratory rehabilitation. There is insufficient evidence to recommend high intensity exercise for COPD patients and investigators should conduct larger high quality trials to evaluate exercise intensities in patients with moderate to severe COPD. PMID:15860711

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.

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.

Comparison between the use of an ultrasonic tip and a microhead handpiece in periradicular surgery: a prospective randomised trial.

PubMed

Shearer, Jane; McManners, Joseph

2009-07-01

Innovations in periradicular surgery for failed treatment of orthograde root canal disease have been well-documented. We know of no prospective studies that have compared success rates of conventional methods with these presumed advances. In this prospective randomised trial we compare the use of an ultrasonic retrotip with a microhead bur in the preparation of a retrograde cavity. Outcome was estimated clinically by estimation of pain, swelling, and sinus, and radiographically by looking at infill of bone and retrograde root filling 2 weeks and 6 months postoperatively. Both methods used other surgical techniques including microinstruments to place the retrograde root filling. The success rate of the ultrasonic method was higher (all patients, n=26) than that of the microhead method (n=19 of 21). A larger study with longer follow up is required to consolidate this evidence.

A cost analysis of inpatient compared with outpatient prostaglandin E2 cervical priming for induction of labour: results from the OPRA trial.

PubMed

Adelson, Pamela L; Wedlock, Garry R; Wilkinson, Chris S; Howard, Kirsten; Bryce, Robert L; Turnbull, Deborah A

2013-09-01

To compare the costs of inpatient (usual care) with outpatient (intervention) care for cervical priming for induction of labour in women with healthy, low-risk pregnancies who are being induced for prolonged pregnancies or for social reasons. Data from a randomised controlled trial at two hospitals in South Australia were matched with hospital financial data. A cost analysis comparing women randomised to inpatient care with those randomised to outpatient care was performed, with an additional analysis focusing on those who received the intervention. Overall, 48% of women randomised into the trial did not receive the intervention. Women randomised to outpatient care had an overall cost saving of $319 per woman (95% CI -$104 to $742) as compared with women randomised to usual care. When restricted to women who actually received the intervention, in-hospital cost savings of $433 (95% CI -$282 to $1148) were demonstrated in the outpatient group. However, these savings were partially offset by the cost of an outpatient priming clinic, reducing the overall cost savings to $156 per woman. Overall cost savings were not statistically significant in women who were randomised to or received the intervention. However, the trend in cost savings favoured outpatient priming.

Mendelian randomisation in cardiovascular research: an introduction for clinicians

PubMed Central

Bennett, Derrick A; Holmes, Michael V

2017-01-01

Understanding the causal role of biomarkers in cardiovascular and other diseases is crucial in order to find effective approaches (including pharmacological therapies) for disease treatment and prevention. Classical observational studies provide naïve estimates of the likely role of biomarkers in disease development; however, such studies are prone to bias. This has direct relevance for drug development as if drug targets track to non-causal biomarkers, this can lead to expensive failure of these drugs in phase III randomised controlled trials. In an effort to provide a more reliable indication of the likely causal role of a biomarker in the development of disease, Mendelian randomisation studies are increasingly used, and this is facilitated by the availability of large-scale genetic data. We conducted a narrative review in order to provide a description of the utility of Mendelian randomisation for clinicians engaged in cardiovascular research. We describe the rationale and provide a basic description of the methods and potential limitations of Mendelian randomisation. We give examples from the literature where Mendelian randomisation has provided pivotal information for drug discovery including predicting efficacy, informing on target-mediated adverse effects and providing potential new evidence for drug repurposing. The variety of the examples presented illustrates the importance of Mendelian randomisation in order to prioritise drug targets for cardiovascular research. PMID:28596306

Reducing electronic media use in 2-3 year-old children: feasibility and efficacy of the Family@play pilot randomised controlled trial.

PubMed

Hinkley, Trina; Cliff, Dylan P; Okely, Anthony D

2015-08-14

Participation in electronic media use among 2-3 year olds is high and associated with adverse health and developmental outcomes. This study sought to test the feasibility and potential efficacy of a family-based program to decrease electronic media (EM) use in 2-3-year-old children. Family@play was a six-session pilot randomised controlled trial delivered to parents of 2-3 year-old children from August to September 2012 in a community environment in the Illawarra region of New South Wales, Australia. Development of program content was guided by Social Cognitive and Family Systems Theories. The primary outcome was children's electronic media use. Secondary outcomes included children's time in sitting, standing and stepping. Data collectors were blinded to group allocation. Parents completed comprehensive process evaluation measures and participated in focus group discussions following completion of the program. Regression analyses were undertaken and effect sizes calculated using principles of intention to treat. Twenty-two participants (n = 12 intervention; n = 10 control) provided complete baseline data; complete data from 16 participants (n = 6 intervention; n = 10 control) were available post-intervention. Process evaluation results were high, showing the acceptability of the program. Compared with children in the control group, there were greater decreases in total EM use among children in the intervention group (adjusted difference [95 % CI] = -31.2 mins/day [-71.0-8.6] Cohen's d = 0.70). Differences for other outcomes were in the hypothesised direction and ranged from small for postural (sitting, standing, stepping) outcomes to moderate to large for individual electronic media (e.g. TV viewing, DVD/video viewing). This is the first family-based study to engage families of 2-3 year old children outside the United States and target multiple EM behaviours. Family@play was shown to be a feasible and acceptable intervention to deliver to families of 2-3 year old children. Potential efficacy is evident from moderate to large effect sizes. A larger trial is warranted to test the efficacy of the program. Australian New Zealand Clinical Trials Registry ( ACTRN12612000470897 ).

Systematic review of randomised controlled trials of the effects of caffeine or caffeinated drinks on blood glucose concentrations and insulin sensitivity in people with diabetes mellitus.

PubMed

Whitehead, N; White, H

2013-04-01

Compounds other than macronutrients have been shown to influence blood glucose concentrations and insulin sensitivity in people with diabetes, with caffeine being one such substance. The present study systematically reviewed the evidence of the effects of caffeine on blood glucose concentrations and/or insulin sensitivity in people with diabetes. Four databases, including MEDLINE and EMBASE, were searched up to 1 February 2012. Randomised controlled trials (RCTs) investigating the effects of caffeine on blood glucose and/or insulin sensitivity in humans, diagnosed with type I, type II or gestational diabetes mellitus (GDM), were included. Quality assessment and data extraction were conducted and agreed by both authors. Of 253 articles retrieved, nine trials (134 participants) were identified. Trials in people with type II diabetes demonstrated that the ingestion of caffeine (approximately 200-500 mg) significantly increased blood glucose concentrations by 16-28% of the area under the curve (AUC) and insulin concentrations by 19-48% of the AUC when taken prior to a glucose load, at the same time as decreasing insulin sensitivity by 14-37%. In type I diabetes, trials indicated enhanced recognition and a reduced duration of hypoglycaemic episodes following ingestion of 400-500 mg caffeine, without altering glycated haemoglobin. In GDM, a single trial demonstrated that approximately 200 mg of caffeine induced a decrease in insulin sensitivity by 18% and a subsequent increase in blood glucose concentrations by 19% of the AUC. Evidence indicates a negative effect of caffeine intake on blood glucose control in individuals with type II diabetes, as replicated in a single trial in GDM. Larger-scale RCTs of longer duration are needed to determine the effects of timing and dose. Early indications of a reduced duration and an improved awareness of hypoglycaemia in type I diabetes require further confirmation. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

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

PubMed

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

2010-09-10

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

A preliminary study of the effect of closed incision management with negative pressure wound therapy over high-risk incisions.

PubMed

Perry, Karen L; Rutherford, Lynda; Sajik, David M R; Bruce, Mieghan

2015-11-09

Certain postoperative wounds are recognised to be associated with more complications than others and may be termed high-risk. Wound healing can be particularly challenging following high-energy trauma where wound necrosis and infection rates are high. Surgical incision for joint arthrodesis can also be considered high-risk as it requires extensive and invasive surgery and postoperative distal limb swelling and wound dehiscence are common. Recent human literature has investigated the use of negative pressure wound therapy (NPWT) over high-risk closed surgical incisions and beneficial effects have been noted including decreased drainage, decreased dehiscence and decreased infection rates. In a randomised, controlled study twenty cases undergoing distal limb high-energy fracture stabilisation or arthrodesis were randomised to NPWT or control groups. All cases had a modified Robert-Jones dressing applied for 72 h postoperatively and NPWT was applied for 24 h in the NPWT group. Morphometric assessment of limb circumference was performed at six sites preoperatively, 24 and 72 h postoperatively. Wound discharge was assessed at 24 and 72 h. Postoperative analgesia protocol was standardised and a Glasgow Composite Measure Pain Score (GCPS) carried out at 24, 48 and 72 h. Complications were noted and differences between groups were assessed. Percentage change in limb circumference between preoperative and 24 and 72 h postoperative measurements was significantly less at all sites for the NPWT group with exception of the joint proximal to the surgical site and the centre of the operated bone at 72 h. Median discharge score was lower in the NPWT group than the control group at 24 h. No significant differences in GCPS or complication rates were noted. Digital swelling and wound discharge were reduced when NPWT was employed for closed incision management. Larger studies are required to evaluate whether this will result in reduced discomfort and complication rates postoperatively.

Antipsychotic medications for the treatment of delirium: a systematic review and meta-analysis of randomised controlled trials.

PubMed

Kishi, Taro; Hirota, Tomoya; Matsunaga, Shinji; Iwata, Nakao

2016-07-01

We performed an updated meta-analysis of antipsychotic treatment in patients with delirium, based on a previous meta-analysis published in 2007. Included in this study were randomised, placebo-controlled or usual care (UC) controlled trials of antipsychotics in adult patients with delirium. Our primary outcome measure was response rate at the study end point. The secondary outcome measures included improvement of severity of delirium, Clinical Global Impression-Severity Scale (CGI-S), time to response (TTR), discontinuation rate and individual adverse effects. The risk ratio (RR), the number-needed-to-treat/harm (NNT/NNH), 95% CIs and standardised mean difference (SMD), were calculated. We identified 15 studies (mean duration: 9.8 days) for the systematic review (total n=949, amisulpride=20, aripiprazole=8, chlorpromazine=13, haloperidol=316, intramuscular olanzapine or haloperidol injection=62, olanzapine=144, placebo=75, quetiapine=125, risperidone=124, UC=30 and ziprasidone=32), 4 of which were conference abstracts and unpublished. When pooled as a group, antipsychotics were superior to placebo/UC in terms of response rate (RR=0.22, NNT=2), delirium severity scales scores (SMD=-1.27), CGI-S scores (SMD=-1.57) and TTR (SMD=-1.22). The pooled antipsychotic group was associated with a higher incidence of dry mouth (RR=13.0, NNH=5) and sedation (RR=4.59, NNH=5) compared with placebo/UC. Pooled second-generation antipsychotics (SGAs) were associated with shorter TTR (SMD=-0.27) and a lower incidence of extrapyramidal symptoms (RR=0.31, NNH=7) compared with haloperidol. Our results suggested that SGAs have a benefit for the treatment of delirium with regard to efficacy and safety compared with haloperidol. However, further study using larger samples is required. 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/

Effectiveness of Educational Poster on Knowledge of Emergency Management of Dental Trauma - Part 2: Cluster Randomised Controlled Trial for Secondary School Students

PubMed Central

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

2014-01-01

Objective To investigate the effectiveness of educational poster on improving secondary school students' knowledge of emergency management of dental trauma. Methods A cluster randomised controlled trial was conducted. 16 schools with total 671 secondary students who can read Chinese or English were randomised into intervention (poster, 8 schools, 364 students) and control groups (8 schools, 305 students) at the school level. Baseline knowledge of dental trauma was obtained by a questionnaire. Poster containing information of dental trauma management was displayed in a classroom for 2 weeks in each school in the intervention group whereas in the control group there was no display of such posters. Students of both groups completed the same questionnarie after 2 weeks. Results Two-week display of posters improved the knowledge score by 1.25 (p-value = 0.0407) on average. Conclusion Educational poster on dental trauma management significantly improved the level of knowledge of secondary school students in Hong Kong. Trial Registration HKClinicalTrial.com HKCTR-1343 ClinicalTrials.gov NCT01809457 PMID:25093728

Feasibility of high-intensity interval training and moderate-intensity continuous training in adults with inactive or mildly active Crohn's disease: study protocol for a randomised controlled trial.

PubMed

Tew, Garry A; Carpenter, Roger; Seed, Michael; Anderson, Simon; Langmead, Louise; Fairhurst, Caroline; Bottoms, Lindsay

2017-01-01

Structured exercise training has been proposed as a useful adjunctive therapy for Crohn's disease by improving immune function and psychological health, reducing fatigue and promoting gains in muscle and bone strength. However, the evidence for exercise in Crohn's disease is sparse, with only a handful of small prospective trials [1, 2], with methodological limitations, including the use of non-randomised and non-controlled study designs and small sample sizes. Here, we describe the protocol for a study that aims to assess the feasibility and acceptability of two common types of exercise training-high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT)-in adults with inactive or mildly active Crohn's disease (CD). This is a randomised, controlled, assessor-blinded, feasibility trial with three parallel groups. Forty-five adults with inactive or mildly active Crohn's disease will be randomly assigned 1:1:1 to HIIT, MICT or usual care control. Participants in the HIIT and MICT groups will be invited to undertake three sessions of supervised exercise each week for 12 consecutive weeks. HIIT sessions will consist of ten 1-min intervals of cycling exercise at 90% of peak power output separated by 1 min of active recovery. MICT sessions will involve 30 min of continuous cycling at 35% of peak power output. Participants will be assessed before randomisation and 13 and 26 weeks after randomisation. Feasibility outcomes include rates of recruitment, retention and adherence. Interviews with participants will explore the acceptability of the exercise programmes and study procedures. Clinical/health outcomes include cardiorespiratory fitness, body mass index, resting blood pressure, markers of disease activity (faecal calprotectin and Crohn's Disease Activity Index) and activated T cell cytokine profiles. Study questionnaires include the Inflammatory Bowel Disease Quality of Life Questionnaire, EQ-5D-5L, IBD Fatigue Scale, Hospital and Anxiety Depression Scale, and International Physical Activity Questionnaire. This study will provide useful information on the feasibility and acceptability of supervised exercise training in adults with inactive and mildly active Crohn's disease and will inform the design of a subsequent, adequately powered, multi-centre trial. The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN13021107). Date registration assigned was 02/12/2015.

The use of pH adjusted lignocaine in controlling operative pain in the day surgery unit: a prospective, randomised trial.

PubMed

Fitton, A R; Ragbir, M; Milling, M A

1996-09-01

We report the results of a randomised, case matched, controlled, double blind study on 40 patients undergoing correction of their prominent ears, comparing efficacy of pH adjusted lignocaine to lignocaine alone in controlling operative pain. Each patient received commercial lignocaine in one ear and the same preparation reconstituted with 1 ml of 8.4% sodium bicarbonate in the other ear according to our randomisation protocol. 30 patients were studied to compare the difference between the buffered and commercial preparation infiltrated at room temperature. A further 10 patients were studied to assess the benefit the buffered preparation at room temperature had over commercial lignocaine warmed to body temperature. Linear analogue pain scores for discomfort at infiltration and during the operation itself were analysed. Buffered lignocaine imparts a significant reduction in pain on infiltration, compared to the commercial preparation at both room and body temperature. Both preparations were equally effective in obliterating pain during the operation itself.

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

PubMed

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

2018-06-11

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

GET.ON Mood Enhancer: efficacy of Internet-based guided self-help compared to psychoeducation for depression: an investigator-blinded randomised controlled trial

PubMed Central

2014-01-01

Background Major depressive disorder (MDD) imposes a considerable disease burden on individuals and societies. A large number of randomised controlled trials (RCTs) have shown the efficacy of Internet-based guided self-help interventions in reducing symptoms of depression. However, study quality varies considerably. The aim of this study is to evaluate the efficacy of a new Internet-based guided self-help intervention (GET.ON Mood Enhancer) compared to online-based psychoeducation in an investigator-blinded RCT. Methods/design A RCT will be conducted to compare the efficacy of GET.ON Mood Enhancer with an active control condition receiving online psychoeducation on depression (OPD). Both treatment groups will have full access to treatment as usual. Adults with MDD (n = 128) will be recruited and randomised to one of the two conditions. Primary outcome will be observer-rated depressive symptoms (HRSD-24) by independent assessors blind to treatment conditions. Secondary outcomes include changes in self-reported depressive symptom severity, anxiety and quality of life. Additionally, potential negative effects of the treatments will systematically be evaluated on several dimensions (for example, symptom deteriorations, attitudes toward seeking psychological help, relationships and stigmatisation). Assessments will take place at baseline, 6 and 12 weeks after randomisation. Discussion This study evaluates a new Internet-based guided self-help intervention for depression using an active control condition (psychoeducation-control) and an independent, blinded outcome evaluation. This study will further enhance the evidence for Internet-based guided self-help interventions for MDD. Trial registration German Clinical Trial Registration (DRKS): DRKS00005025 PMID:24476555

Interventions for oropharyngeal dysphagia in children with neurological impairment.

PubMed

Morgan, Angela T; Dodrill, Pamela; Ward, Elizabeth C

2012-10-17

Oropharyngeal dysphagia encompasses problems with the oral preparatory phase of swallowing (chewing and preparing the food), oral phase (moving the food or fluid posteriorly through the oral cavity with the tongue into the back of the throat) and pharyngeal phase (swallowing the food or fluid and moving it through the pharynx to the oesophagus). Populations of children with neurological impairment who commonly experience dysphagia include, but are not limited to, those with acquired brain impairment (for example, cerebral palsy, traumatic brain injury, stroke), genetic syndromes (for example, Down syndrome, Rett syndrome) and degenerative conditions (for example, myotonic dystrophy). To examine the effectiveness of interventions for oropharyngeal dysphagia in children with neurological impairment. We searched the following electronic databases in October 2011: CENTRAL 2011(3), MEDLINE (1948 to September Week 4 2011), EMBASE (1980 to 2011 Week 40)
, CINAHL (1937 to current)
, ERIC (1966 to current), PsycINFO (1806 to October Week 1 2011), Science Citation Index (1970 to 7 October 2011), Social Science Citation Index (1970 to 7 October 2011), Cochrane Database of Systematic Reviews, 2011(3), DARE 2011(3), Current Controlled Trials (ISRCTN Register) (15 October 2011), ClinicalTrials.gov (15 October 2011) and WHO ICTRP (15 October 2011). We searched for dissertations and theses using Networked Digital Library of Theses and Dissertations, Australasian Digital Theses Program and DART-Europe E-theses Portal (11 October 2011). Finally, additional references were also obtained from reference lists from articles. The review included randomised controlled trials and quasi-randomised controlled trials for children with oropharyngeal dysphagia and neurological impairment. All three review authors (AM, PD and EW) independently screened titles and abstracts for inclusion and discussed results. In cases of uncertainty over whether an abstract met inclusion criterion, review authors obtained the full-text article and independently evaluated each paper for inclusion. The data were categorised for comparisons depending on the nature of the control group (for example, oral sensorimotor treatment versus no treatment). Effectiveness of the oropharyngeal dysphagia intervention was assessed by considering primary outcomes of physiological functions of the oropharyngeal mechanism for swallowing (for example, lip seal maintenance), the presence of chest infection and pneumonia, and diet consistency a child is able to consume. Secondary outcomes were changes in growth, child's level of participation in the mealtime routine and the level of parent or carer stress associated with feeding. Three studies met the inclusion criteria for the review. Two studies were based on oral sensorimotor interventions for participants with cerebral palsy compared to standard care and a third study trialled lip strengthening exercises for children with myotonic dystrophy type 1 compared to no treatment (Sjogreen 2010). A meta-analysis combining results across the three studies was not possible because one of the studies had participants with a different condition, and the remaining two, although using oral sensorimotor treatments, used vastly different approaches with different intensities and durations. The decision not to combine these was in line with our protocol. In this review, we present the results from individual studies for four outcomes: physiological functions of the oropharyngeal mechanism for swallowing, the presence of chest infection and pneumonia, diet consistency, and changes in growth. However, it is not possible to reach definitive conclusions on the effectiveness of particular interventions for oropharyngeal dysphagia based on these studies. One study had a high risk of attrition bias owing to missing data, had statistically significant differences (in weight) across experimental and control groups at baseline, and did not describe other aspects of the trial sufficiently to enable assessment of other potential risks of bias. Another study was at high risk of detection bias as some outcomes were assessed by parents who knew whether their child was in the intervention or control group. The third study overall seemed to be at low risk of bias, but like the other two studies, suffered from a small sample size. The review demonstrates that there is currently insufficient high-quality evidence from randomised controlled trials or quasi-randomised controlled trials to provide conclusive results about the effectiveness of any particular type of oral-motor therapy for children with neurological impairment. There is an urgent need for larger-scale (appropriately statistically powered), randomised trials to evaluate the efficacy of interventions for oropharyngeal dysphagia.

Effectiveness and cost-effectiveness of admissions to women's crisis houses compared with traditional psychiatric wards: pilot patient-preference randomised controlled trial.

PubMed

Howard, L; Flach, C; Leese, M; Byford, S; Killaspy, H; Cole, L; Lawlor, C; Betts, J; Sharac, J; Cutting, P; McNicholas, S; Johnson, S

2010-08-01

Women's crisis houses have been developed in the UK as a less stigmatising and less institutional alternative to traditional psychiatric wards. To examine the effectiveness and cost-effectiveness of women's crisis houses by first examining the feasibility of a pilot patient-preference randomised controlled trial (PP-RCT) design (ISRCTN20804014). We used a PP-RCT study design to investigate women presenting in crisis needing informal admission. The four study arms were the patient preference arms of women's crisis house or hospital admission, and randomised arms of women's crisis house or hospital admission. Forty-one women entered the randomised arms of the trial (crisis house n = 19, wards n = 22) and 61 entered the patient-preference arms (crisis house n = 37, ward n = 24). There was no significant difference in outcomes (symptoms, functioning, perceived coercion, stigma, unmet needs or quality of life) or costs for any of the groups (randomised or preference arms), but women who obtained their preferred intervention were more satisfied with treatment. Although the sample sizes were too small to allow definite conclusions, the results suggest that when services are able to provide interventions preferred by patients, those patients are more likely to be satisfied with treatment. This pilot study provides some evidence that women's crisis houses are as effective as traditional psychiatric wards, and may be more cost-effective.

Children, parents, and pets exercising together (CPET) randomised controlled trial: study rationale, design, and methods.

PubMed

Yam, Philippa S; Morrison, Ryan; Penpraze, Viki; Westgarth, Carri; Ward, Dianne S; Mutrie, Nanette; Hutchison, Pippa; Young, David; Reilly, John J

2012-03-19

Objectively measured physical activity is low in British children, and declines as childhood progresses. Observational studies suggest that dog-walking might be a useful approach to physical activity promotion in children and adults, but there are no published public health interventions based on dog-walking with children. The Children, Parents, and Pets Exercising Together Study aims to develop and evaluate a theory driven, generalisable, family-based, dog walking intervention for 9-11 year olds. The Children, Parents, and Pets Exercising Together Study is an exploratory, assessor-blinded, randomised controlled trial as defined in the UK MRC Framework on the development and evaluation of complex interventions in public health. The trial will follow CONSORT guidance. Approximately 40 dog-owning families will be allocated randomly in a ratio of 1.5:1 to receive a simple behavioural intervention lasting for 10 weeks or to a 'waiting list' control group. The primary outcome is change in objectively measured child physical activity using Actigraph accelerometry. Secondary outcomes in the child, included in part to shape a future more definitive randomised controlled trial, are: total time spent sedentary and patterning of sedentary behaviour (Actigraph accelerometry); body composition and bone health from dual energy x-ray absorptiometry; body weight, height and BMI; and finally, health-related quality of life using the PedsQL. Secondary outcomes in parents and dogs are: changes in body weight; changes in Actigraph accelerometry measured physical activity and sedentary behaviour. Process evaluation will consist of assessment of simultaneous child, parent, and dog accelerometry data and brief interviews with participating families. The Children, Parents, and Pets Exercising Together trial should be the first randomised controlled study to establish and evaluate an intervention aimed at dog-based physical activity promotion in families. It should advance our understanding of whether and how to use pet dogs to promote physical activity and/or to reduce sedentary behaviour in children and adults. The trial is intended to lead to a subsequent more definitive randomised controlled trial, and the work should inform future dog-based public health interventions such as secondary prevention interventions in children or adults. ISRCTN85939423.

Children, parents, and pets exercising together (CPET) randomised controlled trial: study rationale, design, and methods

PubMed Central

2012-01-01

Background Objectively measured physical activity is low in British children, and declines as childhood progresses. Observational studies suggest that dog-walking might be a useful approach to physical activity promotion in children and adults, but there are no published public health interventions based on dog-walking with children. The Children, Parents, and Pets Exercising Together Study aims to develop and evaluate a theory driven, generalisable, family-based, dog walking intervention for 9-11 year olds. Methods/design The Children, Parents, and Pets Exercising Together Study is an exploratory, assessor-blinded, randomised controlled trial as defined in the UK MRC Framework on the development and evaluation of complex interventions in public health. The trial will follow CONSORT guidance. Approximately 40 dog-owning families will be allocated randomly in a ratio of 1.5:1 to receive a simple behavioural intervention lasting for 10 weeks or to a 'waiting list' control group. The primary outcome is change in objectively measured child physical activity using Actigraph accelerometry. Secondary outcomes in the child, included in part to shape a future more definitive randomised controlled trial, are: total time spent sedentary and patterning of sedentary behaviour (Actigraph accelerometry); body composition and bone health from dual energy x-ray absorptiometry; body weight, height and BMI; and finally, health-related quality of life using the PedsQL. Secondary outcomes in parents and dogs are: changes in body weight; changes in Actigraph accelerometry measured physical activity and sedentary behaviour. Process evaluation will consist of assessment of simultaneous child, parent, and dog accelerometry data and brief interviews with participating families. Discussion The Children, Parents, and Pets Exercising Together trial should be the first randomised controlled study to establish and evaluate an intervention aimed at dog-based physical activity promotion in families. It should advance our understanding of whether and how to use pet dogs to promote physical activity and/or to reduce sedentary behaviour in children and adults. The trial is intended to lead to a subsequent more definitive randomised controlled trial, and the work should inform future dog-based public health interventions such as secondary prevention interventions in children or adults. Trial registration number ISRCTN85939423 PMID:22429665

A pragmatic randomised controlled trial of the effectiveness and cost-effectiveness of screening older women for the prevention of fractures: rationale, design and methods for the SCOOP study.

PubMed

Shepstone, L; Fordham, R; Lenaghan, E; Harvey, I; Cooper, C; Gittoes, N; Heawood, A; Peters, T J; O'Neill, T; Torgerson, D; Holland, R; Howe, A; Marshall, T; Kanis, J A; McCloskey, E

2012-10-01

SCOOP is a UK seven-centre, pragmatic, randomised controlled trial with 5-year follow-up, including 11,580 women aged 70 to 85 years, to assess the effectiveness and cost-effectiveness of a community-based screening programme to reduce fractures. It utilises the FRAX algorithm and DXA to assess the 10-year probability of fracture. Introduction Osteoporotic, or low-trauma, fractures present a considerable burden to the National Health Service and have major adverse effects on quality of life, disability and mortality for the individual. Methods Given the availability of efficacious treatments and a risk assessment tool based upon clinical risk factors and bone mineral density, a case exists to undertake a community-based controlled evaluation of screening for subjects at high risk of fracture, under the hypothesis that such a screening programme would reduce fractures in this population. Results This study is a UK seven-centre, unblinded, pragmatic, randomised controlled trial with a 5-year follow-up period. A total of 11,580 women, aged 70 to 85 years and not on prescribed bone protective therapy will be consented to the trial by post via primary care providing 90% power to detect an 18% decrease in fractures. Conclusions Participants will be randomised to either a screening arm or control. Those undergoing screening will have a 10-year fracture probability computed from baseline risk factors together with bone mineral density measured by DXA in selected subjects. Individuals above an age-dependent threshold of fracture probability will be recommended for treatment for the duration of the trial. Subjects in the control arm will receive 'usual care'. Participants will be followed up 6 months after randomisation and annually by postal questionnaires with independent checking of hospital and primary care records. The primary outcome will be the proportion of individuals sustaining fractures in each group. An economic analysis will be carried out to assess cost-effectiveness of screening. A qualitative evaluation will be conducted to examine the acceptability of the process to participants.

A randomised controlled trial of the use of aromatherapy and hand massage to reduce disruptive behaviour in people with dementia.

PubMed

Fu, Chieh-Yu; Moyle, Wendy; Cooke, Marie

2013-07-10

Aromatherapy and hand massage therapies have been reported to have some benefit for people with dementia who display behavioural symptoms; however there are a number of limitations of reported studies. The aim is to investigate the effect of aromatherapy (3% lavender oil spray) with and without hand massage on disruptive behaviour in people with dementia living in long-term care. In a single blinded randomised controlled trial 67 people with a diagnosis of dementia and a history of disruptive behaviour, from three long-term care facilities were recruited and randomised using a random number table into three groups: (1) Combination (aromatherapy and hand massage) (n = 22), (2) Aromatherapy (n = 23), (3) Placebo control (water spray) (n = 22). The intervention was given twice daily for six weeks. Data on residents' behaviour (CMAI) and cognition (MMSE) were collected before, during and after the intervention. Despite a downward trend in behaviours displayed not one of the interventions significantly reduced disruptive behaviour. Further large-scale placebo controlled studies are required where antipsychotic medication is controlled and a comparison of the methods of application of aromatherapy are investigated. ACTRN12612000917831.

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

PubMed

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

2013-05-14

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

A systematic review of randomised controlled trials assessing effectiveness of prosthetic and orthotic interventions

PubMed Central

Farmer, Sybil; Pandyan, Anand; Chockalingam, Nachiappan

2018-01-01

Background Assistive products are items which allow older people and people with disabilities to be able to live a healthy, productive and dignified life. It has been estimated that approximately 1.5% of the world’s population need a prosthesis or orthosis. Objective The objective of this study was to systematically identify and review the evidence from randomized controlled trials assessing effectiveness and cost-effectiveness of prosthetic and orthotic interventions. Methods Literature searches, completed in September 2015, were carried out in fourteen databases between years 1995 and 2015. The search results were independently screened by two reviewers. For the purpose of this manuscript, only randomized controlled trials which examined interventions using orthotic or prosthetic devices were selected for data extraction and synthesis. Results A total of 342 randomised controlled trials were identified (319 English language and 23 non-English language). Only 4 of these randomised controlled trials examined prosthetic interventions and the rest examined orthotic interventions. These orthotic interventions were categorised based on the medical conditions/injuries of the participants. From these studies, this review focused on the medical condition/injuries with the highest number of randomised controlled trials (osteoarthritis, fracture, stroke, carpal tunnel syndrome, plantar fasciitis, anterior cruciate ligament, diabetic foot, rheumatoid and juvenile idiopathic arthritis, ankle sprain, cerebral palsy, lateral epicondylitis and low back pain). The included articles were assessed for risk of bias using the Cochrane Risk of Bias tool. Details of the clinical population examined, the type of orthotic/prosthetic intervention, the comparator/s and the outcome measures were extracted. Effect sizes and odds ratios were calculated for all outcome measures, where possible. Conclusions At present, for prosthetic and orthotic interventions, the scientific literature does not provide sufficient high quality research to allow strong conclusions on their effectiveness and cost-effectiveness. PMID:29538382

Epidurals in Pancreatic Resection Outcomes (E-PRO) study: protocol for a randomised controlled trial

PubMed Central

Pak, Linda Ma; Haroutounian, Simon; Hawkins, William G; Worley, Lori; Kurtz, Monika; Frey, Karen; Karanikolas, Menelaos; Swarm, Robert A; Bottros, Michael M

2018-01-01

Introduction Epidural analgesia provides an important synergistic method of pain control. In addition to reducing perioperative opioid consumption, the deliverance of analgesia into the epidural space, effectively creating a sympathetic blockade, has a multitude of additional potential benefits, from decreasing the incidence of postoperative delirium to reducing the development of persistent postsurgical pain (PPSP). Prior studies have also identified a correlation between the use of epidural analgesia and improved oncological outcomes and survival. The aim of this study is to evaluate the effect of epidural analgesia in pancreatic operations on immediate postoperative outcomes, the development of PPSP and oncological outcomes in a prospective, single-blind, randomised controlled trial. Methods The Epidurals in Pancreatic Resection Outcomes (E-PRO) study is a prospective, single-centre, randomised controlled trial. 150 patients undergoing either pancreaticoduodenectomy or distal pancreatectomy will be randomised to receive an epidural bupivacaine infusion following anaesthetic induction followed by continued epidural bupivacaine infusion postoperatively in addition to the institutional standardised pain regimen of hydromorphone patient-controlled analgesia (PCA), acetaminophen and ketorolac (intervention group) or no epidural infusion and only the standardised postoperative pain regimen (control group). The primary outcome was the postoperative opioid consumption, measured in morphine or morphine-equivalents. Secondary outcomes include patient-reported postoperative pain numerical rating scores, trend and relative ratios of serum inflammatory markers (interleukin (IL)-1β, IL-6, tumour necrosis factor-α, IL-10), occurrence of postoperative delirium, development of PPSP as determined by quantitative sensory testing, and disease-free and overall survival. Ethics and dissemination The E-PRO trial has been approved by the institutional review board. Recruitment began in May 2016 and will continue until the end of May 2018. Dissemination plans include presentations at scientific conferences and scientific publications. Trial registration number NCT02681796. PMID:29374667

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

PubMed

Williams, Margiad Elen; Hutchings, Judy

2015-05-20

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

Randomised controlled trials of veterinary homeopathy: characterising the peer-reviewed research literature for systematic review.

PubMed

Mathie, Robert T; Hacke, Daniela; Clausen, Jürgen

2012-10-01

Systematic review of the research evidence in veterinary homeopathy has never previously been carried out. This paper presents the search methods, together with categorised lists of retrieved records, that enable us to identify the literature that is acceptable for future systematic review of randomised controlled trials (RCTs) in veterinary homeopathy. All randomised and controlled trials of homeopathic intervention (prophylaxis and/or treatment of disease, in any species except man) were appraised according to pre-specified criteria. The following databases were systematically searched from their inception up to and including March 2011: AMED; Carstens-Stiftung Homeopathic Veterinary Clinical Research (HomVetCR) database; CINAHL; Cochrane Central Register of Controlled Trials; Embase; Hom-Inform; LILACS; PubMed; Science Citation Index; Scopus. One hundred and fifty records were retrieved; 38 satisfied the acceptance criteria (substantive report of a clinical treatment or prophylaxis trial in veterinary homeopathic medicine randomised and controlled and published in a peer-reviewed journal), and were thus eligible for future planned systematic review. Approximately half of the rejected records were theses. Seven species and 27 different species-specific medical conditions were represented in the 38 papers. Similar numbers of papers reported trials of treatment and prophylaxis (n=21 and n=17 respectively) and were controlled against placebo or other than placebo (n=18, n=20 respectively). Most research focused on non-individualised homeopathy (n=35 papers) compared with individualised homeopathy (n=3). The results provide a complete and clarified view of the RCT literature in veterinary homeopathy. We will systematically review the 38 substantive peer-reviewed journal articles under the main headings: treatment trials; prophylaxis trials. Copyright © 2012 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

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

PubMed Central

2010-01-01

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

Exercise programs may be effective in preventing a new episode of neck pain: a systematic review and meta-analysis.

PubMed

de Campos, Tarcisio F; Maher, Chris G; Steffens, Daniel; Fuller, Joel T; Hancock, Mark J

2018-06-13

What is the effectiveness of interventions that aim to prevent a new episode of neck pain? Systematic review and meta-analysis of randomised, controlled trials. People without neck pain at study entry. Any intervention aiming to prevent a future episode of neck pain. New episode of neck pain. Five trials including a total of 3852 individuals met the inclusion criteria. The pooled results from two randomised, controlled trials (500 participants) found moderate-quality evidence that exercise reduces the risk of a new episode of neck pain (OR 0.32, 95% CI 0.12 to 0.86). One of the meta-analysed trials included some co-interventions with the exercise. There was low-quality evidence from three randomised, controlled trials (3352 participants) that ergonomic programs do not reduce the risk of a new neck pain episode (OR 1.00, 95% CI 0.74 to 1.35). This review found moderate-quality evidence supporting the effectiveness of an exercise program for reducing the risk of a new episode of neck pain. There is a need for high-quality randomised, controlled trials evaluating interventions to prevent new episodes of neck pain. PROSPERO CRD42017055174. [de Campos TF, Maher CG, Steffens D, Fuller JT, Hancock MJ (2018) Exercise programs may be effective in preventing a new episode of neck pain: a systematic review. Journal of Physiotherapy XX: XX-XX]. Copyright © 2018 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Social Stories in mainstream schools for children with autism spectrum disorder: a feasibility randomised controlled trial.

PubMed

Marshall, David; Wright, Barry; Allgar, Victoria; Adamson, Joy; Williams, Christine; Ainsworth, Hannah; Cook, Liz; Varley, Danielle; Hackney, Lisa; Dempster, Paul; Ali, Shehzad; Trepel, Dominic; Collingridge Moore, Danielle; Littlewood, Elizabeth; McMillan, Dean

2016-08-11

To assess the feasibility of recruitment, retention, outcome measures and intervention training/delivery among teachers, parents and children. To calculate a sample size estimation for full trial. A single-centre, unblinded, cluster feasibility randomised controlled trial examining Social Stories delivered within a school environment compared with an attentional control. 37 primary schools in York, UK. 50 participants were recruited and a cluster randomisation approach by school was examined. Participants were randomised into the treatment group (n=23) or a waiting list control group (n=27). Acceptability and feasibility of the trial, intervention and of measurements required to assess outcomes in a definitive trial. An assessment of the questionnaire completion rates indicated teachers would be most appropriate to complete the primary outcome measure. 2 outcome measures: the Social Responsiveness Scale (SRS)-2 and a goal-based measure showed both the highest levels of completion rates (above 80%) at the primary follow-up point (6 weeks postintervention) and captured relevant social and behaviour outcomes. Power calculations were based on these 2 outcome measures leading to a total proposed sample size of 180 participant groups. Results suggest that a future trial would be feasible to conduct and could inform the policy and practice of using Social Stories in mainstream schools. ISRCTN96286707; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3 Trial Intracranial Bleeding Mechanistic Sub-Study [CRASH-3 IBMS]).

PubMed

Mahmood, Abda; Roberts, Ian; Shakur, Haleema

2017-07-17

Tranexamic acid prevents blood clots from breaking down and reduces bleeding. However, it is uncertain whether tranexamic acid is effective in traumatic brain injury. The CRASH-3 trial is a randomised controlled trial that will examine the effect of tranexamic acid (versus placebo) on death and disability in 13,000 patients with traumatic brain injury. The CRASH-3 trial hypothesizes that tranexamic acid will reduce intracranial haemorrhage, which will reduce the risk of death. Although it is possible that tranexamic acid will reduce intracranial bleeding, there is also a potential for harm. In particular, tranexamic acid may increase the risk of cerebral thrombosis and ischaemia. The protocol detailed here is for a mechanistic sub-study nested within the CRASH-3 trial. This mechanistic sub-study aims to examine the effect of tranexamic acid (versus placebo) on intracranial bleeding and cerebral ischaemia. The CRASH-3 Intracranial Bleeding Mechanistic Sub-Study (CRASH-3 IBMS) is nested within a prospective, double-blind, multi-centre, parallel-arm randomised trial called the CRASH-3 trial. The CRASH-3 IBMS will be conducted in a cohort of approximately 1000 isolated traumatic brain injury patients enrolled in the CRASH-3 trial. In the CRASH-3 IBMS, brain scans acquired before and after randomisation are examined, using validated methods, for evidence of intracranial bleeding and cerebral ischaemia. The primary outcome is the total volume of intracranial bleeding measured on computed tomography after randomisation, adjusting for baseline bleeding volume. Secondary outcomes include progression of intracranial haemorrhage (from pre- to post-randomisation scans), new intracranial haemorrhage (seen on post- but not pre-randomisation scans), intracranial haemorrhage following neurosurgery, and new focal ischaemic lesions (seen on post-but not pre-randomisation scans). A linear regression model will examine whether receipt of the trial treatment can predict haemorrhage volume. Bleeding volumes and new ischaemic lesions will be compared across treatment groups using relative risks and 95% confidence intervals. The CRASH-3 IBMS will provide an insight into the mechanism of action of tranexamic acid in traumatic brain injury, as well as information about the risks and benefits. Evidence from this trial could inform the management of patients with traumatic brain injury. The CRASH-3 trial was prospectively registered and the CRASH-3 IBMS is an addition to the original protocol registered at the International Standard Randomised Controlled Trials registry ( ISRCTN15088122 ) 19 July 2011, and ClinicalTrials.gov on 25 July 2011 (NCT01402882).

Propofol versus thiopental sodium for the treatment of refractory status epilepticus.

PubMed

Prabhakar, Hemanshu; Bindra, Ashish; Singh, Gyaninder Pal; Kalaivani, Mani

2012-08-15

Failure to respond to antiepileptic drugs in uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome. To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (10 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library 2012), and MEDLINE (1946 to May week 1, 2012). We also searched (10 May 2012) ClinicalTrials.gov, The South Asian Database of Controlled Clinical Trials, and IndMED (a bibliographic database of Indian Medical Journals). All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol. Two review authors screened the search results and reviewed abstracts of relevant and eligible trials before retrieving the full text publications. One study was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE and receiving either propofol or thiopental sodium for the control of seizure activity (Rossetti 2011). This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. There was no evidence of a difference between the drugs with respect to the outcome measures such as control of seizure activity and functional outcome at three months. There is lack of robust and randomised controlled evidence that can clarify the efficacy of propofol and thiopental sodium over each other in the treatment of RSE. There is a need for large, randomised controlled trials for this serious condition.

Psychosocial consequences in the Danish randomised controlled lung cancer screening trial (DLCST).

PubMed

Rasmussen, Jakob F; Siersma, V; Pedersen, J H; Brodersen, J

2015-01-01

To measure the psychosocial consequences in the Danish lung cancer screening trial (DLCST) and compare those between the computed tomography (CT) group and the control group. This study was a single centre randomised controlled trial with five annual screening rounds. Healthy current or former heavy smokers aged 50-70 years (men and women) were randomised 1:1 to a CT group and a control group. Heavy smokers were defined by having smoked ≥20 pack years and former smokers by being abstinent ≤10 years. Both groups were invited annually to the screening clinic to complete the validated lung-cancer-specific questionnaire consequences of screening lung cancer (COS-LC). The CT group was also offered a low dose CT scan of the lungs. The COS-LC measures nine scales with psychosocial properties: Anxiety, Behaviour, Dejection, Negative impact on sleep, Self-blame, Focus on Airway Symptoms, Stigmatisation, Introvert, and Harm of Smoking. 4104 participants were randomised to the DLCST and the COS-LC completion rates for the CT group and the control group were 95.5% and 73.6%, respectively. There was a significant increase in negative psychosocial consequences from baseline through rounds 2-5 for both the CT group and the control group (mean increase >0, p<.0001 for 3 of 4 possible scales). During rounds 2-5 the control group experienced significantly more negative psychosocial consequences in seven of nine scales compared with the CT group (mean Δ score >0 and p<.033). Lung cancer CT-screening trials induced more negative psychosocial reactions in both the CT group and the control group compared with the baseline psychosocial profile. The CT group experienced less negative psychosocial consequences compared with the control group, which might be explained by reassurance among those with normal screening results. ClinicalTrials.gov: NCT00496977. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Targeting intensive versus conventional glycaemic control for type 1 diabetes mellitus: a systematic review with meta-analyses and trial sequential analyses of randomised clinical trials

PubMed Central

Kähler, Pernille; Grevstad, Berit; Almdal, Thomas; Gluud, Christian; Wetterslev, Jørn; Vaag, Allan; Hemmingsen, Bianca

2014-01-01

Objective To assess the benefits and harms of targeting intensive versus conventional glycaemic control in patients with type 1 diabetes mellitus. Design A systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. Data sources The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded and LILACS to January 2013. Study selection Randomised clinical trials that prespecified different targets of glycaemic control in participants at any age with type 1 diabetes mellitus were included. Data extraction Two authors independently assessed studies for inclusion and extracted data. Results 18 randomised clinical trials included 2254 participants with type 1 diabetes mellitus. All trials had high risk of bias. There was no statistically significant effect of targeting intensive glycaemic control on all-cause mortality (risk ratio 1.16, 95% CI 0.65 to 2.08) or cardiovascular mortality (0.49, 0.19 to 1.24). Targeting intensive glycaemic control reduced the relative risks for the composite macrovascular outcome (0.63, 0.41 to 0.96; p=0.03), and nephropathy (0.37, 0.27 to 0.50; p<0.00001. The effect estimates of retinopathy, ketoacidosis and retinal photocoagulation were not consistently statistically significant between random and fixed effects models. The risk of severe hypoglycaemia was significantly increased with intensive glycaemic targets (1.40, 1.01 to 1.94). Trial sequential analyses showed that the amount of data needed to demonstrate a relative risk reduction of 10% were, in general, inadequate. Conclusions There was no significant effect towards improved all-cause mortality when targeting intensive glycaemic control compared with conventional glycaemic control. However, there may be beneficial effects of targeting intensive glycaemic control on the composite macrovascular outcome and on nephropathy, and detrimental effects on severe hypoglycaemia. Notably, the data for retinopathy and ketoacidosis were inconsistent. There was a severe lack of reporting on patient relevant outcomes, and all trials had poor bias control. PMID:25138801

Clinical effectiveness of a patient decision aid to improve decision quality and glycaemic control in people with diabetes making treatment choices: a cluster randomised controlled trial (PANDAs) in general practice

PubMed Central

Mathers, Nigel; Ng, Chirk Jenn; Campbell, Michael Joseph; Colwell, Brigitte; Brown, Ian; Bradley, Alastair

2012-01-01

Objective To determine the effectiveness of a patient decision aid (PDA) to improve decision quality and glycaemic control in people with diabetes making treatment choices using a cluster randomised controlled trial (RCT). Design A cluster RCT. Setting 49 general practices in UK randomised into intervention (n=25) and control (n=24). Participants General practices Inclusion criteria: >4 medical partners; list size >7000; and a diabetes register with >1% of practice population. 191 practices assessed for eligibility, and 49 practices randomised and completed the study. Patients People with type 2 diabetes mellitus (T2DM) taking at least two oral glucose-lowering drugs with maximum tolerated dose with a glycosolated haemoglobin (HbA1c) greater than 7.4% (IFCC HbA1c >57 mmol/mol) or advised in the preceeding 6 months to add or consider changing to insulin therapy. Exclusion criteria: currently using insulin therapy; difficulty reading or understanding English; difficulty in understanding the purpose of the study; visual or cognitive impairment or mentally ill. A total of 182 assessed for eligibility, 175 randomised to 95 intervention and 80 controls, and 167 completion and analysis. Intervention Brief training of clinicians and use of PDA with patients in single consultation. Primary outcomes Decision quality (Decisional Conflict Scores, knowledge, realistic expectations and autonomy) and glycaemic control (glycosolated haemoglobin, HbA1c). Secondary outcomes Knowledge and realistic expectations of the risks and benefits of insulin therapy and diabetic complications. Results Intervention group: lower total Decisional Conflict Scores (17.4 vs 25.2, p<0.001); better knowledge (51.6% vs 28.8%, p<0.001); realistic expectations (risk of ‘hypo’, ‘weight gain’, ‘complications’; 81.0% vs 5.2%, 70.5% vs 5.3%, 26.3% vs 5.0% respectively, p<0.001); and were more autonomous in decision-making (64.1% vs 42.9%, p=0.012). No significant difference in the glycaemic control between the two groups. Conclusions Use of the PANDAs decision aid reduces decisional conflict, improves knowledge, promotes realistic expectations and autonomy in people with diabetes making treatment choices in general practice. ISRCTN Trials Register Number 14842077. PMID:23129571

Continuous versus intermittent endotracheal cuff pressure control for the prevention of ventilator-associated respiratory infections in Vietnam: study protocol for a randomised controlled trial.

PubMed

Dat, Vu Quoc; Geskus, Ronald B; Wolbers, Marcel; Loan, Huynh Thi; Yen, Lam Minh; Binh, Nguyen Thien; Chien, Le Thanh; Mai, Nguyen Thi Hoang; Phu, Nguyen Hoan; Lan, Nguyen Phu Huong; Hao, Nguyen Van; Long, Hoang Bao; Thuy, Tran Phuong; Kinh, Nguyen Van; Trung, Nguyen Vu; Phu, Vu Dinh; Cap, Nguyen Trung; Trinh, Dao Tuyet; Campbell, James; Kestelyn, Evelyne; Wertheim, Heiman F L; Wyncoll, Duncan; Thwaites, Guy Edward; van Doorn, H Rogier; Thwaites, C Louise; Nadjm, Behzad

2018-04-04

Ventilator-associated respiratory infection (VARI) comprises ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT). Although their diagnostic criteria vary, together these are the most common hospital-acquired infections in intensive care units (ICUs) worldwide, responsible for a large proportion of antibiotic use within ICUs. Evidence-based strategies for the prevention of VARI in resource-limited settings are lacking. Preventing the leakage of oropharyngeal secretions into the lung using continuous endotracheal cuff pressure control is a promising strategy. The aim of this study is to investigate the efficacy of automated, continuous endotracheal cuff pressure control in preventing the development of VARI and reducing antibiotic use in ICUs in Vietnam. This is an open-label randomised controlled multicentre trial. We will enrol 600 adult patients intubated for ≤ 24 h at the time of enrolment. Eligible patients will be stratified according to admission diagnosis (180 tetanus, 420 non-tetanus) and site and will be randomised in a 1:1 ratio to receive either (1) automated, continuous control of endotracheal cuff pressure or (2) intermittent measurement and control of endotracheal cuff pressure using a manual cuff pressure meter. The primary outcome is the occurrence of VARI, defined as either VAP or VAT during the ICU admission up to a maximum of 90 days after randomisation. Patients in both groups who are at risk for VARI will receive a standardised battery of investigations if their treating physician feels a new infection has occurred, the results of which will be used by an endpoint review committee, blinded to the allocated arm and independent of patient care, to determine the primary outcome. All enrolled patients will be followed for mortality and endotracheal tube cuff-related complications at 28 days and 90 days after randomisation. Other secondary outcomes include antibiotic use; days ventilated, in ICU and in hospital; inpatient mortality; costs of antibiotics in ICU; duration of ICU stay; and duration of hospital stay. This study will provide high-quality evidence concerning the use of continuous endotracheal cuff pressure control as a method to reduce VARI, antibiotic use and hospitalisation costs and to shorten stay. ClinicalTrials.gov, NCT02966392 . Registered on November 9, 2016. Protocol version: 2.0; issue date March 3, 2017.

Randomised controlled trial of biofeedback training in persistent encopresis with anismus

PubMed Central

Nolan, T.; Catto-Smith, T.; Coffey, C.; Wells, J.

1998-01-01

BACKGROUND—Paradoxical external anal sphincter contraction during attempted defecation (anismus) is thought to be an important contributor to chronic faecal retention and encopresis in children. Biofeedback training can be used to teach children to abolish this abnormal contraction.
METHODS—A randomised controlled trial in medical treatment resistant and/or treatment dependent children with anismus using surface electromyographic (EMG) biofeedback training to determine whether such training produces sustained faecal continence. Up to four sessions of biofeedback training were conducted at weekly intervals for each patient. Anorectal manometry was performed before randomisation and six months later. Parents of patients completed the "child behaviour checklist" (CBCL) before randomisation and at follow up.
RESULTS—Sixty eight children underwent anorectal manometry and EMG. Of these, 29 had anismus (ages 4-14 years) and were randomised to either EMG biofeedback training and conventional medical treatment (BFT) (n = 14) or to conventional medical treatment alone (n = 15). All but one child were able to learn relaxation of the external anal sphincter on attempted defecation. At six months' follow up, laxative free remission had been sustained in two of 14 patients in the BFT group and in two of 15 controls (95% confidence interval (CI) on difference, −24% to 26%). Remission or improvement occurred in four of 14 patients in the BFT group and six of 15 controls (95% CI on difference, −46% to 23%). Of subjects available for repeat anorectal manometry and EMG at six months, six of 13 in the BFT group still demonstrated anismus v 11 of 13 controls (95% CI on difference, −75% to −1%). Of the four patients in full remission at six months, only one (in the BFT group) did not exhibit anismus. Rectal hyposensitivity was not associated with remission or improvement in either of the groups. Mean CBCL total behaviour problem scores were not significantly different between the BFT and control groups, but there was a significant improvement in CBCL school scale scores in the BFT group, and this improvement was significantly greater than that seen in the control group.
CONCLUSIONS—The result of this study, together with those reported in other controlled trials, argues against using biofeedback training in children with encopresis.

 PMID:9797593

Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial.

PubMed

Ellis, Paul; Barrett-Lee, Peter; Johnson, Lindsay; Cameron, David; Wardley, Andrew; O'Reilly, Susan; Verrill, Mark; Smith, Ian; Yarnold, John; Coleman, Robert; Earl, Helena; Canney, Peter; Twelves, Chris; Poole, Christopher; Bloomfield, David; Hopwood, Penelope; Johnston, Stephen; Dowsett, Mitchell; Bartlett, John M S; Ellis, Ian; Peckitt, Clare; Hall, Emma; Bliss, Judith M

2009-05-16

Incorporation of a taxane as adjuvant treatment for early breast cancer offers potential for further improvement of anthracycline-based treatment. The UK TACT study (CRUK01/001) investigated whether sequential docetaxel after anthracycline chemotherapy would improve patient outcome compared with standard chemotherapy of similar duration. In this multicentre, open-label, phase III, randomised controlled trial, 4162 women (aged >18 years) with node-positive or high-risk node-negative operable early breast cancer were randomly assigned by computer-generated permuted block randomisation to receive FEC (fluorouracil 600 mg/m(2), epirubicin 60 mg/m(2), cyclophosphamide 600 mg/m(2) at 3-weekly intervals) for four cycles followed by docetaxel (100 mg/m(2) at 3-weekly intervals) for four cycles (n=2073) or control (n=2089). For the control regimen, centres chose either FEC for eight cycles (n=1265) or epirubicin (100 mg/m(2) at 3-weekly intervals) for four cycles followed by CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) at 4-weekly intervals) for four cycles (n=824). The primary endpoint was disease-free survival. Analysis was by intention to treat (ITT). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN79718493. All randomised patients were included in the ITT population. With a median follow-up of 62 months, disease-free survival events were seen in 517 of 2073 patients in the experimental group compared with 539 of 2089 controls (hazard ratio [HR] 0.95, 95% CI 0.85-1.08; p=0.44). 75.6% (95% CI 73.7-77.5) of patients in the experimental group and 74.3% (72.3-76.2) of controls were alive and disease-free at 5 years. The proportion of patients who reported any acute grade 3 or 4 adverse event was significantly greater in the experimental group than in the control group (p<0.0001); the most frequent events were neutropenia (937 events vs 797 events), leucopenia (507 vs 362), and lethargy (456 vs 272). This study did not show any overall gain from the addition of docetaxel to standard anthracycline chemotherapy. Exploration of predictive biomarker-defined subgroups might have the potential to better target the use of taxane-based therapy. Cancer Research UK (CRUK 01/001), Sanofi-Aventis, Pfizer, and Roche.

The efficacy of a brief intervention in reducing hazardous drinking in working age men in Russia: the HIM (Health for Izhevsk men) individually randomised parallel group exploratory trial

PubMed Central

2011-01-01

Background Russia has particularly low life expectancy for an industrialised country, with mortality at working ages having fluctuated dramatically over the past few decades, particularly among men. Alcohol has been identified as the most likely cause of these temporal variations. One approach to reducing the alcohol problem in Russia is 'brief interventions' which seek to change views of the personal acceptability of excessive drinking and to encourage self-directed behaviour change. Very few studies to evaluate the efficacy of brief interventions in Russia have been conducted. Motivational Interviewing (MI) is a person-centred counselling style which can be adapted to brief interventions in which help is offered in thinking through behaviour in the context of values and goals, to decide whether change is needed, and if so, how it may best be achieved. Methods This paper reports on an individually randomised two-armed parallel group exploratory trial. The primary hypothesis is that a brief adaptation of MI will be effective in reducing self-reported hazardous and harmful drinking at 3 months. Participants were drawn from the Izhevsk Family Study II, with eligibility determined based on proxy reports of hazardous and harmful drinking in the past year. All participants underwent a health check, with MI subsequently delivered to those in the intervention arm. Signed consent was obtained from those in the intervention arm only at this point. Both groups were then invited for 3 and 12 month follow ups. The control group did not receive any additional intervention. Results 441 men were randomised. Of these 61 did not have a health check leaving 190 in each trial arm. Follow up at 3 months was high (97% of those having a health check), and very similar in the two trial arms (183 in the intervention and 187 in the control). No significant differences were detected between the randomised groups in either the primary or the secondary outcomes at three months in the intention to treat analyses. The unadjusted odds ratio (95% CI) for the effect of MI on hazardous and harmful drinking was 0.77 (0.51, 1.16). An adjusted odds ratio of 0.52 (0.28, 0.94) was obtained in the pre-specified per protocol analysis. Conclusions This trial demonstrates that it is possible to engage Russian men who drink hazardously in a brief intervention aimed at reducing alcohol related harm. However the results with respect to the efficacy are equivocal and further, larger-scale trials are warranted. Trial Registration ISRCTN: ISRCTN82405938 PMID:22053775

Timing of birth for women with a twin pregnancy at term: a randomised controlled trial

PubMed Central

2010-01-01

Background There is a well recognized risk of complications for both women and infants of a twin pregnancy, increasing beyond 37 weeks gestation. Preterm birth prior to 37 weeks gestation is a recognized complication of a twin pregnancy, however, up to 50% of twins will be born after this time. The aims of this randomised trial are to assess whether elective birth at 37 weeks gestation compared with standard care in women with a twin pregnancy affects the risk of perinatal death, and serious infant complications. Methods/Design Design: Multicentred randomised trial. Inclusion Criteria: women with a twin pregnancy at 366 weeks or more without contraindication to continuation of pregnancy. Trial Entry & Randomisation: Following written informed consent, eligible women will be randomised from 36+6 weeks gestation. The randomisation schedule uses balanced variable blocks, with stratification for centre of birth and planned mode of birth. Women will be randomised to either elective birth or standard care. Treatment Schedules: Women allocated to the elective birth group will be planned for elective birth from 37 weeks gestation. Where the plan is for vaginal birth, this will involve induction of labour. Where the plan is for caesarean birth, this will involve elective caesarean section. For women allocated to standard care, birth will be planned for 38 weeks gestation or later. Where the plan is for vaginal birth, this will involve either awaiting the spontaneous onset of labour, or induction of labour if required. Where the plan is for caesarean birth, this will involve elective caesarean section (after 38 and as close to 39 weeks as possible). Primary Study Outcome: A composite of perinatal mortality or serious neonatal morbidity. Sample Size: 460 women with a twin pregnancy to show a reduction in the composite outcome from 16.3% to 6.7% with adjustment for the clustering of twin infants within mothers (p = 0.05, 80% power). Discussion This is a protocol for a randomised trial, the findings of which will contribute information about the optimal time of birth for women with an uncomplicated multiple pregnancy at and beyond 37 weeks gestation. Clinical Trial Registration Current Controlled Trials ISRCTN15761056 PMID:20973989

Minimal access surgery compared with medical management for gastro-oesophageal reflux disease: five year follow-up of a randomised controlled trial (REFLUX)

PubMed Central

Cotton, S C; Boachie, C; Ramsay, C R; Krukowski, Z H; Heading, R C; Campbell, M K

2013-01-01

Objectives To determine the long term clinical effectiveness of laparoscopic fundoplication as an alternative to drug treatment for chronic gastro-oesophageal reflux disease (GORD). Design Five year follow-up of multicentre, pragmatic randomised trial (with parallel non-randomised preference groups). Setting Initial recruitment in 21 UK hospitals. Participants Responders to annual questionnaires among 810 original participants. At entry, all had had GORD for >12 months. Intervention The surgeon chose the type of fundoplication. Medical therapy was reviewed and optimised by a specialist. Subsequent management was at the discretion of the clinician responsible for care, usually in primary care. Main outcome measures Primary outcome measure was self reported quality of life score on disease-specific REFLUX questionnaire. Other measures were health status (with SF-36 and EuroQol EQ-5D questionnaires), use of antireflux medication, and complications. Results By five years, 63% (112/178) of patients randomised to surgery and 13% (24/179) of those randomised to medical management had received a fundoplication (plus 85% (222/261) and 3% (6/192) of those who expressed a preference for surgery and for medical management). Among responders at 5 years, 44% (56/127) of those randomised to surgery were taking antireflux medication versus 82% (98/119) of those randomised to medical management. Differences in the REFLUX score significantly favoured the randomised surgery group (mean difference 8.5 (95% CI 3.9 to 13.1), P<0.001, at five years). SF-36 and EQ-5D scores also favoured surgery, but were not statistically significant at five years. After fundoplication, 3% (12/364) had surgical treatment for a complication and 4% (16) had subsequent reflux-related operations—most often revision of the wrap. Long term rates of dysphagia, flatulence, and inability to vomit were similar in the two randomised groups. Conclusions After five years, laparoscopic fundoplication continued to provide better relief of GORD symptoms than medical management. Adverse effects of surgery were uncommon and generally observed soon after surgery. A small proportion had re-operations. There was no evidence of long term adverse symptoms caused by surgery. Trial registration Current Controlled Trials ISRCTN15517081. PMID:23599318

Development of a practical approach to expert elicitation for randomised controlled trials with missing health outcomes: Application to the IMPROVE trial.

PubMed

Mason, Alexina J; Gomes, Manuel; Grieve, Richard; Ulug, Pinar; Powell, Janet T; Carpenter, James

2017-08-01

The analyses of randomised controlled trials with missing data typically assume that, after conditioning on the observed data, the probability of missing data does not depend on the patient's outcome, and so the data are 'missing at random' . This assumption is usually implausible, for example, because patients in relatively poor health may be more likely to drop out. Methodological guidelines recommend that trials require sensitivity analysis, which is best informed by elicited expert opinion, to assess whether conclusions are robust to alternative assumptions about the missing data. A major barrier to implementing these methods in practice is the lack of relevant practical tools for eliciting expert opinion. We develop a new practical tool for eliciting expert opinion and demonstrate its use for randomised controlled trials with missing data. We develop and illustrate our approach for eliciting expert opinion with the IMPROVE trial (ISRCTN 48334791), an ongoing multi-centre randomised controlled trial which compares an emergency endovascular strategy versus open repair for patients with ruptured abdominal aortic aneurysm. In the IMPROVE trial at 3 months post-randomisation, 21% of surviving patients did not complete health-related quality of life questionnaires (assessed by EQ-5D-3L). We address this problem by developing a web-based tool that provides a practical approach for eliciting expert opinion about quality of life differences between patients with missing versus complete data. We show how this expert opinion can define informative priors within a fully Bayesian framework to perform sensitivity analyses that allow the missing data to depend upon unobserved patient characteristics. A total of 26 experts, of 46 asked to participate, completed the elicitation exercise. The elicited quality of life scores were lower on average for the patients with missing versus complete data, but there was considerable uncertainty in these elicited values. The missing at random analysis found that patients randomised to the emergency endovascular strategy versus open repair had higher average (95% credible interval) quality of life scores of 0.062 (-0.005 to 0.130). Our sensitivity analysis that used the elicited expert information as pooled priors found that the gain in average quality of life for the emergency endovascular strategy versus open repair was 0.076 (-0.054 to 0.198). We provide and exemplify a practical tool for eliciting the expert opinion required by recommended approaches to the sensitivity analyses of randomised controlled trials. We show how this approach allows the trial analysis to fully recognise the uncertainty that arises from making alternative, plausible assumptions about the reasons for missing data. This tool can be widely used in the design, analysis and interpretation of future trials, and to facilitate this, materials are available for download.

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

PubMed

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

2015-08-12

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

The Effectiveness of Disaster Risk Communication: A Systematic Review of Intervention Studies

PubMed Central

Bradley, Declan T; McFarland, Marie; Clarke, Mike

2014-01-01

Introduction: A disaster is a serious disruption to the functioning of a community that exceeds its capacity to cope within its own resources. Risk communication in disasters aims to prevent and mitigate harm from disasters, prepare the population before a disaster, disseminate information during disasters and aid subsequent recovery. The aim of this systematic review is to identify, appraise and synthesise the findings of studies of the effects of risk communication interventions during four stages of the disaster cycle. Methods: We searched the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, PsycInfo, Sociological Abstracts, Web of Science and grey literature sources for randomised trials, cluster randomised trials, controlled and uncontrolled before and after studies, interrupted time series studies and qualitative studies of any method of disaster risk communication to at-risk populations. Outcome criteria were disaster-related knowledge and behaviour, and health outcomes. Results: Searches yielded 5,224 unique articles, of which 100 were judged to be potentially relevant. Twenty-five studies met the inclusion criteria, and two additional studies were identified from other searching. The studies evaluated interventions in all four stages of the disaster cycle, included a variety of man-made, natural and infectious disease disasters, and were conducted in many disparate settings. Only one randomised trial and one cluster randomised trial were identified, with less robust designs used in the other studies. Several studies reported improvements in disaster-related knowledge and behaviour. Discussion: We identified and appraised intervention studies of disaster risk communication and present an overview of the contemporary literature. Most studies used non-randomised designs that make interpretation challenging. We do not make specific recommendations for practice but highlight the need for high-quality randomised trials and appropriately-analysed cluster randomised trials in the field of disaster risk communication where these can be conducted within an appropriate research ethics framework. PMID:25642365

Results of a multicentre randomised controlled trial of statistical process control charts and structured diagnostic tools to reduce ward-acquired meticillin-resistant Staphylococcus aureus: the CHART Project.

PubMed

Curran, E; Harper, P; Loveday, H; Gilmour, H; Jones, S; Benneyan, J; Hood, J; Pratt, R

2008-10-01

Statistical process control (SPC) charts have previously been advocated for infection control quality improvement. To determine their effectiveness, a multicentre randomised controlled trial was undertaken to explore whether monthly SPC feedback from infection control nurses (ICNs) to healthcare workers of ward-acquired meticillin-resistant Staphylococcus aureus (WA-MRSA) colonisation or infection rates would produce any reductions in incidence. Seventy-five wards in 24 hospitals in the UK were randomised into three arms: (1) wards receiving SPC chart feedback; (2) wards receiving SPC chart feedback in conjunction with structured diagnostic tools; and (3) control wards receiving neither type of feedback. Twenty-five months of pre-intervention WA-MRSA data were compared with 24 months of post-intervention data. Statistically significant and sustained decreases in WA-MRSA rates were identified in all three arms (P<0.001; P=0.015; P<0.001). The mean percentage reduction was 32.3% for wards receiving SPC feedback, 19.6% for wards receiving SPC and diagnostic feedback, and 23.1% for control wards, but with no significant difference between the control and intervention arms (P=0.23). There were significantly more post-intervention 'out-of-control' episodes (P=0.021) in the control arm (averages of 0.60, 0.28, and 0.28 for Control, SPC and SPC+Tools wards, respectively). Participants identified SPC charts as an effective communication tool and valuable for disseminating WA-MRSA data.

Elective repeat caesarean section versus induction of labour for women with a previous caesarean birth.

PubMed

Dodd, Jodie M; Crowther, Caroline A; Grivell, Rosalie M; Deussen, Andrea R

2014-12-19

When a woman has had a previous caesarean birth and requires induction of labour in a subsequent pregnancy there are two options for her care, an elective repeat caesarean or planned induction of labour. While there are risks and benefits for both elective repeat caesarean birth and planned induction of labour, current sources of information are limited to non-randomised cohort studies. Studies designed in this way have significant potential for bias and consequently any conclusions based on these results are limited in their reliability and should be interpreted with caution. To assess, using the best available evidence, the benefits and harms of elective repeat caesarean section and planned induction of labour for women with a previous caesarean birth, who require induction of labour in a subsequent pregnancy. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (31 October 2014). Randomised controlled trials with reported data that compared outcomes in mothers and babies for women who planned an elective repeat caesarean section with outcomes in women who planned induction of labour, where a previous birth had been by caesarean. There was no data extraction performed. There were no randomised controlled trials identified. Both planned elective repeat caesarean section and planned induction of labour for women with a prior caesarean birth are associated with benefits and harms. Evidence for these care practices is drawn from non-randomised studies that are associated with potential bias. Any results and conclusions must therefore be interpreted with caution. Randomised controlled trials are required to provide the most reliable evidence regarding the benefits and harms of both planned elective repeat caesarean section and planned induction of labour for women with a previous caesarean birth.

Inositol for prevention of neural tube defects: a pilot randomised controlled trial - CORRIGENDUM

PubMed Central

Greene, Nicholas D. E.; Leung, Kit-Yi; Gay, Victoria; Burren, Katie; Mills, Kevin; Chitty, Lyn S.; Copp, Andrew J.

2016-01-01

Although peri-conceptional folic acid (FA) supplementation can prevent a proportion of neural tube defects (NTDs), there is increasing evidence that many NTDs are FA non-responsive. The vitamin-like molecule inositol may offer a novel approach to preventing FA-non-responsive NTDs. Inositol prevented NTDs in a genetic mouse model, and was well tolerated by women in a small study of NTD recurrence. In the present study, we report the Prevention of Neural Tube Defects by Inositol (PONTI) pilot study designed to gain further experience of inositol usage in human pregnancy as a preliminary trial to a future large-scale controlled trial to evaluate efficacy of inositol in NTD prevention. Study subjects were UK women with a previous NTD pregnancy who planned to become pregnant again. Of 117 women who made contact, ninety-nine proved eligible and forty-seven agreed to be randomised (double-blind) to peri-conceptional supplementation with inositol plus FA or placebo plus FA. In total, thirty-three randomised pregnancies produced one NTD recurrence in the placebo plus FA group (n 19) and no recurrences in the inositol plus FA group (n 14). Of fifty-two women who declined randomisation, the peri-conceptional supplementation regimen and outcomes of twenty-four further pregnancies were documented. Two NTDs recurred, both in women who took only FA in their next pregnancy. No adverse pregnancy events were associated with inositol supplementation. The findings of the PONTI pilot study encourage a large-scale controlled trial of inositol for NTD prevention, but indicate the need for a careful study design in view of the unwillingness of many high-risk women to be randomised. PMID:26917444

Inositol for the prevention of neural tube defects: a pilot randomised controlled trial.

PubMed

Greene, Nicholas D E; Leung, Kit-Yi; Gay, Victoria; Burren, Katie; Mills, Kevin; Chitty, Lyn S; Copp, Andrew J

2016-03-28

Although peri-conceptional folic acid (FA) supplementation can prevent a proportion of neural tube defects (NTD), there is increasing evidence that many NTD are FA non-responsive. The vitamin-like molecule inositol may offer a novel approach to preventing FA-non-responsive NTD. Inositol prevented NTD in a genetic mouse model, and was well tolerated by women in a small study of NTD recurrence. In the present study, we report the Prevention of Neural Tube Defects by Inositol (PONTI) pilot study designed to gain further experience of inositol usage in human pregnancy as a preliminary trial to a future large-scale controlled trial to evaluate efficacy of inositol in NTD prevention. Study subjects were UK women with a previous NTD pregnancy who planned to become pregnant again. Of 117 women who made contact, ninety-nine proved eligible and forty-seven agreed to be randomised (double-blind) to peri-conceptional supplementation with inositol plus FA or placebo plus FA. In total, thirty-three randomised pregnancies produced one NTD recurrence in the placebo plus FA group (n 19) and no recurrences in the inositol plus FA group (n 14). Of fifty-two women who declined randomisation, the peri-conceptional supplementation regimen and outcomes of twenty-two further pregnancies were documented. Two NTD recurred, both in women who took only FA in their next pregnancy. No adverse pregnancy events were associated with inositol supplementation. The findings of the PONTI pilot study encourage a large-scale controlled trial of inositol for NTD prevention, but indicate the need for a careful study design in view of the unwillingness of many high-risk women to be randomised.

A systematic review of randomised controlled trials evaluating the effect of mother/baby skin-to-skin care on successful breast feeding.

PubMed

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

2003-06-01

to examine the effects of early skin-to-skin contact between mother and baby on the initiation and duration of breast feeding. electronic databases--the Cochrane Library, MEDLINE,CINAHL and EMBASE. References of studies were examined to identify additional trials and contact was made with researchers in the field. Study selection criteria: randomised or quasi-randomised controlled trials in any language in which skin-to-skin contact between mothers and their healthy full-term newborn babies was compared to routine contact. Primary outcomes were success of first breast feed and duration of breast feeding. Secondary outcomes included, baby temperature and behaviour. STUDY-QUALITY ASSESSMENT: validity of included studies was assessed using criteria defined by the Cochrane Collaboration. Application of inclusion criteria, validity assessment and data extraction were carried out independently by two reviewers with a third reviewer to resolve differences. seven randomised controlled trials were identified. Five studies assessed duration of breast feeding with mixed results. None of the studies assessed the success of the first breast-feeding experience. Study quality was variable with methods of randomisation and blinding of assessment unclear in four of the five studies providing relevant results. the findings of this systematic review fail to support the current initiatives to implement changes in clinical practice to include skin-to-skin contact. Methodological flaws within the included studies prohibit firm conclusions being reached with regard to the effect of skin-to-skin contact on the duration of breast feeding, timing of first breast feed or baby physiological factors. The review highlights the need for further primary research to assess the effect of skin-to-skin contact on the breast-feeding experience.

Total or Partial Knee Arthroplasty Trial - TOPKAT: study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background In the majority of patients with osteoarthritis of the knee the disease originates in the medial compartment. There are two fundamentally different approaches to knee replacement for patients with unicompartmental disease: some surgeons feel that it is always best to replace both the knee compartments with a total knee replacement (TKR); whereas others feel it is best to replace just the damaged component of the knee using a partial or unicompartment replacement (UKR). Both interventions are established and well-documented procedures. Little evidence exists to prove the clinical and cost-effectiveness of either management option. This provides an explanation for the high variation in treatment of choice by individual surgeons for the same knee pathology. The aim of the TOPKAT study will be to assess the clinical and cost effectiveness of TKRs compared to UKRs in patients with medial compartment osteoarthritis. Methods/Design The design of the study is a single layer multicentre superiority type randomised controlled trial of unilateral knee replacement patients. Blinding will not be possible as the surgical scars for each procedure differ. We aim to recruit 500 patients from approximately 28 secondary care orthopaedic units from across the UK including district general and teaching hospitals. Participants will be randomised to either UKR or TKR. Randomisation will occur using a web-based randomisation system. The study is pragmatic in terms of implant selection for the knee replacement operation. Participants will be followed up for 5 years. The primary outcome is the Oxford Knee Score, which will be collected via questionnaires at 2 months, 1 year and then annually to 5 years. Secondary outcomes will include cost-effectiveness, patient satisfaction and complications data. Trial registration Current Controlled Trials ISRCTN03013488; ClinicalTrials.gov Identifier: NCT01352247 PMID:24028414

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

PubMed

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

2018-05-01

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

Effect of training and lifting equipment for preventing back pain in lifting and handling: systematic review

PubMed Central

2008-01-01

Objectives To determine whether advice and training on working techniques and lifting equipment prevent back pain in jobs that involve heavy lifting. Data sources Medline, Embase, CENTRAL, Cochrane Back Group’s specialised register, CINAHL, Nioshtic, CISdoc, Science Citation Index, and PsychLIT were searched up to September-November 2005. Review methods The primary search focused on randomised controlled trials and the secondary search on cohort studies with a concurrent control group. Interventions aimed to modify techniques for lifting and handling heavy objects or patients and including measurements for back pain, consequent disability, or sick leave as the main outcome were considered for the review. Two authors independently assessed eligibility of the studies and methodological quality of those included. For data synthesis, we summarised the results of studies comparing similar interventions. We used odds ratios and effect sizes to combine the results in a meta-analysis. Finally, we compared the conclusions of the primary and secondary analyses. Results Six randomised trials and five cohort studies met the inclusion criteria. Two randomised trials and all cohort studies were labelled as high quality. Eight studies looked at lifting and moving patients, and three studies were conducted among baggage handlers or postal workers. Those in control groups received no intervention or minimal training, physical exercise, or use of back belts. None of the comparisons in randomised trials (17 720 participants) yielded significant differences. In the secondary analysis, none of the cohort studies (772 participants) had significant results, which supports the results of the randomised trials. Conclusions There is no evidence to support use of advice or training in working techniques with or without lifting equipment for preventing back pain or consequent disability. The findings challenge current widespread practice of advising workers on correct lifting technique. PMID:18244957

Ursodeoxycholic acid versus placebo, and early term delivery versus expectant management, in women with intrahepatic cholestasis of pregnancy: semifactorial randomised clinical trial.

PubMed

Chappell, Lucy C; Gurung, Vinita; Seed, Paul T; Chambers, Jenny; Williamson, Catherine; Thornton, James G

2012-06-13

To test whether ursodeoxycholic acid reduces pruritus in women with intrahepatic cholestasis of pregnancy, whether early term delivery does not increase the incidence of caesarean section, and the feasibility of recruiting women with intrahepatic cholestasis of pregnancy to trials of these interventions. First phase of a semifactorial randomised controlled trial. Nine consultant led maternity units, United Kingdom. 125 women with intrahepatic cholestasis of pregnancy (pruritus and raised levels of serum bile acids) or pruritus and raised alanine transaminase levels (>100 IU/L) recruited after 24 weeks' gestation and followed until delivery. 56 women were randomised to ursodeoxycholic acid, 55 to placebo, 30 to early term delivery, and 32 to expectant management. Ursodeoxycholic acid 500 mg twice daily or placebo increased as necessary for symptomatic or biochemical improvement until delivery; early term delivery (induction or delivery started between 37+0 and 37+6) or expectant management (spontaneous labour awaited until 40 weeks' gestation or caesarean section undertaken by normal obstetric guidelines, usually after 39 weeks' gestation). The primary outcome for ursodeoxycholic acid was maternal itch (arithmetic mean of measures (100 mm visual analogue scale) of worst itch in past 24 hours) and for the timing of delivery was caesarean section. Secondary outcomes were other maternal and perinatal outcomes and recruitment rates. Ursodeoxycholic acid reduced itching by -16 mm (95% confidence interval -27 mm to -6 mm), less than the 30 mm difference prespecified by clinicians and women as clinically meaningful. 32% (14/44) of women randomised to ursodeoxycholic acid experienced a reduction in worst itching by at least 30 mm compared with 16% (6/37) randomised to placebo. The difference of 16% (95% confidence interval -3 to 34); this would represent a number needed to treat of 6, but it failed to reach significance. Early term delivery did not increase caesarean sections (7/30 (23%) in the early term delivery group versus 11/32 (33%) in the expectant management group (relative risk 0.70, 95% confidence interval 0.31 to 1.57). No serious harms were noted in either trial. 22% (73/325) of eligible women participated in the drug trial and 19% (39/209) in the timing of delivery trial; both groups had a similar spectrum of disease severity to non-participants. Ursodeoxycholic acid significantly reduces pruritus, but the size of the benefit may be too small for most doctors to recommend it, or for most women to want to take it. Women are, however, likely to differ in whether they consider the benefit to be worthwhile. Planned early term delivery seems not to increase incidence of caesarean section, although a small increase cannot be excluded. A trial to test whether ursodeoxycholic acid reduces adverse perinatal outcomes would have to be large, but is feasible. A trial to test the effect of early term delivery on adverse fetal outcomes would have to be significantly larger and may not be feasible. Current Controlled Trials ISRCTN37730443.

Ursodeoxycholic acid versus placebo, and early term delivery versus expectant management, in women with intrahepatic cholestasis of pregnancy: semifactorial randomised clinical trial

PubMed Central

Chappell, Lucy C; Gurung, Vinita; Seed, Paul T; Chambers, Jenny; Williamson, Catherine

2012-01-01

Objectives To test whether ursodeoxycholic acid reduces pruritus in women with intrahepatic cholestasis of pregnancy, whether early term delivery does not increase the incidence of caesarean section, and the feasibility of recruiting women with intrahepatic cholestasis of pregnancy to trials of these interventions. Design First phase of a semifactorial randomised controlled trial. Setting Nine consultant led maternity units, United Kingdom. Participants 125 women with intrahepatic cholestasis of pregnancy (pruritus and raised levels of serum bile acids) or pruritus and raised alanine transaminase levels (>100 IU/L) recruited after 24 weeks’ gestation and followed until delivery. 56 women were randomised to ursodeoxycholic acid, 55 to placebo, 30 to early term delivery, and 32 to expectant management. Interventions Ursodeoxycholic acid 500 mg twice daily or placebo increased as necessary for symptomatic or biochemical improvement until delivery; early term delivery (induction or delivery started between 37+0 and 37+6) or expectant management (spontaneous labour awaited until 40 weeks’ gestation or caesarean section undertaken by normal obstetric guidelines, usually after 39 weeks’ gestation). Main outcome measures The primary outcome for ursodeoxycholic acid was maternal itch (arithmetic mean of measures (100 mm visual analogue scale) of worst itch in past 24 hours) and for the timing of delivery was caesarean section. Secondary outcomes were other maternal and perinatal outcomes and recruitment rates. Results Ursodeoxycholic acid reduced itching by −16 mm (95% confidence interval −27 mm to −6 mm), less than the 30 mm difference prespecified by clinicians and women as clinically meaningful. 32% (14/44) of women randomised to ursodeoxycholic acid experienced a reduction in worst itching by at least 30 mm compared with 16% (6/37) randomised to placebo. The difference of 16% (95% confidence interval −3 to 34); this would represent a number needed to treat of 6, but it failed to reach significance. Early term delivery did not increase caesarean sections (7/30 (23%) in the early term delivery group versus 11/32 (33%) in the expectant management group (relative risk 0.70, 95% confidence interval 0.31 to 1.57). No serious harms were noted in either trial. 22% (73/325) of eligible women participated in the drug trial and 19% (39/209) in the timing of delivery trial; both groups had a similar spectrum of disease severity to non-participants. Conclusions Ursodeoxycholic acid significantly reduces pruritus, but the size of the benefit may be too small for most doctors to recommend it, or for most women to want to take it. Women are, however, likely to differ in whether they consider the benefit to be worthwhile. Planned early term delivery seems not to increase incidence of caesarean section, although a small increase cannot be excluded. A trial to test whether ursodeoxycholic acid reduces adverse perinatal outcomes would have to be large, but is feasible. A trial to test the effect of early term delivery on adverse fetal outcomes would have to be significantly larger and may not be feasible. Trial registration Current Controlled Trials ISRCTN37730443. PMID:22695903

Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on intensity of infection and antibody responses to schistosome antigens: results of a randomised, placebo-controlled trial

PubMed Central

2009-01-01

Background Praziquantel treatment of schistosomiasis during pregnancy was only recommended in 2002; hence the effects of treatment during pregnancy are not fully known. We have therefore evaluated the effects on infection intensity and the immunological effects of praziquantel treatment against Schistosoma mansoni during pregnancy, compared with treatment after delivery. Methods A nested cohort of 387 Schistosoma mansoni infected women was recruited within a larger trial of de-worming during pregnancy. Women were randomised to receive praziquantel or placebo during pregnancy. All women were treated after delivery. Infection intensity after treatment was assessed by a single Kato-Katz examination of stool samples with duplicate slides and categorised as undetected, light (1–99 eggs per gram (epg)), moderate (100–399 epg) or heavy (≥400 epg). Antibodies against S. mansoni worm and egg antigens were measured by ELISA. Results were compared between women first treated during pregnancy and women first treated after delivery. Results At enrolment, 252 (65.1%) of the women had light infection (median (IQR) epg: 35 (11, 59)), 75 (19.3%) moderate (median (IQR) epg: 179(131, 227)) and 60 (15.5%) had heavy infection (median (IQR) epg: 749 (521, 1169)) with S. mansoni. At six weeks after praziquantel treatment during pregnancy S. mansoni infection was not detectable in 81.9% of the women and prevalence and intensity had decreased to 11.8% light, 4.7% moderate and 1.6% heavy a similar reduction when compared with those first treated after delivery (undetected (88.5%), light (10.6%), moderate (0.9%) and heavy (0%), p = 0.16). Parasite specific antibody levels were lower during pregnancy than after delivery. Praziquantel treatment during pregnancy boosted anti-worm IgG isotypes and to a lesser extent IgE, but these boosts were less pronounced than in women whose treatment was delayed until after delivery. Praziquantel had limited effects on antibodies against egg antigens. Conclusion S mansoni antigen-specific antibody levels and praziquantel-induced boosts in antibody levels were broadly suppressed during pregnancy, but this was not associated with major reduction in the efficacy of praziquantel. Long-term implications of these findings in relation to resistance to re-infection remain to be explored. Trial registration International Standard Randomised Controlled Trial Number for the current study: ISRCTN32849447 http://www.controlled-trials.com/ISRCTN32849447/elliott PMID:19296834

Feasibility of an online intervention (STAK-D) to promote physical activity in children with type 1 diabetes: protocol for a randomised controlled trial.

PubMed

Blake, Holly; Quirk, Helen; Leighton, Paul; Randell, Tabitha; Greening, James; Guo, Boliang; Glazebrook, Cris

2016-12-08

Regular physical activity has important health benefits for children with type 1 diabetes mellitus (T1DM), yet children and their parents face barriers to participation such as lack of self-efficacy or concerns around hypoglycaemia. Multimedia interventions are useful for educating children about their health and demonstrate potential to improve children's health-related self-efficacy, but few paediatric clinics offer web-based resources as part of routine care. The Steps to Active Kids with Diabetes (STAK-D) programme is an online intervention grounded in psychological theory (social cognitive theory) and informed by extensive preliminary research. The aim of the programme is to encourage and support safe engagement with physical activity for children with T1DM. The aim of this research is to explore the feasibility of delivering the STAK-D programme to children aged 9-12 years with T1DM, and to assess the feasibility of further research to demonstrate its clinical and cost-effectiveness. Up to 50 children aged 9-12 years with T1DM and their parents will be recruited from two paediatric diabetes clinics in the UK. Child-parent dyads randomised to the intervention group will have access to the intervention website (STAK-D) and a wrist-worn activity monitor for 6 months. The feasibility of intervention and further research will be assessed by rate of recruitment, adherence, retention, data completion and adverse events. Qualitative interviews will be undertaken with a subsample of children and parents (up to 25 dyads) and health care professionals (up to 10). Health outcomes and the feasibility of outcome measurement tools will be assessed. These include self-efficacy (CSAPPA), objective physical activity, self-reported physical activity (PAQ), fear of hypoglycaemia (CHFS; PHFS), glycaemic control (HbA1c), insulin dose, Body Mass Index (BMI), health-related quality of life (CHU9D; CHQ-PF28), health service use and patient-clinician communication. Assessments will be taken at baseline (T0), 8 weeks (T1) and at 6-month follow-up (T2). The goal of this feasibility trial is to assess the delivery of STAK-D to promote physical activity among children with T1DM, and to assess the potential for further, definitive research to demonstrate its effectiveness. Results will provide the information necessary to design a larger randomised controlled trial and maximise the recruitment rate, intervention delivery and trial retention. ISRCTN, ISRCTN48994721 . Registered on 28 October 2016.

Feasibility and preliminary efficacy of the 'HEYMAN' healthy lifestyle program for young men: a pilot randomised controlled trial.

PubMed

Ashton, Lee M; Morgan, Philip J; Hutchesson, Melinda J; Rollo, Megan E; Collins, Clare E

2017-01-13

In young men, unhealthy lifestyle behaviours can be detrimental to their physical and/or mental health and set them on a negative health trajectory into adulthood. Despite this, there is a lack of evidence to guide development of effective health behaviour change interventions for young men. This study assessed the feasibility and preliminary efficacy of the 'HEYMAN' (Harnessing Ehealth to enhance Young men's Mental health, Activity and Nutrition) healthy lifestyle program for young men. A pilot RCT with 50 young men aged 18-25 years randomised to the HEYMAN intervention (n = 26) or waitlist control (n = 24). HEYMAN was a 3-month intervention, targeted for young men to improve eating habits, activity levels and well-being. Intervention development was informed by a participatory research model (PRECEDE-PROCEED). Intervention components included eHealth support (website, wearable device, Facebook support group), face-to-face sessions (group and individual), a personalised food and nutrient report, home-based resistance training equipment and a portion control tool. Outcomes included: feasibility of research procedures (recruitment, randomisation, data collection and retention) and of intervention components. Generalized linear mixed models estimated the treatment effect at 3-months for the primary outcomes: pedometer steps/day, diet quality, well-being and several secondary outcomes. A 7-week recruitment period was required to enrol 50 young men. A retention rate of 94% was achieved at 3-months post-intervention. Retained intervention participants (n = 24) demonstrated reasonable usage levels for most program components and also reported reasonable levels of program component acceptability for attractiveness, comprehension, usability, support, satisfaction and ability to persuade, with scores ranging from 3.0 to 4.6 (maximum 5). No significant intervention effects were observed for the primary outcomes of steps/day (1012.7, 95% CI = -506.2, 2531.6, p = 0.191, d = 0.36), diet quality score (3.6, 95% CI = -0.4, 7.6, p = 0.081, d = 0.48) or total well-being score (0.4, 95% CI = -1.6, 2.5, p = 0.683, d = 0.11). Significant intervention effects were found for daily vegetable servings, energy-dense, nutrient-poor foods, MVPA, weight, BMI, fat mass, waist circumference and cholesterol (all p < 0.05). The HEYMAN program demonstrated feasibility in assisting young men to make some positive lifestyle changes. This provides support for the conduct of a larger, fully-powered RCT, but with minor amendments to research procedures and intervention components required. Australian New Zealand Clinical Trials Registry ACTRN12616000350426 .

Effect of bilberry juice on indices of muscle damage and inflammation in runners completing a half-marathon: a randomised, placebo-controlled trial.

PubMed

Lynn, Anthony; Garner, Samantha; Nelson, Nichola; Simper, Trevor N; Hall, Anna C; Ranchordas, Mayur K

2018-01-01

Emerging evidence indicates that fruits rich in polyphenols may attenuate exercise-induced muscle damage and associated markers of inflammation and soreness. This study was conducted to determine whether bilberry juice (BJ), which is particularly rich in polyphenols, reduces markers of muscle damage in runners completing a half marathon. A total of 21 recreationally trained runners (age 30.9 ± 10.4 y; mass 71.6 ± 11.0 kg; M = 16; F = 5) were recruited to a single blind, randomised, placebo-controlled, parallel study. Participants were block randomised to consume 2 × 200 ml of BJ or energy-matched control drink (PLA) for 5 d before the Sheffield Half Marathon, on race day, and for 2 days post-race. Measurements of delayed onset muscle soreness (DOMS), muscle damage (creatine kinase; CK) and inflammation (c-reactive protein; CRP) were taken at baseline, pre-race, post-race, 24 h post-race and 48 h post-race. The effect of treatment on outcome measures was analysed using magnitude-based inferences based on data from 19 participants; 2 participants were excluded from the analyses because they did not provide samples for all time points. The half marathon caused elevations in DOMS, CRP and CK. BJ had a possibly harmful effect on DOMS from pre-race to immediately post-race (11.6%, 90% CI ± 14.7%), a likely harmful effect on CRP from pre-race to 24 h post-race (mean difference ES 0.56, 90% CI ± 0.72) and a possibly harmful effect on CRP from pre-race to 48 h post-race (ES 0.12, 90% CI ± 0.69). At other time points, the differences between the BJ and PLA groups in DOMS and CRP were unclear, possibly trivial or likely trivial . Differences in the changes in CK between BJ and PLA were unclear at every time point other than from baseline to pre-race, where BJ had a possibly harmful effect on reducing muscle damage (ES 0.23, 90% CI ± 0.57). Despite being a rich source of antioxidant and anti-inflammatory phytochemicals, BJ evoked small to moderate increases in exercise-induced DOMS and CRP. Further larger studies are required to confirm these unexpected preliminary results.

Probiotics for induction of remission in ulcerative colitis.

PubMed

Mallon, P; McKay, D; Kirk, S; Gardiner, K

2007-10-17

Ulcerative Colitis (UC) is an inflammatory condition affecting the colon with an incidence of approximately 10-20 per 100,000 per year. No existing intervention is effective in all patients with a proportion requiring colectomy. There are significant proportion of patients who experience adverse effects with current therapies. Consequently, new alternatives for the treatment of UC are constantly being sought. Probiotics are live microbial feed supplements that may beneficially affect the host by improving intestinal microbial balance, enhancing gut barrier function and improving local immune response. To assess the efficacy of probiotics compared with placebo or standard medical treatment (5-aminosalicylates, sulfasalazine or corticosteroids) for the induction of remission in active ulcerative colitis. A comprehensive search for relevant randomised controlled trials (RCT's) was carried out using MEDLINE (1966-January 2006), EMBASE (January 1985- 2006) and CENTRAL. The Cochrane IBD/FBD Review Group Specialised Trials Registrar was also searched. The Australasian Medical Index, Chinese Biomedical Literature Database, Latin American Caribbean Health Sciences Literature (LILACS), and the Japan Information Centre of Science and Technology File on Science, Technology and Medicine (JICST-E) were also used to identify abstracts. Conference proceedings from the Falk Symposium, Digestive Disease Week (DDW) and the United European Digestive Disease week were hand-searched. Authors of relevant studies and drug companies were contacted regarding ongoing or unpublished trials that may be relevant to the review. Randomised controlled trials investigating the effectiveness of probiotics compared to standard treatments in the induction of remission of active ulcerative colitis Two authors independently assessed trial quality and extracted data for analysis. Data were analysed using RevMan 4.2.7. A formal meta-analysis was not preformed due to differences in probiotics, outcomes and trial methodology. None of the included studies reported any statistically significant differences in remission or clinical improvement rates between probiotic and placebo or active comparator groups. Conventional therapy combined with a probiotic does not improve overall remission rates in patients with mild to moderate ulcerative colitis. However, there is limited evidence that probiotics added to standard therapy may provide modest benefits in terms of reduction of disease activity in patients with mild to moderately severe ulcerative colitis. Whether probiotics are as effective in patients with severe and more extensive disease and whether they can be used as an alternative to existing therapies is unknown. Further well designed, larger randomised controlled trials are needed to determine whether probiotics can be used as an alternative to current treatment modalities.

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.

Metformin and dietary advice to improve insulin sensitivity and promote gestational restriction of weight among pregnant women who are overweight or obese: the GRoW Randomised Trial.

PubMed

Dodd, Jodie M; Grivell, Rosalie M; Deussen, Andrea R; Dekker, Gustaaf; Louise, Jennie; Hague, William

2016-11-21

Obesity is a significant global health problem, with approximately 50% of women entering pregnancy having a body mass index greater than or equal to 25 kg/m 2 . Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant. Currently available data from large scale randomised trials and systematic reviews highlight only modest effects of antenatal dietary and lifestyle interventions in limiting gestational weight gain, with little impact on clinically relevant pregnancy outcomes. Further information evaluating alternative strategies is required. The aims of this randomised controlled trial are to assess whether the use of metformin as an adjunct therapy to dietary and lifestyle advice for overweight and obese women during pregnancy is effective in improving maternal, fetal and infant health outcomes. Design: Multicentre randomised, controlled trial. Women with a singleton, live gestation between 10 +0 -20 +0 weeks who are obese or overweight (defined as body mass index greater than or equal to 25 kg/m 2 ), at the first antenatal visit. Trial Entry & Randomisation: Eligible, consenting women will be randomised between 10 +0 and 20 +0 weeks gestation using an online computer randomisation system, and randomisation schedule prepared by non-clinical research staff with balanced variable blocks. Stratification will be according to maternal BMI at trial entry, parity, and centre where planned to give birth. Treatment Schedules: Women randomised to the Metformin Group will receive a supply of 500 mg oral metformin tablets. Women randomised to the Placebo Group will receive a supply of identical appearing and tasting placebo tablets. Women will be instructed to commence taking one tablet daily for a period of one week, increasing to a maximum of two tablets twice daily over four weeks and then continuing until birth. Women, clinicians, researchers and outcome assessors will be blinded to the allocated treatment group. All women will receive three face-to-face sessions (two with a research dietitian and one with a trained research assistant), and three telephone calls over the course of their pregnancy, in which they will be provided with dietary and lifestyle advice, and encouraged to make change utilising a SMART goals approach. Primary Study Outcome: infant birth weight >4000 grams. 524 women to detect a difference from 15.5% to 7.35% reduction in infants with birth weight >4000 grams (p = 0.05, 80% power, two-tailed). This is a protocol for a randomised trial. The findings will contribute to the development of evidence based clinical practice guidelines. Australian and New Zealand Clinical Trials Registry ACTRN12612001277831 , prospectively registered 10 th of December, 2012.

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

PubMed

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

2015-12-15

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

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

PubMed Central

2014-01-01

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

Physical therapy for Bell s palsy (idiopathic facial paralysis).

PubMed

Teixeira, Lázaro Juliano; Soares, Bernardo Garcia de Oliveira; Vieira, Vanessa Pedrosa; Prado, Gilmar F

2008-07-16

Bell's palsy (idiopathic facial paralysis) is commonly treated by physical therapy services with various therapeutic strategies and devices. There are many questions about their efficacy and effectiveness. To evaluate the efficacy of physical therapies on the outcome of Bell's palsy. We searched the Cochrane Neuromuscular Disease Group Trials Register (February 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2007), MEDLINE (January 1966 to February 2008), EMBASE (January 1980 to February 2008), LILACS (January 1982 to February 2008), PEDro (from 1929 to February 2008), and CINAHL (January 1982 to February 2008). We selected randomised or quasi-randomised controlled trials involving any physical therapy. We included participants of any age with a diagnosis of Bell's palsy and all degrees of severity. The outcome measures were: incomplete recovery six months after randomisation, motor synkinesis, crocodile tears or facial spasm six months after onset, incomplete recovery after one year and adverse effects attributable to the intervention. Titles and abstracts identified from the register were scrutinized. The assessment of methodological quality took into account secure method of randomisation, allocation concealment, observer blinding, patient blinding, differences at baseline of the experimental groups, and completeness of follow-up. Data were extracted using a specially constructed data extraction form. Separate subgroup analyses of participants with more and less severe disability were undertaken. The search identified 45 potentially relevant articles. Six studies met the inclusion criteria. Three trials studied the efficacy of electrostimulation (294 participants) and three exercises (253 participants). Neither treatment produced significantly more improvement than the control treatment or no treatment. There was limited evidence that improvement began earlier in the exercise group. There is no evidence of significant benefit or harm from any physical therapy for idiopathic facial paralysis. The possibility that facial exercise reduces time to recover and sequelae needs confirming with good quality randomised controlled trials.

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

PubMed Central

2012-01-01

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

The LeucoPatch® system in the management of hard-to-heal diabetic foot ulcers: study protocol for a randomised controlled trial.

PubMed

Game, Frances; Jeffcoate, William; Tarnow, Lise; Day, Florence; Fitzsimmons, Deborah; Jacobsen, Judith

2017-10-10

Diabetic foot ulcers are a common and severe complication of diabetes mellitus. Standard treatment includes debridement, offloading, management of infection and revascularisation where appropriate, although healing times may be long. The LeucoPatch® device is used to generate an autologous platelet-rich fibrin and leucocyte wound dressing produced from the patient's own venous blood by centrifugation, but without the addition of any reagents. The final product comprises a thin, circular patch composed predominantly of fibrin together with living platelets and leucocytes. Promising results have been obtained in non-controlled studies this system, but this now needs to be tested in a randomised controlled trial (RCT). If confirmed, the LeucoPatch® may become an important new tool in the armamentarium in the management of diabetic foot ulcers which are hard-to-heal. People with diabetes and hard-to-heal ulcers of the foot will receive either pre-specified good standard care or good standard care supplemented by the application of the LeucoPatch® device. The primary outcome will be the percentage of ulcers healed within 20 weeks. Healing will be defined as complete epithelialisation without discharge that is maintained for 4 weeks and is confirmed by an observer blind to randomisation group. Ulcers of the foot are a major source of morbidity to patients with diabetes and costs to health care economies. The study population is designed to be as inclusive as possible with the aim of maximising the external validity of any findings. The primary outcome measure is healing within 20 weeks of randomisation and the trial also includes a number of secondary outcome measures. Among these are rate of change in ulcer area as a predictor of the likelihood of eventual healing, minor and major amputation of the target limb, the incidence of infection and quality of life. International Standard Randomised Controlled Trial, ISRCTN27665670 . Registered on 5 July 2013.

Enzyme potentiated desensitisation in treatment of seasonal allergic rhinitis: double blind randomised controlled study

PubMed Central

Radcliffe, Michael J; Lewith, George T; Turner, Richard G; Prescott, Philip; Church, Martin K; Holgate, Stephen T

2003-01-01

Objective To assess the efficacy of enzyme potentiated desensitisation in the treatment of severe summer hay fever poorly controlled by pharmacotherapy. Design Double blind randomised placebo controlled parallel group study. Setting Hospital in Hampshire. Participants 183 participants aged between 18 and 64 with a history of severe summer hay fever for at least two years; all were skin prick test positive to timothy grass pollen. 90 randomised to active treatment; 93 randomised to placebo. Interventions Active treatment: two injections of enzyme potentiated desensitisation, given between eight and 11 weeks apart, each comprising 200 Fishman units of β glucuronidase, 50 pg 1,3-cyclohexanediol, 50 ng protamine sulphate, and a mixed inhaled allergen extract (pollen mixes for trees, grasses, and weeds; allergenic fungal spores; cat and dog danders; dust and storage mites) in a total volume of 0.05 ml of buffered saline. Placebo: two injections of 0.05 ml buffered saline solution. Main outcome measures Proportion of problem-free days; global rhinoconjunctivitis quality of life scores assessed weekly during pollen season. Results The active treatment group and the placebo group did not differ in the proportion of problem-free days, quality of life scores, symptom severity scores, change in quantitative skin prick provocation threshold, or change in conjunctival provocation threshold. No clinically significant adverse reactions occurred. Conclusions Enzyme potentiated desensitisation showed no treatment effect in this study. PMID:12896934

The effect of calcium plus vitamin D supplementation on the risk of venous thromboembolism. From the Women's Health Initiative Randomized Controlled Trial.

PubMed

Blondon, Marc; Rodabough, Rebecca J; Budrys, Nicole; Johnson, Karen C; Berger, Jeffrey S; Shikany, James M; Raiesdana, Azad; Heckbert, Susan R; Manson, JoAnn E; LaCroix, Andrea Z; Siscovick, David; Kestenbaum, Bryan; Smith, Nicholas L; de Boer, Ian H

2015-05-01

Experimental and epidemiological studies suggest that vitamin D may be implicated in haemostatic regulations and influence the risk of venous thromboembolism (VTE). The aim of this study was to investigate whether oral supplementation of vitamin D3 combined with calcium reduces the risk of VTE. In the randomised, double-blind, placebo-controlled Women's Health Initiative Calcium Plus Vitamin D trial, 36,282 postmenopausal women aged 50-79 years were randomised to receive 1,000 mg of calcium carbonate and 400 IU of vitamin D3 per day (n=18,176) or a matching placebo (n=18,106) during an average of seven years. This secondary analysis of the trial compared the incidence of VTE by treatment group using an intention-to-treat Cox regression analysis. The incidence of VTE did not differ between women randomised to calcium plus vitamin D and women randomised to placebo (320 vs 348 VTE events, respectively; hazard ratio (HR) 0.92, 95 % confidence interval (CI) 0.79-1.07). Results were not modified in an analysis using inverse-probability weights to take non-adherence into account (HR 0.94, 95 %CI 0.73-1.22) or in multiple subgroups. Whereas the risk of a non-idiopathic VTE was similar between groups, the risk of idiopathic VTE was lower in women randomised to calcium plus vitamin D (40 vs 65 events; HR 0.62, 95 %CI 0.42-0.92). In conclusion, daily supplementation with 1,000 mg of calcium and 400 IU of vitamin D did not reduce the overall incidence of VTE in generally healthy postmenopausal women. However, the observed reduced risk of idiopathic VTE in women randomised to calcium and vitamin D warrants further investigations.

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

PubMed

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

1993-07-01

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

The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant) in patients with traumatic brain injury.

PubMed

Shakur, Haleema; Andrews, Peter; Asser, Toomas; Balica, Laura; Boeriu, Cristian; Quintero, Juan Diego Ciro; Dewan, Yashbir; Druwé, Patrick; Fletcher, Olivia; Frost, Chris; Hartzenberg, Bennie; Mantilla, Jorge Mejia; Murillo-Cabezas, Francisco; Pachl, Jan; Ravi, Ramalingam R; Rätsep, Indrek; Sampaio, Cristina; Singh, Manmohan; Svoboda, Petr; Roberts, Ian

2009-12-03

Cerebral oedema is associated with significant neurological damage in patients with traumatic brain injury. Bradykinin is an inflammatory mediator that may contribute to cerebral oedema by increasing the permeability of the blood-brain barrier. We evaluated the safety and effectiveness of the non-peptide bradykinin B2 receptor antagonist Anatibant in the treatment of patients with traumatic brain injury. During the course of the trial, funding was withdrawn by the sponsor. Adults with traumatic brain injury and a Glasgow Coma Scale score of 12 or less, who had a CT scan showing an intracranial abnormality consistent with trauma, and were within eight hours of their injury were randomly allocated to low, medium or high dose Anatibant or to placebo. Outcomes were Serious Adverse Events (SAE), mortality 15 days following injury and in-hospital morbidity assessed by the Glasgow Coma Scale (GCS), the Disability Rating Scale (DRS) and a modified version of the Oxford Handicap Scale (HIREOS). 228 patients out of a planned sample size of 400 patients were randomised. The risk of experiencing one or more SAEs was 26.4% (43/163) in the combined Anatibant treated group, compared to 19.3% (11/57) in the placebo group (relative risk = 1.37; 95% CI 0.76 to 2.46). All cause mortality in the Anatibant treated group was 19% and in the placebo group 15.8% (relative risk 1.20, 95% CI 0.61 to 2.36). The mean GCS at discharge was 12.48 in the Anatibant treated group and 13.0 in the placebo group. Mean DRS was 11.18 Anatibant versus 9.73 placebo, and mean HIREOS was 3.94 Anatibant versus 3.54 placebo. The differences between the mean levels for GCS, DRS and HIREOS in the Anatibant and placebo groups, when adjusted for baseline GCS, showed a non-significant trend for worse outcomes in all three measures. This trial did not reach the planned sample size of 400 patients and consequently, the study power to detect an increase in the risk of serious adverse events was reduced. This trial provides no reliable evidence of benefit or harm and a larger trial would be needed to establish safety and effectiveness. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN23625128.

Standardised Chinese herbal treatment delivered by GPs compared with individualised treatment administered by practitioners of Chinese herbal medicine for women with recurrent urinary tract infections (RUTI): study protocol for a randomised controlled trial.

PubMed

Flower, Andrew; Harman, Kim; Lewith, George; Moore, Michael; Bishop, Felicity L; Stuart, Beth; Lampert, Nicholas

2016-07-27

In the UK, urinary tract infections (UTIs) are the most common bacterial infection presented by women in primary care. Recurrent urinary tract infections (RUTIs) are defined as three episodes of UTI in the last 12 months, or two episodes in the last 6 months. Between 20 and 30 % of women who have had one episode of UTI will have an RUTI, and approximately 25 % of these will develop subsequent recurrent episodes. RUTIs can have a significant negative effect on the quality of life, and have a high impact on health care costs as a result of outpatient visits, diagnostic tests and prescriptions. Chinese herbal medicine (CHM) has a recorded history of treatments for the symptoms of UTIs for more than 2000 years. More recent clinical research in China has provided some preliminary evidence that CHM can alleviate the symptoms of UTIs and reduce the rate of recurrence, but more rigorous investigation is required. The RUTI trial is a double-blind, randomised, placebo-controlled, feasibility trial. A total of 80 women will be randomised to 'individualised' herbs prescribed by a Chinese herbal practitioner or to 'standardised' herbs provided by primary care clinicians. Both arms will have herbs for prevention of UTIs and treatment of acute episodes. Treatment duration is for 16 weeks. The primary outcomes are the number of episodes of recurrent UTIs during the trial period and in the 6 months of follow-up, and the number of days of symptoms rated moderately bad or worse based on patient diaries. Secondary outcomes will assess participant expectations and beliefs, adherence to the treatment, adverse events and health economics and provide quantitative and qualitative assessments of the impact of recurrent infections on the lives of women. The RUTI trial is the first instance of CHM delivered as a clinical trial of an investigatory medicinal product in the UK. This study provides important information regarding the feasibility and acceptability of researching and using CHM in Primary care. Once completed, it will provide provisional estimates of the variance of change in continuous outcomes to inform a power calculation for a larger, more definitive trial. EudraCT, 2013-004657-24 . Registered on 5 September 2014.

Exercise to prevent falls in older adults: an updated systematic review and meta-analysis.

PubMed

Sherrington, Catherine; Michaleff, Zoe A; Fairhall, Nicola; Paul, Serene S; Tiedemann, Anne; Whitney, Julie; Cumming, Robert G; Herbert, Robert D; Close, Jacqueline C T; Lord, Stephen R

2017-12-01

Previous meta-analyses have found that exercise prevents falls in older people. This study aimed to test whether this effect is still present when new trials are added, and it explores whether characteristics of the trial design, sample or intervention are associated with greater fall prevention effects. Update of a systematic review with random effects meta-analysis and meta-regression. Cochrane Library, CINAHL, MEDLINE, EMBASE, PubMed, PEDro and SafetyLit were searched from January 2010 to January 2016. We included randomised controlled trials that compared fall rates in older people randomised to receive exercise as a single intervention with fall rates in those randomised to a control group. 99 comparisons from 88 trials with 19 478 participants were available for meta-analysis. Overall, exercise reduced the rate of falls in community-dwelling older people by 21% (pooled rate ratio 0.79, 95% CI 0.73 to 0.85, p<0.001, I 2 47%, 69 comparisons) with greater effects seen from exercise programmes that challenged balance and involved more than 3 hours/week of exercise. These variables explained 76% of the between-trial heterogeneity and in combination led to a 39% reduction in falls (incident rate ratio 0.61, 95% CI 0.53 to 0.72, p<0.001). Exercise also had a fall prevention effect in community-dwelling people with Parkinson's disease (pooled rate ratio 0.47, 95% CI 0.30 to 0.73, p=0.001, I 2 65%, 6 comparisons) or cognitive impairment (pooled rate ratio 0.55, 95% CI 0.37 to 0.83, p=0.004, I 2 21%, 3 comparisons). There was no evidence of a fall prevention effect of exercise in residential care settings or among stroke survivors or people recently discharged from hospital. Exercise as a single intervention can prevent falls in community-dwelling older people. Exercise programmes that challenge balance and are of a higher dose have larger effects. The impact of exercise as a single intervention in clinical groups and aged care facility residents requires further investigation, but promising results are evident for people with Parkinson's disease and cognitive impairment. 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/.

Up-skilling associate clinicians in Malawi in emergency obstetric, neonatal care and clinical leadership: the ETATMBA cluster randomised controlled trial.

PubMed

Ellard, David R; Chimwaza, Wanangwa; Davies, David; Simkiss, Doug; Kamwendo, Francis; Mhango, Chisale; Quenby, Siobhan; Kandala, Ngianga-Bakwin; O'Hare, Joseph Paul

2016-01-01

The ETATMBA (Enhancing Training And Technology for Mothers and Babies in Africa) project-trained associate clinicians (ACs/clinical officers) as advanced clinical leaders in emergency obstetric and neonatal care. This trial aimed to evaluate the impact of training on obstetric health outcomes in Malawi. A cluster randomised controlled trial with 14 districts of Malawi (8 intervention, 6 control) as units of randomisation. Intervention districts housed the 46 ACs who received the training programme. The primary outcome was district (health facility-based) perinatal mortality rates. Secondary outcomes included maternal mortality ratios, neonatal mortality rate, obstetric and birth variables. The study period was 2011-2013. Mortality rates/ratios were examined using an interrupted time series (ITS) to identify trends over time. The ITS reveals an improving trend in perinatal mortality across both groups, but better in the control group (intervention, effect -3.58, SE 2.65, CI (-9.85 to 2.69), p=0.20; control, effect -17.79, SE 6.83, CI (-33.95 to -1.64), p=0.03). Maternal mortality ratios are seen to have improved in intervention districts while worsening in the control districts (intervention, effect -38.11, SE 50.30, CI (-157.06 to 80.84), p=0.47; control, effect 11.55, SE 87.72, CI (-195.87 to 218.98), p=0.90). There was a 31% drop in neonatal mortality rate in intervention districts while in control districts, the rate rises by 2%. There are no significant differences in the other secondary outcomes. This is one of the first randomised studies looking at the effect of structured training on health outcomes in this setting. Notwithstanding a number of limitations, this study suggests that up-skilling this cadre is possible, and could impact positively on health outcomes. ISRCTN63294155; Results.

On the Feasibility of Conducting Randomised Trials in Education: Case Study of a Sex Education Intervention

ERIC Educational Resources Information Center

Moore, Laurence; Graham, Anna; Diamond, Ian

2003-01-01

This article reports on the conduct and results of a randomised controlled trial to test the effectiveness of a teacher-led intervention to improve teenagers' knowledge of emergency contraception. The trial was successfully conducted in 24 mixed-sex state secondary schools in Avon, South-west England. The intervention was popular with both…

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).

A randomised controlled trial of a cognitive behavioural intervention for women who have menopausal symptoms following breast cancer treatment (MENOS 1): Trial protocol

PubMed Central

2011-01-01

Background This trial aims to evaluate the effectiveness of a group cognitive behavioural intervention to alleviate menopausal symptoms (hot flushes and night sweats) in women who have had breast cancer treatment. Hot flushes and night sweats are highly prevalent but challenging to treat in this population. Cognitive behaviour therapy has been found to reduce these symptoms in well women and results of an exploratory trial suggest that it might be effective for breast cancer patients. Two hypotheses are tested: Compared to usual care, group cognitive behavioural therapy will: 1. Significantly reduce the problem rating and frequency of hot flushes and nights sweats after six weeks of treatment and at six months post-randomisation. 2. Improve mood and quality of life after six weeks of treatment and at six months post-randomisation. Methods/Design Ninety-six women who have completed their main treatment for breast cancer and who have been experiencing problematic hot flushes and night sweats for over two months are recruited into the trial from oncology and breast clinics in South East London. They are randomised to either six weekly group cognitive behavioural therapy (Group CBT) sessions or to usual care. Group CBT includes information and discussion about hot flushes and night sweats in the context of breast cancer, monitoring and modifying precipitants, relaxation and paced respiration, stress management, cognitive therapy for unhelpful thoughts and beliefs, managing sleep and night sweats and maintaining changes. Prior to randomisation women attend a clinical interview, undergo 24-hour sternal skin conductance monitoring, and complete questionnaire measures of hot flushes and night sweats, mood, quality of life, hot flush beliefs and behaviours, optimism and somatic amplification. Post-treatment measures (sternal skin conductance and questionnaires) are collected six to eight weeks later and follow-up measures (questionnaires and a use of medical services measure) at six months post-randomisation. Discussion MENOS 1 is the first randomised controlled trial of cognitive behavioural therapy for hot flushes and night sweats that measures both self-reported and physiologically indexed symptoms. The results will inform future clinical practice by developing an evidence-based, non-medical treatment, which can be delivered by trained health professionals. Trial Registration Current Controlled Trials ISRCTN13771934 PMID:21281461

Robot Assisted Training for the Upper Limb after Stroke (RATULS): study protocol for a randomised controlled trial.

PubMed

Rodgers, Helen; Shaw, Lisa; Bosomworth, Helen; Aird, Lydia; Alvarado, Natasha; Andole, Sreeman; Cohen, David L; Dawson, Jesse; Eyre, Janet; Finch, Tracy; Ford, Gary A; Hislop, Jennifer; Hogg, Steven; Howel, Denise; Hughes, Niall; Krebs, Hermano Igo; Price, Christopher; Rochester, Lynn; Stamp, Elaine; Ternent, Laura; Turner, Duncan; Vale, Luke; Warburton, Elizabeth; van Wijck, Frederike; Wilkes, Scott

2017-07-20

Loss of arm function is a common and distressing consequence of stroke. We describe the protocol for a pragmatic, multicentre randomised controlled trial to determine whether robot-assisted training improves upper limb function following stroke. Study design: a pragmatic, three-arm, multicentre randomised controlled trial, economic analysis and process evaluation. NHS stroke services. adults with acute or chronic first-ever stroke (1 week to 5 years post stroke) causing moderate to severe upper limb functional limitation. Randomisation groups: 1. Robot-assisted training using the InMotion robotic gym system for 45 min, three times/week for 12 weeks 2. Enhanced upper limb therapy for 45 min, three times/week for 12 weeks 3. Usual NHS care in accordance with local clinical practice Randomisation: individual participant randomisation stratified by centre, time since stroke, and severity of upper limb impairment. upper limb function measured by the Action Research Arm Test (ARAT) at 3 months post randomisation. upper limb impairment (Fugl-Meyer Test), activities of daily living (Barthel ADL Index), quality of life (Stroke Impact Scale, EQ-5D-5L), resource use, cost per quality-adjusted life year and adverse events, at 3 and 6 months. Blinding: outcomes are undertaken by blinded assessors. Economic analysis: micro-costing and economic evaluation of interventions compared to usual NHS care. A within-trial analysis, with an economic model will be used to extrapolate longer-term costs and outcomes. Process evaluation: semi-structured interviews with participants and professionals to seek their views and experiences of the rehabilitation that they have received or provided, and factors affecting the implementation of the trial. allowing for 10% attrition, 720 participants provide 80% power to detect a 15% difference in successful outcome between each of the treatment pairs. Successful outcome definition: baseline ARAT 0-7 must improve by 3 or more points; baseline ARAT 8-13 improve by 4 or more points; baseline ARAT 14-19 improve by 5 or more points; baseline ARAT 20-39 improve by 6 or more points. The results from this trial will determine whether robot-assisted training improves upper limb function post stroke. ISRCTN, identifier: ISRCTN69371850 . Registered 4 October 2013.

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.

Promoting Recruitment using Information Management Efficiently (PRIME): study protocol for a stepped-wedge cluster randomised controlled trial within the REstart or STop Antithrombotics Randomised Trial (RESTART).

PubMed

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

2017-03-01

Research into methods to boost recruitment has been identified as the highest priority for randomised controlled trial (RCT) methodological research in the United Kingdom. Slow recruitment delays the delivery of research and inflates costs. Using electronic patient records has been shown to boost recruitment to ongoing RCTs in primary care by identifying potentially eligible participants, but this approach remains relatively unexplored in secondary care, and for stroke in particular. The REstart or STop Antithrombotics Randomised Trial (RESTART; ISRCTN71907627) is an ongoing RCT of secondary prevention after stroke due to intracerebral haemorrhage. Promoting Recruitment using Information Management Efficiently (PRIME) is a stepped-wedge cluster randomised trial of a complex intervention to help RESTART sites increase their recruitment and attain their own target numbers of participants. Seventy-two hospital sites that were located in England, Wales or Scotland and were active in RESTART in June 2015 opted into PRIME. Sites were randomly allocated (using a computer-generated block randomisation algorithm, stratified by hospital location in Scotland vs. England/Wales) to one of 12 months in which the intervention would be delivered. All sites began in the control state. The intervention was delivered by a recruitment co-ordinator via a teleconference with each site. The intervention involved discussing recruitment strategies, providing software for each site to extract from their own stroke audit data lists of patients who were potentially eligible for RESTART, and a second teleconference to review progress 6 months later. The recruitment co-ordinator was blinded to the timing of the intervention until 2 months before it was due at a site. Staff at RESTART sites were blinded to the nature and timing of the intervention. The primary outcome is the total number of patients randomised into RESTART per month per site and will be analysed in a negative binomial generalised linear mixed model. PRIME began in September 2015. The last intervention was delivered in August 2016. Six-month follow-up will be complete in February 2017. The final results of PRIME will be analysed and disseminated in 2017. The PRIME study was registered in the Northern Ireland Hub for Trials Methodology Research Studies Within a Trial (SWAT) repository (SWAT22) on 23 December 2015.

Hyperbaric oxygen therapy for Bell's palsy.

PubMed

Holland, N Julian; Bernstein, Jonathan M; Hamilton, John W

2012-02-15

Bell's palsy is an idiopathic, acute unilateral facial weakness that evolves rapidly and is maximal within two days. Moderate ear discomfort, sensitivity to sound and reduced tearing may occur. To assess the effects of hyperbaric oxygen therapy on recovery of facial function in adults with moderate to severe Bell's palsy. We searched the Cochrane Neuromuscular Disease Group Specialized Register (January 2012), CENTRAL (2011, Issue 4), MEDLINE (January 1966 to January 2012), EMBASE (January 1980 to January 2012), CINAHL (1937 to January 2012), AMED (1985 to January 2012), LILACS (January 1982 to January 2012). In addition we made a systematic search for relevant controlled trials in specific hyperbaric literature sources. Randomised controlled trials or quasi-randomised controlled trials of adults (over 16 years of age) undergoing hyperbaric oxygen therapy for moderate to severe Bell's palsy. We considered studies to be of sufficient quality for inclusion in the review only if there was blinding in the assessment of the facial palsy grade. We planned to include studies of HBOT used as adjuvant therapy, or in addition to routine medical therapy (including corticosteroids or antivirals, or both). Both treatment and control groups were to receive the same baseline therapy. HBOT had to be delivered at concentrations greater than or equal to 1.2 ATA in a hyperbaric oxygen chamber as a series of dives of 30 to 120 minutes. Two reviewers independently assessed eligibility and study quality and extracted data. We contacted study authors for additional information. Our searches found no randomised controlled trials or quasi-randomised controlled trials that met the eligibility criteria for this review.There is very low quality evidence from one randomised trial involving 79 participants with acute Bell's palsy, but this study was excluded as the outcome assessor was not blinded to treatment allocation and thus did not meet pre-defined eligibility criteria. The trial compared 42 people who received hyperbaric oxygen therapy (2.8 atmospheres for 60 minutes twice daily, five days per week until the facial palsy resolved; maximum 30 'dives') and placebo tablets with 37 people who received placebo hyperbaric oxygen therapy (achieving only a normal partial pressure of oxygen) and prednisone (40 mg twice daily, reducing over eight days). Facial function recovered in more participants treated with hyperbaric oxygen therapy than with prednisone (hyperbaric oxygen therapy, 40/42 (95%); prednisone, 28/37 (76%); risk ratio 1.26, 95% CI 1.04 to 1.53). There were no reported major complications and all participants completed the trial. Very low quality evidence from one trial suggests that hyperbaric oxygen therapy may be an effective treatment for moderate to severe Bell's palsy, but this study was excluded as the outcome assessor was not blinded to treatment allocation. Further randomised controlled trials are needed.

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.

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

PubMed

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

2012-12-01

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

An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom

PubMed Central

2012-01-01

Background To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation. Methods An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises’ customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews. Results The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises. Conclusions It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability. Trial registration UKCRN 7090; ISRCTN: 80875696 PMID:22676069

Effect of a 16-week Bikram yoga program on perceived stress, self-efficacy and health-related quality of life in stressed and sedentary adults: A randomised controlled trial.

PubMed

Hewett, Zoe L; Pumpa, Kate L; Smith, Caroline A; Fahey, Paul P; Cheema, Birinder S

2018-04-01

The purpose of this study was to investigate the effect of 16 weeks of Bikram yoga on perceived stress, self-efficacy and health related quality of life (HRQoL) in sedentary, stressed adults. 16 week, parallel-arm, randomised controlled trial with flexible dosing. Physically inactive, stressed adults (37.2±10.8 years) were randomised to Bikram yoga (three to five classes per week) or control (no treatment) group for 16 weeks. Outcome measures, collected via self-report, included perceived stress, general self-efficacy, and HRQoL. Outcomes were assessed at baseline, midpoint and completion. Individuals were randomised to the experimental (n=29) or control group (n=34). Average attendance in the experimental group was 27±18 classes. Repeated measure analyses of variance (intention-to-treat) demonstrated significantly improved perceived stress (p=0.003, partial η 2 =0.109), general self-efficacy (p=0.034, partial η 2 =0.056), and the general health (p=0.034, partial η 2 =0.058) and energy/fatigue (p=0.019, partial η 2 =0.066) domains of HRQoL in the experimental group versus the control group. Attendance was significantly associated with reductions in perceived stress, and an increase in several domains of HRQoL. 16 weeks of Bikram yoga significantly improved perceived stress, general self-efficacy and HRQoL in sedentary, stressed adults. Future research should consider ways to optimise adherence, and should investigate effects of Bikram yoga intervention in other populations at risk for stress-related illness. Australia New Zealand Clinical Trials Registry ACTRN12616000867493. Registered 04 July 2016. URL: http://www.anzctr.org.au/ACTRN12616000867493.aspx. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Cost analysis of the Communication and Low Mood (CALM) randomised trial of behavioural therapy for stroke patients with aphasia.

PubMed

Humphreys, Ioan; Thomas, Shirley; Phillips, Ceri; Lincoln, Nadina

2015-01-01

To evaluate the cost effectiveness of a behavioural therapy intervention shown to be clinically effective in comparison with usual care for stroke patients with aphasia. Randomised controlled trial with comparison of costs and calculation of incremental cost effectiveness ratio. Community. Participants identified as having low mood on either the Visual Analog Mood Scale sad item (≥50) or Stroke Aphasic Depression Questionnaire Hospital version 21 (SADQH21) (≥6) were recruited. Participants were randomly allocated to behavioural therapy or usual care using internet-based randomisation generated in advance of the study by a clinical trials unit. Outcomes were assessed at six months after randomisation, blind to group allocation. The costs were assessed from a service use questionnaire. Effectiveness was defined as the change in SADQH21 scores and a cost-effectiveness analysis was performed comparing the behavioural group with the usual care control group. The cost analysis was undertaken from the perspective of the UK NHS and Social Services. The greatest difference was in home help costs where there was a saving of £56.20 in the intervention group compared to an increase of £61.40 in the control group. At six months the SADQH21 score for the intervention group was 17.3 compared to the control group value of 20.4. This resulted in a mean increase of 0.7 in the control group, compared to a mean significant different decrease of 6 in the intervention group (P = 0.003). The Incremental Cost-Effectiveness Ratio indicated that the cost per point reduction on the SADQH21 was £263. Overall the behavioural therapy was found to improve mood and resulted in some encouraging savings in resource utilisation over the six months follow-up. © The Author(s) 2014.

PREvention STudy On preventing or reducing disability from musculoskeletal complaints in music school students (PRESTO): protocol of a randomised controlled trial.

PubMed

Baadjou, Vera A E; Verbunt, Jeanine A M C F; Eijsden-Besseling, Marjon D F van; Samama-Polak, Ans L W; Bie, Rob A D E; Smeets, Rob J E M

2014-12-01

Up to 87% of professional musicians develop work-related complaints of the musculoskeletal system during their careers. Music school students are at specific risk for developing musculoskeletal complaints and disabilities. This study aims to evaluate the effectiveness of a biopsychosocial prevention program to prevent or reduce disabilities from playing-related musculoskeletal disorders. Secondary objectives are evaluation of cost-effectiveness and feasibility. Healthy, first or second year students (n=150) will be asked to participate in a multicentre, single-blinded, parallel-group randomised controlled trial. Students randomised to the intervention group (n=75) will participate in a biopsychosocial prevention program that addresses playing-related health problems and provides postural training according to the Mensendieck or Cesar methods of postural exercise therapy, while incorporating aspects from behavioural change theories. A control group (n=75) will participate in a program that stimulates a healthy physical activity level using a pedometer, which conforms to international recommendations. No long-term effects are expected from this control intervention. Total follow-up duration is two years. The primary outcome measure is disability (Disabilities of Arm, Shoulder and Hand questionnaire). The secondary outcome measures are pain, quality of life and changes in health behaviour. Multilevel mixed-effect logistic or linear regression analyses will be performed to analyse the effects of the program on the aforementioned outcome measurements. Furthermore, cost-effectiveness, cost-utility and feasibility will be analysed. It is believed that this is the first comprehensive randomised controlled trial on the effect and rationale of a biopsychosocial prevention program for music students. Copyright © 2014 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Effect of free distribution of safety equipment on usage among motorcycle-taxi drivers in Tanzania--A cluster randomised controlled trial.

PubMed

Sumner, Steven A; Pallangyo, Anthony J; Reddy, Elizabeth A; Maro, Venance; Pence, Brian W; Lynch, Catherine; Turner, Elizabeth L; Egger, Joseph R; Thielman, Nathan M

2014-11-01

Deaths due to road traffic injuries, particularly motorcycle crashes, have increased rapidly in many African nations and context-specific strategies to improve preventative behaviours are needed. Although adhering to conspicuity measures by wearing reflective safety vests is a highly effective crash prevention strategy and mandated by law among motorcycle-taxi drivers in some African countries, actual use is currently low. We aimed to test whether eliminating cost-barriers through the provision of free reflective, fluorescent motorcycle safety vests would lead to increased utilisation among a high-risk population of motorcycle-taxi drivers in Tanzania. A cluster randomised controlled trial was conducted among 180 motorcycle-taxi drivers. Participants randomised to the intervention arm (90) received free, reflective, fluorescent vests; participants randomised to the control arm (90) did not receive free vests. Participants' use of reflective vests was then observed on city streets over a three month period and differential uptake was estimated using mixed-effects logistic regression. Baseline use of reflective vests was 3.3% in both arms. Seventy-nine drivers in the intervention arm and 82 drivers in the control arm were observed during follow-up. The average proportion of observations during which motorcycle drivers were using a reflective vest was 9.5% in the intervention arm, compared to 2.0% in the control arm (odds ratio: 5.5, 95% confidence interval: 1.1-26.9, p-value: 0.04). Although distribution of free reflective vests led to a statistically significant increase in vest usage, the absolute increase was modest. Additional strategies beyond removing economic barriers are important to augment adherence to road safety behaviours for injury prevention. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed Central

2013-01-01

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

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.

Getting the balance right: a randomised controlled trial of physiotherapy and Exercise Interventions for ambulatory people with multiple sclerosis.

PubMed

Coote, Susan; Garrett, Maria; Hogan, Neasa; Larkin, Aidan; Saunders, Jean

2009-07-16

People with Multiple Sclerosis have a life long need for physiotherapy and exercise interventions due to the progressive nature of the disease and their greater risk of the complications of inactivity. The Multiple Sclerosis Society of Ireland run physiotherapy, yoga and exercise classes for their members, however there is little evidence to suggest which form of physical activity optimises outcome for people with the many and varied impairments associated with MS. This is a multi-centre, single blind, block randomised, controlled trial. Participants will be recruited via the ten regional offices of MS Ireland. Telephone screening will establish eligibility and stratification according to the mobility section of the Guys Neurological Disability Scale. Once a block of people of the same strand in the same geographical region have given consent, participants will be randomised. Strand A will concern individuals with MS who walk independently or use one stick to walk outside. Participants will be randomised to yoga, physiotherapy led exercise class, fitness instructor led exercise class or to a control group who don't change their exercise habits.Strand B will concern individuals with MS who walk with bilateral support or a rollator, they may use a wheelchair for longer distance outdoors. Participants will be randomised to 1:1 Physiotherapist led intervention, group intervention led by Physiotherapist, group yoga intervention or a control group who don't change their exercise habits. Participants will be assessed by physiotherapist who is blind to the group allocation at week 1, week 12 (following 10 weeks intervention or control), and at 12 week follow up. The primary outcome measure for both strands is the Multiple Sclerosis Impact Scale. Secondary outcomes are Modified Fatigue Impact Scale, 6 Minute Walk test, and muscle strength measured with hand held dynamometry. Strand B will also use Berg Balance Test and the Modified Ashworth Scale. Confounding variables such as sensation, coordination, proprioception, range of motion and other impairments will be recorded at initial assessment. Data analysis will analyse change in each group, and the differences between groups. Sub group analysis may be performed if sufficient numbers are recruited. ISRCTN77610415.

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.

Evaluating the effect of innovative motivation and supervision approaches on community health worker performance and retention in Uganda and Mozambique: study protocol for a randomised controlled trial.

PubMed

Källander, Karin; Strachan, Daniel; Soremekun, Seyi; Hill, Zelee; Lingam, Raghu; Tibenderana, James; Kasteng, Frida; Vassall, Anna; Meek, Sylvia; Kirkwood, Betty

2015-04-12

If trained, equipped and utilised, community health workers (CHWs) delivering integrated community case management for sick children can potentially reduce child deaths by 60%. However, it is essential to maintain CHW motivation and performance. The inSCALE project aims to evaluate, using a cluster randomised controlled trial, the effect of interventions to increase CHW supervision and performance on the coverage of appropriate treatment for children with diarrhoea, pneumonia and malaria. Participatory methods were used to identify best practices and innovative solutions. Quantitative community based baseline surveys were conducted to allow restricted randomisation of clusters into intervention and control arms. Individual informed consent was obtained from all respondents. Following formative research and stakeholder consultations, two intervention packages were developed in Uganda and one in Mozambique. In Uganda, approximately 3,500 CHWs in 39 clusters were randomised into a mobile health (mHealth) arm, a participatory community engagement arm and a control arm. In Mozambique, 275 CHWs in 12 clusters were randomised into a mHealth arm and a control arm. The mHealth interventions encompass three components: 1) free phone communication between users; 2) data submission using phones with automated feedback, messages to supervisors for targeted supervision, and online data access for district statisticians; and 3) motivational messages. The community engagement arm in Uganda established village health clubs seeking to 1) improve the status and standing of CHWs, 2) increase demand for health services and 3) communicate that CHWs' work is important. Process evaluation was conducted after 10 months and end-line surveys will establish impact after 12 months in Uganda and 18 months in Mozambique. Main outcomes include proportion of sick children appropriately treated, CHW performance and motivation, and cost effectiveness of interventions. Study strengths include a user-centred design to the innovations, while weaknesses include the lack of a robust measurement of coverage of appropriate treatment. Evidence of cost-effective innovations that increase motivation and performance of CHWs can potentially increase sustainable coverage of iCCM at scale. (identifier NCT01972321 ) on 22 April 22 2013.

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

PubMed

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

2016-12-07

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

The effects of transdermal testosterone and oestrogen therapy on dry eye in postmenopausal women: a randomised, placebo-controlled, pilot study.

PubMed

Golebiowski, Blanka; Badarudin, Noor; Eden, John; Gerrand, Leanne; Robinson, Jennifer; Liu, Jinzhu; Hampel, Ulrike; You, Jingjing; Stapleton, Fiona

2017-07-01

Sex hormones could provide a future treatment avenue for dry eye post menopause. However, there are few well-controlled studies. This study investigates the impact of testosterone and oestrogen on dry eye symptoms and signs in postmenopausal women. A randomised double-blind placebo-controlled pilot study was conducted involving 40 women with dry eye (age 63.9±5.1 years, 13.2±6.3 years post menopause). Ten women were assigned to each of four treatment groups: transdermal testosterone, oestradiol, testosterone/oestradiol combination and placebo. Assessment at baseline and after 8 weeks: ocular symptoms, tear osmolarity, tear stability, tear secretion, meibomian gland assessment, corneal and conjunctival sensitivity, serum concentrations of 17β-oestradiol, 3-α-androstanediol-glucuronide and dehydroepiandrosterone sulfate. Differences from placebo were examined using one-way analysis of variance and Dunnett's t-test. Within-group analyses included paired t-tests and Spearman correlation. Dryness intensity after 8 weeks was significantly worse in the oestrogen group compared with placebo (p=0.04). No significant changes in other symptoms, tear function, meibomian gland function, lid morphology, corneal or conjunctival sensitivity were observed in any of the groups when compared with the change in placebo after 8 weeks. Within-group analyses showed increased tear secretion in the testosterone/oestradiol combination group (p=0.03) and a strong association between increased serum androgen and improved tear stability in the testosterone group (ρ=0.83,p=0.01). Oestrogen supplementation may worsen ocular symptoms in postmenopausal women with dry eye, whereas no impact of testosterone therapy on symptoms was apparent. The positive effects of oestrogen and testosterone on tear function require confirmation in a larger study, with sample size calculated from the data generated herein. Placebo control is essential in studies of dry eye therapies. ACTRN12612000281897. 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/.

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).

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.

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.

Evidence for the impact of quality improvement collaboratives: systematic review

PubMed Central

2008-01-01

Objective To evaluate the effectiveness of quality improvement collaboratives in improving the quality of care. Data sources Relevant studies through Medline, Embase, PsycINFO, CINAHL, and Cochrane databases. Study selection Two reviewers independently extracted data on topics, participants, setting, study design, and outcomes. Data synthesis Of 1104 articles identified, 72 were included in the study. Twelve reports representing nine studies (including two randomised controlled trials) used a controlled design to measure the effects of the quality improvement collaborative intervention on care processes or outcomes of care. Systematic review of these nine studies showed moderate positive results. Seven studies (including one randomised controlled trial) reported an effect on some of the selected outcome measures. Two studies (including one randomised controlled trial) did not show any significant effect. Conclusions The evidence underlying quality improvement collaboratives is positive but limited and the effects cannot be predicted with great certainty. Considering that quality improvement collaboratives seem to play a key part in current strategies focused on accelerating improvement, but may have only modest effects on outcomes at best, further knowledge of the basic components effectiveness, cost effectiveness, and success factors is crucial to determine the value of quality improvement collaboratives. PMID:18577559

Efficacy of cognitive-behavioural therapy by general practitioners for unexplained fatigue among employees: Randomised controlled trial.

PubMed

Huibers, Marcus J H; Beurskens, Anna J H M; Van Schayck, Constant P; Bazelmans, Ellen; Metsemakers, Job F M; Knottnerus, J Andre; Bleijenberg, Gijs

2004-03-01

Fatigue is a common complaint that may lead to long-term sick leave and work disability. To assess the efficacy of cognitive-behavioural therapy by general practitioners for unexplained, persistent fatigue among employees. A randomised controlled trial, using a pre-randomisation design in primary care, investigated 151 employees on sick leave with fatigue. Participants in the experimental group were offered five to seven 30 min sessions of cognitive-behavioural therapy by a general practitioner; those in the control group were offered no treatment. Main outcome measures (fatigue severity, self-reported absenteeism, registered absenteeism and clinical recovery) were assessed at 4 months, 8 months and 12 months. At baseline, 44% of the patients already met research criteria for chronic fatigue syndrome. There was no significant difference between the experimental group and the control group on primary or secondary outcomes at any point. Cognitive-behavioural therapy by general practitioners for unexplained, persistent fatigue did not prove to be an effective intervention. Since these doctors were unable to deliver this therapy effectively under ideal circumstances, it is unlikely that doctors in routine practice would be more successful in doing so.

Comparison of characteristics of femtosecond laser-assisted anterior capsulotomy versus manual continuous curvilinear capsulorrhexis: A meta-analysis of 5-year results.

PubMed

Ali, Muhammad Hassaan; Ullah, Samee; Javaid, Usman; Javaid, Mamoona; Jamal, Samreen; Butt, Nadeem Hafeez

2017-10-01

To perform a meta-analysis on the precision and safety of femtosecond laser-assisted anterior capsulotomy versus conventional manual continuous curvilinear capsulorrhexis. This meta-analysis was conducted from February 2010 to November 2014. Literature search on PubMed, Google Scholar, ExcerptaMedica database and Cochrane Library was done to identify randomised controlled trials and case-control studies. SPSS 20 was used for data analysis. Of the 10 articles included, there were 3(30%) randomised controlled trials and 7(70%) non-randomised controlled trials. The meta-analysis was based on a total of 2,882eyes. Of them, 1,498(51.97%) underwent femtosecond laser-assisted capsulotomy and 1,384(48.02%) underwent manual continuous curvilinear capsulorrhexis. The diameter of the capsulotomy and the rates of anterior capsule tear showed no statistical difference between the femtosecond laser group and the manual capsulorrhexis group (p=0.29 and p=0.68). In terms of circularity of capsulotomy, femtosecond laser group had a more significant advantage than the manual capsulorrhexis group (p<0.001). Femtosecond laser performed capsulotomy with more precision and higher reliability than the manual continuous curvilinear capsulorrhexis.

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.

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

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

PubMed

Hodder, Rebecca K; Freund, Megan; Bowman, Jenny; Wolfenden, Luke; Campbell, Elizabeth; Wye, Paula; Hazell, Trevor; Gillham, Karen; Wiggers, John

2012-11-21

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

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

PubMed Central

2012-01-01

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

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.

Using the 'Social Marketing Mix Framework' to explore recruitment barriers and facilitators in palliative care randomised controlled trials? A narrative synthesis review.

PubMed

Dunleavy, Lesley; Walshe, Catherine; Oriani, Anna; Preston, Nancy

2018-05-01

Effective recruitment to randomised controlled trials is critically important for a robust, trustworthy evidence base in palliative care. Many trials fail to achieve recruitment targets, but the reasons for this are poorly understood. Understanding barriers and facilitators is a critical step in designing optimal recruitment strategies. To identify, explore and synthesise knowledge about recruitment barriers and facilitators in palliative care trials using the '6 Ps' of the 'Social Marketing Mix Framework'. A systematic review with narrative synthesis. Medline, CINAHL, PsycINFO and Embase databases (from January 1990 to early October 2016) were searched. Papers included the following: interventional and qualitative studies addressing recruitment, palliative care randomised controlled trial papers or reports containing narrative observations about the barriers, facilitators or strategies to increase recruitment. A total of 48 papers met the inclusion criteria. Uninterested participants (Product), burden of illness (Price) and 'identifying eligible participants' were barriers. Careful messaging and the use of scripts/role play (Promotion) were recommended. The need for intensive resources and gatekeeping by professionals were barriers while having research staff on-site and lead clinician support (Working with Partners) was advocated. Most evidence is based on researchers' own reports of experiences of recruiting to trials rather than independent evaluation. The 'Social Marketing Mix Framework' can help guide researchers when planning and implementing their recruitment strategy but suggested strategies need to be tested within embedded clinical trials. The findings of this review are applicable to all palliative care research and not just randomised controlled trials.

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

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

PubMed Central

2012-01-01

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

A study of sertraline in dialysis (ASSertID): a protocol for a pilot randomised controlled trial of drug treatment for depression in patients undergoing haemodialysis.

PubMed

Friedli, Karin; Almond, Michael; Day, Clara; Chilcot, Joseph; Gane, Maria da Silva; Davenport, Andrew; Guirguis, Ayman; Fineberg, Naomi; Spencer, Benjamin; Wellsted, David; Farrington, Ken

2015-10-26

The prevalence of depression in people receiving haemodialysis is high with estimates varying between 20 and 40 %. There is little research on the effectiveness of antidepressants in dialysis patients with the few clinical trials suffering significant methodological issues. We plan to carry out a study to evaluate the feasibility of conducting a randomised controlled trial in patients on haemodialysis who have diagnosed Major Depressive Disorder. The study has two phases, a screening phase and the randomised controlled trial. Patients will be screened initially with the Beck Depression Inventory to estimate the number of patients who score 16 or above. These patients will be invited to an interview with a psychiatrist who will invite those with a diagnosis of Major Depressive Disorder to take part in the trial. Consenting patients will be randomised to either Sertraline or placebo. Patients will be followed-up for 6 months. Demographic and clinical data will be collected at screening interview, baseline interview and 2 weeks, and every month (up to 6 months) after baseline. The primary outcome is to evaluate the feasibility of conducting a randomised, double blind, placebo pilot trial in haemodialysis patients with depression. Secondary outcomes include estimation of the variability in the outcome measures for the treatment and placebo arms, which will allow for a future adequately powered definitive trial. Analysis will primarily be descriptive, including the number of patients eligible for the trial, drug exposure of Sertraline in haemodialysis patients and the patient experience of participating in this trial. There is an urgent need for this research in the dialysis population because of the dearth of good quality and adequately powered studies. Research with renal patients is particularly difficult as they often have complex medical needs. This research will therefore not only assess the outcome of anti-depressants in haemodialysis patients with depression but also the process of running a randomised controlled trial in this population. Hence, the outputs of this feasibility study will be used to inform the design and methodology of a definitive study, adequately powered to determine the efficacy of anti-depressants in patient on haemodialysis with depression. ISRCTN registry ISRCTN06146268 and EudraCT reference: 2012-000547-27.

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.

Clinical- and cost-effectiveness of the STAR care pathway compared to usual care for patients with chronic pain after total knee replacement: study protocol for a UK randomised controlled trial.

PubMed

Wylde, Vikki; Bertram, Wendy; Beswick, Andrew D; Blom, Ashley W; Bruce, Julie; Burston, Amanda; Dennis, Jane; Garfield, Kirsty; Howells, Nicholas; Lane, Athene; McCabe, Candy; Moore, Andrew J; Noble, Sian; Peters, Tim J; Price, Andrew; Sanderson, Emily; Toms, Andrew D; Walsh, David A; White, Simon; Gooberman-Hill, Rachael

2018-02-21

Approximately 20% of patients experience chronic pain after total knee replacement. There is little evidence for effective interventions for the management of this pain, and current healthcare provision is patchy and inconsistent. Given the complexity of this condition, multimodal and individualised interventions matched to pain characteristics are needed. We have undertaken a comprehensive programme of work to develop a care pathway for patients with chronic pain after total knee replacement. This protocol describes the design of a randomised controlled trial to evaluate the clinical- and cost-effectiveness of a complex intervention care pathway compared with usual care. This is a pragmatic two-armed, open, multi-centred randomised controlled trial conducted within secondary care in the UK. Patients will be screened at 2 months after total knee replacement and 381 patients with chronic pain at 3 months postoperatively will be recruited. Recruitment processes will be optimised through qualitative research during a 6-month internal pilot phase. Patients are randomised using a 2:1 intervention:control allocation ratio. All participants receive usual care as provided by their hospital. The intervention comprises an assessment clinic appointment at 3 months postoperatively with an Extended Scope Practitioner and up to six telephone follow-up calls over 12 months. In the assessment clinic, a standardised protocol is followed to identify potential underlying causes for the chronic pain and enable appropriate onward referrals to existing services for targeted and individualised treatment. Outcomes are assessed by questionnaires at 6 and 12 months after randomisation. The co-primary outcomes are pain severity and pain interference assessed using the Brief Pain Inventory at 12 months after randomisation. Secondary outcomes relate to resource use, function, neuropathic pain, mental well-being, use of pain medications, satisfaction with pain relief, pain frequency, capability, health-related quality of life and bodily pain. After trial completion, up to 30 patients in the intervention group will be interviewed about their experiences of the care pathway. If shown to be clinically and cost-effective, this care pathway intervention could improve the management of chronic pain after total knee replacement. ISRCTN registry ( ISRCTN92545361 ), prospectively registered on 30 August 2016.

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.

Evaluating an extended rehabilitation service for stroke patients (EXTRAS): study protocol for a randomised controlled trial.

PubMed

Rodgers, Helen; Shaw, Lisa; Cant, Robin; Drummond, Avril; Ford, Gary A; Forster, Anne; Hills, Katie; Howel, Denise; Laverty, Anne-Marie; McKevitt, Christopher; McMeekin, Peter; Price, Christopher

2015-05-05

Development of longer term stroke rehabilitation services is limited by lack of evidence of effectiveness for specific interventions and service models. We describe the protocol for a multicentre randomised controlled trial which is evaluating an extended stroke rehabilitation service. The extended service commences when routine 'organised stroke care' (stroke unit and early supported discharge (ESD)) ends. This study is a multicentre randomised controlled trial with health economic and process evaluations. It is set within NHS stroke services which provide ESD. Participants are adults who have experienced a new stroke (and carer if appropriate), discharged from hospital under the care of an ESD team. The intervention group receives an extended stroke rehabilitation service provided for 18 months following completion of ESD. The extended rehabilitation service involves regular contact with a senior ESD team member who leads and coordinates further rehabilitation. Contact is usually by telephone. The control group receives usual stroke care post-ESD. Usual care may involve referral of patients to a range of rehabilitation services upon completion of ESD in accordance with local clinical practice. Randomisation is via a central independent web-based service. The primary outcome is extended activities of daily living (Nottingham Extended Activities of Daily Living Scale) at 24 months post-randomisation. Secondary outcomes (at 12 and 24 months post-randomisation) are health status, quality of life, mood and experience of services for patients, and quality of life, experience of services and carer stress for carers. Resource use and adverse events are also collected. Outcomes are undertaken by a blinded assessor. Implementation and delivery of the extended stroke rehabilitation service will also be described. Semi-structured interviews will be conducted with a subsample of participants and staff to gain insight into perceptions and experiences of rehabilitation services delivered or received. Allowing for 25% attrition, 510 participants are needed to provide 90% power to detect a difference in mean Nottingham Extended Activities of Daily Living Scale score of 6 with a 5% significance level. The provision of longer term support for stroke survivors is currently limited. The results from this trial will inform future stroke service planning and configuration. This trial was registered with ISRCTN (identifier: ISRCTN45203373 ) on 9 August 2012.

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.

Prophylactic intravenous calcium therapy for exchange blood transfusion in the newborn.

PubMed

Ogunlesi, Tinuade A; Lesi, Foluso Ea; Oduwole, Olabisi

2017-10-12

Exchange blood transfusion (EBT) is a form of whole blood transfusion in which the total blood volume is replaced within a few hours. In perinatal and neonatal medicine, EBT is most often used in the management of severe anaemia or severe hyperbilirubinaemia in the first week of life. Hypocalcaemia, one of the common morbidities associated with EBT, is thought to arise from the chelating effects of the citrate commonly used as an anticoagulant in the donor's blood. This disorder manifests with muscular and nervous irritability and cardiac arrhythmias. To determine whether the use of prophylactic calcium reduces the risk of hypocalcaemia-related morbidities and death among newborn infants receiving EBT. We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 5), MEDLINE via PubMed (1966 to 29 June 2016), Embase (1980 to 29 June 2016), and CINAHL (1982 to 29 June 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. All randomised and quasi-randomised trials of prophylactic intravenous calcium in EBT for newborns. Two review authors independently assessed and extracted data on methods, participants, interventions, and outcomes (mean total and ionised serum calcium before and after EBT and the presence of adverse events such as hypoglycaemia, apnoea, cardiac arrest, and death immediately after EBT). We reported results as means difference (MD) with 95% confidence intervals (CI) for continuous outcomes and risk ratio (RR) and risk differences (RD) and 95% CIs for dichotomous outcomes. We assessed quality using the Cochrane 'Risk of bias' assessment tool and the GRADE system. We found only one quasi-randomised trial with 30 participants that met our inclusion criteria. In the small trial, total and ionised serum calcium levels were measured immediately before and immediately after EBT. All the participants were included in the final analysis and all the important outcomes were reported. Primary outcomesThere was one death in each group (RR 1.00, 95% CI 0.07 to 14.55; RD 0.00, 95% CI -0.18 to 0.18; participants = 30; studies = 1). The study did not report the presence of cardiac arrhythmias within one week of EBT and the number of infants with serum calcium levels (total less than 8 mg/dL (2 mmol/L) or ionised less than 4.4 mg/dL (1.1 mmol/L)).Pair-wise comparison of EBT with intravenous 10% calcium gluconate versus EBT without intravenous calcium (change from baseline) showed mean total serum calcium was raised in the intervention group compared to the control group (MD -0.46, 95% CI -0.81 to -0.11; participants = 30; studies = 1). Very low-quality evidence also indicated an increase in the levels of mean ionised serum calcium in the intervention group compared to the control group (MD -0.22, 95% CI -0.33 to -0.11; participants = 30; studies = 1). Secondary outcomesAdverse reactions to intravenous calcium therapy included cardiac arrest in one neonate in the intervention arm (RR 3.00, 95% CI 0.13 to 68.26; RD 0.07, 95% CI -0.10 to 0.23; participants = 30; studies = 1). There was apnoea and hypoglycaemia (RR 1.00, 95% CI 0.07 to 14.55; RD 0.00, 95% CI -0.18 to 0.18; participants = 30; studies = 1) in the two neonates who died. Data were not available for other major secondary outcomes such as the number of infants with reduced serum magnesium, reduced parathormone, increased calcitonin, presence of seizures, carpopedal spasm, jitteriness and prolonged QTc interval on electrocardiography within one week of EBT. Very low-quality data from one quasi-randomised controlled trial suggested that the mean serum total and ionised calcium increased in the study group but decreased in the control group immediately after EBT. However, the mean values of total and ionised calcium in both arms of studies remained within international reference ranges. Unfortunately, data were not available to assess the trend of total and ionised serum calcium to the end of the first week after EBT. Therefore, due to the very low quality of evidence available, it is difficult to support or reject the continual use of prophylactic intravenous calcium in newborn infants receiving EBT. Researchers are encouraged to conduct more robustly designed trials with larger numbers of participants, and particularly, addressing the pattern of differences based on gestational age of participants, type of anticoagulant used, and the volume of blood used.

Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials

PubMed Central

Forman, David; Hunt, Richard H; Yuan, Yuhong; Moayyedi, Paul

2014-01-01

Objectives To determine whether searching for Helicobacter pylori and treating with eradication therapy leads to a reduction in incidence of gastric cancer among healthy asymptomatic infected individuals. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, and the Cochrane central register of controlled trials were searched through to December 2013. Conference proceedings between 2001 and 2013 were hand searched. A recursive search was performed with bibliographies of relevant studies. There were no language restrictions. Eligibility criteria for selecting studies Randomised controlled trials examining the effect of at least seven days of eradication therapy on subsequent occurrence of gastric cancer in adults who tested positive for Helicobacter pylori but otherwise healthy and asymptomatic were eligible. The control arm had to receive placebo or no treatment. Subjects had to be followed for ≥2 years. Main outcome measures Primary outcome, defined a priori, was the effect of eradication therapy on the subsequent occurrence of gastric cancer expressed as a relative risk of gastric cancer with 95% confidence intervals. Results The search strategy identified 1560 citations, of which six individual randomised controlled trials were eligible. Fifty one (1.6%) gastric cancers occurred among 3294 individuals who received eradication therapy versus 76 (2.4%) in 3203 control subjects (relative risk 0.66, 95% confidence interval 0.46 to 0.95), with no heterogeneity between studies (I2=0%, P=0.60). If the benefit of eradication therapy was assumed to persist lifelong the number needed to treat was as low as 15 for Chinese men and as high as 245 for US women. Conclusions These data provide limited, moderate quality evidence that searching for and eradicating H pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but these data cannot necessarily be extrapolated to other populations. PMID:24846275

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.

Efficacy and cost-effectiveness of minimal guided and unguided internet-based mobile supported stress-management in employees with occupational stress: a three-armed randomised controlled trial.

PubMed

Ebert, David Daniel; Lehr, Dirk; Smit, Filip; Zarski, Anna-Carlotta; Riper, Heleen; Heber, Elena; Cuijpers, Pim; Berking, Matthias

2014-08-07

Internet- and mobile based stress-management interventions (iSMI) may be an effective means to address the negative consequences of occupational stress. However, available results from randomised controlled trials are conflicting. Moreover, it is yet not clear whether guided or unguided self-help iSMI provide better value for money. Internet-based mental health interventions without guidance are often much less effective than interventions including at least some guidance from a professional. However, direct comparisons in randomised controlled trials are scarce and, to the best of our knowledge, the comparative (cost)-effectiveness of guided vs. unguided iSMI has not yet been studied. Hence, this study investigates the acceptability and (cost-) effectiveness of minimal guided and unguided iSMI in employees with heightened levels of perceived stress. A three-armed randomised controlled trial (RCT) will be conducted to compare a minimal guided and unguided iSMI with a waiting list control condition (WLC). Both active conditions are based on the same iSMI, i.e. GET.ON Stress, and differ only with regard to the guidance format. Employees with heightened levels of perceived stress (PSS ≥ 22) will be randomised to one of three conditions. Primary outcome will be comparative changes in perceived stress (PSS). Secondary outcomes include changes in self-reported depression, work-engagement, presenteeism and absenteeism. Moreover, a cost-effectiveness analysis will be conducted from a societal perspective, including both direct medical costs and costs related to productivity losses. In addition, a cost-benefit analysis will be conducted from the employer's perspective. Incremental net-benefit regression analyses will address the question if there are any baseline factors (i.e. subgroups of employees) associated with particularly favorable cost-effectiveness when the experimental intervention is offered. Assessments take place at baseline, 7 weeks post-treatment and 6 months after randomisation. Online-based (guided) self-help interventions could be an acceptable, effective and economically sustainable approach to offer evidence-based intervention alternatives to reduce the negative consequences associated with work-related stress. This study evaluates the (cost-) effectiveness of two versions of an iSMI, minimal guided and unguided iSMI. Thus, the present study will further enhance the evidence-base for iSMI and provide valuable information about the optimal balance between outcome and economic costs. German Clinical Trial Registration (DRKS): DRKS00005687.

WITHDRAWN: Corticosteroids for Bell's palsy (idiopathic facial paralysis).

PubMed

Salinas, Rodrigo A; Alvarez, Gonzalo; Ferreira, Joaquim

2009-04-15

Inflammation and oedema of the facial nerve are implicated in causing Bell's palsy. Corticosteroids have a potent anti-inflammatory action which should minimise nerve damage and thereby improve the outcome of patients suffering from this condition. The objective of this review was to assess the effect of steroid therapy in the recovery of patients with Bell's palsy. We searched the Cochrane Neuromuscular Disease Group register (searched November 2005) for randomised trials, as well as MEDLINE (January 1966 to November 2005), EMBASE (January 1980 to November 2005) and LILACS (January 1982 to November 2005). We contacted known experts in the field to identify additional published or unpublished trials. Randomised trials comparing different routes of administration and dosage schemes of corticosteroid or adrenocorticotrophic hormone therapy versus a control group where no therapy considered effective for this condition was administered, unless it was also given in a similar way to the experimental group. Two reviewers independently assessed eligibility, trial quality, and extracted the data. Four trials with a total of 179 patients were included. One trial compared cortisone acetate with placebo; one compared prednisone plus vitamins, with vitamins alone; one compared high-dose prednisone administered intravenously against saline solution, and one, not-placebo controlled, tested the efficacy of methylprednisolone. Allocation concealment was appropriate in two trials, and the data reported allowed an intention-to-treat analysis. The data included in the meta-analyses were collected from three trials with a total of 117 patients. Overall 13/59 (22%) of the patients allocated to steroid therapy had incomplete recovery of facial motor function six months after randomisation, compared with 15/58 (26%) in the control group. This reduction was not significant (relative risk 0.86, 95% confidence interval 0.47 to 1.59). The reduction in the proportion of patients with cosmetically disabling sequelae six months after randomisation was also not significant (relative risk 0.86, 95% confidence interval 0.38 to 1.98). The trial not included in the meta-analysis showed a non-significant difference in outcomes between the arms. The available evidence from randomised controlled trials does not show significant benefit from treating Bell's palsy with corticosteroids. More randomised controlled trials with a greater number of patients are needed to determine reliably whether there is real benefit (or harm) from the use of corticosteroid therapy in patients with Bell's palsy. One trial, with 551 participants, comparing prednisolone with acyclovir with both and with neither has just been published and will be included in an update of this review.

A randomised controlled trial of the use of aromatherapy and hand massage to reduce disruptive behaviour in people with dementia

PubMed Central

2013-01-01

Background Aromatherapy and hand massage therapies have been reported to have some benefit for people with dementia who display behavioural symptoms; however there are a number of limitations of reported studies. The aim is to investigate the effect of aromatherapy (3% lavender oil spray) with and without hand massage on disruptive behaviour in people with dementia living in long-term care. Methods In a single blinded randomised controlled trial 67 people with a diagnosis of dementia and a history of disruptive behaviour, from three long-term care facilities were recruited and randomised using a random number table into three groups: (1) Combination (aromatherapy and hand massage) (n = 22), (2) Aromatherapy (n = 23), (3) Placebo control (water spray) (n = 22). The intervention was given twice daily for six weeks. Data on residents’ behaviour (CMAI) and cognition (MMSE) were collected before, during and after the intervention. Results Despite a downward trend in behaviours displayed not one of the interventions significantly reduced disruptive behaviour. Conclusions Further large-scale placebo controlled studies are required where antipsychotic medication is controlled and a comparison of the methods of application of aromatherapy are investigated. Trial registration ACTRN12612000917831 PMID:23837414

Do maternal pushing techniques during labour affect obstetric or neonatal outcomes?

PubMed

Barasinski, C; Lemery, D; Vendittelli, F

2016-10-01

To assess, through a literature review, the maternal and neonatal morbidity associated with the type of pushing used during the second stage of labour. We searched the Cochrane Library and the Medline database for randomised controlled trials from 1980 to 2015, using the following keywords: "delivery", "birth", "birthing", "bearing down, coached, uncoached, pushing", "second and stage and labour", "randomised controlled trials" and "meta-analysis". Seven randomised controlled trials were found. Interventions varied between the studies. In the intervention groups, open-glottis pushing was spontaneous or coached. The groups did not differ for perineal injuries, episiotomies or type of birth. Impact on pelvic floor structure varied between the studies. Only one study found a better 5-minute Apgar score and a better umbilical artery pH in the "open glottis" group. The low methodological quality of the studies and the differences between the protocols do not justify a recommendation of a particular pushing technique. Further studies appear necessary to study outcomes with each of these techniques. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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.

Post-licence driver education for the prevention of road traffic crashes: a systematic review of randomised controlled trials.

PubMed

Ker, Katharine; Roberts, Ian; Collier, Timothy; Beyer, Fiona; Bunn, Frances; Frost, Chris

2005-03-01

The effectiveness of post-licence driver education for preventing road traffic crashes was quantified using a systematic review and meta-analyses of randomised controlled trials. Searches of appropriate electronic databases, the Internet and reference lists of relevant papers were conducted. The searches were not restricted by language or publication status. Data were pooled from 21 randomised controlled trials, including over 300,000 full licence-holding drivers of all ages. Nineteen trials reported subsequent traffic offences, with a pooled relative risk of 0.96 (95% confidence interval 0.94, 0.98). Fifteen trials reported traffic crashes with a pooled relative risk of 0.98 (0.96, 1.01). Four trials reported injury crashes with a pooled relative risk of 1.12 (0.88, 1.41). The results provide no evidence that post-licence driver education is effective in preventing road injuries or crashes. Although the results are compatible with a small reduction in the occurrence of traffic crashes, this may be due to selection biases or bias in the included trials.

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.

The impact of insecticide-treated school uniforms on dengue infections in school-aged children: study protocol for a randomised controlled trial in Thailand.

PubMed

Wilder-Smith, Annelies; Byass, Peter; Olanratmanee, Phanthip; Maskhao, Pongsri; Sringernyuang, Luechai; Logan, James G; Lindsay, Steve W; Banks, Sarah; Gubler, Duane; Louis, Valérie R; Tozan, Yesim; Kittayapong, Pattamaporn

2012-11-15

There is an urgent need to protect children against dengue since this age group is particularly sensitive to the disease. Since dengue vectors are active mainly during the day, a potential target for control should be schools where children spend a considerable amount of their day. School uniforms are the cultural norm in most developing countries, worn throughout the day. We hypothesise that insecticide-treated school uniforms will reduce the incidence of dengue infection in school-aged children. Our objective is to determine the impact of impregnated school uniforms on dengue incidence. A randomised controlled trial will be conducted in eastern Thailand in a group of schools with approximately 2,000 students aged 7-18 years. Pre-fabricated school uniforms will be commercially treated to ensure consistent, high-quality insecticide impregnation with permethrin. A double-blind, randomised, crossover trial at the school level will cover two dengue transmission seasons. Practical issues and plans concerning intervention implementation, evaluation, analysing and interpreting the data, and possible policy implications arising from the trial are discussed. clinicaltrial.gov. NCT01563640.

Efficacy and safety of primaquine and methylene blue for prevention of Plasmodium falciparum transmission in Mali: a phase 2, single-blind, randomised controlled trial.

PubMed

Dicko, Alassane; Roh, Michelle E; Diawara, Halimatou; Mahamar, Almahamoudou; Soumare, Harouna M; Lanke, Kjerstin; Bradley, John; Sanogo, Koualy; Kone, Daouda T; Diarra, Kalifa; Keita, Sekouba; Issiaka, Djibrilla; Traore, Sekou F; McCulloch, Charles; Stone, Will J R; Hwang, Jimee; Müller, Olaf; Brown, Joelle M; Srinivasan, Vinay; Drakeley, Chris; Gosling, Roly; Chen, Ingrid; Bousema, Teun

2018-06-01

Primaquine and methylene blue are gametocytocidal compounds that could prevent Plasmodium falciparum transmission to mosquitoes. We aimed to assess the efficacy and safety of primaquine and methylene blue in preventing human to mosquito transmission of P falciparum among glucose-6-phosphate dehydrogenase (G6PD)-normal, gametocytaemic male participants. This was a phase 2, single-blind, randomised controlled trial done at the Clinical Research Centre of the Malaria Research and Training Centre (MRTC) of the University of Bamako (Bamako, Mali). We enrolled male participants aged 5-50 years with asymptomatic P falciparum malaria. G6PD-normal participants with gametocytes detected by blood smear were randomised 1:1:1:1 in block sizes of eight, using a sealed-envelope design, to receive either sulfadoxine-pyrimethamine and amodiaquine, sulfadoxine-pyrimethamine and amodiaquine plus a single dose of 0·25 mg/kg primaquine, dihydroartemisinin-piperaquine, or dihydroartemisinin-piperaquine plus 15 mg/kg per day methylene blue for 3 days. Laboratory staff, investigators, and insectary technicians were masked to the treatment group and gametocyte density of study participants. The study pharmacist and treating physician were not masked. Participants could request unmasking. The primary efficacy endpoint, analysed in all infected patients with at least one infectivity measure before and after treatment, was median within-person percentage change in mosquito infectivity 2 and 7 days after treatment, assessed by membrane feeding. This study is registered with ClinicalTrials.gov, number NCT02831023. Between June 27, 2016, and Nov 1, 2016, 80 participants were enrolled and assigned to the sulfadoxine-pyrimethamine and amodiaquine (n=20), sulfadoxine-pyrimethamine and amodiaquine plus primaquine (n=20), dihydroartemisinin-piperaquine (n=20), or dihydroartemisinin-piperaquine plus methylene blue (n=20) groups. Among participants infectious at baseline (54 [68%] of 80), those in the sulfadoxine-pyrimethamine and amodiaquine plus primaquine group (n=19) had a median 100% (IQR 100 to 100) within-person reduction in mosquito infectivity on day 2, a larger reduction than was noted with sulfadoxine-pyrimethamine and amodiaquine alone (n=12; -10·2%, IQR -143·9 to 56·6; p<0·0001). The dihydroartemisinin-piperaquine plus methylene blue (n=11) group had a median 100% (IQR 100 to 100) within-person reduction in mosquito infectivity on day 2, a larger reduction than was noted with dihydroartemisinin-piperaquine alone (n=12; -6·0%, IQR -126·1 to 86·9; p<0·0001). Haemoglobin changes were similar between gametocytocidal arms and their respective controls. After exclusion of blue urine, adverse events were similar across all groups (59 [74%] of 80 participants had 162 adverse events overall, 145 [90%] of which were mild). Adding a single dose of 0·25 mg/kg primaquine to sulfadoxine-pyrimethamine and amodiaquine or 3 days of 15 mg/kg per day methylene blue to dihydroartemisinin-piperaquine was highly efficacious for preventing P falciparum transmission. Both primaquine and methylene blue were well tolerated. Bill & Melinda Gates Foundation, European Research Council. 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.

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.

INVESTIGATE-I (INVasive Evaluation before Surgical Treatment of Incontinence Gives Added Therapeutic Effect?): study protocol for a mixed methods study to assess the feasibility of a future randomised controlled trial of the clinical utility of invasive urodynamic testing

PubMed Central

2011-01-01

Background Urinary incontinence is an important health problem to the individual sufferer and to health services. Stress and stress predominant mixed urinary incontinence are increasingly managed by surgery due to advances in surgical techniques. Despite the lack of evidence for its clinical utility, most clinicians undertake invasive urodynamic testing (IUT) to confirm a functional diagnosis of urodynamic stress incontinence before offering surgery for this condition. IUT is expensive, embarrassing and uncomfortable for women and carries a small risk. Recent systematic reviews have confirmed the lack of high quality evidence of effectiveness. The aim of this pilot study is to test the feasibility of a future definitive randomised control trial that would address whether IUT alters treatment decisions and treatment outcome in these women and would test its clinical and cost effectiveness. Methods/design This is a mixed methods pragmatic multicentre feasibility pilot study with four components:- (a) A multicentre, external pilot randomised trial comparing basic clinical assessment with non-invasive tests and IUT. The outcome measures are rates of recruitment, randomisation and data completion. Data will be used to estimate sample size necessary for the definitive trial. (b) Qualitative interviews of a purposively sampled sub-set of women eligible for the pilot trial will explore willingness to participate, be randomised and their overall trial experience. (c) A national survey of clinicians to determine their views of IUT in this context, the main outcome being their willingness to randomise patients into the definitive trial. (d) Qualitative interviews of a purposively sampled group of these clinicians will explore whether and how they use IUT to inform their decisions. Discussion The pilot trial will provide evidence of feasibility and acceptability and therefore inform the decision whether to proceed to the definitive trial. Results will inform the design and conduct of the definitive trial and ensure its effectiveness in achieving its research aim. Trial registration number Current Controlled Trials ISRCTN71327395 assigned 7th June 2010. PMID:21733166

Hip fracture risk in relation to vitamin D supplementation and serum 25-hydroxyvitamin D levels: a systematic review and meta-analysis of randomised controlled trials and observational studies

PubMed Central

2010-01-01

Background Vitamin D supplementation for fracture prevention is widespread despite conflicting interpretation of relevant randomised controlled trial (RCT) evidence. This study summarises quantitatively the current evidence from RCTs and observational studies regarding vitamin D, parathyroid hormone (PTH) and hip fracture risk. Methods We undertook separate meta-analyses of RCTs examining vitamin D supplementation and hip fracture, and observational studies of serum vitamin D status (25-hydroxyvitamin D (25(OH)D) level), PTH and hip fracture. Results from RCTs were combined using the reported hazard ratios/relative risks (RR). Results from case-control studies were combined using the ratio of 25(OH)D and PTH measurements of hip fracture cases compared with controls. Original published studies of vitamin D, PTH and hip fracture were identified through PubMed and Web of Science databases, searches of reference lists and forward citations of key papers. Results The seven eligible RCTs identified showed no significant difference in hip fracture risk in those randomised to cholecalciferol or ergocalciferol supplementation versus placebo/control (RR = 1.13[95%CI 0.98-1.29]; 801 cases), with no significant difference between trials of <800 IU/day and ≥800 IU/day. The 17 identified case-control studies found 33% lower serum 25(OH)D levels in cases compared to controls, based on 1903 cases. This difference was significantly greater in studies with population-based compared to hospital-based controls (χ21 (heterogeneity) = 51.02, p < 0.001) and significant heterogeneity was present overall (χ216 (heterogeneity) = 137.9, p < 0.001). Serum PTH levels in hip fracture cases did not differ significantly from controls, based on ten case-control studies with 905 cases (χ29 (heterogeneity) = 149.68, p < 0.001). Conclusions Neither higher nor lower dose vitamin D supplementation prevented hip fracture. Randomised and observational data on vitamin D and hip fracture appear to differ. The reason for this is unclear; one possible explanation is uncontrolled confounding in observational studies. Post-fracture PTH levels are unrelated to hip fracture risk. PMID:20540727

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.

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

PubMed

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

2017-01-12

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

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

PubMed

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

2018-03-14

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

Development of a practical approach to expert elicitation for randomised controlled trials with missing health outcomes: Application to the IMPROVE trial

PubMed Central

Mason, Alexina J; Gomes, Manuel; Grieve, Richard; Ulug, Pinar; Powell, Janet T; Carpenter, James

2017-01-01

Background/aims: The analyses of randomised controlled trials with missing data typically assume that, after conditioning on the observed data, the probability of missing data does not depend on the patient’s outcome, and so the data are ‘missing at random’ . This assumption is usually implausible, for example, because patients in relatively poor health may be more likely to drop out. Methodological guidelines recommend that trials require sensitivity analysis, which is best informed by elicited expert opinion, to assess whether conclusions are robust to alternative assumptions about the missing data. A major barrier to implementing these methods in practice is the lack of relevant practical tools for eliciting expert opinion. We develop a new practical tool for eliciting expert opinion and demonstrate its use for randomised controlled trials with missing data. Methods: We develop and illustrate our approach for eliciting expert opinion with the IMPROVE trial (ISRCTN 48334791), an ongoing multi-centre randomised controlled trial which compares an emergency endovascular strategy versus open repair for patients with ruptured abdominal aortic aneurysm. In the IMPROVE trial at 3 months post-randomisation, 21% of surviving patients did not complete health-related quality of life questionnaires (assessed by EQ-5D-3L). We address this problem by developing a web-based tool that provides a practical approach for eliciting expert opinion about quality of life differences between patients with missing versus complete data. We show how this expert opinion can define informative priors within a fully Bayesian framework to perform sensitivity analyses that allow the missing data to depend upon unobserved patient characteristics. Results: A total of 26 experts, of 46 asked to participate, completed the elicitation exercise. The elicited quality of life scores were lower on average for the patients with missing versus complete data, but there was considerable uncertainty in these elicited values. The missing at random analysis found that patients randomised to the emergency endovascular strategy versus open repair had higher average (95% credible interval) quality of life scores of 0.062 (−0.005 to 0.130). Our sensitivity analysis that used the elicited expert information as pooled priors found that the gain in average quality of life for the emergency endovascular strategy versus open repair was 0.076 (−0.054 to 0.198). Conclusion: We provide and exemplify a practical tool for eliciting the expert opinion required by recommended approaches to the sensitivity analyses of randomised controlled trials. We show how this approach allows the trial analysis to fully recognise the uncertainty that arises from making alternative, plausible assumptions about the reasons for missing data. This tool can be widely used in the design, analysis and interpretation of future trials, and to facilitate this, materials are available for download. PMID:28675302

The RESPITE trial: remifentanil intravenously administered patient-controlled analgesia (PCA) versus pethidine intramuscular injection for pain relief in labour: study protocol for a randomised controlled trial.

PubMed

Wilson, Matthew; MacArthur, Christine; Gao Smith, Fang; Homer, Leanne; Handley, Kelly; Daniels, Jane

2016-12-12

The commonest opioid used for pain relief in labour is pethidine (meperidine); however, its effectiveness has long been challenged and the drug has known side effects including maternal sedation, nausea and potential transfer across the placenta to the foetus. Over a third of women receiving pethidine require an epidural due to inadequate pain relief. Epidural analgesia increases the risk of an instrumental vaginal delivery and its associated effects. Therefore, there is a clear need for a safe, effective, alternative analgesic to pethidine. Evidence suggests that remifentanil patient-controlled analgesia (PCA) reduces epidural conversion rates compared to pethidine; however, no trial has yet investigated this as a primary endpoint. We are, therefore, comparing pethidine intramuscular injection to remifentanil PCA in a randomised controlled trial. Women in established labour, requesting systemic opioid pain relief, will be randomised to either intravenously administered remifentanil PCA (intervention) or pethidine intramuscular injection (control) in an unblinded, 1:1 individual randomised trial. Following informed consent, 400 women in established labour, who request systemic opioid pain relief, from NHS Trusts across England will undergo a minimised randomisation by a computer or automated telephone system to either pethidine or remifentanil. In order to balance the groups this minimisation is based on four parameters; parity (nulliparous versus multiparous), maternal age (<20, 20 < 30, 30 < 40, 40+ years), ethnicity (South Asian (Pakistani/Indian/Bangladeshi) versus Other) and induced versus spontaneous labour. The effectiveness of pain relief provided by each technique will be recorded every 30 min after time zero, until epidural placement, delivery or transfer to theatre, quantified by Visual Analogue Scale. Incidence of maternal side effects including sedation, delivery mode, foetal distress requiring delivery, neonatal status at delivery and rate of initiation of breastfeeding within the first hour of birth will also be recorded. Maternal satisfaction with her childbirth experience will be determined by a postpartum questionnaire prior to discharge from the delivery ward. The RESPITE trial's primary outcome is the proportion of women who have an epidural placed for pain relief in labour in each arm. Current Controlled Trials registration number: ISRCTN29654603 . Registered on 23 July 2013.

Randomised controlled trial of site specific advice on school travel patterns.

PubMed

Rowland, D; DiGuiseppi, C; Gross, M; Afolabi, E; Roberts, I

2003-01-01

To evaluate the effect of site specific advice from a school travel coordinator on school travel patterns. Cluster randomised controlled trial of children attending 21 primary schools in the London boroughs of Camden and Islington. A post-intervention survey measured the proportion of children walking, cycling, or using public transport for travel to school, and the proportion of parents/carers very or quite worried about traffic and abduction. The proportion of schools that developed and implemented travel plans was assessed. One year post-intervention, nine of 11 intervention schools and none of 10 control schools had travel plans. Proportions of children walking, cycling, or using public transport on the school journey were similar in intervention and control schools. The proportion of parents who were very or quite worried about traffic danger was similar in the intervention (85%) and control groups (87%). However, after adjusting for baseline and other potential confounding factors we could not exclude the possibility of a modest reduction in parental concern about traffic danger as a result of the intervention. Having a school travel coordinator increased the production of school travel plans but there was no evidence that this changed travel patterns or reduced parental fears. Given the uncertainty about effectiveness, the policy of providing school travel coordinators should only be implemented within the context of a randomised controlled trial.

Sport-specific biomechanical responses to an ACL injury prevention programme: A randomised controlled trial.

PubMed

Taylor, Jeffrey B; Ford, Kevin R; Schmitz, Randy J; Ross, Scott E; Ackerman, Terry A; Shultz, Sandra J

2018-04-19

Anterior cruciate ligament (ACL) injury prevention programmes have not been as successful at reducing injury rates in women's basketball as in soccer. This randomised controlled trial (ClinicalTrials.gov #NCT02530333) compared biomechanical adaptations in basketball and soccer players during jump-landing activities after an ACL injury prevention programme. Eighty-seven athletes were cluster randomised into intervention (6-week programme) and control groups. Three-dimensional biomechanical analyses of drop vertical jump (DVJ), double- (SAG-DL) and single-leg (SAG-SL) sagittal, and double- (FRONT-DL) and single-leg (FRONT-SL) frontal plane jump landing tasks were tested before and after the intervention. Peak angles, excursions, and joint moments were analysed using two-way MANCOVAs of post-test scores while controlling for pre-test scores. During SAG-SL the basketball intervention group exhibited increased peak knee abduction angles (p = .004) and excursions (p = .003) compared to the basketball control group (p = .01) and soccer intervention group (p = .01). During FRONT-SL, the basketball intervention group exhibited greater knee flexion excursion after training than the control group (p = .01), but not the soccer intervention group (p = .11). Although women's soccer players exhibit greater improvements in knee abduction kinematics than basketball players, these athletes largely exhibit similar biomechanical adaptations to ACL injury prevention programmes.

Perineal massage in labour and prevention of perineal trauma: randomised controlled trial.

PubMed

Stamp, G; Kruzins, G; Crowther, C

2001-05-26

To determine the effects of perineal massage in the second stage of labour on perineal outcomes. Randomised controlled trial. At 36 weeks' gestation, women expecting normal birth of a singleton were asked to join the study. Women became eligible to be randomised in labour if they progressed to full dilatation of the cervix or 8 cm or more if nulliparous or 5 cm or more if multiparous. 1340 were randomised into the trial. Massage and stretching of the perineum during the second stage of labour with a water soluble lubricant. rates of intact perineum, episiotomies, and first, second, third, and fourth degree tears. pain at three and 10 days postpartum and pain, dyspareunia, resumption of sexual intercourse, and urinary and faecal incontinence and urgency three months postpartum. Rates of intact perineums, first and second degree tears, and episiotomies were similar in the massage and the control groups. There were fewer third degree tears in the massage group (12 (1.7%) v 23 (3.6%); absolute risk 2.11, relative risk 0.45; 95% confidence interval 0.23 to 0.93, P<0.04), though the trial was underpowered to measure this rarer outcome. Groups did not differ in any of the secondary outcomes at the three assessment points. The practice of perineal massage in labour does not increase the likelihood of an intact perineum or reduce the risk of pain, dyspareunia, or urinary and faecal problems.

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.

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

PubMed

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

2013-06-27

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

A randomised controlled trial of losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis.

PubMed

McPherson, Stuart; Wilkinson, Nina; Tiniakos, Dina; Wilkinson, Jennifer; Burt, Alastair D; McColl, Elaine; Stocken, Deborah D; Steen, Nick; Barnes, Jane; Goudie, Nicola; Stewart, Stephen; Bury, Yvonne; Mann, Derek; Anstee, Quentin M; Day, Christopher P

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease worldwide. Experimental and small clinical trials have demonstrated that angiotensin II blockers (ARB) may be anti-fibrotic in the liver. The aim of this randomised controlled trial was to assess whether treatment with Losartan for 96 weeks slowed, halted or reversed the progression of fibrosis in patients with non-alcoholic steatohepatitis (NASH). Double-blind randomised-controlled trial of Losartan 50 mg once a day versus placebo for 96 weeks in patients with histological evidence of NASH. The primary outcome for the study was change in histological fibrosis stage from pre-treatment to end-of-treatment. The study planned to recruit 214 patients. However, recruitment was slower than expected, and after 45 patients were randomised (median age 55; 56% male; 60% diabetic; median fibrosis stage 2), enrolment was suspended. Thirty-two patients (15 losartan and 17 placebo) completed follow up period: one patient (6.7%) treated with losartan and 4 patients (23.5%) in the placebo group were "responders" (lower fibrosis stage at follow up compared with baseline). The major reason for slow recruitment was that 39% of potentially eligible patients were already taking an ARB or angiotensin converting enzyme inhibitor (ACEI), and 15% were taking other prohibited medications. Due to the widespread use of ACEI and ARB in patients with NASH this trial failed to recruit sufficient patients to determine whether losartan has anti-fibrotic effects in the liver. ISRCTN 57849521.

Effect of Treatment Delay, Stroke Type, and Thrombolysis on the Effect of Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome after Acute Stroke: A Systematic Review and Meta-Analysis of Individual Patient from Randomised Trials.

PubMed

Bath, Philip M; Woodhouse, Lisa; Krishnan, Kailash; Anderson, Craig; Berge, Eivind; Ford, Gary A; Robinson, Thompson G; Saver, Jeffrey L; Sprigg, Nikola; Wardlaw, Joanna M; In Acute Stroke Collaboration Basc, Blood Pressure

2016-01-01

Background. Nitric oxide (NO) donors are a candidate treatment for acute stroke and two trials have suggested that they might improve outcome if administered within 4-6 hours of stroke onset. We assessed the safety and efficacy of NO donors using individual patient data (IPD) from completed trials. Methods. Randomised controlled trials of NO donors in patients with acute or subacute stroke were identified and IPD sought from the trialists. The effect of NO donor versus control on functional outcome was assessed using the modified Rankin scale (mRS) and death, by time to randomisation. Secondary outcomes included measures of disability, mood, and quality of life. Results. Five trials (4,197 participants) were identified, all involving glyceryl trinitrate (GTN). Compared with control, GTN lowered blood pressure by 7.4/3.3 mmHg. At day 90, GTN did not alter any clinical measures. However, in 312 patients randomised within 6 hours of stroke onset, GTN was associated with beneficial shifts in the mRS (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.34-0.78) and reduced death (OR 0.32, 95% CI 0.14-0.78). Conclusions. NO donors do not alter outcome in patients with recent stroke. However, when administered within 6 hours, NO donors might improve outcomes in both ischaemic and haemorrhagic stroke.

The effect of primary midwife-led care on women's experience of childbirth: results from the COSMOS randomised controlled trial.

PubMed

McLachlan, H L; Forster, D A; Davey, M-A; Farrell, T; Flood, M; Shafiei, T; Waldenström, U

2016-02-01

To determine the effect of primary midwife-led care ('caseload midwifery') on women's experiences of childbirth. Randomised controlled trial. Tertiary care women's hospital in Melbourne, Australia. A total of 2314 low-risk pregnant women. Women randomised to caseload care received antenatal, intrapartum and postpartum care from a primary midwife, with some care provided by a 'back-up' midwife. Women in standard care received midwifery-led care with varying levels of continuity, junior obstetric care or community-based medical care. The primary outcome of the study was caesarean section. This paper presents a secondary outcome, women's experience of childbirth. Women's views and experiences were sought using seven-point rating scales via postal questionnaires 2 months after the birth. A total of 2314 women were randomised between September 2007 and June 2010; 1156 to caseload and 1158 to standard care. Response rates to the follow-up questionnaire were 88 and 74%, respectively. Women in the caseload group were more positive about their overall birth experience than women in the standard care group (adjusted odds ratio 1.50, 95% CI 1.22-1.84). They also felt more in control during labour, were more proud of themselves, less anxious, and more likely to have a positive experience of pain. Compared with standard maternity care, caseload midwifery may improve women's experiences of childbirth. Primary midwife-led care ('caseload midwifery') improves women's experiences of childbirth. © 2015 Royal College of Obstetricians and Gynaecologists.

Timing of oral anticoagulant therapy in acute ischemic stroke with atrial fibrillation: study protocol for a registry-based randomised controlled trial.

PubMed

Åsberg, Signild; Hijazi, Ziad; Norrving, Bo; Terént, Andreas; Öhagen, Patrik; Oldgren, Jonas

2017-12-02

Oral anticoagulation therapy is recommended for the prevention of recurrent ischemic stroke in patients with atrial fibrillation (AF). Current guidelines do not provide evidence-based recommendations on optimal time-point to start anticoagulation therapy after an acute ischemic stroke. Non-vitamin K antagonist oral anticoagulants (NOACs) may offer advantages compared to warfarin because of faster and more predictable onset of action and potentially a lower risk of intracerebral haemorrhage also in the acute phase after an ischemic stroke. The TIMING study aims to establish the efficacy and safety of early vs delayed initiation of NOACs in patients with acute ischemic stroke and AF. The TIMING study is a national, investigator-led, registry-based, multicentre, open-label, randomised controlled study. The Swedish Stroke Register is used for enrolment, randomisation and follow-up of 3000 patients, who are randomised (1:1) within 72 h from ischemic stroke onset to either early (≤ 4 days) or delayed (≥ 5-10 days) start of NOAC therapy. The primary outcome is the composite of recurrent ischemic stroke, symptomatic intracerebral haemorrhage, or all-cause mortality within 90 days after randomisation. Secondary outcomes include: individual components of the primary outcome at 90 and 365 days; major haemorrhagic events; functional outcome by the modified Rankin Scale at 90 days; and health economics. In an optional biomarker sub-study, blood samples will be collected after randomisation from approximately half of the patients for central analysis of cardiovascular biomarkers after study completion. The study is funded by the Swedish Medical Research Council. Enrolment of patients started in April 2017. The TIMING study addresses the ongoing clinical dilemma of when to start NOAC after an acute ischemic stroke in patients with AF. By the inclusion of a randomisation module within the Swedish Stroke Register, the advantages of a prospective randomised study design are combined with the strengths of a national clinical quality register in allowing simplified enrolment and follow-up of study patients. In addition, the register adds the possibility of directly assessing the external validity of the study findings. ClinicalTrials.gov, NCT02961348 . Registered on 8 November 2016.

Propofol versus thiopental sodium for the treatment of refractory status epilepticus (Review).

PubMed

Prabhakar, Hemanshu; Bindra, Ashish; Singh, Gyaninder Pal; Kalaivani, Mani

2013-07-01

Failure to respond to antiepileptic drugs in uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome. To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (10 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library 2012), and MEDLINE (1946 to May week 1, 2012). We also searched (10 May 2012) ClinicalTrials.gov, The South Asian Database of Controlled Clinical Trials, and IndMED (a bibliographic database of Indian Medical Journals). All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol. Two review authors screened the search results and reviewed abstracts of relevant and eligible trials before retrieving the full text publications. One study was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE and receiving either propofol or thiopental sodium for the control of seizure activity (Rossetti 2011). This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. There was no evidence of a difference between the drugs with respect to the outcome measures such as control of seizure activity and functional outcome at three months. There is lack of robust and randomised controlled evidence that can clarify the efficacy of propofol and thiopental sodium over each other in the treatment of RSE. There is a need for large, randomised controlled trials for this serious condition. Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Targeting intensive versus conventional glycaemic control for type 1 diabetes mellitus: a systematic review with meta-analyses and trial sequential analyses of randomised clinical trials.

PubMed

Kähler, Pernille; Grevstad, Berit; Almdal, Thomas; Gluud, Christian; Wetterslev, Jørn; Lund, Søren Søgaard; Vaag, Allan; Hemmingsen, Bianca

2014-08-19

To assess the benefits and harms of targeting intensive versus conventional glycaemic control in patients with type 1 diabetes mellitus. A systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded and LILACS to January 2013. Randomised clinical trials that prespecified different targets of glycaemic control in participants at any age with type 1 diabetes mellitus were included. Two authors independently assessed studies for inclusion and extracted data. 18 randomised clinical trials included 2254 participants with type 1 diabetes mellitus. All trials had high risk of bias. There was no statistically significant effect of targeting intensive glycaemic control on all-cause mortality (risk ratio 1.16, 95% CI 0.65 to 2.08) or cardiovascular mortality (0.49, 0.19 to 1.24). Targeting intensive glycaemic control reduced the relative risks for the composite macrovascular outcome (0.63, 0.41 to 0.96; p=0.03), and nephropathy (0.37, 0.27 to 0.50; p<0.00001. The effect estimates of retinopathy, ketoacidosis and retinal photocoagulation were not consistently statistically significant between random and fixed effects models. The risk of severe hypoglycaemia was significantly increased with intensive glycaemic targets (1.40, 1.01 to 1.94). Trial sequential analyses showed that the amount of data needed to demonstrate a relative risk reduction of 10% were, in general, inadequate. There was no significant effect towards improved all-cause mortality when targeting intensive glycaemic control compared with conventional glycaemic control. However, there may be beneficial effects of targeting intensive glycaemic control on the composite macrovascular outcome and on nephropathy, and detrimental effects on severe hypoglycaemia. Notably, the data for retinopathy and ketoacidosis were inconsistent. There was a severe lack of reporting on patient relevant outcomes, and all trials had poor bias control. 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.

Impact of pelvic floor muscle training on sexual function of women with urinary incontinence and a comparison of electrical stimulation versus standard treatment (IPSU trial): a randomised controlled trial.

PubMed

Jha, Swati; Walters, Stephen J; Bortolami, Oscar; Dixon, Simon; Alshreef, Abualbishr

2018-03-01

To evaluate the clinical and cost-effectiveness of electric stimulation plus standard pelvic floor muscle training compared to standard pelvic floor muscle training alone in women with urinary incontinence and sexual dysfunction. Single centre two arm parallel group randomised controlled trial conducted in a Teaching hospital in England. Participants were women presenting with urinary incontinence and sexual dysfunction. The interventions compared were electric stimulation versus standard pelvic floor muscle training. included Prolapse and Incontinence Sexual function Questionnaire (PISQ) physical function dimension at post-treatment (primary); other dimensions of PISQ, SF-36; EQ-5D, EPAQ, resource use, adverse events and cost-effectiveness (secondary outcomes). 114 women were randomised (Intervention n=57; Control group n=57). 64/114 (56%). had valid primary outcome data at follow-up (Intervention 30; Control 34). The mean PISQ-PF dimension scores at follow-up were 33.1 (SD 5.5) and 32.3 (SD 5.2) for the Intervention and Control groups respectively; with the Control group having a higher (better) score. After adjusting for baseline score, BMI, menopausal status, time from randomisation and baseline oxford scale score the mean difference was -1.0 (95% CI: -4.0 to 1.9; P=0.474). There was no differences between the groups in any of the secondary outcomes at follow-up. Within this study, the use of electrical stimulation was cost-effective with very small incremental costs and quality adjusted life years (QALYs). In women presenting with urinary incontinence in conjunction with sexual dysfunction, physiotherapy is beneficial to improve overall sexual function. However no specific form of physiotherapy is beneficial over another. Trial registration ISRCTN09586238. Copyright © 2017 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

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

PubMed Central

2013-01-01

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

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.