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

PubMed

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

2009-07-10

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

Evaluation of different recruitment and randomisation methods in a trial of general practitioner-led interventions to increase physical activity: a randomised controlled feasibility study with factorial design

PubMed Central

2014-01-01

Background Interventions promoting physical activity by General Practitioners (GPs) lack a strong evidence base. Recruiting participants to trials in primary care is challenging. We investigated the feasibility of (i) delivering three interventions to promote physical activity in inactive participants and (ii) different methods of participant recruitment and randomised allocation. Methods We recruited general practices from Devon, Bristol and Coventry. We used a 2-by-2 factorial design for participant recruitment and randomisation. Recruitment strategies were either opportunistic (approaching patients attending their GP surgery) or systematic (selecting patients from practice lists and approaching them by letter). Randomisation strategies were either individual or by practice cluster. Feasibility outcomes included time taken to recruit the target number of participants within each practice. Participants were randomly allocated to one of three interventions: (i) written advice (control); (ii) brief GP advice (written advice plus GP advice on physical activity), and (iii) brief GP advice plus a pedometer to self-monitor physical activity during the trial. Participants allocated to written advice or brief advice each received a sealed pedometer to record their physical activity, and were instructed not to unseal the pedometer before the scheduled day of data collection. Participant level outcomes were reported descriptively and included the mean number of pedometer steps over a 7-day period, and European Quality of Life (EuroQoL)-5 dimensions (EQ-5D) scores, recorded at 12 weeks’ follow-up. Results We recruited 24 practices (12 using each recruitment method; 18 randomising by cluster, 6 randomising by individual participant), encompassing 131 participants. Opportunistic recruitment was associated with less time to target recruitment compared with systematic (mean difference (days) -54.9, 95% confidence interval (CI) -103.6; -6.2) but with greater loss to follow up (28.8% versus. 6.9%; mean difference 21.9% (95% CI 9.6%; 34.1%)). There were differences in the socio-demographic characteristics of participants according to recruitment method. There was no clear pattern of change in participant level outcomes from baseline to 12 weeks across the three arms. Conclusions Delivering and trialling GP-led interventions to promote physical activity is feasible, but trial design influences time to participant recruitment, participant withdrawal, and possibly, the socio-demographic characteristics of participants. Trial registration number ISRCTN73725618. PMID:24746263

Effects of emotion recognition training on mood among individuals with high levels of depressive symptoms: study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background We have developed a new paradigm that targets the recognition of facial expression of emotions. Here we report the protocol of a randomised controlled trial of the effects of emotion recognition training on mood in a sample of individuals with depressive symptoms over a 6-week follow-up period. Methods/Design We will recruit 190 adults from the general population who report high levels of depressive symptoms (defined as a score ≥ 14 on the Beck Depression Inventory-II). Participants will attend a screening session and will be randomised to intervention or control procedures, repeated five times over consecutive days (Monday to Friday). A follow-up session will take place at end-of -treatment, 2-weeks and 6-weeks after training. Our primary study outcome will be depressive symptoms, Beck Depression Inventory- II (rated over the past two weeks). Our secondary outcomes are: depressive symptoms, Hamilton Rating Scale for Depression; anxiety symptoms, Beck Anxiety Inventory (rated over the past month); positive affect, Positive and Negative Affect Schedule (rated as ‘how you feel right now’); negative affect, Positive and Negative Affect Schedule (rated as ‘how you feel right now’); emotion sensitivity, Emotion Recognition Task (test phase); approach motivation and persistence, the Fishing Game; and depressive interpretation bias, Scrambled Sentences Test. Discussion This study is of a novel cognitive bias modification technique that targets biases in emotional processing characteristic of depression, and can be delivered automatically via computer, Internet or Smartphone. It therefore has potential to be a valuable cost-effective adjunctive treatment for depression which may be used together with more traditional psychotherapy, cognitive-behavioural therapy and pharmacotherapy. Trial registration Current Controlled Trials: ISRCTN17767674 PMID:23725208

Effects of emotion recognition training on mood among individuals with high levels of depressive symptoms: study protocol for a randomised controlled trial.

PubMed

Adams, Sally; Penton-Voak, Ian S; Harmer, Catherine J; Holmes, Emily A; Munafò, Marcus R

2013-06-01

We have developed a new paradigm that targets the recognition of facial expression of emotions. Here we report the protocol of a randomised controlled trial of the effects of emotion recognition training on mood in a sample of individuals with depressive symptoms over a 6-week follow-up period. We will recruit 190 adults from the general population who report high levels of depressive symptoms (defined as a score ≥ 14 on the Beck Depression Inventory-II). Participants will attend a screening session and will be randomised to intervention or control procedures, repeated five times over consecutive days (Monday to Friday). A follow-up session will take place at end-of -treatment, 2-weeks and 6-weeks after training. Our primary study outcome will be depressive symptoms, Beck Depression Inventory- II (rated over the past two weeks). Our secondary outcomes are: depressive symptoms, Hamilton Rating Scale for Depression; anxiety symptoms, Beck Anxiety Inventory (rated over the past month); positive affect, Positive and Negative Affect Schedule (rated as 'how you feel right now'); negative affect, Positive and Negative Affect Schedule (rated as 'how you feel right now'); emotion sensitivity, Emotion Recognition Task (test phase); approach motivation and persistence, the Fishing Game; and depressive interpretation bias, Scrambled Sentences Test. This study is of a novel cognitive bias modification technique that targets biases in emotional processing characteristic of depression, and can be delivered automatically via computer, Internet or Smartphone. It therefore has potential to be a valuable cost-effective adjunctive treatment for depression which may be used together with more traditional psychotherapy, cognitive-behavioural therapy and pharmacotherapy. Current Controlled Trials: ISRCTN17767674.

Can mobile phone multimedia messages and text messages improve clinic attendance for Aboriginal children with chronic otitis media? A randomised controlled trial.

PubMed

Phillips, James H; Wigger, Christine; Beissbarth, Jemima; McCallum, Gabrielle B; Leach, Amanda; Morris, Peter S

2014-05-01

Does phone multimedia messages (MMS) to families of Indigenous children with tympanic membrane perforation (TMP): (i) increase clinic attendance; (ii) improve ear health; and (iii) provide a culturally appropriate method of health promotion? Fifty-three Australian Aboriginal children with a TMP living in remote community households with a mobile phone were randomised into intervention (n = 30) and control (n = 23) groups. MMS health messages in local languages were sent to the intervention group over 6 weeks. there was no significant difference in clinic attendance, with 1.3 clinic visits per child in both groups (mean difference -0.1; 95% confidence interval (CI) -1.1, 0.9; P = 0.9). (i) there was no significant change in healed perforation (risk difference 6%; 95% CI -10, 20; P = 0.6), middle ear discharge (risk difference -1%; 95% CI -30, 30; P = 1.0) or perforation size (mean difference 3%; 95% CI -11, 17; P = 0.7) between the groups; (ii) 84% (95% CI 60, 90) in the control and 70% (95% CI 50, 80) in the intervention group were happy to receive MMS health messages in the future. The difference was not significant (risk difference -14%; 95% CI -37, 8; P = 0.3). Although there was no improvement in clinic attendance or ear health, this randomised controlled trial of MMS in Indigenous languages demonstrated that MMS is a culturally appropriate form of health promotion. Mobile phones may enhance management of chronic disease in remote and disadvantaged populations. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

The CLIMATE schools combined study: a cluster randomised controlled trial of a universal Internet-based prevention program for youth substance misuse, depression and anxiety.

PubMed

Teesson, Maree; Newton, Nicola C; Slade, Tim; Chapman, Cath; Allsop, Steve; Hides, Leanne; McBride, Nyanda; Mewton, Louise; Tonks, Zoe; Birrell, Louise; Brownhill, Louise; Andrews, Gavin

2014-02-05

Anxiety, depressive and substance use disorders account for three quarters of the disability attributed to mental disorders and frequently co-occur. While programs for the prevention and reduction of symptoms associated with (i) substance use and (ii) mental health disorders exist, research is yet to determine if a combined approach is more effective. This paper describes the study protocol of a cluster randomised controlled trial to evaluate the effectiveness of the CLIMATE Schools Combined intervention, a universal approach to preventing substance use and mental health problems among adolescents. Participants will consist of approximately 8400 students aged 13 to 14-years-old from 84 secondary schools in New South Wales, Western Australia and Queensland, Australia. The schools will be cluster randomised to one of four groups; (i) CLIMATE Schools Combined intervention; (ii) CLIMATE Schools - Substance Use; (iii) CLIMATE Schools - Mental Health, or (iv) Control (Health and Physical Education as usual). The primary outcomes of the trial will be the uptake and harmful use of alcohol and other drugs, mental health symptomatology and anxiety, depression and substance use knowledge. Secondary outcomes include substance use related harms, self-efficacy to resist peer pressure, general disability, and truancy. The link between personality and substance use will also be examined. Compared to students who receive the universal CLIMATE Schools - Substance Use, or CLIMATE Schools - Mental Health or the Control condition (who received usual Health and Physical Education), we expect students who receive the CLIMATE Schools Combined intervention to show greater delays to the initiation of substance use, reductions in substance use and mental health symptoms, and increased substance use and mental health knowledge. This trial is registered with the Australian and New Zealand Clinical Trials registry, ACTRN12613000723785.

Personalised telehealth intervention for chronic disease management: A pilot randomised controlled trial.

PubMed

Bohingamu Mudiyanselage, Shalika; Stevens, Jo; Watts, Jennifer J; Toscano, Julian; Kotowicz, Mark A; Steinfort, Christopher L; Bell, Jennifer; Byrnes, Janette; Bruce, Stephanie; Carter, Sarah; Hunter, Claire; Barrand, Chris; Hayles, Robyn

2018-01-01

Introduction The aim of this study was to assess the impact of home-based telehealth monitoring on health outcomes, quality of life and costs over 12 months for patients with diabetes and/or chronic obstructive pulmonary disease (COPD) who were identified as being at high risk of readmission to hospital. Methods This pilot study was a randomised controlled trial combined with an economic analysis to examine the outcomes of standard care versus home-based telehealth for people with diabetes and/or COPD who were at risk of hospital readmission within one year. The primary outcomes were (i) hospital admission and length of stay (LOS); and (ii) health-related quality of life (HRQOL); and the secondary outcomes were (i) health-related clinical outcomes; (ii) anxiety and depression scores; and (iii) health literacy. The costs of the intervention and hospitalisations were included. Results A total of 86 and 85 participants were randomised to the intervention and control groups respectively. The difference between groups in hospital LOS was -3.89 (95% confidence interval (CI): -9.40, 1.62) days, and for HRQOL, 0.09 (95% CI: 0.05, 0.14) in favour of the telehealth monitoring group. There was a saving of AUD$6553 (95% CI: -12145, -961) in the cost of hospitalisation over 12 months, which offset the increased cost of tele-monitoring. The intervention group showed an improvement in anxiety, depression and health literacy at 12 months, and in the diabetes group, a reduction in microalbuminuria. Discussion The telehealth monitoring intervention improved patient's health outcomes and quality of life at no additional cost.

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.

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

PubMed

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

2017-08-23

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

The HubBLe trial: haemorrhoidal artery ligation (HAL) versus rubber band ligation (RBL) for haemorrhoids.

PubMed

Tiernan, Jim; Hind, Daniel; Watson, Angus; Wailoo, Allan J; Bradburn, Michael; Shephard, Neil; Biggs, Katie; Brown, Steven

2012-10-25

Haemorrhoids (piles) are a very common condition seen in surgical clinics. After exclusion of more sinister causes of haemorrhoidal symptoms (rectal bleeding, perianal irritation and prolapse), the best option for treatment depends upon persistence and severity of the symptoms. Minor symptoms often respond to conservative treatment such as dietary fibre and reassurance. For more severe symptoms treatment such as rubber band ligation may be therapeutic and is a very commonly performed procedure in the surgical outpatient setting. Surgery is usually reserved for those who have more severe symptoms, as well as those who do not respond to non-operative therapy; surgical techniques include haemorrhoidectomy and haemorrhoidopexy. More recently, haemorrhoidal artery ligation has been introduced as a minimally invasive, non destructive surgical option.There are substantial data in the literature concerning efficacy and safety of 'rubber band ligation including multiple comparisons with other interventions, though there are no studies comparing it to haemorrhoidal artery ligation. A recent overview has been carried out by the National Institute for Health and Clinical Excellence which concludes that current evidence shows haemorrhoidal artery ligation to be a safe alternative to haemorrhoidectomy and haemorrhoidopexy though it also highlights the lack of good quality data as evidence for the advantages of the technique. The aim of this study is to establish the clinical effectiveness and cost effectiveness of haemorrhoidal artery ligation compared with conventional rubber band ligation in the treatment of people with symptomatic second or third degree (Grade II or Grade III) haemorrhoids. A multi-centre, parallel group randomised controlled trial. The primary outcome is patient-reported symptom recurrence twelve months following the intervention. Secondary outcome measures relate to symptoms, complications, health resource use, health related quality of life and cost effectiveness following the intervention. 350 patients with grade II or grade III haemorrhoids will be recruited in surgical departments in up to 14 NHS hospitals. A multi-centre, parallel group randomised controlled trial. Block randomisation by centre will be used, with 175 participants randomised to each group. The results of the research will help inform future practice for the treatment of grade II and III haemorrhoids. ISRCTN41394716.

A randomised, phase II study of repeated rhenium-188-HEDP combined with docetaxel and prednisone versus docetaxel and prednisone alone in castration-resistant prostate cancer (CRPC) metastatic to bone; the Taxium II trial.

PubMed

van Dodewaard-de Jong, Joyce M; de Klerk, John M H; Bloemendal, Haiko J; Oprea-Lager, Daniela E; Hoekstra, Otto S; van den Berg, H Pieter; Los, Maartje; Beeker, Aart; Jonker, Marianne A; O'Sullivan, Joe M; Verheul, Henk M W; van den Eertwegh, Alfons J M

2017-08-01

Rhenium-188-HEDP is a beta-emitting radiopharmaceutical used for palliation of metastatic bone pain. We investigated whether the addition of rhenium-188-HEDP to docetaxel/prednisone improved efficacy of chemotherapy in patients with CRPC. Patients with progressive CRPC and osteoblastic bone metastases were randomised for first-line docetaxel 75 mg/m 2 3-weekly plus prednisone with or without 2 injections of rhenium-188-HEDP after the third (40 MBq/kg) and after the sixth (20 MBq/kg) cycle of docetaxel. Primary endpoint was progression-free survival (PFS), defined as either PSA, radiographic or clinical progression. Patients were stratified by extent of bone metastases and hospital. Forty-two patients were randomised for standard treatment and 46 patients for combination therapy. Median number of cycles of docetaxel was 9 in the control group and 8 in the experimental group. Median follow-up was 18.4 months. Two patients from the experimental group did not start treatment after randomisation. In the intention to treat analysis no differences in PFS, survival and PSA became apparent between the two groups. In an exploratory per-protocol analysis median overall survival was significantly longer in the experimental group (33.8 months (95%CI 31.75-35.85)) than in the control group (21.0 months (95%CI 13.61-28.39); p 0.012). Also median PFS in patients with a baseline phosphatase >220U/L was significantly better with combination treatment (9.0 months (95%CI 3.92-14.08) versus 6.2 months (95%CI 3.08-9.32); log rank p 0.005). As expected, thrombocytopenia (grade I/II) was reported more frequently in the experimental group (25% versus 0%). Combined treatment with rhenium-188-HEDP and docetaxel did not prolong PFS in patients with CRPC. The observed survival benefit in the per-protocol analysis warrants further studies in the combined treatment of chemotherapy and radiopharmaceuticals.

Behavioural activation versus mindfulness-based guided self-help treatment administered through a smartphone application: a randomised controlled trial

PubMed Central

Ly, Kien Hoa; Trüschel, Anna; Jarl, Linnea; Magnusson, Susanna; Windahl, Tove; Johansson, Robert; Carlbring, Per; Andersson, Gerhard

2014-01-01

Objectives Evaluating and comparing the effectiveness of two smartphone-delivered treatments: one based on behavioural activation (BA) and other on mindfulness. Design Parallel randomised controlled, open, trial. Participants were allocated using an online randomisation tool, handled by an independent person who was separate from the staff conducting the study. Setting General community, with recruitment nationally through mass media and advertisements. Participants 40 participants diagnosed with major depressive disorder received a BA treatment, and 41 participants received a mindfulness treatment. 9 participants were lost at the post-treatment. Intervention BA: An 8-week long behaviour programme administered via a smartphone application. Mindfulness: An 8-week long mindfulness programme, administered via a smartphone application. Main outcome measures The Beck Depression Inventory-II (BDI-II) and the nine-item Patient Health Questionnaire Depression Scale (PHQ-9). Results 81 participants were randomised (mean age 36.0 years (SD=10.8)) and analysed. Results showed no significant interaction effects of group and time on any of the outcome measures either from pretreatment to post-treatment or from pretreatment to the 6-month follow-up. Subgroup analyses showed that the BA treatment was more effective than the mindfulness treatment among participants with higher initial severity of depression from pretreatment to the 6-month follow-up (PHQ-9: F (1, 362.1)=5.2, p<0.05). In contrast, the mindfulness treatment worked better than the BA treatment among participants with lower initial severity from pretreatment to the 6-month follow-up (PHQ-9: F (1, 69.3)=7.7, p<0.01); BDI-II: (F(1, 53.60)=6.25, p<0.05). Conclusions The two interventions did not differ significantly from one another. For participants with higher severity of depression, the treatment based on BA was superior to the treatment based on mindfulness. For participants with lower initial severity, the treatment based on mindfulness worked significantly better than the treatment based on BA. Trial registration Clinical Trials NCT01463020. PMID:24413342

Accelerating clinical development of HIV vaccine strategies: methodological challenges and considerations in constructing an optimised multi-arm phase I/II trial design.

PubMed

Richert, Laura; Doussau, Adélaïde; Lelièvre, Jean-Daniel; Arnold, Vincent; Rieux, Véronique; Bouakane, Amel; Lévy, Yves; Chêne, Geneviève; Thiébaut, Rodolphe

2014-02-26

Many candidate vaccine strategies against human immunodeficiency virus (HIV) infection are under study, but their clinical development is lengthy and iterative. To accelerate HIV vaccine development optimised trial designs are needed. We propose a randomised multi-arm phase I/II design for early stage development of several vaccine strategies, aiming at rapidly discarding those that are unsafe or non-immunogenic. We explored early stage designs to evaluate both the safety and the immunogenicity of four heterologous prime-boost HIV vaccine strategies in parallel. One of the vaccines used as a prime and boost in the different strategies (vaccine 1) has yet to be tested in humans, thus requiring a phase I safety evaluation. However, its toxicity risk is considered minimal based on data from similar vaccines. We newly adapted a randomised phase II trial by integrating an early safety decision rule, emulating that of a phase I study. We evaluated the operating characteristics of the proposed design in simulation studies with either a fixed-sample frequentist or a continuous Bayesian safety decision rule and projected timelines for the trial. We propose a randomised four-arm phase I/II design with two independent binary endpoints for safety and immunogenicity. Immunogenicity evaluation at trial end is based on a single-stage Fleming design per arm, comparing the observed proportion of responders in an immunogenicity screening assay to an unacceptably low proportion, without direct comparisons between arms. Randomisation limits heterogeneity in volunteer characteristics between arms. To avoid exposure of additional participants to an unsafe vaccine during the vaccine boost phase, an early safety decision rule is imposed on the arm starting with vaccine 1 injections. In simulations of the design with either decision rule, the risks of erroneous conclusions were controlled <15%. Flexibility in trial conduct is greater with the continuous Bayesian rule. A 12-month gain in timelines is expected by this optimised design. Other existing designs such as bivariate or seamless phase I/II designs did not offer a clear-cut alternative. By combining phase I and phase II evaluations in a multi-arm trial, the proposed optimised design allows for accelerating early stage clinical development of HIV vaccine strategies.

Systematic Review of Integrative Health Care Research: Randomized Control Trials, Clinical Controlled Trials, and Meta-Analysis

DTIC Science & Technology

2010-01-01

to usual care (control). Also, in the pilot study of the 4 individual Noetic therapies, off-site prayer was associated with the lowest absolute...mortality in-hospital and at 6 months [16]. The parallel randomization to 4 different Noetic therapies across 5 study arms limited the assessment of...interventional cardiac care: the Monitoring and Actualisation of Noetic Trainings (MANTRA) II randomised study ,” Lancet, vol. 366, no. 9481, pp. 211–217, 2005. [18

The efficacy of transcutaneous electrical nerve stimulation on the improvement of walking distance in patients with peripheral arterial disease with intermittent claudication: study protocol for a randomised controlled trial: the TENS-PAD study.

PubMed

Besnier, Florent; Sénard, Jean-Michel; Grémeaux, Vincent; Riédel, Mélanie; Garrigues, Damien; Guiraud, Thibaut; Labrunée, Marc

2017-08-10

In patients with peripheral arterial disease (PAD), walking improvements are often limited by early pain onset due to vascular claudication. It would thus appear interesting to develop noninvasive therapeutic strategies, such as transcutaneous electrical nerve stimulation (TENS), to improve the participation of PAD patients in rehabilitation programmes, and thus improve their quality of life. Our team recently tested the efficacy of a single 45-min session of 10-Hz TENS prior to walking. TENS significantly delayed pain onset and increased the pain-free walking distance in patients with class-II PAD. We now seek to assess the efficacy of a chronic intervention that includes the daily use of TENS for 3 weeks (5 days a week) on walking distance in Leriche-Fontaine stage-II PAD patients. This is a prospective, double-blind, multicentre, randomised, placebo-controlled trial. One hundred subjects with unilateral PAD (Leriche-Fontaine stage II) will be randomised into two groups (1:1). For the experimental group (TENS group): the treatment will consist of stimulation of the affected leg (at a biphasic frequency of 10 Hz, with a pulse width of 200 μs, maximal intensity below the motor threshold) for 45 min per day, in the morning before the exercise rehabilitation programme, for 3 weeks, 5 days per week. For the control group (SHAM group): the placebo stimulation will be delivered according to the same modalities as for the TENS group but with a voltage level automatically falling to zero after 10 s of stimulation. First outcome: walking distance without pain. transcutaneous oxygen pressure (TcPO 2 ) measured during a Strandness exercise test, peak oxygen uptake (VO 2 peak), endothelial function (EndoPAT®), Ankle-brachial Pressure Index, Body Mass Index, lipid profile (LDL-C, HDL-C, triglycerides), fasting glycaemia, HbA1c level, and the WELCH questionnaire. TENS-PAD is the first randomised controlled trial that uses transcutaneous electrical therapy as an adjuvant technique to improve vascular function in the treatment of PAD. If the results are confirmed, this technique could be incorporated into the routine care in cardiovascular rehabilitation centers and used in the long term by patients to improve their walking capacity. ClinicalTrials.gov, ID: NCT02678403 . Registered on 9 February 2016. Toulouse University Hospital.

Autofluorescence bronchoscopy with white light bronchoscopy compared with white light bronchoscopy alone for the detection of precancerous lesions: a European randomised controlled multicentre trial.

PubMed

Häussinger, K; Becker, H; Stanzel, F; Kreuzer, A; Schmidt, B; Strausz, J; Cavaliere, S; Herth, F; Kohlhäufl, M; Müller, K-M; Huber, R-M; Pichlmeier, U; Bolliger, Ch T

2005-06-01

The potential of autofluorescence bronchoscopy (AFB) to detect precancerous lesions in the central airways and its role in lung cancer screening is uncertain. A study was undertaken to evaluate the prevalence of moderate/severe dysplasia (dysplasia II-III) and carcinoma in situ (CIS) using a newly developed AFB system in comparison with conventional white light bronchoscopy (WLB) alone. In a prospective randomised multicentre trial, smokers > or = 40 years of age (> or = 20 pack-years) were stratified into four different risk groups and investigated with either WLB+AFB (arm A) or WLB alone (arm B). 1173 patients (916 men) of mean age 58.7 years were included. Overall (arms A and B), preinvasive lesions (dysplasia II-III and CIS) were detected in 3.9% of the patients. The prevalence of patients with preinvasive lesions in the WLB arm was 2.7% compared with 5.1% in the WLB+AFB arm (p = 0.037). For patients with dysplasia II-III, WLB+AFB increased the detection rate by a factor of 2.1 (p = 0.03), while for CIS the factor was only 1.24 (p = 0.75). The biopsy based sensitivity of WLB alone and WLB+AFB for detecting dysplasia II-III and CIS was 57.9% compared with 82.3% (1.42-fold increase). The corresponding specificity was 62.1% compared with 58.4% (0.94-fold decrease). This first randomised study of AFB showed that the combination of WLB+AFB was significantly superior to WLB alone in detecting preneoplastic lesions. Our findings do not support the general use of AFB as a screening tool for lung cancer, but suggest that it may be of use in certain groups. The precise indications await further study.

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.

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.

Randomised, double blind, placebo controlled trial of intravenous antioxidant (n‐acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis

PubMed Central

Siriwardena, Ajith K; Mason, James M; Balachandra, Srinivasan; Bagul, Anil; Galloway, Simon; Formela, Laura; Hardman, Jonathan G; Jamdar, Saurabh

2007-01-01

Background Based on equivocal clinical data, intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomised comparison of this therapy in severe acute pancreatitis. Methods We conducted a randomised, double blind, placebo controlled trial of intravenous antioxidant (n‐acetylcysteine, selenium, vitamin C) therapy in patients with predicted severe acute pancreatitis. Forty‐three patients were enrolled from three hospitals in the Manchester (UK) area over the period June 2001 to November 2004. Randomisation stratified for APACHE‐II score and hospital site, and delivered groups that were similar at baseline. Results Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial. However, at 7 days, there was no statistically significant difference in the primary end point, organ dysfunction (antioxidant vs placebo: 32% vs 17%, p = 0.33) or any secondary end point of organ dysfunction or patient outcome. Conclusions This study provides no evidence to justify continued use of n‐acetylcysteine, selenium, vitamin C based antioxidant therapy in severe acute pancreatitis. In the context of any future trial design, careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study. PMID:17356040

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.

Parental depression and child conduct problems: evaluation of parental service use and associated costs after attending the Incredible Years Basic Parenting Programme.

PubMed

Charles, Joanna M; Bywater, Tracey J; Edwards, Rhiannon Tudor; Hutchings, Judy; Zou, Lu

2013-12-18

There is co-morbidity between parental depression and childhood conduct disorder. The Incredible Years (IY) parenting programmes reduce both conduct disorder in children and depression in their parents. Recent U.K. and Ireland trials of the effectiveness and cost-effectiveness of IY parenting programmes have assessed children's health and social care service use, but little is known about the programme's impact on parental service use. This paper explores whether an above clinical cut-off score on the Beck Depression Inventory II (BDI II) is associated with high or low parental health and social care service use in high-risk families receiving the IY Basic Programme. This is a secondary analysis of a subsample (N = 119) from the first U.K. community-based randomised controlled trial of the 12-week IY Basic Programme (N = 153). Parents with children at risk of developing conduct disorder were randomised to receive the programme or to a waiting-list control group. BDI II total and BDI II clinical depression cut-off scores were compared to frequencies and costs of parents' service use, at baseline, six, twelve and eighteen months post-baseline for the intervention group and at baseline and six months post-baseline for the control group. Intervention group parents who scored above the clinical cut-off on the BDI II at baseline used more health and social care services than those who scored below at baseline, six and eighteen months. Significant reductions in service use frequencies were found for the intervention group only. Parents with higher levels or depression used more health and social care service and parenting programmes have been shown to reduce parental depression and also health and social service use. However, further exploration of depressed parents' service use and the cost implications for publically funded health and social care services is needed.

Protocol for the ProCare Trial: a phase II randomised controlled trial of shared care for follow-up of men with prostate cancer

PubMed Central

Emery, Jon; Doorey, Juanita; Jefford, Michael; King, Madeleine; Pirotta, Marie; Hayne, Dickon; Martin, Andrew; Trevena, Lyndal; Lim, Tee; Constable, Roger; Hawks, Cynthia; Hyatt, Amelia; Hamid, Akhlil; Violet, John; Gill, Suki; Frydenberg, Mark; Schofield, Penelope

2014-01-01

Introduction Men with prostate cancer require long-term follow-up to monitor disease progression and manage common adverse physical and psychosocial consequences of treatment. There is growing recognition of the potential role of primary care in cancer follow-up. This paper describes the protocol for a phase II multisite randomised controlled trial of a novel model of shared care for the follow-up of men after completing treatment for low-moderate risk prostate cancer. Methods and analysis The intervention is a shared care model of follow-up visits in the first 12 months after completing treatment for prostate cancer with the following specific components: a survivorship care plan, general practitioner (GP) management guidelines, register and recall systems, screening for distress and unmet needs and patient information resources. Eligible men will have completed surgery and/or radiotherapy for low-moderate risk prostate cancer within the previous 8 weeks and have a GP who consents to participate. Ninety men will be randomised to the intervention or current hospital follow-up care. Study outcome measures will be collected at baseline, 3, 6 and 12 months and include anxiety, depression, unmet needs, prostate cancer-specific quality of life and satisfaction with care. Clinical processes and healthcare resource usage will also be measured. The principal emphasis of the analysis will be on obtaining estimates of the treatment effect size and assessing feasibility in order to inform the design of a subsequent phase III trial. Ethics and dissemination Ethics approval has been granted by the University of Western Australia and from all hospital recruitment sites in Western Australia and Victoria. Results of this phase II trial will be reported in peer-reviewed publications and in conference presentations. Trial Registration Australian New Zealand Clinical Trial Registry ACTRN12610000938000 PMID:24604487

The CLIMATE schools combined study: a cluster randomised controlled trial of a universal Internet-based prevention program for youth substance misuse, depression and anxiety

PubMed Central

2014-01-01

Background Anxiety, depressive and substance use disorders account for three quarters of the disability attributed to mental disorders and frequently co-occur. While programs for the prevention and reduction of symptoms associated with (i) substance use and (ii) mental health disorders exist, research is yet to determine if a combined approach is more effective. This paper describes the study protocol of a cluster randomised controlled trial to evaluate the effectiveness of the CLIMATE Schools Combined intervention, a universal approach to preventing substance use and mental health problems among adolescents. Methods/design Participants will consist of approximately 8400 students aged 13 to 14-years-old from 84 secondary schools in New South Wales, Western Australia and Queensland, Australia. The schools will be cluster randomised to one of four groups; (i) CLIMATE Schools Combined intervention; (ii) CLIMATE Schools - Substance Use; (iii) CLIMATE Schools - Mental Health, or (iv) Control (Health and Physical Education as usual). The primary outcomes of the trial will be the uptake and harmful use of alcohol and other drugs, mental health symptomatology and anxiety, depression and substance use knowledge. Secondary outcomes include substance use related harms, self-efficacy to resist peer pressure, general disability, and truancy. The link between personality and substance use will also be examined. Discussion Compared to students who receive the universal CLIMATE Schools - Substance Use, or CLIMATE Schools - Mental Health or the Control condition (who received usual Health and Physical Education), we expect students who receive the CLIMATE Schools Combined intervention to show greater delays to the initiation of substance use, reductions in substance use and mental health symptoms, and increased substance use and mental health knowledge. Trial registration This trial is registered with the Australian and New Zealand Clinical Trials registry, ACTRN12613000723785. PMID:24499060

A randomised controlled trial using mobile advertising to promote safer sex and sun safety to young people.

PubMed

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

2011-10-01

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 use of mobile advertising for health promotion. Mobile advertising subscribers aged 16-29 years residing in Victoria, Australia (n = 7606) were randomised to the 'sex' or 'sun' group and received eight messages during the 2008-2009 summer period. Changes in sex- and sun-related knowledge and behaviour were measured by questionnaires completed on mobile phones. At follow-up, the sex group had significantly higher sexual health knowledge and fewer sexual partners than the sun group. The sun group had no change in hat-wearing frequency compared with a significant decline in hat-wearing frequency in the sex group. This is the first study of mobile advertising for health promotion, which can successfully reach most young people. Challenges experienced with project implementation and evaluation should be considered as new technological approaches to health promotion continue to be expanded.

Centre-based day care for children younger than five years of age in low- and middle-income countries.

PubMed

Brown, Taylor W; van Urk, Felix C; Waller, Rebecca; Mayo-Wilson, Evan

2014-09-25

Because of poverty, children and families in low- and middle-income countries often face significant impediments to health and well-being. Centre-based day care services may influence the development of children and the economic situation of parents by providing good quality early childhood care and by freeing parents to participate in the labour force. To assess the effects of centre-based day care without additional interventions (e.g. psychological or medical services, parent training) on the development, health and well-being of children and families in low- and middle-income countries (as defined by the World Bank 2011). In April 2014, we searched CENTRAL, Ovid MEDLINE, EMBASE, PsycINFO, ERIC and 16 other sources, including several World Health Organization (WHO) regional databases. We also searched two trials registers, websites of government and non-government agencies and reference lists of relevant studies. We included randomised and quasi-randomised controlled trials and prospective non-randomised studies with contemporaneous control groups and assessments both before and after intervention. We considered non-randomised controlled trials, as centre-based care in low- and middle-income countries is unlikely to be studied using randomised controlled trials (Higgins 2011). We included the following outcomes: child intellectual development, child psychosocial development, maternal and family outcomes and incidence of infectious diseases. Two review authors independently assessed risk of bias and extracted data from the single included study. Only one trial, involving 256 children, met the inclusion criteria for this review. This study was assessed as having high risk of bias because of non-random allocation, incomplete outcome data and insufficient control of confounding factors. Results from this study suggest that centre-based day care may have a positive effect on child cognitive ability compared with no treatment (care at home) (assessed using a modified version of the British Ability Scale-II (BAS-II) (standardised mean difference (SMD) 0.74, 95% confidence interval (CI) 0.48 to 1.00, 256 participants, 1 study, very low-quality evidence). This study did not measure other variables relevant to this review. The single study included in this review provides limited evidence on the effects of centre-based day care for children younger than five years of age in low- and middle-income countries. This study was at high risk of bias and may have limited generalisability to other low- and middle-income countries. Many of the studies excluded from this review paired day care attendance with co-interventions that are unlikely to be provided in normal day care centres. Effectiveness studies on centre-based day care without these co-interventions are few, and the need for such studies is significant. In future studies, comparisons might include home visits or alternative day care arrangements.

The effects of enteral feeding improvement massage on premature infants: A randomised controlled trial.

PubMed

Kim, Hee-Young; Bang, Kyung-Sook

2018-01-01

To prove the effects of an enteral feeding improvement massage for premature infants with regard to their feeding, growing and superior mesentery artery blood flow aspect by a randomised controlled trial. Premature infants have feeding-related problems related to eating and absorbing nutrition due to their immature gastrointestinal function. Studies regarding the effectiveness of premature infants' enteral feeding improvement by tactile stimulation massage are rare. The study group was composed of 55 patients. Of the 55 patients, 26 were randomised into an experimental group and 29 were randomised into a control group. They were all born <34 weeks of gestational age between 1 July 2011 and 30 March 2012. Premature infants in the experimental group received enteral feeding improvement massage twice a day for 14 days, and infants in the control group received a sham exercise. The collected data were analysed by spss 19.0, through t test, chi-square test (Fisher's exact) and ANCOVA. (i) The experimental group had reached the day of full enteral feeding significantly faster. (ii) The experimental group had a higher superior mesentery artery peak velocity (V max ) and lower RI (resistant index). (iii) The experimental group of the feeding-intolerant subgroup had a higher superior mesentery artery V max and V min . (iv) The experimental group had a heavier weight and larger head circumference after 14 days. This study demonstrates that enteral feeding improvement massage can be helpful for achieving earlier full enteral feeding, more increased superior mesentery artery, and faster growing. In particular, it can be a therapeutic, independent and evidence-based nursing intervention for feeding-intolerant premature infants. Neonatal nurses in neonatal intensive care unit can apply enteral feeding improvement massage massage for feeding-intolerant infants. © 2017 John Wiley & Sons Ltd.

Financial incentives for smoking cessation in pregnancy: randomised controlled trial.

PubMed

Tappin, David; Bauld, Linda; Purves, David; Boyd, Kathleen; Sinclair, Lesley; MacAskill, Susan; McKell, Jennifer; Friel, Brenda; McConnachie, Alex; de Caestecker, Linda; Tannahill, Carol; Radley, Andrew; Coleman, Tim

2015-01-27

To assess the efficacy of a financial incentive added to routine specialist pregnancy stop smoking services versus routine care to help pregnant smokers quit. Phase II therapeutic exploratory single centre, individually randomised controlled parallel group superiority trial. One large health board area with a materially deprived, inner city population in the west of Scotland, United Kingdom. 612 self reported pregnant smokers in NHS Greater Glasgow and Clyde who were English speaking, at least 16 years of age, less than 24 weeks pregnant, and had an exhaled carbon monoxide breath test result of 7 ppm or more. 306 women were randomised to incentives and 306 to control. The control group received routine care, which was the offer of a face to face appointment to discuss smoking and cessation and, for those who attended and set a quit date, the offer of free nicotine replacement therapy for 10 weeks provided by pharmacy services, and four, weekly support phone calls. The intervention group received routine care plus the offer of up to £400 of shopping vouchers: £50 for attending a face to face appointment and setting a quit date; then another £50 if at four weeks' post-quit date exhaled carbon monoxide confirmed quitting; a further £100 was provided for continued validated abstinence of exhaled carbon monoxide after 12 weeks; a final £200 voucher was provided for validated abstinence of exhaled carbon monoxide at 34-38 weeks' gestation. The primary outcome was cotinine verified cessation at 34-38 weeks' gestation through saliva (<14.2 ng/mL) or urine (<44.7 ng/mL). Secondary outcomes included birth weight, engagement, and self reported quit at four weeks. Recruitment was extended from 12 to 15 months to achieve the target sample size. Follow-up continued until September 2013. Of the 306 women randomised, three controls opted out soon after enrolment; these women did not want their data to be used, leaving 306 intervention and 303 control group participants in the intention to treat analysis. No harms of financial incentives were documented. Significantly more smokers in the incentives group than control group stopped smoking: 69 (22.5%) versus 26 (8.6%). The relative risk of not smoking at the end of pregnancy was 2.63 (95% confidence interval 1.73 to 4.01) P<0.001. The absolute risk difference was 14.0% (95% confidence interval 8.2% to 19.7%). The number needed to treat (where financial incentives need to be offered to achieve one extra quitter in late pregnancy) was 7.2 (95% confidence interval 5.1 to 12.2). The mean birth weight was 3140 g (SD 600 g) in the incentives group and 3120 (SD 590) g in the control group (P=0.67). This phase II randomised controlled trial provides substantial evidence for the efficacy of incentives for smoking cessation in pregnancy; as this was only a single centre trial, incentives should now be tested in different types of pregnancy cessation services and in different parts of the United Kingdom. Current Controlled Trials ISRCTN87508788. © Tappin et al 2015.

Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network.

PubMed

Hermine, Olivier; Hoster, Eva; Walewski, Jan; Bosly, André; Stilgenbauer, Stephan; Thieblemont, Catherine; Szymczyk, Michal; Bouabdallah, Reda; Kneba, Michael; Hallek, Michael; Salles, Gilles; Feugier, Pierre; Ribrag, Vincent; Birkmann, Josef; Forstpointner, Roswitha; Haioun, Corinne; Hänel, Mathias; Casasnovas, René Olivier; Finke, Jürgen; Peter, Norma; Bouabdallah, Kamal; Sebban, Catherine; Fischer, Thomas; Dührsen, Ulrich; Metzner, Bernd; Maschmeyer, Georg; Kanz, Lothar; Schmidt, Christian; Delarue, Richard; Brousse, Nicole; Klapper, Wolfram; Macintyre, Elizabeth; Delfau-Larue, Marie-Hélène; Pott, Christiane; Hiddemann, Wolfgang; Unterhalt, Michael; Dreyling, Martin

2016-08-06

Mantle cell lymphoma is characterised by a poor long-term prognosis. The European Mantle Cell Lymphoma Network aimed to investigate whether the introduction of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation (ASCT) improves outcome. This randomised, open-label, parallel-group, phase 3 trial was done in 128 haemato-oncological hospital departments or private practices in Germany, France, Belgium, and Poland. Patients aged 65 years or younger with untreated stage II-IV mantle cell lymphoma were centrally randomised (1:1), with computer-assisted random block selection, to receive either six courses of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by myeloablative radiochemotherapy and ASCT (control group), or six courses of alternating R-CHOP or R-DHAP (rituximab plus dexamethasone, high-dose cytarabine, and cisplatin) followed by a high-dose cytarabine-containing conditioning regimen and ASCT (cytarabine group). Patients were stratified by study group and international prognostic index. The primary outcome was time to treatment failure from randomisation to stable disease after at least four induction cycles, progression, or death from any cause. Patients with stage II-IV mantle cell lymphoma were included in the primary analysis if treatment was started according to randomisation. For safety analyses, patients were assessed according to the treatment actually started. This study is registered with ClinicalTrials.gov, number NCT00209222. Of 497 patients (median age 55 years [IQR 49-60]) randomised from July 20, 2004, to March 18, 2010, 234 of 249 in the control group and 232 of 248 in the cytarabine group were included in the primary analysis. After a median follow-up of 6.1 years (95% CI 5.4-6.4), time to treatment failure was significantly longer in the cytarabine group (median 9.1 years [95% CI 6.3-not reached], 5 year rate 65% [95% CI 57-71]) than in the control group (3.9 years [3.2-4.4], 40% [33-46]; hazard ratio 0.56; p=0.038). During induction immunochemotherapy, patients who received high-dose cytarabine had increased grade 3 or 4 haematological toxicity (haemoglobin 71 [29%] of 241m vs 19 [8%] of 227 controls; platelets 176 [73%] of 240 vs 21 [9%] of 225), grade 3 or 4 febrile neutropenia (39 [17%] of 230 vs 19 [8%] of 224), and grade 1 or 2 renal toxicity (creatinine 102 [43%] of 236 vs 22 [10%] of 224). The number of ASCT-related deaths was similar (eight [3.4%]) in both groups. Immunochemotherapy containing high-dose cytarabine followed by ASCT should be considered standard of care in patients aged 65 years or younger with mantle cell lymphoma. European Commission, Lymphoma Research Foundation, and Roche. Copyright © 2016 Elsevier Ltd. All rights reserved.

A double blind, placebo controlled, phase II randomised cross-over trial investigating the use of duloxetine for the treatment of chemotherapy-induced peripheral neuropathy.

PubMed

Battaglini, Eva; Park, Susanna B; Barnes, Elizabeth H; Goldstein, David

2018-04-20

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of cancer treatment, potentially leading to early cessation of chemotherapy, enduring symptoms and long-lasting disability. Evidence from preclinical and clinical studies suggests that duloxetine, a serotonin-noradrenaline reuptake inhibitor, may be effective in the symptomatic treatment of CIPN. This double blind, placebo controlled, phase II randomised cross-over trial aims to determine whether treatment with duloxetine results in a reduction in chronic neuropathic symptoms experienced as a result of neurotoxic chemotherapy treatment. Participants who have received neurotoxic chemotherapy and experience daily symptoms as a consequence of peripheral neuropathy will be randomly allocated to control or experimental group with a 1:1 allocation, stratified by chemotherapy type. The primary endpoint will be patient-reported CIPN symptoms, as assessed via the FACT/GOG-Ntx. As a secondary objective, the trial will investigate whether duloxetine improves neurophysiological parameters and functional status in patients who have received neurotoxic chemotherapy treatment. This trial will investigate the effectiveness of duloxetine in reducing neuropathic symptoms following chemotherapy treatment, and aims to provide insight into the mechanisms underlying the symptomatic relief that duloxetine may provide. These results will be informative in advancing clinical knowledge regarding the treatment of CIPN. Copyright © 2018 Elsevier Inc. All rights reserved.

Parental depression and child conduct problems: evaluation of parental service use and associated costs after attending the Incredible Years Basic Parenting Programme

PubMed Central

2013-01-01

Background There is co-morbidity between parental depression and childhood conduct disorder. The Incredible Years (IY) parenting programmes reduce both conduct disorder in children and depression in their parents. Recent U.K. and Ireland trials of the effectiveness and cost-effectiveness of IY parenting programmes have assessed children’s health and social care service use, but little is known about the programme’s impact on parental service use. This paper explores whether an above clinical cut-off score on the Beck Depression Inventory II (BDI II) is associated with high or low parental health and social care service use in high-risk families receiving the IY Basic Programme. Methods This is a secondary analysis of a subsample (N = 119) from the first U.K. community-based randomised controlled trial of the 12-week IY Basic Programme (N = 153). Parents with children at risk of developing conduct disorder were randomised to receive the programme or to a waiting-list control group. BDI II total and BDI II clinical depression cut-off scores were compared to frequencies and costs of parents’ service use, at baseline, six, twelve and eighteen months post-baseline for the intervention group and at baseline and six months post-baseline for the control group. Results Intervention group parents who scored above the clinical cut-off on the BDI II at baseline used more health and social care services than those who scored below at baseline, six and eighteen months. Significant reductions in service use frequencies were found for the intervention group only. Conclusion Parents with higher levels or depression used more health and social care service and parenting programmes have been shown to reduce parental depression and also health and social service use. However, further exploration of depressed parents’ service use and the cost implications for publically funded health and social care services is needed. Trial registration Registration of the original RCT of the IY Basic Parenting Programme - Current Controlled Trials ISRCTN46984318 PMID:24350571

Group sequential designs for stepped-wedge cluster randomised trials

PubMed Central

Grayling, Michael J; Wason, James MS; Mander, Adrian P

2017-01-01

Background/Aims: The stepped-wedge cluster randomised trial design has received substantial attention in recent years. Although various extensions to the original design have been proposed, no guidance is available on the design of stepped-wedge cluster randomised trials with interim analyses. In an individually randomised trial setting, group sequential methods can provide notable efficiency gains and ethical benefits. We address this by discussing how established group sequential methodology can be adapted for stepped-wedge designs. Methods: Utilising the error spending approach to group sequential trial design, we detail the assumptions required for the determination of stepped-wedge cluster randomised trials with interim analyses. We consider early stopping for efficacy, futility, or efficacy and futility. We describe first how this can be done for any specified linear mixed model for data analysis. We then focus on one particular commonly utilised model and, using a recently completed stepped-wedge cluster randomised trial, compare the performance of several designs with interim analyses to the classical stepped-wedge design. Finally, the performance of a quantile substitution procedure for dealing with the case of unknown variance is explored. Results: We demonstrate that the incorporation of early stopping in stepped-wedge cluster randomised trial designs could reduce the expected sample size under the null and alternative hypotheses by up to 31% and 22%, respectively, with no cost to the trial’s type-I and type-II error rates. The use of restricted error maximum likelihood estimation was found to be more important than quantile substitution for controlling the type-I error rate. Conclusion: The addition of interim analyses into stepped-wedge cluster randomised trials could help guard against time-consuming trials conducted on poor performing treatments and also help expedite the implementation of efficacious treatments. In future, trialists should consider incorporating early stopping of some kind into stepped-wedge cluster randomised trials according to the needs of the particular trial. PMID:28653550

Group sequential designs for stepped-wedge cluster randomised trials.

PubMed

Grayling, Michael J; Wason, James Ms; Mander, Adrian P

2017-10-01

The stepped-wedge cluster randomised trial design has received substantial attention in recent years. Although various extensions to the original design have been proposed, no guidance is available on the design of stepped-wedge cluster randomised trials with interim analyses. In an individually randomised trial setting, group sequential methods can provide notable efficiency gains and ethical benefits. We address this by discussing how established group sequential methodology can be adapted for stepped-wedge designs. Utilising the error spending approach to group sequential trial design, we detail the assumptions required for the determination of stepped-wedge cluster randomised trials with interim analyses. We consider early stopping for efficacy, futility, or efficacy and futility. We describe first how this can be done for any specified linear mixed model for data analysis. We then focus on one particular commonly utilised model and, using a recently completed stepped-wedge cluster randomised trial, compare the performance of several designs with interim analyses to the classical stepped-wedge design. Finally, the performance of a quantile substitution procedure for dealing with the case of unknown variance is explored. We demonstrate that the incorporation of early stopping in stepped-wedge cluster randomised trial designs could reduce the expected sample size under the null and alternative hypotheses by up to 31% and 22%, respectively, with no cost to the trial's type-I and type-II error rates. The use of restricted error maximum likelihood estimation was found to be more important than quantile substitution for controlling the type-I error rate. The addition of interim analyses into stepped-wedge cluster randomised trials could help guard against time-consuming trials conducted on poor performing treatments and also help expedite the implementation of efficacious treatments. In future, trialists should consider incorporating early stopping of some kind into stepped-wedge cluster randomised trials according to the needs of the particular trial.

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

PubMed Central

2011-01-01

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

Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy: multicentre randomised controlled trial.

PubMed

2009-07-28

To compare the effectiveness of punch biopsy and selective recall for treatment versus a policy of immediate treatment by large loop excision in the management of women with low grade abnormal cervical cytology referred for colposcopy. Multicentre individually randomised controlled trial, nested within the NHS cervical screening programmes. Grampian, Tayside, and Nottingham. 1983 women, aged 20-59, with cytology showing borderline nuclear abnormalities or mild dyskaryosis, October 1999-October 2002. Immediate large loop excision or up to four targeted punch biopsies taken immediately with recall for treatment (by large loop excision) if these showed cervical intraepithelial neoplasia grade II or III or worse. Participants were followed for three years, concluding with an exit colposcopy. Clinical end points: cumulative incidence of cervical intraepithelial neoplasia grade II or worse and grade III or worse at three years. Clinically significant anxiety and depression and self reported after effects assessed six weeks after colposcopy, biopsies, or large loop excision. 879 women (44%) had a normal transformation zone at colposcopy and had no further procedures at that time. Colposcopists were less likely to classify the transformation zone as abnormal when the allocation was large loop excision (603 (60%) in the biopsy and selective recall group; 501 (51%) in the immediate large loop excision group). Of women randomised to biopsy and recall, 157 (16%) required a second clinic visit for treatment. Specimens from almost 60% (n=296) of women who underwent immediate large loop excision showed no cervical intraepithelial neoplasia (31%; n=156) or showed cervical intraepithelial neoplasia grade I (28%; n=140). The percentages of women diagnosed with grade II or worse up to and including the exit examination were 22% (n=216) in the biopsy and recall arm and 23% (n=228) in the immediate large loop excision arm. There was no significant difference between the arms in cumulative incidence of cervical intraepithelial neoplasia grade II or worse (adjusted relative for risk large loop excision v biopsy 1.04, 95% confidence interval 0.86 to 1.25) or grade III or worse (1.03, 0.79 to 1.34). A greater proportion of disease was detected at initial investigation and less during follow-up and at exit in the immediate large loop excision arm, but time of detection did not differ significantly between arms. Levels of anxiety and depression and reported pain did not differ between arms. Higher proportions of women randomised to large loop excision reported moderate or more severe bleeding and discharge. A policy of targeted punch biopsies with subsequent treatment for cervical intraepithelial neoplasia grade II or III and cytological surveillance for grade I or less provides the best balance between benefits and harms for the management of women with low grade abnormal cytology referred for colposcopy. Immediate large loop excision results in overtreatment and more after effects and should not be recommended. ISRCTN 34841617.

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

PubMed

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

2017-07-01

Randomised controlled trials, a gold-standard approach to reduce uncertainties in clinical practice, are growing in cost and are often slow to recruit. We determined whether methodological approaches to facilitate large, efficient clinical trials were acceptable to UK research ethics committees (RECs). We developed a protocol in collaboration with parents, for a comparative-effectiveness, randomised controlled trial comparing two widely used blood transfusion practices in preterm infants. We incorporated four approaches to improve recruitment and efficiency: (i) point-of-care design using electronic patient records for patient identification, randomisation and data acquisition, (ii) short two-page information sheet; (iii) explicit mention of possible inclusion benefit; (iv) opt-out consent with enrolment as the default. With the support of the UK Health Research Authority, we submitted an identical protocol to 12 UK REC. RECs in the UK. Number of REC granting favourable opinions. The use of electronic patient records was acceptable to all RECs; one REC raised concerns about the short parent information sheet, 10 about inclusion benefit and 9 about opt-out consent. Following responses to queries, nine RECs granted a favourable final opinion and three rejected the application because they considered the opt-out consent process invalid. A majority of RECs in this study consider the use of electronic patient record data, short information sheets, opt-out consent and mention of possible inclusion benefit to be acceptable in neonatal comparative-effectiveness research. We identified a need for guidance for RECs in relation to opt-out consent processes. These methods provide opportunity to facilitate large randomised controlled trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Randomised controlled trial of expressive writing and quality of life in men and women treated for colon or rectal cancer.

PubMed

Lepore, Stephen J; Revenson, Tracey A; Roberts, Katherine J; Pranikoff, Julie R; Davey, Adam

2015-01-01

This randomised trial tested (i) whether a home-based expressive writing (EW) intervention improves quality of life in patients with colorectal cancer (CRC) and (ii) whether the intervention is more beneficial for men or for people who feel constrained in disclosing cancer-related concerns and feelings. Patients treated for CRC were randomised to an EW (n = 101) or control writing (CW; n = 92) group. Assessments were completed at 1 month pre- and post-intervention. Sex and perceived social constraints on disclosure were evaluated as moderators. Primary outcomes were depressive symptoms, sleep problems and quality of life indicators. Eighty-one per cent of participants completed all writing assignments. Consistent with hypotheses, relative to the CW group, participants in the EW group expressed more negative emotion in writing and rated their writings as more meaningful, personal and emotionally revealing. There were no significant main effects of EW or moderating effects of sex or social constraints on outcomes. Although EW is feasible to use with persons who have CRC, it was not effective as a stand-alone psychotherapeutic intervention. Neither was it more effective for men nor for people who felt they could not freely disclose cancer-related concerns and feelings.

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

PubMed

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

2014-11-11

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

Herbst appliance with skeletal anchorage versus dental anchorage in adolescents with Class II malocclusion: study protocol for a randomised controlled trial.

PubMed

Batista, Klaus Barretto Dos Santos Lopes; Lima, Tatiana; Palomares, Nathália; Carvalho, Felipe de Assis; Quintão, Cátia; Miguel, José Augusto Mendes; Lin, Yin-Ling; Su, Ting-Li; O'Brien, Kevin

2017-11-25

The Herbst appliance is an orthodontic appliance that is used for the correction of class II malocclusion with skeletal discrepancies. Research has shown that this is effective. However, a potential harm is excessive protrusion of the lower front teeth. This is associated with gingival recession, loss of tooth support, and root resorption. This trial evaluates a method of reducing this problem. The study is a single-center, randomised, assessor-blinded, superiority clinical trial with parallel 1:1 allocation. Male and female young people (10-14 years old) with prominent front teeth (class II, division 1) will be treated in one orthodontic clinic. Group 1 will be treated with the conventional Herbst appliance with dental anchorage and group 2 with the Herbst appliance with indirect skeletal anchorage for 12 months. The primary objective will be to compare the proclination of the lower incisors between the Herbst appliance with dental anchorage and skeletal anchorage. Secondary objectives will be to evaluate the changes occurring between the groups in the mandible, maxilla, lower and upper molars, and in gingival recession and root resorption at the end of the treatment. Additionally, the young patient's experience using the appliances will be assessed. The primary outcome measure will be the amount of lower incisor proclination at the end of treatment. This will be assessed by cone-beam computed tomography (CBCT) superimposition. Secondary outcome measures will be the changes in the mandible, maxilla, lower and upper molars at the end of treatment assessed by tomography superimposition and the young patient's experience using the appliances assessed by self-reported questionnaires and semi-structured interviews. The randomisation method will be blocked randomisation, using software to generate a randomised list. The allocation concealment will be done in opaque envelopes numbered from 1 to 40 containing the treatment modality. The randomisation will be implemented by the secretary of the Department of Orthodontics of Rio de Janeiro State University before the beginning of the study. The patients and the orthodontists who will treat the patients cannot be blinded, as they will know the type of appliance used. The technician who will take the CBCT image and the data analyst will be blinded to patients' group allocation. If this new intervention is effective, the findings can change orthodontic practice and may also be relevant to other forms of treatment in which appliances are fixed to the bones of the jaws. However, if the bone anchoring is not effective, the trial will provide much needed information on the use of this comparatively new development. ClinicalTrials.gov, protocol ID: NCT0241812 . Registered on 26 March 2015.

Supplementation of standard antibiotic therapy with oral probiotics for bacterial vaginosis and aerobic vaginitis: a randomised, double-blind, placebo-controlled trial.

PubMed

Heczko, Piotr B; Tomusiak, Anna; Adamski, Paweł; Jakimiuk, Artur J; Stefański, Grzegorz; Mikołajczyk-Cichońska, Aleksandra; Suda-Szczurek, Magdalena; Strus, Magdalena

2015-12-03

This multicentre, randomised, double-blind, placebo-controlled trial was performed to determine whether the use of oral probiotic preparation (prOVag®) containing three Lactobacillus strains together with standard metronidazole treatment and also targeted antibiotic treatment (following the failure of metronidazole therapy) could reduce the recurrence rates of bacterial vaginosis (BV) and aerobic vaginitis (AV). Patients at private gynaecological clinics in Poland with histories of recurrent BV/AV and current symptoms were randomly allocated to receive metronidazole and probiotic or placebo, and assessed monthly on visits II and III-V. The total number of study visits was 5-6 (I, II, II bis - if applicable, III, IV, V). One probiotic or placebo capsule was administered with metronidazole/targeted antibiotic twice daily for 10 days; during follow up, patients took one capsule daily for 10 days perimenstrually. Clinical examination and vaginal swabbing were performed at each visit. Primary outcomes were clinical or microbiological BV/AV recurrence and probiotic safety. Secondary outcomes were vaginal pH, Nugent score, and Lactobacillus counts in the vaginal microbiota. Safety analysis was performed in 578 (probiotic, n = 285; placebo, n = 293) 18-50-year-old women who were randomised. BV/AV was confirmed microbiologically in 241 (probiotic, n = 118; placebo, n = 123) participants, who continued the trial. Data from 154 (probiotic, n = 73; placebo, n = 81) participants who completed the study were analysed to determine the efficacy of prOVag. Additional analyses included 37 (probiotic, n = 22; placebo, n = 15) participants who received targeted antibiotics and probiotics or placebo. prOVag lengthened the time to clinical relapse of BV/AV symptoms up to 51 % (p < 0.05) compared with placebo; AV relapse was delayed by up to 76 % (p < 0.05). Probiotic use also reduced and maintained low vaginal pH and Nugent score, and increased vaginal Lactobacillus counts following standard treatment. This study demonstrated that oral probiotics lengthened remission in patients with recurrent BV/AV and improved clinical and microbiological parameters. NCT01993524 ; 20 November 2013.

A comparison of three induction regimens using succinylcholine, vecuronium, or no muscle relaxant: impact on the intraoperative monitoring of the lateral spread response in hemifacial spasm surgery: study protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Surgical microvascular decompression (MVD) is the curative treatment for hemifacial spasm (HFS). Monitoring MVD by recording the lateral spread response (LSR) intraoperatively can predict a successful clinical outcome. However, the rate of the LSR varies between trials, and the reason for this variation is unclear. The aim of our trial is to evaluate the rate of the LSR after intubation following treatment with succinylcholine, vecuronium, or no muscle relaxant. Methods and design This trial is a prospective randomised controlled trial of 96 patients with HFS (ASA status I or II) undergoing MVD under general anaesthesia. Patients are randomised to receive succinylcholine, vecuronium, or no muscle relaxant before intubation. Intraoperative LSR will be recorded until dural opening. The primary outcome of this study is the rate of the LSR, and the secondary outcomes are post-intubation pharyngolaryngeal symptoms, the rate of difficult intubations, the rate of adverse haemodynamic events and the relationship between the measurement of LSR or not, and clinical success rates at 30 days after surgery. Discussion This study aims to evaluate the impact of muscle relaxants on the rate of the LSR, and the study may provide evidence supporting the use of muscle relaxants before intubation in patients with HFS undergoing MVD surgery. Trials registration http://www.chictr.org/ ChiCTR-TRC-11001504 Date of registration: 24 June, 2011. The date the first patient was randomised: 30 September, 2011. PMID:22958580

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

PubMed

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

2013-10-29

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

Libertas: rationale and study design of a multicentre, Phase II, double-blind, randomised, placebo-controlled investigation to evaluate the efficacy, safety and tolerability of locally applied NRL001 in patients with faecal incontinence.

PubMed

Siproudhis, L; Jones, D; Shing, R Ng Kwet; Walker, D; Scholefield, J H

2014-03-01

Faecal incontinence affects up to 8% of adults. Associated social isolation and subsequent depression can have devastating effects on quality of life (QoL). Faecal incontinence is an underreported health problem as the social isolation and stigma that patients experience makes it difficult for sufferers to discuss their condition with a physician. There have been few well-designed, placebo-controlled clinical trials of treatment for faecal incontinence and little clinical evidence is available to inform the most appropriate management strategies. Libertas, a robustly designed study will investigate the efficacy and safety of NRL001 (1R,2S-methoxamine), an α1 -adrenoceptor agonist, in the treatment of faecal incontinence. Libertas is a multicentre, Phase II, double-blind, randomised, placebo-controlled, parallel group study. Patient recruitment took place across 55 study centres in Europe. Patients suffering with faecal incontinence were randomised into four groups (approximately 110 each) to receive once daily self-administered doses of NRL001 (5, 7.5 or 10 mg or placebo in a suppository formulation) for 8 weeks. The primary objective of Libertas is to assess the impact of once daily administration of NRL001 on the severity and frequency of incontinence episodes as assessed by the Wexner score at 4 weeks, compared with placebo. Secondary outcomes include measures of efficacy of NRL001 compared with placebo following 8 weeks treatment; safety and tolerability; evaluation of plasma pharmacokinetics; establishment of any pharmacokinetic/pharmacodynamic relationship to adverse events; dose-response relationship; the efficacy of NRL001 therapy at 4 and 8 weeks assessed by the Vaizey score; and QoL using the Faecal Incontinence Quality of Life and the EQ-5D-5L Healthcare Questionnaires following 4 and 8 weeks NRL001 therapy. Overall patient satisfaction with the treatment will also be evaluated. This is the first randomised controlled study to investigate the efficacy and safety of a selective α1 -adrenoceptor agonist for the treatment of faecal incontinence. Furthermore, this is the first time the impact of NRL001 on assessments of QoL, health outcomes and patient satisfaction will be assessed. Innovative strategies were developed to meet the challenge of recruiting patients for this study, for example, media advertising, posters and mailshots as allowed by each study centre. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

The STRIDE (Strategies to Increase confidence, InDependence and Energy) study: cognitive behavioural therapy-based intervention to reduce fear of falling in older fallers living in the community - study protocol for a randomised controlled trial.

PubMed

Parry, Steve W; Deary, Vincent; Finch, Tracy; Bamford, Claire; Sabin, Neil; McMeekin, Peter; O'Brien, John; Caldwell, Alma; Steen, Nick; Whitney, Susan L; Macdonald, Claire; McColl, Elaine

2014-06-06

Around 30% to 62% of older individuals fall each year, with adverse consequences of falls being by no means limited to physical injury and escalating levels of dependence. Many older individuals suffer from a variety of adverse psychosocial difficulties related to falling including fear, anxiety, loss of confidence and subsequent increasing activity avoidance, social isolation and frailty. Such 'fear of falling' is common and disabling, but definitive studies examining the effective management of the syndrome are lacking. Cognitive behavioural therapy has been trialed with some success in a group setting, but there is no adequately powered randomised controlled study of an individually based cognitive behavioural therapy intervention, and none using non-mental health professionals to deliver the intervention. We are conducting a two-phase study examining the role of individual cognitive behavioural therapy delivered by healthcare assistants in improving fear of falling in older adults. In Phase I, the intervention was developed and taught to healthcare assistants, while Phase II is the pragmatic randomised controlled study examining the efficacy of the intervention in improving fear of falling in community-dwelling elders attending falls services. A qualitative process evaluation study informed by Normalization Process Theory is being conducted throughout to examine the potential promoters and inhibitors of introducing such an intervention into routine clinical practice, while a health economic sub-study running alongside the trial is examining the costs and benefits of such an approach to the wider health economy. Current Controlled Trials ISRCTN78396615.

Clinical efficacy of crataegus extract WS 1442 in congestive heart failure NYHA class II.

PubMed

Zapfe jun, G

2001-07-01

In a randomised, placebo-controlled, double-blind clinical study the clinical efficacy and safety of Crataegus extract WS 1442, standardised to 18.75% oligomeric procyanidines, were investigated in 40 female and male outpatients suffering from congestive heart failure NYHA class II. Following a wash-out period of up to seven days, the patients were randomised to be treated for 12 weeks with either WS 1442 (3 x 1 capsule) or placebo. The primary outcome variable was exercise tolerance determined with bicycle exercise testing; as a secondary outcome variable the difference of the double product was calculated. On average, the exercise tolerance increased by 66.3 W x min (10.8%) in the WS 1442 group while in the placebo group a reduction of 105.3 W x min (16.9%) was measured. This difference between the groups was borderline statistically significant (p = 0.06). During the three month therapy the difference of the double product (heart rate x systolic blood pressure x 10(-2)) decreased by 14.4 mmHg s(-1) (26.8%) in the WS 1442 group and by 1.3 mmHg s(-1) (2.7%) in the placebo group, respectively. Recording of laboratory parameters and adverse events showed that WS 1442 was safe and well tolerated. The data show that Crataegus extract WS 1442 is clinically effective in patients with congestive heart failure corresponding to NYHA class II.

A Bayesian adaptive design for biomarker trials with linked treatments.

PubMed

Wason, James M S; Abraham, Jean E; Baird, Richard D; Gournaris, Ioannis; Vallier, Anne-Laure; Brenton, James D; Earl, Helena M; Mander, Adrian P

2015-09-01

Response to treatments is highly heterogeneous in cancer. Increased availability of biomarkers and targeted treatments has led to the need for trial designs that efficiently test new treatments in biomarker-stratified patient subgroups. We propose a novel Bayesian adaptive randomisation (BAR) design for use in multi-arm phase II trials where biomarkers exist that are potentially predictive of a linked treatment's effect. The design is motivated in part by two phase II trials that are currently in development. The design starts by randomising patients to the control treatment or to experimental treatments that the biomarker profile suggests should be active. At interim analyses, data from treated patients are used to update the allocation probabilities. If the linked treatments are effective, the allocation remains high; if ineffective, the allocation changes over the course of the trial to unlinked treatments that are more effective. Our proposed design has high power to detect treatment effects if the pairings of treatment with biomarker are correct, but also performs well when alternative pairings are true. The design is consistently more powerful than parallel-groups stratified trials. This BAR design is a powerful approach to use when there are pairings of biomarkers with treatments available for testing simultaneously.

Randomised controlled trial of a synthetic triglyceride milk formula for preterm infants

PubMed Central

Lucas, A; Quinlan, P; Abrams, S; Ryan, S; Meah, S; Lucas, P

1997-01-01

AIMS—To test whether use of infant formula containing synthetic structured triglycerides results in: (i) increased palmitate absorption; (ii) increased total fat absorption; (iii) reduction in calcium soap formation in the gut; and hence (iv) increased calcium absorption.
METHODS—A randomised study was made of 24 infants comparing three formulas, one containing the synthetic fat Betapol with 74% of palmitate in the 2-position, which was substantially higher than in the two comparison diets (8.4% and 28%). The hypothesised outcomes were tested using balance studies, detailed chemical analysis of stool specimens and dual calcium isotope tracers (44calcium orally and 46calcium intravenously). 
RESULTS—Three of the four hypotheses were confirmed: use of a formula rich in 2-position palmitate (i) improved palmitate (16:0) and also (18:0) absorption; (ii) reduced the formation of insoluble calcium soaps in the stool; and (iii) improved calcium absorption, determined by the dual tracer technique from 42 (SE 3)% to 57 (7)%.
CONCLUSION—Synthetic triglycerides that mimic the stereoisometric structure of those in breast milk may have a valuable role in the design of formulas used for preterm infants in neonatal intensive care units.

 PMID:9462186

Comparison of stapled haemorrhoidopexy with traditional excisional surgery for haemorrhoidal disease (eTHoS): a pragmatic, multicentre, randomised controlled trial.

PubMed

Watson, Angus J M; Hudson, Jemma; Wood, Jessica; Kilonzo, Mary; Brown, Steven R; McDonald, Alison; Norrie, John; Bruhn, Hanne; Cook, Jonathan A

2016-11-12

Two commonly performed surgical interventions are available for severe (grade II-IV) haemorrhoids; traditional excisional surgery and stapled haemorrhoidopexy. Uncertainty exists as to which is most effective. The eTHoS trial was designed to establish the clinical effectiveness and cost-effectiveness of stapled haemorrhoidopexy compared with traditional excisional surgery. The eTHoS trial was a large, open-label, multicentre, parallel-group, pragmatic randomised controlled trial done in adult participants (aged 18 years or older) referred to hospital for surgical treatment for grade II-IV haemorrhoids. Participants were randomly assigned (1:1) to receive either traditional excisional surgery or stapled haemorrhoidopexy. Randomisation was minimised according to baseline EuroQol 5 dimensions 3 level score (EQ-5D-3L), haemorrhoid grade, sex, and centre with an automated system to stapled haemorrhoidopexy or traditional excisional surgery. The primary outcome was area under the quality of life curve (AUC) measured with the EQ-5D-3L descriptive system over 24 months, assessed according to the randomised groups. The primary outcome measure was analysed using linear regression with adjustment for the minimisation variables. This trial is registered with the ISRCTN registry, number ISRCTN80061723. Between Jan 13, 2011, and Aug 1, 2014, 777 patients were randomised (389 to receive stapled haemorrhoidopexy and 388 to receive traditional excisional surgery). Stapled haemorrhoidopexy was less painful than traditional excisional surgery in the short term and surgical complication rates were similar between groups. The EQ-5D-3L AUC score was higher in the traditional excisional surgery group than the stapled haemorrhoidopexy group over 24 months; mean difference -0·073 (95% CI -0·140 to -0·006; p=0·0342). EQ-5D-3L was higher for stapled haemorrhoidopexy in the first 6 weeks after surgery, the traditional excisional surgery group had significantly better quality of life scores than the stapled haemorrhoidopexy group. 24 (7%) of 338 participants who received stapled haemorrhoidopexy and 33 (9%) of 352 participants who received traditional excisional surgery had serious adverse events. As part of a tailored management plan for haemorrhoids, traditional excisional surgery should be considered over stapled haemorrhoidopexy as the surgical treatment of choice. National Institute for Health Research Health Technology Assessment programme. Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Evaluation of hyperglycaemic response to intra-operative dexamethasone administration in patients undergoing elective intracranial surgery: A randomised, prospective study.

PubMed

Sethi, Rakesh; Naqash, Imtiaz A; Bajwa, Sukhminder Jit Singh; Dutta, Vikas; Ramzan, Altaf Umar; Zahoor, Syed Amir

2016-01-01

The glucocorticoid dexamethasone in a bolus dose of 8-10 mg followed by quarterly dose of 4 mg is commonly used during intracranial surgery so as to reduce oedema and vascular permeability. However, the detrimental hyperglycaemic effects of dexamethasone may override its potentially beneficial effects. The present prospective, randomised study aimed at comparing the degree and magnitude of hyperglycaemia induced by prophylactic administration of dexamethasone in patients undergoing elective craniotomy. Sixty American Society of Anaesthesiologist (ASA) grade-I and II patients were randomly assigned to three groups of 20 patients each. Group-I received dexamethasone during surgery for the first time. Group-II received dexamethasone in addition to receiving it pre-operatively, whereas Group-III (control group) patients were administered normal saline as placebo. Baseline blood glucose (BG) was measured in all the three groups before induction of anaesthesia and thereafter after every hour for 4 h and then two-hourly. Besides intra- and intergroup comparison of BG, peak BG concentration was also recorded for each patient. Statistical analysis was carried out with analysis of variance (ANOVA) and Student's t-test and value of P < 0.05 was considered statistically significant. Baseline BG reading were higher and statistically significant in Group-II as compared with Group-I and Group-III (P < 0.05). However, peak BG levels were significantly higher in Group-I than in Group-II and III (P < 0.05). Similarly, the magnitude of change in peak BG was significantly higher in Group-I as compared to Group-II and III (P < 0.05). Peri-operative administration of dexamethasone during neurosurgical procedures can cause significant increase in BG concentration especially in patients who receive dexamethasone intra-operatively only.

Evaluation of hyperglycaemic response to intra-operative dexamethasone administration in patients undergoing elective intracranial surgery: A randomised, prospective study

PubMed Central

Sethi, Rakesh; Naqash, Imtiaz A.; Bajwa, Sukhminder Jit Singh; Dutta, Vikas; Ramzan, Altaf Umar; Zahoor, Syed Amir

2016-01-01

Background and Aim: The glucocorticoid dexamethasone in a bolus dose of 8-10 mg followed by quarterly dose of 4 mg is commonly used during intracranial surgery so as to reduce oedema and vascular permeability. However, the detrimental hyperglycaemic effects of dexamethasone may override its potentially beneficial effects. The present prospective, randomised study aimed at comparing the degree and magnitude of hyperglycaemia induced by prophylactic administration of dexamethasone in patients undergoing elective craniotomy. Materials and Methods: Sixty American Society of Anaesthesiologist (ASA) grade-I and II patients were randomly assigned to three groups of 20 patients each. Group-I received dexamethasone during surgery for the first time. Group-II received dexamethasone in addition to receiving it pre-operatively, whereas Group-III (control group) patients were administered normal saline as placebo. Baseline blood glucose (BG) was measured in all the three groups before induction of anaesthesia and thereafter after every hour for 4 h and then two-hourly. Besides intra- and intergroup comparison of BG, peak BG concentration was also recorded for each patient. Statistical analysis was carried out with analysis of variance (ANOVA) and Student's t-test and value of P < 0.05 was considered statistically significant. Results: Baseline BG reading were higher and statistically significant in Group-II as compared with Group-I and Group-III (P < 0.05). However, peak BG levels were significantly higher in Group-I than in Group-II and III (P < 0.05). Similarly, the magnitude of change in peak BG was significantly higher in Group-I as compared to Group-II and III (P < 0.05). Conclusion: Peri-operative administration of dexamethasone during neurosurgical procedures can cause significant increase in BG concentration especially in patients who receive dexamethasone intra-operatively only. PMID:27057213

Clinical trial design and dissemination: comprehensive analysis of clinicaltrials.gov and PubMed data since 2005

PubMed Central

Davies, Mark; Hingorani, Aroon D; Hunter, Jackie

2018-01-01

Abstract Objective To investigate the distribution, design characteristics, and dissemination of clinical trials by funding organisation and medical specialty. Design Cross sectional descriptive analysis. Data sources Trial protocol information from clinicaltrials.gov, metadata of journal articles in which trial results were published (PubMed), and quality metrics of associated journals from SCImago Journal and Country Rank database. Selection criteria All 45 620 clinical trials evaluating small molecule therapeutics, biological drugs, adjuvants, and vaccines, completed after January 2006 and before July 2015, including randomised controlled trials and non-randomised studies across all clinical phases. Results Industry was more likely than non-profit funders to fund large international randomised controlled trials, although methodological differences have been decreasing with time. Among 27 835 completed efficacy trials (phase II-IV), 15 084 (54.2%) had disclosed their findings publicly. Industry was more likely than non-profit trial funders to disseminate trial results (59.3% (10 444/17 627) v 45.3% (4555/10 066)), and large drug companies had higher disclosure rates than small ones (66.7% (7681/11 508) v 45.2% (2763/6119)). Trials funded by the National Institutes of Health (NIH) were disseminated more often than those of other non-profit institutions (60.0% (1451/2417) v 40.6% (3104/7649)). Results of studies funded by large drug companies and NIH were more likely to appear on clinicaltrials.gov than were those from non-profit funders, which were published mainly as journal articles. Trials reporting the use of randomisation were more likely than non-randomised studies to be published in a journal article (6895/19 711 (34.9%) v 1408/7748 (18.2%)), and journal publication rates varied across disease areas, ranging from 42% for autoimmune diseases to 20% for oncology. Conclusions Trial design and dissemination of results vary substantially depending on the type and size of funding institution as well as the disease area under study. PMID:29875212

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.

Metabolic manipulation in chronic heart failure: study protocol for a randomised controlled trial.

PubMed

Beadle, Roger M; Williams, Lynne K; Abozguia, Khaild; Patel, Kiran; Leon, Francisco Leyva; Yousef, Zaheer; Wagenmakers, Anton; Frenneaux, Michael P

2011-06-06

Heart failure is a major cause of morbidity and mortality in society. Current medical therapy centres on neurohormonal modulation with angiotensin converting enzyme inhibitors and β-blockers. There is growing evidence for the use of metabolic manipulating agents as adjunctive therapy in patients with heart failure. We aim to determine the effect of perhexiline on cardiac energetics and alterations in substrate utilisation in patients with non-ischaemic dilated cardiomyopathy. A multi-centre, prospective, randomised double-blind, placebo-controlled trial of 50 subjects with non-ischaemic dilated cardiomyopathy recruited from University Hospital Birmingham NHS Foundation Trust and Cardiff and Vale NHS Trust. Baseline investigations include magnetic resonance spectroscopy to assess cardiac energetic status, echocardiography to assess left ventricular function and assessment of symptomatic status. Subjects are then randomised to receive 200 mg perhexiline maleate or placebo daily for 4 weeks with serum drug level monitoring. All baseline investigations will be repeated at the end of the treatment period. A subgroup of patients will undergo invasive investigations with right and left heart catheterisation to calculate respiratory quotient, and mechanical efficiency. The primary endpoint is an improvement in the phosphocreatine to adenosine triphosphate ratio at 4 weeks. Secondary end points are: i) respiratory quotient; ii) mechanical efficiency; iii) change in left ventricular (LV) function. ClinicalTrials.gov: NCT00841139 ISRCTN: ISRCTN72887836.

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.

Physiotherapy rehabilitation for whiplash associated disorder II: a systematic review and meta-analysis of randomised controlled trials

PubMed Central

Wright, Chris; Heneghan, Nicola; Eveleigh, Gillian; Calvert, Melanie; Freemantle, Nick

2011-01-01

Objective To evaluate effectiveness of physiotherapy management in patients experiencing whiplash associated disorder II, on clinically relevant outcomes in the short and longer term. Design Systematic review and meta-analysis. Two reviewers independently searched information sources, assessed studies for inclusion, evaluated risk of bias and extracted data. A third reviewer mediated disagreement. Assessment of risk of bias was tabulated across included trials. Quantitative synthesis was conducted on comparable outcomes across trials with similar interventions. Meta-analyses compared effect sizes, with random effects as primary analyses. Data sources Predefined terms were employed to search electronic databases. Additional studies were identified from key journals, reference lists, authors and experts. Eligibility criteria for selecting studies Randomised controlled trials (RCTs) published in English before 31 December 2010 evaluating physiotherapy management of patients (>16 years), experiencing whiplash associated disorder II. Any physiotherapy intervention was included, when compared with other types of management, placebo/sham, or no intervention. Measurements reported on ≥1 outcome from the domains within the international classification of function, disability and health, were included. Results 21 RCTs (2126 participants, 9 countries) were included. Interventions were categorised as active physiotherapy or a specific physiotherapy intervention. 20/21 trials were evaluated as high risk of bias and one as unclear. 1395 participants were incorporated in the meta-analyses on 12 trials. In evaluating short term outcome in the acute/sub-acute stage, there was some evidence that active physiotherapy intervention reduces pain and improves range of movement, and that a specific physiotherapy intervention may reduce pain. However, moderate/considerable heterogeneity suggested that treatments may differ in nature or effect in different trial patients. Differences between participants, interventions and trial designs limited potential meta-analyses. Conclusions Inconclusive evidence exists for the effectiveness of physiotherapy management for whiplash associated disorder II. There is potential benefit for improving range of movement and pain short term through active physiotherapy, and for improving pain through a specific physiotherapy intervention. PMID:22102642

Bevacizumab plus capecitabine in patients with progressive advanced well-differentiated neuroendocrine tumors of the gastro-intestinal (GI-NETs) tract (BETTER trial)--a phase II non-randomised trial.

PubMed

Mitry, Emmanuel; Walter, Thomas; Baudin, Eric; Kurtz, Jean-Emmanuel; Ruszniewski, Philippe; Dominguez-Tinajero, Sophie; Bengrine-Lefevre, Leïla; Cadiot, Guillaume; Dromain, Clarisse; Farace, Françoise; Rougier, Philippe; Ducreux, Michel

2014-12-01

Gastro-intestinal neuroendocrine tumours (GI-NETs) are chemotherapy-resistant tumours. Bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF), has shown promising results in several phase II trials of gastro-entero-pancreatic-NETs. We assessed bevacizumab combined with capecitabine, specifically in GI-NET patients. BEvacizumab in The Treament of neuroEndocrine tumoRs (BETTER) was a multicentre, open-label, non-randomised, two-group phase II trial. Here we present the group of patients with progressive, metastatic, well-differentiated GI-NETs. Patients Eastern Cooperative Oncology Group-performance status (ECOG-PS)⩽2, Ki-67 proliferation rate <15% and no prior systemic chemotherapy were treated with bevacizumab (7.5 mg/kg/q3w) and capecitabine (1000 mg/m2 twice daily, orally d1-14, resumed on d22) for 6-24 months. The primary end-point was progression-free survival (PFS); secondary end-points included overall survival (OS), response rate, safety and quality of life. Of the 49 patients included, 53% were men, median age was 60 years (41-82), primary tumour site was ileal in 82% patients and Ki-67 was <15% in 48 patients and not available for one patient. After a maximum of 24 month follow-up per patient, the median PFS by investigator assessment was 23.4 months [95% confidence interval (CI): 13.2; not reached] and the overall disease control rate was 88% (18% partial response, 70% stable disease). The 2-year survival rate was 85%. Median OS was not reached. The most frequent grade 3-4 adverse events were hypertension (31%), diarrhoea (14%) and hand-foot syndrome (10%). The combination of bevacizumab and capecitabine showed clinical activity and a manageable safety profile in the treatment of GI-NETs that warrant confirmation in a randomised phase III trial. Copyright © 2014 Elsevier Ltd. All rights reserved.

Decision aids for second-line palliative chemotherapy: a randomised phase II multicentre trial.

PubMed

Oostendorp, Linda J M; Ottevanger, Petronella B; Donders, A Rogier T; van de Wouw, Agnes J; Schoenaker, Ivonne J H; Smilde, Tineke J; van der Graaf, Winette T A; Stalmeier, Peep F M

2017-08-31

There is increasing recognition of the delicate balance between the modest benefits of palliative chemotherapy and the burden of treatment. Decision aids (DAs) can potentially help patients with advanced cancer with these difficult treatment decisions, but providing detailed information could have an adverse impact on patients' well-being. The objective of this randomised phase II study was to evaluate the safety and efficacy of DAs for patients with advanced cancer considering second-line chemotherapy. Patients with advanced breast or colorectal cancer considering second-line treatment were randomly assigned to usual care (control group) or usual care plus a DA (intervention group) in a 1:2 ratio. A nurse offered a DA with information on adverse events, tumour response and survival. Outcome measures included patient-reported well-being (primary outcome: anxiety) and quality of the decision-making process and the resulting choice. Of 128 patients randomised, 45 were assigned to the control group and 83 to the intervention group. Median age was 62 years (range 32-81), 63% were female, and 73% had colorectal cancer. The large majority of patients preferred treatment with chemotherapy (87%) and subsequently commenced treatment with chemotherapy (86%). No adverse impact on patients' well-being was found and nurses reported that consultations in which the DAs were offered went well. Being offered the DA was associated with stronger treatment preferences (3.0 vs. 2.5; p=0.030) and increased subjective knowledge (6.7 vs. 6.3; p=0.022). Objective knowledge, risk perception and perceived involvement were comparable between the groups. DAs containing detailed risk information on second-line palliative treatment could be delivered to patients with advanced cancer without having an adverse impact on patient well-being. Surprisingly, the DAs only marginally improved the quality of the decision-making process. The effectiveness of DAs for palliative treatment decisions needs further exploration. Netherlands Trial Registry (NTR): NTR1113 (registered on 2 November 2007).

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

PubMed

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

2016-10-06

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

UK Dermatology Clinical Trials Network's STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial.

PubMed

Craig, Fiona F; Thomas, Kim S; Mitchell, Eleanor J; Williams, Hywel C; Norrie, John; Mason, James M; Ormerod, Anthony D

2012-04-28

Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network's STOP GAP Trial has been designed to address this lack of trial evidence. The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and presence or absence of underlying systemic disease (for example, rheumatoid arthritis).Patients who require topical therapy are asked to enter a parallel observational study (case series). If topical therapy fails and systemic therapy is required, participants are then considered for inclusion in the randomised trial. Current controlled trials: ISRCTN35898459. Eudract No.2008-008291-14.

UK Dermatology Clinical Trials Network’s STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network’s STOP GAP Trial has been designed to address this lack of trial evidence. Methods The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and presence or absence of underlying systemic disease (for example, rheumatoid arthritis). Patients who require topical therapy are asked to enter a parallel observational study (case series). If topical therapy fails and systemic therapy is required, participants are then considered for inclusion in the randomised trial. Trial registration Current controlled trials: ISRCTN35898459. Eudract No.2008-008291-14. PMID:22540770

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

Phase II randomised controlled trial of a 6-month self-managed community exercise programme for people with Parkinson's disease.

PubMed

Collett, Johnny; Franssen, Marloes; Meaney, Andy; Wade, Derick; Izadi, Hooshang; Tims, Martin; Winward, Charlotte; Bogdanovic, Marko; Farmer, Andrew; Dawes, Helen

2017-03-01

Evidence for longer term exercise delivery for people with Parkinson's disease (PwP) is deficient. Evaluate safety and adherence to a minimally supported community exercise intervention and estimate effect sizes (ES). 2-arm parallel phase II randomised controlled trial with blind assessment. PwP able to walk ≥100 m and with no contraindication to exercise were recruited from the Thames valley, UK, and randomised (1:1) to intervention (exercise) or control (handwriting) groups, via a concealed computer-generated list. Groups received a 6-month, twice weekly programme. Exercise was undertaken in community facilities (30 min aerobic and 30 min resistance) and handwriting at home, both were delivered through workbooks with monthly support visits. Primary outcome was a 2 min walk, with motor symptoms (Movement Disorder Society Unified Parkinson's Disease Rating Scale, MDS-UPDRS III), fitness, health and well-being measured. Between December 2011 and August 2013, n=53 (n=54 analysed) were allocated to exercise and n=52 (n=51 analysed) to handwriting. N=37 adhered to the exercise, most attending ≥1 session/week. Aerobic exercise was performed in 99% of attended sessions and resistance in 95%. Attrition and adverse events (AEs) were similar between groups, no serious AEs (n=2 exercise, n=3 handwriting) were related, exercise group-related AEs (n=2) did not discontinue intervention. Largest effects were for motor symptoms (2 min walk ES=0.20 (95% CI -0.44 to 0.45) and MDS-UPDRS III ES=-0.30 (95% CI 0.07 to 0.54)) in favour of exercise over the 12-month follow-up period. Some small effects were observed in fitness and well-being measures (ES>0.1). PwP exercised safely and the possible long-term benefits observed support a substantive evaluation of this community programme. NCT01439022. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Protocol for the melatools skin self-monitoring trial: a phase II randomised controlled trial of an intervention for primary care patients at higher risk of melanoma.

PubMed

Mills, Katie; Emery, Jon; Lantaff, Rebecca; Radford, Michael; Pannebakker, Merel; Hall, Per; Burrows, Nigel; Williams, Kate; Saunders, Catherine L; Murchie, Peter; Walter, Fiona M

2017-11-28

Melanoma is the fifth most common cancer in the UK. Incidence rates have quadrupled over the last 30 years and continue to rise, especially among younger people. As routine screening of the general population is not currently recommended in the UK, a focus on secondary prevention through early detection and prompt treatment in individuals at increased risk of melanoma could make an important contribution to improve melanoma outcomes. This paper describes the protocol for a phase II, multisite, randomised controlled trial, in the primary care setting, for patients at increased risk of melanoma. A skin self-monitoring (SSM) smartphone 'App' was used to improve symptom appraisal and encourage help seeking in primary care, thereby promoting early presentation with skin changes suspicious of melanoma. We aim to recruit 200 participants from general practice waiting rooms in the East of England. Eligible patients are those identified at higher melanoma risk (using a real-time risk assessment tool), without a personal history of melanoma, aged 18 to 75 years. Participants will be invited to a primary care nurse consultation, and randomised to the intervention group (standard written advice on skin cancer detection and sun protection, loading of an SSM 'App' onto the participant's smartphone and instructions on use including self-monitoring reminders) or control group (standard written advice alone). The primary outcomes are consultation rates for changes to a pigmented skin lesion, and the patient interval (time from first noticing a skin change to consultation). Secondary outcomes include patient sun protection behaviours, psychosocial outcomes, and measures of trial feasibility and acceptability. NHS ethical approval has been obtained from Cambridgeshire and Hertfordshire research ethics committee (REC reference 16/EE/0248). The findings from the MelaTools SSM Trial will be disseminated widely through peer-reviewed publications and scientific conferences. ISCTRN16061621. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Dietary sodium intake and overweight and obesity in children and adults: a protocol for a systematic review and meta-analysis.

PubMed

Grimes, Carley A; Bolhuis, Dieuwerke P; He, Feng J; Nowson, Caryl A

2016-01-18

Overweight and obesity in children and adults is a major public health concern. Emerging evidence suggests dietary sodium intake may be associated with obesity. This systematic review and meta-analysis will aim to (i) assess the relation between dietary sodium intake and measures of adiposity in children and adults and (ii) examine the relation between sodium intake and sugar-sweetened beverage (SSB) consumption, which is a known risk factor for obesity. An electronic search will be conducted using Medline Complete, CINAHL, Scopus, Embase and Cochrane central register of controlled trials (CENTRAL). The search strategy will identify published peer-reviewed articles that report on dietary sodium and either a marker of adiposity or SSB consumption. Only human studies (ages >1 year) in English will be included, and no limits will be placed on publication date. No restrictions will be placed on the method of sodium intake assessment. Cross-sectional, prospective studies, and randomised controlled trials with a duration of ≥ 3 months will be included. Studies with participants with renal disease, cancer, type 1 diabetes or heart failure or who are pregnant will be excluded. To assess the quality of studies, the Cochrane's Collaboration tool for assessing risk of bias in randomised trials will be used for randomised controlled trials (RCTs), and the modified Newcastle-Ottawa Scale will be used for cross-sectional and prospective studies. Meta-analysis will be used to assess the relation of sodium intake with two primary outcomes: (i) BMI and body weight in adults and BMI z-score in children and (ii) weight category (i.e. healthy weight vs. overweight/obese). For any outcomes in which meta-analysis is not possible, we will present data as a systematic review. Findings will be grouped and reported separately for children and adolescents (ages 1-17 years) and adults (ages >18 years). This review and meta-analysis will provide insight into the relation between dietary sodium intake and overweight and obesity. This information can be used to inform public health policies which target population sodium consumption. Prospero CRD42015016440.

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.

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

PubMed Central

2012-01-01

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

RITPBC: B-cell depleting therapy (rituximab) as a treatment for fatigue in primary biliary cirrhosis: study protocol for a randomised controlled trial

PubMed Central

Jopson, Laura; Newton, Julia L; Palmer, Jeremy; Floudas, Achilleas; Isaacs, John; Qian, Jessica; Wilkinson, Jennifer; Trenell, Mike; Blamire, Andrew; Howel, Denise; Jones, David E

2015-01-01

Introduction Primary biliary cirrhosis (PBC) is an autoimmune liver disease with approximately 50% of patients experiencing fatigue. This can be a particularly debilitating symptom, affecting quality of life and resulting in social isolation. Fatigue is highlighted by patients as a priority for research and patient support groups were involved in designing this trial. This is the first randomised controlled trial to investigate a treatment for fatigue in PBC. The trial protocol is innovative as it utilises novel magnetic resonance spectroscopy (MRS) techniques as an outcome measure. The protocol will be valuable to research groups planning clinical trials targeting fatigue in PBC and also transferrable to other conditions associated with fatigue. Methods and analysis RITPBC is a Medical Research Council (MRC) and National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation Programme (EME)-funded project. It is a phase II, single-centre, randomised controlled, double-blinded trial comparing rituximab with placebo in fatigued PBC patients. 78 patients with PBC and moderate to severe fatigue will be randomised to receive two infusions of rituximab or placebo. The study aims to assess whether rituximab improves fatigue in patients with PBC, the safety, and tolerability of rituximab in PBC and the sustainability of any beneficial actions. The primary outcome will be an improvement in fatigue domain score of the PBC-40, a disease-specific quality of life measure, evaluated at 12-week assessment. Secondary outcome measures include novel MRS techniques assessing muscle bioenergetic function, physical activity, anaerobic threshold and symptom, and quality of life measures. The trial started recruiting in October 2012 and recruitment is ongoing. Ethics and dissemination The trial has ethical approval from the NRES Committee North East, has Clinical Trial Authorisation from MHRA and local R&D approval. Trial results will be communicated to participants, presented at national and international meetings and published in peer-reviewed journals. Trial registration number ISRCTN03978701. PMID:26297361

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.

The M-OVIN study: does switching treatment to FSH and / or IUI lead to higher pregnancy rates in a subset of women with world health organization type II anovulation not conceiving after six ovulatory cycles with clomiphene citrate – a randomised controlled trial

PubMed Central

2013-01-01

Background Clomiphene citrate (CC) is first line treatment in women with World Health Organization (WHO) type II anovulation and polycystic ovary syndrome (PCOS). Whereas 60% to 85% of these women will ovulate on CC, only about one half will have conceived after six cycles. If women do not conceive, treatment can be continued with gonadotropins or intra-uterine insemination (IUI). At present, it is unclear for how many cycles ovulation induction with CC should be repeated, and when to switch to ovulation induction with gonadotropins and/or IUI. Methods/Design We started a multicenter randomised controlled trial in the Netherlands comparing six cycles of CC plus intercourse or six cycles of gonadotrophins plus intercourse or six cycles of CC plus IUI or six cycles of gonadotrophins plus IUI. Women with WHO type II anovulation who ovulate but did not conceive after six ovulatory cycles of CC with a maximum of 150 mg daily for five days will be included. Our primary outcome is birth of a healthy child resulting from a pregnancy that was established in the first eight months after randomisation. Secondary outcomes are clinical pregnancy, miscarriage, multiple pregnancy and treatment costs. The analysis will be performed according to the intention to treat principle. Two comparisons will be made, one in which CC is compared to gonadotrophins and one in which the addition of IUI is compared to ovulation induction only. Assuming a live birth rate of 40% after CC, 55% after addition of IUI and 55% after ovulation induction with gonadotrophins, with an alpha of 5% and a power of 80%, we need to recruit 200 women per arm (800 women in total). An independent Data and Safety Monitoring Committee has criticized the data of the first 150 women and concluded that a sample size re-estimation should be performed after including 320 patients (i.e. 80 per arm). Discussion The trial will provide evidence on the most effective, safest and most cost effective treatment in women with WHO type II anovulation who do not conceive after six ovulatory cycles with CC with a maximum of 150 mg daily for five days. This evidence could imply the need for changing our guidelines, which may cause a shift in large practice variation to evidence based primary treatment for these women. Trial registration number Netherlands Trial register NTR1449 PMID:24160333

Effectiveness of nurse-led cardiac clinics in adult patients with a diagnosis of coronary heart disease.

PubMed

Page, Tamara; Lockwood, Craig; Conroy-Hiller, Tiffany

2005-02-01

Background  Coronary heart disease is the major cause of illness and death in Western countries and this is likely to increase as the average age of the population rises. Consumers with established coronary heart disease are at the highest risk of experiencing further coronary events. Lifestyle measures can contribute significantly to a reduction in cardiovascular mortality in established coronary heart disease. Improved management of cardiac risk factors by providing education and referrals as required has been suggested as one way of maintaining quality care in patients with established coronary heart disease. There is a need to ascertain whether or not nurse-led clinics would be an effective adjunct for patients with coronary heart disease to supplement general practitioner advice and care. Objectives  The objective of this review was to present the best available evidence related to nurse-led cardiac clinics. Inclusion criteria  This review considered any randomised controlled trials that evaluated cardiac nurse-led clinics. In the absence of randomised controlled trials, other research designs such as non-randomised controlled trials and before and after studies were considered for inclusion. Participants were adults (18 years and older) with new or existing coronary heart disease. The interventions of interest to the review included education, assessment, consultation, referral and administrative structures. Outcomes measured included adverse event rates, readmissions, admissions, clinical and cost effectiveness, consumer satisfaction and compliance with therapy. Results  Based on the search terms used, 80 papers were initially identified and reviewed for inclusion; full reports of 24 of these papers were retrieved. There were no papers included that addressed cost effectiveness or adverse events; and none addressed the outcome of referrals. A critical appraisal of the 24 remaining papers identified a total of six randomised controlled trials that met the inclusion criteria. Two studies addressed nurse-led clinics for patients diagnosed with angina, one looked at medication administration and the other looked at educational plans. A further four studies compared secondary preventative care with a nurse-led clinic and general practitioner clinic. One specifically compared usual care versus shared care introduced by nurses for patients awaiting coronary artery bypass grafting. Of the remaining three studies, two have been combined in the results section, as they are an interim report and a final report of the same study. Because of inconsistencies in reporting styles and outcome measurements, meta-analysis could not be performed on all outcomes. However, a narrative summary of each study and comparisons of specific outcomes assessed from within each study has been developed. Although not all outcomes obtained statistical significance, nurse-led clinics were at least as effective as general practitioner clinics for most outcomes. Recommendations  The following recommendations are made: • The use of nurse-led clinics is recommended for patients with coronary heart disease (Level II). • Utilise nurse-led clinics to increase clinic attendance and follow-up rates (Level II). • Nurse-led clinics are recommended for patients who require lifestyle changes to decrease their risk of adverse outcomes associated with coronary heart disease (Level II).

Debt Counselling for Depression in Primary Care: an adaptive randomised controlled pilot trial (DeCoDer study).

PubMed

Gabbay, Mark B; Ring, Adele; Byng, Richard; Anderson, Pippa; Taylor, Rod S; Matthews, Caryn; Harris, Tirril; Berry, Vashti; Byrne, Paula; Carter, Elliot; Clarke, Pam; Cocking, Laura; Edwards, Suzanne; Emsley, Richard; Fornasiero, Mauro; Frith, Lucy; Harris, Shaun; Huxley, Peter; Jones, Siw; Kinderman, Peter; King, Michael; Kosnes, Liv; Marshall, Daniel; Mercer, Dave; May, Carl; Nolan, Debbie; Phillips, Ceri; Rawcliffe, Tim; Sardani, Alexandra V; Shaw, Elizabeth; Thompson, Sam; Vickery, Jane; Wainman, Brian; Warner, Mark

2017-06-01

Depression and debt are common in the UK. Debt Counselling for Depression in Primary Care: an adaptive randomised controlled pilot trial (DeCoDer) aimed to assess the clinical effectiveness and cost-effectiveness of the addition of a primary care debt counselling advice service to usual care for patients with depression and debt. However, the study was terminated early during the internal pilot trial phase because of recruitment delays. This report describes the rationale, methods and findings of the pilot study, and implications for future research. The overarching aim of the internal pilot was to identify and resolve problems, thereby assessing the feasibility of the main trial. The specific objectives were to confirm methods for practice recruitment and the ability to recruit patients via the proposed approaches; to determine the acceptability of the study interventions and outcome measures; to assess contamination; to confirm the randomisation method for main trial and the level of participant attrition; and to check the robustness of data collection systems. An adaptive, parallel, two-group multicentre randomised controlled pilot trial with a nested mixed-methods process and economic evaluation. Both individual- and cluster (general practice)-level were was used in the pilot phase to assign participants to intervention or control groups. General practices in England and Wales. Individuals were included who were aged ≥ 18 years, scored ≥ 14 on the Beck Depression Inventory II and self-identified as having debt worries. The main exclusion criteria were being actively suicidal or psychotic and/or severely depressed and unresponsive to treatment; having a severe addiction to alcohol/illicit drugs; being unable/unwilling to give written informed consent; currently participating in other research including follow-up phases; having received Citizens Advice Bureau (CAB) debt advice in the past year; and not wanting debt advice via a general practice. The participants in the intervention group were given debt advice provided by the CAB and shared biopsychosocial assessment, in addition to treatment as usual (TAU) and two debt advice leaflets. The participants in the control group were given advice leaflets provided by the general practitioner and TAU only. (1) Outcomes of the pilot trial - the proportion of eligible patients who consented, the number of participants recruited compared with target, assessment of contamination, and assessment of patient satisfaction with intervention and outcome measures. (2) Participant outcomes - primary - Beck Depression Inventory II; secondary - psychological well-being, health and social care utilisation, service satisfaction, substance misuse, record of priority/non-priority debts, life events and difficulties, and explanatory measures. Outcomes were assessed at baseline (pre-randomisation) and at 4 months post randomisation. Other data sources - qualitative interviews were conducted with participants, clinicians and CAB advisors. Of the 238 expressions of interest screened, 61 participants (26%) were recruited and randomised (32 in the intervention group and 29 in the control group). All participants provided baseline outcomes and 52 provided the primary outcome at 4 months' follow-up (14.7% dropout). Seventeen participants allocated to the intervention saw a CAB advisor. Descriptive statistics are reported for participants with complete outcomes at baseline and 4 months' follow-up. Our qualitative findings suggest that the relationship between debt and depression is complex, and the impact of each on the other is compounded by other psychological, social and contextual influences. As a result of low recruitment, this trial was terminated at the internal pilot phase and was too small for inferential statistical analysis. We recommend ways to reduce this risk when conducting complex trials among vulnerable populations recruited in community settings. These cover trial design, the design and delivery of interventions, recruitment strategies and support for sites. Current Controlled Trials ISRCTN79705874. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 35. See the NIHR Journals Library website for further project information. Mark Gabbay and Adele Ring are part-funded by NIHR Collaborations for Leadership in Applied Health Research and Care (CLAHRC) North West Coast and Richard Byng and Rod S Taylor, Vashti Berry and Elizabeth Shaw part-funded by NIHR CLAHRC South West Peninsula.

Co-crystal of Tramadol-Celecoxib in Patients with Moderate to Severe Acute Post-surgical Oral Pain: A Dose-Finding, Randomised, Double-Blind, Placebo- and Active-Controlled, Multicentre, Phase II Trial.

PubMed

López-Cedrún, José; Videla, Sebastián; Burgueño, Miguel; Juárez, Inma; Aboul-Hosn, Samir; Martín-Granizo, Rafael; Grau, Joan; Puche, Miguel; Gil-Diez, José-Luis; Hueto, José-Antonio; Vaqué, Anna; Sust, Mariano; Plata-Salamán, Carlos; Monner, Antoni

2018-06-01

Co-crystal of tramadol-celecoxib (CTC), containing equimolar quantities of the active pharmaceutical ingredients (APIs) tramadol and celecoxib (100 mg CTC = 44 mg rac-tramadol hydrochloride and 56 mg celecoxib), is a novel API-API co-crystal for the treatment of pain. We aimed to establish the effective dose of CTC for treating acute pain following oral surgery. A dose-finding, double-blind, randomised, placebo- and active-controlled, multicentre (nine Spanish hospitals), phase II study (EudraCT number: 2011-002778-21) was performed in male and female patients aged ≥ 18 years experiencing moderate to severe pain following extraction of two or more impacted third molars requiring bone removal. Eligible patients were randomised via a computer-generated list to receive one of six single-dose treatments (CTC 50, 100, 150, 200 mg; tramadol 100 mg; and placebo). The primary efficacy endpoint was the sum of pain intensity difference (SPID) over 8 h assessed in the per-protocol population. Between 10 February 2012 and 13 February 2013, 334 patients were randomised and received study treatment: 50 mg (n = 55), 100 mg (n = 53), 150 mg (n = 57), or 200 mg (n = 57) of CTC, 100 mg tramadol (n = 58), or placebo (n = 54). CTC 100, 150, and 200 mg showed significantly higher efficacy compared with placebo and/or tramadol in all measures: SPID (0-8 h) (mean [standard deviation]): - 90 (234), - 139 (227), - 173 (224), 71 (213), and 22 (228), respectively. The proportion of patients experiencing treatment-emergent adverse events was lower in the 50 (12.7% [n = 7]), 100 (11.3% [n = 6]), and 150 (15.8% [n = 9]) mg CTC groups, and similar in the 200 mg (29.8% [n = 17]) CTC group, compared with the tramadol group (29.3% [n = 17]), with nausea, dizziness, and vomiting the most frequent events. Significant improvement in the benefit-risk ratio was observed for CTC (doses ≥ 100 mg) over tramadol and placebo in the treatment of acute pain following oral surgery. Laboratorios del Dr. Esteve, S.A.U.

EMA401, an orally administered highly selective angiotensin II type 2 receptor antagonist, as a novel treatment for postherpetic neuralgia: a randomised, double-blind, placebo-controlled phase 2 clinical trial.

PubMed

Rice, Andrew S C; Dworkin, Robert H; McCarthy, Tom D; Anand, Praveen; Bountra, Chas; McCloud, Philip I; Hill, Julie; Cutter, Gary; Kitson, Geoff; Desem, Nuket; Raff, Milton

2014-05-10

Existing treatments for postherpetic neuralgia, and for neuropathic pain in general, are limited by modest efficacy and unfavourable side-effects. The angiotensin II type 2 receptor (AT2R) is a new target for neuropathic pain. EMA401, a highly selective AT2R antagonist, is under development as a novel neuropathic pain therapeutic agent. We assessed the therapeutic potential of EMA401 in patients with postherpetic neuralgia. In this multicentre, placebo-controlled, double-blind, randomised, phase 2 clinical trial, we enrolled patients (aged 22-89 years) with postherpetic neuralgia of at least 6 months' duration from 29 centres across six countries. We randomly allocated 183 participants to receive either oral EMA401 (100 mg twice daily) or placebo for 28 days. Randomisation was done according to a centralised randomisation schedule, blocked by study site, which was generated by an independent, unmasked statistician. Patients and staff at each site were masked to treatment assignment. We assessed the efficacy, safety, and pharmacokinetics of EMA401. The primary efficacy endpoint was change in mean pain intensity between baseline and the last week of dosing (days 22-28), measured on an 11-point numerical rating scale. The primary efficacy analysis was intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000822987. 92 patients were assigned to EMA401 and 91 were assigned to placebo. The patients given EMA401 reported significantly less pain compared with baseline values in the final week of treatment than did those given placebo (mean reductions in pain scores -2.29 [SD 1.75] vs -1.60 [1.66]; difference of adjusted least square means -0.69 [SE 0.25]; 95% CI -1.19 to -0.20; p=0.0066). No serious adverse events related to EMA401 occurred. Overall, 32 patients reported 56 treatment-emergent adverse events in the EMA401 group compared with 45 such events reported by 29 patients given placebo. EMA401 (100 mg twice daily) provides superior relief of postherpetic neuralgia compared with placebo at the end of 28 days of treatment. EMA401 was well tolerated by patients. Spinifex Pharmaceuticals. Copyright © 2014 Elsevier Ltd. All rights reserved.

No neurodevelopmental benefit of cerebral oximetry in the first randomised trial in preterm infants during the first days of life (SafeBoosC II).

PubMed

Plomgaard, Anne M; Alderliesten, Thomas; van Bel, Frank; Benders, Manon; Claris, Olivier; Cordeiro, Malaika; Dempsey, Eugene; Fumagalli, Monica; Gluud, Christian; Hyttel-Sorensen, Simon; Lemmers, Petra; Pellicer, Adelina; Pichler, Gerhard; Greisen, Gorm

2018-06-16

Cerebral hypoxia has been associated with neurodevelopmental impairment. We studied whether reducing cerebral hypoxia in extremely preterm infants during the first 72 hours of life affected neurological outcomes at two years of corrected age. In 2012-2013 the phase II randomised Safeguarding the Brains of our Smallest Children trial compared visible cerebral near infrared spectroscopy (NIRS) monitoring in an intervention group and blinded NIRS monitoring in a control group. Cerebral hypoxia was significantly reduced in the intervention group. We followed up 115 survivors from eight European centres at two years of corrected age, by conducting a medical examination and assessing their neurodevelopment with the Bayley Scales of Infant and Toddler Development, Second or Third Edition and the parental Ages and Stages Questionnaire, (ASQ). There were no respective differences between the intervention (n=65) and control (n=50) groups with regard to the mean mental developmental index (89.6 ±19.5 versus 88.4 ±14.7, p=0.77), ASQ score (215 ±58 versus 213 ±58, p=0.88) and the number of children with moderate-to-severe neurodevelopmental impairment (10 versus six, p=0.58). Cerebral NIRS monitoring was not associated with long-term benefits or harm with regard to neurodevelopmental outcome at two years of corrected age. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Using mental visual imagery to improve autobiographical memory and episodic future thinking in relapsing-remitting multiple sclerosis patients: A randomised-controlled trial study.

PubMed

Ernst, Alexandra; Blanc, Frédéric; De Seze, Jérôme; Manning, Liliann

2015-01-01

The co-occurrence of autobiographical memory (AM) and episodic future thinking (EFT) impairment has been documented in relapsing-remitting multiple sclerosis (RR-MS) patients. On these bases, we aimed at probing the efficacy of a mental visual imagery (MVI)-based facilitation programme on AM and EFT functioning in the context of a randomised-controlled trial study in RR-MS patients. Using the Autobiographical Interview (AI), 40 patients presenting with an AM/EFT impairment were randomly assigned in three groups: (i) the experimental (n = 17), who followed the MVI programme, (ii) the verbal control (n = 10), who followed a sham verbal programme, and (iii) the stability groups (n = 13), who underwent the AM/EFT test twice, with no intervention in between. AI's second assessment scores showed a significant improvement of AM and EFT performance only for the experimental group, with a long-term robustness of treatment benefits. The control and stability groups' results ruled out nursing and test learning effects as explanations of AM/EFT improvement. These benefits were corroborated by the patients' comments, which indicated an effective MVI strategy transfer to daily life. Our results suggest that the MVI programme tackles a common cognitive process of scene construction present in AM and EFT.

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.

Protocol for a randomised controlled trial examining the impact of a web-based personally controlled health management system on the uptake of influenza vaccination rates.

PubMed

Lau, Annie Y S; Sintchenko, Vitali; Crimmins, Jacinta; Magrabi, Farah; Gallego, Blanca; Coiera, Enrico

2012-04-02

Online social networking and personally controlled health management systems (PCHMS) offer a new opportunity for developing innovative interventions to prevent diseases of public health concern (e.g., influenza) but there are few comparative studies about patterns of use and impact of these systems. A 2010 CONSORT-compliant randomised controlled trial with a two-group parallel design will assess the efficacy of a web-based PCHMS called Healthy.me in facilitating the uptake of influenza vaccine amongst university students and staff. Eligible participants are randomised either to obtain access to Healthy.me or a 6-month waitlist. Participants complete pre-study, post-study and monthly surveys about their health and utilisation of health services. A post-study clinical audit will be conducted to validate self-reports about influenza vaccination and visits to the university health service due to influenza-like illness (ILI) amongst a subset of participants. 600 participants older than 18 years with monthly access to the Internet and email will be recruited. Participants who (i) discontinue the online registration process; (ii) report obtaining an influenza vaccination in 2010 before the commencement of the study; or (iii) report being influenced by other participants to undertake influenza vaccination will be excluded from analysis. The primary outcome measure is the number of participants obtaining influenza vaccination during the study. Secondary outcome measures include: number of participants (i) experiencing ILI symptoms, (ii) absent from or experiencing impairment in work or study due to ILI symptoms, (iii) using health services or medications due to ILI symptoms; (iv) expressing positive or negative attitudes or experiences towards influenza vaccination, via their reasons of receiving (or not receiving) influenza vaccine; and (v) their patterns of usage of Healthy.me (e.g., frequency and timing of hits, duration of access, uptake of specific functions). This study will provide new insights about the utility of online social networking and PCHMS for public health and health promotion. It will help to assess whether a web-based PCHMS, with connectivity to a health service provider, containing information and self-management tools, can improve the uptake of preventive health services amongst university students and staff. ACTRN12610000386033 (Australian New Zealand Clinical Trials Registry).

Protocol for a randomised controlled trial examining the impact of a web-based personally controlled health management system on the uptake of influenza vaccination rates

PubMed Central

2012-01-01

Background Online social networking and personally controlled health management systems (PCHMS) offer a new opportunity for developing innovative interventions to prevent diseases of public health concern (e.g., influenza) but there are few comparative studies about patterns of use and impact of these systems. Methods/Design A 2010 CONSORT-compliant randomised controlled trial with a two-group parallel design will assess the efficacy of a web-based PCHMS called Healthy.me in facilitating the uptake of influenza vaccine amongst university students and staff. Eligible participants are randomised either to obtain access to Healthy.me or a 6-month waitlist. Participants complete pre-study, post-study and monthly surveys about their health and utilisation of health services. A post-study clinical audit will be conducted to validate self-reports about influenza vaccination and visits to the university health service due to influenza-like illness (ILI) amongst a subset of participants. 600 participants older than 18 years with monthly access to the Internet and email will be recruited. Participants who (i) discontinue the online registration process; (ii) report obtaining an influenza vaccination in 2010 before the commencement of the study; or (iii) report being influenced by other participants to undertake influenza vaccination will be excluded from analysis. The primary outcome measure is the number of participants obtaining influenza vaccination during the study. Secondary outcome measures include: number of participants (i) experiencing ILI symptoms, (ii) absent from or experiencing impairment in work or study due to ILI symptoms, (iii) using health services or medications due to ILI symptoms; (iv) expressing positive or negative attitudes or experiences towards influenza vaccination, via their reasons of receiving (or not receiving) influenza vaccine; and (v) their patterns of usage of Healthy.me (e.g., frequency and timing of hits, duration of access, uptake of specific functions). Discussion This study will provide new insights about the utility of online social networking and PCHMS for public health and health promotion. It will help to assess whether a web-based PCHMS, with connectivity to a health service provider, containing information and self-management tools, can improve the uptake of preventive health services amongst university students and staff. Trial registration ACTRN12610000386033 (Australian New Zealand Clinical Trials Registry) PMID:22462549

A Bayesian adaptive design for biomarker trials with linked treatments

PubMed Central

Wason, James M S; Abraham, Jean E; Baird, Richard D; Gournaris, Ioannis; Vallier, Anne-Laure; Brenton, James D; Earl, Helena M; Mander, Adrian P

2015-01-01

Background: Response to treatments is highly heterogeneous in cancer. Increased availability of biomarkers and targeted treatments has led to the need for trial designs that efficiently test new treatments in biomarker-stratified patient subgroups. Methods: We propose a novel Bayesian adaptive randomisation (BAR) design for use in multi-arm phase II trials where biomarkers exist that are potentially predictive of a linked treatment's effect. The design is motivated in part by two phase II trials that are currently in development. The design starts by randomising patients to the control treatment or to experimental treatments that the biomarker profile suggests should be active. At interim analyses, data from treated patients are used to update the allocation probabilities. If the linked treatments are effective, the allocation remains high; if ineffective, the allocation changes over the course of the trial to unlinked treatments that are more effective. Results: Our proposed design has high power to detect treatment effects if the pairings of treatment with biomarker are correct, but also performs well when alternative pairings are true. The design is consistently more powerful than parallel-groups stratified trials. Conclusions: This BAR design is a powerful approach to use when there are pairings of biomarkers with treatments available for testing simultaneously. PMID:26263479

Fracture in the Elderly Multidisciplinary Rehabilitation (FEMuR): a phase II randomised feasibility study of a multidisciplinary rehabilitation package following hip fracture.

PubMed

Williams, Nefyn H; Roberts, Jessica L; Din, Nafees Ud; Totton, Nicola; Charles, Joanna M; Hawkes, Claire A; Morrison, Val; Hoare, Zoe; Williams, Michelle; Pritchard, Aaron W; Alexander, Swapna; Lemmey, Andrew; Woods, Robert T; Sackley, Catherine; Logan, Pip; Edwards, Rhiannon T; Wilkinson, Clare

2016-10-05

To conduct a rigorous feasibility study for a future definitive parallel-group randomised controlled trial (RCT) and economic evaluation of an enhanced rehabilitation package for hip fracture. Recruitment from 3 acute hospitals in North Wales. Intervention delivery in the community. Older adults (aged ≥65) who received surgical treatment for hip fracture, lived independently prior to fracture, had mental capacity (assessed by clinical team) and received rehabilitation in the North Wales area. Remote randomisation to usual care (control) or usual care+enhanced rehabilitation package (intervention), including six additional home-based physiotherapy sessions delivered by a physiotherapist or technical instructor, novel information workbook and goal-setting diary. Primary: Barthel Activities of Daily Living (BADL). Secondary measures included Nottingham Extended Activities of Daily Living scale (NEADL), EQ-5D, ICECAP capability, a suite of self-efficacy, psychosocial and service-use measures and costs. Outcome measures were assessed at baseline and 3-month follow-up by blinded researchers. 62 participants were recruited, 61 randomised (control 32; intervention 29) and 49 (79%) completed 3-month follow-up. Minimal differences occurred between the 2 groups for most outcomes, including BADL (adjusted mean difference 0.5). The intervention group showed a medium-sized improvement in the NEADL relative to the control group, with an adjusted mean difference between groups of 3.0 (Cohen's d 0.63), and a trend for greater improvement in self-efficacy and mental health, but with small effect sizes. The mean cost of delivering the intervention was £231 per patient. There was a small relative improvement in quality-adjusted life year in the intervention group. No serious adverse events relating to the intervention were reported. The trial methods were feasible in terms of eligibility, recruitment and retention. The effectiveness and cost-effectiveness of the rehabilitation package should be tested in a phase III RCT. ISRCTN22464643; 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/.

Acupuncture and Counselling for Depression in Primary Care: A Randomised Controlled Trial

PubMed Central

MacPherson, Hugh; Richmond, Stewart; Bland, Martin; Brealey, Stephen; Gabe, Rhian; Hopton, Ann; Keding, Ada; Lansdown, Harriet; Perren, Sara; Sculpher, Mark; Spackman, Eldon; Torgerson, David; Watt, Ian

2013-01-01

Background Depression is a significant cause of morbidity. Many patients have communicated an interest in non-pharmacological therapies to their general practitioners. Systematic reviews of acupuncture and counselling for depression in primary care have identified limited evidence. The aim of this study was to evaluate acupuncture versus usual care and counselling versus usual care for patients who continue to experience depression in primary care. Methods and Findings In a randomised controlled trial, 755 patients with depression (Beck Depression Inventory BDI-II score ≥20) were recruited from 27 primary care practices in the North of England. Patients were randomised to one of three arms using a ratio of 2∶2∶1 to acupuncture (302), counselling (302), and usual care alone (151). The primary outcome was the difference in mean Patient Health Questionnaire (PHQ-9) scores at 3 months with secondary analyses over 12 months follow-up. Analysis was by intention-to-treat. PHQ-9 data were available for 614 patients at 3 months and 572 patients at 12 months. Patients attended a mean of ten sessions for acupuncture and nine sessions for counselling. Compared to usual care, there was a statistically significant reduction in mean PHQ-9 depression scores at 3 months for acupuncture (−2.46, 95% CI −3.72 to −1.21) and counselling (−1.73, 95% CI −3.00 to −0.45), and over 12 months for acupuncture (−1.55, 95% CI −2.41 to −0.70) and counselling (−1.50, 95% CI −2.43 to −0.58). Differences between acupuncture and counselling were not significant. In terms of limitations, the trial was not designed to separate out specific from non-specific effects. No serious treatment-related adverse events were reported. Conclusions In this randomised controlled trial of acupuncture and counselling for patients presenting with depression, after having consulted their general practitioner in primary care, both interventions were associated with significantly reduced depression at 3 months when compared to usual care alone. Trial Registration Controlled-Trials.com ISRCTN63787732 Please see later in the article for the Editors' Summary PMID:24086114

The early use of botulinum toxin in post-stroke spasticity: study protocol for a randomised controlled trial.

PubMed

Lindsay, Cameron; Simpson, Julie; Ispoglou, Sissi; Sturman, Steve G; Pandyan, Anand D

2014-01-08

Patients surviving stroke but who have significant impairment of function in the affected arm are at more risk of developing pain, stiffness and contractures. The abnormal muscle activity, associated with post-stroke spasticity, is thought to be causally associated with the development of these complications. Treatment of spasticity is currently delayed until a patient develops signs of these complications. This protocol is for a phase II study that aims to identify whether using OnabotulinumtoxinA (BoNT-A) in combination with physiotherapy early post stroke when initial abnormal muscle activity is neurophysiologically identified can prevent loss of range at joints and improve functional outcomes.The trial uses a screening phase to identify which people are appropriate to be included in a double blind randomised placebo-controlled trial. All patients admitted to Sandwell and West Birmingham NHS Trust Hospitals with a diagnosis of stroke will be screened to identify functional activity in the arm. Those who have no function will be appropriate for further screening. Patients who are screened and have abnormal muscle activity identified on EMG will be given electrical stimulation to forearm extensors for 3 months and randomised to have either injections of BoNT-A or normal saline. The primary outcome measure is the action research arm test - a measure of arm function. Further measures include spasticity, stiffness, muscle strength and fatigue as well as measures of quality of life, participation and caregiver strain. ISRCTN57435427, EudraCT2010-021257-39, NCT01882556.

Budesonide MMX for the Induction of Remission of Mild to Moderate Ulcerative Colitis: A Pooled Safety Analysis.

PubMed

Lichtenstein, Gary R; Travis, Simon; Danese, Silvio; D'Haens, Geert; Moro, Luigi; Jones, Richard; Huang, Michael; Ballard, E David; Bagin, Robert; Hardiman, Yun; Collazo, Raul; Sandborn, William J

2015-09-01

Cumulative safety and tolerability of budesonide MMX, a once-daily oral corticosteroid for inducing mild to moderate ulcerative colitis remission, was examined. Data from three randomized, double-blind, placebo-controlled, phase II or III studies [budesonide MMX 9 mg, 6 mg, or 3mg for 8 weeks]; one phase II study [randomisation to budesonide MMX 9 mg or placebo for 4 weeks, then open-label budesonide MMX 9 mg for 4 weeks]; and one open-label study [budesonide MMX 9 mg for 8 weeks] were pooled. Patients randomised to budesonide MMX 9 mg [n = 288], 6 mg [n = 254], or placebo [n = 293] had similar rates of adverse events [AEs] [27.1%, 24.8%, and 23.9%, respectively] and serious AEs [2.4%, 2.0%, and 2.7%, respectively]; treatment-related AEs and serious AEs were reported by 11.8% and 13.5%, and 5.9% and 2.2%, respectively, of patients receiving budesonide MMX 3mg [n = 17] or open-label budesonide MMX 9 mg [n = 89]. Mean morning plasma cortisol concentrations were normal from baseline to final visit across randomised groups; in patients receiving open-label budesonide, mean cortisol concentration was 129.9 nmol/l after 4 weeks, returning to normal concentrations at final visit. Budesonide MMX was not associated with an overall increased risk for glucocorticoid-related adverse effects. Budesonide MMX 9 mg was associated with normal mean cortisol concentrations at final visit and an AE incidence comparable to placebo. Overall, budesonide MMX was safe and well tolerated for inducing remission of patients with mild to moderate ulcerative colitis. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Budesonide MMX for the Induction of Remission of Mild to Moderate Ulcerative Colitis: A Pooled Safety Analysis

PubMed Central

Travis, Simon; Danese, Silvio; D’Haens, Geert; Moro, Luigi; Jones, Richard; Huang, Michael; Ballard, E. David; Bagin, Robert; Hardiman, Yun; Collazo, Raul; Sandborn, William J.

2015-01-01

Background and aims: Cumulative safety and tolerability of budesonide MMX, a once-daily oral corticosteroid for inducing mild to moderate ulcerative colitis remission, was examined. Methods: Data from three randomized, double-blind, placebo-controlled, phase II or III studies [budesonide MMX 9mg, 6mg, or 3mg for 8 weeks]; one phase II study [randomisation to budesonide MMX 9mg or placebo for 4 weeks, then open-label budesonide MMX 9mg for 4 weeks]; and one open-label study [budesonide MMX 9mg for 8 weeks] were pooled. Results: Patients randomised to budesonide MMX 9mg [n = 288], 6mg [n = 254], or placebo [n = 293] had similar rates of adverse events [AEs] [27.1%, 24.8%, and 23.9%, respectively] and serious AEs [2.4%, 2.0%, and 2.7%, respectively]; treatment-related AEs and serious AEs were reported by 11.8% and 13.5%, and 5.9% and 2.2%, respectively, of patients receiving budesonide MMX 3mg [n = 17] or open-label budesonide MMX 9mg [n = 89]. Mean morning plasma cortisol concentrations were normal from baseline to final visit across randomised groups; in patients receiving open-label budesonide, mean cortisol concentration was 129.9 nmol/l after 4 weeks, returning to normal concentrations at final visit. Budesonide MMX was not associated with an overall increased risk for glucocorticoid-related adverse effects. Conclusions: Budesonide MMX 9mg was associated with normal mean cortisol concentrations at final visit and an AE incidence comparable to placebo. Overall, budesonide MMX was safe and well tolerated for inducing remission of patients with mild to moderate ulcerative colitis. PMID:26094251

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.

Ergonomic positioning or equipment for treating carpal tunnel syndrome.

PubMed

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

2012-01-18

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

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

PubMed

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

2015-03-27

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

Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II).

PubMed

Zeuzem, S; Flisiak, R; Vierling, J M; Mazur, W; Mazzella, G; Thongsawat, S; Abdurakhmanov, D; Van Kính, N; Calistru, P; Heo, J; Stanciu, C; Gould, M; Makara, M; Hsu, S-J; Buggisch, P; Samuel, D; Mutimer, D; Nault, B; Merz, M; Bao, W; Griffel, L H; Brass, C; Naoumov, N V

2015-10-01

Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection. Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy. A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension. Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens. © 2015 John Wiley & Sons Ltd.

A proof-of-concept investigation into ketamine as a pharmacological treatment for alcohol dependence: study protocol for a randomised controlled trial.

PubMed

McAndrew, Amy; Lawn, Will; Stevens, Tobias; Porffy, Lilla; Brandner, Brigitta; Morgan, Celia J A

2017-04-04

Worldwide, alcohol abuse is a burgeoning problem. Abstinence is key to allow recovery of physical and mental health as well as quality of life, but treatment for alcohol dependence is associated with high relapse rates. Preliminary data have suggested that a combined repeated ketamine and psychological therapy programme may be effective in reducing relapse in severe alcohol use disorder. This non-commercial proof-of-concept trial is aimed at making a preliminary assessment of the effectiveness of this combined treatment in this patient group. This is a phase II, randomised, double-blind, placebo-controlled, parallel-group clinical trial taking place in two sites in the UK: the South West of England and London. Ninety-six recently detoxified alcoholics, with comorbid depressive symptoms, will be randomised to one of four treatment arms. Patients will receive either three sessions of ketamine (0.8 mg/kg administered intravenously (IV) over 40 minutes) or placebo (50 ml saline 0.9% IV over 40 minutes) plus either seven sessions of manualised psychological therapy or an alcohol education control. Patients will be assessed at 3 and 6 months on a range of psychological and biological variables. The primary endpoints are (1) relapse rates at 6 months and (2) percentage days abstinent at 6 months. Secondary endpoints include 3 and 6 month percentage days abstinence, tolerability (indicated by dropout), adverse events, depressive symptoms, craving and quality of life. This study will provide important information on a new combined psychological and pharmacological intervention aimed at reducing relapse rates in alcoholics. The findings would have broad application given the worldwide prevalence of alcoholism and its associated medical, psychological and social problems. ClinicalTrials.gov, NCT02649231 . Registered on 5 January 2016.

Smartphone-Supported versus Full Behavioural Activation for Depression: A Randomised Controlled Trial

PubMed Central

Ly, Kien Hoa; Topooco, Naira; Cederlund, Hanna; Wallin, Anna; Bergström, Jan; Molander, Olof; Carlbring, Per; Andersson, Gerhard

2015-01-01

Background There is need for more cost and time effective treatments for depression. This is the first randomised controlled trial in which a blended treatment - including four face-to-face sessions and a smartphone application - was compared against a full behavioural treatment. Hence, the aim of the current paper was to examine whether a blended smartphone treatment was non-inferior to a full behavioural activation treatment for depression. Methods This was a randomised controlled non-inferiority trial (NCT01819025) comparing a blended treatment (n=46) against a full ten-session treatment (n=47) for people suffering from major depression. Primary outcome measure was the BDI-II, that was administered at pre- and post-treatment, as well as six months after the treatment. Results Results showed significant improvements in both groups across time on the primary outcome measure (within-group Cohen’s d=1.35; CI [−0.82, 3.52] to d=1.47; CI [−0.41, 3.35]; between group d=−0.13 CI [−2.37, 2.09] and d=−0.10 CI [−2.53, 2.33]). At the same time, the blended treatment reduced the therapist time with an average of 47%. Conclusions We could not establish whether the blended treatment was non-inferior to a full BA treatment. Nevertheless, this study points to that the blended treatment approach could possibly treat nearly twice as many patients suffering from depression by using a smartphone applica¬tion as add-on. More studies are needed before we can suggest that the blended treatment method is a promising cost-effective alternative to regular face-to-face treatment for depression. Trial Registration Cognitive Behavioral Therapy Treatment of Depression With Smartphone Support NCT01819025 PMID:26010890

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

PubMed Central

2012-01-01

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

Clinical trial design and dissemination: comprehensive analysis of clinicaltrials.gov and PubMed data since 2005.

PubMed

Zwierzyna, Magdalena; Davies, Mark; Hingorani, Aroon D; Hunter, Jackie

2018-06-06

To investigate the distribution, design characteristics, and dissemination of clinical trials by funding organisation and medical specialty. Cross sectional descriptive analysis. Trial protocol information from clinicaltrials.gov, metadata of journal articles in which trial results were published (PubMed), and quality metrics of associated journals from SCImago Journal and Country Rank database. All 45 620 clinical trials evaluating small molecule therapeutics, biological drugs, adjuvants, and vaccines, completed after January 2006 and before July 2015, including randomised controlled trials and non-randomised studies across all clinical phases. Industry was more likely than non-profit funders to fund large international randomised controlled trials, although methodological differences have been decreasing with time. Among 27 835 completed efficacy trials (phase II-IV), 15 084 (54.2%) had disclosed their findings publicly. Industry was more likely than non-profit trial funders to disseminate trial results (59.3% (10 444/17 627) v 45.3% (4555/10 066)), and large drug companies had higher disclosure rates than small ones (66.7% (7681/11 508) v 45.2% (2763/6119)). Trials funded by the National Institutes of Health (NIH) were disseminated more often than those of other non-profit institutions (60.0% (1451/2417) v 40.6% (3104/7649)). Results of studies funded by large drug companies and NIH were more likely to appear on clinicaltrials.gov than were those from non-profit funders, which were published mainly as journal articles. Trials reporting the use of randomisation were more likely than non-randomised studies to be published in a journal article (6895/19 711 (34.9%) v 1408/7748 (18.2%)), and journal publication rates varied across disease areas, ranging from 42% for autoimmune diseases to 20% for oncology. Trial design and dissemination of results vary substantially depending on the type and size of funding institution as well as the disease area under study. 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.

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.

Splint: the efficacy of orthotic management in rest to prevent equinus in children with cerebral palsy, a randomised controlled trial.

PubMed

Maas, Josina C; Dallmeijer, Annet J; Huijing, Peter A; Brunstrom-Hernandez, Janice E; van Kampen, Petra J; Jaspers, Richard T; Becher, Jules G

2012-03-26

Range of motion deficits of the lower extremity occur in about the half of the children with spastic cerebral palsy (CP). Over time, these impairments can cause joint deformities and deviations in the children's gait pattern, leading to limitations in moblity. Preventing a loss of range of motion is important in order to reduce secondary activity limitations and joint deformities. Sustained muscle stretch, imposed by orthotic management in rest, might be an effective method of preventing a decrease in range of motion. However, no controlled study has been performed. A single blind randomised controlled trial will be performed in 66 children with spastic CP, divided over three groups with each 22 participants. Two groups will be treated for 1 year with orthoses to prevent a decrease in range of motion in the ankle (either with static or dynamic knee-ankle-foot-orthoses) and a third group will be included as a control group and will receive usual care (physical therapy, manual stretching). Measurements will be performed at baseline and at 3, 6, 9 and 12 months after treatment allocation. The primary outcome measure will be ankle dorsiflexion at full knee extension, measured with a custom designed hand held dynamometer. Secondary outcome measures will be i) ankle and knee flexion during gait and ii) gross motor function. Furthermore, to gain more insight in the working mechanism of the orthotic management in rest, morphological parameters like achilles tendon length, muscle belly length, muscle fascicle length, muscle physiological cross sectional area length and fascicle pennation angle will be measured in a subgroup of 18 participants using a 3D imaging technique. This randomised controlled trial will provide more insight into the efficacy of orthotic management in rest and the working mechanisms behind this treatment. The results of this study could lead to improved treatments. Nederlands Trial Register NTR2091.

Foot orthoses for adults with flexible pes planus: a systematic review.

PubMed

Banwell, Helen A; Mackintosh, Shylie; Thewlis, Dominic

2014-04-05

Foot orthoses are widely used in the management of flexible pes planus, yet the evidence to support this intervention has not been clearly defined. This systematic review aimed to critically appraise the evidence for the use of foot orthoses for flexible pes planus in adults. Electronic databases (Medline, CINAHL, Cochrane, Web of science, SportDiscus, Embase) were systematically searched in June 2013 for randomised controlled, controlled clinical and repeated measure trials where participants had identified flexible pes planus using a validated and reliable measure of pes planus and the intervention was a rigid or semi-rigid orthoses with the comparison being a no-orthoses (shoes alone or flat non-posted insert) condition. Outcomes of interest were foot pain, rearfoot kinematics, foot kinetics and physical function. Of the 2,211 articles identified by the searches, 13 studies met the inclusion criteria; two were randomised controlled trials, one was a controlled trial and 10 were repeated measure studies. Across the included studies, 59 relevant outcome measures were reported with 17 calculated as statistically significant large or medium effects observed with use of foot orthoses compared to the no orthoses condition (SMD range 1.13 to -4.11). No high level evidence supported the use of foot orthoses for flexible pes planus. There is good to moderate level evidence that foot orthoses improve physical function (medial-lateral sway in standing (level II) and energy cost during walking (level III)). There is low level evidence (level IV) that foot orthoses improve pain, reduce rearfoot eversion, alter loading and impact forces; and reduce rearfoot inversion and eversion moments in flexible pes planus. Well-designed randomised controlled trials that include appropriate sample sizes, clinical cohorts and involve a measure of symptom change are required to determine the efficacy of foot orthoses to manage adult flexible pes planus.

Foot orthoses for adults with flexible pes planus: a systematic review

PubMed Central

2014-01-01

Background Foot orthoses are widely used in the management of flexible pes planus, yet the evidence to support this intervention has not been clearly defined. This systematic review aimed to critically appraise the evidence for the use of foot orthoses for flexible pes planus in adults. Methods Electronic databases (Medline, CINAHL, Cochrane, Web of science, SportDiscus, Embase) were systematically searched in June 2013 for randomised controlled, controlled clinical and repeated measure trials where participants had identified flexible pes planus using a validated and reliable measure of pes planus and the intervention was a rigid or semi-rigid orthoses with the comparison being a no-orthoses (shoes alone or flat non-posted insert) condition. Outcomes of interest were foot pain, rearfoot kinematics, foot kinetics and physical function. Results Of the 2,211 articles identified by the searches, 13 studies met the inclusion criteria; two were randomised controlled trials, one was a controlled trial and 10 were repeated measure studies. Across the included studies, 59 relevant outcome measures were reported with 17 calculated as statistically significant large or medium effects observed with use of foot orthoses compared to the no orthoses condition (SMD range 1.13 to -4.11). Conclusions No high level evidence supported the use of foot orthoses for flexible pes planus. There is good to moderate level evidence that foot orthoses improve physical function (medial-lateral sway in standing (level II) and energy cost during walking (level III)). There is low level evidence (level IV) that foot orthoses improve pain, reduce rearfoot eversion, alter loading and impact forces; and reduce rearfoot inversion and eversion moments in flexible pes planus. Well-designed randomised controlled trials that include appropriate sample sizes, clinical cohorts and involve a measure of symptom change are required to determine the efficacy of foot orthoses to manage adult flexible pes planus. PMID:24708560

Clinical effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: the CoBalT randomised controlled trial.

PubMed

Wiles, Nicola; Thomas, Laura; Abel, Anna; Barnes, Maria; Carroll, Fran; Ridgway, Nicola; Sherlock, Sofie; Turner, Nicholas; Button, Katherine; Odondi, Lang'o; Metcalfe, Chris; Owen-Smith, Amanda; Campbell, John; Garland, Anne; Hollinghurst, Sandra; Jerrom, Bill; Kessler, David; Kuyken, Willem; Morrison, Jill; Turner, Katrina; Williams, Chris; Peters, Tim; Lewis, Glyn

2014-05-01

Only one-third of patients with depression respond fully to treatment with antidepressant medication. However, there is little robust evidence to guide the management of those whose symptoms are 'treatment resistant'. The CoBalT trial examined the clinical effectiveness and cost-effectiveness of cognitive behavioural therapy (CBT) as an adjunct to usual care (including pharmacotherapy) for primary care patients with treatment-resistant depression (TRD) compared with usual care alone. Pragmatic, multicentre individually randomised controlled trial with follow-up at 3, 6, 9 and 12 months. A subset took part in a qualitative study investigating views and experiences of CBT, reasons for completing/not completing therapy, and usual care for TRD. General practices in Bristol, Exeter and Glasgow, and surrounding areas. Patients aged 18-75 years who had TRD [on antidepressants for ≥ 6 weeks, had adhered to medication, Beck Depression Inventory, 2nd version (BDI-II) score of ≥ 14 and fulfilled the International Classification of Diseases and Related Health Problems, Tenth edition criteria for depression]. Individuals were excluded who (1) had bipolar disorder/psychosis or major alcohol/substance abuse problems; (2) were unable to complete the questionnaires; or (3) were pregnant, as were those currently receiving CBT/other psychotherapy/secondary care for depression, or who had received CBT in the past 3 years. Participants were randomised, using a computer-generated code, to usual care or CBT (12-18 sessions) in addition to usual care. The primary outcome was 'response', defined as ≥ 50% reduction in depressive symptoms (BDI-II score) at 6 months compared with baseline. Secondary outcomes included BDI-II score as a continuous variable, remission of symptoms (BDI-II score of < 10), quality of life, anxiety and antidepressant use at 6 and 12 months. Data on health and social care use, personal costs, and time off work were collected at 6 and 12 months. Costs from these three perspectives were reported using a cost-consequence analysis. A cost-utility analysis compared health and social care costs with quality adjusted life-years. A total of 469 patients were randomised (intervention: n = 234; usual care: n = 235), with 422 participants (90%) and 396 (84%) followed up at 6 and 12 months. Ninety-five participants (46.1%) in the intervention group met criteria for 'response' at 6 months compared with 46 (21.6%) in the usual-care group {odds ratio [OR] 3.26 [95% confidence interval (CI) 2.10 to 5.06], p < 0.001}. In repeated measures analyses using data from 6 and 12 months, the OR for 'response' was 2.89 (95% CI 2.03 to 4.10, p < 0.001) and for a secondary 'remission' outcome (BDI-II score of < 10) 2.74 (95% CI 1.82 to 4.13, p < 0.001). The mean cost of CBT per participant was £ 910, the incremental health and social care cost £ 850, the incremental QALY gain 0.057 and incremental cost-effectiveness ratio £ 14,911. Forty participants were interviewed. Patients described CBT as challenging but helping them to manage their depression; listed social, emotional and practical reasons for not completing treatment; and described usual care as mainly taking medication. Among patients who have not responded to antidepressants, augmenting usual care with CBT is effective in reducing depressive symptoms, and these effects, including outcomes reflecting remission, are maintained over 12 months. The intervention was cost-effective based on the National Institute for Health and Care Excellence threshold. Patients may experience CBT as difficult but effective. Further research should evaluate long-term effectiveness, as this would have major implications for the recommended treatment of depression. Current Controlled Trials ISRCTN38231611.

Somatropin treatment of spinal muscular atrophy: a placebo-controlled, double-blind crossover pilot study.

PubMed

Kirschner, J; Schorling, D; Hauschke, D; Rensing-Zimmermann, C; Wein, U; Grieben, U; Schottmann, G; Schara, U; Konrad, K; Müller-Felber, W; Thiele, S; Wilichowski, E; Hobbiebrunken, E; Stettner, G M; Korinthenberg, R

2014-02-01

In preclinical studies growth hormone and its primary mediator IGF-1 have shown potential to increase muscle mass and strength. A single patient with spinal muscular atrophy reported benefit after compassionate use of growth hormone. Therefore we evaluated the efficacy and safety of growth hormone treatment for spinal muscular atrophy in a multicenter, randomised, double-blind, placebo-controlled, crossover pilot trial. Patients (n = 19) with type II/III spinal muscular atrophy were randomised to receive either somatropin (0.03 mg/kg/day) or placebo subcutaneously for 3 months, followed by a 2-month wash-out phase before 3 months of treatment with the contrary remedy. Changes in upper limb muscle strength (megascore for elbow flexion and hand-grip in Newton) were assessed by hand-held myometry as the primary measure of outcome. Secondary outcome measures included lower limb muscle strength, motor function using the Hammersmith Functional Motor Scale and other functional tests for motor function and pulmonary function. Somatropin treatment did not significantly affect upper limb muscle strength (point estimate mean: 0.08 N, 95% confidence interval (CI:-3.79;3.95, p = 0.965), lower limb muscle strength (point estimate mean: 2.23 N, CI:-2.19;6.63, p = 0.302) or muscle and pulmonary function. Side effects occurring during somatropin treatment corresponded with well-known side effects of growth hormone substitution in patients with growth hormone deficiency. In this pilot study, growth hormone treatment did not improve muscle strength or function in patients with spinal muscular atrophy type II/III. Copyright © 2013 Elsevier B.V. All rights reserved.

Efficacy evaluation of an anti-caries varnish: protocol for a phase II randomised controlled trial

PubMed Central

Tut, Ohnmar; Rothen, Marilynn; Mancl, Lloyd; Gallen, Marcelle; Tanzer, Jason M

2017-01-01

Introduction Dental caries (tooth decay) is a common disease in which the products of sugar metabolism by certain bacteria that populate the tooth surface induce the development and progression of lesions (cavities). This is a phase II single-centre randomised, double-blind, active-controlled, parallel-group trial to assess the efficacy of a combination povidone iodine and sodium fluoride dental varnish to determine if it is superior to a varnish containing only sodium fluoride in the prevention of new caries lesions. The objective of this report is to describe the rationale and protocol for the trial. Methods and analysis The study site is Pohnpei State, Federated States of Micronesia. The study population is 284 children 48–84 months old. The primary outcome will be the surface-level primary molar caries increment (d2-3mfs/DMFS) at 2 years post baseline. The incremental dental caries at 1 year will also be compared between the two interventions. The secondary outcome is the Facial Image Scale after the initial treatment and after the fifth treatment at 1 year that gauges the child’s response to the treatment. Ethics and dissemination The Western Institutional Review Board (designated IRB) and the Institutional Review Board of the College of Micronesia-FSM approved all study procedures. The US Food and Drug Administration (FDA) has issued IND 128835 covering this study. The study results will be published and submitted to the FDA in support of a new drug application. Trialregistration number NCT03082196. PMID:28667230

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.

Effectiveness of a multicomponent intervention to enhance implementation of a healthy canteen policy in Australian primary schools: a randomised controlled trial.

PubMed

Nathan, Nicole; Yoong, Sze Lin; Sutherland, Rachel; Reilly, Kathryn; Delaney, Tessa; Janssen, Lisa; Robertson, Katie; Reynolds, Renee; Chai, Li Kheng; Lecathelinais, Christophe; Wiggers, John; Wolfenden, Luke

2016-10-07

The implementation of school nutrition policies, which govern the provision of food in schools, is recommended as a public health strategy to support the development of healthy dietary behaviours in school-aged children. Despite this, research internationally and in Australia indicates that few schools implement such policies. This study aims to examine whether a theoretically designed, multi-strategy intervention was effective in increasing the implementation of a healthy canteen policy in Australian primary schools. A parallel group randomised controlled trial was conducted with all government and Catholic primary schools within one region in New South Wales, Australia who had an operational canteen that provided food to primary school aged children (5-12 years) and were not currently receiving an intervention to change their canteen practices. Schools randomised to the intervention arm received a 9-month multicomponent intervention including ongoing support, provision of resources, performance monitoring and feedback, executive support and recognition. The primary outcomes were the proportion of the schools with a canteen menu that: i) did not include 'red' or 'banned' items according to the healthy canteen policy; and ii) had more than 50 % 'green' items. The primary outcome was assessed via menu audit at baseline and follow up by dietitians blinded to group allocation. Fifty-three eligible schools were randomised to either the intervention or control group (28 intervention; 25 control). Analyses with 51 schools who returned school menus found that intervention schools were significantly more likely relative to control schools to have a menu without 'red' or 'banned' items (RR = 5.78 (1.45-23.05); p = 0.002) and have at least 50 % of menu items classified as green (RR = 2.03 (1.01-4.08); p = 0.03). This study found that a multi-component intervention was effective in improving primary schools' compliance with a healthy canteen policy. Given the lack of evidence regarding how best to support schools with implementing evidence-based policies to improve child diet, this trial for the first time provides high quality evidence to practitioners and policy makers seeking to improve nutrition policy implementation in schools. This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12614001148662 ) 30th October 2014.

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

ERIC Educational Resources Information Center

Torgerson, Carole J.

2009-01-01

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

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

PubMed

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

2002-03-23

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

Exercise response in Parkinson’s disease: insights from a cross-sectional comparison with sedentary controls and a per-protocol analysis of a randomised controlled trial

PubMed Central

Collett, Johnny; Franssen, Marloes; Meaney, Andy; Sexton, Claire; Dennis-West, Andrea; Betts, Jill F; Izadi, Hooshang; Bogdanovic, Marko; Tims, Martin; Farmer, Andrew; Dawes, Helen

2017-01-01

Objectives To investigate the acute and adaptation cardiovascular and metabolic training responses in people with Parkinson’s disease (pwP). Design (1) A cross-sectional study of exercise response of pwP compared with sedentary controls and (2) an interventional study of exercise training in pwP. Setting Community leisure facilities. Participants pwP (n=83) and sedentary controls (n=55). Interventions Study 1 included participants from a two-arm-parallel single-blind phase II randomised controlled trial (RCT), that undertook a baseline maximal incremental exercise test and study 2 included those randomised to the exercise group in the RCT, who completed a 6-month weekly exercise programme (n=37). The intervention study 2 was a prescribed exercise program consisting of sessions lasting 60 min, two times a week over a 6-month period. The control group followed the same protocol which derived the same cardiorespiratory parameters, except that they were instructed to aim for a cadence of ~60 revolutions per minute and the unloaded phase lasted 3 min with an initial step of 25 W. Primary and secondary outcome measures Stepwise incremental exercise test to volitional exhaustion was the primary outcome measure. Results Study 1 showed higher maximum values for heart rate (HR), VO2 L/min, VCO2 L/min and ventilation L/min for the control group; respiratory exchange ratio (RER), perceived exertion and O2 pulse (VO2 L/min/HR) did not differ between groups. In study 2, for pwP who adhered to training (n=37), RER increased significantly and although there was no significant change in aerobic capacity or HR response, reduced blood pressure was found. Conclusions An abnormal cardiovascular response to exercise was observed in pwP compared to controls. After the exercise programme, metabolic deficiencies remained for pwP. These observations add to the pathogenic understanding of PD, acknowledge an underling metabolic contribution and support that certain cardiovascular symptoms may improve as a result of this type of exercise. PMID:29282259

[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.

Trial Sequential Analysis in systematic reviews with meta-analysis.

PubMed

Wetterslev, Jørn; Jakobsen, Janus Christian; Gluud, Christian

2017-03-06

Most meta-analyses in systematic reviews, including Cochrane ones, do not have sufficient statistical power to detect or refute even large intervention effects. This is why a meta-analysis ought to be regarded as an interim analysis on its way towards a required information size. The results of the meta-analyses should relate the total number of randomised participants to the estimated required meta-analytic information size accounting for statistical diversity. When the number of participants and the corresponding number of trials in a meta-analysis are insufficient, the use of the traditional 95% confidence interval or the 5% statistical significance threshold will lead to too many false positive conclusions (type I errors) and too many false negative conclusions (type II errors). We developed a methodology for interpreting meta-analysis results, using generally accepted, valid evidence on how to adjust thresholds for significance in randomised clinical trials when the required sample size has not been reached. The Lan-DeMets trial sequential monitoring boundaries in Trial Sequential Analysis offer adjusted confidence intervals and restricted thresholds for statistical significance when the diversity-adjusted required information size and the corresponding number of required trials for the meta-analysis have not been reached. Trial Sequential Analysis provides a frequentistic approach to control both type I and type II errors. We define the required information size and the corresponding number of required trials in a meta-analysis and the diversity (D 2 ) measure of heterogeneity. We explain the reasons for using Trial Sequential Analysis of meta-analysis when the actual information size fails to reach the required information size. We present examples drawn from traditional meta-analyses using unadjusted naïve 95% confidence intervals and 5% thresholds for statistical significance. Spurious conclusions in systematic reviews with traditional meta-analyses can be reduced using Trial Sequential Analysis. Several empirical studies have demonstrated that the Trial Sequential Analysis provides better control of type I errors and of type II errors than the traditional naïve meta-analysis. Trial Sequential Analysis represents analysis of meta-analytic data, with transparent assumptions, and better control of type I and type II errors than the traditional meta-analysis using naïve unadjusted confidence intervals.

Experiences of recruiting to a pilot trial of Cardiac Rehabilitation In patients with Bowel cancer (CRIB) with an embedded process evaluation: lessons learned to improve recruitment.

PubMed

Hubbard, Gill; Campbell, Anna; Davies, Zoe; Munro, Julie; Ireland, Aileen V; Leslie, Stephen; Watson, Angus Jm; Treweek, Shaun

2015-01-01

Recruitment to randomised controlled trials (RCTs) is a perennial problem. Calls have been made for trialists to make recruitment performance publicly available. This article presents our experience of recruiting to a pilot RCT of cardiac rehabilitation for patients with bowel cancer with an embedded process evaluation. Recruitment took place at three UK hospitals. Recruitment figures were based on the following: i) estimated number of patient admissions, ii) number of patients likely to meet inclusion criteria from clinician input and iii) recruitment rates in previous studies. The following recruitment procedure was used:Nurse assessed patients for eligibility.Patients signed a screening form indicating interest in and agreement to be approached by a researcher about the study.An appointment was made at which the patient signed a consent form and was randomised to the intervention or control group. Information about all patients considered for the study and subsequently included or excluded at each stage of the recruitment process and reasons given were recorded. There were variations in the time taken to award Research Management approval to run the study at the three sites (45-359 days). Sixty-two percent of the original recruitment estimate was reached. The main reason for under-recruitment was due to over-estimation of the number of patient admissions; other reasons were i) not assessing all patients for eligibility, ii) not completing a screening form for eligible patients and iii) patients who signed a screening form being lost to the study before consenting and randomisation. Pilot trials should not simply aim to improve recruitment estimates but should also identify factors likely to influence recruitment performance in a future trial and inform the development of that trial's recruitment strategies. Pilot trials are a crucial part of RCT design. Nevertheless, pilot trials are likely to be small scale, involving only a small number of sites, and contextual differences between sites are likely to impact recruitment performance in any future trial. This means that ongoing monitoring and evaluation in trials are likely to be required. ISRCTN63510637; UKCRN id 14092.

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

Evaluating a computer aid for assessing stomach symptoms (ECASS): study protocol for a randomised controlled trial.

PubMed

Moore, Helen J; Nixon, Catherine; Tariq, Anisah; Emery, Jon; Hamilton, Willie; Hoare, Zoë; Kershenbaum, Anne; Neal, Richard D; Ukoumunne, Obioha C; Usher-Smith, Juliet; Walter, Fiona M; Whyte, Sophie; Rubin, Greg

2016-04-04

For most cancers, only a minority of patients have symptoms meeting the National Institute for Health and Clinical Excellence guidance for urgent referral. For gastro-oesophageal cancers, the 'alarm' symptoms of dysphagia and weight loss are reported by only 32 and 8 % of patients, respectively, and their presence correlates with advanced-stage disease. Electronic clinical decision-support tools that integrate with clinical computer systems have been developed for general practice, although uncertainty remains concerning their effectiveness. The objectives of this trial are to optimise the intervention and establish the acceptability of both the intervention and randomisation, confirm the suitability and selection of outcome measures, finalise the design for the phase III definitive trial, and obtain preliminary estimates of the intervention effect. This is a two-arm, multi-centre, cluster-randomised, controlled phase II trial design, which will extend over a 16-month period, across 60 general practices within the North East and North Cumbria and the Eastern Local Clinical Research Network areas. Practices will be randomised to receive either the intervention (the electronic clinical decision-support tool) or to act as a control (usual care). From these practices, we will recruit 3000 adults who meet the trial eligibility criteria and present to their GP with symptoms suggestive of gastro-oesophageal cancer. The main measures are the process data, which include the practitioner outcomes, service outcomes, diagnostic intervals, health economic outcomes, and patient outcomes. One-on-one interviews in a sub-sample of 30 patient-GP dyads will be undertaken to understand the impact of the use or non-use of the electronic clinical decision-support tool in the consultation. A further 10-15 GPs will be interviewed to identify and gain an understanding of the facilitators and constraints influencing implementation of the electronic clinical decision-support tool in practice. We aim to generate new knowledge on the process measures regarding the use of electronic clinical decision-support tools in primary care in general and to inform a subsequent definitive phase III trial. Preliminary data on the impact of the support tool on resource utilisation and health care costs will also be collected. ISRCTN Registry, ISRCTN12595588 .

RITPBC: B-cell depleting therapy (rituximab) as a treatment for fatigue in primary biliary cirrhosis: study protocol for a randomised controlled trial.

PubMed

Jopson, Laura; Newton, Julia L; Palmer, Jeremy; Floudas, Achilleas; Isaacs, John; Qian, Jessica; Wilkinson, Jennifer; Trenell, Mike; Blamire, Andrew; Howel, Denise; Jones, David E

2015-08-20

Primary biliary cirrhosis (PBC) is an autoimmune liver disease with approximately 50% of patients experiencing fatigue. This can be a particularly debilitating symptom, affecting quality of life and resulting in social isolation. Fatigue is highlighted by patients as a priority for research and patient support groups were involved in designing this trial. This is the first randomised controlled trial to investigate a treatment for fatigue in PBC. The trial protocol is innovative as it utilises novel magnetic resonance spectroscopy (MRS) techniques as an outcome measure. The protocol will be valuable to research groups planning clinical trials targeting fatigue in PBC and also transferrable to other conditions associated with fatigue. RITPBC is a Medical Research Council (MRC) and National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation Programme (EME)-funded project. It is a phase II, single-centre, randomised controlled, double-blinded trial comparing rituximab with placebo in fatigued PBC patients. 78 patients with PBC and moderate to severe fatigue will be randomised to receive two infusions of rituximab or placebo. The study aims to assess whether rituximab improves fatigue in patients with PBC, the safety, and tolerability of rituximab in PBC and the sustainability of any beneficial actions. The primary outcome will be an improvement in fatigue domain score of the PBC-40, a disease-specific quality of life measure, evaluated at 12-week assessment. Secondary outcome measures include novel MRS techniques assessing muscle bioenergetic function, physical activity, anaerobic threshold and symptom, and quality of life measures. The trial started recruiting in October 2012 and recruitment is ongoing. The trial has ethical approval from the NRES Committee North East, has Clinical Trial Authorisation from MHRA and local R&D approval. Trial results will be communicated to participants, presented at national and international meetings and published in peer-reviewed journals. ISRCTN03978701. 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.

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

PubMed

Kidger, Judi; Evans, Rhiannon; Tilling, Kate; Hollingworth, William; Campbell, Rona; Ford, Tamsin; Murphy, Simon; Araya, Ricardo; Morris, Richard; Kadir, Bryar; Moure Fernandez, Aida; Bell, Sarah; Harding, Sarah; Brockman, Rowan; Grey, Jill; Gunnell, David

2016-10-18

Teachers are reported to be at increased risk of common mental health disorders compared to other occupations. Failure to support teachers adequately may lead to serious long-term mental disorders, poor performance at work (presenteeism), sickness absence and health-related exit from the profession. It also jeopardises student mental health, as distressed staff struggle to develop supportive relationships with students, and such relationships are protective against student depression. A number of school-based trials have attempted to improve student mental health, but these have mostly focused on classroom based approaches and have failed to establish effectiveness. Only a few studies have introduced training for teachers in supporting students, and none to date have included a focus on improving teacher mental health. This paper sets out the protocol (version 4.4 20/07/16) for a study aiming to address this gap. Cluster randomised controlled trial with secondary schools as the unit of randomisation. Intervention schools will receive: i) Mental Health First Aid (MHFA) training for a group of staff nominated by their colleagues, after which they will set up a confidential peer support service for colleagues ii) training in MHFA for schools and colleges for a further group of teachers, which will equip them to more effectively support student mental health iii) a short mental health awareness raising session and promotion of the peer support service for all teachers. Comparison schools will continue with usual practice. The primary outcome is teacher wellbeing measured using the Warwick Edinburgh Mental Wellbeing Scale (WEMWBS). Secondary outcomes are teacher depression, absence and presenteeism, and student wellbeing, mental health difficulties, attendance and attainment. Measures will be taken at baseline, one year follow up (teachers only) and two year follow up. Economic and process evaluations will be embedded within the study. This study will establish the effectiveness and cost-effectiveness of an intervention that supports secondary school teachers' wellbeing and mental health, and improves their skills in supporting students. It will also provide information regarding intervention implementation and sustainability. International Standard Randomised Controlled Trial Number: ISRCTN95909211 registered 24/03/16.

Communication interventions to improve adherence to infection control precautions: a randomised crossover trial.

PubMed

Ong, Mei-Sing; Magrabi, Farah; Post, Jeffrey; Morris, Sarah; Westbrook, Johanna; Wobcke, Wayne; Calcroft, Ross; Coiera, Enrico

2013-02-06

Ineffective communication of infection control requirements during transitions of care is a potential cause of non-compliance with infection control precautions by healthcare personnel. In this study, interventions to enhance communication during inpatient transfers between wards and radiology were implemented, in the attempt to improve adherence to precautions during transfers. Two interventions were implemented, comprising (i) a pre-transfer checklist used by radiology porters to confirm a patient's infectious status; (ii) a coloured cue to highlight written infectious status information in the transfer form. The effectiveness of the interventions in promoting adherence to standard precautions by radiology porters when transporting infectious patients was evaluated using a randomised crossover trial at a teaching hospital in Australia. 300 transfers were observed over a period of 4 months. Compliance with infection control precautions in the intervention groups was significantly improved relative to the control group (p < 0.01). Adherence rate in the control group was 38%. Applying the coloured cue resulted in a compliance rate of 73%. The pre-transfer checklist intervention achieved a comparable compliance rate of 71%. When both interventions were applied, a compliance rate of 74% was attained. Acceptability of the coloured cue was high, but adherence to the checklist was low (40%). Simple measures to enhance communication through the provision of a checklist and the use a coloured cue brought about significant improvement in compliance with infection control precautions by transport personnel during inpatient transfers. The study underscores the importance of effective communication in ensuring compliance with infection control precautions during transitions of care.

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

No change in developmental outcome with incubator covers and nesting for very preterm infants in a randomised controlled trial.

PubMed

Maguire, C M; Walther, F J; van Zwieten, P H T; Le Cessie, S; Wit, J M; Veen, S

2009-03-01

To investigate in a randomised controlled trial the effect of basic elements of developmental care (incubator covers and positioning aids) on growth and neurodevelopment in infants born at < 32 weeks. Infants were randomised within 48 h of birth to a developmental care (DC) or standard care (C) group. Outcome measures at 1 and 2 years corrected age were growth, standardised neurological examinations, and mental (MDI) and psychomotor (PDI) development (Dutch version of the Bayley Scales of Infant Development II). 192 infants were recruited (DC = 98; C = 94). Thirteen infants (DC = 7, C = 6) were excluded because they were admitted for <5 days or died within the first 5 days. In total, 179 infants met the inclusion criteria. In-hospital mortality was 12/91 (13.2%) in the DC group and 8/88 (9.1%) in the C group. Assessments were carried out on 147 children (DC = 74, C = 73) at 1 year and 142 children (DC = 72, C = 70) at 2 years. No significant difference in growth, neurological outcomes or MDI was found. A positive trend in PDI at 1 year (p = 0.05) did not continue once the children reached 2 years. There was no difference found when neurological and developmental scores were combined. Basic developmental care has no positive effect on neurological and mental development or growth at 1 and 2 years of age in infants born at <32 weeks. A positive effect on psychomotor development at 1 year did not continue at 2 years of age.

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

PubMed

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

2016-03-07

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

Back School programme for nurses has reduced low back pain levels: A randomised controlled trial.

PubMed

Járomi, Melinda; Kukla, Aniko; Szilágyi, Brigitta; Simon-Ugron, Ágnes; Bobály, Viktória Kovácsné; Makai, Alexandra; Linek, Pawel; Ács, Pongrác; Leidecker, Eleonóra

2018-03-01

(i) To examine patient lifting techniques used by nurses, and (ii) to evaluate an effectiveness of the Spine Care for Nurses programme in chronic nonspecific low back pain syndrome reduction and the execution of proper patient lifting techniques. Millions of nurses around the world suffer from occupational-related chronic nonspecific low back pain (chronic nonspecific low back pain syndrome). Generally, low back pain in nurses is a result of increased pressure on the spine and can be associated with improperly conducted patient lifting techniques. A randomised controlled trial was conducted among 137 nurses with chronic nonspecific low back pain syndrome. Participants were randomised into an experimental and control group (experimental group n = 67, control group n = 70). Nurses in the experimental group attended the Spine Care for Nurses programme for 3 months. The programme consisted of didactic education, spine-strengthening exercises and education on safe patient handling techniques. The control group only received a brief written lifestyle guidance. The Zebris WinSpine Triple Lumbar examination was used to analyse nurses' patient lifting techniques (horizontal and vertical lifting). The lumbar pain intensity was measured with a 0-100 visual analogue scale. The pre-intervention average chronic nonspecific low back pain syndrome intensity score on visual analogue scale decreased from 49.3 to the postintervention score of 7.5. The correct execution of vertical lifting techniques in the experimental group increased from 8.91%-97.01% (control group: 8.57% pre-intervention test and postintervention test 11.42%). The horizontal patient lifting technique pre-intervention increased from 10.44%-100% correct execution in the experimental group (control group: pre-intervention test 10.00% and postintervention test 11.42%). The Spine Care for Nurses programme significantly reduced chronic nonspecific low back pain syndrome and increased the number of properly executed horizontal and vertical patient lifting techniques in nurses. We recommend that healthcare organisations should consider the implementation of regular Spine Care for Nurses programmes as successful low back injury prevention programmes. © 2017 John Wiley & Sons Ltd.

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

PubMed

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

2016-10-01

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

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.

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.

Online group-based cognitive-behavioural therapy for adolescents and young adults after cancer treatment: A multicenter randomised controlled trial of Recapture Life-AYA

PubMed Central

2012-01-01

Background A cancer diagnosis is 2.9 times more likely to occur during the adolescent and young adult years than in younger children. This spike in incidence coincides with a life stage characterised by psychological vulnerability as young people strive to attain numerous, critical developmental milestones. The distress young people experience after cancer treatment seriously jeopardises their ability to move into well-functioning adulthood. Methods/Design This article presents the protocol of the Recapture Life study, a phase II three-arm randomised controlled trial designed to evaluate the feasibility and efficacy of a new intervention in reducing distress and improving quality of life for adolescent and young adult cancer survivors. The novel intervention, “ReCaPTure LiFe” will be compared to a both a wait-list, and a peer-support group control. Ninety young people aged 15–25 years who have completed cancer treatment in the past 1–6 months will be recruited from hospitals around Australia. Those randomised to receive Recapture Life will participate in six, weekly, 90-minute online group sessions led by a psychologist, involving peer-discussion around cognitive-behavioural coping skills (including: behavioural activation, thought challenging, communication and assertiveness skills training, problem-solving and goal-setting). Participants randomised to the peer-support group control will receive non-directive peer support delivered in an identical manner. Participants will complete psychosocial measures at baseline, post-intervention, and 12-months post-intervention. The primary outcome will be quality of life. Secondary outcomes will include depression, anxiety, stress, family functioning, coping, and cancer-related identity. Discussion This article reviews the empirical rationale for using group-based, online cognitive-behavioural therapy in young people after cancer treatment. The potential challenges of delivering skills-based programs in an online modality are highlighted, and the role of both peer and caregiver support in enhancing the effectiveness of this skills-based intervention is also discussed. The innovative videoconferencing delivery method Recapture Life uses has the potential to address the geographic and psychological isolation of adolescents and young adults as they move toward cancer survivorship. It is expected that teaching AYAs coping skills as they resume their normal lives after cancer may have long-term implications for their quality of life. Trial Registration ACTRN12610000717055 PMID:22862906

Pregabalin versus placebo in targeting pro-nociceptive mechanisms to prevent chronic pain after whiplash injury in at-risk individuals - a feasibility study for a randomised controlled trial.

PubMed

Nikles, J; Keijzers, G; Mitchell, G; Schug, S; Ware, R; McLean, S A; Connelly, L; Gibson, S; Farrell, S F; Sterling, M

2018-01-17

Whiplash-associated disorders (WAD) are an enormous and costly burden to Australian society. Up to 50% of people who experience a whiplash injury will never fully recover. Whiplash is resistant to treatment and no early management approach has yet been shown to prevent chronic pain. The early presence of central sensitization is associated with poor recovery. Pregabalin's effects on central sensitization indicate the potential to prevent or modulate these processes after whiplash injury and to improve health outcomes, but this has not been investigated. This paper describes the protocol for a feasibility study for a randomised controlled trial of pregabalin plus evidence-based advice compared to placebo plus evidence-based advice for individuals with acute whiplash injury who are at risk of poor recovery. This double blind, placebo-controlled randomised feasibility study will examine the feasibility and potential effectiveness of pregabalin and evidence-based advice (intervention) compared to placebo and evidence-based advice (control) for individuals with acute whiplash injury at risk of poor recovery. Thirty participants (15 per group) aged 18-65 years with Grade II WAD, within 48 hours of injury and currently experiencing at least moderate pain (NRS: ≥ 5/10) will be recruited from Emergency Departments of public hospitals in Queensland, Australia. Pregabalin will be commenced at 75 mg bd and titrated up to 300 mg bd as tolerated for 4 weeks followed by 1 week of weaning. The feasibility of trial procedures will be tested, as well as the potential effect of the intervention on the outcomes. The primary outcome of neck pain intensity at 3 months from randomisation will be compared between the treatment groups using standard analysis of variance techniques. Feasibility and potential effectiveness data will inform an appropriately powered full trial, which if successful, will provide an effective and cost-effective intervention for a costly and treatment resistant condition. It will also have implications for the early management of other traumatic conditions beyond whiplash. Clinical Trials Primary Registry: Australian and New Zealand Clinical Trials Registry. ACTRN12617000059369 . Date of Registration: 11/01/2017. Primary Trial Sponsor: The University of Queensland, Brisbane QLD 4072 Australia.

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

PubMed

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

2017-08-14

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

Online group-based cognitive-behavioural therapy for adolescents and young adults after cancer treatment: a multicenter randomised controlled trial of Recapture Life-AYA.

PubMed

Sansom-Daly, Ursula M; Wakefield, Claire E; Bryant, Richard A; Butow, Phyllis; Sawyer, Susan; Patterson, Pandora; Anazodo, Antoinette; Thompson, Kate; Cohn, Richard J

2012-08-03

A cancer diagnosis is 2.9 times more likely to occur during the adolescent and young adult years than in younger children. This spike in incidence coincides with a life stage characterised by psychological vulnerability as young people strive to attain numerous, critical developmental milestones. The distress young people experience after cancer treatment seriously jeopardises their ability to move into well-functioning adulthood. This article presents the protocol of the Recapture Life study, a phase II three-arm randomised controlled trial designed to evaluate the feasibility and efficacy of a new intervention in reducing distress and improving quality of life for adolescent and young adult cancer survivors. The novel intervention, "ReCaPTure LiFe" will be compared to a both a wait-list, and a peer-support group control. Ninety young people aged 15-25 years who have completed cancer treatment in the past 1-6 months will be recruited from hospitals around Australia. Those randomised to receive Recapture Life will participate in six, weekly, 90-minute online group sessions led by a psychologist, involving peer-discussion around cognitive-behavioural coping skills (including: behavioural activation, thought challenging, communication and assertiveness skills training, problem-solving and goal-setting). Participants randomised to the peer-support group control will receive non-directive peer support delivered in an identical manner. Participants will complete psychosocial measures at baseline, post-intervention, and 12-months post-intervention. The primary outcome will be quality of life. Secondary outcomes will include depression, anxiety, stress, family functioning, coping, and cancer-related identity. This article reviews the empirical rationale for using group-based, online cognitive-behavioural therapy in young people after cancer treatment. The potential challenges of delivering skills-based programs in an online modality are highlighted, and the role of both peer and caregiver support in enhancing the effectiveness of this skills-based intervention is also discussed. The innovative videoconferencing delivery method Recapture Life uses has the potential to address the geographic and psychological isolation of adolescents and young adults as they move toward cancer survivorship. It is expected that teaching AYAs coping skills as they resume their normal lives after cancer may have long-term implications for their quality of life. ACTRN12610000717055.

A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trial

PubMed Central

Deeks, Jonathan J; Griffith, Michael; Lip, Gregory YH; Mehta, Samir; Slinn, Gemma; Stanbury, Mary; Steeds, Richard P; Townend, Jonathan N

2017-01-01

Background and objective Atrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article, we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity. Such a trial should concentrate on the long-term effects of treatment in the largest proportion of patients with AF, those with symptomatic permanent AF, with the aim of improving patient well-being. Design and intervention The RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial will enrol 160 participants with a prospective, randomised, open-label, blinded end point design comparing initial rate control with digoxin or bisoprolol. This will be the first head-to-head randomised trial of digoxin and beta-blockers in AF. Participants Recruited patients will be aged ≥60 years with permanent AF and symptoms of breathlessness (equivalent to New York Heart Association class II or above), with few exclusion criteria to maximise generalisability to routine clinical practice. Outcome measures The primary outcome is patient-reported quality of life, with secondary outcomes including echocardiographic ventricular function, exercise capacity and biomarkers of cellular and clinical response. Follow-up will occur at 6 and 12 months, with feasibility components to inform the design of a future trial powered to detect a difference in hospital admission. The RATE-AF trial will underpin an integrated approach to management including biomarkers, functions and symptoms that will guide future research into optimal, personalised rate control in patients with AF. Ethics and dissemination East Midlands-Derby Research Ethics Committee (16/EM/0178); peer-reviewed publications. Trial registration Clinicaltrials.gov: NCT02391337; ISRCTN: 95259705. Pre-results. PMID:28729311

A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trial.

PubMed

Kotecha, Dipak; Calvert, Melanie; Deeks, Jonathan J; Griffith, Michael; Kirchhof, Paulus; Lip, Gregory Yh; Mehta, Samir; Slinn, Gemma; Stanbury, Mary; Steeds, Richard P; Townend, Jonathan N

2017-07-20

Atrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article , we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity. Such a trial should concentrate on the long-term effects of treatment in the largest proportion of patients with AF, those with symptomatic permanent AF, with the aim of improving patient well-being. The RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial will enrol 160 participants with a prospective, randomised, open-label, blinded end point design comparing initial rate control with digoxin or bisoprolol. This will be the first head-to-head randomised trial of digoxin and beta-blockers in AF. Recruited patients will be aged ≥60 years with permanent AF and symptoms of breathlessness (equivalent to New York Heart Association class II or above), with few exclusion criteria to maximise generalisability to routine clinical practice. The primary outcome is patient-reported quality of life, with secondary outcomes including echocardiographic ventricular function, exercise capacity and biomarkers of cellular and clinical response. Follow-up will occur at 6 and 12 months, with feasibility components to inform the design of a future trial powered to detect a difference in hospital admission. The RATE-AF trial will underpin an integrated approach to management including biomarkers, functions and symptoms that will guide future research into optimal, personalised rate control in patients with AF. East Midlands-Derby Research Ethics Committee (16/EM/0178); peer-reviewed publications. Clinicaltrials.gov: NCT02391337; ISRCTN: 95259705. 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.

Effects of patient safety culture interventions on incident reporting in general practice: a cluster randomised trial

PubMed Central

Verbakel, Natasha J; Langelaan, Maaike; Verheij, Theo JM; Wagner, Cordula; Zwart, Dorien LM

2015-01-01

Background A constructive safety culture is essential for the successful implementation of patient safety improvements. Aim To assess the effect of two patient safety culture interventions on incident reporting as a proxy of safety culture. Design and setting A three-arm cluster randomised trial was conducted in a mixed method study, studying the effect of administering a patient safety culture questionnaire (intervention I), the questionnaire complemented with a practice-based workshop (intervention II) and no intervention (control) in 30 general practices in the Netherlands. Method The primary outcome, the number of reported incidents, was measured with a questionnaire at baseline and a year after. Analysis was performed using a negative binomial model. Secondary outcomes were quality and safety indicators and safety culture. Mixed effects linear regression was used to analyse the culture questionnaires. Results The number of incidents increased in both intervention groups, to 82 and 224 in intervention I and II respectively. Adjusted for baseline number of incidents, practice size and accreditation status, the study showed that practices that additionally participated in the workshop reported 42 (95% confidence interval [CI] = 9.81 to 177.50) times more incidents compared to the control group. Practices that only completed the questionnaire reported 5 (95% CI = 1.17 to 25.49) times more incidents. There were no statistically significant differences in staff perception of patient safety culture at follow-up between the three study groups. Conclusion Educating staff and facilitating discussion about patient safety culture in their own practice leads to increased reporting of incidents. It is beneficial to invest in a team-wise effort to improve patient safety. PMID:25918337

Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson's disease: a double blind, placebo controlled, randomised, multicentre study.

PubMed

Pinter, M M; Pogarell, O; Oertel, W H

1999-04-01

Pramipexole, a non-ergot dopamine D2/D3 receptor agonist, was investigated as an add on drug in advanced parkinsonian patients with motor fluctuations to assess efficacy, safety, and tolerance. Seventy eight patients of either sex with advanced Parkinson's disease and treatment complications such as motor fluctuations were enrolled into a double blind, placebo controlled, randomised, multicentre study (phase II) and assigned to add on treatment with pramipexole (n=34) versus placebo (n=44) to a previously stabilised antiparkinsonian medication (7 week dose titration interval, 4 week maintenance period). The primary end point of efficacy was the change from baseline in the total score of the unified Parkinson's disease rating scale (UPDRS) in the on "period" (2 hours after intake of study medication). Safety and tolerability were assessed on the basis of adverse events, vital signs, laboratory measurements, and ECG recordings. There was a significant improvement of the pramipexole group in UPDRS total scores, subscores part II, III (activities of daily living and motor examination), and IV (complications of therapy). Mean UPDRS total score decreased by 37.3% under pramipexole compared with 12.2% under placebo (p<0.001). Patients under pramipexole reported an overall reduction in "off" periods of 12%--resulting in 1.7 more hours "on" time a day--compared with an increase in "off" periods of 2% under placebo. There were no unexpected safety results. The adverse event profile disclosed a high tolerability. The most important adverse events under pramipexole were fatigue, dyskinesia, and vivid dreams. Pramipexole administration is an efficacious and well tolerated add on therapy in patients with advanced Parkinson's disease with an improvement in activities of daily living, motor function, and treatment associated complications.

Effects of patient safety culture interventions on incident reporting in general practice: a cluster randomised trial.

PubMed

Verbakel, Natasha J; Langelaan, Maaike; Verheij, Theo J M; Wagner, Cordula; Zwart, Dorien L M

2015-05-01

A constructive safety culture is essential for the successful implementation of patient safety improvements. To assess the effect of two patient safety culture interventions on incident reporting as a proxy of safety culture. A three-arm cluster randomised trial was conducted in a mixed method study, studying the effect of administering a patient safety culture questionnaire (intervention I), the questionnaire complemented with a practice-based workshop (intervention II) and no intervention (control) in 30 general practices in the Netherlands. The primary outcome, the number of reported incidents, was measured with a questionnaire at baseline and a year after. Analysis was performed using a negative binomial model. Secondary outcomes were quality and safety indicators and safety culture. Mixed effects linear regression was used to analyse the culture questionnaires. The number of incidents increased in both intervention groups, to 82 and 224 in intervention I and II respectively. Adjusted for baseline number of incidents, practice size and accreditation status, the study showed that practices that additionally participated in the workshop reported 42 (95% confidence interval [CI] = 9.81 to 177.50) times more incidents compared to the control group. Practices that only completed the questionnaire reported 5 (95% CI = 1.17 to 25.49) times more incidents. There were no statistically significant differences in staff perception of patient safety culture at follow-up between the three study groups. Educating staff and facilitating discussion about patient safety culture in their own practice leads to increased reporting of incidents. It is beneficial to invest in a team-wise effort to improve patient safety. © British Journal of General Practice 2015.

A literature review of applied adaptive design methodology within the field of oncology in randomised controlled trials and a proposed extension to the CONSORT guidelines.

PubMed

Mistry, Pankaj; Dunn, Janet A; Marshall, Andrea

2017-07-18

The application of adaptive design methodology within a clinical trial setting is becoming increasingly popular. However the application of these methods within trials is not being reported as adaptive designs hence making it more difficult to capture the emerging use of these designs. Within this review, we aim to understand how adaptive design methodology is being reported, whether these methods are explicitly stated as an 'adaptive design' or if it has to be inferred and to identify whether these methods are applied prospectively or concurrently. Three databases; Embase, Ovid and PubMed were chosen to conduct the literature search. The inclusion criteria for the review were phase II, phase III and phase II/III randomised controlled trials within the field of Oncology that published trial results in 2015. A variety of search terms related to adaptive designs were used. A total of 734 results were identified, after screening 54 were eligible. Adaptive designs were more commonly applied in phase III confirmatory trials. The majority of the papers performed an interim analysis, which included some sort of stopping criteria. Additionally only two papers explicitly stated the term 'adaptive design' and therefore for most of the papers, it had to be inferred that adaptive methods was applied. Sixty-five applications of adaptive design methods were applied, from which the most common method was an adaptation using group sequential methods. This review indicated that the reporting of adaptive design methodology within clinical trials needs improving. The proposed extension to the current CONSORT 2010 guidelines could help capture adaptive design methods. Furthermore provide an essential aid to those involved with clinical trials.

Inhaled, dual release liposomal ciprofloxacin in non-cystic fibrosis bronchiectasis (ORBIT-2): a randomised, double-blind, placebo-controlled trial

PubMed Central

Serisier, David J; Bilton, Diana; De Soyza, Anthony; Thompson, Philip J; Kolbe, John; Greville, Hugh W; Cipolla, David; Bruinenberg, Paul; Gonda, Igor

2013-01-01

Background The delivery of antipseudomonal antibiotics by inhalation to Pseudomonas aeruginosa-infected subjects with non-cystic fibrosis (CF) bronchiectasis is a logical extension of treatment strategies successfully developed in CF bronchiectasis. Dual release ciprofloxacin for inhalation (DRCFI) contains liposomal ciprofloxacin, formulated to optimise airway antibiotic delivery. Methods Phase II, 24-week Australian/New Zealand multicentre, randomised, double-blind, placebo-controlled trial in 42 adult bronchiectasis subjects with ≥2 pulmonary exacerbations in the prior 12 months and ciprofloxacin-sensitive P aeruginosa at screening. Subjects received DRCFI or placebo in three treatment cycles of 28 days on/28 days off. The primary outcome was change in sputum P aeruginosa bacterial density to the end of treatment cycle 1 (day 28), analysed by modified intention to treat (mITT). Key secondary outcomes included safety and time to first pulmonary exacerbation—after reaching the pulmonary exacerbation endpoint subjects discontinued study drug although remained in the study. Results DRCFI resulted in a mean (SD) 4.2 (3.7) log10 CFU/g reduction in P aeruginosa bacterial density at day 28 (vs −0.08 (3.8) with placebo, p=0.002). DRCFI treatment delayed time to first pulmonary exacerbation (median 134 vs 58 days, p=0.057 mITT, p=0.046 per protocol). DRCFI was well tolerated with a similar incidence of systemic adverse events to the placebo group, but fewer pulmonary adverse events. Conclusions Once-daily inhaled DRCFI demonstrated potent antipseudomonal microbiological efficacy in adults with non-CF bronchiectasis and ciprofloxacin-sensitive P aeruginosa. In this modest-sized phase II study, DRCFI was also well tolerated and delayed time to first pulmonary exacerbation in the per protocol population. PMID:23681906

Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia

PubMed Central

2013-01-01

Background As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in Phase II efficiently select regimens for subsequent evaluation in larger-scale Phase III trials. Methods We propose the screened selection design (SSD), which is a practical multi-stage, randomised Phase II design for two experimental arms. Activity is first evaluated by applying Simon’s two-stage design (1989) on each arm. If both are active, the play-the-winner selection strategy proposed by Simon, Wittes and Ellenberg (SWE) (1985) is applied to select the superior arm. A variant of the design, Modified SSD, also allows the arm with the higher response rates to be recommended only if its activity rate is greater by a clinically-relevant value. The operating characteristics are explored via a simulation study and compared to a Bayesian Selection approach. Results Simulations showed that with the proposed SSD, it is possible to retain the sample size as required in SWE and obtain similar probabilities of selecting the correct superior arm of at least 90%; with the additional attractive benefit of reducing the probability of selecting ineffective arms. This approach is comparable to a Bayesian Selection Strategy. The Modified SSD performs substantially better than the other designs in selecting neither arm if the underlying rates for both arms are desirable but equivalent, allowing for other factors to be considered in the decision making process. Though its probability of correctly selecting a superior arm might be reduced, it still performs reasonably well. It also reduces the probability of selecting an inferior arm. Conclusions SSD provides an easy to implement randomised Phase II design that selects the most promising treatment that has shown sufficient evidence of activity, with available R codes to evaluate its operating characteristics. PMID:23819695

Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia.

PubMed

Yap, Christina; Pettitt, Andrew; Billingham, Lucinda

2013-07-03

As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in Phase II efficiently select regimens for subsequent evaluation in larger-scale Phase III trials. We propose the screened selection design (SSD), which is a practical multi-stage, randomised Phase II design for two experimental arms. Activity is first evaluated by applying Simon's two-stage design (1989) on each arm. If both are active, the play-the-winner selection strategy proposed by Simon, Wittes and Ellenberg (SWE) (1985) is applied to select the superior arm. A variant of the design, Modified SSD, also allows the arm with the higher response rates to be recommended only if its activity rate is greater by a clinically-relevant value. The operating characteristics are explored via a simulation study and compared to a Bayesian Selection approach. Simulations showed that with the proposed SSD, it is possible to retain the sample size as required in SWE and obtain similar probabilities of selecting the correct superior arm of at least 90%; with the additional attractive benefit of reducing the probability of selecting ineffective arms. This approach is comparable to a Bayesian Selection Strategy. The Modified SSD performs substantially better than the other designs in selecting neither arm if the underlying rates for both arms are desirable but equivalent, allowing for other factors to be considered in the decision making process. Though its probability of correctly selecting a superior arm might be reduced, it still performs reasonably well. It also reduces the probability of selecting an inferior arm. SSD provides an easy to implement randomised Phase II design that selects the most promising treatment that has shown sufficient evidence of activity, with available R codes to evaluate its operating characteristics.

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.

Improving educational achievement and anaemia of school children: design of a cluster randomised trial of school-based malaria prevention and enhanced literacy instruction in Kenya

PubMed Central

2010-01-01

Background Improving the health of school-aged children can yield substantial benefits for cognitive development and educational achievement. However, there is limited experimental evidence on the benefits of school-based malaria prevention or how health interventions interact with other efforts to improve education quality. This study aims to evaluate the impact of school-based malaria prevention and enhanced literacy instruction on the health and educational achievement of school children in Kenya. Design A factorial, cluster randomised trial is being implemented in 101 government primary schools on the coast of Kenya. The interventions are (i) intermittent screening and treatment of malaria in schools by public health workers and (ii) training workshops and support for teachers to promote explicit and systematic literacy instruction. Schools are randomised to one of four groups: receiving either (i) the malaria intervention alone; (ii) the literacy intervention alone; (iii) both interventions combined; or (iv) control group where neither intervention is implemented. Children from classes 1 and 5 are randomly selected and followed up for 24 months. The primary outcomes are educational achievement and anaemia, the hypothesised mediating variables through which education is affected. Secondary outcomes include malaria parasitaemia, school attendance and school performance. A nested process evaluation, using semi-structured interviews, focus group discussion and a stakeholder analysis will investigate the community acceptability, feasibility and cost-effectiveness of the interventions. Discussion Across Africa, governments are committed to improve health and education of school-aged children, but seek clear policy and technical guidance as to the optimal approach to address malaria and improved literacy. This evaluation will be one of the first to simultaneously evaluate the impact of health and education interventions in the improvement of educational achievement. Reflection is made on the practical issues encountered in conducting research in schools in Africa. Trial Registration National Institutes of Health NCT00878007 PMID:20929566

Improving educational achievement and anaemia of school children: design of a cluster randomised trial of school-based malaria prevention and enhanced literacy instruction in Kenya.

PubMed

Brooker, Simon; Okello, George; Njagi, Kiambo; Dubeck, Margaret M; Halliday, Katherine E; Inyega, Hellen; Jukes, Matthew C H

2010-10-07

Improving the health of school-aged children can yield substantial benefits for cognitive development and educational achievement. However, there is limited experimental evidence on the benefits of school-based malaria prevention or how health interventions interact with other efforts to improve education quality. This study aims to evaluate the impact of school-based malaria prevention and enhanced literacy instruction on the health and educational achievement of school children in Kenya. A factorial, cluster randomised trial is being implemented in 101 government primary schools on the coast of Kenya. The interventions are (i) intermittent screening and treatment of malaria in schools by public health workers and (ii) training workshops and support for teachers to promote explicit and systematic literacy instruction. Schools are randomised to one of four groups: receiving either (i) the malaria intervention alone; (ii) the literacy intervention alone; (iii) both interventions combined; or (iv) control group where neither intervention is implemented. Children from classes 1 and 5 are randomly selected and followed up for 24 months. The primary outcomes are educational achievement and anaemia, the hypothesised mediating variables through which education is affected. Secondary outcomes include malaria parasitaemia, school attendance and school performance. A nested process evaluation, using semi-structured interviews, focus group discussion and a stakeholder analysis will investigate the community acceptability, feasibility and cost-effectiveness of the interventions. Across Africa, governments are committed to improve health and education of school-aged children, but seek clear policy and technical guidance as to the optimal approach to address malaria and improved literacy. This evaluation will be one of the first to simultaneously evaluate the impact of health and education interventions in the improvement of educational achievement. Reflection is made on the practical issues encountered in conducting research in schools in Africa. National Institutes of Health NCT00878007.

Evidence-based care of older people with suspected cognitive impairment in general practice: protocol for the IRIS cluster randomised trial.

PubMed

McKenzie, Joanne E; French, Simon D; O'Connor, Denise A; Mortimer, Duncan S; Browning, Colette J; Russell, Grant M; Grimshaw, Jeremy M; Eccles, Martin P; Francis, Jill J; Michie, Susan; Murphy, Kerry; Kossenas, Fiona; Green, Sally E

2013-08-19

Dementia is a common and complex condition. Evidence-based guidelines for the management of people with dementia in general practice exist; however, detection, diagnosis and disclosure of dementia have been identified as potential evidence-practice gaps. Interventions to implement guidelines into practice have had varying success. The use of theory in designing implementation interventions has been limited, but is advocated because of its potential to yield more effective interventions and aid understanding of factors modifying the magnitude of intervention effects across trials. This protocol describes methods of a randomised trial that tests a theory-informed implementation intervention that, if effective, may provide benefits for patients with dementia and their carers. This trial aims to estimate the effectiveness of a theory-informed intervention to increase GPs' (in Victoria, Australia) adherence to a clinical guideline for the detection, diagnosis, and management of dementia in general practice, compared with providing GPs with a printed copy of the guideline. Primary objectives include testing if the intervention is effective in increasing the percentage of patients with suspected cognitive impairment who receive care consistent with two key guideline recommendations: receipt of a i) formal cognitive assessment, and ii) depression assessment using a validated scale (primary outcomes for the trial). The design is a parallel cluster randomised trial, with clusters being general practices. We aim to recruit 60 practices per group. Practices will be randomised to the intervention and control groups using restricted randomisation. Patients meeting the inclusion criteria, and GPs' detection and diagnosis behaviours directed toward these patients, will be identified and measured via an electronic search of the medical records nine months after the start of the intervention. Practitioners in the control group will receive a printed copy of the guideline. In addition to receipt of the printed guideline, practitioners in the intervention group will be invited to participate in an interactive, opinion leader-led, educational face-to-face workshop. The theory-informed intervention aims to address identified barriers to and enablers of implementation of recommendations. Researchers responsible for identifying the cohort of patients with suspected cognitive impairment, and their detection and diagnosis outcomes, will be blind to group allocation. Australian New Zealand Clinical Trials Registry: ACTRN12611001032943 (date registered 28 September, 2011).

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

PubMed

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

2018-01-01

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

L-arginine plus drospirenone-ethinyl estradiol in the treatment of patients with PCOS: a prospective, placebo controlled, randomised, pilot study.

PubMed

Battaglia, Cesare; Mancini, Fulvia; Battaglia, Bruno; Facchinetti, Fabio; Artini, Paolo G; Venturoli, Stefano

2010-12-01

To verify the effects of a pill containing drospirenone on the surrogate markers of arterial function and to evaluate the possible improvements induced by the addition of L-arginine. A prospective, placebo controlled, randomised, pilot study. University of Bologna. Twenty-eight young women with PCOS. Random submission to: drospirenone + ethinylestradiol+ a placebo (Group I; n = 15) or drospirenone + ethinylestradiol + oral L-arginine (4 g × 2/daily) (Group II, n = 13). Medical examination; blood measurement of nitrites/nitrates, biochemical and hormonal parameters; ultrasonographic analysis and colour Doppler evaluation of uterine, stromal ovarian and ophthalmic arteries; analysis of brachial artery flow-mediated vasodilatation; and 24-h ambulatory blood pressure monitoring. The above parameters were evaluated before and after 6 months. The low dose oral contraceptive containing drospirenone favoured a pre-hypertensive state. The L-arginine supplementation increased the circulating levels of nitrites/nitrates and improved the endothelium-dependent vasodilatation counteracting the negative effect of the contraceptive pill. Although, the present pilot study was conducted in a limited number of patients, it seems that the L-arginine co-treatment may improve the long-term side effects of the pill reducing the risk of cardiovascular diseases.

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

PubMed

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

2016-03-01

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

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

PubMed

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

2016-04-01

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

Probiotic prophylaxis in patients with predicted severe acute pancreatitis (PROPATRIA): design and rationale of a double-blind, placebo-controlled randomised multicenter trial [ISRCTN38327949

PubMed Central

Besselink, Marc GH; Timmerman, Harro M; Buskens, Erik; Nieuwenhuijs, Vincent B; Akkermans, Louis MA; Gooszen, Hein G

2004-01-01

Background Infectious complications are the major cause of death in acute pancreatitis. Small bowel bacterial overgrowth and subsequent bacterial translocation are held responsible for the vast majority of these infections. Goal of this study is to determine whether selected probiotics are capable of preventing infectious complications without the disadvantages of antibiotic prophylaxis; antibiotic resistance and fungal overgrowth. Methods/design PROPATRIA is a double-blind, placebo-controlled randomised multicenter trial in which 200 patients will be randomly allocated to a multispecies probiotic preparation (Ecologic 641) or placebo. The study is performed in all 8 Dutch University Hospitals and 7 non-University hospitals. The study-product is administered twice daily through a nasojejunal tube for 28 days or until discharge. Patients eligible for randomisation are adult patients with a first onset of predicted severe acute pancreatitis: Imrie criteria 3 or more, CRP 150 mg/L or more, APACHE II score 8 or more. Exclusion criteria are post-ERCP pancreatitis, malignancy, infection/sepsis caused by a second disease, intra-operative diagnosis of pancreatitis and use of probiotics during the study. Administration of the study product is started within 72 hours after onset of abdominal pain. The primary endpoint is the total number of infectious complications. Secondary endpoints are mortality, necrosectomy, antibiotic resistance, hospital stay and adverse events. To demonstrate that probiotic prophylaxis reduces the proportion of patients with infectious complications from 50% to 30%, with alpha 0,05 and power 80%, a total sample size of 200 patients was calculated. Conclusion The PROPATRIA study is aimed to show a reduction in infectious complications due to early enteral use of multispecies probiotics in severe acute pancreatitis. PMID:15456517

Safety and feasibility of xenon as an adjuvant to sevoflurane anaesthesia in children undergoing interventional or diagnostic cardiac catheterization: study protocol for a randomised controlled trial.

PubMed

Devroe, Sarah; Lemiere, Jurgen; Van de Velde, Marc; Gewillig, Marc; Boshoff, Derize; Rex, Steffen

2015-03-04

Xenon has minimal haemodynamic side effects when compared to volatile or intravenous anaesthetics. Moreover, in in vitro and in animal experiments, xenon has been demonstrated to convey cardio- and neuroprotective effects. Neuroprotection could be advantageous in paediatric anaesthesia as there is growing concern, based on both laboratory studies and retrospective human clinical studies, that anaesthetics may trigger an injury in the developing brain, resulting in long-lasting neurodevelopmental consequences. Furthermore, xenon-mediated neuroprotection could help to prevent emergence delirium/agitation. Altogether, the beneficial haemodynamic profile combined with its putative organ-protective properties could render xenon an attractive option for anaesthesia of children undergoing cardiac catheterization. In a phase-II, mono-centre, prospective, single-blind, randomised, controlled study, we will test the hypothesis that the administration of 50% xenon as an adjuvant to general anaesthesia with sevoflurane in children undergoing elective cardiac catheterization is safe and feasible. Secondary aims include the evaluation of haemodynamic parameters during and after the procedure, emergence characteristics, and the analysis of peri-operative neuro-cognitive function. A total of 40 children ages 4 to 12 years will be recruited and randomised into two study groups, receiving either a combination of sevoflurane and xenon or sevoflurane alone. Children undergoing diagnostic or interventional cardiac catheterization are a vulnerable patient population, one particularly at risk for intra-procedural haemodynamic instability. Xenon provides remarkable haemodynamic stability and potentially has cardio- and neuroprotective properties. Unfortunately, evidence is scarce on the use of xenon in the paediatric population. Our pilot study will therefore deliver important data required for prospective future clinical trials. EudraCT: 2014-002510-23 (5 September 2014).

Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial.

PubMed

Noordman, Bo Jan; Wijnhoven, Bas P L; Lagarde, Sjoerd M; Boonstra, Jurjen J; Coene, Peter Paul L O; Dekker, Jan Willem T; Doukas, Michael; van der Gaast, Ate; Heisterkamp, Joos; Kouwenhoven, Ewout A; Nieuwenhuijzen, Grard A P; Pierie, Jean-Pierre E N; Rosman, Camiel; van Sandick, Johanna W; van der Sangen, Maurice J C; Sosef, Meindert N; Spaander, Manon C W; Valkema, Roelf; van der Zaag, Edwin S; Steyerberg, Ewout W; van Lanschot, J Jan B

2018-02-06

Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care.

A Phase II randomised controlled trial assessing the feasibility, acceptability and potential effectiveness of dignity therapy for older people in care homes: study protocol.

PubMed

Hall, Sue; Chochinov, Harvey; Harding, Richard; Murray, Scott; Richardson, Alison; Higginson, Irene J

2009-03-24

Although most older people living in nursing homes die there, there is a dearth of robust evaluations of interventions to improve their end-of-life care. Residents usually have multiple health problems making them heavily reliant on staff for their care, which can erode their sense of dignity. Dignity Therapy has been developed to help promote dignity and reduce distress. It comprises a recorded interview, which is transcribed, edited then returned to the patient, who can bequeath it to people of their choosing. Piloting has suggested that Dignity Therapy is beneficial to people dying of cancer and their families. The aims of this study are to assess the feasibility, acceptability and potential effectiveness of Dignity Therapy to reduce psychological and spiritual distress in older people reaching the end of life in care homes, and to pilot the methods for a Phase III RCT. A randomised controlled open-label trial. Sixty-four residents of care homes for older people are randomly allocated to one of two groups: (i) Intervention (Dignity Therapy offered in addition to any standard care), and (ii) Control group (standard care). Recipients of the "generativity" documents are asked their views on taking part in the study and the therapy. Both quantitative and qualitative outcomes are assessed in face-to-face interviews at baseline and at approximately one and eight weeks after the intervention (equivalent in the control group). The primary outcome is residents' sense of dignity (potential effectiveness) assessed by the Patient Dignity Inventory. Secondary outcomes for residents include depression, hopefulness and quality of life. In view of the relatively small sample size, quantitative analysis is mainly descriptive. The qualitative analysis uses the Framework method. Dignity Therapy is brief, can be done at the bedside and could help both patients and their families. This detailed exploratory research shows if it is feasible to offer Dignity Therapy to residents of care homes, whether it is acceptable to them, their families and care home staff, if it is likely to be effective, and determine whether a Phase III RCT is desirable. Current Controlled Clinical Trials: ISRCTN37589515.

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

PubMed

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

2015-01-01

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

Affective instability and the course of bipolar depression: results from the STEP-BD randomised controlled trial of psychosocial treatment

PubMed Central

Stange, Jonathan P.; Sylvia, Louisa G.; da Silva Magalhães, Pedro Vieira; Miklowitz, David J.; Otto, Michael W.; Frank, Ellen; Yim, Christine; Berk, Michael; Dougherty, Darin D.; Nierenberg, Andrew A.; Deckersbach, Thilo

2016-01-01

Background Little is known about predictors of recovery from bipolar depression. Aims We investigated affective instability (a pattern of frequent and large mood shifts over time) as a predictor of recovery from episodes of bipolar depression and as a moderator of response to psychosocial treatment for acute depression. Method A total of 252 out-patients with DSM-IV bipolar I or II disorder and who were depressed enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and were randomised to one of three types of intensive psychotherapy for depression (n = 141) or a brief psychoeducational intervention (n = 111). All analyses were by intention-to-treat. Results Degree of instability of symptoms of depression and mania predicted a lower likelihood of recovery and longer time until recovery, independent of the concurrent effects of symptom severity. Affective instability did not moderate the effects of psychosocial treatment on recovery from depression. Conclusions Affective instability may be a clinically relevant characteristic that influences the course of bipolar depression. PMID:26795426

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.

The STAR trial protocol: a randomised multi-stage phase II/III study of Sunitinib comparing temporary cessation with allowing continuation, at the time of maximal radiological response, in the first-line treatment of locally advanced/metastatic Renal Cancer

PubMed Central

2012-01-01

Background Over recent years a number of novel therapies have shown promise in advanced renal cell carcinoma (RCC). Internationally the standard of care of first-line therapy is sunitinib™, after a clear survival benefit was demonstrated over interferon-α. Convention dictates that sunitinib is continued until evidence of disease progression, assuming tolerability, although there is no evidence that this approach is superior to intermittent periods of treatment. The purpose of the STAR trial is to compare the standard treatment strategy (conventional continuation strategy, CCS) with a novel drug free interval strategy (DFIS) which includes planned treatment breaks. Methods/Design The STAR trial is an NIHR HTA-funded UK pragmatic randomised phase II/III clinical trial in the first-line treatment of advanced RCC. Participants will be randomised (1:1) to either a sunitinib CCS or a DFIS. The overall aim of the trial is to determine whether a DFIS is non-inferior, in terms of 2-year overall survival (OS) and quality adjusted life years (QALY) (averaged over treatment and follow up), compared to a CCS. The QALY primary endpoint was selected to assess whether any detriment in terms of OS could be balanced with improvements in quality of life (QoL). This is a complex trial with a number of design challenges, and to address these issues a feasibility stage is incorporated into the trial design. Predetermined recruitment (stage A) and efficacy (stage B) intermediary endpoints must be met to allow continuation to the overall phase III trial (stage C). An integral qualitative patient preference and understanding study will occur alongside the feasibility stage to investigate patients’ feelings regarding participation or non-participation in the trial. Discussion The optimal duration of continuing sunitinib in advanced RCC is unknown. Novel targeted therapies do not always have the same constraints to treatment duration as standard chemotherapeutic agents and currently there are no randomised data comparing different treatment durations. Incorporating planned treatment breaks has the potential to improve QoL and cost effectiveness, hopefully without significant detriment on OS, as has been demonstrated in other cancer types with other treatments. Trial Registration Controlled-trials.com ISRCTN 06473203 PMID:23241439

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

PubMed

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

2015-09-07

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

Prophylactic antibiotics for penetrating abdominal trauma.

PubMed

Brand, Martin; Grieve, Andrew

2013-11-18

Penetrating abdominal trauma occurs when the peritoneal cavity is breached. Routine laparotomy for penetrating abdominal injuries began in the 1800s, with antibiotics first being used in World War II to combat septic complications associated with these injuries. This practice was marked with a reduction in sepsis-related mortality and morbidity. Whether prophylactic antibiotics are required in the prevention of infective complications following penetrating abdominal trauma is controversial, however, as no randomised placebo controlled trials have been published to date. There has also been debate about the timing of antibiotic prophylaxis. In 1972 Fullen noted a 7% to 11% post-surgical infection rate with pre-operative antibiotics, a 33% to 57% infection rate with intra-operative antibiotic administration and 30% to 70% infection rate with only post-operative antibiotic administration. Current guidelines state there is sufficient class I evidence to support the use of a single pre-operative broad spectrum antibiotic dose, with aerobic and anaerobic cover, and continuation (up to 24 hours) only in the event of a hollow viscus perforation found at exploratory laparotomy. To assess the benefits and harms of prophylactic antibiotics administered for penetrating abdominal injuries for the reduction of the incidence of septic complications, such as septicaemia, intra-abdominal abscesses and wound infections. Searches were not restricted by date, language or publication status. We searched the following electronic databases: the Cochrane Injuries Group Specialised Register, CENTRAL (The Cochrane Library 2013, issue 12 of 12), MEDLINE (OvidSP), Embase (OvidSP), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of Science: Conference Proceedings Citation Index- Science (CPCI-S) and PubMed. Searches were last conducted in January 2013. All randomised controlled trials of antibiotic prophylaxis in patients with penetrating abdominal trauma versus no antibiotics or placebo. Two authors screened the literature search results independently. We identified no trials meeting the inclusion criteria. There is currently no information from randomised controlled trials to support or refute the use of antibiotics for patients with penetrating abdominal trauma.

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

PubMed Central

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

2014-01-01

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

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.

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.

Celecoxib versus ibuprofen in the prevention of heterotopic ossification following total hip replacement: a prospective randomised trial.

PubMed

Saudan, M; Saudan, P; Perneger, T; Riand, N; Keller, A; Hoffmeyer, P

2007-02-01

We examined whether a selective cyclooxygenase-2 (COX-2) inhibitor (celecoxib) was as effective as a non-selective inhibitor (ibuprofen) for the prevention of heterotopic ossification following total hip replacement. A total of 250 patients were randomised to receive celecoxib (200 mg b/d) or ibuprofen (400 mg t.d.s) for ten days after surgery. Anteroposterior radiographs of the pelvis were examined for heterotopic ossification three months after surgery. Of the 250 patients, 240 were available for assessment. Heterotopic ossification was more common in the ibuprofen group (none 40.7% (50), Brooker class I 46.3% (57), classes II and III 13.0% (16)) than in the celecoxib group (none 59.0% (69), Brooker class I 35.9% (42), classes II and III 5.1% (6), p=0.002). Celecoxib was more effective than ibuprofen in preventing heterotopic bone formation after total hip replacement.

Effectiveness of robot-assisted training added to conventional rehabilitation in patients with humeral fracture early after surgical treatment: protocol of a randomised, controlled, multicentre trial.

PubMed

Nerz, Corinna; Schwickert, Lars; Becker, Clemens; Studier-Fischer, Stefan; Müßig, Janina Anna; Augat, Peter

2017-12-06

The incidence of proximal humeral fractures increases with age. The functional recovery of the upper arm after such fractures is slow, and results are often disappointing. Treatment is associated with long immobilisation periods. Evidence-based exercise guidelines are missing. Loss of muscle mass as well as reduced range of motion and motor performance are common consequences. These losses could be partly counteracted by training interventions using robot-assisted arm support of the affected arm derived from neurorehabilitation. Thus, shorter immobilisation could be reached. Thus far, this approach has been tested in only a few small studies. The aim of the present study is to examine whether assistive robotic training augmenting conventional occupational and physical therapy can improve functional shoulder outcomes. Patients aged between 35 and 66 years with proximal humeral fracture and surgical treatment will be recruited at three different clinics in Germany and randomised into an intervention group and a control group. Participants will be assessed before randomisation and followed after completing an intervention period of 3 weeks and additionally after 3, 6 and 12 months. The baseline assessment will include cognition (Short Orientation-Memory-Concentration Test); level of pain in the affected arm; ability to work; gait speed (10-m walk); disability of the arm, shoulder and hand (Disabilities of the Arm, Shoulder and Hand Outcome Measure [DASH]); range of motion of the affected arm (goniometer measurement); visual acuity; and motor function of orthopaedic patients (Wolf Motor Function Test-Orthopaedic version [WMFT-O]). Clinical follow-up directly after the intervention will include assessment of disability of the arm, shoulder and hand (DASH) as well as range of motion and motor function (WMFT-O). The primary outcome parameter will be the DASH, and the secondary outcome parameter will be the WMFT-O. The long-term results will be assessed prospectively by postal follow-up. All patients will receive conventional occupational and physical therapy. The intervention group will receive additional robot-assisted training using the Armeo®Spring robot for 3 weeks. This study protocol describes a phase II, randomised, controlled, single-blind, multicentre intervention study. The results will guide and possibly improve methods of rehabilitation after proximal humeral fracture. Clinicaltrials.gov, NCT03100201 . Registered on 28 March 2017.

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

PubMed

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

2017-06-23

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

Exercise in children with joint hypermobility syndrome and knee pain: a randomised controlled trial comparing exercise into hypermobile versus neutral knee extension

PubMed Central

2013-01-01

Background Knee pain in children with Joint Hypermobility Syndrome (JHS) is traditionally managed with exercise, however the supporting evidence for this is scarce. No trial has previously examined whether exercising to neutral or into the hypermobile range affects outcomes. This study aimed to (i) determine if a physiotherapist-prescribed exercise programme focused on knee joint strength and control is effective in reducing knee pain in children with JHS compared to no treatment, and (ii) whether the range in which these exercises are performed affects outcomes. Methods A prospective, parallel-group, randomised controlled trial conducted in a tertiary hospital in Sydney, Australia compared an 8 week exercise programme performed into either the full hypermobile range or only to neutral knee extension, following a minimum 2 week baseline period without treatment. Randomisation was computer-generated, with allocation concealed by sequentially numbered opaque sealed envelopes. Knee pain was the primary outcome. Quality of life, thigh muscle strength, and function were also measured at (i) initial assessment, (ii) following the baseline period and (iii) post treatment. Assessors were blinded to the participants’ treatment allocation and participants blinded to the difference in the treatments. Results Children with JHS and knee pain (n=26) aged 7-16 years were randomly assigned to the hypermobile (n=12) or neutral (n=14) treatment group. Significant improvements in child-reported maximal knee pain were found following treatment, regardless of group allocation with a mean 14.5 mm reduction on the visual analogue scale (95% CI 5.2 – 23.8 mm, p=0.003). Significant differences between treatment groups were noted for parent-reported overall psychosocial health (p=0.009), specifically self-esteem (p=0.034), mental health (p=0.001) and behaviour (p=0.019), in favour of exercising into the hypermobile range (n=11) compared to neutral only (n=14). Conversely, parent-reported overall physical health significantly favoured exercising only to neutral (p=0.037). No other differences were found between groups and no adverse events occurred. Conclusions Parents perceive improved child psychosocial health when children exercise into the hypermobile range, while exercising to neutral only is perceived to favour the child’s physical health. A physiotherapist prescribed, supervised, individualised and progressed exercise programme effectively reduces knee pain in children with JHS. Trial registration Australia & New Zealand Clinical Trials Registry; ACTRN12606000109505. PMID:23941143

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

PubMed

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

2017-10-01

Evidence-based treatments in ophthalmology are often based on the results of randomised controlled trials. Biased conclusions from randomised controlled trials may lead to inappropriate management recommendations. This systematic review investigates the prevalence of bias risk in randomised controlled trials published in high-impact ophthalmology journals and ophthalmology trials from general medical journals. Using Ovid MEDLINE, randomised controlled trials in the top 10 high-impact ophthalmology journals in 2015 were systematically identified and critically appraised for the prevalence of bias risk. Included randomised controlled trials were assessed in all domains of bias as defined by the Cochrane Collaboration. In addition, the prevalence of conflict of interest and industry sponsorship was investigated. A comparison with ophthalmology articles from high-impact general medical journals was performed. Of the 259 records that were screened from ophthalmology-specific journals, 119 trials met all inclusion criteria and were critically appraised. In total, 29.4% of domains had an unclear risk, 13.8% had a high risk and 56.8% had a low risk of bias. In comparison, ophthalmology articles from general medical journals had a lower prevalence of unclear risk (17.1%), higher prevalence of high risk (21.9%) and a higher prevalence of low risk domains (61.9%). Furthermore, 64.7% of critically appraised trials from ophthalmology-specific journals did not report any conflicts of interest, while 70.6% did not report an industry sponsor of their trial. In closing, it is essential that authors, peer reviewers and readers closely follow published risk of bias guidelines. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

PubMed Central

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

2016-01-01

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

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).

Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia between 34 and 37 weeks' gestation (HYPITAT-II): a multicentre, open-label randomised controlled trial.

PubMed

Langenveld, Josje; Broekhuijsen, Kim; van Baaren, Gert-Jan; van Pampus, Maria G; van Kaam, Anton H; Groen, Henk; Porath, Martina; Oudijk, Martijn A; Bloemenkamp, Kitty W; Groot, Christianne J de; van Beek, Erik; van Huizen, Marloes E; Oosterbaan, Herman P; Willekes, Christine; Wijnen-Duvekot, Ella J; Franssen, Maureen T M; Perquin, Denise A M; Sporken, Jan M J; Woiski, Mallory D; Bremer, Henk A; Papatsonis, Dimitri N M; Brons, Jozien T J; Kaplan, Mesruwe; Nij Bijvanck, Bas W A; Mol, Ben-Willen J

2011-07-07

Gestational hypertension (GH) and pre-eclampsia (PE) can result in severe complications such as eclampsia, placental abruption, syndrome of Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) and ultimately even neonatal or maternal death. We recently showed that in women with GH or mild PE at term induction of labour reduces both high risk situations for mothers as well as the caesarean section rate. In view of this knowledge, one can raise the question whether women with severe hypertension, pre-eclampsia or deterioration chronic hypertension between 34 and 37 weeks of gestation should be delivered or monitored expectantly. Induction of labour might prevent maternal complications. However, induction of labour in late pre-term pregnancy might increase neonatal morbidity and mortality compared with delivery at term. Pregnant women with severe gestational hypertension, mild pre-eclampsia or deteriorating chronic hypertension at a gestational age between 34+0 and 36+6 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant monitoring. In the expectant monitoring arm, women will be induced only when the maternal or fetal condition detoriates or at 37+0 weeks of gestation. The primary outcome measure is a composite endpoint of maternal mortality, severe maternal complications (eclampsia, HELLP syndrome, pulmonary oedema and thromboembolic disease) and progression to severe pre-eclampsia. Secondary outcomes measures are respiratory distress syndrome (RDS), neonatal morbidity and mortality, caesarean section and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be intention to treat. The power calculation is based on an expectant reduction of the maternal composite endpoint from 5% to 1% for an expected increase in neonatal RDS from 1% at 37 weeks to 10% at 34 weeks. This implies that 680 women have to be randomised. This trial will provide insight as to whether in women with hypertensive disorders late pre-term, induction of labour is an effective treatment to prevent severe maternal complications without compromising the neonatal morbidity. NTR1792 CLINICAL TRIAL REGISTRATION: http://www.trialregister.nl.

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.

Personalised Normative Feedback for Preventing Alcohol Misuse in University Students: Solomon Three-Group Randomised Controlled Trial

PubMed Central

Moreira, Maria T.; Oskrochi, Reza; Foxcroft, David R.

2012-01-01

Background Young people tend to over-estimate peer group drinking levels. Personalised normative feedback (PNF) aims to correct this misperception by providing information about personal drinking levels and patterns compared with norms in similar aged peer groups. PNF is intended to raise motivation for behaviour change and has been highlighted for alcohol misuse prevention by the British Government Behavioural Insight Team. The objective of the trial was to assess the effectiveness of PNF with college students for the prevention of alcohol misuse. Methodology Solomon three-group randomised controlled trial. 1751 students, from 22 British Universities, allocated to a PNF group, a normal control group, or a delayed measurement control group to allow assessment of any measurement effects. PNF was provided by email. Participants completed online questionnaires at baseline, 6- and 12-months (only 12-months for the delayed measurement controls). Drinking behaviour measures were (i) alcohol disorders; (ii) frequency; (iii) typical quantity, (iv) weekly consumption; (v) alcohol-related problems; (vi) perceived drinking norms; and (vii) positive alcohol expectancies. Analyses focused on high-risk drinkers, as well as all students, because of research evidence for the prevention paradox in student drinkers. Principal Findings Follow-up rates were low, with only 50% and 40% responding at 6- and 12-months, respectively, though comparable to similar European studies. We found no evidence for any systematic attrition bias. Overall, statistical analyses with the high risk sub-sample, and for all students, showed no significant effects of the intervention, at either time-point, in a completed case analysis and a multiple imputation analysis. Conclusions We found no evidence for the effectiveness of PNF for the prevention of alcohol misuse and alcohol-related problems in a UK student population. Registration Controlled-Trials.com ISRCTN30784467 PMID:22984466

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

PubMed

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

2010-02-01

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

A randomised double blind placebo controlled clinical trial of a standardised extract of fresh Crataegus berries (Crataegisan) in the treatment of patients with congestive heart failure NYHA II.

PubMed

Degenring, F H; Suter, A; Weber, M; Saller, R

2003-01-01

A placebo controlled, randomised, parallel group, multicentre trial conducted in accordance with the guidelines of Good Clinical Practice (GCP) shows the efficacy and safety of a standardised extract of fresh berries of Crataegus oxyacantha L. and monogyna Jacq. (Crataegisan) in patients with cardiac failure NYHA class II. A total of 143 patients (72 men, 71 women, mean age of 64.8 (8.0 years) were recruited and treated with 3 times 30 drops of the extract (n = 69) or placebo (n = 74) for 8 weeks. The primary variable for the evaluation of efficacy was the change in exercise tolerance determined with bicycle exercise testing, secondary variables included the blood pressure-heart rate product (BHP). Subjective cardiac symptoms at rest and at higher levels of exertion were assessed by the patient on a categorical rating scale. An overall assessment of efficacy at the final visit was provided by the patient and the investigator. In the ITT population there was a significant increase in exercise tolerance in both groups between visit 1 and visit 3. The difference between the treatment groups was 8.3 watts in favour of the standardised extract of fresh Crataegus berries (p = 0.045). The result is confirmed in the PP population (p = 0.047). Changes in BHP at 50 watts and at comparable maximum load were in favour of Crataegus extract but the results are not statistically significant. The subjective assessment of cardiac symptoms at rest and at higher levels of exertion did not change significantly and the patient and investigator overall assessment of efficacy were similar for the two groups. The medication was well tolerated and had a high level of patient acceptability. The significant improvement, due to the fact that dyspnoea and fatigue do not occur until a significantly higher wattage has been reached in the bicycle exercise testing allows the conclusion that the recruited NYHA II patients may expect an improvement in their heart failure condition under long term therapy with the standardised extract of fresh Crataegus berries.

Effect of an E-mental health approach to workers' health surveillance versus control group on work functioning of hospital employees: a cluster-RCT.

PubMed

Ketelaar, Sarah M; Nieuwenhuijsen, Karen; Gärtner, Fania R; Bolier, Linda; Smeets, Odile; Sluiter, Judith K

2013-01-01

To evaluate an e-mental health (EMH) approach to workers' health surveillance (WHS) targeting work functioning (WF) and mental health (MH) of healthcare professionals in a randomised controlled trial. Nurses and allied health professionals (N = 1140) were cluster-randomised at ward level to the intervention (IG) or control group (CG). The intervention consisted of two parts: (a) online screening and personalised feedback on impaired WF and MH, followed by (b) a tailored offer of self-help EMH interventions. CG received none of these parts. Primary outcome was impaired WF (Nurses Work Functioning Questionnaire), assessed at baseline and after three and six months. Analyses were performed in the positively screened subgroup (i) and in all participants (ii). Participation rate at baseline was 32% (NIG = 178; NCG = 188). Eighty-two percent screened positive for at least mild impairments in WF and/or MH (NIG = 139; NCG = 161). All IG-participants (N = 178) received part (a) of the intervention, nine participants (all positively screened, 6%) followed an EMH intervention to at least some extent. Regarding the subgroup of positively screened participants (i), both IG and CG improved over time regarding WF (non-significant between-group difference). After six months, 36% of positively screened IG-participants (18/50) had a relevant WF improvement compared to baseline, versus 28% (32/115) of positively screened CG-participants (non-significant difference). In the complete sample (ii), IG and CG improved over time but IG further improved between three and six months while CG did not (significant interaction effect). In our study with a full compliance rate of 6% and substantial drop-out leading to a small and underpowered sample, we could not demonstrate that an EMH-approach to WHS is more effective to improve WF and MH than a control group. The effect found in the complete sample of participants is not easily interpreted. Reported results may be useful for future meta-analytic work. Dutch Trial Register NTR2786.

Effect of an E-mental Health Approach to Workers' Health Surveillance versus Control Group on Work Functioning of Hospital Employees: A Cluster-RCT

PubMed Central

Ketelaar, Sarah M.; Nieuwenhuijsen, Karen; Gärtner, Fania R.; Bolier, Linda; Smeets, Odile; Sluiter, Judith K.

2013-01-01

Objective To evaluate an e-mental health (EMH) approach to workers' health surveillance (WHS) targeting work functioning (WF) and mental health (MH) of healthcare professionals in a randomised controlled trial. Methods Nurses and allied health professionals (N = 1140) were cluster-randomised at ward level to the intervention (IG) or control group (CG). The intervention consisted of two parts: (a) online screening and personalised feedback on impaired WF and MH, followed by (b) a tailored offer of self-help EMH interventions. CG received none of these parts. Primary outcome was impaired WF (Nurses Work Functioning Questionnaire), assessed at baseline and after three and six months. Analyses were performed in the positively screened subgroup (i) and in all participants (ii). Results Participation rate at baseline was 32% (NIG = 178; NCG = 188). Eighty-two percent screened positive for at least mild impairments in WF and/or MH (NIG = 139; NCG = 161). All IG-participants (N = 178) received part (a) of the intervention, nine participants (all positively screened, 6%) followed an EMH intervention to at least some extent. Regarding the subgroup of positively screened participants (i), both IG and CG improved over time regarding WF (non-significant between-group difference). After six months, 36% of positively screened IG-participants (18/50) had a relevant WF improvement compared to baseline, versus 28% (32/115) of positively screened CG-participants (non-significant difference). In the complete sample (ii), IG and CG improved over time but IG further improved between three and six months while CG did not (significant interaction effect). Conclusions In our study with a full compliance rate of 6% and substantial drop-out leading to a small and underpowered sample, we could not demonstrate that an EMH-approach to WHS is more effective to improve WF and MH than a control group. The effect found in the complete sample of participants is not easily interpreted. Reported results may be useful for future meta-analytic work. Trial Registration Dutch Trial Register NTR2786 PMID:24069148

Community-based physical activity and nutrition programme for adults with metabolic syndrome in Vietnam: study protocol for a cluster-randomised controlled trial

PubMed Central

Tran, Van Dinh; Lee, Andy H; Jancey, Jonine; James, Anthony P; Howat, Peter; Thi Phuong Mai, Le

2016-01-01

Introduction Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular diseases and type II diabetes. In Vietnam, more than one-quarter of its population aged 50–65 have MetS. This cluster-randomised controlled trial aims to evaluate the effectiveness of interventions to increase levels of physical activity and improve dietary behaviours among Vietnamese adults aged 50–65 years with MetS. Method and analysis This 6-month community-based intervention includes a range of strategies to improve physical activity and nutrition for adults with MetS in Hanam, a province located in northern Vietnam. 600 participants will be recruited from 6 communes with 100 participants per commune. The 6 selected communes will be randomly allocated to either an intervention group (m=3; n=300) or a control group (m=3; n=300). The intervention comprises booklets, education sessions, resistance bands and attending local walking groups that provide information and encourage participants to improve their physical activity and healthy eating behaviours during the 6-month period. The control group participants will receive standard and 1-time advice. Social cognitive theory is the theoretical concept underpinning this study. Measurements will be taken at baseline and postintervention to evaluate programme effectiveness. Ethics and dissemination The research protocol was approved by the Curtin University Human Research Ethics Committee (approval number: HR139/2014). The results of the study will be disseminated through publications, reports and conference presentations. Trial registration number ACTRN12614000811606. PMID:27256094

Does a combination of physical training, specific exercises and pain education improve health-related quality of life in patients with chronic neck pain? A randomised control trial with a 4-month follow up.

PubMed

Ris, I; Søgaard, K; Gram, B; Agerbo, K; Boyle, E; Juul-Kristensen, B

2016-12-01

To investigate the effect of combining pain education, specific exercises and graded physical activity training (exercise) compared with pain education alone (control) on physical health-related quality of life (HR-QoL) in chronic neck pain patients. A multicentre randomised controlled trial of 200 neck pain patients receiving pain education. The exercise group received additional exercises for neck/shoulder, balance and oculomotor function, plus graded physical activity training. Patient-reported outcome measures (Short Form-36 Physical and Mental component summary scores, EuroQol-5D, Beck Depression Inventory-II, Neck Disability Index, Pain Bothersomeness, Patient-Specific Functioning Scale, Tampa Scale of Kinesiophobia, Global Perceived Effect) and clinical tests (Aastrand Physical Fitness, cervical Range of Motion, Pressure Pain Threshold at infraspinatus, tibialis anterior and cervical spine, Cranio-cervical Flexion, Cervical Extension muscle function, and oculomotion) were recorded at baseline and after 4 months. The exercise group showed statistically significant improvement in physical HR-QoL, mental HR-QoL, depression, cervical pressure pain threshold, cervical extension movement, muscle function, and oculomotion. Per protocol analyses confirmed these results with additional significant improvements in the exercise group compared with controls. This multimodal intervention may be an effective intervention for chronic neck pain patients. The trial was registered on www.ClinicalTrials.govNCT01431261 and at the Regional Scientific Ethics Committee of Southern Denmark S-20100069. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2017-12-28

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

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…

Effects of motivational enhancement therapy plus cognitive behaviour therapy on depressive symptoms and health-related quality of life in adults with type II diabetes mellitus: a randomised controlled trial.

PubMed

Huang, Chiung-Yu; Lai, Hui-Ling; Chen, Chun-I; Lu, Yung-Chuan; Li, Su-Chen; Wang, Long-Whou; Su, Yi

2016-05-01

This paper evaluates the effectiveness of motivational enhancement therapy plus cognitive behavioural therapy on depressive symptoms, glycosylated haemoglobin, fasting glucose, body mass index (BMI), and health-related quality of life in type II diabetes patients. A controlled trial was conducted to compare patients who received the behavioural intervention with untreated controls on measures of health outcomes. A total of 31 intervention group participants and 30 controls were selected from patients that met the inclusion criteria from a hospital-based endocrinology outpatient department. The outcome measures including depressive symptoms, glycosylated haemoglobin, fasting glucose, BMI, and both physical and mental quality of life were collected before (T1), after (T2), and after 90 days (T3) following the intervention. The experimental group showed a significant reduction in glycosylated haemoglobin, fasting glucose, and depressive symptoms and a significant increase in physical quality of life and mental quality of life at T2 and T3, while patients in the control group with usual care showed no changes over time. The behavioural intervention facilitated a significant improvement in psychological adjustment and glycemic control, thus strengthening diabetes control skills and leading to healthy outcomes. It is feasible that nurses and psychiatrists can deliver the behavioural intervention for diabetes patients to decrease their depressive symptoms. Sharing discussion and problem-solving experiences is particularly helpful method for self-control, and these will be beneficially influential on further research.

EOS-based cup navigation: Randomised controlled trial in 78 total hip arthroplasties.

PubMed

Verdier, N; Billaud, A; Masquefa, T; Pallaro, J; Fabre, T; Tournier, C

2016-06-01

Minimising the risk of cup implantation outside the safe zone is among the objectives of navigation during total hip arthroplasty (THA). However, given the technical challenges raised by navigation when the patient is lying on the side, many surgeons still use the freehand technique. We conducted a randomised controlled trial to evaluate the new navigation system NAVEOS in the iliac plane, which is easily identified in the lateral decubitus position, with the objective of determining whether NAVEOS navigation decreased the frequency of cup implantation outside the safe zone compared to freehand cup positioning, without increasing the operative time or the frequency of complications. NAVEOS navigation decreases the frequency of cup positioning outside the safe zone compared to freehand positioning. This randomised controlled trial compared cup positioning using NAVEOS navigation versus the freehand technique in patients undergoing primary THA. The safe zone was defined according to Lewinnek as 15±10° of radiological anteversion and 40±10° of radiological inclination. Cup position parameters were measured on computed tomography images obtained 3months after THA. The images were read by two independent observers who were blinded to group assignment. The primary evaluation criterion was cup position within the safe zone. A 1:1 randomisation scheme was used to assign 78 patients (mean age, 68years; age range, 44-91years) to NAVEOS navigation or freehand cup positioning. The two groups were comparable for age, gender distribution, body mass index, and preoperative functional scores. In the NAVEOS group, navigation was discontinued prematurely in 6 patients, because of technical difficulties (n=2) or a marked discrepancy with clinical findings (n=4); however, the intention-to-treat approach was used for the analysis. The proportion of cups in the safe zone was 67% (28/39) in the NAVEOS group and 38% (17/39) in the freehand group (P=0.012). Anteversion was within the 5-25° range for 72% (28/39) cups in the NAVEOS group and 46% (18/39) in the freehand group (P=0.021). Inclination was within the 30-50° range for 95% (37/39) of cups with NAVEOS navigation and 85% (33/39) with freehand positioning (P=0.135). The odds ratio for cup implantation outside the safe zone was significantly lower with NAVEOS compared to freehand positioning (0.54; 95% confidence interval, 0.31-0.91). Mean operative time was 74 (range, 45-115) minutes with NAVEOS navigation and 70 (range, 40-105) minutes with freehand positioning (P=0.382). Complications consisted of 1 case each of anterior dislocation and infection, both in the freehand group. Compared to freehand positioning, NAVEOS navigation significantly lowered the risk of cup positioning outside the safe zone, chiefly via improved achievement of the anteversion target. NAVEOS was not associated with increases in operative time or morbidity. II, randomised controlled trial with limited statistical power. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

PubMed Central

Glenton, Claire; Oxman, Andrew D

2009-01-01

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

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.

The effectiveness of an enhanced invitation letter on uptake of National Health Service Health Checks in primary care: a pragmatic quasi-randomised controlled trial.

PubMed

Sallis, Anna; Bunten, Amanda; Bonus, Annabelle; James, Andrew; Chadborn, Tim; Berry, Daniel

2016-03-24

The National Health Service Health Check (NHS HC) is a population level public health programme. It is a primary prevention initiative offering cardiovascular risk assessment and management for adults aged 40-74 years (every five years). It was designed to reduce the incidence of major vascular disease events by preventing or delaying the onset of diabetes, heart and kidney disease, stroke and vascular dementia . Effectiveness of the programme has been modelled on a national uptake of 75% however in 2012/13 uptake, nationally, was 49%. Ensuring a high percentage of those offered an NHS HC actually receive one is key to optimising the clinical and cost effectiveness of the programme. A pragmatic quasi-randomised controlled trial was conducted in four general practitioner practices in Medway, England with randomisation of 3511 patients. The aim was to compare attendance at the NHS HC using the standard national invitation template letter (control) compared to an enhanced invitation letter using insights from behavioural science (intervention). The intervention letter includes i) simplification - reducing letter content for less effortful processing ii) behavioural instruction - action focused language iii) personal salience - appointment due rather than invited and iv) addressing implementation intentions with a tear off slip to record the date, time and location of the appointment. Logistic Regression explored the association between control and intervention group and attendance at a health check. 29.3% of patients who received the control letter and 33.5% of those who received the intervention letter attended their NHS HC (adjusted odds ratio 1.26, 95% confidence interval 1.09-1.47, p < 0.01). This was an absolute difference in uptake of 4.2 percentage points for those receiving the intervention letter. An invitation letter applying behavioural insights was more effective than the existing national template letter at encouraging attendance at an NHS HC. Making small, no cost behaviourally informed changes to letter invitations can improve uptake of the NHS HC. Further research is required to replicate the effect with more robust methodology and powered for sub-group analysis including socio-economic status. Current Controlled Trials ISRCTN66757664 , date of registration 28/3/2014.

Multimodal infiltration of local anaesthetic in total knee arthroplasty; is posterior capsular infiltration worth the risk? a prospective, double-blind, randomised controlled trial.

PubMed

Pinsornsak, P; Nangnual, S; Boontanapibul, K

2017-04-01

Multimodal infiltration of local anaesthetic provides effective control of pain in patients undergoing total knee arthroplasty (TKA). There is little information about the added benefits of posterior capsular infiltration (PCI) using different combinations of local anaesthetic agents. Our aim was to investigate the effectiveness of the control of pain using multimodal infiltration with and without infiltration of the posterior capsule of the knee. In a double-blind, randomised controlled trial of patients scheduled for unilateral primary TKA, 86 were assigned to be treated with multimodal infiltration with (Group I) or without (Group II) PCI. Routine associated analgesia included the use of bupivacaine, morphine, ketorolac and epinephrine. All patients had spinal anaesthesia and patient-controlled analgesia (PCA) post-operatively. A visual analogue scale (VAS) for pain and the use of morphine were recorded 24 hours post-operatively. Side effects of the infiltration, blood loss, and length of stay in hospital were recorded. There were no statistically significant differences between the groups in relation to: VAS pain scores in the first 24 hours post-operatively (p = 0.693), the use of morphine in the PCA (p = 0.647), blood loss (p = 0.625), and length of stay (p = 0.17). There were no neurovascular complications in either group. The multimodal infiltration of local anaesthetic with infiltration of the posterior capsule did not provide significant added analgesic benefits or reduce the use of morphine after TKA. Multimodal infiltration is a satisfactory technique for the management of pain in these patients without the attendant risks of PCI. Cite this article: Bone Joint J 2017; 99-B:483-8. ©2017 The British Editorial Society of Bone & Joint Surgery.

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.

Study design and rationale for a randomised, placebo-controlled, double-blind study to assess the efficacy of selumetinib (AZD6244; ARRY-142886) in combination with dacarbazine in patients with metastatic uveal melanoma (SUMIT).

PubMed

Carvajal, Richard D; Schwartz, Gary K; Mann, Helen; Smith, Ian; Nathan, Paul D

2015-06-10

Uveal melanoma is characterised by mutations in GNAQ and GNA11, resulting in Ras/Raf/MEK/ERK pathway activation. Treatment with selumetinib (AZD6244, ARRY-142886), a MEK1/2 inhibitor, results in antitumour effects in uveal melanoma pre-clinical models. A randomised phase II trial demonstrated improved progression-free survival (PFS) and response rate (RR) with selumetinib monotherapy versus chemotherapy with temozolomide or dacarbazine in patients with metastatic uveal melanoma. Pre-clinically, selumetinib in combination with alkylating agents enhanced antitumour activity compared with chemotherapy alone. We hypothesise that selumetinib in combination with dacarbazine will result in improved clinical outcomes in patients with metastatic uveal melanoma versus dacarbazine alone. SUMIT is a randomised, international, double-blind, placebo-controlled, phase III study assessing the efficacy and safety of selumetinib in combination with dacarbazine in patients with metastatic uveal melanoma who have not received prior systemic therapy. Primary endpoint is PFS. Secondary endpoints include objective RR, duration of response, change in tumour size at Week 6, overall survival, safety and tolerability. Exploratory endpoints include efficacy in tumours with GNAQ or GNA11 mutations. Eligible patients must have: ≥1 lesion that can be accurately measured at baseline, and is suitable for accurate repeated measurements; ECOG performance status 0-1; life expectancy>12 weeks. Mutation status for GNAQ/GNA11 will be assessed retrospectively. An estimated 128 patients from approximately 50 sites globally will be randomised (3:1) to selumetinib 75 mg twice daily or placebo in combination with dacarbazine 1000 mg/m(2) on Day 1 of every 21-day cycle until objective disease progression, intolerable toxicity or occurrence of another discontinuation criterion. Randomisation will be stratified by the presence/absence of liver metastases. Tumours will be evaluated by RECIST v1.1 every 6 weeks. All patients have the option of receiving selumetinib with or without dacarbazine at disease progression. Study enrolment began in April 2014 and is expected to complete in early 2015. Treatment of patients with metastatic uveal melanoma represents an area of high unmet medical need. This study evaluating selumetinib in combination with dacarbazine was designed with input from the US FDA, and is the first potential registration trial to be conducted in patients with metastatic uveal melanoma. Clinicaltrials.gov (Date of registration, October 10, 2013) REGISTRATION NUMBER: NCT01974752 Trial abbreviation: SUMIT.

The effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled clinical trial.

PubMed

Hirayama, S; Terasawa, K; Rabeler, R; Hirayama, T; Inoue, T; Tatsumi, Y; Purpura, M; Jäger, R

2014-04-01

Attention-deficit hyperactivity disorder (ADHD) is the most commonly diagnosed behavioural disorder of childhood, affecting 3-5% of school-age children. The present study investigated whether the supplementation of soy-derived phosphatidylserine (PS), a naturally occurring phospholipid, improves ADHD symptoms in children. Thirty six children, aged 4-14 years, who had not previously received any drug treatment related to ADHD, received placebo (n = 17) or 200 mg day(-1) PS (n = 19) for 2 months in a randomised, double-blind manner. Main outcome measures included: (i) ADHD symptoms based on DSM-IV-TR; (ii) short-term auditory memory and working memory using the Digit Span Test of the Wechsler Intelligence Scale for Children; and (iii) mental performance to visual stimuli (GO/NO GO task). PS supplementation resulted in significant improvements in: (i) ADHD (P < 0.01), AD (P < 0.01) and HD (P < 0.01); (ii) short-term auditory memory (P < 0.05); and (iii) inattention (differentiation and reverse differentiation, P < 0.05) and inattention and impulsivity (P < 0.05). No significant differences were observed in other measurements and in the placebo group. PS was well-tolerated and showed no adverse effects. PS significantly improved ADHD symptoms and short-term auditory memory in children. PS supplementation might be a safe and natural nutritional strategy for improving mental performance in young children suffering from ADHD. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

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…

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

PubMed Central

Talley, Nicholas J; Jones, Michael P

2015-01-01

Background: Hypnotherapy has been reported as being beneficial in the treatment of irritable bowel syndrome (IBS). We aimed to test the hypothesis that patients with IBS treated ‘holistically’ by hypnosis (i.e. by combined psychological and physiological symptom imagery) would have greater improvement in their IBS symptoms than patients treated by hypnosis using standard ‘gut-directed’ hypnotherapy, and both would be superior to simple relaxation therapy. Methods: Patients (n = 51) with Rome II criteria were randomised to ‘individualised’ (holistic) hypnotherapy, standard ‘gut-directed’ hypnotherapy or relaxation therapy for a period of 11 weeks with two follow-up assessments at 2 weeks and at 3 months after the completion of the trial. The primary outcome was bowel symptom severity scale (BSSS). Results: All the participants in this study improved their IBS symptoms (pain, bloating, constipation and diarrhoea) and physical functioning at the end of the treatment from baseline, but this was not significantly different across the treatment arms. Conclusion: Neither ‘individualised’ nor ‘gut-directed’ hypnotherapy is superior to relaxation therapy in IBS. PMID:28070348

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.

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.

Cost Effectiveness of Stapled Haemorrhoidopexy and Traditional Excisional Surgery for the Treatment of Haemorrhoidal Disease.

PubMed

Kilonzo, Mary M; Brown, Steven R; Bruhn, Hanne; Cook, Jonathan A; Hudson, Jemma; Norrie, John; Watson, Angus J M; Wood, Jessica

2017-08-25

Our objective was to compare the cost effectiveness of stapled haemorrhoidopexy (SH) and traditional haemorrhoidectomy (TH) in the treatment of grade II-IV haemorrhoidal disease from the perspective of the UK national health service. An economic evaluation was conducted alongside an open, two-arm, parallel-group, pragmatic, multicentre, randomised controlled trial conducted in several hospitals in the UK. Patients were randomised into either SH or TH surgery between January 2011 and August 2014 and were followed up for 24 months. Intervention and subsequent resource use data were collected using case review forms and questionnaires. Benefits were collected using the EQ-5D-3L (EuroQoL-five dimensions-three levels) instrument. The primary economic outcome was incremental cost measured in pounds (£), year 2016 values, relative to the incremental benefit, which was estimated using quality-adjusted life-years (QALYs). Cost and benefits accrued in the second year were discounted at 3.5%. The base-case analysis was based on imputed data. Uncertainty was explored using univariate sensitivity analyses. Participants (n = 777) were randomised to SH (n = 389) or TH (n = 388). The mean cost of SH was £337 (95% confidence interval [CI] 251-423) higher than that of TH and the mean QALYs were -0.070 (95% CI -0.127 to -0.011) lower than for TH. The base-case cost-utility analysis indicated that SH has zero probability of being cost effective at both the £20,000 and the £30,000 threshold. Results from the sensitivity analyses were similar to those from the base-case analysis. The evidence suggests that, on average, the total mean costs over the 24-month follow-up period were significantly higher for the SH arm than for the TH arm. The QALYs were also, on average, significantly lower for the SH arm. These results were supported by the sensitivity analyses. Therefore, in terms of cost effectiveness, TH is a superior surgical treatment for the management of grade II-IV haemorrhoids when compared with SH.

Systematic reviews of randomised clinical trials examining the effects of psychotherapeutic interventions versus "no intervention" for acute major depressive disorder and a randomised trial examining the effects of "third wave" cognitive therapy versus mentalization-based treatment for acute major depressive disorder.

PubMed

Jakobsen, Janus Christian

2014-10-01

Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Cognitive therapy and psychodynamic therapy may be effective treatment options for major depressive disorder, but the effects have only had limited assessment in systematic reviews. The two modern forms of psychotherapy, "third wave" cognitive therapy and mentalization-based treatment, have both gained some ground as treatments of psychiatric disorders. No randomised trial has compared the effects of these two interventions for major depressive disorder. We performed two systematic reviews with meta-analyses and trial sequential analyses using The Cochrane Collaboration methodology examining the effects of cognitive therapy and psycho-dynamic therapy for major depressive disorder. We developed a thorough treatment protocol for a randomised trial with low risks of bias (systematic error) and low risks of random errors ("play of chance") examining the effects of third wave' cognitive therapy versus mentalization-based treatment for major depressive disorder. We conducted a randomised trial according to good clinical practice examining the effects of "third wave" cognitive therapy versus mentalisation-based treatment for major depressive disorder. The first systematic review included five randomised trials examining the effects of psychodynamic therapy versus "no intervention' for major depressive disorder. Altogether the five trials randomised 365 participants who in each trial received similar antidepressants as co-interventions. All trials had high risk of bias. Four trials assessed "interpersonal psychotherapy" and one trial "short psychodynamic supportive psychotherapy". Both of these interventions are different forms of psychodynamic therapy. Meta-analysis showed that psychodynamic therapy significantly reduced depressive symptoms on the Hamilton Depression Rating Scale (HDRS) compared with "no intervention" (mean difference -3.01 (95% confidence interval -3.98 to -2.03; p = 0.00001), no significant heterogeneity between trials). Trial sequential analysis confirmed this result. The second systematic review included 12 randomised trials examining the effects of cognitive therapy versus "no intervention" for major depressive disorder. Altogether a total of 669 participants were randomised. All trials had high risk of bias. Meta-analysis showed that cognitive therapy significantly reduced depressive symptoms on the HDRS compared with "no intervention" (four trials; mean difference -3.05 (95% confidence interval, -5.23 to -0.87; p = 0.006)). Trial sequential analysis could not confirm this result. The trial protocol showed that it seemed feasible to conduct a randomised trial with low risks of bias and low risks of random errors examining the effects of "third wave" cognitive therapy versus mentalization-based therapy in a setting in the Danish healthcare system. It turned out to be much more difficult to recruit participants in the randomised trial than expected. We only included about half of the planned participants. The results from the randomised trial showed that participants randomised to "third wave" therapy compared with participants randomised to mentalization-based treatment had borderline significantly lower HDRS scores at 18 weeks in an unadjusted analysis (mean difference -4.14 score; 95% CI -8.30 to 0.03; p = 0.051). In the adjusted analysis, the difference was significant (p = 0.039). Five (22.7%) of the participants randomised to "third wave" cognitive therapy had remission at 18 weeks versus none of the participants randomised to mentalization-based treatment (p = 0.049). Sequential analysis showed that these findings could be due to random errors. No significant differences between the two groups was found regarding Beck's Depression Inventory (BDI II), Symptom Checklist 90 Revised (SCL 90-R), and The World Health Organization-Five Well-being Index 1999 (WHO 5). We concluded that cognitive therapy and psychodynamic therapy might be effective interventions for depression measured on HDRS and BDI, but the review results might be erroneous due to risks of bias and random errors. Furthermore, the effects seem relatively small. The trial protocol showed that it was possible to develop a protocol for a randomised trial examining the effects of "third wave" cognitive therapy versus mentalization-based treatment with low risks of bias and low risks of random errors. Our trial results showed that "third wave" cognitive therapy might be a more effective intervention for depressive symptoms measured on the HDRS compared with mentalization-based treatment. The two interventions did not seem to differ significantly regarding BDI II, SCL 90-R, and WHO 5. More randomised trials with low risks of bias and low risks of random errors are needed to assess the effects of cognitive therapy, psychodynamic therapy, "third wave" cognitive therapy, and mentalization-based treatment.

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

Internet-based treatment of major depression for patients on a waiting list for inpatient psychotherapy: protocol for a multi-centre randomised controlled trial

PubMed Central

2013-01-01

Background Major depressive disorder (MDD) is a prevalent and severe disorder. Although effective treatments for MDD are available, many patients remain untreated, mainly because of insufficient treatment capacities in the health care system. Resulting waiting periods are often associated with prolonged suffering and impairment as well as a higher risk of chronification. Web-based interventions may help to alleviate these problems. Numerous studies provided evidence for the efficacy of web-based interventions for depression. The aim of this study is to evaluate a new web-based guided self-help intervention (GET.ON-Mood Enhancer-WL) specifically developed for patients waiting to commence inpatient therapy for MDD. Methods In a two-armed randomised controlled trial (n = 200), the web-based guided intervention GET.ON-Mood Enhancer-WL in addition to treatment as usual (TAU) will be compared with TAU alone. The intervention contains six modules (psycho education, behavioural activation I & II, problem solving I & II, and preparation for subsequent inpatient depression therapy). The participants will be supported by an e-coach, who will provide written feedback after each module. Inclusion criteria include a diagnosis of MDD assessed with a structured clinical interview [SCID] and a waiting period of at least three weeks before start of inpatient treatment. The primary outcome is observer-rated depressive symptom severity (HRSD24). Further (explorative) questions include whether remission will be achieved earlier and by more patients during inpatient therapy because of the web-based preparatory intervention. Discussion If GET.ON-Mood Enhancer-WL is proven to be effective, patients may start inpatient therapy with reduced depressive symptom severity, ideally leading to higher remission rates, shortened inpatient therapy, reduced costs, and decreased waiting times. Trial registration German Clinical Trial Registration (DRKS): DRKS00004708. PMID:24279841

Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial).

PubMed

Eastwood, Glenn M; Schneider, Antoine G; Suzuki, Satoshi; Peck, Leah; Young, Helen; Tanaka, Aiko; Mårtensson, Johan; Warrillow, Stephen; McGuinness, Shay; Parke, Rachael; Gilder, Eileen; Mccarthy, Lianne; Galt, Pauline; Taori, Gopal; Eliott, Suzanne; Lamac, Tammy; Bailey, Michael; Harley, Nerina; Barge, Deborah; Hodgson, Carol L; Morganti-Kossmann, Maria Cristina; Pébay, Alice; Conquest, Alison; Archer, John S; Bernard, Stephen; Stub, Dion; Hart, Graeme K; Bellomo, Rinaldo

2016-07-01

In intensive care observational studies, hypercapnia after cardiac arrest (CA) is independently associated with improved neurological outcome. However, the safety and feasibility of delivering targeted therapeutic mild hypercapnia (TTMH) for such patients is untested. In a phase II safety and feasibility multi-centre, randomised controlled trial, we allocated ICU patients after CA to 24h of targeted normocapnia (TN) (PaCO2 35-45mmHg) or TTMH (PaCO2 50-55mmHg). The primary outcome was serum neuron specific enolase (NSE) and S100b protein concentrations over the first 72h assessed in the first 50 patients surviving to day three. Secondary end-points included global measure of function assessment at six months and mortality for all patients. We enrolled 86 patients. Their median age was 61 years (58, 64 years) and 66 (79%) were male. Of these, 50 patients (58%) survived to day three for full biomarker assessment. NSE concentrations increased in the TTMH group (p=0.02) and TN group (p=0.005) over time, with the increase being significantly more pronounced in the TN group (p(interaction)=0.04). S100b concentrations decreased over time in the TTMH group (p<0.001) but not in the TN group (p=0.68). However, the S100b change over time did not differ between the groups (p(interaction)=0.23). At six months, 23 (59%) TTMH patients had good functional recovery compared with 18 (46%) TN patients. Hospital mortality occurred in 11 (26%) TTMH patients and 15 (37%) TN patients (p=0.31). In CA patients admitted to the ICU, TTMH was feasible, appeared safe and attenuated the release of NSE compared with TN. These findings justify further investigation of this novel treatment. Copyright © 2016. Published by Elsevier Ireland Ltd.

COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss.

PubMed

Crabb, Simon J; Martin, Karen; Abab, Julia; Ratcliffe, Ian; Thornton, Roger; Lineton, Ben; Ellis, Mary; Moody, Ronald; Stanton, Louise; Galanopoulou, Angeliki; Maishman, Tom; Geldart, Thomas; Bayne, Mike; Davies, Joe; Lamb, Carolynn; Popat, Sanjay; Joffe, Johnathan K; Nutting, Chris; Chester, John; Hartley, Andrew; Thomas, Gareth; Ottensmeier, Christian; Huddart, Robert; King, Emma

2017-12-01

Cisplatin is one of the most ototoxic chemotherapy drugs, resulting in a permanent and irreversible hearing loss in up to 50% of patients. Cisplatin and gentamicin are thought to damage hearing through a common mechanism, involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin-induced ototoxicity. We, therefore, tested the hypothesis that aspirin could also reduce ototoxicity from cisplatin-based chemotherapy. A total of 94 patients receiving cisplatin-based chemotherapy for multiple cancer types were recruited into a phase II, double-blind, placebo-controlled trial and randomised in a ratio of 1:1 to receive aspirin 975 mg tid and omeprazole 20 mg od, or matched placebos from the day before, to 2 days after, their cisplatin dose(s), for each treatment cycle. Patients underwent pure tone audiometry before and at 7 and 90 days after their final cisplatin dose. The primary end-point was combined hearing loss (cHL), the summed hearing loss at 6 kHz and 8 kHz, in both ears. Although aspirin was well tolerated, it did not protect hearing in patients receiving cisplatin (p-value = 0.233, 20% one-sided level of significance). In the aspirin arm, patients demonstrated mean cHL of 49 dB (standard deviation [SD] 61.41) following cisplatin compared with placebo patients who demonstrated mean cHL of 36 dB (SD 50.85). Women had greater average hearing loss than men, and patients treated for head and neck malignancy experienced the greatest cHL. Aspirin did not protect from cisplatin-related ototoxicity. Cisplatin and gentamicin may therefore have distinct ototoxic mechanisms, or cisplatin-induced ototoxicity may be refractory to the aspirin regimen used here. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Phase-II trials in osteosarcoma recurrences: A systematic review of past experience.

PubMed

Omer, Natacha; Le Deley, Marie-Cécile; Piperno-Neumann, Sophie; Marec-Berard, Perrine; Italiano, Antoine; Corradini, Nadège; Bellera, Carine; Brugières, Laurence; Gaspar, Nathalie

2017-04-01

The most appropriate design of Phase-II trials evaluating new therapies in osteosarcoma remains poorly defined. To study consistency in phase-II clinical trials evaluating new therapies for osteosarcoma recurrences with respect to eligibility criteria, response assessment, end-points, statistical design and reported results. Systematic review of clinical trials registered on clinicaltrials.gov, clinicaltrialsregister.eu and French National Cancer Institute website or referenced in PubMed and American Society of Clinical Oncology websites, between 2003 and 2016, using the following criteria: (osteosarcoma OR bone sarcoma) AND (Phase-II). Among the 99 trials identified, 80 were Phase-II, 17 I/II and 2 II/III, evaluating mostly targeted therapy (n = 40), and chemotherapy alone (n = 26). Results were fully (n = 28) or partially (abstract, n = 6) published. Twenty-four trials were dedicated to osteosarcoma, 22 had an osteosarcoma stratum. Twenty-eight out of 99 trials refer to the age range observed at recurrence (28%). Overall, 65 trials were run in multicentre settings, including 17 international trials. Only 9 trials were randomised. The primary end-point was tumour response in 71 trials (response rate, n = 40 or best response, n = 31), with various definitions (complete + partial ± minor response and stable disease), mainly evaluated with RECIST criteria (n = 69); it was progression-free survival in 24 trials and OS in 3. In single-arm trials evaluating response rate, the null hypothesis tested (when available, n = 12) varied from 5% to 25%. No robust historical data can currently be derived from past efficacy Phase-II trials. There is an urgent need to develop international randomised Phase-II trials across all age ranges with standardised primary end-point. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Phase II randomised controlled trial assessing the feasibility, acceptability and potential effectiveness of Dignity Therapy for older people in care homes: Study protocol

PubMed Central

Hall, Sue; Chochinov, Harvey; Harding, Richard; Murray, Scott; Richardson, Alison; Higginson, Irene J

2009-01-01

Background Although most older people living in nursing homes die there, there is a dearth of robust evaluations of interventions to improve their end-of-life care. Residents usually have multiple health problems making them heavily reliant on staff for their care, which can erode their sense of dignity. Dignity Therapy has been developed to help promote dignity and reduce distress. It comprises a recorded interview, which is transcribed, edited then returned to the patient, who can bequeath it to people of their choosing. Piloting has suggested that Dignity Therapy is beneficial to people dying of cancer and their families. The aims of this study are to assess the feasibility, acceptability and potential effectiveness of Dignity Therapy to reduce psychological and spiritual distress in older people reaching the end of life in care homes, and to pilot the methods for a Phase III RCT. Methods/design A randomised controlled open-label trial. Sixty-four residents of care homes for older people are randomly allocated to one of two groups: (i) Intervention (Dignity Therapy offered in addition to any standard care), and (ii) Control group (standard care). Recipients of the "generativity" documents are asked their views on taking part in the study and the therapy. Both quantitative and qualitative outcomes are assessed in face-to-face interviews at baseline and at approximately one and eight weeks after the intervention (equivalent in the control group). The primary outcome is residents' sense of dignity (potential effectiveness) assessed by the Patient Dignity Inventory. Secondary outcomes for residents include depression, hopefulness and quality of life. In view of the relatively small sample size, quantitative analysis is mainly descriptive. The qualitative analysis uses the Framework method. Discussion Dignity Therapy is brief, can be done at the bedside and could help both patients and their families. This detailed exploratory research shows if it is feasible to offer Dignity Therapy to residents of care homes, whether it is acceptable to them, their families and care home staff, if it is likely to be effective, and determine whether a Phase III RCT is desirable. Trial registration Current Controlled Clinical Trials: ISRCTN37589515 PMID:19317898

Individualised pelvic floor muscle training in women with pelvic organ prolapse (POPPY): a multicentre randomised controlled trial.

PubMed

Hagen, Suzanne; Stark, Diane; Glazener, Cathryn; Dickson, Sylvia; Barry, Sarah; Elders, Andrew; Frawley, Helena; Galea, Mary P; Logan, Janet; McDonald, Alison; McPherson, Gladys; Moore, Kate H; Norrie, John; Walker, Andrew; Wilson, Don

2014-03-01

Pelvic organ prolapse is common and is strongly associated with childbirth and increasing age. Women with prolapse are often advised to do pelvic floor muscle exercises, but evidence supporting the benefits of such exercises is scarce. We aimed to establish the effectiveness of one-to-one individualised pelvic floor muscle training for reducing prolapse symptoms. We did a parallel-group, multicentre, randomised controlled trial at 23 centres in the UK, one in New Zealand, and one in Australia, between June 22, 2007, and April 9, 2010. Female outpatients with newly-diagnosed, symptomatic stage I, II, or III prolapse were randomly assigned (1:1), by remote computer allocation with minimsation, to receive an individualised programme of pelvic floor muscle training or a prolapse lifestyle advice leaflet and no muscle training (control group). Outcome assessors, and investigators who were gynaecologists at trial sites, were masked to group allocation; the statistician was masked until after data analysis. Our primary endpoint was participants' self-report of prolapse symptoms at 12 months. Analysis was by intention-to-treat analysis. This trial is registered, number ISRCTN35911035. 447 eligible patients were randomised to the intervention group (n=225) or the control group (n=222). 377 (84%) participants completed follow-up for questionnaires at 6 months and 295 (66%) for questionnaires at 12 months. Women in the intervention group reported fewer prolapse symptoms (ie, a significantly greater reduction in the pelvic organ prolapse symptom score [POP-SS]) at 12 months than those in the control group (mean reduction in POP-SS from baseline 3.77 [SD 5.62] vs 2.09 [5.39]; adjusted difference 1.52, 95% CI 0.46-2.59; p=0.0053). Findings were robust to missing data. Eight adverse events (six vaginal symptoms, one case of back pain, and one case of abdominal pain) and one unexpected serious adverse event, all in women from the intervention group, were regarded as unrelated to the intervention or to participation in the study. One-to-one pelvic floor muscle training for prolapse is effective for improvement of prolapse symptoms. Long-term benefits should be investigated, as should the effects in specific subgroups. Chief Scientist Office of the Scottish Government Health and Social Care Directorates, New Zealand Lottery Board, and National Health and Medical Research Council (Australia). Copyright © 2014 Elsevier Ltd. All rights reserved.

EMBalance - validation of a decision support system in the early diagnostic evaluation and management plan formulation of balance disorders in primary care: study protocol of a feasibility randomised controlled trial.

PubMed

Rammazzo, Laura; Kikidis, Dimitris; Anwer, Amal; Macdonald, Nora; Kyrodimos, Efthymios; Maurer, Christoph; Wuyts, Floris; Luxon, Linda; Bibas, Athanasios; Bamiou, Doris-Eva

2016-09-05

Balance problems are caused by multiple factors and often lead to falls and related fractures, bringing large socio-economic costs. The complexity of balance control mechanisms, the lack of medical expertise, and the absence of specialised equipment contribute to the delayed or incorrect diagnosis and management ofthese patients. Advances in computer science have allowed the development of computer systems that support clinical diagnosis and treatment decisions based on individualised patient data. The aim of the EMBalance decision support system (DSS) is to support doctors facing this clinical challenge, to make a definitive diagnosis and implement an effective management plan. The EMBalance study will determine the accuracy of this supportive tool when used by non-specialist doctors. This study is funded by the European Union's Seventh Framework Programme. EMBalance is a proof-of-concept study designed as a non-commercial, international, multi-centre, single-blind, parallel-group randomised controlled trial to be carried out at four clinical sites in the United Kingdom, Germany, Greece and Belgium. The study is comprised of three stages: internal pilot, phase I (diagnosis) and stage II (management). For this purpose, 200 patients presenting with persistent dizziness (>3 months' duration) to primary care services will be randomised to either the intervention group (diagnostic assessment with the DSS) or a control group (diagnostic assessment without the DSS). Patients allocated to the intervention group will be assessed by a doctor with the support of the EMBalance DSS, while patients allocated to the control group will receive a visit as per standard practice. Ultimately, all patients' diagnoses and management plans will be certified by a consultant in neuro-otology. EMBalance is the first trial to test the accuracy of a DSS in both the diagnosis of and the management plan for vestibular disorders across the healthcare systems of four different countries. The EMBalance study is the result of a combined effort of engineers and physicians to develop an accurate tool to support non-specialist doctors, with no risk for the patient. This trial will provide reliable information about the benefits of implementing DSSs in primary care while supporting the feasibility of testing the EMBalance algorithms in further research. ClinicalTrials.gov NCT02704819 . Registered 29 February 2016.

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

PubMed

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

2015-12-29

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

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.

Efficacy and safety of oral solithromycin versus oral moxifloxacin for treatment of community-acquired bacterial pneumonia: a global, double-blind, multicentre, randomised, active-controlled, non-inferiority trial (SOLITAIRE-ORAL).

PubMed

Barrera, Carlos M; Mykietiuk, Analia; Metev, Hristo; Nitu, Mimi Floarea; Karimjee, Najumuddin; Doreski, Pablo Alexis; Mitha, Ismail; Tanaseanu, Cristina Mihaela; Molina, Joseph McDermott; Antonovsky, Yuri; Van Rensburg, Dirkie Johanna; Rowe, Brian H; Flores-Figueroa, Jose; Rewerska, Barbara; Clark, Kay; Keedy, Kara; Sheets, Amanda; Scott, Drusilla; Horwith, Gary; Das, Anita F; Jamieson, Brian; Fernandes, Prabhavathi; Oldach, David

2016-04-01

Community-acquired bacterial pneumonia (CABP) is a leading cause of morbidity and mortality, and treatment recommendations, each with specific limitations, vary globally. We aimed to compare the efficacy and safety of solithromycin, a novel macrolide, with moxifloxacin for treatment of CABP. We did this global, double-blind, double-dummy, randomised, active-controlled, non-inferiority trial at 114 centres in North America, Latin America, Europe, and South Africa. Patients (aged ≥18 years) with clinically and radiographically confirmed pneumonia of Pneumonia Outcomes Research Team (PORT) risk class II, III, or IV were randomly assigned (1:1), via an internet-based central block randomisation procedure (block size of four), to receive either oral solithromycin (800 mg on day 1, 400 mg on days 2-5, placebo on days 6-7) or oral moxifloxacin (400 mg on days 1-7). Randomisation was stratified by geographical region, PORT risk class (II vs III or IV), and medical history of asthma or chronic obstructive pulmonary disease. The study sponsor, investigators, staff, and patients were masked to group allocation. The primary outcome was early clinical response, defined as an improvement in at least two of four symptoms (cough, chest pain, sputum production, dyspnoea) with no worsening in any symptom at 72 h after the first dose of study drug, with a 10% non-inferiority margin. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT-01756339. Between Jan 3, 2013, and Sept 24, 2014, we randomly assigned 860 patients to receive solithromycin (n=426) or moxifloxacin (n=434). Patients were followed up to days 28-35 after first dose. Solithromycin was non-inferior to moxifloxacin in achievement of early clinical response: 333 (78·2%) patients had an early clinical response in the solithromycin group versus 338 (77·9%) patients in the moxifloxacin group (difference 0·29, 95% CI -5·5 to 6·1). Both drugs had a similar safety profile. 43 (10%) of 155 treatment-emergent adverse events in the solithromycin group and 54 (13%) of 154 such events in the moxifloxacin group were deemed to be related to study drug. The most common adverse events, mostly of mild severity, were gastrointestinal disorders, including diarrhoea (18 [4%] patients in the solithromycin group vs 28 [6%] patients in the moxifloxacin group), nausea (15 [4%] vs 17 [4%] patients) and vomiting (ten [2%] patients in each group); and nervous system disorders, including headache (19 [4%] vs 11 [3%] patients) and dizziness (nine [2%] vs seven [2%] patients). Oral solithromycin was non-inferior to oral moxifloxacin for treatment of patients with CABP, showing the potential to restore macrolide monotherapy for this indication. Cempra. Copyright © 2016 Elsevier Ltd. All rights reserved.

Self-management toolkit and delivery strategy for end-of-life pain: the mixed-methods feasibility study.

PubMed

Bennett, Michael I; Mulvey, Matthew R; Campling, Natasha; Latter, Sue; Richardson, Alison; Bekker, Hilary; Blenkinsopp, Alison; Carder, Paul; Closs, Jose; Farrin, Amanda; Flemming, Kate; Gallagher, Jean; Meads, David; Morley, Stephen; O'Dwyer, John; Wright-Hughes, Alexandra; Hartley, Suzanne

2017-12-01

Pain affects most people approaching the end of life and can be severe for some. Opioid analgesia is effective, but evidence is needed about how best to support patients in managing these medicines. To develop a self-management support toolkit (SMST) and delivery strategy and to test the feasibility of evaluating this intervention in a future definitive trial. Phase I - evidence synthesis and qualitative interviews with patients and carers. Phase II - qualitative semistructured focus groups and interviews with patients, carers and specialist palliative care health professionals. Phase III - multicentre mixed-methods single-arm pre-post observational feasibility study. Phase I - six patients and carers. Phase II - 15 patients, four carers and 19 professionals. Phase III - 19 patients recruited to intervention that experienced pain, living at home and were treated with strong opioid analgesia. Process evaluation interviews with 13 patients, seven carers and 11 study nurses. Self-Management of Analgesia and Related Treatments at the end of life (SMART) intervention comprising a SMST and a four-step educational delivery approach by clinical nurse specialists in palliative care over 6 weeks. Recruitment rate, treatment fidelity, treatment acceptability, patient-reported outcomes (such as scores on the Brief Pain Inventory, Self-Efficacy for Managing Chronic Disease Scale, Edmonton Symptom Assessment Scale, EuroQol-5 Dimensions, Satisfaction with Information about Medicines Scale, and feasibility of collecting data on health-care resource use for economic evaluation). Phase I - key themes on supported self-management were identified from evidence synthesis and qualitative interviews. Phase II - the SMST was developed and refined. The delivery approach was nested within a nurse-patient consultation. Phase III - intervention was delivered to 17 (89%) patients, follow-up data at 6 weeks were available on 15 patients. Overall, the intervention was viewed as acceptable and valued. Descriptive analysis of patient-reported outcomes suggested that interference from pain and self-efficacy were likely to be candidates for primary outcomes in a future trial. No adverse events related to the intervention were reported. The health economic analysis suggested that SMART could be cost-effective. We identified key limitations and considerations for a future trial: improve recruitment through widening eligibility criteria, refine the SMST resources content, enhance fidelity of intervention delivery, secure research nurse support at recruiting sites, refine trial procedures (including withdrawal process and data collection frequency), and consider a cluster randomised design with nurse as cluster unit. (1) The recruitment rate was lower than anticipated. (2) The content of the intervention was focused on strong opioids only. (3) The fidelity of intervention delivery was limited by the need for ongoing training and support. (4) Recruitment sites where clinical research nurse support was not secured had lower recruitment rates. (5) The process for recording withdrawal was not sufficiently detailed. (6) The number of follow-up visits was considered burdensome for some participants. (7) The feasibility trial did not have a control arm or assess randomisation processes. A future randomised controlled trial is feasible and acceptable. This study is registered as PROSPERO CRD42014013572; Current Controlled Trials ISRCTN35327119; and National Institute for Health Research (NIHR) Portfolio registration 162114. The NIHR Health Technology Assessment programme.

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

Over ground walking and body weight supported walking improve mobility equally in cerebral palsy: a randomised controlled trial.

PubMed

Swe, Ni Ni; Sendhilnnathan, Sunitha; van Den Berg, Maayken; Barr, Christopher

2015-11-01

To assess partial body weight supported treadmill training versus over ground training for walking ability in children with mild to moderate cerebral palsy. Randomised controlled trial. A Special Needs school in Singapore. Thirty children with cerebral palsy, aged 6-18, with a Gross Motor Function Classification System score of II-III. Two times 30 minute sessions of walking training per week for 8 weeks, progressed as tolerated, either over ground (control) or using partial body weight supported treadmill training (intervention). The 10 metre walk test, and the 6 minute walk test. Secondary measures were sub-sections D and E on the Gross Motor Function Measure. Outcomes were assessed at baseline, and after 4 and 8 weeks of training. There was no effect of group allocation on any outcome measure, while time was a significant factor for all outcomes. Walking speed improved significantly more in the intervention group by week 4 (0.109 (0.067)m/s vs 0.048 (0.071)m/s, P=0.024) however by week 8 the change from baseline was similar (intervention 0.0160 (0.069)m/s vs control 0.173 (0.109)m/s, P=0.697). All gains made by week 4 were significantly improved on by week 8 for the 10 metre walk test, 6 minute walk test, and the gross motor function measure. Partial body weight supported treadmill training is no more effective than over ground walking at improving aspects of walking and function in children with mild to moderate cerebral palsy. Gains seen in 4 weeks can be furthered by 8 weeks. © The Author(s) 2015.

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

PubMed

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

2014-10-06

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

Rich micronutrient fortification of locally produced infant food does not improve mental and motor development of Zambian infants: a randomised controlled trial

PubMed Central

Manno, Daniela; Kowa, Priscilla K.; Bwalya, Hellen K.; Siame, Joshua; Grantham-McGregor, Sally; Baisley, Kathy; De Stavola, Bianca L.; Jaffar, Shabbar; Filteau, Suzanne

2013-01-01

It is uncertain whether multiple micronutrients benefit the mental and psychomotor development of young children in developing countries. We conducted a randomised double-blind controlled trial to evaluate the effect of a richly micronutrient-fortified v. a basal fortified porridge on mental and psychomotor development in Zambian infants. Infants (n 743) were randomised at age 6 months to receive either the richly fortified or the basal fortified infant food and were followed up until 18 months of age. All the infants were evaluated monthly for achievement of a series of developmental milestones. The Bayley scales of infant development II were administered to a subsample of 502 infants at 6, 12 and 18 months. Rich micronutrient fortification had no significant benefit on the following: (a) number of developmental milestones achieved (rate ratio at 12 months = 1·00; 95 % CI 0·96, 1·05; P=0·81, adjusted for sex, socio-economic status and maternal education, with similar results at 15 and 18 months); (b) ages of walking unsupported (hazard ratio (HR) 1·04; 95 % CI 0·88, 1·24; P=0·63, adjusted for the above covariates) and of speaking three or four clear words (HR 1·01; 95 % CI 0·84, 1·20; P=0·94, adjusted for the above covariates); (c) mental development index (MDI) and psychomotor development index (PDI) of the Bayley scales (scores difference adjusted for baseline scores, age at the assessment, sex, socio-economic status, maternal education, language, age and HIV status: MDI 0·3 (95 % CI −0·5, 1·1), P=0·43; PDI −0·1 (95 % CI −0·9, 0·7), P=0·78). In conclusion, the results do not support the hypothesis that rich micronutrient fortification improves Zambian infants’ mental and motor development. PMID:21733297

The use of instrumented gait analysis for individually tailored interdisciplinary interventions in children with cerebral palsy: a randomised controlled trial protocol.

PubMed

Rasmussen, Helle Mätzke; Pedersen, Niels Wisbech; Overgaard, Søren; Hansen, Lars Kjaersgaard; Dunkhase-Heinl, Ulrike; Petkov, Yanko; Engell, Vilhelm; Baker, Richard; Holsgaard-Larsen, Anders

2015-12-07

Children with cerebral palsy (CP) often have an altered gait. Orthopaedic surgery, spasticity management, physical therapy and orthotics are used to improve the gait. Interventions are individually tailored and are planned on the basis of clinical examinations and standardised measurements to assess walking ('care as usual'). However, these measurements do not describe features in the gait that reflect underlying neuro-musculoskeletal impairments. This can be done with 3-dimensional instrumented gait analysis (IGA). The aim of this study is to test the hypothesis that improvements in gait following individually tailored interventions when IGA is used are superior to those following 'care as usual'. A prospective, single blind, randomised, parallel group study will be conducted. Children aged 5 to 8 years with spastic CP, classified at Gross Motor Function Classification System levels I or II, will be included. The interventions under investigation are: 1) individually tailored interdisciplinary interventions based on the use of IGA, and 2) 'care as usual'. The primary outcome is gait measured by the Gait Deviation Index. Secondary outcome measures are: walking performance (1-min walk test) and patient-reported outcomes of functional mobility (Pediatric Evaluation of Disability Inventory), health-related quality of life (The Pediatric Quality of Life Inventory Cerebral Palsy Module) and overall health, pain and participation (The Pediatric Outcome Data Collection Instrument). The primary endpoint for assessing the outcome of the two interventions will be 52 weeks after start of intervention. A follow up will also be performed at 26 weeks; however, exclusively for the patient-reported outcomes. To our knowledge, this is the first randomised controlled trial comparing the effects of an individually tailored interdisciplinary intervention based on the use of IGA versus 'care as usual' in children with CP. Consequently, the study will provide novel evidence for the use of IGA. ClinicalTrials.gov NCT02160457 . Registered June 2, 2014.

Effects of dabigatran on the cellular and protein phase of coagulation in patients with coronary artery disease on dual antiplatelet therapy with aspirin and clopidogrel. Results from a prospective, randomised, double-blind, placebo-controlled study.

PubMed

Franchi, Francesco; Rollini, Fabiana; Cho, Jung Rae; King, Rhodri; Phoenix, Fladia; Bhatti, Mona; DeGroat, Christopher; Tello-Montoliu, Antonio; Zenni, Martin M; Guzman, Luis A; Bass, Theodore A; Ajjan, Ramzi A; Angiolillo, Dominick J

2016-03-01

There is growing interest in understanding the effects of adding an oral anticoagulant in patients on dual antiplatelet therapy (DAPT). Vitamin K antagonists (VKAs) and clopidogrel represent the most broadly utilised oral anticoagulant and P2Y12 receptor inhibitor, respectively. However, VKAs can interfere with clopidogrel metabolism via the cytochrome P450 (CYP) system which in turn may result in an increase in platelet reactivity. Dabigatran is a direct acting (anti-II) oral anticoagulant which does not interfere with CYP and has favourable safety and efficacy profiles compared with VKAs. The pharmacodynamic (PD) effects on platelet reactivity and clot kinetic of adjunctive dabigatran therapy in patients on DAPT are poorly explored. In this prospective, randomised, double-blind, placebo-controlled PD study, patients (n=30) on maintenance DAPT with aspirin and clopidogrel were randomised to either dabigatran 150 mg bid or placebo for seven days. PD testing was performed before and after treatment using four different assays exploring multiple pathways of platelet aggregation and fibrin clot kinetics: light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA), kaolin-activated thromboelastography (TEG) and turbidimetric assays. There were no differences in multiple measures of platelet reactivity investigating purinergic and non-purinergic signaling pathways assessed by LTA, MEA and TEG platelet mapping. Dabigatran significantly increased parameters related to thrombin activity and thrombus generation, and delayed fibrin clot formation, without affecting clot structure or fibrinolysis. In conclusion, in patients on DAPT with aspirin and clopidogrel, adjunctive dabigatran therapy is not associated with modulation of profiles of platelet reactivity as determined by several assays assessing multiple platelet signalling pathways. However, dabigatran significantly interferes with parameters related to thrombin activity and delays fibrin clot formation.

Post-prandial reflux suppression by a raft-forming alginate (Gaviscon Advance) compared to a simple antacid documented by magnetic resonance imaging and pH-impedance monitoring: mechanistic assessment in healthy volunteers and randomised, controlled, double-blind study in reflux patients.

PubMed

Sweis, R; Kaufman, E; Anggiansah, A; Wong, T; Dettmar, P; Fried, M; Schwizer, W; Avvari, R K; Pal, A; Fox, M

2013-06-01

Alginates form a raft above the gastric contents, which may suppress gastro-oesophageal reflux; however, inconsistent effects have been reported in mechanistic and clinical studies. To visualise reflux suppression by an alginate-antacid [Gaviscon Advance (GA), Reckitt Benckiser, UK] compared with a nonraft-forming antacid using magnetic resonance imaging (MRI), and to determine the feasibility of pH-impedance monitoring for assessment of reflux suppression by alginates. Two studies were performed: (i) GA and antacid (Alucol, Wander Ltd, Switzerland) were visualised in the stomach after ingestion in 12 healthy volunteers over 30 min after a meal by MRI, with reflux events documented by manometry. (ii) A randomised controlled, double-blind cross-over trial of post-prandial reflux suppression documented by pH-impedance in 20 patients randomised to GA or antacid (Milk of Magnesia; Boots, UK) after two meals taken 24 h apart. MRI visualized a "mass" of GA form at the oesophago-gastric junction (OGJ); simple antacid sank to the distal stomach. The number of post-prandial common cavity reflux events was less with GA than antacid [median 2 (0-5) vs. 5 (1-11); P < 0.035]. Distal reflux events and acid exposure measured by pH-impedance were similar after GA and antacid. There was a trend to reduced proximal reflux events with GA compared with antacid [10.5 (8.9) vs. 13.9 (8.3); P = 0.070]. Gaviscon Advance forms a 'mass' close to the OGJ and significantly suppresses reflux compared with a nonraft-forming antacid. Standard pH-impedance monitoring is suitable for clinical studies of GA in gastro-oesophageal reflux disease patients where proximal reflux is the primary outcome. © 2013 Blackwell Publishing Ltd.

Scoliosis and dental occlusion: a review of the literature

PubMed Central

2011-01-01

Background Idiopathic scoliosis is a deformity without clear etiology. It is unclear wether there is an association between malocclusion and scoliosis. Several types of occlusion were described in subjects with scoliosis, mostly case-reports. Objectives The aim of this review was to evaluate the type of occluslins more prevalent in subjects with scoliosis Search strategy All randomised and controlled clinical trials identified from the Cochrane Oral Health Group Trials Register, a MEDLINE search using the Mesh term scoliosis, malocclusion, and relevant free text words, and the bibliographies of papers and review articles which reported the outcome of orthodontic treatment in subjects with scoliosis that were published as abstracts or papers between 1970 and 2010. Selection criteria All randomised and controlled clinical trials published as full papers or abstracts which reported quantitative data on the outcomes malocclusion in subjects with scoliosis. Data collection and analysis Data were extracted without blinding to the authors, age of patients or type of occlusion. Main results Using the search strategy eleven observational longitudinal studies were identified. No randomized clinical trials were recorded. Twenty-three cross-sectional studies were recorderd, and the others studies were reviews, editorials, case-reports, or opinions. The clinical trials were often not controlled and were about the cephalometric evaluation after treatment with the modified Milwuakee brace, followed by the orthodontic treatment of the class II relationship with a functional appliance. Clinical trials also included the study of the associations between scoliosis and unilateral crossbite, in children with asymmetry of the upper cervical spine. This association was also investigated in rats, pigs and rabbits in clinical trials. The other associations between scoliosis and occlusion seems to be based only on cross-sectional studies, case-reports, opinions. Authors' conclusions Based on selected studies, this review concludes that there is plausible evidence for an increased prevalence of unilateral Angle Class II malocclusions associated with scoliosis, and an increased risk of lateral crossbite, midline deviation in children affected by scoliosis. Also, documentation of associations between reduced range of lateral movements and scoliosis seem convincing. Data are also mentioned about the association between plagiocephaly and scoliosis. PMID:21801357

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

Evaluation of the clinical benefit of an electromagnetic navigation system for CT-guided interventional radiology procedures in the thoraco-abdominal region compared with conventional CT guidance (CTNAV II): study protocol for a randomised controlled trial.

PubMed

Rouchy, R C; Moreau-Gaudry, A; Chipon, E; Aubry, S; Pazart, L; Lapuyade, B; Durand, M; Hajjam, M; Pottier, S; Renard, B; Logier, R; Orry, X; Cherifi, A; Quehen, E; Kervio, G; Favelle, O; Patat, F; De Kerviler, E; Hughes, C; Medici, M; Ghelfi, J; Mounier, A; Bricault, I

2017-07-06

Interventional radiology includes a range of minimally invasive image-guided diagnostic and therapeutic procedures that have become routine clinical practice. Each procedure involves a percutaneous needle insertion, often guided using computed tomography (CT) because of its availability and usability. However, procedures remain complicated, in particular when an obstacle must be avoided, meaning that an oblique trajectory is required. Navigation systems track the operator's instruments, meaning the position and progression of the instruments are visualised in real time on the patient's images. A novel electromagnetic navigation system for CT-guided interventional procedures (IMACTIS-CT®) has been developed, and a previous clinical trial demonstrated improved needle placement accuracy in navigation-assisted procedures. In the present trial, we are evaluating the clinical benefit of the navigation system during the needle insertion step of CT-guided procedures in the thoraco-abdominal region. This study is designed as an open, multicentre, prospective, randomised, controlled interventional clinical trial and is structured as a standard two-arm, parallel-design, individually randomised trial. A maximum of 500 patients will be enrolled. In the experimental arm (navigation system), the procedures are carried out using navigation assistance, and in the active comparator arm (CT), the procedures are carried out with conventional CT guidance. The randomisation is stratified by centre and by the expected difficulty of the procedure. The primary outcome of the trial is a combined criterion to assess the safety (number of serious adverse events), efficacy (number of targets reached) and performance (number of control scans acquired) of navigation-assisted, CT-guided procedures as evaluated by a blinded radiologist and confirmed by an expert committee in case of discordance. The secondary outcomes are (1) the duration of the procedure, (2) the satisfaction of the operator and (3) the irradiation dose delivered, with (4) subgroup analysis according to the expected difficulty of the procedure, as well as an evaluation of (5) the usability of the device. This trial addresses the lack of published high-level evidence studies in which navigation-assisted CT-guided interventional procedures are evaluated. This trial is important because it addresses the problems associated with conventional CT guidance and is particularly relevant because the number of interventional radiology procedures carried out in routine clinical practice is increasing. ClinicalTrials.gov identifier: NCT01896219 . Registered on 5 July 2013.

Developing and piloting a peer mentoring intervention to reduce teenage pregnancy in looked-after children and care leavers: an exploratory randomised controlled trial.

PubMed

Mezey, Gillian; Meyer, Deborah; Robinson, Fiona; Bonell, Chris; Campbell, Rona; Gillard, Steve; Jordan, Peter; Mantovani, Nadia; Wellings, Kaye; White, Sarah

2015-10-01

Looked-after children (LAC) are at greater risk of teenage pregnancy than non-LAC, which is associated with adverse health and social consequences. Existing interventions have failed to reduce rates of teenage pregnancy in LAC. Peer mentoring is proposed as a means of addressing many of the factors associated with the increased risk of teenage pregnancy in this group. To develop a peer mentoring intervention to reduce teenage pregnancy in LAC. Phase I and II randomised controlled trial of a peer mentoring intervention for LAC; scoping exercise and literature search; national surveys of social care professionals and LAC; and focus groups and interviews with social care professionals, mentors and mentees. Three local authorities (LAs) in England. LAC aged 14-18 years (mentees/care as usual) and 19-25 years (mentors). Recruitment and training of mentors; randomisation and matching of mentors to mentees; and 1-year individual peer mentoring. pregnancy in LAC aged 14-18 years. sexual attitudes, behaviour and knowledge; psychological health; help-seeking behaviour; locus of control; and attachment style. A health economic evaluation was also carried out. In total, 54% of target recruitment was reached for the exploratory trial and 13 out of 20 mentors (65%) and 19 out of 30 LAC aged 14-18 years (63%) (recruited during Phases I and II) were retained in the research. The training programme was acceptable and could be manualised and replicated. Recruitment and retention difficulties were attributed to systemic problems and LA lack of research infrastructure and lack of additional funding to support and sustain such an intervention. Mentees appeared to value the intervention but had difficulty in meeting weekly as required. Only one in four of the relationships continued for the full year. A future Phase III trial would require the intervention to be modified to include provision of group and individual peer mentoring; internal management of the project, with support from an external agency such as a charity or the voluntary sector; funds to cover LA research costs, including the appointment of a dedicated project co-ordinator; a reduction in the lower age for mentee recruitment and an increase in the mentor recruitment age to 21 years; and the introduction of a more formal recruitment and support structure for mentors. Given the problems identified and described in mounting this intervention, a new development phase followed by a small-scale exploratory trial incorporating these changes would be necessary before proceeding to a Phase III trial. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 85. See the NIHR Journals Library website for further project information.

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 study of short message service text messaging as a surveillance tool for alcohol consumption and vehicle for interventions in university students

PubMed Central

2013-01-01

Background Practitioners who come into contact with the intoxicated, such as those in unscheduled care, often have limited resources to provide structured interventions. There is therefore a need for cost-effective alcohol interventions requiring minimal input. This study assesses the barriers, acceptability and validity of text messaging to collect daily alcohol consumption data and explores the feasibility of a text-delivered intervention in an exploratory randomised controlled trial. Methods Study I. Participants (n = 82) completed the initial online screening survey and those eligible were asked each day, for 157 days via text message, to reply with the number of alcohol units consumed the previous day. Analyses compared standard measures of hazardous consumption with self-report alcohol use. Attrition and sampling biases were examined. Study I included secondary exploratory analyses using data from 70 participants to determine associations between events (including Christmas and other celebratory occasions) and consumption. Study I further included the thematic analysis of semi-structured interview data and assessed the feasibility of and barriers to surveillance and interventions delivered through text messaging. Developing findings from Study I, Study II developed an exploratory randomised control trial that delivered a single message on monthly alcohol expenditure in order to assess effect size and test generalisability. Results Self-report alcohol consumption data was significantly associated with FAST and AUDIT scores. Attrition from the study was not associated with greater alcohol use. Greater alcohol use was observed on Fridays, Saturdays and Wednesdays as were notable celebratory events. Interview data indicated that text messaging was acceptable to participants and preferred over email and web-based methods. The exploratory randomised controlled trial suggested that a simple text delivered intervention might be effective in eliciting a reduction in alcohol consumption in a future trial. Conclusions The ubiquity of mobile telephones and the acceptability of text messaging suggests that this approach can be developed as a surveillance tool to collect high frequency consumption data to identify periods of vulnerability and that it can offer a platform through which targeted interventions can be delivered. PMID:24160674

Fast-track surgery after gynaecological oncological surgery: study protocol for a prospective randomised controlled trial.

PubMed

Cui, Ling; Shi, Yu; Zhang, G N

2016-12-15

Fast-track surgery (FTS), also known as enhanced recovery after surgery, is a multidisciplinary approach to accelerate recovery, reduce complications, minimise hospital stay without increasing readmission rates, and reduce health care costs, all without compromising patient safety. The advantages of FTS in abdominal surgery most likely extend to gynaecological surgery, but this is an assumption, as FTS in elective gynaecological surgery has not been well studied. No consensus guidelines have been developed for gynaecological oncological surgery although surgeons have attempted to introduce slightly modified FTS programmes for patients undergoing such surgery. To our knowledge, there are no published randomised controlled trials; however, some studies have shown that FTS in gynaecological oncological surgery leads to early hospital discharge with high levels of patient satisfaction. The aim of this study is whether FTS reduces the length of stay in hospital compared to traditional management. The secondary aim is whether FTS is associated with any increase in post-surgical complications compared to traditional management (for both open and laparoscopic surgery). This trial will prospectively compare FTS and traditional management protocols. The primary endpoint is the length of post-operative hospitalisation (days, mean ± standard deviation), defined as the number of days between the date of discharge and the date of surgery. The secondary endpoints are complications in both groups (FTS versus traditional protocol) occurring during the first 3 months post-operatively including infection (wound infection, lung infection, intraperitoneal infection), post-operative nausea and vomiting, ileus, post-operative haemorrhage, post-operative thrombosis, and the Acute Physiology and Chronic Health Enquiry II score. The advantages of FTS most likely extend to gynaecology, although, to our knowledge, there are no randomised controlled trials. The aim of this study is to compare the post-operative length of hospitalisation after major gynaecological or gynaecological oncological surgery and to analyse patients' post-operative complications. This trial may reveal whether FTS leads to early hospital discharge with few complications after gynaecological surgery. NCT02687412 . Approval Number: SCCHEC20160001. Date of registration: registered on 23 February 2016.

A written self-help intervention for depressed adults comparing behavioural activation combined with physical activity promotion with a self-help intervention based upon behavioural activation alone: study protocol for a parallel group pilot randomised controlled trial (BAcPAc).

PubMed

Farrand, Paul; Pentecost, Claire; Greaves, Colin; Taylor, Rod S; Warren, Fiona; Green, Colin; Hillsdon, Melvyn; Evans, Phil; Welsman, Jo; Taylor, Adrian H

2014-05-29

Challenges remain to find ways to support patients with depression who have low levels of physical activity (PA) to overcome perceived barriers and enhance the perceived value of PA for preventing future relapse. There is an evidence-base for behavioural activation (BA) for depression, which focuses on supporting patients to restore activities that have been avoided, but practitioners have no specific training in promoting PA. We aimed to design and evaluate an integrated BA and PA (BAcPAc) practitioner-led, written, self-help intervention to enhance both physical and mental health. This study is informed by the Medical Research Council Complex Intervention Framework and describes a protocol for a pilot phase II randomised controlled trial (RCT) to test the feasibility and acceptability of the trial methods to inform a definitive phase III RCT. Following development of the augmented written self-help intervention (BAcPAc) incorporating behavioural activation with physical activity promotion, depressed adults are randomised to receive up to 12 sessions over a maximum of 4 months of either BAcPAc or behavioural activation alone within a written self-help format, which represents treatment as usual. The study is located within two 'Improving Access to Psychological Therapies' services in South West England, with both written self-help interventions supported by mental health paraprofessionals. Measures assessed at 4, 9, and 12 month follow-up include the following: CIS-R, PHQ-9, accelerometer recorded (4 months only) and self-reported PA, body mass index, blood pressure, Insomnia Severity Index, quality of life, and health and social care service use. Process evaluation will include analysis of recorded support sessions and patient and practitioner interviews. At the time of writing the study has recruited 60 patients. The feasibility outcomes will inform a definitive RCT to assess the clinical and cost-effectiveness of the augmented BAcPAc written self-help intervention to reduce depression and depressive relapse, and bring about improvements across a range of physical health outcomes. Current Controlled Trials ISRCTN74390532, 26.03.2013.

A randomised controlled trial of an intervention to increase the implementation of a healthy canteen policy in Australian primary schools: study protocol.

PubMed

Wolfenden, Luke; Nathan, Nicole; Williams, Christopher M; Delaney, Tessa; Reilly, Kathryn L; Freund, Megan; Gillham, Karen; Sutherland, Rachel; Bell, Andrew C; Campbell, Libby; Yoong, Serene; Wyse, Rebecca; Janssen, Lisa M; Preece, Sarah; Asmar, Melanie; Wiggers, John

2014-10-11

The implementation of healthy school canteen policies has been recommended as a strategy to help prevent unhealthy eating and excessive weight gain. Internationally, research suggests that schools often fail to implement practices consistent with healthy school canteen policies. Without a population wide implementation, the potential benefits of these policies will not be realised. The aim of this trial is to assess the effectiveness of an implementation intervention in increasing school canteen practices consistent with a healthy canteen policy of the New South Wales (NSW), Australia, government known as the 'Fresh Tastes @ School NSW Healthy School Canteen Strategy'. The parallel randomised trial will be conducted in 70 primary schools located in the Hunter region of New South Wales, Australia. Schools will be eligible to participate if they are not currently meeting key components of the healthy canteen policy. Schools will be randomly allocated after baseline data collection in a 1:1 ratio to either an intervention or control group using a computerised random number function in Microsoft Excel. Thirty-five schools will be selected to receive a multi-component intervention including implementation support from research staff, staff training, resources, recognition and incentives, consensus and leadership strategies, follow-up support and implementation feedback. The 35 schools allocated to the control group will not receive any intervention support as part of the research trial. The primary outcome measures will be i) the proportion of schools with a canteen menu that does not contain foods or beverages restricted from regular sale ('red' and 'banned' items) and ii) the proportion of schools where healthy canteen items ('green' items) represent the majority (>50%) of products listed on the menu. Outcome data will be collected via a comprehensive menu audit, conducted by dietitians blind to group allocation. Intervention effectiveness will be assessed using logistic regression models adjusting for baseline values. The proposed trial will represent a novel contribution to the literature, being the first randomised trial internationally to examine the effectiveness of an intervention to facilitate implementation of a healthy canteen policy. Australian New Zealand Clinical Trials Registry ACTRN12613000311752.

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.

Benefits of Bifidobacterium breve M-16V Supplementation in Preterm Neonates - A Retrospective Cohort Study.

PubMed

Patole, Sanjay K; Rao, Shripada C; Keil, Anthony D; Nathan, Elizabeth A; Doherty, Dorota A; Simmer, Karen N

2016-01-01

Systematic reviews of randomised controlled trials report that probiotics reduce the risk of necrotising enterocolitis (NEC) in preterm neonates. To determine whether routine probiotic supplementation (RPS) to preterm neonates would reduce the incidence of NEC. The incidence of NEC ≥ Stage II and all-cause mortality was compared for an equal period of 24 months 'before' (Epoch 1) and 'after' (Epoch 2) RPS with Bifidobacterium breve M-16V in neonates <34 weeks. Multivariate logistic regression analysis was conducted to adjust for relevant confounders. A total of 1755 neonates (Epoch I vs. II: 835 vs. 920) with comparable gestation and birth weights were admitted. There was a significant reduction in NEC ≥ Stage II: 3% vs. 1%, adjusted odds ratio (aOR) = 0.43 (95%CI: 0.21-0.87); 'NEC ≥ Stage II or all-cause mortality': 9% vs. 5%, aOR = 0.53 (95%CI: 0.32-0.88); but not all-cause mortality alone: 7% vs. 4%, aOR = 0.58 (95% CI: 0.31-1.06) in Epoch II. The benefits in neonates <28 weeks did not reach statistical significance: NEC ≥ Stage II: 6% vs. 3%, aOR 0.51 (95%CI: 0.20-1.27), 'NEC ≥ Stage II or all-cause mortality', 21% vs. 14%, aOR = 0.59 (95%CI: 0.29-1.18); all-cause mortality: 17% vs. 11%, aOR = 0.63 (95%CI: 0.28-1.41). There was no probiotic sepsis. RPS with Bifidobacterium breve M-16V was associated with decreased NEC≥ Stage II and 'NEC≥ Stage II or all-cause mortality' in neonates <34 weeks. Large sample size is required to assess the potential benefits of RPS in neonates <28 weeks.

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.

Efficacy and safety of the angiotensin II receptor blocker losartan for hypertrophic cardiomyopathy: the INHERIT randomised, double-blind, placebo-controlled trial.

PubMed

Axelsson, Anna; Iversen, Kasper; Vejlstrup, Niels; Ho, Carolyn; Norsk, Jakob; Langhoff, Lasse; Ahtarovski, Kiril; Corell, Pernille; Havndrup, Ole; Jensen, Morten; Bundgaard, Henning

2015-02-01

No medical treatment has been reliably shown to halt or reverse disease progression in hypertrophic cardiomyopathy, but the results of several pilot studies have suggested beneficial effects of angiotensin II receptor blockers on left ventricular hypertrophy and fibrosis, which are predictive of an adverse outcome. We aimed to assess the effect of the angiotensin II receptor blocker losartan on left ventricular hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy. In this single-centre, randomised, double-blind, placebo-controlled trial, adult patients (aged 18 years and older) with obstructive or non-obstructive hypertrophic cardiomyopathy were randomly assigned via computer-based system to losartan (100 mg per day) or placebo for 12 months. Patients and investigators were masked to assigned treatment. The primary endpoint was change in left ventricular mass as assessed by cardiac magnetic resonance imaging (CMR) or CT. Efficacy analyses were done in the modified intention-to-treat population (all patients with data available at the 12-month follow-up). The trial is registered with ClinicalTrials.gov, number NCT01447654. Between Dec 1, 2011, and May 1, 2013, 318 patients were screened. 133 patients (mean age 52 years [SD 13], 35% women) consented and were randomly assigned to placebo (n=69) or losartan (n=64). 124 (93%) patients completed the study and were included in the modified intention-to-treat analysis for the primary endpoint. After 12 months we noted no significant difference in the change in left ventricular mass between the placebo group and the losartan group (mean difference 1 g/m(2), 95% CI -3 to 6; p=0·60). A decrease in systolic blood pressure in the losartan group (from mean 127 mm Hg [SD 12] to 121 mm Hg [14]; p=0·0001) confirmed drug compliance; blood pressure did not decrease in the placebo group. Two (2%) patients, both in the placebo group, died from sudden cardiac death during follow-up. In the losartan group, one (1%) patient had angioedema, one (1%) had deterioration of renal function, and one (1%) had hyperkalaemia. Treatment was well tolerated by patients with left ventricular outflow obstruction at baseline. Our findings challenge the generally held view that angiotensin II receptor blockers reduce cardiac hypertrophy. Treatment with losartan was safe, suggesting that it can be used for other indications in patients with hypertrophic cardiomyopathy, irrespective of obstructive physiology. Additional studies are needed to assess the effect of angiotensin II receptor blockers in preclinical hypertrophic cardiomyopathy-eg, in genotype-positive but phenotype-negative individuals. Copyright © 2015 Elsevier Ltd. All rights reserved.

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…

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.

A mobile phone application for the assessment and management of youth mental health problems in primary care: health service outcomes from a randomised controlled trial of mobiletype.

PubMed

Reid, Sophie C; Kauer, Sylvia D; Hearps, Stephen J C; Crooke, Alexander H D; Khor, Angela S; Sanci, Lena A; Patton, George C

2013-06-19

GPs detect at best 50c of mental health problems in young people. Barriers to detecting mental health problems include lack of screening tools, limited appointment times and young people's reluctance to report mental health symptoms to GPs. The mobiletype program is a mobile phone mental health assessment and management application which monitors mood, stress and everyday activities then transmits this information to general practitioners (GPs) via a secure website in summary format for medical review. The current aims were to examine: (i) mobiletype as a clinical assistance tool, ii) doctor-patient rapport and, iii) pathways to care. We conducted a randomised controlled trial in primary care with patients aged 14 to 24 years recruited from rural and metropolitan general practices. GPs identified and referred eligible participants (those with mild or more mental health concerns) who were randomly assigned to either the intervention group (where mood, stress and daily activities were monitored) or the attention-comparison group (where only daily activities were monitored). Both groups self-monitored for 2 to 4 weeks and reviewed the monitoring data with their GP. GPs, participants and researchers were blind to group allocation at randomisation. GPs assessed the mobiletype program as a clinical assistant tool. Doctor-patient rapport was assessed using the General Practice Assessment Questionnaire Communication and Enablement subscales, and the Trust in Physician Scale (TPS). Pathways to care was measured using The Party Project's Exit Interview. Of the 163 participants assessed for eligibility, 118 were randomised and 114 participants were included in analyses (intervention n = 68, attention-comparison n = 46). T-tests showed that the intervention program increased understanding of patient mental health, assisted in decisions about medication/referral and helped in diagnosis when compared to the attention-comparison program. Mixed model analysis showed no differences in GP-patient rapport nor in pathways to care. We conducted the first RCT of a mobile phone application in the mental health assessment and management of youth mental health in primary care. This study suggests that mobiletype has much to offer GPs in the often difficult and time-consuming task of assessment and management of youth mental health problems in primary care. ClinicalTrials.gov NCT00794222.

Speech therapy for children with dysarthria acquired before three years of age.

PubMed

Pennington, Lindsay; Parker, Naomi K; Kelly, Helen; Miller, Nick

2016-07-18

Children with motor impairments often have the motor speech disorder dysarthria, a condition which effects the tone, strength and co-ordination of any or all of the muscles used for speech. Resulting speech difficulties can range from mild, with slightly slurred articulation and breathy voice, to profound, with an inability to produce any recognisable words. Children with dysarthria are often prescribed communication aids to supplement their natural forms of communication. However, there is variation in practice regarding the provision of therapy focusing on voice and speech production. Descriptive studies have suggested that therapy may improve speech, but its effectiveness has not been evaluated. To assess whether any speech and language therapy intervention aimed at improving the speech of children with dysarthria is more effective in increasing children's speech intelligibility or communicative participation than no intervention at all , and to compare the efficacy of individual types of speech language therapy in improving the speech intelligibility or communicative participation of children with dysarthria. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015 , Issue 7 ), MEDLINE, EMBASE, CINAHL , LLBA, ERIC, PsychInfo, Web of Science, Scopus, UK National Research Register and Dissertation Abstracts up to July 2015, handsearched relevant journals published between 1980 and July 2015, and searched proceedings of relevant conferences between 1996 to 2015. We placed no restrictions on the language or setting of the studies. A previous version of this review considered studies published up to April 2009. In this update we searched for studies published from April 2009 to July 2015. We considered randomised controlled trials and studies using quasi-experimental designs in which children were allocated to groups using non-random methods. One author (LP) conducted searches of all databases, journals and conference reports. All searches included a reliability check in which a second review author independently checked a random sample comprising 15% of all identified reports. We planned that two review authors would independently assess the quality and extract data from eligible studies. No randomised controlled trials or group studies were identified. This review found no evidence from randomised trials of the effectiveness of speech and language therapy interventions to improve the speech of children with early acquired dysarthria. Rigorous, fully powered randomised controlled trials are needed to investigate if the positive changes in children's speech observed in phase I and phase II studies are generalisable to the population of children with early acquired dysarthria served by speech and language therapy services. Research should examine change in children's speech production and intelligibility. It must also investigate children's participation in social and educational activities, and their quality of life, as well as the cost and acceptability of interventions.

Promoting smoking cessation in Pakistani and Bangladeshi men in the UK: pilot cluster randomised controlled trial of trained community outreach workers

PubMed Central

2011-01-01

Background Smoking prevalence is high among Pakistani and Bangladeshi men in the UK, but there are few tailored smoking cessation programmes for Pakistani and Bangladeshi communities. The aim of this study was to pilot a cluster randomised controlled trial comparing the effectiveness of Pakistani and Bangladeshi smoking cessation outreach workers with standard care to improve access to and the success of English smoking cessation services. Methods A pilot cluster randomised controlled trial was conducted in Birmingham, UK. Geographical lower layer super output areas were used to identify natural communities where more than 10% of the population were of Pakistani and Bangladeshi origin. 16 agglomerations of super output areas were randomised to normal care controls vs. outreach intervention. The number of people setting quit dates using NHS services, validated abstinence from smoking at four weeks, and stated abstinence at three and six months were assessed. The impact of the intervention on choice and adherence to treatments, attendance at clinic appointments and patient satisfaction were also assessed. Results We were able to randomise geographical areas and deliver the outreach worker-based services. More Pakistani and Bangladeshi men made quit attempts with NHS services in intervention areas compared with control areas, rate ratio (RR) 1.32 (95%CI: 1.03-1.69). There was a small increase in the number of 4-week abstinent smokers in intervention areas (RR 1.30, 95%CI: 0.82-2.06). The proportion of service users attending weekly appointments was lower in intervention areas than control areas. No difference was found between intervention and control areas in choice and adherence to treatments or patient satisfaction with the service. The total cost of the intervention was £124,000; an estimated cost per quality-adjusted life year (QALY) gained of £8,500. Conclusions The intervention proved feasible and acceptable. Outreach workers expanded reach of smoking cessation services in diverse locations of relevance to Pakistani and Bangladeshi communities. The outreach worker model has the potential to increase community cessation rates and could prove cost-effective, but needs evaluating definitively in a larger, appropriately powered, randomised controlled trial. These future trials of outreach interventions need to be of sufficient duration to allow embedding of new models of service delivery. Trial registration Current Controlled Trials ISRCTN82127540 PMID:21854596

An Audit and Feedback Intervention for Reducing Antibiotic Prescribing in General Dental Practice: The RAPiD Cluster Randomised Controlled Trial.

PubMed

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

2016-08-01

Dentists prescribe approximately 10% of antibiotics dispensed in UK community pharmacies. Despite clear clinical guidance, dentists often prescribe antibiotics inappropriately. This cluster-randomised controlled trial used routinely collected National Health Service (NHS) dental prescribing and treatment claim data to compare the impact of individualised audit and feedback (A&F) interventions on dentists' antibiotic prescribing rates. All 795 antibiotic prescribing NHS general dental practices in Scotland were included. Practices were randomised to the control (practices = 163; dentists = 567) or A&F intervention group (practices = 632; dentists = 1,999). A&F intervention practices were allocated to one of two A&F groups: (1) individualised graphical A&F comprising a line graph plotting an individual dentist's monthly antibiotic prescribing rate (practices = 316; dentists = 1,001); or (2) individualised graphical A&F plus a written behaviour change message synthesising and reiterating national guidance recommendations for dental antibiotic prescribing (practices = 316; dentists = 998). Intervention practices were also simultaneously randomised to receive A&F: (i) with or without a health board comparator comprising the addition of a line to the graphical A&F plotting the monthly antibiotic prescribing rate of all dentists in the health board; and (ii) delivered at 0 and 6 mo or at 0, 6, and 9 mo, giving a total of eight intervention groups. The primary outcome, measured by the trial statistician who was blinded to allocation, was the total number of antibiotic items dispensed per 100 NHS treatment claims over the 12 mo post-delivery of the baseline A&F. Primary outcome data was available for 152 control practices (dentists = 438) and 609 intervention practices (dentists = 1,550). At baseline, the number of antibiotic items prescribed per 100 NHS treatment claims was 8.3 in the control group and 8.5 in the intervention group. At follow-up, antibiotic prescribing had decreased by 0.4 antibiotic items per 100 NHS treatment claims in control practices and by 1.0 in intervention practices. This represents a significant reduction (-5.7%; 95% CI -10.2% to -1.1%; p = 0.01) in dentists' prescribing rate in the intervention group relative to the control group. Intervention subgroup analyses found a 6.1% reduction in the antibiotic prescribing rate of dentists who had received the written behaviour change message relative to dentists who had not (95% CI -10.4% to -1.9%; p = 0.01). There was no significant between-group difference in the prescribing rate of dentists who received a health board comparator relative to those who did not (-4.3%; 95% CI -8.6% to 0.1%; p = 0.06), nor between dentists who received A&F at 0 and 6 mo relative to those who received A&F at 0, 6, and 9 mo (0.02%; 95% CI -4.2% to 4.2%; p = 0.99). The key limitations relate to the use of routinely collected datasets which did not allow evaluation of any effects on inappropriate prescribing. A&F derived from routinely collected datasets led to a significant reduction in the antibiotic prescribing rate of dentists. Current Controlled Trials ISRCTN49204710.

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.

A pilot randomised clinical trial of physiotherapy (manual therapy, exercise, and education) for early-onset hip osteoarthritis post-hip arthroscopy.

PubMed

Kemp, Joanne; Moore, Kate; Fransen, Marlene; Russell, Trevor; Freke, Matthew; Crossley, Kay M

2018-01-01

Despite the increasing use of hip arthroscopy for hip pain, there is no level 1 evidence to support physiotherapy rehabilitation programs following this procedure. The aims of this study were to determine (i) what is the feasibility of a randomised controlled trial (RCT) investigating a targeted physiotherapy intervention for early-onset hip osteoarthritis (OA) post-hip arthroscopy? and (ii) what are the within-group treatment effects of the physiotherapy intervention and a health-education control group? This study was a pilot single-blind RCT conducted in a private physiotherapy clinic in Hobart, Australia. Patients included 17 volunteers (nine women; age 32 ± 8 years; body mass index = 25.6 ± 5.1 kg/m 2 ) who were recruited 4-14 months post-hip arthroscopy, with chondropathy and/or labral pathology at the time of surgery. Interventions included a physiotherapy treatment program that was semi-standardised and consisted of (i) manual therapy; (ii) hip strengthening and functional retraining; and (iii) health education. Control treatment encompassed individualised health education sessions. The primary outcome measure was feasibility, which was reported as percentage of eligible participants enrolled, adherence with the intervention, and losses to follow-up. The research process was evaluated using interviews, and an estimated sample size for a definitive study is offered. Secondary outcomes included the Hip disability and Osteoarthritis Outcome Score (HOOS) and the International Hip Outcome Tool (IHOT-33) patient-reported outcomes. Seventeen out of 48 eligible patients (35%) were randomised. Adherence to the intervention was 100%, with no losses to follow-up. The estimated sample size for a full-scale RCT was 142 patients. The within-group (95% confidence intervals) change scores for the physiotherapy group were HOOS-Symptoms 6 points (-4 to 16); HOOS-Pain 10 points (-2 to 22); HOOS-Activity of Daily Living 8 points (0 to 16); HOOS-Sport 3 points (-12 to 19); HOOS-Quality of Life 3 points (-7 to 13); and IHOT-33 7 points (-10 to 25). The within-group (95% confidence intervals) change scores for the control group were HOOS-Symptoms -4 points (-17 to 9); HOOS-Pain -2 points (-18 to 13); HOOS-Activity of Daily Living -7 points (-17 to 4); HOOS-Sport 4 points (-16 to 23); HOOS-Quality of Life -5 points (-18 to 9); and IHOT-33 -4 points (-27 to 19). Suggestions to improve study design included greater supervision of exercises and increased access to physiotherapy appointments. Results support the feasibility of a full-scale RCT, and recommendations for an adequately powered and improved study to determine the efficacy of this physiotherapy intervention post-hip arthroscopy to reduce pain and improve function are provided. Australian Clinical Trials Registry, ACTRN12614000426684.

Cost effectiveness of recombinant activated factor VII for the control of bleeding in patients with severe blunt trauma injuries in the United Kingdom.

PubMed

Morris, S; Ridley, S; Munro, V; Christensen, M C

2007-01-01

The aim of this study was to assess the lifetime cost effectiveness of recombinant activated factor VII vs placebo as adjunctive therapy for control of bleeding in patients with severe blunt trauma in the UK. We developed a cost-effectiveness model based on patient level data from a 30-day international, randomised, placebo-controlled Phase II trial. The data were supplemented with secondary data from UK sources to estimate lifetime costs and benefits. The model produced a baseline estimate of the incremental cost per life year gained with recombinant activated factor VII relative to placebo of 12 613 UK pounds. The incremental cost per quality adjusted life year gained was 18 825 UK pounds. These estimates are sensitive to the choice of discount rate and health state utility values used. Preliminary results suggest that relative to placebo, recombinant activated factor VII may be a cost-effective therapy to the UK National Health Service.

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.

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.

Naturalistic conversation improves daytime motorway driving performance under a benzodiazepine: a randomised, crossover, double-blind, placebo-controlled study.

PubMed

Moták, Ladislav; Bayssac, Laëtitia; Taillard, Jacques; Sagaspe, Patricia; Huet, Nathalie; Terrier, Patrice; Philip, Pierre; Daurat, Agnès

2014-06-01

The adverse effects of benzodiazepines on driving are widely recognised. The aims of this study were both to determine the impact of naturalistic conversation on the driving ability of drivers under a benzodiazepine, and to measure the accuracy of drivers' assessments of the joint effects of the benzodiazepine and conversation. Sixteen healthy male participants (29.69 ± 3.30 years) underwent a randomised, crossover, double-blind, placebo-controlled study with the benzodiazepine lorazepam (2mg). They drove 200 km (125 miles) on a motorway in the morning. We measured two driving ability-related variables (i.e., lane-keeping performance), and collected a set of self-assessed variables (i.e., self-assessment of driving performance) during two 10-min sequences of interest (no conversation vs. conversation). An analysis of variance revealed an interaction whereby lane-keeping performance under lorazepam was worse in the no-conversation condition than in the conversation condition. No such difference was detected under placebo. Pearson's correlation coefficients revealed that self-assessments were (i) not at all predictive of lane-keeping when performed before the drive, but (ii) moderately predictive of lane-keeping performance when performed during or after the drive. We conclude that conversation with a passenger may contribute to safer lane-keeping when driving under a benzodiazepine. Moreover, a degree of awareness may be attained after some experience of driving under the influence of this type of medication. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

The MUK five protocol: a phase II randomised, controlled, parallel group, multi-centre trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs. cyclophosphamide, bortezomib (Velcade) and dexamethasone (CVD) for first relapse and primary refractory multiple myeloma.

PubMed

Brown, Sarah; Hinsley, Samantha; Ballesteros, Mónica; Bourne, Sue; McGarry, Paul; Sherratt, Debbie; Flanagan, Louise; Gregory, Walter; Cavenagh, Jamie; Owen, Roger; Williams, Cathy; Kaiser, Martin; Low, Eric; Yong, Kwee

2016-01-01

Multiple myeloma is a plasma cell tumour with an annual incidence in the UK of approximately 40-50 per million i.e. about 4500 new cases per annum. The triple combination cyclophosphamide, bortezomib (Velcade®) and dexamethasone (CVD) is an effective regimen at relapse and has emerged in recent years as the standard therapy at first relapse in the UK. Carfilzomib has good activity as a single agent in the relapsed setting, and it is expected that efficacy will be improved when used in combination with dexamethasone and cyclophosphamide. MUK Five is a phase II open label, randomised, controlled, parallel group, multi-centre trial that will compare the activity of carfilzomib, cyclophosphamide and dexamethasone (CCD) with that of CVD, given over an equivalent treatment period (24 weeks), in participants with multiple myeloma at first relapse, or refractory to no more than 1 line of treatment. In addition, the study also aims to assess the utility of a maintenance schedule of carfilzomib in these participants. The primary objective of the trial is to assess whether CCD provides non-inferior activity in terms of ≥ VGPR rates at 24 weeks, and whether the addition of maintenance treatment with carfilzomib to CCD provides superior activity in terms of progression-free survival, as compared to CCD with no maintenance. Secondary objectives include comparing toxicity profiles, further summarizing and comparing the activity of the different treatment arms and analysis of the effect of each treatment arm on minimal residual disease status. The development of carfilzomib offers the opportunity to further explore the anti-tumour efficacy of proteasome inhibition and, based on the available evidence, it is important and timely to obtain data on the activity, toxicity and tolerability of this drug. In contrast to ongoing phase III trials, this phase II trial has a unique subset of participants diagnosed with multiple myeloma at first relapse or refractory to no more than 1 line of treatment and will also evaluate the utility of maintenance with carfilzomib for up to 18 months and investigate minimal residual disease status to provide information on depth of response and the prognostic impact thereof. The trial is registered under ISRCTN17354232, December 2012.

No effect of forearm band and extensor strengthening exercises for the treatment of tennis elbow: a prospective randomised study.

PubMed

Luginbühl, Rolf; Brunner, Florian; Schneeberger, Alberto G

2008-01-01

The objective of this prospective randomised study was to analyse the effect of the forearm support band and of strengthening exercises for the treatment of tennis elbow. Twenty-nine patients with 30 tennis elbows were randomised into 3 groups of treatment: (I) forearm support band, (II) strengthening exercises and (III) both methods. The patients had a standardised examination at their first visit, and then after 6 weeks, 3 months and 1 year. At the latest follow-up, there was a significant improvement of the symptoms compared to before treatment (p<0.0001), considering all patients independently of the methods of treatment. However, no differences in the scores were found between the 3 groups of treatment (p=0.27), indicating that no beneficial influence was found either for the strengthening exercises or for the forearm support band. Improvement seems to occur with time, independent of the method of treatment used.

Pathways to change: Use trajectories following trauma-informed treatment of women with co-occurring post-traumatic stress disorder and substance use disorders.

PubMed

López-Castro, Teresa; Hu, Mei-Chen; Papini, Santiago; Ruglass, Lesia M; Hien, Denise A

2015-05-01

Despite advances towards integration of care for women with co-occurring substance use disorder (SUD) and post-traumatic stress disorder (PTSD), low abstinence rates following SUD/PTSD treatment remain the norm. The utility of investigating distinct substance use trajectories is a critical innovation in the detection and refining of effective interventions for this clinical population. The present study reanalysed data from the largest randomised clinical trial to date for co-occurring SUD and PTSD in women (National Drug Abuse Treatment Clinical Trials Network; Women and Trauma Study). Randomised participants (n = 353) received one of two interventions in addition to treatment as usual for SUD: (i) trauma-informed integrative treatment for PTSD/SUD; or (ii) an active control psychoeducation course on women's health. The present study utilised latent growth mixture models (LGMM) with multiple groups to estimate women's substance use patterns during the 12-month follow-up period. Findings provided support for three different trajectories of substance use in the post-treatment year: (i) consistently low likelihood and use frequency; (ii) consistently high likelihood and use frequency; and (iii) high likelihood and moderate use frequency. Covariate analyses revealed improvement in PTSD severity was associated with membership in a specific substance use trajectory, although receiving trauma-informed treatment was not. Additionally, SUD severity, age and after-care efforts were shown to be related to trajectory membership. Findings highlight the necessity of accounting for heterogeneity in post-treatment substance use, relevance of trauma-informed care in SUD recovery and benefits of incorporating methodologies like LGMM when evaluating SUD treatment outcomes. © 2015 Australasian Professional Society on Alcohol and other Drugs.

Vitamin D supplementation has minor effects on parathyroid hormone and bone turnover markers in vitamin D-deficient bedridden older patients.

PubMed

Björkman, Mikko; Sorva, Antti; Risteli, Juha; Tilvis, Reijo

2008-01-01

to evaluate the effects of vitamin D supplementation on parathyroid function and bone turnover in aged, chronically immobile patients. a randomised double-blind controlled trial. two hundred and eighteen long-term inpatients aged over 65 years. the patients were randomised into treatment groups of I-III, each receiving 0 IU, 400 IU and 1200 IU cholecalciferol per day, respectively. In case of inadequate consumption of dairy products, patients received a daily calcium substitution of 500 mg. plasma concentrations of 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone (PTH), amino-terminal propeptide of type I procollagen (PINP), a marker of bone formation, and carboxy-terminal telopeptide of type I collagen (ICTP), a marker of bone resorption, were measured at baseline and after 6 months. the patients (age 84.5 years) were chronically bedridden. The baseline 25-OHD was low (23 nmol/l), correlated inversely with PINP, and tended to associate inversely with PTH. The prevalence of vitamin D deficiency (VDD) (25-OHD < 50 nmol/l) was 98% and PTH was elevated in 23% of the patients. Vitamin D supplementation significantly increased 25-OHD concentrations (124% group II, 204% group III) and decreased PTH (-7% group II, -8% group III). PINP tended to decrease, but ICTP tended to increase, and only their ratio decreased significantly. The tendency of ICTP to increase was inconsistent. Changes in 25-OHD correlated inversely with those in PTH and PINP. vitamin D supplementation has minor effects on PTH and bone turnover in chronically immobilised aged patients with VDD. Further comparative studies and meta-analyses are warranted to elucidate the confounding effects of different mobility levels on the benefits of vitamin D supplementation in patients with differing baseline PTH levels.

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 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

A cluster randomised controlled trial of an intervention to promote healthy lifestyle habits to school leavers: study rationale, design, and methods

PubMed Central

2014-01-01

Background Physical inactivity and a poor diet predict lifestyle diseases such as diabetes, cardiovascular disease, and certain types of cancer. Marked declines in physical activity occur during late adolescence, coinciding with the point at which many young people leave school and enter the workforce and begin to take greater control over their lifestyle behaviours. The work outlined within this paper sought to test a theoretically-informed intervention aimed at supporting increased engagement in physical activity and healthy eating habits in young people at the point of transition from school to work or work-based learning. As actively engaging young people in initiatives based on health messages is challenging, we also tested the efficacy of financial incentives in promoting initial engagement with the programme. Methods/design A three-arm cluster-randomised design was used. Participants were school pupils from Year 11 and 13 (i.e., in their final year of study), aged 16–18 years. To reduce contamination effects, the unit of randomisation was school. Participants were randomly allocated to receive (i) a 12-week behavioural support intervention consisting of six appointments, (ii) a behavioural support intervention plus incentives (totalling £40), or (iii) an information-only control group. Behavioural support was provided by fitness advisors at local leisure centres following an initial consultation with a dietician. Sessions focused on promoting habit formation through setting implementation intentions as part of an incremental goal setting process. Consistent with self-determination theory, all advisors were trained to provide guidance in an autonomy-supportive manner so that they were equipped to create a social context supportive of autonomous forms of participant motivation. The primary outcome was objectively assessed physical activity (via GT1M accelerometers). Secondary outcome measures were diet, motivation and habit strength. Data were collected at baseline, post-intervention (12 weeks) and 12 months. Discussion Findings of this trial will provide valuable insight into the feasibility of promoting autonomous engagement in healthy physical activity and dietary habits among school leavers. The research also provides much needed data and detailed information related to the use of incentives for the initial promotion of young peoples’ behaviour change during this important transition. Trial registration The trial is registered as Current Controlled Trials ISRCTN55839517. PMID:24592967

A cluster randomised controlled trial of an intervention to promote healthy lifestyle habits to school leavers: study rationale, design, and methods.

PubMed

Gillison, Fiona; Standage, Martyn; Verplanken, Bas

2014-03-04

Physical inactivity and a poor diet predict lifestyle diseases such as diabetes, cardiovascular disease, and certain types of cancer. Marked declines in physical activity occur during late adolescence, coinciding with the point at which many young people leave school and enter the workforce and begin to take greater control over their lifestyle behaviours. The work outlined within this paper sought to test a theoretically-informed intervention aimed at supporting increased engagement in physical activity and healthy eating habits in young people at the point of transition from school to work or work-based learning. As actively engaging young people in initiatives based on health messages is challenging, we also tested the efficacy of financial incentives in promoting initial engagement with the programme. A three-arm cluster-randomised design was used. Participants were school pupils from Year 11 and 13 (i.e., in their final year of study), aged 16-18 years. To reduce contamination effects, the unit of randomisation was school. Participants were randomly allocated to receive (i) a 12-week behavioural support intervention consisting of six appointments, (ii) a behavioural support intervention plus incentives (totalling £40), or (iii) an information-only control group. Behavioural support was provided by fitness advisors at local leisure centres following an initial consultation with a dietician. Sessions focused on promoting habit formation through setting implementation intentions as part of an incremental goal setting process. Consistent with self-determination theory, all advisors were trained to provide guidance in an autonomy-supportive manner so that they were equipped to create a social context supportive of autonomous forms of participant motivation. The primary outcome was objectively assessed physical activity (via GT1M accelerometers). Secondary outcome measures were diet, motivation and habit strength. Data were collected at baseline, post-intervention (12 weeks) and 12 months. Findings of this trial will provide valuable insight into the feasibility of promoting autonomous engagement in healthy physical activity and dietary habits among school leavers. The research also provides much needed data and detailed information related to the use of incentives for the initial promotion of young peoples' behaviour change during this important transition. The trial is registered as Current Controlled Trials ISRCTN55839517.

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

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.

Omission of doxorubicin from the treatment of stage II-III, intermediate-risk Wilms' tumour (SIOP WT 2001): an open-label, non-inferiority, randomised controlled trial.

PubMed

Pritchard-Jones, Kathy; Bergeron, Christophe; de Camargo, Beatriz; van den Heuvel-Eibrink, Marry M; Acha, Tomas; Godzinski, Jan; Oldenburger, Foppe; Boccon-Gibod, Liliane; Leuschner, Ivo; Vujanic, Gordan; Sandstedt, Bengt; de Kraker, Jan; van Tinteren, Harm; Graf, Norbert

2015-09-19

Before this study started, the standard postoperative chemotherapy regimen for stage II-III Wilms' tumour pretreated with chemotherapy was to include doxorubicin. However, avoidance of doxorubicin-related cardiotoxicity effects is important to improve long-term outcomes for childhood cancers that have excellent prognosis. We aimed to assess whether doxorubicin can be omitted safely from chemotherapy for stage II-III, histological intermediate-risk Wilms' tumour when a newly defined high-risk blastemal subtype was excluded from randomisation. For this international, multicentre, open-label, non-inferiority, phase 3, randomised SIOP WT 2001 trial, we recruited children aged 6 months to 18 years at the time of diagnosis of a primary renal tumour from 251 hospitals in 26 countries who had received 4 weeks of preoperative chemotherapy with vincristine and actinomycin D. Children with stage II-III intermediate-risk Wilms' tumours assessed after delayed nephrectomy were randomly assigned (1:1) by a minimisation technique to receive vincristine 1·5 mg/m(2) at weeks 1-8, 11, 12, 14, 15, 17, 18, 20, 21, 23, 24, 26, and 27, plus actinomycin D 45 μg/kg every 3 weeks from week 2, either with five doses of doxorubicin 50 mg/m(2) given every 6 weeks from week 2 (standard treatment) or without doxorubicin (experimental treatment). The primary endpoint was non-inferiority of event-free survival at 2 years, analysed by intention to treat and a margin of 10%. Assessment of safety and adverse events included systematic monitoring of hepatic toxicity and cardiotoxicity. This trial is registered with EudraCT, number 2007-004591-39, and is closed to new participants. Between Nov 1, 2001, and Dec 16, 2009, we recruited 583 patients, 341 with stage II and 242 with stage III tumours, and randomly assigned 291 children to treatment including doxorubicin, and 292 children to treatment excluding doxorubicin. Median follow-up was 60·8 months (IQR 40·8-79·8). 2 year event-free survival was 92·6% (95% CI 89·6-95·7) for treatment including doxorubicin and 88·2% (84·5-92·1) for treatment excluding doxorubicin, a difference of 4·4% (95% CI 0·4-9·3) that did not exceed the predefined 10% margin. 5 year overall survival was 96·5% (94·3-98·8) for treatment including doxorubicin and 95·8% (93·3-98·4) for treatment excluding doxorubicin. Four children died from a treatment-related toxic effect; one (<1%) of 291 receiving treatment including doxorubicin died of sepsis, three (1%) of 292 receiving treatment excluding doxorubicin died of varicella, metabolic seizure, and sepsis during treatment for relapse. 17 patients (3%) had hepatic veno-occlusive disease. Cardiotoxic effects were reported in 15 (5%) of 291 children receiving treatment including doxorubicin. 12 children receiving treatment including doxorubicin, and ten children receiving treatment excluding doxorubicin, died, with the remaining deaths from tumour recurrence. Doxorubicin does not need to be included in treatment of stage II-III intermediate risk Wilms' tumour when the histological response to preoperative chemotherapy is incorporated into the risk stratification. See Acknowledgments for funders. Copyright © 2015 Pritchard-Jones et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

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.

Audiovisual biofeedback breathing guidance for lung cancer patients receiving radiotherapy: a multi-institutional phase II randomised clinical trial.

PubMed

Pollock, Sean; O'Brien, Ricky; Makhija, Kuldeep; Hegi-Johnson, Fiona; Ludbrook, Jane; Rezo, Angela; Tse, Regina; Eade, Thomas; Yeghiaian-Alvandi, Roland; Gebski, Val; Keall, Paul J

2015-07-18

There is a clear link between irregular breathing and errors in medical imaging and radiation treatment. The audiovisual biofeedback system is an advanced form of respiratory guidance that has previously demonstrated to facilitate regular patient breathing. The clinical benefits of audiovisual biofeedback will be investigated in an upcoming multi-institutional, randomised, and stratified clinical trial recruiting a total of 75 lung cancer patients undergoing radiation therapy. To comprehensively perform a clinical evaluation of the audiovisual biofeedback system, a multi-institutional study will be performed. Our methodological framework will be based on the widely used Technology Acceptance Model, which gives qualitative scales for two specific variables, perceived usefulness and perceived ease of use, which are fundamental determinants for user acceptance. A total of 75 lung cancer patients will be recruited across seven radiation oncology departments across Australia. Patients will be randomised in a 2:1 ratio, with 2/3 of the patients being recruited into the intervention arm and 1/3 in the control arm. 2:1 randomisation is appropriate as within the interventional arm there is a screening procedure where only patients whose breathing is more regular with audiovisual biofeedback will continue to use this system for their imaging and treatment procedures. Patients within the intervention arm whose free breathing is more regular than audiovisual biofeedback in the screen procedure will remain in the intervention arm of the study but their imaging and treatment procedures will be performed without audiovisual biofeedback. Patients will also be stratified by treating institution and for treatment intent (palliative vs. radical) to ensure similar balance in the arms across the sites. Patients and hospital staff operating the audiovisual biofeedback system will complete questionnaires to assess their experience with audiovisual biofeedback. The objectives of this clinical trial is to assess the impact of audiovisual biofeedback on breathing motion, the patient experience and clinical confidence in the system, clinical workflow, treatment margins, and toxicity outcomes. This clinical trial marks an important milestone in breathing guidance studies as it will be the first randomised, controlled trial providing the most comprehensive evaluation of the clinical impact of breathing guidance on cancer radiation therapy to date. This study is powered to determine the impact of AV biofeedback on breathing regularity and medical image quality. Objectives such as determining the indications and contra-indications for the use of AV biofeedback, evaluation of patient experience, radiation toxicity occurrence and severity, and clinician confidence will shed light on the design of future phase III clinical trials. This trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), its trial ID is ACTRN12613001177741 .

Multi-stage versus single-stage inflation and deflation cycle for alternating low pressure air mattresses to prevent pressure ulcers in hospitalised patients: a randomised-controlled clinical trial.

PubMed

Demarré, L; Beeckman, D; Vanderwee, K; Defloor, T; Grypdonck, M; Verhaeghe, S

2012-04-01

The duration and the amount of pressure and shear must be reduced in order to minimize the risk of pressure ulcer development. Alternating low pressure air mattresses with multi-stage inflation and deflation cycle of the air cells have been developed to relieve pressure by sequentially inflating and deflating the air cells. Evidence about the effectiveness of this type of mattress in clinical practice is lacking. This study aimed to compare the effectiveness of an alternating low pressure air mattress that has a standard single-stage inflation and deflation cycle of the air cells with an alternating low pressure air mattress with multi-stage inflation and deflation cycle of the air cells. A randomised controlled trial was performed in a convenience sample of 25 wards in five hospitals in Belgium. In total, 610 patients were included and randomly assigned to the experimental group (n=298) or the control group (n=312). In the experimental group, patients were allocated to an alternating low pressure air mattress with multi-stage inflation and deflation cycle of the air cells. In the control group, patients were allocated to an alternating low pressure air mattress with a standard single-stage inflation and deflation cycle of the air cells. The outcome was defined as cumulative pressure ulcer incidence (Grade II-IV). An intention-to-treat analysis was performed. There was no significant difference in cumulative pressure ulcer incidence (Grade II-IV) between both groups (Exp.=5.7%, Contr.=5.8%, p=0.97). When patients developed a pressure ulcer, the median time was 5.0 days in the experimental group (IQR=3.0-8.5) and 8.0 days in the control group (IQR=3.0-8.5) (Mann-Whitney U-test=113, p=0.182). The probability to remain pressure ulcer free during the observation period in this trial did not differ significantly between the experimental group and the control group (log-rank χ(2)=0.013, df=1, p=0.911). An alternating low pressure air mattress with multi-stage inflation and deflation of the air cells does not result in a significantly lower pressure ulcer incidence compared to an alternating low pressure air mattress with a standard single-stage inflation and deflation cycle of the air cells. Both alternating mattress types are equally effective to prevent pressure ulcer development. © 2011 Elsevier Ltd. All rights reserved.

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.

All great truths are iconoclastic: selective decontamination of the digestive tract moves from heresy to level 1 truth.

PubMed

van Saene, Hendrick K F; Petros, Andy J; Ramsay, Graham; Baxby, Derrick

2003-05-01

The objective was to compare evidence of the effectiveness, costs and safety of the traditional parenteral antibiotic-only approach against that gathered from 53 randomised trials involving more than 8,500 patients and six meta-analyses on selective decontamination of the digestive tract (SDD) to control infection on the intensive care unit (ICU). PHILOSOPHY: Traditionalists believe that all infections are due to breaches of hygiene except those established in the first 2 days, and that all micro-organisms can cause death. In contrast, newer insights show that transmission via the hands of carers are responsible only for infections occurring after one week, and that only a limited range of 15 potential pathogens contribute to mortality. INTERVENTIONS TO PREVENT ICU INFECTION: The traditional approach is based on hand disinfection aiming at the prevention of transmission of all micro-organisms, to control all infections that occur after 2 days on the ICU. The second feature is the restrictive use of systemic antibiotics, only in cases of microbiologically proven infection. In contrast, SDD aims to control the three types of infection: primary, secondary endogenous and exogenous due to 15 potential pathogens. The classical SDD tetralogy comprises four components: (i) a parenteral antibiotic, cefotaxime, administered for three days to prevent primary endogenous infections typically occurring "early"; (ii) the oropharyngeal and enteral antimicrobials, polymyxin E, tobramycin and amphotericin B administered in throat and gut throughout the treatment on the ICU to prevent secondary endogenous infections tending to develop "late"; (iii) a high standard of hygiene to control transmission of potential pathogens; and (iv) surveillance samples of throat and rectum to monitor the efficacy of the treatment. (i) Infectious morbidity; (ii) mortality; (iii) antimicrobial resistance; and (iv) costs. Properly designed trials on hand disinfection have never demonstrated a reduction in either pneumonia and septicaemia, or mortality. Two randomised trials using restrictive antibiotic policies failed to show a survival benefit at 28 days. In both trials the proportion of resistant isolates obtained from the lower ways was >60% despite significantly less use of antibiotics in the test group. A formal cost effectiveness analysis of the traditional antibiotic policies has not been performed. On the other hand, two meta-analyses have shown that SDD reduces the odds ratio for lower airway infections to 0.35 (0.29-0.41) and mortality to 0.80 (0.69-0.93), with a 6% overall mortality reduction from 30% to 24%. No increase in the rate of super infections due to resistant bacteria could be demonstrated over a period of 20 years of clinical research. Four randomised trials found the cost per survivor to be substantially lower in patients receiving SDD than for those traditionally managed. The traditionalists still rely on level 5 evidence, i.e. expert opinion, with a grade E recommendation, whilst the proponents of SDD are able to cite level 1 evidence allowing a grade A recommendation in their attempts to control infection on the ICU. The main reason for SDD not being widely used is the primacy of opinion over evidence.

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

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

Post-operative analgesic effect of dexmedetomidine administration in wound infiltration for abdominal hysterectomy: A randomised control study

PubMed Central

Singh, Swati; Prasad, Chandrakant

2017-01-01

Background and Aims: Local infiltration of the surgical wound is one of the important components of multimodal analgesia for post-operative pain relief. This study determines the post-operative analgesic effect of addition of dexmedetomidine to bupivacaine for local infiltration of the surgical wound. Methods: Sixty women belonging to American Society of Anesthesiologists’ Grade 1 or 2 posted for abdominal hysterectomy were randomly allocated to Group I (control group) where patients received wound infiltration with 30 mL 0.25% bupivacaine at the end of surgery, or Group II, where patients received wound infiltration with 1.0 μg/kg dexmedetomidine diluted in 30 mL 0.25% bupivacaine. The primary objective of the study was to assess post-operative pain scores. Number of patients requiring rescue analgesia and total morphine consumption during 24 h after surgery were also recorded. Statistical significance for analgesic requirement was determined by one-way analysis of variance. Results: Pain scores were lower at rest for 12 h and on cough for 6 h in Group II (<0.01). All patients in Group I required supplemental morphine compared to only 3 patients in Group II (P < 0.003). Post-operative analgesia requirement was significantly less in patients receiving dexmedetomidine in wound infiltration compared to patients receiving bupivacaine alone (P < 0.001). Conclusions: Wound infiltration of dexmedetomidine with bupivacaine provides superior pain relief compared to bupivacaine alone. PMID:28655956

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.

Early add-on treatment vs alternative monotherapy in patients with partial epilepsy.

PubMed

Semah, Franck; Thomas, Pierre; Coulbaut, Safia; Derambure, Philippe

2014-06-01

The aim of this study was to evaluate the impact of two different therapeutic strategies in patients with partial seizures who were intractable to the first prescribed antiepileptic drug (AED); alternative monotherapy vs early add-on treatment. We conducted an open, cluster-randomised, prospective, controlled trial in patients with persistent partial seizures, despite treatment with one AED, who were never administered any other AEDs. Neurologists were randomised to two strategies: in group A, an alternative monotherapy with a second AED was employed; in group B, add-on treatment with a second AED was employed. The primary outcome was the percentage of seizure-free patients during a two-month period after six months of treatment. The secondary outcomes were: (i) the percentage of patients achieving a 50% reduction in the number of seizures at six months; (ii) the quality of life based on the Quality Of Life In Epilepsy scale; and (iii) tolerability. A total of 143 neurologists were included and randomised, and 264 patients were evaluated. At six months, the primary outcome was 51% in group A and 45% in group B (p=0.34). The percentage of patients achieving a 50% reduction in the number of seizures at six months was 76% in group A and 84% in group B (p=0.53). The quality of life and the tolerability did not significantly differ between the two groups. Alternative monotherapy or early treatment initiation with another AED drug resulted in similar efficacy, and the side effects associated with monotherapy and combined therapies were similar, which suggests that individual susceptibility is more important than the number and burden of AEDs used.

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…

The Salford Lung Study protocol: a pragmatic, randomised phase III real-world effectiveness trial in asthma.

PubMed

Woodcock, Ashley; Bakerly, Nawar Diar; New, John P; Gibson, J Martin; Wu, Wei; Vestbo, Jørgen; Leather, David

2015-12-10

Novel therapies need to be evaluated in normal clinical practice to allow a true representation of the treatment effectiveness in real-world settings. The Salford Lung Study is a pragmatic randomised controlled trial in adult asthma, evaluating the clinical effectiveness and safety of once-daily fluticasone furoate (100 μg or 200 μg)/vilanterol 25 μg in a novel dry-powder inhaler, versus existing asthma maintenance therapy. The study was initiated before this investigational treatment was licensed and conducted in real-world clinical practice to consider adherence, co-morbidities, polypharmacy, and real-world factors. Asthma Control Test at week 24; safety endpoints include the incidence of serious pneumonias. The study utilises the Salford electronic medical record, which allows near to real-time collection and monitoring of safety data. The Salford Lung Study is the world's first pragmatic randomised controlled trial of a pre-licensed medication in asthma. Use of patients' linked electronic health records to collect clinical endpoints offers minimal disruption to patients and investigators, and also ensures patient safety. This highly innovative study will complement standard double-blind randomised controlled trials in order to improve our understanding of the risk/benefit profile of fluticasone furoate/vilanterol in patients with asthma in real-world settings. Clinicaltrials.gov, NCT01706198; 04 October 2012.

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

PubMed

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

2017-10-01

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

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

PubMed

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

2012-03-23

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

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

PubMed Central

Barber, Julie A; Thompson, Simon G

1998-01-01

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

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

PubMed

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

2018-02-01

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

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

Physical health care monitoring for people with serious mental illness.

PubMed

Tosh, Graeme; Clifton, Andrew; Mala, Shereen; Bachner, Mick

2010-03-17

Current guidance suggests that we should monitor the physical health of people with serious mental illness and there has been a significant financial investment over recent years to provide this. To assess the effectiveness of physical health monitoring as a means of reducing morbidity, mortality and reduction in quality of life in people with serious mental illness. We searched the Cochrane Schizophrenia Group Trials Register (October 2009) which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. All randomised or quasi-randomised clinical trials focusing on physical health monitoring versus standard care or comparing i) self monitoring vs monitoring by health care professional; ii) simple vs complex monitoring; iii) specific vs non-specific checks iv) once only vs regular checks or v) comparison of different guidance. The authors (GT, AC, SM) independently screened search results and identified three studies as possibly fulfilling the review's criteria. On examination, however, all three were subsequently excluded. We did not identify any randomised trials which assessed the effectiveness of physical health monitoring in people with serious mental illness. There is no evidence from randomised trials to support current guidance and practice. Guidance and practice are based on expert consensus, clinical experience and good intentions rather than high quality evidence.

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.

Process evaluation of a randomised controlled trial of a diabetes prevention intervention in Dutch primary health care: the SLIMMER study.

PubMed

van Dongen, Ellen Ji; Duijzer, Geerke; Jansen, Sophia C; Ter Beek, Josien; Huijg, Johanna M; Leerlooijer, Joanne N; Hiddink, Gerrit J; Feskens, Edith Jm; Haveman-Nies, Annemien

2016-11-01

To investigate (i) how the SLIMMER intervention was delivered and received in Dutch primary health care and (ii) how this could explain intervention effectiveness. A randomised controlled trial was conducted and subjects were randomly allocated to the intervention (10-month combined dietary and physical activity intervention) or the control group. A process evaluation including quantitative and qualitative methods was conducted. Data on process indicators (recruitment, reach, dose received, acceptability, implementation integrity and applicability) were collected via semi-structured interviews with health-care professionals (n 45) and intervention participant questionnaires (n 155). SLIMMER was implemented in Dutch primary health care in twenty-five general practices, eleven dietitians, nine physiotherapist practices and fifteen sports clubs. Subjects at increased risk of developing type 2 diabetes were included. It was possible to recruit the intended high-risk population (response rate 54 %) and the SLIMMER intervention was very well received by both participants and health-care professionals (mean acceptability rating of 82 and 80, respectively). The intervention programme was to a large extent implemented as planned and was applicable in Dutch primary health care. Higher dose received and participant acceptability were related to improved health outcomes and dietary behaviour, but not to physical activity behaviour. The present study showed that it is feasible to implement a diabetes prevention intervention in Dutch primary health care. Higher dose received and participant acceptability were associated with improved health outcomes and dietary behaviour. Using an extensive process evaluation plan to gain insight into how an intervention is delivered and received is a valuable way of identifying intervention components that contribute to implementation integrity and effective prevention of type 2 diabetes in primary health care.

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.

Cognitive training of self-initiation of semantic encoding strategies in schizophrenia: A pilot study.

PubMed

Guimond, Synthia; Lepage, Martin

2016-01-01

Available cognitive remediation interventions have a significant but relatively small to moderate impact on episodic memory in schizophrenia. The present study aimed to evaluate the efficacy and feasibility of a brief novel episodic memory training targeting the self-initiation of semantic encoding strategies. To select patients with such deficits, 28 participants with schizophrenia performed our Semantic Encoding Memory Task (SEMT) that provides a measure of self-initiated semantic encoding strategies. This task identified a deficit in 13 participants who were then offered two 60-minute training sessions one week apart. After the training, patients performed an alternate version of the SEMT. The CVLT-II (a standardised measure of semantic encoding strategies) and the BVMT-R (a control spatial memory task) were used to quantify memory pre- and post-training. After the training, participants were significantly better at self-initiating semantic encoding strategies in the SEMT (p = .004) and in the CVLT-II (p = .002). No significant differences were found in the BVMT-R. The current study demonstrates that a brief and specific training in memory strategies can help patients to improve a deficient memory process in schizophrenia. Future studies will need to test this intervention further using a randomised controlled trial, and to explore its functional impact.

The effectiveness of crisis resource management and team debriefing in resuscitation education of nursing students: A randomised controlled trial.

PubMed

Coppens, Imgard; Verhaeghe, Sofie; Van Hecke, Ann; Beeckman, Dimitri

2018-01-01

The aim of this study was to investigate (i) whether integrating a course on crisis resource management principles and team debriefings in simulation training, increases self-efficacy, team efficacy and technical skills of nursing students in resuscitation settings and (ii) which phases contribute the most to these outcomes. Crisis resource management principles have been introduced in health care to optimise teamwork. Simulation training offers patient safe training opportunities. There is evidence that simulation training increases self-efficacy and team efficacy but the contribution of the different phases like crisis resource management principles, simulation training and debriefing on self-efficacy, team efficacy and technical skills is not clear. Randomised controlled trial in a convenience sample (n = 116) in Belgium. Data were collected between February 2015-April 2015. Participants in the intervention group (n = 60) completed a course on crisis resource management principles, followed by a simulation training session, a team debriefing and a second simulation training session. Participants in the control group (n = 56) only completed two simulation training sessions. The outcomes self-efficacy, team efficacy and technical skills were assessed after each simulation training. An ancillary analysis of the learning effect was conducted. The intervention group increased on self-efficacy (2.13%, p = .02) and team efficacy (9.92%, p < .001); the control group only increased significantly on team efficacy (4.5%, p = .001). The intervention group scored significantly higher on team efficacy (8.49%, p < .001) compared to the control group. Combining crisis resource management principles and team debriefings in simulation training increases self-efficacy and team efficacy. The debriefing phase contributes the most to these effects. By partnering with healthcare settings, it becomes possible to offer interdisciplinary simulation training that can increase patient safety. © 2017 John Wiley & Sons Ltd.

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

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.

Randomised comparison of three tools for improving compliance with occlusion therapy: an educational cartoon story, a reward calendar, and an information leaflet for parents.

PubMed

Tjiam, A M; Holtslag, G; Van Minderhout, H M; Simonsz-Tóth, B; Vermeulen-Jong, M H L; Borsboom, G J J M; Loudon, S E; Simonsz, H J

2013-01-01

We previously demonstrated that compliance with occlusion therapy for amblyopia was improved by the use of an educational programme, especially in children of parents of foreign origin and who spoke Dutch poorly. The programme consisted of: (i) a cartoon story for amblyopic children that explained without words why they should patch, (ii) a calendar with reward stickers, and (iii) an information leaflet for parents. In the current study, we assessed the individual effect of each component on compliance. We recruited 120 3- to 6-year-old children who lived in a low socio-economic status (SES) area in The Hague and were starting occlusion therapy for the first time. They were randomised to receive one of the components (three intervention groups), or a picture to colour (control group). The randomisation was blinded for treating orthoptist and researcher. Compliance was measured electronically using the Occlusion Dose Monitor (ODM). Primary outcome was percentage of compliance (actual/prescribed occlusion time). Secondary outcome was absolute occlusion hours per day. Parental fluency in Dutch was rated on a five-point scale. Compliance could be measured electronically in 88 of the 120 children; in 32 others, it failed for various reasons. Parental fluency in Dutch was moderate or worse in 36.4 % (p = 0.327). Average compliance was 55 % standard deviation (SD) 40 (n = 18) in the control group, 89 % SD 25 in the group receiving the educational cartoon (n = 25, P = 0.002 compared with control group), 67 % SD 33 (n = 24, P = 0.301) in the reward-calendar group and 73 % SD 40 (n = 21, P = 0.119) in the parent-information-leaflet group. On average, children in the control group occluded 1:46 SD1:19 hours/day, 2:33 SD 1:18 hours/day in the group receiving the educational cartoon, 1:59 SD 1:13 hours/day in the reward-calendar group and 2:18 SD 1:13 hours/day in the parent-information-leaflet group. No child who received the cartoon story occluded less than 1 hour per day, against seven in the reward-calendar group, five in the parent-information-leaflet group and five in the control group. Although all three components of the programme improved compliance with occlusion therapy in children in low-SES areas, the educational cartoon had the strongest effect, as it explained without words to a 4- to 5-year-old child why it should wear the eye patch.

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.

SPIRE - combining SGI-110 with cisplatin and gemcitabine chemotherapy for solid malignancies including bladder cancer: study protocol for a phase Ib/randomised IIa open label clinical trial.

PubMed

Crabb, Simon; Danson, Sarah J; Catto, James W F; McDowell, Cathy; Lowder, James N; Caddy, Joshua; Dunkley, Denise; Rajaram, Jessica; Ellis, Deborah; Hill, Stephanie; Hathorn, David; Whitehead, Amy; Kalevras, Mihalis; Huddart, Robert; Griffiths, Gareth

2018-04-03

Urothelial bladder cancer (UBC) accounts for 10,000 new diagnoses and 5000 deaths annually in the UK (Cancer Research UK, http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bladder-cancer , Cancer Research UK, Accessed 26 Mar 2018). Cisplatin-based chemotherapy is standard of care therapy for UBC for both palliative first-line treatment of advanced/metastatic disease and radical neoadjuvant treatment of localised muscle invasive bladder cancer. However, cisplatin resistance remains a critical cause of treatment failure and a barrier to therapeutic advance in UBC. Based on supportive pre-clinical data, we hypothesised that DNA methyltransferase inhibition would circumvent cisplatin resistance in UBC and potentially other cancers. The addition of SGI-110 (guadecitabine, a DNA methyltransferase inhibitor) to conventional doublet therapy of gemcitabine and cisplatin (GC) is being tested within the phase Ib/IIa SPIRE clinical trial. SPIRE incorporates an initial, modified rolling six-dose escalation phase Ib design of up to 36 patients with advanced solid tumours followed by a 20-patient open-label randomised controlled dose expansion phase IIa component as neoadjuvant treatment for UBC. Patients are being recruited from UK secondary care sites. The dose escalation phase will determine a recommended phase II dose (RP2D, primary endpoint) of SGI-110, by subcutaneous injection, on days 1-5 for combination with GC at conventional doses (cisplatin 70 mg/m 2 , IV infusion, day 8; gemcitabine 1000 mg/m 2 , IV infusion, days 8 and 15) in every 21-day cycle. In the dose expansion phase, patients will be randomised 1:1 to GC with or without SGI-110 at the proposed RP2D. Secondary endpoints will include toxicity profiles, SGI-110 pharmacokinetics and pharmacodynamic biomarkers, and pathological complete response rates in the dose expansion phase. Analyses will not be powered for formal statistical comparisons and descriptive statistics will be used to describe rates of toxicity, efficacy and translational endpoints by treatment arm. SPIRE will provide evidence for whether SGI-110 in combination with GC chemotherapy is safe and biologically effective prior to future phase II/III trials as a neoadjuvant therapy for UBC and potentially in other cancers treated with GC. EudraCT Number: 2015-004062-29 (entered Dec 7, 2015) ISRCTN registry number: 16332228 (registered on Feb 3, 2016).

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

The Watcombe housing study: the short-term effect of improving housing conditions on the indoor environment.

PubMed

Richardson, George; Barton, Andrew; Basham, Meryl; Foy, Chris; Eick, Susan Ann; Somerville, Margaret

2006-05-15

A three-year study (1999-2001) was initiated in the UK to assess the effect of improving housing conditions in 3-4 bedroom, single-family unit, social rented sector houses on the health of the occupants. The houses were randomised into two groups. Phase I houses received extensive upgrading including wet central heating, on demand ventilation, double-glazed doors, cavity wall and roof/loft insulation. An identical intervention for Phase II houses was delayed for one year. As part of this randomised waiting list study, discrete measurements were made of indoor environmental variables in each house, to assess the short-term effects of improving housing conditions on the indoor environment. Variables representative of indoor environmental conditions were measured in the living room, bedroom and outdoors in each of the three years of the study. In 2000, there was a significant difference between the changes from 1999 to 2000 between Phase I (upgraded) and II (not then upgraded) houses for bedroom temperatures (p=0.002). Changes in wall surface dampness and wall dampness in Phase I houses were also significantly different to the change in Phase II houses in 2000 (p=0.001), but by 2001 the Phase I houses had reverted to the same dampness levels they had before upgrading. The housing upgrades increased bedroom temperatures in all houses. Other indoor environmental variables were not affected.

An Audit and Feedback Intervention for Reducing Antibiotic Prescribing in General Dental Practice: The RAPiD Cluster Randomised Controlled Trial

PubMed Central

Elouafkaoui, Paula; Young, Linda; Newlands, Rumana; Duncan, Eilidh M.; Elders, Andrew; Ramsay, Craig R.

2016-01-01

Background Dentists prescribe approximately 10% of antibiotics dispensed in UK community pharmacies. Despite clear clinical guidance, dentists often prescribe antibiotics inappropriately. This cluster-randomised controlled trial used routinely collected National Health Service (NHS) dental prescribing and treatment claim data to compare the impact of individualised audit and feedback (A&F) interventions on dentists’ antibiotic prescribing rates. Methods and Findings All 795 antibiotic prescribing NHS general dental practices in Scotland were included. Practices were randomised to the control (practices = 163; dentists = 567) or A&F intervention group (practices = 632; dentists = 1,999). A&F intervention practices were allocated to one of two A&F groups: (1) individualised graphical A&F comprising a line graph plotting an individual dentist’s monthly antibiotic prescribing rate (practices = 316; dentists = 1,001); or (2) individualised graphical A&F plus a written behaviour change message synthesising and reiterating national guidance recommendations for dental antibiotic prescribing (practices = 316; dentists = 998). Intervention practices were also simultaneously randomised to receive A&F: (i) with or without a health board comparator comprising the addition of a line to the graphical A&F plotting the monthly antibiotic prescribing rate of all dentists in the health board; and (ii) delivered at 0 and 6 mo or at 0, 6, and 9 mo, giving a total of eight intervention groups. The primary outcome, measured by the trial statistician who was blinded to allocation, was the total number of antibiotic items dispensed per 100 NHS treatment claims over the 12 mo post-delivery of the baseline A&F. Primary outcome data was available for 152 control practices (dentists = 438) and 609 intervention practices (dentists = 1,550). At baseline, the number of antibiotic items prescribed per 100 NHS treatment claims was 8.3 in the control group and 8.5 in the intervention group. At follow-up, antibiotic prescribing had decreased by 0.4 antibiotic items per 100 NHS treatment claims in control practices and by 1.0 in intervention practices. This represents a significant reduction (-5.7%; 95% CI -10.2% to -1.1%; p = 0.01) in dentists' prescribing rate in the intervention group relative to the control group. Intervention subgroup analyses found a 6.1% reduction in the antibiotic prescribing rate of dentists who had received the written behaviour change message relative to dentists who had not (95% CI -10.4% to -1.9%; p = 0.01). There was no significant between-group difference in the prescribing rate of dentists who received a health board comparator relative to those who did not (-4.3%; 95% CI -8.6% to 0.1%; p = 0.06), nor between dentists who received A&F at 0 and 6 mo relative to those who received A&F at 0, 6, and 9 mo (0.02%; 95% CI -4.2% to 4.2%; p = 0.99). The key limitations relate to the use of routinely collected datasets which did not allow evaluation of any effects on inappropriate prescribing. Conclusions A&F derived from routinely collected datasets led to a significant reduction in the antibiotic prescribing rate of dentists. Trial Registration Current Controlled Trials ISRCTN49204710 PMID:27575599

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

Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2).

PubMed

Rosenberg, Jonathan E; Hahn, Noah M; Regan, Meredith M; Werner, Lillian; Alva, Ajjai; George, Saby; Picus, Joel; Alter, Robert; Balar, Arjun; Hoffman-Censits, Jean; Grivas, Petros; Lauer, Richard; Guancial, Elizabeth A; Hoimes, Christopher; Sonpavde, Guru; Albany, Constantine; Stein, Mark N; Breen, Tim; Jacobs, Cindy; Anderson, Kirsten; Bellmunt, Joaquim; Lalani, Aly-Khan A; Pal, Sumanta; Choueiri, Toni K

2018-05-16

A randomised study to assess the addition of apatorsen, an antisense oligonucleotide that inhibits Hsp27 expression, to docetaxel in patients with metastatic urothelial carcinoma (mUC) relapsed after prior platinum-based chemotherapy. Multicentre, phase II study with 1:1 randomisation to apatorsen (three loading doses at 600 mg intravenous followed by weekly doses) plus docetaxel (75 mg/m 2 intravenous every 21 days) (A/D) or docetaxel alone. Overall survival (OS) was the primary end point with a P value <0.1 (one-sided) being positive. Progression-free survival (PFS), objective response rate (ORR), safety, and effect of Hsp27 levels on outcomes were secondary end points. Patients randomised to A/D (n = 99) had improved OS compared to docetaxel alone (n = 101): HR: 0.80, 80% CI: 0.65-0.98, P = 0.0784, median 6.4 vs 5.9 months. PFS and ORR were similar in both arms. A/D had more incidence of sepsis and urinary tract infections. Patients with baseline Hsp27 levels <5.7 ng/mL had improved OS compared to those with levels ≥5.7 ng/mL. Patients with a decline or ≤20.5% increase in Hsp27 from baseline benefited more from A/D than those with >20.5% increase. A/D met its predefined OS end point in patients with platinum-refractory mUC in this phase II trial. This trial is hypothesis generating requiring further study before informing practice.

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.

Developing and piloting a peer mentoring intervention to reduce teenage pregnancy in looked-after children and care leavers: an exploratory randomised controlled trial.

PubMed Central

Mezey, Gillian; Meyer, Deborah; Robinson, Fiona; Bonell, Chris; Campbell, Rona; Gillard, Steve; Jordan, Peter; Mantovani, Nadia; Wellings, Kaye; White, Sarah

2015-01-01

BACKGROUND: Looked-after children (LAC) are at greater risk of teenage pregnancy than non-LAC, which is associated with adverse health and social consequences. Existing interventions have failed to reduce rates of teenage pregnancy in LAC. Peer mentoring is proposed as a means of addressing many of the factors associated with the increased risk of teenage pregnancy in this group. OBJECTIVE: To develop a peer mentoring intervention to reduce teenage pregnancy in LAC. DESIGN: Phase I and II randomised controlled trial of a peer mentoring intervention for LAC; scoping exercise and literature search; national surveys of social care professionals and LAC; and focus groups and interviews with social care professionals, mentors and mentees. SETTING: Three local authorities (LAs) in England. PARTICIPANTS: LAC aged 14-18 years (mentees/care as usual) and 19-25 years (mentors). INTERVENTION: Recruitment and training of mentors; randomisation and matching of mentors to mentees; and 1-year individual peer mentoring. MAIN OUTCOME MEASURES: PRIMARY OUTCOME: pregnancy in LAC aged 14-18 years. SECONDARY OUTCOMES: sexual attitudes, behaviour and knowledge; psychological health; help-seeking behaviour; locus of control; and attachment style. A health economic evaluation was also carried out. RESULTS: In total, 54% of target recruitment was reached for the exploratory trial and 13 out of 20 mentors (65%) and 19 out of 30 LAC aged 14-18 years (63%) (recruited during Phases I and II) were retained in the research. The training programme was acceptable and could be manualised and replicated. Recruitment and retention difficulties were attributed to systemic problems and LA lack of research infrastructure and lack of additional funding to support and sustain such an intervention. Mentees appeared to value the intervention but had difficulty in meeting weekly as required. Only one in four of the relationships continued for the full year. A future Phase III trial would require the intervention to be modified to include provision of group and individual peer mentoring; internal management of the project, with support from an external agency such as a charity or the voluntary sector; funds to cover LA research costs, including the appointment of a dedicated project co-ordinator; a reduction in the lower age for mentee recruitment and an increase in the mentor recruitment age to 21 years; and the introduction of a more formal recruitment and support structure for mentors. CONCLUSIONS: Given the problems identified and described in mounting this intervention, a new development phase followed by a small-scale exploratory trial incorporating these changes would be necessary before proceeding to a Phase III trial. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 85. See the NIHR Journals Library website for further project information. PMID:26497730

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.

How many patients with coronary heart disease are not achieving their risk-factor targets? Experience in Victoria 1996-1998 versus 1999-2000.

PubMed

Vale, Margarite J; Jelinek, Michael V; Best, James D

2002-03-04

To determine the proportion of patients with established coronary heart disease (CHD) in two Australian studies (VIC-I in 1996-1998, and VIC-II in 1999-2000) who achieved their risk-factor targets as recommended by the National Heart Foundation of Australia, and to compare this proportion with those in studies from the United Kingdom (ASPIRE), Europe (EUROASPIRE I and II) and the United States (L-TAP). Prospective cohort study with VIC-I set in a single Melbourne university teaching hospital and VIC-II set in six university teaching hospitals in Melbourne, Victoria. 460 patients (112 in VIC-I, 348 in VIC-II) who completed follow-up in the control groups of two randomised controlled trials of a coaching intervention in patients with established CHD. The treatment gap (100%, minus the percentage of patients achieving the target level for a particular modifiable risk factor) at six months after hospitalisation. The treatment gap declined from 96.4% (95% CI, 91%-99%) to 74.1% (95% CI, 69%-79%) for total cholesterol concentration (TC) < 4.0 mmol/L (P = 0.0001) and from 90.2% (95% CI, 83%-95%) to 54.0% (95% CI, 49%-59%) for TC < 4.5 mmol/L (P = 0.0001). This reduction in the treatment gap between VIC-I and VIC-II appears to be entirely explained by an increase in the number of patients prescribed lipid-lowering drugs. The treatment gaps in the UK and two European studies were substantially greater. The treatment gap for blood pressure (systolic > or = 140 mmHg and/or diastolic > or = 90 mmHg) in VIC-II was 39.5%, again less than corresponding European data. There were 8.1% of patients who had unrecognised diabetes in VIC-II (fasting glucose level > or = 7 mmol/L), making a total of 25.6% of VIC-II patients with diabetes, self-reported or unrecognised. The proportion of patients in VIC-II who were obese (body mass index > or = 30 kg/m2) was similar to the overseas studies, while fewer patients in VIC-II smoked compared with those in the UK and European studies. A substantial treatment gap exists in Victorian patients with established CHD. The treatment gap compares well with international surveys and, at least in the lipid area, is diminishing.

Midtrimester preterm prelabour rupture of membranes (PPROM): expectant management or amnioinfusion for improving perinatal outcomes (PPROMEXIL - III trial).

PubMed

van Teeffelen, Augustinus S P; van der Ham, David P; Willekes, Christine; Al Nasiry, Salwan; Nijhuis, Jan G; van Kuijk, Sander; Schuyt, Ewoud; Mulder, Twan L M; Franssen, Maureen T M; Oepkes, Dick; Jansen, Fenna A R; Woiski, Mallory D; Bekker, Mireille N; Bax, Caroline J; Porath, Martina M; de Laat, Monique W M; Mol, Ben W; Pajkrt, Eva

2014-04-04

Babies born after midtrimester preterm prelabour rupture of membranes (PPROM) are at risk to develop neonatal pulmonary hypoplasia. Perinatal mortality and morbidity after this complication is high. Oligohydramnios in the midtrimester following PPROM is considered to cause a delay in lung development. Repeated transabdominal amnioinfusion with the objective to alleviate oligohydramnios might prevent this complication and might improve neonatal outcome. Women with PPROM and persisting oligohydramnios between 16 and 24 weeks gestational age will be asked to participate in a multi-centre randomised controlled trial. random allocation to (repeated) abdominal amnioinfusion (intervention) or expectant management (control). The primary outcome is perinatal mortality. Secondary outcomes are lethal pulmonary hypoplasia, non-lethal pulmonary hypoplasia, survival till discharge from NICU, neonatal mortality, chronic lung disease (CLD), number of days ventilatory support, necrotizing enterocolitis (NEC), periventricular leucomalacia (PVL) more than grade I, severe intraventricular hemorrhage (IVH) more than grade II, proven neonatal sepsis, gestational age at delivery, time to delivery, indication for delivery, successful amnioinfusion, placental abruption, cord prolapse, chorioamnionitis, fetal trauma due to puncture. The study will be evaluated according to intention to treat. To show a decrease in perinatal mortality from 70% to 35%, we need to randomise two groups of 28 women (two sided test, β-error 0.2 and α-error 0.05). This study will answer the question if (repeated) abdominal amnioinfusion after midtrimester PPROM with associated oligohydramnios improves perinatal survival and prevents pulmonary hypoplasia and other neonatal morbidities. Moreover, it will assess the risks associated with this procedure. NTR3492 Dutch Trial Register (http://www.trialregister.nl).

Randomised, double-blind, placebo-controlled trial of EPs 7630 in adults with COPD.

PubMed

Matthys, Heinrich; Pliskevich, Dina A; Bondarchuk, Oleksandr M; Malek, Fathi A; Tribanek, Michael; Kieser, Meinhard

2013-05-01

Preventing and managing exacerbations is one major component in COPD treatment. We investigated whether EPs 7630, a herbal drug preparation from the roots of Pelargonium sidoides, could prolong time to acute exacerbation in patients with COPD stage II/III. In this randomised, double-blind, placebo-controlled clinical trial, patients were randomly allocated to oral 24-week add-on therapy with 3 × 30 drops/day EPs 7630 (n = 99) or placebo (n = 101) to a standardised baseline-treatment. Primary endpoint was time to first exacerbation of COPD. Secondary endpoints were number of exacerbations, consumption of antibiotics, quality of life, patient satisfaction, inability to work, and tolerability. Median time to exacerbation was significantly prolonged with EPs 7630 compared to placebo (57 versus 43 days, Kaplan-Maier-estimate; p = 0.005, one-sided centre-stratified log-rank test). The superiority of EPs 7630 was also confirmed in secondary endpoints, e.g., fewer exacerbations, less patients with antibiotic use, improved quality of life, higher patient satisfaction, and less days of inability to work. The incidence of minor gastrointestinal adverse events was higher in the EPs 7630 group. The results demonstrate a statistically significant and clinically relevant superiority of add-on therapy with EPs 7630 over placebo and a good long-term tolerability in the treatment of moderate to severe COPD. EPs 7630 prolonged time to exacerbations and reduced exacerbation frequency and antibiotic use. Trial Registration No.: ISRCTN01681733. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

Usage, adherence and attrition: how new mothers engage with a nurse-moderated web-based intervention to support maternal and infant health. A 9-month observational study

PubMed Central

Sawyer, Michael G; Reece, Christy E; Bowering, Kerrie; Jeffs, Debra; Sawyer, Alyssa C P; Peters, Jacqueline D; Mpundu-Kaambwa, Christine; Clark, Jennifer J; McDonald, Denise; Mittinty, Murthy N; Lynch, John W

2016-01-01

Objectives To identify factors predicting use, adherence and attrition with a nurse-moderated web-based group intervention designed to support mothers of infants aged 0–6 months. Design 9-Month observational study. Setting Community maternal and child health service. Participants 240 mothers attending initial postnatal health checks at community clinics who were randomly assigned to the intervention arm of a pragmatic preference randomised trial (total randomised controlled trial, n=819; response rate=45%). Intervention In the first week (phase I), mothers were assisted with their first website login by a research assistant. In weeks 2–7 (phase II), mothers participated in the web-based intervention with an expectation of weekly logins. The web-based intervention was comparable to traditional face-to-face new mothers’ groups. During weeks 8–26 (phase III), mothers participated in an extended programme at a frequency of their choosing. Primary outcome measures Number of logins and posted messages. Standard self-report measures assessed maternal demographic and psychosocial characteristics. Results In phase II, the median number of logins was 9 logins (IQR=1–25), and in phase III, it was 10 logins (IQR=0–39). Incident risk ratios from multivariable analyses indicated that compared to mothers with the lowest third of logins in phase I, those with the highest third had 6.43 times as many logins in phase II and 7.14 times in phase III. Fifty per cent of mothers logged-in at least once every 30 days for 147 days after phase I and 44% logged-in at least once in the last 30 days of the intervention. Frequency of logins during phase I was a stronger predictor of mothers’ level of engagement with the intervention than their demographic and psychosocial characteristics. Conclusions Mothers’ early use of web-based interventions could be employed to customise engagement protocols to the circumstances of individual mothers with the aim of improving adherence and reducing attrition with web-based interventions. Trial registration number ACTRN12613000204741; Results. PMID:27496227

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

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.

Efficacy of rasagiline in patients with the parkinsonian variant of multiple system atrophy: a randomised, placebo-controlled trial.

PubMed

Poewe, Werner; Seppi, Klaus; Fitzer-Attas, Cheryl J; Wenning, Gregor K; Gilman, Sid; Low, Phillip A; Giladi, Nir; Barone, Paolo; Sampaio, Cristina; Eyal, Eli; Rascol, Olivier

2015-02-01

Multiple system atrophy is a complex neurodegenerative disorder for which no effective treatment exists. We aimed to assess the effect of rasagiline on symptoms and progression of the parkinsonian variant of multiple system atrophy. We did this randomised, double-blind, placebo-controlled trial between Dec 15, 2009, and Oct 20, 2011, at 40 academic sites specialised in the care of patients with multiple systemic atrophy across 12 countries. Eligible participants aged 30 years or older with possible or probable parkinsonian variant multiple system atrophy were randomly assigned (1:1), via computer-generated block randomisation (block size of four), to receive either rasagiline 1 mg per day or placebo. Randomisation was stratified by study centre. The investigators, study funder, and personnel involved in patient assessment, monitoring, analysis and data management were masked to group assignment. The primary endpoint was change from baseline to study end in total Unified Multiple System Atrophy Rating Scale (UMSARS) score (parts I and II). Analysis was by modified intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00977665. We randomly assigned 174 participants to the rasagiline group (n=84) or the placebo group (n=90); 21 (25%) patients in the rasagiline group and 15 (17%) in the placebo group withdrew from the study early. At week 48, patients in the rasagiline group had progressed by an adjusted mean of 7·2 (SE 1·2) total UMSARS units versus 7·8 (1·1) units in those in the placebo group. This treatment difference of -0·60 (95% CI -3·68 to 2·47; p=0·70) was not significant. 68 (81%) patients in the rasagiline group and 67 (74%) patients in the placebo group reported adverse events, and we recorded serious adverse events in 29 (35%) versus 23 (26%) patients. The most common adverse events in the rasagiline group were dizziness (n=10 [12%]), peripheral oedema (n=9 [11%]), urinary tract infections (n=9 [11%]), and orthostatic hypotension (n=8 [10%]). In this population of patients with the parkinsonian variant of multiple system atrophy, treatment with rasagiline 1 mg per day did not show a significant benefit as assessed by UMSARS. The study confirms the sensitivity of clinical outcomes for multiple system atrophy to detect clinically significant decline, even in individuals with early disease. Teva Pharmaceutical Industries and H Lundbeck A/S. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Impact of a pharmacist-delivered discharge and follow-up intervention for patients with acute coronary syndromes in Qatar: a study protocol for a randomised controlled trial.

PubMed

Zidan, Amani; Awaisu, Ahmed; Kheir, Nadir; Mahfoud, Ziyad; Kaddoura, Rasha; AlYafei, Sumaya; El Hajj, Maguy Saffouh

2016-11-18

Acute coronary syndrome (ACS) is one of the leading causes of morbidity and mortality worldwide. Secondary cardiovascular risk reduction therapy (consisting of an aspirin, a β-blocker, an ACE inhibitor or an angiotensin II receptor blocker and a statin) is needed for all patients with ACS. Less than 80% of patients with ACS in Qatar use this combination after discharge. This study is aimed to evaluate the effectiveness of clinical pharmacist-delivered intervention at discharge and tailored follow-up postdischarge on decreasing hospital readmissions, emergency department (ED) visits and mortality among patients with ACS. A prospective, randomised controlled trial will be conducted at the Heart Hospital in Qatar. Patients are eligible for enrolment if they are at least 18 years of age and are discharged from any non-surgical cardiology service with ACS. Participants will be randomised into 1 of 3 arms: (1) 'control' arm which includes patients discharged during weekends or after hours; (2) 'clinical pharmacist delivered usual care at discharge' arm which includes patients receiving the usual care at discharge by clinical pharmacists; and (3) 'clinical pharmacist-delivered structured intervention at discharge and tailored follow-up postdischarge' arm which includes patients receiving intensive structured discharge interventions in addition to 2 follow-up sessions by intervention clinical pharmacists. Outcomes will be measured by blinded research assistants at 3, 6 and 12 months after discharge and will include: all-cause hospitalisations and cardiac-related hospital readmissions (primary outcome), all-cause mortality including cardiac-related mortality, ED visits including cardiac-related ED visits, adherence to medications and treatment burden. Percentage of readmissions between the 3 arms will be compared on intent-to-treat basis using χ 2 test with Bonferroni's adjusted pairwise comparisons if needed. The study was ethically approved by the Qatar University and the Hamad Medical Corporation Institutional Review Boards. The results shall be disseminated in international conferences and peer-reviewed publications. NCT02648243; 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 preventive care activities in general practice be sustained when financial incentives and external audit plus feedback are removed? ACCEPt-able: a cluster randomised controlled trial protocol.

PubMed

Hocking, Jane S; Temple-Smith, Meredith; van Driel, Mieke; Law, Matthew; Guy, Rebecca; Bulfone, Liliana; Wood, Anna; Low, Nicola; Donovan, Basil; Fairley, Christopher K; Kaldor, John; Gunn, Jane

2016-09-13

Financial incentives and audit plus feedback on performance are two strategies commonly used by governments to motivate general practitioners (GP) to undertake specific healthcare activities. However, in recent years, governments have reduced or removed incentive payments without evidence of the potential impact on GP behaviour and patient outcomes. This trial (known as ACCEPt-able) aims to determine whether preventive care activities in general practice are sustained when financial incentives and/or external audit plus feedback on preventive care activities are removed. The activity investigated is annual chlamydia testing for 16- to 29-year-old adults, a key preventive health strategy within this age group. ACCEPt-able builds on a large cluster randomised controlled trial (RCT) that evaluated a 3-year chlamydia testing intervention in general practice. GPs were provided with a support package to facilitate annual chlamydia testing of all sexually active 16- to 29-year-old patients. This package included financial incentive payments to the GP for each chlamydia test conducted and external audit plus feedback on each GP's chlamydia testing rates. ACCEPt-able is a factorial cluster RCT in which general practices are randomised to one of four groups: (i) removal of audit plus feedback-continue to receive financial incentive payments for each chlamydia test; (ii) removal of financial incentive payments-continue to receive audit plus feedback; (iii) removal of financial incentive payments and audit plus feedback; and (iv) continue financial incentive payments and audit plus feedback. The primary outcome is chlamydia testing rate measured as the proportion of sexually active 16- to 29-year-olds who have a GP consultation within a 12-month period and at least one chlamydia test. This will be the first RCT to examine the impact of removal of financial incentive payments and audit plus feedback on the chlamydia testing behaviour of GPs. This trial is particularly timely and will increase our understanding about the impact of financial incentives and audit plus feedback on GP behaviour when governments are looking for opportunities to control healthcare budgets and maximise clinical outcomes for money spent. The results of this trial will have implications for supporting preventive health measures beyond the content area of chlamydia. The trial has been registered on the Australian and New Zealand Clinical Trials Registry ( ACTRN12614000595617 ).

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.

Efficacy of a multifaceted podiatry intervention to improve balance and prevent falls in older people: study protocol for a randomised trial.

PubMed

Spink, Martin J; Menz, Hylton B; Lord, Stephen R

2008-11-25

Falls in older people are a major public health problem, with at least one in three people aged over 65 years falling each year. There is increasing evidence that foot problems and inappropriate footwear increase the risk of falls, however no studies have been undertaken to determine whether modifying these risk factors decreases the risk of falling. This article describes the design of a randomised trial to evaluate the efficacy of a multifaceted podiatry intervention to reduce foot pain, improve balance, and reduce falls in older people. Three hundred community-dwelling men and women aged 65 years and over with current foot pain and an increased risk of falling will be randomly allocated to a control or intervention group. The "usual cae" control group will receive routine podiatry (i.e. nail care and callus debridement). The intervention group will receive usual care plus a multifaceted podiatry intervention consisting of: (i) prefabricated insoles customised to accommodate plantar lesions; (ii) footwear advice and assistance with the purchase of new footwear if current footwear is inappropriate; (iii) a home-based exercise program to strengthen foot and ankle muscles; and (iv) a falls prevention education booklet. Primary outcome measures will be the number of fallers, number of multiple fallers and the falls rate recorded by a falls diary over a 12 month period. Secondary outcome measures assessed six months after baseline will include the Medical Outcomes Study Short Form 12 (SF-12), the Manchester Foot Pain and Disability Index, the Falls Efficacy Scale International, and a series of balance and functional tests. Data will be analysed using the intention to treat principle. This study is the first randomised trial to evaluate the efficacy of podiatry in improving balance and preventing falls. The trial has been pragmatically designed to ensure that the findings can be generalised to clinical practice. If found to be effective, the multifaceted podiatry intervention will be a unique addition to common falls prevention strategies already in use. Australian New Zealand Clinical Trials Registry: ACTRN12608000065392.

Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2×2 clinical trial

PubMed Central

Savitz, Jonathan; Preskorn, Sheldon; Teague, T Kent; Drevets, Douglas; Yates, William

2012-01-01

Introduction New medication classes are needed to improve treatment effectiveness in the depressed phase of bipolar disorder (BD). Extant evidence suggests that BD is characterised by neural changes such as dendritic remodelling and glial and neuronal cell loss. These changes have been hypothesised to result from chronic inflammation. The principal aims of the proposed research is to evaluate the antidepressant efficacy in bipolar depression of minocycline, a drug with neuroprotective and immune-modulating properties, and of aspirin, at doses expected to selectively inhibit cyclooxygenase 1 (COX-1). Methods and analysis 120 outpatients between 18 and 55 years of age, who meet DSM-IV-TR criteria for BD (type I or II) and for a current major depressive episode will be recruited to take part in a randomised, double-blind, placebo-controlled, parallel-group, proof-of-concept clinical trial following a 2×2 design. As adjuncts to existing treatment, subjects will be randomised to receive one of the four treatment combinations: placebo-minocycline plus placebo-aspirin, active-minocycline plus placebo-aspirin, placebo-minocycline plus active-aspirin or active-minocycline plus active-aspirin. The dose of minocycline and aspirin is 100 mg twice daily and 81 mg twice daily, respectively. Antidepressant response will be evaluated by assessing changes in the Montgomery–Asberg Depression Rating Scale scores between baseline and the end of the 6-week trial. As secondary outcome measures, the anti-inflammatory effects of minocycline and aspirin will be tested by measuring pre-treatment and post-treatment levels of C reactive protein and inflammatory cytokines. Ethics and dissemination Minocycline has been widely used as an antibiotic in doses up to 400 mg/day. Low-dose aspirin has been safely used on a worldwide scale for its role as an antithrombotic and thrombolytic. The study progress will be overseen by a Data, Safety and Monitoring Board, which will meet once every 6 months. Results of the study will be published in peer-reviewed publications. Trial registration number Clinical Trials.gov: NCT01429272. PMID:22357572

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.

The effect of mindfulness training prior to total joint arthroplasty on post-operative pain and physical function: study protocol for a randomised controlled trial.

PubMed

Dowsey, Michelle M; Castle, David J; Knowles, Simon R; Monshat, Kaveh; Salzberg, Michael R; Choong, Peter F M

2014-06-05

Osteoarthritis is a leading cause of disability in developed nations. In Australia it afflicts 16.5% of the adult population. Total joint arthroplasty is considered the treatment of choice for end stage osteoarthritis. The number of total joint arthroplasties undertaken in Australia has doubled over the last decade (more than 80,000 procedures in 2011). The incidence of pre-operative psychological distress in this group of patients is reported between 30% and 60% and pre-operative psychological distress is associated with poorer pain and functional outcomes after surgery. This study will use a mindfulness-based psychological intervention to enhance outcomes in people undergoing total joint arthroplasty and, in addition, will test hypotheses about coping with chronic illness in an aged population. This study is the first of its kind and will provide a greater understanding of the role of a mental health enhancement program on the physical recovery of total joint arthroplasty patients. One hundred and fifty people with end-stage arthritis on the waiting list for total hip or knee arthroplasty will be recruited and randomly allocated to one of two groups using computer-generated block randomisation. A randomised controlled trial adhering to CONSORT guidelines will evaluate the efficacy of a mindfulness training program (weekly group-based classes in mindfulness practice, 2 ½ hours, for 8 weeks plus a 7-hour Saturday session in Week 6) prior to total joint arthroplasty, compared to a "standard care" group who will undergo routine total joint arthroplasty. Primary outcomes will be evaluated by a blinded examiner at baseline, 3 and 12 months post-surgery, using a validated self-reported pain and physical function scale. Secondary outcomes will include i) a range of validated measures of psychological wellbeing and ii) health economic analysis. All analyses will be conducted on an intention to treat basis using linear regression models. Health economic modelling will be applied to estimate the potential cost-effectiveness of mindfulness training and total joint arthroplasty. Australian New Zealand Clinical Trials Registry (ANZCTRN12611001184965). Date of registration; 15th November 2011.

Linking quality of care and training costs: cost-effectiveness in health professions education.

PubMed

Tolsgaard, Martin G; Tabor, Ann; Madsen, Mette E; Wulff, Camilla B; Dyre, Liv; Ringsted, Charlotte; Nørgaard, Lone N

2015-12-01

To provide a model for conducting cost-effectiveness analyses in medical education. The model was based on a randomised trial examining the effects of training midwives to perform cervical length measurement (CLM) as compared with obstetricians on patients' waiting times. (CLM), as compared with obstetricians. The model included four steps: (i) gathering data on training outcomes, (ii) assessing total costs and effects, (iii) calculating the incremental cost-effectiveness ratio (ICER) and (iv) estimating cost-effectiveness probability for different willingness to pay (WTP) values. To provide a model example, we conducted a randomised cost-effectiveness trial. Midwives were randomised to CLM training (midwife-performed CLMs) or no training (initial management by midwife, and CLM performed by obstetrician). Intervention-group participants underwent simulation-based and clinical training until they were proficient. During the following 6 months, waiting times from arrival to admission or discharge were recorded for women who presented with symptoms of pre-term labour. Outcomes for women managed by intervention and control-group participants were compared. These data were then used for the remaining steps of the cost-effectiveness model. Intervention-group participants needed a mean 268.2 (95% confidence interval [CI], 140.2-392.2) minutes of simulator training and a mean 7.3 (95% CI, 4.4-10.3) supervised scans to attain proficiency. Women who were scanned by intervention-group participants had significantly reduced waiting time compared with those managed by the control group (n = 65; mean difference, 36.6 [95% CI 7.3-65.8] minutes; p = 0.008), which corresponded to an ICER of 0.45 EUR minute(-1) . For WTP values less than EUR 0.26 minute(-1) , obstetrician-performed CLM was the most cost-effective strategy, whereas midwife-performed CLM was cost-effective for WTP values above EUR 0.73 minute(-1) . Cost-effectiveness models can be used to link quality of care to training costs. The example used in the present study demonstrated that different training strategies could be recommended as the most cost-effective depending on administrators' willingness to pay per unit of the outcome variable. © 2015 Medical Education Published by John Wiley & Sons Ltd.

Interpretation of health news items reported with or without spin: protocol for a prospective meta-analysis of 16 randomised controlled trials

PubMed Central

Haneef, Romana; Yavchitz, Amélie; Ravaud, Philippe; Baron, Gabriel; Oranksy, Ivan; Schwitzer, Gary; Boutron, Isabelle

2017-01-01

Introduction We aim to compare the interpretation of health news items reported with or without spin. ‘Spin’ is defined as a misrepresentation of study results, regardless of motive (intentionally or unintentionally) that overemphasises the beneficial effects of the intervention and overstates safety compared with that shown by the results. Methods and analysis We have planned a series of 16 randomised controlled trials (RCTs) to perform a prospective meta-analysis. We will select a sample of health news items reporting the results of four types of study designs, evaluating the effect of pharmacological treatment and containing the highest amount of spin in the headline and text. News items reporting four types of studies will be included: (1) preclinical studies; (2) phase I/II (non-randomised) trials; (3) RCTs and (4) observational studies. We will rewrite the selected news items and remove the spin. The original news and rewritten news will be appraised by four types of populations: (1) French-speaking patients; (2) French-speaking general public; (3) English-speaking patients and (4) English-speaking general public. Each RCT will explore the interpretation of news items reporting one of the four study designs by each type of population and will include a sample size of 300 participants. The primary outcome will be participants’ interpretation of the benefit of treatment after reading the news items: (What do you think is the probability that treatment X would be beneficial to patients? (scale, 0 (very unlikely) to 10 (very likely)). This study will evaluate the impact of spin on the interpretation of health news reporting results of studies by patients and the general public. Ethics and dissemination This study has obtained ethics approval from the Institutional Review Board of the Institut national de la santé et de la recherche médicale (INSERM) (registration no: IRB00003888). The description of all the steps and the results of this prospective meta-analysis will be available online and will be disseminated as a published article. On the completion of this study, the results will be sent to all participants. PROSPERO registration number CRD42017058941. PMID:29151047

Efficacy of acupuncture for chronic knee pain: protocol for a randomised controlled trial using a Zelen design

PubMed Central

2012-01-01

Background Chronic knee pain is a common and disabling condition in people over 50 years of age, with knee joint osteoarthritis being a major cause. Acupuncture is a popular form of complementary and alternative medicine for treating pain and dysfunction associated with musculoskeletal conditions. This pragmatic Zelen-design randomised controlled trial is investigating the efficacy and cost-effectiveness of needle and laser acupuncture, administered by medical practitioners, in people with chronic knee pain. Methods/Design Two hundred and eighty two people aged over 50 years with chronic knee pain have been recruited from metropolitan Melbourne and regional Victoria, Australia. Participants originally consented to participate in a longitudinal natural history study but were then covertly randomised into one of four treatment groups. One group continued as originally consented (ie natural history group) and received no acupuncture treatment. The other three were treatment groups: i) laser acupuncture, ii) sham laser or, iii) needle acupuncture. Acupuncture treatments used a combined Western and Traditional Chinese Medicine style, were delivered by general practitioners and comprised 8–12 visits over 12 weeks. Follow-up is currently ongoing. The primary outcomes are pain measured by an 11-point numeric rating scale (NRS) and self-reported physical function measured by the Western Ontario and McMaster (WOMAC) Universities Osteoarthritis Index subscale at the completion of treatment at 12 weeks. Secondary outcomes include quality of life, global rating of change scores and additional measures of pain (other NRS and WOMAC subscale) and physical function (NRS). Additional parameters include a range of psychosocial measures in order to evaluate potential relationships with acupuncture treatment outcomes. Relative cost-effectiveness will be determined from health service usage and outcome data. Follow-up assessments will also occur at 12 months. Discussion The findings from this study will help determine whether laser and/or needle acupuncture is efficacious, and cost-effective, in the management of chronic knee pain in older people. Trial registration Australian New Zealand Clinical Trials Registry reference: ACTRN12609001001280 PMID:22992309

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

Review article: novel oral-targeted therapies in inflammatory bowel disease.

PubMed

White, J R; Phillips, F; Monaghan, T; Fateen, W; Samuel, S; Ghosh, S; Moran, G W

2018-06-01

There is a great unmet clinical need for efficacious, tolerable, economical and orally administrated drugs for the treatment of inflammatory bowel disease (IBD). New therapeutic avenues have become possible including the development of medications that target specific genetic pathways found to be relevant in other immune mediated diseases. To provide an overview of recent clinical trials for new generation oral targeted medications that may have a future role in IBD management. Pubmed and Medline searches were performed up to 1 March 2018 using keywords: "IBD", "UC", "CD", "inflammatory bowel disease" "ulcerative colitis", "Crohn's disease" in combination with "phase", "study", "trial" and "oral". A manual search of the clinical trial register, article reference lists, abstracts from meetings of Digestive Disease Week, United European Gastroenterology Week and ECCO congress were also conducted. In randomised controlled trials primary efficacy endpoints were met for tofacitinib (JAK 1/3 inhibitor-phase III), upadacitinib (JAK 1 inhibitor-phase II) and AJM300 (α4-integrin antagonist-phase II) in ulcerative colitis. Ozanimod (S1P receptor agonist-phase II) also demonstrated clinical remission. For Crohn's disease, filgotinib (JAK1 inhibitor-phase II) met primary endpoints and laquinimod (quinolone-3-carboxide small molecule-phase II) was also efficacious. Trials using mongersen (SMAD7 inhibitor) and vidofludimus (dihydroorotate dehydrogenase inhibitor) have been halted. This is potentially the start of an exciting new era in which multiple therapeutic options are at the disposal of physicians to treat IBD on an individualised basis. Head-to-head studies with existing treatments and longer term safety data are needed for this to be possible. © 2018 John Wiley & Sons Ltd.

Asthma control using fluticasone propionate/salmeterol in Asian and non-Asian populations: a post hoc analysis of the GOAL study.

PubMed

Bousquet, Jean; Barnes, Neil; Gibbs, Michael; Gul, Nadeem; Tomkins, Susan A; Zhou, Xin; Cho, Young-Joo; Park, Hae-Sim; Busse, William; Zhong, Nanshan

2017-04-28

To analyse the efficacy of fluticasone propionate (FP) alone and combined with salmeterol (SAL) in achieving guideline-defined asthma control in Asian patients. A post hoc analysis of the GOAL study in which patients were stratified by prior-medication use into inhaled corticosteroid (ICS)-naïve (Stratum [S] 1), low-dose ICS (S2), and medium-dose ICS (S3), and randomised to receive FP/SAL or FP. Doses were stepped-up every 12 weeks until Totally Controlled asthma or maximum dose was reached (PhI) and then maintained until study end (PhII). The primary endpoint was the proportion of patients achieving Well-Controlled asthma during PhI. Additional endpoints included Total Control and adverse events. Asian and non-Asian patients were analysed separately. In Asian patients in PhI, 74% (n = 87/118) in S1 achieved Well-Controlled asthma with FP/SAL versus 74% (n = 89/121) with FP alone (p = 0.839); corresponding values were 76% (n = 81/107) versus 60% (n = 62/104; p = 0.005) in S2, and 58% (n = 59/102) versus 43% (n = 41/95; p = 0.015) in S3. More patients in all three strata achieved Totally Controlled asthma with FP/SAL versus FP alone. Control was achieved more rapidly and with lower ICS doses with FP/SAL versus FP. A high proportion of patients who achieved control during PhI maintained control during PhII. Similar trends were found in non-Asian patients. No new safety concerns were identified. A greater proportion of Asian patients (S2 and S3, for Well-Controlled; all strata, for Totally Controlled) achieved guideline-defined asthma control with FP/SAL versus FP alone. High proportions of Asian patients in S1 achieved Well-Controlled asthma in both treatment groups.

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.

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

Low-fat yogurt consumption reduces biomarkers of chronic inflammation and inhibits markers of endotoxin exposure in healthy premenopausal women: a randomised controlled trial.

PubMed

Pei, Ruisong; DiMarco, Diana M; Putt, Kelley K; Martin, Derek A; Gu, Qinlei; Chitchumroonchokchai, Chureeporn; White, Heather M; Scarlett, Cameron O; Bruno, Richard S; Bolling, Bradley W

2017-12-01

The anti-inflammatory mechanisms of low-fat dairy product consumption are largely unknown. The objective of this study was to determine whether low-fat yogurt reduces biomarkers of chronic inflammation and endotoxin exposure in women. Premenopausal women (BMI 18·5-27 and 30-40 kg/m2) were randomised to consume 339 g of low-fat yogurt (yogurt non-obese (YN); yogurt obese (YO)) or 324 g of soya pudding (control non-obese; control obese (CO)) daily for 9 weeks (n 30/group). Fasting blood samples were analysed for IL-6, TNF-α/soluble TNF II (sTNF-RII), high-sensitivity C-reactive protein, 2-arachidonoyl glycerol, anandamide, monocyte gene expression, soluble CD14 (sCD14), lipopolysaccharide (LPS), LPS binding protein (LBP), IgM endotoxin-core antibody (IgM EndoCAb), and zonulin. BMI, waist circumference and blood pressure were also determined. After 9-week yogurt consumption, YO and YN had decreased TNF-α/sTNFR-RII. Yogurt consumption increased plasma IgM EndoCAb regardless of obesity status. sCD14 was not affected by diet, but LBP/sCD14 was lowered by yogurt consumption in both YN and YO. Yogurt intervention increased plasma 2-arachidonoylglycerol in YO but not YN. YO peripheral blood mononuclear cells expression of NF-κB inhibitor α and transforming growth factor β1 increased relative to CO at 9 weeks. Other biomarkers were unchanged by diet. CO and YO gained approximately 0·9 kg in body weight. YO had 3·6 % lower diastolic blood pressure at week 3. Low-fat yogurt for 9 weeks reduced biomarkers of chronic inflammation and endotoxin exposure in premenopausal women compared with a non-dairy control food. This trial was registered as NCT01686204.

Adding glucose to food and solutions to enhance fructose absorption is not effective in preventing fructose-induced functional gastrointestinal symptoms: randomised controlled trials in patients with fructose malabsorption.

PubMed

Tuck, C J; Ross, L A; Gibson, P R; Barrett, J S; Muir, J G

2017-02-01

In healthy individuals, the absorption of fructose in excess of glucose in solution is enhanced by the addition of glucose. The present study aimed to assess the effects of glucose addition to fructose or fructans on absorption patterns and genesis of gastrointestinal symptoms in patients with functional bowel disorders. Randomised, blinded, cross-over studies were performed in healthy subjects and functional bowel disorder patients with fructose malabsorption. The area-under-the-curve (AUC) was determined for breath hydrogen and symptom responses to: (i) six sugar solutions (fructose in solution) (glucose; sucrose; fructose; fructose + glucose; fructan; fructan + glucose) and (ii) whole foods (fructose in foods) containing fructose in excess of glucose given with and without additional glucose. Intake of fermentable short chain carbohydrates (FODMAPs; fermentable, oligo-, di-, monosaccharides and polyols) was controlled. For the fructose in solution study, in 26 patients with functional bowel disorders, breath hydrogen was reduced after glucose was added to fructose compared to fructose alone [mean (SD) AUC 92 (107) versus 859 (980) ppm 4 h -1 , respectively; P = 0.034). Glucose had no effect on breath hydrogen response to fructans (P = 1.000). The six healthy controls showed breath hydrogen patterns similar to those with functional bowel disorders. No differences in symptoms were experienced with the addition of glucose, except more nausea when glucose was added to fructose (P = 0.049). In the fructose in foods study, glucose addition to whole foods containing fructose in excess of glucose in nine patients with functional bowel disorders and nine healthy controls had no significant effect on breath hydrogen production or symptom response. The absence of a favourable response on symptoms does not support the concomitant intake of glucose with foods high in either fructose or fructans in patients with functional bowel disorders. © 2016 The British Dietetic Association Ltd.

Do questions help? The impact of audience response systems on medical student learning: a randomised controlled trial.

PubMed

Mains, Tyler E; Cofrancesco, Joseph; Milner, Stephen M; Shah, Nina G; Goldberg, Harry

2015-07-01

Audience response systems (ARSs) are electronic devices that allow educators to pose questions during lectures and receive immediate feedback on student knowledge. The current literature on the effectiveness of ARSs is contradictory, and their impact on student learning remains unclear. This randomised controlled trial was designed to isolate the impact of ARSs on student learning and students' perception of ARSs during a lecture. First-year medical student volunteers at Johns Hopkins were randomly assigned to either (i) watch a recorded lecture on an unfamiliar topic in which three ARS questions were embedded or (ii) watch the same lecture without the ARS questions. Immediately after the lecture on 5 June 2012, and again 2 weeks later, both groups were asked to complete a questionnaire to assess their knowledge of the lecture content and satisfaction with the learning experience. 92 students participated. The mean (95% CI) initial knowledge assessment score was 7.63 (7.17 to 8.09) for the ARS group (N=45) and 6.39 (5.81 to 6.97) for the control group (N=47), p=0.001. Similarly, the second knowledge assessment mean score was 6.95 (6.38 to 7.52) for the ARS group and 5.88 (5.29 to 6.47) for the control group, p=0.001. The ARS group also reported higher levels of engagement and enjoyment. Embedding three ARS questions within a 30 min lecture increased students' knowledge immediately after the lecture and 2 weeks later. We hypothesise that this increase was due to forced information retrieval by students during the learning process, a form of the testing effect. 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.

Milk minerals modify the effect of fat intake on serum lipid profile: results from an animal and a human short-term study.

PubMed

Lorenzen, Janne K; Jensen, Søren K; Astrup, Arne

2014-04-28

Despite a high content of saturated fat, evidence from observational studies indicates that the consumption of dairy products may have a neutral effect or may be inversely associated with the risk of CVD. We aimed to examine whether milk minerals modify the effect of saturated fat on serum lipid profile. We present data from two studies. Study I had a randomised, blinded, parallel design (n 24 pigs) with a 10 d adaptation period during which a high-fat diet was fed to the pigs and a 14 d intervention period during which the same diet either enriched with milk minerals (MM group) or placebo (control group) was fed to the pigs. Study II had a randomised cross-over design (n 9 men) where the subjects were fed either a high-fat diet enriched with milk minerals (MM period) or a regular diet (control period). In both the studies, blood variables were measured before and after the intervention and faecal and urine samples were collected at the end of the dietary periods. The increase in plasma total cholesterol and LDL-cholesterol concentrations but not in HDL-cholesterol concentration was markedly lowered by milk minerals in both the studies. In the animal study, baseline adjusted total cholesterol and LDL-cholesterol concentrations in the MM group were 11% (P = 0.004) and 13% (P = 0.03) lower compared with those in the control group after the intervention. Similarly in the human study, baseline adjusted total cholesterol and LDL-cholesterol concentrations were 6% (P = 0.002) and 9% (P = 0.03) lower after the MM period compared with those in the control period. HDL-cholesterol concentration was not lowered by milk minerals. These short-term studies indicate that the addition of milk minerals to a high-fat diet to some extent attenuates the increase in total cholesterol and LDL-cholesterol concentrations, without affecting HDL-cholesterol concentration.

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.

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

Identifying trial recruitment uncertainties using a James Lind Alliance Priority Setting Partnership - the PRioRiTy (Prioritising Recruitment in Randomised Trials) study.

PubMed

Healy, Patricia; Galvin, Sandra; Williamson, Paula R; Treweek, Shaun; Whiting, Caroline; Maeso, Beccy; Bray, Christopher; Brocklehurst, Peter; Moloney, Mary Clarke; Douiri, Abdel; Gamble, Carrol; Gardner, Heidi R; Mitchell, Derick; Stewart, Derek; Jordan, Joan; O'Donnell, Martin; Clarke, Mike; Pavitt, Sue H; Guegan, Eleanor Woodford; Blatch-Jones, Amanda; Smith, Valerie; Reay, Hannah; Devane, Declan

2018-03-01

Despite the problem of inadequate recruitment to randomised trials, there is little evidence to guide researchers on decisions about how people are effectively recruited to take part in trials. The PRioRiTy study aimed to identify and prioritise important unanswered trial recruitment questions for research. The PRioRiTy study - Priority Setting Partnership (PSP) included members of the public approached to take part in a randomised trial or who have represented participants on randomised trial steering committees, health professionals and research staff with experience of recruiting to randomised trials, people who have designed, conducted, analysed or reported on randomised trials and people with experience of randomised trials methodology. This partnership was aided by the James Lind Alliance and involved eight stages: (i) identifying a unique, relevant prioritisation area within trial methodology; (ii) establishing a steering group (iii) identifying and engaging with partners and stakeholders; (iv) formulating an initial list of uncertainties; (v) collating the uncertainties into research questions; (vi) confirming that the questions for research are a current recruitment challenge; (vii) shortlisting questions and (viii) final prioritisation through a face-to-face workshop. A total of 790 survey respondents yielded 1693 open-text answers to 6 questions, from which 1880 potential questions for research were identified. After merging duplicates, the number of questions was reduced to 496. Questions were combined further, and those that were submitted by fewer than 15 people and/or fewer than 6 of the 7 stakeholder groups were excluded from the next round of prioritisation resulting in 31 unique questions for research. All 31 questions were confirmed as being unanswered after checking relevant, up-to-date research evidence. The 10 highest priority questions were ranked at a face-to-face workshop. The number 1 ranked question was "How can randomised trials become part of routine care and best utilise current clinical care pathways?" The top 10 research questions can be viewed at www.priorityresearch.ie . The prioritised questions call for a collective focus on normalising trials as part of clinical care, enhancing communication, addressing barriers, enablers and motivators around participation and exploring greater public involvement in the research process.

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

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.

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

Adding a PECS II block for proximal arm arteriovenous access - a randomised study.

PubMed

Quek, K H; Low, E Y; Tan, Y R; Ong, A S C; Tang, T Y; Kam, J W; Kiew, A S C

2018-05-01

Brachial plexus block is often utilised for proximal arm arteriovenous access creation. However, the medial upper arm and axilla are often inadequately anaesthetised, requiring repeated, intraoperative local anaesthetic supplementation, or conversion into general anaesthesia. We hypothesised that the addition of a PECS II block would improve anaesthesia and analgesia for proximal arm arteriovenous access surgery. In this prospective, double-blinded, randomised proof-of-concept study, 36 consenting adults with end-stage renal disease aged between 21 and 90 years received either a combined supraclavicular and PECS II block (Group PECS, n = 18), or combined supraclavicular and sham block (Group SCB, n = 18) for proximal arm arteriovenous access surgery. Primary outcome was whether patients required intraoperative local anaesthetic supplementation by the surgeon. In Group PECS, 33.3% (6/18) needed local anaesthetic supplementation vs. 100% (18/18) in Group SCB. Group SCB had three times (RR 3.0, 95% CI 1.6-5.8; P < 0.001) the risk of requiring intraoperative local anaesthetic supplementation. Group PECS required lower volume of supplemental local anaesthetic compared to Group SCB (0.0 ml, IQR 0.0-6.3 ml vs. 15.0 ml, IQR 7.4-17.8 ml; P < 0.001). Group SCB had twice [RR 2.2, 95% CI 1.1-4.4; (P = 0.019)] the risk of needing additional sedation or analgesia. There were no significant differences between the groups with respect to postoperative visual analogue scale pain scores, time to first rescue analgesia or patient satisfaction. The results suggest that adding a PECS II block to a supraclavicular block improves regional anaesthesia for patients with end-stage renal disease undergoing proximal arm arteriovenous access surgery. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

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.

Survival results of a randomised two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of S-1 plus cisplatin (SC) and paclitaxel plus cisplatin (PC) followed by D2 gastrectomy for resectable advanced gastric cancer.

PubMed

Yoshikawa, Takaki; Morita, Satoshi; Tanabe, Kazuaki; Nishikawa, Kazuhiro; Ito, Yuichi; Matsui, Takanori; Fujitani, Kazumasa; Kimura, Yutaka; Fujita, Junya; Aoyama, Toru; Hayashi, Tsutomu; Cho, Haruhiko; Tsuburaya, Akira; Miyashita, Yumi; Sakamoto, Junichi

2016-07-01

The prognosis for stage III gastric cancer is unsatisfactory by D2 gastrectomy and S-1 adjuvant chemotherapy. Both S-1 plus cisplatin (SC) and paclitaxel plus cisplatin (PC) are promising regimens as neoadjuvant chemotherapy; however, the optimal duration remains unclear. In this 2×2 randomised phase II trial, stage III gastric cancer patients, those with a prognosis corresponding to stage III, and macroscopically resectable stage IV cases were randomised to two or four courses of S-1 (80 mg/m(2) for 21 d with 1 week rest)/cisplatin (60 mg/m(2) at day 8) or PC (80 and 25 mg/m(2), respectively, on days 1, 8, and 15 with 1 week rest) as neoadjuvant chemotherapy. The primary end-point was the 3-year overall survival (OS). Between October 2009 and July 2011, 83 patients received 2 courses of SC (n=21), 4 courses of SC (n=20), 2 courses of PC (n=21) and 4 courses of PC (n=21). The 3-year OS was 60.9% for SC and 64.3% for PC and 64.3% for the two courses and 61.0% for the four courses. Subset analyses demonstrated no subgroup which showed any potential survival benefit by PC in comparison to SC or by four courses as in comparison to two courses. Two courses of SC as neoadjuvant chemotherapy are recommended as a test arm of a future phase III study for patients with locally advanced gastric cancer. UMIN-000002595. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Postoperative analgesic efficacy of ultrasound-guided ilioinguinal-iliohypogastric nerve block compared with medial transverse abdominis plane block in inguinal hernia repair: A prospective, randomised trial.

PubMed

Bhatia, Nidhi; Sen, Indu Mohini; Mandal, Banashree; Batra, Ankita

2018-03-29

Analgesic efficacy of ultrasound-guided transverse abdominis plane block, administered a little more medially, just close to the origin of the transverse abdominis muscle has not yet been investigated in patients undergoing unilateral inguinal hernia repair. We hypothesised that medial transverse abdominis plane block would provide comparable postoperative analgesia to ilioinguinal-iliohypogastric nerve block in inguinal hernia repair patients. This prospective, randomised trial was conducted in 50 ASA I and II male patients≥18 years of age. Patients were randomised into two groups to receive either pre-incisional ipsilateral ultrasound-guided ilioinguinal-iliohypogastric nerve block or medial transverse abdominis plane block, with 0.3ml/kg of 0.25% bupivacaine. Our primary objective was postoperative 24-hour analgesic consumption and secondary outcomes included pain scores, time to first request for rescue analgesic and side effects, if any, in the postoperative period. There was no significant difference in the total postoperative analgesic consumption [group I: 66.04mg; group II: 68.33mg (P value 0.908)]. Time to first request for rescue analgesic was delayed, though statistically non-significant (P value 0.326), following medial transverse abdominis plane block, with excellent pain relief seen in 58.3% patients as opposed to 45.8% patients in ilioinguinal-iliohypogastric nerve block group. Medial transverse abdominis plane block being a novel, simple and easily performed procedure can serve as an useful alternative to ilioinguinal-iliohypogastric nerve block for providing postoperative pain relief in inguinal hernia repair patients. Copyright © 2018 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in adults with tuberculosis: A phase II randomised study.

PubMed

Gillard, Paul; Yang, Pan-Chyr; Danilovits, Manfred; Su, Wei-Juin; Cheng, Shih-Lung; Pehme, Lea; Bollaerts, Anne; Jongert, Erik; Moris, Philippe; Ofori-Anyinam, Opokua; Demoitié, Marie-Ange; Castro, Marcela

2016-09-01

Previous studies have shown that the M72/AS01E candidate tuberculosis vaccine is immunogenic with a clinically acceptable safety profile in healthy and Mycobacterium tuberculosis-infected adults. This phase II, observer-blind, randomised study compared the safety, reactogenicity, and immunogenicity of M72/AS01E in 3 cohorts: tuberculosis-naïve adults (n = 80), adults previously treated for tuberculosis (n = 49), and adults who have completed the intensive phase of tuberculosis treatment (n = 13). In each cohort, 18-59-year-old adults were randomised (1:1) to receive two doses of M72/AS01E (n = 71) or placebo (n = 71) and followed-up until six months post-dose 2. Safety and reactogenicity were assessed as primary objective. Recruitment in the study ended prematurely because of a high incidence of large injection site redness/swelling reactions in M72/AS01E-vaccinated adults undergoing tuberculosis treatment. No additional clinically relevant adverse events were observed, except one possibly vaccine-related serious adverse event (hypersensitivity in a tuberculosis-treated-M72/AS01E participant). Robust and persistent M72-specific humoral and polyfunctional CD4(+) T-cell-mediated immune responses were observed post-M72/AS01E vaccination in each cohort. In conclusion, the M72/AS01E vaccine was immunogenic in adults previously or currently treated for tuberculosis, but further analyses are needed to explain the high local reactogenicity in adults undergoing tuberculosis treatment. ClinicalTrials.gov: NCT01424501. Copyright © 2016 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

The HubBLe Trial: haemorrhoidal artery ligation (HAL) versus rubber band ligation (RBL) for symptomatic second- and third-degree haemorrhoids: a multicentre randomised controlled trial and health-economic evaluation.

PubMed

Brown, Steven; Tiernan, Jim; Biggs, Katie; Hind, Daniel; Shephard, Neil; Bradburn, Mike; Wailoo, Allan; Alshreef, Abualbishr; Swaby, Lizzie; Watson, Angus; Radley, Simon; Jones, Oliver; Skaife, Paul; Agarwal, Anil; Giordano, Pasquale; Lamah, Marc; Cartmell, Mark; Davies, Justin; Faiz, Omar; Nugent, Karen; Clarke, Andrew; MacDonald, Angus; Conaghan, Phillip; Ziprin, Paul; Makhija, Rohit

2016-11-01

Optimal surgical intervention for low-grade haemorrhoids is unknown. Rubber band ligation (RBL) is probably the most common intervention. Haemorrhoidal artery ligation (HAL) is a novel alternative that may be more efficacious. The comparison of HAL with RBL for the treatment of grade II/III haemorrhoids. A multicentre, parallel-group randomised controlled trial. UK NHS and Personal Social Services. 17 NHS Trusts. Patients aged ≥ 18 years presenting with grade II/III (second- and third-degree) haemorrhoids, including those who have undergone previous RBL. HAL with Doppler probe compared with RBL. Primary outcome - recurrence at 1 year post procedure; secondary outcomes - recurrence at 6 weeks; haemorrhoid severity score; European Quality of Life-5 Dimensions, 5-level version (EQ-5D-5L); Vaizey incontinence score; pain assessment; complications; and cost-effectiveness. A total of 370 participants entered the trial. At 1 year post procedure, 30% of the HAL group had evidence of recurrence compared with 49% after RBL [adjusted odds ratio (OR) = 2.23, 95% confidence interval (CI) 1.42 to 3.51; p  = 0.0005]. The main reason for the difference was the number of extra procedures required to achieve improvement/cure. If a single HAL is compared with multiple RBLs then only 37.5% recurred in the RBL arm (adjusted OR 1.35, 95% CI 0.85 to 2.15; p  = 0.20). Persistence of significant symptoms at 6 weeks was lower in both arms than at 1 year (9% HAL and 29% RBL), suggesting significant deterioration in both groups over the year. Symptom score, EQ-5D-5L and Vaizey score improved in both groups compared with baseline, but there was no difference between interventions. Pain was less severe and of shorter duration in the RBL group; most of the HAL group who had pain had mild to moderate pain, resolving by 3 weeks. Complications were low frequency and not significantly different between groups. It appeared that HAL was not cost-effective compared with RBL. In the base-case analysis, the difference in mean total costs was £1027 higher for HAL. Quality-adjusted life-years (QALYs) were higher for HAL; however, the difference was very small (0.01) resulting in an incremental cost-effectiveness ratio of £104,427 per additional QALY. At 1 year, although HAL resulted in fewer recurrences, recurrence was similar to repeat RBL. Symptom scores, complications, EQ-5D-5L and continence score were no different, and patients had more pain in the early postoperative period after HAL. HAL is more expensive and unlikely to be cost-effective in terms of incremental cost per QALY. Blinding of participants and site staff was not possible. The incidence of recurrence may continue to increase with time. Further follow-up would add to the evidence regarding long-term clinical effectiveness and cost-effectiveness. The polysymptomatic nature of haemorrhoidal disease requires a validated scoring system, and the data from this trial will allow further assessment of validity of such a system. These data add to the literature regarding treatment of grade II/III haemorrhoids. The results dovetail with results from the eTHoS study [Watson AJM, Hudson J, Wood J, Kilonzo M, Brown SR, McDonald A, et al. Comparison of stapled haemorrhoidopexy with traditional excisional surgery for haemorrhoidal disease (eTHoS): a pragmatic, multicentre, randomised controlled trial. Lancet 2016, in press.] comparing stapled haemorrhoidectomy with excisional haemorrhoidectomy. Combined results will allow expansion of analysis, allowing surgeons to tailor their treatment options to individual patients. Current Controlled Trials ISRCTN41394716. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 20, No. 88. See the NIHR Journals Library website for further project information.

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

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.

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

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 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.

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.

Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study.

PubMed

van der Heijde, Désirée; Deodhar, Atul; Wei, James C; Drescher, Edit; Fleishaker, Dona; Hendrikx, Thijs; Li, David; Menon, Sujatha; Kanik, Keith S

2017-08-01

To compare efficacy and safety of various doses of tofacitinib, an oral Janus kinase inhibitor, with placebo in patients with active ankylosing spondylitis (AS, radiographic axial spondyloarthritis). In this 16-week (12-week treatment, 4-week washout), phase II, multicentre, dose-ranging trial, adult patients with active AS were randomised (N=51, 52, 52, 52, respectively) to placebo or tofacitinib 2, 5 or 10 mg twice daily. The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response rate at week 12. Secondary endpoints included objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine. Safety was monitored. Emax model analysis of the primary endpoint predicted a tofacitinib 10 mg twice daily ASAS20 response rate of 67.4%, 27.3% higher than placebo. Supportive normal approximation analysis demonstrated tofacitinib 5 mg twice daily ASAS20 response rate significantly higher than placebo (80.8% vs 41.2%; p<0.001); tofacitinib 2 and 10 mg twice daily demonstrated greater response rate than placebo (51.9% and 55.8%, respectively; not significant). Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10 mg twice daily than placebo. Objective (including MRI) endpoints demonstrated clear dose response. Adverse events were similar across treatment groups with no unexpected safety findings. Dose-dependent laboratory outcome changes returned close to baseline by week 16. Tofacitinib 5 and 10 mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs, symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications. NCT01786668. 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/.

Optimising text messaging to improve adherence to web-based smoking cessation treatment: a randomised control trial protocol

PubMed Central

Graham, Amanda L; Jacobs, Megan A; Cohn, Amy M; Cha, Sarah; Abroms, Lorien C; Papandonatos, George D; Whittaker, Robyn

2016-01-01

Introduction Millions of smokers use the Internet for smoking cessation assistance each year; however, most smokers engage minimally with even the best designed websites. The ubiquity of mobile devices and their effectiveness in promoting adherence in other areas of health behaviour change make them a promising tool to address adherence in Internet smoking cessation interventions. Text messaging is used by most adults, and messages can proactively encourage use of a web-based intervention. Text messaging can also be integrated with an Internet intervention to facilitate the use of core Internet intervention components. Methods and analysis We identified four aspects of a text message intervention that may enhance its effectiveness in promoting adherence to a web-based smoking cessation programme: personalisation, integration, dynamic tailoring and message intensity. Phase I will use a two-level full factorial design to test the impact of these four experimental features on adherence to a web-based intervention. The primary outcome is a composite metric of adherence that incorporates general utilisation metrics (eg, logins, page views) and specific feature utilisation shown to predict abstinence. Participants will be N=860 adult smokers who register on an established Internet cessation programme and enrol in its text message programme. Phase II will be a two-arm randomised trial to compare the efficacy of the web-based cessation programme alone and in conjunction with the optimised text messaging intervention on 30-day point prevalence abstinence at 9 months. Phase II participants will be N=600 adult smokers who register to use an established Internet cessation programme and enrol in text messaging. Secondary analyses will explore whether adherence mediates the effect of treatment condition on outcome. Ethics and dissemination This protocol was approved by Chesapeake IRB. We will disseminate study results through peer-reviewed manuscripts and conference presentations related to the methods and design, outcomes and exploratory analyses. Trial registration number NCT02585206. PMID:27029775

Impact of etanercept tapering on work productivity in patients with early rheumatoid arthritis: results from the PRIZE study

PubMed Central

Zhang, Wei; Bansback, Nick; Sun, Huiying; Pedersen, Ronald; Kotak, Sameer; Anis, Aslam H

2016-01-01

Objective To assess changes in work productivity in patients who have achieved response using etanercept (ETN) 50 mg+methotrexate (MTX) (phase I) are randomised to ETN 25 mg+MTX versus MTX versus placebo (phase II) and then withdrawn from treatment (phase III). Methods Patients included in the analysis were in employment entering phase II of the PRIZE trial and had one or more follow-ups. Phase II was a 39-week, randomised and double-blind comparison of the 3 dose-reduction treatments. Phase III was a 26-week observational study where treatment was withdrawn. The Valuation of Lost Productivity was completed approximately every 13 weeks to estimate productivity impacts from a societal perspective. Results A total of 120 participants were included in our analyses. During phase II, ETN25+MTX or MTX improved paid work productivity by over 100 hours compared with placebo, amounting to a gain of €1752 or €1503, respectively. ETN25+MTX compared with placebo gains €1862 in total paid/unpaid productivity. At week 52, the 3-month paid work productivity loss was 21.8, 12.8 and 14.0 hours, respectively. The productivity loss increased at week 64 from week 52, dropped at week 76 for all treatment groups and then continued rising after week 76 for the placebo group (71.9 hours at week 91) but not for the other 2 groups (21.9 hours for ETX25+MTX and 27.6 hours for MTX). Conclusions The work productivity gain in phase I as a result of ETN50+MTX was marginally lost in the dose-reduction treatment groups, ETN25+MTX and MTX, but substantially lost in the placebo group during phase II. Trial registration number NCT00913458; Results. PMID:27486524

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…

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: subgroup analysis of the DISTINCT randomised trial.

PubMed

Mancia, G; Cha, G; Gil-Extremera, B; Harvey, P; Lewin, A J; Villa, G; Kjeldsen, S E

2017-03-01

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS-Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min -1 , n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy.

Midtrimester preterm prelabour rupture of membranes (PPROM): expectant management or amnioinfusion for improving perinatal outcomes (PPROMEXIL – III trial)

PubMed Central

2014-01-01

Background Babies born after midtrimester preterm prelabour rupture of membranes (PPROM) are at risk to develop neonatal pulmonary hypoplasia. Perinatal mortality and morbidity after this complication is high. Oligohydramnios in the midtrimester following PPROM is considered to cause a delay in lung development. Repeated transabdominal amnioinfusion with the objective to alleviate oligohydramnios might prevent this complication and might improve neonatal outcome. Methods/Design Women with PPROM and persisting oligohydramnios between 16 and 24 weeks gestational age will be asked to participate in a multi-centre randomised controlled trial. Intervention: random allocation to (repeated) abdominal amnioinfusion (intervention) or expectant management (control). The primary outcome is perinatal mortality. Secondary outcomes are lethal pulmonary hypoplasia, non-lethal pulmonary hypoplasia, survival till discharge from NICU, neonatal mortality, chronic lung disease (CLD), number of days ventilatory support, necrotizing enterocolitis (NEC), periventricular leucomalacia (PVL) more than grade I, severe intraventricular hemorrhage (IVH) more than grade II, proven neonatal sepsis, gestational age at delivery, time to delivery, indication for delivery, successful amnioinfusion, placental abruption, cord prolapse, chorioamnionitis, fetal trauma due to puncture. The study will be evaluated according to intention to treat. To show a decrease in perinatal mortality from 70% to 35%, we need to randomise two groups of 28 women (two sided test, β-error 0.2 and α-error 0.05). Discussion This study will answer the question if (repeated) abdominal amnioinfusion after midtrimester PPROM with associated oligohydramnios improves perinatal survival and prevents pulmonary hypoplasia and other neonatal morbidities. Moreover, it will assess the risks associated with this procedure. Trial registration NTR3492 Dutch Trial Register (http://www.trialregister.nl). PMID:24708702

Butorphanol pre-treatment prevents myoclonus induced by etomidate: a randomised, double-blind, controlled clinical trial.

PubMed

He, Liang; Ding, Ying; Chen, Huiyu; Qian, Yanning; Li, Zhong

2014-01-01

Myoclonic movements are common problems during induction of anaesthesia with etomidate. The myoclonus occurring after etomidate administration may represent a form of seizure. Agonistic modulation of the κ opiate receptor may reduce seizures, and butorphanol acts in such a manner. The aim of this randomised, double-blind, placebo-controlled clinical trial was to test our hypothesis that pre-treatment with butorphanol might reduce the incidence and severity of myoclonus induced by etomidate. Patients (108) with American Society of Anaesthesiologists physical status I or II were randomly assigned to one of two groups to receive either 0.015 mg/kg of butorphanol (n = 54) or saline (n = 54) intravenously. At two minutes after infusion of butorphanol or saline, 0.3 mg/kg etomidate was given. The occurrence and severity (observational score of 0-3) of myoclonus was assessed during 2 minutes after administration of etomidate. For each patient, blood pressure (BP), saturation of peripheral oxygen (SpO₂), and heart rate (HR) were measured. The incidence of myoclonus was significantly lower in Group Butorphanol than in Group Saline (13.0% vs 79.6%; RR = 0.163, 95%CI: 0.081-0.329; χ² = 48.265, p <0.0001). The severity levels of myoclonic movement were also significantly lower in Group Butorphanol than in Group Saline (p <0.0001). Throughout the procedure, changes of BP, SpO₂, and HR did not differ between the groups. There were no problems with bradycardia or hypotension. Infusion of 0.015 mg/kg butorphanol 2 minutes before etomidate administration is effective for suppressing myoclonus induced by etomidate during induction of general anaesthesia.

A randomised controlled trial comparing ProSeal laryngeal mask airway, i-gel and Laryngeal Tube Suction-D under general anaesthesia for elective surgical patients requiring controlled ventilation.

PubMed

Das, Bikramjit; Varshney, Rahul; Mitra, Subhro

2017-12-01

The ProSeal™ laryngeal mask airway (PLMA), i-gel™ and Laryngeal Tube Suction-D (LTS-D™) have previously been evaluated alone or in pair-wise comparisons but differing study designs make it difficult to compare the results. The aim of this study was to compare the clinical performance of these three devices in terms of efficacy and safety in patients receiving mechanical ventilation during elective surgical procedures. This prospective, randomised, double-blind study was conducted on 150 American Society of Anesthesiologists physical status I-II patients, randomly allocated into 3 groups, undergoing elective surgical procedures under general anaesthesia. PLMA, i-gel™ or LTS-D™ appropriate for weight or/and height was inserted. Primary outcome measured was airway sealing pressure. Insertion time, ease of insertion, number of attempts, overall success rate and the incidence of airway trauma and complications were also recorded. Intergroup differences were compared using one-way analysis of variance with post hoc correction for continuous data and Chi-square test for categorical variables. Overall success rate was comparable between the three devices (i-gel™ 100%, LTS-D™ 94%, PLMA 96%). Airway sealing pressure was lower with i-gel™ (23.38 ± 2.06 cm H 2 O) compared to LTS-D™ (26.06 ± 2.11 cm H 2 O) and PLMA (28.5 ± 2.8 cm H 2 O; P < 0.0005). The mean insertion time was significantly more in PLMA (38.77 ± 3.2 s) compared to i-gel™ (27.9 ± 2.53 s) and LTS-D™ (21.66 ± 2.31 s; P < 0.0005). Airway sealing pressure and insertion time were significantly higher in PLMA compared to i-gel™ and LTS-D™.

Seasonal malaria chemoprevention in an area of extended seasonal transmission in Ashanti, Ghana: an individually randomised clinical trial.

PubMed

Tagbor, Harry; Antwi, Gifty Dufie; Acheampong, Princess Ruhama; Bart Plange, Constance; Chandramohan, Daniel; Cairns, Matthew

2016-02-01

To investigate the effectiveness of seasonal malaria chemoprevention (SMC) and community case management with long-acting artemisinin-based combination therapies (ACTs) for the control of malaria in areas of extended seasonal malaria transmission. Individually randomised, placebo-controlled trial in the Ashanti Region of Ghana. A total of 2400 children aged 3-59 months received either: (i) a short-acting ACT for case management of malaria (artemether-lumefantrine, AL) plus placebo SMC, or (ii) a long-acting ACT (dihydroartemisinin-piperaquine, DP) for case management plus placebo SMC or (iii) AL for case management plus active SMC with sulphadoxine-pyrimethamine and amodiaquine. SMC or placebo was delivered on five occasions during the rainy season. Malaria cases were managed by community health workers, who used rapid diagnostic tests to confirm infection prior to treatment. The incidence of malaria was lower in children given SMC during the rainy season. Compared to those given placebo SMC and AL for case management, the adjusted hazard ratio (aHR) was 0.62 (95% CI: 0.41, 0.93), P = 0.020 by intention to treat and 0.53 (95% CI: 0.29, 0.95), P = 0.033 among children given five SMC courses. There were no major differences between groups given different ACTs for case management (aHR DP vs. AL 1.18 (95% CI 0.83, 1.67), P = 0.356). SMC may have an important public health impact in areas with a longer transmission season, but further optimisation of SMC schedules is needed to maximise its impact in such settings. © 2015 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials.

PubMed

Talley, N J; Tack, J; Ptak, T; Gupta, R; Giguère, M

2008-06-01

Functional dyspepsia (FD) is a common disorder but there is currently little efficacious drug therapy. Itopride, a prokinetic approved in several countries, showed promising efficacy in FD in a phase IIb trial. The aim of this study was to test the efficacy and safety of this drug in FD. Two similar placebo-controlled clinical trials were conducted (International and North America). Males and females, 18-65 years old, with a diagnosis of FD (Rome II) and the absence (by upper endoscopy) of any relevant structural disease were recruited. All were negative for Helicobacter pylori and, if present, heartburn could not exceed one episode per week. Following screening, patients were randomised to itopride 100 mg three times daily or identical placebo. The co-primary end points were: (1) global patient assessment (GPA) of efficacy; and (2) Leeds Dyspepsia Questionnaire (LDQ). Symptoms were evaluated at weeks 2, 4 and 8. Secondary measures of efficacy included Nepean Dyspepsia Index (NDI) quality of life. The GPA responder rates at week 8 on itopride versus placebo were similar in both trials (45.2% vs 45.6% and 37.8 vs 35.4%, respectively; p = NS). A significant benefit of itopride over placebo was observed for the LDQ responders in the International (62% vs 52.7%, p = 0.04) but not the North American trial (46.9% vs 44.8%). The safety and tolerability profile were comparable with placebo, with the exception of prolactin elevations, which occurred more frequently on itopride (18/579) than placebo (1/591). In this population with FD, itopride did not show a difference in symptom response from placebo.

Impact of N-acetylcysteine on endothelial function, B-type natriuretic peptide and renal function in patients with the cardiorenal syndrome: a pilot cross over randomised controlled trial.

PubMed

Camuglia, Anthony C; Maeder, Micha T; Starr, Jennifer; Farrington, Catherine; Kaye, David M

2013-04-01

Both heart and renal failure are characterised by increased systemic oxidative stress and endothelial dysfunction and occur in the cardiorenal syndrome (CRS). The aim of the present study was to assess the impact of N-acetylcysteine (NAC), a potent antioxidant, on endothelial function, B-type natriuretic peptide (BNP) and renal function in patients with CRS. In a double blind, placebo controlled manner, we randomised nine stable outpatients with both heart failure (LVEF<40% and NYHA class II or III) and renal failure (Cockroft Gault clearance of 20-60ml/min) to placebo or NAC (500mg orally twice daily) for 28 days followed by a wash out period (>7 days) and crossover to the other treatment. Eight patients completed the study and all data (N=9) was used in the analysis. Mean forearm blood flow improved significantly with NAC with mean ratio of improvement of 1.99 (SEM: ±0.49) for NAC and 0.73 (SEM: ±0.23) for placebo with a p-value of 0.047. There was no significant difference in BNP (p=0.25), renal function (p=0.71) or NYHA class (p=0.5). No deaths occurred during the trial. In this pilot trial of patients with CRS, NAC therapy was associated with improved forearm blood flow. This may represent a general improvement in endothelial function and warrants further investigation of antioxidant therapy in these patients. Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Effect of addition of dexamethasone to ropivacaine on post-operative analgesia in ultrasonography-guided transversus abdominis plane block for inguinal hernia repair: A prospective, double-blind, randomised controlled trial.

PubMed

Sharma, Uma Datt; Prateek; Tak, Himani

2018-05-01

Ultrasonography (USG)-guided transversus abdominis plane (TAP) block is an abdominal field block with high efficacy. This study was undertaken with the aim of determining the effect of the addition of dexamethasone to 0.5% ropivacaine on post-operative analgesia in USG-guided TAP block for inguinal hernia repair. A double-blind randomised control study was conducted on sixty patients posted for inguinal hernia repair with the American Society of Anesthesiologists physical Status I or II, who were allocated two groups of 30 each. Patients in Group RS received 0.5% ropivacaine (20 ml) and normal saline (2 ml) whereas patients in Group RD received 0.5% ropivacaine (20 ml) and dexamethasone (2 ml, i.e., 8 mg), in USG-guided TAP Block on the same side, after repair of inguinal hernia under spinal anaesthesia. Visual analogue scale (VAS) scores, time for request of first analgesia and total tramadol consumption in first 24 h were compared. Unpaired Student's t -test and Mann-Whitney U-test were performed using SPSS 23 Software. Patients in Group RD had significantly lower VAS scores as compared to Group RS from 4 th to 12 th h, postoperatively. Duration of analgesia was significantly more in Group RD (547.50 [530,530] min) when compared with Group RS (387.50 [370,400] min) ( P < 0.001). The demand for intravenous tramadol was significantly low in Group RD (223.33 ± 56.83 mg) as compared to Group RS (293.33 ± 25.71 mg) ( P < 0.001). Addition of dexamethasone to ropivacaine in USG-guided TAP block significantly reduces post-operative pain and prolongs the duration of post-operative analgesia, thereby reducing analgesic consumption.

A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol.

PubMed

Slater, Rebeccah; Hartley, Caroline; Moultrie, Fiona; Adams, Eleri; Juszczak, Ed; Rogers, Richard; Norman, Jane E; Patel, Chetan; Stanbury, Kayleigh; Hoskin, Amy; Green, Gabrielle

2016-11-15

Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants. A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP) screening and heel lancing provides effective analgesia. 
156 infants between 34 and 42 weeks' gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg) or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration. The primary outcome will be the Premature Infant Pain Profile-revised (PIPP-R) score 30 seconds after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet .

Stop Stroke: development of an innovative intervention to improve risk factor management after stroke.

PubMed

Redfern, Judith; Rudd, Anthony D; Wolfe, Charles D A; McKevitt, Christopher

2008-08-01

Stroke survivors are at high risk of stroke recurrence yet current strategies to reduce recurrence risk are sub-optimal. The UK Medical Research Council (MRC) have proposed a framework for developing and evaluating complex interventions, such as community management of stroke secondary prevention. The Framework outlines a five-phased approach from theory through to implementation of effective interventions. This paper reports Phases I-III of the development of a novel intervention to improve risk factor management after stroke. The pre-clinical/theoretical phase entailed reviewing the literature and undertaking quantitative and qualitative studies to identify current practices and barriers to secondary prevention. In Phase I (modelling), findings were used to design an intervention with the potential to overcome barriers to effective stroke secondary prevention management. The feasibility of delivering the intervention and its acceptability were tested in the Phase II exploratory trial involving 25 stroke survivors and their general practitioners. This led to the development of the definitive risk factor management intervention. This comprises multiple components and involves using an on-going population stroke register to target patients, carers and health care professionals with tailored secondary prevention advice. Clinical, socio-demographic and service use data collected by the stroke register are transformed to provide an individualised secondary prevention package for patients, carers and health care professionals at three time points: within 10 weeks, 3 and 6 months post-stroke. The intervention is currently being evaluated in a randomised controlled trial. Further research is needed to test generalisability to other aspects of stroke management and for other chronic diseases. The MRC Framework for complex interventions provides a structured approach to guide the development of novel interventions in public health. Implications for practice in stroke secondary prevention will emerge when the results of our randomised controlled trial are published.

The effects, safety and acceptability of compact, pre-filled, autodisable injection devices when delivered by lay health workers.

PubMed

Glenton, Claire; Khanna, Rajesh; Morgan, Chris; Nilsen, Elin Strømme

2013-08-01

To systematically assess (i) the effects and safety and (ii) the acceptability of using lay health workers (LHWs) to deliver vaccines and medicines to mothers and children through compact pre-filled autodisable devices (CPADs). We searched electronic databases and grey literature. For the systematic review of effects and safety, we sought randomised and non-randomised controlled trials, controlled before-after studies and interrupted time series studies. For the systematic review of acceptability, we sought qualitative studies. Two researchers independently carried out data extraction, study quality assessment and thematic analysis of the qualitative data. No studies met our criteria for the review exploring the effects and safety of using LHWs to deliver CPADs. For the acceptability review, six qualitative studies assessed the acceptability of using LHWs to deliver hepatitis B vaccine, tetanus toxoid vaccine, gentamicin or oxytocin using Uniject™ devices. All studies took place in low- or middle-income countries and explored the perceptions of community members, LHWs, supervisors, health professionals or programme managers. Most of the studies were of low quality. Recipients generally accepted the intervention. Most health professionals were confident that LHWs could deliver the intervention with sufficient training and supervision, but some had problems delivering supervision. The LHWs perceived Uniject™ as effective and important and were motivated by positive responses from the community. However, some LHWs feared the consequences if harm should come to recipients. Evidence of the effects and safety of using CPADs delivered by LHWs is lacking. Evidence regarding acceptability suggests that this intervention may be acceptable although LHWs may feel vulnerable to blame. © 2013 John Wiley & Sons Ltd.

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.