Minimally invasive 'step-up approach' versus maximal necrosectomy in patients with acute necrotising pancreatitis (PANTER trial): design and rationale of a randomised controlled multicenter trial [ISRCTN38327949

PubMed Central

Besselink, Marc GH; van Santvoort, Hjalmar C; Nieuwenhuijs, Vincent B; Boermeester, Marja A; Bollen, Thomas L; Buskens, Erik; Dejong, Cornelis HC; van Eijck, Casper HJ; van Goor, Harry; Hofker, Sijbrand S; Lameris, Johan S; van Leeuwen, Maarten S; Ploeg, Rutger J; van Ramshorst, Bert; Schaapherder, Alexander FM; Cuesta, Miguel A; Consten, Esther CJ; Gouma, Dirk J; van der Harst, Erwin; Hesselink, Eric J; Houdijk, Lex PJ; Karsten, Tom M; van Laarhoven, Cees JHM; Pierie, Jean-Pierre EN; Rosman, Camiel; Bilgen, Ernst Jan Spillenaar; Timmer, Robin; van der Tweel, Ingeborg; de Wit, Ralph J; Witteman, Ben JM; Gooszen, Hein G

2006-01-01

Background The initial treatment of acute necrotizing pancreatitis is conservative. Intervention is indicated in patients with (suspected) infected necrotizing pancreatitis. In the Netherlands, the standard intervention is necrosectomy by laparotomy followed by continuous postoperative lavage (CPL). In recent years several minimally invasive strategies have been introduced. So far, these strategies have never been compared in a randomised controlled trial. The PANTER study (PAncreatitis, Necrosectomy versus sTEp up appRoach) was conceived to yield the evidence needed for a considered policy decision. Methods/design 88 patients with (suspected) infected necrotizing pancreatitis will be randomly allocated to either group A) minimally invasive 'step-up approach' starting with drainage followed, if necessary, by videoscopic assisted retroperitoneal debridement (VARD) or group B) maximal necrosectomy by laparotomy. Both procedures are followed by CPL. Patients will be recruited from 20 hospitals, including all Dutch university medical centres, over a 3-year period. The primary endpoint is the proportion of patients suffering from postoperative major morbidity and mortality. Secondary endpoints are complications, new onset sepsis, length of hospital and intensive care stay, quality of life and total (direct and indirect) costs. To demonstrate that the 'step-up approach' can reduce the major morbidity and mortality rate from 45 to 16%, with 80% power at 5% alpha, a total sample size of 88 patients was calculated. Discussion The PANTER-study is a randomised controlled trial that will provide evidence on the merits of a minimally invasive 'step-up approach' in patients with (suspected) infected necrotizing pancreatitis. PMID:16606471

Alimentazione del neonato pretermine IUGR: studio multicentrico ADEPT (Abnormal Doppler Enteral Prescription Trial). (Feeding the IUGR premature newborn infant: the multicenter ADEPT study).

PubMed

Leaf, A

2010-06-01

Pregnancies complicated by abnormal antenatal Doppler blood flow often result in the preterm delivery of a growth restricted baby. These babies have a high risk of milk intolerance and necrotising enterocolitis (1), and introduction of milk feeds is frequently delayed. Our aim was to determine the effect of early or late introduction on success of achieving full milk feeds and on adverse outcomes including NEC. Eligible babies with birthweight below 10th centile and gestation below 34+6 weeks, born after abnormal antenatal Dopplers, were randomised between 20 and 48 hours to either early (24-48 hours) or late (120-144 hours) introduction of milk feeds. Babies with major congenital anomaly, in-utero transfusion, multi-organ failure or need for inotropes were excluded. Feed volumes and rate of increase were standardised, and were the same for both groups. Daily feed logs were kept. 404 babies were randomised from 56 units in U.K. and Ireland (202 in each group). There were no important differences between groups at randomisation. growth restricted preterm infants born after absent or reversed end-diastolic flow in the umbilical artery who are fed from the second day after birth achieve full feeds faster than those commencing feeds on day six. No difference was been seen in the incidence of NEC, in preliminary analysis. Final data analysis is currently being completed and will be presented at the conference.

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

PubMed

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

2009-10-23

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

The effectiveness of video interaction guidance in parents of premature infants: A multicenter randomised controlled trial

PubMed Central

2012-01-01

Background Studies have consistently found a high incidence of neonatal medical problems, premature births and low birth weights in abused and neglected children. One of the explanations proposed for the relation between neonatal problems and adverse parenting is a possible delay or disturbance in the bonding process between the parent and infant. This hypothesis suggests that due to neonatal problems, the development of an affectionate bond between the parent and the infant is impeded. The disruption of an optimal parent-infant bond -on its turn- may predispose to distorted parent-infant interactions and thus facilitate abusive or neglectful behaviours. Video Interaction Guidance (VIG) is expected to promote the bond between parents and newborns and is expected to diminish non-optimal parenting behaviour. Methods/design This study is a multi-center randomised controlled trial to evaluate the effectiveness of Video Interaction Guidance in parents of premature infants. In this study 210 newborn infants with their parents will be included: n = 70 healthy term infants (>37 weeks GA), n = 70 moderate term infants (32–37 weeks GA) which are recruited from maternity wards of 6 general hospitals and n = 70 extremely preterm infants or very low birth weight infants (<32 weeks GA) recruited by the NICU of 2 specialized hospitals. The participating families will be divided into 3 groups: a reference group (i.e. full term infants and their parents, receiving care as usual), a control group (i.e. premature infants and their parents, receiving care as usual) and an intervention group (i.e. premature infants and their parents, receiving VIG). The data will be collected during the first six months after birth using observations of parent-infant interactions, questionnaires and semi-structured interviews. Primary outcomes are the quality of parental bonding and parent-infant interactive behaviour. Parental secondary outcomes are (posttraumatic) stress symptoms, depression, anxiety and feelings of anger and hostility. Infant secondary outcomes are behavioral aspects such as crying, eating, and sleeping. Discussion This is the first prospective study to empirically evaluate the effect of VIG in parents of premature infants. Family recruitment is expected to be completed in January 2012. First results should be available by 2012. Trail registration number NTR3423 PMID:22709245

Rationale and methods of the multicenter randomised trial of a heart failure management programme among geriatric patients (HF-Geriatrics)

PubMed Central

2011-01-01

Background Disease management programmes (DMPs) have been shown to reduce hospital readmissions and mortality in adults with heart failure (HF), but their effectiveness in elderly patients or in those with major comorbidity is unknown. The Multicenter Randomised Trial of a Heart Failure Management Programme among Geriatric Patients (HF-Geriatrics) assesses the effectiveness of a DMP in elderly patients with HF and major comorbidity. Methods/Design Clinical trial in 700 patients aged ≥ 75 years admitted with a primary diagnosis of HF in the acute care unit of eight geriatric services in Spain. Each patient should meet at least one of the following comorbidty criteria: Charlson index ≥ 3, dependence in ≥ 2 activities of daily living, treatment with ≥ 5 drugs, active treatment for ≥ 3 diseases, recent emergency hospitalization, severe visual or hearing loss, cognitive impairment, Parkinson's disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), anaemia, or constitutional syndrome. Half of the patients will be randomly assigned to a 1-year DMP led by a case manager and the other half to usual care. The DMP consists of an educational programme for patients and caregivers on the management of HF, COPD (knowledge of the disease, smoking cessation, immunizations, use of inhaled medication, recognition of exacerbations), diabetes (knowledge of the disease, symptoms of hyperglycaemia and hypoglycaemia, self-adjustment of insulin, foot care) and depression (knowledge of the disease, diagnosis and treatment). It also includes close monitoring of the symptoms of decompensation and optimisation of treatment compliance. The main outcome variables are quality of life, hospital readmissions, and overall mortality during a 12-month follow-up. Discussion The physiological changes, lower life expectancy, comorbidity and low health literacy associated with aging may influence the effectiveness of DMPs in HF. The HF-Geriatrics study will provide direct evidence on the effect of a DMP in elderly patients with HF and high comorbidty, and will reduce the need to extrapolate the results of clinical trials in adults to elderly patients. Trial registration (ClinicalTrials.gov number, NCT01076465). PMID:21819564

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

PubMed

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

2016-04-08

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

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.

The nutrition-based comprehensive intervention study on childhood obesity in China (NISCOC): a randomised cluster controlled trial.

PubMed

Li, Yanping; Hu, Xiaoqi; Zhang, Qian; Liu, Ailing; Fang, Hongyun; Hao, Linan; Duan, Yifan; Xu, Haiquan; Shang, Xianwen; Ma, Jun; Xu, Guifa; Du, Lin; Li, Ying; Guo, Hongwei; Li, Tingyu; Ma, Guansheng

2010-05-02

Childhood obesity and its related metabolic and psychological abnormalities are becoming serious health problems in China. Effective, feasible and practical interventions should be developed in order to prevent the childhood obesity and its related early onset of clinical cardiovascular diseases. The objective of this paper is to describe the design of a multi-centred random controlled school-based clinical intervention for childhood obesity in China. The secondary objective is to compare the cost-effectiveness of the comprehensive intervention strategy with two other interventions, one only focuses on nutrition education, the other only focuses on physical activity. The study is designed as a multi-centred randomised controlled trial, which included 6 centres located in Beijing, Shanghai, Chongqing, Shandong province, Heilongjiang province and Guangdong province. Both nutrition education (special developed carton style nutrition education handbook) and physical activity intervention (Happy 10 program) will be applied in all intervention schools of 5 cities except Beijing. In Beijing, nutrition education intervention will be applied in 3 schools and physical activity intervention among another 3 schools. A total of 9750 primary students (grade 1 to grade 5, aged 7-13 years) will participate in baseline and intervention measurements, including weight, height, waist circumference, body composition (bioelectrical impendence device), physical fitness, 3 days dietary record, physical activity questionnaire, blood pressure, plasma glucose and plasma lipid profiles. Data concerning investments will be collected in our study, including costs in staff training, intervention materials, teachers and school input and supervising related expenditure. Present study is the first and biggest multi-center comprehensive childhood obesity intervention study in China. Should the study produce comprehensive results, the intervention strategies would justify a national school-based program to prevent childhood obesity in China.

A multicenter randomised, 1-year comparative effectiveness, parallel-group trial protocol of a physical therapy approach compared to corticosteroid injection on pain and function related to knee osteoarthritis (PTA Trial)

PubMed

Deyle, Gail D; Gill, Norman W; Rhon, Daniel I; Allen, Chris S; Allison, Stephen C; Hando, Ben R; Petersen, Evan J; Dusenberry, Douglas I; Bellamy, Nicholas

2016-03-31

Corticosteroid injections (CSIs) are commonly used as an initial or a primary intervention for knee osteoarthritis (OA). Consistent evidence indicates CSIs offer symptom relief with conflicting reports regarding long-term efficacy. Physical therapy (PT) offers a non-invasive alternative. There is moderate evidence suggesting short-term and long-term symptom relief and functional improvement with PT interventions. Patients with knee OA are more commonly prescribed CSI than PT prior to total joint replacement. UnitedHealthcare and Military Health System data show substantially more total knee replacement patients receive preoperative CSI than PT. There are no studies comparing CSI to a PT approach in individuals with knee OA. The primary objective of this study is to compare the effectiveness of CSI to PT in individuals with knee OA at 1, 2 and 12 months. We plan to recruit 156 participants meeting established knee OA criteria. Following informed consent, participants will be randomised to receive either CSI or PT. All participants will receive instruction on recommended exercise and weight control strategies plus usual medical care. The CSI intervention consisting of 3 injections and the PT intervention consisting of 8-12 sessions will be spaced over 12 months. Measures of the dependent variables (DVs) will occur at baseline, 4 weeks, 8 weeks, 6 months and 12 months post enrolment. This pragmatic, randomised clinical trial will be a mixed-model 2×5 factorial design. The independent variables are treatment (CSI and PT) and time with five levels from baseline to 1 year. The primary DV is the Western Ontario & McMaster Universities Arthritis Index (WOMAC). We will also compare healthcare utilisation between the 2 groups. The protocol was approved by the Madigan Army Medical Center Institutional Review Board. The authors intend to publish the results in a peer-reviewed source. NCT01427153. 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/

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

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.

Add-on anticholinergic therapy for residual nocturia in patients with lower urinary tract symptoms receiving α1-blocker treatment: a multi-centre, prospective, randomised study.

PubMed

Yokoyama, Osamu; Tsujimura, Akira; Akino, Hironobu; Segawa, Naoki; Tamada, Satoshi; Oguchi, Naoki; Kitagawa, Yasuhide; Tsuji, Hidenori; Watanabe, Akihiko; Inamoto, Teruo; Shimizu, Nobutaka; Fujiuchi, Yasuyoshi; Katsuoka, Yoji; Azuma, Haruhito; Matsuda, Tadashi; Namiki, Mikio; Uemura, Hirotsugu; Okuyama, Akihiko; Nonomura, Norio; Fuse, Hideki; Nakatani, Tatsuya

2015-05-01

To evaluate the efficacy and safety of imidafenacin (IM), a novel short half-life anticholinergic, as add-on therapy for male LUTS with nocturia and nocturnal polyuria. This multicenter, prospective, randomized, open-labelled study was conducted and involved men who had frequency, urgency, and nocturia despite receiving a stable dose of α1-blocker for ≥1 month. Subjects were randomised to control (α1-blocker alone), IM twice/day (α1-blocker +0.1 mg imidafenacin twice daily), or IM nightly (α1-blocker plus 0.1 mg imidafenacin nightly) group; the treatment period was 8 weeks. Primary endpoints included improvements in night-time frequency and Nocturia Quality of Life Questionnaire (N-QOL) scores. Secondary endpoints included changes from the baseline in frequency volume chart variables, and post-void residual volume. Compared with the controls, IM twice/day and IM nightly patients had a significantly lower night-time frequency (changes from baseline: 0.1 ± 0.8 in control, -0.6 ± 0.9 in IM twice/day, and -0.4 ± 1.0 in IM nightly, p = 0.5227, 0.0006 and 0.0143, respectively). The hours of undisturbed sleep and N-QOL score were significantly improved in IM twice/day group, though not IM nightly group. Nocturnal urine volume was significantly reduced in IM nightly group, although total urine volume remained unchanged. A short half-life anticholinergic is suggested to be safe and effective as an add-on therapy for residual nocturia in patients with male LUTS receiving α1-blocker treatment. Anticholinergic administration nightly could reduce the nocturnal urine volume.

The efficacy and safety of Crataegus extract WS 1442 in patients with heart failure: the SPICE trial.

PubMed

Holubarsch, Christian J F; Colucci, Wilson S; Meinertz, Thomas; Gaus, Wilhelm; Tendera, Michal

2008-12-01

Crataegus preparations have been used for centuries especially in Europe. To date, no proper data on their efficacy and safety as an add-on-treatment are available. Therefore a large morbidity/mortality trial was performed. To investigate the efficacy and safety of an add-on treatment with Crataegus extract WS 1442 in patients with congestive heart failure. In this randomised, double-blind, placebo-controlled multicenter study, adults with NYHA class II or III CHF and reduced left ventricular ejection fraction (LVEF< or =35%) were included and received 900 mg/day WS 1442 or placebo for 24 months. Primary endpoint was time until first cardiac event. 2681 patients (WS 1442: 1338; placebo: 1343) were randomised. Average time to first cardiac event was 620 days for WS 1442 and 606 days for placebo (event rates: 27.9% and 28.9%, hazard ratio (HR): 0.95, 95% CI [0.82;1.10]; p=0.476). The trend for cardiac mortality reduction with WS 1442 (9.7% at month 24; HR: 0.89 [0.73;1.09]) was not statistically significant (p=0.269). In the subgroup with LVEF> or =25%, WS 1442 reduced sudden cardiac death by 39.7% (HR 0.59 [0.37;0.94] at month 24; p=0.025). Adverse events were comparable in both groups. In this study, WS 1442 had no significant effect on the primary endpoint. WS 1442 was safe to use in patients receiving optimal medication for heart failure. In addition, the data may indicate that WS 1442 can potentially reduce the incidence of sudden cardiac death, at least in patients with less compromised left ventricular function.

Bell's Palsy in Children (BellPIC): protocol for a multicentre, placebo-controlled randomized trial.

PubMed

Babl, Franz E; Mackay, Mark T; Borland, Meredith L; Herd, David W; Kochar, Amit; Hort, Jason; Rao, Arjun; Cheek, John A; Furyk, Jeremy; Barrow, Lisa; George, Shane; Zhang, Michael; Gardiner, Kaya; Lee, Katherine J; Davidson, Andrew; Berkowitz, Robert; Sullivan, Frank; Porrello, Emily; Dalziel, Kim Marie; Anderson, Vicki; Oakley, Ed; Hopper, Sandy; Williams, Fiona; Wilson, Catherine; Williams, Amanda; Dalziel, Stuart R

2017-02-13

Bell's palsy or acute idiopathic lower motor neurone facial paralysis is characterized by sudden onset paralysis or weakness of the muscles to one side of the face controlled by the facial nerve. While there is high level evidence in adults demonstrating an improvement in the rate of complete recovery of facial nerve function when treated with steroids compared with placebo, similar high level studies on the use of steroids in Bell's palsy in children are not available. The aim of this study is to assess the utility of steroids in Bell's palsy in children in a randomised placebo-controlled trial. We are conducting a randomised, triple-blinded, placebo controlled trial of the use of prednisolone to improve recovery from Bell's palsy at 1 month. Study sites are 10 hospitals within the Australian and New Zealand PREDICT (Paediatric Research in Emergency Departments International Collaborative) research network. 540 participants will be enrolled. To be eligible patients need to be aged 6 months to < 18 years and present within 72 hours of onset of clinician diagnosed Bell's palsy to one of the participating hospital emergency departments. Patients will be excluded in case of current use of or contraindications to steroids or if there is an alternative diagnosis. Participants will receive either prednisolone 1 mg/kg/day to a maximum of 50 mg/day or taste matched placebo for 10 days. The primary outcome is complete recovery by House-Brackmann scale at 1 month. Secondary outcomes include assessment of recovery using the Sunnybrook scale, the emotional and functional wellbeing of the participants using the Pediatric Quality of Life Inventory and Child Health Utility 9D Scale, pain using Faces Pain Scale Revised or visual analogue scales, synkinesis using a synkinesis assessment questionnaire and health utilisation costs at 1, 3 and 6 months. Participants will be tracked to 12 months if not recovered earlier. Data analysis will be by intention to treat with primary outcome presented as differences in proportions and an odds ratio adjusted for site and age. This large multicenter randomised trial will allow the definitive assessment of the efficacy of prednisolone compared with placebo in the treatment of Bell's palsy in children. The study is registered with the Australian New Zealand Clinical Trials Registry ACTRN12615000563561 (1 June 2015).

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

PubMed

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

2017-12-01

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

The pediatric heart network: meeting the challenges to multicenter studies in pediatric heart disease

PubMed Central

Burns, Kristin M.; Pemberton, Victoria L.; Pearson, Gail D.

2017-01-01

Purpose of review Because of the relatively small numbers of pediatric patients with congenital heart disease cared for in any individual center, there is a significant need for multicenter clinical studies to validate new medical or surgical therapies. The Pediatric Heart Network (PHN), with 15 years of experience in multicenter clinical research, has tackled numerous challenges when conducting multicenter studies. Recent findings This review describes the challenges encountered and the strategies employed to conduct high-quality, collaborative research in pediatric cardiovascular disease. Summary Sharing lessons learned from the PHN can provide guidance to investigators interested in conducting pediatric multicenter studies. PMID:26196261

The Celiac Disease and Diabetes-Dietary Intervention and Evaluation Trial (CD-DIET) protocol: a randomised controlled study to evaluate treatment of asymptomatic coeliac disease in type 1 diabetes.

PubMed

Mahmud, Farid H; De Melo, Emilia N; Noordin, Karima; Assor, Esther; Sahota, Kamaljeet; Davies-Shaw, Jolie; Cutz, Ernest; Somers, Gino; Lawson, Margaret; Mack, David R; Gallego, Patricia; McDonald, Charlotte; Beaton, Melanie D; Bax, Kevin; Saibil, Fred; Gilbert, Jeremy; Kirsch, Susan; Perkins, Bruce A; Cino, Maria; Szentgyorgyi, Eva; Koltin, Dror; Parikh, Amish; Mukerji, Geetha; Advani, Andrew; Lou, Olivia; Marcon, Margaret A

2015-05-11

Coeliac disease (CD) is an autoimmune condition characterised by gluten-induced intestinal inflammation, and observed at a 5-10 fold greater prevalence in type 1 diabetes. While universal screening for CD in patients with diabetes is frequently advocated, objective data is limited as to benefits on diabetes control, bone health or quality of life related to the adoption of a gluten-free diet (GFD) in the large proportion of patients with diabetes with asymptomatic CD. The Celiac Disease and Diabetes-Dietary Intervention and Evaluation Trial (CD-DIET) study is a multicenter, randomised controlled trial to evaluate the efficacy and safety of a GFD in patients with type 1 diabetes with asymptomatic CD. Children and adults (8-45 years) with type 1 diabetes will be screened for asymptomatic CD. Eligible patients with biopsy-proven CD will be randomly assigned in a 1:1 ratio to treatment with a GFD for 1 year, or continue with a gluten-containing diet. The primary outcome will evaluate the impact of the GFD on change in glycated haemoglobin. Secondary outcomes will evaluate changes in bone mineral density, blood glucose variability and health-related quality of life between GFD-treated and the regular diet group over a 1-year period. The study was initiated in 2012 and has subsequently expanded to multiple paediatric and adult centres in Ontario, Canada. The findings from this study will provide high-quality evidence as to the impact of GFD treatment on glycaemic control and complications in asymptomatic children and adults with CD and type 1 diabetes. NCT01566110. 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.

[Multicenter evaluation of the Nutri-Expert Telematic System in diabetic patients].

PubMed

Turnin, M C; Bolzonella-Pene, C; Dumoulin, S; Cerf, I; Charpentier, G; Sandre-Banon, D; Valensi, P; Grenier, J L; Cathelineau, G; Mattei, C

1995-02-01

Nutri-Expert is a system for self-monitoring and dietetic education, accessible through Minitel. A preliminary randomised evaluation of one hundred diabetic patients in the Midi-Pyrénées region showed that Nutri-Expert improved dietetic knowledge, dietary habits and metabolic balance. The aim of the present study was to show that the system can be successfully prescribed to patients by physicians outside the center which originated it, indicating the benefit of a wider use of Nutri-Expert, among the diabetic population. One hundred and fifty-five patients, recruited by six French centres of diabetology, used Nutri-Expert from their homes for six months. Clinical examination, tests of dietetic knowledge and biological tests, including lipid fractions, were carried out before and after six months of use. After six months, there was a significant improvement in the patients' dietetic knowledge and in some biological parameters. Nutri-Expert is thus useful even when prescribed by a centre other than the hospital which devised the system. It is an additional beneficial tool in the ambulatory management of diabetic patients.

Efficacy of brief behavioral counselling by allied health professionals to promote physical activity in people with peripheral arterial disease (BIPP): study protocol for a multi-center randomized controlled trial.

PubMed

Burton, Nicola W; Ademi, Zanfina; Best, Stuart; Fiatarone Singh, Maria A; Jenkins, Jason S; Lawson, Kenny D; Leicht, Anthony S; Mavros, Yorgi; Noble, Yian; Norman, Paul; Norman, Richard; Parmenter, Belinda J; Pinchbeck, Jenna; Reid, Christopher M; Rowbotham, Sophie E; Yip, Lisan; Golledge, Jonathan

2016-11-09

Physical activity is recommended for people with peripheral arterial disease (PAD), and can improve walking capacity and quality of life; and reduce pain, requirement for surgery and cardiovascular events. This trial will assess the efficacy of a brief behavioral counselling intervention delivered by allied health professionals to improve physical activity in people with PAD. This is a multi-center randomised controlled trial in four cities across Australia. Participants (N = 200) will be recruited from specialist vascular clinics, general practitioners and research databases and randomised to either the control or intervention group. Both groups will receive usual medical care, a written PAD management information sheet including advice to walk, and four individualised contacts from a protocol-trained allied health professional over 3 months (weeks 1, 2, 6, 12). The control group will receive four 15-min telephone calls with general discussion about PAD symptoms and health and wellbeing. The intervention group will receive behavioral counselling via two 1-h face-to-face sessions and two 15-min telephone calls. The counselling is based on the 5A framework and will promote interval walking for 3 × 40 min/week. Assessments will be conducted at baseline, and 4, 12 and 24 months by staff blinded to participant allocation. Objectively assessed outcomes include physical activity (primary), sedentary behavior, lower limb body function, walking capacity, cardiorespiratory fitness, event-based claudication index, vascular interventions, clinical events, cardiovascular function, circulating markers, and anthropometric measures. Self-reported outcomes include physical activity and sedentary behavior, walking ability, pain severity, and health-related quality of life. Data will be analysed using an intention-to-treat approach. An economic evaluation will assess whether embedding the intervention into routine care would likely be value for money. A cost-effectiveness analysis will estimate change in cost per change in activity indicators due to the intervention, and a cost-utility analysis will assess change in cost per quality-adjusted life year. A full uncertainty analysis will be undertaken, including a value of information analysis, to evaluate the economic case for further research. This trial will evaluate the efficacy and cost-effectiveness of a brief behavioral counselling intervention for a common cardiovascular disease with significant burden. ACTRN 12614000592640 Australian New Zealand Clinical Trials Registry. Registration Date 4 June 2014.

77 FR 12598 - Notice Correction; A Multi-Center International Hospital-Based Case-Control Study of Lymphoma in...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Notice Correction; A Multi-Center International Hospital-Based Case-Control Study of Lymphoma in Asia (AsiaLymph) (NCI) The Federal... project titled, ``A multi-center international hospital-based case-control study of lymphoma in Asia (Asia...

[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.

A bio-psycho-social exercise program (RÜCKGEWINN) for chronic low back pain in rehabilitation aftercare--study protocol for a randomised controlled trial.

PubMed

Hentschke, Christian; Hofmann, Jana; Pfeifer, Klaus

2010-11-17

There is strong, internationally confirmed evidence for the short-term effectiveness of multimodal interdisciplinary specific treatment programs for chronic back pain. However, the verification of long-term sustainability of achieved effects is missing so far. For long-term improvement of pain and functional ability high intervention intensity or high volume seems to be necessary (> 100 therapy hours). Especially in chronic back pain rehabilitation, purposefully refined aftercare treatments offer the possibility to intensify positive effects or to increase their sustainability. However, quality assured goal-conscious specific aftercare programs for the rehabilitation of chronic back pain are absent. This study aims to examine the efficacy of a specially developed bio-psycho-social chronic back pain specific aftercare intervention (RÜCKGEWINN) in comparison to the current usual aftercare (IRENA) and a control group that is given an educational booklet addressing pain-conditioned functional ability and back pain episodes. Overall rehabilitation effects as well as predictors for compliance to the aftercare programs are analysed. Therefore, a multicenter prospective 3-armed randomised controlled trial is conducted. 456 participants will be consecutively enrolled in inpatient and outpatient rehabilitation and assigned to either one of the three study arms. Outcomes are measured before and after rehabilitation. Aftercare programs are assessed at ten month follow up after dismissal form rehabilitation. Special methodological and logistic challenges are to be mastered in this trial, which accrue from the interconnection of aftercare interventions to their residential district and the fact that the proportion of patients who take part in aftercare programs is low. The usability of the aftercare program is based on the transference into the routine care and is also reinforced by developed manuals with structured contents, media and material for organisation assistance as well as training manuals for therapists in the aftercare.

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.

Multicenter AIDS Cohort Study Quantitative Coronary Plaque Progression Study: rationale and design.

PubMed

Nakanishi, Rine; Post, Wendy S; Osawa, Kazuhiro; Jayawardena, Eranthi; Kim, Michael; Sheidaee, Nasim; Nezarat, Negin; Rahmani, Sina; Kim, Nicholas; Hathiramani, Nicolai; Susarla, Shriraj; Palella, Frank; Witt, Mallory; Blaha, Michael J; Brown, Todd T; Kingsley, Lawrence; Haberlen, Sabina A; Dailing, Christopher; Budoff, Matthew J

2018-01-01

The association of HIV with coronary atherosclerosis has been established; however, the progression of coronary atherosclerosis over time among participants with HIV is not well known. The Multicenter AIDS Cohort Study Quantitative Coronary Plaque Progression Study is a large prospective multicenter study quantifying progression of coronary plaque assessed by serial coronary computed tomography angiography (CTA). HIV-infected and uninfected men who were enrolled in the Multicenter AIDS Cohort Study Cardiovascular Substudy were eligible to complete a follow-up contrast coronary CTA 3-6 years after baseline. We measured coronary plaque volume and characteristics (calcified and noncalcified plaque including fibrous, fibrous-fatty, and low attenuation) and vulnerable plaque among HIV-infected and uninfected men using semiautomated plaque software to investigate the progression of coronary atherosclerosis over time. We describe a novel, large prospective multicenter study investigating incidence, transition of characteristics, and progression in coronary atherosclerosis quantitatively assessed by serial coronary CTAs among HIV-infected and uninfected men.

Conducting multicenter research in healthcare simulation: Lessons learned from the INSPIRE network.

PubMed

Cheng, Adam; Kessler, David; Mackinnon, Ralph; Chang, Todd P; Nadkarni, Vinay M; Hunt, Elizabeth A; Duval-Arnould, Jordan; Lin, Yiqun; Pusic, Martin; Auerbach, Marc

2017-01-01

Simulation-based research has grown substantially over the past two decades; however, relatively few published simulation studies are multicenter in nature. Multicenter research confers many distinct advantages over single-center studies, including larger sample sizes for more generalizable findings, sharing resources amongst collaborative sites, and promoting networking. Well-executed multicenter studies are more likely to improve provider performance and/or have a positive impact on patient outcomes. In this manuscript, we offer a step-by-step guide to conducting multicenter, simulation-based research based upon our collective experience with the International Network for Simulation-based Pediatric Innovation, Research and Education (INSPIRE). Like multicenter clinical research, simulation-based multicenter research can be divided into four distinct phases. Each phase has specific differences when applied to simulation research: (1) Planning phase , to define the research question, systematically review the literature, identify outcome measures, and conduct pilot studies to ensure feasibility and estimate power; (2) Project Development phase , when the primary investigator identifies collaborators, develops the protocol and research operations manual, prepares grant applications, obtains ethical approval and executes subsite contracts, registers the study in a clinical trial registry, forms a manuscript oversight committee, and conducts feasibility testing and data validation at each site; (3) Study Execution phase , involving recruitment and enrollment of subjects, clear communication and decision-making, quality assurance measures and data abstraction, validation, and analysis; and (4) Dissemination phase , where the research team shares results via conference presentations, publications, traditional media, social media, and implements strategies for translating results to practice. With this manuscript, we provide a guide to conducting quantitative multicenter research with a focus on simulation-specific issues.

Local versus general anaesthesia in carotid endarterectomy: a systematic review of the evidence.

PubMed

Tangkanakul, C; Counsell, C E; Warlow, C P

1997-05-01

To determine whether carotid endarterectomy under local anaesthesia is safer and as effective as under general anaesthesia. Systematic review of the randomised and non-randomised studies. Studies were identified from the Cochrane Stroke Group's database plus additional handsearching and electronic searching. Two authors independently selected studies for inclusion and extracted details of trial quality and data on death, any stroke, myocardial infarction and other operative complications. Meta-analysis was performed using the Peto method. There were 17 non-randomised studies (about 5970 patients) and only three randomised studies (143 patients). The non-randomised studies suggested that the use of local anaesthesia may be associated with clinically important reductions (approximately 50%) in the odds of stroke, stroke or death, myocardial infarction and pulmonary complications during the perioperative period, and with reductions in hospital stay. There were far too little data from the randomised trials to confirm or refute these findings: only one death and seven strokes were reported. Non-randomised studies suggest potentially important benefits from performing carotid endarterectomy under local anaesthesia. However, these studies were seriously flawed and can only be hypothesis generating. The results must be confirmed in large well-designed randomised trials before any recommendations on the use of local anaesthetic can be made.

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.

Stakeholders' views on data sharing in multicenter studies.

PubMed

Mazor, Kathleen M; Richards, Allison; Gallagher, Mia; Arterburn, David E; Raebel, Marsha A; Nowell, W Benjamin; Curtis, Jeffrey R; Paolino, Andrea R; Toh, Sengwee

2017-09-01

To understand stakeholders' views on data sharing in multicenter comparative effectiveness research studies and the value of privacy-protecting methods. Semistructured interviews with five US stakeholder groups. We completed 11 interviews, involving patients (n = 15), researchers (n = 10), Institutional Review Board and regulatory staff (n = 3), multicenter research governance experts (n = 2) and healthcare system leaders (n = 4). Perceptions of the benefits and value of research were the strongest influences toward data sharing; cost and security risks were primary influences against sharing. Privacy-protecting methods that share summary-level data were acknowledged as being appealing, but there were concerns about increased cost and potential loss of research validity. Stakeholders were open to data sharing in multicenter studies that offer value and minimize security risks.

Interlaboratory quality control of total HIV-1 DNA load measurement for multicenter reservoir studies.

PubMed

Gantner, Pierre; Mélard, Adeline; Damond, Florence; Delaugerre, Constance; Dina, Julia; Gueudin, Marie; Maillard, Anne; Sauné, Karine; Rodallec, Audrey; Tuaillon, Edouard; Plantier, Jean-Christophe; Rouzioux, Christine; Avettand-Fenoel, Véronique

2017-11-01

Viral reservoirs represent an important barrier to HIV cure. Accurate markers of HIV reservoirs are needed to develop multicenter studies. The aim of this multicenter quality control (QC) was to evaluate the inter-laboratory reproducibility of total HIV-1-DNA quantification. Ten laboratories of the ANRS-AC11 working group participated by quantifying HIV-DNA with a real-time qPCR assay (Biocentric) in four samples (QCMD). Good reproducibility was found between laboratories (standard deviation ≤ 0.2 log 10 copies/10 6 PBMC) for the three positive QC that were correctly classified by each laboratory (QC1

Practicalities of Using a Modified Version of the Cochrane Collaboration Risk of Bias Tool for Randomised and Non-Randomised Study Designs Applied in a Health Technology Assessment Setting

ERIC Educational Resources Information Center

Robertson, Clare; Ramsay, Craig; Gurung, Tara; Mowatt, Graham; Pickard, Robert; Sharma, Pawana

2014-01-01

We describe our experience of using a modified version of the Cochrane risk of bias (RoB) tool for randomised and non-randomised comparative studies. Objectives: (1) To assess time to complete RoB assessment; (2) To assess inter-rater agreement; and (3) To explore the association between RoB and treatment effect size. Methods: Cochrane risk of…

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.

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.

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.

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

PubMed

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

2018-05-02

Cluster randomised clinical trials present unique challenges in meeting ethical obligations to those who are treated at a randomised site. Obtaining informed consent for research within the context of clinical care is one such challenge. In order to solve this problem it is important that an informed consent process be effective and efficient, and that it does not impede the research or the healthcare. The innovative approach to informed consent employed in the COMPASS study demonstrates the feasibility of upholding ethical standards without imposing undue burden on clinical workflows, staff members or patients who may participate in the research by virtue of their presence in a cluster randomised facility. The COMPASS study included 40 randomised sites and compared the effectiveness of a postacute stroke intervention with standard care. Each site provided either the comprehensive postacute stroke intervention or standard care according to the randomisation assignment. Working together, the study team, institutional review board and members of the community designed an ethically appropriate and operationally reasonable consent process which was carried out successfully at all randomised sites. This achievement is noteworthy because it demonstrates how to effectively conduct appropriate informed consent in cluster randomised trials, and because it provides a model that can easily be adapted for other pragmatic studies. With this innovative approach to informed consent, patients have access to the information they need about research occurring where they are seeking care, and medical researchers can conduct their studies without ethical concerns or unreasonable logistical impediments. NCT02588664, recruiting. This article covers the development of consent process that is currentlty being employed in the study. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Interventions to increase immunisation coverage among children 12–23 months of age in India through participatory learning and community engagement: pilot study for a cluster randomised trial

PubMed Central

Johri, Mira; Chandra, Dinesh; Koné, Georges K; Dudeja, Sakshi; Sylvestre, Marie-Pierre; Sharma, Jitendar K; Pahwa, Smriti

2015-01-01

Objective With the aim of conducting a future cluster randomised trial to assess intervention impact on child vaccination coverage, we designed a pilot study to assess feasibility and aid in refining methods for the larger study. Trial design Cluster-randomised design with a 1:1 allocation ratio. Methods Clusters were 12 villages in rural Uttar Pradesh. All women residing in a selected village who were mothers of a child 0–23 months of age were eligible; participants were chosen at random. Over 4 months, intervention group (IG) villages received: (1) home visits by volunteers; (2) community mobilisation events to promote immunisation. Control group (CG) villages received community mobilisation to promote nutrition. A toll-free number for immunisation was offered to all IG and CG village residents. Primary outcomes were ex-ante criteria for feasibility of the main study related to processes for recruitment and randomisation (50% of villages would agree to participate and accept randomisation; 30 women could be recruited in 70% of villages), and retention of participants (50% of women retained from baseline to endline). Clusters were assigned to IG or CG using a computer-generated randomisation schedule. Neither participants nor those delivering interventions were blinded, but those assessing outcomes were blinded to group assignment. Results All villages contacted agreed to participate and accepted randomisation. 36 women were recruited per village; 432 participants were randomised (IG n=216; CG n=216). No clusters were lost to follow-up. The main analysis included 86% (373/432) of participants, 90% (195/216) from the IG and 82% (178/216) from the CG. Conclusions Criteria related to feasibility were satisfied, giving us confidence that we can successfully conduct a larger cluster randomised trial. Methodological lessons will inform design of the main study. Trial registration number ISRCTN16703097 PMID:26384721

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

Routine versus aggressive upstream rhythm control for prevention of early atrial fibrillation in heart failure: background, aims and design of the RACE 3 study.

PubMed

Alings, M; Smit, M D; Moes, M L; Crijns, H J G M; Tijssen, J G P; Brügemann, J; Hillege, H L; Lane, D A; Lip, G Y H; Smeets, J R L M; Tieleman, R G; Tukkie, R; Willems, F F; Vermond, R A; Van Veldhuisen, D J; Van Gelder, I C

2013-07-01

Rhythm control for atrial fibrillation (AF) is cumbersome because of its progressive nature caused by structural remodelling. Upstream therapy refers to therapeutic interventions aiming to modify the atrial substrate, leading to prevention of AF. The Routine versus Aggressive upstream rhythm Control for prevention of Early AF in heart failure (RACE 3) study hypothesises that aggressive upstream rhythm control increases persistence of sinus rhythm compared with conventional rhythm control in patients with early AF and mild-to-moderate early systolic or diastolic heart failure undergoing electrical cardioversion. RACE 3 is a prospective, randomised, open, multinational, multicenter trial. Upstream rhythm control consists of angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers, mineralocorticoid receptor antagonists, statins, cardiac rehabilitation therapy, and intensive counselling on dietary restrictions, exercise maintenance, and drug adherence. Conventional rhythm control consists of routine rhythm control therapy without cardiac rehabilitation therapy and intensive counselling. In both arms, every effort is made to keep patients in the rhythm control strategy, and ion channel antiarrhythmic drugs or pulmonary vein ablation may be instituted if AF relapses. Total inclusion will be 250 patients. If upstream therapy proves to be effective in improving maintenance of sinus rhythm, it could become a new approach to rhythm control supporting conventional pharmacological and non-pharmacological rhythm control.

Variability in the performance of preventive services and in the degree of control of identified health problems: A primary care study protocol

PubMed Central

Bolíbar, Bonaventura; Pareja, Clara; Astier-Peña, M Pilar; Morán, Julio; Rodríguez-Blanco, Teresa; Rosell-Murphy, Magdalena; Iglesias, Manuel; Juncosa, Sebastián; Mascort, Juanjo; Violan, Concepció; Magallón, Rosa; Apezteguia, Javier

2008-01-01

Background Preventive activities carried out in primary care have important variability that makes necessary to know which factors have an impact in order to establish future strategies for improvement. The present study has three objectives: 1) To describe the variability in the implementation of 7 preventive services (screening for smoking status, alcohol abuse, hypertension, hypercholesterolemia, obesity, influenza and tetanus immunization) and to determine their related factors; 2) To describe the degree of control of 5 identified health problems (smoking, alcohol abuse, hypertension, hypercholesterolemia and obesity); 3) To calculate intraclass correlation coefficients. Design Multi-centered cross-sectional study of a randomised sample of primary health care teams from 3 regions of Spain designed to analyse variability and related factors of 7 selected preventive services in years 2006 and 2007. At the end of 2008, we will perform a cross-sectional study of a cohort of patients attended in 2006 or 2007 to asses the degree of control of 5 identified health problems. All subjects older than16 years assigned to a randomised sample of 22 computerized primary health care teams and attended during the study period are included in each region providing a sample with more than 850.000 subjects. The main outcome measures will be implementation of 7 preventive services and control of 5 identified health problems. Furthermore, there will be 3 levels of data collection: 1) Patient level (age, gender, morbidity, preventive services, attendance); 2) Health-care professional level (professional characteristics, years working at the team, workload); 3) Team level (characteristics, electronic clinical record system). Data will be transferred from electronic clinical records to a central database with prior encryption and dissociation of subject, professional and team identity. Global and regional analysis will be performed including standard analysis for primary health care teams and health-care professional level. Linear and logistic regression multilevel analysis adjusted for individual and cluster variables will also be performed. Variability in the number of preventive services implemented will be calculated with Poisson multilevel models. Team and health-care professional will be considered random effects. Intraclass correlation coefficients, standard error and variance components for the different outcome measures will be calculated. PMID:18691407

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

Impact of the Patient-Reported Outcomes Management Information System (PROMIS) upon the design and operation of multi-center clinical trials: a qualitative research study.

PubMed

Eisenstein, Eric L; Diener, Lawrence W; Nahm, Meredith; Weinfurt, Kevin P

2011-12-01

New technologies may be required to integrate the National Institutes of Health's Patient Reported Outcome Management Information System (PROMIS) into multi-center clinical trials. To better understand this need, we identified likely PROMIS reporting formats, developed a multi-center clinical trial process model, and identified gaps between current capabilities and those necessary for PROMIS. These results were evaluated by key trial constituencies. Issues reported by principal investigators fell into two categories: acceptance by key regulators and the scientific community, and usability for researchers and clinicians. Issues reported by the coordinating center, participating sites, and study subjects were those faced when integrating new technologies into existing clinical trial systems. We then defined elements of a PROMIS Tool Kit required for integrating PROMIS into a multi-center clinical trial environment. The requirements identified in this study serve as a framework for future investigators in the design, development, implementation, and operation of PROMIS Tool Kit technologies.

Impact of the Patient-Reported Outcomes Management Information System (PROMIS) upon the Design and Operation of Multi-center Clinical Trials: a Qualitative Research Study

PubMed Central

Diener, Lawrence W.; Nahm, Meredith; Weinfurt, Kevin P.

2013-01-01

New technologies may be required to integrate the National Institutes of Health’s Patient Reported Outcome Management Information System (PROMIS) into multi-center clinical trials. To better understand this need, we identified likely PROMIS reporting formats, developed a multi-center clinical trial process model, and identified gaps between current capabilities and those necessary for PROMIS. These results were evaluated by key trial constituencies. Issues reported by principal investigators fell into two categories: acceptance by key regulators and the scientific community, and usability for researchers and clinicians. Issues reported by the coordinating center, participating sites, and study subjects were those faced when integrating new technologies into existing clinical trial systems. We then defined elements of a PROMIS Tool Kit required for integrating PROMIS into a multi-center clinical trial environment. The requirements identified in this study serve as a framework for future investigators in the design, development, implementation, and operation of PROMIS Tool Kit technologies. PMID:20703765

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

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

The value of INnovative ICT guided disease management combined with Telemonitoring in OUtpatient clinics for Chronic Heart failure patients. Design and methodology of the IN TOUCH study: a multicenter randomised trial

PubMed Central

2011-01-01

Background Although the value of telemonitoring in heart failure patients is increasingly studied, little is known about the value of the separate components of telehealth: ICT guided disease management and telemonitoring. The aim of this study is to investigate the value of telemonitoring added to ICT guided disease management (DM) on the quality and efficiency of care in patients with chronic heart failure (CHF) after a hospitalisation. Methods/Design The study is divided in two arms; a control arm (DM) and an intervention arm (DM+TM) in 10 hospitals in the Netherlands. In total 220 patients will be included after worsening of CHF (DM: N = 90, DM+TM: N = 130). Total follow-up will be 9 months. Data will be collected at inclusion and then after 2 weeks, 4.5 and 9 months. The primary endpoint of this study is a composite score of: 1: death from any cause during the follow-up of the study, 2: first readmission for HF and 3: change in quality of life compared to baseline, assessed by the Minnesota Living with Heart failure Questionnaire. The study has started in December 2009 and results are expected in 2012. Conclusions The IN TOUCH study is the first to investigate the effect of telemonitoring on top of ICT guided DM on the quality and efficiency of care in patients with worsening HF and will use a composite score as its primary endpoint. Trial registration Netherlands Trial Register (NTR): NTR1898 PMID:21752280

The value of INnovative ICT guided disease management combined with Telemonitoring in OUtpatient clinics for Chronic Heart failure patients. Design and methodology of the IN TOUCH study: a multicenter randomised trial.

PubMed

de Vries, Arjen E; de Jong, Richard M; van der Wal, Martje H L; Jaarsma, Tiny; van Dijk, Rene B; Hillege, Hans L

2011-07-13

Although the value of telemonitoring in heart failure patients is increasingly studied, little is known about the value of the separate components of telehealth: ICT guided disease management and telemonitoring. The aim of this study is to investigate the value of telemonitoring added to ICT guided disease management (DM) on the quality and efficiency of care in patients with chronic heart failure (CHF) after a hospitalisation. The study is divided in two arms; a control arm (DM) and an intervention arm (DM+TM) in 10 hospitals in the Netherlands. In total 220 patients will be included after worsening of CHF (DM: N = 90, DM+TM: N = 130). Total follow-up will be 9 months. Data will be collected at inclusion and then after 2 weeks, 4.5 and 9 months. The primary endpoint of this study is a composite score of: 1: death from any cause during the follow-up of the study, 2: first readmission for HF and 3: change in quality of life compared to baseline, assessed by the Minnesota Living with Heart failure Questionnaire. The study has started in December 2009 and results are expected in 2012. The IN TOUCH study is the first to investigate the effect of telemonitoring on top of ICT guided DM on the quality and efficiency of care in patients with worsening HF and will use a composite score as its primary endpoint. Netherlands Trial Register (NTR): NTR1898.

Multicenter Guidelines | Division of Cancer Prevention

Cancer.gov

A Lead Organization conducting multi-institutional studies in the consortium has specific responsibilities in order to comply with the DCP Multicenter Guidelines. The Lead Organization is responsible for the following at all Participating Organizations as well as the Lead Organization: |

Randomised studies of income supplementation: a lost opportunity to assess health outcomes.

PubMed

Connor, J; Rodgers, A; Priest, P

1999-11-01

Despite the wealth of evidence linking low income to ill health, there is little information from randomised studies on how much and how quickly these risks can be reversed by improvements in income. To conduct a systematic review of randomised studies of income supplementation, with particular reference to health outcomes. Extensive searches of electronic databases and contact with previous authors. As well as searching for trials that were specifically designed to assess the effects of increased income, studies of winners and losers of lotteries were also sought: if winning is purely chance, such studies are, in effect, randomised trials of increased income. Ten relevant studies were identified, all conducted in North America, mostly in the late 1960s and 1970s. Five trials were designed to assess the effects of income supplementation on workforce participation and randomised a total of 10,000 families to 3-5 years of various combinations of minimum income guarantees and reduced tax rates. Two trials were designed to assess re-offending rates in recently released prisoners and randomised a total of 2400 people to 3-6 months of benefits. One trial was designed to assess housing allowances and randomised 3500 families to three years of income supplements. One trial assessed the health effects of 12 months of income supplementation in 54 people with severe mental illness. Finally, one study compared three groups of people who won different amounts of money in a state lottery. In all these studies the interventions resulted in increases in income of at least one fifth. However, no reliable analyses of health outcome data are available. Extensive opportunities to reliably assess the effects of increases in income on health outcomes have been missed. Such evidence might have increased the consideration of potential health effects during deliberations about policies that have major implications for income, such as taxation rates, benefit policies, and minimum wage levels. Randomised evidence could still be obtained with innovative new studies, such as trials of full benefit uptake or prospective studies of lottery winners in which different sized winnings are paid in monthly installments over many years.

Effectiveness and safety of moderate-intensity aerobic water exercise during pregnancy for reducing use of epidural analgesia during labor: protocol for a randomized clinical trial.

PubMed

Navas, Araceli; Artigues, Catalina; Leiva, Alfonso; Portells, Elena; Soler, Aina; Cladera, Antonia; Ortas, Silvia; Alomar, Margarita; Gual, Marina; Manzanares, Concepción; Brunet, Marina; Julià, Magdalena; López, Lidia; Granda, Lorena; Bennasar-Veny, Miquel; Carrascosa, Mari Carmen

2018-04-11

Epidural analgesia during labor can provide effective pain relief, but can also lead to adverse effects. The practice of moderate exercise during pregnancy is associated with an increased level of endorphins in the blood, and this could also provide pain relief during labor. Aerobic water exercises, rather than other forms of exercise, do not negatively impact articulations, reduce edema, blood pressure, and back pain, and increase diuresis. We propose a randomized controlled trial (RCT) to evaluate the effectiveness and safety of a moderate water exercise program during pregnancy on the need for epidural analgesia during labor. A multi-center, parallel, randomized, evaluator blinded, controlled trial in a primary care setting. We will randomised 320 pregnant women (14 to 20 weeks gestation) who have low risk of complications to a moderate water exercise program or usual care. The findings of this research will contribute toward understanding of the effects of a physical exercise program on pain and the need for analgesia during labor. ISRCTN Registry identifier: 14097513 register on 04 September 2017. Retrospectively registered.

Cost analysis of the Dutch obstetric system: low-risk nulliparous women preferring home or short-stay hospital birth--a prospective non-randomised controlled study.

PubMed

Hendrix, Marijke Jc; Evers, Silvia Maa; Basten, Marloes Cm; Nijhuis, Jan G; Severens, Johan L

2009-11-19

In the Netherlands, pregnant women without medical complications can decide where they want to give birth, at home or in a short-stay hospital setting with a midwife. However, a decrease in the home birth rate during the last decennium may have raised the societal costs of giving birth. The objective of this study is to compare the societal costs of home births with those of births in a short-stay hospital setting. This study is a cost analysis based on the findings of a multicenter prospective non-randomised study comparing two groups of nulliparous women with different preferences for where to give birth, at home or in a short-stay hospital setting. Data were collected using cost diaries, questionnaires and birth registration forms. Analysis of the data is divided into a base case analysis and a sensitivity analysis. In the group of home births, the total societal costs associated with giving birth at home were euro3,695 (per birth), compared with euro3,950 per birth in the group for short-stay hospital births. Statistically significant differences between both groups were found regarding the following cost categories 'Cost of contacts with health care professionals during delivery' (euro138.38 vs. euro87.94, -50 (2.5-97.5 percentile range (PR)-76;-25), p < 0.05), 'cost of maternity care at home' (euro1,551.69 vs. euro1,240.69, -311 (PR -485; -150), p < 0.05) and 'cost of hospitalisation mother' (euro707.77 vs. 959.06, 251 (PR 69;433), p < 0.05). The highest costs are for hospitalisation (41% of all costs). Because there is a relatively high amount of (partly) missing data, a sensitivity analysis was performed, in which all missing data were included in the analysis by means of general mean substitution. In the sensitivity analysis, the total costs associated with home birth are euro4,364 per birth, and euro4,541 per birth for short-stay hospital births. The total costs associated with pregnancy, delivery, and postpartum care are comparable for home birth and short-stay hospital birth. The most important differences in costs between the home birth group and the short-stay hospital birth group are associated with maternity care assistance, hospitalisation, and travelling costs.

Cost Analysis of the Dutch Obstetric System: low-risk nulliparous women preferring home or short-stay hospital birth - a prospective non-randomised controlled study

PubMed Central

2009-01-01

Background In the Netherlands, pregnant women without medical complications can decide where they want to give birth, at home or in a short-stay hospital setting with a midwife. However, a decrease in the home birth rate during the last decennium may have raised the societal costs of giving birth. The objective of this study is to compare the societal costs of home births with those of births in a short-stay hospital setting. Methods This study is a cost analysis based on the findings of a multicenter prospective non-randomised study comparing two groups of nulliparous women with different preferences for where to give birth, at home or in a short-stay hospital setting. Data were collected using cost diaries, questionnaires and birth registration forms. Analysis of the data is divided into a base case analysis and a sensitivity analysis. Results In the group of home births, the total societal costs associated with giving birth at home were €3,695 (per birth), compared with €3,950 per birth in the group for short-stay hospital births. Statistically significant differences between both groups were found regarding the following cost categories 'Cost of contacts with health care professionals during delivery' (€138.38 vs. €87.94, -50 (2.5-97.5 percentile range (PR)-76;-25), p < 0.05), 'cost of maternity care at home' (€1,551.69 vs. €1,240.69, -311 (PR -485; -150), p < 0.05) and 'cost of hospitalisation mother' (€707.77 vs. 959.06, 251 (PR 69;433), p < 0.05). The highest costs are for hospitalisation (41% of all costs). Because there is a relatively high amount of (partly) missing data, a sensitivity analysis was performed, in which all missing data were included in the analysis by means of general mean substitution. In the sensitivity analysis, the total costs associated with home birth are €4,364 per birth, and €4,541 per birth for short-stay hospital births. Conclusion The total costs associated with pregnancy, delivery, and postpartum care are comparable for home birth and short-stay hospital birth. The most important differences in costs between the home birth group and the short-stay hospital birth group are associated with maternity care assistance, hospitalisation, and travelling costs. PMID:19925673

Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis.

PubMed

Frejo, L; Martin-Sanz, E; Teggi, R; Trinidad, G; Soto-Varela, A; Santos-Perez, S; Manrique, R; Perez, N; Aran, I; Almeida-Branco, M S; Batuecas-Caletrio, A; Fraile, J; Espinosa-Sanchez, J M; Perez-Guillen, V; Perez-Garrigues, H; Oliva-Dominguez, M; Aleman, O; Benitez, J; Perez, P; Lopez-Escamez, J A

2017-12-01

To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD. A cross-sectional study with a two-step cluster analysis. A tertiary referral multicenter study. Nine hundred and eighty-eight adult patients with unilateral MD. best predictors to define clinical subgroups with potential different aetiologies. We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni- and bilateral MD. Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials. © 2017 John Wiley & Sons Ltd.

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

Treatment of hydrocele: randomised prospective study of simple aspiration and sclerotherapy with tetracycline.

PubMed

Breda, G; Giunta, A; Gherardi, L; Xausa, D; Silvestre, P; Tamai, A

1992-07-01

Following reports in the literature on the efficacy of tetracycline sclerotherapy in the treatment of hydroceles, we carried out a randomised prospective study of 45 patients (50 hydroceles), comparing simple evacuation with tetracycline sclerotherapy. The results revealed no statistically significant difference in the percentage of success between the 2 groups, but complications were more common in the patients treated with tetracycline. The good results reported by other authors in non-randomised studies are, therefore, not confirmed.

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

PubMed

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

2016-06-13

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

Single-Incision Multiport/Single Port Laparoscopic Abdominal Surgery (SILAP): A Prospective Multicenter Observational Quality Study.

PubMed

Mantke, Rene; Diener, Markus; Kropf, Siegfried; Otto, Ronny; Manger, Thomas; Vestweber, Boris; Mirow, Lutz; Winde, Günther; Lippert, Hans

2016-09-07

Increasing experience with minimally invasive surgery and the development of new instruments has resulted in a tendency toward reducing the number of abdominal skin incisions. Retrospective and randomized prospective studies could show the feasibility of single-incision surgery without any increased risk to the patient. However, large prospective multicenter observational datasets do not currently exist. This prospective multicenter observational quality study will provide a relevant dataset reflecting the feasibility and safety of single-incision surgery. This study focuses on external validity, clinical relevance, and the patients' perspective. Accordingly, the single-incision multiport/single port laparoscopic abdominal surgery (SILAP) study will supplement the existing evidence, which does not currently allow evidence-based surgical decision making. The SILAP study is an international prospective multicenter observational quality study. Mortality, morbidity, complications during surgery, complications postoperatively, patient characteristics, and technical aspects will be monitored. We expect more than 100 surgical centers to participate with 5000 patients with abdominal single-incision surgery during the study period. Funding was obtained in 2012. Enrollment began on January 01, 2013, and will be completed on December 31, 2018. As of January 2016, 2119 patients have been included, 106 German centers are registered, and 27 centers are very active (>5 patients per year). This prospective multicenter observational quality study will provide a relevant dataset reflecting the feasibility and safety of single-incision surgery. An international enlargement and recruitment of centers outside of Germany is meaningful. German Clinical Trials Register: DRKS00004594; https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004594 (Archived by WebCite at http://www.webcitation.org/6jK6ZVyUs).

Prospective, Multicenter Validation Study of Magnetic Resonance Volumetry for Response Assessment After Preoperative Chemoradiation in Rectal Cancer: Can the Results in the Literature be Reproduced?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martens, Milou H., E-mail: mh.martens@hotmail.com; Department of Surgery, Maastricht University Medical Center, Maastricht; GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht

2015-12-01

Purpose: To review the available literature on tumor size/volume measurements on magnetic resonance imaging for response assessment after chemoradiotherapy, and validate these cut-offs in an independent multicenter patient cohort. Methods and Materials: The study included 2 parts. (1) Review of the literature: articles were included that assessed the accuracy of tumor size/volume measurements on magnetic resonance imaging for tumor response assessment. Size/volume cut-offs were extracted; (2) Multicenter validation: extracted cut-offs from the literature were tested in a multicenter cohort (n=146). Accuracies were calculated and compared with reported results from the literature. Results: The review included 14 articles, in which 3more » different measurement methods were assessed: (1) tumor length; (2) 3-dimensonial tumor size; and (3) whole volume. Study outcomes consisted of (1) complete response (ypT0) versus residual tumor; (2) tumor regression grade 1 to 2 versus 3 to 5; and (3) T-downstaging (ypT« less

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

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…

Feasibility study of Transcutaneous Electrical Nerve Stimulation (TENS) for cancer bone pain.

PubMed

Bennett, Michael I; Johnson, Mark I; Brown, Sarah R; Radford, Helen; Brown, Julia M; Searle, Robert D

2010-04-01

This multicenter study assessed the feasibility of conducting a phase III trial of transcutaneous electrical nerve stimulation (TENS) in patients with cancer bone pain recruited from palliative care services. Eligible patients received active and placebo TENS for 1 hour at site of pain in a randomized crossover design; median interval between applications 3 days. Responses assessed at 30 and 60 minutes included numerical and verbal ratings of pain at rest and on movement, and pain relief. Recruitment, tolerability, adverse events, and effectiveness of blinding were also evaluated. Twenty-four patients were randomised and 19 completed both applications. The intervention was well tolerated. Five patients withdrew: 3 due to deteriorating performance status, and 2 due to increased pain (1 each following active and placebo TENS). Confidence interval estimation around the differences in outcomes between active and placebo TENS suggests that TENS has the potential to decrease pain on movement more than pain on rest. Nine patients did not consider that a placebo was used; the remaining 10 correctly identified placebo TENS. Feasibility studies are important in palliative care prior to undertaking clinical trials. Our findings suggest that further work is required on recruitment strategies and refining the control arm before evaluating TENS in cancer bone pain. Cancer bone pain is common and severe, and partly mediated by hyperexcitability. Animal studies suggest that Transcutaneous Electrical Nerve Stimulation can reduce hyperalgesia. This study examined the feasibility of evaluating TENS in patients with cancer bone pain in order to optimize methods before a phase III trial. Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.

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.

The Randomised Intervention Treatment of Angina (RITA) Trial protocol: a long term study of coronary angioplasty and coronary artery bypass surgery in patients with angina.

PubMed Central

Henderson, R A

1989-01-01

The Randomised Intervention Treatment of Angina (RITA) Trial is a prospective, randomised study to compare the short term and long term effects of percutaneous transluminal coronary angioplasty and coronary artery bypass surgery. During the study a register of patients undergoing coronary arteriography at the fourteen participating centres is being maintained to assess the overall context of patient recruitment. Patients with arteriographically proven coronary artery disease are considered for the trial if the participating cardiologist and surgeon agree that equivalent revascularisation could be achieved by either treatment method. Patients who satisfy the trial entry criteria are randomised to treatment by coronary angioplasty or coronary artery bypass surgery, with prospective stratification into groups with one, two, or three treatment vessels. Randomisation implies an intention to treat the patient by the assigned procedure and the analysis of long term results will include all randomised cases. The trial will recruit at least 1000 patients who will be followed for five years. The major trial end points include death, new myocardial infarction, and new coronary angioplasty or coronary artery bypass procedures. Other outcome measures include symptom and employment status, quality of life, exercise tolerance, and left ventricular function. PMID:2486557

Timing of oral anticoagulant therapy in acute ischemic stroke with atrial fibrillation: study protocol for a registry-based randomised controlled trial.

PubMed

Åsberg, Signild; Hijazi, Ziad; Norrving, Bo; Terént, Andreas; Öhagen, Patrik; Oldgren, Jonas

2017-12-02

Oral anticoagulation therapy is recommended for the prevention of recurrent ischemic stroke in patients with atrial fibrillation (AF). Current guidelines do not provide evidence-based recommendations on optimal time-point to start anticoagulation therapy after an acute ischemic stroke. Non-vitamin K antagonist oral anticoagulants (NOACs) may offer advantages compared to warfarin because of faster and more predictable onset of action and potentially a lower risk of intracerebral haemorrhage also in the acute phase after an ischemic stroke. The TIMING study aims to establish the efficacy and safety of early vs delayed initiation of NOACs in patients with acute ischemic stroke and AF. The TIMING study is a national, investigator-led, registry-based, multicentre, open-label, randomised controlled study. The Swedish Stroke Register is used for enrolment, randomisation and follow-up of 3000 patients, who are randomised (1:1) within 72 h from ischemic stroke onset to either early (≤ 4 days) or delayed (≥ 5-10 days) start of NOAC therapy. The primary outcome is the composite of recurrent ischemic stroke, symptomatic intracerebral haemorrhage, or all-cause mortality within 90 days after randomisation. Secondary outcomes include: individual components of the primary outcome at 90 and 365 days; major haemorrhagic events; functional outcome by the modified Rankin Scale at 90 days; and health economics. In an optional biomarker sub-study, blood samples will be collected after randomisation from approximately half of the patients for central analysis of cardiovascular biomarkers after study completion. The study is funded by the Swedish Medical Research Council. Enrolment of patients started in April 2017. The TIMING study addresses the ongoing clinical dilemma of when to start NOAC after an acute ischemic stroke in patients with AF. By the inclusion of a randomisation module within the Swedish Stroke Register, the advantages of a prospective randomised study design are combined with the strengths of a national clinical quality register in allowing simplified enrolment and follow-up of study patients. In addition, the register adds the possibility of directly assessing the external validity of the study findings. ClinicalTrials.gov, NCT02961348 . Registered on 8 November 2016.

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.

Variability of the institutional review board process within a national research network.

PubMed

Khan, Muhammad A; Barratt, Michelle S; Krugman, Scott D; Serwint, Janet R; Dumont-Driscoll, Marilyn

2014-06-01

To determine the variability of the institutional review board (IRB) process for a minimal risk multicenter study. Participants included 24 Continuity Research Network (CORNET) sites of the Academic Pediatric Association that participated in a cross-sectional study. Each site obtained individual institutional IRB approval. An anonymous questionnaire went to site investigators about the IRB process at their institution. Twenty-two of 24 sites (92%) responded. Preparation time ranged from 1 to 20 hours, mean of 7.1 hours. Individuals submitting ≤3 IRB applications/year required more time for completion than those submitting >3/year (P < .05). Thirteen of 22 (59%) study sites received approval with "exempt" status, and 6 (27%) approved as "expedited" studies. IRB experiences were highly variable across study sites. These findings indicate that multicenter research projects should anticipate barriers to timely study implementation. Improved IRB standardization or centralization for multicenter clinical studies would facilitate this type of practice-based clinical research.

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

Spine device clinical trials: design and sponsorship.

PubMed

Cher, Daniel J; Capobianco, Robyn A

2015-05-01

Multicenter prospective randomized clinical trials represent the best evidence to support the safety and effectiveness of medical devices. Industry sponsorship of multicenter clinical trials is purported to lead to bias. To determine what proportion of spine device-related trials are industry-sponsored and the effect of industry sponsorship on trial design. Analysis of data from a publicly available clinical trials database. Clinical trials of spine devices registered on ClinicalTrials.gov, a publicly accessible trial database, were evaluated in terms of design, number and location of study centers, and sample size. The relationship between trial design characteristics and study sponsorship was evaluated using logistic regression and general linear models. One thousand six hundred thrity-eight studies were retrieved from ClinicalTrials.gov using the search term "spine." Of the 367 trials that focused on spine surgery, 200 (54.5%) specifically studied devices for spine surgery and 167 (45.5%) focused on other issues related to spine surgery. Compared with nondevice trials, device trials were far more likely to be sponsored by the industry (74% vs. 22.2%, odds ratio (OR) 9.9 [95% confidence interval 6.1-16.3]). Industry-sponsored device trials were more likely multicenter (80% vs. 29%, OR 9.8 [4.8-21.1]) and had approximately four times as many participating study centers (p<.0001) and larger sample sizes. There were very few US-based multicenter randomized trials of spine devices not sponsored by the industry. Most device-related spine research is industry-sponsored. Multicenter trials are more likely to be industry-sponsored. These findings suggest that previously published studies showing larger effect sizes in industry-sponsored vs. nonindustry-sponsored studies may be biased as a result of failure to take into account the marked differences in design and purpose. Copyright © 2015 Elsevier Inc. All rights reserved.

Factors Influencing Medical Student Attrition and Their Implications in a Large Multi-Center Randomized Education Trial

ERIC Educational Resources Information Center

Kalet, A.; Ellaway, R. H.; Song, H. S.; Nick, M.; Sarpel, U.; Hopkins, M. A.; Hill, J.; Plass, J. L.; Pusic, M. V.

2013-01-01

Participant attrition may be a significant threat to the generalizability of the results of educational research studies if participants who do not persist in a study differ from those who do in ways that can affect the experimental outcomes. A multi-center trial of the efficacy of different computer-based instructional strategies gave us the…

Alcohol Consumption among University Students in North Rhine-Westphalia, Germany--Results from a Multicenter Cross-Sectional Study

ERIC Educational Resources Information Center

Akmatov, Manas K.; Mikolajczyk, Rafael T.; Meier, Sabine; Kramer, Alexander

2011-01-01

Objective: To assess alcohol use and problem drinking among university students in the German Federal State of North Rhine-Westphalia (NRW) and to examine the associated factors. Method: A multicenter cross-sectional study was conducted in 16 universities in 2006-2007 in NRW by a standardized questionnaire and 3,306 students provided information…

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/.

RANDOMISED ASPIRIN ASSIGNMENT AND RISK OF ADULT-ONSET ASTHMA IN THE WOMEN'S HEALTH STUDY

PubMed Central

Kurth, Tobias; Barr, R. Graham; Gaziano, J. Michael; Buring, Julie E.

2008-01-01

Rationale Randomised data in men showed a small but significant reduction in risk of adult-onset asthma among those assigned to aspirin. Results from an observational study in women suggest that frequent use of aspirin decreased the risk of adult-onset asthma. Randomised data in women are lacking. Objective To test the effect of 100 mg of aspirin on alternate days or placebo on the risk of adult-onset asthma in the Women's Health Study. Methods Post-hoc analyses from a randomised, double-blind, placebo-controlled clinical trial of aspirin and vitamin E in apparently healthy US women with no indication or contraindication to aspirin therapy and free of a history of asthma at study entry. Measurements Female health professionals could self-report an asthma diagnosis on yearly questionnaires. Results Among 37,270 women without reported history of asthma prior to randomisation and during 10 years of follow-up, there were 872 new reports of asthma diagnosis in the aspirin group and 963 in the placebo group (hazard ratio=0.90; 95% confidence interval=0.82−0.99; P=0.027). This apparent 10% lower relative risk of incident adult-onset asthma among those assigned to aspirin was significantly modified by body mass index, indicating no effect among women with a body mass index of ≥30 kg/m2. There was no significant effect modification by age, smoking status, exercise levels, postmenopausal hormone use, or randomised vitamin E assignment. Conclusions In this large, randomised clinical trial of apparently healthy adult women, assignment of 100 mg of aspirin on alternate days reduced the relative risk of newly reported diagnosis of asthma. PMID:18339679

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

PubMed Central

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

2014-01-01

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

Identification and Validation of Established and Novel Biomarkers for Infections in Burns

DTIC Science & Technology

2017-10-01

in burn patients have been proposed, but not validated. In our four site study , we are enrolling severely burned adults and children , and...identify the early stages of infection prior to clinical detection. This multicenter study will enable us to identify novel biomarkers, validate whether...a multicenter study 3. Develop a model of prediction of infection using clinical data and proteomic information. Relevance: 5% of combat-sustained

Theoretical study of electron impact triple differential cross sections of N2O by a multicenter distorted-wave method

NASA Astrophysics Data System (ADS)

Gong, Maomao; Li, Xingyu; Zhang, Song Bin; Chen, Xiangjun

2018-05-01

A coplanar asymmetric (e, 2e) measurement on N2O has been reported in 1999 by Cavanagh and Lohmann (1999 J. Phys. B: At. Mol. Opt. Phys. 32 L261), however, the relevant ab initio theoretical study is not available even up to now. In this work, we report theoretical studies of (e, 2e) triple differential cross sections of N2O at the same kinematics using a multicenter distorted-wave method. The influence of the multicenter nature of N2O molecule on the continuum wave function of the ejected electron has been largely considered. The computed results show good agreement with the experimental data for both outer valence 2π and inner valence 4σ orbitals.

Who Donates Their Body to Science? An International, Multicenter, Prospective Study

ERIC Educational Resources Information Center

Cornwall, Jon; Perry, Gary F.; Louw, Graham; Stringer, Mark D.

2012-01-01

The altruistic act of body donation provides a precious resource for both teaching and researching human anatomy. However, relatively little is known about individuals who donate their bodies to science (donors), and in particular whether donors in different geographical locations share similar characteristics. A multicenter prospective survey of…

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.

No Higher Risk of CRPS After External Fixation of Distal Radial Fractures - Subgroup Analysis Under Randomised Vitamin C Prophylaxis.

PubMed

Zollinger, Paul E; Kreis, Robert W; van der Meulen, Hub G; van der Elst, Maarten; Breederveld, Roelf S; Tuinebreijer, Wim E

2010-02-17

Operative and conservative treatment of wrist fractures might lead to complex regional pain syndrome (CRPS) type I.In our multicenter dose response study in which patients with distal radial fractures were randomly allocated to placebo or vitamin C in a daily dose of 200mg, 500mg or 1500mg during 50 days, an operated subgroup was analyzed.48 (of 427) fractures) were operated (11.2%). Twenty-nine patients (60%) were treated with external fixation, 14 patients (29%) with K-wiring according to Kapandji and five patients (10%) with internal plate fixation. The 379 remaining patients were treated with a plaster.In the operated group of patients who received vitamin C no CRPS (0/37) was seen in comparison with one case of CRPS (Kapandji technique) in the operated group who received placebo (1/11 = 9%, p=.23). There was no CRPS after external fixation.In the conservatively treated group 17 cases of CRPS (17/379 = 4.5%) occurred in comparison with one in case of CRPS in the operated group (1/48 = 2.1%, p=.71).External fixation doesn't necessarily lead to a higher incidence of CRPS in distal radial fractures. Vitamin C may also play a role in this. This subgroup analysis in operated distal radial fractures showed no CRPS occurrence with vitamin C prophylaxis.

Economic analysis of centralized vs. decentralized electronic data capture in multi-center clinical studies.

PubMed

Walden, Anita; Nahm, Meredith; Barnett, M Edwina; Conde, Jose G; Dent, Andrew; Fadiel, Ahmed; Perry, Theresa; Tolk, Chris; Tcheng, James E; Eisenstein, Eric L

2011-01-01

New data management models are emerging in multi-center clinical studies. We evaluated the incremental costs associated with decentralized vs. centralized models. We developed clinical research network economic models to evaluate three data management models: centralized, decentralized with local software, and decentralized with shared database. Descriptive information from three clinical research studies served as inputs for these models. The primary outcome was total data management costs. Secondary outcomes included: data management costs for sites, local data centers, and central coordinating centers. Both decentralized models were more costly than the centralized model for each clinical research study: the decentralized with local software model was the most expensive. Decreasing the number of local data centers and case book pages reduced cost differentials between models. Decentralized vs. centralized data management in multi-center clinical research studies is associated with increases in data management costs.

Economic Analysis of Centralized vs. Decentralized Electronic Data Capture in Multi-Center Clinical Studies

PubMed Central

Walden, Anita; Nahm, Meredith; Barnett, M. Edwina; Conde, Jose G.; Dent, Andrew; Fadiel, Ahmed; Perry, Theresa; Tolk, Chris; Tcheng, James E.; Eisenstein, Eric L.

2012-01-01

Background New data management models are emerging in multi-center clinical studies. We evaluated the incremental costs associated with decentralized vs. centralized models. Methods We developed clinical research network economic models to evaluate three data management models: centralized, decentralized with local software, and decentralized with shared database. Descriptive information from three clinical research studies served as inputs for these models. Main Outcome Measures The primary outcome was total data management costs. Secondary outcomes included: data management costs for sites, local data centers, and central coordinating centers. Results Both decentralized models were more costly than the centralized model for each clinical research study: the decentralized with local software model was the most expensive. Decreasing the number of local data centers and case book pages reduced cost differentials between models. Conclusion Decentralized vs. centralized data management in multi-center clinical research studies is associated with increases in data management costs. PMID:21335692

Prospective Multicenter Study of Pneumocystis jirovecii Colonization among Cystic Fibrosis Patients in France

PubMed Central

Hernández-Hernández, Francisca; Fréalle, Emilie; Caneiro, Patrick; Salleron, Julia; Durand-Joly, Isabelle; Accoceberry, Isabelle; Bouchara, Jean-Philippe; Wallaert, Benoit; Dei-Cas, Eduardo

2012-01-01

Pneumocystis carriage was detected in 12.5% of 104 cystic fibrosis (CF) patients during a prospective multicenter French study, with a prevalence of genotype 85C/248C and geographic variations. It was significantly associated with the absence of Pseudomonas aeruginosa colonization and a greater forced expiratory volume in 1 s. Results are discussed considering the natural history of CF. PMID:23015669

Prospective multicenter study of Pneumocystis jirovecii colonization among cystic fibrosis patients in France.

PubMed

Hernández-Hernández, Francisca; Fréalle, Emilie; Caneiro, Patrick; Salleron, Julia; Durand-Joly, Isabelle; Accoceberry, Isabelle; Bouchara, Jean-Philippe; Wallaert, Benoit; Dei-Cas, Eduardo; Delhaes, Laurence

2012-12-01

Pneumocystis carriage was detected in 12.5% of 104 cystic fibrosis (CF) patients during a prospective multicenter French study, with a prevalence of genotype 85C/248C and geographic variations. It was significantly associated with the absence of Pseudomonas aeruginosa colonization and a greater forced expiratory volume in 1 s. Results are discussed considering the natural history of CF.

ICT-based system to predict and prevent falls (iStoppFalls): study protocol for an international multicenter randomized controlled trial.

PubMed

Gschwind, Yves J; Eichberg, Sabine; Marston, Hannah R; Ejupi, Andreas; Rosario, Helios de; Kroll, Michael; Drobics, Mario; Annegarn, Janneke; Wieching, Rainer; Lord, Stephen R; Aal, Konstantin; Delbaere, Kim

2014-08-20

Falls are very common, especially in adults aged 65 years and older. Within the current international European Commission's Seventh Framework Program (FP7) project 'iStoppFalls' an Information and Communication Technology (ICT) based system has been developed to regularly assess a person's risk of falling in their own home and to deliver an individual and tailored home-based exercise and education program for fall prevention. The primary aims of iStoppFalls are to assess the feasibility and acceptability of the intervention program, and its effectiveness to improve balance, muscle strength and quality of life in older people. This international, multicenter study is designed as a single-blinded, two-group randomized controlled trial. A total of 160 community-dwelling older people aged 65 years and older will be recruited in Germany (n = 60), Spain (n = 40), and Australia (n = 60) between November 2013 and May 2014. Participants in the intervention group will conduct a 16-week exercise program using the iStoppFalls system through their television set at home. Participants are encouraged to exercise for a total duration of 180 minutes per week. The training program consists of a variety of balance and strength exercises in the form of video games using exergame technology. Educational material about a healthy lifestyle will be provided to each participant. Final reassessments will be conducted after 16 weeks. The assessments include physical and cognitive tests as well as questionnaires assessing health, fear of falling, quality of life and psychosocial determinants. Falls will be followed up for six months by monthly falls calendars. We hypothesize that the regular use of this newly developed ICT-based system for fall prevention at home is feasible for older people. By using the iStoppFalls sensor-based exercise program, older people are expected to improve in balance and strength outcomes. In addition, the exercise training may have a positive impact on quality of life by reducing the risk of falls. Taken together with expected cognitive improvements, the individual approach of the iStoppFalls program may provide an effective model for fall prevention in older people who prefer to exercise at home. Australian New Zealand Clinical Trials Registry Trial ID: ACTRN12614000096651.International Standard Randomised Controlled Trial Number: ISRCTN15932647.

ICT-based system to predict and prevent falls (iStoppFalls): study protocol for an international multicenter randomized controlled trial

PubMed Central

2014-01-01

Background Falls are very common, especially in adults aged 65 years and older. Within the current international European Commission’s Seventh Framework Program (FP7) project ‘iStoppFalls’ an Information and Communication Technology (ICT) based system has been developed to regularly assess a person’s risk of falling in their own home and to deliver an individual and tailored home-based exercise and education program for fall prevention. The primary aims of iStoppFalls are to assess the feasibility and acceptability of the intervention program, and its effectiveness to improve balance, muscle strength and quality of life in older people. Methods/Design This international, multicenter study is designed as a single-blinded, two-group randomized controlled trial. A total of 160 community-dwelling older people aged 65 years and older will be recruited in Germany (n = 60), Spain (n = 40), and Australia (n = 60) between November 2013 and May 2014. Participants in the intervention group will conduct a 16-week exercise program using the iStoppFalls system through their television set at home. Participants are encouraged to exercise for a total duration of 180 minutes per week. The training program consists of a variety of balance and strength exercises in the form of video games using exergame technology. Educational material about a healthy lifestyle will be provided to each participant. Final reassessments will be conducted after 16 weeks. The assessments include physical and cognitive tests as well as questionnaires assessing health, fear of falling, quality of life and psychosocial determinants. Falls will be followed up for six months by monthly falls calendars. Discussion We hypothesize that the regular use of this newly developed ICT-based system for fall prevention at home is feasible for older people. By using the iStoppFalls sensor-based exercise program, older people are expected to improve in balance and strength outcomes. In addition, the exercise training may have a positive impact on quality of life by reducing the risk of falls. Taken together with expected cognitive improvements, the individual approach of the iStoppFalls program may provide an effective model for fall prevention in older people who prefer to exercise at home. Trial registration Australian New Zealand Clinical Trials Registry Trial ID: ACTRN12614000096651. International Standard Randomised Controlled Trial Number: ISRCTN15932647. PMID:25141850

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.

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.

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.

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.

Comparative effectiveness of fourth-line anti-hypertensive agents in resistant hypertension: A systematic review and meta-analysis.

PubMed

Sinnott, Sarah-Jo; Tomlinson, Laurie A; Root, Adrian A; Mathur, Rohini; Mansfield, Kathryn E; Smeeth, Liam; Douglas, Ian J

2017-02-01

Aim We assessed the effectiveness of fourth-line mineralocorticoid receptor antagonists in comparison with other fourth-line anti-hypertensive agents in resistant hypertension. Methods and results We systematically searched Medline, EMBASE and the Cochrane library from database inception until January 2016. We included randomised and non-randomised studies that compared mineralocorticoid receptor antagonists with other fourth-line anti-hypertensive agents in patients with resistant hypertension. The outcome was change in systolic blood pressure, measured in the office, at home or by ambulatory blood pressure monitoring. Secondary outcomes were changes in serum potassium and occurrence of hyperkalaemia. We used random effects models and assessed statistical heterogeneity using the I 2 test and corresponding 95% confidence intervals. From 2,506 records, 5 studies met our inclusion criteria with 755 included patients. Two studies were randomised and three were non-randomised. Comparative fourth-line agents included bisoprolol, doxazosin, furosemide and additional blockade of the renin angiotensin-aldosterone system. Using data from randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 7.4 mmHg (95%CI 3.2 - 11.6) more than the active comparator. When limited to non-randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 11.9 mmHg (95% CI 9.3 - 14.4) more than the active comparator. Conclusion On the basis of this meta-analysis, mineralocorticoid receptor antagonists reduce blood pressure more effectively than other fourth-line agents in resistant hypertension. Effectiveness stratified by ethnicity and comorbidities, in addition to information on clinical outcomes such as myocardial infarction and stroke, now needs to be determined.

The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: study protocol for a randomised controlled trial.

PubMed

Al-Shahi Salman, Rustam; Dennis, Martin S; Murray, Gordon D; Innes, Karen; Drever, Jonathan; Dinsmore, Lynn; Williams, Carol; White, Philip M; Whiteley, William N; Sandercock, Peter A G; Sudlow, Cathie L M; Newby, David E; Sprigg, Nikola; Werring, David J

2018-03-05

For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs results in an increase in the risk of recurrent ICH or a beneficial net reduction of all serious vascular events compared to avoiding antiplatelet drugs. The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, randomised, open, assessor-blind, parallel-group, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH at 122 hospital sites in the United Kingdom. RESTART uses a central, web-based randomisation system using a minimisation algorithm, with 1:1 treatment allocation to which central research staff are masked. Central follow-up includes annual postal or telephone questionnaires to participants and their general (family) practitioners, with local provision of information about adverse events and outcome events. The primary outcome is recurrent symptomatic ICH. The secondary outcomes are: symptomatic haemorrhagic events; symptomatic vaso-occlusive events; symptomatic stroke of uncertain type; other fatal events; modified Rankin Scale score; adherence to antiplatelet drug(s). The magnetic resonance imaging (MRI) sub-study involves the conduct of brain MRI according to a standardised imaging protocol before randomisation to investigate heterogeneity of treatment effect according to the presence of brain microbleeds. Recruitment began on 22 May 2013. The target sample size is at least 720 participants in the main trial (at least 550 in the MRI sub-study). Final results of RESTART will be analysed and disseminated in 2019. ISRCTN71907627 ( www.isrctn.com/ISRCTN71907627 ). Prospectively registered on 25 April 2013.

In vivo measurements of proton relaxation times in human brain, liver, and skeletal muscle: a multicenter MRI study.

PubMed

de Certaines, J D; Henriksen, O; Spisni, A; Cortsen, M; Ring, P B

1993-01-01

Quantitative magnetic resonance imaging may offer unique potential for tissue characterization in vivo. In this connection texture analysis of quantitative MR images may be of special importance. Because evaluation of texture analysis needs large data material, multicenter approaches become mandatory. Within the frame of BME Concerted Action on Tissue Characterization by MRI and MRS, a pilot multicenter study was launched in order to evaluate the technical problems including comparability of relaxation time measurements carried out in the individual sites. Human brain, skeletal muscle, and liver were used as models. A total of 218 healthy volunteers were studied. Fifteen MRI scanners with field strength ranging from 0.08 T to 1.5 T were induced. Measurement accuracy was tested on the Eurospin relaxation time test object (TO5) and the obtained calibration curve was used for correction of the in vivo data. The results established that, by following a standardized procedure, comparable quantitative measurements can be obtained in vivo from a number of MR sites. The overall variation coefficient in vivo was in the same order of magnitude as ex vivo relaxometry. Thus, it is possible to carry out international multicenter studies on quantitative imaging, provided that quality control with respect to measurement accuracy and calibration of the MR equipments are performed.

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.

Hemicraniectomy after middle cerebral artery infarction with life-threatening Edema trial (HAMLET). Protocol for a randomised controlled trial of decompressive surgery in space-occupying hemispheric infarction.

PubMed

Hofmeijer, Jeannette; Amelink, G Johan; Algra, Ale; van Gijn, Jan; Macleod, Malcolm R; Kappelle, L Jaap; van der Worp, H Bart

2006-09-11

Patients with a hemispheric infarct and massive space-occupying brain oedema have a poor prognosis. Despite maximal conservative treatment, the case fatality rate may be as high as 80%, and most survivors are left severely disabled. Non-randomised studies suggest that decompressive surgery reduces mortality substantially and improves functional outcome of survivors. This study is designed to compare the efficacy of decompressive surgery to improve functional outcome with that of conservative treatment in patients with space-occupying supratentorial infarction The study design is that of a multi-centre, randomised clinical trial, which will include 112 patients aged between 18 and 60 years with a large hemispheric infarct with space-occupying oedema that leads to a decrease in consciousness. Patients will be randomised to receive either decompressive surgery in combination with medical treatment or best medical treatment alone. Randomisation will be stratified for the intended mode of conservative treatment (intensive care or stroke unit care). The primary outcome measure will be functional outcome, as determined by the score on the modified Rankin Scale, at one year.

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.

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.

A Multicenter Study of Volumetric Computed Tomography for Staging Malignant Pleural Mesothelioma

PubMed Central

Rusch, Valerie W.; Gill, Ritu; Mitchell, Alan; Naidich, David; Rice, David C.; Pass, Harvey I.; Kindler, Hedy; De Perrot, Marc; Friedberg, Joseph

2016-01-01

Background Standard imaging modalities are inaccurate in staging malignant pleural mesothelioma (MPM). Single institution studies suggest that volumetric computed tomography (VolCT) is more accurate but labor intensive. We established a multicenter network to test interobserver variability, accuracy (relative to pathologic stage) and prognostic significance of semi-automated VolCT. Methods Six institutions electronically submitted clinical and pathologic data to an established multicenter database on patients with MPM who had surgery. Institutional radiologists reviewed preoperative CT scans for quality then submitted via electronic network (AG mednet) to biostatistical center (BC). Two reference radiologists, blinded to clinical data, performed semi-automated tumor volume calculations using commercially available software (Vitrea Enterprise 6.0), then submitted readings to BC. Study endpoints included: feasibility of network; interobserver variability for VolCT; correlation of tumor volume to pTN stages, and overall survival (OS). Results Of 164 cases, 129 were analyzable and read by reference radiologists. Most tumors were <500cm3. A small bias was observed between readers, as one provided consistently larger measurements than the other (mean difference=47.9, p=.0027), but for 80% of cases, the absolute difference was ≤ 200cm3. Spearman correlation between readers was 0.822. Volume correlated with pTN stages and OS, best defined by 3 groups with average volumes of: 91.2, 245.3, 511.3cm3, associated with median OS of 37, 18, 8 months respectively. Conclusions For the first time, a multicenter network was established and initial correlations of tumor volume to pTN stages and OS shown. A larger multicenter international study is planned to confirm results and refine correlations. PMID:27596916

Obtaining real-world evidence: the Salford Lung Study

PubMed Central

New, John P; Bakerly, Nawar Diar; Leather, David; Woodcock, Ashley

2014-01-01

We need to assess clinical treatments in real-life settings outside of randomised controlled trials (RCTs). Pragmatic RCT (pRCT) data can supplement RCTs by providing effectiveness information to support healthcare decisions. Electronic health records can facilitate concurrent safety monitoring and data collection without direct patient contact for large randomised study populations in pRCTs. The Salford Lung Study is the world's first phase III pRCT in asthma and chronic obstructive pulmonary disease (COPD), which aims to randomise over 7000 patients. This paper describes the hurdles overcome and the enormous effort and resource required to establish this comparative effectiveness study of a prelicence intervention. GlaxoSmithKline protocol HZC115151 Asthma study clinicaltrials.gov registration NCT01706198 COPD study clinicaltrials.gov registration NCT01551758 PMID:24603195

A novel drug management system in the Febuxostat versus Allopurinol Streamlined Trial: A description of a pharmacy system designed to supply medications directly to patients within a prospective multicenter randomised clinical trial.

PubMed

Rogers, Amy; Flynn, Robert Wv; McDonnell, Patrick; Mackenzie, Isla S; MacDonald, Thomas M

2016-12-01

Trials of investigational medicinal products are required to adhere to strict guidelines with regard to the handling and supply of medication. Information technology offers opportunities to approach clinical trial methodology in new ways. This report summarises a novel pharmacy system designed to supply trial medications directly to patients by post in the Febuxostat versus Allopurinol Streamlined Trial. A bespoke web-based software package was designed to facilitate the direct supply of trial medications to Febuxostat versus Allopurinol Streamlined Trial participants from a pharmacy based in the Medicines Monitoring Unit, University of Dundee. To date, 65,467 packs of medication have been dispensed using the system to 3978 patients. Up to 238 packs per day have been dispensed. The Medicines Monitoring Unit Febuxostat versus Allopurinol Streamlined Trial drug management system is an effective method of administering the complex drug supply requirements of a large-scale clinical trial with advantages over existing arrangements. A low rate of loss to follow-up in the Febuxostat versus Allopurinol Streamlined Trial may be attributable to the drug management system. © The Author(s) 2016.

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

Premature Discontinuation of Prospective Clinical Studies Approved by a Research Ethics Committee - A Comparison of Randomised and Non-Randomised Studies.

PubMed

Blümle, Anette; Schandelmaier, Stefan; Oeller, Patrick; Kasenda, Benjamin; Briel, Matthias; von Elm, Erik

2016-01-01

Premature discontinuation of clinical studies affects about 25% of randomised controlled trials (RCTs) which raises concerns about waste of scarce resources for research. The risk of discontinuation of non-randomised prospective studies (NPSs) is yet unclear. To compare the proportion of discontinued studies between NPSs and RCTs that received ethical approval. We systematically surveyed prospective longitudinal clinical studies that were approved by a single REC in Freiburg, Germany between 2000 and 2002. We collected study characteristics, identified subsequent publications, and surveyed investigators to elucidate whether a study was discontinued and, if so, why. Of 917 approved studies, 547 were prospective longitudinal studies (306 RCTs and 241 NPSs). NPSs were on average smaller than RCTs, more frequently single centre and pilot studies, and less frequently funded by industry. NPSs were less frequently discontinued than RCTs: 32/221 (14%) versus 78/288 (27%, p<0.001, missing data excluded). Poor recruitment was the most frequent reason for discontinuation in both NPSs (36%) and RCTs (37%). Compared to RCTs, NPSs were at lower risk for discontinuation. Measures to reliably predict, sustain, and stimulate recruitment could prevent discontinuation of many RCTs but also of some NPSs.

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

PubMed Central

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

2018-01-01

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

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.

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

A Multicenter, Open-Label Trial to Evaluate the Quality of Life in Adults with ADHD Treated with Long-Acting Methylphenidate (OROS MPH): Concerta Quality of Life (CONQoL) Study

ERIC Educational Resources Information Center

Mattos, Paulo; Rodrigues Louza, Mario; Fernandes Palmini, Andre Luis; de Oliveira, Irismar Reis; Lopes Rocha, Fabio

2013-01-01

The available literature provides few studies on the effectiveness of methylphenidate in improving quality of life in individuals with ADHD. Objective: To assess the effectiveness of Methyphenidate OROS formulation (OROS MPH) through QoL in adults with ADHD. Method: A 12-week, multicenter, open-label trial involving 60 patients was used. The…

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.

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).

Does Quality of Radiation Therapy Predict Outcomes of Multicenter Cooperative Group Trials? A Literature Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fairchild, Alysa, E-mail: alysa.fairchild@albertahealthservices.ca; Straube, William; Laurie, Fran

2013-10-01

Central review of radiation therapy (RT) delivery within multicenter clinical trials was initiated in the early 1970s in the United States. Early quality assurance publications often focused on metrics related to process, logistics, and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. A MEDLINE search was performed to identify multicenter studies that described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicenter studies (1980-2012) were identified, plus one Patterns of Care Study. Diseasemore » sites were hematologic, head and neck, lung, breast, and pancreas. Between 0 and 97% of treatment plans received an overall grade of acceptable. In 7 trials, failure rates were significantly higher after inadequate versus adequate RT. Five of 9 and 2 of 5 trials reported significantly worse overall and progression-free survival after poor-quality RT, respectively. One reported a significant correlation, and 2 reported nonsignificant trends toward increased toxicity with noncompliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question.« less

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.

[Two-year results of a prospective randomised controlled multicenter trial to compare open operative therapy vs. endoluminal venous laser therapy with and without high ligation for the therapy of varicose greater saphenous veins].

PubMed

Flessenkämper, I H; Stenger, D; Hartmann, M; Hartmann, K; Roll, S

2015-02-01

Therapeutic options for the treatment of varicosis of the great saphenous vein (gsv) include endoluminal laser therapy, crossectomy/stripping and a combination of both. In this paper we present data for clinical and sonographic inguinal recurrencies up to two years post operation. In an open multicentre, randomised three-arm trial, sonographic and clinical parameters were compared perioperatively, after 2, 6, 12 and 24 months between endoluminal venous laser therapy, high ligation and invaginating stripping and a combination of both (laser: 980 nm, continuous mode, 30 W, Biolitec®, Jena, Germany). Data of 449 patients were available for the perioperative and 2 months examination. 388 patients were followed up until 6, 380 patients for 12 and 332 patients for 24 months. We compared clinical recurrences, sonographic reflux findings, and reflux side branches in the inguinal region at the saphenofemoral junction. We found significantly more inguinal reflux and reflux side branches in the laser groups (p < 0.0001), however, there was no statistically significant relation between clinical recurrences and sonographic reflux. Over time, there were no intraindividual constant refluxes. Regarding the secondary endpoints oedema, lymphatic oedema, local disturbances of sensibility and irritations of the saphenous nerve, lymphatic oedema and irritations of the saphenous nerve were significantly more present in the two laser groups. After two years pain and restrictions in professional life were no longer relevant in all groups. Clinical recurrences developed both in the C/S and in the laser group but reflux into the gsv and into proximal side branches developed significantly more often in the laser group. In a long-term follow-up we have to investigate the importance of reflux side branches for the development of clinical recurrences to reveal differences between the three therapeutic strategies. Georg Thieme Verlag KG Stuttgart · New York.

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

PubMed

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

2016-12-07

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

Recruitment of patients into head and neck clinical trials: acceptability of studies to patients from perspective of the research team.

PubMed

Ho, M W; Pick, A S; Sutton, D N; Dyker, K; Cardale, K; Gilbert, K; Johnson, J; Quantrill, J; McCaul, J A

2018-05-01

We reviewed longitudinal recruitment data to assess recruitment into head and neck cancer trials, and to identify factors that could influence this and affect their acceptability to patients. We retrieved data from the prospective computerised database (2009-2016) to measure acceptability to patients using the recruitment:screening ratio, and compared observational with interventional studies, single specialty (or site) with multispecialty (or site) studies, and "step-up" randomisation with "non-inferiority" randomisation designs. A total of 1283 patients were screened and 583 recruited. The recruitment:screening ratio for all National Institute for Health Research (NIHR) portfolio studies combined was 0.47 (486/1133). Studies that involved treatment by several specialties or at several sites had a significantly adverse impact on acceptability (p=0.01). Recruitment into non-inferiority randomised controlled studies was lower than that into step-up randomised studies (p=0.06). The complexity of a study's design did not compromise recruitment. Treatment across several specialties or several sites and perceived non-inferiority designs, reduced the acceptability of some trials. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

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.

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.

Applying the intention-to-treat principle in practice: Guidance on handling randomisation errors

PubMed Central

Sullivan, Thomas R; Voysey, Merryn; Lee, Katherine J; Cook, Jonathan A; Forbes, Andrew B

2015-01-01

Background: The intention-to-treat principle states that all randomised participants should be analysed in their randomised group. The implications of this principle are widely discussed in relation to the analysis, but have received limited attention in the context of handling errors that occur during the randomisation process. The aims of this article are to (1) demonstrate the potential pitfalls of attempting to correct randomisation errors and (2) provide guidance on handling common randomisation errors when they are discovered that maintains the goals of the intention-to-treat principle. Methods: The potential pitfalls of attempting to correct randomisation errors are demonstrated and guidance on handling common errors is provided, using examples from our own experiences. Results: We illustrate the problems that can occur when attempts are made to correct randomisation errors and argue that documenting, rather than correcting these errors, is most consistent with the intention-to-treat principle. When a participant is randomised using incorrect baseline information, we recommend accepting the randomisation but recording the correct baseline data. If ineligible participants are inadvertently randomised, we advocate keeping them in the trial and collecting all relevant data but seeking clinical input to determine their appropriate course of management, unless they can be excluded in an objective and unbiased manner. When multiple randomisations are performed in error for the same participant, we suggest retaining the initial randomisation and either disregarding the second randomisation if only one set of data will be obtained for the participant, or retaining the second randomisation otherwise. When participants are issued the incorrect treatment at the time of randomisation, we propose documenting the treatment received and seeking clinical input regarding the ongoing treatment of the participant. Conclusion: Randomisation errors are almost inevitable and should be reported in trial publications. The intention-to-treat principle is useful for guiding responses to randomisation errors when they are discovered. PMID:26033877

Applying the intention-to-treat principle in practice: Guidance on handling randomisation errors.

PubMed

Yelland, Lisa N; Sullivan, Thomas R; Voysey, Merryn; Lee, Katherine J; Cook, Jonathan A; Forbes, Andrew B

2015-08-01

The intention-to-treat principle states that all randomised participants should be analysed in their randomised group. The implications of this principle are widely discussed in relation to the analysis, but have received limited attention in the context of handling errors that occur during the randomisation process. The aims of this article are to (1) demonstrate the potential pitfalls of attempting to correct randomisation errors and (2) provide guidance on handling common randomisation errors when they are discovered that maintains the goals of the intention-to-treat principle. The potential pitfalls of attempting to correct randomisation errors are demonstrated and guidance on handling common errors is provided, using examples from our own experiences. We illustrate the problems that can occur when attempts are made to correct randomisation errors and argue that documenting, rather than correcting these errors, is most consistent with the intention-to-treat principle. When a participant is randomised using incorrect baseline information, we recommend accepting the randomisation but recording the correct baseline data. If ineligible participants are inadvertently randomised, we advocate keeping them in the trial and collecting all relevant data but seeking clinical input to determine their appropriate course of management, unless they can be excluded in an objective and unbiased manner. When multiple randomisations are performed in error for the same participant, we suggest retaining the initial randomisation and either disregarding the second randomisation if only one set of data will be obtained for the participant, or retaining the second randomisation otherwise. When participants are issued the incorrect treatment at the time of randomisation, we propose documenting the treatment received and seeking clinical input regarding the ongoing treatment of the participant. Randomisation errors are almost inevitable and should be reported in trial publications. The intention-to-treat principle is useful for guiding responses to randomisation errors when they are discovered. © The Author(s) 2015.

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

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

PubMed

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

2016-08-01

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

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.

Role of CCL3L1-CCR5 Genotypes in the Epidemic Spread of HIV-1 and Evaluation of Vaccine Efficacy

DTIC Science & Technology

2008-08-01

S) 12. DISTRIBUTION/AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13 . SUPPLEMENTARY NOTES 14. ABSTRACT Background...GRG-defined population groups to the overall epidemic varied significantly (0 to 13 %). Consistent with findings shown in Figure 2c, the highest AFs...Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC). Science 279: 389–393. 13 . Gonzalez E

Randomised Vitamin E Supplementation and Risk of Chronic Lung Disease in the Women’s Health Study

PubMed Central

Agler, Anne H.; Kurth, Tobias; Gaziano, J. Michael; Buring, Julie E.; Cassano, Patricia A.

2011-01-01

Background The oxidant/antioxidant balance in lung tissue is hypothesised to contribute to chronic obstructive pulmonary disease (COPD) risk. Observational studies consistently report higher antioxidant status associated with lower COPD risk, but few randomised studies have been reported. Methods A post-hoc analysis of 38,597 women without chronic lung disease at baseline was conducted in the Women’s Health Study (WHS) to test the effect of vitamin E on risk of incident chronic lung disease. The WHS was a randomised, double-blind, placebo-controlled, factorial trial of vitamin E (600 IU every other day) and aspirin (100 mg every other day) in female health professionals aged ≥45. Using Cox proportional hazards models, the effect of randomised vitamin E assignment on self-reported, physician-diagnosed chronic lung disease was evaluated. Results During 10 years of follow-up (376,710 person-years), 760 first occurrences of chronic lung disease were reported in the vitamin E arm compared to 846 in the placebo arm (Hazard Ratio [HR] 0.90; 95% confidence interval [CI] 0.81–0.99; p=0.029). This 10% reduction in the risk of incident chronic lung disease was not modified by cigarette smoking, age, randomised aspirin assignment, multivitamin use, or dietary vitamin E intake (minimum P for interaction = 0.19). Current cigarette smoking was a strong predictor of chronic lung disease risk (HR 4.17; 95% CI 3.70–4.70; versus never smokers). Conclusions In this large, randomised trial, assignment to 600 IU of vitamin E led to a 10% reduction in the risk of chronic lung disease in women. PMID:21257986

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

FIRST-line support for Assistance in Breathing in Children (FIRST-ABC): protocol for a multicentre randomised feasibility trial of non-invasive respiratory support in critically ill children.

PubMed

Ramnarayan, Padmanabhan; Lister, Paula; Dominguez, Troy; Habibi, Parviz; Edmonds, Naomi; Canter, Ruth; Mouncey, Paul; Peters, Mark J

2017-06-12

Over 18 000 children are admitted annually to UK paediatric intensive care units (PICUs), of whom nearly 75% receive respiratory support (invasive and/or non-invasive). Continuous positive airway pressure (CPAP) has traditionally been used to provide first-line non-invasive respiratory support (NRS) in PICUs; however, high-flow nasal cannula therapy (HFNC), a novel mode of NRS, has recently gained popularity despite the lack of high-quality trial evidence to support its effectiveness. This feasibility study aims to inform the design and conduct of a future definitive randomised clinical trial (RCT) comparing the two modes of respiratory support. We will conduct a three-centre randomised feasibility study over 12 months. Patients admitted to participating PICUs who satisfy eligibility criteria will be recruited to either group A (primary respiratory failure) or group B (postextubation). Consent will be obtained from parents/guardians prior to randomisation in 'planned' group B, and deferred in emergency situations (group A and 'rescue' group B). Participants will be randomised (1:1) to either CPAP or HFNC using sealed, opaque envelopes, from a computer-generated randomisation sequence with variable block sizes. The study protocol specifies algorithms for the initiation, maintenance and weaning of HFNC and CPAP. The primary outcomes are related to feasibility, including the number of eligible patients in each group, feasibility of randomising >50% of eligible patients and measures of adherence to the treatment protocols. Data will also be collected on patient outcomes (eg, mortality and length of PICU stay) to inform the selection of an appropriate outcome measure in a future RCT. We aim to recruit 120 patients to the study. Ethical approval was granted by the National Research Ethics Service Committee North East-Tyne&Wear South (15/NE/0296). Study findings will be disseminated through peer-reviewed journals, national and international conferences. NCT02612415; 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.

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

PubMed Central

2010-01-01

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

FIRST-line support for Assistance in Breathing in Children (FIRST-ABC): protocol for a multicentre randomised feasibility trial of non-invasive respiratory support in critically ill children

PubMed Central

Ramnarayan, Padmanabhan; Lister, Paula; Dominguez, Troy; Habibi, Parviz; Edmonds, Naomi; Canter, Ruth; Mouncey, Paul; Peters, Mark J

2017-01-01

Introduction Over 18 000 children are admitted annually to UK paediatric intensive care units (PICUs), of whom nearly 75% receive respiratory support (invasive and/or non-invasive). Continuous positive airway pressure (CPAP) has traditionally been used to provide first-line non-invasive respiratory support (NRS) in PICUs; however, high-flow nasal cannula therapy (HFNC), a novel mode of NRS, has recently gained popularity despite the lack of high-quality trial evidence to support its effectiveness. This feasibility study aims to inform the design and conduct of a future definitive randomised clinical trial (RCT) comparing the two modes of respiratory support. Methods and analysis We will conduct a three-centre randomised feasibility study over 12 months. Patients admitted to participating PICUs who satisfy eligibility criteria will be recruited to either group A (primary respiratory failure) or group B (postextubation). Consent will be obtained from parents/guardians prior to randomisation in ‘planned’ group B, and deferred in emergency situations (group A and ‘rescue’ group B). Participants will be randomised (1:1) to either CPAP or HFNC using sealed, opaque envelopes, from a computer-generated randomisation sequence with variable block sizes. The study protocol specifies algorithms for the initiation, maintenance and weaning of HFNC and CPAP. The primary outcomes are related to feasibility, including the number of eligible patients in each group, feasibility of randomising >50% of eligible patients and measures of adherence to the treatment protocols. Data will also be collected on patient outcomes (eg, mortality and length of PICU stay) to inform the selection of an appropriate outcome measure in a future RCT. We aim to recruit 120 patients to the study. Ethics and dissemination Ethical approval was granted by the National Research Ethics Service Committee North East—Tyne&Wear South (15/NE/0296). Study findings will be disseminated through peer-reviewed journals, national and international conferences. Trials registration number NCT02612415; pre-results. PMID:28606907

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.

When and how should multiple imputation be used for handling missing data in randomised clinical trials - a practical guide with flowcharts.

PubMed

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

2017-12-06

Missing data may seriously compromise inferences from randomised clinical trials, especially if missing data are not handled appropriately. The potential bias due to missing data depends on the mechanism causing the data to be missing, and the analytical methods applied to amend the missingness. Therefore, the analysis of trial data with missing values requires careful planning and attention. The authors had several meetings and discussions considering optimal ways of handling missing data to minimise the bias potential. We also searched PubMed (key words: missing data; randomi*; statistical analysis) and reference lists of known studies for papers (theoretical papers; empirical studies; simulation studies; etc.) on how to deal with missing data when analysing randomised clinical trials. Handling missing data is an important, yet difficult and complex task when analysing results of randomised clinical trials. We consider how to optimise the handling of missing data during the planning stage of a randomised clinical trial and recommend analytical approaches which may prevent bias caused by unavoidable missing data. We consider the strengths and limitations of using of best-worst and worst-best sensitivity analyses, multiple imputation, and full information maximum likelihood. We also present practical flowcharts on how to deal with missing data and an overview of the steps that always need to be considered during the analysis stage of a trial. We present a practical guide and flowcharts describing when and how multiple imputation should be used to handle missing data in randomised clinical.

MiDas: Automatic Extraction of a Common Domain of Discourse in Sleep Medicine for Multi-center Data Integration

PubMed Central

Sahoo, Satya S.; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S.; Zhang, Guo-Qiang

2011-01-01

Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI’s Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry. PMID:22195180

MiDas: automatic extraction of a common domain of discourse in sleep medicine for multi-center data integration.

PubMed

Sahoo, Satya S; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S; Zhang, Guo-Qiang

2011-01-01

Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI's Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry.

Has time come for a re-assessment of spa therapy? The NAIADE survey in Italy

NASA Astrophysics Data System (ADS)

Coccheri, S.; Gasbarrini, G.; Valenti, M.; Nappi, G.; di Orio, F.

2008-01-01

Goal of this study was to investigate whether appropriately applied spa therapy in several indications could be associated with a subsequent fall in the need for costly health services and missed working days due to sick-leave. The Naiade project was a multicenter observational, longitudinal, questionnaire-based study comparing an “entry” inquiry addressed to patients before an entry thermal cycle, and a “return” inquiry after 1 year. Routine statistical methods were used for comparisons. The study was carried out in 297 of the 340 certified Italian spa centers. Inquiries were managed by the spa doctor(s), with the collaboration of family doctors, and when necessary, hospitals, other health services, labour offices and employers. After exclusion of regular customers and of patients with acute disease phases or severe health conditions, 39,943 patients divided into eight diseases subgroups (rheumatic, respiratory, dermatologic, gynaecologic, otorhynologic, urinary, vascular and gastroenteric) underwent entry inquiry and appropriate spa treatment. Patients who returned for treatment after 1 year (“index year”) were 23,680 (59.2%) and received return inquiry. Outcomes considered were: frequency and duration of hospitalisation periods; missed working days; regular use of disease-specific drugs; and resort to “non-spa” rehabilitation therapies. The data collected at return inquiry were compared with those of entry inquiry. All the considered outcomes appeared to be significantly reduced in the index year in seven of the eight disease subgroups in comparison with the previous year. In conclusion, disease-appropriate spa treatments were followed by a reduction in the need of subsequent health interventions in most disease subgroups. The health promoting value of spa treatments should therefore undergo more rigorous assessment with randomised controlled studies.

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…

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.

Adjuvant chemotherapy in older women (ACTION) study – what did we learn from the pilot phase?

PubMed Central

Leonard, R; Ballinger, R; Cameron, D; Ellis, P; Fallowfield, L; Gosney, M; Johnson, L; Kilburn, L S; Makris, A; Mansi, J; Reed, M; Ring, A; Robinson, A; Simmonds, P; Thomas, G; Bliss, J M

2011-01-01

Background: The ACTION trial was initiated to provide evidence from a randomised trial on the effects of chemotherapy in women aged over 70 years where evidence for risk and benefit are lacking. Methods: This was a randomised, phase III clinical trial for high risk, oestrogen receptor (ER) negative/ER weakly positive early breast cancer. The trial planned to recruit 1000 women aged 70 years and older, randomised to receive 4 cycles of anthracycline chemotherapy or observation. The primary endpoint was relapse-free interval. The trial included a pilot phase to assess the acceptability and feasibility of recruitment. Results: The trial opened at 43 UK centres. Information on number of patients approached was available from 38 centres. Of the 43 eligible patients that were approached, 39 were not randomised due to patients declining entry. After 10 months only 4 patients had been randomised and after discussion with the research funder, the trial was closed and funding terminated. Conclusion: Despite widespread support at several public meetings, input from patient groups including representation on the Trial Management Group, the trial failed to recruit due to the inability to convince patients to accept randomisation. It would therefore seem that randomising the patients to receive chemotherapy vs observation is not a viable design in the current era for this patient population. PMID:21989185

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.

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

PubMed

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

2015-07-01

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

Premature Discontinuation of Prospective Clinical Studies Approved by a Research Ethics Committee – A Comparison of Randomised and Non-Randomised Studies

PubMed Central

Oeller, Patrick; Kasenda, Benjamin; Briel, Matthias; von Elm, Erik

2016-01-01

Background Premature discontinuation of clinical studies affects about 25% of randomised controlled trials (RCTs) which raises concerns about waste of scarce resources for research. The risk of discontinuation of non-randomised prospective studies (NPSs) is yet unclear. Objectives To compare the proportion of discontinued studies between NPSs and RCTs that received ethical approval. Methods We systematically surveyed prospective longitudinal clinical studies that were approved by a single REC in Freiburg, Germany between 2000 and 2002. We collected study characteristics, identified subsequent publications, and surveyed investigators to elucidate whether a study was discontinued and, if so, why. Results Of 917 approved studies, 547 were prospective longitudinal studies (306 RCTs and 241 NPSs). NPSs were on average smaller than RCTs, more frequently single centre and pilot studies, and less frequently funded by industry. NPSs were less frequently discontinued than RCTs: 32/221 (14%) versus 78/288 (27%, p<0.001, missing data excluded). Poor recruitment was the most frequent reason for discontinuation in both NPSs (36%) and RCTs (37%). Conclusions Compared to RCTs, NPSs were at lower risk for discontinuation. Measures to reliably predict, sustain, and stimulate recruitment could prevent discontinuation of many RCTs but also of some NPSs. PMID:27792749

Multicenter neonatal databases: Trends in research uses.

PubMed

Creel, Liza M; Gregory, Sean; McNeal, Catherine J; Beeram, Madhava R; Krauss, David R

2017-01-13

In the US, approximately 12.7% of all live births are preterm, 8.2% of live births were low birth weight (LBW), and 1.5% are very low birth weight (VLBW). Although technological advances have improved mortality rates among preterm and LBW infants, improving overall rates of prematurity and LBW remains a national priority. Monitoring short- and long-term outcomes is critical for advancing medical treatment and minimizing morbidities associated with prematurity or LBW; however, studying these infants can be challenging. Several large, multi-center neonatal databases have been developed to improve research and quality improvement of treatments for and outcomes of premature and LBW infants. The purpose of this systematic review was to describe three multi-center neonatal databases. We conducted a literature search using PubMed and Google Scholar over the period 1990 to August 2014. Studies were included in our review if one of the databases was used as a primary source of data or comparison. Included studies were categorized by year of publication; study design employed, and research focus. A total of 343 studies published between 1991 and 2014 were included. Studies of premature and LBW infants using these databases have increased over time, and provide evidence for both neonatology and community-based pediatric practice. Research into treatment and outcomes of premature and LBW infants is expanding, partially due to the availability of large, multicenter databases. The consistency of clinical conditions and neonatal outcomes studied since 1990 demonstrates that there are dedicated research agendas and resources that allow for long-term, and potentially replicable, studies within this population.

Reliability of 3-Dimensional Measures of Single-Leg Cross Drop Landing Across 3 Different Institutions: Implications for Multicenter Biomechanical and Epidemiological Research on ACL Injury Prevention.

PubMed

DiCesare, Christopher A; Bates, Nathaniel A; Barber Foss, Kim D; Thomas, Staci M; Wordeman, Samuel C; Sugimoto, Dai; Roewer, Benjamin D; Medina McKeon, Jennifer M; Di Stasi, Stephanie; Noehren, Brian W; Ford, Kevin R; Kiefer, Adam W; Hewett, Timothy E; Myer, Gregory D

2015-12-01

Anterior cruciate ligament (ACL) injuries are physically and financially devastating but affect a relatively small percentage of the population. Prospective identification of risk factors for ACL injury necessitates a large sample size; therefore, study of this injury would benefit from a multicenter approach. To determine the reliability of kinematic and kinetic measures of a single-leg cross drop task across 3 institutions. Controlled laboratory study. Twenty-five female high school volleyball players participated in this study. Three-dimensional motion data of each participant performing the single-leg cross drop were collected at 3 institutions over a period of 4 weeks. Coefficients of multiple correlation were calculated to assess the reliability of kinematic and kinetic measures during the landing phase of the movement. Between-centers reliability for kinematic waveforms in the frontal and sagittal planes was good, but moderate in the transverse plane. Between-centers reliability for kinetic waveforms was good in the sagittal, frontal, and transverse planes. Based on these findings, the single-leg cross drop task has moderate to good reliability of kinematic and kinetic measures across institutions after implementation of a standardized testing protocol. Multicenter collaborations can increase study numbers and generalize results, which is beneficial for studies of relatively rare phenomena, such as ACL injury. An important step is to determine the reliability of risk assessments across institutions before a multicenter collaboration can be initiated.

Participation of a coordinating center pharmacy in a multicenter international study.

PubMed

Jeon, Jihyun Esther; Mighty, Janet; Lane, Karen; McBee, Nichol; Majkowski, Ryan; Mayo, Steven; Hanley, Daniel

2016-11-15

The activities of a coordinating center pharmacy (CCP) supporting a multicenter, international clinical trial are described. Serving in a research support role comparable to that of a commercial clinical trial supply company, a CCP within the Johns Hopkins Hospital Investigational Drug Service (JHH IDS) uses its management expertise and infrastructure to support multicenter trials, such as the recently completed Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage, Phase III (CLEAR III) trial. The role of the CCP staff in supporting the CLEAR III trial was overall investigational product (IP) management through coordination of IP-related operations to ensure high-quality care for study participants at study sites in the United States and abroad. For the CLEAR III trial, the CCP coordinated IP supply activities; provided education to site pharmacists; developed study-specific documents, including pharmacy manuals; communicated with trial stakeholders, including third-party IP distributors; monitored treatment assignments; and performed quality assurance monitoring to ensure compliance with institutional, state, federal, and international regulations regarding IP procurement and storage. Acting as a CCP for a multicenter international study poses a number of operational challenges while providing opportunities for the CCP to contribute to research of global importance and enrich the skill sets of its personnel. The development and implementation of the CCP at JHH IDS for the CLEAR III trial included several responsibilities, such as IP supply management, communication, and database, regulatory, and finance management. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

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

PubMed

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

2016-04-23

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

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

PubMed

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

2018-06-20

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

Multi-investigator collaboration in orthopaedic surgery research compared to other medical fields.

PubMed

Brophy, Robert H; Smith, Matthew V; Latterman, Christian; Jones, Morgan H; Reinke, Emily K; Flanigan, David C; Wright, Rick W; Wolf, Brian R

2012-10-01

An increasing emphasis has been placed across health care on evidence-based medicine with higher level studies, such as randomized trials and prospective cohort studies. Historically, clinical research in orthopaedic surgery has been dominated by studies with low patient numbers from a limited number of surgeons. The purpose of this study was to test our hypothesis that orthopaedics has fewer multi-center collaborative studies as compared to other medical disciplines. We chose three leading journals from general medicine, a leading journal from the surgical subspecialties of obstetrics and gynecology, ophthalmology and otolaryngology, and three leading journals from orthopaedic surgery based on highest impact factor. We compared the percentage of collaborative studies and the number of contributing institutions and authors in original research manuscripts published in 2009 between general medical, surgical subspecialty and orthopaedic surgery journals. A significantly higher percentage of manuscripts resulted from multicenter collaborative efforts in the general medical literature (p < 0.000001) and the other surgical subspecialty literature (p < 0.000001) compared to the orthopaedic surgery literature. Manuscripts published in the general medical journals came from more institutions (p < 0.0001) and had significantly more authors (p < 0.000001) than those published in the orthopaedic surgery journals. There is an opportunity to stimulate greater multicenter collaborative research, which correlates with increased patient numbers, a higher level of evidence and more generalizable findings, in the orthopaedic surgery community. These efforts can be supported through increased funding, surgeon participation, and appropriate expansion of authorship for multicenter studies in orthopaedic journals. Copyright © 2012 Orthopaedic Research Society.

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].

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.

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.

Supplemental parenteral nutrition in critically ill patients: a study protocol for a phase II randomised controlled trial.

PubMed

Ridley, Emma J; Davies, Andrew R; Parke, Rachael; Bailey, Michael; McArthur, Colin; Gillanders, Lyn; Cooper, David J; McGuinness, Shay

2015-12-24

Nutrition is one of the fundamentals of care provided to critically ill adults. The volume of enteral nutrition received, however, is often much less than prescribed due to multiple functional and process issues. To deliver the prescribed volume and correct the energy deficit associated with enteral nutrition alone, parenteral nutrition can be used in combination (termed "supplemental parenteral nutrition"), but benefits of this method have not been firmly established. A multi-centre, randomised, clinical trial is currently underway to determine if prescribed energy requirements can be provided to critically ill patients by using a supplemental parenteral nutrition strategy in the critically ill. This prospective, multi-centre, randomised, stratified, parallel-group, controlled, phase II trial aims to determine whether a supplemental parenteral nutrition strategy will reliably and safely increase energy intake when compared to usual care. The study will be conducted for 100 critically ill adults with at least one organ system failure and evidence of insufficient enteral intake from six intensive care units in Australia and New Zealand. Enrolled patients will be allocated to either a supplemental parenteral nutrition strategy for 7 days post randomisation or to usual care with enteral nutrition. The primary outcome will be the average energy amount delivered from nutrition therapy over the first 7 days of the study period. Secondary outcomes include protein delivery for 7 days post randomisation; total energy and protein delivery, antibiotic use and organ failure rates (up to 28 days); duration of ventilation, length of intensive care unit and hospital stay. At both intensive care unit and hospital discharge strength and health-related quality of life assessments will be undertaken. Study participants will be followed up for health-related quality of life, resource utilisation and survival at 90 and 180 days post randomisation (unless death occurs first). This trial aims to determine if provision of a supplemental parenteral nutrition strategy to critically ill adults will increase energy intake compared to usual care in Australia and New Zealand. Trial outcomes will guide development of a subsequent larger randomised controlled trial. NCT01847534 (First registered 5 February 2013, last updated 14 October 2015).

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.

Physical Activity and School Performance: Evidence from a Danish Randomised School-Intervention Study

ERIC Educational Resources Information Center

Quinto Romani, A.; Klausen, T. B.

2017-01-01

It has been claimed that physical activity has a positive effect on not only health but also on school performance. Using data from a randomised school-intervention study, this paper investigates whether different interventions promoting physical activity affect school performance in primary school children. The results indicate that on average,…

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…

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.

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…

Choice of Moisturiser for Eczema Treatment (COMET): feasibility study of a randomised controlled parallel group trial in children recruited from primary care.

PubMed

Ridd, Matthew J; Garfield, Kirsty; Gaunt, Daisy M; Hollinghurst, Sandra; Redmond, Niamh M; Powell, Kingsley; Wilson, Victoria; Guy, Richard H; Ball, Nicola; Shaw, Lindsay; Purdy, Sarah; Metcalfe, Chris

2016-11-16

To determine the feasibility of a randomised controlled trial of 'leave on' emollients for children with eczema. Single-centre, pragmatic, 4-arm, observer-blinded, parallel, randomised feasibility trial. General practices in the UK. Children with eczema aged 1 month to <5 years. Primary outcome-proportion of parents who reported use of the allocated study emollient every day for the duration of follow-up (12 weeks). Other feasibility outcomes-participant recruitment and retention, data collection and completeness and blinding of observers to allocation. Aveeno lotion, Diprobase cream, Doublebase gel, Hydromol ointment. 197 children were recruited-107 by self-referral (mainly via practice mail-outs) and 90 by inconsultation (clinician consenting and randomising) pathways. Participants recruited inconsultation were younger, had more severe Patient-Oriented Eczema Measure scores and were more likely to withdraw than self-referrals. Parents of 20 (10%) of all the randomised participants reported using the allocated emollient daily for 84 days. The use of other non-study emollients was common. Completeness of data collected by parent-held daily diaries and at monthly study visits was good. Daily diaries were liked (81%) but mainly completed on paper rather than via electronic ('app') form. Major costs drivers were general practitioner consultations and eczema-related prescriptions. Observer unblinding was infrequent, and occurred at the baseline or first follow-up visit through accidental disclosure. It is feasible in a primary care setting to recruit and randomise young children with eczema to emollients, follow them up and collect relevant trial data, while keeping observers blinded to their allocation. However, reported use of emollients (study and others) has design implications for future trials. ISRCTN21828118/EudraCT2013-003001-26. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Effectiveness of recruitment to a smartphone-delivered nutrition intervention in New Zealand: analysis of a randomised controlled trial

PubMed Central

Volkova, Ekaterina; Michie, Jo; Corrigan, Callie; Sundborn, Gerhard; Eyles, Helen; Jiang, Yannan; Mhurchu, Cliona Ni

2017-01-01

Objectives Delivery of interventions via smartphone is a relatively new initiative in public health, and limited evidence exists regarding optimal strategies for recruitment. We describe the effectiveness of approaches used to recruit participants to a smartphone-enabled nutrition intervention trial. Methods Internet and social media advertising, mainstream media advertising and research team networks were used to recruit New Zealand adults to a fully automated smartphone-delivered nutrition labelling trial (no face-to-face visits were required). Recruitment of Māori and Pacific participants was a key focus and ethically relevant recruitment materials and approaches were used where possible. The effectiveness of recruitment strategies was evaluated using Google Analytics, monitoring of study website registrations and randomisations, and self-reported participant data. The cost of the various strategies and associations with participant demographics were assessed. Results Over a period of 13 months, there were 2448 registrations on the study website, and 1357 eligible individuals were randomised into the study (55%). Facebook campaigns were the most successful recruitment strategy overall (43% of all randomised participants) and for all ethnic groups (Māori 44%, Pacific 44% and other 43%). Significant associations were observed between recruitment strategy and age (p<0.001), household size (p<0.001), ethnicity (p<0.001), gender (p=0.005) and interest in healthy eating (p=0.022). Facebook campaigns resulted in the highest absolute numbers of study registrations and randomisations (966 and 584, respectively). Network strategies and Facebook campaigns cost least per randomised participant (NZ$4 and NZ$5, respectively), whereas radio advertising costs most (NZ$179 per participant). Conclusion Internet and social media advertising were the most effective and least costly approaches to recruiting participants to a smartphone-delivered trial. These approaches also reached diverse ethnic groups. However, more culturally appropriate recruitment strategies are likely to be necessary in studies where large numbers of participants from specific ethnic groups are sought. Trial registration ACTRN12614000644662; Post-results. PMID:28674144

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.

Choice of Moisturiser for Eczema Treatment (COMET): feasibility study of a randomised controlled parallel group trial in children recruited from primary care

PubMed Central

Ridd, Matthew J; Garfield, Kirsty; Gaunt, Daisy M; Redmond, Niamh M; Powell, Kingsley; Wilson, Victoria; Guy, Richard H; Ball, Nicola; Shaw, Lindsay; Purdy, Sarah; Metcalfe, Chris

2016-01-01

Objectives To determine the feasibility of a randomised controlled trial of ‘leave on’ emollients for children with eczema. Design Single-centre, pragmatic, 4-arm, observer-blinded, parallel, randomised feasibility trial. Setting General practices in the UK. Participants Children with eczema aged 1 month to <5 years. Outcome measures Primary outcome—proportion of parents who reported use of the allocated study emollient every day for the duration of follow-up (12 weeks). Other feasibility outcomes—participant recruitment and retention, data collection and completeness and blinding of observers to allocation. Interventions Aveeno lotion, Diprobase cream, Doublebase gel, Hydromol ointment. Results 197 children were recruited—107 by self-referral (mainly via practice mail-outs) and 90 by inconsultation (clinician consenting and randomising) pathways. Participants recruited inconsultation were younger, had more severe Patient-Oriented Eczema Measure scores and were more likely to withdraw than self-referrals. Parents of 20 (10%) of all the randomised participants reported using the allocated emollient daily for 84 days. The use of other non-study emollients was common. Completeness of data collected by parent-held daily diaries and at monthly study visits was good. Daily diaries were liked (81%) but mainly completed on paper rather than via electronic (‘app’) form. Major costs drivers were general practitioner consultations and eczema-related prescriptions. Observer unblinding was infrequent, and occurred at the baseline or first follow-up visit through accidental disclosure. Conclusions It is feasible in a primary care setting to recruit and randomise young children with eczema to emollients, follow them up and collect relevant trial data, while keeping observers blinded to their allocation. However, reported use of emollients (study and others) has design implications for future trials. Trial registration number ISRCTN21828118/EudraCT2013-003001-26. PMID:27852708

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

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.

Making randomised trials more efficient: report of the first meeting to discuss the Trial Forge platform.

PubMed

Treweek, Shaun; Altman, Doug G; Bower, Peter; Campbell, Marion; Chalmers, Iain; Cotton, Seonaidh; Craig, Peter; Crosby, David; Davidson, Peter; Devane, Declan; Duley, Lelia; Dunn, Janet; Elbourne, Diana; Farrell, Barbara; Gamble, Carrol; Gillies, Katie; Hood, Kerry; Lang, Trudie; Littleford, Roberta; Loudon, Kirsty; McDonald, Alison; McPherson, Gladys; Nelson, Annmarie; Norrie, John; Ramsay, Craig; Sandercock, Peter; Shanahan, Daniel R; Summerskill, William; Sydes, Matt; Williamson, Paula; Clarke, Mike

2015-06-05

Randomised trials are at the heart of evidence-based healthcare, but the methods and infrastructure for conducting these sometimes complex studies are largely evidence free. Trial Forge ( www.trialforge.org ) is an initiative that aims to increase the evidence base for trial decision making and, in doing so, to improve trial efficiency.This paper summarises a one-day workshop held in Edinburgh on 10 July 2014 to discuss Trial Forge and how to advance this initiative. We first outline the problem of inefficiency in randomised trials and go on to describe Trial Forge. We present participants' views on the processes in the life of a randomised trial that should be covered by Trial Forge.General support existed at the workshop for the Trial Forge approach to increase the evidence base for making randomised trial decisions and for improving trial efficiency. Agreed upon key processes included choosing the right research question; logistical planning for delivery, training of staff, recruitment, and retention; data management and dissemination; and close down. The process of linking to existing initiatives where possible was considered crucial. Trial Forge will not be a guideline or a checklist but a 'go to' website for research on randomised trials methods, with a linked programme of applied methodology research, coupled to an effective evidence-dissemination process. Moreover, it will support an informal network of interested trialists who meet virtually (online) and occasionally in person to build capacity and knowledge in the design and conduct of efficient randomised trials.Some of the resources invested in randomised trials are wasted because of limited evidence upon which to base many aspects of design, conduct, analysis, and reporting of clinical trials. Trial Forge will help to address this lack of evidence.

Consistency of clinical biomechanical measures between three different institutions: implications for multi-center biomechanical and epidemiological research.

PubMed

Myer, Gregory D; Wordeman, Samuel C; Sugimoto, Dai; Bates, Nathaniel A; Roewer, Benjamin D; Medina McKeon, Jennifer M; DiCesare, Christopher A; Di Stasi, Stephanie L; Barber Foss, Kim D; Thomas, Staci M; Hewett, Timothy E

2014-05-01

Multi-center collaborations provide a powerful alternative to overcome the inherent limitations to single-center investigations. Specifically, multi-center projects can support large-scale prospective, longitudinal studies that investigate relatively uncommon outcomes, such as anterior cruciate ligament injury. This project was conceived to assess within- and between-center reliability of an affordable, clinical nomogram utilizing two-dimensional video methods to screen for risk of knee injury. The authors hypothesized that the two-dimensional screening methods would provide good-to-excellent reliability within and between institutions for assessment of frontal and sagittal plane biomechanics. Nineteen female, high school athletes participated. Two-dimensional video kinematics of the lower extremity during a drop vertical jump task were collected on all 19 study participants at each of the three facilities. Within-center and between-center reliability were assessed with intra- and inter-class correlation coefficients. Within-center reliability of the clinical nomogram variables was consistently excellent, but between-center reliability was fair-to-good. Within-center intra-class correlation coefficient for all nomogram variables combined was 0.98, while combined between-center inter-class correlation coefficient was 0.63. Injury risk screening protocols were reliable within and repeatable between centers. These results demonstrate the feasibility of multi-site biomechanical studies and establish a framework for further dissemination of injury risk screening algorithms. Specifically, multi-center studies may allow for further validation and optimization of two-dimensional video screening tools. 2b.

Bupropion for the treatment of apathy in Huntington’s disease: A multicenter, randomised, double-blind, placebo-controlled, prospective crossover trial

PubMed Central

Gelderblom, Harald; Wüstenberg, Torsten; McLean, Tim; Mütze, Lisanne; Fischer, Wilhelm; Saft, Carsten; Hoffmann, Rainer; Süssmuth, Sigurd; Schlattmann, Peter; van Duijn, Erik; Landwehrmeyer, Bernhard; Priller, Josef

2017-01-01

Objective To evaluate the efficacy and safety of bupropion in the treatment of apathy in Huntington’s disease (HD). Methods In this phase 2b multicentre, double-blind, placebo-controlled crossover trial, individuals with HD and clinical signs of apathy according to the Structured Clinical Interview for Apathy—Dementia (SCIA-D), but not depression (n = 40) were randomized to receive either bupropion 150/300mg or placebo daily for 10 weeks. The primary outcome parameter was a significant change of the Apathy Evaluation Scale (AES) score after ten weeks of treatment as judged by an informant (AES-I) living in close proximity with the study participant. The secondary outcome parameters included changes of 1. AES scores determined by the patient (AES-S) or the clinical investigator (AES-C), 2. psychiatric symptoms (NPI, HADS-SIS, UHDRS-Behavior), 3. cognitive performance (SDMT, Stroop, VFT, MMSE), 4. motor symptoms (UHDRS-Motor), 5. activities of daily function (TFC, UHDRS-Function), and 6. caregiver distress (NPI-D). In addition, we investigated the effect of bupropion on brain structure as well as brain responses and functional connectivity during reward processing in a gambling task using magnetic resonance imaging (MRI). Results At baseline, there were no significant treatment group differences in the clinical primary and secondary outcome parameters. At endpoint, there was no statistically significant difference between treatment groups for all clinical primary and secondary outcome variables. Study participation, irrespective of the intervention, lessened symptoms of apathy according to the informant and the clinical investigator. Conclusion Bupropion does not alleviate apathy in HD. However, study participation/placebo effects were observed, which document the need for carefully controlled trials when investigating therapeutic interventions for the neuropsychiatric symptoms of HD. Trial registration ClinicalTrials.gov 01914965 PMID:28323838

A self-management approach using self-initiated action plans for symptoms with ongoing nurse support in patients with Chronic Obstructive Pulmonary Disease (COPD) and comorbidities: the COPE-III study protocol.

PubMed

Lenferink, Anke; Frith, Peter; van der Valk, Paul; Buckman, Julie; Sladek, Ruth; Cafarella, Paul; van der Palen, Job; Effing, Tanja

2013-09-01

Chronic Obstructive Pulmonary Disease (COPD) frequently coexists with other diseases. Whereas COPD action plans are currently part of usual care, they are less suitable and potentially unsafe for use in the presence of comorbidities. This study evaluates whether an innovative treatment approach directed towards COPD and frequently existing comorbidities can reduce COPD exacerbation days. We hypothesise that this approach, which combines self-initiated action plans and nurse support, will accelerate proper treatment actions and lead to better control of deteriorating symptoms. In this multicenter randomised controlled trial we aim to include 300 patients with COPD (GOLD II-IV), and with at least one comorbidity (cardiovascular disease, diabetes, anxiety and/or depression). Patients will be recruited from hospitals in the Netherlands (n = 150) and Australia (n = 150) and will be assigned to an intervention or control group. All patients will learn to complete daily symptom diaries for 12-months. Intervention group patients will participate in self-management training sessions to learn the use of individualised action plans for COPD and comorbidities, linked to the diary. The primary outcome is the number of COPD exacerbation days. Secondary outcomes include hospitalisations, quality of life, self-efficacy, adherence, patient's satisfaction and confidence, health care use and cost data. Intention-to-treat analyses (random effect negative binomial regression and random effect mixed models) and cost-effectiveness analyses will be performed. Prudence should be employed before extrapolating the use of COPD specific action plans in patients with comorbidities. This study evaluates the efficacy of tailored action plans for both COPD and common comorbidities. Copyright © 2013 Elsevier Inc. All rights reserved.

Treatment of severe fear of childbirth with haptotherapy: design of a multicenter randomized controlled trial.

PubMed

Klabbers, Gert A; Wijma, Klaas; Paarlberg, K Marieke; Emons, Wilco Hm; Vingerhoets, Ad Jjm

2014-10-08

About six percent of pregnant women suffer from severe fear of childbirth. These women are at increased risk of obstetric labour and delivery interventions and pre- and postpartum complications, e.g., preterm delivery, emergency caesarean section, caesarean section at maternal request, severe postpartum fear of childbirth and trauma anxiety. During the last decade, there is increasing clinical evidence suggesting that haptotherapy might be an effective intervention to reduce fear of childbirth in pregnant women. The present study has been designed to evaluate the effects of such intervention. Included are singleton pregnant women with severe fear of childbirth, age ≥ 18 year, randomised into three arms: (1) treatment with haptotherapy, (2) internet psycho-education or (3) care as usual. The main study outcome is fear of childbirth. Measurements are taken at baseline in gestation week 20-24, directly after the intervention is completed in gestation week 36, six weeks postpartum and six months postpartum. Secondary study outcomes are distress, general anxiety, depression, somatization, social support, mother-child bonding, pregnancy and delivery complications, traumatic anxiety symptoms, duration of delivery, birth weight, and care satisfaction. The treatment, a standard haptotherapeutical treatment for pregnant women with severe fear of childbirth, implies teaching a combination of skills in eight one hour sessions. The internet group follows an eight-week internet course containing information about pregnancy and childbirth comparable to childbirth classes. The control group has care as usual according to the standards of the Royal Dutch Organisation of Midwives and the Dutch Organization of Obstetrics and Gynaecology. This trial was entered in the Dutch Trial Register and registered under number NTR3339 on March 4th, 2012.

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

PubMed

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

2016-05-01

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

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.

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.

Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis.

PubMed

White, Jon; Sofat, Reecha; Hemani, Gibran; Shah, Tina; Engmann, Jorgen; Dale, Caroline; Shah, Sonia; Kruger, Felix A; Giambartolomei, Claudia; Swerdlow, Daniel I; Palmer, Tom; McLachlan, Stela; Langenberg, Claudia; Zabaneh, Delilah; Lovering, Ruth; Cavadino, Alana; Jefferis, Barbara; Finan, Chris; Wong, Andrew; Amuzu, Antoinette; Ong, Ken; Gaunt, Tom R; Warren, Helen; Davies, Teri-Louise; Drenos, Fotios; Cooper, Jackie; Ebrahim, Shah; Lawlor, Debbie A; Talmud, Philippa J; Humphries, Steve E; Power, Christine; Hypponen, Elina; Richards, Marcus; Hardy, Rebecca; Kuh, Diana; Wareham, Nicholas; Ben-Shlomo, Yoav; Day, Ian N; Whincup, Peter; Morris, Richard; Strachan, Mark W J; Price, Jacqueline; Kumari, Meena; Kivimaki, Mika; Plagnol, Vincent; Whittaker, John C; Smith, George Davey; Dudbridge, Frank; Casas, Juan P; Holmes, Michael V; Hingorani, Aroon D

2016-04-01

Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis. We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease. We then used a conventional Mendelian randomisation approach to investigate the causal relevance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs). To account for potential pleiotropic associations of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelian randomisation analysis, in which the genetic associations of SNPs with systolic and diastolic blood pressure, HDL cholesterol, and triglycerides were included as covariates, and an Egger Mendelian randomisation (MR-Egger) analysis to estimate a causal effect accounting for unmeasured pleiotropy. In the meta-analysis of 17 prospective observational studies (166 486 individuals; 9784 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (OR) for coronary heart disease of 1·07 (95% CI 1·04-1·10). The corresponding OR estimates from the conventional, multivariable adjusted, and Egger Mendelian randomisation analysis (58 studies; 198 598 individuals; 65 877 events) were 1·18 (95% CI 1·08-1·29), 1·10 (1·00-1·22), and 1·05 (0·92-1·20), respectively, per 1 SD increment in plasma urate. Conventional and multivariate Mendelian randomisation analysis implicates a causal role for urate in the development of coronary heart disease, but these estimates might be inflated by hidden pleiotropy. Egger Mendelian randomisation analysis, which accounts for pleiotropy but has less statistical power, suggests there might be no causal effect. These results might help investigators to determine the priority of trials of urate lowering for the prevention of coronary heart disease compared with other potential interventions. UK National Institute for Health Research, British Heart Foundation, and UK Medical Research Council. Copyright © 2016 White et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis

PubMed Central

White, Jon; Sofat, Reecha; Hemani, Gibran; Shah, Tina; Engmann, Jorgen; Dale, Caroline; Shah, Sonia; Kruger, Felix A; Giambartolomei, Claudia; Swerdlow, Daniel I; Palmer, Tom; McLachlan, Stela; Langenberg, Claudia; Zabaneh, Delilah; Lovering, Ruth; Cavadino, Alana; Jefferis, Barbara; Finan, Chris; Wong, Andrew; Amuzu, Antoinette; Ong, Ken; Gaunt, Tom R; Warren, Helen; Davies, Teri-Louise; Drenos, Fotios; Cooper, Jackie; Ebrahim, Shah; Lawlor, Debbie A; Talmud, Philippa J; Humphries, Steve E; Power, Christine; Hypponen, Elina; Richards, Marcus; Hardy, Rebecca; Kuh, Diana; Wareham, Nicholas; Ben-Shlomo, Yoav; Day, Ian N; Whincup, Peter; Morris, Richard; Strachan, Mark W J; Price, Jacqueline; Kumari, Meena; Kivimaki, Mika; Plagnol, Vincent; Whittaker, John C; Smith, George Davey; Dudbridge, Frank; Casas, Juan P; Holmes, Michael V; Hingorani, Aroon D

2016-01-01

Summary Background Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis. Methods We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease. We then used a conventional Mendelian randomisation approach to investigate the causal relevance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs). To account for potential pleiotropic associations of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelian randomisation analysis, in which the genetic associations of SNPs with systolic and diastolic blood pressure, HDL cholesterol, and triglycerides were included as covariates, and an Egger Mendelian randomisation (MR-Egger) analysis to estimate a causal effect accounting for unmeasured pleiotropy. Findings In the meta-analysis of 17 prospective observational studies (166 486 individuals; 9784 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (OR) for coronary heart disease of 1·07 (95% CI 1·04–1·10). The corresponding OR estimates from the conventional, multivariable adjusted, and Egger Mendelian randomisation analysis (58 studies; 198 598 individuals; 65 877 events) were 1·18 (95% CI 1·08–1·29), 1·10 (1·00–1·22), and 1·05 (0·92–1·20), respectively, per 1 SD increment in plasma urate. Interpretation Conventional and multivariate Mendelian randomisation analysis implicates a causal role for urate in the development of coronary heart disease, but these estimates might be inflated by hidden pleiotropy. Egger Mendelian randomisation analysis, which accounts for pleiotropy but has less statistical power, suggests there might be no causal effect. These results might help investigators to determine the priority of trials of urate lowering for the prevention of coronary heart disease compared with other potential interventions. Funding UK National Institute for Health Research, British Heart Foundation, and UK Medical Research Council. PMID:26781229

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

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…

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.

Interventions for waterpipe tobacco smoking prevention and cessation: a systematic review

PubMed Central

Jawad, Mohammed; Jawad, Sena; Waziry, Reem K.; Ballout, Rami A.; Akl, Elie A.

2016-01-01

Waterpipe tobacco smoking is growing in popularity despite adverse health effects among users. We systematically reviewed the literature, searching MEDLINE, EMBASE and Web of Science, for interventions targeting prevention and cessation of waterpipe tobacco smoking. We assessed the evidence quality using the Cochrane (randomised studies), GRADE (non-randomised studies) and CASP (qualitative studies) frameworks. Data were synthesised narratively due to heterogeneity. We included four individual-level, five group-level, and six legislative interventions. Of five randomised controlled studies, two showed significantly higher quit rates in intervention groups (bupropion/behavioural support versus placebo in Pakistan; 6 month abstinence relative risk (RR): 2.3, 95% CI 1.4–3.8); group behavioural support versus no intervention in Egypt, 12 month abstinence RR 3.3, 95% CI 1.4–8.9). Non-randomised studies showed mixed results for cessation, behavioural, and knowledge outcomes. One high quality modelling study from Lebanon calculated that a 10% increase in waterpipe tobacco taxation would reduce waterpipe tobacco demand by 14.5% (price elasticity of demand −1.45). In conclusion, there is a lack of evidence of effectiveness for most waterpipe interventions. While few show promising results, higher quality interventions are needed. Meanwhile, tobacco policies should place waterpipe on par with cigarettes. PMID:27167891

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.

Multicenter validation of the VITEK MS v2.0 MALDI-TOF mass spectrometry system for the identification of fastidious gram-negative bacteria.

PubMed

Branda, John A; Rychert, Jenna; Burnham, Carey-Ann D; Bythrow, Maureen; Garner, Omai B; Ginocchio, Christine C; Jennemann, Rebecca; Lewinski, Michael A; Manji, Ryhana; Mochon, A Brian; Procop, Gary W; Richter, Sandra S; Sercia, Linda F; Westblade, Lars F; Ferraro, Mary Jane

2014-02-01

The VITEK MS v2.0 MALDI-TOF mass spectrometry system's performance in identifying fastidious gram-negative bacteria was evaluated in a multicenter study. Compared with the reference method (DNA sequencing), the VITEK MS system provided an accurate, species-level identification for 96% of 226 isolates; an additional 1% were accurately identified to the genus level. © 2013.

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…

High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European Neuroblastoma Study Group.

PubMed

Pritchard, Jon; Cotterill, Simon J; Germond, Shirley M; Imeson, John; de Kraker, Jan; Jones, David R

2005-04-01

High dose myeloablative chemotherapy ("megatherapy"), with haematopoietic stem cell support, is now widely used to consolidate response to induction chemotherapy in patients with advanced neuroblastoma. In this study (European Neuroblastoma Study Group, ENSG1), the value of melphalan myeloablative "megatherapy" was evaluated in a randomised, multi-centre trial. Between 1982 and 1985, 167 children with stages IV and III neuroblastoma (123 stage IV > 1 year old at diagnosis and 44 stage III and stage IV from 6 to 12 months old at diagnosis) were treated with oncovin, cisplatin, epipodophyllotoxin, and cyclophosphamide (OPEC) induction chemotherapy every 3 weeks. After surgical excision of primary tumour, the 90 patients (69% of the total) who achieved complete response (CR) or good partial response (GPR) were eligible for randomisation either to high dose melphalan (180 mg per square meter) with autologous bone marrow support or to no further treatment. Sixty-five (72%) of eligible children were actually randomised and 21 of these patients were surviving at time of this analysis, with median follow-up from randomisation of 14.3 years. Five year event-free survival (EFS) was 38% (95% confidence interval (CI) 21-54%) in the melphalan-treated group and 27% (95% CI 12-42%) in the "no-melphalan" group. This difference was not statistically significant (P = 0.08, log rank test) but for the 48 randomised stage IV patients aged >1 year at diagnosis outcome was significantly better in the melphalan-treated group-5 year EFS 33% versus 17% (P = 0.01, log rank test). In this trial, high dose melphalan improved the length of EFS and overall survival of children with stage IV neuroblastoma >1 year of age who achieved CR or GPR after OPEC induction therapy and surgery. Multi-agent myeloablative regimens are now widely used as consolidation therapy for children with stage IV disease and in those with other disease stages when the MYCN gene copy number in tumour cells is amplified. Because they are more toxic, complex, and costly these combination megatherapy regimens should be compared with single agent melphalan in randomised clinical trials.

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.

Management of haemothoraces in blunt thoracic trauma: study protocol for a randomised controlled trial

PubMed Central

Carver, David A; Bressan, Alexsander K; Schieman, Colin; Grondin, Sean C; Kirkpatrick, Andrew W; Lall, Rohan; McBeth, Paul B; Dunham, Michael B; Ball, Chad G

2018-01-01

Introduction Haemothorax following blunt thoracic trauma is a common source of morbidity and mortality. The optimal management of moderate to large haemothoraces has yet to be defined. Observational data have suggested that expectant management may be an appropriate strategy in stable patients. This study aims to compare the outcomes of patients with haemothoraces following blunt thoracic trauma treated with either chest drainage or expectant management. Methods and analysis This is a single-centre, dual-arm randomised controlled trial. Patients presenting with a moderate to large sized haemothorax following blunt thoracic trauma will be assessed for eligibility. Eligible patients will then undergo an informed consent process followed by randomisation to either (1) chest drainage (tube thoracostomy) or (2) expectant management. These groups will be compared for the rate of additional thoracic interventions, major thoracic complications, length of stay and mortality. Ethics and dissemination This study has been approved by the institution’s research ethics board and registered with ClinicalTrials.gov. All eligible participants will provide informed consent prior to randomisation. The results of this study may provide guidance in an area where there remains significant variation between clinicians. The results of this study will be published in peer-reviewed journals and presented at national and international conferences. Trial registration number NCT03050502. PMID:29502092

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…

Reliability of 3-Dimensional Measures of Single-Leg Drop Landing Across 3 Institutions: Implications for Multicenter Research for Secondary ACL-Injury Prevention.

PubMed

Myer, Gregory D; Bates, Nathaniel A; DiCesare, Christopher A; Barber Foss, Kim D; Thomas, Staci M; Wordeman, Samuel C; Sugimoto, Dai; Roewer, Benjamin D; Medina McKeon, Jennifer M; Di Stasi, Stephanie L; Noehren, Brian W; McNally, Michael; Ford, Kevin R; Kiefer, Adam W; Hewett, Timothy E

2015-05-01

Due to the limitations of single-center studies in achieving appropriate sampling with relatively rare disorders, multicenter collaborations have been proposed to achieve desired sampling levels. However, documented reliability of biomechanical data is necessary for multicenter injury-prevention studies and is currently unavailable. To measure the reliability of 3-dimensional (3D) biomechanical waveforms from kinetic and kinematic variables during a single-leg landing (SLL) performed at 3 separate testing facilities. Multicenter reliability study. 3 laboratories. 25 female junior varsity and varsity high school volleyball players who visited each facility over a 1-mo period. Subjects were instrumented with 43 reflective markers to record 3D motion as they performed SLLs. During the SLL the athlete balanced on 1 leg, dropped down off of a 31-cm-high box, and landed on the same leg. Kinematic and kinetic data from both legs were processed from 2 trials across the 3 laboratories. Coefficients of multiple correlations (CMC) were used to statistically compare each joint angle and moment waveform for the first 500 ms of landing. Average CMC for lower-extremity sagittal-plane motion was excellent between laboratories (hip .98, knee .95, ankle .99). Average CMC for lower-extremity frontal-plane motion was also excellent between laboratories (hip .98, knee .80, ankle .93). Kinetic waveforms were repeatable in each plane of rotation (3-center mean CMC ≥.71), while knee sagittal-plane moments were the most consistent measure across sites (3-center mean CMC ≥.94). CMC waveform comparisons were similar relative to the joint measured to previously published reports of between-sessions reliability of sagittal- and frontal-plane biomechanics performed at a single institution. Continued research is needed to further standardize technology and methods to help ensure that highly reliable results can be achieved with multicenter biomechanical screening models.

The Salford Lung Study protocol: a pragmatic, randomised phase III real-world effectiveness trial in chronic obstructive pulmonary disease.

PubMed

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

2015-09-04

New treatments need to be evaluated in real-world clinical practice to account for co-morbidities, adherence and polypharmacy. Patients with chronic obstructive pulmonary disease (COPD), ≥ 40 years old, with exacerbation in the previous 3 years are randomised 1:1 to once-daily fluticasone furoate 100 μg/vilanterol 25 μg in a novel dry-powder inhaler versus continuing their existing therapy. The primary endpoint is the mean annual rate of COPD exacerbations; an electronic medical record allows real-time collection and monitoring of endpoint and safety data. The Salford Lung Study is the world's first pragmatic randomised controlled trial of a pre-licensed medication in COPD. Clinicaltrials.gov identifier NCT01551758.

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.

A Multicenter Study of the Presentation, Treatment, and Outcomes of Cervical Dural Tears.

PubMed

O'Neill, Kevin R; Fehlings, Michael G; Mroz, Thomas E; Smith, Zachary A; Hsu, Wellington K; Kanter, Adam S; Steinmetz, Michael P; Arnold, Paul M; Mummaneni, Praveen V; Chou, Dean; Nassr, Ahmad; Qureshi, Sheeraz A; Cho, Samuel K; Baird, Evan O; Smith, Justin S; Shaffrey, Christopher; Tannoury, Chadi A; Tannoury, Tony; Gokaslan, Ziya L; Gum, Jeffrey L; Hart, Robert A; Isaacs, Robert E; Sasso, Rick C; Bumpass, David B; Bydon, Mohamad; Corriveau, Mark; De Giacomo, Anthony F; Derakhshan, Adeeb; Jobse, Bruce C; Lubelski, Daniel; Lee, Sungho; Massicotte, Eric M; Pace, Jonathan R; Smith, Gabriel A; Than, Khoi D; Riew, K Daniel

2017-04-01

Retrospective multicenter case series study. Because cervical dural tears are rare, most surgeons have limited experience with this complication. A multicenter study was performed to better understand the presentation, treatment, and outcomes following cervical dural tears. Multiple surgeons from 23 institutions retrospectively identified 21 rare complications that occurred between 2005 and 2011, including unintentional cervical dural tears. Demographic data and surgical history were obtained. Clinical outcomes following surgery were assessed, and any reoperations were recorded. Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA), Nurick classification (NuC), and Short-Form 36 (SF36) scores were recorded at baseline and final follow-up at certain centers. All data were collected, collated, and analyzed by a private research organization. There were 109 cases of cervical dural tears among 18 463 surgeries performed. In 101 cases (93%) there was no clinical sequelae following successful dural tear repair. There were statistical improvements ( P < .05) in mJOA and NuC scores, but not NDI or SF36 scores. No specific baseline or operative factors were found to be associated with the occurrence of dural tears. In most cases, no further postoperative treatments of the dural tear were required, while there were 13 patients (12%) that required subsequent treatment of cerebrospinal fluid drainage. Analysis of those requiring further treatments did not identify an optimum treatment strategy for cervical dural tears. In this multicenter study, we report our findings on the largest reported series (n = 109) of cervical dural tears. In a vast majority of cases, no subsequent interventions were required and no clinical sequelae were observed.

Gone fishing in a fluid trial.

PubMed

Hjortrup, Peter B; Haase, Nicolai; Wetterslev, Jørn; Perner, Anders

2016-03-01

To maximise the yield of existing data by assessing the effect on mortality of being born under the zodiac sign Pisces in a trial of intravenous (IV) fluids. A retrospective observational study, with no predefined hypothesis or statistical analysis plan, of 26 Scandinavian intensive care units between 2009 and 2011. Patients aged 18 years or older with severe sepsis and in need of fluid resuscitation, randomised in the Scandinavian Starch for Severe Sepsis/ Septic Shock (6S) trial. Ninety-day mortality. We included all 798 randomised patients in our study; 70 (9%) were born under the sign of Pisces. The primary outcome (death within 90 days after randomisation) occurred in 25 patients (35.7%) in the Pisces group, compared with 348 patients (48%) in the non-Pisces group (relative risk, 0.75; 95% CI, 0.54-1.03; one-sided P = 0.03). In a multicentre randomised clinical trial of IV fluids, being born under the sign of Pisces was associated with a decreased risk of death. Our study shows that with convenient use of statistics and an enticing explanatory hypothesis, it is possible to achieve significant findings in post-hoc analyses of data from large trials.

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

The effectiveness of disease management programmes in reducing hospital re-admission in older patients with heart failure: a systematic review and meta-analysis of published reports.

PubMed

Gonseth, Jonás; Guallar-Castillón, Pilar; Banegas, José R; Rodríguez-Artalejo, Fernando

2004-09-01

To systematically evaluate the published evidence regarding the effectiveness of disease management programmes (DMPs) reducing hospital re-admissions among elderly patients with heart failure (HF). Computerised search of MEDLINE (1966 to 31 August 2003) and EMBASE (1966 to 31 August 2003). The Cochrane Library was also searched, and reference lists of review articles on the topic, and of all relevant studies identified, were scanned. Search and selection of studies, data-extraction using standardised forms, and assessment of study quality was performed by two reviewers. The end-point was the proportion of persons who underwent hospital re-admission, and pooled relative risks (RR) were used to summarise the effectiveness of DMPs. The meta-analysis included 54 articles, comprising 27 randomised and 27 non-randomised controlled studies. Randomised studies consistently suggested that, in comparison with usual care, DMP reduced the frequency of re-admission for HF or cardiovascular disease by 30% (pooled RR 0.70; confidence interval (CI) 95% 0.62-0.79), all-cause re-admission by 12% (pooled RR 0.88, 95% CI: 0.79-0.97), and the combined event of re-admission or death by 18% (pooled RR 0.82, 95% CI: 0.72-0.94). The results displayed no substantial variation when only DMPs with home visits, out-patient visits to a clinic, or patient follow-up longer than 6 months were included. For DMPs with out-patient clinical visits, however, the reduction in re-admission for HF or cardiovascular disease, and for all causes, did not attain statistical significance. The magnitude of DMP benefits reported by non-randomised studies was more than double that reported by randomised studies. Practically all the non-randomised studies failed to control for confounding factors, such as severity, co-morbidity and drug therapy. DMPs are effective at reducing re-admissions among elderly patients with HF. Their effectiveness is close to that observed in clinical trials evaluating drugs for HF, such as angiotensin-converting enzyme inhibitors, beta-blockers or digoxin. However, since none of the DMP studies compared different interventions directly, we do not know the relative effectiveness of types of healthcare delivery within the DMP.

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…

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…

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

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.

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.

Communication skills in the training of psychiatrists: A systematic review of current approaches.

PubMed

Ditton-Phare, Philippa; Loughland, Carmel; Duvivier, Robbert; Kelly, Brian

2017-07-01

A range of communication skills training programmes have been developed targeting trainees in various medical specialties, predominantly in oncology but to a lesser extent in psychiatry. Effective communication is fundamental to the assessment and treatment of psychiatric conditions, but there has been less attention to this in clinical practice for psychiatrists in training. This review examines the outcomes of communication skills training interventions in psychiatric specialty training. The published English-language literature was examined using multiple online databases, grey literature and hand searches. The review was conducted and reported using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies examining the efficacy of communication skills training were included. Randomised controlled trials, pseudo-randomised studies and quasi-experimental studies, as well as observational analytical studies and qualitative studies that met criteria, were selected and critically appraised. No limits were applied for date of publication up until 16 July 2016. Total search results yielded 2574 records. Of these, 12 studies were identified and reviewed. Two were randomised controlled trials and the remaining 10 were one-group pretest/posttest designs or posttest-only designs, including self-report evaluations of communication skills training and objective evaluations of trainee skills. There were no studies with outcomes related to behaviour change or patient outcomes. Two randomised controlled trials reported an improvement in clinician empathy and psychotherapeutic interviewing skills due to specific training protocols focused on those areas. Non-randomised studies showed varying levels of skills gains and self-reported trainee satisfaction ratings with programmes, with the intervention being some form of communication skills training. The heterogeneity of communication skills training is a barrier to evaluating the efficacy of different communication skills training programmes. Further validation studies examining specific models and frameworks would support a stronger evidence base for communication skills training in psychiatry. It remains a challenge to develop research to investigate behaviour change over time in clinical practice or to measure patient outcomes due to the effects of communication skills training.

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.

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

PubMed Central

2014-01-01

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

Effectiveness of recruitment to a smartphone-delivered nutrition intervention in New Zealand: analysis of a randomised controlled trial.

PubMed

Volkova, Ekaterina; Michie, Jo; Corrigan, Callie; Sundborn, Gerhard; Eyles, Helen; Jiang, Yannan; Mhurchu, Cliona Ni

2017-07-02

Delivery of interventions via smartphone is a relatively new initiative in public health, and limited evidence exists regarding optimal strategies for recruitment. We describe the effectiveness of approaches used to recruit participants to a smartphone-enabled nutrition intervention trial. Internet and social media advertising, mainstream media advertising and research team networks were used to recruit New Zealand adults to a fully automated smartphone-delivered nutrition labelling trial (no face-to-face visits were required). Recruitment of Māori and Pacific participants was a key focus and ethically relevant recruitment materials and approaches were used where possible. The effectiveness of recruitment strategies was evaluated using Google Analytics, monitoring of study website registrations and randomisations, and self-reported participant data. The cost of the various strategies and associations with participant demographics were assessed. Over a period of 13 months, there were 2448 registrations on the study website, and 1357 eligible individuals were randomised into the study (55%). Facebook campaigns were the most successful recruitment strategy overall (43% of all randomised participants) and for all ethnic groups (Māori 44%, Pacific 44% and other 43%). Significant associations were observed between recruitment strategy and age (p<0.001), household size (p<0.001), ethnicity (p<0.001), gender (p=0.005) and interest in healthy eating (p=0.022). Facebook campaigns resulted in the highest absolute numbers of study registrations and randomisations (966 and 584, respectively). Network strategies and Facebook campaigns cost least per randomised participant (NZ$4 and NZ$5, respectively), whereas radio advertising costs most (NZ$179 per participant). Internet and social media advertising were the most effective and least costly approaches to recruiting participants to a smartphone-delivered trial. These approaches also reached diverse ethnic groups. However, more culturally appropriate recruitment strategies are likely to be necessary in studies where large numbers of participants from specific ethnic groups are sought. ACTRN12614000644662; Post-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.

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.

A randomised study of leadership interventions for healthcare managers.

PubMed

Lornudd, Caroline; Bergman, David; Sandahl, Christer; von Thiele Schwarz, Ulrica

2016-10-03

Purpose The purpose of this paper was to assess two different leader development interventions by comparing their effects on leadership behaviour and evaluating their combined impact after two years, from the viewpoints of both the participating managers and external raters. Design/methodology/approach The study was a longitudinal randomised controlled trial with a cross-over design. Health care managers ( n = 177) were first randomised to either of two 10-month interventions and a year later were switched to the other intervention. Leadership behaviour was rated at pre-test and 12 and 24 months by participating managers and their superiors, colleagues and subordinates using a 360-degree instrument. Analysis of variance and multilevel regression analysis was performed. Findings No difference in effect on leadership behaviour was found between the two interventions. The evaluation of the combined effect of the interventions on leadership behaviour showed inconsistent (i.e. both increased and decreased) ratings by the various rater sources. Practical implications This study provides some evidence that participation in leadership development programmes can improve managers' leadership behaviours, but the results also highlight the interpretive challenges connected with using a 360-degree instrument to evaluate such development. Originality/value The longitudinal randomised controlled design and the large sample comprising both managers and external raters make this study unusually rigorous in the field of leadership development evaluations.

A pragmatic approach to sonothrombolysis in acute ischaemic stroke: the Norwegian randomised controlled sonothrombolysis in acute stroke study (NOR-SASS).

PubMed

Nacu, Aliona; Kvistad, Christopher E; Logallo, Nicola; Naess, Halvor; Waje-Andreassen, Ulrike; Aamodt, Anne Hege; Solhoff, Ragnar; Lund, Christian; Tobro, Håkon; Rønning, Ole Morten; Salvesen, Rolf; Idicula, Titto T; Thomassen, Lars

2015-07-11

Ultrasound accelerates thrombolysis with tPA (sonothrombolysis). Ultrasound in the absence of tPA also accelerates clot break-up (sonolysis). Adding intravenous gaseous microbubbles may potentiate the effect of ultrasound in both sonothrombolysis and sonolysis. The Norwegian Sonothrombolysis in Acute Stroke Study aims in a pragmatic approach to assess the effect and safety of contrast enhanced ultrasound treatment in unselected acute ischaemic stroke patients. Acute ischaemic stroke patients ≥ 18 years, with or without visible arterial occlusion on computed tomography angiography (CTA) and treatable ≤ 4(½) hours after symptom onset, are included in NOR-SASS. NOR-SASS is superimposed on a separate trial randomising patients with acute ischemic stroke to either tenecteplase or alteplase (The Norwegian Tenecteplase Stroke Trial NOR-TEST). The NOR-SASS trial has two arms: 1) the thrombolysis-arms (NOR-SASS A and B) includes patients given intravenous thrombolysis (tenecteplase or alteplase), and 2) the no-thrombolysis-arm (NOR-SASS C) includes patients with contraindications to thrombolysis. First step randomisation of NOR-SASS A is embedded in NOR-TEST as a 1:1 randomisation to either tenecteplase or alteplase. Second step NOR-SASS randomisation is 1:1 to either contrast enhanced sonothrombolysis (CEST) or sham CEST. Randomisation in NOR-SASS B (routine alteplase group) is 1:1 to either CEST or sham CEST. Randomisation of NOR-SASS C is 1:1 to either contrast enhanced sonolysis (CES) or sham CES. Ultrasound is given for one hour using a 2-MHz pulsed-wave diagnostic ultrasound probe. Microbubble contrast (SonoVue®) is given as a continuous infusion for ~30 min. Recanalisation is assessed at 60 min after start of CEST/CES. Magnetic resonance imaging and angiography is performed after 24 h of stroke onset. Primary study endpoints are 1) major neurological improvement measured with NIHSS score at 24 h and 2) favourable functional outcome defined as mRS 0-1 at 90 days. NOR-SASS is the first randomised controlled trial designed to test the superiority of contrast enhanced ultrasound treatment given ≤ 4(½) hours after stroke onset in an unselected acute ischaemic stroke population eligible or not eligible for intravenous thrombolysis, with or without a defined arterial occlusion on CTA. If a positive effect and safety can be proven, contrast enhanced ultrasound treatment will be an option for all acute ischaemic stroke patients. EudraCT No 201200032341; www.clinicaltrials.gov NCT01949961.

Safety and efficacy of polymer-free biolimus-eluting stents in all-comer patients: the RUDI-FREE study.

PubMed

Sardella, Gennaro; Stefanini, Giulio G; Briguori, Carlo; Tamburino, Corrado; Fabbiocchi, Franco; Rotolo, Francesco; Tomai, Fabrizio; Paggi, Anita; Lombardi, Mario; Gioffrè, Gaetano; Sclafani, Rocco; Rolandi, Andrea; Sciahbasi, Alessandro; Scardaci, Francesco; Signore, Nicola; Calcagno, Simone; Mancone, Massimo; Chiarito, Mauro; Giordano, Arturo

2018-05-21

Polymer-free biolimus-eluting stents (PF-BES) have been shown superior to bare metal stents in high bleeding risk (HBR) patients treated with 1-month dual antiplatelet therapy (DAPT). However, limited evidence is available on PF-BES in non-HBR patients. We aim to evaluate the safety and efficacy of PF-BES in all-comer patients undergoing percutaneous coronary interventions (PCI). Patients with stable coronary artery disease or acute coronary syndromes (ACS) undergoing PCI with PF-BES in routine clinical practice were included in a multicenter, prospective registry. DAPT duration was left at the discretion of the operator. The primary endpoint was the composite of cardiovascular death, myocardial infarction (MI), and definite/probable stent thrombosis (ST) at 1 year. Overall, 1,104 consecutive patients treated with PF-BES were included at 16 Italian centers. Mean age was 68.7±11.2 years, 77.2% of patients were men, 30% had diabetes, 15.1% had chronic kidney disease, and 40.5% had ACS at baseline. Mean CRUSADE score was 24.1±13.1, and 83.7% of patients did not have high bleeding risk features. At 1-year, the primary endpoint occurred in 4.1% of patients, cardiovascular death in 2.4%, MI in 1.8%, and definite/probable ST in 1.1%. With respect to efficacy, target-lesion revascularization occurred in 1.2% of patients. This is the first study providing clinical evidence on the use of PF-BES in all-comer patients irrespective of HBR status. Our findings suggest that PF-BES has a favorable safety and efficacy profile in a real world clinical setting. Further investigation in randomised clinical trials against new-generation DES is warranted.

Sjögren SER: National registry of the Spanish Society of Rheumatology of patients with primary Sjögren syndrome: Objectives and methodology.

PubMed

Fernández Castro, Mónica; Andreu, Jose Luis; Sánchez-Piedra, Carlos; Martínez Taboada, Víctor; Olivé, Alejandro; Rosas, José; Sánchez-Alonso, Fernando

2016-01-01

To describe the objectives and methods of the Spanish Society of Rheumatology primary Sjögren syndrome (pSS) registry (SJOGREN-SER) METHODS: This is a multicenter descriptive transversal study of a cohort of pSS patients fulfilling European/American consensus criteria collected from Rheumatology clinics all over Spain. Patients were included by randomisation from an anonymised list provided by every department. Data were collected by reviewing clinical records and an interviewing the patients. Two hundred and ninety eight variables were investigated: epidemiological, clinical, serological characteristics, treatments and complications. Informed consent was obtained and local ethics committees approved the study. Variables were analysed by descriptive statistical methods, using means, medians, and rates, with their deviations and interquartile ranges (p25-p75). A total of 3 rheumatology departments participated in the registry. A total of 437 patients were included. And 95% of them were women, with a median age of 58. Median age at pSS 's diagnosis was 50 years. Dryness symptoms (95%) were the most frequent complaint and anti-Ro/SS-A were present in 94% of the cases. Only 27% of the patients fulfilled the new 2012 SICCA-ACR classification criteria. SJOGREN-SER has been designed in order to characterize a representative pSS Spanish cohort, in clinical daily practice, to analyze the magnitude and distribution of its manifestations, activity, accumulated damage and therapeutic management of the disease. This will allow broadening the knowledge of this disease and plan strategies of action in pSS. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Impact of peer review on reports of randomised trials published in open peer review journals: retrospective before and after study

PubMed Central

Collins, Gary S; Boutron, Isabelle; Yu, Ly-Mee; Cook, Jonathan; Shanyinde, Milensu; Wharton, Rose; Shamseer, Larissa; Altman, Douglas G

2014-01-01

Objective To investigate the effectiveness of open peer review as a mechanism to improve the reporting of randomised trials published in biomedical journals. Design Retrospective before and after study. Setting BioMed Central series medical journals. Sample 93 primary reports of randomised trials published in BMC-series medical journals in 2012. Main outcome measures Changes to the reporting of methodological aspects of randomised trials in manuscripts after peer review, based on the CONSORT checklist, corresponding peer reviewer reports, the type of changes requested, and the extent to which authors adhered to these requests. Results Of the 93 trial reports, 38% (n=35) did not describe the method of random sequence generation, 54% (n=50) concealment of allocation sequence, 50% (n=46) whether the study was blinded, 34% (n=32) the sample size calculation, 35% (n=33) specification of primary and secondary outcomes, 55% (n=51) results for the primary outcome, and 90% (n=84) details of the trial protocol. The number of changes between manuscript versions was relatively small; most involved adding new information or altering existing information. Most changes requested by peer reviewers had a positive impact on the reporting of the final manuscript—for example, adding or clarifying randomisation and blinding (n=27), sample size (n=15), primary and secondary outcomes (n=16), results for primary or secondary outcomes (n=14), and toning down conclusions to reflect the results (n=27). Some changes requested by peer reviewers, however, had a negative impact, such as adding additional unplanned analyses (n=15). Conclusion Peer reviewers fail to detect important deficiencies in reporting of the methods and results of randomised trials. The number of these changes requested by peer reviewers was relatively small. Although most had a positive impact, some were inappropriate and could have a negative impact on reporting in the final publication. PMID:24986891

Treatment of missing data in follow-up studies of randomised controlled trials: A systematic review of the literature.

PubMed

Sullivan, Thomas R; Yelland, Lisa N; Lee, Katherine J; Ryan, Philip; Salter, Amy B

2017-08-01

After completion of a randomised controlled trial, an extended follow-up period may be initiated to learn about longer term impacts of the intervention. Since extended follow-up studies often involve additional eligibility restrictions and consent processes for participation, and a longer duration of follow-up entails a greater risk of participant attrition, missing data can be a considerable threat in this setting. As a potential source of bias, it is critical that missing data are appropriately handled in the statistical analysis, yet little is known about the treatment of missing data in extended follow-up studies. The aims of this review were to summarise the extent of missing data in extended follow-up studies and the use of statistical approaches to address this potentially serious problem. We performed a systematic literature search in PubMed to identify extended follow-up studies published from January to June 2015. Studies were eligible for inclusion if the original randomised controlled trial results were also published and if the main objective of extended follow-up was to compare the original randomised groups. We recorded information on the extent of missing data and the approach used to treat missing data in the statistical analysis of the primary outcome of the extended follow-up study. Of the 81 studies included in the review, 36 (44%) reported additional eligibility restrictions and 24 (30%) consent processes for entry into extended follow-up. Data were collected at a median of 7 years after randomisation. Excluding 28 studies with a time to event primary outcome, 51/53 studies (96%) reported missing data on the primary outcome. The median percentage of randomised participants with complete data on the primary outcome was just 66% in these studies. The most common statistical approach to address missing data was complete case analysis (51% of studies), while likelihood-based analyses were also well represented (25%). Sensitivity analyses around the missing data mechanism were rarely performed (25% of studies), and when they were, they often involved unrealistic assumptions about the mechanism. Despite missing data being a serious problem in extended follow-up studies, statistical approaches to addressing missing data were often inadequate. We recommend researchers clearly specify all sources of missing data in follow-up studies and use statistical methods that are valid under a plausible assumption about the missing data mechanism. Sensitivity analyses should also be undertaken to assess the robustness of findings to assumptions about the missing data mechanism.

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.

Reasons for non-recruitment of eligible patients to a randomised controlled trial of secondary prevention after intracerebral haemorrhage: observational study.

PubMed

Maxwell, Amy E; MacLeod, Mary Joan; Joyson, Anu; Johnson, Sharon; Ramadan, Hawraman; Bellfield, Ruth; Byrne, Anthony; McGhee, Caroline; Rudd, Anthony; Price, Fiona; Vasileiadis, Evangelos; Holden, Melinda; Hewitt, Jonathan; Carpenter, Michael; Needle, Ann; Valentine, Stacey; Patel, Farzana; Harrington, Frances; Mudd, Paul; Emsley, Hedley; Gregary, Bindu; Kane, Ingrid; Muir, Keith; Tiwari, Divya; Owusu-Agyei, Peter; Temple, Natalie; Sekaran, Lakshmanan; Ragab, Suzanne; England, Timothy; Hedstrom, Amanda; Jones, Phil; Jones, Sarah; Doherty, Mandy; McCarron, Mark O; Cohen, David L; Tysoe, Sharon; Al-Shahi Salman, Rustam

2017-04-05

Recruitment to randomised prevention trials is challenging, not least for intracerebral haemorrhage (ICH) associated with antithrombotic drug use. We investigated reasons for not recruiting apparently eligible patients at hospital sites that keep screening logs in the ongoing REstart or STop Antithrombotics Randomised Trial (RESTART), which seeks to determine whether to start antiplatelet drugs after ICH. By the end of May 2015, 158 participants had been recruited at 108 active sites in RESTART. The trial coordinating centre invited all sites that kept screening logs to submit screening log data, followed by one reminder. We checked the integrity of data, focused on the completeness of data about potentially eligible patients and categorised the reasons they were not randomised. Of 108 active sites, 39 (36%) provided usable screening log data over a median of ten (interquartile range = 5-13) months of recruitment per site. During this time, sites screened 633 potentially eligible patients and randomised 53 (8%) of them. The main reasons why 580 patients were not randomised were: 43 (7%) patients started anticoagulation, 51 (9%) patients declined, 148 (26%) patients' stroke physicians were not uncertain about using antiplatelet drugs, 162 (28%) patients were too unwell and 176 (30%) patients were not randomised due to other reasons. RESTART recruited ~8% of eligible patients. If more physicians were uncertain about the therapeutic dilemma that RESTART is addressing, RESTART could have recruited up to four times as many participants. The trial coordinating centre continues to engage with physicians about their uncertainty. EU Clinical Trials, EudraCT 2012-003190-26 . Registered on 3 July 2012.

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

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.

Tolerability of a probiotic in subjects with a history of methicillin-resistant Staphylococcus aureus colonisation.

PubMed

Warrack, S; Panjikar, P; Duster, M; Safdar, N

2014-12-01

Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen of major public health importance. Colonisation precedes infection; thus reducing MRSA carriage may be of benefit for reducing infection. Probiotics represent a novel approach to reducing MRSA carriage. We undertook a pilot feasibility randomised controlled trial of the tolerability and acceptability of probiotics for reducing nasal and intestinal carriage of MRSA. In addition, subjects were screened for vancomycin-resistant enterocococci (VRE). Subjects with a history of MRSA were recruited from a large, academic medical center and randomised to take either a placebo or probiotic (Lactobacillus rhamnosus HN001). Subjects returned to the clinic after four weeks for further testing to determine adherence to the probiotic regimen and colonisation of MRSA. 48 subjects were enrolled and randomised. Nearly 25% were transplant recipients and 30% had diabetes. The probiotic was well tolerated in the study population though minor side effects, such as nausea and bloating, were observed. A majority of the subjects randomised to HN001 had good adherence to the regimen. At the four week time point among subjects randomised to the probiotic, MRSA was detected in 67 and 50% of subjects colonised in the nares and the gastrointestinal tract, respectively. Three subjects who initially tested positive for VRE were negative after four weeks of probiotic exposure. Probiotics were well tolerated in our study population of largely immunocompromised subjects with multiple comorbidities. Adherence to the intervention was good. Probiotics should be studied further for their potential to reduce colonisation by multidrug resistant bacteria.

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

PubMed

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

2015-12-01

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

Socio-demographic and clinical profiles of paranoid and nonparanoid schizophrenia: a prospective, multicenter study in China.

PubMed

Xiang, Yu-Tao; Wang, Chuan-Yue; Chiu, Helen F K; Weng, Yong-Zhen; Bo, Qi-Jing; Chan, Sandra S M; Lee, Edwin H M; Ungvari, Gabor S

2011-07-01

This study aimed to explore the socio-demographic and clinical characteristics of paranoid and nonparanoid subtypes of schizophrenia. In a multicenter, randomized, controlled, longitudinal study, 374 clinically stable schizophrenia patients were interviewed at entry with standardized assessment instruments and followed for 12-26 months. In the multivariate analysis, male sex, married marital status, urban abode, and more frequent relapse over the study period were independently associated with paranoid schizophrenia. The socio-demographic and clinical characteristics of Chinese patients with the paranoid subtype of schizophrenia are different from those of their Caucasian counterparts who are more likely to be women and have a better outcome. © 2010 Wiley Periodicals, Inc.

Influence of applied quantity of sunscreen products on the sun protection factor--a multicenter study organized by the DGK Task Force Sun Protection.

PubMed

Bimczok, R; Gers-Barlag, H; Mundt, C; Klette, E; Bielfeldt, S; Rudolph, T; Pflucker, F; Heinrich, U; Tronnier, H; Johncock, W; Klebon, B; Westenfelder, H; Flosser-Muller, H; Jenni, K; Kockott, D; Lademann, J; Herzog, B; Rohr, M

2007-01-01

It is often debated that the protection against solar-induced erythema under real conditions is dependent upon the amount of sunscreen applied. It is believed that when too little is applied a lower sun protection than indicated on the label will result. The aim of this study was to quantify this effect. In this multicenter study, the influence of three different amounts (0.5, 1.0, 2.0 mg/cm(2)) of three commercial sunscreen products in three reliable test centers was investigated according to the test protocol of The International Sun Protection Factor Test Method. The main result was a linear dependence of the SPF on the quantity applied. Taking into consideration the volunteer-specific variations, an exponential dependence of confidence interval of the in vivo SPF and amount applied was found. The highest amount applied (2.0 mg/cm(2)) was linked to the lowest confidence intervals. Thus, from the point of view of producing reliable and reproducible in vivo results under laboratory conditions, the recommendation of this multicenter study is an application quantity of 2.0 mg/cm(2).

Two Phase III randomised double-blind studies of fixed-dose TC-5214 (dexmecamylamine) adjunct to ongoing antidepressant therapy in patients with major depressive disorder and an inadequate response to prior antidepressant therapy.

PubMed

Möller, Hans-Jürgen; Demyttenaere, Koen; Olausson, Bengt; Szamosi, Johan; Wilson, Ellis; Hosford, David; Dunbar, Geoffrey; Tummala, Raj; Eriksson, Hans

2015-10-01

To evaluate the neuronal nicotinic channel modulator TC-5214 (dexmecamylamine) as adjunct therapy in patients with major depressive disorder (MDD) and inadequate response to prior antidepressant treatment. Study 004 (D4130C00004) and Study 005 (D4130C00005) comprised an 8-week open-label antidepressant (SSRI/SNRI) treatment period followed by an 8-week randomised, active treatment with twice-daily TC-5214 (0.5, 2 or 4 mg in Study 004; 0.1, 1 or 4 mg in Study 005) or placebo, adjunct to ongoing SSRI/SNRI. Primary efficacy endpoint was change in MADRS total score from randomisation (Week 8) to treatment end (Week 16). Secondary endpoints included MADRS response and remission, and changes in SDS and HAM-D-17-item scores. Safety and tolerability were monitored throughout. Studies 004 and 005 randomised 640 and 696 patients, respectively, to TC-5214 or placebo. No statistically significant improvements in MADRS total score or any secondary endpoints were seen with TC-5214 versus placebo in either study at treatment end. The most commonly reported adverse events (> 10%) with TC-5214 were constipation, dizziness and dry mouth. TC-5214 adjunct to antidepressant was generally well tolerated. However, the studies were not supportive of an antidepressant effect for TC-5214 in patients with MDD and inadequate response to prior antidepressant therapy.

Management of haemothoraces in blunt thoracic trauma: study protocol for a randomised controlled trial.

PubMed

Carver, David A; Bressan, Alexsander K; Schieman, Colin; Grondin, Sean C; Kirkpatrick, Andrew W; Lall, Rohan; McBeth, Paul B; Dunham, Michael B; Ball, Chad G

2018-03-03

Haemothorax following blunt thoracic trauma is a common source of morbidity and mortality. The optimal management of moderate to large haemothoraces has yet to be defined. Observational data have suggested that expectant management may be an appropriate strategy in stable patients. This study aims to compare the outcomes of patients with haemothoraces following blunt thoracic trauma treated with either chest drainage or expectant management. This is a single-centre, dual-arm randomised controlled trial. Patients presenting with a moderate to large sized haemothorax following blunt thoracic trauma will be assessed for eligibility. Eligible patients will then undergo an informed consent process followed by randomisation to either (1) chest drainage (tube thoracostomy) or (2) expectant management. These groups will be compared for the rate of additional thoracic interventions, major thoracic complications, length of stay and mortality. This study has been approved by the institution's research ethics board and registered with ClinicalTrials.gov. All eligible participants will provide informed consent prior to randomisation. The results of this study may provide guidance in an area where there remains significant variation between clinicians. The results of this study will be published in peer-reviewed journals and presented at national and international conferences. NCT03050502. © 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.

Cognitive behavioural therapy for the management of inflammatory bowel disease-fatigue with a nested qualitative element: study protocol for a randomised controlled trial.

PubMed

Artom, Micol; Czuber-Dochan, Wladyslawa; Sturt, Jackie; Norton, Christine

2017-05-11

Fatigue is one of the most prevalent and burdensome symptoms for patients with inflammatory bowel disease (IBD). Although fatigue increases during periods of inflammation, for some patients it persists when disease is in remission. Compared to other long-term conditions where fatigue has been extensively researched, optimal management of fatigue in patients with IBD is unknown and fatigue has rarely been the primary outcome in intervention studies. To date, interventions for the management of IBD-fatigue are sparse, have short-term effects and have not been implemented within the existing health system. There is a need to integrate current best evidence across different conditions, patient experience and clinical expertise in order to develop interventions for IBD-fatigue management that are feasible and effective. Modifying an existing intervention for patients with multiple sclerosis, this study aims to assess the feasibility and initial estimates of efficacy of a cognitive behavioural therapy (CBT) intervention for the management of fatigue in patients with IBD. The study will be a two-arm pilot randomised controlled trial. Patients will be recruited from one outpatient IBD clinic and randomised individually to either: Group 1 (CBT manual for the management of fatigue, one 60-min session and seven 30-min telephone/Skype sessions with a therapist over an eight-week period); or Group 2 (fatigue information sheet to use without therapist help). Self-reported IBD-fatigue (Inflammatory Bowel Disease-Fatigue Scale) and IBD-quality of life (United Kingdom Inflammatory Bowel Disease Questionnaire) and self-reported disease activity will be collected at baseline, three, six and 12 months post randomisation. Illness perceptions, daytime sleepiness, anxiety and depression explanatory variables will be collected only at three months post randomisation. Clinical and sociodemographic data will be retrieved from the patients' medical notes. A nested qualitative study will evaluate patient and therapist experience, and healthcare professionals' perceptions of the intervention. The study will provide evidence of the feasibility and initial estimates of efficacy of a CBT intervention for the management of fatigue in patients with IBD. Quantitative and qualitative findings from the study will contribute to the development and implementation of a large-scale randomised controlled trial assessing the efficacy of CBT interventions for IBD-fatigue. ISRCTN Registry, ISRCTN17917944 . Registered on 2 September 2016.

HLM in Cluster-Randomised Trials--Measuring Efficacy across Diverse Populations of Learners

ERIC Educational Resources Information Center

Hegedus, Stephen; Tapper, John; Dalton, Sara; Sloane, Finbarr

2013-01-01

We describe the application of Hierarchical Linear Modelling (HLM) in a cluster-randomised study to examine learning algebraic concepts and procedures in an innovative, technology-rich environment in the US. HLM is applied to measure the impact of such treatment on learning and on contextual variables. We provide a detailed description of such…

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…

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

DUrable polymer-based sTent CHallenge of Promus ElemEnt versus ReSolute integrity (DUTCH PEERS): rationale and study design of a randomized multicenter trial in a Dutch all-comers population.

PubMed

Tandjung, Kenneth; Basalus, Mounir W Z; Sen, Hanim; Jessurun, Gillian A J; Danse, Peter W; Stoel, Martin; Linssen, Gerard C M; Derks, Anita; van Loenhout, Ton T; Nienhuis, Mark B; Hautvast, Raymond W M; von Birgelen, Clemens

2012-04-01

Drug-eluting stents (DES) are increasingly used for the treatment of coronary artery disease. An optimized DES performance is desirable to successfully treat various challenging coronary lesions in a broad population of patients. In response to this demand, third-generation DES with an improved deliverability were developed. Promus Element (Boston Scientific, Natick, MA) and Resolute Integrity (Medtronic Vascular, Santa Rosa, CA) are 2 novel third-generation DES for which limited clinical data are available. Accordingly, we designed the current multicenter study to investigate in an all-comers population whether the clinical outcome is similar after stenting with Promus Element versus Resolute Integrity. DUTCH PEERS is a multicenter, prospective, single-blinded, randomized trial in a Dutch all-comers population. Patients with all clinical syndromes who require percutaneous coronary interventions with DES implantation are eligible. In these patients, the type of DES implanted will be randomized in a 1:1 ratio between Resolute Integrity versus Promus Element. The trial is powered based on a noninferiority hypothesis. For each stent arm, 894 patients will be enrolled, resulting in a total study population of 1,788 patients. The primary end point is the incidence of target vessel failure at 1-year follow-up. DUTCH PEERS is the first randomized multicenter trial with a head-to-head comparison of Promus Element and Resolute Integrity to investigate the safety and efficacy of these third-generation DES. Copyright © 2012 Mosby, Inc. All rights reserved.

Renal Replacement Therapy in Severe Burns: A Multicenter Observational Study.

PubMed

Chung, Kevin K; Coates, Elsa C; Hickerson, William L; Arnold-Ross, Angela L; Caruso, Daniel M; Albrecht, Marlene; Arnoldo, Brett D; Howard, Christina; Johnson, Laura S; McLawhorn, Melissa M; Friedman, Bruce; Sprague, Amy M; Mosier, Michael J; Conrad, Peggie F; Smith, David J; Karlnoski, Rachel A; Aden, James K; Mann-Salinas, Elizabeth A; Wolf, Steven E

2018-06-20

Acute kidney injury (AKI) after severe burns is historically associated with a high mortality. Over the past two decades, various modes of renal replacement therapy (RRT) have been utilized in this population. The purpose of this multicenter study was to evaluate demographic, treatment and outcomes data among severe burn patients treated with RRT collectively at various burn centers around the United States. After institutional review board approval, a multicenter observational study was conducted. All adult patients 18 or older, admitted with severe burns who were placed on RRT for acute indications but not randomized into a concurrently enrolling interventional trial were included. Across 8 participating burn centers, 171 subjects were enrolled during a 4 year period. Complete data was available in 170 subjects with a mean age of 51±17, percent total body surface area (TBSA) burn of 38±26% and Injury Severity Score of 27±21. 80% of subjects were male and 34% were diagnosed with smoke inhalation injury. The preferred mode of therapy was continuous venovenous hemofiltration at a mean delivered dose of 37±19 (mL/kg/hr) and a treatment duration of 13±24 days. Overall, in hospital mortality was 50%. Among survivors, 21% required RRT upon discharge from the hospital while 9% continued to require RRT 6 months after discharge. This is the first multi-center cohort of burn patients who underwent RRT reported to date. Overall mortality is comparable to other critically ill populations who undergo RRT. Most patients who survive to discharge eventually recover renal function.

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.

INVESTIGATE-I (INVasive Evaluation before Surgical Treatment of Incontinence Gives Added Therapeutic Effect?): study protocol for a mixed methods study to assess the feasibility of a future randomised controlled trial of the clinical utility of invasive urodynamic testing

PubMed Central

2011-01-01

Background Urinary incontinence is an important health problem to the individual sufferer and to health services. Stress and stress predominant mixed urinary incontinence are increasingly managed by surgery due to advances in surgical techniques. Despite the lack of evidence for its clinical utility, most clinicians undertake invasive urodynamic testing (IUT) to confirm a functional diagnosis of urodynamic stress incontinence before offering surgery for this condition. IUT is expensive, embarrassing and uncomfortable for women and carries a small risk. Recent systematic reviews have confirmed the lack of high quality evidence of effectiveness. The aim of this pilot study is to test the feasibility of a future definitive randomised control trial that would address whether IUT alters treatment decisions and treatment outcome in these women and would test its clinical and cost effectiveness. Methods/design This is a mixed methods pragmatic multicentre feasibility pilot study with four components:- (a) A multicentre, external pilot randomised trial comparing basic clinical assessment with non-invasive tests and IUT. The outcome measures are rates of recruitment, randomisation and data completion. Data will be used to estimate sample size necessary for the definitive trial. (b) Qualitative interviews of a purposively sampled sub-set of women eligible for the pilot trial will explore willingness to participate, be randomised and their overall trial experience. (c) A national survey of clinicians to determine their views of IUT in this context, the main outcome being their willingness to randomise patients into the definitive trial. (d) Qualitative interviews of a purposively sampled group of these clinicians will explore whether and how they use IUT to inform their decisions. Discussion The pilot trial will provide evidence of feasibility and acceptability and therefore inform the decision whether to proceed to the definitive trial. Results will inform the design and conduct of the definitive trial and ensure its effectiveness in achieving its research aim. Trial registration number Current Controlled Trials ISRCTN71327395 assigned 7th June 2010. PMID:21733166

Reporting non-adherence in cluster randomised trials: A systematic review.

PubMed

Agbla, Schadrac C; DiazOrdaz, Karla

2018-06-01

Treatment non-adherence in randomised trials refers to situations where some participants do not receive their allocated treatment as intended. For cluster randomised trials, where the unit of randomisation is a group of participants, non-adherence may occur at the cluster or individual level. When non-adherence occurs, randomisation no longer guarantees that the relationship between treatment receipt and outcome is unconfounded, and the power to detect the treatment effects in intention-to-treat analysis may be reduced. Thus, recording adherence and estimating the causal treatment effect adequately are of interest for clinical trials. To assess the extent of reporting of non-adherence issues in published cluster trials and to establish which methods are currently being used for addressing non-adherence, if any, and whether clustering is accounted for in these. We systematically reviewed 132 cluster trials published in English in 2011 previously identified through a search in PubMed. One-hundred and twenty three cluster trials were included in this systematic review. Non-adherence was reported in 56 cluster trials. Among these, 19 reported a treatment efficacy estimate: per protocol in 15 and as treated in 4. No study discussed the assumptions made by these methods, their plausibility or the sensitivity of the results to deviations from these assumptions. The year of publication of the cluster trials included in this review (2011) could be considered a limitation of this study; however, no new guidelines regarding the reporting and the handling of non-adherence for cluster trials have been published since. In addition, a single reviewer undertook the data extraction. To mitigate this, a second reviewer conducted a validation of the extraction process on 15 randomly selected reports. Agreement was satisfactory (93%). Despite the recommendations of the Consolidated Standards of Reporting Trials statement extension to cluster randomised trials, treatment adherence is under-reported. Among the trials providing adherence information, there was substantial variation in how adherence was defined, handled and reported. Researchers should discuss the assumptions required for the results to be interpreted causally and whether these are scientifically plausible in their studies. Sensitivity analyses to study the robustness of the results to departures from these assumptions should be performed.

Aneurysmal SubArachnoid Hemorrhage—Red Blood Cell Transfusion And Outcome (SAHaRA): a pilot randomised controlled trial protocol

PubMed Central

English, Shane W; Fergusson, D; Chassé, M; Lauzier, F; Griesdale, D; Algird, A; Kramer, A; Tinmouth, A; Lum, C; Sinclair, J; Marshall, S; Dowlatshahi, D; Boutin, A; Pagliarello, G; McIntyre, L A

2016-01-01

Introduction Anaemia is common in aneurysmal subarachnoid haemorrhage (aSAH) and is a potential critical modifiable factor affecting secondary injury. Despite physiological evidence and management guidelines that support maintaining a higher haemoglobin level in patients with aSAH, current practice is one of a more restrictive approach to transfusion. The goal of this multicentre pilot trial is to determine the feasibility of successfully conducting a red blood cell (RBC) transfusion trial in adult patients with acute aSAH and anaemia (Hb ≤100 g/L), comparing a liberal transfusion strategy (Hb ≤100 g/L) with a restrictive strategy (Hb ≤80 g/L) on the combined rate of death and severe disability at 12 months. Methods Design This is a multicentre open-label randomised controlled pilot trial at 5 academic tertiary care centres. Population We are targeting adult aSAH patients within 14 days of their initial bleed and with anaemia (Hb ≤110 g/L). Randomisation Central computer-generated randomisation, stratified by centre, will be undertaken from the host centre. Randomisation into 1 of the 2 treatment arms will occur when the haemoglobin levels of eligible patients fall to ≤100 g/L. Intervention Patients will be randomly assigned to either a liberal (threshold: Hb ≤100 g/L) or a restrictive transfusion strategy (threshold: Hb ≤80 g/L). Outcome Primary: Centre randomisation rate over the study period. Secondary: (1) transfusion threshold adherence; (2) study RBC transfusion protocol adherence; and (3) outcome assessment including vital status at hospital discharge, modified Rankin Score at 6 and 12 months and Functional Independence Measure and EuroQOL Quality of Life Scale scores at 12 months. Outcome measures will be reported in aggregate. Ethics and dissemination The study protocol has been approved by the host centre (OHSN-REB 20150433-01H). This study will determine the feasibility of conducting the large pragmatic RCT comparing 2 RBC transfusion strategies examining the effect of a liberal strategy on 12-month outcome following aSAH. Trial registration number NCT02483351; Pre-results. PMID:27927658

An evaluation of the effectiveness of a multi-modal intervention in frail and pre-frail older people with type 2 diabetes - the MID-Frail study: study protocol for a randomised controlled trial

PubMed Central

2014-01-01

Background Diabetes, a highly prevalent, chronic disease, is associated with increasing frailty and functional decline in older people, with concomitant personal, social, and public health implications. We describe the rationale and methods of the multi-modal intervention in diabetes in frailty (MID-Frail) study. Methods/Design The MID-Frail study is an open, randomised, multicentre study, with random allocation by clusters (each trial site) to a usual care group or an intervention group. A total of 1,718 subjects will be randomised with each site enrolling on average 14 or 15 subjects. The primary objective of the study is to evaluate, in comparison with usual clinical practice, the effectiveness of a multi-modal intervention (specific clinical targets, education, diet, and resistance training exercise) in frail and pre-frail subjects aged ≥70 years with type 2 diabetes in terms of the difference in function 2 years post-randomisation. Difference in function will be measured by changes in a summary ordinal score on the short physical performance battery (SPPB) of at least one point. Secondary outcomes include daily activities, economic evaluation, and quality of life. Discussion The MID-Frail study will provide evidence on the clinical, functional, social, and economic impact of a multi-modal approach in frail and pre-frail older people with type 2 diabetes. Trial registration ClinicalTrials.gov: NCT01654341. PMID:24456998

An evaluation of the effectiveness of a multi-modal intervention in frail and pre-frail older people with type 2 diabetes--the MID-Frail study: study protocol for a randomised controlled trial.

PubMed

Rodríguez-Mañas, Leocadio; Bayer, Antony J; Kelly, Mark; Zeyfang, Andrej; Izquierdo, Mikel; Laosa, Olga; Hardman, Timothy C; Sinclair, Alan J; Moreira, Severina; Cook, Justin

2014-01-24

Diabetes, a highly prevalent, chronic disease, is associated with increasing frailty and functional decline in older people, with concomitant personal, social, and public health implications. We describe the rationale and methods of the multi-modal intervention in diabetes in frailty (MID-Frail) study. The MID-Frail study is an open, randomised, multicentre study, with random allocation by clusters (each trial site) to a usual care group or an intervention group. A total of 1,718 subjects will be randomised with each site enrolling on average 14 or 15 subjects. The primary objective of the study is to evaluate, in comparison with usual clinical practice, the effectiveness of a multi-modal intervention (specific clinical targets, education, diet, and resistance training exercise) in frail and pre-frail subjects aged ≥70 years with type 2 diabetes in terms of the difference in function 2 years post-randomisation. Difference in function will be measured by changes in a summary ordinal score on the short physical performance battery (SPPB) of at least one point. Secondary outcomes include daily activities, economic evaluation, and quality of life. The MID-Frail study will provide evidence on the clinical, functional, social, and economic impact of a multi-modal approach in frail and pre-frail older people with type 2 diabetes. ClinicalTrials.gov: NCT01654341.

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.

Development and Feasibility Testing of a Critical Care EEG Monitoring Database for Standardized Clinical Reporting and Multicenter Collaborative Research.

PubMed

Lee, Jong Woo; LaRoche, Suzette; Choi, Hyunmi; Rodriguez Ruiz, Andres A; Fertig, Evan; Politsky, Jeffrey M; Herman, Susan T; Loddenkemper, Tobias; Sansevere, Arnold J; Korb, Pearce J; Abend, Nicholas S; Goldstein, Joshua L; Sinha, Saurabh R; Dombrowski, Keith E; Ritzl, Eva K; Westover, Michael B; Gavvala, Jay R; Gerard, Elizabeth E; Schmitt, Sarah E; Szaflarski, Jerzy P; Ding, Kan; Haas, Kevin F; Buchsbaum, Richard; Hirsch, Lawrence J; Wusthoff, Courtney J; Hopp, Jennifer L; Hahn, Cecil D

2016-04-01

The rapid expansion of the use of continuous critical care electroencephalogram (cEEG) monitoring and resulting multicenter research studies through the Critical Care EEG Monitoring Research Consortium has created the need for a collaborative data sharing mechanism and repository. The authors describe the development of a research database incorporating the American Clinical Neurophysiology Society standardized terminology for critical care EEG monitoring. The database includes flexible report generation tools that allow for daily clinical use. Key clinical and research variables were incorporated into a Microsoft Access database. To assess its utility for multicenter research data collection, the authors performed a 21-center feasibility study in which each center entered data from 12 consecutive intensive care unit monitoring patients. To assess its utility as a clinical report generating tool, three large volume centers used it to generate daily clinical critical care EEG reports. A total of 280 subjects were enrolled in the multicenter feasibility study. The duration of recording (median, 25.5 hours) varied significantly between the centers. The incidence of seizure (17.6%), periodic/rhythmic discharges (35.7%), and interictal epileptiform discharges (11.8%) was similar to previous studies. The database was used as a clinical reporting tool by 3 centers that entered a total of 3,144 unique patients covering 6,665 recording days. The Critical Care EEG Monitoring Research Consortium database has been successfully developed and implemented with a dual role as a collaborative research platform and a clinical reporting tool. It is now available for public download to be used as a clinical data repository and report generating tool.

A Multi-center Comparison of the Safety of Oral versus Intravenous Acetylcysteine for Treatment of Acetaminophen Overdose

PubMed Central

2010-01-01

Oral and intravenous (IV) acetylcysteine are used for treatment of acetaminophen poisoning. The objective of this multi-center study was to compare the safety of these two routes of administration. METHODS We conducted a multi-center chart review of all patients treated with acetylcysteine for acetaminophen poisoning. The primary safety outcome was the percentage of patients with of acetylcysteine-related adverse events. RESULTS A total of 503 subjects were included in the safety analysis (306 IV only, 145 oral only and 52 both routes).There were no serious adverse events related to acetylcysteine for either route. Nausea and vomiting were the most common related adverse events and were more common with oral treatment (23% vs 9%). Anaphylactoid reactions were more common with IV administration (6% vs 2%). Conclusions Intravenous and oral acetylcysteine are both associated with minimal side effects and are safe for treatment of acetaminophen toxicity. PMID:20524832

[The PreFord Study. A prospective cohort study to evaluate the risk of a cardiovascular event (overall-collective) as well as a prospective, randomized, controlled, multicentre clinical intervention study (high-risk-collective) on primary prevention of cardiovascular diseases in the Ford Motor Company employees in Germany].

PubMed

Gysan, D B; Latsch, J; Bjarnason-Wehrens, B; Albus, C; Falkowski, G; Herold, G; Mey, E; Heinzler, R; Montiel, G; Schneider, C A; Stützer, H; Türk, S; Weisbrod, M; Predel, H G

2004-02-01

The PreFord Study is a multicenter prospective cohort study to evaluate guideline based risk management on primary prevention of cardiovascular diseases. Furthermore a randomised controlled trial (RCT) will be designed to analyse the effect of a special intervention program. 40,000 employees of the Ford Motor Company, Visteon Company and Deutz Company in Germany will be included, monitored for ten years and the following primary endpoints will be investigated: 1. evaluation and comparison of established and newly developed risk-scores, 2. the relative impact of single and combined cardiovascular risk factors on cardiovascular diseases, 3. the influence of a novel occupationally integrated ambulant rehabilitation program in combination with a guideline oriented optimal drug therapy within a high risk group on the primary endpoint: risk reduction by, 4. the influence of this intervention on secondary endpoints: death, myocardial infarction and stroke, combined appearance of angina pectoris and hospitalisation, occurrence of cerebral circulatory disorder and hospitalisation, occurrence of peripheral occlusive arterial disease and hospitalisation and single cardiovascular risk factors and cost-benefit-analysis. Beginning with an cross sectional study there will be a systemic screening of cardiovascular risk profiles, of anthropometric data and different lifestyle-factors. Based on these data participants will be differentiated into three risk-groups according to the risk score of the European Society of Cardiology (risk of a lethal primary acute cardiovascular event: I < or = 1%; II > 1-< 5% and III > or = 5%). In the following longitudinal study different strategies will be applied: Group I: low risk (< 0.5% per year): repetition of the investigation after five and ten years. Group II: middle risk, (0.6% to 1.4% per year), repetition of the investigation every two years, instruction of the patients general practitioner (GP) with respect to a risk factor oriented and evidence based treatment. Group III: high risk, (> 1.5% per year or >15% within the next 10 years) will be randomised into two interventional groups. The first one, the intervention-group "PreFord" will perform an occupational integrated rehabilitation program (2,5-3 hours twice a week, for 15 weeks according to the BAR guidelines) with a following engagement in heart-groups and an annual repetition of the check-ups. The second group, the "classic" intervention-group will be treated evidence based in cooperation with their GP. As a result of this long term interventional study efficient, area wide implementable and economically feasible prevention concepts with special regards to operational healthcare will be developed and evaluated. Core elements will be exercise- and lifestyle-oriented concepts as well as guideline-based pharmacotherapy.

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.

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.

A study of sertraline in dialysis (ASSertID): a protocol for a pilot randomised controlled trial of drug treatment for depression in patients undergoing haemodialysis.

PubMed

Friedli, Karin; Almond, Michael; Day, Clara; Chilcot, Joseph; Gane, Maria da Silva; Davenport, Andrew; Guirguis, Ayman; Fineberg, Naomi; Spencer, Benjamin; Wellsted, David; Farrington, Ken

2015-10-26

The prevalence of depression in people receiving haemodialysis is high with estimates varying between 20 and 40 %. There is little research on the effectiveness of antidepressants in dialysis patients with the few clinical trials suffering significant methodological issues. We plan to carry out a study to evaluate the feasibility of conducting a randomised controlled trial in patients on haemodialysis who have diagnosed Major Depressive Disorder. The study has two phases, a screening phase and the randomised controlled trial. Patients will be screened initially with the Beck Depression Inventory to estimate the number of patients who score 16 or above. These patients will be invited to an interview with a psychiatrist who will invite those with a diagnosis of Major Depressive Disorder to take part in the trial. Consenting patients will be randomised to either Sertraline or placebo. Patients will be followed-up for 6 months. Demographic and clinical data will be collected at screening interview, baseline interview and 2 weeks, and every month (up to 6 months) after baseline. The primary outcome is to evaluate the feasibility of conducting a randomised, double blind, placebo pilot trial in haemodialysis patients with depression. Secondary outcomes include estimation of the variability in the outcome measures for the treatment and placebo arms, which will allow for a future adequately powered definitive trial. Analysis will primarily be descriptive, including the number of patients eligible for the trial, drug exposure of Sertraline in haemodialysis patients and the patient experience of participating in this trial. There is an urgent need for this research in the dialysis population because of the dearth of good quality and adequately powered studies. Research with renal patients is particularly difficult as they often have complex medical needs. This research will therefore not only assess the outcome of anti-depressants in haemodialysis patients with depression but also the process of running a randomised controlled trial in this population. Hence, the outputs of this feasibility study will be used to inform the design and methodology of a definitive study, adequately powered to determine the efficacy of anti-depressants in patient on haemodialysis with depression. ISRCTN registry ISRCTN06146268 and EudraCT reference: 2012-000547-27.

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.

Multicenter surveillance of species distribution and antifungal susceptibilities of Candida bloodstream isolates in South Korea.

PubMed

Jung, Sook-In; Shin, Jong Hee; Song, Jae-Hoon; Peck, Kyong Ran; Lee, Kyungwon; Kim, Mi-Na; Chang, Hyun Ha; Moon, Chi Sook

2010-06-01

Multicenter data on in vitro susceptibility of Candida bloodstream isolates to echinocandin antifungal agents is still lacking in South Korea. We performed a prospective multicenter study to determine the species distribution of Candida bloodstream isolates and their susceptibility to five antifungal agents, including caspofungin and micafungin. A total of 639 isolates were collected from 20 tertiary hospitals between September 2006 and August 2007. Antifungal susceptibilities were determined through the use of the CLSI broth microdilution method M27-A3. The overall species distribution was as follows; Candida albicans (38%), Candida parapsilosis (26%), Candia tropicalis (20%), Candida glabrata (11%), and miscellaneous Candida species (5%). Although C. parapsilosis and miscellaneous Candida species were less susceptible to both echinocandins, all 639 isolates were susceptible to both caspofungin and micafungin (MIC,

Creatine for women in pregnancy for neuroprotection of the fetus.

PubMed

Dickinson, Hayley; Bain, Emily; Wilkinson, Dominic; Middleton, Philippa; Crowther, Caroline A; Walker, David W

2014-12-19

Creatine is an amino acid derivative and, when phosphorylated (phosphocreatine), is involved in replenishing adenosine triphosphate (ATP) via the creatine kinase reaction. Cells obtain creatine from a diet rich in fish, meat, or dairy and by endogenous synthesis from the amino acids arginine, glycine, and methionine in an approximate 50:50 ratio. Animal studies have shown that creatine may provide fetal neuroprotection when given to the mother through her diet in pregnancy. It is important to assess whether maternally administered creatine in human pregnancy (at times of known, suspected, or potential fetal compromise) may offer neuroprotection to the fetus and may accordingly reduce the risk of adverse neurodevelopmental outcomes, such as cerebral palsy and associated impairments and disabilities arising from fetal brain injury. To assess the effects of creatine when used for neuroprotection of the fetus. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2014). We planned to include all published, unpublished, and ongoing randomised trials and quasi-randomised trials. We planned to include studies reported as abstracts only as well as full-text manuscripts. Trials using a cross-over or cluster-randomised design were not eligible for inclusion.We planned to include trials comparing creatine given to women in pregnancy for fetal neuroprotection (regardless of the route, timing, dose, or duration of administration) with placebo, no treatment, or with an alternative agent aimed at providing fetal neuroprotection. We also planned to include comparisons of different regimens for administration of creatine. We identified no completed or ongoing randomised controlled trials. We found no randomised controlled trials for inclusion in this review. As we did not identify any randomised controlled trials for inclusion in this review, we are unable to comment on implications for practice. Although evidence from animal studies has supported a fetal neuroprotective role for creatine when administered to the mother during pregnancy, no trials assessing creatine in pregnant women for fetal neuroprotection have been published to date. If creatine is established as safe for the mother and her fetus, research efforts should first be directed towards randomised trials comparing creatine with either no intervention (ideally using a placebo), or with alternative agents aimed at providing fetal neuroprotection (including magnesium sulphate for the very preterm infant). If appropriate, these trials should then be followed by studies comparing different creatine regimens (dosage and duration of exposure). Such trials should be high quality and adequately powered to evaluate maternal and infant short and longer-term outcomes (including neurodevelopmental disabilities such as cerebral palsy), and should consider utilisation/costs of health care.

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…

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…

Filgrastim mobilization and collection of allogeneic blood progenitor cells from adult family donors: first interim report of a prospective German multicenter study.

PubMed

Beelen, D W; Ottinger, H; Kolbe, K; Pönisch, W; Sayer, H G; Knauf, W; Stockschläder, M; Scheid, C; Schaefer, U W

2002-12-01

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) mobilized peripheral blood progenitor cells (PBPCs) from healthy individuals are a rapidly emerging alternative source to bone marrow for allogeneic transplantation. Although widely applied in the meantime, only limited information on feasibility and safety of mobilization and collection of PBPCs is currently available from prospective multicenter studies specifically designed to investigate this donation modality. This ongoing multicenter study on the performance as well as the short- and long-term safety profile of rhG-CSF-induced mobilization and collection of PBPCs was initiated in October 1999. The study is designed to recruit a total of 300 healthy family donors who will be followed regularly for a period of 5 years after donation. The first interim report presented here summarizes results obtained after enrollment of 150 donors from nine German institutions. The study protocol allowed the individual choice between two dose regimens of rh-CSF (10 micro g/kg per day vs 2x8 micro g/kg per day of donor body weight). The primary endpoint was defined as a yield of > or =5x10(6) CD34(+) cells/kg of recipient body weight in a single leukapheresis product. This endpoint was attained by 50% of donors receiving the lower rhG-CSF dose regimen and by 75% of donors with the higher dose regimen ( p<0.0009). A total of 478 acute adverse events attributable to the mobilization procedure were recorded and manifested predominantly as transient bone pain and headaches (80%). No persistent hematologic or nonhematologic adverse events have occurred in this study so far. Thus, the current experience in a prospective multicenter study supports previous single-center and retrospective registry reports in that the collection of PBPCs after rhG-CSF mobilization is feasible and associated with frequent, but generally mild and acceptable side effects.

Accuracy of cotinine serum test to detect the smoking habit and its association with periodontal disease in a multicenter study.

PubMed

Duque, A; Martínez, P-J; Giraldo, A; Gualtero, D-F; Ardila, C-M; Contreras, A; Duarte, S; Lafaurie, G-I

2017-07-01

The validity of the surveys on self-reported smoking status is often questioned because smokers underestimate cigarette use and deny the habit. It has been suggested that self-report should be accompanied by cotinine test. This report evaluates the usefulness of serum cotinine test to assess the association between smoking and periodontal status in a study with a large sample population to be used in studies with other serum markers in epidemiologic and periodontal medicine researches. 578 patients who were part of a multicenter study on blood biomarkers were evaluated about smoking and its relation to periodontal disease. Severity of periodontal disease was determinate using clinical attachment loss (CAL). Smoking was assessed by a questionnaire and a blood sample drawn for serum cotinine determination. The optimal cut-off point for serum cotinine was 10 ng/ml. Serum cotinine showed greater association with severity of CAL than self-report for mild-moderate CAL [OR 2.03 (CI95% 1.16-3.53) vs. OR 1.08 (CI95% 0.62-1.87) ] advanced periodontitis [OR 2.36 (CI95% 1.30- 4.31) vs. OR 2.06 (CI95% 0.97-4.38) ] and extension of CAL > 3 mm [ OR 1.78 (CI95% 1.16-1.71) vs. 1.37 (CI95% 0.89-2.11)]. When the two tests were evaluated together were not shown to be better than serum cotinine test. Self-reported smoking and serum cotinine test ≥ 10ng/ml are accurate ,complementary and more reliable methods to assess the patient's smoking status and could be used in studies evaluating serum samples in large population and multicenter studies. The serum cotinine level is more reliable to make associations with the patient's periodontal status than self-report questionnaire and could be used in multicenter and periodontal medicine studies.

Accuracy of cotinine serum test to detect the smoking habit and its association with periodontal disease in a multicenter study

PubMed Central

Duque, Andrés; Martínez, Paula-Juliana; Giraldo, Astrid; Gualtero, Diego F.; Ardila, Carlos-Martín; Contreras, Adolfo; Duarte, Silvia

2017-01-01

Background The validity of the surveys on self-reported smoking status is often questioned because smokers underestimate cigarette use and deny the habit. It has been suggested that self-report should be accompanied by cotinine test. This report evaluates the usefulness of serum cotinine test to assess the association between smoking and periodontal status in a study with a large sample population to be used in studies with other serum markers in epidemiologic and periodontal medicine researches. Material and Methods 578 patients who were part of a multicenter study on blood biomarkers were evaluated about smoking and its relation to periodontal disease. Severity of periodontal disease was determinate using clinical attachment loss (CAL). Smoking was assessed by a questionnaire and a blood sample drawn for serum cotinine determination. Results The optimal cut-off point for serum cotinine was 10 ng/ml. Serum cotinine showed greater association with severity of CAL than self-report for mild-moderate CAL [OR 2.03 (CI95% 1.16-3.53) vs. OR 1.08 (CI95% 0.62-1.87) ] advanced periodontitis [OR 2.36 (CI95% 1.30- 4.31) vs. OR 2.06 (CI95% 0.97-4.38) ] and extension of CAL > 3 mm [ OR 1.78 (CI95% 1.16-1.71) vs. 1.37 (CI95% 0.89-2.11)]. When the two tests were evaluated together were not shown to be better than serum cotinine test. Conclusions Self-reported smoking and serum cotinine test ≥ 10ng/ml are accurate, complementary and more reliable methods to assess the patient’s smoking status and could be used in studies evaluating serum samples in large population and multicenter studies. Clinical Relevance: The serum cotinine level is more reliable to make associations with the patient’s periodontal status than self-report questionnaire and could be used in multicenter and periodontal medicine studies. Key words:Biological markers, serum, cotinine, periodontitis, smoking. PMID:28578367

A dose response randomised controlled trial of docosahexaenoic acid (DHA) in preterm infants.

PubMed

Collins, C T; Sullivan, T R; McPhee, A J; Stark, M J; Makrides, M; Gibson, R A

2015-08-01

Thirty one infants born less than 30 weeks׳ gestational age were randomised to receive either 40 (n=11), 80 (n=9) or 120 (n=11) mg/kg/day of docosahexaenoic acid (DHA) respectively as an emulsion, via the feeding tube, commenced within 4 days of the first enteral feed. Twenty three infants were enroled in non-randomised reference groups; n=11 who had no supplementary DHA and n=12 who had maternal DHA supplementation. All levels of DHA in the emulsion were well tolerated with no effect on number of days of interrupted feeds or days to full enteral feeds. DHA levels in diets were directly related to blood DHA levels but were unrelated to arachidonic acid (AA) levels. All randomised groups and the maternal supplementation reference group prevented the drop in DHA levels at study end that was evident in infants not receiving supplementation. Australian New Zealand Clinical Trials Registry: ACTRN12610000382077. Copyright © 2015 Elsevier Ltd. All rights reserved.

Retrieval of the Leadless Cardiac Pacemaker: A Multicenter Experience.

PubMed

Reddy, Vivek Y; Miller, Marc A; Knops, Reinoud E; Neuzil, Petr; Defaye, Pascal; Jung, Werner; Doshi, Rahul; Castellani, Mark; Strickberger, Adam; Mead, R Hardwin; Doppalapudi, Harish; Lakkireddy, Dhanunjaya; Bennett, Matthew; Sperzel, Johannes

2016-12-01

Leadless cardiac pacemakers have emerged as a safe and effective alternative to conventional transvenous single-chamber ventricular pacemakers. Herein, we report a multicenter experience on the feasibility and safety of acute retrieval (<6 weeks) and chronic retrieval (>6 weeks) of the leadless cardiac pacemaker in humans. This study included patients enrolled in 3 multicenter trials, who received a leadless cardiac pacemaker implant and who subsequently underwent a device removal attempt. The overall leadless pacemaker retrieval success rate was 94%: for patients whose leadless cardiac pacemaker had been implanted for <6 weeks (acute retrieval cohort), complete retrieval was achieved in 100% (n=5/5); for those implanted for ≥ 6 weeks (chronic retrieval cohort), retrieval was achieved in 91% (n=10/11) of patients. The mean duration of time from implant to retrieval attempt was 346 days (range, 88-1188 days) in the chronic retrieval cohort, and nearly two thirds (n=7; 63%) had been implanted for >6 months before the retrieval attempt. There were no procedure-related adverse events at 30 days post retrieval procedure. This multicenter experience demonstrated the feasibility and safety of retrieving a chronically implanted single-chamber (right ventricle) active fixation leadless pacemaker. URL: https://www.clinicaltrials.gov. Unique identifiers: NCT02051972, NCT02030418, and NCT01700244. © 2016 American Heart Association, Inc.

Biomarker combinations for diagnosis and prognosis in multicenter studies: Principles and methods.

PubMed

Meisner, Allison; Parikh, Chirag R; Kerr, Kathleen F

2017-01-01

Many investigators are interested in combining biomarkers to predict a binary outcome or detect underlying disease. This endeavor is complicated by the fact that many biomarker studies involve data from multiple centers. Depending upon the relationship between center, the biomarkers, and the target of prediction, care must be taken when constructing and evaluating combinations of biomarkers. We introduce a taxonomy to describe the role of center and consider how a biomarker combination should be constructed and evaluated. We show that ignoring center, which is frequently done by clinical researchers, is often not appropriate. The limited statistical literature proposes using random intercept logistic regression models, an approach that we demonstrate is generally inadequate and may be misleading. We instead propose using fixed intercept logistic regression, which appropriately accounts for center without relying on untenable assumptions. After constructing the biomarker combination, we recommend using performance measures that account for the multicenter nature of the data, namely the center-adjusted area under the receiver operating characteristic curve. We apply these methods to data from a multicenter study of acute kidney injury after cardiac surgery. Appropriately accounting for center, both in construction and evaluation, may increase the likelihood of identifying clinically useful biomarker combinations.

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.

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

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

PubMed

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

2015-08-01

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

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

PubMed

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

2004-06-01

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

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

PubMed

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

2017-02-01

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

Design and Conduct of an Internet-Based Preconception Cohort Study in North America: Pregnancy Study Online.

PubMed

Wise, Lauren A; Rothman, Kenneth J; Mikkelsen, Ellen M; Stanford, Joseph B; Wesselink, Amelia K; McKinnon, Craig; Gruschow, Siobhan M; Horgan, Casie E; Wiley, Aleta S; Hahn, Kristen A; Sørensen, Henrik Toft; Hatch, Elizabeth E

2015-07-01

We launched the Boston University Pregnancy Study Online (PRESTO) to assess the feasibility of carrying out an Internet-based preconception cohort study in the US and Canada. We recruited female participants age 21-45 and their male partners through Internet advertisements, word of mouth, and flyers. Female participants were randomised with 50% probability to receive a subscription to FertilityFriend.com (FF), a web-based programme that collects real-time data on menstrual characteristics. We compared recruitment methods within PRESTO, assessed the cost-efficiency of PRESTO relative to its Danish counterpart (Snart-Gravid), and validated retrospectively reported date of last menstrual period (LMP) against the FF data. After 99 weeks of recruitment (2013-15), 2421 women enrolled; 1384 (57%) invited their male partners to participate, of whom 693 (50%) enrolled. Baseline characteristics were balanced across randomisation groups. Cohort retention was similar among those randomised vs. not randomised to FF (84% vs. 81%). At study enrollment, 56%, 22%, and 22% couples had been trying to conceive for < 3, 3-5, and ≥ 6 months, respectively. The cost per subject enrolled was $146 (2013 US$), which was similar to our companion Danish study and half that of a traditional cohort study. Among FF users who conceived, > 97% reported their LMP on the PRESTO questionnaire within 1 day of the LMP recorded via FF. Use of the Internet as a method of recruitment and follow-up in a North American preconception cohort study was feasible and cost-effective. © 2015 John Wiley & Sons Ltd.

Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials

PubMed Central

Panés, Julian; Sandborn, William J; Schreiber, Stefan; Sands, Bruce E; Vermeire, Séverine; D'Haens, Geert; Panaccione, Remo; Higgins, Peter D R; Colombel, Jean-Frederic; Feagan, Brian G; Chan, Gary; Moscariello, Michele; Wang, Wenjin; Niezychowski, Wojciech; Marren, Amy; Healey, Paul; Maller, Eric

2017-01-01

Objective Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD). Design We conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks. Those achieving clinical response-100 or remission were re-randomised to maintenance treatment with placebo, tofacitinib 5 or 10 mg twice daily for 26 weeks. Primary endpoints were clinical remission at the end of the induction study, and clinical response-100 or remission at the end of the maintenance study. Results 180/280 patients randomised in the induction study were enrolled in the maintenance study. At week 8 of induction, the proportion of patients with clinical remission was 43.5% and 43.0% with 5 and 10 mg twice daily, respectively, compared with 36.7% in the placebo group (p=0.325 and 0.392 for 5 and 10 mg twice daily vs placebo). At week 26 of maintenance, the proportion of patients with clinical response-100 or remission was 55.8% with tofacitinib 10 mg twice daily compared with 39.5% with tofacitinib 5 mg twice daily and 38.1% with placebo (p=0.130 for 10 mg twice daily vs placebo). Compared with placebo, the change in C-reactive protein from baseline was statistically significant (p<0.0001) with 10 mg twice daily after both induction and maintenance treatments. Conclusions Primary efficacy endpoints were not significantly different from placebo, although there was evidence of a minor treatment effect. No new safety signals were observed for tofacitinib. Trial registration numbers NCT01393626 and NCT01393899. PMID:28209624

Protocol for Birmingham Atrial Fibrillation Treatment of the Aged study (BAFTA): a randomised controlled trial of warfarin versus aspirin for stroke prevention in the management of atrial fibrillation in an elderly primary care population [ISRCTN89345269

PubMed Central

Mant, Jonathan WF; Richards, Suzanne H; Hobbs, FD Richard; Fitzmaurice, David; Lip, Gregory YH; Murray, Ellen; Banting, Miriam; Fletcher, Kate; Rahman, Joy; Allan, Teresa; Raftery, James; Bryan, Stirling

2003-01-01

Background Atrial fibrillation (AF) is an important independent risk factor for stroke. Randomised controlled trials have shown that this risk can be reduced substantially by treatment with warfarin or more modestly by treatment with aspirin. Existing trial data for the effectiveness of warfarin are drawn largely from studies in selected secondary care populations that under-represent the elderly. The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study will provide evidence of the risks and benefits of warfarin versus aspirin for the prevention of stroke for older people with AF in a primary care setting. Study design A randomised controlled trial where older patients with AF are randomised to receive adjusted dose warfarin or aspirin. Patients will be followed up at three months post-randomisation, then at six monthly intervals there after for an average of three years by their general practitioner. Patients will also receive an annual health questionnaire. 1240 patients will be recruited from over 200 practices in England. Patients must be aged 75 years or over and have AF. Patients will be excluded if they have a history of any of the following conditions: rheumatic heart disease; major non-traumatic haemorrhage; intra-cranial haemorrhage; oesophageal varices; active endoscopically proven peptic ulcer disease; allergic hypersensitivity to warfarin or aspirin; or terminal illness. Patients will also be excluded if the GP considers that there are clinical reasons to treat a patient with warfarin in preference to aspirin (or vice versa). The primary end-point is fatal or non-fatal disabling stroke (ischaemic or haemorrhagic) or significant arterial embolism. Secondary outcomes include major extra-cranial haemorrhage, death (all cause, vascular), hospital admissions (all cause, vascular), cognition, quality of life, disability and compliance with study medication. PMID:12939169

Study protocol for a randomised controlled trial of invasive versus conservative management of primary spontaneous pneumothorax

PubMed Central

Brown, Simon G A; Ball, Emma L; Perrin, Kyle; Read, Catherine A; Asha, Stephen E; Beasley, Richard; Egerton-Warburton, Diana; Jones, Peter G; Keijzers, Gerben; Kinnear, Frances B; Kwan, Ben C H; Lee, Y C Gary; Smith, Julian A; Summers, Quentin A; Simpson, Graham

2016-01-01

Introduction Current management of primary spontaneous pneumothorax (PSP) is variable, with little evidence from randomised controlled trials to guide treatment. Guidelines emphasise intervention in many patients, which involves chest drain insertion, hospital admission and occasionally surgery. However, there is evidence that conservative management may be effective and safe, and it may also reduce the risk of recurrence. Significant questions remain regarding the optimal initial approach to the management of PSP. Methods and analysis This multicentre, prospective, randomised, open label, parallel group, non-inferiority study will randomise 342 participants with a first large PSP to conservative or interventional management. To maintain allocation concealment, randomisation will be performed in real time by computer and stratified by study site. Conservative management will involve a period of observation prior to discharge, with intervention for worsening symptoms or physiological instability. Interventional treatment will involve insertion of a small bore drain. If drainage continues after 1 hour, the patient will be admitted. If drainage stops, the drain will be clamped for 4 hours. The patient will be discharged if the lung remains inflated. Otherwise, the patient will be admitted. The primary end point is the proportion of participants with complete lung re-expansion by 8 weeks. Secondary end points are as follows: days in hospital, persistent air leak, predefined complications and adverse events, time to resolution of symptoms, and pneumothorax recurrence during a follow-up period of at least 1 year. The study has 95% power to detect an absolute non-inferiority margin of 9%, assuming 99% successful expansion at 8 weeks in the invasive treatment arm. The primary analysis will be by intention to treat. Ethics and dissemination Local ethics approval has been obtained for all sites. Study findings will be disseminated by publication in a high-impact international journal and presentation at major international Emergency Medicine and Respiratory meetings. Trial registration number ACTRN12611000184976; Pre-results. PMID:27625060

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

PubMed Central

2010-01-01

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

General vs. neuraxial anaesthesia in hip fracture patients: a systematic review and meta-analysis.

PubMed

Van Waesberghe, Julia; Stevanovic, Ana; Rossaint, Rolf; Coburn, Mark

2017-06-28

Hip fracture is a trauma of the elderly. The worldwide number of patients in need of surgery after hip fracture will increase in the coming years. The 30-day mortality ranges between 4 and 14%. Patients' outcome may be improved by anaesthesia technique (general vs. neuraxial anaesthesia). There is a dearth of evidence from randomised studies regarding to the optimal anaesthesia technique. However, several large non-randomised studies addressing this question have been published from the onset of 2010. To compare the 30-day mortality rate, in-hospital mortality rate and length of hospital stay after neuraxial (epidural/spinal) or general anaesthesia in hip fracture patients (≥ 18 years old) we prepared a systematic review and meta-analysis. A systematic search for appropriate retrospective observational and prospective randomised studies in Embase and PubMed databases was performed in the time-period from 01.01.2010 to 21.11.2016. Additionally a forward searching in google scholar, a level one reference list searching and a formal searching of trial registries was performed. Twenty retrospective observational and three prospective randomised controlled studies were included. There was no difference in the 30-day mortality [OR 0.99; 95% CI (0.94 to 1.04), p = 0.60] between the general and the neuraxial anaesthesia group. The in-hospital mortality [OR 0.85; 95% CI (0.76 to 0.95), p = 0.004] and the length of hospital stay were significantly shorter in the neuraxial anaesthesia group [MD -0.26; 95% CI (-0.36 to -0.17); p < 0.00001]. Neuraxial anaesthesia is associated with a reduced in-hospital mortality and length of hospitalisation. However, type of anaesthesia did not influence the 30-day mortality. In future there is a need for large randomised studies to examine the association between the type of anaesthesia, post-operative complications and mortality.

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

Systematic review of the clinical and cost effectiveness of cholecystectomy versus observation/conservative management for uncomplicated symptomatic gallstones or cholecystitis.

PubMed

Brazzelli, Miriam; Cruickshank, Moira; Kilonzo, Mary; Ahmed, Irfan; Stewart, Fiona; McNamee, Paul; Elders, Andy; Fraser, Cynthia; Avenell, Alison; Ramsay, Craig

2015-03-01

Gallstone disease is a common gastrointestinal disorder in industrialised countries. Although symptoms can be severe, some people can be symptom free for many years after the original attack. Surgery is the current treatment of choice, but evidence suggests that observation is also feasible and safe. We reviewed the evidence on cholecystectomy versus observation for uncomplicated symptomatic gallstones and conducted a cost-effectiveness analysis. We searched six electronic databases (last search April 2014). We included randomised controlled trials (RCTs) or non-randomised comparative studies where adults received either cholecystectomy or observation/conservative management for the first episode of symptomatic gallstone disease (biliary pain or cholecystitis) being considered for surgery in secondary care. Meta-analysis was used to combine results. A de novo Markov model was developed to assess the cost effectiveness of the interventions. Two RCTs (201 participants) were included. Eighty-eight percent of people randomised to surgery and 45 % of people randomised to observation underwent cholecystectomy during the 14-year follow-up period. Participants randomised to observation were significantly more likely to experience gallstone-related complications (RR = 6.69, 95 % CI = 1.57-28.51, p = 0.01), in particular acute cholecystitis (RR = 9.55, 95 % CI = 1.25-73.27, p = 0.03), and less likely to undergo surgery (RR = 0.50, 95 % CI = 0.34-0.73, p = 0.0004) or experience surgery-related complications (RR = 0.36, 95 % CI = 0.16-0.81, p = 0.01) than those randomised to surgery. Fifty-five percent of people randomised to observation did not require surgery, and 12 % of people randomised to cholecystectomy did not undergo surgery. On average, surgery costs £1,236 more per patient than conservative management, but was more effective. Cholecystectomy is the preferred treatment for symptomatic gallstones. However, approximately half the observation group did not require surgery or suffer complications indicating that it may be a valid alternative to surgery. A multicentre trial is needed to establish the effects, safety and cost effectiveness of observation/conservative management relative to cholecystectomy.

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

PubMed

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

2016-03-22

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

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

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

PubMed

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

2017-12-04

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

Computerised therapy for depression with clinician vs. assistant and brief vs. extended phone support: study protocol for a randomised controlled trial.

PubMed

Gega, Lina; Swift, Louise; Barton, Garry; Todd, Gillian; Reeve, Nesta; Bird, Kelly; Holland, Richard; Howe, Amanda; Wilson, Jon; Molle, Jo

2012-08-27

Computerised cognitive behaviour therapy (cCBT) involves standardised, automated, interactive self-help programmes delivered via a computer. Randomised controlled trials (RCTs) and observational studies have shown than cCBT reduces depressive symptoms as much as face-to-face therapy and more than waiting lists or treatment as usual. cCBT's efficacy and acceptability may be influenced by the "human" support offered as an adjunct to it, which can vary in duration and can be offered by people with different levels of training and expertise. This is a two-by-two factorial RCT investigating the effectiveness, cost-effectiveness and acceptability of cCBT supplemented with 12 weekly phone support sessions are either brief (5-10 min) or extended (20-30 min) and are offered by either an expert clinician or an assistant with no clinical training. Adults with non-suicidal depression in primary care can self-refer into the study by completing and posting to the research team a standardised questionnaire. Following an assessment interview, eligible referrals have access to an 8-session cCBT programme called Beating the Blues and are randomised to one of four types of support: brief-assistant, extended-assistant, brief-clinician or extended-clinician.A sample size of 35 per group (total 140) is sufficient to detect a moderate effect size with 90% power on our primary outcome measure (Work and Social Adjustment Scale); assuming a 30% attrition rate, 200 patients will be randomised. Secondary outcome measures include the Beck Depression and Anxiety Inventories and the PHQ-9 and GAD-7. Data on clinical outcomes, treatment usage and patient experiences are collected in three ways: by post via self-report questionnaires at week 0 (randomisation) and at weeks 12 and 24 post-randomisation; electronically by the cCBT system every time patients log-in; by phone during assessments, support sessions and exit interviews. The study's factorial design increases its efficiency by allowing the concurrent investigation of two types of adjunct support for cCBT with a single sample of participants. Difficulties in recruitment, uptake and retention of participants are anticipated because of the nature of the targeted clinical problem (depression impairs motivation) and of the studied interventions (lack of face-to-face contact because referrals, assessments, interventions and data collection are completed by phone, computer or post). Current Controlled Trials ISRCTN98677176.

Preventing recurrence of endometriosis by means of long-acting progestogen therapy (PRE-EMPT): report of an internal pilot, multi-arm, randomised controlled trial incorporating flexible entry design and adaption of design based on feasibility of recruitment.

PubMed

Middleton, Lee J; Daniels, Jane P; Weckesser, Annalise; Bhattacharya, Siladitya

2017-03-11

Endometriosis is associated with the growth of endometrium in ectopic sites mainly within the pelvis. This results in inflammation and scarring, causing pain and impaired quality of life. Endometriotic lesions can be excised or ablated surgically, but the risk of recurrence is high. A Heath Technology Assessment commissioning call in 2011 sought applications for trials aimed at evaluating long-term effectiveness of postoperative, long-acting, reversible contraceptives (LARCs) in preventing recurrence of endometriosis. A survey of gynaecologists indicated that there was no consensus about which LARC (Levonorgestrel Intrauterine System (LNG-IUS) or depot medroxyprogesterone acetate injection (DMPA)) or comparator (combined oral contraceptive pill (COCP) or no treatment) should be evaluated. Hence, we designed a 'flexible-entry' internal pilot to assess whether a four-arm trial was feasible including a possible design adaption based on pilot findings. In this pilot, women could be randomised to two, three or four treatment options provided that one was a LARC and one was a non-LARC. An assessment of feasibility based on recruitment to these options and a revised substantive trial design was considered by an independent oversight committee. The study ran for 1 year from April 2014 and 77 women were randomised. Only 5 (6%) women accepted randomisation to all groups, with 63 (82%) having a LARC preference and 55 (71%) a non-LARC preference. Four-way and three-way designs were ruled out with a two-way LARC versus COCP design, stratified by prerandomisation choice of LARC and optional subrandomisation to LNG-IUS versus DMPA considered a feasible substantive study. Multi-arm studies are potentially efficient as they can answer multiple questions simultaneously but are difficult to recruit to if there are strong patient or clinician preferences. A flexible approach to randomisation in a pilot phase can be used to assess feasibility of such studies and modify a trial design based on chosen recruitment options, but trialists should consider carefully any practical arrangements should groups need to be dropped during a study. International Standard Randomised Controlled Trial Number, ISRCTN97865475 . Registered on 20 March 2014.

Effects of continuous positive airway pressure on neurocognitive architecture and function in patients with obstructive sleep apnoea: study protocol for a multicentre randomised controlled trial

PubMed Central

Xu, Huajun; Wang, Hui; Guan, Jian; Yi, Hongliang; Qian, Yingjun; Zou, Jianyin; Xia, Yunyan; Fu, Yiqun; Li, Xinyi; Jiao, Xiao; Huang, Hengye; Dong, Pin; Yu, Ziwei; Yang, Jun; Xiang, Mingliang; Li, Jiping; Chen, Yanqing; Wang, Peihua; Sun, Yizhou; Li, Yuehua; Zheng, Xiaojian; Jia, Wei; Yin, Shankai

2017-01-01

Objectives Many clinical studies have indicated that obstructive sleep apnoea (OSA), the most common chronic sleep disorder, may affect neurocognitive function, and that treatment for continuous positive airway pressure (CPAP) has some neurocognitive protective effects against the adverse effects of OSA. However, the effects of CPAP treatment on neurocognitive architecture and function remain unclear. Therefore, this multicentre trial was designed to investigate whether and when neurocognitive architecture and function in patients with OSA can be improved by CPAP treatment and to explore the role of gut microbiota in improving neurocognitive function during treatment. Methods/design This study will be a multicentre, randomised, controlled trial with allocation concealment and assessor blinding. A total of 148 eligible patients with moderate to severe OSA will be enrolled from five sleep centres and randomised to receive CPAP with best supportive care (BSC) intervention or BSC intervention alone. Cognitive function, structure and function of brain regions, gut microbiota, metabolites, biochemical variables, electrocardiography, echocardiography, pulmonary function and arterial stiffness will be assessed at baseline before randomisation and at 3, 6 and 12 months. Ethics and dissemination This study has been approved by the Medical Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital (approval number 2015-79). The results from this study will be published in peer-reviewed journals and at relevant conferences. Trial registration number NCT02886156; pre-results. PMID:28550021

A feasibility study of educational tools for osteomalacia.

PubMed

Waxman, R; Adebajo, A; Robinson, S; Walker, D; Johnson, M; Rahman, A; Samanta, A; Kumar, K; Raza, K; Helliwell, P

2017-03-01

Many people in the UK, particularly people of South Asian origin, are advised to supplement their vitamin D intake, yet most do not. This suggests an unmet educational need. The osteomalacia mind map was developed to meet this need. The mind map contains culturally sensitive images, translated into Urdu and made interactive on a DVD. This study explores the feasibility of a randomised controlled study to measure the effect of education on improving vitamin D knowledge and adherence. This was a pilot and feasibility study. Cluster randomisation was used to avoid inter person contamination. Two South Asian women's groups were recruited to receive information about osteomalacia either by interactive DVD or an Arthritis Research UK leaflet. Knowledge and compliance were tested before and after the educational interventions via a knowledge questionnaire and the measurement of vitamin D and parathormone levels. The groups were found to be mismatched for knowledge, educational attainment and language at baseline. There were also organisational difficulties and possible confounding due to different tutors and translators. The DVD group had high knowledge at baseline which did not improve. The leaflet group had low knowledge at baseline that did improve. The DVD group had lower parathormone which did not change. The leaflet group had an increase in vitamin D but parathormone remained high. Performing a randomised study with this population utilising an educational intervention was difficult to execute. If cluster randomisation is used, extreme care must be taken to match the groups at baseline.

Do maternal pushing techniques during labour affect obstetric or neonatal outcomes?

PubMed

Barasinski, C; Lemery, D; Vendittelli, F

2016-10-01

To assess, through a literature review, the maternal and neonatal morbidity associated with the type of pushing used during the second stage of labour. We searched the Cochrane Library and the Medline database for randomised controlled trials from 1980 to 2015, using the following keywords: "delivery", "birth", "birthing", "bearing down, coached, uncoached, pushing", "second and stage and labour", "randomised controlled trials" and "meta-analysis". Seven randomised controlled trials were found. Interventions varied between the studies. In the intervention groups, open-glottis pushing was spontaneous or coached. The groups did not differ for perineal injuries, episiotomies or type of birth. Impact on pelvic floor structure varied between the studies. Only one study found a better 5-minute Apgar score and a better umbilical artery pH in the "open glottis" group. The low methodological quality of the studies and the differences between the protocols do not justify a recommendation of a particular pushing technique. Further studies appear necessary to study outcomes with each of these techniques. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Minimum number of clusters and comparison of analysis methods for cross sectional stepped wedge cluster randomised trials with binary outcomes: A simulation study.

PubMed

Barker, Daniel; D'Este, Catherine; Campbell, Michael J; McElduff, Patrick

2017-03-09

Stepped wedge cluster randomised trials frequently involve a relatively small number of clusters. The most common frameworks used to analyse data from these types of trials are generalised estimating equations and generalised linear mixed models. A topic of much research into these methods has been their application to cluster randomised trial data and, in particular, the number of clusters required to make reasonable inferences about the intervention effect. However, for stepped wedge trials, which have been claimed by many researchers to have a statistical power advantage over the parallel cluster randomised trial, the minimum number of clusters required has not been investigated. We conducted a simulation study where we considered the most commonly used methods suggested in the literature to analyse cross-sectional stepped wedge cluster randomised trial data. We compared the per cent bias, the type I error rate and power of these methods in a stepped wedge trial setting with a binary outcome, where there are few clusters available and when the appropriate adjustment for a time trend is made, which by design may be confounding the intervention effect. We found that the generalised linear mixed modelling approach is the most consistent when few clusters are available. We also found that none of the common analysis methods for stepped wedge trials were both unbiased and maintained a 5% type I error rate when there were only three clusters. Of the commonly used analysis approaches, we recommend the generalised linear mixed model for small stepped wedge trials with binary outcomes. We also suggest that in a stepped wedge design with three steps, at least two clusters be randomised at each step, to ensure that the intervention effect estimator maintains the nominal 5% significance level and is also reasonably unbiased.

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

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

PubMed

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

2017-05-26

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

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.

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

PubMed Central

Page, Valerie J; Ely, E Wesley; Gates, Simon; Zhao, Xiao Bei; Alce, Timothy; Shintani, Ayumi; Jackson, Jim; Perkins, Gavin D; McAuley, Daniel F

2016-01-01

Background Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or in coma. Methods We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2·5mgs or 0·9% saline placebo intravenously every 8 h irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days treatment, which ever came first. Delirium was assessed using the confusion assessment method - for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14-day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. Findings 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0-10] vs 6 days [0-11] days; p= 0·53). The most common adverse events were oversedation (11 patients in the haloperidol group vs. six in the placebo) and QTc prolongation (seven in haloperidol group and six in the placebo group). No patient had a serious adverse event related to study drug. Interpretation These results do not support the hypothesis that haloperidol modifies duration of delirium in critically ill patients. Although haloperidol can be used safely in this population of patients, pending the results of trials in progress, the use of intravenous haloperidol should be reserved for the short-term management of acute agitation. Funding National Institute for Health Research PMID:24461612

Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial.

PubMed

Page, Valerie J; Ely, E Wesley; Gates, Simon; Zhao, Xiao Bei; Alce, Timothy; Shintani, Ayumi; Jackson, Jim; Perkins, Gavin D; McAuley, Daniel F

2013-09-01

Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or coma. We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2.5 mg or 0.9% saline placebo intravenously every 8 h, irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days of treatment, whichever came first. Delirium was assessed using the confusion assessment method for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14 day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0-10] vs 6 days [0-11] days; p=0.53). The most common adverse events were oversedation (11 patients in the haloperidol group vs six in the placebo group) and QTc prolongation (seven patients in the haloperidol group vs six in the placebo group). No patient had a serious adverse event related to the study drug. These results do not support the hypothesis that haloperidol modifies duration of delirium in critically ill patients. Although haloperidol can be used safely in this population of patients, pending the results of trials in progress, the use of intravenous haloperidol should be reserved for short-term management of acute agitation. National Institute for Health Research. Copyright © 2013 Elsevier Ltd. All rights reserved.

Information for patients with cancer. Does personalization make a difference? Pilot study results and randomised trial in progress.

PubMed Central

Jones, R.; Pearson, J.; Cawsey, A.; Barrett, A.

1996-01-01

Although there are a number of groups working on the provision of personalized patient information there has been little evaluation. We have developed and piloted a method of giving patients on-line access to their own medical records with associated explanations. We are comparing, in a randomised trial, personalized with general computer based information for patients undergoing radiotherapy for cancer. We present results from the pilot study and the evaluation methods to be employed. PMID:8947701

Idelalisib or Placebo in Combination with Bendamustine and Rituximab in Patients with Relapsed/Refractory CLL - Interim Results of a Phase 3 Randomized, Double-blind Placebo-Controlled Trial

PubMed Central

Zelenetz, Andrew D.; Barrientos, Jacqueline C.; Brown, Jennifer R.; Coiffier, Bertrand; Delgado, Julio; Egyed, Miklós; Ghia, Paolo; Illés, Árpád; Jurczak, Wojciech; Marlton, Paula; Montillo, Marco; Morschhauser, Franck; Pristupa, Alexander S.; Robak, Tadeusz; Sharman, Jeff P.; Simpson, David; Smolej, Lukáš; Tausch, Eugen; Adewoye, Adeboye H.; Dreiling, Lyndah K.; Kim, Yeonhee; Stilgenbauer, Stephan; Hillmen, Peter

2017-01-01

Summary Background Bendamustine and rituximab (BR) has been a standard of care for the management of patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). We evaluated the efficacy and safety of adding idelalisib, a first-in-class targeted PI3Kδ inhibitor, to BR in patients with R/R CLL Methods This trial was a global, multicenter, double-blind, placebo -controlled trial in adult patients (≥18 years) with R/R CLL requiring treatment for their disease. Patients had to have measurable lymphadenopathy (≥1 nodal lesion ≥2.0 cm in the longest diameter and ≥1.0 cm in the longest perpendicular diameter) by computer tomography or magnetic resonance imaging, disease progression within <36 months since last prior therapy, a Karnofsky Performance Status score ≥60 and adequate bone marrow, liver and kidney function. Key exclusion criteria included histological transformation to an aggressive lymphoma (eg, Richter transformation) or disease refractory to bendamustine. Patients were randomised 1:1 using a central interactive web response system that assigned a unique treatment code for each patient, to receive intravenous BR infusions for a maximum of 6 cycles in addition to blinded study drug matching the assigned treatment of either twice-daily oral idelalisib 150 mg or placebo administered continuously until disease progression or intolerable study drug-related toxicity. Randomisation was stratified based on high-risk features (IGHV, del(17p)/TP53 mutation) and refractory vs relapsed disease. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee in the intent-to-treat population. Overall survival was a key secondary endpoint. Crossover was not permitted to the idelalisib arm at progression. The trial is ongoing (ClinicalTrials.gov # NCT01569295). Findings Between 26 June 2012 and 21 August 2014, 416 patients with R/R CLL were enrolled; 207 patients were randomised to the idelalisib and 209 to the placebo arm. After the prespecified interim analysis, the Independent Data Monitoring Committee (IDMC) recommended discontinuation and unblinding of the trial due to efficacy. Updated data are presented in this manuscript with a cutoff date of 07 October 2015. Median (95% CI) PFS was 20·8 (16·6, 26·4) and 11·1 (8·9, 11·1) months in the idelalisib and placebo arms, respectively (hazard ratio [HR], 0·33; 95% CI, 0·25, 0·44; P<0·0001) at a median (Q1, Q3) follow-up of 14 (7, 18) months. The most frequent grade 3 or greater AEs were neutropenia (124/207 [60%]) and febrile neutropenia (48/207 [23%]) in the idelalisib arm and neutropenia (99/209 [47%]) and thrombocytopenia (27/209 [13%]) in the placebo arm. Serious AEs included febrile neutropenia, pneumonia and pyrexia and were common in both treatment arms. An increased risk of infection was observed in the idelalisib vs placebo arm. Interpretation Idelalisib plus BR is superior to BR alone, improving PFS and OS. This regimen represents an important new treatment option for patients with R/R CLL. PMID:28139405

Stable Atlas-based Mapped Prior (STAMP) machine-learning segmentation for multicenter large-scale MRI data.

PubMed

Kim, Eun Young; Magnotta, Vincent A; Liu, Dawei; Johnson, Hans J

2014-09-01

Machine learning (ML)-based segmentation methods are a common technique in the medical image processing field. In spite of numerous research groups that have investigated ML-based segmentation frameworks, there remains unanswered aspects of performance variability for the choice of two key components: ML algorithm and intensity normalization. This investigation reveals that the choice of those elements plays a major part in determining segmentation accuracy and generalizability. The approach we have used in this study aims to evaluate relative benefits of the two elements within a subcortical MRI segmentation framework. Experiments were conducted to contrast eight machine-learning algorithm configurations and 11 normalization strategies for our brain MR segmentation framework. For the intensity normalization, a Stable Atlas-based Mapped Prior (STAMP) was utilized to take better account of contrast along boundaries of structures. Comparing eight machine learning algorithms on down-sampled segmentation MR data, it was obvious that a significant improvement was obtained using ensemble-based ML algorithms (i.e., random forest) or ANN algorithms. Further investigation between these two algorithms also revealed that the random forest results provided exceptionally good agreement with manual delineations by experts. Additional experiments showed that the effect of STAMP-based intensity normalization also improved the robustness of segmentation for multicenter data sets. The constructed framework obtained good multicenter reliability and was successfully applied on a large multicenter MR data set (n>3000). Less than 10% of automated segmentations were recommended for minimal expert intervention. These results demonstrate the feasibility of using the ML-based segmentation tools for processing large amount of multicenter MR images. We demonstrated dramatically different result profiles in segmentation accuracy according to the choice of ML algorithm and intensity normalization chosen. Copyright © 2014 Elsevier Inc. All rights reserved.

A multicenter observational study of US adults with acute asthma: who are the frequent users of the emergency department?

PubMed

Hasegawa, Kohei; Sullivan, Ashley F; Tovar Hirashima, Eva; Gaeta, Theodore J; Fee, Christopher; Turner, Stuart J; Massaro, Susan; Camargo, Carlos A

2014-01-01

Despite the substantial burden of asthma-related emergency department (ED) visits, there have been no recent multicenter efforts to characterize this high-risk population. We aimed to characterize patients with asthma according to their frequency of ED visits and to identify factors associated with frequent ED visits. A multicenter chart review study of 48 EDs across 23 US states. We identified ED patients ages 18 to 54 years with acute asthma during 2011 and 2012. Primary outcome was frequency of ED visits for acute asthma in the past year, excluding the index ED visit. Of the 1890 enrolled patients, 863 patients (46%) had 1 or more (frequent) ED visits in the past year. Specifically, 28% had 1 to 2 visits, 11% had 3 to 5 visits, and 7% had 6 or more visits. Among frequent ED users, guideline-recommended management was suboptimal. For example, of patients with 6 or more ED visits, 85% lacked evidence of prior evaluation by an asthma specialist, and 43% were not treated with inhaled corticosteroids. In a multivariable model, significant predictors of frequent ED visits were public insurance, no insurance, and markers for chronic asthma severity (all P < .05). Stronger associations were found among those with a higher frequency of asthma-related ED visits (eg, 6 or more ED visits). This multicenter study of US adults with acute asthma demonstrated many frequent ED users and suboptimal preventive management in this high-risk population. Future reductions in asthma morbidity and associated health care utilization will require continued efforts to bridge these major gaps in asthma care. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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…

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

A combined randomised and observational study of surgery for fractures in the distal radius in the elderly (CROSSFIRE)—a study protocol

PubMed Central

Harris, Ian, A; Naylor, Justine, M; Buchbinder, Rachelle; Ivers, Rebecca; Balogh, Zsolt; Smith, Paul; Mittal, Rajat; Xuan, Wei; Howard, Kirsten; Vafa, Arezoo; Yates, Piers; Rieger, Bertram; Smith, Geoff; Elkinson, Ilia; Kim, Woosung; Chehade, Mellick; Sungaran, Jai; Latendresse, Kim; Wong, James; Viswanathan, Sameer; Richardson, Martin; Shrestha, Kush; Drobetz, Herwig; Tran, Phong; Loveridge, Jeremy; Page, Richard; Hau, Raphael; Bingham, Roger; Mulford, Jonathan; Incoll, Ian

2017-01-01

Fractures of the distal radius are common and occur in all age groups. The incidence is high in older populations due to osteoporosis and increased falls risk. Considerable practice variation exists in the management of distal radius fractures in older patients ranging from closed reduction with cast immobilisation to open reduction with plate fixation. Plating is currently the most common surgical treatment. While there is evidence showing no significant advantage for some forms of surgical fixation over conservative treatment, and no difference between different surgical techniques, there is a lack of evidence comparing two of the most common treatments used: closed reduction and casting versus plating. Surgical management involves significant costs and risks compared with conservative management. High-level evidence is required to address practice variation, justify costs and to provide the best clinical outcomes for patients. Methods and analysis This pragmatic, multicentre randomised comparative effectiveness trial aims to determine whether plating leads to better pain and function and is more cost-effective than closed reduction and casting of displaced distal radius fractures in adults aged 60 years and older. The trial will compare the two techniques but will also follow consenting patients who are unwilling to be randomised in a separate, observational cohort. Inclusion of non-randomised patients addresses selection bias, provides practice and outcome insights about standard care, and improves the generalisability of the results from the randomised trial. Ethics and dissemination CROSSFIRE(Combined Randomised and Observational Study of Surgery for Fractures In the distal Radius in the Elderly) was reviewed and approved by The Hunter New England HREC (HNEHREC Reference No: 16/02/17/3.04). The results of the trial will be published in a peer-reviewed journal and will be disseminated via various forms of media. Results will be incorporated in clinical recommendations and practice guidelines produced by professional bodies. Registration CROSSFIRE has been registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR: ACTRN12616000969460). PMID:28645976

A combined randomised and observational study of surgery for fractures in the distal radius in the elderly (CROSSFIRE)-a study protocol.

PubMed

Harris, Ian A; Naylor, Justine M; Lawson, Andrew; Buchbinder, Rachelle; Ivers, Rebecca; Balogh, Zsolt; Smith, Paul; Mittal, Rajat; Xuan, Wei; Howard, Kirsten; Vafa, Arezoo; Yates, Piers; Rieger, Bertram; Smith, Geoff; Elkinson, Ilia; Kim, Woosung; Chehade, Mellick; Sungaran, Jai; Latendresse, Kim; Wong, James; Viswanathan, Sameer; Richardson, Martin; Shrestha, Kush; Drobetz, Herwig; Tran, Phong; Loveridge, Jeremy; Page, Richard; Hau, Raphael; Bingham, Roger; Mulford, Jonathan; Incoll, Ian

2017-06-23

Fractures of the distal radius are common and occur in all age groups. The incidence is high in older populations due to osteoporosis and increased falls risk. Considerable practice variation exists in the management of distal radius fractures in older patients ranging from closed reduction with cast immobilisation to open reduction with plate fixation. Plating is currently the most common surgical treatment. While there is evidence showing no significant advantage for some forms of surgical fixation over conservative treatment, and no difference between different surgical techniques, there is a lack of evidence comparing two of the most common treatments used: closed reduction and casting versus plating. Surgical management involves significant costs and risks compared with conservative management. High-level evidence is required to address practice variation, justify costs and to provide the best clinical outcomes for patients. This pragmatic, multicentre randomised comparative effectiveness trial aims to determine whether plating leads to better pain and function and is more cost-effective than closed reduction and casting of displaced distal radius fractures in adults aged 60 years and older. The trial will compare the two techniques but will also follow consenting patients who are unwilling to be randomised in a separate, observational cohort. Inclusion of non-randomised patients addresses selection bias, provides practice and outcome insights about standard care, and improves the generalisability of the results from the randomised trial. CROSSFIRE(Combined Randomised and Observational Study of Surgery for Fractures In the distal Radius in the Elderly) was reviewed and approved by The Hunter New England HREC (HNEHREC Reference No: 16/02/17/3.04). The results of the trial will be published in a peer-reviewed journal and will be disseminated via various forms of media. Results will be incorporated in clinical recommendations and practice guidelines produced by professional bodies. CROSSFIRE has been registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR: ACTRN12616000969460). © 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.

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.

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.

ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): study methodology, recruitment, and baseline demographic and disease characteristics.

PubMed

Mitsumoto, Hiroshi; Factor-Litvak, Pam; Andrews, Howard; Goetz, Raymond R; Andrews, Leslie; Rabkin, Judith G; McElhiney, Martin; Nieves, Jeri; Santella, Regina M; Murphy, Jennifer; Hupf, Jonathan; Singleton, Jess; Merle, David; Kilty, Mary; Heitzman, Daragh; Bedlack, Richard S; Miller, Robert G; Katz, Jonathan S; Forshew, Dallas; Barohn, Richard J; Sorenson, Eric J; Oskarsson, Bjorn; Fernandes Filho, J Americo M; Kasarskis, Edward J; Lomen-Hoerth, Catherine; Mozaffar, Tahseen; Rollins, Yvonne D; Nations, Sharon P; Swenson, Andrea J; Shefner, Jeremy M; Andrews, Jinsy A; Koczon-Jaremko, Boguslawa A

2014-06-01

Abstract In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods utilize an extensive structured telephone interview ascertaining environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3-6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Three hundred and fifty-five patients were recruited. Subjects were enrolled over a 36-month period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Results showed that demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, the only difference being type of health insurance among enrolled patients. Sites were divided into three groups by the number of enrolled subjects. Comparing these three groups, the Columbia site had fewer 'definite ALS' diagnoses. This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and has been accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized.

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

PubMed

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

2017-05-01

The National Institute for Health and Care Excellence (NICE) 2009 guidelines for persistent low back pain (LBP) do not recommend the injection of therapeutic substances into the back as a treatment for LBP because of the absence of evidence for their effectiveness. This feasibility study aimed to provide a stable platform that could be used to evaluate a randomised controlled trial (RCT) on the clinical effectiveness and cost-effectiveness of intra-articular facet joint injections (FJIs) when added to normal care. To explore the feasibility of running a RCT to test the hypothesis that, for people with suspected facet joint back pain, adding the option of intra-articular FJIs (local anaesthetic and corticosteroids) to best usual non-invasive care is clinically effective and cost-effective. The trial was a mixed design. The RCT pilot protocol development involved literature reviews and a consensus conference followed by a randomised pilot study with an embedded mixed-methods process evaluation. Five NHS acute trusts in England. Participants were patients aged ≥ 18 years with moderately troublesome LBP present (> 6 months), who had failed previous conservative treatment and who had suspected facet joint pain. The study aimed to recruit 150 participants (approximately 30 per site). Participants were randomised sequentially by a remote service to FJIs combined with 'best usual care' (BUC) or BUC alone. All participants were to receive six sessions of a bespoke BUC rehabilitation package. Those randomised into the intervention arm were, in addition, given FJIs with local anaesthetic and steroids (at up to six injection sites). Randomisation occurred at the end of the first BUC session. Process and clinical outcomes. Clinical outcomes included a measurement of level of pain on a scale from 0 to 10, which was collected daily and then weekly via text messaging (or through a written diary). Questionnaire follow-up was at 3 months. Fifty-two stakeholders attended the consensus meeting. Agreement informed several statistical questions and three design considerations: diagnosis, the process of FJI and the BUC package and informing the design for the randomised pilot study. Recruitment started on 26 June 2015 and was terminated by the funder (as a result of poor recruitment) on 11 December 2015. In total, 26 participants were randomised. Process data illuminate some of the reasons for recruitment problems but also show that trial processes after enrolment ran smoothly. No between-group analysis was carried out. All pain-related outcomes show the expected improvement between baseline and follow-up. The mean total cost of the overall treatment package (injection £419.22 and BUC £264.00) was estimated at £683.22 per participant. This is similar to a NHS tariff cost for a course of FJIs of £686.84. Poor recruitment was a limiting factor. This feasibility study achieved consensus on the main challenges in a trial of FJIs for people with persistent non-specific low back pain. Further work is needed to test recruitment from alternative clinical situations. EudraCT 2014-000682-50 and Current Controlled Trials ISRCTN93184143. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 30. See the NIHR Journals Library website for further project information.

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.

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.

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

PubMed

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

2004-02-01

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

Reporting quality and risk of bias in randomised trials in health professions education.

PubMed

Horsley, Tanya; Galipeau, James; Petkovic, Jennifer; Zeiter, Jeanie; Hamstra, Stanley J; Cook, David A

2017-01-01

Complete reporting of research is essential to enable consumers to accurately appraise, interpret and apply findings. Quality appraisal checklists are giving way to tools that judge the risk for bias. We sought to determine the prevalence of these complementary aspects of research reports (completeness of reporting and perceived risk for bias) of randomised studies in health professions education. We searched bibliographic databases for randomised studies of health professions education. We appraised two cohorts representing different time periods (2008-2010 and 2014, respectively) and worked in duplicate to apply the CONSORT guidelines and Cochrane Risk of Bias tool. We explored differences between time periods using independent-samples t-tests or the chi-squared test, as appropriate. We systematically identified 180 randomised studies (2008-2010, n = 150; 2014, n = 30). Frequencies of reporting of CONSORT elements within full-text reports were highly variable and most elements were reported in fewer than 50% of studies. We found a statistically significant difference in the CONSORT reporting index (maximum score: 500) between the 2008-2010 (mean ± standard deviation [SD]: 242.7 ± 55.6) and 2014 (mean ± SD: 311.6 ± 53.2) cohorts (p < 0.001). High or unclear risk for bias was most common for allocation concealment (157, 87%) and blinding of participants (147, 82%), personnel (152, 84%) and outcome assessors (112, 62%). Most risk for bias elements were judged to be unclear (range: 51-84%). Risk for bias elements significantly improved over time for blinding of participants (p = 0.007), incomplete data (p < 0.001) and the presence of other sources of bias (p < 0.001). Reports of randomised studies in health professions education frequently omit elements recommended by the CONSORT statement. Most reports were assessed as having a high or unclear risk for bias. Greater attention to how studies are reported at study outset and in manuscript preparation could improve levels of complete transparent reporting. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Bridging the gap between the randomised clinical trial world and the real world by combination of population-based registry and electronic health record data: A case study in haemato-oncology.

PubMed

Kibbelaar, R E; Oortgiesen, B E; van der Wal-Oost, A M; Boslooper, K; Coebergh, J W; Veeger, N J G M; Joosten, P; Storm, H; van Roon, E N; Hoogendoorn, M

2017-11-01

Randomised clinical trials (RCTs) are considered the basis of evidence-based medicine. It is recognised more and more that application of RCT results in daily practice of clinical decision-making is limited because the RCT world does not correspond with the clinical real world. Recent strategies aiming at substitution of RCT databases by improved population-based registries (PBRs) or by improved electronic health record (EHR) systems to provide significant data for clinical science are discussed. A novel approach exemplified by the HemoBase haemato-oncology project is presented. In this approach, a PBR is combined with an advanced EHR, providing high-quality data for observational studies and support of best practice development. This PBR + EHR approach opens a perspective on randomised registry trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Uptake of Workplace HIV Counselling and Testing: A Cluster-Randomised Trial in Zimbabwe

PubMed Central

Corbett, Elizabeth L; Dauya, Ethel; Matambo, Ronnie; Cheung, Yin Bun; Makamure, Beauty; Bassett, Mary T; Chandiwana, Steven; Munyati, Shungu; Mason, Peter R; Butterworth, Anthony E; Godfrey-Faussett, Peter; Hayes, Richard J

2006-01-01

Background HIV counselling and testing is a key component of both HIV care and HIV prevention, but uptake is currently low. We investigated the impact of rapid HIV testing at the workplace on uptake of voluntary counselling and testing (VCT). Methods and Findings The study was a cluster-randomised trial of two VCT strategies, with business occupational health clinics as the unit of randomisation. VCT was directly offered to all employees, followed by 2 y of open access to VCT and basic HIV care. Businesses were randomised to either on-site rapid HIV testing at their occupational clinic (11 businesses) or to vouchers for off-site VCT at a chain of free-standing centres also using rapid tests (11 businesses). Baseline anonymised HIV serology was requested from all employees. HIV prevalence was 19.8% and 18.4%, respectively, at businesses randomised to on-site and off-site VCT. In total, 1,957 of 3,950 employees at clinics randomised to on-site testing had VCT (mean uptake by site 51.1%) compared to 586 of 3,532 employees taking vouchers at clinics randomised to off-site testing (mean uptake by site 19.2%). The risk ratio for on-site VCT compared to voucher uptake was 2.8 (95% confidence interval 1.8 to 3.8) after adjustment for potential confounders. Only 125 employees (mean uptake by site 4.3%) reported using their voucher, so that the true adjusted risk ratio for on-site compared to off-site VCT may have been as high as 12.5 (95% confidence interval 8.2 to 16.8). Conclusions High-impact VCT strategies are urgently needed to maximise HIV prevention and access to care in Africa. VCT at the workplace offers the potential for high uptake when offered on-site and linked to basic HIV care. Convenience and accessibility appear to have critical roles in the acceptability of community-based VCT. PMID:16796402

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

Mobile phone text messaging to improve medication adherence in secondary prevention of cardiovascular disease.

PubMed

Adler, Alma J; Martin, Nicole; Mariani, Javier; Tajer, Carlos D; Owolabi, Onikepe O; Free, Caroline; Serrano, Norma C; Casas, Juan P; Perel, Pablo

2017-04-29

Worldwide at least 100 million people are thought to have prevalent cardiovascular disease (CVD). This population has a five times greater chance of suffering a recurrent cardiovascular event than people without known CVD. Secondary CVD prevention is defined as action aimed to reduce the probability of recurrence of such events. Drug interventions have been shown to be cost-effective in reducing this risk and are recommended in international guidelines. However, adherence to recommended treatments remains sub-optimal. In order to influence non-adherence, there is a need to develop scalable and cost-effective behaviour-change interventions. To assess the effects of mobile phone text messaging in patients with established arterial occlusive events on adherence to treatment, fatal and non-fatal cardiovascular events, and adverse effects. We searched CENTRAL, MEDLINE, Embase, the Conference Proceedings Citation Index - Science on Web of Science on 7 November 2016, and two clinical trial registers on 12 November 2016. We contacted authors of included studies for missing information and searched reference lists of relevant papers. We applied no language or date restrictions. We included randomised trials with at least 50% of the participants with established arterial occlusive events. We included trials investigating interventions using short message service (SMS) or multimedia messaging service (MMS) with the aim to improve adherence to medication for the secondary prevention of cardiovascular events. Eligible comparators were no intervention or other modes of communication. We used standard methodological procedures expected by Cochrane. In addition, we attempted to contact all authors on how the SMS were developed. We included seven trials (reported in 13 reports) with 1310 participants randomised. Follow-up ranged from one month to 12 months. Due to heterogeneity in the methods, population and outcome measures, we were unable to conduct meta-analysis on these studies. All seven studies reported on adherence, but using different methods and scales. Six out of seven trials showed a beneficial effect of mobile phone text messaging for medication adherence. Dale 2015a, reported significantly greater medication adherence score in the intervention group (Mean Difference (MD) 0.58, 95% confidence interval (CI) 0.19 to 0.97; 123 participants randomised) at six months. Khonsari 2015 reported less adherence in the control group (Relative Risk (RR) 4.09, 95% CI 1.82 to 9.18; 62 participants randomised) at eight weeks. Pandey 2014 (34 participants randomised) assessed medication adherence through self-reported logs with 90% adherence in the intervention group compared to 70% in the control group at 12 months. Park 2014a (90 participants randomised) reported a greater increase of the medication adherence score in the control group, but also measured adherence with an event monitoring system for a number of medications with adherence levels ranging from 84.1% adherence to 86.2% in the intervention group and 79.7% to 85.7% in the control group at 30 days. Quilici 2013, reported reduced odds of non-adherence in the intervention group (Odds Ratio (OR) 0.43, 95% CI 0.22 to 0.86, 521 participants randomised) at 30 days. Fang 2016, reported that participants given SMS alone had reduced odds of being non-adherent compared to telephone reminders (OR 0.40 95% CI 0.18 to 0.63; 280 patients randomised). Kamal 2015 reported higher levels of adherence in the intervention arm (adjusted MD 0.54, 95% CI 0.22 to 0.85; 200 participants randomised). Khonsari 2015 was the only study to report fatal cardiovascular events and only reported two events, both in the control arm. No study reported on the other primary outcomes. No study reported repetitive thumb injury or road traffic crashes or other adverse events that were related to the intervention.Four authors replied to our questionnaire on SMS development. No study reported examining causes of non-adherence or provided SMS tailored to individual patient characteristics.The included studies were small, heterogeneous and included participants recruited directly after acute events. All studies were assessed as having high risk of bias across at least one domain. Most of the studies came from high-income countries, with two studies conducted in an upper middle-income country (China, Malaysia), and one study from a lower middle-income country (Pakistan). The quality of the evidence was found to be very low. There was no obvious conflicts of interest from authors, although only two declared their funding. While the results of this systematic review are promising, there is insufficient evidence to draw conclusions on the effectiveness of text message-based interventions for adherence to medications for secondary prevention of CVD. Sufficiently powered, high-quality randomised trials are needed, particularly in low- and middle-income countries.

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.

Cognitive bias modification for social anxiety in adults who stutter: a feasibility study of a randomised controlled trial

PubMed Central

Gascoine, Sally; Carroll, Amy; Humby, Kate; Kingston, Mary; Shepstone, Lee; Risebro, Helen; Mackintosh, Bundy; Thompson, Tammy Davidson; Hodgekins, Jo

2017-01-01

Objective To determine the feasibility and acceptability of a computerised treatment for social anxiety disorder for adults who stutter including identification of recruitment, retention and completion rates, large cost drivers and selection of most appropriate outcome measure(s) to inform the design of a future definitive trial. Design Two-group parallel design (treatment vs placebo), double-blinded feasibility study. Participants: 31 adults who stutter. Intervention Attention training via an online probe detection task in which the stimuli were images of faces displaying neutral and disgusted expressions. Main outcome measures Psychological measures: Structured Clinical Interview Global Assessment of Functioning score; Liebowitz Social Anxiety Scale; Social Phobia and Anxiety Inventory; State-Trait Anxiety Inventory; Unhelpful Thoughts and Beliefs about Stuttering. Speech fluency: percent syllables stuttered. Economic evaluation: resource use questionnaire; EuroQol three-dimension questionnaire. Acceptability: Likert Scale questionnaire of experience of trial, acceptability of the intervention and randomisation procedure. Results Feasibility of recruitment strategy was demonstrated. Participant feedback indicated that the intervention and definitive trial, including randomisation, would be acceptable to adults who stutter. Of the 31 participants who were randomised, 25 provided data at all three data collection points. Conclusions The feasibility study informed components of the intervention. Modifications to the design are needed before a definitive trial can be undertaken. Trial registration number I SRCTN55065978; Post-results. PMID:29061602

Feasibility and potential effectiveness of a non-pharmacological multidisciplinary care programme for persons with generalised osteoarthritis: a randomised, multiple-baseline single-case study

PubMed Central

Kwakkenbos, Linda; Rietveld, Leonie; den Broeder, Alfons A; de Bie, Rob A; van den Ende, Cornelia H M

2012-01-01

Objectives To evaluate the feasibility and potential effectiveness of a 12-week, non-pharmacological multidisciplinary intervention in patients with generalised osteoarthritis (GOA). Design A randomised, concurrent, multiple-baseline single-case design. During the baseline period, the intervention period and the postintervention period, all participants completed several health outcomes twice a week on Visual Analogue Scales. Setting Rheumatology outpatient department of a specialised hospital in the Netherlands. Participants 1 man and four women (aged 51–76 years) diagnosed with GOA. Primary outcome measures To assess feasibility, the authors assessed the number of dropouts and adverse events, adherence rates and patients' satisfaction. Secondary outcome measures To assess the potential effectiveness, the authors assessed pain and self-efficacy using visual data inspection and randomisation tests. Results The intervention was feasible in terms of adverse events (none) and adherence rate but not in terms of participants' satisfaction with the intervention. Visual inspection of the data and randomisation testing demonstrated no effects on pain (p=0.93) or self-efficacy (p=0.85). Conclusions The results of the present study indicate that the proposed intervention for patients with GOA was insufficiently feasible and effective. The data obtained through this multiple-baseline study have highlighted several areas in which the therapy programme can be optimised. PMID:22815466

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

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.

Randomised trials in context: practical problems and social aspects of evidence-based medicine and policy.

PubMed

Pearce, Warren; Raman, Sujatha; Turner, Andrew

2015-09-01

Randomised trials can provide excellent evidence of treatment benefit in medicine. Over the last 50 years, they have been cemented in the regulatory requirements for the approval of new treatments. Randomised trials make up a large and seemingly high-quality proportion of the medical evidence-base. However, it has also been acknowledged that a distorted evidence-base places a severe limitation on the practice of evidence-based medicine (EBM). We describe four important ways in which the evidence from randomised trials is limited or partial: the problem of applying results, the problem of bias in the conduct of randomised trials, the problem of conducting the wrong trials and the problem of conducting the right trials the wrong way. These problems are not intrinsic to the method of randomised trials or the EBM philosophy of evidence; nevertheless, they are genuine problems that undermine the evidence that randomised trials provide for decision-making and therefore undermine EBM in practice. Finally, we discuss the social dimensions of these problems and how they highlight the indispensable role of judgement when generating and using evidence for medicine. This is the paradox of randomised trial evidence: the trials open up expert judgment to scrutiny, but this scrutiny in turn requires further expertise.

Mass Spectrometry Imaging of Biological Tissue: An Approach for Multicenter Studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rompp, Andreas; Both, Jean-Pierre; Brunelle, Alain

2015-03-01

Mass spectrometry imaging has become a popular tool for probing the chemical complexity of biological surfaces. This led to the development of a wide range of instrumentation and preparation protocols. It is thus desirable to evaluate and compare the data output from different methodologies and mass spectrometers. Here, we present an approach for the comparison of mass spectrometry imaging data from different laboratories (often referred to as multicenter studies). This is exemplified by the analysis of mouse brain sections in five laboratories in Europe and the USA. The instrumentation includes matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF), MALDI-QTOF, MALDIFourier transform ion cyclotronmore » resonance (FTICR), atmospheric-pressure (AP)-MALDI-Orbitrap, and cluster TOF-secondary ion mass spectrometry (SIMS). Experimental parameters such as measurement speed, imaging bin width, and mass spectrometric parameters are discussed. All datasets were converted to the standard data format imzML and displayed in a common open-source software with identical parameters for visualization, which facilitates direct comparison of MS images. The imzML conversion also allowed exchange of fully functional MS imaging datasets between the different laboratories. The experiments ranged from overview measurements of the full mouse brain to detailed analysis of smaller features (depending on spatial resolution settings), but common histological features such as the corpus callosum were visible in all measurements. High spatial resolution measurements of AP-MALDI-Orbitrap and TOF-SIMS showed comparable structures in the low-micrometer range. We discuss general considerations for planning and performing multicenter studies in mass spectrometry imaging. This includes details on the selection, distribution, and preparation of tissue samples as well as on data handling. Such multicenter studies in combination with ongoing activities for reporting guidelines, a common data format (imzML) and a public data repository can contribute to more reliability and transparency of MS imaging studies.« less

Are mass-media campaigns effective in preventing drug use? A Cochrane systematic review and meta-analysis

PubMed Central

Allara, Elias; Ferri, Marica; Bo, Alessandra; Gasparrini, Antonio; Faggiano, Fabrizio

2015-01-01

Objective To determine whether there is evidence that mass-media campaigns can be effective in reducing illicit drug consumption and the intent to consume. Design Systematic review of randomised and non-randomised studies. Methods We searched four electronic databases (MEDLINE, EMBASE, ProQuest Dissertations & Theses A&I and CENTRAL) and further explored seven additional resources to obtain both published and unpublished materials. We appraised the quality of included studies using standardised tools. We carried out meta-analyses of randomised controlled trials and a pooled analysis of interrupted time-series and controlled before-and-after studies. Results We identified 19 studies comprising 184 811 participants. Pooled analyses and narrative synthesis provided mixed evidence of effectiveness. Eight interventions evaluated with randomised controlled trials leaned towards no evidence of an effect, both on drug use (standardised mean difference (SMD) −0.02; 95% CI −0.15 to 0.12) and the intention to use drugs (SMD −0.07; 95% CI −0.19 to 0.04). Four campaigns provided some evidence of beneficial effects in preventing drug use and two interventions provided evidence of iatrogenic effects. Conclusions Studies were considerably heterogeneous in type of mass-media intervention, outcome measures, underlying theory, comparison groups and design. Such factors can contribute to explaining the observed variability in results. Owing to the risk of adverse effects, caution is needed in disseminating mass-media campaigns tackling drug use. Large studies conducted with appropriate methodology are warranted to consolidate the evidence base. PMID:26338836

Advancing the evidence base in cancer: psychosocial multicenter trials

PubMed Central

2012-01-01

Background The diagnosis and treatment of cancer is associated with significant distress and psychosocial morbidity. Although psychosocial interventions have been developed in an attempt to improve psychosocial outcomes in cancer patients and survivors, there is continued debate about whether there is adequate high-level evidence to establish the effectiveness of these interventions. The evidence base is limited as a result of numerous challenges faced by those attempting to conduct psychosocial intervention trials within the health system. Barriers include insufficient participant recruitment, difficulty generalizing from single-trial studies, difficulty in building and managing research teams with multidisciplinary expertise, lack of research design expertise and a lack of incentives for researchers conducting intervention research. To strengthen the evidence base, more intervention studies employing methodologically rigorous research designs are necessary. Methods In order to advance the evidence base of interventions designed to improve psychosocial outcomes for cancer patients and survivors, we propose the formation of a collaborative trials group that conducts multicenter trials to test the effectiveness of such interventions. Results Establishment of such a group would improve the quality of the evidence base in psychosocial research in cancer patients, by increasing support for conducting intervention research and providing intervention research training opportunities. A multidisciplinary collaborative group conducting multicenter trials would have the capacity to overcome many of the barriers that currently exist. Conclusions A stronger evidence base is necessary to identify effective psychosocial interventions for cancer patients. The proposed formation of a psycho-oncology collaborative trials group that conducts multicenter trials to test the effectiveness of psychosocial interventions would assist in achieving this outcome. PMID:22992443

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

PubMed

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

2015-05-27

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

Binocular treatment of amblyopia using videogames (BRAVO): study protocol for a randomised controlled trial.

PubMed

Guo, Cindy X; Babu, Raiju J; Black, Joanna M; Bobier, William R; Lam, Carly S Y; Dai, Shuan; Gao, Tina Y; Hess, Robert F; Jenkins, Michelle; Jiang, Yannan; Kowal, Lionel; Parag, Varsha; South, Jayshree; Staffieri, Sandra Elfride; Walker, Natalie; Wadham, Angela; Thompson, Benjamin

2016-10-18

Amblyopia is a common neurodevelopmental disorder of vision that is characterised by visual impairment in one eye and compromised binocular visual function. Existing evidence-based treatments for children include patching the nonamblyopic eye to encourage use of the amblyopic eye. Currently there are no widely accepted treatments available for adults with amblyopia. The aim of this trial is to assess the efficacy of a new binocular, videogame-based treatment for amblyopia in older children and adults. We hypothesise that binocular treatment will significantly improve amblyopic eye visual acuity relative to placebo treatment. The BRAVO study is a double-blind, randomised, placebo-controlled multicentre trial to assess the effectiveness of a novel videogame-based binocular treatment for amblyopia. One hundred and eight participants aged 7 years or older with anisometropic and/or strabismic amblyopia (defined as ≥0.2 LogMAR interocular visual acuity difference, ≥0.3 LogMAR amblyopic eye visual acuity and no ocular disease) will be recruited via ophthalmologists, optometrists, clinical record searches and public advertisements at five sites in New Zealand, Canada, Hong Kong and Australia. Eligible participants will be randomised by computer in a 1:1 ratio, with stratification by age group: 7-12, 13-17 and 18 years and older. Participants will be randomised to receive 6 weeks of active or placebo home-based binocular treatment. Treatment will be in the form of a modified interactive falling-blocks game, implemented on a 5th generation iPod touch device viewed through red/green anaglyphic glasses. Participants and those assessing outcomes will be blinded to group assignment. The primary outcome is the change in best-corrected distance visual acuity in the amblyopic eye from baseline to 6 weeks post randomisation. Secondary outcomes include distance and near visual acuity, stereopsis, interocular suppression, angle of strabismus (where applicable) measured at baseline, 3, 6, 12 and 24 weeks post randomisation. Treatment compliance and acceptability will also be assessed along with quality of life for adult participants. The BRAVO study is the first randomised controlled trial of a home-based videogame treatment for older children and adults with amblyopia. The results will indicate whether a binocular approach to amblyopia treatment conducted at home is effective for patients aged 7 years or older. This trial was registered in Australia and New Zealand Clinical Trials Registry ( ACTRN12613001004752 ) on 10 September 2013.

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.

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

PubMed

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

2014-05-02

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

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.

The effectiveness of Stepping Stones Triple P: the design of a randomised controlled trial on a parenting programme regarding children with mild intellectual disability and psychosocial problems versus care as usual.

PubMed

Kleefman, Marijke; Jansen, Daniëlle E M C; Reijneveld, Sijmen A

2011-08-30

Children with an intellectual disability are at increased risk of psychosocial problems. This leads to serious restrictions in the daily functioning of the children and to parental stress. Stepping Stones Triple P aims to prevent severe behavioural, emotional and developmental problems in children with a (intellectual) disability by enhancing parenting knowledge and skills, and the self-confidence of parents. This paper aims to describe the design of a study of the effectiveness of parenting counselling using Stepping Stones Triple P compared to Care as Usual. The effects of Stepping Stones Triple P will be studied in a Randomised Controlled Trial. Parents of children aged 5-12 years with an IQ of 50-85 will be recruited from schools. Prior to randomisation, parents complete a screening questionnaire about their child's psychosocial problems and their parenting skills. Subsequently, parents of children with increased levels of psychosocial problems (score on Strengths and Difficulties Questionnaire ≥ 14) will be invited to participate in the intervention study. After obtaining consent, parents will be randomised either to the experimental group (Stepping Stones Triple P) or to Care as Usual. The primary outcome is a change in the child's psychosocial problems according to parents and teachers. The secondary outcome is a change in parenting skills. Data will be collected before the start of the intervention, immediately after the intervention, and six months after. This paper presents an outline of the background and design of a randomised controlled trial to investigate the effectiveness of Stepping Stones Triple P, which aims to decrease psychosocial problems in children with a mild intellectual disability. Stepping Stones Triple P seems promising, but evidence on its effectiveness for this population is still lacking. This study provides evidence about the effects of this intervention in a community-based population of children with a mild intellectual disability. Netherlands Trial Register (NTR): NTR2624.

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

Efficacy and safety of renal denervation for Chinese patients with resistant hypertension using a microirrigated catheter: study design and protocol for a prospective multicentre randomised controlled trial.

PubMed

Liu, Zongjun; Shen, Li; Huang, Weijian; Zhao, Xianxian; Fang, Weiyi; Wang, Changqian; Yin, Zhaofang; Wang, Jianan; Fu, Guosheng; Liu, Xuebo; Jiang, Jianjun; Zhang, Zhihui; Li, Jingbo; Lu, Yingmin; Ge, Junbo

2017-09-01

Available data show that approximately 8%-18% of patients with primary hypertension will develop resistant hypertension. In recent years, catheter-based renal denervation (RDN) has emerged as a potential treatment option for resistant hypertension. A number of observational studies and randomised controlled trials among non-Chinese patients have demonstrated its potential safety and efficacy. This is a multicentre, randomised, open-label, parallel-group, active controlled trial that will investigate the efficacy and safety of a 5F saline-irrigated radiofrequency ablation (RFA) used for RDN in the treatment of Chinese patients with resistant hypertension. A total of 254 patients who have failed pharmacological therapy will be enrolled. Eligible subjects will be randomised in a 1:1 ratio to undergo RDN using the RFA plus antihypertensive medication or to receive treatment with antihypertensive medication alone. The primary outcome measure is the change in 24 hours average ambulatory systolic blood pressure from baseline to 3 months, comparing the RDN-plus-medication group with the medication-alone group. Important secondary endpoints include the change in office blood pressure from baseline to 6 months after randomisation. Safety endpoints such as changes in renal function will also be evaluated. The full analysis set, according to the intent-to-treat principle, will be established as the primary analysis population. All participants will provide informed consent; the study protocol has been approved by the Independent Ethics Committee for each site. This study is designed to investigate the efficacy and safety of RDN using a 5F saline microirrigated RFA. Findings will be shared with participating hospitals, policymakers and the academic community to promote the clinical management of resistant hypertension in China. ClinicalTrials.gov ID: NCT02900729; 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.

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

PubMed

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

2003-09-18

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

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

A case report of evaluating a large-scale health systems improvement project in an uncontrolled setting: a quality improvement initiative in KwaZulu-Natal, South Africa.

PubMed

Mate, Kedar S; Ngidi, Wilbroda Hlolisile; Reddy, Jennifer; Mphatswe, Wendy; Rollins, Nigel; Barker, Pierre

2013-11-01

New approaches are needed to evaluate quality improvement (QI) within large-scale public health efforts. This case report details challenges to large-scale QI evaluation, and proposes solutions relying on adaptive study design. We used two sequential evaluative methods to study a QI effort to improve delivery of HIV preventive care in public health facilities in three districts in KwaZulu-Natal, South Africa, over a 3-year period. We initially used a cluster randomised controlled trial (RCT) design. During the RCT study period, tensions arose between intervention implementation and evaluation design due to loss of integrity of the randomisation unit over time, pressure to implement changes across the randomisation unit boundaries, and use of administrative rather than functional structures for the randomisation. In response to this loss of design integrity, we switched to a more flexible intervention design and a mixed-methods quasiexperimental evaluation relying on both a qualitative analysis and an interrupted time series quantitative analysis. Cluster RCT designs may not be optimal for evaluating complex interventions to improve implementation in uncontrolled 'real world' settings. More flexible, context-sensitive evaluation designs offer a better balance of the need to adjust the intervention during the evaluation to meet implementation challenges while providing the data required to evaluate effectiveness. Our case study involved HIV care in a resource-limited setting, but these issues likely apply to complex improvement interventions in other settings.

Methodological aspects of multicenter studies with quantitative PET.

PubMed

Boellaard, Ronald

2011-01-01

Quantification of whole-body FDG PET studies is affected by many physiological and physical factors. Much of the variability in reported standardized uptake value (SUV) data seen in the literature results from the variability in methodology applied among these studies, i.e., due to the use of different scanners, acquisition and reconstruction settings, region of interest strategies, SUV normalization, and/or corrections methods. To date, the variability in applied methodology prohibits a proper comparison and exchange of quantitative FDG PET data. Consequently, the promising role of quantitative PET has been demonstrated in several monocentric studies, but these published results cannot be used directly as a guideline for clinical (multicenter) trials performed elsewhere. In this chapter, the main causes affecting whole-body FDG PET quantification and strategies to minimize its inter-institute variability are addressed.

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.

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…

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…

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.

Evidence for the impact of quality improvement collaboratives: systematic review

PubMed Central

2008-01-01

Objective To evaluate the effectiveness of quality improvement collaboratives in improving the quality of care. Data sources Relevant studies through Medline, Embase, PsycINFO, CINAHL, and Cochrane databases. Study selection Two reviewers independently extracted data on topics, participants, setting, study design, and outcomes. Data synthesis Of 1104 articles identified, 72 were included in the study. Twelve reports representing nine studies (including two randomised controlled trials) used a controlled design to measure the effects of the quality improvement collaborative intervention on care processes or outcomes of care. Systematic review of these nine studies showed moderate positive results. Seven studies (including one randomised controlled trial) reported an effect on some of the selected outcome measures. Two studies (including one randomised controlled trial) did not show any significant effect. Conclusions The evidence underlying quality improvement collaboratives is positive but limited and the effects cannot be predicted with great certainty. Considering that quality improvement collaboratives seem to play a key part in current strategies focused on accelerating improvement, but may have only modest effects on outcomes at best, further knowledge of the basic components effectiveness, cost effectiveness, and success factors is crucial to determine the value of quality improvement collaboratives. PMID:18577559

A social media intervention to improve hypoglycemia management at a multicenter hospital: a quality improvement pilot for clinical nurses.

PubMed

De Sousa, Filomena; Jackson, Jennifer; Knight, Ruth; Cloutier, Edith; Basa, Rosemary; Fourney, Anne; Devecseri, Kathleen

2018-02-01

Hypoglycemia poses significant risk to inpatients. Nursing management of hypoglycemia is a challenge, despite established best practice guidelines. Social media is an effective tool for sharing information and could overcome barriers to clinical education at a multicenter hospital. The purpose of this quality improvement intervention was to create and disseminate social media posts about best practices in hypoglycemia management. An unmatched pre-and post-survey assessed nursing knowledge of hypoglycemia management. Social media posts were created to visually outline the steps for hypoglycemia management over 2 weeks, across a nursing social media platform. We assessed the reach of the posts via Facebook and a survey. The posts reached 2962 users during the first week, and 1491 users the second week. A social media intervention can have a substantial reach and distribute information across a multicenter hospital. Additional study is needed to determine what factors could support an increase in nursing knowledge through a social media campaign.

Conjugation in multi-tetrazole derivatives: a new design direction for energetic materials.

PubMed

Sun, Shuyang; Lu, Ming

2018-06-23

Multi-tetrazole derivatives with conjugated structures were designed and investigated in this study. Using quantum chemistry methods, the crystal structures, electrostatic potentials (ESPs), multicenter bond orders, HOMO-LUMO energy gaps, and detonation properties of the derivatives were calculated. As expected, these molecules with conjugated structures showed low energies of their crystal structures, molecular layering in their crystals, high average ESPs, high multicenter bond order values, and enhanced detonation properties. The derivative 1,2-di(1H-tetrazol-5-yl)diazene (N2) was predicted to have the best density (1.87 g/cm 3 ), detonation velocity (9006 m/s), and detonation pressure (36.8 GPa) of the designed molecules, while its total crystal energy was low, suggesting that it is relatively stable. Its sensitivity was also low, as the molecular stacking that occurs in its crystal allows external forces to be dissipated into movements of crystal layers. Finally, its multicenter bond order was high, indicating a highly conjugated structure.

Cerebral near-infrared spectroscopy monitoring for prevention of brain injury in very preterm infants.

PubMed

Hyttel-Sorensen, Simon; Greisen, Gorm; Als-Nielsen, Bodil; Gluud, Christian

2017-09-04

Cerebral injury and long-term neurodevelopmental impairment is common in extremely preterm infants. Cerebral near-infrared spectroscopy (NIRS) enables continuous estimation of cerebral oxygenation. This diagnostic method coupled with appropriate interventions if NIRS is out of normal range (that is cerebral oxygenation within the 55% to 85% range) may offer benefits without causing more harms. Therefore, NIRS coupled with appropriate responses to abnormal findings on NIRS needs assessment in a systematic review of randomised clinical trials and quasi-randomised studies. To evaluate the benefits and harms of interventions that attempt to alter cerebral oxygenation guided by cerebral NIRS monitoring in order to prevent cerebral injury, improve neurological outcome, and increase survival in preterm infants born more than 8 weeks preterm. We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 8), MEDLINE via PubMed (1966 to 10 September 2016), Embase (1980 to 10 September 2016), and CINAHL (1982 to 10 September 2016). We also searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised clinical trials and quasi-randomised studies. Randomised clinical trials and quasi-randomised clinical studies comparing continuous cerebral NIRS monitoring for at least 24 hours versus blinded NIRS or versus no NIRS monitoring. Two review authors independently selected, assessed the quality of, and extracted data from the included trials and studies. If necessary, we contacted authors for further information. We conducted assessments of risks of bias; risks of design errors; and controlled the risks of random errors with Trial Sequential Analysis. We assessed the quality of the evidence with GRADE. One randomised clinical trial met inclusion criteria, including infants born more than 12 weeks preterm. The trial employed adequate methodologies and was assessed at low risk of bias. One hundred and sixty-six infants were randomised to start continuous cerebral NIRS monitoring less than 3 hours after birth until 72 hours after birth plus appropriate interventions if NIRS was out of normal range according to a guideline versus conventional monitoring with blinded NIRS. There was no effect of NIRS plus guideline of mortality until term-equivalent age (RR 0.50, 95% CI 0.29 to 1.00; one trial; 166 participants). There were no effects of NIRS plus guideline on intraventricular haemorrhages: all grades (RR 0.93, 95% CI 0.65 to 1.34; one trial; 166 participants); grade III/IV (RR 0.57, 95% CI 0.25 to 1.31; one trial; 166 participants); and cystic periventricular leukomalacia (which did not occur in either group). Likewise, there was no effect of NIRS plus guideline on the occurrence of a patent ductus arteriosus (RR 1.96, 95% CI 0.94 to 4.08; one trial; 166 participants); chronic lung disease (RR 1.27, 95% CI 0.94 to 1.50; one trial; 166 participants); necrotising enterocolitis (RR 0.83, 95% CI 0.33 to 1.94; one trial; 166 participants); and retinopathy of prematurity (RR 1.64, 95% CI 0.75 to 3.00; one trial; 166 participants). There were no serious adverse events in any of the intervention groups. NIRS plus guideline caused more skin marks from the NIRS sensor in the control group than in the experimental group (unadjusted RR 0.31, 95% CI 0.10 to 0.92; one trial; 166 participants). There are no data regarding neurodevelopmental outcome, renal impairment or air leaks.The quality of evidence for all comparisons discussed above was assessed as very low apart from all-cause mortality and adverse events: these were assessed as low and moderate, respectively. The validity of all comparisons is hampered by a small sample of randomised infants, risk of bias due to lack of blinding, and indirectness of outcomes. The only eligible randomised clinical trial did not demonstrate any consistent effects of NIRS plus a guideline on the assessed clinical outcomes. The trial was, however, only powered to detect difference in cerebral oxygenation, not morbidities or mortality. Our systematic review did not reach sufficient power to prove or disprove effects on clinical outcomes. Further randomised clinical trials with low risks of bias and low risks of random errors are needed.

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.

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

PubMed

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

2014-07-01

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

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

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.

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.

Results of a Multicenter, Randomized, Double-Masked, Placebo-Controlled Clinical Study of the Efficacy and Safety of Visomitin Eye Drops in Patients with Dry Eye Syndrome.

PubMed

Brzheskiy, Vladimir V; Efimova, Elena L; Vorontsova, Tatiana N; Alekseev, Vladimir N; Gusarevich, Olga G; Shaidurova, Ksenia N; Ryabtseva, Alla A; Andryukhina, Olga M; Kamenskikh, Tatiana G; Sumarokova, Elena S; Miljudin, Eugeny S; Egorov, Eugeny A; Lebedev, Oleg I; Surov, Alexander V; Korol, Andrii R; Nasinnyk, Illia O; Bezditko, Pavel A; Muzhychuk, Olena P; Vygodin, Vladimir A; Yani, Elena V; Savchenko, Alla Y; Karger, Elena M; Fedorkin, Oleg N; Mironov, Alexander N; Ostapenko, Victoria; Popeko, Natalia A; Skulachev, Vladimir P; Skulachev, Maxim V

2015-12-01

This article presents the results of an international, multicenter, randomized, double-masked, placebo-controlled clinical study of Visomitin (Mitotech LLC, Moscow, Russian Federation) eye drops in patients with dry eye syndrome (DES). Visomitin is the first registered (in Russia) drug with a mitochondria-targeted antioxidant (SkQ1) as the active ingredient. In this multicenter (10 sites) study of 240 subjects with DES, study drug (Visomitin or placebo) was self-administered three times daily (TID) for 6 weeks, followed by a 6-week follow-up period. Seven in-office study visits occurred every 2 weeks during both the treatment and follow-up periods. Efficacy measures included Schirmer's test, tear break-up time, fluorescein staining, meniscus height, and visual acuity. Safety measures included adverse events, slit lamp biomicroscopy, tonometry, blood pressure, and heart rate. Tolerability was also evaluated. This clinical study showed the effectiveness of Visomitin eye drops in the treatment of signs and symptoms of DES compared with placebo. The study showed that a 6-week course of TID topical instillation of Visomitin significantly improved the functional state of the cornea; Visomitin increased tear film stability and reduced corneal damage. Significant reduction of dry eye symptoms (such as dryness, burning, grittiness, and blurred vision) was also observed. Based on the results of this study, Visomitin is effective and safe for use in eye patients with DES for protection from corneal damage. Mitotech LLC.

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

PubMed

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

1993-07-01

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

The HysNiche trial: hysteroscopic resection of uterine caesarean scar defect (niche) in patients with abnormal bleeding, a randomised controlled trial.

PubMed

Vervoort, A J M W; Van der Voet, L F; Witmer, M; Thurkow, A L; Radder, C M; van Kesteren, P J M; Quartero, H W P; Kuchenbecker, W K H; Bongers, M Y; Geomini, P M A J; de Vleeschouwer, L H M; van Hooff, M H A; van Vliet, H A A M; Veersema, S; Renes, W B; van Meurs, H S; Bosmans, J; Oude Rengerink, K; Brölmann, H A M; Mol, B W J; Huirne, J A F

2015-11-12

A caesarean section (CS) can cause a defect or disruption of the myometrium at the site of the uterine scar, called a niche. In recent years, an association between a niche and postmenstrual spotting after a CS has been demonstrated. Hysteroscopic resection of these niches is thought to reduce spotting and menstrual pain. However, there are no randomised trials assessing the effectiveness of a hysteroscopic niche resection. We planned a multicentre randomised trial comparing hysteroscopic niche resection to no intervention. We study women with postmenstrual spotting after a CS and a niche with a residual myometrium of at least 3 mm during sonohysterography. After informed consent is obtained, eligible women will be randomly allocated to hysteroscopic resection of the niche or expectant management for 6 months. The primary outcome is the number of days with postmenstrual spotting during one menstrual cycle 6 months after randomisation. Secondary outcomes are menstrual characteristics, menstruation related pain and experienced discomfort due to spotting or menstrual pain, quality of life, patient satisfaction, sexual function, urological symptoms, medical consultations, medication use, complications, lost productivity and medical costs. Measurements will be performed at baseline and at 3 and 6 months after randomisation. A cost-effectiveness analysis will be performed from a societal perspective at 6 months after randomisation. This trial will provide insight in the (cost)effectiveness of hysteroscopic resection of a niche versus expectant management in women who have postmenstrual spotting and a niche with sufficient residual myometrium to perform a hysteroscopic niche resection. Dutch Trial Register NTR3269 . Registered 1 February 2012. ZonMw Grant number 80-82305-97-12030.

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

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

PubMed

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

2018-03-26

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

Effects of continuous positive airway pressure on neurocognitive architecture and function in patients with obstructive sleep apnoea: study protocol for a multicentre randomised controlled trial.

PubMed

Xu, Huajun; Wang, Hui; Guan, Jian; Yi, Hongliang; Qian, Yingjun; Zou, Jianyin; Xia, Yunyan; Fu, Yiqun; Li, Xinyi; Jiao, Xiao; Huang, Hengye; Dong, Pin; Yu, Ziwei; Yang, Jun; Xiang, Mingliang; Li, Jiping; Chen, Yanqing; Wang, Peihua; Sun, Yizhou; Li, Yuehua; Zheng, Xiaojian; Jia, Wei; Yin, Shankai

2017-05-25

Many clinical studies have indicated that obstructive sleep apnoea (OSA), the most common chronic sleep disorder, may affect neurocognitive function, and that treatment for continuous positive airway pressure (CPAP) has some neurocognitive protective effects against the adverse effects of OSA. However, the effects of CPAP treatment on neurocognitive architecture and function remain unclear. Therefore, this multicentre trial was designed to investigate whether and when neurocognitive architecture and function in patients with OSA can be improved by CPAP treatment and to explore the role of gut microbiota in improving neurocognitive function during treatment. This study will be a multicentre, randomised, controlled trial with allocation concealment and assessor blinding. A total of 148 eligible patients with moderate to severe OSA will be enrolled from five sleep centres and randomised to receive CPAP with best supportive care (BSC) intervention or BSC intervention alone. Cognitive function, structure and function of brain regions, gut microbiota, metabolites, biochemical variables, electrocardiography, echocardiography, pulmonary function and arterial stiffness will be assessed at baseline before randomisation and at 3, 6 and 12 months. This study has been approved by the Medical Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People's Hospital (approval number 2015-79). The results from this study will be published in peer-reviewed journals and at relevant conferences. NCT02886156; 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.

The effect of mobile application interventions on influencing healthy maternal behaviour and improving perinatal health outcomes: a systematic review protocol.

PubMed

Daly, Lisa M; Horey, Dell; Middleton, Philippa F; Boyle, Frances M; Flenady, Vicki

2017-02-08

Perinatal morbidity and mortality remain significant public health issues globally, with enduring impact on the health and well-being of women and their families. Pregnant women who adopt, practice and maintain healthy behaviours can potentially improve the health of themselves and their babies. Mobile applications are an increasingly popular mode of accessing, storing and sharing health information among pregnant women. The main objective of this review is to evaluate the effects of mobile application interventions during pregnancy on maternal behaviour and associated maternal and infant outcomes. This review will include randomised and non-randomised studies which tested use of mobile applications designed to improve either maternal knowledge or behaviours to address known risk factors associated with adverse perinatal health outcomes. This review will include studies which included pregnant women and/or women during birth. The search strategy will utilise a combination of keywords and MeSH terms. Literature databases such as PubMed, Embase, The Cochrane Library, CINAHL and WHO Global Health Library will be searched. Two reviewers will independently screen retrieved citations to determine if they meet inclusion criteria. Studies will be selected that provide information about interventions commenced in early pregnancy, late pregnancy or labour. Comparisons to be made include mobile applications versus interventions relying on paper-based or text-messaging-based communication; interpersonal communication such as face-to-face or telephone conversation; and no intervention or standard care. Quality assessment of included randomised studies will utilise established guidelines provided in the Cochrane Handbook for Systematic Reviews of Interventions. Quality assessment of non-randomised studies will be based on the Risk of Bias in Non-randomised Studies-of Interventions (ROBINS-I) assessment tool. Quality of the evidence will be evaluated using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Separate comparisons and analyses for primary and secondary outcomes will be performed. Results of the review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review will identify and synthesize evidence about the effect of interventions delivered through mobile applications on influencing maternal behaviour and improving perinatal health outcomes. PROSPERO CRD42016037344 .

Comparing glycaemic benefits of Active Versus passive lifestyle Intervention in kidney Allograft Recipients (CAVIAR): study protocol for a randomised controlled trial.

PubMed

Wilcox, Joanne; Waite, Chantelle; Tomlinson, Lyndsey; Driscoll, Joanne; Karim, Asra; Day, Edward; Sharif, Adnan

2016-08-22

Lifestyle modification is widely recommended to kidney allograft recipients post transplantation due to the cardiometabolic risks associated with immunosuppression including new-onset diabetes, weight gain and cardiovascular events. However, we have no actual evidence that undertaking lifestyle modification protects from any adverse outcomes post transplantation. The aim of this study is to compare whether a more proactive versus passive interventional approach to modify lifestyle is associated with superior outcomes post kidney transplantation. We designed this prospective, single-centre, open-label, randomised controlled study to compare the efficacy of active versus passive lifestyle intervention for kidney allograft recipients early post transplantation. A total of 130 eligible patients, who are stable, nondiabetic and between 3 and 24 months post kidney transplantation, will be recruited. Randomisation is being undertaken by random block permutations into passive (n = 65, leaflet guidance only) versus active lifestyle modification (n = 65, supervised intervention) over a 6-month period. Supervised intervention is being facilitated by two dietitians during the 6-month intervention period to provide continuous lifestyle intervention guidance, support and encouragement. Both dietitians are accredited with behavioural intervention skills and will utilise motivational aids to support study recruits randomised to active intervention. The primary outcome is change in abnormal glucose metabolism parameters after 6 months of comparing active versus passive lifestyle intervention. Secondary outcomes include changes in a wide array of cardiometabolic parameters, kidney allograft function and patient-reported outcome measures. Long-term tracking of patients via data linkage to electronic patient records and national registries will facilitate long-term comparison of outcomes after active versus passive lifestyle intervention beyond the 6-month intervention period. This is the first randomised controlled study to investigate the benefits of active versus passive lifestyle intervention in kidney allograft recipients for the prevention of abnormal cardiometabolic outcomes. In addition, this is the first example of utilising behaviour therapy intervention post kidney transplantation to achieve clinically beneficial outcomes, which has potential implications on many spheres of post-transplant care. This study was registered with the Clinical Trials Registry on 27 August 2014 (ClinicalTrials.org Identifier: NCT02233491 ).

A randomised controlled trial of intravenous zoledronic acid in malignant pleural disease: a proof of principle pilot study.

PubMed

Clive, Amelia O; Hooper, Clare E; Edey, Anthony J; Morley, Anna J; Zahan-Evans, Natalie; Hall, David; Lyburn, Iain; White, Paul; Braybrooke, Jeremy P; Sequeiros, Iara; Lyen, Stephen M; Milton, Tim; Kahan, Brennan C; Maskell, Nick A

2015-01-01

Animal studies have shown Zoledronic Acid (ZA) may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD). We performed a pilot study to evaluate its effects in humans. We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1) to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS) score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC) on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) from randomisation to week 5. Multiple secondary endpoints were also evaluated. Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline). At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD) 4.16 (95%CI -4.7 to 13.0)) or change in DCE-MRI iAUC (AMD -15.4 (95%CI -58.1 to 27.3). Two of nine (22%) in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo). There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9)), side effects or serious adverse event rates. This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further. UK Clinical Research Network ID 8877 ISRCTN17030426 www.isrctn.com.

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

PubMed Central

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

2014-01-01

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

Spinal Cord Injury

MedlinePlus

... A recent prospective multicenter trial called STASCIS is exploring whether performing decompression surgery early (less than 24 ... A recent prospective multicenter trial called STASCIS is exploring whether performing decompression surgery early (less than 24 ...

Evaluating multicenter DTI data in Huntington's disease on site specific effects: An ex post facto approach.

PubMed

Müller, Hans-Peter; Grön, Georg; Sprengelmeyer, Reiner; Kassubek, Jan; Ludolph, Albert C; Hobbs, Nicola; Cole, James; Roos, Raymund A C; Duerr, Alexandra; Tabrizi, Sarah J; Landwehrmeyer, G Bernhard; Süssmuth, Sigurd D

2013-01-01

Assessment of the feasibility to average diffusion tensor imaging (DTI) metrics of MRI data acquired in the course of a multicenter study. Sixty-one early stage Huntington's disease patients and forty healthy controls were studied using four different MR scanners at four European sites with acquisition protocols as close as possible to a given standard protocol. The potential and feasibility of averaging data acquired at different sites was evaluated quantitatively by region-of-interest (ROI) based statistical comparisons of coefficients of variation (CV) across centers, as well as by testing for significant group-by-center differences on averaged fractional anisotropy (FA) values between patients and controls. In addition, a whole-brain based statistical between-group comparison was performed using FA maps. The ex post facto statistical evaluation of CV and FA-values in a priori defined ROIs showed no differences between sites above chance indicating that data were not systematically biased by center specific factors. Averaging FA-maps from DTI data acquired at different study sites and different MR scanner types does not appear to be systematically biased. A suitable recipe for testing on the possibility to pool multicenter DTI data is provided to permit averaging of DTI-derived metrics to differentiate patients from healthy controls at a larger scale.

Use of psi(alpha)-ETOs in the unified treatment of electronic attraction, electric field and electric field gradient multicenter integrals of screened Coulomb potentials over Slater orbitals.

PubMed

Guseinov, Israfil

2004-02-01

In this study, using complete orthonormal sets of Psi(alpha)-ETOs (where alpha=1, 0, -1, -2, ...) introduced by the author, a large number of series expansion formulae for the multicenter electronic attraction (EA), electric field (EF) and electric field gradient (EFG) integrals of the Yukawa-like screened Coulomb potentials (SCPs) is presented through the new central and noncentral potentials and the overlap integrals with the same screening constants. The final results obtained are valid for arbitrary locations of STOs and their parameters.

Frontal fibrosing alopecia: a multicenter review of 355 patients.

PubMed

Vañó-Galván, Sergio; Molina-Ruiz, Ana M; Serrano-Falcón, Cristina; Arias-Santiago, Salvador; Rodrigues-Barata, Ana R; Garnacho-Saucedo, Gloria; Martorell-Calatayud, Antonio; Fernández-Crehuet, Pablo; Grimalt, Ramón; Aranegui, Beatriz; Grillo, Emiliano; Diaz-Ley, Blanca; Salido, Rafael; Pérez-Gala, Sivia; Serrano, Salvio; Moreno, Jose Carlos; Jaén, Pedro; Camacho, Francisco M

2014-04-01

To our knowledge, there are no large multicenter studies concerning frontal fibrosing alopecia (FFA) that could give clues about its pathogenesis and best treatment. We sought to describe the epidemiology, comorbidities, clinical presentation, diagnostic findings, and therapeutic choices in a large series of patients with FFA. This retrospective multicenter study included patients given the diagnosis of FFA. Clinical severity was classified based on the recession of the frontotemporal hairline. In all, 355 patients (343 women [49 premenopausal] and 12 men) with a mean age of 61 years (range 23-86) were included. Early menopause was detected in 49 patients (14%), whereas 46 (13%) had undergone hysterectomy. Severe FFA was observed in 131 patients (37%). Independent factors associated with severe FFA after multivariate analysis were: eyelash loss, facial papules, and body hair involvement. Eyebrow loss as the initial clinical presentation was associated with mild forms. Antiandrogens such as finasteride and dutasteride were used in 111 patients (31%), with improvement in 52 (47%) and stabilization in 59 (53%). The retrospective design is a limitation. Eyelash loss, facial papules, and body hair involvement were associated with severe FFA. Antiandrogens were the most useful treatment. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Adjusted regression trend test for a multicenter clinical trial.

PubMed

Quan, H; Capizzi, T

1999-06-01

Studies using a series of increasing doses of a compound, including a zero dose control, are often conducted to study the effect of the compound on the response of interest. For a one-way design, Tukey et al. (1985, Biometrics 41, 295-301) suggested assessing trend by examining the slopes of regression lines under arithmetic, ordinal, and arithmetic-logarithmic dose scalings. They reported the smallest p-value for the three significance tests on the three slopes for safety assessments. Capizzi et al. (1992, Biometrical Journal 34, 275-289) suggested an adjusted trend test, which adjusts the p-value using a trivariate t-distribution, the joint distribution of the three slope estimators. In this paper, we propose an adjusted regression trend test suitable for two-way designs, particularly for multicenter clinical trials. In a step-down fashion, the proposed trend test can be applied to a multicenter clinical trial to compare each dose with the control. This sequential procedure is a closed testing procedure for a trend alternative. Therefore, it adjusts p-values and maintains experimentwise error rate. Simulation results show that the step-down trend test is overall more powerful than a step-down least significant difference test.

[Attaching importance to study on acute health risk assessment and adaptation of air pollution and climate change].

PubMed

Shi, X M

2017-03-10

Air pollution and climate change have become key environmental and public health problems around the world, which poses serious threat to human health. How to assess and mitigate the health risks and increase the adaptation of the public have become an urgent topic of research in this area. The six papers in this issue will provide important and rich information on design, analysis method, indicator selection and setting about acute health risk assessment and adaptation study of air pollution and climate change in China, reflecting the advanced conceptions of multi-center and area-specific study and multi-pollutant causing acute effect study. However, the number and type of the cities included in these studies were still limited. In future, researchers should further expand detailed multi-center and multi-area study coverage, conduct area specific predicting and early warning study and strengthen adaptation study.

Vedolizumab provides clinical benefit over 1 year in patients with active inflammatory bowel disease - a prospective multicenter observational study.

PubMed

Stallmach, A; Langbein, C; Atreya, R; Bruns, T; Dignass, A; Ende, K; Hampe, J; Hartmann, F; Neurath, M F; Maul, J; Preiss, J C; Schmelz, R; Siegmund, B; Schulze, H; Teich, N; von Arnim, U; Baumgart, D C; Schmidt, C

2016-12-01

Vedolizumab, a monoclonal antibody targeting the α4β7-integrin, is effective in inducing and maintaining clinical remission in Crohn's disease and ulcerative colitis according to randomised clinical trials. To determine the long-term effectiveness of vedolizumab in a real-world clinical setting. This observational registry assessed the clinical outcome in patients treated with vedolizumab for clinically active Crohn's disease (n = 67) or ulcerative colitis (n = 60). Primary endpoint was clinical remission (HBI ≤ 4/pMayo ≤ 1) at week 54. Secondary endpoints included clinical response rates (HBI/pMayo score drop ≥3) and steroid-free clinical remission at weeks 30 and 54. Vedolizumab was stopped in 69/127 (56%) patients after a median time of 18 weeks (range 2-49) predominantly owing to lack or loss of response. Using nonresponder imputation analysis, clinical remission and steroid-free remission rates were 21% and 15% in Crohn's disease and 25% and 22% in ulcerative colitis, respectively. Lack of clinical remission was associated with prior treatment with anti-TNF or with steroids for more than 3 months in the last 6 months in ulcerative colitis. At week 14, the absence of remission in Crohn's disease or nonresponse in ulcerative colitis indicated a low likelihood of clinical remission at week 54 [2/31 (7%) in Crohn's disease, 4/41 (10%) in ulcerative colitis]. Accordingly, declining C-reactive protein in inflammatory bowel disease and/or lower faecal calprotectin in ulcerative colitis at week 14 predicted remission at week 54. Among patients who started vedolizumab for active inflammatory bowel disease, clinical remission rates are 21-25% after 54 weeks. © 2016 John Wiley & Sons Ltd.

Finding atrial fibrillation in stroke patients: Randomized evaluation of enhanced and prolonged Holter monitoring--Find-AF(RANDOMISED) --rationale and design.

PubMed

Weber-Krüger, Mark; Gelbrich, Götz; Stahrenberg, Raoul; Liman, Jan; Kermer, Pawel; Hamann, Gerhard F; Seegers, Joachim; Gröschel, Klaus; Wachter, Rolf

2014-10-01

Detecting paroxysmal atrial fibrillation (AF) in patients with ischemic strokes presenting in sinus rhythm is challenging because episodes are often short, occur randomly, and are frequently asymptomatic. If AF is detected, recurrent thromboembolism can be prevented efficiently by oral anticoagulation. Numerous uncontrolled studies using various electrocardiogram (ECG) devices have established that prolonged ECG monitoring increases the yield of AF detection, but most established procedures are time-consuming and costly. The few randomized trials are mostly limited to cryptogenic strokes. The optimal method, duration, and patient selection remain unclear. Repeated prolonged continuous Holter ECG monitoring to detect paroxysmal AF within an unspecific stroke population may prove to be a widely applicable, effective secondary prevention strategy. Find-AFRANDOMISED is a randomized and controlled prospective multicenter trial. Four hundred patients 60 years or older with manifest (symptoms ≥24 hours or acute computed tomography/magnetic resonance imaging lesion) and acute (symptoms ≤7 days) ischemic strokes will be included at 4 certified stroke centers in Germany. Those with previously diagnosed AF/flutter, indications/contraindications for oral anticoagulation, or obvious causative blood vessel pathologies will be excluded. Patients will be randomized 1:1 to either enhanced and prolonged Holter ECG monitoring (10 days at baseline and after 3 and 6 months) or standard of care (≥24-hour continuous ECG monitoring, according to current stroke guidelines). All patients will be followed up for at least 12 months. The primary end point is newly detected AF (≥30 seconds) after 6 months, confirmed by an independent adjudication committee. We plan to complete recruitment in autumn 2014. First results can be expected by spring 2016. Copyright © 2014 Mosby, Inc. All rights reserved.

The use of a biologic topical haemostatic agent (TachoSil(®)) for the prevention of postoperative bleeding in patients on antithrombotic therapy undergoing thyroid surgery: A randomised controlled pilot trial.

PubMed

Erdas, Enrico; Medas, Fabio; Podda, Francesco; Furcas, Silvia; Pisano, Giuseppe; Nicolosi, Angelo; Calò, Pietro Giorgio

2015-08-01

Anticoagulants and antiplatelet agents are well-known risk factors for post-operative bleeding. The aim of this prospective, randomized pilot study was to evaluate the effectiveness of a topical haemostatic agent, namely TachoSil, for the prevention of postoperative bleeding in patients on antithrombotic therapy undergoing thyroidectomy. Perioperative management and some distinctive aspects of cervical haematomas were also discussed. Between January 2012 and May 2014, all patients taking vitamin K antagonists (VKAs) or acetyl salicylic acid (ASA) scheduled for total thyroidectomy were enrolled and randomly allocated to group 1 (standard haemostasis) and group 2 (standard haemostasis + TachoSil). Antithrombotic drugs were always suspended prior to surgery and, when indicated, replaced by bridging anticoagulation with low-molecular-weight heparin. The primary endpoint was the incidence of postoperative cervical haematomas. A total of 70 patients were included in the study, representing 8.5% (70/820) of all patients who underwent thyroidectomies in the same period. The overall rate of post-operative cervical haematoma was 7.1% (5/70) and reached 14.8% (4/27) in patients on VKA therapy. All but one occurred more than 24 h after surgery (32nd hour, 8th, 10th, and 13th days). Group 1 (37 patients) and group 2 (33 patients) were well-matched according to clinical and demographic features. Postoperative haematoma was observed in 2/37 patients (5.4%) recruited in the Group 1 and 3/33 patients (9.1%) recruited in the Group 2 (P = 0.661). Patients taking antithrombotic drugs represent a major problem in thyroid surgery. The incidence of bleeding after thyroidectomy is significantly high and the use of TachoSil do not seem effective in preventing its occurrence. However, larger multicenter study is needed to confirm these results. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

CASINO: surgical or nonsurgical treatment for cervical radiculopathy, a randomised controlled trial.

PubMed

van Geest, Sarita; Kuijper, Barbara; Oterdoom, Marinus; van den Hout, Wilbert; Brand, Ronald; Stijnen, Theo; Assendelft, Pim; Koes, Bart; Jacobs, Wilco; Peul, Wilco; Vleggeert-Lankamp, Carmen

2014-04-14

Cervical radicular syndrome (CRS) due to a herniated disc can be safely treated by surgical decompression of the spinal root. In the vast majority of cases this relieves pain in the arm and restores function. However, conservative treatment also has a high chance on relieving symptoms. The objective of the present study is to evaluate the (cost-) effectiveness of surgery versus prolonged conservative care during one year of follow-up, and to evaluate the timing of surgery. Predisposing factors in favour of one of the two treatments will be evaluated. Patients with disabling radicular arm pain, suffering for at least 2 months, and an MRI-proven herniated cervical disc will be randomised to receive either surgery or prolonged conservative care with surgery if needed. The surgical intervention will be an anterior discectomy or a posterior foraminotomy that is carried out according to usual care. Surgery will take place within 2-4 weeks after randomisation. Conservative care starts immediately after randomisation. The primary outcome measure is the VAS for pain or tingling sensations in the arm one year after randomisation. In addition, timing of surgery will be studied by correlating the primary outcome to the duration of symptoms. Secondary outcome measures encompass quality of life, costs and perceived recovery. Predefined prognostic factors will be evaluated. The total follow-up period will cover two years. A sample size of 400 patients is needed. Statistical analysis will be performed using a linear mixed model which will be based on the 'intention to treat' principle. In addition, a new CRS questionnaire for patients will be developed, the Leiden Cervical Radicular Syndrome Functioning (LCRSF) scale. The outcome will contribute to better decision making for the treatment of cervical radicular syndrome. NTR3504.

Non-invasive versus invasive management in patients with prior coronary artery bypass surgery with a non-ST segment elevation acute coronary syndrome: study design of the pilot randomised controlled trial and registry (CABG-ACS)

PubMed Central

Lee, Matthew M Y; Petrie, Mark C; Rocchiccioli, Paul; Simpson, Joanne; Jackson, Colette; Brown, Ammani; Corcoran, David; Mangion, Kenneth; McEntegart, Margaret; Shaukat, Aadil; Rae, Alan; Hood, Stuart; Peat, Eileen; Findlay, Iain; Murphy, Clare; Cormack, Alistair; Bukov, Nikolay; Balachandran, Kanarath; Papworth, Richard; Ford, Ian; Briggs, Andrew; Berry, Colin

2016-01-01

Introduction There is an evidence gap about how to best treat patients with prior coronary artery bypass grafts (CABGs) presenting with non-ST segment elevation acute coronary syndromes (NSTE-ACS) because historically, these patients were excluded from pivotal randomised trials. We aim to undertake a pilot trial of routine non-invasive management versus routine invasive management in patients with NSTE-ACS with prior CABG and optimal medical therapy during routine clinical care. Our trial is a proof-of-concept study for feasibility, safety, potential efficacy and health economic modelling. We hypothesise that a routine invasive approach in patients with NSTE-ACS with prior CABG is not superior to a non-invasive approach with optimal medical therapy. Methods and analysis 60 patients will be enrolled in a randomised clinical trial in 4 hospitals. A screening log will be prospectively completed. Patients not randomised due to lack of eligibility criteria and/or patient or physician preference and who give consent will be included in a registry. We will gather information about screening, enrolment, eligibility, randomisation, patient characteristics and adverse events (including post-discharge). The primary efficacy outcome is the composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction and hospitalisation for heart failure. The primary safety outcome is the composite of bleeding, stroke, procedure-related myocardial infarction and worsening renal function. Health status will be assessed using EuroQol 5 Dimensions (EQ-5D) assessed at baseline and 6 monthly intervals, for at least 18 months. Trial registration number NCT01895751 (ClinicalTrials.gov). PMID:27110377

Testing the methodology for dosimetry audit of heterogeneity corrections and small MLC-shaped fields: Results of IAEA multi-center studies

PubMed Central

Izewska, Joanna; Wesolowska, Paulina; Azangwe, Godfrey; Followill, David S.; Thwaites, David I.; Arib, Mehenna; Stefanic, Amalia; Viegas, Claudio; Suming, Luo; Ekendahl, Daniela; Bulski, Wojciech; Georg, Dietmar

2016-01-01

Abstract The International Atomic Energy Agency (IAEA) has a long tradition of supporting development of methodologies for national networks providing quality audits in radiotherapy. A series of co-ordinated research projects (CRPs) has been conducted by the IAEA since 1995 assisting national external audit groups developing national audit programs. The CRP ‘Development of Quality Audits for Radiotherapy Dosimetry for Complex Treatment Techniques’ was conducted in 2009–2012 as an extension of previously developed audit programs. Material and methods. The CRP work described in this paper focused on developing and testing two steps of dosimetry audit: verification of heterogeneity corrections, and treatment planning system (TPS) modeling of small MLC fields, which are important for the initial stages of complex radiation treatments, such as IMRT. The project involved development of a new solid slab phantom with heterogeneities containing special measurement inserts for thermoluminescent dosimeters (TLD) and radiochromic films. The phantom and the audit methodology has been developed at the IAEA and tested in multi-center studies involving the CRP participants. Results. The results of multi-center testing of methodology for two steps of dosimetry audit show that the design of audit procedures is adequate and the methodology is feasible for meeting the audit objectives. A total of 97% TLD results in heterogeneity situations obtained in the study were within 3% and all results within 5% agreement with the TPS predicted doses. In contrast, only 64% small beam profiles were within 3 mm agreement between the TPS calculated and film measured doses. Film dosimetry results have highlighted some limitations in TPS modeling of small beam profiles in the direction of MLC leave movements. Discussion. Through multi-center testing, any challenges or difficulties in the proposed audit methodology were identified, and the methodology improved. Using the experience of these studies, the participants could incorporate the auditing procedures in their national programs. PMID:26934916

Multicenter Evaluation Of Coronary Dual-Source CT angiography in patients with intermediate Risk of Coronary Artery Stenoses (MEDIC): study design and rationale.

PubMed

Marwan, Mohamed; Hausleiter, Jörg; Abbara, Suhny; Hoffmann, Udo; Becker, Christoph; Ovrehus, Kristian; Ropers, Dieter; Bathina, Ravi; Berman, Dan; Anders, Katharina; Uder, Michael; Meave, Aloha; Alexánderson, Erick; Achenbach, Stephan

2014-01-01

The diagnostic performance of multidetector row CT to detect coronary artery stenosis has been evaluated in numerous single-center studies, with only limited data from large cohorts with low-to-intermediate likelihood of coronary disease and in multicenter trials. The Multicenter Evaluation of Coronary Dual-Source CT Angiography in Patients with Intermediate Risk of Coronary Artery Stenoses (MEDIC) trial determines the accuracy of dual-source CT (DSCT) to identify persons with at least 1 coronary artery stenosis among patients with low-to-intermediate pretest likelihood of disease. The MEDIC trial was designed as a prospective, multicenter, international trial to evaluate the diagnostic performance of DSCT for the detection of coronary artery stenosis compared with invasive coronary angiography. The study includes 8 sites in Germany, India, Mexico, the United States, and Denmark. The study population comprises patients referred for a diagnostic coronary angiogram because of suspected coronary artery disease with an intermediate pretest likelihood as determined by sex, age, and symptoms. All evaluations are performed by blinded core laboratory readers. The primary outcome of the MEDIC trial is the accuracy of DSCT to identify the presence of coronary artery stenoses with a luminal diameter narrowing of 50% or more on a per-vessel basis. Secondary outcome parameters include per-patient and per-segment diagnostic accuracy for 50% stenoses and accuracy to identify stenoses of 70% or more. Furthermore, secondary outcome parameters include the influence of heart rate, Agatston score, body weight, body mass index, image quality, and diagnostic confidence on the accuracy to detect coronary artery stenoses >50% on a per-vessel basis. The results of the MEDIC trial will assess the clinical utility of coronary CT angiography in the evaluation of patients with intermediate pretest likelihood of coronary artery disease. Copyright © 2014 Society of Cardiovascular Computed Tomography. All rights reserved.

Diagnostic performance of computed tomography coronary angiography (from the Prospective National Multicenter Multivendor EVASCAN Study).

PubMed

Gueret, Pascal; Deux, Jean-François; Bonello, Laurent; Sarran, Anthony; Tron, Christophe; Christiaens, Luc; Dacher, Jean-Nicolas; Bertrand, David; Leborgne, Laurent; Renard, Cedric; Caussin, Christophe; Cluzel, Philippe; Helft, Gerard; Crochet, Dominique; Vernhet-Kovacsik, Hélène; Chabbert, Valérie; Ferrari, Emile; Gilard, Martine; Willoteaux, Serge; Furber, Alain; Barone-Rochette, Gilles; Jankowski, Adrien; Douek, Philippe; Mousseaux, Elie; Sirol, Marc; Niarra, Ralph; Chatellier, Gilles; Laissy, Jean-Pierre

2013-02-15

Computed tomographic coronary angiography (CTCA) has been proposed as a noninvasive test for significant coronary artery disease (CAD), but only limited data are available from prospective multicenter trials. The goal of this study was to establish the diagnostic accuracy of CTCA compared to coronary angiography (CA) in a large population of symptomatic patients with clinical indications for coronary imaging. This national, multicenter study was designed to prospectively evaluate stable patients able to undergo CTCA followed by conventional CA. Data from CTCA and CA were analyzed in a blinded fashion at central core laboratories. The main outcome was the evaluation of patient-, vessel-, and segment-based diagnostic performance of CTCA to detect or rule out significant CAD (≥50% luminal diameter reduction). Of 757 patients enrolled, 746 (mean age 61 ± 12 years, 71% men) were analyzed. They underwent CTCA followed by CA 1.7 ± 0.8 days later using a 64-detector scanner. The prevalence of significant CAD in native coronary vessels by CA was 54%. The rate of nonassessable segments by CTCA was 6%. In a patient-based analysis, sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of CTCA were 91%, 50%, 68%, 83%, 1.82, and 0.18, respectively. The strongest predictors of false-negative results on CTCA were high estimated pretest probability of CAD (odds ratio [OR] 1.97, p <0.001), male gender (OR 1.5, p <0.002), diabetes (OR 1.5, p <0.0001), and age (OR 1.2, p <0.0001). In conclusion, in this large multicenter study, CTCA identified significant CAD with high sensitivity. However, in routine clinical practice, each patient should be individually evaluated, and the pretest probability of obstructive CAD should be taken into account when deciding which method, CTCA or CA, to use to diagnose its presence and severity. Copyright © 2013 Elsevier Inc. All rights reserved.

Testing the methodology for dosimetry audit of heterogeneity corrections and small MLC-shaped fields: Results of IAEA multi-center studies.

PubMed

Izewska, Joanna; Wesolowska, Paulina; Azangwe, Godfrey; Followill, David S; Thwaites, David I; Arib, Mehenna; Stefanic, Amalia; Viegas, Claudio; Suming, Luo; Ekendahl, Daniela; Bulski, Wojciech; Georg, Dietmar

2016-07-01

The International Atomic Energy Agency (IAEA) has a long tradition of supporting development of methodologies for national networks providing quality audits in radiotherapy. A series of co-ordinated research projects (CRPs) has been conducted by the IAEA since 1995 assisting national external audit groups developing national audit programs. The CRP 'Development of Quality Audits for Radiotherapy Dosimetry for Complex Treatment Techniques' was conducted in 2009-2012 as an extension of previously developed audit programs. The CRP work described in this paper focused on developing and testing two steps of dosimetry audit: verification of heterogeneity corrections, and treatment planning system (TPS) modeling of small MLC fields, which are important for the initial stages of complex radiation treatments, such as IMRT. The project involved development of a new solid slab phantom with heterogeneities containing special measurement inserts for thermoluminescent dosimeters (TLD) and radiochromic films. The phantom and the audit methodology has been developed at the IAEA and tested in multi-center studies involving the CRP participants. The results of multi-center testing of methodology for two steps of dosimetry audit show that the design of audit procedures is adequate and the methodology is feasible for meeting the audit objectives. A total of 97% TLD results in heterogeneity situations obtained in the study were within 3% and all results within 5% agreement with the TPS predicted doses. In contrast, only 64% small beam profiles were within 3 mm agreement between the TPS calculated and film measured doses. Film dosimetry results have highlighted some limitations in TPS modeling of small beam profiles in the direction of MLC leave movements. Through multi-center testing, any challenges or difficulties in the proposed audit methodology were identified, and the methodology improved. Using the experience of these studies, the participants could incorporate the auditing procedures in their national programs.

Long-Term Renal Function Recovery following Radical Nephrectomy for Kidney Cancer: Results from a Multicenter Confirmatory Study.

PubMed

Zabor, Emily C; Furberg, Helena; Lee, Byron; Campbell, Steven; Lane, Brian R; Thompson, R Houston; Antonio, Elvis Caraballo; Noyes, Sabrina L; Zaid, Harras; Jaimes, Edgar A; Russo, Paul

2018-04-01

We sought to confirm the findings from a previous single institution study of 572 patients from Memorial Sloan Kettering Cancer Center in which we found that 49% of patients recovered to the preoperative estimated glomerular filtration rate within 2 years following radical nephrectomy for renal cell carcinoma. A multicenter retrospective study was performed in 1,928 patients using data contributed from 3 independent centers. The outcome of interest was postoperative recovery to the preoperative estimated glomerular filtration rate. Data were analyzed using cumulative incidence and competing risks regression with death from any cause treated as a competing event. This study demonstrated that 45% of patients had recovered to the preoperative estimated glomerular filtration rate by 2 years following radical nephrectomy. Furthermore, this study confirmed that recovery of renal function differed according to preoperative renal function such that patients with a lower preoperative estimated glomerular filtration rate had an increased chance of recovery. This study also suggested that larger tumor size and female gender were significantly associated with an increased chance of renal function recovery. In this multicenter retrospective study we confirmed that in the long term a large proportion of patients recover to preoperative renal function following radical nephrectomy for kidney tumors. Recovery is more likely among those with a lower preoperative estimated glomerular filtration rate. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Simplified follow-up after medical abortion using a low-sensitivity urinary pregnancy test and a pictorial instruction sheet in Rajasthan, India--study protocol and intervention adaptation of a randomised control trial.

PubMed

Paul, Mandira; Iyengar, Kirti; Iyengar, Sharad; Gemzell-Danielsson, Kristina; Essén, Birgitta; Klingberg-Allvin, Marie

2014-08-15

The World Health Organisation suggests that simplification of the medical abortion regime will contribute to an increased acceptability of medical abortion, among women as well as providers. It is expected that a home-based follow-up after a medical abortion will increase the willingness to opt for medical abortion as well as decrease the workload and service costs in the clinic. This study protocol describes a study that is a randomised, controlled, non-superiority trial. Women screened to participate in the study are those with unwanted pregnancies and gestational ages equal to or less than nine weeks. The randomisation list will be generated using a computerized random number generator and opaque sealed envelopes with group allocation will be prepared. Randomization of the study participants will occur after the first clinical encounter with the doctor. Eligible women randomised to the home-based assessment group will use a low-sensitivity pregnancy test and a pictorial instruction sheet at home, while the women in the clinic follow-up group will return to the clinic for routine follow-up carried out by a doctor. The primary objective of the study this study protocol describes is to evaluate the efficacy of home-based assessment using a low-sensitivity pregnancy test and a pictorial instruction sheet 10-14 days after an early medical abortion. Providers or research assistants will not be blinded during outcome assessment. To ensure feasibility of the self-assessment intervention an adaption phase took place at the selected study sites before study initiation. This resulted in an optimized, tailor-made intervention and in the development of the pictorial instruction sheet with a guide on how to use the low-sensitivity pregnancy test and the danger signs after a medical abortion. In this paper, we will describe the study protocol for a randomised control trial investigating the efficacy of simplified follow-up in terms of home-based assessment, 10-14 days after a medical abortion. Moreover, a description of the adaptation phase is included for a better understanding of the implementation of the intervention in a setting where literacy is low and the road-connections are poor. Clinicaltrials.gov NCT01827995. Registered 04 May 2013.

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

PubMed Central

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

2009-01-01

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

Maternal positions and mobility during first stage labour

PubMed Central

Lawrence, Annemarie; Lewis, Lucy; Hofmeyr, G Justus; Dowswell, Therese; Styles, Cathy

2014-01-01

Background It is more common for women in the developed world, and those in low-income countries giving birth in health facilities, to labour in bed. There is no evidence that this is associated with any advantage for women or babies, although it may be more convenient for staff. Observational studies have suggested that if women lie on their backs during labour this may have adverse effects on uterine contractions and impede progress in labour. Objectives The purpose of the review is to assess the effects of encouraging women to assume different upright positions (including walking, sitting, standing and kneeling) versus recumbent positions (supine, semi-recumbent and lateral) for women in the first stage of labour on length of labour, type of delivery and other important outcomes for mothers and babies. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (November 2008). Selection criteria Randomised and quasi-randomised trials comparing women randomised to upright versus recumbent positions in the first stage of labour. Data collection and analysis We used methods described in the Cochrane Handbook for Systematic Reviews of Interventions for carrying out data collection, assessing study quality and analysing results. A minimum of two review authors independently assessed each study. Main results The review includes 21 studies with a total of 3706 women. Overall, the first stage of labour was approximately one hour shorter for women randomised to upright as opposed to recumbent positions (MD −0.99, 95% CI −1.60 to −0.39). Women randomised to upright positions were less likely to have epidural analgesia (RR 0.83 95% CI 0.72 to 0.96).There were no differences between groups for other outcomes including length of the second stage of labour, mode of delivery, or other outcomes related to the wellbeing of mothers and babies. For women who had epidural analgesia there were no differences between those randomised to upright versus recumbent positions for any of the outcomes examined in the review. Little information on maternal satisfaction was collected, and none of the studies compared different upright or recumbent positions. Authors’ conclusions There is evidence that walking and upright positions in the first stage of labour reduce the length of labour and do not seem to be associated with increased intervention or negative effects on mothers’ and babies’ wellbeing. Women should be encouraged to take up whatever position they find most comfortable in the first stage of labour. PMID:19370591

The effectiveness and safety of amisulpride in Chinese patients with schizophrenia: An 8‐week, prospective, open‐label, multicenter, single‐arm study

PubMed Central

Liang, Ying; Cao, Changan; Zhu, Cheng; Wang, Chuanyue; Zhang, Congpei; Dong, Fang; Yang, Fude; Deng, Hong; Yu, Jingjie; Tang, Jisheng; Su, Lei; Xin, Limin; Hong, Ling; Gao, Minglong; Tang, Muni; Xie, Shiping; Lu, Shuiping; Liu, Tiebang; Xu, Xiaojin; Wang, Xijin; Li, Xuanzi; Wang, Xueyi; Li, Yi; Zhang, Yong; Chen, Zhiyu

2016-01-01

Abstract Introduction This study evaluated the effectiveness and safety of amisulpride in Chinese schizophrenia patients. Methods A multicenter, single‐arm Phase IV study (NCT01795183). Chinese patients with schizophrenia received amisulpride for 8 weeks. The primary endpoint was ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. Results A total of 316 patients were enrolled; 295 were included in the effectiveness analysis; 66.8% (197/295) achieved ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. Nine patients discontinued treatment because of adverse events. Discussion Amisulpride had clinical effectiveness and was relatively well tolerated in Chinese patients with schizophrenia. PMID:27020720

Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial.

PubMed

Ferreri, Andrés J M; Cwynarski, Kate; Pulczynski, Elisa; Fox, Christopher P; Schorb, Elisabeth; La Rosée, Paul; Binder, Mascha; Fabbri, Alberto; Torri, Valter; Minacapelli, Eleonora; Falautano, Monica; Ilariucci, Fiorella; Ambrosetti, Achille; Roth, Alexander; Hemmaway, Claire; Johnson, Peter; Linton, Kim M; Pukrop, Tobias; Sønderskov Gørløv, Jette; Balzarotti, Monica; Hess, Georg; Keller, Ulrich; Stilgenbauer, Stephan; Panse, Jens; Tucci, Alessandra; Orsucci, Lorella; Pisani, Francesco; Levis, Alessandro; Krause, Stefan W; Schmoll, Hans J; Hertenstein, Bernd; Rummel, Mathias; Smith, Jeffery; Pfreundschuh, Michael; Cabras, Giuseppina; Angrilli, Francesco; Ponzoni, Maurilio; Deckert, Martina; Politi, Letterio S; Finke, Jürgen; Reni, Michele; Cavalli, Franco; Zucca, Emanuele; Illerhaus, Gerald

2017-11-01

The International Extranodal Lymphoma Study Group-32 (IELSG32) trial is an international randomised phase 2 study that addresses two key clinical questions in the treatment of patients with newly diagnosed primary CNS lymphoma. Results of the first randomisation have demonstrated that methotrexate, cytarabine, thiotepa, and rituximab (called the MATRix regimen) is the induction combination associated with significantly better outcome compared with the other induction combinations tested. Here, we report the results of the second randomisation that addresses the efficacy of myeloablative chemotherapy supported by autologous stem-cell transplantation (ASCT), as an alternative to whole-brain radiotherapy (WBRT), as consolidation after high-dose-methotrexate-based chemoimmunotherapy. HIV-negative patients (aged 18-70 years) with newly diagnosed primary CNS lymphoma and an Eastern Cooperative Oncology Group performance status of 0-3 were randomly assigned to receive four courses of methotrexate 3·5 g/m 2 on day 1 plus cytarabine 2 g/m 2 twice daily on days 2 and 3 (group A); or the same combination plus two doses of rituximab 375 mg/m 2 on days -5 and 0 (group B); or the same methotrexate-cytarabine-rituximab combination plus thiotepa 30 mg/m 2 on day 4 (group C), with the three groups repeating treatment every 3 weeks. Patients with responsive or stable disease after induction treatment, with adequate autologous peripheral blood stem-cell collection, and without persistent iatrogenic side-effects, were eligible for the second randomisation between WBRT (photons of 4-10 MeV; five fractions per week; fraction size 180 cGy; started within 4 weeks from the last induction course; group D) and carmustine-thiotepa conditioned ASCT (carmustine 400 mg/m 2 on day -6, and thiotepa 5 mg/kg every 12 h on days -5 and -4, followed by reinfusion of autologous peripheral blood stem cells; group E). A permuted block randomised design was adopted for both randomisations, and a computer-generated randomisation list was used within each stratum. No masking after assignment to intervention was adopted. The primary endpoint was 2-year progression-free survival, with induction group and response to induction chemotherapy as stratification parameters. Analyses were done on a modified intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT01011920. Between Feb 19, 2010, and Aug 27, 2014, 227 patients were recruited from 53 centres in five countries. 219 of 227 enrolled patients were assessable. Of the 122 patients eligible for the second randomisation, 118 patients were randomly assigned to WBRT or ASCT (59 patients per group) and constitute the study population. WBRT and ASCT were both effective, and achieved the predetermined efficacy threshold of at least 40 progression-free survivors at 2 years among the first 52 patients in both groups D and E. There were no significant differences in 2-year progression-free survival between WBRT and ASCT: 80% (95% CI 70-90) in group D and 69% (59-79) in group E (hazard ratio 1·50, 95% CI 0·83-2·71; p=0·17). Both consolidation therapies were well tolerated. Grade 4 non-haematological toxicity was uncommon; as expected, haematological toxicity was more common in patients treated with ASCT than in those who received WBRT. Two toxic deaths (infections) were recorded, both in patients who received ASCT. WBRT and ASCT are both feasible and effective as consolidation therapies after high-dose methotrexate-based chemoimmunotherapy in patients aged 70 years or younger with primary CNS lymphoma. The risks and implications of cognitive impairment after WBRT should be considered at the time of therapeutic decision. Agenzia Italiana del Farmaco, Cancer Research UK, Oncosuisse, and Swiss National Science Foundation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of the Cancer Prevention and Control Research Network

PubMed Central

Ribisl, Kurt M.; Fernandez, Maria E.; Friedman, Daniela B.; Hannon, Peggy; Leeman, Jennifer; Moore, Alexis; Olson, Lindsay; Ory, Marcia; Risendal, Betsy; Sheble, Laura; Taylor, Vicky; Williams, Rebecca; Weiner, Bryan J.

2018-01-01

The Cancer Prevention and Control Research Network (CPCRN) is a thematic network dedicated to accelerating the adoption of evidence-based cancer prevention and control practices in communities by advancing dissemination and implementation science. Funded by the Centers for Disease Control and Prevention and National Cancer Institute, CPCRN has operated at two levels: Each participating Network Center conducts research projects with primarily local partners as well as multicenter collaborative research projects with state and national partners. Through multicenter collaboration, thematic networks leverage the expertise, resources, and partnerships of participating centers to conduct research projects collectively that might not be feasible individually. Although multicenter collaboration often is advocated, it is challenging to promote and assess. Using bibliometric network analysis and other graphical methods, this paper describes CPCRN’s multicenter publication progression from 2004 to 2014. Searching PubMed, Scopus, and Web of Science in 2014 identified 249 peer-reviewed CPCRN publications involving two or more centers out of 6,534 total. The research and public health impact of these multicenter collaborative projects initiated by CPCRN during that 10-year period were then examined. CPCRN established numerous workgroups around topics such as: 2-1-1, training and technical assistance, colorectal cancer control, federally qualified health centers, cancer survivorship, and human papillomavirus. The paper discusses the challenges that arise in promoting multicenter collaboration and the strategies that CPCRN uses to address those challenges. The lessons learned should broadly interest those seeking to promote multisite collaboration to address public health problems, such as cancer prevention and control. PMID:28215371

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

PubMed

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

2013-06-27

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

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.

Rationale and design of a randomised clinical trial comparing vascular closure device and manual compression to achieve haemostasis after diagnostic coronary angiography: the Instrumental Sealing of ARterial puncture site - CLOSURE device versus manual compression (ISAR-CLOSURE) trial.

PubMed

Xhepa, Erion; Byrne, Robert A; Schulz, Stefanie; Helde, Sandra; Gewalt, Senta; Cassese, Salvatore; Linhardt, Maryam; Ibrahim, Tareq; Mehilli, Julinda; Hoppe, Katharina; Grupp, Katharina; Kufner, Sebastian; Böttiger, Corinna; Hoppmann, Petra; Burgdorf, Christof; Fusaro, Massimiliano; Ott, Ilka; Schneider, Simon; Hengstenberg, Christian; Schunkert, Heribert; Laugwitz, Karl-Ludwig; Kastrati, Adnan

2014-06-01

Vascular closure devices (VCD) have been introduced into clinical practice with the aim of increasing the procedural efficiency and clinical safety of coronary angiography. However, clinical studies comparing VCD and manual compression have yielded mixed results, and large randomised clinical trials comparing the two strategies are missing. Moreover, comparative efficacy studies between different VCD in routine clinical use are lacking. The Instrumental Sealing of ARterial puncture site - CLOSURE device versus manual compression (ISAR-CLOSURE) trial is a prospective, randomised clinical trial designed to compare the outcomes associated with the use of VCD or manual compression to achieve femoral haemostasis. The test hypothesis is that femoral haemostasis after coronary angiography achieved using VCD is not inferior to manual compression in terms of access-site-related vascular complications. Patients undergoing coronary angiography via the common femoral artery will be randomised in a 1:1:1 fashion to receive FemoSeal VCD, EXOSEAL VCD or manual compression. The primary endpoint is the incidence of the composite of arterial access-related complications (haematoma ≥5 cm, pseudoaneurysm, arteriovenous fistula, access-site-related bleeding, acute ipsilateral leg ischaemia, the need for vascular surgical/interventional treatment or documented local infection) at 30 days after randomisation. According to power calculations based on non-inferiority hypothesis testing, enrolment of 4,500 patients is planned. The trial is registered at www.clinicaltrials.gov (study identifier: NCT01389375). The safety of VCD as compared to manual compression in patients undergoing transfemoral coronary angiography remains an issue of clinical equipoise. The aim of the ISAR-CLOSURE trial is to assess whether femoral haemostasis achieved through the use of VCD is non-inferior to manual compression in terms of access-site-related vascular complications.

Acute Whiplash Injury Study (AWIS): a protocol for a cluster randomised pilot and feasibility trial of an Active Behavioural Physiotherapy Intervention in an insurance private setting

PubMed Central

Wiangkham, Taweewat; Duda, Joan; Haque, M Sayeed; Price, Jonathan; Rushton, Alison

2016-01-01

Introduction Whiplash-associated disorder (WAD) causes substantial social and economic burden internationally. Up to 60% of patients with WAD progress to chronicity. Research therefore needs to focus on effective management in the acute stage to prevent the development of chronicity. Approximately 93% of patients are classified as WADII (neck complaint and musculoskeletal sign(s)), and in the UK, most are managed in the private sector. In our recent systematic review, a combination of active and behavioural physiotherapy was identified as potentially effective in the acute stage. An Active Behavioural Physiotherapy Intervention (ABPI) was developed through combining empirical (modified Delphi study) and theoretical (social cognitive theory focusing on self-efficacy) evidence. This pilot and feasibility trial has been designed to inform the design of an adequately powered definitive randomised controlled trial. Methods and analysis Two parallel phases. (1) An external pilot and feasibility cluster randomised double-blind (assessor and participants), parallel two-arm (ABPI vs standard physiotherapy) clinical trial to evaluate procedures and feasibility. Six UK private physiotherapy clinics will be recruited and cluster randomised by a computer-generated randomisation sequence. Sixty participants (30 each arm) will be assessed at recruitment (baseline) and at 3 months postbaseline. The planned primary outcome measure is the neck disability index. (2) An embedded exploratory qualitative study using semistructured indepth interviews (n=3–4 physiotherapists) and a focus group (n=6–8 patients) and entailing the recruitment of purposive samples will explore perceptions of the ABPI. Quantitative data will be analysed descriptively. Qualitative data will be coded and analysed deductively (identify themes) and inductively (identify additional themes). Ethics and dissemination This trial is approved by the University of Birmingham Ethics Committee (ERN_15-0542). Trial registration number ISRCTN84528320. PMID:27412105

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.

Acute Whiplash Injury Study (AWIS): a protocol for a cluster randomised pilot and feasibility trial of an Active Behavioural Physiotherapy Intervention in an insurance private setting.

PubMed

Wiangkham, Taweewat; Duda, Joan; Haque, M Sayeed; Price, Jonathan; Rushton, Alison

2016-07-13

Whiplash-associated disorder (WAD) causes substantial social and economic burden internationally. Up to 60% of patients with WAD progress to chronicity. Research therefore needs to focus on effective management in the acute stage to prevent the development of chronicity. Approximately 93% of patients are classified as WADII (neck complaint and musculoskeletal sign(s)), and in the UK, most are managed in the private sector. In our recent systematic review, a combination of active and behavioural physiotherapy was identified as potentially effective in the acute stage. An Active Behavioural Physiotherapy Intervention (ABPI) was developed through combining empirical (modified Delphi study) and theoretical (social cognitive theory focusing on self-efficacy) evidence. This pilot and feasibility trial has been designed to inform the design of an adequately powered definitive randomised controlled trial. Two parallel phases. (1) An external pilot and feasibility cluster randomised double-blind (assessor and participants), parallel two-arm (ABPI vs standard physiotherapy) clinical trial to evaluate procedures and feasibility. Six UK private physiotherapy clinics will be recruited and cluster randomised by a computer-generated randomisation sequence. Sixty participants (30 each arm) will be assessed at recruitment (baseline) and at 3 months postbaseline. The planned primary outcome measure is the neck disability index. (2) An embedded exploratory qualitative study using semistructured indepth interviews (n=3-4 physiotherapists) and a focus group (n=6-8 patients) and entailing the recruitment of purposive samples will explore perceptions of the ABPI. Quantitative data will be analysed descriptively. Qualitative data will be coded and analysed deductively (identify themes) and inductively (identify additional themes). This trial is approved by the University of Birmingham Ethics Committee (ERN_15-0542). ISRCTN84528320. 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/

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

Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials.

PubMed

Panés, Julian; Sandborn, William J; Schreiber, Stefan; Sands, Bruce E; Vermeire, Séverine; D'Haens, Geert; Panaccione, Remo; Higgins, Peter D R; Colombel, Jean-Frederic; Feagan, Brian G; Chan, Gary; Moscariello, Michele; Wang, Wenjin; Niezychowski, Wojciech; Marren, Amy; Healey, Paul; Maller, Eric

2017-06-01

Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD). We conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks. Those achieving clinical response-100 or remission were re-randomised to maintenance treatment with placebo, tofacitinib 5 or 10 mg twice daily for 26 weeks. Primary endpoints were clinical remission at the end of the induction study, and clinical response-100 or remission at the end of the maintenance study. 180/280 patients randomised in the induction study were enrolled in the maintenance study. At week 8 of induction, the proportion of patients with clinical remission was 43.5% and 43.0% with 5 and 10 mg twice daily, respectively, compared with 36.7% in the placebo group (p=0.325 and 0.392 for 5 and 10 mg twice daily vs placebo). At week 26 of maintenance, the proportion of patients with clinical response-100 or remission was 55.8% with tofacitinib 10 mg twice daily compared with 39.5% with tofacitinib 5 mg twice daily and 38.1% with placebo (p=0.130 for 10 mg twice daily vs placebo). Compared with placebo, the change in C-reactive protein from baseline was statistically significant (p<0.0001) with 10 mg twice daily after both induction and maintenance treatments. Primary efficacy endpoints were not significantly different from placebo, although there was evidence of a minor treatment effect. No new safety signals were observed for tofacitinib. NCT01393626 and NCT01393899. 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/.

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

PubMed

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

2015-03-08

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

Study protocol for a randomised controlled trial of invasive versus conservative management of primary spontaneous pneumothorax.

PubMed

Brown, Simon G A; Ball, Emma L; Perrin, Kyle; Read, Catherine A; Asha, Stephen E; Beasley, Richard; Egerton-Warburton, Diana; Jones, Peter G; Keijzers, Gerben; Kinnear, Frances B; Kwan, Ben C H; Lee, Y C Gary; Smith, Julian A; Summers, Quentin A; Simpson, Graham

2016-09-13

Current management of primary spontaneous pneumothorax (PSP) is variable, with little evidence from randomised controlled trials to guide treatment. Guidelines emphasise intervention in many patients, which involves chest drain insertion, hospital admission and occasionally surgery. However, there is evidence that conservative management may be effective and safe, and it may also reduce the risk of recurrence. Significant questions remain regarding the optimal initial approach to the management of PSP. This multicentre, prospective, randomised, open label, parallel group, non-inferiority study will randomise 342 participants with a first large PSP to conservative or interventional management. To maintain allocation concealment, randomisation will be performed in real time by computer and stratified by study site. Conservative management will involve a period of observation prior to discharge, with intervention for worsening symptoms or physiological instability. Interventional treatment will involve insertion of a small bore drain. If drainage continues after 1 hour, the patient will be admitted. If drainage stops, the drain will be clamped for 4 hours. The patient will be discharged if the lung remains inflated. Otherwise, the patient will be admitted. The primary end point is the proportion of participants with complete lung re-expansion by 8 weeks. Secondary end points are as follows: days in hospital, persistent air leak, predefined complications and adverse events, time to resolution of symptoms, and pneumothorax recurrence during a follow-up period of at least 1 year. The study has 95% power to detect an absolute non-inferiority margin of 9%, assuming 99% successful expansion at 8 weeks in the invasive treatment arm. The primary analysis will be by intention to treat. Local ethics approval has been obtained for all sites. Study findings will be disseminated by publication in a high-impact international journal and presentation at major international Emergency Medicine and Respiratory meetings. ACTRN12611000184976; 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/

ESCAPS study protocol: a feasibility randomised controlled trial of ‘Early electrical stimulation to the wrist extensors and wrist flexors to prevent the post-stroke complications of pain and contractures in the paretic arm’

PubMed Central

Fletcher-Smith, Joanna C; Walker, Dawn-Marie; Sprigg, Nikola; James, Marilyn; Walker, Marion F; Allatt, Kate; Mehta, Rajnikant; Pandyan, Anand D

2016-01-01

Introduction Approximately 70% of patients with stroke experience impaired arm function, which is persistent and disabling for an estimated 40%. Loss of function reduces independence in daily activities and impacts on quality of life. Muscles in those who do not recover functional movement in the stroke affected arm are at risk of atrophy and contractures, which can be established as early as 6 weeks following stroke. Pain is also common. This study aims to evaluate the feasibility of a randomised controlled trial to test the efficacy and cost-effectiveness of delivering early intensive electrical stimulation (ES) to prevent post-stroke complications in the paretic upper limb. Methods and analysis This is a feasibility randomised controlled trial (n=40) with embedded qualitative studies (patient/carer interviews and therapist focus groups) and feasibility economic evaluation. Patients will be recruited from the Stroke Unit at the Nottingham University Hospitals National Health Service (NHS) Trust within 72 h after stroke. Participants will be randomised to receive usual care or usual care and early ES to the wrist flexors and extensors for 30 min twice a day, 5 days a week for 3 months. The initial treatment(s) will be delivered by an occupational therapist or physiotherapist who will then train the patient and/or their nominated carer to self-manage subsequent treatments. Ethics and dissemination This study has been granted ethical approval by the National Research Ethics Service, East Midlands Nottingham1 Research Ethics Committee (ref: 15/EM/0006). To our knowledge, this is the first study of its kind of the early application (within 72 h post-stroke) of ES to both the wrist extensors and wrist flexors of stroke survivors with upper limb impairment. The results will inform the design of a definitive randomised controlled trial. Dissemination will include 2 peer-reviewed journal publications and presentations at national conferences. Trial registration number ISRCTN1648908; Pre-results. Clinicaltrials.gov ID: NCT02324634. PMID:26729394

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

PubMed

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

2017-08-28

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

Anchor Trial Launch

Cancer.gov

NCI has launched a multicenter phase III clinical trial called the ANCHOR Study -- Anal Cancer HSIL (High-grade Squamous Intraepithelial Lesion) Outcomes Research Study -- to determine if treatment of HSIL in HIV-infected individuals can prevent anal canc

Emerging indications of endoscopic radiofrequency ablation

PubMed Central

Becq, Aymeric; Camus, Marine; Rahmi, Gabriel; de Parades, Vincent; Marteau, Philippe

2015-01-01

Introduction Radiofrequency ablation (RFA) is a well-validated treatment of dysplastic Barrett's esophagus. Other indications of endoscopic RFA are under evaluation. Results Four prospective studies (total 69 patients) have shown that RFA achieved complete remission of early esophageal squamous intra-epithelial neoplasia at a rate of 80%, but with a substantial risk of stricture. In the setting of gastric antral vascular ectasia, two prospective monocenter studies, and a retrospective multicenter study, (total 51 patients), suggest that RFA is efficacious in terms of reducing transfusion dependency. In the setting of chronic hemorrhagic radiation proctopathy, a prospective monocenter study and a retrospective multicenter study (total 56 patients) suggest that RFA is an efficient treatment. A retrospective comparative study (64 patients) suggests that RFA improves stents patency in malignant biliary strictures. Conclusions Endoscopic RFA is an upcoming treatment modality in early esophageal squamous intra-epithelial neoplasia, as well as in gastric, rectal, and biliary diseases. PMID:26279839

[Information management in multicenter studies: the Brazilian longitudinal study for adult health].

PubMed

Duncan, Bruce Bartholow; Vigo, Álvaro; Hernandez, Émerson; Luft, Vivian Cristine; Ahlert, Hubert; Bergmann, Kaiser; Mota, Eduardo

2013-06-01

Information management in large multicenter studies requires a specialized approach. The Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil - Brazilian Longitudinal Study for Adult Health) has created a Datacenter to enter and manage its data system. The aim of this paper is to describe the steps involved, including the information entry, transmission and management methods. A web system was developed in order to allow, in a safe and confidential way, online data entry, checking and editing, as well as the incorporation of data collected on paper. Additionally, a Picture Archiving and Communication System was implemented and customized for echocardiography and retinography. It stores the images received from the Investigation Centers and makes them available at the Reading Centers. Finally, data extraction and cleaning processes were developed to create databases in formats that enable analyses in multiple statistical packages.

[The tinnitus questionnaire. A standard instrument for grading the degree of tinnitus. Results of a multicenter study with the tinnitus questionnaire].

PubMed

Goebel, G; Hiller, W

1994-03-01

The clinical examination of patients with severe and chronic tinnitus must include associated psychological disturbances. The present paper describes traditional diagnostic methods of ENT practice as well as the Tinnitus Questionnaire (TQ) which has been evaluated in a number of studies. This instrument differentiates between emotional and cognitive distress, auditory perceptual difficulties and self-experienced intrusiveness produced by the tinnitus. The results of a German multicenter study are presented which show that the TQ can be used to demonstrate differences of tinnitus distress under different clinical conditions (e.g., ENT clinic vs psychosomatic clinic and in- vs out-patient care). The TQ can be employed for comparative studies in different tinnitus-related institutions and for the evaluation of the relative effects of different treatment approaches.

Reliability of 3-Dimensional Measures of Single-Leg Cross Drop Landing Across 3 Different Institutions

PubMed Central

DiCesare, Christopher A.; Bates, Nathaniel A.; Barber Foss, Kim D.; Thomas, Staci M.; Wordeman, Samuel C.; Sugimoto, Dai; Roewer, Benjamin D.; Medina McKeon, Jennifer M.; Di Stasi, Stephanie; Noehren, Brian W.; Ford, Kevin R.; Kiefer, Adam W.; Hewett, Timothy E.; Myer, Gregory D.

2015-01-01

Background: Anterior cruciate ligament (ACL) injuries are physically and financially devastating but affect a relatively small percentage of the population. Prospective identification of risk factors for ACL injury necessitates a large sample size; therefore, study of this injury would benefit from a multicenter approach. Purpose: To determine the reliability of kinematic and kinetic measures of a single-leg cross drop task across 3 institutions. Study Design: Controlled laboratory study. Methods: Twenty-five female high school volleyball players participated in this study. Three-dimensional motion data of each participant performing the single-leg cross drop were collected at 3 institutions over a period of 4 weeks. Coefficients of multiple correlation were calculated to assess the reliability of kinematic and kinetic measures during the landing phase of the movement. Results: Between-centers reliability for kinematic waveforms in the frontal and sagittal planes was good, but moderate in the transverse plane. Between-centers reliability for kinetic waveforms was good in the sagittal, frontal, and transverse planes. Conclusion: Based on these findings, the single-leg cross drop task has moderate to good reliability of kinematic and kinetic measures across institutions after implementation of a standardized testing protocol. Clinical Relevance: Multicenter collaborations can increase study numbers and generalize results, which is beneficial for studies of relatively rare phenomena, such as ACL injury. An important step is to determine the reliability of risk assessments across institutions before a multicenter collaboration can be initiated. PMID:26779550

Surgical treatment of liver metastasis of gastric cancer: a retrospective multicenter cohort study (KSCC1302).

PubMed

Oki, Eiji; Tokunaga, Shoji; Emi, Yasunori; Kusumoto, Tetsuya; Yamamoto, Manabu; Fukuzawa, Kengo; Takahashi, Ikuo; Ishigami, Sumiya; Tsuji, Akihito; Higashi, Hidefumi; Nakamura, Toshihiko; Saeki, Hiroshi; Shirabe, Ken; Kakeji, Yoshihiro; Sakai, Kenji; Baba, Hideo; Nishimaki, Tadashi; Natsugoe, Shoji; Maehara, Yoshihiko

2016-07-01

The necessity of surgical treatment of liver metastases of gastric cancer is still controversial. We conducted a multicenter retrospective cohort study of liver-limited metastasis of gastric cancer treated surgically between 2000 and 2010. In this study, 103 patients were registered, with nine patients excluded from the analysis as they did not meet the eligibility criteria. Of the 94 patients, 69 underwent surgical resection, 11 underwent surgical resection combined with radiofrequency ablation or microwave coagulation therapy for small or deep tumors, and 14 underwent radiofrequency ablation or microwave coagulation therapy only. Synchronous and metachronous metastases were found in 37 and 57 patients, respectively. The 3- and 5-year overall survival rates of all the patients were 51.4 and 42.3 %, respectively. The 3- and 5-year relapse-free survival rates were 29.2 and 27.7 %, respectively. No significant difference in prognosis was observed between the patients who underwent surgical resection and those who underwent ablation therapy. The patients with hepatic solitary lesions and low-grade lymph node metastases of primary gastric cancer had significantly better overall survival and relapse-free survival. To our knowledge, this study is the largest series and first multicenter cohort study of liver-limited metastasis of gastric cancer. The study indicated that patients with a single liver metastasis with a grade lower than N2 lymph node metastasis of the primary lesion are the best candidates for liver resection.

Application of the cultured epidermal autograft "JACE(®") for treatment of severe burns: Results of a 6-year multicenter surveillance in Japan.

PubMed

Matsumura, Hajime; Matsushima, Asako; Ueyama, Masashi; Kumagai, Norio

2016-06-01

In the 1970s, Green et al. developed a method that involved culturing keratinocyte sheets and used for treatment of burns. Since then, the take rate of cultured epidermal autograft (CEA) onto fascia, granulation tissue, or allografts has been extensively reported, while that on an artificial dermis in a large case series is not. Moreover, the contribution of CEA to patient survival has not been analyzed in a multicenter study. We conducted a 6-year multicenter surveillance on the application of the CEA "JACE(®") for treatment of burns >30% total body surface area (TBSA) across 118 Japanese hospitals. This surveillance included 216 patients and 718 graft sites for efficacy analysis. The CEA take rate at 4 weeks after grafting was evaluated, and safety was monitored until 52 weeks. In addition, the survival curve obtained in this study and the data obtained from the Tokyo Burn Unit Association (TBUA) were compared. The mean CEA take rates at week 4 were 66% (sites) and 68% (patients), and the rate on the artificial dermis was 65% for 226 sites. CEA application combined with wide split-thickness auto or patch autograft increased the CEA take rate. On comparison with the data obtained from the TBUA, which included data on individuals with burns of the same severity, CEA application was found to contribute to patient survival until 7 weeks after burn. We reported the take rate of CEA based on a 6-year multicenter surveillance. From our results, we found that the application of CEA is a useful treatment for the patients with extensive burns. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Effectiveness of preoperative medical consultations by internal medicine physicians: a systematic review

PubMed Central

Pham, Clarabelle T; Gibb, Catherine L; Fitridge, Robert A; Karnon, Jonathan D

2017-01-01

Objective Clinics have been established to provide preoperative medical consultations, and enable the anaesthetist and surgeon to deliver the best surgical outcome for patients. However, there is uncertainty regarding the effect of such clinics on surgical, in-hospital and long-term outcomes. A systematic review of the literature was conducted to determine the effectiveness of preoperative medical consultations by internal medicine physicians for patients listed for elective surgery. Design Systematic searches of MEDLINE, EMBASE, CINAHL, PubMed, Current Contents and the NHS Centre for Reviews and Dissemination were conducted up to 30 April 2017. Setting Elective surgery. Study selection Randomised controlled trials and non-randomised comparative studies conducted in adults. Outcome measures Length of hospital stay, perioperative morbidity and mortality, costs and quality of life. Results The one randomised trial reported that preadmission preoperative assessment was more effective than the option of an inpatient medical assessment in reducing the frequency of unnecessary admissions with significantly fewer surgical cancellations following admission for surgery. A small reduction in length of stay in patients was also observed. The three non-randomised studies reported increased lengths of stay, costs and postoperative complications in patients who received preoperative assessment. The timing and delivery of the preoperative medical consultation in the intervention group differed across the included studies. Conclusion Further research is required to inform the design and implementation of coordinated involvement of physicians and surgeons in the provision of care for high-risk surgical patients. A standardised approach to perioperative decision-making processes should be developed with a clear protocol or guideline for the assessment and management of surgical patients. PMID:29203506

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

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

Systematic review of the use of honey as a wound dressing

PubMed Central

Moore, Owen A; Smith, Lesley A; Campbell, Fiona; Seers, Kate; McQuay, Henry J; Moore, R Andrew

2001-01-01

Objective To investigate topical honey in superficial burns and wounds though a systematic review of randomised controlled trials. Data sources Cochrane Library, MEDLINE, EMBASE, PubMed, reference lists and databases were used to seek randomised controlled trials. Seven randomised trials involved superficial burns, partial thickness burns, moderate to severe burns that included full thickness injury, and infected postoperative wounds. Review methods Studies were randomised trials using honey, published papers, with a comparator. Main outcomes were relative benefit and number-needed-to-treat to prevent an outcome relating to wound healing time or infection rate. Results One study in infected postoperative wounds compared honey with antiseptics plus systemic antibiotics. The number needed to treat with honey for good wound healing compared with antiseptic was 2.9 (95% confidence interval 1.7 to 9.7). Five studies in patients with partial thickness or superficial burns involved less than 40% of the body surface. Comparators were polyurethane film, amniotic membrane, potato peel and silver sulphadiazine. The number needed to treat for seven days with honey to produce one patient with a healed burn was 2.6 (2.1 to 3.4) compared with any other treatment and 2.7 (2.0 to 4.1) compared with potato and amniotic membrane. For some or all outcomes honey was superior to all these treatments. Time for healing was significantly shorter for honey than all these treatments. The quality of studies was low. Conclusion Confidence in a conclusion that honey is a useful treatment for superficial wounds or burns is low. There is biological plausibility. PMID:11405898

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-06-23

Nasal high-flow (nHF) therapy is a popular mode of respiratory support for newborn infants. Evidence for nHF use is predominantly from neonatal intensive care units (NICUs). There are no randomised trials of nHF use in non-tertiary special care nurseries (SCNs). We hypothesise that nHF is non-inferior to nasal continuous positive airway pressure (CPAP) as primary support for newborn infants with respiratory distress, in the population cared for in non-tertiary SCNs. The HUNTER trial is an unblinded Australian multicentre, randomised, non-inferiority trial. Infants are eligible if born at a gestational age ≥31 weeks with birth weight ≥1200 g and admitted to a participating non-tertiary SCN, are <24 hours old at randomisation and require non-invasive respiratory support or supplemental oxygen for >1 hour. Infants are randomised to treatment with either nHF or CPAP. The primary outcome is treatment failure within 72 hours of randomisation, as determined by objective oxygenation, apnoea or blood gas criteria or by a clinical decision that urgent intubation and mechanical ventilation, or transfer to a tertiary NICU, is required. Secondary outcomes include incidence of pneumothorax requiring drainage, duration of respiratory support, supplemental oxygen and hospitalisation, costs associated with hospital care, cost-effectiveness, parental stress and satisfaction and nursing workload. Multisite ethical approval for the study has been granted by The Royal Children's Hospital, Melbourne, Australia (Trial Reference No. 34222), and by each participating site. The trial is currently recruiting in eight centres in Victoria and New South Wales, Australia, with one previous site no longer recruiting. The trial results will be published in a peer-reviewed journal and will be presented at national and international conferences. Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614001203640; pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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.

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

Validation of standard operating procedures in a multicenter retrospective study to identify -omics biomarkers for chronic low back pain.

PubMed

Dagostino, Concetta; De Gregori, Manuela; Gieger, Christian; Manz, Judith; Gudelj, Ivan; Lauc, Gordan; Divizia, Laura; Wang, Wei; Sim, Moira; Pemberton, Iain K; MacDougall, Jane; Williams, Frances; Van Zundert, Jan; Primorac, Dragan; Aulchenko, Yurii; Kapural, Leonardo; Allegri, Massimo

2017-01-01

Chronic low back pain (CLBP) is one of the most common medical conditions, ranking as the greatest contributor to global disability and accounting for huge societal costs based on the Global Burden of Disease 2010 study. Large genetic and -omics studies provide a promising avenue for the screening, development and validation of biomarkers useful for personalized diagnosis and treatment (precision medicine). Multicentre studies are needed for such an effort, and a standardized and homogeneous approach is vital for recruitment of large numbers of participants among different centres (clinical and laboratories) to obtain robust and reproducible results. To date, no validated standard operating procedures (SOPs) for genetic/-omics studies in chronic pain have been developed. In this study, we validated an SOP model that will be used in the multicentre (5 centres) retrospective "PainOmics" study, funded by the European Community in the 7th Framework Programme, which aims to develop new biomarkers for CLBP through three different -omics approaches: genomics, glycomics and activomics. The SOPs describe the specific procedures for (1) blood collection, (2) sample processing and storage, (3) shipping details and (4) cross-check testing and validation before assays that all the centres involved in the study have to follow. Multivariate analysis revealed the absolute specificity and homogeneity of the samples collected by the five centres for all genetics, glycomics and activomics analyses. The SOPs used in our multicenter study have been validated. Hence, they could represent an innovative tool for the correct management and collection of reliable samples in other large-omics-based multicenter studies.

Action 3:30R: protocol for a cluster randomised feasibility study of a revised teaching assistant-led extracurricular physical activity intervention for 8- to 10-year-olds.

PubMed

Tibbitts, Byron; Porter, Alice; Sebire, Simon J; Metcalfe, Chris; Bird, Emma; Powell, Jane; Jago, Russell

2017-01-01

Approximately half of 7-year-old children do not meet physical activity (PA) recommendations. Interventions targeting primary school children's afterschool discretionary time could increase PA. Teaching assistants (TAs) are a school resource and could be trained to deliver after-school PA programmes. Building on earlier work, this paper describes the protocol for a cluster randomised feasibility study of a teaching assistant-led after-school intervention aimed at increasing PA levels of year 4 and 5 children (8-10 years old). Phase 1-pre-baseline: 12 schools will be recruited. In all schools, self-reported PA will be measured in all consenting year 3 and 4 children. In four schools, pupils will additionally wear a waist-worn Actigraph accelerometer for 7 days.Phase 2-baseline: schools will be randomised to one of two enhanced recruitment strategies being tested for children: (1) a club briefing and (2) the briefing plus a taster Action 3:30 session. Up to 30 children per school will be able to attend Action 3:30 sessions and will provide baseline data on height, weight, psychosocial variables and accelerometer-measured PA.Phase 3-intervention and follow-up: Schools randomised into intervention or control arm. Intervention schools ( n  = 6) will receive a 15-week after-school programme when children are in years 4 and 5, run by TAs who have attended a 25-h Action 3:30 training programme. Control schools ( n  = 6) will continue with normal practice. Follow-up measures will be a repeat of baseline measures at the end of the 15-week intervention.Phase 4-process evaluation: session attendance, perceived enjoyment and perceived exertion will be assessed during the intervention, as well as the economic impact on schools. Post-study qualitative assessments with TAs, school contacts and pupils will identify how the programme could be refined. Accelerometer-determined minutes of moderate-to-vigorous physical activity (MVPA) per day will be calculated as this is likely to be the primary outcome in a future definitive trial. The Action 3:30 cluster randomised feasibility trial will assess the public health potential of this intervention approach and provide the information necessary to progress to a definitive cluster randomised controlled trial. ISRCTN34001941. Registered 01/12/2016.

Spectacle wearing in children randomised to ready-made or custom spectacles, and potential cost savings to programmes: study protocol for a randomised controlled trial.

PubMed

Morjaria, Priya; Murali, Kaushik; Evans, Jennifer; Gilbert, Clare

2016-01-19

Uncorrected refractive errors are the commonest cause of visual impairment in children, with myopia being the most frequent type. Myopia usually starts around 9 years of age and progresses throughout adolescence. Hyperopia usually affects younger children, and astigmatism affects all age groups. Many children have a combination of myopia and astigmatism. To correct refractive errors, the type and degree of refractive error are measured and appropriate corrective lenses prescribed and dispensed in the spectacle frame of choice. Custom spectacles (that is, with the correction specifically required for that individual) are required if astigmatism is present, and/or the refractive error differs between eyes. Spectacles without astigmatic correction and where the refractive error is the same in both eyes are straightforward to dispense. These are known as 'ready-made' spectacles. High-quality spectacles of this type can be produced in high volume at an extremely low cost. Although spectacle correction improves visual function, a high proportion of children do not wear their spectacles for a variety of reasons. The aim of this study is to compare spectacle wear at 3-4 months amongst school children aged 11 to 15 years who have significant, simple uncorrected refractive error randomised to ready-made or custom spectacles of equivalent quality, and to evaluate cost savings to programmes. The study will take place in urban and semi-urban government schools in Bangalore, India. The hypothesis is that similar proportions of children randomised to ready-made or custom spectacles will be wearing their spectacles at 3-4 months. The trial is a randomised, non-inferiority, double masked clinical trial of children with simple uncorrected refractive errors. After screening, children will be randomised to ready-made or custom spectacles. Children will choose their preferred frame design. After 3-4 months the children will be followed up to assess spectacle wear. Ready-made spectacles have benefits for providers as well as parents and children, as a wide range of prescriptions and frame types can be taken to schools and dispensed immediately. In contrast, custom spectacles have to be individually made up in optical laboratories, and taken back to the school and given to the correct child. ISRCTN14715120 (Controlled-Trials.com) Date registered: 04 February 2015.

The NAtional randomised controlled Trial of Tonsillectomy IN Adults (NATTINA): a clinical and cost-effectiveness study: study protocol for a randomised control trial.

PubMed

Rubie, Isabel; Haighton, Catherine; O'Hara, James; Rousseau, Nikki; Steen, Nick; Stocken, Deborah D; Sullivan, Frank; Vale, Luke; Wilkes, Scott; Wilson, Janet

2015-06-06

The role of tonsillectomy in the management of adult tonsillitis remains uncertain and UK regional variation in tonsillectomy rates persists. Patients, doctors and health policy makers wish to know the costs and benefits of tonsillectomy against conservative management and whether therapy can be better targeted to maximise benefits and minimise risks of surgery, hence maximising cost-effective use of resources. NATTINA incorporates the first attempt to map current NHS referral criteria against other metrics of tonsil disease severity. A UK multi-centre, randomised, controlled trial for adults with recurrent tonsillitis to compare the clinical and cost-effectiveness of tonsillectomy versus conservative management. An initial feasibility study comprises qualitative interviews to investigate the practicality of the protocol, including willingness to randomise and be randomised. Approximately 20 otolaryngology staff, 10 GPs and 15 ENT patients will be recruited over 5 months in all 9 proposed main trial participating sites. A 6-month internal pilot will then recruit 72 patients across 6 of the 9 sites. Participants will be adults with recurrent acute tonsillitis referred by a GP to secondary care. Randomisation between tonsillectomy and conservative management will be according to a blocked allocation method in a 1:1 ratio stratified by centre and baseline disease severity. If the pilot is successful, the main trial will recruit a further 528 patients over 18 months in all 9 participating sites. All participants will be followed up for a total of 24 months, throughout which both primary and secondary outcome data will be collected. The primary outcome is the number of sore throat days experienced over the 24-month follow-up. The pilot and main trials include an embedded qualitative process evaluation. NATTINA is designed to evaluate the relative effectiveness and efficiency of tonsillectomy versus conservative management in patients with recurrent sore throat who are eligible for surgery. Most adult tonsil disease and surgery has an impact on economically active age groups, with individual and societal costs through loss of earnings and productivity. Avoidance of unnecessary operations and prioritisation of those individuals likely to gain most from tonsillectomy would reduce costs to the NHS and society. ISRCTN55284102, Date of Registration: 4 August 2014.

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

PubMed

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

2017-07-01

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

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

PubMed

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

2017-08-24

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

Feasibility study of a single-blind randomised controlled trial of an occupational therapy intervention.

PubMed

Gantschnig, Brigitte E; Nilsson, Ingeborg; Fisher, Anne G; Künzle, Christoph; Page, Julie

2016-07-01

Several factors facilitate or hinder efficacy research in occupational therapy. Strategies are needed, therefore, to support the successful implementation of trials. To assess the feasibility of conducting a randomised controlled trial (RCT). The main feasibility objectives of this study were to assess the process, resources, management, and scientific basis of a trial RCT. A total of 10 occupational therapists, between the ages of 30 and 55 (M 43.4; SD 8.3) with seven to 26 years' (M 14.3; SD 6.1) experience, participated in this study. Qualitative data collected included minutes of meetings, reports, and field notes. The data were analysed based on the principles of content analysis, using feasibility objectives as the main categories. Data analysis revealed strengths in relation to retention and inclusion criteria of participants, the study protocol, study organisation, and the competence of researchers. Weaknesses were found related to recruitment, randomisation, data collection, time for training and communication, commitment, and design. The findings indicated that there are several factors which had a considerable impact on the implementation of an RCT in practice. However, it was useful to assess methods and procedures of the trial RCT as a basis to refine research plans.

The Effects of Skill Training on Social Workers' Professional Competences in Norway: Results of a Cluster-Randomised Study

PubMed Central

Malmberg-Heimonen, Ira; Natland, Sidsel; Tøge, Anne Grete; Hansen, Helle Cathrine

2016-01-01

Using a cluster-randomised design, this study analyses the effects of a government-administered skill training programme for social workers in Norway. The training programme aims to improve social workers' professional competences by enhancing and systematising follow-up work directed towards longer-term unemployed clients in the following areas: encountering the user, system-oriented efforts and administrative work. The main tools and techniques of the programme are based on motivational interviewing and appreciative inquiry. The data comprise responses to baseline and eighteen-month follow-up questionnaires administered to all social workers (n = 99) in eighteen participating Labour and Welfare offices randomised into experimental and control groups. The findings indicate that the skill training programme positively affected the social workers' evaluations of their professional competences and quality of work supervision received. The acquisition and mastering of combinations of specific tools and techniques, a comprehensive supervision structure and the opportunity to adapt the learned skills to local conditions were important in explaining the results. PMID:27559232

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.

A Bayesian Hybrid Adaptive Randomisation Design for Clinical Trials with Survival Outcomes.

PubMed

Moatti, M; Chevret, S; Zohar, S; Rosenberger, W F

2016-01-01

Response-adaptive randomisation designs have been proposed to improve the efficiency of phase III randomised clinical trials and improve the outcomes of the clinical trial population. In the setting of failure time outcomes, Zhang and Rosenberger (2007) developed a response-adaptive randomisation approach that targets an optimal allocation, based on a fixed sample size. The aim of this research is to propose a response-adaptive randomisation procedure for survival trials with an interim monitoring plan, based on the following optimal criterion: for fixed variance of the estimated log hazard ratio, what allocation minimizes the expected hazard of failure? We demonstrate the utility of the design by redesigning a clinical trial on multiple myeloma. To handle continuous monitoring of data, we propose a Bayesian response-adaptive randomisation procedure, where the log hazard ratio is the effect measure of interest. Combining the prior with the normal likelihood, the mean posterior estimate of the log hazard ratio allows derivation of the optimal target allocation. We perform a simulation study to assess and compare the performance of this proposed Bayesian hybrid adaptive design to those of fixed, sequential or adaptive - either frequentist or fully Bayesian - designs. Non informative normal priors of the log hazard ratio were used, as well as mixture of enthusiastic and skeptical priors. Stopping rules based on the posterior distribution of the log hazard ratio were computed. The method is then illustrated by redesigning a phase III randomised clinical trial of chemotherapy in patients with multiple myeloma, with mixture of normal priors elicited from experts. As expected, there was a reduction in the proportion of observed deaths in the adaptive vs. non-adaptive designs; this reduction was maximized using a Bayes mixture prior, with no clear-cut improvement by using a fully Bayesian procedure. The use of stopping rules allows a slight decrease in the observed proportion of deaths under the alternate hypothesis compared with the adaptive designs with no stopping rules. Such Bayesian hybrid adaptive survival trials may be promising alternatives to traditional designs, reducing the duration of survival trials, as well as optimizing the ethical concerns for patients enrolled in the trial.

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.

Re-estimating sample size in cluster randomised trials with active recruitment within clusters.

PubMed

van Schie, S; Moerbeek, M

2014-08-30

Often only a limited number of clusters can be obtained in cluster randomised trials, although many potential participants can be recruited within each cluster. Thus, active recruitment is feasible within the clusters. To obtain an efficient sample size in a cluster randomised trial, the cluster level and individual level variance should be known before the study starts, but this is often not the case. We suggest using an internal pilot study design to address this problem of unknown variances. A pilot can be useful to re-estimate the variances and re-calculate the sample size during the trial. Using simulated data, it is shown that an initially low or high power can be adjusted using an internal pilot with the type I error rate remaining within an acceptable range. The intracluster correlation coefficient can be re-estimated with more precision, which has a positive effect on the sample size. We conclude that an internal pilot study design may be used if active recruitment is feasible within a limited number of clusters. Copyright © 2014 John Wiley & Sons, Ltd.

Home-based management of severely acute malnutrition: feasibility of ethically designed, community-based randomised clinical trials.

PubMed

Patil, Rajan R

2015-01-01

The Indian Council of Medical Research had, on May 31, 2011, called for research proposals on severely acute malnourished (SAM) children to generate evidence for the development of practical and scalable regimens to medically rehabilitate children suffering from SAM, without serious complications, at the home/community level and/or peripheral inpatient facilities. The primary outcomes of the proposed research study are recovery from SAM in the short term, as well as sustenance of recovery (for at least six months after the initiation of treatment). The secondary outcomes are the acceptability, feasibility and safety of the regimes being tested. It was suggested that the studies be designed as individual or cluster randomised or quasi randomised controlled trials (RCTs). This paper analyses the methodological, operational, and most importantly, ethical challenges and implications of conducting community-based RCTs involving SAM children. The paper dwells in detail on why and how the RCT design is inappropriate and unsuitable for studying the effectiveness of home-based management of SAM children in the community.

Behaviour modification interventions to optimise red blood cell transfusion practices: a systematic review and meta-analysis.

PubMed

Soril, Lesley J J; Noseworthy, Thomas W; Dowsett, Laura E; Memedovich, Katherine; Holitzki, Hannah M; Lorenzetti, Diane L; Stelfox, Henry Thomas; Zygun, David A; Clement, Fiona M

2018-05-18

To assess the impact of behaviour modification interventions to promote restrictive red blood cell (RBC) transfusion practices. Systematic review and meta-analysis. Seven electronic databases were searched to January 2018. Published randomised controlled trials (RCTs) or non-randomised studies examining an intervention to modify healthcare providers' RBC transfusion practice in any healthcare setting were included. The primary outcome was the proportion of patients transfused. Secondary outcomes included the proportion of inappropriate transfusions, RBC units transfused per patient, in-hospital mortality, length of stay (LOS), pretransfusion haemoglobin and healthcare costs. Meta-analysis was conducted using a random-effects model and meta-regression was performed in cases of heterogeneity. Publication bias was assessed by Begg's funnel plot. Eighty-four low to moderate quality studies were included: 3 were RCTs and 81 were non-randomised studies. Thirty-one studies evaluated a single intervention, 44 examined a multimodal intervention. The comparator in all studies was standard of care or historical control. In 33 non-randomised studies, use of an intervention was associated with reduced odds of transfusion (OR 0.63 (95% CI 0.56 to 0.71)), odds of inappropriate transfusion (OR 0.46 (95% CI 0.36 to 0.59)), RBC units/patient weighted mean difference (WMD: -0.50 units (95% CI -0.85 to -0.16)), LOS (WMD: -1.14 days (95% CI -2.12 to -0.16)) and pretransfusion haemoglobin (-0.28 g/dL (95% CI -0.48 to -0.08)). There was no difference in odds of mortality (OR 0.90 (95% CI 0.80 to 1.02)). Protocol/algorithm and multimodal interventions were associated with the greatest decreases in the primary outcome. There was high heterogeneity among estimates and evidence for publication bias. The literature examining the impact of interventions on RBC transfusions is extensive, although most studies are non-randomised. Despite this, pooled analysis of 33 studies revealed improvement in the primary outcome. Future work needs to shift from asking, 'does it work?' to 'what works best and at what cost?' CRD42015024757. © 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.

Transport for abciximab facilitated primary angioplasty versus on-site thrombolysis with a liberal rescue policy: the randomised Holland Infarction Study (HIS).

PubMed

Dieker, Hendrik-Jan; van Horssen, Elvira V; Hersbach, Ferry M R J; Brouwer, Marc A; van Boven, Ad J; van 't Hof, Arnoud W J; Aengevaeren, Wim R M; Verheugt, Freek W A; Bär, Frits W H M

2006-08-01

As of to date, the only large transportation trial comparing on-site fibrin-specific thrombolysis with transfer for primary angioplasty in patients presenting in a referral centre is the DANAMI-2 trial, with only 3% rescue angioplasty. The Holland Infarction Study (HIS) compared abciximab facilitated primary angioplasty (FP) with on-site fibrin-specific thrombolytic therapy (TT) with a liberal protocol-driven rescue angioplasty (transport to intervention centre in case < 50% ST resolution at 60 min). Patients in a referral centre without shock and < 4.5 h of chest pain presenting with ST-elevation having > or = 12 mm ST-segment shift were randomised to either strategy. Of the originally planned 900 patients only 48 were included due to suspension of financial funding. Death, recurrent MI and stroke at one year was 8% for the FP-group and 22% for the TT-group (p = 0.2). Two hours after randomisation the rates of complete ST-segment resolution (> or =70%) were 52% and 35%, respectively (p = 0.2). This prematurely discontinued randomised transportation trial shows favorable trends with respect to long-term clinical outcome and early ST-resolution for abciximab facilitated primary angioplasty. In view of the real world delays associated with interhospital transport for primary angioplasty, treatment strategies focusing on early fibrin-specific lysis with a liberal selective rescue policy are warranted.

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

A family intervention to reduce delirium in hospitalised ICU patients: A feasibility randomised controlled trial.

PubMed

Mitchell, Marion L; Kean, Susanne; Rattray, Janice E; Hull, Alastair M; Davis, Chelsea; Murfield, Jenny E; Aitken, Leanne M

2017-06-01

Family members could play an important role in preventing and reducing the development of delirium in Intensive Care Units (ICU) patients. This study sought to assess the feasibility of design and recruitment, and acceptability for family members and nurses of a family delivered intervention to reduce delirium in ICU patients. A single centre randomised controlled trial in an Australian medical/surgical ICU was conducted. Sixty-one family members were randomised (29 in intervention and 32 in non-intervention group). Following instructions, the intervention comprised the family members providing orientation or memory clues (family photographs, orientation to surroundings) to their relative each day. In addition, family members conducted sensory checks (vision and hearing with glasses and hearing aids); and therapeutic or cognitive stimulation (discussing family life, reminiscing) daily. Eleven ICU nurses were interviewed to gain insight into the feasibility and acceptability of implementing the intervention from their perspective. Recruitment rate was 28% of eligible patients (recruited n=90, attrition n=1). Following instruction by the research nurse the family member delivered the intervention which was assessed to be feasible and acceptable by family members and nurses. Protocol adherence could be improved with alternative data collection methods. Nurses considered the activities acceptable. The study was able to recruit, randomise and retain family member participants. Further strategies are required to assess intervention fidelity and improve data collection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Coordination and management of multicenter clinical studies in trauma: Experience from the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study.

PubMed

Rahbar, Mohammad H; Fox, Erin E; del Junco, Deborah J; Cotton, Bryan A; Podbielski, Jeanette M; Matijevic, Nena; Cohen, Mitchell J; Schreiber, Martin A; Zhang, Jiajie; Mirhaji, Parsa; Duran, Sarah J; Reynolds, Robert J; Benjamin-Garner, Ruby; Holcomb, John B

2012-04-01

Early death due to hemorrhage is a major consequence of traumatic injury. Transfusion practices differ among hospitals and it is unknown which transfusion practices improve survival. This report describes the experience of the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study Data Coordination Center in designing and coordinating a study to examine transfusion practices at ten Level 1 trauma centers in the US. PROMMTT was a multisite prospective observational study of severely injured transfused trauma patients. The clinical sites collected real-time information on the timing and amounts of blood product infusions as well as colloids and crystalloids, vital signs, initial diagnostic and clinical laboratory tests, life saving interventions and other clinical care data. Between July 2009 and October 2010, PROMMTT screened 12,561 trauma admissions and enrolled 1245 patients who received one or more blood transfusions within 6h of Emergency Department (ED) admission. A total of 297 massive transfusions were observed over the course of the study at a combined rate of 5.0 massive transfusion patients/week. PROMMTT is the first multisite study to collect real-time prospective data on trauma patients requiring transfusion. Support from the Department of Defense and collaborative expertise from the ten participating centers helped to demonstrate the feasibility of prospective trauma transfusion studies. The observational data collected from this study will be an invaluable resource for research in trauma surgery and it will guide the design and conduct of future randomized trials. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Coordination and management of multicenter clinical studies in trauma: Experience from the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study

PubMed Central

Rahbar, Mohammad H.; Fox, Erin E.; del Junco, Deborah J.; Cotton, Bryan A.; Podbielski, Jeanette M.; Matijevic, Nena; Cohen, Mitchell J.; Schreiber, Martin A.; Zhang, Jiajie; Mirhaji, Parsa; Duran, Sarah; Reynolds, Robert J.; Benjamin-Garner, Ruby; Holcomb, John B.

2011-01-01

Aim Early death due to hemorrhage is a major consequence of traumatic injury. Transfusion practices differ among hospitals and it is unknown which transfusion practices improve survival. This report describes the experience of the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study Data Coordination Center in designing and coordinating a study to examine transfusion practices at ten Level 1 trauma centers in the U.S. Methods PROMMTT was a multisite prospective observational study of severely injured transfused trauma patients. The clinical sites collected real-time information on the timing and amounts of blood product infusions as well as colloids and crystalloids, vital signs, initial diagnostic and clinical laboratory tests, life saving interventions and other clinical care data. Results Between July 2009 and October 2010, PROMMTT screened 12,561 trauma admissions and enrolled 1,245 patients who received one or more blood transfusions within 6 hours of ED admission. A total of 297 massive transfusions were observed over the course of the study at a combined rate of 5.0 massive transfusion patients/week. Conclusion PROMMTT is the first multisite study to collect real-time prospective data on trauma patients requiring transfusion. Support from the Department of Defense and collaborative expertise from the ten participating centers helped to demonstrate the feasibility of prospective trauma transfusion studies. The observational data collected from this study will be an invaluable resource for research in trauma surgery and it will guide the design and conduct of future randomized trials. PMID:22001613

General practitioner use of a C-reactive protein point-of-care test to help target antibiotic prescribing in patients with acute exacerbations of chronic obstructive pulmonary disease (the PACE study): study protocol for a randomised controlled trial.

PubMed

Bates, Janine; Francis, Nick A; White, Patrick; Gillespie, David; Thomas-Jones, Emma; Breen, Rachel; Kirby, Nigel; Hood, Kerry; Gal, Micaela; Phillips, Rhiannon; Naik, Gurudutt; Cals, Jochen; Llor, Carl; Melbye, Hasse; Wootton, Mandy; Riga, Evgenia; Cochrane, Ann; Howe, Robin; Fitzsimmons, Deborah; Sewell, Bernadette; Alam, Mohammed Fasihul; Butler, Christopher C

2017-09-29

Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed an antibiotic, which may not always be appropriate and may cause harm. C-reactive protein (CRP) is an acute-phase biomarker that can be rapidly measured at the point of care and may predict benefit from antibiotic treatment in AECOPD. It is not clear whether the addition of a CRP point-of-care test (POCT) to clinical assessment leads to a reduction in antibiotic consumption without having a negative impact on COPD health status. This is a multicentre, individually randomised controlled trial (RCT) aiming to include 650 participants with a diagnosis of AECOPD in primary care. Participants will be randomised to be managed according to usual care (control) or with the addition of a CRP POCT to guide antibiotic prescribing. Antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status (total score) measured by the Clinical COPD Questionnaire (CCQ) at 2 weeks post randomisation will be co-primary outcomes. Primary analysis (by intention-to-treat) will determine differences in antibiotic consumption for superiority and COPD health status for non-inferiority. Secondary outcomes include: COPD health status, CCQ domain scores, use of other COPD treatments (weeks 1, 2 and 4), EQ-5D utility scores (weeks 1, 2 and 4 and month 6), disease-specific, health-related quality of life (HRQoL) at 6 months, all-cause antibiotic consumption (antibiotic use for any condition) during first 4 weeks post randomisation, total antibiotic consumption (number of days during first 4 weeks of antibiotic consumed for AECOPD/any reason), antibiotic prescribing at the index consultation and during following 4 weeks, adverse effects over the first 4 weeks, incidence of pneumonia (weeks 4 and 6 months), health care resource use and cost comparison over the 6 months following randomisation. Prevalence and resistance profiles of bacteria will be assessed using throat and sputum samples collected at baseline and 4-week follow-up. A health economic evaluation and qualitative process evaluation will be carried out. If shown to be effective (i.e. leads to a reduction in antibiotic use with no worse COPD health status), the use of the CRP POCT could lead to better outcomes for patients with AECOPD and help reduce selective pressures driving the development of antimicrobial resistance. PACE will be one of the first studies to evaluate the cost-effectiveness of a POCT biomarker to guide clinical decision-making in primary care on patient-reported outcomes, antibiotic prescribing and antibiotic resistance for AECOPD. ISRCTN registry, ID: ISRCTN24346473 . Registered on 20 August 2014.

A multicenter tractography study of deep white matter tracts in bipolar I disorder: psychotic features and interhemispheric disconnectivity.

PubMed

Sarrazin, Samuel; Poupon, Cyril; Linke, Julia; Wessa, Michèle; Phillips, Mary; Delavest, Marine; Versace, Amelia; Almeida, Jorge; Guevara, Pamela; Duclap, Delphine; Duchesnay, Edouard; Mangin, Jean-François; Le Dudal, Katia; Daban, Claire; Hamdani, Nora; D'Albis, Marc-Antoine; Leboyer, Marion; Houenou, Josselin

2014-04-01

Tractography studies investigating white matter (WM) abnormalities in patients with bipolar disorder have yielded heterogeneous results owing to small sample sizes. The small size limits their generalizability, a critical issue for neuroimaging studies of biomarkers of bipolar I disorder (BPI). To study WM abnormalities using whole-brain tractography in a large international multicenter sample of BPI patients and to compare these alterations between patients with or without a history of psychotic features during mood episodes. A cross-sectional, multicenter, international, Q-ball imaging tractography study comparing 118 BPI patients and 86 healthy control individuals. In addition, among the patient group, we compared those with and without a history of psychotic features. University hospitals in France, Germany, and the United States contributed participants. Participants underwent assessment using the Diagnostic Interview for Genetic Studies at the French sites or the Structured Clinical Interview for DSM-IV at the German and US sites. Diffusion-weighted magnetic resonance images were acquired using the same acquisition parameters and scanning hardware at each site. We reconstructed 22 known deep WM tracts using Q-ball imaging tractography and an automatized segmentation technique. Generalized fractional anisotropy values along each reconstructed WM tract. Compared with controls, BPI patients had significant reductions in mean generalized fractional anisotropy values along the body and the splenium of the corpus callosum, the left cingulum, and the anterior part of the left arcuate fasciculus when controlling for age, sex, and acquisition site (corrected for multiple testing). Patients with a history of psychotic features had a lower mean generalized fractional anisotropy value than those without along the body of the corpus callosum (corrected for multiple testing). In this multicenter sample, BPI patients had reduced WM integrity in interhemispheric, limbic, and arcuate WM tracts. Interhemispheric pathways are more disrupted in patients with than in those without psychotic symptoms. Together these results highlight the existence of an anatomic disconnectivity in BPI and further underscore a role for interhemispheric disconnectivity in the pathophysiological features of psychosis in BPI.

Design-corrected variation by centre in mortality reduction in the ERSPC randomised prostate cancer screening trial.

PubMed

Hakama, Matti; Moss, Sue M; Stenman, Ulf-Hakan; Roobol, Monique J; Zappa, Marco; Carlsson, Sigrid; Randazzo, Marco; Nelen, Vera; Hugosson, Jonas

2017-06-01

Objectives To calculate design-corrected estimates of the effect of screening on prostate cancer mortality by centre in the European Randomised Study of Screening for Prostate Cancer (ERSPC). Setting The ERSPC has shown a 21% reduction in prostate cancer mortality in men invited to screening with follow-up truncated at 13 years. Centres either used pre-consent randomisation (effectiveness design) or post-consent randomisation (efficacy design). Methods In six centres (three effectiveness design, three efficacy design) with follow-up until the end of 2010, or maximum 13 years, the effect of screening was estimated as both effectiveness (mortality reduction in the target population) and efficacy (reduction in those actually screened). Results The overall crude prostate cancer mortality risk ratio in the intervention arm vs control arm for the six centres was 0.79 ranging from a 14% increase to a 38% reduction. The risk ratio was 0.85 in centres with effectiveness design and 0.73 in those with efficacy design. After correcting for design, overall efficacy was 27%, 24% in pre-consent and 29% in post-consent centres, ranging between a 12% increase and a 52% reduction. Conclusion The estimated overall effect of screening in attenders (efficacy) was a 27% reduction in prostate cancer mortality at 13 years' follow-up. The variation in efficacy between centres was greater than the range in risk ratio without correction for design. The centre-specific variation in the mortality reduction could not be accounted for by the randomisation method.

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

PubMed

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

2014-10-24

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

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.

Logistics and quality control for DNA sampling in large multicenter studies.

PubMed

Nederhand, R J; Droog, S; Kluft, C; Simoons, M L; de Maat, M P M

2003-05-01

To study associations between genetic variation and disease, large bio-banks need to be created in multicenter studies. Therefore, we studied the effects of storage time and temperature on DNA quality and quantity in a simulation experiment with storage up to 28 days frozen, at 4 degrees C and at room temperature. In the simulation experiment, the conditions did not influence the amount or quality of DNA to an unsatisfactory level. However, the amount of extracted DNA was decreased in frozen samples and in samples that were stored for > 7 days at room temperature. In a sample of patients from 24 countries of the EUROPA trial obtained by mail with transport times up to 1 month DNA yield and quality were adequate. From these results we conclude that transport of non-frozen blood by ordinary mail is usable and practical for DNA isolation for polymerase chain reaction in clinical and epidemiological studies.

An introduction to instrumental variables analysis: part 1.

PubMed

Bennett, Derrick A

2010-01-01

There are several examples in the medical literature where the associations of treatment effects predicted by observational studies have been refuted by evidence from subsequent large-scale randomised trials. This is because of the fact that non-experimental studies are subject to confounding - and confounding cannot be entirely eliminated even if all known confounders have been measured in the study as there may be unknown confounders. The aim of this 2-part methodological primer is to introduce an emerging methodology for estimating treatment effects using observational data in the absence of good randomised evidence known as the method of instrumental variables. Copyright © 2010 S. Karger AG, Basel.

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.

A multicentre, open-label, randomised phase III study comparing a new levonorgestrel intrauterine contraceptive system (LNG-IUS 8) with combined oral contraception in young women of reproductive age.

PubMed

Borgatta, Lynn; Buhling, Kai J; Rybowski, Sarah; Roth, Katrin; Rosen, Kimberly

2016-10-01

To compare user satisfaction and adverse events (AEs) with a levonorgestrel intrauterine system (LNG-IUS 8; average levonorgestrel release rate approximately 8 μg/24 h over the first year [total content 13.5 mg]) and a 30 μg ethinyl estradiol/3 mg drospirenone (EE/DRSP) combined oral contraceptive (COC) in a population of young women. Nulliparous and parous women (aged 18-29 years) with regular menstrual cycles (21-35 days) were randomised to LNG-IUS 8 or EE/DRSP for 18 months. The primary endpoint was the overall user satisfaction rate at month 18/end of study visit. Overall, 279 women were randomised to LNG-IUS 8 with attempted placement and 281 women were randomised to EE/DRSP and took ≥1 pill; the mean age was 23.7 and 23.9 years, and 77.4% and 73.3% were nulliparous, respectively. At month 18/end of study, 82.1% and 81.9% of women, respectively, reported being 'very satisfied' or 'satisfied' with their treatment; however, significantly more LNG-IUS 8 users reported a preference to continue their treatment post-study (66.2% vs 48.8%; p = 0.0001). There were two pregnancies (one ectopic pregnancy, one spontaneous abortion) reported in the LNG-IUS 8 group and six (three live births, two spontaneous abortions, one induced abortion) in the EE/DRSP group. LNG-IUS 8 and EE/DRSP were associated with similarly high user satisfaction rates. However, LNG-IUS 8 users were significantly more likely to prefer to continue their contraceptive method post-study, indicating that a levonorgestrel intrauterine system is an appealing contraceptive option for young women.

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

PubMed

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

2015-01-01

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

Towards evidence-based vitamin D supplementation in infants: vitamin D intervention in infants (VIDI) - study design and methods of a randomised controlled double-blinded intervention study.

PubMed

Helve, Otto; Viljakainen, Heli; Holmlund-Suila, Elisa; Rosendahl, Jenni; Hauta-Alus, Helena; Enlund-Cerullo, Maria; Valkama, Saara; Heinonen, Kati; Räikkönen, Katri; Hytinantti, Timo; Mäkitie, Outi; Andersson, Sture

2017-03-29

Vitamin D is important for bone mass accrual during growth. Additionally, it is considered a requirement for a multitude of processes associated with, for example, the development of immunity. Many countries apply vitamin D supplementation strategies in infants, but the guidelines are not based on scientific evidence and aim at prevention of rickets. It remains unclear whether the recommended doses are sufficient for the wide array of other effects of vitamin D. The VIDI trial performed in Finland is the first large randomised controlled study for evaluation of the effects of different vitamin D supplemental doses in infancy on: 1. bone strength 2. infections and immunity 3. allergy, atopy and asthma 4. cognitive development 5. genetic regulation of mineral homeostasis METHODS/DESIGN: VIDI, a randomised controlled double-blinded single-centre intervention study is conducted in infants from the age of 2 weeks to 24 months. Participants, recruited at Helsinki Maternity Hospital, are randomised to receive daily either 10 μg (400 IU) or 30 μg (1 200 IU) of vitamin D3 supplementation. Both groups are assessed at 6 months of age for calcium homeostasis, and at 12 and 24 months of age for parameters associated with bone strength, growth, developmental milestones, infections, immunity, atopy-related diseases, and genetic factors involved in these functions. The study enables evaluation of short and long term effects of supplemental vitamin D on growth, immune functions and skeletal and developmental parameters in infants, and the effects of genetic factors therein. The results enable institution of evidence-based guidelines for vitamin D supplementation in infancy. ClinicalTrials.gov, NCT01723852 , registration date 6.11.2012.

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

PubMed Central

2013-01-01

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

Organizational structure and communication strategies of the bypass angioplasty revascularization investigation: a multicenter clinical trial.

PubMed

Naydeck, B L; Sutton-Tyrrell, K; Burek, K; Sopko, G S

1996-06-01

Efficient communication is a challenge for the many operating components of a multicenter randomized clinical trial. Traditional management theory states that communications generally flow along a path established by a hierarchical organizational structure. A multicenter clinical trial does not fit traditional organizational models well and requires modification of traditional communication techniques. While the scientific community typically views a clinical trial as one large and cohesive enterprise, at each site the trial may actually be conducted as a small project related to the medical specialty of the investigator. Therefore overall trial management must be accomplished through collaboration rather than through direct management. In the Bypass Angioplasty Revascularization Investigation (BARI), the BARI clinical coordinating center has designed and utilized several mechanisms that facilitate effective communication and administrative control of a multicenter clinical trial. These mechanisms provide a framework of communication techniques that accommodate the specific needs of a complex organization.

Prospective Validation of Objective Prognostic Score for Advanced Cancer Inpatients in South Korea: A Multicenter Study.

PubMed

Yoon, Seok Joon; Suh, Sang-Yeon; Lee, Yong Joo; Park, Jeanno; Hwang, Sunwook; Lee, Sanghee Shiny; Ahn, Hong Yup; Koh, Su-Jin; Park, Keon Uk

2017-01-01

Objective Prognostic Score (OPS) was developed as an easy and simple prognosticating tool in South Korea. It has been validated retrospectively in a single center in South Korea. We aimed to validate the OPS prospectively for advanced cancer inpatients in South Korea using a multicenter study. This was a prospective cohort study. We enrolled 243 advanced cancer patients admitted in five palliative care units in South Korea from May 2013 till March 2015. Seven members of the Korean Palliative Medicine Research Network who are experts of palliative care led the study. Clinical variables (dyspnea/anorexia/performance status) and laboratory variables (total leukocyte counts/serum total bilirubin/serum creatinine/lactate dehydrogenase) were collected at the enrollment. Survival time was calculated as days from enrollment to death during admission. A total of 217 patients were included in the final analysis (feasibility: 89.3%). Survival time of the higher OPS group (OPS ≥3) and the lower OPS group (OPS <3) was 10.0 (95% confidence interval (CI) 7.72-12.28) days and 32.0 (95% CI 25.44-38.56) days, respectively. There were significant differences between the 2 groups (p < 0.001). Overall accuracy of OPS ≥3 for predicting survival less than three weeks was 71.0%. OPS was successfully validated using a prospective multicenter study in South Korea. It is a useful method to predict three-week survival of Korean inpatients with advanced cancer.

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

Efficacy and cost-effectiveness of minimal guided and unguided internet-based mobile supported stress-management in employees with occupational stress: a three-armed randomised controlled trial.

PubMed

Ebert, David Daniel; Lehr, Dirk; Smit, Filip; Zarski, Anna-Carlotta; Riper, Heleen; Heber, Elena; Cuijpers, Pim; Berking, Matthias

2014-08-07

Internet- and mobile based stress-management interventions (iSMI) may be an effective means to address the negative consequences of occupational stress. However, available results from randomised controlled trials are conflicting. Moreover, it is yet not clear whether guided or unguided self-help iSMI provide better value for money. Internet-based mental health interventions without guidance are often much less effective than interventions including at least some guidance from a professional. However, direct comparisons in randomised controlled trials are scarce and, to the best of our knowledge, the comparative (cost)-effectiveness of guided vs. unguided iSMI has not yet been studied. Hence, this study investigates the acceptability and (cost-) effectiveness of minimal guided and unguided iSMI in employees with heightened levels of perceived stress. A three-armed randomised controlled trial (RCT) will be conducted to compare a minimal guided and unguided iSMI with a waiting list control condition (WLC). Both active conditions are based on the same iSMI, i.e. GET.ON Stress, and differ only with regard to the guidance format. Employees with heightened levels of perceived stress (PSS ≥ 22) will be randomised to one of three conditions. Primary outcome will be comparative changes in perceived stress (PSS). Secondary outcomes include changes in self-reported depression, work-engagement, presenteeism and absenteeism. Moreover, a cost-effectiveness analysis will be conducted from a societal perspective, including both direct medical costs and costs related to productivity losses. In addition, a cost-benefit analysis will be conducted from the employer's perspective. Incremental net-benefit regression analyses will address the question if there are any baseline factors (i.e. subgroups of employees) associated with particularly favorable cost-effectiveness when the experimental intervention is offered. Assessments take place at baseline, 7 weeks post-treatment and 6 months after randomisation. Online-based (guided) self-help interventions could be an acceptable, effective and economically sustainable approach to offer evidence-based intervention alternatives to reduce the negative consequences associated with work-related stress. This study evaluates the (cost-) effectiveness of two versions of an iSMI, minimal guided and unguided iSMI. Thus, the present study will further enhance the evidence-base for iSMI and provide valuable information about the optimal balance between outcome and economic costs. German Clinical Trial Registration (DRKS): DRKS00005687.

Antibiotic prophylaxis for surgical site infection in people undergoing liver transplantation.

PubMed

Almeida, Ricardo A M B; Hasimoto, Claudia N; Kim, Anna; Hasimoto, Erica N; El Dib, Regina

2015-12-05

Surgical site infection is more frequent in liver transplantation than in other types of solid organ transplantation with different antibiotics. Studies have shown that the rate of surgical site infection varies from 8.8% to 37.5% after liver transplantation. Therefore, antimicrobial prophylaxis is likely an essential tool for reducing these infections. However, the literature lacks evidence indicating the best prophylactic antibiotic regimen that can be used for liver transplantation. To assess the benefits and harms of antibiotic prophylactic regimens for surgical site infection in people undergoing liver transplantation. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded and Latin American Caribbean Health Sciences Literature (LILACS). The most recent search was performed on 11 September 2015. All eligible randomised clinical trials comparing any antibiotic regimen versus placebo, versus no intervention or versus another antibiotic regimen for surgical site infection in liver transplant recipients, regardless of age, sex and reason for transplantation. Quasi-randomised studies and other observational studies were considered for data on harm if retrieved with search results for randomised clinical trials. Two review authors selected relevant trials, assessed risk of bias of studies and extracted data. The electronic search identified 786 publications after removal of duplicates. From this search, only one seemingly randomised clinical trial, published in abstract form, fulfilled the inclusion criteria of this review. This trial was conducted at Shiraz Transplant Centre, Shiraz, Iran, where investigators randomly assigned a total of 180 consecutive liver transplant recipients. We judged the overall risk of bias of the trial published in abstract form as high. Researchers reported no numerical data but mentioned that 163 participants met the inclusion criteria after randomisation, and hence were included in the analyses. Most probably, the 17 excluded participants were high-risk liver transplant recipients. Trial authors concluded that they could find no differences between the two antibiotic regimens - ceftriaxone plus metronidazole versus ampicillin-sulbactam plus ceftizoxime - when given to liver transplant recipients. Review authors could not reconfirm the analyses because, as it has been mentioned, trial authors provided no trial data for analyses. Benefits and harms of antibiotic prophylactic regimens for surgical site infection in liver transplantation remain unclear. Additional well-conducted randomised clinical trials adhering to SPIRIT (Spirit Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) guidelines are needed to determine the exact role of antibiotic prophylactic regimens in patients undergoing liver transplantation.

The Pediatric Emergency Care Applied Research Network: a history of multicenter collaboration in the United States.

PubMed

Tzimenatos, Leah; Kim, Emily; Kuppermann, Nathan

2014-12-01

In this article, we review the history and progress of a large multicenter research network pertaining to emergency medical services for children. We describe the history, organization, infrastructure, and research agenda of the Pediatric Emergency Care Applied Research Network (PECARN), and highlight some of the important accomplishments since its inception. We also describe the network's strategy to grow its research portfolio, train new investigators, and study how to translate new evidence into practice. This strategy ensures not only the sustainability of the network in the future, but the growth of research in emergency medical services for children in general.

The Pediatric Emergency Care Applied Research Network: a history of multicenter collaboration in the United States.

PubMed

Tzimenatos, Leah; Kim, Emily; Kuppermann, Nathan

2015-01-01

In this article, we review the history and progress of a large multicenter research network pertaining to emergency medical services for children. We describe the history, organization, infrastructure, and research agenda of the Pediatric Emergency Care Applied Research Network and highlight some of the important accomplishments since its inception. We also describe the network's strategy to grow its research portfolio, train new investigators, and study how to translate new evidence into practice. This strategy ensures not only the sustainability of the network in the future but the growth of research in emergency medical services for children in general.

Identification of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa in Blood Cultures: a Multicenter Performance Evaluation of a Three-Color Peptide Nucleic Acid Fluorescence In Situ Hybridization Assay▿

PubMed Central

Della-Latta, Phyllis; Salimnia, Hossein; Painter, Theresa; Wu, Fann; Procop, Gary W.; Wilson, Deborah A.; Gillespie, Wendy; Mender, Alayna; Crystal, Benjamin S.

2011-01-01

A multicenter evaluation was undertaken to evaluate the performance of a new three-color peptide nucleic acid fluorescence in situ hybridization assay that identifies isolates directly from blood cultures positive for Gram-negative bacilli (GNB). The assay correctly identified 100% (186/186) of the Escherichia coli isolates, 99.1% (109/110) of the Klebsiella pneumoniae isolates, and 95.8% (46/48) of the Pseudomonas aeruginosa isolates in this study. Negative assay results were correctly obtained for 162 of 165 other GNB (specificity, 98.2%). PMID:21490185

Clinical effectiveness and cost-effectiveness of cholecystectomy compared with observation/conservative management for preventing recurrent symptoms and complications in adults presenting with uncomplicated symptomatic gallstones or cholecystitis: a systematic review and economic evaluation.

PubMed

Brazzelli, Miriam; Cruickshank, Moira; Kilonzo, Mary; Ahmed, Irfan; Stewart, Fiona; McNamee, Paul; Elders, Andrew; Fraser, Cynthia; Avenell, Alison; Ramsay, Craig

2014-08-01

Approximately 10-15% of the adult population suffer from gallstone disease, cholelithiasis, with more women than men being affected. Cholecystectomy is the treatment of choice for people who present with biliary pain or acute cholecystitis and evidence of gallstones. However, some people do not experience a recurrence after an initial episode of biliary pain or cholecystitis. As most of the current research focuses on the surgical management of the disease, less attention has been dedicated to the consequences of conservative management. To determine the clinical effectiveness and cost-effectiveness of cholecystectomy compared with observation/conservative management in people presenting with uncomplicated symptomatic gallstones (biliary pain) or cholecystitis. We searched all major electronic databases (e.g. MEDLINE, EMBASE, Science Citation Index, Bioscience Information Service, Cochrane Central Register of Controlled Trials) from 1980 to September 2012 and we contacted experts in the field. Evidence was considered from randomised controlled trials (RCTs) and non-randomised comparative studies that enrolled people with symptomatic gallstone disease (pain attacks only and/or acute cholecystitis). Two reviewers independently extracted data and assessed the risk of bias of included studies. Standard meta-analysis techniques were used to combine results from included studies. A de novo Markov model was developed to assess the cost-effectiveness of the interventions. Two Norwegian RCTs involving 201 participants were included. Eighty-eight per cent of people randomised to surgery and 45% of people randomised to observation underwent cholecystectomy during the 14-year follow-up period. Participants randomised to observation were significantly more likely to experience gallstone-related complications [risk ratio = 6.69; 95% confidence interval (CI) 1.57 to 28.51; p = 0.01], in particular acute cholecystitis (risk ratio = 9.55; 95% CI 1.25 to 73.27; p = 0.03), and less likely to undergo surgery (risk ratio = 0.50; 95% CI 0.34 to 0.73; p = 0.0004), experience surgery-related complications (risk ratio = 0.36; 95% CI 0.16 to 0.81; p = 0.01) or, more specifically, minor surgery-related complications (risk ratio = 0.11; 95% CI 0.02 to 0.56; p = 0.008) than those randomised to surgery. Fifty-five per cent of people randomised to observation did not require an operation during the 14-year follow-up period and 12% of people randomised to cholecystectomy did not undergo the scheduled operation. The results of the economic evaluation suggest that, on average, the surgery strategy costs £1236 more per patient than the conservative management strategy but was, on average, more effective. An increase in the number of people requiring surgery while treated conservatively corresponded to a reduction in the cost-effectiveness of the conservative strategy. There was uncertainty around some of the parameters used in the economic model. The results of this assessment indicate that cholecystectomy is still the treatment of choice for many symptomatic people. However, approximately half of the people in the observation group did not require surgery or suffer complications in the long term indicating that a conservative therapeutic approach may represent a valid alternative to surgery in this group of people. Owing to the dearth of current evidence in the UK setting a large, well-designed, multicentre trial is needed. The study was registered as PROSPERO CRD42012002817. The National Institute for Health Research Health Technology Assessment programme.

Hyperbaric oxygen therapy for Bell's palsy.

PubMed

Holland, N Julian; Bernstein, Jonathan M; Hamilton, John W

2012-02-15

Bell's palsy is an idiopathic, acute unilateral facial weakness that evolves rapidly and is maximal within two days. Moderate ear discomfort, sensitivity to sound and reduced tearing may occur. To assess the effects of hyperbaric oxygen therapy on recovery of facial function in adults with moderate to severe Bell's palsy. We searched the Cochrane Neuromuscular Disease Group Specialized Register (January 2012), CENTRAL (2011, Issue 4), MEDLINE (January 1966 to January 2012), EMBASE (January 1980 to January 2012), CINAHL (1937 to January 2012), AMED (1985 to January 2012), LILACS (January 1982 to January 2012). In addition we made a systematic search for relevant controlled trials in specific hyperbaric literature sources. Randomised controlled trials or quasi-randomised controlled trials of adults (over 16 years of age) undergoing hyperbaric oxygen therapy for moderate to severe Bell's palsy. We considered studies to be of sufficient quality for inclusion in the review only if there was blinding in the assessment of the facial palsy grade. We planned to include studies of HBOT used as adjuvant therapy, or in addition to routine medical therapy (including corticosteroids or antivirals, or both). Both treatment and control groups were to receive the same baseline therapy. HBOT had to be delivered at concentrations greater than or equal to 1.2 ATA in a hyperbaric oxygen chamber as a series of dives of 30 to 120 minutes. Two reviewers independently assessed eligibility and study quality and extracted data. We contacted study authors for additional information. Our searches found no randomised controlled trials or quasi-randomised controlled trials that met the eligibility criteria for this review.There is very low quality evidence from one randomised trial involving 79 participants with acute Bell's palsy, but this study was excluded as the outcome assessor was not blinded to treatment allocation and thus did not meet pre-defined eligibility criteria. The trial compared 42 people who received hyperbaric oxygen therapy (2.8 atmospheres for 60 minutes twice daily, five days per week until the facial palsy resolved; maximum 30 'dives') and placebo tablets with 37 people who received placebo hyperbaric oxygen therapy (achieving only a normal partial pressure of oxygen) and prednisone (40 mg twice daily, reducing over eight days). Facial function recovered in more participants treated with hyperbaric oxygen therapy than with prednisone (hyperbaric oxygen therapy, 40/42 (95%); prednisone, 28/37 (76%); risk ratio 1.26, 95% CI 1.04 to 1.53). There were no reported major complications and all participants completed the trial. Very low quality evidence from one trial suggests that hyperbaric oxygen therapy may be an effective treatment for moderate to severe Bell's palsy, but this study was excluded as the outcome assessor was not blinded to treatment allocation. Further randomised controlled trials are needed.

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2017-12-04

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

BIOCHEMICAL CONTROL DURING LONG-TERM FOLLOW-UP OF 230 ADULT PATIENTS WITH CUSHING DISEASE: A MULTICENTER RETROSPECTIVE STUDY.

PubMed

Geer, Eliza B; Shafiq, Ismat; Gordon, Murray B; Bonert, Vivien; Ayala, Alejandro; Swerdloff, Ronald S; Katznelson, Laurence; Lalazar, Yelena; Manuylova, Ekaterina; Pulaski-Liebert, Karen J; Carmichael, John D; Hannoush, Zeina; Surampudi, Vijaya; Broder, Michael S; Cherepanov, Dasha; Eagan, Marianne; Lee, Jackie; Said, Qayyim; Neary, Maureen P; Biller, Beverly M K

2017-08-01

Cushing disease (CD) results from excessive exposure to glucocorticoids caused by an adrenocorticotropic hormone-secreting pituitary tumor. Inadequately treated CD is associated with significant morbidity and elevated mortality. Multicenter data on CD patients treated in routine clinical practice are needed to assess treatment outcomes in this rare disorder. The study purpose was to describe the burden of illness and treatment outcomes for CD patients. Eight pituitary centers in four U.S. regions participated in this multicenter retrospective chart review study. Subjects were CD patients diagnosed at ≥18 years of age within the past 20 years. Descriptive statistical analyses were conducted to examine presenting signs, symptoms, comorbidities, and treatment outcomes. Of 230 patients, 79% were female (median age at diagnosis, 39 years; range, 18 to 78 years). Length of follow-up was 0 to 27.5 years (median, 1.9 years). Pituitary adenomas were 0 to 51 mm. The most common presenting comorbidities included hypertension (67.3%), polycystic ovary syndrome (43.5%), and hyperlipidemia (41.5%). Biochemical control was achieved with initial pituitary surgery in 41.4% patients (91 of 220), not achieved in 50.0% of patients (110 of 220), and undetermined in 8.6% of patients (19 of 220). At the end of follow-up, control had been achieved with a variety of treatment methods in 49.1% of patients (110 of 224), not achieved in 29.9% of patients (67 of 224), and undetermined in 21.0% of patients (47 of 224). Despite multiple treatments, at the end of follow-up, biochemical control was still not achieved in up to 30% of patients. These multicenter data demonstrate that in routine clinical practice, initial and long-term control is not achieved in a substantial number of patients with CD. BLA = bilateral adrenalectomy CD = Cushing disease CS = Cushing syndrome eCRF = electronic case report form MRI = magnetic resonance imaging PCOS = polycystic ovary syndrome.

Minimal access surgery compared with medical management for chronic gastro-oesophageal reflux disease: UK collaborative randomised trial

PubMed Central

Wileman, Samantha M; Ramsay, Craig R; Mowat, N Ashley; Krukowski, Zygmunt H; Heading, Robert C; Thursz, Mark R; Campbell, Marion K

2008-01-01

Objective To determine the relative benefits and risks of laparoscopic fundoplication surgery as an alternative to long term drug treatment for chronic gastro-oesophageal reflux disease (GORD). Design Multicentre, pragmatic randomised trial (with parallel preference groups). Setting 21 hospitals in the United Kingdom. Participants 357 randomised participants (178 surgical, 179 medical) and 453 preference participants (261, 192); mean age 46; 66% men. All participants had documented evidence of GORD and symptoms for >12 months. Intervention The type of laparoscopic fundoplication used was left to the discretion of the surgeon. Those allocated to medical treatment had their treatment reviewed and adjusted as necessary by a local gastroenterologist, and subsequent clinical management was at the discretion of the clinician responsible for care. Main outcome measures The disease specific REFLUX quality of life score (primary outcome), SF-36, EQ-5D, and medication use, measured at time points equivalent to three and 12 months after surgery, and surgical complications. Main results Randomised participants had received drugs for GORD for median of 32 months before trial entry. Baseline REFLUX scores were 63.6 (SD 24.1) and 66.8 (SD 24.5) in the surgical and medical randomised groups, respectively. Of those randomised to surgery, 111 (62%) actually had total or partial fundoplication. Surgical complications were uncommon with a conversion rate of 0.6% and no mortality. By 12 months, 38% (59/154) randomised to surgery (14% (14/104) among those who had fundoplication) were taking reflux medication versus 90% (147/164) randomised medical management. The REFLUX score favoured the randomised surgical group (14.0, 95% confidence interval 9.6 to 18.4; P<0.001). Differences of a third to half of 1 SD in other health status measures also favoured the randomised surgical group. Baseline scores in the preference for surgery group were the worst; by 12 months these were better than in the preference for medical treatment group. Conclusion At least up to 12 months after surgery, laparoscopic fundoplication significantly increased measures of health status in patients with GORD. Trial registration ISRCTN15517081. PMID:19074946

Minimal access surgery compared with medical management for chronic gastro-oesophageal reflux disease: UK collaborative randomised trial.

PubMed

Grant, Adrian M; Wileman, Samantha M; Ramsay, Craig R; Mowat, N Ashley; Krukowski, Zygmunt H; Heading, Robert C; Thursz, Mark R; Campbell, Marion K

2008-12-15

To determine the relative benefits and risks of laparoscopic fundoplication surgery as an alternative to long term drug treatment for chronic gastro-oesophageal reflux disease (GORD). Multicentre, pragmatic randomised trial (with parallel preference groups). 21 hospitals in the United Kingdom. 357 randomised participants (178 surgical, 179 medical) and 453 preference participants (261, 192); mean age 46; 66% men. All participants had documented evidence of GORD and symptoms for >12 months. The type of laparoscopic fundoplication used was left to the discretion of the surgeon. Those allocated to medical treatment had their treatment reviewed and adjusted as necessary by a local gastroenterologist, and subsequent clinical management was at the discretion of the clinician responsible for care. The disease specific REFLUX quality of life score (primary outcome), SF-36, EQ-5D, and medication use, measured at time points equivalent to three and 12 months after surgery, and surgical complications. Randomised participants had received drugs for GORD for median of 32 months before trial entry. Baseline REFLUX scores were 63.6 (SD 24.1) and 66.8 (SD 24.5) in the surgical and medical randomised groups, respectively. Of those randomised to surgery, 111 (62%) actually had total or partial fundoplication. Surgical complications were uncommon with a conversion rate of 0.6% and no mortality. By 12 months, 38% (59/154) randomised to surgery (14% (14/104) among those who had fundoplication) were taking reflux medication versus 90% (147/164) randomised medical management. The REFLUX score favoured the randomised surgical group (14.0, 95% confidence interval 9.6 to 18.4; P<0.001). Differences of a third to half of 1 SD in other health status measures also favoured the randomised surgical group. Baseline scores in the preference for surgery group were the worst; by 12 months these were better than in the preference for medical treatment group. At least up to 12 months after surgery, laparoscopic fundoplication significantly increased measures of health status in patients with GORD. ISRCTN15517081.

Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis.

PubMed

Davis, Stephanie D; Ratjen, Felix; Brumback, Lyndia C; Johnson, Robin C; Filbrun, Amy G; Kerby, Gwendolyn S; Panitch, Howard B; Donaldson, Scott H; Rosenfeld, Margaret

2016-05-01

The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint. Secondary analysis of ISIS data was conducted in order to assess feasibility of iPFT measures and their associations with respiratory symptoms. Standard deviations were calculated to aid in power calculations for future clinical trials. Seventy-three participants enrolled, 70 returned for the final visit; 62 (89%) and 45 (64%) had acceptable paired functional residual capacity (FRC) and raised volume measurements, respectively. Mean baseline FEV0.5, FEF75 and FRC z-scores were 0.3 (SD: 1.2), -0.2 (SD: 2.0), and 1.8 (SD: 2.0). iPFTs are not appropriate primary endpoints for multicenter clinical trials due to challenges of obtaining acceptable data and near-normal average raised volume measurements. Raised volume measures have potential to serve as secondary endpoints in future clinical CF trials. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Development of a Multicenter Density Functional Tight Binding Model for Plutonium Surface Hydriding.

PubMed

Goldman, Nir; Aradi, Bálint; Lindsey, Rebecca K; Fried, Laurence E

2018-05-08

We detail the creation of a multicenter density functional tight binding (DFTB) model for hydrogen on δ-plutonium, using a framework of new Slater-Koster interaction parameters and a repulsive energy based on the Chebyshev Interaction Model for Efficient Simulation (ChIMES), where two- and three-center atomic interactions are represented by linear combinations of Chebyshev polynomials. We find that our DFTB/ChIMES model yields a total electron density of states for bulk δ-Pu that compares well to that from Density Functional Theory, as well as to a grid of energy calculations representing approximate H 2 dissociation paths on the δ-Pu (100) surface. We then perform molecular dynamics simulations and minimum energy pathway calculations to determine the energetics of surface dissociation and subsurface diffusion on the (100) and (111) surfaces. Our approach allows for the efficient creation of multicenter repulsive energies with a relatively small investment in initial DFT calculations. Our efforts are particularly pertinent to studies that rely on quantum calculations for interpretation and validation, such as experimental determination of chemical reactivity both on surfaces and in condensed phases.

The effectiveness of Stepping stones Triple P: the design of a randomised controlled trial on a parenting programme regarding children with mild intellectual disability and psychosocial problems versus care as usual

PubMed Central

2011-01-01

Background Children with an intellectual disability are at increased risk of psychosocial problems. This leads to serious restrictions in the daily functioning of the children and to parental stress. Stepping Stones Triple P aims to prevent severe behavioural, emotional and developmental problems in children with a (intellectual) disability by enhancing parenting knowledge and skills, and the self-confidence of parents. This paper aims to describe the design of a study of the effectiveness of parenting counselling using Stepping Stones Triple P compared to Care as Usual. Methods/Design The effects of Stepping Stones Triple P will be studied in a Randomised Controlled Trial. Parents of children aged 5-12 years with an IQ of 50-85 will be recruited from schools. Prior to randomisation, parents complete a screening questionnaire about their child's psychosocial problems and their parenting skills. Subsequently, parents of children with increased levels of psychosocial problems (score on Strengths and Difficulties Questionnaire ≥ 14) will be invited to participate in the intervention study. After obtaining consent, parents will be randomised either to the experimental group (Stepping Stones Triple P) or to Care as Usual. The primary outcome is a change in the child's psychosocial problems according to parents and teachers. The secondary outcome is a change in parenting skills. Data will be collected before the start of the intervention, immediately after the intervention, and six months after. Discussion This paper presents an outline of the background and design of a randomised controlled trial to investigate the effectiveness of Stepping Stones Triple P, which aims to decrease psychosocial problems in children with a mild intellectual disability. Stepping Stones Triple P seems promising, but evidence on its effectiveness for this population is still lacking. This study provides evidence about the effects of this intervention in a community-based population of children with a mild intellectual disability. Trial registration Netherlands Trial Register (NTR): NTR2624 PMID:21878093

Effect of Baduanjin exercise on cognitive function in older adults with mild cognitive impairment: study protocol for a randomised controlled trial.

PubMed

Zheng, Guohua; Huang, Maomao; Li, Shuzhen; Li, Moyi; Xia, Rui; Zhou, Wenji; Tao, Jing; Chen, Lidian

2016-04-11

Mild cognitive impairment (MCI) is an intermediate stage between the cognitive changes of normal aging and dementia characterised by a reduction in memory and/or other cognitive processes. An increasing number of studies have indicated that regular physical activity/exercise may have beneficial association with cognitive function of older adults with or without cognitive impairment. As a traditional Chinese Qigong exercise, Baduanjin may be even more beneficial in promoting cognitive ability in older adults with MCI, but the evidence is still insufficient. The main purpose of this study is to investigate the effect of Baduanjin exercise on neuropsychological outcomes of community-dwelling older adults with MCI, and to explore its mechanism of action from neuroimaging based on functional MRI (fMRI) and cerebrovascular function. The design of this study is a randomised, controlled trial with three parallel groups in a 1:1:1 allocation ratio with allocation concealment and assessor blinding. A total of 135 participants will be enrolled and randomised to the 24-week Baduanjin exercise intervention, 24-week brisk walking intervention and 24-week usual physical activity control group. Global cognitive function and the specific domains of cognition (memory, processing speed, executive function, attention and verbal learning and memory) will be assessed at baseline and 9, 17, 25 and 37 weeks after randomisation, while the structure and function of brain regions related to cognitive function and haemodynamic variables of the brain will be measured by fMRI and transcranial Doppler, respectively, at baseline and 25 and 37 weeks after randomisation. Ethics approval was given by the Medical Ethics Committee of the Second People's Hospital of Fujian Province (approval number 2014-KL045-02). The findings will be disseminated through peer-reviewed publications and at scientific conferences. ChiCTR-ICR-15005795; 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/

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

PubMed Central

2013-01-01

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

β-Blockers for the prevention of acute exacerbations of chronic obstructive pulmonary disease (βLOCK COPD): a randomised controlled study protocol

PubMed Central

Bhatt, Surya P; Connett, John E; Voelker, Helen; Lindberg, Sarah M; Westfall, Elizabeth; Wells, J Michael; Lazarus, Stephen C; Criner, Gerard J; Dransfield, Mark T

2016-01-01

Introduction A substantial majority of chronic obstructive pulmonary disease (COPD)-related morbidity, mortality and healthcare costs are due to acute exacerbations, but existing medications have only a modest effect on reducing their frequency, even when used in combination. Observational studies suggest β-blockers may reduce the risk of COPD exacerbations; thus, we will conduct a randomised, placebo-controlled trial to definitively assess the impact of metoprolol succinate on the rate of COPD exacerbations. Methods and analyses This is a multicentre, placebo-controlled, double-blind, prospective randomised trial that will enrol 1028 patients with at least moderately severe COPD over a 3-year period. Participants with at least moderate COPD will be randomised in a 1:1 fashion to receive metoprolol or placebo; the cohort will be enriched for patients at high risk for exacerbations. Patients will be screened and then randomised over a 2-week period and will then undergo a dose titration period for the following 6 weeks. Thereafter, patients will be followed for 42 additional weeks on their target dose of metoprolol or placebo followed by a 4-week washout period. The primary end point is time to first occurrence of an acute exacerbation during the treatment period. Secondary end points include rates and severity of COPD exacerbations; rate of major cardiovascular events; all-cause mortality; lung function (forced expiratory volume in 1 s (FEV1)); dyspnoea; quality of life; exercise capacity; markers of cardiac stretch (pro-NT brain natriuretic peptide) and systemic inflammation (high-sensitivity C reactive protein and fibrinogen). Analyses will be performed on an intent-to-treat basis. Ethics and dissemination The study protocol has been approved by the Department of Defense Human Protection Research Office and will be approved by the institutional review board of all participating centres. Study findings will be disseminated through presentations at national and international conferences and publications in peer-reviewed journals. Trial registration number NCT02587351; Pre-results. PMID:27267111

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.

β-Blockers for the prevention of acute exacerbations of chronic obstructive pulmonary disease (βLOCK COPD): a randomised controlled study protocol.

PubMed

Bhatt, Surya P; Connett, John E; Voelker, Helen; Lindberg, Sarah M; Westfall, Elizabeth; Wells, J Michael; Lazarus, Stephen C; Criner, Gerard J; Dransfield, Mark T

2016-06-07

A substantial majority of chronic obstructive pulmonary disease (COPD)-related morbidity, mortality and healthcare costs are due to acute exacerbations, but existing medications have only a modest effect on reducing their frequency, even when used in combination. Observational studies suggest β-blockers may reduce the risk of COPD exacerbations; thus, we will conduct a randomised, placebo-controlled trial to definitively assess the impact of metoprolol succinate on the rate of COPD exacerbations. This is a multicentre, placebo-controlled, double-blind, prospective randomised trial that will enrol 1028 patients with at least moderately severe COPD over a 3-year period. Participants with at least moderate COPD will be randomised in a 1:1 fashion to receive metoprolol or placebo; the cohort will be enriched for patients at high risk for exacerbations. Patients will be screened and then randomised over a 2-week period and will then undergo a dose titration period for the following 6 weeks. Thereafter, patients will be followed for 42 additional weeks on their target dose of metoprolol or placebo followed by a 4-week washout period. The primary end point is time to first occurrence of an acute exacerbation during the treatment period. Secondary end points include rates and severity of COPD exacerbations; rate of major cardiovascular events; all-cause mortality; lung function (forced expiratory volume in 1 s (FEV1)); dyspnoea; quality of life; exercise capacity; markers of cardiac stretch (pro-NT brain natriuretic peptide) and systemic inflammation (high-sensitivity C reactive protein and fibrinogen). Analyses will be performed on an intent-to-treat basis. The study protocol has been approved by the Department of Defense Human Protection Research Office and will be approved by the institutional review board of all participating centres. Study findings will be disseminated through presentations at national and international conferences and publications in peer-reviewed journals. NCT02587351; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

[A systematic review of the effectiveness of alternative weight-loss products' ingredients].

PubMed

de Lira-García, Cynthia; Souto-Gallardo, María; Bacardí-Gascón, Monserrat; Jiménez-Cruz, Arturo

2008-01-01

The high demand for obesity treatment and conventional therapies' lack of effectiveness increases the use of alternative products. This study was aimed at assessing evidence from randomised clinical trials regarding the effectiveness of alternative weight-loss products' ingredients. A survey was conducted in Ensenada, Baja California, to assess the frequency of consuming alternative products used for weight reduction. The ingredients in the products most in demand were included in this review. The Pubmed database was searched for all randomised clinical trial papers including these ingredients and assessing weight loss. Thirty-six percent of the subjects questioned had used alternative methods for weight-loss, 83% of them being women. The most frequently used products were shakes, tea, pills and flaxseed/linseed. Sixteen randomised clinical trials using four ingredients were used: Garcinia cambogia, green tea, L-carnitina and flaxseed. Only two studies (green tea and Garcinia cambogia) showed significant weight-loss (25%) amongst control and experimental groups. There was no significant difference between the groups in the studies regarding L-carnitina and flaxseed. There is a lack of evidence regarding quality studies justifying the use of alternative products for weight loss.

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

PubMed

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

2018-03-20

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

Current concepts in cleft care: A multicenter analysis.

PubMed

Thiele, Oliver C; Kreppel, Matthias; Dunsche, Anton; Eckardt, Andre M; Ehrenfeld, Michael; Fleiner, Bernd; Gaßling, Volker; Gehrke, Gerd; Gerressen, Marcus; Gosau, Martin; Gröbe, Alexander; Haßfeld, Stefan; Heiland, Max; Hoffmeister, Bodo; Hölzle, Frank; Klein, Cornelius; Krüger, Maximilian; Kübler, Alexander C; Kübler, Norbert R; Kuttenberger, Johannes J; Landes, Constantin; Lauer, Günter; Martini, Markus; Merholz, Erich T; Mischkowski, Robert A; Al-Nawas, Bilal; Nkenke, Emeka; Piesold, Jörn U; Pradel, Winnie; Rasse, Michael; Rachwalski, Martin; Reich, Rudolf H; Rothamel, Daniel; Rustemeyer, Jan; Scheer, Martin; Schliephake, Henning; Schmelzeisen, Rainer; Schramm, Alexander; Schupp, Wiebke; Spitzer, Wolfgang J; Stocker, Erwin; Stoll, Christian; Terheyden, Hendrik; Voigt, Alexander; Wagner, Wilfried; Weingart, Dieter; Werkmeister, Richard; Wiltfang, Jörg; Ziegler, Christoph M; Zöller, Joachim E

2018-04-01

The current surgical techniques used in cleft repair are well established, but different centers use different approaches. To determine the best treatment for patients, a multi-center comparative study is required. In this study, we surveyed all craniofacial departments registered with the German Society of Maxillofacial Surgery to determine which cleft repair techniques are currently in use. Our findings revealed much variation in cleft repair between different centers. Although most centers did use a two-stage approach, the operative techniques and timing of lip and palate closure were different in every center. This shows that a retrospective comparative analysis of patient outcome between the participating centers is not possible and illustrates the need for prospective comparative studies to establish the optimal technique for reconstructive cleft surgery. Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Prospective multi-center study of an automatic online seizure detection system for epilepsy monitoring units.

PubMed

Fürbass, F; Ossenblok, P; Hartmann, M; Perko, H; Skupch, A M; Lindinger, G; Elezi, L; Pataraia, E; Colon, A J; Baumgartner, C; Kluge, T

2015-06-01

A method for automatic detection of epileptic seizures in long-term scalp-EEG recordings called EpiScan will be presented. EpiScan is used as alarm device to notify medical staff of epilepsy monitoring units (EMUs) in case of a seizure. A prospective multi-center study was performed in three EMUs including 205 patients. A comparison between EpiScan and the Persyst seizure detector on the prospective data will be presented. In addition, the detection results of EpiScan on retrospective EEG data of 310 patients and the public available CHB-MIT dataset will be shown. A detection sensitivity of 81% was reached for unequivocal electrographic seizures with false alarm rate of only 7 per day. No statistical significant differences in the detection sensitivities could be found between the centers. The comparison to the Persyst seizure detector showed a lower false alarm rate of EpiScan but the difference was not of statistical significance. The automatic seizure detection method EpiScan showed high sensitivity and low false alarm rate in a prospective multi-center study on a large number of patients. The application as seizure alarm device in EMUs becomes feasible and will raise the efficiency of video-EEG monitoring and the safety levels of patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Test-retest and between-site reliability in a multicenter fMRI study.

PubMed

Friedman, Lee; Stern, Hal; Brown, Gregory G; Mathalon, Daniel H; Turner, Jessica; Glover, Gary H; Gollub, Randy L; Lauriello, John; Lim, Kelvin O; Cannon, Tyrone; Greve, Douglas N; Bockholt, Henry Jeremy; Belger, Aysenil; Mueller, Bryon; Doty, Michael J; He, Jianchun; Wells, William; Smyth, Padhraic; Pieper, Steve; Kim, Seyoung; Kubicki, Marek; Vangel, Mark; Potkin, Steven G

2008-08-01

In the present report, estimates of test-retest and between-site reliability of fMRI assessments were produced in the context of a multicenter fMRI reliability study (FBIRN Phase 1, www.nbirn.net). Five subjects were scanned on 10 MRI scanners on two occasions. The fMRI task was a simple block design sensorimotor task. The impulse response functions to the stimulation block were derived using an FIR-deconvolution analysis with FMRISTAT. Six functionally-derived ROIs covering the visual, auditory and motor cortices, created from a prior analysis, were used. Two dependent variables were compared: percent signal change and contrast-to-noise-ratio. Reliability was assessed with intraclass correlation coefficients derived from a variance components analysis. Test-retest reliability was high, but initially, between-site reliability was low, indicating a strong contribution from site and site-by-subject variance. However, a number of factors that can markedly improve between-site reliability were uncovered, including increasing the size of the ROIs, adjusting for smoothness differences, and inclusion of additional runs. By employing multiple steps, between-site reliability for 3T scanners was increased by 123%. Dropping one site at a time and assessing reliability can be a useful method of assessing the sensitivity of the results to particular sites. These findings should provide guidance toothers on the best practices for future multicenter studies.

Evaluating multicenter DTI data in Huntington's disease on site specific effects: An ex post facto approach☆

PubMed Central

Müller, Hans-Peter; Grön, Georg; Sprengelmeyer, Reiner; Kassubek, Jan; Ludolph, Albert C.; Hobbs, Nicola; Cole, James; Roos, Raymund A.C.; Duerr, Alexandra; Tabrizi, Sarah J.; Landwehrmeyer, G. Bernhard; Süssmuth, Sigurd D.

2013-01-01

Purpose Assessment of the feasibility to average diffusion tensor imaging (DTI) metrics of MRI data acquired in the course of a multicenter study. Materials and methods Sixty-one early stage Huntington's disease patients and forty healthy controls were studied using four different MR scanners at four European sites with acquisition protocols as close as possible to a given standard protocol. The potential and feasibility of averaging data acquired at different sites was evaluated quantitatively by region-of-interest (ROI) based statistical comparisons of coefficients of variation (CV) across centers, as well as by testing for significant group-by-center differences on averaged fractional anisotropy (FA) values between patients and controls. In addition, a whole-brain based statistical between-group comparison was performed using FA maps. Results The ex post facto statistical evaluation of CV and FA-values in a priori defined ROIs showed no differences between sites above chance indicating that data were not systematically biased by center specific factors. Conclusion Averaging FA-maps from DTI data acquired at different study sites and different MR scanner types does not appear to be systematically biased. A suitable recipe for testing on the possibility to pool multicenter DTI data is provided to permit averaging of DTI-derived metrics to differentiate patients from healthy controls at a larger scale. PMID:24179771

Prognostic values of common clinical parameters in advanced pancreatic ductal adenocarcinoma: a large multicenter cohort study of ten years.

PubMed

Zhang, Chenyue; Dong, Shu; Wang, Lei; Yu, Songlin; Zheng, Yuwei; Geng, Yanyan; Shen, Xiaoheng; Ying, Haifeng; Guo, Yuanbiao; Yu, Jinming; Deng, Qinglong; Meng, Zhiqiang; Li, Zhaoshen; Chen, Hao; Shen, Yehua; Chen, Qiwen

2018-03-01

We conducted a multicenter cohort study to investigate the prognostic value of some commonly-used laboratory indices in advanced pancreatic ductal adenocarcinoma (PDAC). A multicenter cohort study was conducted from 2004 to 2013. The associations between laboratory indices and prognosis of advanced PDAC were examined. This cohort consisted of 553 females (36.2%) and 973 males (63.8%). Patients at cancer stage III and IV were 595 (39.0%) and 931 (61.0%), respectively. The median survival of stage III patients was 9.0 months, with 3-, 6-, and 12-month survival rates of 94.5%, 73.4%, and 28.5%, respectively. The median survival of stage IV patients was 5.4 months, with 3-, 6-, and 12-month survival rates of 79.3%, 42.9%, and 15.0%, respectively. In multivariate analyses, primary tumor diameter, low albumin, and elevated CA19-9 were associated with decreased survival for stage III patients. Age, smoking, primary tumor diameter, elevated ALT or AST, low albumin, and elevated CA19-9 were associated with decreased survival for stage IV patients. Elevated CA19-9 level, decreased albumin level, and tumor size were associated with worse survival in stage III patients. Meanwhile, advanced age, smoking, and ALT or AST level were negatively correlated to prognosis in stage IV patients.

Prediction of accrual closure date in multi-center clinical trials with discrete-time Poisson process models.

PubMed

Tang, Gong; Kong, Yuan; Chang, Chung-Chou Ho; Kong, Lan; Costantino, Joseph P

2012-01-01

In a phase III multi-center cancer clinical trial or a large public health study, sample size is predetermined to achieve desired power, and study participants are enrolled from tens or hundreds of participating institutions. As the accrual is closing to the target size, the coordinating data center needs to project the accrual closure date on the basis of the observed accrual pattern and notify the participating sites several weeks in advance. In the past, projections were simply based on some crude assessment, and conservative measures were incorporated in order to achieve the target accrual size. This approach often resulted in excessive accrual size and subsequently unnecessary financial burden on the study sponsors. Here we proposed a discrete-time Poisson process-based method to estimate the accrual rate at time of projection and subsequently the trial closure date. To ensure that target size would be reached with high confidence, we also proposed a conservative method for the closure date projection. The proposed method was illustrated through the analysis of the accrual data of the National Surgical Adjuvant Breast and Bowel Project trial B-38. The results showed that application of the proposed method could help to save considerable amount of expenditure in patient management without compromising the accrual goal in multi-center clinical trials. Copyright © 2012 John Wiley & Sons, Ltd.

Collaborative multicenter trials in Latin America: challenges and opportunities in orthopedic and trauma surgery.

PubMed

Moraes, Vinicius Ynoe de; Belloti, Joao Carlos; Faloppa, Flavio; Bhandari, Mohit

2013-01-01

CONTEXT AND OBJECTIVE Orthopedic research agendas should be considered from a worldwide perspective. Efforts should be planned as the means for obtaining evidence that is valid for health promotion with global outreach. DESIGN AND SETTING Exploratory study conducted at Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil, and McMaster University, Hamilton, Canada. METHODS We identified and analyzed collaborative and multicenter research in Latin America, taking into account American and Canadian efforts as the reference points. We explored aspects of the data available from official sources and used data from traffic accidents as a model for discussing collaborative research in these countries. RESULTS The evaluation showed that the proportion of collaborative and multicenter studies in our setting is small. A brief analysis showed that the death rate due to traffic accidents is very high. Thus, it seems clear to us that initiatives involving collaborative studies are important for defining and better understanding the patterns of injuries resulting from orthopedic trauma and the forms of treatment. Orthopedic research may be an important tool for bringing together orthopedic surgeons, researchers and medical societies for joint action. CONCLUSIONS We have indicated some practical guidelines for initiatives in collaborative research and have proposed some solutions with a summarized plan of action for conducting evidence-based research involving orthopedic trauma.

Addressing data privacy in matched studies via virtual pooling.

PubMed

Saha-Chaudhuri, P; Weinberg, C R

2017-09-07

Data confidentiality and shared use of research data are two desirable but sometimes conflicting goals in research with multi-center studies and distributed data. While ideal for straightforward analysis, confidentiality restrictions forbid creation of a single dataset that includes covariate information of all participants. Current approaches such as aggregate data sharing, distributed regression, meta-analysis and score-based methods can have important limitations. We propose a novel application of an existing epidemiologic tool, specimen pooling, to enable confidentiality-preserving analysis of data arising from a matched case-control, multi-center design. Instead of pooling specimens prior to assay, we apply the methodology to virtually pool (aggregate) covariates within nodes. Such virtual pooling retains most of the information used in an analysis with individual data and since individual participant data is not shared externally, within-node virtual pooling preserves data confidentiality. We show that aggregated covariate levels can be used in a conditional logistic regression model to estimate individual-level odds ratios of interest. The parameter estimates from the standard conditional logistic regression are compared to the estimates based on a conditional logistic regression model with aggregated data. The parameter estimates are shown to be similar to those without pooling and to have comparable standard errors and confidence interval coverage. Virtual data pooling can be used to maintain confidentiality of data from multi-center study and can be particularly useful in research with large-scale distributed data.

Admission temperatures following radiant warmer or incubator transport for preterm infants <28 weeks: a randomised study.

PubMed

Meyer, Michael P; Bold, Geoff T

2007-07-01

Sixty two infants <28 weeks were occlusively wrapped and randomised to radiant warmer or incubator transport to the neonatal unit. Median axillary temperature on arrival was 36.8 degrees C in both groups. Target temperatures (36.5-37.5 degrees C) were achieved in 60% of the incubator group compared to 75% in the warmer group (not statistically significant). While powered to detect a 35% difference between warming devices, a more modest difference is not excluded.

Hybrid learning in signalling games

NASA Astrophysics Data System (ADS)

Barrett, Jeffrey A.; Cochran, Calvin T.; Huttegger, Simon; Fujiwara, Naoki

2017-09-01

Lewis-Skyrms signalling games have been studied under a variety of low-rationality learning dynamics. Reinforcement dynamics are stable but slow and prone to evolving suboptimal signalling conventions. A low-inertia trial-and-error dynamical like win-stay/lose-randomise is fast and reliable at finding perfect signalling conventions but unstable in the context of noise or agent error. Here we consider a low-rationality hybrid of reinforcement and win-stay/lose-randomise learning that exhibits the virtues of both. This hybrid dynamics is reliable, stable and exceptionally fast.

Evaluating the impact and use of Transparent Reporting of Evaluations with Non-randomised Designs (TREND) reporting guidelines

PubMed Central

Fuller, Thomas; Pearson, Mark; Peters, Jaime L; Anderson, Rob

2012-01-01

Introduction Accurate and full reporting of evaluation of interventions in health research is needed for evidence synthesis and informed decision-making. Evidence suggests that biases and incomplete reporting affect the assessment of study validity and the ability to include this data in secondary research. The Transparent Reporting of Evaluations with Non-randomised Designs (TREND) reporting guideline was developed to improve the transparency and accuracy of the reporting of behavioural and public health evaluations with non-randomised designs. Evaluations of reporting guidelines have shown that they can be effective in improving reporting completeness. Although TREND occupies a niche within reporting guidelines, and despite it being 8 years since publication, no study yet has assessed its impact on reporting completeness or investigated what factors affect its use by authors and journal editors. This protocol describes two studies that aim to redress this. Methods and analysis Study 1 will use an observational design to examine the uptake and use of TREND by authors, and by journals in their instructions to authors. A comparison of reporting completeness and study quality of papers that do and do not use TREND to inform reporting will be made. Study 2 will use a cross-sectional survey to investigate what factors inhibit or facilitate authors’ and journal editors’ use of TREND. Semistructured interviews will also be conducted with a subset of authors and editors to explore findings from study 1 and the surveys in greater depth. Ethics and dissemination These studies will generate evidence of how implementation and dissemination of the TREND guideline has affected reporting completeness in studies with experimental, non-randomised designs within behavioural and public health research. The project has received ethics approval from the Research Ethics Committee of the Peninsula College of Medicine and Dentistry, Universities of Exeter and Plymouth. PMID:23257774

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis.

PubMed

Papachristou, Georgios I; Machicado, Jorge D; Stevens, Tyler; Goenka, Mahesh Kumar; Ferreira, Miguel; Gutierrez, Silvia C; Singh, Vikesh K; Kamal, Ayesha; Gonzalez-Gonzalez, Jose A; Pelaez-Luna, Mario; Gulla, Aiste; Zarnescu, Narcis O; Triantafyllou, Konstantinos; Barbu, Sorin T; Easler, Jeffrey; Ocampo, Carlos; Capurso, Gabriele; Archibugi, Livia; Cote, Gregory A; Lambiase, Louis; Kochhar, Rakesh; Chua, Tiffany; Tiwari, Subhash Ch; Nawaz, Haq; Park, Walter G; de-Madaria, Enrique; Lee, Peter J; Wu, Bechien U; Greer, Phil J; Dugum, Mohannad; Koutroumpakis, Efstratios; Akshintala, Venkata; Gougol, Amir

2017-01-01

We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials.

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.

Home-based, early intervention with mechatronic toys for preterm infants at risk of neurodevelopmental disorders (CARETOY): a RCT protocol.

PubMed

Sgandurra, Giuseppina; Bartalena, Laura; Cioni, Giovanni; Greisen, Gorm; Herskind, Anna; Inguaggiato, Emanuela; Lorentzen, Jakob; Nielsen, Jens Bo; Sicola, Elisa

2014-10-15

Preterm infants are at risk for neurodevelopmental disorders, including motor, cognitive or behavioural problems, which may potentially be modified by early intervention. The EU CareToy Project Consortium (http://www.caretoy.eu) has developed a new modular system for intensive, individualized, home-based and family-centred early intervention, managed remotely by rehabilitation staff. A randomised controlled trial (RCT) has been designed to evaluate the efficacy of CareToy training in a first sample of low-risk preterm infants. The trial, randomised, multi-center, evaluator-blinded, parallel group controlled, is designed according to CONSORT Statement. Eligible subjects are infants born preterm without major complications, aged 3-9 months of corrected age with specific gross-motor abilities defined by Ages & Stages Questionnaire scores. Recruited infants, whose parents will sign a written informed consent for participation, will be randomized in CareToy training and control groups at baseline (T0). CareToy group will perform four weeks of personalized activities with the CareToy system, customized by the rehabilitation staff. The control group will continue standard care. Infant Motor Profile Scale is the primary outcome measure and a total sample size of 40 infants has been established. Bayley-Cognitive subscale, Alberta Infants Motor Scale and Teller Acuity Cards are secondary outcome measures. All measurements will be performed at T0 and at the end of training/control period (T1). For ethical reasons, after this first phase infants enrolled in the control group will perform the CareToy training, while the training group will continue standard care. At the end of open phase (T2) all infants will be assessed as at T1. Further assessment will be performed at 18 months corrected age (T3) to evaluate the long-term effects on neurodevelopmental outcome. Caregivers and rehabilitation staff will not be blinded whereas all the clinical assessments will be performed, videotaped and scored by blind assessors. The trial is ongoing and it is expected to be completed by April 2015. This paper describes RCT methodology to evaluate CareToy as a new tool for early intervention in preterm infants, first contribution to test this new type of system. It presents background, hypotheses, outcome measures and trial methodology. ClinicalTrials.gov: NCT01990183. EU grant ICT-2011.5.1-287932.

Similar early migration when comparing CR and PS in Triathlon™ TKA: A prospective randomised RSA trial.

PubMed

Molt, Mats; Toksvig-Larsen, Sören

2014-10-01

The objective of this study was to compare the early migration of the cruciate retaining and posterior stabilising versions of the recently introduced Triathlon™ total knee system, with a view to predicting long term fixation performance. Sixty patients were prospectively randomised to receive either Triathlon™ posterior stabilised cemented knee prosthesis or Triathlon™ cruciate retaining cemented knee prosthesis. Tibial component migration was measured by radiostereometric analysis postoperatively and at three months, one year and two years. Clinical outcome was measured by the American Knee Society Score and Knee Osteoarthritis and Injury Outcome Score. There were no differences in rotation around the three coordinal axes or in the maximum total point motion (MTPM) during the two year follow-up. The posterior stabilised prosthesis had more posterior-anterior translation at three months and one year and more caudal-cranial translation at one year and two years. There were no differences in functional outcome between the groups. The tibial tray of the Triathlon™ cemented knee prosthesis showed similar early stability. Level I. Article focus: This was a prospective randomised trial aiming to compare the single radius posterior stabilised (PS) Triathlon™ total knee arthroplasty (TKA) to the cruciate retaining Triathlon™ TKA system with regard to fixation. Strengths and limitations of this study: Strength of this study was that it is a randomised prospective trial using an objective measuring tool. The sample size of 25-30 patients was reportedly sufficient for the screening of implants using RSA [1]. ClinicalTrials.gov Identifier: NCT00436982. Copyright © 2014 Elsevier B.V. All rights reserved.

The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project: an open-label pragmatic randomised control trial comparing the efficacy of differing therapeutic agents for primary care detoxification from either street heroin or methadone [ISRCTN07752728].

PubMed

Oldham, Nicola S; Wright, Nat M J; Adams, Clive E; Sheard, Laura; Tompkins, Charlotte N E

2004-04-29

Heroin is a synthetic opioid with an extensive illicit market leading to large numbers of people becoming addicted. Heroin users often present to community treatment services requesting detoxification and in the UK various agents are used to control symptoms of withdrawal. Dissatisfaction with methadone detoxification 8 has lead to the use of clonidine, lofexidine, buprenorphine and dihydrocodeine; however, there remains limited evaluative research. In Leeds, a city of 700,000 people in the North of England, dihydrocodeine is the detoxification agent of choice. Sublingual buprenorphine, however, is being introduced. The comparative value of these two drugs for helping people successfully and comfortably withdraw from heroin has never been compared in a randomised trial. Additionally, there is a paucity of research evaluating interventions among drug users in the primary care setting. This study seeks to address this by randomising drug users presenting in primary care to receive either dihydrocodeine or buprenorphine. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project is a pragmatic randomised trial which will compare the open use of buprenorphine with dihydrocodeine for illicit opiate detoxification, in the UK primary care setting. The LEEDS project will involve consenting adults and will be run in specialist general practice surgeries throughout Leeds. The primary outcome will be the results of a urine opiate screening at the end of the detoxification regimen. Adverse effects and limited data to three and six months will be acquired.

Psychological interventions for mental health disorders in children with chronic physical illness: a systematic review.

PubMed

Bennett, Sophie; Shafran, Roz; Coughtrey, Anna; Walker, Susan; Heyman, Isobel

2015-04-01

Children with chronic physical illness are significantly more likely to develop common psychiatric symptoms than otherwise healthy children. These children therefore warrant effective integrated healthcare yet it is not established whether the known, effective, psychological treatments for symptoms of common childhood mental health disorders work in children with chronic physical illness. EMBASE, MEDLINE, PsycINFO and CINAHL databases were searched with predefined terms relating to evidence-based psychological interventions for psychiatric symptoms in children with chronic physical illness. We included all studies (randomised and non-randomised designs) investigating interventions aimed primarily at treating common psychiatric symptoms in children with a chronic physical illness in the review. Two reviewers independently assessed the relevance of abstracts identified, extracted data and undertook quality analysis. Ten studies (209 children, including 70 in control groups) met the criteria for inclusion in the review. All studies demonstrated some positive outcomes of cognitive behavioural therapy for the treatment of psychiatric symptoms in children with chronic physical illness. Only two randomised controlled trials, both investigating interventions for symptoms of depression, were found. There is preliminary evidence that cognitive behavioural therapy has positive effects in the treatment of symptoms of depression and anxiety in children with chronic physical illness. However, the current evidence base is weak and fully powered randomised controlled trials are needed to establish the efficacy of psychological treatments in this vulnerable population. 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.

Chocolate frogs do not increase completion of parent survey: randomised study.

PubMed

Price, Anna M H; Coates, Cathy; Symeonides, Christos; Hiscock, Harriet; Smith, Libby; York, Elissa; Hennel, Sabine

2014-11-01

Four months into a year-long, national survey assessing parents' experiences of a child's diagnosis of autism spectrum disorder, our response fraction was only 23%. We aimed to determine whether including a chocolate incentive in the postal survey would increase the response fraction. Families enrolled between 15 March and 25 May 2012 were randomised to receive a chocolate frog versus no chocolate frog. Both groups received a written reminder and replacement survey 2 weeks after the survey was posted and up to two telephone reminders thereafter. We analysed the effect of the incentive using χ(2) tests for the categorical response variable and t-tests for the continuous reminder and length of response variables at the end of (i) randomisation and (ii) the study (1 November 2012). A total of 137 families were randomised in the 6-week period. Parents who received an incentive were more likely to return a completed survey in the 6 weeks than those who did not (21% vs. 6%, P = 0.009). This effect faded by the end of the study (53% vs. 42%, P = 0.4). There were no differences between groups at either follow-up in the number of reminders that parents received or the number of days it took parents to return the survey. Including a chocolate-based incentive does not significantly increase response rate in a postal survey over and above standard reminder techniques like posting follow-up survey packs or phoning families. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Total ankle replacement versus arthrodesis (TARVA): protocol for a multicentre randomised controlled trial

PubMed Central

Goldberg, Andrew J; Zaidi, Razi; Thomson, Claire; Doré, Caroline J; Cro, Suzie; Round, Jeff; Molloy, Andrew; Davies, Mark; Karski, Michael; Kim, Louise; Cooke, Paul

2016-01-01

Introduction Total ankle replacement (TAR) or ankle arthrodesis (fusion) is the main surgical treatments for end-stage ankle osteoarthritis (OA). The popularity of ankle replacement is increasing while ankle fusion rates remain static. Both treatments have efficacy but to date all studies comparing the 2 have been observational without randomisation, and there are no published guidelines as to the most appropriate management. The TAR versus arthrodesis (TARVA) trial aims to compare the clinical and cost-effectiveness of TAR against ankle arthrodesis in the treatment of end-stage ankle OA in patients aged 50–85 years. Methods and analysis TARVA is a multicentre randomised controlled trial that will randomise 328 patients aged 50–85 years with end-stage ankle arthritis. The 2 arms of the study will be TAR or ankle arthrodesis with 164 patients in each group. Up to 16 UK centres will participate. Patients will have clinical assessments and complete questionnaires before their operation and at 6, 12, 26 and 52 weeks after surgery. The primary clinical outcome of the study is a validated patient-reported outcome measure, the Manchester Oxford foot questionnaire, captured preoperatively and 12 months after surgery. Secondary outcomes include quality-of-life scores, complications, revision, reoperation and a health economic analysis. Ethics and dissemination The protocol has been approved by the National Research Ethics Service Committee (London, Bloomsbury 14/LO/0807). This manuscript is based on V.5.0 of the protocol. The trial findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration number NCT02128555. PMID:27601503

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

PubMed Central

2014-01-01

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

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

PubMed Central

2013-01-01

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

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

PubMed

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

2013-03-27

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

Tug-of-war between classical and multicenter bonds in H-(Be)n-H species

NASA Astrophysics Data System (ADS)

Lundell, Katie A.; Boldyrev, Alexander I.

2018-05-01

Quantum chemical calculations were performed for beryllium homocatenated compounds [H-(Be)n-H]. Global minimum structures were found using machine searches (Coalescence Kick method) with density functional theory. Chemical bonding analysis was performed with the Adaptive Natural Density Partitioning method. It was found that H-(Be)2-H and H-(Be)3-H clusters are linear with classical two-center two-electron bonds, while for n > 3, three-dimensional structures are more stable with multicenter bonding. Thus, at n = 4, multicenter bonding wins the tug-of-war vs. the classical bonding.

Evaluation of the effects of an offer of a monetary incentive on the rate of questionnaire return during follow-up of a clinical trial: a randomised study within a trial.

PubMed

Hardy, Pollyanna; Bell, Jennifer L; Brocklehurst, Peter

2016-07-15

A systematic review on the use of incentives to promote questionnaire return in clinical trials suggest they are effective, but not all studies have sufficient funds to use them. Promising an incentive once data are returned can reduce the cost-burden of this approach, with possible further cost-savings if the offer were restricted to reminder letters only. This study aimed to evaluate the effect of promising a monetary incentive at first mailout versus a promise on reminder letters only. This was a randomised Study Within A Trial (SWAT) nested within BUMPES, a multicentre randomised controlled trial of maternal position in the late stage of labour in women with an epidural. The follow-up questionnaire asked for information on the women's health, wellbeing and health service use one year following the birth of their baby. Women who consented to be contacted were randomised to a promise of a monetary incentive at first mailout or a promise on reminder letters only. Women were given an option of completing the questionnaire on paper or on online. The incentive was posted out on receipt of a completed questionnaire. The primary outcome was the overall return rate, and secondary outcomes were the return rate without any chasing from the study office, and the total cost of the vouchers. A total of 1,029 women were randomised, 508 to the first mailout group and 518 to the reminder group. There was no evidence to suggest a difference between groups in the overall return rate (adjusted RR 1.03 (95 % CI 0.96 to 1.11), however the proportion returned without chasing was higher in the first mailout group (adjusted RR 1.22, 95 % CI 1.07 to 1.39). The total cost of the vouchers per participant was higher in the first mailout group (mean difference £4.56, 95 % CI £4.02 to £5.11). Offering a monetary incentive when a reminder is required could be cost-effective depending on the sample size of the study and the resources available to administer the reminder letters. The BUMPES Trial is registered with Current Controlled Trials: ISRCTN35706297 , 26(th) August 2009.

Does early intervention improve outcomes in physiotherapy management of lumbar radicular syndrome? A mixed-methods study protocol

PubMed Central

Walters, Stephen J; Baxter, Susan

2017-01-01

Introduction Lumbar radicular syndrome (LRS) can be a painful and debilitating condition. The optimum management strategies and their timing remain elusive despite extensive research. Surgery provides good short-term outcomes but has concomitant risks and costs. Physiotherapy is commonly practised for patients with LRS but its effects remain equivocal and there is a lack of consensus on the type, duration and timing of physiotherapy intervention. There is a lack of high-quality evidence into new and innovative management strategies and the timings of those strategies for LRS. This pilot trial is an essential preliminary to a definitive randomised controlled trial (RCT) assessing the effectiveness and cost-effectiveness of early physiotherapy intervention for patients with LRS. The study will test the protocol, the intervention, the use of outcome measures and the ability to set-up and run the trial to enable refinement of a future definitive RCT. Methods and analysis This is a mixed-methods study encompassing an external pilot RCT with integrated qualitative interviews with patients, clinicians and other key stakeholders. 80 patients will be recruited from primary care and randomised, after consent into 1 of 2 groups. Both groups will receive individually tailored, goal orientated physiotherapy. The usual care group will begin their physiotherapy 6 weeks after randomisation and the intervention group at 2 weeks after randomisation. Outcome measures will primarily be feasibility parameters including the ability to recruit and retain patients and to deliver the intervention. Data will be collected at baseline, and 6, 12 and 26 weeks following randomisation. Ethics and dissemination The study has received favourable ethical review from the East of Scotland Research Ethics Service (EoSRES) on the 20 August 2015 (15/ES/0130). Recruitment began on the 1 March 2016 and is expected to close in January 2017. Data collection is anticipated to be complete in July 2017. The study results will be made available to participants, clinicians involved in the study and the wider clinical community through publication in a peer reviewed journal and at conference presentations. Trial registration number ISRCTN: 25018352, Pre-results; Clinical Trials.Gov: NCT02618278 Document version V1.1 23.9.2016. PMID:28259854

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.

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.

Development of a framework to improve the process of recruitment to randomised controlled trials (RCTs): the SEAR (Screened, Eligible, Approached, Randomised) framework.

PubMed

Wilson, Caroline; Rooshenas, Leila; Paramasivan, Sangeetha; Elliott, Daisy; Jepson, Marcus; Strong, Sean; Birtle, Alison; Beard, David J; Halliday, Alison; Hamdy, Freddie C; Lewis, Rebecca; Metcalfe, Chris; Rogers, Chris A; Stein, Robert C; Blazeby, Jane M; Donovan, Jenny L

2018-01-19

Research has shown that recruitment to trials is a process that stretches from identifying potentially eligible patients, through eligibility assessment, to obtaining informed consent. The length and complexity of this pathway means that many patients do not have the opportunity to consider participation. This article presents the development of a simple framework to document, understand and improve the process of trial recruitment. Eight RCTs integrated a QuinteT Recruitment Intervention (QRI) into the main trial, feasibility or pilot study. Part of the QRI required mapping the patient recruitment pathway using trial-specific screening and recruitment logs. A content analysis compared the logs to identify aspects of the recruitment pathway and process that were useful in monitoring and improving recruitment. Findings were synthesised to develop an optimised simple framework that can be used in a wide range of RCTs. The eight trials recorded basic information about patients screened for trial participation and randomisation outcome. Three trials systematically recorded reasons why an individual was not enrolled in the trial, and further details why they were not eligible or approached, or declined randomisation. A framework to facilitate clearer recording of the recruitment process and reasons for non-participation was developed: SEAR - Screening, to identify potentially eligible trial participants; Eligibility, assessed against the trial protocol inclusion/exclusion criteria; Approach, the provision of oral and written information and invitation to participate in the trial, and Randomised or not, with the outcome of randomisation or treatment received. The SEAR framework encourages the collection of information to identify recruitment obstacles and facilitate improvements to the recruitment process. SEAR can be adapted to monitor recruitment to most RCTs, but is likely to add most value in trials where recruitment problems are anticipated or evident. Further work to test it more widely is recommended.

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.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-03-01

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

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

Treatment strategies in colorectal cancer patients with initially unresectable liver-only metastases, a study protocol of the randomised phase 3 CAIRO5 study of the Dutch Colorectal Cancer Group (DCCG).

PubMed

Huiskens, Joost; van Gulik, Thomas M; van Lienden, Krijn P; Engelbrecht, Marc R W; Meijer, Gerrit A; van Grieken, Nicole C T; Schriek, Jonne; Keijser, Astrid; Mol, Linda; Molenaar, I Quintus; Verhoef, Cornelis; de Jong, Koert P; Dejong, Kees H C; Kazemier, Geert; Ruers, Theo M; de Wilt, Johanus H W; van Tinteren, Harm; Punt, Cornelis J A

2015-05-06

Colorectal cancer patients with unresectable liver-only metastases may be cured after downsizing of metastases by neoadjuvant systemic therapy. However, the optimal neoadjuvant induction regimen has not been defined, and the lack of consensus on criteria for (un)resectability complicates the interpretation of published results. CAIRO5 is a multicentre, randomised, phase 3 clinical study. Colorectal cancer patients with initially unresectable liver-only metastases are eligible, and will not be selected for potential resectability. The (un)resectability status is prospectively assessed by a central panel consisting of at least one radiologist and three liver surgeons, according to predefined criteria. Tumours of included patients will be tested for RAS mutation status. Patients with RAS wild type tumours will be treated with doublet chemotherapy (FOLFOX or FOLFIRI) and randomised between the addition of either bevacizumab or panitumumab, and patients with RAS mutant tumours will be randomised between doublet chemotherapy (FOLFOX or FOLFIRI) plus bevacizumab or triple chemotherapy (FOLFOXIRI) plus bevacizumab. Radiological evaluation to assess conversion to resectability will be performed by the central panel, at an interval of two months. The primary study endpoint is median progression-free survival. Secondary endpoints are the R0/1 resection rate, median overall survival, response rate, toxicity, pathological response of resected lesions, postoperative morbidity, and correlation of baseline and follow-up evaluation with respect to outcomes by the central panel. CAIRO5 is a prospective multicentre trial that investigates the optimal systemic induction therapy for patients with initially unresectable, liver-only colorectal cancer metastases. CAIRO 5 is registered at European Clinical Trials Database (EudraCT) (2013-005435-24). CAIRO 5 is registered at ClinicalTrials.gov: NCT02162563 , June 10, 2014.

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

PubMed

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

2017-08-04

Frail patients have decreased physiological reserves and consequently, they are unable to recover as quickly from surgery. Frailty, as an entity, is a risk factor of increased morbidity and mortality. It is also associated with a longer time to discharge. This trial is undertaken to determine if a novel prehabilitation protocol (10-day bundle of interventions-physiotherapy, nutritional supplementation and cognitive training) can reduce the postoperative length of stay of frail patients who are undergoing elective abdominal surgery, compared with standard care. This is a prospective, single-centre, randomised controlled trial with two parallel arms. 62 patients who are frail and undergoing elective abdominal surgery will be recruited and randomised to receive either a novel prehabilitation protocol or standard care. Participants will receive telephone reminders preoperatively to encourage protocol compliance. Data will be collected for up to 30 days postoperatively. The primary outcome of the trial will be the postoperative length of stay and the secondary outcomes are the postoperative complications and functional recovery during the hospital admission. This study has been approved by the Singapore General Hospital Institutional Review Board (CIRB Ref: 2016/2584). The study is also listed on ClinicalTrials.gov (Trial number: NCT02921932). All participants will sign an informed consent form before randomisation and translators will be made available to non-English speaking patients. The results of this study will be published in peer-reviewed journals as well as national and international conferences. The data collected will also be made available in a public data repository. NCT02921932 (ClinicalTrials.gov). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study.

PubMed

Tazaki, Y; Sakai, F; Otomo, E; Kutsuzawa, T; Kameyama, M; Omae, T; Fujishima, M; Sakuma, A

1988-02-01

A multicenter double-blind placebo-controlled study of cytidine 5'-diphosphocholine (CDP-choline) was conducted to evaluate possible clinical benefits of the drug in patients with acute, moderate to severe cerebral infarction. The patients included also suffered from moderate to mild disturbances of consciousness, and all were admitted within 14 days of the ictus. Patients were allocated randomly to treatment with either CDP-choline (1,000 mg/day i.v. once daily for 14 days) or with placebo (physiological saline). One hundred thirty-three patients received CDP-choline treatment, and 139 received placebo. The group treated with CDP-choline showed significant improvements in level of consciousness compared with the placebo-treated group, and CDP-choline was an entirely safe treatment.

A prospective, multicenter, post marketing surveillance study to evaluate the safety and effectiveness of the Superia-Sirolimus Eluting Coronary Stent System (SSECSS) implanted during routine clinical practice in India.

PubMed

Chandra, Praveen; Kumar, Tarun

2014-01-01

A prospective, multicenter, post marketing surveillance study to evaluate the safety and effectiveness of the Superia-Sirolimus Eluting Coronary Stent System (SSECSS) implanted during routine clinical practice in India. 1. To study the MACE and in stent and In-segment Loss at Six Months (in a pre selected group of 50 patients). 1. Clinical and procedural success. This is a prospective, open label, single-arm, multicenter (16 sites), post marketing observational study enrolling patients implanted with Superia-Sirolimus Eluting Coronary Stent (SSECS) in routine clinical practice in India. A total of 200 Patients of coronary Artery Disease (CAD) implanted with Superia-Sirolimus Eluting Coronary Stent (SSECS) were enrolled. Clinical assessments were done at 30 days, 180 days and at 1, 2 years either telephonically or office visit. A cohort of 50 pre-selected patients were followed up for angiographic evaluation at 180 days. MACE at 12 month of follow up was 1.71%.Late lumen loss, in segment was 0.14 and in stent was 0.10 mm at 6 month of follow-up. TLR was required only in 2 patients. Superia stent is as safe as other biodegradable polymer stent in the market and time has come for biodegradable polymer stent with thin struts. Copyright © 2014 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Memantine in frontotemporal lobar degeneration: A multicenter, randomised, double-blind, placebo-controlled trial

PubMed Central

Boxer, Adam L.; Knopman, David S.; Kaufer, Daniel I.; Grossman, Murray; Onyike, Chiadi; Graf-Radford, Neill; Mendez, Mario; Kerwin, Diana; Lerner, Alan; Wu, Chuang-Kuo; Koestler, Mary; Shapira, Jill; Sullivan, Kathryn; Klepac, Kristen; Lipowski, Kristine; Ullah, Jerin; Fields, Scott; Kramer, Joel H.; Merrilees, Jennifer; Neuhaus, John; Mesulam, M. Marsel; Miller, Bruce L.

2013-01-01

Background Memantine has been used off-label to treat frontotemporal lobar degeneration (FTD). A previous 26 week open label study suggested a transient, modest benefit on neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory (NPI). Methods We performed a randomized, parallel group, double blind, placebo controlled trial of 20 mg memantine taken orally daily for 26 weeks in FTD. Participants met Neary criteria for behavioral variant (bvFTD) or semantic dementia (SD) and had characteristic brain atrophy. Use of cholinesterase inhibitors was prohibited. The objective of the study was to determine whether memantine is an effective treatment for FTD. Individuals were randomized to memantine or matched placebo tablets in blocks of two and four. Primary endpoints were the change in total NPI score and Clinical Global Impression of Change (CGIC) scores after 26 weeks. Secondary outcomes included a neuropsychological battery, and other cognitive, global and activity of daily living measures. Clinicaltrials.gov identifier: NCT00545974 Findings 100 subjects were screened, 81 were randomized, 5 (6%) discontinued and 76 completed all visits. Enrollment numbers were lower than planned due to many subjects’ preference to take memantine or cholinesterase inhibitors off-label rather than participate in a clinical trial. 39 memantine and 42 placebo subjects entered the primary intent to treat analysis. There was no effect of memantine treatment on either the NPI (mean difference [MD] 2.2, 95%CI: −3.9, 8.3, p = 0.47) or CGIC (MD 0, 95%CI: −0.4, 0.4, p = 0.90) after 26 weeks of treatment. Memantine was generally well tolerated, however there were more frequent cognitive adverse events in the memantine group. Interpretation There was no benefit of memantine treatment in bvFTD or SD. These data do not support memantine use in FTD. Funding Forest Research Institute PMID:23290598

ECLAMC Study: prevalence patterns of hypospadias in South America: multi-national analysis over a 24-year period

PubMed Central

Fernández, Nicolás; Pérez, Jaime; Monterrey, Pedro; Poletta, Fernando A.; Bägli, Darius J.; Lorenzo, Armando J.; Zarante, Ignacio

2017-01-01

ABSTRACT Objective To evaluate prevalence trends of hypospadias in South-America it is essential to perform multicenter and multinational studies with the same methodology. Herein we present systematic data as part of an international multicenter initiative evaluating congenital malformations in South America over a 24-year period. Materials and Methods A nested case-control study was conducted using the Latin American Collaborative Study of Congenital Malformations (ECLAMC), between January 1989 and December 2012. Cases were stratified as isolated (IH) and non-isolated hypospadias (NIH). Global prevalence was calculated and discriminated by country. Associations between birth weight and gestational age, and NIH distribution by associated abnormality and severity of hypospadias, were analyzed. Results A total of 159 hospitals from six countries participated, reporting surveillance on 4.020.384 newborns. A total of 4.537 hypospadias cases were detected, with a global prevalence of 11.3/10.000 newborns. Trend analyses showed in Chile, Brazil and Uruguay a statistically significant increase in prevalence. Analysis of severity and associated anomalies did not to find an association for distal cases, but did for proximal (RR=1.64 [95% CI=1.33-2.03]). Conclusion This is one of only a few Latin American multicenter studies reporting on the epidemiology of hypospadias in South America in the last two decades. Our data adds to evidence suggesting an increase in some countries in the region at different times. There were also variations in prevalence according to severity. This study adds to literature describing associated anomalies at a hospital-based level. PMID:27802003