An evaluation of a nurse-led rehabilitation programme (the ProBalance Programme) to improve balance and reduce fall risk of community-dwelling older people: a randomised controlled trial

info:eu-repo/semantics/publishedVersion

An evaluation of a nurse-led rehabilitation programme (the ProBalance Programme) to improve balance and reduce fall risk of community-dwelling older people: a randomised controlled trial

info:eu-repo/semantics/publishedVersion

Vocational Rehabilitation in Early Psychosis: Cluster Randomised Trial

Background Individual placement and support (IPS) is effective in helping patients return to work but is poorly implemented because of clinical ambivalence and fears of relapse. Aims To assess whether a motivational intervention (motivational interviewing) directed at clinical staff to address ambivalence about employment improved patients’ occupational outcomes. Method Two of four early intervention teams that already provided IPS were randomised to receive motivational interviewing training for clinicians, focused on attitudinal barriers to employment. The trial was registered with the International Standard Randomised Controlled Trial Register (ISRCTN71943786). Results Of 300 eligible participants, 159 consented to the research. Occupational outcomes were obtained for 134 patients (85%) at 12-month follow-up. More patients in the intervention teams than in the IPS-only teams achieved employment by 12 months (29/68 v. 12/66). A random effects logistic regression accounting for clustering by care coordinator, and adjusted for participants’ gender, ethnicity, educational and employment history and clinical status scores, confirmed superiority of the intervention (odds ratio = 4.3, 95% CI 1.5-16.6). Conclusions Employment outcomes were enhanced by addressing clinicians’ ambivalence about their patients returning to work.

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

OBJECTIVE: To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. DESIGN: Cohort of protocols of randomised controlled trial and subsequent full journal publications. SETTING: Six research ethics committees in Switzerland, Germany, and Canada. DATA SOURCES: 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. RESULTS: 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. CONCLUSIONS: 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 BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant) in patients with traumatic brain injury

BACKGROUND Cerebral oedema is associated with significant neurological damage in patients with traumatic brain injury. Bradykinin is an inflammatory mediator that may contribute to cerebral oedema by increasing the permeability of the blood-brain barrier. We evaluated the safety and effectiveness of the non-peptide bradykinin B2 receptor antagonist Anatibant in the treatment of patients with traumatic brain injury. During the course of the trial, funding was withdrawn by the sponsor. METHODS Adults with traumatic brain injury and a Glasgow Coma Scale score of 12 or less, who had a CT scan showing an intracranial abnormality consistent with trauma, and were within eight hours of their injury were randomly allocated to low, medium or high dose Anatibant or to placebo. Outcomes were Serious Adverse Events (SAE), mortality 15 days following injury and in-hospital morbidity assessed by the Glasgow Coma Scale (GCS), the Disability Rating Scale (DRS) and a modified version of the Oxford Handicap Scale (HIREOS). RESULTS 228 patients out of a planned sample size of 400 patients were randomised. The risk of experiencing one or more SAEs was 26.4% (43/163) in the combined Anatibant treated group, compared to 19.3% (11/57) in the placebo group (relative risk = 1.37; 95% CI 0.76 to 2.46). All cause mortality in the Anatibant treated group was 19% and in the placebo group 15.8% (relative risk 1.20, 95% CI 0.61 to 2.36). The mean GCS at discharge was 12.48 in the Anatibant treated group and 13.0 in the placebo group. Mean DRS was 11.18 Anatibant versus 9.73 placebo, and mean HIREOS was 3.94 Anatibant versus 3.54 placebo. The differences between the mean levels for GCS, DRS and HIREOS in the Anatibant and placebo groups, when adjusted for baseline GCS, showed a non-significant trend for worse outcomes in all three measures. CONCLUSION This trial did not reach the planned sample size of 400 patients and consequently, the study power to detect an increase in the risk of serious adverse events was reduced. This trial provides no reliable evidence of benefit or harm and a larger trial would be needed to establish safety and effectiveness. TRIAL REGISTRATION This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN23625128.

Impact of electronic monitoring of drug adherence on blood pressure control in primary care: a cluster 12-month randomised controlled study.

BACKGROUND: Poor long-term adherence is an important cause of uncontrolled hypertension. We examined whether monitoring drug adherence with an electronic system improves long-term blood pressure (BP) control in hypertensive patients followed by general practitioners (GPs). METHODS: A pragmatic cluster randomised controlled study was conducted over one year in community pharmacists/GPs' networks randomly assigned either to usual care (UC) where drugs were dispensed as usual, or to intervention (INT) group where drug adherence could be monitored with an electronic system (Medication Event Monitoring System). No therapy change was allowed during the first 2 months in both groups. Thereafter, GPs could modify therapy and use electronic monitors freely in the INT group. The primary outcome was a target office BP<140/90 mmHg. RESULTS: Sixty-eight treated uncontrolled hypertensive patients (UC: 34; INT: 34) were enrolled. Over the 12-month period, the likelihood of reaching the target BP was higher in the INT group compared to the UC group (p<0.05). At 4 months, 38% in the INT group reached the target BP vs. 12% in the UC group (p<0.05), and 21% vs. 9% at 12 months (p: ns). Multivariate analyses, taking account of baseline characteristics, therapy modification during follow-up, and clustering effects by network, indicate that being allocated to the INT group was associated with a greater odds of reaching the target BP at 4 months (p<0.01) and at 12 months (p=0.051). CONCLUSION: GPs monitoring drug adherence in collaboration with pharmacists achieved a better BP control in hypertensive patients, although the impact of monitoring decreased with time.

Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial.

BACKGROUND: Enteral nutrition (EN) is recommended for patients in the intensive-care unit (ICU), but it does not consistently achieve nutritional goals. We assessed whether delivery of 100% of the energy target from days 4 to 8 in the ICU with EN plus supplemental parenteral nutrition (SPN) could optimise clinical outcome. METHODS: This randomised controlled trial was undertaken in two centres in Switzerland. We enrolled patients on day 3 of admission to the ICU who had received less than 60% of their energy target from EN, were expected to stay for longer than 5 days, and to survive for longer than 7 days. We calculated energy targets with indirect calorimetry on day 3, or if not possible, set targets as 25 and 30 kcal per kg of ideal bodyweight a day for women and men, respectively. Patients were randomly assigned (1:1) by a computer-generated randomisation sequence to receive EN or SPN. The primary outcome was occurrence of nosocomial infection after cessation of intervention (day 8), measured until end of follow-up (day 28), analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00802503. FINDINGS: We randomly assigned 153 patients to SPN and 152 to EN. 30 patients discontinued before the study end. Mean energy delivery between day 4 and 8 was 28 kcal/kg per day (SD 5) for the SPN group (103% [SD 18%] of energy target), compared with 20 kcal/kg per day (7) for the EN group (77% [27%]). Between days 9 and 28, 41 (27%) of 153 patients in the SPN group had a nosocomial infection compared with 58 (38%) of 152 patients in the EN group (hazard ratio 0·65, 95% CI 0·43-0·97; p=0·0338), and the SPN group had a lower mean number of nosocomial infections per patient (-0·42 [-0·79 to -0·05]; p=0·0248). INTERPRETATION: Individually optimised energy supplementation with SPN starting 4 days after ICU admission could reduce nosocomial infections and should be considered as a strategy to improve clinical outcome in patients in the ICU for whom EN is insufficient. FUNDING: Foundation Nutrition 2000Plus, ICU Quality Funds, Baxter, and Fresenius Kabi.

Randomised controlled trials of homeopathy in hyperactive children: treatment procedure leads to an unconventional study design. Experience with open-label homeopathic treatment preceding the Swiss ADHD placebo controlled, randomised, double-blind, cross-over trial

BACKGROUND: Treatment of patients with attention deficit hyperactivity disorder (ADHD) with homeopathy is difficult. The Swiss randomised, placebo controlled, cross-over trial in ADHD patients (Swiss ADHD trial) was designed with an open-label screening phase prior to the randomised controlled phase. During the screening phase, the response of each child to successive homeopathic medications was observed until the optimal medication was identified. Only children who reached a predefined level of improvement participated in the randomised, cross-over phase. Although the randomised phase revealed a significant beneficial effect of homeopathy, the cross-over caused a strong carryover effect diminishing the apparent difference between placebo and verum treatment. METHODS: This retrospective analysis explores the screening phase data with respect to the risk of failure to demonstrate a specific effect of a randomised controlled trial (RCT) with randomisation at the start of the treatment. RESULTS: During the screening phase, 84% (70/83) of the children responded to treatment and reached eligibility for the randomised trial after a median time of 5 months (range 1-18), with a median of 3 different medications (range 1-9). Thirteen children (16%) did not reach eligibility. Five months after treatment start, the difference in Conners Global Index (CGI) rating between responders and non-responders became highly significant (p = 0.0006). Improvement in CGI was much greater following the identification of the optimal medication than in the preceding suboptimal treatment period (p < 0.0001). CONCLUSIONS: Because of the necessity of identifying an optimal medication before response to treatment can be expected, randomisation at the start of treatment in an RCT of homeopathy in ADHD children has a high risk of failure to demonstrate a specific treatment effect, if the observation time is shorter than 12 months.

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

OBJECTIVE To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. DESIGN Cohort of protocols of randomised controlled trial and subsequent full journal publications. SETTING Six research ethics committees in Switzerland, Germany, and Canada. DATA SOURCES 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. RESULTS 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. CONCLUSIONS 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.

Efficacy of memantine for agitation in Alzheimer's dementia:a randomised double-blind placebo controlled trial

Background - Agitation in Alzheimer’s disease (AD) is common and associated with poor patient life-quality and carer distress. The best evidence-based pharmacological treatments are antipsychotics which have limited benefits with increased morbidity and mortality. There are no memantine trials in clinically significant agitation but post-hoc analyses in other populations found reduced agitation. We tested the primary hypothesis, memantine is superior to placebo for clinically significant agitation, in patients with moderate-to-severe AD. Methods and Findings - We recruited 153 participants with AD and clinically significant agitation from care-homes or hospitals for a double-blind randomised-controlled trial and 149 people started the trial of memantine versus placebo. The primary outcome was 6 weeks mixed model autoregressive analysis of Cohen-Mansfield Agitation Inventory (CMAI). Secondary outcomes were: 12 weeks CMAI; 6 and 12 weeks Neuropsychiatric symptoms (NPI), Clinical Global Impression Change (CGI-C), Standardised Mini Mental State Examination, Severe Impairment Battery. Using a mixed effects model we found no significant differences in the primary outcome, 6 weeks CMAI, between memantine and placebo (memantine lower -3.0; -8.3 to 2.2, p = 0.26); or 12 weeks CMAI; or CGI-C or adverse events at 6 or 12 weeks. NPI mean difference favoured memantine at weeks 6 (-6.9; -12.2 to -1.6; p = 0.012) and 12 (-9.6; -15.0 to -4.3 p = 0.0005). Memantine was significantly better than placebo for cognition. The main study limitation is that it still remains to be determined whether memantine has a role in milder agitation in AD. Conclusions - Memantine did not improve significant agitation in people with in moderate-to-severe AD. Future studies are urgently needed to test other pharmacological candidates in this group and memantine for neuropsychiatric symptoms.

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

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 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 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. 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 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. 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 short-term management of acute agitation. Funding: National Institute for Health Research. © 2013 Elsevier Ltd.

Can Early Intervention Policies Improve Well-being? Evidence from a randomized controlled trial

Many authors have proposed incorporating measures of well-being into evaluations of public policy. Yet few evaluations use experimental design or examine multiple aspects of well-being, thus the causal impact of public policies on well-being is largely unknown. In this paper we examine the effect of an intensive early intervention program on maternal well-being in a targeted disadvantaged community. Using a randomized controlled trial design we estimate and compare treatment effects on global well-being using measures of life satisfaction, experienced well-being using both the Day Reconstruction Method (DRM) and a measure of mood yesterday, and also a standardized measure of parenting stress. The intervention has no significant impact on negative measures of well-being, such as experienced negative affect as measured by the DRM and global measures of well-being such as life satisfaction or a global measure of parenting stress. Significant treatment effects are observed on experienced measures of positive affect using the DRM, and a measure of mood yesterday. The DRM treatment effects are primarily concentrated during times spent without the target child which may reflect the increased effort and burden associated with additional parental investment. Our findings suggest that a maternal-focused intervention may produce meaningful improvements in experienced well-being. Incorporating measures of experienced affect may thus alter cost-benefit calculations for public policies.

Universal screening and decolonization for control of MRSA in nursing homes : a cluster randomized controlled study

OBJECTIVE The risk of carrying methicillin-resistant Staphylococcus aureus (MRSA) is higher among nursing home (NH) residents than in the general population. However, control strategies are not clearly defined in this setting. In this study, we compared the impact of standard precautions either alone (control) or combined with screening of residents and decolonization of carriers (intervention) to control MRSA in NHs. DESIGN Cluster randomized controlled trial SETTING NHs of the state of Vaud, Switzerland PARTICIPANTS Of 157 total NHs in Vaud, 104 (67%) participated in the study. INTERVENTION Standard precautions were enforced in all participating NHs, and residents underwent MRSA screening at baseline and 12 months thereafter. All carriers identified in intervention NHs, either at study entry or among newly admitted residents, underwent topical decolonization combined with environmental disinfection, except in cases of MRSA infection, MRSA bacteriuria, or deep skin ulcers. RESULTS NHs were randomly allocated to a control group (51 NHs, 2,412 residents) or an intervention group (53 NHs, 2,338 residents). Characteristics of NHs and residents were similar in both groups. The mean screening rates were 86% (range, 27%-100%) in control NHs and 87% (20%-100%) in intervention NHs. Prevalence of MRSA carriage averaged 8.9% in both control NHs (range, 0%-43%) and intervention NHs (range, 0%-38%) at baseline, and this rate significantly declined to 6.6% in control NHs and to 5.8% in intervention NHs after 12 months. However, the decline did not differ between groups (P=.66). CONCLUSION Universal screening followed by decolonization of carriers did not significantly reduce the prevalence of the MRSA carriage rate at 1 year compared with standard precautions

Adalimumab in Severe and Acute Sciatica (ASAS) : a multicentre, randomized, double-blind, placebo-controlled trial : 1240

Background Based on several experimental results and on a preliminary study, a trial was undertaken to assess the efficacy of adalimumab, a TNF-α inhibitor, in patients with radicular pain due to lumbar disc herniation. Methods A multicentre, double-blind, randomised controlled trial was conducted between May 2005 and December 2007 in Switzerland. Patients with acute (< 12 weeks) and severe (Oswestry Disability index > 50) radicular leg pain and imaging-confirmed lumbar disc herniation were randomised to receive as adjuvant therapy either two subcutaneous injections of adalimumab (40 mg) at 7 days interval or matching placebo. The primary outcome was leg pain, which was recorded every day for 10 days and at 6-weeks and 6- months based on a visual analogue scale (0 to 100). Results Of the 265 patients screened, 61 were enrolled (adalimumab= 31) and 4 were lost to follow-up. Over time, the evolution of leg pain was more favourable in the adalimumab group than in the placebo group (p<0.001). However, the effect size was relatively small and at last follow-up the difference was 13.8 (CI95% -11.5 - 39.0). In the adalimumab group twice as many patients fulfilled the criteria for "responders" and for "low residual disease impact" ( p<0.05) and fewer surgical discectomies were performed (6 versus 13, p=0.04). Conclusion The addition of a short course of adalimumab to the treatment regimen of patients suffering from acute and severe sciatica resulted in a small decrease in leg pain and in significantly fewer surgical procedures.

Nadolol plus isosorbide mononitrate alone or associated with band ligation in the prevention of recurrent bleeding: A multicenter randomized controlled trial.

Background and aims: Previous clinical trials suggest that adding non-selective beta-blockers improves the efficacy of endoscopic band ligation (EBL) in the prevention of recurrent bleeding, but no study has evaluated whether EBL improves the efficacy of beta-blockers + isosorbide-5-mononitrate. The present study was aimed at evaluating this issue in a multicentre randomised controlled trial (RCT) and to correlate changes in hepatic venous pressure gradient (HVPG) during treatment with clinical outcomes. Methods: 158 patients with cirrhosis, admitted because of variceal bleeding, were randomised to receive nadolol+isosorbide-5-mononitrate alone (Drug: n=78) or combined with EBL (Drug+EBL; n=80). HVPG measurements were performed at randomisation and after 4¿6 weeks on medical therapy. Results: Median follow-up was 15 months. One-year probability of recurrent bleeding was similar in both groups (33% vs 26%: p=0.3). There were no significant differences in survival or need of rescue shunts. Overall adverse events or those requiring hospital admission were significantly more frequent in the Drug+EBL group. Recurrent bleeding was significantly more frequent in HVPG non-responders than in responders (HVPG reduction ¿20% or ¿12 mm Hg). Among non-responders recurrent bleeding was similar in patients treated with Drugs or Drugs+EBL. Conclusions: Adding EBL to pharmacological treatment did not reduce recurrent bleeding, the need for rescue therapy, or mortality, and was associated with more adverse events. Furthermore, associating EBL to drug therapy did not reduce the high rebleeding risk of HVPG non-responders.