Explore the vast range of titles available.

The number of robotic assisted radical cystectomy (RARC) procedures is increasing despite the lack of Level I evidence showing any advantages over open radical cystectomy (ORC). However, several systematic reviews with meta-analyses including non-randomised studies, suggest an overall benefit for RARC compared to ORC. We performed a systematic review with meta-analysis of randomised controlled trials (RCTs) to evaluate the perioperative morbidity and efficacy of RARC compared to ORC in patients with bladder cancer. Literature searches of Medline/Pubmed, Embase, Web of Science and clinicaltrials.gov databases up to 10th March 2016 were performed. The inclusion criteria for eligible studies were RCTs which compared perioperative outcomes of ORC and RARC for bladder cancer. Primary objective was perioperative and histopathological outcomes of RARC versus ORC while the secondary objective was quality of life assessment (QoL), oncological outcomes and cost analysis. Four RCTs (from 5 articles) met the inclusion criteria, with a total of 239 patients all with extracorporeal urinary diversion. Patient demographics and clinical characteristics of RARC and ORC patients were evenly matched. There was no significant difference between groups in perioperative morbidity, length of stay, positive surgical margin, lymph node yield and positive lymph node status. RARC group had significantly lower estimated blood loss (p<0.001) and wound complications (p = 0.03) but required significantly longer operating time (p<0.001). QoL was not measured uniformly across trials and cost analysis was reported in one RCTs. A test for heterogeneity did highlight differences across operating time of trials suggesting that surgeon experience may influence outcomes. This study does not provide evidence to support a benefit for RARC compared to ORC. These results may not have inference for RARC with intracorporeal urinary diversion. Well-designed trials with appropriate endpoints conducted by equally experienced ORC and RARC surgeons will be needed to address this.

IntroductionParkinson’s disease (PD) is a common neurodegenerative disorder with substantial morbidity. No disease-modifying treatments currently exist. The glucagon like peptide-1 receptor agonist exenatide has been associated in single-centre studies with reduced motor deterioration over 1 year. The aim of this multicentre UK trial is to confirm whether these previous positive results are maintained in a larger number of participants over 2 years and if effects accumulate with prolonged drug exposure.Methods and analysisThis is a phase 3, multicentre, double-blind, randomised, placebo-controlled trial of exenatide at a dose of 2 mg weekly in 200 participants with mild to moderate PD. Treatment duration is 96 weeks. Randomisation is 1:1, drug to placebo. Assessments are performed at baseline, week 12, 24, 36, 48, 60, 72, 84 and 96 weeks.The primary outcome is the comparison of Movement Disorders Society Unified Parkinson’s Disease Rating Scale part 3 motor subscore in the practically defined OFF medication state at 96 weeks between participants according to treatment allocation. Secondary outcomes will compare the change between groups among other motor, non-motor and cognitive scores. The primary outcome will be reported using descriptive statistics and comparisons between treatment groups using a mixed model, adjusting for baseline scores. Secondary outcomes will be summarised between treatment groups using summary statistics and appropriate statistical tests to assess for significant differences.Ethics and disseminationThis trial has been approved by the South Central-Berkshire Research Ethics Committee and the Health Research Authority. Results will be disseminated in peer-reviewed journals, presented at scientific meetings and to patients in lay-summary format.Trial registration numbersNCT04232969, ISRCTN14552789.

Background Bacterial infection is a major cause of mortality in patients with cirrhosis. Spontaneous bacterial peritonitis (SBP) is a serious and common infection in patients with cirrhosis and ascites. Secondary prophylactic antibiotic therapy has been shown to improve outcomes after an episode of SBP but primary prophylaxis to prevent the first episode of SBP remains contentious. The aim of this trial is to assess whether primary antibiotic prophylaxis with co-trimoxazole improves overall survival compared to placebo in adults with cirrhosis and ascites. Methods The ASEPTIC trial is a multicentre, placebo-controlled, double-blinded, randomised controlled trial (RCT) in England, Scotland, and Wales. Patients aged 18 years and older with cirrhosis and ascites requiring diuretic treatment or paracentesis, and no current or previous episodes of SBP, are eligible, subject to exclusion criteria. The trial aims to recruit 432 patients from at least 30 sites. Patients will be randomised in a 1:1 ratio to receive either oral co-trimoxazole 960 mg or an identical placebo once daily for 18 months, with 6 monthly follow-up visits thereafter (with a maximum possible follow-up period of 48 months, and a minimum of 18 months). The primary outcome is overall survival. Secondary outcomes include the time to the first incidence of SBP, hospital admission rates, incidence of other infections (including Clostridium difficile ) and antimicrobial resistance, patients’ health-related quality of life, health and social care resource use, incidence of cirrhosis-related decompensation events, liver transplantation, and treatment-related serious adverse events. Discussion This trial will investigate the efficacy, safety, and cost-effectiveness of co-trimoxazole for patients with liver cirrhosis and ascites to determine whether this strategy improves clinical outcomes. Given there are no treatments that improve survival in decompensated cirrhosis outside of liver transplant, if the trial has a positive outcome, we anticipate widespread adoption of primary antibiotic prophylaxis. Trial registration ClinicalTrials.gov NCT043955365 . Registered on 18 April 2020. Research ethical approval was granted by the Research Ethics Committee (South Central – Oxford B; REC 19/SC/0311) and the Medicines and Healthcare products Regulatory Agency (MHRA).

Background Evidence-based guidelines for management of mild traumatic brain injury (mTBI) in the emergency department (ED) are now widely available; however, clinical practice remains inconsistent with these guidelines. A targeted, theory-informed implementation intervention (Neurotrauma Evidence Translation (NET) intervention) was designed to increase the uptake of three clinical practice recommendations regarding the management of patients who present to Australian EDs with mild head injuries. The intervention involved local stakeholder meetings, identification and training of nursing and medical local opinion leaders, train-the-trainer workshops and standardised education materials and interactive workshops delivered by the opinion leaders to others within their EDs during a 3 month period. This paper reports on the effects of this intervention. Methods EDs (clusters) were allocated to receive either access to a clinical practice guideline (control) or the implementation intervention, using minimisation, a method that allocates clusters to groups using an algorithm to minimise differences in predefined factors between the groups. We measured clinical practice outcomes at the patient level using chart audit. The primary outcome was appropriate screening for post-traumatic amnesia (PTA) using a validated tool until a perfect score was achieved (indicating absence of acute cognitive impairment) before the patient was discharged home. Secondary outcomes included appropriate CT scanning and the provision of written patient information upon discharge. Patient health outcomes (anxiety, primary outcome: Hospital Anxiety and Depression Scale) were also assessed using follow-up telephone interviews. Outcomes were assessed by independent auditors and interviewers, blinded to group allocation. Results Fourteen EDs were allocated to the intervention and 17 to the control condition; 1943 patients were included in the chart audit. At 2 months follow-up, patients attending intervention EDs ( n  = 893) compared with control EDs ( n  = 1050) were more likely to have been appropriately assessed for PTA (adjusted odds ratio (OR) 20.1, 95%CI 6.8 to 59.3; adjusted absolute risk difference (ARD) 14%, 95%CI 8 to 19). The odds of compliance with recommendations for CT scanning and provision of written patient discharge information were small (OR 1.2, 95%CI 0.8 to 1.6; ARD 3.2, 95%CI − 3.7 to 10 and OR 1.2, 95%CI 0.8 to 1.8; ARD 3.1, 95%CI − 3.0 to 9.3 respectively). A total of 343 patients at ten interventions and 14 control sites participated in follow-up interviews at 4.3 to 10.7 months post-ED presentation. The intervention had a small effect on anxiety levels (adjusted mean difference − 0.52, 95%CI − 1.34 to 0.30; scale 0–21, with higher scores indicating greater anxiety). Conclusions Our intervention was effective in improving the uptake of the PTA recommendation; however, it did not appreciably increase the uptake of the other two practice recommendations. Improved screening for PTA may be clinically important as it leads to appropriate periods of observation prior to safe discharge. The estimated intervention effect on anxiety was of limited clinical significance. We were not able to compare characteristics of EDs who declined trial participation with those of participating sites, which may limit the generalizability of the results. Trial registration Australian New Zealand Clinical Trials Registry (ACTRN12612001286831), date registered 12 December 2012.

ObjectiveTo explore whether systematic reviewers selectively include trial effect estimates in meta-analyses when multiple are available, and what impact this may have on meta-analytic effects.DesignCross-sectional study.Data sourcesWe randomly selected systematic reviews of interventions from 2 clinical specialties published between January 2010 and 2012. The first presented meta-analysis of a continuous outcome in each review was selected (index meta-analysis), and all trial effect estimates that were eligible for inclusion in the meta-analysis (eg, from multiple scales or time points) were extracted from trial reports.AnalysisWe calculated a statistic (the Potential Bias Index (PBI)) to quantify and test for evidence of selective inclusion. The PBI ranges from 0 to 1; values above or below 0.5 are suggestive of selective inclusion of effect estimates more or less favourable to the intervention, respectively. The impact of any potential selective inclusion was investigated by comparing the index meta-analytic standardised mean difference (SMD) to the median of a randomly constructed distribution of meta-analytic SMDs (representing the meta-analytic SMD expected when there is no selective inclusion).Results31 reviews (250 trials) were included. The estimated PBI was 0.57 (95% CI 0.50 to 0.63), suggesting that trial effect estimates that were more favourable to the intervention were included in meta-analyses slightly more often than expected under a process consistent with random selection; however, the 95% CI included the null hypothesis of no selective inclusion. Any potential selective inclusion did not have an important impact on the meta-analytic effects.ConclusionThere was no clear evidence that selective inclusion of trial effect estimates occurred in this sample of meta-analyses. Further research on selective inclusion in other clinical specialties is needed. To enable readers to assess the risk of selective inclusion bias, we recommend that systematic reviewers report the methods used to select effect estimates to include in meta-analyses.

Background Evidence-based guidelines for the management of mild traumatic brain injury (mTBI) in the emergency department (ED) are now widely available, and yet, clinical practice remains inconsistent with the guidelines. The Neurotrauma Evidence Translation (NET) intervention was developed to increase the uptake of guideline recommendations and improve the management of minor head injury in Australian emergency departments (EDs). However, the adoption of this type of intervention typically entails an upfront investment that may or may not be fully offset by improvements in clinical practice, health outcomes and/or reductions in health service utilisation. The present study estimates the cost and cost-effectiveness of the NET intervention, as compared to the passive dissemination of the guideline, to evaluate whether any improvements in clinical practice or health outcomes due to the NET intervention can be obtained at an acceptable cost. Methods and findings Study setting: The NET cluster randomised controlled trial [ACTRN12612001286831]. Study sample: Seventeen EDs were randomised to the control condition and 14 to the intervention. One thousand nine hundred forty-three patients were included in the analysis of clinical practice outcomes (NET sample). A total of 343 patients from 14 control and 10 intervention EDs participated in follow-up interviews and were included in the analysis of patient-reported health outcomes (NET-Plus sample). Outcome measures: Appropriate post-traumatic amnesia (PTA) screening in the ED (primary outcome). Secondary clinical practice outcomes: provision of written information on discharge (INFO) and safe discharge (defined as CT scan appropriately provided plus PTA plus INFO). Secondary patient-reported, post-discharge health outcomes: anxiety (Hospital Anxiety and Depression Scale), post-concussive symptoms (Rivermead), and preference-based health-related quality of life (SF6D). Methods: Trial-based economic evaluations from a health sector perspective, with time horizons set to coincide with the final follow-up for the NET sample (2 months post-intervention) and to 1-month post-discharge for the NET-Plus sample. Results: Intervention and control groups were not significantly different in health service utilisation received in the ED/inpatient ward following the initial mTBI presentation (adjusted mean difference $23.86 per patient; 95%CI − $106, $153; p = 0.719) or over the longer follow-up in the NET-plus sample (adjusted mean difference $341.78 per patient; 95%CI − $58, $742; p = 0.094). Savings from lower health service utilisation are therefore unlikely to offset the significantly higher upfront cost of the intervention (mean difference $138.20 per patient; 95%CI $135, $141; p  < 0.000). Estimates of the net effect of the intervention on total cost (intervention cost net of health service utilisation) suggest that the intervention entails significantly higher costs than the control condition (adjusted mean difference $169.89 per patient; 95%CI $43, $297, p = 0.009). This effect is larger in absolute magnitude over the longer follow-up in the NET-plus sample (adjusted mean difference $505.06; 95%CI $96, $915; p = 0.016), mostly due to additional health service utilisation. For the primary outcome, the NET intervention is more costly and more effective than passive dissemination; entailing an additional cost of $1246 per additional patient appropriately screened for PTA ($169.89/0.1363; Fieller’s 95%CI $525, $2055). For NET to be considered cost-effective with 95% confidence, decision-makers would need to be willing to trade one quality-adjusted life year (QALY) for 25 additional patients appropriately screened for PTA. While these results reflect our best estimate of cost-effectiveness given the data, it is possible that a NET intervention that has been scaled and streamlined ready for wider roll-out may be more or less cost-effective than the NET intervention as delivered in the trial. Conclusions While the NET intervention does improve the management of mTBI in the ED, it also entails a significant increase in cost and—as delivered in the trial—is unlikely to be cost-effective at currently accepted funding thresholds. There may be a scope for a scaled-up and streamlined NET intervention to achieve a better balance between costs and outcomes. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12612001286831 , date registered 12 December 2012.

Knowledge of the breadth, nature, and volume of traumatic brain injury (TBI) and spinal cord injury (SCI) research can aid in research planning. This study aimed to provide an overview of existing TBI and SCI research to inform identification of knowledge translation (KT), systematic review (SR), and primary research opportunities. Topics and relevant articles from three large neurotrauma evidence resources were synthesized: the Global Evidence Mapping (GEM) Initiative (129 topics and 1644 articles), the Acquired Brain Injury Evidence-Based Review (ERABI; 152 topics and 732 articles), and the Spinal Cord Injury Rehabilitation Evidence (SCIRE) Project (297 topics and 1650 articles). A de-duplicated dataset of SRs, randomized controlled trials (RCTs), and other studies identified by these projects was created. In all, 145 topics were identified (66 TBI and 79 SCI), yielding 3466 research articles (1256 TBI and 2210 SCI). Topics with KT potential included cognitive therapies for TBI and prevention/management of urinary tract problems post-SCI, which accounted for 17% and 18%, respectively, of the TBI and SCI yield. Topics that may require SR included management of raised intracranial pressure in TBI, and ventilation and intermittent positive pressure interventions following SCI. Topics for which primary research may be needed included pharmacological therapies for neurological recovery post-TBI, and management of sleep-disordered breathing post-SCI. There was a larger volume of non-intervention (epidemiological) studies in SCI than in TBI. This comprehensive overview of TBI and SCI research can aid funding agencies, researchers, clinicians, and other stakeholders in prioritizing and planning TBI and SCI research.

Preoperative anaemia affects a high proportion of patients undergoing major elective surgery and is associated with poor outcomes. We aimed to test the hypothesis that intravenous iron given to anaemic patients before major open elective abdominal surgery would correct anaemia, reduce the need for blood transfusions, and improve patient outcomes. In a double-blind, parallel-group randomised trial, we recruited adult participants identified with anaemia at preoperative hospital visits before elective major open abdominal surgery at 46 UK tertiary care centres. Anaemia was defined as haemoglobin less than 130 g/L for men and 120 g/L for women. We randomly allocated participants (1:1) via a secure web-based service to receive intravenous iron or placebo 10–42 days before surgery. Intravenous iron was administered as a single 1000 mg dose of ferric carboxymaltose in 100 mL normal saline, and placebo was 100 mL normal saline, both given as an infusion over 15 min. Unblinded study personnel prepared and administered the study drug; participants and other clinical and research staff were blinded to treatment allocation. Coprimary endpoints were risk of the composite outcome of blood transfusion or death, and number of blood transfusions from randomisation to 30 days postoperatively. The primary analysis included all randomly assigned patients with data available for the primary endpoints; safety analysis included all randomly assigned patients according to the treatment received. This study is registered, ISRCTN67322816, and is closed to new participants. Of 487 participants randomly assigned to placebo (n=243) or intravenous iron (n=244) between Jan 6, 2014, and Sept 28, 2018, complete data for the primary endpoints were available for 474 (97%) individuals. Death or blood transfusion occurred in 67 (28%) of the 237 patients in the placebo group and 69 (29%) of the 237 patients in the intravenous iron group (risk ratio 1·03, 95% CI 0·78–1·37; p=0·84). There were 111 blood transfusions in the placebo group and 105 in the intravenous iron group (rate ratio 0·98, 95% CI 0·68–1·43; p=0·93). There were no significant differences between the two groups for any of the prespecified safety endpoints. Preoperative intravenous iron was not superior to placebo to reduce need for blood transfusion when administered to patients with anaemia 10–42 days before elective major abdominal surgery. UK National Institute of Health Research Health Technology Assessment Program.

The Neurotrauma Evidence Translation (NET) program was funded in 2009 to increase the uptake of research evidence in the clinical care of patients who have sustained traumatic brain injury. This paper reports the rationale and plan for this five-year knowledge translation research program. The overarching aims of the program are threefold: to improve outcomes for people with traumatic brain injury; to create a network of neurotrauma clinicians and researchers with expertise in knowledge translation and evidence-based practice; and to contribute knowledge to the field of knowledge translation research. The program comprises a series of interlinked projects spanning varying clinical environments and disciplines relevant to neurotrauma, anchored within four themes representing core knowledge translation activities: reviewing research evidence; understanding practice; developing and testing interventions for practice change; and building capacity for knowledge translation in neurotrauma. The program uses a range of different methods and study designs, including: an evidence fellowship program; conduct of and training in systematic reviews; mixed method study designs to describe and understand factors that influence current practices ( e.g. , semi-structured interviews and surveys); theory-based methods to develop targeted interventions aiming to change practice; a cluster randomised trial to test the effectiveness of a targeted theory-informed intervention; stakeholder involvement activities; and knowledge translation events such as consensus conferences.

The optimal timing of anticoagulation for patients with acute ischaemic stroke with atrial fibrillation is uncertain. We investigated the efficacy and safety of early compared with delayed initiation of direct oral anticoagulants (DOACs) in patients with acute ischaemic stroke associated with atrial fibrillation. We performed a multicentre, open-label, blinded-endpoint, parallel-group, phase 4, randomised controlled trial at 100 UK hospitals. Adults with atrial fibrillation and a clinical diagnosis of acute ischaemic stroke and whose physician was uncertain of the optimal timing for DOAC initiation were eligible for inclusion in the study. We randomly assigned participants (1:1) to early (ie, ≤4 days from stroke symptom onset) or delayed (ie, 7–14 days) anticoagulation initiation with any DOAC, using an independent online randomisation service with random permuted blocks and varying block length, stratified by stroke severity at randomisation. Participants and treating clinicians were not masked to treatment assignment, but all outcomes were adjudicated by a masked independent external adjudication committee using all available clinical records, brain imaging reports, and source images. The primary outcome was a composite of recurrent ischaemic stroke, symptomatic intracranial haemorrhage, unclassifiable stroke, or systemic embolism incidence at 90 days in a modified intention-to-treat population. We used a gatekeeper approach by sequentially testing for a non-inferiority margin of 2 percentage points, followed by testing for superiority. OPTIMAS is registered with ISRCTN (ISRCTN17896007) and ClinicalTrials.gov (NCT03759938), and the trial is ongoing. Between July 5, 2019, and Jan 31, 2024, 3648 patients were randomly assigned to early or delayed DOAC initiation. 27 participants did not fulfil the eligibility criteria or withdrew consent to include their data, leaving 3621 patients (1814 in the early group and 1807 in the delayed group; 1981 men and 1640 women) in the modified intention-to-treat analysis. The primary outcome occurred in 59 (3·3%) of 1814 participants in the early DOAC initiation group compared with 59 (3·3%) of 1807 participants in the delayed DOAC initiation group (adjusted risk difference [RD] 0·000, 95% CI –0·011 to 0·012). The upper limit of the 95% CI for the adjusted RD was less than the non-inferiority margin of 2 percentage points (pnon-inferiority=0·0003). Superiority was not identified (psuperiority=0·96). Symptomatic intracranial haemorrhage occurred in 11 (0·6%) participants allocated to the early DOAC initiation group compared with 12 (0·7%) participants allocated to the delayed DOAC initiation group (adjusted RD 0·001, –0·004 to 0·006; p=0·78). Early DOAC initiation within 4 days after ischaemic stroke associated with atrial fibrillation was non-inferior to delayed initiation for the composite outcome of ischaemic stroke, intracranial haemorrhage, unclassifiable stroke, or systemic embolism at 90 days. Our findings do not support the current common and guideline-supported practice of delaying DOAC initiation after ischaemic stroke with atrial fibrillation. British Heart Foundation.