Multicentre randomised controlled trial of nasal diamorphine for analgesia in children and teenagers with clinical fractures.

OBJECTIVE: To compare the effectiveness of nasal diamorphine spray with intramuscular morphine for analgesia in children and teenagers with acute pain due to a clinical fracture, and to describe the safety profile of the spray. DESIGN: Multicentre randomised controlled trial. SETTING: Emergency departments in eight UK hospitals. PARTICIPANTS: Patients aged between 3 and 16 years presenting with a clinical fracture of an upper or lower limb. MAIN OUTCOME MEASURES: Patients' reported pain using the Wong Baker face pain scale, ratings of reaction to treatment of the patients and acceptability of treatment by staff and parents, and adverse events. RESULTS: 404 eligible patients completed the trial (204 patients given nasal diamorphine spray and 200 given intramuscular morphine). Onset of pain relief was faster in the spray group than in the intramuscular group, with lower pain scores in the spray group at 5, 10, and 20 minutes after treatment but no difference between the groups after 30 minutes. 80% of patients given the spray showed no obvious discomfort compared with 9% given intramuscular morphine (difference 71%, 95% confidence interval 65% to 78%). Treatment administration was judged acceptable by staff and parents, respectively, for 98% (199 of 203) and 97% (186 of 192) of patients in the spray group compared with 32% (64 of 199) and 72% (142 of 197) in the intramuscular group. No serious adverse events occurred in the spray group, and the frequencies of all adverse events were similar in both groups (spray 24.1% v intramuscular morphine 18.5%; difference 5.6%, -2.3% to 13.6%). CONCLUSION: Nasal diamorphine spray should be the preferred method of pain relief in children and teenagers presenting to emergency departments in acute pain with clinical fractures. The diamorphine spray should be used in place of intramuscular morphine

A comparison of anterior and posterior chamber lenses after cataract extraction in rural Africa: a within patient randomised trial.

BACKGROUND: Extracapsular cataract extraction (ECCE) with a posterior chamber intraocular lens (PC IOL) is the preferred method of cataract surgery in developed countries. However, intracapsular cataract extraction (ICCE) with an anterior chamber lens (AC IOL) may be appropriate in rural Africa. A randomised controlled trial was carried out to compare these surgical strategies. METHODS: Participants over 50 years requiring bilateral cataract surgery were recruited from outreach clinics in rural north and east Uganda. One eye was randomly allocated to AC IOL or PC IOL, the other eye being allocated to the second strategy. The main outcome measure was WHO distance visual acuity (VA) category after a minimum of 1 year. Secondary outcomes were numbers and causes of complications and refractive corrections. RESULTS: Of the 110 participants recruited, 98 (89%) were assessed at least 1 year after the operation (median follow up 17.5 months). Nine eyes randomised to PC IOL were converted to AC IOL; one eye randomised to AC IOL inadvertently received PC IOL. There was no difference in VA between 95 pairs of eyes for which data for both eyes were available (uncorrected VA, p = 0.26; corrected VA, p = 0.59). 80 (82%, 95% CI 73 to 89) and 82 (84%, 95% CI 75 to 90) eyes randomised to AC IOL and PC IOL respectively had corrected VA of 6/18 or better. 16 (16%, 95% CI 10 to 25) and eight (8%, 95% CI 4 to 15) eyes respectively had secondary procedures or other complications. CONCLUSIONS: Where both strategies are available, ECCE with PC IOL should be first choice because of fewer complications. Where ECCE with PC IOL is not immediately feasible, ICCE with AC IOL is an acceptable interim technique

Critical appraisal skills training for health care professionals: a randomized controlled trial [ISRCTN46272378].

This is the final version of the article. Available from BioMed Central via the DOI in this record.INTRODUCTION: Critical appraisal skills are believed to play a central role in an evidence-based approach to health practice. The aim of this study was to evaluate the effectiveness and costs of a critical appraisal skills educational intervention aimed at health care professionals. METHODS: This prospective controlled trial randomized 145 self-selected general practitioners, hospital physicians, professions allied to medicine, and healthcare managers/administrators from the South West of England to a half-day critical appraisal skills training workshop (based on the model of problem-based small group learning) or waiting list control. The following outcomes were assessed at 6-months follow up: knowledge of the principles necessary for appraising evidence; attitudes towards the use of evidence about healthcare; evidence seeking behaviour; perceived confidence in appraising evidence; and ability to critically appraise a systematic review article. RESULTS: At follow up overall knowledge score [mean difference: 2.6 (95% CI: 0.6 to 4.6)] and ability to appraise the results of a systematic review [mean difference: 1.2 (95% CI: 0.01 to 2.4)] were higher in the critical skills training group compared to control. No statistical significant differences in overall attitude towards evidence, evidence seeking behaviour, perceived confidence, and other areas of critical appraisal skills ability (methodology or generalizability) were observed between groups. Taking into account the workshop provision costs and costs of participants time and expenses of participants, the average cost of providing the critical appraisal workshops was approximately pound 250 per person. CONCLUSIONS: The findings of this study challenge the policy of funding 'one-off' educational interventions aimed at enhancing the evidence-based practice of health care professionals. Future evaluations of evidence-based practice interventions need to take in account this trial's negative findings and methodological difficulties.NHS R&D Executive: Evaluating methods to practice the implementation of R&D [project no. IMP 12-9

Findings of the International Subarachnoid Aneurysm Trial and the National Study of Subarachnoid Haemorrhage in context.

Concern has been expressed about the applicability of the findings of the International Subarachnoid Aneurysm Trial (ISAT) with respect to the relative effects on outcome of coiling and clipping. It has been suggested that the findings of the National Study of Subarachnoid Haemorrhage may have greater relevance for neurosurgical practice. The objective of this paper was to interpret the findings of these two studies in the context of differences in their study populations, design, execution and analysis. Because of differences in design and analysis, the findings of the two studies are not directly comparable. The ISAT analysed all randomized patients by intention-to-treat, including some who did not undergo a repair, and obtained the primary outcome for 99% of participants. The National Study only analysed participants who underwent clipping or coiling, according to the method of repair, and obtained the primary outcome for 91% of participants. Time to repair was also considered differently in the two studies. The comparison between coiling and clipping was susceptible to confounding in the National Study, but not in the ISAT. The two study populations differed to some extent, but inspection of these differences does not support the view that coiling was applied inappropriately in the National Study. Therefore, there are many reasons why the two studies estimated different sizes of effect. The possibility that there were real, systematic differences in practice between the ISAT and the National Study cannot be ruled out, but such explanations must be seen in the context of other explanations relating to chance, differences in design or analysis, or confounding

Clinical effectiveness of a rehabilitation program integrating exercise, self-management, and active coping strategies for chronic knee pain: a cluster randomized trial.

OBJECTIVE: Chronic knee pain is a major cause of disability and health care expenditure, but there are concerns about efficacy, cost, and side effects associated with usual primary care. Conservative rehabilitation may offer a safe, effective, affordable alternative. We compared the effectiveness of a rehabilitation program integrating exercise, self-management, and active coping strategies (Enabling Self-management and Coping with Arthritic Knee Pain through Exercise [ESCAPE-knee pain]) with usual primary care in improving functioning in persons with chronic knee pain. METHODS: We conducted a single-blind, pragmatic, cluster randomized controlled trial. Participants age >/=50 years, reporting knee pain for >6 months, were recruited from 54 inner-city primary care practices. Primary care practices were randomized to continued usual primary care (i.e., whatever intervention a participant's primary care physician deemed appropriate), usual primary care plus the rehabilitation program delivered to individual participants, or usual primary care plus the rehabilitation program delivered to groups of 8 participants. The primary outcome was self-reported functioning (Western Ontario and McMaster Universities Osteoarthritis Index physical functioning [WOMAC-func]) 6 months after completing rehabilitation. RESULTS: A total of 418 participants were recruited; 76 (18%) withdrew, only 5 (1%) due to adverse events. Rehabilitated participants had better functioning than participants continuing usual primary care (-3.33 difference in WOMAC-func score; 95% confidence interval [95% CI] -5.88, -0.78; P = 0.01). Improvements were similar whether participants received individual rehabilitation (-3.53; 95% CI -6.52, -0.55) or group rehabilitation (-3.16; 95% CI -6.55, -0.12). CONCLUSION: ESCAPE-knee pain provides a safe, relatively brief intervention for chronic knee pain that is equally effective whether delivered to individuals or groups of participants

Isolated human pulmonary artery structure and function pre‐ and post‐cardiopulmonary bypass surgery

Background: Pulmonary dysfunction is a known complication after cardiac surgery using cardiopulmonary bypass, ranging from subclinical functional changes to prolonged postoperative ventilation, acute lung injury, and acute respiratory distress syndrome. Whether human pulmonary arterial function is compromised is unknown. The aim of the present study was to compare the structure and function of isolated and cannulated human pulmonary arteries obtained from lung biopsies after the chest was opened (pre–cardiopulmonary bypass) to those obtained at the end of cardiopulmonary bypass (post–cardiopulmonary bypass) from patients undergoing coronary artery bypass graft surgery. Methods and Results: Pre‐ and post–cardiopulmonary bypass lung biopsies were received from 12 patients undergoing elective surgery. Intralobular small arteries were dissected, cannulated, pressurized, and imaged using confocal microscopy. Functionally, the thromboxane mimetic U46619 produced concentration‐dependent vasoconstriction in 100% and 75% of pre‐ and post–cardiopulmonary bypass arteries, respectively. The endothelium‐dependent agonist bradykinin stimulated vasodilation in 45% and 33% of arteries pre‐ and post–cardiopulmonary bypass, respectively. Structurally, in most arteries smooth muscle cells aligned circumferentially; live cell viability revealed that although 100% of smooth muscle and 90% of endothelial cells from pre–cardiopulmonary bypass biopsies had intact membranes and were considered viable, only 60% and 58%, respectively, were viable from post–cardiopulmonary bypass biopsies. Conclusions: We successfully investigated isolated pulmonary artery structure and function in fresh lung biopsies from patients undergoing heart surgery. Pulmonary artery contractile tone and endothelium‐dependent dilation were significantly reduced in post–cardiopulmonary bypass biopsies. The decreased functional responses were associated with reduced cell viability. Clinical Trial Registration: URL: http://www.isrctn.com/ISRCTN34428459. Unique identifier: ISRCTN 34428459.</p

New drugs on the horizon for cerebral edema: what’s in the clinical development pipeline?

This is the author accepted manuscript. the final version is available from Taylor & Francis via the DOI in this recordIntroduction: Research has advanced our understanding of the molecular and cellular mechanisms of cerebral edema and has propelled the development of novel antiedema therapeutics. Current evidence supports aberrant neuro-glial ion transport as a central mechanism that underlies pathological fluid accumulation after central nervous system injury. Areas covered: Novel agents in clinical development show potential in altering the natural history and treatment of cerebral edema. Using the PubMed and Google Scholar databases, we review recent advances in our understanding of cerebral edema and describe agents under active investigation, their mechanism, and their application in recent and ongoing clinical trials. Expert opinion: Pharmacotherapies that target molecular mechanisms underlying the compensatory post-injury response of ion channels and transporters that lead to pathological alteration of osmotic gradients are the most promising therapeutic strategies. Repurposing of drugs such as glyburide that inhibit the aberrant upregulation of ion channels such as SUR1-TRPM4, and novel agents, such as ZT-1a, which reestablish physiological regulation of ion channels such as NKCC1/KCC, could be useful adjuvants to prevent and even reverse fluid accumulation in the brain parenchyma

Are lower levels of red blood cell transfusion more cost-effective than liberal levels after cardiac surgery? Findings from the TITRe2 randomised controlled trial.

OBJECTIVE: To assess the incremental cost and cost-effectiveness of a restrictive versus a liberal red blood cell transfusion threshold after cardiac surgery. DESIGN: A within-trial cost-effectiveness analysis with a 3-month time horizon, based on a multicentre superiority randomised controlled trial from the perspective of the National Health Service (NHS) and personal social services in the UK. SETTING: 17 specialist cardiac surgery centres in UK NHS hospitals. PARTICIPANTS: 2003 patients aged >16 years undergoing non-emergency cardiac surgery with a postoperative haemoglobin of <9 g/dL. INTERVENTIONS: Restrictive (transfuse if haemoglobin <7.5 g/dL) or liberal (transfuse if haemoglobin <9 g/dL) threshold during hospitalisation after surgery. MAIN OUTCOME MEASURES: Health-related quality of life measured using the EQ-5D-3L to calculate quality-adjusted life years (QALYs). RESULTS: The total costs from surgery up to 3 months were £17 945 and £18 127 in the restrictive and liberal groups (mean difference is -£182, 95% CI -£1108 to £744). The cost difference was largely attributable to the difference in the cost of red blood cells. Mean QALYs to 3 months were 0.18 in both groups (restrictive minus liberal difference is 0.0004, 95% CI -0.0037 to 0.0045). The point estimate for the base-case cost-effectiveness analysis suggested that the restrictive group was slightly more effective and slightly less costly than the liberal group and, therefore, cost-effective. However, there is great uncertainty around these results partly due to the negligible differences in QALYs gained. CONCLUSIONS: We conclude that there is no clear difference in the cost-effectiveness of restrictive and liberal thresholds for red blood cell transfusion after cardiac surgery. TRIAL REGISTRATION NUMBER: ISRCTN70923932; Results