CESAR: conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure.

BACKGROUND: An estimated 350 adults develop severe, but potentially reversible respiratory failure in the UK annually. Current management uses intermittent positive pressure ventilation, but barotrauma, volutrauma and oxygen toxicity can prevent lung recovery. An alternative treatment, extracorporeal membrane oxygenation, uses cardio-pulmonary bypass technology to temporarily provide gas exchange, allowing ventilator settings to be reduced. While extracorporeal membrane oxygenation is proven to result in improved outcome when compared to conventional ventilation in neonates with severe respiratory failure, there is currently no good evidence from randomised controlled trials to compare these managements for important clinical outcomes in adults, although evidence from case series is promising. METHODS/DESIGN: The aim of the randomised controlled trial of Conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR) is to assess whether, for patients with severe, but potentially reversible, respiratory failure, extracorporeal membrane oxygenation will increase the rate of survival without severe disability ('confined to bed' and 'unable to wash or dress') by six months post-randomisation, and be cost effective from the viewpoints of the NHS and society, compared to conventional ventilatory support. Following assent from a relative, adults (18-65 years) with severe, but potentially reversible, respiratory failure (Murray score >/= 3.0 or hypercapnea with pH < 7.2) will be randomised for consideration of extracorporeal membrane oxygenation at Glenfield Hospital, Leicester or continuing conventional care in a centre providing a high standard of conventional treatment. The central randomisation service will minimise by type of conventional treatment centre, age, duration of high pressure ventilation, hypoxia/hypercapnea, diagnosis and number of organs failed, to ensure balance in key prognostic variables. Extracorporeal membrane oxygenation will not be available for patients meeting entry criteria outside the trial. 180 patients will be recruited to have 80% power to be able to detect a one third reduction in the primary outcome from 65% at 5% level of statistical significance (2-sided test). Secondary outcomes include patient morbidity and health status at 6 months. DISCUSSION: Analysis will be based on intention to treat. A concurrent economic evaluation will also be performed to compare the costs and outcomes of both treatments

The inclusion of disability within efforts to address menstrual health during humanitarian emergencies: A systematized review

Introduction: Women and girls with disabilities may be excluded from efforts to achieve menstrual health during emergencies. The review objectives were to (1) identify and map the scope of available evidence on the inclusion of disability in menstrual health during emergencies and (2) understand its focus in comparison to menstrual health for people without disabilities in emergencies. Methods: Eligible papers covered all regions and emergencies. Peer-reviewed papers were identified by conducting searches, in February 2020 and August 2021, across six online databases (PubMed, MEDLINE, EMBASE, Global Health, ReliefWeb, and Cinahal Plus); gray literature was identified through OpenGrey, Gray Literature Report, Google Scholar, and Million Short. Eligible papers included data on menstrual health for women and girls with and without disabilities in emergencies. Results: Fifty-one papers were included; most focused on Southern Asia and man-made hazards. Nineteen papers contained primary research, whilst 32 did not. Four of the former were published in peer-reviewed journals; 34 papers were high quality. Only 26 papers mentioned menstrual health and disability in humanitarian settings, but the discussion was fleeting and incredibly light. Social support, behavioral expectations, knowledge, housing, shelter, water and sanitation infrastructure, disposal facilities, menstrual material availability, and affordability were investigated. Women and girls with disabilities rarely participated in menstrual health efforts, experienced reduced social support, and were less able to access water, sanitation and hygiene facilities, including disposal facilities. Cash transfers and hygiene kit distribution points were often inaccessible for people with disabilities; few outreach schemes existed. Hygiene kits provided were not always appropriate for people with disabilities. Caregivers (all genders) require but lack guidance about how to support an individual with disabilities to manage menstruation. Conclusion: Minimal evidence exists on menstrual health and disabilities in emergencies; what does exist rarely directly involves women and girls with disabilities or their caregivers. Deliberate action must be taken to generate data about their menstrual health requirements during humanitarian crises and develop subsequent evidence-based solutions. All efforts must be made in meaningful participation with women and girls with disabilities and their caregivers to ensure interventions are appropriate

A randomised controlled trial investigating the effect of n-3 long-chain polyunsaturated fatty acid supplementation on cognitive and retinal function in cognitively healthy older people: the Older People And n-3 Long-chain polyunsaturated fatty acids (OPAL) study protocol [ISRCTN72331636].

The number of individuals with age-related cognitive impairment is rising dramatically in the UK and globally. There is considerable interest in the general hypothesis that improving the diet of older people may slow the progression of cognitive decline. To date, there has been little attention given to the possible protective role of n-3 long-chain polyunsaturated fatty acids (n-3 LCPs) most commonly found in oily fish, in age-related loss of cognitive function. The main research hypothesis of this study is that an increased dietary intake of n-3 LCPs will have a positive effect on cognitive performance in older people in the UK. To test this hypothesis, a double-blind randomised placebo-controlled trial will be carried out among adults aged 70-79 years in which the intervention arm will receive daily capsules containing n-3 LCP (0.5 g/day docosahexaenoic acid and 0.2 g/day eicosapentaenoic acid) while the placebo arm will receive daily capsules containing olive oil. The main outcome variable assessed at 24 months will be cognitive performance and a second major outcome variable will be retinal function. Retinal function tests are included as the retina is a specifically differentiated neural tissue and therefore represents an accessible window into the functioning of the brain. The overall purpose of this public-health research is to help define a simple and effective dietary intervention aimed at maintaining cognitive and retinal function in later life. This will be the first trial of its kind aiming to slow the decline of cognitive and retinal function in older people by increasing daily dietary intake of n-3 LCPs. The link between cognitive ability, visual function and quality of life among older people suggests that this novel line of research may have considerable public health importance.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Comparison of the effectiveness of trauma services provided by secondary and tertiary hospitals in Malaysia.

STUDY OBJECTIVE: The trauma services provided by 6 hospitals operating at 2 levels of care (4 secondary or district general hospitals and 2 tertiary care hospitals) in Malaysia are compared in terms of mortality and disability for direct admissions to emergency departments to test the hypothesis that care at a tertiary care hospital is better than at a district general hospital. METHODS: All cases were recruited prospectively for 1 year. The hospitals were purposefully selected as typical for Malaysia. There are 3 primary outcome measures: death, musculoskeletal impairment, and disability at discharge. Adjustment was made for potential covariates and within-hospital clustering by using multivariable random-effects logistic regression analysis. RESULTS: For direct admissions, logistic-regression-identified odds of dying were associated with older age (>55 years), odds ratio (OR) 1.9 (95% confidence interval [CI] 1.3 to 2.8); head injury, OR 2.7 (95% CI 1.9 to 3.9); arrival by means other than ambulance, OR 0.6 (95% CI 0.4 to 0.8); severe injuries (Injury Severity Score >15) at a district general hospital, OR 45.2 (95% CI 27.0 to 75.7); severe injuries at a tertiary care hospital, OR 11.2 (95% CI 7.3 to 17.3); and admission to a tertiary care hospital compared to a district general hospital if severely injured (Injury Severity Score >15), OR 0.2 (95% CI 0.1 to 0.4). Admission to a tertiary care hospital was associated with increased odds of disability (OR 1.9; 95% CI 1.5 to 2.3) and musculoskeletal impairment (OR 3.5; 95% CI 2.7 to 4.4) at discharge. CONCLUSION: Care at a tertiary care hospital was associated with reduced mortality (by 83% in severe injuries), but with a higher likelihood of disability and impairment, which has implications for improving access to trauma services for the severely injured in Malaysia and other low- and middle-income settings

Data monitoring in randomized controlled trials: surveys of recent practice and policies.

BACKGROUND: Data Monitoring Committees (DMCs) are increasingly involved in the conduct of randomized controlled trials, but there is little documented evidence of what they do. Three interlinked surveys were carried out as part of the DAMOCLES project to explore recent and current DMC practice and policy. METHODS: 1) A questionnaire about DMC practice was sent to sample of 45 authors of trials published in selected journals in 2000. The sample was stratified by centre (single/multiple), disease area, and presence of DMC. 2) A sample of investigators in trials ongoing in the United Kingdom in 2001-02 was also sent a questionnaire about DMC practice. The sample was drawn from trials funded by the Medical Research Council, the United Kingdom Department of Health's Health Technology Assessment Programme, and a local and a multicentre research ethics committee. The sample was additionally stratified by funder (public/industry), centre (single/ multiple), and disease area. 3) A sample of major organisations involved in randomised controlled trials was sent a questionnaire about DMC policies. RESULTS: Information about DMC practice from the first survey was obtained from 31 trials (69%), of which four had a DMC. Information about DMC practice from the second survey was obtained about 36 trials (90%), of which 20 had a DMC. Information about DMC policy from the third survey was obtained from 25 out of 25 organisations. There was general agreement about the sorts of trials particularly needing independent DMCs, but there were few uniform approaches to their modes of functioning, and few of the organisations surveyed had developed formal policies. CONCLUSIONS: The roles of existing DMCs and policies governing DMC functioning vary widely across trials and organisations that sponsor or oversee trials, both within the UK and internationally. These findings reinforce previous calls for development of such policies across a wider range of organisations, better means to monitor their implementation within trials, and wider use of structured "charters", which set out DMC modus operandi in advance. Clinical Trials 2005; 2: 22-33. www.SCTjournal.co

Lifetime exposure to arsenic in residential drinking water in Central Europe.

OBJECTIVE: Methods and results are presented for an arsenic exposure assessment integral to an epidemiological case-control study of arsenic and cancer-the European Commission funded ASHRAM (Arsenic Health Risk Assessment and Molecular Epidemiology) study carried out in some counties of Hungary, Romania and Slovakia. METHODS: The exposure history of each participant (N = 1,392) was constructed by taking into account how much water they consumed (as water, in drinks and in food), sources of drinking water in their various residences over their lifetime, and the concentrations of arsenic in their various water supplies measured by Hydride Generation-Atomic Absorption Spectrometry (HG-AAS). Concentrations of arsenic in previous water supplies were either derived from contemporary analyses of the same source, or from routine historical data from measurements performed by the authorities in each country. Using this approach, 80% of the recorded lifetime residential history was matched to an arsenic concentration. Seven indices of current, life time, and peak exposure were calculated. RESULTS: The exposure indices were all log-normally distributed and the mean and median lifetime average concentrations were in Hungary 14.7 and 13.3 microg l(-1), Romania 3.8 and 0.7 microg l(-1) and in Slovakia 1.9 and 0.8 microg l(-1), respectively. Overall 25% of the population had average concentrations over 10 microg l(-1) and 8% with exposure over 50 microg l(-1). CONCLUSIONS: Careful assessment of arsenic in drinking water supplies (both current and previous) enabled the majority of study participants' cumulative lifetime of potential exposure to arsenic in residential water to be characterised

Lifestyle of UK commercial aircrews relative to air traffic controllers and the general population.

INTRODUCTION: Commercial aircrews are exposed to potential occupational hazards and, recently, epidemiological studies have examined their morbidity and mortality relative to the general population. Aircrews are, however, likely to differ from the general population in several respects which may affect the validity of such comparisons. METHODS: A cohort of 17,990 commercial aircrews was identified through the United Kingdom (UK) Civil Aviation Authority medical records and is being followed for morbidity and mortality. Demographic, lifestyle, reproductive, and medical characteristics of commercial aircrews were compared with those of: 1) UK air traffic control officers (ATCOs; N = 3386) identified in a similar way as aircrews; and 2) estimates for the UK general population. RESULTS: Aircrews and ATCOs had similar characteristics, except that sex-age-adjusted prevalences for current smoking, obesity, and hypertension were statistically significantly higher in the latter. Both aircrews and ATCOs differed considerably from the general population with, for instance, much lower sex-age-adjusted prevalences of current smoking, obesity, and hypertension but higher levels of regular physical exercise. Age-adjusted fertility rates among female aircrews and ATCOs were only one-third of those in the general population. These differences were slightly attenuated when comparisons with the general population were restricted to its highest socio-economic stratum. DISCUSSION: The differences between aircrews and the general population are consistent with a strong "healthy worker effect." Aircrews and ATCOs undergo a similar employment selection process and thus taking the latter as the reference population, in addition to the general population, will help to minimize the "healthy worker effect" and gain insight into its biases

Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial.

BACKGROUND: Severe acute respiratory failure in adults causes high mortality despite improvements in ventilation techniques and other treatments (eg, steroids, prone positioning, bronchoscopy, and inhaled nitric oxide). We aimed to delineate the safety, clinical efficacy, and cost-effectiveness of extracorporeal membrane oxygenation (ECMO) compared with conventional ventilation support. METHODS: In this UK-based multicentre trial, we used an independent central randomisation service to randomly assign 180 adults in a 1:1 ratio to receive continued conventional management or referral to consideration for treatment by ECMO. Eligible patients were aged 18-65 years and had severe (Murray score >3.0 or pH 30 cm H(2)O of peak inspiratory pressure) or high FiO(2) (>0.8) ventilation for more than 7 days; intracranial bleeding; any other contraindication to limited heparinisation; or any contraindication to continuation of active treatment. The primary outcome was death or severe disability at 6 months after randomisation or before discharge from hospital. Primary analysis was by intention to treat. Only researchers who did the 6-month follow-up were masked to treatment assignment. Data about resource use and economic outcomes (quality-adjusted life-years) were collected. Studies of the key cost generating events were undertaken, and we did analyses of cost-utility at 6 months after randomisation and modelled lifetime cost-utility. This study is registered, number ISRCTN47279827. FINDINGS: 766 patients were screened; 180 were enrolled and randomly allocated to consideration for treatment by ECMO (n=90 patients) or to receive conventional management (n=90). 68 (75%) patients actually received ECMO; 63% (57/90) of patients allocated to consideration for treatment by ECMO survived to 6 months without disability compared with 47% (41/87) of those allocated to conventional management (relative risk 0.69; 95% CI 0.05-0.97, p=0.03). Referral to consideration for treatment by ECMO led to a gain of 0.03 quality-adjusted life-years (QALYs) at 6-month follow-up [corrected]. A lifetime model predicted the cost per QALY of ECMO to be pound19 252 (95% CI 7622-59 200) at a discount rate of 3.5%. INTERPRETATION: We recommend transferring of adult patients with severe but potentially reversible respiratory failure, whose Murray score exceeds 3.0 or who have a pH of less than 7.20 on optimum conventional management, to a centre with an ECMO-based management protocol to significantly improve survival without severe disability. This strategy is also likely to be cost effective in settings with similar services to those in the UK. FUNDING: UK NHS Health Technology Assessment, English National Specialist Commissioning Advisory Group, Scottish Department of Health, and Welsh Department of Health