Visible minority status and occupation were associated with increased COVID-19 infection in Greater Vancouver British Columbia between June and November 2020: an ecological study.

Background: The COVID-19 pandemic has highlighted health disparities, especially among specific population groups. This study examines the spatial relationship between the proportion of visible minorities (VM), occupation types and COVID-19 infection in the Greater Vancouver region of British Columbia, Canada. Methods: Provincial COVID-19 case data between June 24, 2020, and November 7, 2020, were aggregated by census dissemination area and linked with sociodemographic data from the Canadian 2016 census. Bayesian spatial Poisson regression models were used to examine the association between proportion of visible minorities, occupation types and COVID-19 infection. Models were adjusted for COVID-19 testing rates and other sociodemographic factors. Relative risk (RR) and 95% Credible Intervals (95% CrI) were calculated. Results: We found an inverse relationship between the proportion of the Chinese population and risk of COVID-19 infection (RR = 0.98 95% CrI = 0.96, 0.99), whereas an increased risk was observed for the proportions of the South Asian group (RR = 1.10, 95% CrI = 1.08, 1.12), and Other Visible Minority group (RR = 1.06, 95% CrI = 1.04, 1.08). Similarly, a higher proportion of frontline workers (RR = 1.05, 95% CrI = 1.04, 1.07) was associated with higher infection risk compared to non-frontline. Conclusion: Despite adjustments for testing, housing, occupation, and other social economic status variables, there is still a substantial association between the proportion of visible minorities, occupation types, and the risk of acquiring COVID-19 infection in British Columbia. This ecological analysis highlights the existing disparities in the burden of diseases among different visible minority populations and occupation types.

Systematic review and meta-analysis of disease clustering in multimorbidity: a study protocol.

INTRODUCTION: Multimorbidity is defined as the presence of two or more chronic diseases. Co-occurring diseases can have synergistic negative effects, and are associated with significant impacts on individual health outcomes and healthcare systems. However, the specific effects of diseases in combination will vary between different diseases. Identifying which diseases are most likely to co-occur in multimorbidity is an important step towards population health assessment and development of policies to prevent and manage multimorbidity more effectively and efficiently. The goal of this project is to conduct a systematic review and meta-analysis of studies of disease clustering in multimorbidity, in order to identify multimorbid disease clusters and test their stability. METHODS AND ANALYSIS: We will review data from studies of multimorbidity that have used data clustering methodologies to reveal patterns of disease co-occurrence. We propose a network-based meta-analytic approach to perform meta-clustering on a select list of chronic diseases that are identified as priorities for multimorbidity research. We will assess the stability of obtained disease clusters across the research literature to date, in order to evaluate the strength of evidence for specific disease patterns in multimorbidity. ETHICS AND DISSEMINATION: This study does not require ethics approval as the work is based on published research studies. The study findings will be published in a peer-reviewed journal and disseminated through conference presentations and meetings with knowledge users in health systems and public health spheres. PROSPERO REGISTRATION NUMBER: CRD42023411249.

Cause-specific mortality in professional flight crew and air traffic control officers: findings from two UK population-based cohorts of over 20,000 subjects.

OBJECTIVE: Flight crew are exposed to several potential occupational hazards. This study compares mortality rates in UK flight crew to those in air traffic control officers (ATCOs) and the general population. METHODS: A total of 19,489 flight crew and ATCOs were identified from the UK Civil Aviation Authority medical records and followed to the end of 2006. Consented access to medical records and questionnaire data provided information on demographic, behavioral, clinical, and occupational variables. Standardized mortality ratios (SMR) were estimated for these two occupational groups using the UK general population. Adjusted mortality hazard ratios (HR) for flight crew versus ATCOs were estimated via Cox regression models. RESULTS: A total of 577 deaths occurred during follow-up. Relative to the general population, both flight crew (SMR 0.32; 95% CI 0.30, 0.35) and ATCOs (0.39; 0.32, 0.47) had lower all-cause mortality, mainly due to marked reductions in mortality from neoplasms and cardiovascular diseases, although flight crew had higher mortality from aircraft accidents (SMR 42.8; 27.9, 65.6). There were no differences in all-cause mortality (HR 0.99; 95% CI 0.79, 1.25), or in mortality from any major cause, between the two occupational groups after adjustment for health-related variables, again except for those from aircraft accidents. The latter ratios, however, declined with increasing number of hours. CONCLUSIONS: The low all-cause mortality observed in both occupational groups relative to the general population is consistent with a strong "healthy worker effect" and their low prevalence of smoking and other risk factors. Mortality among flight crew did not appear to be influenced by occupational exposures, except for a rise in mortality from aircraft accidents.

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 <7.20) but potentially reversible respiratory failure. Exclusion criteria were: high pressure (>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.

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.

Inadequate control of heart rate in patients with stable angina: results from the European heart survey.

AIMS: To examine resting heart rate (HR) in a population presenting with stable angina in relation to prior and subsequent pharmacological treatment, comorbid conditions and clinical outcome. METHODS AND RESULTS: The European Heart Survey was a prospective, observational, cohort study of 3779 patients with stable angina newly presenting to cardiology services. Mean baseline resting HR was 73 beats/min (bpm) and 52.3% of patients had a baseline HR > 70 bpm. Over half of patients were on no chronotropic medication at baseline. Patients with chronic respiratory disease or diabetes had higher resting HRs (75-76 bpm), and were more likely to have been receiving calcium channel blockers at baseline assessment. Overall, beta-blockers were the most common treatment administered following cardiologist assessment, but were used less frequently in patients with chronic respiratory disease and diabetes, and the dosages used were less than that found to be effective in clinical trials. Mean daily doses of metoprolol, bisoprolol, carvedilol, and atenolol were 75 mg, 6 mg, 19 mg and 55 mg, respectively. Higher HR at baseline was associated with higher rates of cardiovascular mortality and hospitalisation for heart failure. CONCLUSION: Control of ischaemic symptoms through heart rate modification in patients with angina is currently inadequate, both by primary referring physicians and cardiologists. Given the adverse outcome associated with higher resting heart rates in this as in other studies, and the availability of specific HR reducing strategies, attention should be given to achieving optimal HR control.

Methods of data collection and analysis for the economic evaluation alongside a national, multi-centre trial in the UK: conventional ventilation or ECMO for Severe Adult Respiratory Failure (CESAR).

BACKGROUND: Extracorporeal Membrane Oxygenation (ECMO) is a technology used in treatment of patients with severe but potentially reversible respiratory failure. A multi-centre randomised controlled trial (CESAR) was funded in the UK to compare care including ECMO with conventional intensive care management. The protocol and funding for the CESAR trial included plans for economic data collection and analysis. Given the high cost of treatment, ECMO is considered an expensive technology for many funding systems. However, conventional treatment for severe respiratory failure is also one of the more costly forms of care in any health system. METHODS/DESIGN: The objectives of the economic evaluation are to compare the costs of a policy of referral for ECMO with those of conventional treatment; to assess cost-effectiveness and the cost-utility at 6 months follow-up; and to assess the cost-utility over a predicted lifetime. Resources used by patients in the trial are identified. Resource use data are collected from clinical report forms and through follow up interviews with patients. Unit costs of hospital intensive care resources are based on parallel research on cost functions in UK NHS intensive care units. Other unit costs are based on published NHS tariffs. Cost effectiveness analysis uses the outcome: survival without severe disability. Cost utility analysis is based on quality adjusted life years gained based on the Euroqol EQ-5D at 6 months. Sensitivity analysis is planned to vary assumptions about transport costs and method of costing intensive care. Uncertainty will also be expressed in analysis of individual patient data. Probabilities of cost effectiveness given different funding thresholds will be estimated. DISCUSSION: In our view it is important to record our methods in detail and present them before publication of the results of the trial so that a record of detail not normally found in the final trial reports can be made available in the public domain. TRIAL REGISTRATIONS: The CESAR trial registration number is ISRCTN47279827.

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.

Gender differences in the management and clinical outcome of stable angina.

BACKGROUND: We sought to examine the impact of gender on the investigation and subsequent management of stable angina and to assess gender differences in clinical outcome at 1 year. METHODS AND RESULTS: The Euro Heart Survey of Stable Angina enrolled patients with a clinical diagnosis of stable angina on initial assessment by a cardiologist. Baseline clinical details and cardiac investigations planned or performed within a 4-week period of the assessment were recorded, and follow-up data were collected at 1 year. A total of 3779 patients were included in the survey; 42% were female. Women were less likely to undergo an exercise ECG (odds ratio, 0.81; 95% CI, 0.69 to 0.95) and less likely to be referred for coronary angiography (odds ratio, 0.59; 95% CI, 0.48 to 0.72). Antiplatelet and statin therapies were used significantly less in women than in men, both at initial assessment and at 1 year, even in those in whom coronary disease had been confirmed. Women with confirmed coronary disease were less likely to be revascularized than their male counterparts and were twice as likely to suffer death or nonfatal myocardial infarction during the 1-year follow-up period (hazard ratio, 2.09; 95% CI, 1.13 to 3.85), even after multivariable adjustment for age, abnormal ventricular function, severity of coronary disease, and diabetes. CONCLUSIONS: Significant gender bias has been identified in the use of investigations and evidence-based medical therapy in stable angina. Women were also less likely to be revascularized. The observed bias is of particular concern in light of the adverse prognosis observed among women with stable angina and confirmed coronary disease.

Use of recombinant activated factor VII in primary postpartum hemorrhage: the Northern European registry 2000-2004.

OBJECTIVE: To collect data from nine European countries for cases of obstetric hemorrhage between 2000 and 2004 in which recombinant activated factor VII (rFVIIa) was used. METHODS: The cases were identified through national surveys. Standardized case report forms included sociodemographic details, past medical and obstetric history, and details of the progress and management of labor in which the postpartum hemorrhage occurred. Clinicians were asked to describe subjectively the effect of rFVIIa administration using two mutually exclusive categories: 1) bleeding reduced or 2) bleeding unchanged or worse. RESULTS: A total of 113 forms were returned (88%) with 97 (86%) classified as treatment, and 16 (14%) as "secondary prophylaxis." Clinicians noted improvements after a single dose for 80% of women in the treatment group, and for 75% in the secondary "prophylaxis" group. However, rFVIIa failed in 15 cases (13.8%). Few serious adverse events were noted related to rFVIIa administration; there were four cases of thromboembolism, one myocardial infarction, and one skin rash. CONCLUSION: Clinical reports and hematologic data suggest improvement for more than 80% of women after rFVIIa administration and few adverse effects. LEVEL OF EVIDENCE: II.

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.

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.

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.

Smoking cessation interventions for COPD: a review of the literature.

The aim of this systematic review is to establish the most effective stop smoking intervention approach for smokers with COPD. The search strategy included the electronic databases MEDLINE, EMBASE, AMED, PsycINFO, DARE, Cochrane Library, and CINAHL, between January 2006 and January 2010. References of the included studies were also screened for additional papers, and further hand searches were conducted. The selection criteria included randomized controlled trials or quasi-randomized controlled trials with at least one subject group diagnosed with COPD. Two independent reviewers reviewed the included studies, using a quality assessment form developed from the selection criteria. Divergence of quality assessment scores was resolved by the 2 reviewers agreeing on a score. The 4 studies selected indicate that psychosocial interventions combined with pharmacotherapy are effective in smoking cessation at 12 months post-intervention, although the effect is not statistically significant, due to small sample size and heterogeneity between the studies (odds ratio 2.35, 95% CI 0.25-21.74,). However, despite this medium effect size, due to a lack of universal use of pharmacotherapies in most of the studies, it makes a definitive comparison of efficacy difficult to determine. This review also shows the effectiveness of psychosocial treatment for people with or without COPD symptoms at 12 months, although the effect of disease severity is not clear. This review also highlights the difficulty of maintaining attendance at community-based locations, compared to acute or research settings.

Inorganic arsenic and basal cell carcinoma in areas of Hungary, Romania, and Slovakia: a case-control study.

BACKGROUND: Inorganic arsenic (iAs) is a potent carcinogen, but there is a lack of information about cancer risk for concentrations < 100 µg/L in drinking water. OBJECTIVES: We aimed to quantify skin cancer relative risks in relation to iAs exposure < 100 µg/L and the modifying effects of iAs metabolism. METHODS: The Arsenic Health Risk Assessment and Molecular Epidemiology (ASHRAM) study, a case-control study, was conducted in areas of Hungary, Romania, and Slovakia with reported presence of iAs in groundwater. Consecutively diagnosed cases of basal cell carcinoma (BCC) of the skin were histologically confirmed; controls were general surgery, orthopedic, and trauma patients who were frequency matched to cases by age, sex, and area of residence. Exposure indices were constructed based on information on iAs intake over the lifetime of participants. iAs metabolism status was classified based on urinary concentrations of methylarsonic acid (MA) and dimethylarsinic acid (DMA). Associations were estimated by multivariable logistic regression. RESULTS: A total of 529 cases with BCC and 540 controls were recruited for the study. BCC was positively associated with three indices of iAs exposure: peak daily iAs dose rate, cumulative iAs dose, and lifetime average water iAs concentration. The adjusted odds ratio per 10-µg/L increase in average lifetime water iAs concentration was 1.18 (95% confidence interval: 1.08, 1.28). The estimated effect of iAs on cancer was stronger in participants with urinary markers indicating incomplete metabolism of iAs: higher percentage of MA in urine or a lower percentage of DMA. CONCLUSION: We found a positive association between BCC and exposure to iAs through drinking water with concentrations < 100 µg/L.

The BLISS cluster randomised controlled trial of the effect of 'active dissemination of information' on standards of care for premature babies in England (BEADI) study protocol [ISRCTN89683698].

BACKGROUND: Gaps between research knowledge and practice have been consistently reported. Traditional ways of communicating information have limited impact on practice changes. Strategies to disseminate information need to be more interactive and based on techniques reported in systematic reviews of implementation of changes. There is a need for clarification as to which dissemination strategies work best to translate evidence into practice in neonatal units across England. The objective of this trial is to assess whether an innovative active strategy for the dissemination of neonatal research findings, recommendations, and national neonatal guidelines is more likely to lead to changes in policy and practice than the traditional (more passive) forms of dissemination in England. METHODS/DESIGN: Cluster randomised controlled trial of all neonatal units in England (randomised by hospital, n = 182 and stratified by neonatal regional networks and neonatal units level of care) to assess the relative effectiveness of active dissemination strategies on changes in local policies and practices. Participants will be mainly consultant lead clinicians in each unit. The intervention will be multifaceted using: audit and feedback; educational meetings for local staff (evidence-based lectures on selected topics, interactive workshop to examine current practice and draw up plans for change); and quality improvement and organisational changes methods. Policies and practice outcomes for the babies involved will be collected before and after the intervention. Outcomes will assess all premature babies born in England during a three month period for timing of surfactant administration at birth, temperature control at birth, and resuscitation team (qualification and numbers) present at birth.

Single nucleotide polymorphisms in DNA repair genes and basal cell carcinoma of skin.

In addition to environmental exposures like UV radiation and, in some cases, arsenic contamination of drinking water, genetic factors may also influence the individual susceptibility to basal cell carcinoma of skin (BCC). In the present study, 529 cases diagnosed with BCC and 533 controls from Hungary, Romania and Slovakia were genotyped for one polymorphism in each of seven DNA repair genes. The variant allele for T241M (C>T) polymorphism in the XRCC3 gene was associated with a decreased cancer risk [odds ratio (OR), 0.73; 95% confidence interval (CI), 0.61-0.88; P = 0.0007, multiple testing corrected P = 0.004]. The risk of multiple BCC was significantly lower among variant allele carriers than in non-carriers (P = 0.04). Men homozygous for the C-allele for E185Q (G>C) polymorphism in the NBS1 gene showed an increased BCC risk (OR, 2.19; 95% CI, 1.23-3.91), but not women (OR, 0.84; 95% CI, 0.49-1.47). In men, the age and nationality adjusted OR for the genotype CC (XRCC3)/CC (NBS1) was 8.79 (95% CI, 2.10-36.8), compared with the genotype TT (XRCC3)/GG (NBS1). The data from this study show overall risk modulation of BCC by variant allele for T241M polymorphism in XRCC3 and gender-specific effect by E185Q polymorphism in NBS1.

Predicting prognosis in stable angina--results from the Euro heart survey of stable angina: prospective observational study.

OBJECTIVES: To investigate the prognosis associated with stable angina in a contemporary population as seen in clinical practice, to identify the key prognostic features, and from this to construct a simple score to assist risk prediction. DESIGN: Prospective observational cohort study. SETTING: Pan-European survey in 156 outpatient cardiology clinics. PARTICIPANTS: 3031 patients were included on the basis of a new clinical diagnosis by a cardiologist of stable angina with follow-up at one year. MAIN OUTCOME MEASURE: Death or non-fatal myocardial infarction. RESULTS: The rate of death and non-fatal myocardial infarction in the first year was 2.3 per 100 patient years; the rate was 3.9 per 100 patient years in the subgroup (n = 994) with angiographic confirmation of coronary disease. The clinical and investigative factors most predictive of adverse outcome were comorbidity, diabetes, shorter duration of symptoms, increasing severity of symptoms, abnormal ventricular function, resting electrocardiogaphic changes, or not having any stress test done. Results of non-invasive stress tests did not significantly predict outcome in the population who had tests done. A score was constructed using the parameters predictive of outcome to estimate the probability of death or myocardial infarction within one year of presentation with stable angina. CONCLUSIONS: A score based on the presence of simple, objective clinical and investigative variables makes it possible to discriminate effectively between very low risk and very high risk patients and to estimate the probability of death or non-fatal myocardial infarction over one year.

The impact of guideline compliant medical therapy on clinical outcome in patients with stable angina: findings from the Euro Heart Survey of stable angina.

AIMS: The European Society of Cardiology published guidelines for the management of stable angina in 1997, with the objective of promoting an evidence-based approach to the condition. This study focuses on the impact of guideline compliant medical treatment on clinical outcome in patients with stable angina. METHODS AND RESULTS: The Euro Heart Survey of Stable Angina is a multicentre prospective observational study conducted between 2002 and 2003. Patients with a clinical diagnosis of stable angina by a cardiologist were enrolled and follow-up was conducted at 1 year. The primary outcome of interest was death or myocardial infarction (MI). The increasing intensity of guideline compliant medical therapy was quantified by means of a simple treatment score based on the use of guideline advocated therapies: antiplatelets, statins, and beta-blockers. A total of 3779 patients were included in the initial survey. Increasing intensity of guideline compliant therapy at initial assessment was associated with a reduction in death and MI during follow-up in patients with angina and confirmed coronary disease (HR 0.68; 95% CI 0.49-0.95 per unit increase in treatment score). All cardiovascular events were also significantly reduced in this subgroup (HR 0.82; 95% CI 0.69-0.97). The benefits of guideline compliant therapy were only observed in patients with objective evidence of coronary disease. CONCLUSION: Guideline compliant medical therapy improves clinical outcome in patients with stable angina and objective evidence of coronary disease.

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.com