Error Rates, Decisive Outcomes and Publication Bias with Several Inferential Methods

Correction to this article published Hopkins, W.G. & Batterham, A.M. Sports Med (2016) 46: 923. doi:10.1007/s40279-016-0530-

Population screening for hereditary haemochromatosis in Australia: Construction and validation of a state-transition cost-effectiveness model

INTRODUCTION: HFE-associated haemochromatosis, the most common monogenic disorder amongst populations of northern European ancestry, is characterised by iron overload. Excess iron is stored in parenchymal tissues, leading to morbidity and mortality. Population screening programmes are likely to improve early diagnosis, thereby decreasing associated disease. Our aim was to develop and validate a health economics model of screening using utilities and costs from a haemochromatosis cohort. METHODS: A state-transition model was developed with Markov states based on disease severity. Australian males (aged 30 years) and females (aged 45 years) of northern European ancestry were the target populations. The screening strategy was the status quo approach in Australia; the model was run over a lifetime horizon. Costs were estimated from the government perspective and reported in 2015 Australian dollars ($A); costs and quality-adjusted life-years (QALYs) were discounted at 5$A22,737 (3670-85,793) for males and $A13,840 (1335-67,377) for females. Sensitivity analyses revealed discount rates and prevalence had the greatest impacts on outcomes. CONCLUSION: We have developed a transparent, validated health economics model of C282Y homozygote haemochromatosis. The model will be useful to decision makers to identify cost-effective screening strategies

Effects of C282Y, H63D, and S65C HFE gene mutations, diet, and life-style factors on iron status in a general Mediterranean population from Tarragona, Spain

Mutations in the HFE gene result in iron overload and can produce hereditary hemochromatosis (HH), a disorder of iron metabolism characterized by increased intestinal iron absorption. Dietary quality, alcoholism and other life-style factors can increase the risk of iron overload, especially among genetically at risk populations. Polymorphisms of the HFE gene (C282Y, H63D and S65C) were measured together with serum ferritin (SF), transferrin saturation (TS) and hemoglobin, to measure iron status, in randomly-selected healthy subjects living in the Spanish Mediterranean coast (n = 815; 425 females, 390 males), 18 to 75 years of age. The intake of dietary components that affect iron absorption was calculated from 3-day dietary records. The presence of C282Y/H63D compound heterozygote that had a prevalence of 2.8% in males and 1.2% in females was associated with an elevated TS and SF. No subject was homozygous for C282Y or S65C. The C282Y heterozygote, H63D heterozygote and homozygote and H63D/S65C compound heterozygote genotypes were associated with increased TS relative to the wild type in the general population. These genotypes together with the alcohol and iron intake increase the indicators of iron status, while calcium intake decreases them. We did not observe any affect of the S65C heterozygote genotype on these levels. All the HFE genotypes except for the S65C heterozygote together with the alcohol, iron and calcium intake affect the indicators of iron status. The C282Y/H63D compound heterozygote genotype has the higher phenotypic expression in our Spanish Mediterranean population

HFE gene mutations increase the risk of coronary heart disease in women

The purpose of the present study is to examine HFE gene mutations in relation to newly diagnosed (incident) coronary heart disease (CHD). In a population-based follow-up study of 7,983 individuals aged 55 years and older, we compared the risk of incident CHD between HFE carriers and non-carriers, overall and stratified by sex and smoking status. HFE mutations were significantly associated with an increased risk of incident CHD in women but not in men (hazard ratio [HR] for women = 1.7, 95% confidence interval [CI] 1.2–2.4 versus HR for men = 0.9, 95% CI 0.7–1.2). This increased CHD risk associated with HFE mutations in women was statistically significant in never smokers (HR = 1.8, 95% CI 1.1–2.8) and current smokers (HR = 3.1, 95% CI 1.4–7.1), but not in former smokers (HR = 1.3, 95% CI 0.7–2.4). HFE mutations are associated with increased risk of incident CHD in women

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions

Introduction: Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare-related interventions. Methods and analysis: The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in, (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies and will help patients by protecting them from the influence of false data on their healthcare. Ethics and dissemination: The University of Manchester ethics decision tool was used, and this returned the result that ethical approval was not required for this project (30 September 2022), which incorporates secondary research and surveys of professionals about subjects relating to their expertise. Informed consent will be obtained from all survey participants. All results will be published as open-access articles. The final tool will be made freely available.National Institute for Health and Care Research (NIHR) Research for Patient Benefit programme (NIHR203568)

Relationship between Vehicle Emissions Laws and Incidence of Suicide by Motor Vehicle Exhaust Gas in Australia, 2001-06: An Ecological Analysis

BACKGROUND: Globally, suicide accounts for 5.2% of deaths among persons aged 15 to 44 years and its incidence is rising. In Australia, suicide rates peaked in 1997 and have been declining since. A substantial part of that decline stems from a plunge in suicides by one particular method: asphyxiation by motor vehicle exhaust gas (MVEG). Although MVEG remains the second most common method of suicide in Australia, its incidence decreased by nearly 70% in the decade to 2006. The extent to which this phenomenon has been driven by national laws in 1986 and 1999 that lowered permissible levels of carbon monoxide (CO) emissions is unknown. The objective of this ecological study was to test the relationship by investigating whether areas of Australia with fewer noxious vehicles per capita experienced lower rates of MVEG suicide. METHODS AND FINDINGS: We merged data on MVEG suicides in Australia (2001-06) with data on the number and age of vehicles in the national fleet, as well as socio-demographic data from the national census. Poisson regression was used to analyse the relationship between the incidence of suicide within two levels of geographical area--postcodes and statistical subdivisions (SSDs)--and the population density of pre-1986 and pre-1999 passenger vehicles in those areas. (There was a mean population of 8,302 persons per postcode in the study dataset and 87,413 persons per SSD.) The annual incidence of MVEG suicides nationwide decreased by 57% (from 2.6 per 100,000 in 2001 to 1.1 in 2006) during the study period; the population density of pre-1986 and pre-1999 vehicles decreased by 55% (from 14.2 per 100 persons in 2001 to 6.4 in 2006) and 26% (from 44.5 per 100 persons in 2001 to 32.9 in 2006), respectively. Area-level regression analysis showed that the suicide rates were significantly and positively correlated with the presence of older vehicles. A percentage point decrease in the population density of pre-1986 vehicles was associated with a 6% decrease (rate ratio [RR] = 1.06; 95% confidence interval [CI] 1.05-1.08) in the incidence of MVEG suicide within postcode areas; a percentage point decrease in the population density of pre-1999 vehicles was associated with a 3% decrease (RR = 1.03; 95% CI 1.02-1.04) in the incidence of MVEG suicide. CONCLUSIONS: Areas of Australia with fewer vehicles predating stringent CO emission laws experience lower rates of MVEG suicide. Although those emission laws were introduced primarily for environmental reasons, countries that lack them may miss the benefits of a serendipitous suicide prevention strategy. Please see later in the article for the Editors' Summary