SUMMARYIreland reports the highest incidence of verotoxigenic Escherichia coli (VTEC) infection in Europe. This study investigated potential risk factors for confirmed sporadic and outbreak primary VTEC infections during 2008-2013. Overall, 989 VTEC infections including 521 serogroup O157 and 233 serogroup O26 were geo-referenced to 931 of 18 488 census enumeration areas. The geographical distribution of human population, livestock, unregulated groundwater sources, domestic wastewater treatment systems (DWWTS) and a deprivation index were examined relative to notification of VTEC events in 524 of 6242 rural areas. Multivariate modelling identified three spatially derived variables associated with VTEC notification: private well usage [odds ratio (OR) 6·896, P < 0·001], cattle density (OR 1·002, P < 0·001) and DWWTS density (OR 0·978, P = 0·002). Private well usage (OR 18·727, P < 0·001) and cattle density (OR 1·001, P = 0·007) were both associated with VTEC O157 infection, while DWWTS density (OR 0·987, P = 0·028) was significant within the VTEC O26 model. Findings indicate that VTEC infection in the Republic of Ireland is particularly associated with rural areas, which are associated with a ubiquity of pathogen sources (cattle) and pathways (unregulated groundwater supplies).

Objective-To assess the risk of ischaemic stroke associated with total serum homocyst(e)ine (tHcy) concentration. Design-Cohort study. Setting-Caerphilly, South Wales Participants-2254 men age 50 to 64 years recruited between 1984 and 1988. Results-107 men developed ischaemic stroke and mean follow up time was 10.2 years. There was no significant diVerence in mean serum total homocyst(e)ine levels between stroke cases (12.2 µmol 95% CI 11.6 to 13.1) and non-cases (11.7 µmol 95% CI 11.5 to 11.9) (p=0.14). There was no significant risk for a standard deviation increase in homocyst(e)ine (adjusted hazard ratio = 1.1, 95% CI 0.9 to 1.4). An interaction was observed between homocyst(e)ine and age at entry (p=0.003). The adjusted odds ratio comparing the top quintile of homocyst(e)ine with the rest was 2.5 (95% CI 1.0 to 6.2) for strokes occurring under 65 years and 0.5 (95% CI 0.2 to 1.3) at 65 years or older (p value for interaction =0.02). Risk also diVered by blood pressure status. The adjusted hazard ratio for a standard deviation increase in homocyst(e)ine was 0.8, (95% CI 0.6 to 1.2) for normotensive men and 1.3 (95% CI 1.1 to 1.7) for hypertensive men (p value for interaction =0.01). Conclusions-Overall, there is no significant relation between homocyst(e)ine and ischaemic stroke in this cohort. However, its aetiological importance may be greater for premature ischaemic strokes (<65 years) and in hypertensive men. (J Epidemiol Community Health 2001;55:91-96)

Objective-Prospective assessment of the risk of coronary heart disease associated with total serum homocyst(e)ine (homocysteine) concentration. Design-Nested case-control study. Setting-Caerphilly and surrounding villages in south Wales, UK. Participants-2290 men who participated in phase II of the study in 1984. After a mean follow up of 10 years, 312 men developed coronary heart disease and were compared with 1248 randomly selected, age frequency matched controls. Main outcome measure-Acute myocardial infarction or death from coronary heart disease. Results-The geometric mean serum homocysteine concentration was higher in cases (12.2 µmol/l, 95% confidence interval (CI) 11.8 to 12.6 µmol/l) than in controls (11.8 µmol/l, 95% CI 11.3 to 12.5 µmol/l) (p = 0.09). There was a graded increase in the odds ratio of coronary heart disease across quintiles of the homocysteine concentration distribution compared with the first (p = 0.04), which was attenuated when adjusted for confounding variables (p = 0.4). There was a small but non-significant increase in the adjusted odds ratio of coronary heart disease per standard deviation change in the log distribution of homocysteine concentration (OR = 1.07 (95% CI .93 to 1.24), p = 0.34). Comparing the top quintile of the homocysteine concentration with the remaining 80%, the adjusted odds ratio of coronary heart disease was 1.03 (95% CI 0.73 to 1.45) (p = 0.8) and comparing the top 5% with the remaining 95% it was 1.05 (95% CI 0.56 to 1.95) (p = 0.9). Conclusions-These findings do not support the hypothesis that a raised homocysteine concentration is a strong independent risk factor for coronary heart disease. Randomised controlled trials of homocysteine lowering treatment such as folic acid are needed before generalising the early positive results of observational studies. (Heart 2001;85:153-158) Keywords: homocysteine; coronary heart disease; cohort Hyperhomocysteinaemia has been proposed as an independent risk factor for atherosclerotic vascular disease. 1 This is an important hypothesis because blood homocysteine concentrations can be easily and cheaply reduced by taking folic acid. 2 Although there is no proof of causality, the homocysteine cardiovascular disease hypothesis is biologically plausible as homocysteine is known to be toxic to vascular endothelium at very high concentrations, and young adults with congenital hyperhomocysteinuria die prematurely of atherosclerosis and thrombosis. 3 In recent years population based epidemiological studies have examined the influence of raised total serum homocyst(e)ine (homocysteine) concentration on atherosclerotic vascular disease, particularly coronary heart disease. The initial evidence suggesting that this is a strong independent risk factor for coronary heart disease came predominantly from cross sectional 4 and retrospective case-control studies. 5 A meta-analysis estimated an odds ratio of coronary heart disease of 1.6 (95% confidence interval (CI) 1.4 to 1.7) for every 5 µmol increase in plasma homocysteine...