The specificity of the familial aggregation of early-onset bipolar disorder: A controlled 10-year follow-up study of offspring of parents with mood disorders.

BACKGROUND: Two major sources of heterogeneity of mood disorders that have been demonstrated in clinical, family and genetic studies are the mood disorder subtype (i.e. bipolar (BPD) and major depressive disorder (MDD)) and age of onset of mood episodes. Using a prospective high-risk study design, our aims were to test the specificity of the parent-child transmission of BPD and MDD and to establish the risk of psychopathology in offspring in function of the age of onset of the parental disorder. METHODS: Clinical information was collected on 208 probands (n=81 with BPD, n=64 with MDD, n=63 medical controls) as well as their 202 spouses and 372 children aged 6-17 years at study entry. Parents and children were directly interviewed every 3 years (mean duration of follow-up=10.6 years). Parental age of onset was dichotomized at age 21. RESULTS: Offspring of parents with early onset BPD entailed a higher risk of BPD HR=7.9(1.8-34.6) and substance use disorders HR=5.0(1.1-21.9) than those with later onset and controls. Depressive disorders were not significantly increased in offspring regardless of parental mood disorder subtype or age of onset. LIMITATIONS: Limited sample size, age of onset in probands was obtained retrospectively, age of onset in co-parents was not adequately documented, and a quarter of the children had no direct interview. CONCLUSIONS: Our results provide support for the independence of familial aggregation of BPD from MDD and the heterogeneity of BPD based on patterns of onset. Future studies should further investigate correlates of early versus later onset BPD.

Dietary intake according to gender and education : a twenty-year trend in a Swiss adult population

We assessed trends in dietary intake according to gender and education using repeated cross-sectional, population-based surveys conducted between 1993 and 2012 in Geneva, Switzerland (17,263 participants, 52.0 ± 10.6 years, 48% male). In 1993-1999, higher educated men had higher monounsaturated fatty acids (MUFA), carotene and vitamin D intakes than lower educated men, and the differences decreased in 2006-2012. In 1993-1999, higher educated women had higher fiber, iron, carotene, vitamin D and alcohol intakes than lower educated women, and the differences decreased in 2006-2012. Total energy, polyunsaturated fatty acids, retinol and alcohol intakes decreased, while mono/disaccharides, MUFA and carotene intake increased in both genders. Lower educated men had stronger decreases in saturated fatty acid (SFA) and calcium intakes than higher educated men: multivariate-adjusted slope and 95% confidence interval -0.11 (-0.15; -0.06) vs. -0.03 (-0.08; 0.02) g/day/year for SFA and -5.2 (-7.8; -2.7) vs. -1.03 (-3.8; 1.8) mg/day/year for calcium, p for interaction <0.05. Higher educated women had a greater decrease in iron intake than lower educated women: -0.03 (-0.04; -0.02) vs. -0.01 (-0.02; 0.00) mg/day/year, p for interaction = 0.002. We conclude that, in Switzerland, dietary intake evolved similarly between 1993 and 2012 in both educational groups. Educational differences present in 1993 persisted in 2012.

Association between parental history and genetic risk scores for coronary heart disease prediction: The population-based CoLaus study.

BACKGROUND AND AIMS: Parental history (PH) and genetic risk scores (GRSs) are separately associated with coronary heart disease (CHD), but evidence regarding their combined effects is lacking. We aimed to evaluate the joint associations and predictive ability of PH and GRSs for incident CHD. METHODS: Data for 4283 Caucasians were obtained from the population-based CoLaus Study, over median follow-up time of 5.6 years. CHD was defined as incident myocardial infarction, angina, percutaneous coronary revascularization or bypass grafting. Single nucleotide polymorphisms for CHD identified by genome-wide association studies were used to construct unweighted and weighted versions of three GRSs, comprising of 38, 53 and 153 SNPs respectively. RESULTS: PH was associated with higher values of all weighted GRSs. After adjustment for age, sex, smoking, diabetes, systolic blood pressure, low and high density lipoprotein cholesterol, PH was significantly associated with CHD [HR 2.61, 95% CI (1.47-4.66)] and further adjustment for GRSs did not change this estimate. Similarly, one standard deviation change of the weighted 153-SNPs GRS was significantly associated with CHD [HR 1.50, 95% CI (1.26-1.80)] and remained so, after further adjustment for PH. The weighted, 153-SNPs GRS, but not PH, modestly improved discrimination [(C-index improvement, 0.016), p = 0.048] and reclassification [(NRI improvement, 8.6%), p = 0.027] beyond cardiovascular risk factors. After including both the GRS and PH, model performance improved further [(C-index improvement, 0.022), p = 0.006]. CONCLUSION: After adjustment for cardiovascular risk factors, PH and a weighted, polygenic GRS were jointly associated with CHD and provided additive information for coronary events prediction.

Five year trends in dyslipidaemia prevalence and management in Switzerland: The CoLaus study.

BACKGROUND AND AIMS: Data from prospective cohorts describing dyslipidaemia prevalence and treatment trends are lacking. Using data from the prospective CoLaus study, we aimed to examine changes in serum lipid levels, dyslipidaemia prevalence and management in a population-based sample of Swiss adults. METHODS AND RESULTS: Cardiovascular risk was assessed using PROCAM. Dyslipidaemia and low-density lipoprotein cholesterol (LDL-C) target levels were defined according to the Swiss Group for Lipids and Atherosclerosis. Complete baseline and follow up (FU) data were available for n = 4863 subjects during mean FU time of 5.6 years. Overall, 32.1% of participants were dyslipidaemic at baseline vs 46.3% at FU (p < 0.001). During this time, lipid lowering medication (LLM) rates among dyslipidaemic subjects increased from 34.0% to 39.2% (p < 0.001). In secondary prevention, LLM rates were 42.7% at baseline and 53.2% at FU (p = 0.004). In multivariate analysis, LLM use among dyslipidaemic subjects, between baseline and FU, was positively associated with personal history of CVD, older age, hypertension, higher BMI and diabetes, while negatively associated with higher educational level. Among treated subjects, LDL-C target achievement was positively associated with diabetes and negatively associated with personal history of CVD and higher BMI. Among subjects treated at baseline, LLM discontinuation was negatively associated with older age, male sex, smoking, hypertension and parental history of CVD. CONCLUSIONS: In Switzerland, the increase over time in dyslipidaemia prevalence was not paralleled by a similar increase in LLM. In a real-life setting, dyslipidaemia management remains far from optimal, both in primary and secondary prevention.

Effect of Cumulating Exposure to Abacavir on the Risk of Cardiovascular Disease Events in Patients From the Swiss HIV Cohort Study.

BACKGROUND: Patients with HIV exposed to the antiretroviral drug abacavir may have an increased risk of cardiovascular disease (CVD). There is concern that this association arises because of a channeling bias. Even if exposure is a risk, it is not clear how that risk changes as exposure cumulates. METHODS: We assess the effect of exposure to abacavir on the risk of CVD events in the Swiss HIV Cohort Study. We use a new marginal structural Cox model to estimate the effect of abacavir as a flexible function of past exposures while accounting for risk factors that potentially lie on a causal pathway between exposure to abacavir and CVD. RESULTS: A total of 11,856 patients were followed for a median of 6.6 years; 365 patients had a CVD event (4.6 events per 1000 patient-years). In a conventional Cox model, recent--but not cumulative--exposure to abacavir increased the risk of a CVD event. In the new marginal structural Cox model, continued exposure to abacavir during the past 4 years increased the risk of a CVD event (hazard ratio = 2.06; 95% confidence interval: 1.43 to 2.98). The estimated function for the effect of past exposures suggests that exposure during the past 6-36 months caused the greatest increase in risk. CONCLUSIONS: Abacavir increases the risk of a CVD event: the effect of exposure is not immediate, rather the risk increases as exposure cumulates over the past few years. This gradual increase in risk is not consistent with a rapidly acting mechanism, such as acute inflammation.

Trends and characteristics of attendance at the emergency department of a Swiss university hospital: 2002-2012.

BACKGROUND: The numbers of people attending emergency departments (EDs) at hospitals are increasing. We aimed to analyse trends in ED attendance at a Swiss university hospital between 2002 and 2012, focussing on age-related differences and hospital admission criteria. METHODS: We used hospital administrative data for all patients aged ≥16 years who attended the ED (n = 298,306) at this university hospital between 1 January 2002, and 31 December 2012. We descriptively analysed the numbers of ED visits according to the admission year and stratified by age (≥65 vs <65 years). RESULTS: People attending the ED were on average 46.6 years old (standard deviation 20 years, maximum range 16‒99 years). The annual number of ED attendances grew by n = 6,639 (27.6%) from 24,080 in 2002 to 30,719 in 2012. In the subgroup of patients aged ≥65 the relative increase was 42.3%, which is significantly higher (Pearson's χ2 = 350.046, df = 10; p = 0.000) than the relative increase of 23.4% among patients <65 years. The subgroup of patients ≥65 years attended the ED more often because of diseases (n = 56,307; 85%) than accidents (n = 9,844; 14.9%). This subgroup (patients ≥65 years) was also more often admitted to hospital (Pearson's χ2 = 23,377.190; df = 1; p = 0.000) than patients <65 years. CONCLUSIONS: ED attendance of patients ≥65 years increased in absolute and relative terms. The study findings suggest that staff of this ED may want to assess the needs of patients ≥65 years and, if necessary, adjust the services (e.g., adapted triage scales, adapted geriatric screenings, and adapted hospital admission criteria).