Non-specific effects of measles, mumps, and rubella (MMR) vaccination in high income setting: population based cohort study in the Netherlands.

Objectives To investigate whether measles, mumps, and rubella (MMR) vaccine has positive non-specific effects in a high income setting and to compare rates of hospital admissions for infections between children aged ≤2 years who received live MMR vaccine and those who received an inactivated vaccine against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) as their most recent vaccination.Design Nationwide population based cohort study.Setting In the Netherlands, DTaP-IPV-Hib+pneumococcal vaccination (PCV) is recommended at ages 2, 3, 4, and 11 months and MMR + meningococcal C (MenC) vaccination at age 14 months. Data from the national vaccine register were linked to hospital admission data.Participants 1 096 594 children born in 2005-11 who received the first four DTaP-IPV-Hib+PCV vaccines.Main outcome measures Hazard ratio for admission to hospital for infection in children with MMR+MenC compared with the fourth DTaP-IPV-Hib+PCV as their most recent vaccination. Cox regression was performed with most recent vaccination as time dependent variable, adjusted for potential confounders. Analyses were repeated with admission for injuries or poisoning as a negative control outcome. In addition, rate of admission for infection was compared between the fourth and third DTaP-IPV-Hib+PCVas most recent vaccination.Results Having had MMR+MenC as the most recent vaccination was associated with a hazard ratio of 0.62 (95% confidence interval 0.57 to 0.67) for admission to hospital for infection and 0.84 (0.73 to 0.96) for injuries or poisoning, compared with the fourth DTaP-IPV-Hib+PCV as most recent vaccination. The fourth DTaP-IPV-Hib+PCV as most recent vaccination was associated with a hazard ratio of 0.69 (0.63 to 0.76) for admission to hospital for infection, compared with the third DTaP-IPV-Hib+PCV as most recent vaccination.Conclusions Healthy vaccinee bias could at least partly explain the observed lower rate of admission to hospital with infection after MMR vaccination. The lower rate is associated with receipt of any additional vaccine, not specifically MMR vaccine. This emphasises the caution required in the interpretation of findings from observational studies on non-specific effects of vaccination.

Essential amino acids in the gluten-free diet and serum in relation to depression in patients with celiac disease.

INTRODUCTION: Celiac disease (CD) is associated with an increased risk of major depressive disorder, possibly due to deficiencies in micronutrients in the gluten-free diet. We aimed to investigate whether essential amino acids (i.e., the precursors of serotonin, dopamine and other neurotransmitters) are depleted in the diet and serum of CD patients with major depressive disorder. METHODS: In a cross-sectional study we assessed dietary intake of amino acids and serum levels of amino acids, in 77 CD patients on a gluten-free diet and in 33 healthy controls. Major depressive disorder was assessed with structured interviews (using the Mini International Neuropsychiatric Interview Plus). Dietary intake was assessed using a 203-item food frequency questionnaire. RESULTS: Participants had a mean age of 55 years and 74% were women. The intake of vegetable protein was significantly lower in CD patients than in healthy controls (mean difference of 7.8 g/d; 95% CI: 4.7-10.8), as were serum concentrations of tyrosine, phenylalanine and tryptophan (all p < 0.005). However, within the CD patient group, the presence of major depressive disorder (n = 42) was not associated with intake or serum levels of essential amino acids. CONCLUSIONS: Patients with CD on a long-term gluten-free diet, with good adherence, consume significantly less vegetable protein than controls, and their serum levels of several essential amino acids were also lower. Despite its potential adverse effect, intake and serum levels of essential amino acids were not related to major depression.

Ten-year blood pressure trajectories, cardiovascular mortality, and life years lost in 2 extinction cohorts: the Minnesota Business and Professional Men Study and the Zutphen Study.

BACKGROUND: Blood pressure (BP) trajectories derived from measurements repeated over years have low measurement error and may improve cardiovascular disease prediction compared to single, average, and usual BP (single BP adjusted for regression dilution). We characterized 10-year BP trajectories and examined their association with cardiovascular mortality, all-cause mortality, and life years lost. METHODS AND RESULTS: Data from 2 prospective and nearly extinct cohorts of middle-aged men­the Minnesota Business and Professional Men Study (n=261) and the Zutphen Study (n=632)­were used. BP was measured annually during 1947-1957 in Minnesota and 1960-1970 in Zutphen. BP trajectories were identified by latent mixture modeling. Cox proportional hazards and linear regression models examined BP trajectories with cardiovascular mortality, all-cause mortality, and life years lost. Associations were adjusted for age, serum cholesterol, smoking, and diabetes mellitus. Mean initial age was about 50 years in both cohorts. After 10 years of BP measurements, men were followed until death on average 20 years later. All Minnesota men and 98% of Zutphen men died. Four BP trajectories were identified, in which mean systolic BP increased by 5 to 49 mm Hg in Minnesota and 5 to 20 mm Hg in Zutphen between age 50 and 60. The third systolic BP trajectories were associated with 2 to 4 times higher cardiovascular mortality risk, 2 times higher all-cause mortality risk, and 4 to 8 life years lost, compared to the first trajectory. CONCLUSIONS: Ten-year BP trajectories were the strongest predictors, among different BP measures, of cardiovascular mortality, all-cause mortality, and life years lost in Minnesota. However, average BP was the strongest predictor in Zutphen.

Twenty-four hour urinary urea excretion and 9-year risk of hypertension: the PREVEND study.

OBJECTIVES: It is not yet clear whether dietary protein could help maintaining a healthy blood pressure (BP). We investigated the association between total protein intake, estimated from 24-h urinary urea excretion, and incident hypertension in Dutch men and women. METHODS: We analyzed data of 3997 men and women (aged 28-75 years) who participated in the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, a prospective cohort study. Urea excretion was assessed in two consecutive 24-h urine collections at baseline and approximately 4 years later, from which total protein intake was estimated using the Maroni method. Participants were followed for 9 years for hypertension incidence, defined as BP at least 140/90 mmHg or initiation of antihypertensive medication. Hazard ratios (HR) were obtained in sex-specific quintiles of protein intake using time-dependent Cox regression, adjusted for age, sex, BMI, smoking, alcohol use, and 24-h urinary excretions of sodium and potassium. RESULTS: Baseline BP was on average 119/70 mmHg and 976 participants developed hypertension during follow-up. Mean protein intake (in g/kg ideal body weight) was 1.18 ±â€Š0.26 for men and 1.12 ±â€Š0.25 for women. Estimated protein intake was nonlinearly inversely associated with incident hypertension in the fully adjusted model, with nonsignificant HR of 0.77, 0.75, 0.82, and 0.83 in consecutive quintiles compared with the lowest quintile (P-trend: 0.52). CONCLUSION: Protein intake, as assessed by urinary urea excretion, was not significantly associated with 9-year hypertension incidence in Dutch men and women.

Joint associations of alcohol consumption and physical activity with all-cause and cardiovascular mortality.

Individual associations of alcohol consumption and physical activity with cardiovascular disease are relatively established, but the joint associations are not clear. Therefore, the aim of this study was to examine prospectively the joint associations between alcohol consumption and physical activity with cardiovascular mortality (CVM) and all-cause mortality. Four population-based studies in the United Kingdom were included, the 1997 and 1998 Health Surveys for England and the 1998 and 2003 Scottish Health Surveys. In men and women, respectively, low physical activity was defined as 0.1 to 5 and 0.1 to 4 MET-hours/week and high physical activity as ≥5 and ≥4 MET-hours/week. Moderate or moderately high alcohol intake was defined as >0 to 35 and >0 to 21 units/week and high levels of alcohol intake as >35 and >21 units/week. In total, there were 17,410 adults without prevalent cardiovascular diseases and complete data on alcohol and physical activity (43% men, median age 55 years). During a median follow-up period of 9.7 years, 2,204 adults (12.7%) died, 638 (3.7%) with CVM. Cox proportional-hazards models were adjusted for potential confounders such as marital status, social class, education, ethnicity, and longstanding illness. In the joint associations analysis, low activity combined with high levels of alcohol (CVM: hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.28 to 2.96, p = 0.002; all-cause mortality: HR 1.64, 95% CI 1.32 to 2.03, p <0.001) and low activity combined with no alcohol (CVM: HR 1.93, 95% CI 1.35 to 2.76, p <0.001; all-cause mortality: HR 1.50, 95% CI 1.24 to 1.81, p <0.001) were linked to the highest risk, compared with moderate drinking and higher levels of physical activity. Within each given alcohol group, low activity was linked to increased CVM risk (e.g., HR 1.48, 95% CI 1.08 to 2.03, p = 0.014, for the moderate drinking group), but in the presence of high physical activity, high alcohol intake was not linked to increased CVM risk (HR 1.32, 95% CI 0.52 to 3.34, p = 0.555). In conclusion, high levels of drinking and low physical activity appear to increase the risk for cardiovascular and all-cause mortality, although these data suggest that physical activity levels are more important.