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Microvascular dysfunction (MVD) is a common pathophysiological change that occurs in various diseases, such as type 2 diabetes mellitus (T2DM), heart failure, dementia, and depression. Recent technical advances have enabled noninvasive measurement and quantification of microvascular changes in humans. In this paper, we describe the protocols of the microvascular measurements applied in the Maastricht Study, an ongoing prospective, population-based cohort study of persons aged 40–75 years being carried out in the southern part of the Netherlands (baseline data assessment, November 2010–January 2020). The study includes a variety of noninvasive measurements in skin, retina, brain, and sublingual tissue, as well as plasma and urine biomarker assessments. Following this, we summarize our main findings involving these microvascular measurements through the end of 2018. Finally, we provide a brief perspective on future microvascular investigations within the framework of the Maastricht Study. [ABSTRACT FROM AUTHOR]

Characteristics of the localities in which Jews lived have received little attention in research on Holocaust-related deaths. We examined associations between locality-level and individual-level characteristics with the odds of being deported by applying multilevel mixed-effects logistic regression models to data for about 118,000 Jews in 102 Dutch municipalities listed in 1941–1942 and linked to postwar victims and returnees lists. We examined associations between individual-level characteristics and risk of death of deported Jews in multilevel mixed-effects Weibull regression models. Locality-level characteristics, per standard deviation increase, associated with higher deportation chance were more collaborating policemen (OR = 1.07, 95% CI: 1.02, 1.12), strongest segregation mentality (OR = 2.01, 95% CI: 1.15, 3.50), and less employment in agriculture (OR = 0.95, 95% CI: 0.88, 1.01). Higher percentage of Catholics (OR = 0.81, 95% CI: 0.70, 0.94) and stronger electoral support for the National Socialist Movement (OR = 0.90, 95% CI: 0.85, 0.97) unexpectedly reduced deportation chance. Individual-level characteristics associated with lower deportation chance were female sex, ages 0–5 or 15–30 years, and being immigrants, intermarried, or converts to Christianity. Deported males aged 15–30 years had reduced risk of death between July 1942 and July 1943 but increased risk thereafter, consistent with young adult men being selected for work after deportation but this selection not offering long-term protection. Holocaust survival chances were influenced by both locality-level and individual-level characteristics. [ABSTRACT FROM AUTHOR]

Earlier studies report inconsistent associations between education and cognitive aging. We assessed the association, accounting for selective dropout due to death or dementia, and, in a subsample, accounting for confounding by early-life intelligence. Data from the Danish component of the Survey of Health, Ageing and Retirement in Europe (n = 3,400) were linked to registry data (education records, dementia diagnoses, and mortality) and the Danish Conscription Database (youth intelligence measurements for 854 men). Word recall and verbal fluency were assessed up to 4 times over 10 years (2004–2013) and combined by averaging the z scores. We fitted a joint model linking a time-to-event model for dementia or death to a linear mixed-effects model for cognitive change. Rate of cognitive decline was slower among people with high education compared with low education (β = 0.112, 95% confidence interval (CI): 0.056, 0.170). Adjusting for youth intelligence did not attenuate the association between education and cognitive decline (crude β = 0.136, 95% CI: 0.028, 0.244 vs. adjusted β = 0.145, 95% CI: 0.022, 0.269). The results suggest that higher education may slow cognitive decline in later life. In this sample, results changed little when accounting for selective attrition and confounding by intelligence. [ABSTRACT FROM AUTHOR]

Recurrence of bladder cancer can occur repeatedly in the same patient after treatment of the primary tumor. Models predicting the risk of a next recurrence may inform individualized decision-making on surveillance frequency. We aimed to assess the usefulness of extensions of the Cox proportional hazards model for repeated events in this context. We analyzed 531 Dutch patients with bladder cancer (1990-2012) with information on 7 pre-specified predictors at the time of diagnosis of the primary and recurrent tumors. We considered 3 aspects of model variants: how to model time to the repeated events (calendar time, gap time, elapsed time); the number of preceding events (predictor, stratum variable); and the within-subject correlation (ignored in a simple Cox model, robust standard errors in a variance-correction model, random effect in a frailty model). First to fourth recurrences of bladder cancer occurred in 313, 174, 103, and 66 patients, respectively, with median calendar follow-up times of 1.1, 2.5, 3.8, and 4.5 years, respectively. We focused on gap time in the detailed analyses, allowing for clinically meaningful predictions. Variance-correction models may be useful if predictor selection is part of the model development. Frailty models may be useful when within-subject correlation is strong. [ABSTRACT FROM AUTHOR]

We assessed associations between modeled and perceived exposure to radiofrequency electromagnetic fields (RF-EMF) from mobile-phone base stations and the development of nonspecific symptoms and sleep disturbances over time. A population-based Dutch cohort study, the Occupational and Environmental Health Cohort Study (AMIGO) (n = 14,829; ages 31-65 years), was established in 2011/2012 (T0), with follow-up of a subgroup (n = 3,992 invited) in 2013 (T1; n = 2,228) and 2014 (T2; n = 1,740). We modeled far-field RF-EMF exposure from mobile-phone base stations at the home addresses of the participants using a 3-dimensional geospatial model (NISMap). Perceived exposure (0 = not at all; 6 = very much), nonspecific symptoms, and sleep disturbances were assessed by questionnaire. We performed cross-sectional and longitudinal analyses, including fixed-effects regression. We found small correlations between modeled and perceived exposure in AMIGO participants at baseline (n = 14,309; rSpearman = 0.10). For 222 follow-up participants, modeled exposure increased substantially (>0.030 mW/m²) between T0 and T1. This increase in modeled exposure was associated with an increase in perceived exposure during the same time period. In contrast to modeled RF-EMF exposure from mobile-phone base stations, perceived exposure was associated with higher symptom reporting scores in both cross-sectional and longitudinal analyses, as well as with sleep disturbances in cross-sectional analyses. [ABSTRACT FROM AUTHOR]

Intuitively, researchers do not include subjects who do not have the opportunity to be exposed, such as men in studies on oral contraceptives (OCs). We aimed to explore in which situations it is nevertheless beneficial to do so. We considered the effect of including men in case-control analyses of 8 different hypothetical data sets on the effect of OC use and venous thrombosis. In all scenarios, OC use was the exposure of interest, sex the factor that determined exposure opportunity, and air travel another risk factor. In some of these scenarios, sex and air travel were included as confounders or effect modifiers. Logistic regression was used to estimate odds ratios. Standard errors of the estimated log odds ratios, including and excluding men, were compared. We also studied the effect of including men using data from 1999-2004 from a case-control study on risk factors for venous thrombosis, conducted in the Netherlands. In all hypothetical examples, and in the real-data study, addition of men to the analysis yielded the same odds ratios when correctly adjusting for confounding. Moreover, use of additional subjects often led to more precise estimates. We suggest that subjects who do not have the opportunity to be exposed should not routinely be excluded from epidemiologic studies. [ABSTRACT FROM AUTHOR]