Erasmus University Rotterdam

About: Erasmus University Rotterdam is a education organization based out in Rotterdam, Zuid-Holland, Netherlands. It is known for research contribution in the topics: Population & Health care. The organization has 35466 authors who have published 91288 publications receiving 4510972 citations. The organization is also known as: EUR.

Adherence to cardiovascular therapy: a meta-analysis of prevalence and clinical consequences

Abstract: Aims The aim of this study was to determine the extent to which adherence to individual vascular medications, assessed by different methods, influences the absolute and relative risks (RRs) of cardiovascular disease (CVD) and all-cause mortality. Methods and results We performed a systematic review and meta-analysis of prospective epidemiological studies (cohort, nested case–control, or clinical trial) identified through electronic searches using MEDLINE, Web of Science, EMBASE, and Cochrane databases, involving adult populations (≥18 years old) and reporting risk estimates of cardiovascular medication adherence with any CVD (defined as any fatal or non-fatal coronary heart disease, stroke or sudden cardiac death) and/or all-cause mortality (defined as mortality from any cause) outcomes. Relative risks were combined using random-effects models. Forty-four unique prospective studies comprising 1 978 919 non-overlapping participants, with 135 627 CVD events and 94 126 cases of all-cause mortality. Overall, 60% (95% CI: 52–68%) of included participants had good adherence (adherence ≥80%) to cardiovascular medications. The RRs (95% CI) of development of CVD in those with good vs. poor (<80%) adherence were 0.85 (0.81–0.89) and 0.81 (0.76–0.86) for statins and antihypertensive medications, respectively. Corresponding RRs of all-cause mortality were 0.55 (0.46–0.67) and 0.71 (0.64–0.78) for good adherence to statins and antihypertensive agents. These associations remained consistent across subgroups representing different study characteristics. Estimated absolute risk differences for any CVD associated with poor medication adherence were 13 cases for any vascular medication, 9 cases for statins and 13 cases for antihypertensive agents, per 100 000 individuals per year. Conclusion A substantial proportion of people do not adhere adequately to cardiovascular medications, and the prevalence of suboptimal adherence is similar across all individual CVD medications. Absolute and relative risk assessments demonstrate that a considerable proportion of all CVD events (∼9% in Europe) could be attributed to poor adherence to vascular medications alone, and that the level of optimal adherence confers a significant inverse association with subsequent adverse outcomes. Measures to enhance adherence to help maximize the potentials of effective cardiac therapies in the clinical setting are urgently required.

DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis

Abstract: Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.

In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma.

Abstract: Although dendritic cells (DCs) play an important role in sensitization to inhaled allergens, their function in ongoing T helper (Th)2 cell–mediated eosinophilic airway inflammation underlying bronchial asthma is currently unknown. Here, we show in an ovalbumin (OVA)-driven murine asthma model that airway DCs acquire a mature phenotype and interact with CD4+ T cells within sites of peribronchial and perivascular inflammation. To study whether DCs contributed to inflammation, we depleted DCs from the airways of CD11c-diphtheria toxin (DT) receptor transgenic mice during the OVA aerosol challenge. Airway administration of DT depleted CD11c+ DCs and alveolar macrophages and abolished the characteristic features of asthma, including eosinophilic inflammation, goblet cell hyperplasia, and bronchial hyperreactivity. In the absence of CD11c+ cells, endogenous or adoptively transferred CD4+ Th2 cells did not produce interleukin (IL)-4, IL-5, and IL-13 in response to OVA aerosol. In CD11c-depleted mice, eosinophilic inflammation and Th2 cytokine secretion were restored by adoptive transfer of CD11c+ DCs, but not alveolar macrophages. These findings identify lung DCs as key proinflammatory cells that are necessary and sufficient for Th2 cell stimulation during ongoing airway inflammation.