From evidence to practice:development of web-based Dutch lipid reference values

Introduction: In the Netherlands, the total number of yearly measured lipid profiles exceeds 500,000. While lipid values are strongly affected by age and sex, until recently, no up-to-date age- and sex-specific lipid reference values were available. We describe the translation of big-cohort lipid data into accessible reference values, which can be easily incorporated in daily clinical practice. Methods: Lipid values (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides) from all healthy adults and children in the LifeLines cohort were used to generate age- and sex-specific percentiles. A combination of RStudio, Cascading Style Sheets and HyperText Markup Language was used to interactively display the percentiles in a responsive web layout. Results: After exclusion of subjects reporting cardiovascular disease or lipid-lowering therapy at baseline, 141,611 subjects were included. On the website, input fields were created for age, sex and all main plasma lipids. Upon input of these values, corresponding percentiles are calculated, and output is displayed in a table and an interactive graph for each lipid. The website has been made available in both Dutch and English and can be accessed at www.lipidtools.com. Conclusion: We constructed the first searchable, national lipid reference value tool with graphical display in the Netherlands to use in screening for dyslipidaemias and to reduce the underuse of lipid-lowering therapy in Dutch primary prevention. This study illustrates that data collected in big-cohort studies can be made easily accessible with modern digital techniques and preludes the digital health revolution yet to come

Time to improve statin prescription guidelines in low-risk patients?

Background The challenge of the primary prevention of cardiovascular disease (CVD) is to identify patients who would benefit from treatment with statins. Statins are currently prescribed to many patients, even those at a low 10-year risk of CVD. These latter patients may not be eligible for statins according to current guidelines. Design This study investigated the prescription of guideline-consistent (according to guidelines) and guideline-inconsistent (not according to guidelines) lipid-lowering treatment in primary prevention in a large contemporary Dutch cohort study (Lifelines). Methods Lifelines is a large cohort study from the Netherlands. Participants were recruited between 2006 and 2013. They completed questionnaires and underwent a physical examination. Participants with previous CVD were excluded. Statins and ezetimibe were grouped as statin treatment. The Dutch guideline on cardiovascular management was used to assess eligibility for statins. Results Of 147,785 participants, 7092 (4.8%) reported statin treatment. In 4667 (66%) participants, statin treatment was inconsistent with the Dutch guideline. A total of 78% of these participants had a low 10-year predicted CVD risk. Multivariable logistic regression analysis showed that female sex and smoking were strongly associated with guideline-inconsistent treatment. Interestingly, 65% of the these participants had low-density lipoprotein cholesterol levels above the 95(th) percentile, adjusted for age and sex, two or more major risk factors of CVD or a positive family history of premature CVD. Therefore treatment might be reasonable. Conclusions There is a large inconsistency between guideline recommendations and the prescription of statins in clinical practice in the Netherlands. This is especially true for patients with low CVD risk. Many of these patients probably had risk-increasing circumstances justifying treatment

Pediatric lipid reference values in the general population:The Dutch lifelines cohort study

Background: Atherosclerosis starts in childhood and its progression is influenced by lifelong low-density lipoprotein cholesterol (LDL-c) exposure, the so-called cholesterol burden. Early identification of children and adolescents with severely elevated LDL-c is thus of major clinical significance. This is especially true for children with familial hypercholesterolemia (FH), a frequent but undertreated genetic disorder. To identify children with possible FH, insight in the distribution of lipid levels in children is a prerequisite. Objective: To provide health care professionals with contemporary age- and gender-based pediatric reference values for lipid and lipoprotein levels to help the identification of children with dyslipidemia, especially FH. Methods: Lifelines is a large prospective population-based Dutch cohort study. Children from 8 till 18 years of age were included and fasting lipid levels were measured. Smoothed reference curves and percentiles (5th, 10th, 25th, 50th, 75t h, 90th, and 95th) were generated using the Generalized Additive Models for Location, Scale and Shape package in the statistical software R. Results: A total of 8071 children (3823 boys and 4248 girls) were included. In the total cohort we noted marked dynamic changes in lipid and lipoprotein levels over age, which were in part gender specific. Our data highlight a high and unexpected prevalence of severely elevated LDL-c (>190 mg/dL) in both boys and girls. Conclusion: Our cross-sectional data provide contemporary reference ranges for plasma lipids that can assist physicians in identifying children at increased risk of premature atherosclerosis, especially FH

2020 ESC Guidelines on acute coronary syndrome without ST-segment elevation Recommendations and critical appraisal from the Dutch ACS and Interventional Cardiology working groups

Recently, the European Society of Cardiology (ESC) has updated its guidelines for the management of patients with acute coronary syndrome (ACS) without ST-segment elevation. The current consensus document of the Dutch ACS working group and the Working Group of Interventional Cardiology of the Netherlands Society of Cardiology aims to put the 2020 ESC Guidelines into the Dutch perspective and to provide practical recommendations for Dutch cardiologists, focusing on antiplatelet therapy, risk assessment and criteria for invasive strategy.</p

Differential information in large games with strategic complementarities

We study equilibrium in large games of strategic complementarities (GSC) with differential information. We define an appropriate notion of distributional Bayesian Nash equilibrium and prove its existence. Furthermore, we characterize order-theoretic properties of the equilibrium set, provide monotone comparative statics for ordered perturbations of the space of games, and provide explicit algorithms for computing extremal equilibria. We complement the paper with new results on the existence of Bayesian Nash equilibrium in the sense of Balder and Rustichini (J Econ Theory 62(2):385–393, 1994) or Kim and Yannelis (J Econ Theory 77(2):330–353, 1997) for large GSC and provide an analogous characterization of the equilibrium set as in the case of distributional Bayesian Nash equilibrium. Finally, we apply our results to riot games, beauty contests, and common value auctions. In all cases, standard existence and comparative statics tools in the theory of supermodular games for finite numbers of agents do not apply in general, and new constructions are required

“My Lung Disease Won’t Go Away, it’s There to Stay”: Profiles of Adaptation to Functional Limitations in Workers with Asthma and COPD

Purpose Earlier research has shown that adaptation (i.e., the way in which employees cope with limitations resulting from their disease) is associated with sick leave. Our aim was to investigate signs of adequate or inadequate adaptation in employees with asthma and COPD. Methods A Q-methodological study was carried out among 34 workers with asthma or COPD. Results Four adaptation profiles were distinguished: the eager, the adjusted, the cautious, and the worried workers. The adaptation profiles provide insight into the different ways in which workers with asthma and COPD cope with their illness at work. Conclusions The adaptation profiles serve as a starting point for the design of appropriate (occupational) care. The eager workers experience little difficulties at work; the cautious workers may need assistance in learning how to accept their disease; the worried workers need reassurance, and may need reactivation; the adjusted workers deserve extra attention, and, when necessary, advice on how to live with their asthma or COPD

Comparative analysis and supragenome modeling of twelve Moraxella catarrhalis clinical isolates

Contains fulltext : 97744.pdf (publisher's version ) (Open Access)BACKGROUND: M. catarrhalis is a gram-negative, gamma-proteobacterium and an opportunistic human pathogen associated with otitis media (OM) and exacerbations of chronic obstructive pulmonary disease (COPD). With direct and indirect costs for treating these conditions annually exceeding $33 billion in the United States alone, and nearly ubiquitous resistance to beta-lactam antibiotics among M. catarrhalis clinical isolates, a greater understanding of this pathogen's genome and its variability among isolates is needed. RESULTS: The genomic sequences of ten geographically and phenotypically diverse clinical isolates of M. catarrhalis were determined and analyzed together with two publicly available genomes. These twelve genomes were subjected to detailed comparative and predictive analyses aimed at characterizing the supragenome and understanding the metabolic and pathogenic potential of this species. A total of 2383 gene clusters were identified, of which 1755 are core with the remaining 628 clusters unevenly distributed among the twelve isolates. These findings are consistent with the distributed genome hypothesis (DGH), which posits that the species genome possesses a far greater number of genes than any single isolate. Multiple and pair-wise whole genome alignments highlight limited chromosomal re-arrangement. CONCLUSIONS: M. catarrhalis gene content and chromosomal organization data, although supportive of the DGH, show modest overall genic diversity. These findings are in stark contrast with the reported heterogeneity of the species as a whole, as wells as to other bacterial pathogens mediating OM and COPD, providing important insight into M. catarrhalis pathogenesis that will aid in the development of novel therapeutic regimens