Geloof in kloppend bewijs

Rede, In verkorte vorm uitgesproken ter gelegenheid van het aanvaarden van het ambt van bijzonder hoogleraar Klinische epidemiologie van hart- en vaatziekten aan het Erasmus MC, faculteit van de Erasmus Universiteit Rotterdam op 20 maart 2009. De leidende gedachte binnen het vakgebied Klinische epidemiologie is dat medisch handelen gebaseerd dient te zijn op het best beschikbare bewijs van zijn werkzaamheid en doeltreffendheid. Dat bewijs is niet gegrond op de persoonlijke ervaring van patiënten, noch op de klinische expertise van individuele artsen, hoe waardevol deze elementen ook zijn. Maar het bewijs voor de effectiviteit van het klinisch handelen is bij voorkeur afkomstig van wetenschappelijk onderzoek onder groepen patiënten, waarin theoretische concepten worden getoetst, en waarbij gezocht wordt naar relaties tussen het optreden en het beloop van ziekten enerzijds, en verklarende factoren of determinanten daarvan anderzijds.|1 Deze determinanten kunnen zowel oorzakelijke als niet-oorzakelijke factoren zijn. Vanzelfsprekend dient onderzoek naar determinant-uitkomst relaties te worden opgezet en uitgevoerd in overeenstemming met kwalitatief hoogstaande standaarden

Case study: Ticagrelor in plato and prasugrel in triton-timi 38 and trilogy-acs trials in patients with acute coronary syndromes

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Tailored reperfusion therapy of patients with evolving myocardial infarction: Models to guide clinical decision making

Myocardial infarction is one of the leading causes of death among adults in the Western World. In The Netherlands, yearly approximately 20,000 men and 10,000 women are admitted with this diseas

Joint Models with Multiple Longitudinal Outcomes and a Time-to-Event Outcome: a Corrected Two-Stage Approach

Joint models for longitudinal and survival data have gained a lot of attention in recent years, with the development of myriad extensions to the basic model, including those which allow for multivariate longitudinal data, competing risks and recurrent events. Several software packages are now also available for their implementation. Although mathematically straightforward, the inclusion of multiple longitudinal outcomes in the joint model remains computationally difficult due to the large number of random effects required, which hampers the practical application of this extension. We present a novel approach that enables the fitting of such models with more realistic computational times. The idea behind the approach is to split the estimation of the joint model in two steps; estimating a multivariate mixed model for the longitudinal outcomes, and then using the output from this model to fit the survival submodel. So called two-stage approaches have previously been proposed, and shown to be biased. Our approach differs from the standard version, in that we additionally propose the application of a correction factor, adjusting the estimates obtained such that they more closely resemble those we would expect to find with the multivariate joint model. This correction is based on importance sampling ideas. Simulation studies show that this corrected-two-stage approach works satisfactorily, eliminating the bias while maintaining substantial improvement in computational time, even in more difficult settings.Comment: 33 pages, 7 figures and 7 tables including appendices. Accepted in Statistics and Computin

The multimarket labour-managed firm and the effects of devaluation

Digitised version produced by the EUI Library and made available online in 2020

Aortic Valve Calcium in Relation to Subclinical Cardiac Dysfunction and Risk of Heart Failure

Background: The link between (mild) aortic valve calcium (AVC) with subclinical cardiac dysfunction and with risk of heart failure (HF) remains unclear. This research aims to determine the association of computed tomography-assessed AVC with echocardiographic measurements of cardiac dysfunction, and with HF in the general population. Methods: We included 2348 participants of the Rotterdam Study cohort (mean age 68.5 years, 52% women), who had AVC measurement between 2003 and 2006, and without history of HF at baseline. Linear regression models were used to explore relationship between AVC and echocardiographic measures at baseline. Participants were followed until December 2016. Fine and Gray subdistribution hazard models were used to assess the association of AVC with incident HF, accounting for death as a competing risk. Results: The presence of AVC or greater AVC were associated with larger mean left ventricular mass and larger mean left atrial size. In particular, AVC ≥800 showed a strong association (body surface area indexed left ventricular mass, β coefficient: 22.01; left atrium diameter, β coefficient: 0.17). During a median of 9.8 years follow-up, 182 incident HF cases were identified. After accounting for death events and adjusting for cardiovascular risk factors, one-unit larger log (AVC+1) was associated with a 10% increase in the subdistribution hazard of HF (subdistribution hazard ratio, 1.10 [95% CI, 1.03-1.18]), but the presence of AVC was not significantly associated with HF risk in fully adjusted models. Compared with the AVC=0, AVC between 300 and 799 (subdistribution hazard ratio, 2.36 [95% CI, 1.32-4.19]) and AVC ≥800 (subdistribution hazard ratio, 2.54 [95% CI, 1.31-4.90]) were associated with a high risk of HF. Conclusions: Presence and high levels of AVC were associated with markers of left ventricular structure, independent of traditional cardiovascular risk factors. Larger computed tomography-assessed AVC is an indicative of increased risk for the development of HF.</p