Women with breast cancer often wonder whether they should have their other breast removed as well, to prevent a potential tumor from developing there. The exact risks vary significantly per person.... Show moreWomen with breast cancer often wonder whether they should have their other breast removed as well, to prevent a potential tumor from developing there. The exact risks vary significantly per person. We used information about patients, breast cancer characteristics and treatments, and rare and common genetic variant correlated with a higher or lower risk of developing breast cancer in the other breast in large datasets to develop and validate statistical models to predict each patient’s risk of developing a tumor. We investigated whether and how these models might be clinically useful to better inform patients and physicians to tailor clinical decision making about potential strategies to prevent or early detect a tumor in the opposite breast. We discussed statistical aspects about model development and validation, and we provided frameworks about how to develop and assess prediction performance of risk prediction models using motivating examples in breast cancer. Show less
The main objective of work presented in this thesis was to explore the clinical utility of the Polygenic Risk Score (PRS) based on breast cancer associated common low risk variants, which explain ... Show moreThe main objective of work presented in this thesis was to explore the clinical utility of the Polygenic Risk Score (PRS) based on breast cancer associated common low risk variants, which explain ~18% of the familial relative risk, for individual breast cancer risk prediction. It did so by generating knowledge about the PRS in the Dutch general population and in clinic-based breast cancer families, as well as in a large international population of BRCA1/2 pathogenic variant carriers. We have validated the association of the PRS with breast cancer for women in both the Dutch population and breast cancer families and showed a better risk-discrimination by adding the PRS to family-based risk prediction. Secondly, we have shown that addition of the PRS to family-based risk prediction has an impact on screening recommendations for many non-carriers and carriers of a pathogenic variant in a moderate breast cancer gene. The results will support implementation of comprehensive risk prediction in the clinic, and may help women to make more informed choices about their optimal clinical management. Show less
Stalenhoef voerde een een gerandomiseerd onderzoek uit op de Spoedeisende Hulp-afdelingen van het LUMC en geaffilieerde ziekenhuizen onder leiding van prof. Jaap van Dissel (Infectieziekten), over... Show moreStalenhoef voerde een een gerandomiseerd onderzoek uit op de Spoedeisende Hulp-afdelingen van het LUMC en geaffilieerde ziekenhuizen onder leiding van prof. Jaap van Dissel (Infectieziekten), over de toepassing van een klinische beslisregel om het risico in te schatten bij patiënten die zich presenteren met pyelonefritis, acute prostatitis of urosepsis.Het onderzoek waaraan 370 patiënten deelnamen, toonde aan dat het aantal ziekenhuisopnames met de toepassing van deze beslisregel significant werd verlaagd. Het aantal thuis behandelde patiënten dat op een later moment toch werd opgenomen, was hierbij hoger dan verwacht. Dit kwam mede doordat er bij een aantal patiënten toch een andere diagnose werd gesteld op het moment dat de kweekuitslagen bekend werden. Verder onderzoek richt zich op verbetering van de beslisregel door deze te combineren met een biomarker die de acute immuunrespons reflecteert. Show less
RA is a chronic and progressive autoimmune disease affecting approximately 1% of the population worldwide, and has a large risk for causing disability of patients and consequently high costs in... Show moreRA is a chronic and progressive autoimmune disease affecting approximately 1% of the population worldwide, and has a large risk for causing disability of patients and consequently high costs in health care if left un- or improperly treated. To prevent this, patients with RA need to be identified as early as possible and treated adequately to prevent worse outcome. Early recognition, together with prediction of the disease outcome at the individual patient level would allow to achieve personalized medicine. The main scope of this thesis was to identify and evaluate the quality of risk factors for their usefulness in predicting disease course and outcome of RA. To this end, characteristics and disease outcome of RA patients included in the Leiden EAC were studied. Show less
The aim of this thesis was to study cardiovascular risk management in old age, in order to facilitate the development of age specific guidelines. In part one the current status of cardiovascular... Show moreThe aim of this thesis was to study cardiovascular risk management in old age, in order to facilitate the development of age specific guidelines. In part one the current status of cardiovascular prevention in old age is described, including a study into general practitioners__ attitudes and perceived barriers in this respect. The second part explores the incremental value of routine-ECGs for cardiovascular risk management in older persons from the general population, beyond existing information from medical records. The third part focuses on primary prevention, exploring the performance of classic risk factors, and some new biomarkers, in predicting cardiovascular mortality in very old people from the general population. It was concluded that a homocysteine level alone accurately identifies those at high risk of cardiovascular mortality, whereas classic risk factors included in the Framingham risk score do not. Next, in various age strata from age 55 years onwards, the association between blood pressure and mortality was studied. Finally, a systematic review into the diagnostic accuracy of natriuretic peptides for the diagnosis of chronic heart failure in older persons from the general population was performed, followed by a study in a cohort of nonagenarians into the prognostic value of NT-proBNP. A general discussion is provided, including directions for future research. Show less
