The studies described in this thesis contribute to the identification of biomarkers for risk stratification in systemic sclerosis (SSc). Luckily, nowadays many SSc prospective cohorts have been set... Show moreThe studies described in this thesis contribute to the identification of biomarkers for risk stratification in systemic sclerosis (SSc). Luckily, nowadays many SSc prospective cohorts have been set up worldwide which allows high-quality research. Given the rarity and the heterogeneity of the disease, relatively large cohorts are needed to draw valuable conclusions. For the studies described in the current thesis, I was able to incorporate data from the Leiden prospective SSc cohort and data from other prospective cohorts in Europe, which made it possible to strengthen the data. In this final chapter, I summarize the main findings of the studies presented in this thesis, put our findings in a broader perspective, discuss future perspectives and formulate research questions that are relevant to assess in the years ahead of us. Show less
Due to the increased incidence of breast cancer and improved survival, more women are at risk of developing contralateral breast cancer (CBC). The aim of this thesis was to explore risk factors... Show moreDue to the increased incidence of breast cancer and improved survival, more women are at risk of developing contralateral breast cancer (CBC). The aim of this thesis was to explore risk factors associated with CBC. We observed significant associations for a polygenic risk score of common germline variants (PRS313) and for different adjuvant systemic therapy regimens with (subtype-specific) CBC risk. These factors may be incorporated in CBC risk prediction models together with other known and available risk factors. For support of clinical decision making more biological information is needed to understand CBC development in women with invasive breast cancer and DCIS. As a first step towards implementation of a risk prediction model, we performed an exploratory interview study, which showed that patients had varying preferences for graphical presentation of probabilities in a CBC prediction model. In future studies, the prediction model should be incorporated in a decision support tool and implemented in clinical practice. This tool can then help to better identify women at high risk of CBC who may benefit from prophylactic surgery, while the estimates can also be used to reassure patients who are at low risk of developing CBC. Show less
The longevity of total knee implants may be impaired by aseptic loosening of the components within the bone. Aseptic loosening remains the leading cause of revision surgery. In the past decades,... Show moreThe longevity of total knee implants may be impaired by aseptic loosening of the components within the bone. Aseptic loosening remains the leading cause of revision surgery. In the past decades, many implant design aspects and surgical techniques have been changed in an attempt to decrease the risk of loosening. Given that radiostereometric analysis (RSA) is a highly accurate method to detect early implant migration which is predictive for late loosening, new implant designs should ideally be tested with RSA before widespread introduction onto the market. In this thesis, we present the results of four randomized controlled trials studying the effect of such changes in design on implant migration with use of RSA. We also pooled several RSA studies to be able to analyze the effect of other possible risk factors, including patient characteristics and surgical technique. We show that slight changes in implant design may increase the risk of loosening considerably, while other factors that are often thought to be associated with an increased risk (such as a high body mass index) do not appear to have a large effect. Show less
In dit proefschrift is gekeken naar de kwaliteit van uitname en naar de uitkomsten na transplantatie om zo goed mogelijk om te gaan met het tekort aan donororganen. Met de ET-DSRI kan de kans op... Show moreIn dit proefschrift is gekeken naar de kwaliteit van uitname en naar de uitkomsten na transplantatie om zo goed mogelijk om te gaan met het tekort aan donororganen. Met de ET-DSRI kan de kans op acceptatie voor een donorlever ingeschat worden. Daardoor kunnen er in een vroeg stadium maatregelen genomen worden om de kans op transplantatie te vergroten voor suboptimale levers. Alhoewel het aantal levers geschikt voor transplantatie geoptimaliseerd kan worden zal het tekort de komende jaren blijven bestaan. Daarmee zal ook de toewijzing van levers aan patiënten op de wachtlijsten complex blijven. De uitkomst na transplantatie is daarin een belangrijk punt. De resultaten beschreven in dit proefschrift laten zien dat statistische modellen een goede benadering kunnen geven van deze uitkomsten. Het toepassen van deze modellen zal leiden tot een meer evidence-based manier van het selecteren, toewijzen en daadwerkelijk transplanteren van levers in patiënten op de wachtlijst. Show less
The aim of this thesis is to identify emerging risk factors for VTE. To achieve this goal, we describe the supposedly causal role of statin and glucocorticoid use (i.e. two drugs that can influence... Show moreThe aim of this thesis is to identify emerging risk factors for VTE. To achieve this goal, we describe the supposedly causal role of statin and glucocorticoid use (i.e. two drugs that can influence inflammation) with changes in hemostasis and VTE risk. Systemic glucocorticoid use increases the relative risk of first VTE by more than three-fold and confers an 5% absolute risk of recurrent VTE per year. On the other hand, rosuvastatin use may reduce the risk of first VTE by 40%. Although the mechanisms behind this association are not fully elucidated, this thesis shows that rosuvastatin is capable of decreasing the thrombin generation potential by 10% in patients with a prior VTE. This thesis has shown that both statins and systemic glucocorticoids can affect the risk of VTE, improving the knowledge on the influence of these two commonly prescribed drugs on VTE pathophysiology. These findings have the potential to further refine the assessment of VTE risk since they highlight that the use of these drugs should be considered when evaluating the risk of VTE. Finally, this thesis provides insight into new therapeutic approaches since the results underscore that treatment strategies on VTE prevention in patients already taken statins, which may be sufficient for VTE prevention, are lacking. Treatment strategies to prevent glucocorticoid-associated VTE are also needed. Show less
In this thesis the impact of donor and recipient risk factors and the development of risk models in liver transplantation was investigated. These models can be used for multiple purposes, including... Show moreIn this thesis the impact of donor and recipient risk factors and the development of risk models in liver transplantation was investigated. These models can be used for multiple purposes, including risk indication, outcome prediction and benchmarking between transplant centers. As such, several steps have been made towards evidence-based liver allocation and proper selection of liver allografts in times of organ shortage and the current system of severitybased liver allocation (by MELD the score). Further refinement of these models is necessary in order to optimize donor to recipient matching and achieve an objective, transparent and well-informed system of liver allocation. Altogether, the efforts made here to improve waitlist and transplantation outcomes, are meant for the individual transplant candidate on the liver transplant waitlist and as a whole, for the transplant community. Show less
In this thesis the risk factors of venous thrombosis will be discussed in the general and particularly the elderly population. The goal of this thesis is to provide insights on risk factors of... Show moreIn this thesis the risk factors of venous thrombosis will be discussed in the general and particularly the elderly population. The goal of this thesis is to provide insights on risk factors of thrombosis in the elderly population, in order to advance our basic understanding of physiological age-related changes that increase the risk of venous thrombosis and which may ultimately lead to improved personalized interventions. In this chapter firstly background information will be provided on risk factors for venous thrombosis, focussing specifically on age as a risk factor. Secondly, the role of veins and venous valves in the development of venous thrombosis will be discussed and thirdly, global assays as a potential tool to identify patients at high risk for venous thrombosis will be considered. The study populations used in this thesis will discussed, and an outline of this thesis will be provided. Show less
The main objective of this thesis was to improve cardiovascular risk assessment in primary care. Chapter 2 provides evidence that coded diagnosis from general practice electronic health... Show moreThe main objective of this thesis was to improve cardiovascular risk assessment in primary care. Chapter 2 provides evidence that coded diagnosis from general practice electronic health records are a feasible and valid alternative to self-report to define diabetes cases in epidemiological studies. Based on the results of focus group discussions with research participants confronted with an incidental finding, as described in Chapter 3, we concluded that a detailed study protocol is needed on the disclosure of incidental findings before recruitment of participants. We gave several recommendations to improve the disclosure of incidental findings. Our findings in Chapter 4 suggest that it is important to inform the general practitioner and the research participants about the individual cardiovascular test results. Only participants with an estimated intermediate of high cardiovascular risk should receive a recommendation to consult their general practitioner. In Chapter 5, we concluded that inviting patients with overweight or obesity for cardiovascular risk assessment can help to identify a substantial additional group of patients at increased cardiovascular risk. In Chapter 6, we did not find evidence that cardiovascular risk assessment can be improved when non-invasive markers of hepatic steatosis are added to an established risk estimation system. Show less
Patients with deep vein thrombosis or pulmonary embolism remain at risk for recurrent venous thrombosis. This risk is pronounced in the first months after the acute episode and declines in... Show morePatients with deep vein thrombosis or pulmonary embolism remain at risk for recurrent venous thrombosis. This risk is pronounced in the first months after the acute episode and declines in subsequent years. Although the existence of an extensive list of risk factors may seem reassuring, it does not come close to give us all the answers: many people have several of these risk factors but never develop thrombosis; others suffer from thrombosis but have none. Therefore, the challenge that we are facing today is not to just add more risk factors to this list but rather to integrate them all in a causal model that allows us to understand how and when thrombotic disease develops. The idea behind “the thrombosis potential model” is that an individual is at risk for venous thrombosis throughout life, which is reflected in the ‘thrombosis potential’ and that each risk factor contributes to increase the potential. Only when the combination of thrombosis risk factors reach a certain potential, venous thrombosis will occur. In this thesis, the thrombosis potential model will be applied to several known risk factors for venous thrombosis to better understand why first and recurrent venous thrombosis can develop in an individual patient. Show less
