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
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
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
The pathogenesis of OA is largely unknown; however, several risk factors are known to contribute to disease development. Treatment modalities are currently limited to alleviation of symptoms. In... Show moreThe pathogenesis of OA is largely unknown; however, several risk factors are known to contribute to disease development. Treatment modalities are currently limited to alleviation of symptoms. In order to develop better treatment modalities, increase of the understanding of the underlying mechanisms leading to OA development may provide targets for disease modification. Furthermore, knowledge regarding appropriate outcome measures that can be applied in OA research has to be increased for adequate assessment of potential treatment effects. Therefore, part I of this thesis describes studies aiming to increase the understanding of mechanisms underlying the association between known risk factors and OA, especially focussing on obesity in relation to OA in weight-bearing and non-weight-bearing joints. Furthermore, it was investigated which specific structural abnormalities on specific locations within the knee joint could best discriminate presence of symptomatic OA, and impact of knee OA and its modifiable or preventable risk on health-related quality of life was evaluated. Part II of this thesis describes two systematic reviews, assessing available instruments for measurement of the domains pain, physical function, patient global assessment and imaging in hand OA in order to enable recommendations for use in clinical trials. Show less
Venous thrombosis is a disease that occurs in 1-2 per 1000 people per year. At the time of their first venous thrombosis, approximately 50% of women are exposed to reproductive risk factors (oral... Show moreVenous thrombosis is a disease that occurs in 1-2 per 1000 people per year. At the time of their first venous thrombosis, approximately 50% of women are exposed to reproductive risk factors (oral contraception, postmenopausal hormone therapy, pregnancy and the puerperium). In this thesis, we showed that these women are at particularly high risk of venous thrombosis if they have previously experienced an episode of superficial vein thrombosis, or are over the age of 50 years (Chapters 2 and 3). There is no known male counterpart to female reproductive risk factors. Nevertheless, the incidence of venous thrombosis is approximately similar in men and women. In this thesis we established that, once female reproductive risk factors are taken into account, men have an approximately twofold higher risk of both first and recurrent venous thrombosis than women (Chapters 4 and 5). Further to these findings, in Chapter 6, we reviewed the literature on sex-specific risk factors for venous thrombosis. We hypothesized that sex-specific genetic risk factors, an excess in overweight and smoking, or hypercoagulable changes such as microalbuminuria may explain the higher risk of venous thrombosis in men than in women. Show less
H2: Hensgens MP, Goorhuis A, Notermans DW, van Benthem BH, Kuijper EJ. Decrease of hypervirulent Clostridium difficile PCR ribotype 027 in the Netherlands. Euro Surveill. 2009 H3: Hensgens MP,... Show moreH2: Hensgens MP, Goorhuis A, Notermans DW, van Benthem BH, Kuijper EJ. Decrease of hypervirulent Clostridium difficile PCR ribotype 027 in the Netherlands. Euro Surveill. 2009 H3: Hensgens MP, Keessen EC, Squire M, Riley TV, Koene MG, de Boer E, Lipman LJ, Kuijper EJ. Clostridium difficile infection in the community: a zoonotic disease? Clin Microbiol Infect. 2012 H4: Hensgens MP / Goorhuis A, van Kinschot CM, Crobach MJ, Harmanus C, Kuijper EJ. Clostridium difficile infection in an endemic setting in the Netherlands. Eur J Clin Microbiol Infect Dis. 2011 H5: Hensgens MP, Goorhuis A, Dekkers OM, Kuijper EJ. Time-interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother. 2012 H7: Hensgens MP, Goorhuis A, Dekkers OM, van Benthem BH, Kuijper EJ. Outcome of nosocomial Clostridium difficile infections; results of a multicenter cohort study. Clin Infect Dis. 2013 H8: Hensgens MP / Bauer MP, Miller M, Gerding DN, Wilcox MH, Dale AP, Fawley WN, Kuijper EJ, Gorbach SL. Renal failure and leukocytosis are predictors of a complicated course of Clostridium difficile infection (CDI) if measured on day of diagnosis. Clin Infect Dis. 2012 H9: Hensgens MP, Kuijper EJ. Clostridium difficile infection due to binary toxin positive strains. Emerg Infect Dis. 2013 H10: Hensgens MP, Dekkers OM, Goorhuis A, Le Cessie S, Kuijper EJ. Predicting a severe course of Clostridium difficile infection at the bedside. Clin Microbiol Infect. 2012 Show less
Pulmonary embolism is traditionally, since autopsy studies by Virchow in the mid 1800s, thought to originate from embolization of a deep-vein thrombosis, resulting in two clinical manifestations of... Show morePulmonary embolism is traditionally, since autopsy studies by Virchow in the mid 1800s, thought to originate from embolization of a deep-vein thrombosis, resulting in two clinical manifestations of one disease: venous thrombosis. The incidence of deep-vein thrombosis in the population is twice as high as the incidence of pulmonary embolism, i.e. 1 per 1000 and 0.5 per 1000 person-years respectively. The aim of this thesis was to assess whether pulmonary embolism and deep-vein thrombosis are always the same disease or not, and to answer this question with regard to etiology (genetic and acquired risk factors) and anatomical distribution of thrombi in the veins. We studied this question in two populations: the PEDLAR study and the MEGA case-control study. In the PEDLAR study we assessed the origin of pulmonary embolism using a total body Magnetic Resonance Direct Thrombus Imaging technique. We proposed several mecha nisms for the absence of deep-vein thrombi in more than half of the patients with pulmonary embolism. In addition, we investigated the effect of aging on venous valve thickness. This was performed in an ultrasonography study, with participants from 20 to 80 years old (the aging venous valves study). We hypothesized that part of the increasing incidence in venous thrombosis with age can be explained by increasing valve thickness. Show less
Surgical site infections (SSI) are the most-common healthcare-associated infections among surgical patients and have severe adverse consequences. Surveillance is the ongoing systematic collection,... Show moreSurgical site infections (SSI) are the most-common healthcare-associated infections among surgical patients and have severe adverse consequences. Surveillance is the ongoing systematic collection, analysis, interpretation, and feedback of data, and has been accepted worldwide as a primary step toward prevention of healthcare-associated infections. In the Netherlands, a national network for the surveillance of healthcare-associated infections was set up in 1996 and called PREZIES (__PREventie van ZIEkenhuisinfecties door Surveillance__). In this thesis, the quality of the SSI surveillance within this network is evaluated. The method for postdischarge surveillance recommended by PREZIES seemed feasible and effective, and the mandatory validation visits ensured reliability and robustness of the surveillance data. Furthermore, the predictive power of the NNIS risk index was sufficient for several surgical procedures and could not be significantly improved by using other procedure-specific determinants. Analysis of the time-trend in SSI rates for five surgical procedures showed encouraging decreasing trends, although mostly not statistically significant. Comparison of the Dutch and German SSI surveillance data revealed that even though similar infection surveillance protocols were used, differences occurred in the implementation which hampered the comparison of SSI rates. Additionally, PREZIES contributed to a multi-center intervention project to improve the quality of surgical prophylaxis. Show less
