The post-thromotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (CTEPH) are the most feared long term complication of a deep venous thrombosis (DVT) and pulmonary embolism (PE)... Show moreThe post-thromotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (CTEPH) are the most feared long term complication of a deep venous thrombosis (DVT) and pulmonary embolism (PE) respectively. We have reviewed the literature on arguments for and against routine screening of CTEPH in patients after an episode of an acute PE. The incidence of CTEPH is relevant in this evaluation. In a systematic review and meta-analysis we showed a CTEPH incidence of 0.56% in all comers and of ~3% in the survivors. We showed that a very recent developed screening algorithm, the InShape II algorithm, is sensitive and reproducible for detecting early CTEPH in the course of an acute PE. Beside this, most patient who were diagnosed with CTEPH in the course of an acute PE already showed signs of CTEPH on the initial CT scan made for PE diagnosis.In the last chapter we focus on PTS in the course of a DVT. In patients included in the MEGA database the 0-1 year incidence was 21.8%, after 8 years of follow-up an additional 7% developed PTS. During follow-up PTS symptoms improves in almost 70% of patients. Show less
This dissertation aimed to identify opportunities to slow down disease progression and improve health-related quality of life (HRQOL) in patients with chronic kidney disease (CKD). Biopsychosocial,... Show moreThis dissertation aimed to identify opportunities to slow down disease progression and improve health-related quality of life (HRQOL) in patients with chronic kidney disease (CKD). Biopsychosocial, patient-centred and self-regulation perspectives were employed and enabled this dissertation to shed light on the importance of patients’ health behaviours and illness perceptions in the treatment of CKD. Taken together, this dissertation indicates that patients in early CKD stages are in need of behavioural support to cope with the broad range of barriers that they experience when reducing sodium intake. The results demonstrate that a multicomponent patient-centred self-regulation program would fit patients' needs, and can reduce risk factors for disease progression and improve psychosocial outcomes. Furthermore, this dissertation suggests that support strategies should be implemented to increase the impaired HRQOL that many patients experience during predialysis care. The results underline the need for personalized treatment approaches in light of the differences between patients in relation to their HRQOL and how their HRQOL evolves over time (e.g., differences with regard to age and cardiovascular disease). Moreover, illness perceptions were found to be key factors in HRQOL and disease progression, and therefore, treatment strategies in predialysis care should take into account patients’ illness perceptions as well. Show less
This study investigated the prevalence of child maltreatment in a cross-cultural perspective, the changes in prevalence estimates in Vietnam over time, child and family risk factors of maltreatment... Show moreThis study investigated the prevalence of child maltreatment in a cross-cultural perspective, the changes in prevalence estimates in Vietnam over time, child and family risk factors of maltreatment, and possible consequences of child maltreatment. We administered questionnaires and a working memory test to 1,851 secondary and high school students (12-17 years old) in four Northern provinces of Vietnam. We compared current Vietnamese prevalence estimates with those from the Dutch prevalence study on child maltreatment (NPM-2010) and from a prevalence study in Vietnam 10 years ago to achieve a cross-cultural and chronological comparison. We found that although there was a decrease in emotional and physical abuse over time, all types of child maltreatment were still highly prevalent, ranging from 2.6% for sexual abuse to 31.8% for emotional abuse. Most types were more common in Vietnam than in the Netherlands. Only the past year sexual abuse prevalence in Vietnam was lower. Single parenthood, being a boy, and older age were risk factors for child maltreatment. Child maltreatment was related to negative child well-being aspects with the largest effect on emotional functioning. Our study draws a clearer picture on child maltreatment in Vietnam. It highlights the importance of prompt responses to child maltreatment. 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
In this thesis we show the results of the AT-AGE study, a two-center, population based case-control study in Leiden, the Netherlands and Burlington, Vermont, US, in which consecutive patients aged... Show moreIn this thesis we show the results of the AT-AGE study, a two-center, population based case-control study in Leiden, the Netherlands and Burlington, Vermont, US, in which consecutive patients aged 70 years and older with deep venous thrombosis (DVT) in the leg or a pulmonary embolism (PE), were identified. The AT-AGE study was specifically designed to optimise the participation-rate in the older population. Therefore, we performed home visits to all participants. We showed that conventional risk factors such as immobilisation due to hospital admission, and also immobility at home, due to for instance infection and minor injury, increase the risk of venous thrombosis. Also genetic risk factors, such as Factor V Leiden (FVL, rs6025) and the prothrombin 20210A mutation (PT20210, rs1799963) increase the risk of venous thrombosis. We report the presence of age-specific risk factors: functional impairment, low hand grip strength and venous insufficiency, such as varicose veins and leg oedema. Also we identified new high risk groups in older people, e.g., recent hospital discharge in which preventive measures could be of special interest. Show less
In this thesis the epidemiology of suicidal ideation and suicide attempts (together referred to as 'suicidality') in Huntington's disease (HD) is investigated and coping styles and support... Show moreIn this thesis the epidemiology of suicidal ideation and suicide attempts (together referred to as 'suicidality') in Huntington's disease (HD) is investigated and coping styles and support strategies that may serve to help suicidal HD mutation carriers are explored. Suicidality frequently occurs in HD, with a 1-month prevalence of up to 20%. Mutation carriers who were most likely to currently experience suicidal ideation or suicidality had a shorter disease duration, were anxious, aggressive, previously attempted suicide, used antidepressants, and had a depressed mood. The presence of a depressed mood and use of benzodiazepines were the only significant independent predictors of incident suicidal ideation or suicidality. Biological parameters, in particular functioning of the immune system and the hypothalamus-pituitary-adrenal axis were not found to be associated with suicidality in HD. In a qualitative study it was shown that suicidal HD mutation carriers generally used four strategies to cope with suicidality: talking about suicidality, employing self-management activities, using medication, and discussing end-of-life wishes. Lastly, in a meta-analysis, we examined whether the expression of suicidal ideation predicted subsequent completed suicide. Effect estimates differed substantially among different populations, but none of the included studies investigated this association in HD. 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
978-94-6182-393-9 The first part of this thesis identified several high-risk sub-populations to improve the care and risk stratification of patients with ST-elevation myocardial infarction (STEMI).... Show more978-94-6182-393-9 The first part of this thesis identified several high-risk sub-populations to improve the care and risk stratification of patients with ST-elevation myocardial infarction (STEMI). It was observed that common patient characteristics such as female gender, cancer and age have a strong impact on the delay to reperfusion therapy and the prognosis after STEMI. Furthermore, the historically devastating complication of out-of-hospital cardiac arrest continues to have an impact of the STEMI population. Angiographic determinants of the occurrence and prognosis of out-of-hospital cardiac arrest were identified, which may improve the care of these high-risk patients. The second part of this thesis investigated the use of second generation drug-eluting stents (DES) for the treatment of coronary heart disease. Among the second generation DES, everolimus-eluting stents showed superior results compared to Endeavor zotarolimus-eluting stents in a real world cohort of STEMI patients. A randomized acute MI trial subsequently established the non-inferiority of the everolimus-eluting stent to the first generation sirolimus-eluting stent, with results suggesting superiority. However, these stents performed similarly during long term follow-up, both in patients with and without STEMI. Low rates of stent thrombosis and similar efficacy confirmed the usefulness of both stents in the full range of coronary heart disease. Show less
The aim of this set of studies was to provide more insight in individual characteristics that influence care-giving abilities, in particular precursors of harsh and abusive parenting. We examined... Show moreThe aim of this set of studies was to provide more insight in individual characteristics that influence care-giving abilities, in particular precursors of harsh and abusive parenting. We examined how different subtypes of childhood abuse were related to child abuse potential in adulthood. Emotional neglect in childhood was related to child abuse potential, which is in line with earlier research showing the long-lasting effects of emotional maltreatment and neglect in childhood. With regard to the effects of oxytocin on the neural basis of parenting, we used fMRI to examine how oxytocin influenced emotion recognition using pictures of both adult and infant faces, taking experiences of maternal love withdrawal into account as potential moderator. Oxytocin enhanced neural activity in regions involved in emotion processing, such as the IFG, insula and STG. Our findings regarding the moderating role of experiences of maternal love withdrawal are inconsistent for emotion recognition in adult faces and in infant faces. Lastly, a new paradigm (LISSA) to observe sensitivity in response to standardized infant cues was developed and tested. Our results show that sensitivity can be reliably assessed using this procedure, making the LISSA a promising method for future research and clinical practice. 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
The scope of the work described in this thesis is to examine whether potential transfusion related and clinical risk factors modulate the risk of alloimmunization in a general, previously not... Show moreThe scope of the work described in this thesis is to examine whether potential transfusion related and clinical risk factors modulate the risk of alloimmunization in a general, previously not transfused, non alloimmunized population of transfusion recipients. In these studies we emphasize the methodological aspects of observational research in clinical transfusion medicine Show less
Background As maintenance of lifestyle change and risk factor modification following completion of cardiac rehabilitation (CR) has been shown to be notoriously difficult, we developed a brief self... Show moreBackground As maintenance of lifestyle change and risk factor modification following completion of cardiac rehabilitation (CR) has been shown to be notoriously difficult, we developed a brief self-regulation lifestyle program for post-CR patients. Design Randomized-controlled trial. Method Following completion of CR 210 patients were randomized to receive either a lifestyle maintenance program (n=112) or standard care (n=98). The program was based on self-regulation principles and consisted of a motivational interview, 7 group sessions and home assignments. Risk factors and health behaviors were assessed at baseline (end of CR), and 6 and 15 months thereafter. Results ANCOVAs showed a significant effect of the lifestyle program after 6 months on blood pressure, waist circumference and exercise behavior, only the latter of which remained significant at follow-up (15 months). Mediation analysis demonstrated that the treatment effect on exercise behavior could be explained by an effect on self-regulation skills. Furthermore, the lifestyle intervention program was associated with a 12% reduction in self-reported cardiac hospital admission rates. In addition, patients in the intervention group had significantly fewer uncontrolled risk factors as compared to the control group. However, there was only a long-term beneficial intervention effect on obesity and physical inactivity, but not on other individual risk factors (increased waist circumference, raised blood pressure, raised TC/HDLC-ratio and smoking). Conclusion This trial indicates that a relatively brief, theory-based lifestyle program is capable of inciting and maintaining improvements in exercise adherence. It is suggested that patients may need ongoing attention and guidance, for example in the form of (internet-based) booster sessions, as long-term consolidation of changes is arduous. 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
This thesis describes the epidemiology of emerging infections with Clostridium difficile. Outbreaks of severe disease with high mortality were found to be associated with certain types of this... Show moreThis thesis describes the epidemiology of emerging infections with Clostridium difficile. Outbreaks of severe disease with high mortality were found to be associated with certain types of this bacterium and type specific risk factors were identified. Moreover, highly discriminatory typing techniques were useful in understanding clonal disseminations across healthcare institutions. 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
This thesis elaborates the occurrence of venous thrombosis in cancer patients. Cancer is known to be associated with venous thrombosis with a spectrum of clinical manifestations varying from deep... Show moreThis thesis elaborates the occurrence of venous thrombosis in cancer patients. Cancer is known to be associated with venous thrombosis with a spectrum of clinical manifestations varying from deep vein thrombosis of the leg and pulmonary embolism, recurrent thrombophlebitits saltans et migrans (also called Trousseau__s syndrome) to disseminated intravascular coagulation and arterial embolism. The causes of venous thrombosis can be divided in environmental risk factors such as bed rest, surgery, plaster cast, trauma, long-distance travel, oral contraceptives or pregnancy and puerperium and genetic risk factors such as factor V Leiden and prothrombin 20210A mutation. Various factors may contribute to the development of venous thrombosis in cancer patients, and circulating mucins as well as circulating microparticles which express active TF on their surface may provide a missing link between cancer and thrombosis in (adeno) carcinoma patients. Treatment options include vitamin K antagonists and low-molecular-weight heparins, and the long-term use of these heparins in prevention of venous thrombosis may improve the outcome in comparison with oral anticoagulants. Further research is needed to better understand the morbidity and mortality associated with thrombosis in cancer patients and to optimize strategies of prevention and treatment Show less
To improve quality of cancer care treatment-related information is needed. This could be acquired by registries. Since January 1984, the Leiden University Medical Center (LUMC) collects... Show moreTo improve quality of cancer care treatment-related information is needed. This could be acquired by registries. Since January 1984, the Leiden University Medical Center (LUMC) collects prospectively more than 200 relevant clinical and pathological parameters of women with cervical cancer treated in the LUMC. The purpose of this thesis was to use the treatment-related information of this database, to get inside information and to become aware of possibilities for improvement in the current treatment procedures, in order to monitor the quality of treatment. Furthermore, when results of cancer treatment in terms of survival are good it is also important to focus on the sequelae of the treatment. The incidence of lymphedema, urinary and colorectal dysfunction has been reported with variable rates and sexual dysfunction after radical hysterectomy has been shown to occur in about 25% of the patients. Furthermore, a study assessed by vaginal plethysmography, showed that radical hysterectomy seems to be associated with a disturbed vaginal blood flow response during sexual arousal. The second purpose of this thesis was to monitor the sequelae of the treatment of women with a history of early stage cervical cancer in order to have measures in attempts to improve the quality of life. Show less
Osteoarthritis (OA) refers to a heterogeneous group of conditions. This thesis focuses on OA with a hereditary background; Familial OA at multiple joint sites and radiological hand OA at middle age... Show moreOsteoarthritis (OA) refers to a heterogeneous group of conditions. This thesis focuses on OA with a hereditary background; Familial OA at multiple joint sites and radiological hand OA at middle age. The main objective is to identify risk factors that play a role in the development of OA in order to gain further insight in the aetiology of OA. The secondary objective is to investigate factors that determine the outcome in OA. This thesis provides evidence that familial clustering of symptomatic OA is most prominent for hand and hip OA. In search for genetic risk factors, we present data suggesting that a proportion of the genetic susceptibility for OA at multiple sites is encoded by variation in innate cytokine activity. Further, we find HLA-DR antigens to be associated with radiological hand OA. In addition to genetic risk factors, this thesis demonstrates that other systemic risk factors such as hormonal status and local factors, to be important in the susceptibility of familial OA at multiple sites, underscoring the multicausal etioliology of this phenotype. Finally, this thesis addresses the resulting disability from OA. Using the International Classification of Functioning, Disability and Health as framework, we show illness perceptions and mental health to be important modifying factors in OA in the hands and lower extremities. Show less
This thesis examines different risk factors, in relation to restenosis after Percutaneous coronary interventions (PCI), with its main focus on genetic markers. Restenosis is the main drawback of... Show moreThis thesis examines different risk factors, in relation to restenosis after Percutaneous coronary interventions (PCI), with its main focus on genetic markers. Restenosis is the main drawback of PCI. Genetic variance poses an opportunity to enhance stratification of individuals who will be more prone to develop restenosis. Restenosis is a multifactorial process, therefore only limited part of the number of candidate genes that are potentially involved in restenosis can be described. Since the inflammatory reaction is known to be highly important in restenosis, our study has its main focus on inflammatory markers. To examine various candidate genes and their polymorphisms we made use of the GENetic DEterminants of Restenosis (GENDER) study, a multicenter follow-up study, including 3,104 consecutive patients, who were successfully treated with PCI. In the different chapters we describe the study population and the clinical and genetic factors investigated. Furthermore, we made use of a mouse model to improve our understanding of restenosis. Our results have contributed to a better understanding of the restenotic process, they could provide novel therapeutic targets as well as contribute to development of improved risk stratification of patients who are scheduled for elective PCI, thereby creating the opportunity to individualize treatment in the future. Show less
