Cholesterol-lowering medications aim to prevent cardiovascular events, caused by arteriosclerosis. Older adults (75 years and older) have a high cardiovascular risk based on age alone, and it is... Show moreCholesterol-lowering medications aim to prevent cardiovascular events, caused by arteriosclerosis. Older adults (75 years and older) have a high cardiovascular risk based on age alone, and it is estimated that 1 in 3 older adults use cholesterol-lowering medication. The vast majority (96% in the Netherlands) use a statin.The appropriateness of cholesterol-lowering medication for older adults is under debate. While there is strong evidence for the benefits of statins in relatively healthy older adults with a history of cardiovascular disease, for other groups the evidence is less convincing. Also, statins are associated with hindering side effects. In this thesis, various aspects of the appropriateness of cholesterol-lowering medication for older adults were studied, using different research designs. Five recurrent themes were of the utmost importance in the assessment of the appropriateness of cholesterol-lowering medication in older adults; 1) the individual context of a patient, 2) life expectancy, 3) hindering side effects, 4) cardiovascular history, and 5) the complexity of health problems. Based in these five themes, five key questions were distilled that can be used in a systematic evaluation of the appropriateness of cholesterol- lowering treatment for an individual patient. Show less
Dit proefschrift richt zich op het symptomatische voorstadium van reumatoïde artritis, clinically suspect arthalgia, met de volgende doelstellingen: beter begrijpen van de symptomen en de hieraan... Show moreDit proefschrift richt zich op het symptomatische voorstadium van reumatoïde artritis, clinically suspect arthalgia, met de volgende doelstellingen: beter begrijpen van de symptomen en de hieraan onderliggende mechanismen (deel I), met MRI in de CSA-fase meerleren over het ontstaan van RA en identificeren van mensen met een verhoogd risico op RA (deel II), onderzoeken of medicamenteuze behandeling in de CSA-fase zin heeft en hoe deze behandeling eruit zou moeten zien (deel III). Show less
The aim of this dissertation was to identify gaps in knowledge and room for improvements in certain aspects of the current system of prevention and care regarding RBC alloimmunization in pregnancy.... Show moreThe aim of this dissertation was to identify gaps in knowledge and room for improvements in certain aspects of the current system of prevention and care regarding RBC alloimmunization in pregnancy. The focus in this thesis was to evaluate the performance of new measures in the prevention program, the follow-up with laboratory monitoring in alloimmunized pregnancies and the counseling of pregnant women and their partners, in cases of RBC alloimmunization. Show less
The focus of this thesis is the improvement of diagnosis, early detection and treatment of CD in children. Increased knowledge, available guidelines and reliable diagnostics allow for timely... Show moreThe focus of this thesis is the improvement of diagnosis, early detection and treatment of CD in children. Increased knowledge, available guidelines and reliable diagnostics allow for timely diagnosis which can prevent complications and improve QoL, but the current healthcare approach is often unable to make the diagnosis in a timely manner. Moreover, despite timely diagnosis and effective therapy, there is a need to improve the follow up. Show less
Hodgkin lymphoma and testicular cancer survivors have an increased risk of developing second primary gastrointestinal malignancies. Whether the pathogenesis of the gastrointestinal malignancies in... Show moreHodgkin lymphoma and testicular cancer survivors have an increased risk of developing second primary gastrointestinal malignancies. Whether the pathogenesis of the gastrointestinal malignancies in cancer survivors differs from cancer in the general population is unknown. This thesis investigated the pathogenesis of gastrointestinal malignancies in Hodgkin lymphoma and testicular cancer survivors. Furthermore, the effectiveness of colorectal cancer surveillance is investigated in these cancer survivors. Additionally, this thesis will focus on mismatch repair deficiency, as identification of Lynch syndrome could have implications for the patients and implications for treatment choice. Show less
Bleeding events are frequently encountered in hemato-oncology patients. To prevent this, in periods of thrombocytopenia patients receive prophylactic platelet transfusions, based on the platelet... Show moreBleeding events are frequently encountered in hemato-oncology patients. To prevent this, in periods of thrombocytopenia patients receive prophylactic platelet transfusions, based on the platelet counts. However, beside platelet counts many other patients factors likely contribute to the bleeding risk.In this thesis we focus on describing current clinical practice to prevent bleedings in a subpopulation of patients with persistent deep thrombocytopenia, risk factors for bleeding, and prediction of bleeding. We also describe a ongoing study which aims to identify and quantify risk factors in future.With this knowledge, in the ultimate goal is to predict bleeding more accurate based on patient characteristics and/or biomarkers. This could be a first step towards more personalized bleeding prevention strategies. Show less
This thesis aims to improve the early identification of mental healthproblems (MHPs) in children by developing a prediction model for MHPs inchildren based on readily available information from... Show moreThis thesis aims to improve the early identification of mental healthproblems (MHPs) in children by developing a prediction model for MHPs inchildren based on readily available information from electronic patient recordsfrom general practice.The prediction models for child MHPs, based on the data from the electronichealth records of general practitioners (GPs), have not yet performed wellenough to be used safely in daily practice. A number of relevant predictivecharacteristics have been identified: characteristics such as physicalcomplaints (e.g. abdominal pain or headache) and characteristics related tohigher health care use (e.g. more than two GP visits or a laboratoryexamination in the previous year) were age-independent predictors of MHPs.Awareness of (a combination of) these characteristics can help GPs to identifyMHPs at an early stage.To investigate whether merging information from preventive youth healthcare(PYH) and GPs in one algorithm can improve the identification of MHPs, wecombined information from the electronic files of PYH and GPs. However, themodels based on these combined data did not outperform the models based on GPdata alone. Several individual characteristics measured in PYH turned out to bepredictors for MHPs in general practice. Show less
The ageing of the world’s population requires new methods to prevent adverse outcomes such as delirium in older patients after surgery. Delirium is an expression of depleted reserves, which in turn... Show moreThe ageing of the world’s population requires new methods to prevent adverse outcomes such as delirium in older patients after surgery. Delirium is an expression of depleted reserves, which in turn decreases a patient’s resilience and makes a patient more frail. It may be triggered due to precipitating risk factors that shift the balance and overflow a patient’s resilience. A systematic review and meta-analysis demonstrated that delirium can be prevented by implementing multicomponent interventions. Therefore, a new multicomponent prehabilitation intervention was designed. The incidence of delirium was successfully reduced by implementing this prehabilitation program, however no effects were seen on all other short-term outcomes. On the long term, postoperative delirium increases the risk of 1-year mortality over 4 times and is associated with decreased functional outcomes after 6 and 12 months. Moreover, surgery and subsequent delirium affect the quality of life of patients and caregivers and may lead to depressive symptoms. Faster return to preoperative functioning may therefore be key to a faster return to preoperative quality of life. Future perioperative care pathways focusing on delirium prevention, optimisation and fast return to baseline functioning after surgery, should begin prior to hospital admission and end long after discharge. Show less
The diversity in medicine and the scope of both non-invasive and invasive diagnostic instruments and treatments for ischemic heart disease have grown exponentially the last few decades. The... Show moreThe diversity in medicine and the scope of both non-invasive and invasive diagnostic instruments and treatments for ischemic heart disease have grown exponentially the last few decades. The objective of this thesis was to establish the value of different imaging techniques and treatments targeting different stages of ischemic heart disease. The results reported have demonstrated that multimodality imaging is of high relevance in patients with ischemic heart disease, facilitating the decision-making process in different groups of patients and allowing medical and (non-)invasive treatments to be better tailored to individual cases from prevention to treatment while potentially improving prognoses. Show less
Cardiovascular disease (CVD) is the leading cause of death in women in the Western world. In this thesis, several studies are presented examining the association between recurrent miscarriage and... Show moreCardiovascular disease (CVD) is the leading cause of death in women in the Western world. In this thesis, several studies are presented examining the association between recurrent miscarriage and cardiovascular disease. Main aim of this thesis was to assess whether miscarriages are independently associated with an increased risk of cardiovascular disease later in life. And, if this was true, to identify cardiovascular risk factors and predict long term cardiovascular disease risk in women with a history of recurrent miscarriage. We found an increased risk of ischemic heart disease in women with a history of two (multivariate analysis HR 1.82) and three or more miscarriages (HR 3.18), irrespective whether consecutive or not (chapter 2). Women with a history of recurrent miscarriage have significantly higher 10- and 30-year cardiovascular risk scores compared to women with a history of no miscarriage. These results indicate an opportunity for the early identification of women prone to cardiovascular disease later in life. Women with a history of two or more miscarriages must be made aware of their increased cardiovascular risk and appropriate risk factor modifications will have to be offered, for example life style advises; weight management and smoking control. Show less
This thesis shows that an attempt to deprescribe preventive cardiovascular medication in 40 to 70 year old low-risk patients under surveillance of the GP is safe in the short term. The... Show moreThis thesis shows that an attempt to deprescribe preventive cardiovascular medication in 40 to 70 year old low-risk patients under surveillance of the GP is safe in the short term. The deprescribing consultation should be patient-centered in order to optimally judge overtreatment.Decision-making could be improved if more personalised risk scores were available, that assess an individual’s CVD risk and benefit of treatment. Opportunities for future development of these personalised risk scores lie in the use of routinely registered patient data.Overall, this thesis’ findings provide both practical tools for GPs to judge overtreatment in low-risk patients, as well as valuable information for policy makers revising the cardiovascular risk management guideline. 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
Without a proper treatment, critical congenital heart defects (CCHD) lead to death in the first month of life. Timely diagnosis is pivotal for reducing morbidity and mortality. Pulse oximetry is... Show moreWithout a proper treatment, critical congenital heart defects (CCHD) lead to death in the first month of life. Timely diagnosis is pivotal for reducing morbidity and mortality. Pulse oximetry is used in many countries to screen newborns for CCHD. However, this screening has not been implemented in the Netherlands, because of the unique perinatal care system, with a high home birth rate and early discharge after hospital deliveries. This thesis describes research performed to assess the feasibility, accuracy, acceptability and costs of neonatal screening for CCHD with pulse oximetry in the Dutch perinatal care system. To do this, the protocol that is used in the United States and Scandinavia was adapted to fit the working scheme of community midwives. Show less
Coeliac disease (CD) is an immune-mediated systemic disorder elicited by gluten in genetically susceptible individuals. The aim of this thesis was to investigate the influence of infant feeding on... Show moreCoeliac disease (CD) is an immune-mediated systemic disorder elicited by gluten in genetically susceptible individuals. The aim of this thesis was to investigate the influence of infant feeding on prevention and development of childhood CD (part 1) and to explore new strategies for improvement of care for CD children and young adults (part 2). In part 1, the European multi-centre randomized double-blind placebo-controlled dietary intervention-study in high-risk children (www.preventcd.com) is presented. Based on retrospective studies suggesting a ‘window of opportunity’ for primary prevention of CD, parents were advised to introduce gluten between 4–6 months of age. Our results show that this did not reduce the risk of CD by 3 years of age and contributed to a new European guideline stating that gluten may be introduced between age 4-12 months. Part 2 shows that physicians overestimate the CD specific health-related quality-of-life (HRQOL) of CD patients, supporting implementation of self-reported CD-specific HRQOL measurements during follow-up. Compared to traditional hospital visits for treated CD, E-health was cost-saving, satisfactory, and significantly improved the CD-specific HRQOL. As E-health requires a point-of-care test suitable for follow-up of treated CD, three different tests were compared with conventional ELISA and one was found to be suitable. Show less
Hemoglobinopathies (HBP) are the most common autosomal recessive genetic disorder in Oman. Carriers are usually asymptomatic but carrier couples are at 25% risk of getting a severely affected child... Show moreHemoglobinopathies (HBP) are the most common autosomal recessive genetic disorder in Oman. Carriers are usually asymptomatic but carrier couples are at 25% risk of getting a severely affected child. Public health authorities have focused not only on state of the art management and patient care but also on prevention. The focus of this thesis is to study the molecular spectrum of HBP and the associated genetic determinants to work towards the development of prevention strategies for severe HBP__s in Oman. We have defined the molecular spectrum of the disease all around the country, including beta, alpha and delta globin gene mutations. Furthermore, genotype/phenotype correlation studies were investigated in patients with sickle cell disease (SCD) by looking at determinants such as haplotype/sub-haplotype, alpha thalassemia and hydroxyurea response based on XmnI polymorphism. Identifying genetic determinants is necessary for prognostic purposes, accurate diagnosis and planning for the best tailored treatment to the affected patients. While providing tools for a better care and a better insight on the management of these severe diseases in Oman, the results from this thesis will help to facilitate the prevention of HBP in the country. Show less
Urinary tract infections (UTI) are among the most frequently reported infections among older persons. UTI not only causes several days of illness but may have more severe consequences, such as a... Show moreUrinary tract infections (UTI) are among the most frequently reported infections among older persons. UTI not only causes several days of illness but may have more severe consequences, such as a decline in functioning, as well as delirium, dehydration, urosepsis, hospitalization, or even death. Annually, 20% of all older persons visit their general practitioner for a UTI and about 50% of the residents in long-term care facilities (LTCF) get a UTI. This thesis describes the possibilities for and the effects of the prevention of UTI in vulnerable very old persons. The first part of this thesis investigates the effect of infections on functioning and explores which vulnerable very old persons would benefit most from UTI prevention. The second part of this thesis describes the results of the CRANBERRY study. A double-blind randomized placebo-controlled multicentre trial in LTCF. This study investigates the effectiveness and costs of cranberry capsule use in the prevention of clinical UTI. Show less
Demographic changes will result in a tidal wave of hip fractures in the growing group of frail octo- and nonagenarian citizens. These osteoporotic fractures are a major burden to the patients__... Show moreDemographic changes will result in a tidal wave of hip fractures in the growing group of frail octo- and nonagenarian citizens. These osteoporotic fractures are a major burden to the patients__ quality of life. Despite all preventive measures, predominantly focusing on osteoporosis medication, the total number of second, contralateral hip fractures has not declined over the past decades. Complications and institutionalization after surgery of these second hip fractures are increased and can be held responsible for a decrease in quality of life for these patients and high healthcare costs. In this thesis Elastomer femoroplasty (EF) is introduced as a new modality in the prevention of hip fracture surgey We found that in, in-vitro, cadaver, biomechanical experiments, EF prevents dislocation after fracture and after fracture-loading compared to untreated control femurs. These preventively treated hip fractures can be cyclically loaded with forces that well exceed the loads during normal gait. Elastomer Femoroplasty is a feasible and a readily available, minimal invasive technique to prevent second hip fracture surgery. It can be applied during ipsilateral hip fracture surgery and does not need a separate operation or anesthesia. Furermore, due to the nature of this surgical intervention, patient compliance after EF is 100%. Show less
The aim of preventive care traditionally refers to measures taken to prevent disease and injury. However, for vulnerable older people the aim to maintain independence and wellbeing seems to be... Show moreThe aim of preventive care traditionally refers to measures taken to prevent disease and injury. However, for vulnerable older people the aim to maintain independence and wellbeing seems to be appropriate. Although a 'gold standard' to stratify for vulnerability in the general older population is lacking, GPs share the same concept of vulnerability for somatic and psychological patient characteristics. However, within the vulnerable older population, there is no evidence (except for physical activity) that a collective screening approach, with a standardized intervention program, will be the most appropriate way to contribute to the maintenance of independence and wellbeing. Moreover, since te majority of vulnerable older people already receive medical care for their chronic disease(s), more benefit can be expected from improving the individual regular care than from a separate screening program. According to GPs, te main topic in the prevention of disease in the general older population is (apart from national programs) cardiovascular risk management. A collective approach, consisting of high risk stratification and treatment, appeared to be possible even at high age. Show less
The fight against torture and inhuman or degrading treatment or punishment is of fundamental importance, which has been broadly acknowledged, and resulted in different ways to pursue the... Show moreThe fight against torture and inhuman or degrading treatment or punishment is of fundamental importance, which has been broadly acknowledged, and resulted in different ways to pursue the effectuation of this prohibition. The coexistence of multiple monitoring mechanisms in the same field can raise important questions concerning overlap, collision and alignment. The subject of this study relates to the coexistence of the European Court of Human Rights (ECtHR) and the European Committee for the Prevention of Torture and Inhuman or Degrading Treatment or Punishment (CPT) and focuses on the relation between these bodies from an organisational, terminological and normative perspective. It concentrates on answering the question how the relationship between the ECtHR and the CPT can be described and whether the current status between these bodies contributes to an effective and efficient protection of detainees against torture and inhuman or degrading treatment or punishment. Show less
Skin carcinomas develop at a high rate in organ-transplant recipients who are kept on immune suppressive drugs to prevent graft rejection. The present study dealt with a broad range of aspects of... Show moreSkin carcinomas develop at a high rate in organ-transplant recipients who are kept on immune suppressive drugs to prevent graft rejection. The present study dealt with a broad range of aspects of this elevated carcinoma risk, starting from the earliest oncogenic events to the ultimate therapy. Advancements on any of these aspects may be of significant benefit to the patient and his/her physician in the management of multiple and progressive skin carcinomas. The studies presented in Chapter 2 - 4 focused on the early pathogenesis of skin cancer in organ-transplant recipients to gain a better understanding of the underlying mechanism(s) of the increased skin cancer risk in these patients. We specifically focused on the role of p53 and beta-PV in early skin carcinogenesis. The clinical studies in Chapter 5 - 7 investigated the management of skin cancer in organ-transplant recipients. Show less
