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
This thesis provides an overview of the current epidemiology of neonatal NI, including CLABSI. While highlighting the importance of this complication, it has laid the foundation for the development... Show moreThis thesis provides an overview of the current epidemiology of neonatal NI, including CLABSI. While highlighting the importance of this complication, it has laid the foundation for the development and evaluation of several prevention and reduction strategies. The incidence of sepsis among certain neonatal subpopulations such as neonates with hemolytic disease of the fetus and newborn remains high, illustrating the need to re-calibrate indications for central-line placement and CLABSI prevention measures. In contrast to what was hypothesized, a significant positive effect of several interventions and changes in clinical practice, including the implementation of single-room care and a multi-modal strategy, could not be supported. On the other hand, support was found for behavioral change tools such as ‘nudges’ which seem to be a more promising avenue in the reduction of NI, providing such tools can be tailored to the clinical micro-system and context-specific needs of NICU-healthcare workers. Furthermore, nationwide CLABSI surveillance provided a unique insight into the current burden of neonatal CLABSI in The Netherlands, although the optimization of digital infrastructures, data availability and accessibility are urgently needed to perform forthcoming benchmarking initiatives. Even though much progress has been made, we are far from done in the battle against neonatal NI. 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
De kans op CIN in verschillende pati_ntenpopulaties bleek gering en zelden tot dialyse te leiden na CT-scan. Daarnaast worden er een drietal multi-center RCTs beschreven. Twee van deze studies... Show moreDe kans op CIN in verschillende pati_ntenpopulaties bleek gering en zelden tot dialyse te leiden na CT-scan. Daarnaast worden er een drietal multi-center RCTs beschreven. Twee van deze studies tonen aan dat een __n uur durende voorbehandeling met natriumbicarbonaat pre- en posthydratie ter preventie van CIN veilig kan vervangen bij pati_nten die CT-scan of intra-arteri_le contrasttoediening ondergaan. Dankzij de kortere duur van dit natriumbicarbonaatinfuus zijn de kostenbesparingen die gepaard zouden gaan bij landelijke invoering van deze preventieve methode groot. De derde gerandomiseerde studie toont aan dat het gebruik van maatregelen om CIN te voorkomen achterwege gelaten kunnen worden bij pati_nten die een CT-scan ondergaan omdat zij verdacht worden van een acute longembolie. Het in America uitgevoerde onderzoek (in samenwerking met de Universiteit van Michigan) beschreven in dit proefschrift concentreert zich op de pati_ntenpopulatie die jodiumhoudende contrastmiddelen toegediend krijgt ten tijden van percutane coronair interventies. Dit onderzoek heeft geleid tot de ontwikkeling van een risicomodel waarmee betrouwbaar het risico op CIN en de noodzaak tot dialyse na percutane coronair interventies ingeschat kan worden. Daarnaast is uit dit onderzoek naar voren gekomen dat bijna een derde van de overlijdens na percutane coronair interventies toe te schrijven zijn aan het ontstaan van CIN. 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
