This thesis examines cancer prognosis (Part 1) and treatment effects (Part 2) using statistical models. In Part 1, nationwide data from Dutch cancer patients (1989–2019) showed improved life expectancy due to better detection and treatments, though some cancers have poor outcomes. For melanoma patients undergoing sentinel lymph node biopsy, a model was developed to predict recurrence and mortality risks. Part 2 highlights that treatment decisions should consider personalized effects rather than averages. For patients with diffuse large B-cell lymphoma, high-risk patients benefit most from intensified treatment. Methodological advances were made in quantifying individualized treatment effects. This thesis makes five recommendations: 1) use life expectancy as a measure for prognosis and treatment effects, 2) use simple models, 3) update existing models before developing a new one but validate new models if you do, 4) strive to make personalized predictions, and 5) critically evaluate data analysis to ensure accurate information influences decisions.
Patiënten met Barrett slokdarm hebben een verhoogd risico op het ontwikkelen van een adenocarcinoom van de slokdarm. Endoscopische surveillance met het nemen van biopten in dit weefsel wordt uitgevoerd om vroege neoplastische veranderingen tijdig te detecteren en indien nodig te behandelen. In de praktijk is er door een hoge interobserver variabiliteit tussen pathologen en sampling error bij het nemen van biopten een grote kans op misclassificatie van de histologische diagnose. Dat veroorzaakt wisselende diagnoses in mate van ernst van neoplasie met als gevolg oversurveillance en overbehandeling, resulterende in een hoge druk op de gezondheidszorg.
In dit proefschrift wordt er een predictiemodel opgesteld, waarbij per individuele Barrett patient meerdere metingen van de graad van dysplasie worden meegenomen, evenals veelbelovende immuunhistochemische biomarkers. Door de multipele metingen per patient wordt het risico van een enkele misclassificatie in histologische diagnose verkleind. Tevens faciliteert dit model een gepersonaliseerde risico-inschatting die per meetmoment geüpdate kan worden.
De voorspellende waarde van dit model wordt hoger geschat dan wanneer surveillance volgens de huidige richtlijn wordt uitgevoerd. Tevens laten simulatiestudies zien dat wanneer dit predictiemodel in de praktijk gebruikt zou worden, er een geschatte 65% van de patiënten geen surveillance meer zou hoeven ondergaan door een dermate geschat laag risico op het ontwikkelen van slokdarmkanker en een totale afname van de kosten met 25%, met gelijkblijvende effectiviteit. In afwachting van externe validatie in een bestaand (niet gesimuleerd) cohort, zou deze alternatieve strategie belangrijk kunnen zijn om veel onnodige scopieën in de toekomst te kunnen voorkomen met als gevolg het vrijkomen van capaciteit om de kwaliteit van surveillance in hoogrisico patiënten te verbeteren.
Psychosocial health in early childhood plays a crucial role in long-term well-being, yet disparities persist due to socioeconomic and environmental factors, especial for children in the early life. This thesis investigates the relative factors associated with psychosocial health in young children, focusing on three key areas. Part I explores the influence of socioeconomic status and parental migration background on psychosocial health in two-year-olds and its development over time. Part II examines the impact of stressful life events on psychosocial and general health from ages two to four. Part III addresses parental help-seeking for psychosocial concerns and the factors related to parenting stress. By identifying early risk factors and the role of parental behaviors, this research provides insights for policymakers and healthcare professionals to support mental health interventions for young children and their families.
Dementia is a brain condition affecting memory, thinking, learning, language, judgment, mood, and personality. Key features of dementia are that symptoms get worse over time and they become severe enough to disrupt daily life. Rather than being one specific disease, dementia includes a range of disorders that cause permanent brain damage. The most common type is Alzheimer’s disease. Dementia is common among older people and affects over 55 million people worldwide. This thesis introduces a new microsimulation model for dementia and demonstrates its use in addressing epidemiological and health-economic questions. The thesis is divided into three parts. In Part I – Dementia Disease Prognosis, two reviews of the literature are presented that investigate how long people with dementia live after their diagnosis, how long they live independently and how much time they spend in different severity stages. In Part II – Projections of Dementia Outcomes, the development of the new microsimulation model MISCAN-Dementia is presented and its use is shown in two applications that predict the future burden of dementia in terms of dementia prevalence, and costs and quality of life. In Part III – Dementia Prevention and Intervention, the newly developed microsimulation model is used to evaluate prevention strategies for dementia. Two studies reporting on the participation in comparative modeling exercises for the evaluation of interventions are also included. In summary, this thesis introduces a new microsimulation model for dementia, providing valuable insights into the future burden of the disease.
This thesis examines the interrelations and contributing factors of frailty, polypharmacy, medication-related problems, and loneliness in older European community-dwelling adults, using data from the Urban Health Centres Europe (UHCE) Project. It is structured into three main parts:
Part I focuses on frailty, divided into physical, psychological, and social domains. Findings indicate various demographic, lifestyle, and health factors associated with these frailty domains. Notably, physical frailty was shown to have a reciprocal relationship with psychological frailty and a unidirectional association with social frailty, highlighting the complex interplay between these domains.
Part II investigates the factors linked with polypharmacy and a high risk of medication-related problems. Significant associations were found with sociodemographic characteristics, health status, and healthcare usage. Additionally, a cycle was observed where higher levels of frailty increased the risk of medication-related problems, which in turn could lead to increased frailty, suggesting a bidirectional relationship.
Part III explores the relationship between loneliness and frailty. It was found that loneliness, particularly social loneliness, significantly contributes to all frailty domains. A bidirectional association between overall loneliness and frailty was identified, with emotional loneliness specifically influencing psychological frailty.
The thesis underscores the need for a holistic approach to address these interconnected issues, recommending the integration of medical, psychological, and social elements into health strategies to enhance aging well-being and resilience.
Value-based healthcare in inherited bleeding disorders
Value-based healthcare (VBHC) was first introduced in 2006 as a strategy to combat the rising healthcare cost and unwanted variation in outcomes and quality of care. According to VBHC framework, healthcare organizations should aim to maximize patient value, where value is defined as the health outcomes that matter to patients relative to the cost of achieving those outcomes. From 2011 onwards, hospitals in the Netherlands have been implementing VBHC principles to improve the care for patients with various medical conditions. The Dutch interpretation of VBHC, however, deviates slightly from the original concept. While the objective of maximizing patient value through the routine collection of outcomes that matter to patients prevails, Dutch healthcare organizations often bypass the immediate need to measure cost. In addition, in the Dutch context, emphasis is placed on the use of outcome information to improve shared decision making and to create a culture of continuous learning and quality improvement.
This PhD thesis aimed to assess the added value of the implementation of VBHC, as defined within the Dutch healthcare context, in routine clinical care for patients with an inherited bleeding disorder. To achieve this aim, this thesis includes research on all the steps necessary to facilitate the implementation and evaluation of VBHC in this patient population. This thesis provides a recommendation on which patient-reported outcomes should be measured in the care for patients with inherited bleeding disorders, and which patient-reported outcomes should be used to collect these outcomes. In addition, this thesis provides insight into the possible variation in the care provision for patients with hemophilia which can be used as both a starting point for continuous learning and quality improvement initiatives, as well as guide the collection and use of outcome information. Moreover, this thesis provides insight into patient experiences with the collection of outcome information in routine care provision.
The main aims of this thesis are to study i) the association between psychosocial factors and mental health among university students, and ii) the influence of mental health on work participation.
In the first part of the thesis, potential determinants of students’ mental health were investigated. Chapter 2 and chapter 4 investigate the associations between the dimensions of the effort-reward imbalance (ERI) model and, respectively, psychological distress and burnout symptoms among Italian university students. These studies were among the first using the ERI model in the university setting as determinant of mental health outcomes among university students. Chapter 2 presents a cross-sectional study among 4760 students. In the sample, more than one out of three students experienced severe psychological distress. Moreover, effort, reward, ERI, and overcommitment were found to be associated with psychological distress, in particular with severe psychological distress. Moreover, ERI and overcommitment partially explained the higher prevalence of psychological distress among female students, suggesting that part of the gender difference in psychological distress may be explained by psychosocial factors. Chapter 3 provides additional evidence about potential targets for interventions by showing that student life challenges, in particular high workload, faculty shortcomings and unsupportive climate, were associated with students’ mental and self-rated health. Notably, the between-within model utilized in chapter 3 and chapter 4 allows to investigate both differences between individuals and changes within individuals over time. Results indicate that, while most of the variance in exposure is attributable to difference between individuals, this exposure may change to some extent within individuals even within a relative short timeframe. This suggests that tackling the exposure in student life challenges, ERI and overcommitment may result in better mental health among students. Additionally, chapter 5 studied in across-sectional study among 1858 Italian medical students the psychometric properties of the Italian version of the University Stress Scale (USS) as a tool to measure sources of academic stress. Results suggests that the use of a short version of the scale (USS-S) is preferable to assess the level of students’ stress compared to the 19 item version.
In the second part of the thesis the consequences of mental health problems on work participation were studied. Chapter 6 and chapter 7 illustrate different mechanisms of the negative impact of mental health problems on work participation. Using register information of 2,346,393 young adults who graduated from secondary vocational and higher vocational education or university, chapter 6 contributes to the literature suggesting that mental disorders during later stages of higher education may negatively impact work participation via two mechanisms. On the one hand, students who experience a mental health problem in the year before completing higher education were less likely to enter paid employment during 10 years of follow-up. On the other hand, graduates who entered paid employment were more likely to exit from paid employment during the follow-up period. Meanwhile, differences across type of disorders in the association between mental disorders and work participation were identified. Chapter 7 investigated in a longitudinal study the association between depressive symptoms among 5,263 older European workers and early exit from paid employment during four years follow-up differentiating exit due to unemployment and disability. The study showed that depressive symptoms were associated with higher risk of early exit from paid employment via disability benefits among men and women and, to a much lesser extent, also unemployment among men.
Chapter 8 provides insights about the available literature concerning mental health among students in higher education, with recommendations for future research. Refining methodologies in prevalence estimation of mental problems and a comprehensive investigation of individual and environmental determinants are crucial. Given its more advanced state, research on mental health in the workforce may inform student-focused research.
In the general discussion, methodological implications of the studies included in this thesis are discussed, together with an overall frame of observational studies in mental health. In particular, the definitions of mental health and mental disorders together with strategies to assess them are discoursed. The complexity behind the concept of mental health and mental disorders requires further reflections over their definition, and transdisciplinary efforts to investigate their multifaceted concepts. Recommendations for policy and practice, and students are also discussed. In particular, the development of interventions aiming at primary prevention for mental health problems is recommended, together with efforts toward a more inclusive labor market / academic environment. A safe psychosocial academic environment is needed. Students are invited to invest resources in protecting their own mental health and passion, as a personal and professional investment.
Lastly, opportunities offered by social media to researchers are discussed. Social media may enable researchers to bidirectionally connect with the public, offering the opportunity to improve the quality and the communication of one’s research. Visibility on social media may also lead to scientific cooperation, invitations to academic events and teaching opportunities. Overall, social media can help public health researchers to make their work more meaningful, and can remind them why they do it.
In the thesis “Health Effects of Lifestyle Promotion among Youth,” two main objectives are leading: 1.) the association between organized activities and mental health in children and adolescents, and 2.) the long-term effects of primary school-based interventions for the prevention of obesity.
The first part demonstrates favorable associations between organized sports activities and mental health in children and adolescents. There was insufficient evidence available to draw conclusions about the relationship between other types of organized activities and mental health. Organized sports activities are a promising starting point for future interventions to prevent mental health problems.
The second part investigates the long-term effects of primary school-based interventions for obesity prevention. A systematic review and meta-analysis found no convincing evidence for long-term effects on indicators of overweight and obesity. In a naturalistic effect evaluation and longitudinal cohort study no positive long-term effects of Lekker Fit! on a broad set of health outcomes were found.
The thesis emphasizes the need for continuous monitoring of intervention effects and more initiatives to improve fitness among youth in the city of Rotterdam. For effective obesity prevention, additional interventions or extension of existing programs to secondary schools might be necessary.