This thesis describes the long-term consequences of growth hormone and insulin-like growth factor I excess in patients cured from acromegaly for a mean duration of 17 years. Regarding the... Show moreThis thesis describes the long-term consequences of growth hormone and insulin-like growth factor I excess in patients cured from acromegaly for a mean duration of 17 years. Regarding the considerable prevalence of diverse morbidity in these patients, during the active phase of the disease but even more so after 17 years of disease cure, we suggest the screening of acromegalic patients on highly frequent comorbidities, such as osteoarthritis, vertebral fractures, colonic polyps, and colonic diverticulae. It is of great concern to recognize the long-term consequences of the disease in order to offer the patients adequate follow-up and multidisciplinary care. The aim should be to control the persisting complex morbidity as much as possible in order to prevent the patients from a further decrease in quality of life. The patients__ physician as well as the patient itself should be aware of the long-term consequences of acromegaly in order to eliminate surreal expectations concerning recovery of certain comorbidities. Show less
Arthropathies are the most common extra-intestinal manifestations of inflammatory bowel disease (IBD), affecting approximately 30% of patients. Symptoms may be debilitating and have a... Show moreArthropathies are the most common extra-intestinal manifestations of inflammatory bowel disease (IBD), affecting approximately 30% of patients. Symptoms may be debilitating and have a considerable impact on quality of life. IBD-associated arthropathies can be divided into inflammatory and non-inflammatory joint pain and may involve both axial and peripheral joints. Non-inflammatory joint pain, or arthralgia, is one of the most common complaint in daily IBD practice, but has not yet been studied systematically. For the gastroenterologist, joint/back pain can be challenging symptoms to diagnose and many have difficulties in differentiating arthralgia from arthritis. Since gastroenterologists are, in general, unfamiliar with the diagnosis and management of joint/back pain, it seems warranted that IBD joint complaints should be classified according to existing rheumatologic standards, thus allowing appropriate multi-disciplinary management. Show less
In this thesis we aimed to investigate the burden of axial spondyloarthritis (axSpA) in an early phase. We have emphasized three main themes: (1) the value of a positive family history of SpA; (2)... Show moreIn this thesis we aimed to investigate the burden of axial spondyloarthritis (axSpA) in an early phase. We have emphasized three main themes: (1) the value of a positive family history of SpA; (2) the impact of axSpA on health outcomes in an early phase of axSpA; and (3) illness perceptions and coping strategies of patients with axSpA.We have shown that when broad HLA-B27 testing is not useful, the presence of a positive family history of axSpA or uveitis could be used to predict HLA-B27 positivity in patients suspected of axSpA. We have demonstrated that health-related quality of life work productivity, and daily activities are seriously impacted even in the earliest phase of the axSpA and remain substantial over time. We have further shown that illness perceptions are important in the relationship between back pain and health outcomes in patients with axSpA. Our results suggest that illness perceptions and coping strategies do not change spontaneously and are rather independent of a decrease in disease status in patients with early axSpA.The knowledge and insights of this thesis could help us in making a timely diagnosis, providing treatment sooner, and exploring additional treatment options, which in turn could hopefully reduce the burden of axSpA. Show less
Since cancer survival rates are rising, there is growing attention for longterm side effects of cancer and its treatment. A common side effect is the negative impact of treatment on sexuality of... Show moreSince cancer survival rates are rising, there is growing attention for longterm side effects of cancer and its treatment. A common side effect is the negative impact of treatment on sexuality of patients and their partners. Patient and partners as well as healthcare professionals experience several barriers to discuss this topic, like lack of time and lack of knowlegde. Two-thirds of the cancer patients reported to be in need of information regarding sexual health; especially those who were younger, who reported a negative impact of cancer on sexuality and those who were diagnosed less than two years ago. Patients and partners reported to prefer to discuss sexual health with nurse practitioners throughout the treatment proces. Besides, satisfaction with sexual life after treatment is related to satisfaction before treatment, not only with current sexual function.Widely available information and defining responsibility within the oncology treatment team would be helpful to improve communication around sexual health in cancer care. Additionally, specialized clinics would tackle soms frequently reported barriers of discussing sexuality. More reseach is needed on the implementation of sexual healthcare in oncology practice to deliver continuum of care, which will ultimately improve patient care. Show less
In conclusion, the results of the present studies show how schizotypal symptoms may develop following child psychiatric psychopathology and how these symptoms unfavorably influence a persons__... Show moreIn conclusion, the results of the present studies show how schizotypal symptoms may develop following child psychiatric psychopathology and how these symptoms unfavorably influence a persons__ quality of life. It is important for clinicians to be aware of the complex dynamics of psychopathology and the higher risk for adult schizotypal symptomatology following behavioral problems and psychiatric disorders at child and adolescent age. Show less
Patients with DTC are initially treated with a total thyroidectomy and radioiodine therapy. Hereafter, all patients are treated with high doses of thyroxin aiming at significantly suppressing... Show morePatients with DTC are initially treated with a total thyroidectomy and radioiodine therapy. Hereafter, all patients are treated with high doses of thyroxin aiming at significantly suppressing thyrotropin (TSH) levels, resulting in a subclinical hyperthyroid state. The rationale of this approach is based on the potential harmful effects of TSH on tumor recurrence. Furthermore, thyroxin replacement therapy can be transiently stopped in these patients to detect residual or recurrent disease by TSH stimulated thyroglobulin levels. As a result of this standardized procedure, patients become overtly hypothyroid. In this thesis, questions about the clinical consequences of exogenous subclinical hyperthyroidism and hypothyroidism on bone metabolism, glucose metabolism, the autonomic nervous system and quality of life in patients with DTC are addressed. Show less
This thesis describes the Leiden Artificial Reproductive Techniques Follow-up Project. In this project, the potential long-term effects of intracytoplasmic sperm injection (ICSI) were assessed in 5... Show moreThis thesis describes the Leiden Artificial Reproductive Techniques Follow-up Project. In this project, the potential long-term effects of intracytoplasmic sperm injection (ICSI) were assessed in 5 __ 8-year-old singleton children. ICSI is the method of artificial reproduction in which a sperm cel is injected into an oocyte using a microinjection pipette. The technique is mainly successful in overcoming male factor infertility. Concerns about the development and health of ICSI-children have existed since the introduction of the technique in 1992, because ICSI is more invasive than the more widespread technique of in vitro fertilisation (IVF). In this project, 87 ICSI-children born as a singleton were compared with 87 singletons born after IVF and 85 singletons born after natural conception at 5-8 years of age, on various parameters: neuromotor development, cognitive development, pregnancy, perinatal outcome, congenital malformations, general health, growth, medical care utilisation, behaviour, parenting stress, and child quality of life. Although the results remain inconclusive on some outcomes, the majority of concerns regarding development and health of ICSI-children can be dispelled up to 8 years of age, in particular when ICSI is compared to IVF. 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
This thesis shows the results of a 16-week very low calorie diet on insulin resistance, Quality of Life, low-grade inflammation and ectopic fat depositions
The current knowledge on ABI is focused on children and the physical and cognitive outcomes. Fatigue is one of the most reported symptoms after ABI. The current thesis focuses on the adolescent... Show moreThe current knowledge on ABI is focused on children and the physical and cognitive outcomes. Fatigue is one of the most reported symptoms after ABI. The current thesis focuses on the adolescent and young adult age group and the impact of ABI on fatigue, physical activity and participation. Show less
This thesis addresses current treatment strategies in older cancer patients, as well as the consequences of these decisions for clinical outcomes. In addition, this thesis investigated the value of... Show moreThis thesis addresses current treatment strategies in older cancer patients, as well as the consequences of these decisions for clinical outcomes. In addition, this thesis investigated the value of frailty assessment in different cancer populations and described the implementation of a multidisciplinary team approach in frail older cancer patients. Show less
Patients with chronic obstructive pulmonary disease (COPD) may benefit from palliative care including advance care planning, because of their severe symptom burden and high mortality rates. However... Show morePatients with chronic obstructive pulmonary disease (COPD) may benefit from palliative care including advance care planning, because of their severe symptom burden and high mortality rates. However, this care is poorly implemented due to various reasons. Therefore, this thesis aimed to study the effectiveness of palliative care for patients with COPD and how a palliative care approach can be successfully integrated into regular COPD care.A national survey among pulmonologists and general practitioners was conducted to identify the current content and organization of palliative care in COPD in the Netherlands (Chapter 2). A systematic review revealed that very little was known about the effectiveness of palliative care interventions in COPD and how best to implement it in practice (Chapter 3). To close this knowledge gap, the COMPASSION study was designed (Chapter 4). In a cluster randomized controlled trial in eight hospital regions, health care providers of intervention regions were trained to identify palliative patients with COPD using the ProPal-COPD tool, do advance care planning conversations, and manage dyspnea. The effectiveness on patient outcomes was studied (Chapter 5) and factors for successful implementation identified (Chapter 6). Finally, the ProPal-COPD tool was externally validated and user experiences examined (Chapter 7). Show less
Celiac disease is an intolerance to dietary gluten in genetically predisposed individuals, leading to alterations of the small bowel mucosa. The treatment consists of a life-long, gluten-free diet.... Show moreCeliac disease is an intolerance to dietary gluten in genetically predisposed individuals, leading to alterations of the small bowel mucosa. The treatment consists of a life-long, gluten-free diet. The aims of this thesis were to measure some of the environmental factors considered to play a role in the prevention of celiac disease. For that purpose breast milk was studied on the presence of glutenpeptides and a food frequency questionnaire was developed and validated to quantify gluten intake in young infants. Furthermore, the current treatment at different ages and the ability to develop gluten tolerance were studied. It became clear that the nutrient intake of adolescents on a gluten-free diet can be ameliorated, and that the rather new naturally gluten-free cereal tef is frequently used by Dutch celiac patients and a wide majority of them can consume tef without clinical symptoms. Therefore tef can be a valuable addition to their diet. Although celiac disease is considered to be a permanent condition, we made an attempt to find patients who have become tolerant to gluten. We found 2 of these exceptional patients and found that one of them had HLA-typing different from HLA-DQ2/DQ8, suggesting that genetic factors may play a role in the development of tolerance. The underlying mechanisms leading to prevention, disease development or tolerance to gluten are complex and need to be further studied. Show less
This thesis contains the results of several studies on the long-term consequences of the myeloablative conditioning for haematopoietic stem cell transplantation (SCT) during infancy and childhood,... Show moreThis thesis contains the results of several studies on the long-term consequences of the myeloablative conditioning for haematopoietic stem cell transplantation (SCT) during infancy and childhood, with the emphasis on late effects on endocrine functions. After a general introduction, effects of total-body irradiation (TBI) on pituitary and thyroid glands in rhesus monkeys and effects of irradiation on growth plates in growing rats are discussed. After these experimental animal data, effects of different conditioning regimens for SCT in children on growth, pubertal development, thyroid function and quality of life are discussed in subsequent chapters, and results of growth hormone therapy in these patients are presented. All study results presented in the thesis and relevant data from the literature are integrated into a general discussion at the end of the thesis. Show less
The findings of the present thesis can be summarized in the following conclusions: 1. In Leiden, the so-called ‘founder effect’ resulted in genetic clustering with an extremely high prevalence of... Show moreThe findings of the present thesis can be summarized in the following conclusions: 1. In Leiden, the so-called ‘founder effect’ resulted in genetic clustering with an extremely high prevalence of one single SDHD mutation, the SDHD-c.274G>T (p.Asp92Tyr) mutation. 2. Patients with head-and-neck paragangliomas have a considerable impairment of quality of life. 3. Patients with head-and-neck paragangliomas have serious subjective sleep complaints. 4. Patients with SDHD-associated head-and-neck paragangliomas have an increased risk for development of pheochromocytomas and paragangliomas at other locations and life long, repetitive follow up with protocolized clinical, biochemical and radiological screening is therefore mandatory. 5. The use of [123I]-MIBG for detection of intra- and extra-adrenal paragangliomas combined, revealed a sensitivity and specificity of only 80% and 75%, respectively. The sensitivity is dependent on tumor localization and tumor behavior, with an increase in sensitivity to 92% if (intra-adrenal) pheochromocytomas are investigated separately. 6. The practical clinical implications of non-secreting intra-adrenal paragangliomas are currently uncertain. 7. Patients with SDHD mutations have malignant disease in at least ~2.5% of the cases. 8. Mediastinal paragangliomas are associated with mutations in the succinate dehydrogenase genes (either SDHB or SDHD) and aggressive behavior and might be more prevalent than hitherto appreciated. 9. Although the consequences of missing non-secreting and mediastinal paragangliomas in an SDHD-associated population are currently unclear, their possible presence should be taken into consideration in the development of future screening protocols. 10. In the future, [18F]-FDOPA and/or [18F]-FDA are expected to (at least partly) replace MIBG in diagnostic imaging for pheochromocytoma and paraganglioma. Show less
This is the first time developmental outcome following hearing screening in children with permanent childhood hearing impairment was studied in a unique, pseudo-randomized design. We found that... Show moreThis is the first time developmental outcome following hearing screening in children with permanent childhood hearing impairment was studied in a unique, pseudo-randomized design. We found that early detection of hearing loss by newborn hearing screening (and subsequent early intervention) is beneficial for the development of children with permanent childhood hearing impairment, although their development at 3-5 years is not yet comparable to that of children with normal hearing. We showed that the yield of the current hearing screening program is large, but that there is ample room for improvement in the timing following early detection of hearing loss. We would like to emphasize that the aetiology of permanent childhood hearing impairment should be investigated and the cause taken into account when evaluating the development of the child. Show less
The aim of this thesis is to examine employment and driving ability in gene carriers with Huntington’s disease (HD). HD is an autosomal-dominant inherited neurodegenerative disorder and manifests... Show moreThe aim of this thesis is to examine employment and driving ability in gene carriers with Huntington’s disease (HD). HD is an autosomal-dominant inherited neurodegenerative disorder and manifests during mid adulthood. The disease is clinically characterized by motor disturbances, cognitive decline and behavioral changes. Since there is currently no cure for HD, the focus of treatment is on improving quality of life and providing the necessary support to patients and families. Maintaining independence through employment and driving, for as long and as safely as possible, has a substantial influence on a patient’s general functioning. Our results consistently showed that the cognitive and behavioral changes of HD are more debilitating in daily life than the characteristic motor signs, and are associated with employment and driving a car. Healthcare professionals should be educated about HD to allow them to provide appropriate information to patients and families when discussing possible changes in working and driving as a result of HD. Individual evaluation of driving ability is warranted and the recommendation to stop driving should not solely be based on disease stage or a genetic confirmation. Multidisciplinary screening, using a HD-specific test battery, is recommended and should be embedded in the clinic. Show less
Oral anticoagulant therapy has changed little since the development of the coumarin drugs after the Second World War. The basic nature of the therapy, i.e. the balancing between thrombosis and... Show moreOral anticoagulant therapy has changed little since the development of the coumarin drugs after the Second World War. The basic nature of the therapy, i.e. the balancing between thrombosis and haemorrhage, makes it a therapy difficult to manage. Add to this the many influences from co-morbidity, co-medication, diet, metabolism, etc, and it becomes clear that there is little inherent stability to coumarin anti-vitamin K treatment. The studies included in this thesis were set up to look at different ways in which the quality of oral anticoagulant treatment can be improved. We looked at the percentage of time spent within the predefined INR target range with different coumarins (acenocoumarol and phenprocoumon), at patient self-management to further improve treatment quality in the setting of a highly structured system of anticoagulation clinics and the effects of this treatment modality on the quality of life of the patients. We also looked at the effects of chronic paracetamol intake on the INR, and at the relationship between the quality of oral anticoagulant therapy and recurrent thrombosis. Show less
In the current dissertation the effectiveness and cost-effectiveness of Featback, an internet-based self-help intervention for eating disorders, and online support by individuals with a lived... Show moreIn the current dissertation the effectiveness and cost-effectiveness of Featback, an internet-based self-help intervention for eating disorders, and online support by individuals with a lived experience of an eating disorder were investigated. The findings suggest that low-threshold internet-based interventions for eating disorders, such as Featback, can complement existing treatment options in three ways. First, they have been repeatedly found to be effective in reducing eating disorder symptomatology. Second, such interventions can reach individuals that are currently not reached by other forms of treatment and stimulate them to get professional help. Finally, internet-based interventions are likely to be cost-effective compared to care as usual. Concordantly, implementing highly scalable and easily accessible interventions like Featback likely helps to reduce both the individual and societal burden of eating disorders. Show less
Although modern treatment strategies have made Hodgkin Lymphoma (HL) a highly curable disease, there is a life-long increased risk of morbidity and mortality due to treatment. Over time it has... Show moreAlthough modern treatment strategies have made Hodgkin Lymphoma (HL) a highly curable disease, there is a life-long increased risk of morbidity and mortality due to treatment. Over time it has become increasingly evident that the historically used extensive treatment fields can potentially lead to numerous long-term adverse effects, often presenting clinically with a delay of more than 10-15 years. Epidemiological studies have shown an increased risks of second malignancies in HL survivors. HL survivors treated with mediastinal radiotherapy also have increased risk of late cardiac complications such as myocardial infarction, which might be due to radiation-induced coronary artery stenosis. All these adverse effects can severely impact health-related quality of life. This thesis investigates the long-term sequelae that HL survivors may encounter. The long-term risk of secondary skin cancers after radiotherapy in HL survivors was evaluated, and compared to the risks in the general Dutch population. The feasibility of screening for coronary artery disease by means of computed tomography coronary angiography (CTA) in HL survivors was investigated, and also satisfaction with information provision and the psychological burden of screening. Furthermore, the prevalence of fatigue in HL survivors compared with the general Dutch population, and associations with predisposing factors were assessed. Show less
