This thesis investigates different aspects of apathy - as a distinct clinical syndrome assessed with the Apathy Scale- in older persons with and without concurrent depression. In Chapter 2,... Show moreThis thesis investigates different aspects of apathy - as a distinct clinical syndrome assessed with the Apathy Scale- in older persons with and without concurrent depression. In Chapter 2, clinically relevant subtypes of apathy according to the Apathy Scale in older persons from the PROMODE study are examined, using data-driven Latent Class Analysis (LCA). Further, specific characteristics across the classes identified by LCA are investigated. Then, in Chapter 3, cross-sectionally the prevalence, severity and clinical profile of apathy in depressed and non-depressed older persons, in relation to various possible determinants is described. Chapter 4 examines which characteristics predict, over a 2-year period, the incidence and course of apathy in at baseline depressed older persons from the NESDO study. Chapter 5, using data of the NESDO and NESDA, investigates the presence of apathy in late-life compared to early-life depression, and various determinants of clinically relevant apathy in older compared to younger depressed persons. In Chapter 6 the association of the presence of apathy among community-dwelling older persons from the PROMODE study and a diminished quality of life is examined. All results are placed a current perspective in Chapter 7 that also discusses clinical implications, and makes some recommendations for future research. Show less
In this thesis, quantitative and qualitative evidence was gathered in an attempt to improve and extend the current sexual health care of gynaecological cancer survivors. Although surgery has a... Show moreIn this thesis, quantitative and qualitative evidence was gathered in an attempt to improve and extend the current sexual health care of gynaecological cancer survivors. Although surgery has a major impact on sexual functioning, vaginal changes and symptoms have been shown to be more profound after intensive radiotherapy. Therefore, the studies in this thesis were especially focused on gynaecological cancer survivors who received radiotherapy, and mainly concerned cervical cancer patients; a relatively young patient population often treated with intensive external-beam radiation therapy (EBRT) in combination concurrent chemotherapy, and intrauterine and vaginal brachytherapy (BT), although the results are equally relevant to other gynaecological cancer patients treated with EBRT with or without BT. In order to assess what type of patient education and/or support would be needed to minimise the impact of gynaecological cancer treatment on sexual functioning, and to improve the survivors’ sexual recovery we followed several approaches: assessment of survivors’ experience with sexual distress after treatment, and unmet needs for psychosexual counselling and support; it was explored how survivors and professionals could best deal with treatment-induced vaginal changes; and, partly based on the previous findings, a sexual rehabilitation intervention was developed and evaluated in a pilot study. Show less
In this thesis long-term effects and quality of life after treatment for rectal cancer are evaluated. Long-term data were assessed from the TME trial. In this trial 1530 Dutch patients with... Show moreIn this thesis long-term effects and quality of life after treatment for rectal cancer are evaluated. Long-term data were assessed from the TME trial. In this trial 1530 Dutch patients with rectal cancer were included between 1996 and 1999. These patients were randomly assigned to total mesorectal excision (TME) or to short-course preoperative radiotherapy (5x5 Gy) followed by TME surgery. Show less
Concluderend, er worden drie hoofdthema__s in dit proefschrift besproken: ten eerste incidentie en epidemiologie van BC__s, ten tweede de kwaliteit van zorg en ten derde de kwaliteit van leven.... Show moreConcluderend, er worden drie hoofdthema__s in dit proefschrift besproken: ten eerste incidentie en epidemiologie van BC__s, ten tweede de kwaliteit van zorg en ten derde de kwaliteit van leven. Deze drie thema__s leggen het fundament voor meer (medisch) onderzoek binnen de Nederlandse krijgsmacht. Optimalisatie van de behandeling van gevechtsgewonden gaat verder dan de medisch ondersteunende organisatie. Vroege betrokkenheid van buddy__s, familieleden, medisch personeel en tactisch commandanten is bevorderlijk voor eenieder. Een volledig ge_ntegreerde aanpak binnen de Defensie organisatie is noodzakelijk. Militaire Geneeskunde is een continu evoluerend proces, waarbij alle mogelijkheden moeten worden aangewend om dit proces te optimaliseren. De integratie van prospectieve studies zal de kwaliteit van lessons learned van elk gewapend conflict verhogen. Er is een sterke overeenkomst met rampengeneeskunde en rampenchirurgie. Samenwerking van rampengeneeskunde en militaire geneeskunde kan daarom nuttig zijn. Als de resultaten omschreven in dit proefschrift kunnen bijdragen aan de verbetering van de kwaliteit van de medisch ondersteunende organisatie, de opleiding van medisch en niet-medisch personeel en de kwaliteit van leven van alle betrokkenen met meer dan een procent, dan is het doel bereikt. 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
Systemic lupus erythematosus (SLE) and its immunosuppressive treatment have a great impact on the patient__s life. Previous studies on SLE have focused on the optimisation of diagnosis and... Show moreSystemic lupus erythematosus (SLE) and its immunosuppressive treatment have a great impact on the patient__s life. Previous studies on SLE have focused on the optimisation of diagnosis and treatment. Less attention has been given to the impact of diagnosis and treatment on patients__ well-being. According to Engel__s biopsychosocial model there is a reciprocal and multifactorial relationship between disease characteristics and patients__ well-being and therefore the patient and not the disease should be the centre of focus. This thesis aimed to produce a biopsychosocial perspective on SLE by investigating both medical care and psychological functioning in patients with SLE. The main results show that a selective use of diagnostic procedures and monitoring of serum drug concentrations do not hamper disease outcome and may even reduce treatment burden. However, also low dose immunosuppressive treatment for SLE remains burdensome. This burden is reflected by a lowered HRQoL and lowered sexual functioning. In view of limitations in the extent to which immunosuppressive treatment can be further lowered, patients' illness perceptions may be targeted to enhance psychological functioning. In addition, treatment outcome may benefit from illness perception modification through a beneficial effect of positive (i.e. more adaptive) treatment perceptions on level of treatment adherence. Show less
Dit proefschrift richt zich op het monitoren van ziekte bij zowel RA als UA pati_nten en kijkt daarbij naar de waarde van de beeldvorming, het beoordelen van de ziekteactiviteit, het vast te... Show moreDit proefschrift richt zich op het monitoren van ziekte bij zowel RA als UA pati_nten en kijkt daarbij naar de waarde van de beeldvorming, het beoordelen van de ziekteactiviteit, het vast te stellen behandeldoel en de implementatie van monitoring in de dagelijkse praktijk. Naar aanleiding van dit proefschrift kunnen de volgende conclusies worden getrokken: -Systematisch literatuur onderzoek laat zien dat afwijkingen op conventionele r_ntgenfoto__s waardevol zijn voor het voorspellen van de prognose van UA pati_nten. Voor de aanvullende waarde van echografie en MRI in UA pati_nten werd weinig bewijs gevonden. -Gewrichtsschade ter plaatste van de pols, met name erosieve schade, heeft een belangrijke invloed op het dagelijks functioneren van pati_nten met reumato_de artritis. -Een versimpelde DAS zonder gegradeerde of gegroepeerde pijnscore kan goed worden gebruikt voor het in kaart brengen van ziekteactiviteit, zowel met een VAS voor algemene gezondheid als met een VAS voor ziekteactiviteit. -De mate van ziekteactiviteit gescoord door pati_nten en artsen komt niet goed overeen. Pati_nten scoren over het algemeen hoger waarbij pijn een belangrijke factor van invloed is. Artsen baseren hun score meer op de bezinking en het aantal gezwollen gewrichten. -De relatie tussen verschillende definities van remissie (inclusief de nieuwe ACR/EULAR remissie criteria) en radiologische schade of HAQ is vergelijkbaar. -Verbetering in ziekteactiviteit geeft een verbetering in kwaliteit van leven gemeten met de Physical Component Scale van de SF-36. Dit geldt ook voor pati_nten met reeds een lage ziekteactiviteit die in remissie komen. -Pati_nten zijn bereid tot het online monitoren van lichamelijk functioneren, maar doen dit in de thuissituatie weinig. Meer begeleiding en het benadrukken van het nut van regelmatige ziektemonitoring voor het uiteindelijke behandelresultaat is nodig om dit te kunnen verbeteren. 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
This thesis describes the results of the first en second Post Operative Radiation Therapy in Endometrial Cancer (PORTEC) trials. The 15-year results of PORTEC-1 confirm the importance of the... Show moreThis thesis describes the results of the first en second Post Operative Radiation Therapy in Endometrial Cancer (PORTEC) trials. The 15-year results of PORTEC-1 confirm the importance of the prognostic factors age, grade and depth of myometrial invasion for selection of patients with high-intermediate risk (HIR) features. Postoperative pelvic external beam radiotherapy (EBRT) reduces the risk of locoregional recurrence (mainly due to a decrease in vaginal recurrences), without a survival benefit compared to no additional therapy. The PORTEC-2 trial has shown that EBRT and vaginal brachytherapy (VBT) offer excellent rates of vaginal control and similar overall survival for HIR patients, while VBT has a clearly more favourable health related quality of life profile, with results similar to an age-matched norm population. EBRT is associated with a higher risk of long-lasting bowel symptoms that impact on patients__ daily lives and physical functioning. Therefore, VBT is the treatment of choice for HIR patients. Finally, a pilot study in PORTEC-2 patients showed that the presence of multiple activated oncogenic pathways was the most powerful independent prognostic factor for decreased disease free survival, indicating that molecular prognostic factors refine the currently used system for risk classification. Show less
The research presented in this thesis provides several novel insights regarding the _-thalassemia intermedia phenotype. Earlier studies observed that patients with _-thalassemia intermedia... Show moreThe research presented in this thesis provides several novel insights regarding the _-thalassemia intermedia phenotype. Earlier studies observed that patients with _-thalassemia intermedia experience a clinical complications profile that is different from that in patients with _-thalassemia major; which was primarily attributed to their transfusion-independence. In this work, a variety of clinical morbidities were explored and their associations with the underlying disease pathophysiology and risk factors were examined. The morbidities evaluated throughout the studies involved several organs and organ systems including the vasculature (venous thrombosis, pulmonary artery hypertension, cerebrovascular disease, and leg ulcers), heart, liver, kidney, endocrine glands (diabetes mellitus, hypothyroidism, and hypogonadism), bone (osteoporosis), and the hematopoietic system (extramedullary hematopoietic tumors). Findi ngs confirm that _-thalassemia intermedia should no longer be regarded as a mild form of thalassemia as patients experience serious manifestations involving almost every organ system. Show less
The general aim of this thesis was to assess the effectiveness of a standardized psychosocial education program. The first studies of this thesis were aimed to assess the effectiveness of the... Show moreThe general aim of this thesis was to assess the effectiveness of a standardized psychosocial education program. The first studies of this thesis were aimed to assess the effectiveness of the Patient Education Program for Parkinson__s disease (PEPP), as the original program was directed at Parkinson__s disease. Thereafter, it was aimed to assess the program__s feasibility in other diseases. A second step in the thesis was an evaluation of the feasibility of the program adapted to a new disease-specific form for Huntington__s disease (PEP-HD). The third step was to evaluate a generic form of the program in a heterogeneous group of patients with chronic diseases and co-morbid psychiatric problems (PEP-CD). Show less
Nowadays, pituitary adenomas can be appropriately treated, but patients continue to report impaired quality of life (QoL) despite long-term remission or cure. In patients with Cushing__s disease,... Show moreNowadays, pituitary adenomas can be appropriately treated, but patients continue to report impaired quality of life (QoL) despite long-term remission or cure. In patients with Cushing__s disease, Cushing__s syndrome or acromegaly, doctors should be aware of subtle cognitive impairments and the increased prevalence of psychopathology and maladaptive personality traits after long-term remission. In addition, these patients use ineffective coping strategies and have negative illness perceptions that are not always correct. Patients are labeled __cured__, but still experience chronic and persisting impairments due to their pituitary disease. Doctors should consider informing patients better about the long-term consequences and act as a guide in this __acceptance process__ of the patient. In addition, a multi-disciplinary team of endocrinologists, psychologists, and community health workers might also help patients in accepting and dealing with the consequences of their pituitary disease. Show less
Improving survival rates in children and adolescents with malignant bone tumours, paved the way to the application of new surgical extremity-salvage techniques. For the surgical treatment of... Show moreImproving survival rates in children and adolescents with malignant bone tumours, paved the way to the application of new surgical extremity-salvage techniques. For the surgical treatment of malignant bone tumours of the lower extremity, there are a number of resection options (amputation, limb sparing, and rotationplasty) available. Each option has its own indication and after the surgery different advantages and disadvantages. The debate is whether limb-salvage or ablative surgery is advantageous for the individual patient. Purpose of the studies presented in this thesis are evaluate and compare QoL, functional ability and physical activity levels among children and young adults in the first years after bone cancer surgery of the leg. A cross sectional and a prospective study were conducted in the Dutch university bone cancer centres. The results of the cross-sectional study show that outcomes are equivalent for those undergoing limb salvage or ablative surgery. The results of the prospective study showed that; survivors improve in the two years following resection of the bone tumour and the resulting limb-sparing or ablative surgery at all domains evaluated, with the exception of the mental QoL domains. These improvements were most pronounced over the first year after surgery. 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
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
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
Vestibular schwannomas are benign intracranial tumors which generally arise from the Schwann cells of the superior part of the vestibular portion of the eight cranial nerve. The most common... Show moreVestibular schwannomas are benign intracranial tumors which generally arise from the Schwann cells of the superior part of the vestibular portion of the eight cranial nerve. The most common symptoms accompanying vestibular schwannoma (VS) are unilateral hearing loss, tinnitus, vertigo and unsteadiness. For many years, microsurgical treatment of VS has been considered the __gold standard__. However, the treatment of VS continues to evolve with the advent of alternative treatment options such as wait and scan and stereotactic irradiation. Moreover, advances in MRI techniques have allowed for an early diagnosis and exact measurement of growth, which has led to an increased number of patients with small and minimally symptomatic tumors. As a result, the treatment of VS no longer involves life saving surgery, but prophylactic management of future morbidity. These developments have also created new insights into how vestibular schwannoma can be best treated, as it has become clear that the tumor may remain unchanged for many years. However, the treatment of VS patients still remains a matter of debate with advocates and opponents of each modality. Traditionally, the evaluation of VS treatment was performed using primary outcome measures such as mortality and morbidity. But the subject of quality of life (QoL) has increasingly become an important outcome measure in VS. QoL may provide clinicians valuable informati on that is not always 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
What kinds of personal goals, aspirations and plans do Dutch youths consider important in their lives? And how does experience of setbacks when pursuing these goals and means of coping with these... Show moreWhat kinds of personal goals, aspirations and plans do Dutch youths consider important in their lives? And how does experience of setbacks when pursuing these goals and means of coping with these frustrations influence their psychological well-being and experience of headache? These are some of the main questions addressed in this research project by means of a series of questionnaire and diary studies among high-school students. Goals were most commonly reported in the area of interpersonal relationships, followed by health and body, their future, school, leisure and personal development. Importance of adolescent aspirations and thoughts and emotions related to these goals were shaped to a large extent by personal and contextual characteristics such as gender, age and ethnicity. Goal importance did not differ according to experience of headache, however, youths with weekly headache reported higher levels of frustration in personal goal pursuits compared to their headache-free peers. Frustration in pursuit of especially self and health goals was related to higher depressive symptoms and lower quality of life in a cross-sectional questionnaire study. Furthermore, frustration predicted next-day lower well-being and greater headache complaints in a prospective diary study. Moreover, dwelling on the negative aspects of the situation (catastrophizing), repetitive thoughts about the frustration (rumination) and the belief that one is unable to cope well with the setback predicted next-day poorer psychological well-being. This was one of the first studies to assess the contribution of self and emotion regulation factors to well-being and headache in adolescence and offers insights into possible targets for intervention with youths Show less
The thesis “Non-motor symptoms in Parkinson’s disease” is part of the PROPARK study, a longitudinal cohort study of approximately 400 patients with Parkinson’s disease (PD), who are profiled on... Show moreThe thesis “Non-motor symptoms in Parkinson’s disease” is part of the PROPARK study, a longitudinal cohort study of approximately 400 patients with Parkinson’s disease (PD), who are profiled on genotype, phenotype, disability, and global outcomes of health, using valid and reliable assessment instruments for PD. The aims of this thesis were to characterize the non-motor domains important in PD such as olfactory, autonomic, sleep, cognitive, and psychiatric problems. Additionally, their relations with other domains of the disease were evaluated on a cross-sectional level, as well as their impact on disability and health-related quality of life. Furthermore, the phenotypic characteristics of mutation carriers in the cohort were evaluated. The most important conclusions from this thesis are: 1. Non-motor symptoms are frequently present in patients with PD 2. Non-motor symptoms are related to each other 3. Non-motor symptoms greatly influence quality of life in patients with PD The results as described in this thesis will serve as guideline for future research which will be aimed at underlying disease mechanisms. Show less
