The work described in this thesis had two objectives, specifically focusing on people aged 70 years and older: first, we aimed to investigate the associations between several thrombosis-related... Show moreThe work described in this thesis had two objectives, specifically focusing on people aged 70 years and older: first, we aimed to investigate the associations between several thrombosis-related risk factors described in young and middle-aged populations and the risk of venous thrombosis (VT) in the elderly; second, we aimed to provide insight into several long-term consequences (i.e., health-related quality of life (HRQoL) and long-term risk of mortality) after a first VT at old age. 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
Persons with dementia may not always be able to set their own goals and expectations. When persons with dementia are no longer able to assess their own Quality of life (QoL), family, friends and... Show morePersons with dementia may not always be able to set their own goals and expectations. When persons with dementia are no longer able to assess their own Quality of life (QoL), family, friends and professional caregivers need to be their voice, as they are most familiar with their values, goals and needs. QoL in persons with advanced dementia is influenced by many factors, such as environment, background and psychological factors such as depression and agitation.The Q-PID study was a 13-week double-blind, randomised, placebo-controlled crossover trial that assessed the effect of paracetamol on QoL, discomfort, pain, neuropsychiatric symptoms, care dependency and daily functioning in 95 persons with moderate to advanced dementia living in long-term care facilities (LTCF).This thesis provides evidence that administration of paracetamol or placebo alone is not effective, i.e., no ‘panacea’, for improving QoL, discomfort, pain, neuropsychiatric symptoms, care dependency and dailyfunctioning in persons with advanced dementia living in LTCF. Personalizing interventions, collaborationbetween different health care workers and family/friends, and combining pharmacological and non-pharmacological interventions are important to maintain the best QoL possible, and we recognize that this will be challenging, but not impossible. Show less
With the introduction of population-based screening, early-stage colorectal cancers (T1CRCs) are increasingly detected. The treatment of patients with T1CRC is complex, as these tumors have... Show moreWith the introduction of population-based screening, early-stage colorectal cancers (T1CRCs) are increasingly detected. The treatment of patients with T1CRC is complex, as these tumors have metastatic potential despite their early stage. As a result, local organ-sparing endoscopic tumor resection is not always sufficient, thereby giving rise to various challenges throughout the entire treatment process.The overarching goal of this thesis is to improve clinical care for T1CRC patients. Part 1 is centered around the biology and translational potential of the tumor microenvironment, and in particular cancer-associated fibroblasts (CAFs), in T1CRC. The studies in this part show that CAFs in T1CRCs exhibit T1 stage-specific phenotypic traits and can promote cancer cell invasion in T1CRC through diverse mechanisms. These findings provide promising leads for developing better predictors of metastasis, which can be used to determine which T1CRC patients will (not) benefit from major bowel surgery.Part 2 focuses on the clinical aspects of T1CRC treatment. The studies in this part show that local endoscopic tumor resection has become a mature alternative to surgery, from both the patient’s and oncological perspective. However, further optimizations of local resection techniques and surveillance thereafter are needed to increase the use of organ-sparing treatment for T1CRC patients. 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
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
