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
This thesis aims to improve patient outcomes after major oncological gastrointestinal surgery, by identifying targets for optimizing perioperative care. On the one hand, identifying (adjustable)... Show moreThis thesis aims to improve patient outcomes after major oncological gastrointestinal surgery, by identifying targets for optimizing perioperative care. On the one hand, identifying (adjustable) prognostic factors for postoperative complications and then using them in prediction models, and gaining insight into the quality of life after surgery. Improving preoperative risk assessment and subsequent personalization of postoperative care can reduce the rate of postoperative complications and mortality. In addition, risk prediction can support clinical knowledge in making treatment decisions. Modifiable prognostic factors are particularly important to identify as they may be optimized prior to surgery. Modifiable prognostic factors can then be used in prehabilitation programs to improve a patient's physical condition and thus improve patient outcomes. In addition, information about treatment consequences and treatment-related health problems is important for treatment decision-making for patients and healthcare professionals. Especially, if several treatment options are available, knowledge about (long-term) consequences of the treatment options is important for shared decision-making. This knowledge can also contribute to optimizing postoperative care and rehabilitation programs. In conclusion, the leads described in this thesis for improving postoperative care can be used to improve short- and long-term patient outcomes after complex oncological gastrointestinal surgery. Show less
This thesis describes studies of individuals with systemic lupus erythematosus (SLE) presenting with neuropsychiatric (NP) symptoms at the Leiden NPSLE clinic. A diverse range of studies, including... Show moreThis thesis describes studies of individuals with systemic lupus erythematosus (SLE) presenting with neuropsychiatric (NP) symptoms at the Leiden NPSLE clinic. A diverse range of studies, including laboratory, radiological, clinical and patient´s reported outcomes are presented.The Leiden NPSLE clinic is a tertiary referral center for patients with SLE and neuropsychiatric (NP) symptoms. In the NPSLE clinic, patients are assessed by a multidisciplinary team. Thereafter, clinical, radiological and laboratory measures are weighed in a consensus meeting to correctly attribute the NP symptoms: related to lupus activity (NPSLE) or not. This extensive and standardized assessment of NPSLE, a rare and heterogenous disease lacking a gold standard, is unique and creates the opportunity to explore many aspects of NPSLE in well-defined phenotypes.In the first part of this thesis, we evaluate both classification and treatment of patients withSLE and NP symptoms. The second part of this thesis focuses on a diverse range of clinicaloutcomes of NPSLE, including both morbidity and mortality. The last part of this thesisassesses potential biomarkers for (specific manifestations of) NPSLE. Show less
Road traffic accidents (RTA) contribute significantly to the global burden of trauma. The World Health Organization indicates that approximately 1.3 million people die each year on the world's... Show moreRoad traffic accidents (RTA) contribute significantly to the global burden of trauma. The World Health Organization indicates that approximately 1.3 million people die each year on the world's roads and between 20 and 50 million sustain non-fatal injuries. The introduction of extensive traffic safety laws, preventive governmental programs and substantial changes in (the organisation of) pre- and in-hospital trauma care have resulted in a gradual decrease in road traffic injuries and fatalities in the 1990s and onward in the Netherlands. Since 2006, however, the number of seriously injured road traffic participants has been increasing despite these government measures to improve road safety. In 2018, an estimated 21,700 people were seriously injured in traffic in the Netherlands, approximately 1,000 more than in 2017.The primary aim of this thesis was to analyse injury patterns, injury severity and mortality for different types of road traffic participants involved in accidents in the Netherlands. Secondly, the association between blood alcohol concentrations, TBI patterns and patient outcome was analysed. Finally, patient and injury characteristics associated with HRQoL, fatigue and societal participation in polytrauma patients were identified. Show less
Het aantal heupfracturen zal de komende jaren stijgen. Bovendien zijn de morbiditeit en mortaliteit na een heupfractuur groot. Het eerste deel van het proefschrift gaat over prothesiologie bij... Show moreHet aantal heupfracturen zal de komende jaren stijgen. Bovendien zijn de morbiditeit en mortaliteit na een heupfractuur groot. Het eerste deel van het proefschrift gaat over prothesiologie bij heupfractuurpatiënten. Uit eerder onderzoek is gebleken dat een prothese de voorkeur heeft ten opzichte van osteosynthese. Hoofdstuk drie beschrijft een multicenter trail waarbij we 201 patiënten hebben gerandomiseerd tussen een gecementeerde en een ongecementeerde kophalsprothese. De patiënten met een gecementeerde prothese kregen minder complicaties (minder periprothetische fracturen en luxaties). In hoofdstuk twee beschrijven we de 22.675 patiënten die de afgelopen 10 jaar na een heupfractuur in het landelijk register zijn opgenomen. Uit dit hoofdstuk blijkt dat er minder re-operaties worden uitgevoerd na een gecementeerde prothesesteelfixatie en een niet-posterolaterale benadering. Het tweede deel van het proefschrift toont dat een heupfractuur een enorme impact heeft op het leven van de patiënt. Het percentage delier na de fractuur was hoog (27%) evenals het percentage mensen dat overleed binnen 30 dagen (8%). Kwaliteit van leven en dagelijks functioneren gingen fors achteruit en herstelden niet volledig. De patiënten die het meest achteruit gingen waren jong en mobiel voorafgaand aan de fractuur. We adviseren dan ook meer aandacht te hebben voor deze groep. Show less
Ewing and chondrosaroma are two forms of primary bone cancer. The few clinical studies that are published in recent decades show disappointing results. With a 5 year survival of 10% for inoperable... Show moreEwing and chondrosaroma are two forms of primary bone cancer. The few clinical studies that are published in recent decades show disappointing results. With a 5 year survival of 10% for inoperable Ewing sarcoma and 2% for inoperable chondrosarcoma patients the outcome is poor. If a patient has not responded to standard treatment, they are often treated with combinations based on expert opinion of the treating physician. These treatment combinations have not been investigated in studies because of the small patient numbers which makes starting a study very difficult and time-consuming. One combination is of the chemotherapeutic agents etoposide with carboplatin or cisplatin. Analysis of the survival data of patients treated with these combinations shows that they are comparable to other standard treatment options. New non-chemotherapy treatment options are currently being investigated. Examples are the IGF-1R and PARP route. The current knowledge of both routes shows that disregulation causes malignant transformation and / or disease progression. Inhibition of these routes is therefore a possible treatment. In clinical studies, the results are not positive for all patients. This is due to incorrect patient selection and not being tested in combination with already used treatments. Show less
The rate of adverse health outcomes 90 days after an emergency department (ED) visit is high for older patients.A comprehensive geriatric assessment (CGA) can effectively identify patients at... Show moreThe rate of adverse health outcomes 90 days after an emergency department (ED) visit is high for older patients.A comprehensive geriatric assessment (CGA) can effectively identify patients at highest risk and improve outcomes. Unfortunately, the fast-paced environment and the medical condition of the acutely ill older patient make it virtually impossible to perform a CGA in all patients in the ED. Therefore, it was the aim of the present thesis to develop a screening instrument for the ED setting to identify older patients at high risk for adverse health outcomes, in order to target them for future interventions to preserve their independency and quality of life. In a multicenter prospective cohort study a total of 2629 older ED patients were included with a mean age of 79 years old. After 90 days 805 patients (30.6%) experienced functional decline or mortality. A new screeninginstrument to identify older ED patients at risk for adverse health outcomes was developed and validated: the APOP screener. The APOP screener adequately identifies older ED patients at highest risk for functional decline or mortality and is promising for clinical use. Show less
This thesis has provided more knowledge on the disease course and its determinants of outcome in hand osteoarthritis. The role of joint-specific factors and coping styles on disability, the... Show moreThis thesis has provided more knowledge on the disease course and its determinants of outcome in hand osteoarthritis. The role of joint-specific factors and coping styles on disability, the prevelance of aesthetic dissatisfaction, its impact on daily life and their determinants were evaluated. Additionally, the association between MR Imaging features with hand pain and the association of MR Imaging features with radiographic progression were investigated. Another part of the thesis focused on the association between osteoarthritis and mortality. Show less
SDHD-related head and neck paragangliomas are, hereditary and generally benign, neuroendocrine tumors that arise from paraganglionic tissue associated with the parasympathetic nervous system.... Show moreSDHD-related head and neck paragangliomas are, hereditary and generally benign, neuroendocrine tumors that arise from paraganglionic tissue associated with the parasympathetic nervous system. The primary aim of this thesis was to gain more insight in the natural course of SDHD-related head and neck paragangliomas and ultimately improve surveillance and treatment strategies, as well as counseling of both patients and their family members. The risk of occult and metachronous paragangliomas, tumor growth, clinical progression and survival of SDHD germline mutation carriers were addressed. Show less
The comorbidities of epilepsy include those conditions, somatic and psychiatric, that are associated with epilepsy. These associations with epilepsy may be direct and indirect, causal and spurious.... Show moreThe comorbidities of epilepsy include those conditions, somatic and psychiatric, that are associated with epilepsy. These associations with epilepsy may be direct and indirect, causal and spurious. The comorbidities of epilepsy are relevant in that they provide an opportunity to improve our understanding of the pathophysiology of epilepsy, as well as allow us to better understand factors determinant of outcome. This PhD thesis examines the comorbidities of epilepsy, as a general construct, delving into particular examples, and finally demonstrating its impact on premature mortality in epilepsy. Show less
Current evidence on older adults is derived from population-based cohort studies and randomized controlled trials, which may not include frail individuals. Data are lacking on older outpatients, a... Show moreCurrent evidence on older adults is derived from population-based cohort studies and randomized controlled trials, which may not include frail individuals. Data are lacking on older outpatients, a potentially diverse population. Therefore, we initiated the Milan Geriatrics 75+ Cohort Study, a prospective hospital-based outpatient cohort study. Chapter 1 of this thesis provides a background on the controversies regarding the homeostasis of older adults. Chapter 2, 3 and 4 report findings from the Milan Geriatrics 75+ Cohort Study. Chapter 2 explores the association between blood pressure and cognition, and whether it varies according to age and functional status. Chapter 3 examines the relationship between blood pressure and mortality risk, and whether it varies according to functional and cognitive status. Chapter 4 investigates the association between thyroid status and mortality risk in euthyroid older adults, and whether it differs by sex and age. Chapter 5 and 6 report findings from the PROSPER cohort, which includes older adults at high cardiovascular risk. Chapter 5 presents new evidence on the association of heart rate and heart rate variability with functional decline. Chapter 6 analyses the relationship between blood pressure variability and functional decline. Chapter 7 summarises and discusses the main findings of this thesis. Show less
This thesis aimed to identify possible risks associated with erythropoiesis-simulating agent (ESA) use. First, trends in anemia management are described, showing less ESA use in Swedish patients... Show moreThis thesis aimed to identify possible risks associated with erythropoiesis-simulating agent (ESA) use. First, trends in anemia management are described, showing less ESA use in Swedish patients with chronic kidney disease (CKD) and less ESA-treated patients had a hemoglobin above 12 g/dL. Furthermore it is shown that ESA- treated pre-dialysis patients in the Netherlands received more antihypertensive agents than patients without ESA, confirming the hypertensive effect of ESA. However, no relevant difference in routinely measured blood pressure was observed between patients with and without ESA treatment, thus the hypertensive effect of ESAs could be controlled in clinical practice. In addition, no excess of thrombotic events was shown in ESA-treated dialysis patients compared to patients without ESA treatment. In contrast, a higher risk of cardiovascular events with ESA use was indicated in Danish patients with multiple myeloma and myelodyslastic syndrome. Also, with two analytical approaches, a harmful effect of high ESA doses on mortality was indicated in Dutch dialysis patients. Last, it was shown that ESA resistance was associated with mortality in both hemodialysis and peritoneal dialysis patients. To conclude, treatment with high ESA doses was associated with a higher risk of mortality, but the mechanism is largely unknown. Show less
With increasing age, incidence and prevalence of cardiovascular disease increase. Many physicians face the dilemma whether or not to start preventive treatment in old age. To help physicians decide... Show moreWith increasing age, incidence and prevalence of cardiovascular disease increase. Many physicians face the dilemma whether or not to start preventive treatment in old age. To help physicians decide whether to advise preventive medication to their older patients, prediction of those at highest or lowest (relative) risk using (preferably) inexpensive and easy to use cardiovascular risk factors is important. However, in old age there is a lack of good cardiovascular risk predictors. This thesis shows that the use of multiple blood pressure measurements expressed in the variability (in diastolic blood pressure) or trends in blood pressure can identify older persons with high cardiovascular risk. It also shows that in the oldest old, the absence or presence of heart failure does not influence the prognostic value of low systolic blood pressure regarding risk of death. The serological biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP) is found to be an interesting candidate in cardiovascular risk prediction in old age, especially in secondary prevention. In the oldest old, an increase in NT-proBNP still reflects increased risk of (cardiovascular) death, independent of decreasing renal function and is associated with incident heart failure and atrial fibrillation. Show less
Patients with end-stage renal disease have an approximate eight fold increased mortality rate due to cardiovascular causes as compared with individuals of equal age and sex without renal... Show morePatients with end-stage renal disease have an approximate eight fold increased mortality rate due to cardiovascular causes as compared with individuals of equal age and sex without renal dysfunction. Whereas traditional cardiovascular risk factors (such as smoking, hypertension and obesity) fail to completely explain this surplus in risk, nontraditional risk factors seem of pathophysiological importance. This thesis aimed at studying the impact of an increased inflammatory state and nonthyroidal illness as potential nontraditional cardiovascular risk factors in patients with end-stage renal disease. Show less
This thesis aims to assess clinical characteristics of paraganglioma (PGLs) patients, with focus on SDH mutation carriers, evaluate psychological aspects in these subjects and to review various... Show moreThis thesis aims to assess clinical characteristics of paraganglioma (PGLs) patients, with focus on SDH mutation carriers, evaluate psychological aspects in these subjects and to review various treatment options for PGLs. Show less
H2: Hensgens MP, Goorhuis A, Notermans DW, van Benthem BH, Kuijper EJ. Decrease of hypervirulent Clostridium difficile PCR ribotype 027 in the Netherlands. Euro Surveill. 2009 H3: Hensgens MP,... Show moreH2: Hensgens MP, Goorhuis A, Notermans DW, van Benthem BH, Kuijper EJ. Decrease of hypervirulent Clostridium difficile PCR ribotype 027 in the Netherlands. Euro Surveill. 2009 H3: Hensgens MP, Keessen EC, Squire M, Riley TV, Koene MG, de Boer E, Lipman LJ, Kuijper EJ. Clostridium difficile infection in the community: a zoonotic disease? Clin Microbiol Infect. 2012 H4: Hensgens MP / Goorhuis A, van Kinschot CM, Crobach MJ, Harmanus C, Kuijper EJ. Clostridium difficile infection in an endemic setting in the Netherlands. Eur J Clin Microbiol Infect Dis. 2011 H5: Hensgens MP, Goorhuis A, Dekkers OM, Kuijper EJ. Time-interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother. 2012 H7: Hensgens MP, Goorhuis A, Dekkers OM, van Benthem BH, Kuijper EJ. Outcome of nosocomial Clostridium difficile infections; results of a multicenter cohort study. Clin Infect Dis. 2013 H8: Hensgens MP / Bauer MP, Miller M, Gerding DN, Wilcox MH, Dale AP, Fawley WN, Kuijper EJ, Gorbach SL. Renal failure and leukocytosis are predictors of a complicated course of Clostridium difficile infection (CDI) if measured on day of diagnosis. Clin Infect Dis. 2012 H9: Hensgens MP, Kuijper EJ. Clostridium difficile infection due to binary toxin positive strains. Emerg Infect Dis. 2013 H10: Hensgens MP, Dekkers OM, Goorhuis A, Le Cessie S, Kuijper EJ. Predicting a severe course of Clostridium difficile infection at the bedside. Clin Microbiol Infect. 2012 Show less
The aim of this thesis was to identify new risk factors for first and recurrent venous thrombosis of both the upper and lower extremity, and assess the incidence of recurrence and mortality after a... Show moreThe aim of this thesis was to identify new risk factors for first and recurrent venous thrombosis of both the upper and lower extremity, and assess the incidence of recurrence and mortality after a first venous thrombosis. An overview was provided of the current literature on risk factors and treatment for a first venous thrombosis of the upper extremity (chapter 2). We investigated the association between levels of coagulation factors, blood group and a first venous thrombosis of the upper extremity (chapter 3), and studied risk factors for a recurrent event in patients with a first venous thrombosis of the upper extremity (chapter 4). Furthermore, we studied the association between venous thrombosis and long-term mortality (chapter 5). In this study we found that patients with thrombosis died more of chronic obstructive pulmonary disease (COPD) than expected from population figures. COPD was found to be a risk factor for a first venous thrombosis in chapter 6. We studied the incidence of recurrent venous thrombosis, as well as sex, age and an idiopathic first venous thrombosis as risk factors for recurrence (chapter 7). Body height was studied as a risk factor for both first and recurrent venous thrombosis in combination with mobility (chapter 8). Show less
This thesis describes the epidemiology of emerging infections with Clostridium difficile. Outbreaks of severe disease with high mortality were found to be associated with certain types of this... Show moreThis thesis describes the epidemiology of emerging infections with Clostridium difficile. Outbreaks of severe disease with high mortality were found to be associated with certain types of this bacterium and type specific risk factors were identified. Moreover, highly discriminatory typing techniques were useful in understanding clonal disseminations across healthcare institutions. Show less
In the Netherlands 1 of 1.000 inhibitants undergo cardiac surgery annually. To compensate blood loss these patients receive often blood transfusions, which can cause unexpected adverse reactions.... Show moreIn the Netherlands 1 of 1.000 inhibitants undergo cardiac surgery annually. To compensate blood loss these patients receive often blood transfusions, which can cause unexpected adverse reactions. Allogeneic leukocytes may play a prominent role in the development of these adverse reactions. We found in a randomized trial in cardiac valve surgery that patients receiving buffy-coat depleted (which contain 20-30% donor leukocytes) red blood cell (RBC) transfusions had dose-dependently higher hospital-mortality and postoperative infections than patients receiving leukocyte-depleted RBCs. Cost-effectiveness analysis revealed that leukodepletion of RBCs reduces the costs after cardiac valve surgery. Additional analyses revealed that plasma transfusions were associated with mortality and platelet transfusions with postoperative infections and longer ICU-stay. Patients who received more than 3 red blood cell units had significantly higher cytokine IL-6 concentrations after leukocyte-containing, buffy-coat depleted red blood cells (RBC) as compared to patients who had received similar numbers of leukocyte-depleted RBC units. Patients who developed postoperative infections and multiple-organ-dysfunction-syndrome showed, respectively, increased concentrations of cytokines IL-6 and IL-12 in the group that received leukocyte-containing RBCs. This laboratory analysis suggests that buffy-coat depleted erythrocytes may affect the development of postoperative complications by modulation of the postoperative proinflammatory response after cardiac surgery. Show less
Op de lijst van potentiële 'hot topics' voor de komende EU-verkiezingen vinden we vergrijzing, economische malaise en de vraag met welke maatregelen Europa's lage geboortecijfers opgekrikt kunnen... Show moreOp de lijst van potentiële 'hot topics' voor de komende EU-verkiezingen vinden we vergrijzing, economische malaise en de vraag met welke maatregelen Europa's lage geboortecijfers opgekrikt kunnen worden. De problematiek van de nog verse 21ste eeuw. Maar die is niet zonder precedenten volgens oud-historici gespecialiseerd in de sociaal-economische en demografische geschiedenis van Romeins Italië. De laatste twee eeuwen voor Christus, toen Rome van een stadstaatje tot een wereldrijk werd, waren roerige tijden voor de burgers van Italië. Zij werden betrokken in oorlogen, waren getuige van grootscheepse politieke veranderingen en leefden met snel groeiende immigranten en slaven in een nog sneller verstedelijkende samenlevering, volop dynamiek, dus. Lang werd gedacht dat het bestaan van de 'oude kern' van Romeinen temidden van deze hectiek van meerdere kanten af werd uitgehold. Met, inderdaad, economische maliase en vergrijzing en ontvolking als gevolg. Deze dissertatie betoogt echter dat het allemaal wel meeviel. Terwijl burgers met in name de landbouwsector in de regio rond Rome getroffen werd, groeiden de kansen in andere sectoren van de Romeinse economie. Gunstige klimaatomstandigheden en de voordelen van imperialise verzachten de problematiek. De economische schade bleef, met andere woorden, beperkt. En die baby's dan? Hier speelden specifieke culturele en sociale omstandigheden een rol. Een 'mamacultuur'en het dorpsleven met familie en buren nabij, ondervingen een goed deel van de potentieel nagatieve gevolgen van armoede voor het Romeinse geboortecijfer. Deze en andere factoren doen vermoeden dat de periode zelfs, in tegenstelling tot wat eerder gedacht werd, ruimte liet voor bevolkingsgroei. Een gedachte die aansluiting vindtin een nieuwe interpretatie van de met raadsels omgeven volkstellingscijfers van Rome's eerste keizer, Augustus. Doemdenkers en pessimisten onder oudere generaties oud-historici lijken daarmee door de geschiedenis te worden ingehaald. Een geruststellend lichtpuntje anno 2009 Show less
