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
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
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
Patients__ perceptions can influence their responses to end-stage renal disease (ESRD) and dialysis, and subsequent health outcomes such as health-related quality of life (HRQL) and survival. This... Show morePatients__ perceptions can influence their responses to end-stage renal disease (ESRD) and dialysis, and subsequent health outcomes such as health-related quality of life (HRQL) and survival. This thesis explores the association between illness perceptions and health outcomes of patients on dialysis. For example, we found a single self-rated health (SRH) item: __How would you say your health is in general__ to be a strong predictor of mortality. Patients who perceive their health as poor, fair or good had a higher mortality risk than those with excellent/very good health, independent of a range of risk factors. Compared with haemodialysis (HD) patients, peritoneal dialysis (PD) patients reported more personal control and had a better understanding of the illness. Patients who perceived having more symptoms, more consequences and lower personal control reported poorer HRQL. In terms of social support, both HD and PD patients who perceived a discrepancy between the received and expected levels of social companionship, daily emotional support, and total support had a higher risk of mortality. However, patients who received or perceived having inadequate emotional support with problems had no higher mortality risks. Therefore, different aspects of social support is of varying importance to dialysis patients. Show less
Lifespan in under genetic control. In this thesis we translated genes regulating lifespan in model organisms to humans. First we identified DAF-12 as a critical gene for lifespan regulation in the... Show moreLifespan in under genetic control. In this thesis we translated genes regulating lifespan in model organisms to humans. First we identified DAF-12 as a critical gene for lifespan regulation in the nematode worm C. elegans. Then we found that the Liver X Receptors and the Vitamin D Receptor are the most similar human proteins. We tested these genetic variation in these human genes in the Leiden 85-plus Study and found them to associate with with lifespan and cognitive decline respectively. Apolipoprotein E is a target gene of the Liver X Receptor. We found that plasma levels of apolipoprotein E associated with increased risk of cardiovascular mortality, cognitive decline and stroke in a manner independent of classical cardiovascular risk factors. Finally we reviewed the evidence from human candidate gene studies. We conclude that the use of model organisms provides useful directions for research into the genetics of human longevity. However, as the human signalling systems are more complex and our environment is different from that of model organisms, it is unclear to what extent results obtained in model organisms can be extrapolated to humans. Show less
This thesis describes the results of the Leiden Follow-Up Project on Prematurity (LFUPP): a prospective study in three health regions in the Netherlands, which included all live born infants with... Show moreThis thesis describes the results of the Leiden Follow-Up Project on Prematurity (LFUPP): a prospective study in three health regions in the Netherlands, which included all live born infants with gestational age (GA) <32 weeks, born in 1996/1997. Mortality, neonatal morbidity and the neurological examination as well as mental and psychomotor development according to the BSID I are described until the corrected age of 2 years. Special attention is paid to the infants with GA <27 weeks and the ethics of maintaining these extremely preterm infants. Growth (length, weight and head circumference) until 2 years of age is compared with the Dutch reference group. The influence of preterm growth restraint is compared with the influence of intrauterine growth restriction. The development and respiratory status at 2 years of age in infants with bronchopulmonary dysplasia are described. Finally, a comparison was made between the outcome of 2 cohorts, POPS (1983) and LFUPP (1996/1997) at time of hospital discharge and at 2 years of age. Show less
Colorectal cancer is one of the most common malignancies in the world. A family history of colon cancer has been shown to increase an individual’s risk of developing the disease. Approximately 2-3%... Show moreColorectal cancer is one of the most common malignancies in the world. A family history of colon cancer has been shown to increase an individual’s risk of developing the disease. Approximately 2-3% of all colorectal cancers occur in the setting of a well described autosomal dominant inherited syndrome: The Lynch syndrome. It is essential to identify individuals at increased risk to offer adequate surveillance programs to prevent the development of tumors or recognize them at an early stage. This thesis gives a laboratory workup of suspected Lynch syndrome, including analysis of tumor tissue by microsatellite instability analysis and immunohistochemistry, and germline DNA analysis. Several aspects of surveillance in Lynch syndrome are described. The appropriate screening interval is discussed and the effect on mortality because of surveillance is shown. Further, we sought to establish whether individuals from dominant families without mismatch repair deficiency are also at increased risk by examining the incidence of advanced neoplasia during surveillance. Finally, the prevalence of the frequency of a positive family history for CRC, within a random cohort among the Dutch population is presented and also the prevalence of adenomas among young individuals at average risk for colorectal cancer is shown. Show less
Nonfunctioning pituitary macroadenomas are benign tumors of the pituitary. In this thesis the natural course, optimal treatment strategy and the effect of the disease on quality of life are assessed.
