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
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
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
