The objectives of this thesis are to simplify, to validate and compare diagnostic strategies in patients with clinical suspicion of acute pulmonary embolism (PE). The revised Geneva score was... Show moreThe objectives of this thesis are to simplify, to validate and compare diagnostic strategies in patients with clinical suspicion of acute pulmonary embolism (PE). The revised Geneva score was simplified and validated. Furthermore, four widely used clinical decision rules (CDRs) were directly compared in excluding PE. It was concluded that the four CDRs in combination with a D-dimer test performed similarly in the exclusion of acute PE. And we confirmed that a normal CT-scan alone can safely exclude PE in patients in whom CTPA is required to rule out VTE in these patients. We showed that the algorithm consisting of a CRD, D-dimer test and CT-scan is also effective in the management of patients with clinically suspected recurrent acute PE. In addition, the role of NT-pro-BNP has been evaluated for the risk assessment for adverse clinical outcome for patients with proven acute PE and we showed the ability to distinguish an increased risk with elevated NT-pro-BNP values for complications during the hospital stay and 30-day mortality. Finally, it is concluded that home treatment with anticoagulant seems effective and safe in patients with acute PE, when selected according to pre defined criteria. Show less
Laarse, A. van der; Cobbaert, C.M.; Gorgels, A.P.M.; Swenne, C.A. 2013
To improve patient outcome, point-of-care (POC) cardiac troponin I/T (cTn I/T) tests applied in a prehospital setting and/or emergency department might play a role as a substitute for central... Show moreTo improve patient outcome, point-of-care (POC) cardiac troponin I/T (cTn I/T) tests applied in a prehospital setting and/or emergency department might play a role as a substitute for central hospital laboratory high-sensitivity (hs) cTn I/T testing if their analytical and clinical performance are equivalent to central hospital laboratory hs cTn I/T tests and if they fulfill an unmet clinical need in the diagnostic work-up of patients with acute coronary syndrome (ACS). To date, current point-of-care (POC) cTn I/T tests are not yet sufficiently analytically sensitive and do not provide accurate and precise values in the reference range nor at the 99th percentile of a healthy reference population. Awaiting the development of improved hs POC cTn I/T tests, current POC cTn I/T tests should be combined with ECG as it takes several hours to detect a rise of cTn I/T in the circulation whereas ischemia-induced ECG changes may be observed soon after onset of chest pain. Although patients with acute ST-segment elevation myocardial infarction (STEMI) are generally diagnosed by ischemic symptoms and ECG only, hospitalized patients with non-STEMI and unstable angina pectoris (UAP) should preferentially be tested with ECG and central hospital laboratory hs cTn I/T tests unless the ECG has already demonstrated diagnostic changes. More evidence and future trials are needed to find out whether in patients with NSTE ACS hs cTn I/T tests should be combined with other tests, such as a test of B-type natriuretic peptide or NT-proBNP. Show less
The current health care system is severely challenged by for instance rising costs, fewer new blockbuster drugs and increasing numbers of hospitalizations due to side effects. Especially in the... Show moreThe current health care system is severely challenged by for instance rising costs, fewer new blockbuster drugs and increasing numbers of hospitalizations due to side effects. Especially in the area of chronic diseases the current disease fighting strategy is failing and a more personalized medicine approach is needed. In this thesis new sub-types of rheumatoid arthritis are characterized with metabolomics analysis and symptoms patterns. The sub-types are based on diagnostic knowledge from Chinese medicine. The two sub-types of RA patients were found to have differences in apoptosis regulation of T-cells and differences in urine acylcarnitine levels. A questionnaire was designed to distinguish the two sub-types and to evaluate symptom patterns of arthritis patients. In the future the response to treatment of these sub-types of patients can be studied and specific treatment can be targeted to these sub-types. Show less
In this dissertation we present the results of our research on Helicobacter pylori infections in childhood, focusing on the prevalence, diagnosis and treatment of the infection. Our studies were... Show moreIn this dissertation we present the results of our research on Helicobacter pylori infections in childhood, focusing on the prevalence, diagnosis and treatment of the infection. Our studies were conducted in the Netherlands, Europe and Indonesia. We discuss diagnostic tests, therapeutic regimens, resistance and preventive measurements. We highlight clinical and pathophysiological aspects of the infection and describe which particular strains are prevalent and how transmission occurs. Presently, there are no established correlations between a Helicobacter pylori infection and recurrent abdominal pain, gastroesophageal reflux disease or growth retardation. We present data on the prevalence of Helicobacter pylori in young infants in the Netherlands and observe that children with at least one non-Dutch parent form a risk group. We assess risk factors in a Europe-wide study on gastroduodenal erosions and ulcers in childhood. In our study, Helicobacter pylori infection and gastrotoxic medications were relatively little implicated as etiology of that pathology. The prevalence of Helicobacter pylori infection in Indonesian young children is relatively high and points at an early acquisition of the infection. Finally, the resistance of Helicobacter pylori to clarithromycin and metronidazole was assessed for adults and children in the Netherlands. Low resistance rates were found, but the resistance in adults is increasing. We conclude that a test-and-treat regimen is justified for the Netherlands. Show less
Non-invasive imaging plays an increasingly important role in the diagnosis and risk stratification of coronary artery disease. Several techniques such as stress echocardiography and myocardial... Show moreNon-invasive imaging plays an increasingly important role in the diagnosis and risk stratification of coronary artery disease. Several techniques such as stress echocardiography and myocardial perfusion imaging have become available to assess cardiac function and myocardial perfusion. With the arrival of multi-slice computed tomography coronary angiography (CTA), non-invasive imaging of coronary anatomy has also become possible. CTA is a relatively new imaging technique; the objective of the thesis is therefore to explore the value of CTA for diagnosis and risk stratification of CAD in patients presenting with suspected and known CAD, in order to further define its role in clinical practice. The results of this thesis show that CTA provides important diagnostic information relative to existing non-invasive imaging strategies. In addition the detailed anatomic information obtained using CTA was shown to provide important prognostic information. CTA supplies complementary information to existing non-invasive imaging techniques, and has the potential to provide a more patient tailored approach to patient management. What remains to be determined is how CTA and non-invasive functional imaging should be integrated into clinical practice. Show less
The first chapters of this thesis describe the treatment of radioiodine non-avid thyroid carcinoma with the tyrosine kinase inhibitor sorafenib. The remainder of the thesis describes the clinical... Show moreThe first chapters of this thesis describe the treatment of radioiodine non-avid thyroid carcinoma with the tyrosine kinase inhibitor sorafenib. The remainder of the thesis describes the clinical consequences of the treatment of thyroid carcinoma. Show less
Bildt, A. de; Oosterling, I.J.; Lang, N.D.J. van; Sytema, S.; Minderaa, R.B.; Engeland, H. van; ... ; Jonge, M.V. de 2011
The therapy of choice in patients suffering from differentiated thyroid cancer (DTC), subdivided into papillary and follicular thyroid carcinoma, is (near-)total thyroidectomy. This is routinely... Show moreThe therapy of choice in patients suffering from differentiated thyroid cancer (DTC), subdivided into papillary and follicular thyroid carcinoma, is (near-)total thyroidectomy. This is routinely followed by the administration of radioiodine (RaI)-131 (131I) to destroy any remaining benign or malignant thyroid tissue, so-called ablation. This thesis has addressed some important clinical questions, related to the application of conventional (131I) and experimental therapies with radionuclides in DTC. Iodine-131 has been used for many years to ablate thyroid remnants following thyroid surgery, but a single optimal activity has not yet been established. Two protocols are commonly used in the Netherlands: the uptake-related ablation strategy in which relatively low activities of 131I are used and the fixed-dose or tumor-related ablation strategy in which higher ablation activities are used. The main aim of this thesis was to study the short-term and long-term outcome parameters in DTC according to the uptake-related ablation protocol and to compare the success rates of both ablation strategies. Furthermore, we investigated whether there was a relation between ablation failure and pre-ablation 24-hour uptake measurement of 131I (by the so-called stunning effect). By assessing the prevalence of second primary tumors in patients treated for thyroid cancer we wanted to confirm that 131I can be used safely regarding long-term effects. Finally, this thesis focused on 111In-DTPA-octreotide scintigraphy and therapy as an alternative tool in progressive radioiodine non-responsive thyroid cancer. Show less
This thesis focuses on patients with Binge Eating Disorder. The thesis consists of three parts. In the first part the validity of the diagnosis of BED will be discussed. The results of two... Show moreThis thesis focuses on patients with Binge Eating Disorder. The thesis consists of three parts. In the first part the validity of the diagnosis of BED will be discussed. The results of two literature reviews and an empirical cross-sectional study suggested that BED is a distinct eating disorder and should be added to a next version of the DSM. In the second part results of a randomized controlled trial were described. The effectiveness of cognitive behavioural therapy was compared to a waiting list control group. As expected, objective binge eating frequency, eating disordered psychopathology, and comorbid psychopathology decreased significantly in the CBT group whereas no reduction was found in the control (WLC) group. Mediator analyses indicated that abstinence from binge eating at post treatment was fully mediated by changes in weight concerns and marginally by changes in concerns about shape and eating, depressive symptoms, and more general psychopathological symptoms. In the third and last part the results of two experimental studies were presented. The purpose of the studies was to investigate the causal relationship between negative mood and binge eating. Both experimental studies found evidence for the fact that in individuals with BED depressive symptoms and caloric intake are positively related. Show less
This thesis focuses on cellular immunity against mycobacteria during latency with the aim to contribute to improved immunodiagnosis of latent TB and to gain insight into immune responses which play... Show moreThis thesis focuses on cellular immunity against mycobacteria during latency with the aim to contribute to improved immunodiagnosis of latent TB and to gain insight into immune responses which play a role in controlling latent infection. Several new highly M. tuberculosis-specific peptides mixtures were identified to optimize the sensitivity of immunodiagnostic assays. The performance of interferon-gamma-release-assays (IGRA) for detection of latent TB were evaluated. Two short-incubation IGRA, QuantiFERON-TB Gold and T-SPOTTM.TB, were found to correlate better to the level of exposure to M. tuberculosis than the tuberculin skin test (TST), indicating that these assays are very sensitive for detection of recent infections. However, short-incubation IGRA are less sensitive than prolonged-incubation IGRA and TST for detection of latent TB acquired in the past. The search for proteins that are specifically targeted by the immune system during latency led to the identification of several antigens encoded within the DosR-regulon. This set of genes of M. tuberculosis is strongly upregulated by during in vitro models of latency. These antigens, including 16kDa _-crystallin, were preferentially recognized by latently infected individuals, which suggest that T-cell responses to latency antigens are associated with natural protection against reactivation of TB, warranting their further study as vaccine candidates. Show less
