Pulmonary embolism (PE) is a serious and sometimes life-threatening condition that refers to a blood clot that occludes the arteries of the lung. Despite all improvements over the past decades,... Show morePulmonary embolism (PE) is a serious and sometimes life-threatening condition that refers to a blood clot that occludes the arteries of the lung. Despite all improvements over the past decades, diagnosing PE is still a difficult process due to the non-specific symptoms, which can frequently overlap with symptoms of other cardiopulmonary diseases. Currently recommended diagnostic strategies for suspected acute PE consist of standardized assessment of the clinical pre-test probability (CPTP) using validated clinical decision rules (CDRs) and D-dimer testing. PE is considered safely ruled out in patients with a non-high CPTP and a normal D-dimer test. Imaging tests as computed tomography pulmonary angiography (CTPA) are required in the case of a high CPTP and/or abnormal D-dimer test to confirm the diagnosis. The first part of this thesis describes the challenges of diagnosing PE in general and in specific clinically relevant patient subgroups. Moreover, this part evaluates the diagnostic performance of non-invasive diagnostic strategies for suspected PE in specific relevant patient subgroups. The second part of this thesis focuses on venous thrombotic complications in hospitalized patients with COVID-19. Show less
Research on the prevalence, diagnostic and prognostic value for treatment of personality pathology – i.e., both personality disorders and problematic personality characteristics – was... Show more Research on the prevalence, diagnostic and prognostic value for treatment of personality pathology – i.e., both personality disorders and problematic personality characteristics – was carried out within a mainly Dutch forensic mental health setting. Issues such as (dis)simulation and unintentional self-deception limit the utility of self-report instruments within a pre-trial setting. Personality disorders and psychopathic traits in suspected offenders in the Netherlands often lead to court rulings of enforced psychiatric treatment – an internationally unique situation. A prospective study on the predictive value of personality disorder isolated factors that can affect enforced treatment length, such as crime type and comorbidity, that can be a focus for policy makers and forensic mental health experts. Caution is advised when using self-report instruments within the forensic context, especially in the absence of response bias scales and in the case of (legal) incentives for certain outcomes. There is urgent need for international standardization of instruments and terminology and a test battery that is specifically designed for and validated within forensic populations. An increase in (detail of) digital registration of patient, treatment and risk characteristics is necessary for meaningful scientific research, a better assessment of personality and risks, fewer incidents, lower recidivism and shorter treatment. Show less
This thesis consists of a number of studies revolving around the leading research theme, i.e., the derivation of new vectorcardiographic diagnostic & prognostic information from the 12-lead... Show moreThis thesis consists of a number of studies revolving around the leading research theme, i.e., the derivation of new vectorcardiographic diagnostic & prognostic information from the 12-lead electrocardiogram (ECG). Various research questions have been addressed, but most studies use a similar data processing approach, consisting of initial mathematical synthesis of a vectorcardiogram (VCG) from a standard 12-lead ECG, followed by the measurement of general VCG characteristics like maximal QRS- and T vectors, QRS- and T integrals, the spatial QRS-T angle (SA) and the ventricular gradient (VG). Studies focus on methodological as well as on clinical issues, and are discussed in the thesis. Show less
Distale radius fracturen komen veel voor. Bij ongeveer de helft van de distale radius fracturen komt een processus styloideus ulnae (PSU, distale ulna fractuur) voor. Een PSU fractuur is een... Show moreDistale radius fracturen komen veel voor. Bij ongeveer de helft van de distale radius fracturen komt een processus styloideus ulnae (PSU, distale ulna fractuur) voor. Een PSU fractuur is een indicator voor toegenomen instabiliteit. In een meta-analyse wordt geen verschil aangetoond in uitkomst van een distale radius fracturen met of zonder PSU fractuur. Hetzelfde geldt voor het al dan niet vastgroeien van het PSU. In ongeveer 33% van de distale radius fracturen komt distale radioulnaire (DRU) instabiliteit voor. Klinische testen en radiologische onderzoeken om dit te diagnosticeren zijn weinig betrouwbaar. Een CT-scan additioneel aan een r_ntgenfoto zorgt niet voor toename in overeenstemming over de uitslag. De overeenstemming tussen beoordelaars van CT-scans valt tegen, naast een grote normale spreiding. Wanneer DRU instabiliteit gediagnostiseerd is, zal de ossale anatomie genormaliseerd moeten worden. In dit proefschrift worden operatie-technieken beschreven die veilig en effectief zijn voor het oplossen van DRU instabiliteit. De auteur concludeert dat DRU instabiliteit een diagnostisch dilemma is. Onderzoek zal zich moeten richten op individuele normaalwaarden, zodat de diagnose makkelijker te stellen is. De aanbeveling wordt gedaan dat distale radius fracturen behandeld dienen te worden door gespecialiseerde teams zodat de complicaties beperkt blijven en indien nodig herkend en optimaal behandeld worden. Show less
Venous thromboembolism is a common disease that can lead to potential fatal complications. The diagnosis and treatment of a first venous thromboembolism has been well studied, however the... Show moreVenous thromboembolism is a common disease that can lead to potential fatal complications. The diagnosis and treatment of a first venous thromboembolism has been well studied, however the diagnostic management and therapy of recurrent venous thromboembolism still have limitations. This thesis discusses a new imaging technique for recurrent deep venous thrombosis and the duration of treatment after a recurrent venous thromboembolism. It shows that Magnetic Resonance Direct Thrombus Imaging might be a potential diagnostic tool for the diagnostic management of recurrent venous thromboembolism. Furthermore the prognosis after a first deep vein thrombosis is discussed by means of recurrence and bleeding risks. Show less
Spondyloarthritis (SpA) is a heterogeneous group of rheumatic diseases, characterized by sacroiliac-joint inflammation (sacroiliitis), peripheral and extra-articular complaints. The lack of... Show moreSpondyloarthritis (SpA) is a heterogeneous group of rheumatic diseases, characterized by sacroiliac-joint inflammation (sacroiliitis), peripheral and extra-articular complaints. The lack of diagnostic criteria makes diagnosing SpA challenging, yet, classification criteria are available. We tested the performance (sensitivity, specificity) of various classification criteria; the recently developed Assessment of SpondyloArthritis international Society (ASAS) criteria outperformed all other criteria. We investigated the discrepancies in interpretation MRIs and conventional radiographs on the presence of sacroiliitis; agreement on radiographic sacroiliitis between different readers is only moderate, but agreement regarding sacroiliitis on MRI is substantial. Rheumatologists take into account all clinical and laboratory results in addition to the imaging results in the diagnostic process. The diagnostic Berlin algorithm - in which all relevant results are taken into account __ can assist rheumatologists. We proposed a modification of this algorithm, which is accepted by ASAS and also included in the recently published guidelines for the diagnosis and treatment of SpA by the Dutch Society for Rheumatology. Besides, we performed systematic literature reviews, forming the base for the update of the ASAS management recommendations. With these results, SpA-patients can be recognized earlier, offering better treatment options and better outcomes. However, further improvements of care for SpA-patients are necessary. Show less
Since a decade, Clostridium difficile infection (CDI) has increased progressively in incidence and severity of disease. Currently, CDI is considered the leading cause of nosocomial diarrhoea,... Show moreSince a decade, Clostridium difficile infection (CDI) has increased progressively in incidence and severity of disease. Currently, CDI is considered the leading cause of nosocomial diarrhoea, associated with an increased duration of hospitalization, healthcare expenses, morbidity and mortality. This thesis describes our findings with outbreak control, diagnosis, identification of specific risk factors and treatment of CDI after the discovery of the emergence of C. difficile PCR-ribotype 027 in the Netherlands. The studies illustrate the role of antibiotics in relation to persistence, severeness and spreading of CDI. Antibiotics are shown to be a primary risk factor for the development of (ribotype-specific) CDI and an essential part of the outbreak control measures (__bundle-approach__), namely antibiotic stewardship. The use of antibacterials is a risk for selection of novel endemic C. difficile strains in e.g. animals, which introduce an increasing risk of alternative zoonotic transmission routes. Except for very mild CDI, which is clearly induced by usage of specific antibiotics, antibacterial treatment is advised. This thesis reviews the comparative effectiveness of the currently available treatment modalities, thereby providing evidence-based recommendations for CDI remedies. Treatment options include: oral and non-oral antibiotics, toxin-binding resins and polymers, immunotherapy, probiotics, faecal or bacterial intestinal transplantation. 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
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
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
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
In the first part of this thesis we described two new diagnostic algorithms for patients with clinically suspected deep venous thrombosis and pulmonary embolism. These management strategies include... Show moreIn the first part of this thesis we described two new diagnostic algorithms for patients with clinically suspected deep venous thrombosis and pulmonary embolism. These management strategies include both pretest clinical probability and D-dimer assay, and reduce the need for non-invasive imaging tests. These novel strategies are safe in excluding deep venous thrombosis and pulmonary embolism. The results of the first part of this thesis led to a different, more simple diagnostic strategy in patients with venous thromboembolism. In the second part of this thesis we described two follow-up studies which led to the identification of new risk factors and early predictors for PTS. At present, the results of these studies enable us to provide individualized information to patients with a first deep venous thrombosis about their risk for the development of PTS. Future research should focus on validating and standardizing diagnostic criteria for PTS. A standardized diagnosis is necessary to improve the uniformity of the diagnosis and to enhance the ability to compare results of different studies. Moreover, objective diagnosis of PTS will allow physicians to monitor the development and course of PTS in their own patients. Show less
Schistosomiasis, also known as bilharzia, is a disease that still occurs in many parts of Africa, the Middle East and Southern America, mainly Brasil and the Caribbean. Schistosomiasis is, after... Show moreSchistosomiasis, also known as bilharzia, is a disease that still occurs in many parts of Africa, the Middle East and Southern America, mainly Brasil and the Caribbean. Schistosomiasis is, after malaria, the second most common parasitic infection. Currently 200 million people are infected with the worms that cause the disease. Schistosoma mansoni is the most common schistosome species that infects humans. The schistosome produces many different sugar structures (glycans) that are not made by humans. Central to this thesis are sugar structures with a __double fucose__. Such fucosylated glycans are mainly produced by the eggs, which play a major role in the disease schistosomiasis. The human immune defence system responds to these parasite glycans in several ways. High antibody responses have been measured against sugar structures with a __double fucose__ moiety and different types of immune cells interact with these glycan structures. Despite these immunological responses the human host is not able to clear the parasitic infection. Glycans are thought to play a role in the mechanisms that S. mansoni has developed to survive in the hostile environment of the human blood. In this thesis the structures of several glycans containing the __double fucose__ moiety have been characterised using different mass spectrometric techniques. Show less
Human schistosomiasis (bilharzia) is one of the major parasitic diseases in the world, affecting 200 million people predominantly in third world countries. In areas where the disease is highly... Show moreHuman schistosomiasis (bilharzia) is one of the major parasitic diseases in the world, affecting 200 million people predominantly in third world countries. In areas where the disease is highly prevalent it causes important health problems, and it also has socially-economic effects on the population. Schistosomiasis is caused by the presence of the blood-fluke Schistosoma in the blood-vessels of mammalian hosts. The current method for diagnosis of schistosomiasis in developing countries is the parasitological examination of urine and faeces for the presence of Schistosoma eggs. An alternative method which is now increasingly used is based on the detection of Schistosoma antigens in the circulatory system or the urine of the host. The gut of the parasite is an important source of these antigens since many gut-associated antigens are excreted into the circulation of the host following digestion of food (e.g. blood cells, proteins) by the parasite. Two major gut–associated antigens which have been thoroughly studied with regard to diagnostic detectability, are the circulating anodic antigen (CAA) and the circulating cathodic antigen (CCA). In this thesis, these two unique antigens are further analysed with respect to their biochemical carbohydrate structure, localization, in vitro and in vivo excretion and detection patterns, and their role in a number of host-parasite immune interactions (granulocytes, complement system). Show less
