Diagnostic tests are performed for various reasons. Testing has both positive and negative effects on patient outcome. The main effects are indirect, mediated through treatment decisions and their... Show moreDiagnostic tests are performed for various reasons. Testing has both positive and negative effects on patient outcome. The main effects are indirect, mediated through treatment decisions and their impact on patient outcome. To base test decisions on expected net benefit, it is important to estimate or measure those effects in a structured manner. Positive and negative effects vary over the different stakeholders in test decisions: the healthcare provider, patient and society. While testing in a situation with low pre-test probability for a certain condition can be highly valued by patients, the associated costs of testing, with limited effect on patient outcome, diverts resources from societal areas with higher benefit. In this thesis we quantified the benefit of testing across different aspects of value of diagnostic information using a pediatric example, and provided argumentation and guidance for structured evaluation of existing screening programs. We explored practice variation in pediatric testing and interviewed pediatricians to elucidate their considerations in test decisions. The general discussion provides guidance on how to increase the efficiency and thus quality of testing through both system-level interventions and interventions directed at individual providers and patients. We argue that limiting testing in diagnostic situations with a (very) low pre-test probability is equally important as a structured evaluation of test consequences for efficient use of public resources. Show less
Leprosy is an infectious disease that affects peripheral nerves and can lead to severe lifelong disabilities. Despite the availability of an effective cure, a fairly stable number of about 200,000... Show moreLeprosy is an infectious disease that affects peripheral nerves and can lead to severe lifelong disabilities. Despite the availability of an effective cure, a fairly stable number of about 200,000 new leprosy patients per year has been reported since 2010. This stagnation shows that the transmission of the mycobacteria that cause leprosy, Mycobacterium leprae and Mycobacterium lepromatosis, is still taking place. Timely diagnosis of leprosy patients is therefore vital, so that the time frame in which a person is contagious is shortened, but also irreversible nerve damage and leprosy-associated disabilities can be prevented. However, tools that confirm the diagnosis of leprosy are not yet available. This thesis investigated which factors in blood (the so-called biomarkers) can help to diagnose leprosy. The clinical signs of leprosy have a spectral character and are influenced by the immune response of the host. A combination of biomarkers is described that is able to identify patients with a lot of bacteria (multibacillary) as well as the more difficult to diagnose patients with few bacteria (paucibacillary). Subsequently, these biomarkers have been implemented in user-friendly lateral flow assays, which have been extensively validated in leprosy endemic areas. Show less
Mitsikostas, D.D.; Ashina, M.; Craven, A.; Diener, H.C.; Goadsby, P.J.; Ferrari, M.D.; ... ; EHF Comm 2016