Even after thousands of years of experience in treating patients with TBI, decisions regarding the optimal treatment strategy remain difficult for both healthcare workers as policy makers. The... Show moreEven after thousands of years of experience in treating patients with TBI, decisions regarding the optimal treatment strategy remain difficult for both healthcare workers as policy makers. The first part of this thesis investigated the challenges of the treatment decision-making process in patients with (severe) TBI by focussing on three factors considered to be important in this process: patient outcome, in-hospital healthcare consumption, and in-hospital costs. The second part investigated the procedural difficulties in TBI research efficiency by focussing on the process of institutional review board approval and the use of informed consent procedures in patients with TBI with an inability to provide informed consent. Finally, we elaborate on the role of patient outcome and in-hospital costs in the acute treatment decision-making process in patients with severe TBI and make suggestions to optimize future research initiatives. Show less
In this thesis we aimed to investigate ways to optimize treatment strategies and the choice of treatment for individual patients, to be implemented in a worldwide context. Although major advances... Show moreIn this thesis we aimed to investigate ways to optimize treatment strategies and the choice of treatment for individual patients, to be implemented in a worldwide context. Although major advances have been made in the treatment of RA, it is still uncertain which treatment is the best choice for each individual patient. This can result in both overtreatment and undertreatment, increasing the burden of RA for patients as well as for society. In clinical trials and daily practice there appears to be a development towards earlier treatment, with higher dosages of medication and more stringent treatment targets. In part 1 of this thesis, some of these developments were investigated and challenged. In countries across the world, patients do not benefit similarly from recent advances in the treatment of RA. In part 2 of this thesis, we aimed to identify contributing factors to inequalities in access to treatment and care and clinical outcomes across countries, as a first step towards improvement. Show less
The Induction therapy with Methotrexate and Prednisone in Rheumatoid Or Very Early arthritic Disease (IMPROVED)-study is a multicentre two-step randomized single-blinded clinical trial in 610 early... Show moreThe Induction therapy with Methotrexate and Prednisone in Rheumatoid Or Very Early arthritic Disease (IMPROVED)-study is a multicentre two-step randomized single-blinded clinical trial in 610 early rheumatoid arthritis (RA) and undifferentiated arthritis (UA) patients. Intensive induction therapy (methotrexate (MTX) and a tapered high dose of prednisone) was started in the first 4 months. Treatment adjustments aimed at clinical remission (Disease Activity Score (DAS)<1.6): if DAS<1.6, medication was tapered and stopped, if DAS≥1.6, medication was intensified or restarted. Patients not in DAS-remission after 4 months were randomized to triple therapy (MTX, hydroxychloroquine and sulfasalazine) with prednisone (arm 1) or MTX+adalimumab (arm 2).After 4 months 61% was in DAS-remission (early DAS-remission group). After 5 years, 48% were in DAS-remission and 22% in drug-free remission (DFR). Patients in early DAS-remission group had better functional ability and more often achieved DAS-remission and DFR than patients that were randomized, without differences between the arms. UA patients had lower DAS and less autoantibody positivity at baseline compared to the RA patients. DAS-remission percentages were comparable between RA and UA patients, but more UA patients did achieve DFR (33% vs 19%). Autoantibody (rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA)) negative patients more often achieved DFR. Show less
The main objective of this thesis was to evaluate the role of new advanced multimodal CT imaging techniques in acute ischemic stroke.Important findings are that collateral assessment with dynamic... Show moreThe main objective of this thesis was to evaluate the role of new advanced multimodal CT imaging techniques in acute ischemic stroke.Important findings are that collateral assessment with dynamic CT angiography (CTA) better predicts radiological outcome and clinical outcome compared with conventional single-phase CTA. Dynamic CTA also enabled us to study dynamic cortical venous outflow in stroke which had not been described before. We have shown that venous outflow, as assessed with dynamic CTA, is a new predictor of functional outcome in acute large vesselvanterior circulation stroke. By combining the extent and velocity of optimal CVF, we observed a decreased risk of poor outcome in patients with good and fast optimal CVF. Moreover, we have demonstrated an interaction between IAT treatment effect and cortical venous filling which could potentially be useful for future treatment decision-making. Show less
Narcolepsy is a disorder of the regulation of sleep and wakefulness, with as its major features excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis and... Show moreNarcolepsy is a disorder of the regulation of sleep and wakefulness, with as its major features excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis and disturbed nocturnal sleep. The first part of this thesis concernes an overview of the pathophysiology, symptoms and treatment of narcolepsy type 1. The second part elaborates some pathophysiological aspects, focussing on the autoimmune hypothesis of narcolepsy. The third part focuses on alterations of temperature regulation and on measuring treatment effects of symptomatic treatment on sustained attention, i.e. vigilance. Show less
The general aim of this thesis is to investigate small fiber neuropathy in sarcoidosis and to asses whether ARA290 is a possible new agent to treat the neuropathic complaints in sarcoidosis... Show moreThe general aim of this thesis is to investigate small fiber neuropathy in sarcoidosis and to asses whether ARA290 is a possible new agent to treat the neuropathic complaints in sarcoidosis population. The results of the various ARA290 trials in painful sarcoidosis are discussed. Painful neuropathy is common, difficult to treat complication.The limited efficacy of current treatment options dictates a rationalized design of novel compounds. ARA290 treatment was consistently associated with a significant improvement of neuropathic pain symptoms in sarcoidosis patients, evidenced by a decrease in pain scores on validated questionnaires. Moreover,ARA290 treatment resulted in significant increases in corneal nerve fibers, improved sensory pain thresholds,improved quality of life and physical functioning. Given the excellent safety profile while reducing neuropathy symptoms,the prospects of ARA290 treatment in sarcoidosis related neuropathy seem promising.The long lasting beneficial effects of ARA290 on both pain related and non pain related symptoms in sarcoidosis patients prompt additional studies on potential disease modifying properties of ARA290. The data collected so far suggest that ARA290 will be equally effective in SFN associated with other syndromes, including diabetes mellitus. Show less
