Thromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it... Show moreThromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it at the same time increases risk of bleeding. With nationwide data from Statistics Netherlands, antithrombotic therapy and relevant clinical outcomes were comprehensively examined in the patient population of atrial fibrillation, overall or among those with comorbid cancer. The results suggest the patient population was increasingly receiving anticoagulants, driven by the newly introduced medication- direct oral anticoagulant and guided by the CHA2DS2-VASc score, and meanwhile the patient population experienced fewer ischemic stroke and major bleeding. In spite of these promising changes, suboptimal medication adherence and potential underuse of anticoagulants remain directions for further improvement. Antithrombotic agent use during pregnancy was also examined in the general Dutch pregnant population, which featured a surge in antiplatelet prescriptions, and risk of preeclampsia/eclampsia decreased and several newborn outcomes improved simultaneously. Together, the studies presented in this thesis provide an overview of antithrombotic therapy in the Netherlands in recent years, providing insights for further improving this treatment and relevant patient outcomes. Show less
Myasthenia gravis (MG) is hallmarked by acquired and fluctuating weakness of voluntary muscles. In the majority of patients, weakness is caused by autoantibodies to the postsynaptic acetylcholine... Show moreMyasthenia gravis (MG) is hallmarked by acquired and fluctuating weakness of voluntary muscles. In the majority of patients, weakness is caused by autoantibodies to the postsynaptic acetylcholine receptor (AChR) in the neuromuscular junction. Approximately 10% of MG patients are seronegative (SNMG). In 2001, antibodies to muscle-specific kinase (MuSK) were discovered within this group. This dissertation describes the epidemiology, clinical characteristics and immunological aspects of this new disease. In the Netherlands, MuSK MG is rare. Incidence was 0.17 per million person-years. Prevalence was 2.8 per million on January 1st 2004. Weakness was more often bulbar, and lead to frequent respiratory crises. MuSK MG was linked to the HLA-DR14-DQ5 haplotype and the disease severity was associated to antigen-specific IgG4 antibodies instead of IgG1. This is in contrast to AChR MG in which autoantibodies are mainly of the IgG1 and IgG3 subclass, and the disease is linked to HLA-B8-DR3. In SNMG patients, no antibodies to postsynaptic ErbB receptors were found. A case-report describes the transmission of MuSK autoantibodies from mother to her newborn child, causing transient weakness in the infant. A second case-report illustrates the effect of MuSK antibodies on both pre- and postsynaptic signal transmission in the neuromuscular junction. Show less
