Neuraminidases are enzymes that cleave glycosidic linkages of sialic acid. These enzymes are involved in influenza infections as well as in many cellular processes in mammals and micro-organisms.... Show moreNeuraminidases are enzymes that cleave glycosidic linkages of sialic acid. These enzymes are involved in influenza infections as well as in many cellular processes in mammals and micro-organisms. Development of molecules that irreversibly inhibit these enzymes, as well as molecules that can covalently bind and also label these enzymes, is described in this thesis. These newly developed molecular tools can be used to study neuraminidsases. Better understanding of these enzymes could for example contribute to the timely invervention if new influenza strains emerge. Show less
Objectives: The benefit of oseltamivir treatment in patients admitted with influenza virus infection and the design of studies addressing this issue have been questioned extensively. As the burden... Show moreObjectives: The benefit of oseltamivir treatment in patients admitted with influenza virus infection and the design of studies addressing this issue have been questioned extensively. As the burden of influenza disease is substantial and oseltamivir treatment is biologically plausible, this study assessed the clinical benefit of oseltamivir treatment in adult patients admitted with severe seasonal influenza virus infection in daily practice.Patients and methods: A multi-centre, retrospective cohort study was conducted to compare the effectiveness of treatment with and without oseltamivir <48 h after admission in patients admitted with laboratory-confirmed influenza virus infection in three large hospitals in the Netherlands. Propensity score matching was used to compare clinically relevant outcome variables.Results: In total, 390 patients were included in this study, of whom 80% had comorbidities. Thirty-day mortality, as well as the composite endpoint of 30-day mortality or intensive care unit admission >48 h after admission, were reduced by 9% (P = 0.04) and 11% (P = 0.02), respectively. Length of hospital stay and in-hospital mortality rates all showed a trend towards reduction. The median duration between symptom onset and initiation of treatment was 3 days.Conclusions: This study supports that, in daily practice, patients admitted with influenza virus infection should be treated with oseltamivir within 48 h of admission, even if they have had complaints for >48 h. (C) 2020 The Author(s). Published by Elsevier Ltd. Show less