No abstract

Leflunomide is a prodrug for teruflunomide and used for rheumatic diseases. Teriflunomide is considered to be teratogenic and should be avoided in pregnancy. We describe a case of teriflunomide exposure up to the third trimester of pregnancy. A healthy baby was delivered, despite substantial drug exposure. Multiple washout procedures were required to reduce teriflunomide concentrations below the safe target concentration 0.02 mg/L.

Since early 2020, the world has been dealing with a raging pandemic outbreak: COVID-19. A year later, vaccines have become accessible, but in limited quantities, so that governments needed to devise a strategy to decide which part of the population to prioritize when assigning the available doses, and how to manage the interval between doses for multi-dose vaccines. In this paper, we present an optimization framework to address the dynamic double-dose vaccine allocation problem whereby the available vaccine doses must be administered to different age-groups to minimize specific societal objectives. In particular, we first identify an age-dependent Susceptible-Exposed-Infected-Recovered (SEIR) epidemic model including an extension capturing partially and fully vaccinated people, whereby we account for agedependent immunity and infectiousness levels together with disease severity. Second, we leverage our model to frame the dynamic age-dependent vaccine allocation problem for different societal objectives, such as the minimization of infections or fatalities, and solve it with nonlinear programming techniques. Finally, we carry out a numerical case study with real-world data from The Netherlands. Our results show how different societal objectives can significantly alter the optimal vaccine allocation strategy. For instance, we find that minimizing the overall number of infections results in delaying second doses, whilst to minimize fatalities it is important to fully vaccinate the elderly first.