Because of their developmental toxicity, some antiseizure medication (ASM) should be avoided during pregnancy. This may lead to discontinuation or switching of ASM after recognition of pregnancy, but some of these changes may be suboptimal. Trends in ASM use at conception were analyzed in 3,763 pregnancies prospectively ascertained by a teratology information service in Germany between 2000 and 2018. Focusing on women with epilepsy (n = 2,395), changes of treatment pattern during the 1st trimester were evaluated. There was an increase in women using ASMs for non-epilepsy indications from 19% in 2000 to 39% in 2018. Although a shift from non-recommended teratogenic ASMs to recommended ASMs was observed, 13% of women were still receiving non-recommended ASMs in early pregnancy at the end of the study period. Among women with epilepsy, ASM regimen remained unchanged during the 1st trimester in 90%, 6% switched to other ASMs, and only 4% discontinued. Valproate, oxcarbazepine, and topiramate were more likely to be discontinued or switched than other ASMs. This first analysis of treatment pattern in ASM exposed pregnancies in Germany confirms the general trend towards less teratogenic and newer ASMs. However, it remains questionable whether women still using non-recommended ASMs are refractory to lower-risk ASMs or disregard treatment guidelines and risk minimization measures.

INTRODUCTION:Epilepsy is a common neurological disease requiring long-term therapy also during pregnancy. Most studies on pregnancy outcomes in women with epilepsy are based on antiseizure medication (ASM) in monotherapy. However, about 20-30% of epilepsy patients require polytherapy and newer ASMs are an option, when seizure control is not achieved with first line ASMs.METHODS:Observational study evaluating the use of newer ASMs with marketing authorization since 2005 reported to the Embryotox Center of Clinical Teratology and Drug Safety in Pregnancy between 2004 and 2019. In addition, course and outcome of lacosamide exposed pregnancies were analysed.RESULTS:Our study confirms the increasing use of newer ASMs also in pregnant women. This is especially true for lacosamide, eslicarbazepine and brivaracetam with rising numbers of exposed pregnancies soon after marketing authorization. Analysis of 55 prospectively and 10 retrospectively ascertained lacosamide exposed pregnancies does not indicate increased risks of major birth defects or spontaneous abortion. However, bradycardia observed in 3 neonates might be related to prenatal lacosamide exposure.CONCLUSION:Available data do not support the assumption of lacosamide being a major teratogen. The increasing use of newer ASMs during pregnancy underscores the need for more studies to guide preconception counselling, especially for lacosamide, eslicarbazepine and brivaracetam.

This paper describes the simulation, implementation and performance assessment of model predictive control (MPC) for a coal communition circuit, and describes, as far as can be ascertained, the first implementation of MPC in the coal processing industry.Dynamic models of an actual coal comminution circuit were derived in previous publications using the principle of mass conservation with unknown parameters that were identified with actual plant production data. The identified dynamic models are used in nonlinear MPC simulations to determine the process control objectives and to calculate a potential process improvement in throughput. This increase in potential throughput was estimated to be 5% and was used as motivation in a business case to obtain funding to implement MPC on the actual plant.After performing a tender process, General Electric was contracted to implement the MPC. The MPC was implemented successfully on the comminution system and compared to current manual plant operational performance. After evaluating the MPC through a statistical performance assessment, it was found that throughput was improved by a significant 8.22%. The methodology followed is presented in this paper and the improved production throughput motivates for further MPC technologies to be implemented at other plant operations.