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  • Brantley Omar posted an update 2 days, 10 hours ago

    “Treatment for all” is the vision statement of the World Federation of Hemophilia (WFH) which works to improve and sustain care for people with inherited bleeding disorders around the World. ISO1 2020 sees the publication of the third and latest edition of the WFH haemophilia guidelines, aimed at harmonising the delivery of haemophilia care worldwide (1). Initiated and sponsored by the Federation, the guidelines published as a supplement in the Haemophilia journal, represent an extraordinary collaborative effort.Objectives Recommendations on lithium dosing around delivery vary, with several guidelines suggesting that lithium should be discontinued prior to delivery. We aimed to evaluate the validity of these recommendations by investigating 1) maternal lithium blood level changes following delivery, and 2) the association between neonatal lithium blood levels at delivery and neonatal outcomes. Methods In this retrospective observational cohort study, we included women with at least one lithium blood level measurement during the final week of pregnancy and the first postpartum week. For aim 2, we included a subcohort of women with neonates for whom neonatal lithium blood levels (obtained from the umbilical cord or a neonatal vein puncture within 24 hours of delivery) were available. Results There were a total of 233 maternal lithium blood level measurements; 55 (23.6%) in the week before delivery and 178 (76.4%) in the week after. There was no association between time and lithium blood level/dose ratio (Pearson correlation coefficient -0.03, P = .63). Additionally, we included a total of 29 neonates for whom a lithium measurement was performed within 24 hours postpartum. Maternal and neonatal lithium blood levels were strongly correlated. We observed no associations between neonatal lithium blood levels at delivery and neonatal outcomes. Conclusion Based on our findings, we do not recommend lowering the dosage or discontinuation of lithium prior to delivery. Stable dosing can prevent subtherapeutic lithium serum levels, which is especially important in the postpartum period when relapse risks are highest.The considerations for use of compact nuclear magnetic resonance in a large-scale industrial environment clearly differ from those in academic and educational settings and even from those in smaller companies. In the first part of this article, these differences will be discussed along with the additional requirements that need to be fulfilled for successful applicability in different use cases. In the second part of the article, outcomes from different research activities aiming to fulfill these requirements will be presented with a focus on an online reaction-monitoring study on a lab-scale nucleophilic chlorination reaction.Understanding the determinants of antibody specificity is one of the challenging tasks in antibody development. Monospecific antibodies are still dominant in approved antibody therapeutics but there is a significant body of work to show that multispecific antibodies can increase the overall therapeutic effect. Dual-specific or “Two-in-One” antibodies can bind to two different antigens separately with the same antigen-binding site as opposed to bispecifics, which simultaneously bind to two different antigens through separate antigen-binding units. These nonstandard dual-specific antibodies were recently shown to be promising for new antibody-based therapeutics. Here, we physicochemically and structurally analyzed six different antibodies of which two are monospecific and four are dual-specific antibodies derived from monospecific templates to gain insight about dual-specificity determinants. These dual-specific antibodies can target both human epidermal growth factor receptor 2 and vascular endothelial growth factor at different binding affinities. We showed that a particular region of clustered Vernier zone residues might play key roles in gaining dual specificity. While there are minimal intramolecular interactions between a certain Vernier zone region, namely LV4 and LCDR1 of monospecific template, there is a significant structural change and consequently close contact formation between LV4-LCDR1 loops of derived dual-specific antibodies. Although Vernier zone residues were previously shown to be important for humanization applications, they are mostly underestimated in the literature. Here, we also aim to resurrect Vernier zone residues for antibody engineering efforts.Objective To determine health perceptions of patients with rheumatic diseases in the early phase of the coronavirus disease 2019 (COVID-19) pandemic. Methods Rheumatology patients at a single centre received via text message the national Rheumatology Association COVID-19 information sheet and an invitation to participate in a de-identified survey. Patient concerns regarding risks conferred by their rheumatological disease or medications, impact of receiving the information sheet on the likelihood of staying on medication, and acceptance of telehealth, were ascertained. Results 2,630 patients received the message and the survey response rate was 21% (n=550). Mean (±SD) age was 52 (±15.2) years and 75% were female. Participants’ highest ranked concern was that their medications would increase their severity of COVID-19 (76.1%). The highest levels of concern were seen in patients on combination conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and/or a biologic/targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD). There was no association between prednisolone dose and concern. While 63% of patients planned to continue their anti-rheumatic medications, a further 30% were more likely to stay on their medications as a result of receiving the information. Telehealth was acceptable to 98.4% of patients, but 28.1% felt this was only appropriate while infection control measures were in place. Conclusion Concerns regarding the risk of COVID-19 among patients on anti-rheumatic drugs are common. Proactive dissemination of information is needed to address misconceptions relating to medication risk, improve medication adherence and minimise the risk of flares. Telehealth is acceptable to a majority of patients during the COVID-19 pandemic.

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