Notes

Important strategies to programmed quantification of fast-scan-cyclic-voltammetry recognized chemicals.
7% (14/19) of deliveries that were not covered by prophylaxis compared with 54.2% (32/59) of deliveries that were (OR = 2.36, 95% CI 0.75-7.40). Neonatal bleeding complications were reported in 10.0% (8/80) of deliveries. In all (6/6) deliveries with neonatal bleeding complications wherein the presence of alloantibodies was investigated, either antiplatelet or anti-HLA antibodies were detected. DISCUSSION/CONCLUSION Menstrual and particularly obstetrical bleeding problems frequently occur in women with IPRD, based on small case reports and series of poor quality. International collaboration, preferably on prospective studies, is needed to improve clinical management of women-specific bleeding in IPRD. © 2020 The Authors. Haemophilia published by John Wiley & Sons Ltd.Warfarin is a narrow therapeutic index anticoagulant drug and its use is associated with infrequent but significant adverse bleeding events. The international normalized ratio (INR) is the most commonly used biomarker to monitor and titrate warfarin therapy. However, INR is derived from a functional assay, which determines clotting efficiency at the time of measurement and is susceptible to technical variability. Protein induced by vitamin K antagonist-II (PIVKA-II) has been suggested as a biomarker of long-term vitamin K status, providing mechanistic insights about variation in the functional assay. However, the currently available antibody-based PIVKA-II assay does not inform on the position and number of des-carboxylation sites in prothrombin. The assay presented in this paper provides simultaneous quantification of carboxy and des-carboxy prothrombin that are essential for monitoring early changes in INR and, thus, serves as the superior tool for managing warfarin therapy. Additionally, this assay permits the quantification of total prothrombin level, which is affected by warfarin treatment. Prothrombin recovery from plasma was 95% and the liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was linear (r2 = 0.98) with a dynamic range of 1-100 µg/mL. The assay interday precision was within 20%. A des-carboxy peptide of prothrombin (GNLER) was negatively correlated with active prothrombin (Pearson r = 0.99, P less then 0.0001), whereas its association was positively linked with INR values (Pearson r = 0.75, P less then 0.015). This novel LC-MS/MS assay for active and inactive prothrombin quantification can be applied to titrate anticoagulant therapy and to monitor the impact of diseases, such as hepatocellular carcinoma on clotting physiology. © 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.Single nucleotide variants in the open reading frames (ORFs) of pharmacogenes are important causes of interindividual variability in drug response. The functional characterization of variants of unknown significance within ORFs remains a major challenge for pharmacogenomics. Deep mutational scanning (DMS) is a high-throughput technique that makes it possible to analyze the functional effect of hundreds of variants in a parallel and scalable fashion. We adapted a "landing pad" DMS system to study the function of missense variants in the ORFs of cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and cytochrome P450 family 2 subfamily C member 19 (CYP2C19). We studied 230 observed missense variants in the CYP2C9 and CYP2C19 ORFs and found that 19 of 109 CYP2C9 and 36 of 121 CYP2C19 variants displayed less than ~ 25% of the wild-type protein expression, a level that may have clinical relevance. Our results support DMS as an efficient method for the identification of damaging ORF variants that might have potential clinical pharmacogenomic application. Selleckchem AGK2 © 2020 Mayo Clinic. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.I read the 2019 Update of the ACR recommended RA disease activity measures by England, et al with great interest; it discusses the appropriate metrics to be used by practicing rheumatologists employing a Treat-to-Target approach. The article is comprehensive and written. I would like to make 2 comments and clarify one point, however. © 2020, American College of Rheumatology.Clinical trials and cohort studies are required to meet target recruitment of study participants within stipulated timelines, especially when the priority is to include populations traditionally unrepresented in biomedical research. By the third quarter of 2019, the University of Arizona-Banner Health Provider Organization (UA-Banner HPO) has enrolled >30,000 core participants into the All of Us Research Program (AoURP), the research cohort of the Precision Medicine Initiative. Majority of enrolled participants meet the criteria for individuals underrepresented in biomedical research. The enrollment goals were calculated based on a target of 20,000 as set by the National Institutes of Health (NIH) and our health provider organization achieved enrollment numbers between 17-86% above the targeted daily enrollment. We evaluated enrollment methods and challenges to enrollments encountered by the UA-Banner Health Provider Organization into the AoURP. Challenges to enrollment centered around the need for high-touch engagement methods, time investment necessary for stakeholder inclusion, and the use of purely digital enrollment methods especially in populations underrepresented in biomedical research. These challenges occurred at the level of the individual, provider, institutions and community, and cumulatively impacted participant enrollment. Successful strategies for engagement and enrollment leveraged provider partners as advocates for the program. For high-volume enrollment in clinical research, it is important to engage leaders in the healthcare setting, patient providers and tailor engagement and enrollment to potential participant needs. We emphasize the need for precision engagement and enrollment methods tailored to individual needs. © 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.
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