Recommendations for Clinical CYP2C9 Genotyping Allele Selection: A Joint Recommendation of the Association for Molecular Pathology and College of American Pathologists

The goals of the Association for Molecular Pathology Pharmacogenomics (PGx) Working Group of the Association for Molecular Pathology Clinical Practice Committee are to define the key attributes of PGx alleles recommended for clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This document provides recommendations for a minimum panel of variant alleles (Tier 1) and an extended panel of variant alleles (Tier 2) that will aid clinical laboratories when designing assays for CYP2C9 testing. The Working Group considered the functional impact of the variants, allele frequencies in different populations and ethnicities, the availability of reference materials, and other technical considerations for PGx testing when developing these recommendations. Our goal is to promote standardization of testing PGx genes and alleles across clinical laboratories. These recommendations are not to be interpreted as restrictive but to provide a reference guide. The current document will focus on CYP2C9 testing that can be applied to all CYP2C9-related medications. A separate recommendation on warfarin PGx testing is being developed to include recommendations on CYP2C9 alleles and additional warfarin sensitivity–associated genes and alleles

Pharmacogenetic allele nomenclature: International workgroup recommendations for test result reporting

This manuscript provides nomenclature recommendations developed by an international workgroup to increase transparency and standardization of pharmacogenetic (PGx) result reporting. Presently, sequence variants identified by PGx tests are described using different nomenclature systems. In addition, PGx analysis may detect different sets of variants for each gene, which can affect interpretation of results. This practice has caused confusion and may thereby impede the adoption of clinical PGx testing. Standardization is critical to move PGx forward

A useful tool for drug interaction evaluation: The University of Washington Metabolism and Transport Drug Interaction Database

<p>Abstract</p> <p>The Metabolism and Transport Drug Interaction Database (<url>http://www.druginteractioninfo.org</url>) is a web-based research and analysis tool developed in the Department of Pharmaceutics at the University of Washington. The database has the largest manually curated collection of data related to drug interactions in humans. The tool integrates information from the literature, public repositories, reference textbooks, guideline documents, product prescribing labels and clinical review sections of new drug approval (NDA) packages. The database's easy-to-use web portal offers tools for visualisation, reporting and filtering of information. The database helps scientists to mine kinetics information for drug-metabolising enzymes and transporters, to assess the extent of <it>in vivo </it>drug interaction studies, as well as case reports for drugs, therapeutic proteins, food products and herbal derivatives. This review provides a brief description of the database organisation, its search functionalities and examples of use.</p

Integration von Klimawandel und Gesundheitsthemen in den medizinischen Lehrplan - eine quantitative Bedarfsanalyse unter Medizinstudierenden an der Universität Heidelberg

Objectives: Climate change (CC) is of major importance for physicians as they are directly confronted with changing disease patterns, work in a greenhouse gas intensive sector and can be potential advocates for healthy people on a healthy planet. Methods: We assessed third to fifth year medical students' needs to support the integration of CC topics into medical curricula. A questionnaire with 54 single choice-based items was newly designed with the following sections: role perception, knowledge test, learning needs, preference of educational strategies and demographic characteristics. It was administered online to students at Heidelberg medical faculty. Data sets were used for descriptive statistics and regression modelling. Results: 72.4% of students (N=170, 56.2% female, 76% aged 20-24 years) (strongly) agreed that physicians carry a responsibility to address CC in their work setting while only 4.7% (strongly) agreed that their current medical training had given them enough skills to do so. Knowledge was high in the area of CC, health impacts of CC, vulnerabilities and adaptation (70.1% correct answers). Knowledge gaps were greatest for health co-benefits and climate-friendly healthcare (55.5% and 16.7% of correct answers, respectively). 79.4% wanted to see CC and health included in the medical curriculum with a preference for integration into existing mandatory courses. A multilinear regression model with factors age, gender, semester, aspired work setting, political leaning, role perception and knowledge explained 45.9% of variance for learning needs. Conclusion: The presented results encourage the integration of CC and health topics including health co-benefits and climate-friendly healthcare, as well as respective professional role development into existing mandatory courses of the medical curriculum.Zielsetzungen: Der Klimawandel ist für Ärzt*innen von großer Bedeutung, da sie mit sich verändernden Krankheitsbildern konfrontiert sind, in einem treibhausgasintensiven Sektor arbeiten und potenzielle Fürsprecher für gesunde Menschen auf einem gesunden Planeten sind. Methoden: Wir untersuchten die Lernbedürfnisse der Medizinstudierenden im dritten bis fünften Studienjahr im Bezug auf die Integration von Klimawandel und Gesundheits-Themen in die medizinischen Lehrpläne. Es wurde ein neuer Fragebogen mit 54 Items entwickelt. Dieser enthält die folgenden Abschnitte: Rollenwahrnehmung, Wissen, Lernbedürfnisse, Präferenz von Lernstrategien und demografische Merkmale. Der Fragebogen wurde online an Studierende der Medizinischen Fakultät Heidelberg verschickt. Die Datensätze wurden mittels deskriptiver Statistik und Regressionsanalyse ausgewertet. Ergebnisse: 72,4% der Studierenden (n=170, 56,2% weiblich, 76% im Alter von 20-24 Jahren) stimmten (stark) zu, dass Ärzt*innen Verantwortung dafür tragen, den Klimawandel in ihrem Arbeitsumfeld zu adressieren. Nur 4,7% stimmten (stark) zu, dass in ihrer bisherigen medizinischen Ausbildung genügend Fähigkeiten und Wissen vermittelt wurden, um dies zu tun. Der Wissensstand war in den Bereichen Klimawandel, gesundheitliche Auswirkungen, Vulnerabilität und Anpassung hoch (70,1% richtige Antworten). Die größten Wissenslücken gab es bei den gesundheitlichen Zusatznutzen ("Health Co-Benefits") und der nachhaltigen Gesundheitsversorgung (55,5% bzw. 16,7% richtige Antworten). 79,4% der Befragten wünschten sich, dass die Themen im Bereich Klimawandel und Gesundheit in das medizinische Curriculum aufgenommen werden ("Lernbedürfnis"), wobei sie eine Integration in bestehende Pflichtkurse bevorzugten. Ein multiples lineares Regressionsmodell mit den Faktoren Alter, Geschlecht, Semester, angestrebtes Arbeitsumfeld, politische Orientierung, Rollenwahrnehmung und Wissen erklärte 45,9% der Varianz des Lernbedürfnisses. Schlussfolgerung: Die vorgestellten Ergebnisse ermutigen dazu, Themen zu Klimawandel und Gesundheit, in bestehende Pflichtkurse des medizinischen Curriculums zu integrieren. Dabei sollten auch gesundheitliche Co-Benefits, eine klimafreundliche Gesundheitsversorgung und die Entwicklung eines entsprechenden ärztlichen Rollenverständnisses berücksichtigt werden

Evidence-based guideline: Antiepileptic drug selection for people with HIV/AIDS: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Ad Hoc Task Force of the Commission on Therapeutic Strategies of the International League Against Epilepsy.Quality Standards Subcommittee of the American Academy of Neurology; Ad Hoc Task Force of the Commission on Therapeutic Strategies of the International League Against Epilepsy.

OBJECTIVE: To develop guidelines for selection of antiepileptic drugs (AEDs) among people with HIV/AIDS. METHODS: The literature was systematically reviewed to assess the global burden of relevant comorbid entities, to determine the number of patients who potentially utilize AEDs and antiretroviral agents (ARVs), and to address AED-ARV interactions. Results and Recommendations: AED-ARV administration may be indicated in up to 55% of people taking ARVs. Patients receiving phenytoin may require a lopinavir/ritonavir dosage increase of ~50% to maintain unchanged serum concentrations (Level C). Patients receiving valproic acid may require a zidovudine dosage reduction to maintain unchanged serum zidovudine concentrations (Level C). Coadministration of valproic acid and efavirenz may not require efavirenz dosage adjustment (Level C). Patients receiving ritonavir/atazanavir may require a lamotrigine dosage increase of ∼50% to maintain unchanged lamotrigine serum concentrations (Level C). Coadministration of raltegravir/atazanavir and lamotrigine may not require lamotrigine dosage adjustment (Level C). Coadministration of raltegravir and midazolam may not require midazolam dosage adjustment (Level C). Patients may be counseled that it is unclear whether dosage adjustment is necessary when other AEDs and ARVs are combined (Level U). It may be important to avoid enzyme-inducing AEDs in people on ARV regimens that include protease inhibitors or nonnucleoside reverse transcriptase inhibitors, as pharmacokinetic interactions may result in virologic failure, which has clinical implications for disease progression and development of ARV resistance. If such regimens are required for seizure control, patients may be monitored through pharmacokinetic assessments to ensure efficacy of the ARV regimen (Level C)

Recommendations for Clinical Warfarin Genotyping Allele Selection

The goal of the Association for Molecular Pathology (AMP) Clinical Practice Committee's AMP Pharmacogenomics (PGx) Working Group is to define the key attributes of PGx alleles recommended for clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This document series provides recommendations for a minimum panel of variant alleles (tier 1) and an extended panel of variant alleles (tier 2) that will aid clinical laboratories when designing assays for PGx testing. The AMP PGx Working Group considered functional impact of the variants, allele frequencies in multiethnic populations, the availability of reference materials, as well as other technical considerations for PGx testing when developing these recommendations. The ultimate goal is to promote standardization of PGx gene/allele testing across clinical laboratories. These recommendations are not to be interpreted as prescriptive but to provide a reference guide. Of note, a separate article with recommendations for CYP2C9 allele selection was previously developed by the PGx Working Group that can be applied broadly to CYP2C9-related medications. The warfarin allele recommendations in this report incorporate the previous CYP2C9 allele recommendations and additional genes and alleles that are specific to warfarin testing

Antiepileptic drug selection for people with HIV/AIDS: Evidence-based guidelines from the ILAE and AAN

A joint panel of the American Academy of Neurology (AAN) and the International League Against Epilepsy (ILAE) convened to develop guidelines for selection of antiepileptic drugs (AEDs) among people with HIV/AIDS. The literature was systematically reviewed to assess the global burden of relevant comorbid entities, to determine the number of patients who potentially utilize AEDs and antiretroviral agents (ARVs), and to address AED-ARV interactions. Key findings from this literature search included the following: AED-ARV administration may be indicated in up to 55% of people taking ARVs. Patients receiving phenytoin may require a lopinavir/ritonavir dosage increase of approximately 50% to maintain unchanged serum concentrations (Level C). Patients receiving valproic acid may require a zidovudine dosage reduction to maintain unchanged serum zidovudine concentrations (Level C). Coadministration of valproic acid and efavirenz may not require efavirenz dosage adjustment (Level C). Patients receiving ritonavir/atazanavir may require a lamotrigine dosage increase of approximately 50% to maintain unchanged lamotrigine serum concentrations (Level C). Coadministration of raltegravir/atazanavir and lamotrigine may not require lamotrigine dosage adjustment (Level C). Coadministration of raltegravir and midazolam may not require midazolam dosage adjustment (Level C). Patients may be counseled that it is unclear whether dosage adjustment is necessary when other AEDs and ARVs are combined (Level U). It may be important to avoid enzyme-inducing AEDs in people on ARV regimens that include protease inhibitors or nonnucleoside reverse transcriptase inhibitors because pharmacokinetic interactions may result in virologic failure, which has clinical implications for disease progression and development of ARV resistance. If such regimens are required for seizure control, patients may be monitored through pharmacokinetic assessments to ensure efficacy of the ARV regimen (Level C)

<i>CYP3A4 </i>and <i>CYP3A5 </i>Genotyping Recommendations:A Joint Consensus Recommendation of the Association for Molecular Pathology, Clinical Pharmacogenetics Implementation Consortium, College of American Pathologists, Dutch Pharmacogenetics Working Group of the Royal Dutch Pharmacists Association, European Society for Pharmacogenomics and Personalized Therapy, and Pharmacogenomics Knowledgebase

The goals of the Association for Molecular Pathology Clinical Practice Committee's Pharmacogenomics (PGx) Working Group are to define the key attributes of pharmacogenetic alleles recommended for clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This document series provides recommendations for a minimum panel of variant alleles (tier 1) and an extended panel of variant alleles (tier 2) that will aid clinical laboratories when designing assays for PGx testing. The Association for Molecular Pathology PGx Working Group considered functional impact of the variant alleles, allele frequencies in multiethnic populations, the availability of reference materials, and other technical considerations for PGx testing when developing these recommendations. The goal of this Working Group is to promote standardization of PGx gene/allele testing across clinical laboratories. This document will focus on clinical CYP3A4 and CYP3A5 PGx testing that may be applied to all CYP3A4- and CYP3A5-related medications. These recommendations are not to be interpreted as prescriptive but to provide a reference guide.</p