GMKBPharmacotherapy – Since its approval by the United States Food and Drug Administration in 2002, voriconazole has become a key component in the successful treatment of many invasive fungal infections, including the most common, aspergillosis and candidiasis. Despite voriconazole’s widespread use, optimizing its treatment in an individual can be challenging due to significant interpatient variability in plasma concentrations of the drug. Variability is due to nonlinear pharmacokinetics and the influence of patient characteristics such as age, sex, weight, liver disease, and genetic polymorphisms in the cytochrome P450 2C19 gene (CYP2C19) encoding for the CYP2C19 enzyme, the primary enzyme responsible for metabolism of voriconazole. CYP2C19 polymorphisms account for the largest portion of variability in voriconazole exposure, posing significant difficulty to clinicians in targeting therapeutic concentrations. In this review, we discuss the role of CYP2C19 polymorphisms and their influence on voriconazole’s pharmacokinetics, adverse effects, and clinical efficacy.
The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1 and Simvastatin-Induced Myopathy: 2014 Update
Clinical Pharmacology & Therapeutics – Simvastatin is among the most commonly used prescription medications for cholesterol reduction. A single coding single-nucleotide polymorphism, rs4149056T>C, in SLCO1B1 increases systemic exposure to simvastatin and the risk of muscle toxicity.
Providing patient education: impact on quantity and quality of family health history collection
Familial Cancer – Patient education improves FHH collection and subsequent risk stratification utilized in providing actionable evidence-based care recommendations for cancer risk management.
Return of Genomic Results to Research Participants: The Floor, the Ceiling, and the Choices In Between
American Journal of Human Genetics – As more research studies incorporate next-generation sequencing (including whole-genome or whole-exome sequencing), investigators and institutional review boards face difficult questions regarding which genomic results to return to research participants and how. An American College of Medical Genetics and Genomics 2013 policy paper suggesting that pathogenic mutations in 56 specified genes should be returned in the clinical setting has raised the question of whether comparable recommendations should be considered in research settings.
Identifying Patients at Increased Disease Risk: Comparing Clinical Judgment and a Clinical Risk Assessment Tool
Journal of Family Medicine & Community Health –
There are several barriers to the appropriate use of Family Health History (FHH)for risk management within primary care. Among these is a lack of physician confidence in their ability to identify high risk individuals and determine guideline concordant care. In this study, we compared Primary Care Providers’ (PCP) clinical assessment of appropriate risk-management for patients to guideline based recommendations generated by an IT platform, MeTree. In addition, we compared MeTree with clinical assessments of Genetic Counselors (GC).
Warfarin Pharmacogenetics: An Illustration of the Importance of Studies in Minority Populations
Clinical Pharmacology & Therapeutics – Translation of pharmacogenetics to clinical practice is increasingly common. However, most data arise in people of European ancestry, so clinical translation in non-Europeans can be challenging. Depending on the population being assessed, a polymorphism’s effect can differ in magniture or be absent. Studies in minorities are therefore essential as they present opportunities for discovery that would be missed through European-only studies, and they ensure that all populations benefit from clinical pharmacogenetics.
Clinical Pharmacogenetics Implementation
American Journal of Medical Genetics – Current challenges exist to widespread clinical implementation of genomic medicine and pharmacogenetics. The University of Florida (UF) Health Personalized Medicine Program (PMP) is a pharmacist-led, multidisciplinary initiative created in 2011 within the UF Clinical Translational Science Institute. Initial efforts focused on pharmacogenetics, with long-term goals to include expansion to disease-risk prediction and disease stratification. Herein we describe the processes for development of the program, the challenges that were encountered and the clinical acceptance by clinicians of the genomic medicine implementation.
Implementing family health history risk stratification in primary care: Impact of guideline criteria on populations and resource demand
American Journal of Medical Genetics – The Genomic Medicine Model aims to facilitate patient engagement, patient/provider education of genomics/personalized medicine, and uptake of risk‐stratified evidence‐based prevention guidelines using MeTree, a patient‐facing family health history (FHH) collection and clinical decision support (CDS) program. Here we report the number of increased risk (above population‐level risk) patients identified for breast/ovarian cancer, colon cancer, hereditary syndrome risk, and thrombosis; the prevalence of FHH elements triggering increased‐risk status; and the resources needed to manage their risk.
Attitudes toward Adopting Genome-Guided Prescribing through Clinical Decision Support
Journal of Personalized Medicine – This study assessed physician attitudes toward adopting genome-guided prescribing through clinical decision support (CDS), prior to enlisting in the Clinical Implementation of Personalized Medicine through Electronic Health Records and Genomics pilot pharmacogenomics project (CLIPMERGE PGx).
Quality of family history collection with use of a patient facing family history assessment tool
BMC Family Practice – Studies have shown that the quality of family health history (FHH) collection in primary care is inadequate to assess disease risk. To use FHH for risk assessment, collected data must have adequate detail