A5021831441- Pharmacogenetics and Drug Metabolism
- Antiplatelet Therapy and Cardiovascular Diseases
- Health Systems, Economic Evaluations, Quality of Life
- Renal Transplantation Outcomes and Treatments
- Lipoproteins and Cardiovascular Health
- Pharmaceutical studies and practices
- Statistical Methods in Clinical Trials
- Pharmacological Effects and Toxicity Studies
- Organ Transplantation Techniques and Outcomes
- Diabetes Treatment and Management
- Venous Thromboembolism Diagnosis and Management
- Genomics and Rare Diseases
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Acute Myocardial Infarction Research
- Neurological Complications and Syndromes
- Cancer therapeutics and mechanisms
- BRCA gene mutations in cancer
- Genetic Associations and Epidemiology
- Pharmaceutical Practices and Patient Outcomes
- Coronary Interventions and Diagnostics
- Colorectal Cancer Treatments and Studies
- COVID-19 Clinical Research Studies
- Clinical Nutrition and Gastroenterology
- Pharmaceutical Economics and Policy
- Pancreatic and Hepatic Oncology Research
University of Pennsylvania
2016-2025
Philadelphia VA Medical Center
2019-2025
Baylor College of Medicine
2023
American College of Medical Genetics
2023
University of Pennsylvania Health System
2022
California University of Pennsylvania
2021
Translational Therapeutics (United States)
2012-2020
Hospital of the University of Pennsylvania
2018-2019
University of Iowa
2008-2016
Applied Genetic Technologies (United States)
2013
Statins reduce cholesterol, prevent cardiovascular disease, and are among the most commonly prescribed medications in world. Statin‐associated musculoskeletal symptoms (SAMS) impact statin adherence ultimately can impede long‐term effectiveness of therapy. There several identified pharmacogenetic variants that disposition adverse events during SLCO1B1 encodes a transporter (SLCO1B1; alternative names include OATP1B1 or OATP‐C) facilitates hepatic uptake all statins. ABCG2 an efflux (BCRP)...
<h3>Importance</h3> Implementation of pharmacogenetic testing to guide drug prescribing has potential improve response and prevent adverse events. Robust data exist for more than 30 gene-drug pairs linking genotype phenotypes; however, it is unclear which tests, if implemented, would provide the greatest utility a given patient population. <h3>Objectives</h3> To project proportion veterans in US Veterans Health Administration (VHA) with actionable variants evaluate how might be associated...
CYP2C19 genotype-guided antiplatelet therapy following percutaneous coronary intervention is increasingly implemented in clinical practice. However, challenges such as selecting a testing platform, communicating test results, building decision support processes, providing patient and provider education, integrating methods to the translation of emerging evidence practice are barriers broad adoption. In this report, we compare contrast implementation strategies 12 early adopters, describing...
<h3>Importance</h3> Current guidelines recommend prasugrel hydrochloride and ticagrelor as preferred therapies for patients with acute coronary syndrome (ACS) treated percutaneous intervention (PCI). However, it is not well known how frequently these newer agents are being used in clinical practice or adherence varies among the platelet adenosine diphosphate P2Y<sub>12</sub>receptor (P2Y<sub>12</sub>) inhibitors. <h3>Objectives</h3> To determine trends use of different...
The increased availability of clinical pharmacogenetic (PGx) guidelines and decreasing costs for genetic testing have slowly led to utilization PGx in practice. Pre-emptive testing, where is performed advance drug prescribing, one means ensure results are available at the time prescribing decisions. However, most efficient effective methods clinically implement this strategy remain unclear.In report, we compare contrast implementation strategies pre-emptive by 15 early-adopter institutions....
Background Studies have demonstrated increased risk of major atherothrombotic events in CYP2C19 loss‐of‐function (LOF) variant carriers versus non‐carriers treated with clopidogrel after percutaneous coronary intervention (PCI). We sought to evaluate real‐world outcomes the clinical implementation ‐guided antiplatelet therapy PCI. Methods and Results Data from 9 medical centers where genotyping was performed setting PCI were included. Alternative prasugrel or ticagrelor recommended for...
Coronavirus disease 2019 (COVID-19) confers significant risk of acute kidney injury (AKI). Patients with COVID-19 AKI have high mortality rates.Individuals African ancestry 2 copies apolipoprotein L1 (APOL1) variants G1 or G2 (high-risk group) significantly increased rates disease. We tested the hypothesis that APOL1 high-risk group is associated a higher-risk COVID-19-associated and death.This retrospective cohort study included 990 participants enrolled in Million Veteran Program who were...
To examine community pharmacists' attitudes towards pharmacogenetic (PGx) testing, including their views of the clinical utility PGx and ethical, social, legal practical implications testing.A web-based survey administered to 5600 licensed pharmacists in states Ohio Pennsylvania (USA).Of 580 respondents, 78% had a Bachelor Science degree pharmacy 58% worked chain drug store. Doctors pharmacy-trained significantly higher knowledge score than those with (3.2 ± 0.9 vs 2.6 0.6; p < 0.0001). All...
The value of utilizing a multigene pharmacogenetic panel to tailor pharmacotherapy is contingent on the prevalence prescribed medications with an actionable association. Clinical Pharmacogenetics Implementation Consortium (CPIC) has categorized over 35 gene-drug pairs as "level A," for which there sufficiently strong evidence recommend that genetic information be used guide drug prescribing. opportunity use among adult patients was determined by elucidating exposure CPIC level A drugs 11...
Background. Tacrolimus, a substrate of CYP3A, has low and variable bioavailability similar to cyclosporine. Co-administration ketoconazole, potent inhibitor gut hepatic been shown increase tacrolimus in healthy volunteers. The purpose this study is assess the role metabolism overall renal transplant population. Methods. We prospectively studied 19 adult recipients who were receiving as part quadruple, sequential immunosuppression regimen. Each patient received (4-hr intravenous dose 0.04...
Background: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after percutaneous coronary intervention, but the clinical impact of implementing genotyping in a real-world setting is unknown. The purpose study was to determine whether returning genotype results along with genotype-guided pharmacotherapy recommendations using rapid turnaround test would change antiplatelet prescribing following intervention.The primary outcome rate prasugrel or ticagrelor each arm. Secondary...
Genotyping for CYP2C19 no function alleles to guide antiplatelet therapy after percutaneous coronary intervention (PCI) improves clinical outcomes. Although results the increased CYP2C19*17 allele are also reported, its relevance in this setting remains unclear. A collaboration across nine sites examined prescribing and outcomes 3,342 patients implementation of CYP2C19-guided therapy. Risk major atherothrombotic bleeding events over 12 months PCI were compared cytochrome P450 2C19 isozyme...
Technologies in genomic medicine have rapidly evolved and transformed the ability to deliver precision nearly every field of health care. As has advanced, electronic record (EHR) simultaneously been adopted into routine practice. A recent Points Consider Statement by American College Medical Genetics Genomics (ACMG) provides a framework for optimal integration data EHR.1.Grebe T.A. et al.The interface information with record: points consider statement (ACMG).10.1038/s41436-020-0841-2Genet....
<h3>Importance</h3> Genotype-guided prescribing in pediatrics could prevent adverse drug reactions and improve therapeutic response. Clinical pharmacogenetic implementation guidelines are available for many medications commonly prescribed to children. Frequencies of medication prescription actionable genotypes (genotypes where a change may be indicated) inform the potential value implementation. <h3>Objective</h3> To assess opportunities genotype-guided pediatric populations among multiple...
Abstract Background Pharmacogenetic (PGx) testing for germline variants in the DPYD and UGT1A1 genes can be used to guide fluoropyrimidine irinotecan dosing, respectively. Despite known association between PGx chemotherapy toxicity, preemptive prior initiation is rarely performed routine practice. Methods We conducted a qualitative study of oncology clinicians identify barriers using dosing patients with gastrointestinal malignancies. Each participant completed semi-structured interview...
Clopidogrel, an anti-platelet drug, is used to prevent thrombosis after percutaneous coronary intervention. Clopidogrel resistance results in recurring ischemic events, with African Americans (AA) suffering disproportionately. The aim of this study was discover novel biomarkers clopidogrel using genome and transcriptome data. We conducted a genome-wide association (GWAS), including local ancestry adjustment, 141 AA on identify genetic associations high on-treatment platelet reactivity...
The safety of systemic fluoropyrimidines (e.g., 5-fluorouracil, capecitabine) is impacted by germline genetic variants in DPYD, which encodes the dihydropyrimidine dehydrogenase (DPD) enzyme that functions as rate-limiting step catabolism this drug class. Genetic testing to identify those with DPD deficiency can help mitigate risk severe and life-threatening fluoropyrimidine-induced toxicities. Globally, integration DPYD into patient care has varied greatly, ranging from being required...
Sustained smooth muscle contraction is mediated by protein kinase C (PKC) through a signal transduction cascade leading to contraction. Heat-shock 27 (HSP27) appears be the link between these two major events, i.e., and sustained We have investigated involvement of HSP27 in association with contractile proteins (e.g., actin, myosin, tropomyosin, caldesmon) resulting carried out confocal microscopy investigate cellular reorganization colocalization immunoprecipitation caldesmon as detected...