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Marco Alessandrini, Mamoonah Chaudhry, Tyren M Dodgen, Michael S Pepper
In a move indicative of the enthusiastic support of precision medicine, the U.S. President Barack Obama announced the Precision Medicine Initiative in January 2015. The global precision medicine ecosystem is, thus, receiving generous support from the United States ($215 million), and numerous other governments have followed suit. In the context of precision medicine, drug treatment and prediction of its outcomes have been important for nearly six decades in the field of pharmacogenomics. The field offers an elegant solution for minimizing the effects and occurrence of adverse drug reactions (ADRs)...
October 2016: Omics: a Journal of Integrative Biology
Ingolf Cascorbi, Anneke Nina Werk
INTRODUCTION: Cancer pharmacogenetics usually considers tumor-specific targets. However, hereditary genetic variants may interfere with the pharmacokinetics of antimetabolites and other anti-cancer drugs, which may lead to severe adverse events. AREAS COVERED: Here, the impact of hereditary genes considered in drug labels such as thiopurine S-methyltransferase (TPMT), UDP-glucuronosyltransferase 1A1 (UTG1A1) and dihydropyrimidine dehydrogenase (DPYD) are discussed with respect to guidelines of the Clinical Pharmacogenetics Implementation Consortium (CPIC)...
September 16, 2016: Expert Opinion on Drug Metabolism & Toxicology
David Ng, Celine S Hong, Larry N Singh, Jennifer J Johnston, James C Mullikin, Leslie G Biesecker
PURPOSE: The aim of the study was to assess exome data for preemptive pharmacogenetic screening for 203 clinically relevant pharmacogenetic variant positions from the Pharmacogenomics Knowledgebase and Clinical Pharmacogenetics Implementation Consortium and identify copy-number variants (CNVs) in CYP2D6. METHODS: We examined the coverage and genotype quality of 203 pharmacogenetic variant positions in 973 exomes compared with five genomes and with five genotyping chip data sets...
August 18, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Kelly E Caudle, Henry M Dunnenberger, Robert R Freimuth, Josh F Peterson, Jonathan D Burlison, Michelle Whirl-Carrillo, Stuart A Scott, Heidi L Rehm, Marc S Williams, Teri E Klein, Mary V Relling, James M Hoffman
INTRODUCTION: Reporting and sharing pharmacogenetic test results across clinical laboratories and electronic health records is a crucial step toward the implementation of clinical pharmacogenetics, but allele function and phenotype terms are not standardized. Our goal was to develop terms that can be broadly applied to characterize pharmacogenetic allele function and inferred phenotypes. MATERIALS AND METHODS: Terms currently used by genetic testing laboratories and in the literature were identified...
July 21, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Andrea Gaedigk, Katrin Sangkuhl, Michelle Whirl-Carrillo, Teri Klein, J Steven Leeder
PURPOSE: Owing to its highly polymorphic nature and major contribution to the metabolism and bioactivation of numerous clinically used drugs, CYP2D6 is one of the most extensively studied drug-metabolizing enzymes and pharmacogenes. CYP2D6 alleles confer no, decreased, normal, or increased activity and cause a wide range of activity among individuals and between populations. However, there is no standard approach to translate diplotypes into predicted phenotype. METHODS: We exploited CYP2D6 allele-frequency data that have been compiled for Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines (>60,000 subjects, 173 reports) in order to estimate genotype-predicted phenotype status across major world populations based on activity score (AS) assignments...
July 7, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
W Yang, G Wu, U Broeckel, C A Smith, V Turner, C E Haidar, S Wang, R Carter, S E Karol, G Neale, K R Crews, J J Yang, C G Mullighan, J R Downing, W E Evans, M V Relling
We compared whole exome sequencing (WES, n = 176 patients) and whole genome sequencing (WGS, n = 68) and clinical genotyping (DMET array-based approach) for interrogating 13 genes with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. We focused on 127 CPIC important variants: 103 single nucleotide variations (SNV), 21 insertion/deletions (Indel), HLA-B alleles, and two CYP2D6 structural variations. WES and WGS provided interrogation of nonoverlapping sets of 115 SNV/Indels with call rate >98%...
October 2016: Clinical Pharmacology and Therapeutics
Christine A Lam, Cathy Sherbourne, Lingqi Tang, Thomas R Belin, Pluscedia Williams, Angela Young-Brinn, Jeanne Miranda, Kenneth B Wells
BACKGROUND: Disparities in depression care exist among the poor. Community Partners in Care (CPIC) compared a community coalition model with technical assistance to improve depression services in under-resourced communities. We examine effects on health, social, and utilization outcomes among the poor and, non-poor depressed, and poor subgroups. METHODS: This study analyzed clients living above (n = 268) and below (n = 750) the federal-poverty level and, among the poor, 3 nonoverlapping subgroups: justice-involved (n = 158), homeless and not justice-involved (n = 298), and other poor (n = 294)...
May 2016: Journal of the American Board of Family Medicine: JABFM
James M Hoffman, Henry M Dunnenberger, J Kevin Hicks, Kelly E Caudle, Michelle Whirl Carrillo, Robert R Freimuth, Marc S Williams, Teri E Klein, Josh F Peterson
To move beyond a select few genes/drugs, the successful adoption of pharmacogenomics into routine clinical care requires a curated and machine-readable database of pharmacogenomic knowledge suitable for use in an electronic health record (EHR) with clinical decision support (CDS). Recognizing that EHR vendors do not yet provide a standard set of CDS functions for pharmacogenetics, the Clinical Pharmacogenetics Implementation Consortium (CPIC) Informatics Working Group is developing and systematically incorporating a set of EHR-agnostic implementation resources into all CPIC guidelines...
July 2016: Journal of the American Medical Informatics Association: JAMIA
Jennifer S Chang, Duyen-Anh Pham, Maithao T Dang, Yiting Lu, Sheri VanOsdol, Jaekyu Shin
BACKGROUND: Pharmacogenomics is the study of how genes affect a person's response to drugs. This descriptive study assessed whether popular drug information resources provide clinically useful pharmacogenomic (PGx) information. METHODS: Four resources (package inserts, Lexicomp, Micromedex 2.0, and Epocrates) were evaluated for information about twenty-seven drugs. RESULTS: There was wide variability of PGx information. Whereas Lexicomp included relevant PGx biomarker information for all 27 drugs, Epocrates did in less than 50% of the drugs...
January 2016: Journal of the Medical Library Association: JMLA
R S Gammal, M H Court, C E Haidar, O F Iwuchukwu, A H Gaur, M Alvarellos, C Guillemette, J L Lennox, M Whirl-Carrillo, S S Brummel, M J Ratain, T E Klein, B R Schackman, K E Caudle, D W Haas
The antiretroviral protease inhibitor atazanavir inhibits hepatic uridine diphosphate glucuronosyltransferase (UGT) 1A1, thereby preventing the glucuronidation and elimination of bilirubin. Resultant indirect hyperbilirubinemia with jaundice can cause premature discontinuation of atazanavir. Risk for bilirubin-related discontinuation is highest among individuals who carry two UGT1A1 decreased function alleles (UGT1A1*28 or *37). We summarize published literature that supports this association and provide recommendations for atazanavir prescribing when UGT1A1 genotype is known (updates at www...
April 2016: Clinical Pharmacology and Therapeutics
Y Saito, L K Stamp, K E Caudle, M S Hershfield, E M McDonagh, J T Callaghan, W Tassaneeyakul, T Mushiroda, N Kamatani, B R Goldspiel, E J Phillips, T E Klein, M T M Lee
The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for HLA-B*58:01 Genotype and Allopurinol Dosing was originally published in February 2013. We reviewed the recent literature and concluded that none of the evidence would change the therapeutic recommendations in the original guideline; therefore, the original publication remains clinically current. However, we have updated the Supplemental Material and included additional resources for applying CPIC guidelines into the electronic health record...
January 2016: Clinical Pharmacology and Therapeutics
J K Hicks, J R Bishop, K Sangkuhl, D J Müller, Y Ji, S G Leckband, J S Leeder, R L Graham, D L Chiulli, A LLerena, T C Skaar, S A Scott, J C Stingl, T E Klein, K E Caudle, A Gaedigk
Selective serotonin reuptake inhibitors (SSRIs) are primary treatment options for major depressive and anxiety disorders. CYP2D6 and CYP2C19 polymorphisms can influence the metabolism of SSRIs, thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide dosing recommendations for fluvoxamine, paroxetine, citalopram, escitalopram, and sertraline based on CYP2D6 and/or CYP2C19 genotype (updates at
August 2015: Clinical Pharmacology and Therapeutics
Payman Shahabi, Marie-Pierre Dubé
Pharmacogenomics (PGx) is the science that examines how an individual's genetic make-up affects the safety and efficacy of therapeutic drugs. PGx of response to cardiovascular (CV) medications is of the most successfully translated branches of PGx into the clinical workout. However, the clinical implementation of PGx of CV drugs is yet far beyond the growth of our understanding of the role of genetics in drug therapy. A considerable amount of efforts have been devoted by the regulatory agents like the food and drug administration (FDA) as well as the expert-based networks such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) to overcome the existing barriers...
April 1, 2015: International Journal of Cardiology
K A Birdwell, B Decker, J M Barbarino, J F Peterson, C M Stein, W Sadee, D Wang, A A Vinks, Y He, J J Swen, J S Leeder, Rhn van Schaik, K E Thummel, T E Klein, K E Caudle, I A M MacPhee
Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation. Individuals who express CYP3A5 (extensive and intermediate metabolizers) generally have decreased dose-adjusted trough concentrations of tacrolimus as compared with those who are CYP3A5 nonexpressers (poor metabolizers), possibly delaying achievement of target blood concentrations. We summarize evidence from the published literature supporting this association and provide dosing recommendations for tacrolimus based on CYP3A5 genotype when known (updates at www...
July 2015: Clinical Pharmacology and Therapeutics
Joseph Mango, Eileen Cabiling, Loretta Jones, Aziza Lucas-Wright, Pluscedia Williams, Kenneth Wells, Esmeralda Pulido, Marcia Meldrum, Ana Ramos, Bowen Chung
"Community Partners in Care (CPIC): Video Summary of Rationale, Study Approach / Implementation, and Client 6-month Outcomes" is a 2 minute, 46 second video summarizing the study rationale, study approach, and the 6-month outcomes. The video was produced by four agencies: Healthy African American Families II, a health advocacy organization in South Los Angeles; Behavioral Health Services, the largest substance/alcohol abuse service provider in LA County; UCLA; and RAND Health; contract filmmakers Eileen Cabiling and Joe Mango handled cinematography, editing, and video support...
February 25, 2014:
K E Caudle, A E Rettie, M Whirl-Carrillo, L H Smith, S Mintzer, M T M Lee, T E Klein, J T Callaghan
Phenytoin is a widely used antiepileptic drug with a narrow therapeutic index and large interpatient variability, partly due to genetic variations in the gene encoding cytochrome P450 (CYP)2C9 (CYP2C9). Furthermore, the variant allele HLA-B*15:02, encoding human leukocyte antigen, is associated with an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in response to phenytoin treatment. We summarize evidence from the published literature supporting these associations and provide recommendations for the use of phenytoin based on CYP2C9 and/or HLA-B genotype (also available on PharmGKB: http://www...
November 2014: Clinical Pharmacology and Therapeutics
Dmitry Khodyakov, Esmeralda Pulido, Ana Ramos, Elizabeth Dixon
THE PROBLEM: Conducting community-partnered research conferences is a powerful yet underutilized approach to translating research into practice and improving result dissemination and intervention sustainability strategies. Nonetheless, detailed descriptions of conference features and ways to use them in empirical research are rare. PURPOSE: We describe how community-partnered conferences may be integrated into research projects by using an example of Community Partners in Care (CPIC), a large, cluster-randomized, controlled, trial (RCT) that uses community-partnered participatory research (CPPR) principles...
2014: Progress in Community Health Partnerships: Research, Education, and Action
M V Relling, E M McDonagh, T Chang, K E Caudle, H L McLeod, C E Haidar, T Klein, L Luzzatto
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with development of acute hemolytic anemia (AHA) induced by a number of drugs. We provide guidance as to which G6PD genotypes are associated with G6PD deficiency in males and females. Rasburicase is contraindicated in G6PD-deficient patients due to the risk of AHA and possibly methemoglobinemia. Unless preemptive genotyping has established a positive diagnosis of G6PD deficiency, quantitative enzyme assay remains the mainstay of screening prior to rasburicase use...
August 2014: Clinical Pharmacology and Therapeutics
L Li
In light of the increasing need by decision makers for a method of evaluating genomic applications based on the weight of evidence for their efficacy, several agencies have developed systems of classification. Here I review the horizon-scanning method for prioritizing genomics applications as described by Dotson et al. in this issue of CPT. Using the examples of the authors' Tier 1/Green classification for KRAS and Tier 2/Yellow for TPMT, I discuss differences between the guidelines issued by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and those by the National Comprehensive Cancer Network (NCCN)...
April 2014: Clinical Pharmacology and Therapeutics
J P Clancy, S G Johnson, S W Yee, E M McDonagh, K E Caudle, T E Klein, M Cannavo, K M Giacomini
Cystic fibrosis (CF) is a life-shortening disease arising as a consequence of mutations within the CFTR gene. Novel therapeutics for CF are emerging that target CF transmembrane conductance regulator protein (CFTR) defects resulting from specific CFTR variants. Ivacaftor is a drug that potentiates CFTR gating function and is specifically indicated for CF patients with a particular CFTR variant, G551D-CFTR (rs75527207). Here, we provide therapeutic recommendations for ivacaftor based on preemptive CFTR genotype results...
June 2014: Clinical Pharmacology and Therapeutics
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