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Clinical Pharmacogenetics Implementation Consortium

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https://www.readbyqxmd.com/read/28699646/review-of-opioid-pharmacogenetics-and-considerations-for-pain-management
#1
Aniwaa Owusu Obeng, Issam Hamadeh, Michael Smith
Opioid analgesics are the standards of care for the treatment of moderate to severe nociceptive pain, particularly in the setting of cancer and surgery. Their analgesic properties mainly emanate from stimulation of the μ receptors, which are encoded by the OPRM1 gene. Hepatic metabolism represents the major route of elimination, which, for some opioids, namely codeine and tramadol, is necessary for their bioactivation into more potent analgesics. The highly polymorphic nature of the genes coding for phase I and phase II enzymes (pharmacokinetics genes) that are involved in the metabolism and bioactivation of opioids suggests a potential interindividual variation in their disposition and, most likely, response...
July 12, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28654154/commentary-should-pharmacogenomic-evidence-be-considered-in-clinical-decision-making-focus-on-select-cardiovascular-drugs
#2
Michael B Bottorff, David R Bright, David F Kisor
Despite advances in technology and guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) that focus on how to utilize pharmacogene test results, hurdles remain that have delayed the widespread application of pharmacogenomics in clinical practice. These hurdles include a lack of prospective randomized controlled trials to address the utility of pharmacogenomics on clinical outcomes, what the clinical algorithm for pharmacogenomics should be, and whether or not pharmacogenomics is cost-effective...
June 27, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28315856/an-update-on-hla-alleles-associated-with-adverse-drug-reactions
#3
REVIEW
Ingrid Fricke-Galindo, Adrián LLerena, Marisol López-López
Adverse drug reactions (ADRs) are considered as an important cause of morbidity and mortality. The hypersensitivity reactions are immune-mediated ADRs, which are dose-independent, unpredictable and have been associated with several HLA alleles. The present review aimed to describe HLA alleles that have been associated with different ADRs in populations worldwide, the recommendations of regulatory agencies and pharmacoeconomic information and databases for the study of HLA alleles in pharmacogenetics. A systematic search was performed in June 2016 of articles relevant to this issue in indexed journals and in scientific databases (PubMed and PharmGKB)...
May 24, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28198005/clinical-pharmacogenetics-implementation-consortium-cpic-guideline-for-pharmacogenetics-guided-warfarin-dosing-2017-update
#4
J A Johnson, K E Caudle, L Gong, M Whirl-Carrillo, C M Stein, S A Scott, M T Lee, B F Gage, S E Kimmel, M A Perera, J L Anderson, M Pirmohamed, T E Klein, N A Limdi, L H Cavallari, M Wadelius
This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype-guided warfarin dosing to achieve a target international normalized ratio of 2-3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry...
February 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28090649/the-pharmacogenomics-research-network-translational-pharmacogenetics-program-outcomes-and-metrics-of-pharmacogenetic-implementations-across-diverse-healthcare-systems
#5
J A Luzum, R E Pakyz, A R Elsey, C E Haidar, J F Peterson, M Whirl-Carrillo, S K Handelman, K Palmer, J M Pulley, M Beller, J S Schildcrout, J R Field, K W Weitzel, R M Cooper-DeHoff, L H Cavallari, P H O'Donnell, R B Altman, N Pereira, M J Ratain, D M Roden, P J Embi, W Sadee, T E Klein, J A Johnson, M V Relling, L Wang, R M Weinshilboum, A R Shuldiner, R R Freimuth
Numerous pharmacogenetic clinical guidelines and recommendations have been published, but barriers have hindered the clinical implementation of pharmacogenetics. The Translational Pharmacogenetics Program (TPP) of the National Institutes of Health (NIH) Pharmacogenomics Research Network was established in 2011 to catalog and contribute to the development of pharmacogenetic implementations at eight US healthcare systems, with the goal to disseminate real-world solutions for the barriers to clinical pharmacogenetic implementation...
January 16, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28044932/ubiquitous-pharmacogenomics-u-pgx-the-time-for-implementation-is-now-an-horizon2020-program-to-drive-pharmacogenomics-into-clinical-practice
#6
Erika Cecchin, Rossana Roncato, Hendrik Jan Guchelaar, Giuseppe Toffoli, and for the Ubiquitous Pharmacogenomics Consortium
Although the clinical validity of a number of pharmacogenetic markers is nowadays a matter of fact, and led authoritative scientific consortia as the Dutch Pharmacogenetic Working Group (DPWG) and the Clinical Pharmacogenomics Implementation Consortium (CPIC) to publish pharmacogenetic guidelines, the clinical implementation in the real life remains challenging. Ubiquitous Pharmacogenomics (U-PGx) program is a coordinated effort that put together scientific and clinical expertise in the pharmacogenomic field, to implement the pre-emptive pharmacogenomic approach in the clinical practice in Europe, and to demonstrate its benefit in both patients clinical outcome and quality of life, with an economic advantage for the healthcare system...
January 2, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28002639/clinical-pharmacogenetics-implementation-consortium-cpic-guideline-for-cyp2d6-genotype-and-use-of-ondansetron-and-tropisetron
#7
G C Bell, K E Caudle, M Whirl-Carrillo, R J Gordon, K Hikino, C A Prows, A Gaedigk, Jag Agundez, S Sadhasivam, T E Klein, M Schwab
No abstract text is available yet for this article.
August 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27997040/clinical-pharmacogenetics-implementation-consortium-guideline-cpic-for-cyp2d6-and-cyp2c19-genotypes-and-dosing-of-tricyclic-antidepressants-2016-update
#8
J K Hicks, K Sangkuhl, J J Swen, V L Ellingrod, D J Müller, K Shimoda, J R Bishop, E D Kharasch, T C Skaar, A Gaedigk, H M Dunnenberger, T E Klein, K E Caudle, J C Stingl
No abstract text is available yet for this article.
December 20, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27981572/clinical-pharmacogenetics-implementation-consortium-cpic-guidelines-for-cyp2c19-and-voriconazole-therapy
#9
B Moriyama, A Owusu Obeng, J Barbarino, S R Penzak, S A Henning, S A Scott, Jag Agúndez, J R Wingard, H L McLeod, T E Klein, S J Cross, K E Caudle, T J Walsh
Voriconazole, a triazole antifungal agent, demonstrates wide interpatient variability in serum concentrations, due in part to variant CYP2C19 alleles. Individuals who are CYP2C19 ultrarapid metabolizers have decreased trough voriconazole concentrations, delaying achievement of target blood concentrations; whereas poor metabolizers have increased trough concentrations and are at increased risk of adverse drug events. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of voriconazole for treatment based on CYP2C19 genotype (updates at https://cpicpgx...
December 16, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27864205/evidence-and-resources-to-implement-pharmacogenetic-knowledge-for-precision-medicine
#10
Kelly E Caudle, Roseann S Gammal, Michelle Whirl-Carrillo, James M Hoffman, Mary V Relling, Teri E Klein
PURPOSE: The current state of pharmacogenetic data curation and dissemination is described, and evidence-based resources for applying pharmacogenetic data in clinical practice are reviewed. SUMMARY: Implementation of pharmacogenetics in clinical practice has been relatively slow despite substantial scientific progress in understanding linkages between genetic variation and variability of drug response and effect. One factor that has inhibited the adoption of genetic data to guide medication use is a lack of knowledge of how to translate genetic test results into clinical action based on currently available evidence...
December 1, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27864204/integrating-pharmacogenomics-into-electronic-health-records-with-clinical-decision-support
#11
J Kevin Hicks, Henry M Dunnenberger, Karl F Gumpper, Cyrine E Haidar, James M Hoffman
PURPOSE: Existing pharmacogenomic informatics models, key implementation steps, and emerging resources to facilitate the development of pharmacogenomic clinical decision support (CDS) are described. SUMMARY: Pharmacogenomics is an important component of precision medicine. Informatics, especially CDS in the electronic health record (EHR), is a critical tool for the integration of pharmacogenomics into routine patient care. Effective integration of pharmacogenomic CDS into the EHR can address implementation challenges, including the increasing volume of pharmacogenomic clinical knowledge, the enduring nature of pharmacogenomic test results, and the complexity of interpreting results...
December 1, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27864202/implementation-of-inpatient-models-of-pharmacogenetics-programs
#12
Larisa H Cavallari, Craig R Lee, Julio D Duarte, Edith A Nutescu, Kristin W Weitzel, George A Stouffer, Julie A Johnson
PURPOSE: The operational elements essential for establishing an inpatient pharmacogenetic service are reviewed, and the role of the pharmacist in the provision of genotype-guided drug therapy in pharmacogenetics programs at three institutions is highlighted. SUMMARY: Pharmacists are well positioned to assume important roles in facilitating the clinical use of genetic information to optimize drug therapy given their expertise in clinical pharmacology and therapeutics...
December 1, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27643672/pharmacogenomics-and-global-precision-medicine-in-the-context-of-adverse-drug-reactions-top-10-opportunities-and-challenges-for-the-next-decade
#13
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
https://www.readbyqxmd.com/read/27603572/advances-and-challenges-in-hereditary-cancer-pharmacogenetics
#14
REVIEW
Ingolf Cascorbi, Anneke Nina Werk
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)...
January 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27537706/assessing-the-capability-of-massively-parallel-sequencing-for-opportunistic-pharmacogenetic-screening
#15
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...
March 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/27441996/standardizing-terms-for-clinical-pharmacogenetic-test-results-consensus-terms-from-the-clinical-pharmacogenetics-implementation-consortium-cpic
#16
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...
February 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/27388693/prediction-of-cyp2d6-phenotype-from-genotype-across-world-populations
#17
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...
January 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/27383664/a-systematic-analysis-and-comparison-of-warfarin-initiation-strategies
#18
COMPARATIVE STUDY
Benjamin French, Le Wang, Brian F Gage, Richard B Horenstein, Nita A Limdi, Stephen E Kimmel
OBJECTIVE: Randomized trials have reported inconsistent evidence on the effectiveness of algorithms that use genotypes to initiate warfarin therapy. The Clarification of Optimal Anticoagulation through Genetics (COAG) trial initiated therapy on the basis of predicted maintenance doses, with a pharmacogenetic-guided algorithm in one study group and a clinically guided algorithm in the other. The European Pharmacogenetics of Anticoagulant Therapy (EU-PACT) consortium initiated therapy on the basis of loading doses, with an algorithm-based prediction in one study group and a fixed-dose regimen in the other...
October 2016: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/27312955/implementation-of-clinical-pharmacogenomics-within-a-large-health-system-from-electronic-health-record-decision-support-to-consultation-services
#19
J Kevin Hicks, David Stowe, Marc A Willner, Maya Wai, Thomas Daly, Steven M Gordon, Bret A Lashner, Sumit Parikh, Robert White, Kathryn Teng, Timothy Moss, Angelika Erwin, Jeffrey Chalmers, Charis Eng, Scott Knoer
The number of clinically relevant gene-based guidelines and recommendations pertaining to drug prescribing continues to grow. Incorporating gene-drug interaction information into the drug-prescribing process can help optimize pharmacotherapy outcomes and improve patient safety. However, pharmacogenomic implementation barriers exist such as integration of pharmacogenomic results into electronic health records (EHRs), development and deployment of pharmacogenomic decision support tools to EHRs, and feasible models for establishing ambulatory pharmacogenomic clinics...
August 2016: Pharmacotherapy
https://www.readbyqxmd.com/read/27311679/comparison-of-genome-sequencing-and-clinical-genotyping-for-pharmacogenes
#20
COMPARATIVE STUDY
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
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