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https://www.readbyqxmd.com/read/29793377/projected-impact-of-a-multigene-pharmacogenetic-test-to-optimize-medication-prescribing-in-cardiovascular-patients
#1
Olivia M Dong, Amy Li, Oscar Suzuki, Akinyemi Oni-Orisan, Ricardo Gonzalez, George A Stouffer, Craig R Lee, Tim Wiltshire
AIM: To determine the projected impact of a multigene pharmacogenetic (PGx) test on medication prescribing. MATERIALS & METHODS: A retrospective analysis was conducted with 122 cardiac catheterization laboratory patients undergoing angiography for eligibility of potential PGx-guided interventions that could have occurred if multigene PGx information was pre-emptively available at the time of the procedure. Medication data and presence of actionable at-risk genotypes were used to determine eligibility of a PGx intervention...
May 25, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29673183/ten-years-experience-with-the-cyp2d6-activity-score-a-perspective-on-future-investigations-to-improve-clinical-predictions-for-precision-therapeutics
#2
REVIEW
Andrea Gaedigk, Jean C Dinh, Hyunyoung Jeong, Bhagwat Prasad, J Steven Leeder
The seminal paper on the CYP2D6 Activity Score (AS) was first published ten years ago and, since its introduction in 2008, it has been widely accepted in the field of pharmacogenetics. This scoring system facilitates the translation of highly complex CYP2D6 diplotype data into a patient’s phenotype to guide drug therapy and is at the core of all CYP2D6 gene/drug pair guidelines issued by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The AS, however, only explains a portion of the variability observed among individuals and ethnicities...
April 17, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29589775/role-of-cyp2c19-genotype-testing-in-clinical-use-of-clopidogrel-is-it-really-useful
#3
Irfan Zeb, Nassim Krim, Jonathan Bella
P2Y12 inhibitors, including clopidogrel have become an integral part of treatment for patients receiving coronary stent placement as a result of stable coronary artery disease or acute coronary syndromes (ACS) and also for medically managed ACS patients. Areas covered: Clopidogrel efficacy can be significantly modified by polymorphism of CYP2C19 genotype (more than 25 allelic variants) involved in its metabolism that can adversely affect its anti-platelet activity. As a result, a substantial number of patients (20-30%) with ACS show an inadequate response to clopidogrel despite a standardized dosing regimen...
May 2018: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/29473149/cyp2d6-and-endoxifen-in-tamoxifen-therapy-a-tribute-to-david-a-flockhart
#4
Todd C Skaar, Zeruesenay Desta
This issue of Clinical Pharmacology & Therapeutics (CPT) includes the Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for using CYP2D6 genotyping to guide tamoxifen therapy for breast cancer patients. CYP2D6 metabolizes tamoxifen to its more active metabolite, endoxifen, and patients with reduced CYP2D6 activity have reduced circulating endoxifen concentrations. In this associated commentary, we recognize and honor the late Dr. David Flockhart, who began the research and made early fundamental discoveries on tamoxifen that have now resulted in this guideline...
May 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29385237/clinical-pharmacogenetics-implementation-consortium-cpic-guideline-for-cyp2d6-and-tamoxifen-therapy
#5
Matthew P Goetz, Katrin Sangkuhl, Henk-Jan Guchelaar, Matthias Schwab, Michael Province, Michelle Whirl-Carrillo, W Fraser Symmans, Howard L McLeod, Mark J Ratain, Hitoshi Zembutsu, Andrea Gaedigk, Ron H van Schaik, James N Ingle, Kelly E Caudle, Teri E Klein
Tamoxifen is biotransformed by CYP2D6 to 4-hydroxytamoxifen and 4-hydroxy N-desmethyl tamoxifen (endoxifen), both with greater antiestrogenic potency than the parent drug. Patients with certain CYP2D6 genetic polymorphisms and patients who receive strong CYP2D6 inhibitors exhibit lower endoxifen concentrations and a higher risk of disease recurrence in some studies of tamoxifen adjuvant therapy of early breast cancer. We summarize evidence from the literature and provide therapeutic recommendations for tamoxifen based on CYP2D6 genotype...
May 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29313967/clinical-pharmacogenetics-implementation-consortium-cpic-guidelines-for-cyp2c19-and-voriconazole-therapy
#6
(no author information available yet)
No abstract text is available yet for this article.
February 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29152729/clinical-pharmacogenetics-implementation-consortium-cpic-guideline-for-dihydropyrimidine-dehydrogenase-genotype-and-fluoropyrimidine-dosing-2017-update
#7
Ursula Amstutz, Linda M Henricks, Steven M Offer, Julia Barbarino, Jan H M Schellens, Jesse J Swen, Teri E Klein, Howard L McLeod, Kelly E Caudle, Robert B Diasio, Matthias Schwab
The purpose of this guideline is to provide information for the interpretation of clinical dihydropyrimidine dehydrogenase (DPYD) genotype tests so that the results can be used to guide dosing of fluoropyrimidines (5-fluorouracil and capecitabine). Detailed guidelines for the use of fluoropyrimidines, their clinical pharmacology, as well as analyses of cost-effectiveness are beyond the scope of this document. The Clinical Pharmacogenetics Implementation Consortium (CPIC® ) guidelines consider the situation of patients for which genotype data are already available (updates available at https://cpicpgx...
February 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29099060/clinical-pharmacogenetics-of-cytochrome-p450-associated-drugs-in-children
#8
Ida Aka, Christiana J Bernal, Robert Carroll, Angela Maxwell-Horn, Kazeem A Oshikoya, Sara L Van Driest
Cytochrome P450 (CYP) enzymes are commonly involved in drug metabolism, and genetic variation in the genes encoding CYPs are associated with variable drug response. While genotype-guided therapy has been clinically implemented in adults, these associations are less well established for pediatric patients. In order to understand the frequency of pediatric exposures to drugs with known CYP interactions, we compiled all actionable drug-CYP interactions with a high level of evidence using Clinical Pharmacogenomic Implementation Consortium (CPIC) data and surveyed 10 years of electronic health records (EHR) data for the number of children exposed to CYP-associated drugs...
November 2, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29032700/improving-depression-care-for-adults-with-serious-mental-illness-in-underresourced-areas-community-coalitions-versus-technical-support
#9
Enrico G Castillo, Roderick Shaner, Lingqi Tang, Bowen Chung, Felica Jones, Yolanda Whittington, Jeanne Miranda, Kenneth B Wells
OBJECTIVE: Community Partners in Care (CPIC) was a group-randomized study of two approaches to implementing expanded collaborative depression care: Community Engagement and Planning (CEP), a coalition approach, and Resources for Services (RS), a technical assistance approach. Collaborative care networks in both arms involved health care and other agencies in five service sectors. This study examined six- and 12-month outcomes for CPIC participants with serious mental illness. METHODS: This secondary analysis focused on low-income CPIC participants from racial-ethnic minority groups with serious mental illness in underresourced Los Angeles communities (N=504)...
February 1, 2018: Psychiatric Services: a Journal of the American Psychiatric Association
https://www.readbyqxmd.com/read/28994452/comparison-of-the-guidelines-of-the-clinical-pharmacogenetics-implementation-consortium-and-the-dutch-pharmacogenetics-working-group
#10
REVIEW
P C D Bank, K E Caudle, J J Swen, R S Gammal, M Whirl-Carrillo, T E Klein, M V Relling, H-J Guchelaar
Both the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetics Working Group provide therapeutic recommendations for well-known gene-drug pairs. Published recommendations show a high rate of concordance. However, as a result of different guideline development methods used by these two consortia, differences between the published guidelines exist. The aim of this paper is to compare both initiatives and explore these differences, with the objective to achieve harmonization.
April 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28811733/community-partners-in-care-6-month-outcomes-of-two-quality-improvement-depression-care-interventions-in-male-participants
#11
Pratik Mehta, Anthony Brown, Bowen Chung, Felica Jones, Lingqi Tang, James Gilmore, Jeanne Miranda, Kenneth Wells
OBJECTIVE: Limited data exist on approaches to improve depression services for men in under-resourced communities. This article explores this issue using a sub-analysis of male participants in Community Partners in Care (CPIC). DESIGN: Community partnered, cluster, randomized trial. SETTING: Hollywood-Metropolitan and South Los Angeles, California. PARTICIPANTS: 423 adult male clients with modified depression (PHQ-8 score≥10)...
2017: Ethnicity & Disease
https://www.readbyqxmd.com/read/28749586/patient-decisions-to-receive-secondary-pharmacogenomic-findings-and-development-of-a-multidisciplinary-practice-model-to-integrate-results-into-patient-care
#12
J Kevin Hicks, Amy Shealy, Allison Schreiber, Marissa Coleridge, Ryan Noss, Marvin Natowicz, Rocio Moran, Timothy Moss, Angelika Erwin, Charis Eng
Whole exome sequencing (WES) has the potential of identifying secondary findings that are predictive of poor pharmacotherapy outcomes. The purpose of this study was to investigate patients' wishes regarding the reporting of secondary pharmacogenomic findings. WES results (n = 106 patients) were retrospectively reviewed to determine the number of patients electing to receive secondary pharmacogenomic results. Phenotypes were assigned based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines...
January 2018: Clinical and Translational Science
https://www.readbyqxmd.com/read/28654154/commentary-should-pharmacogenomic-evidence-be-considered-in-clinical-decision-making-focus-on-select-cardiovascular-drugs
#13
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 use 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 pharmacogenomics is cost-effective...
September 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28629370/pharmacogenetic-testing-through-the-direct-to-consumer-genetic-testing-company-23andme
#14
Mengfei Lu, Cathryn M Lewis, Matthew Traylor
BACKGROUND: Rapid advances in scientific research have led to an increase in public awareness of genetic testing and pharmacogenetics. Direct-to-consumer (DTC) genetic testing companies, such as 23andMe, allow consumers to access their genetic information directly through an online service without the involvement of healthcare professionals. Here, we evaluate the clinical relevance of pharmacogenetic tests reported by 23andMe in their UK tests. METHODS: The research papers listed under each 23andMe report were evaluated, extracting information on effect size, sample size and ethnicity...
June 19, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28467824/core-mediator-structure-at-3-4-%C3%A3-extends-model-of-transcription-initiation-complex
#15
Kayo Nozawa, Thomas R Schneider, Patrick Cramer
Mediator is a multiprotein co-activator that binds the transcription pre-initiation complex (PIC) and regulates RNA polymerase (Pol) II. The Mediator head and middle modules form the essential core Mediator (cMed), whereas the tail and kinase modules play regulatory roles. The architecture of Mediator and its position on the PIC are known, but atomic details are limited to Mediator subcomplexes. Here we report the crystal structure of the 15-subunit cMed from Schizosaccharomyces pombe at 3.4 Å resolution...
May 11, 2017: Nature
https://www.readbyqxmd.com/read/28198005/clinical-pharmacogenetics-implementation-consortium-cpic-guideline-for-pharmacogenetics-guided-warfarin-dosing-2017-update
#16
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...
September 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
#17
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...
September 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28046094/analysis-of-genetic-variation-in-cyp450-genes-for-clinical-implementation
#18
Liuh Ling Goh, Chia Wei Lim, Wey Cheng Sim, Li Xian Toh, Khai Pang Leong
BACKGROUND: Genetic determinants of drug response remain stable throughout life and offer great promise to patient-tailored drug therapy. The adoption of pharmacogenetic (PGx) testing in patient care requires accurate, cost effective and rapid genotyping with clear guidance on the use of the results. Hence, we evaluated a 32 SNPs panel for implementing PGx testing in clinical laboratories. METHODS: We designed a 32-SNP panel for PGx testing in clinical laboratories...
2017: PloS One
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
#19
REVIEW
Erika Cecchin, Rossana Roncato, Hendrik J Guchelaar, Giuseppe Toffoli
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 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...
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
#20
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
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