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Pharmacogenomics May 2020genotyping is used to guide antiplatelet therapy after percutaneous coronary intervention (PCI). This study evaluated the potential impact of and multigene... (Observational Study)
Observational Study
genotyping is used to guide antiplatelet therapy after percutaneous coronary intervention (PCI). This study evaluated the potential impact of and multigene pharmacogenomics (PGx) testing on medications beyond antiplatelet therapy in a real-world cohort of PCI patients that underwent testing. Multiple medications with actionable PGx recommendations, including proton pump inhibitors, antidepressants and opioids, were commonly prescribed. Approximately 50% received a CYP2C19 metabolized medication beyond clopidogrel and 7% met criteria for a genotype-guided intervention. A simulation analysis projected that 17.5 PGx-guided medication interventions per 100 PCI patients could have been made if multigene PGx results were available. This suggests that and multigene PGx results could be used to optimize medication prescribing beyond antiplatelet therapy in PCI patients.
Topics: Aged; Clopidogrel; Cohort Studies; Cytochrome P-450 CYP2C19; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Pharmacogenetics; Pharmacogenomic Testing; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Retrospective Studies; Ticagrelor
PubMed: 32343201
DOI: 10.2217/pgs-2019-0185 -
Clinical and Translational Science Jan 2024The DPYD gene encodes dihydropyrimidine dehydrogenase, the rate-limiting enzyme for the metabolism of fluoropyrimidines 5-fluorouracil and capecitabine. Genetic variants...
The DPYD gene encodes dihydropyrimidine dehydrogenase, the rate-limiting enzyme for the metabolism of fluoropyrimidines 5-fluorouracil and capecitabine. Genetic variants in DPYD have been associated with altered enzyme activity, therefore accurate detection and interpretation is critical to predict metabolizer status for individualized fluoropyrimidine therapy. The most commonly observed deleterious variation is the causal variant linked to the previously described HapB3 haplotype, c.1129-5923C>G (rs75017182) in intron 10, which introduces a cryptic splice site. A benign synonymous variant in exon 11, c.1236G>A (rs56038477) is also linked to HapB3 and is commonly used for testing. Previously, these single-nucleotide polymorphisms (SNPs) have been reported to be in perfect linkage disequilibrium (LD); therefore, c.1236G>A is often utilized as a proxy for the function-altering intronic variant. Clinical genotyping of DPYD identified a patient who had c.1236G>A, but not c.1129-5923C>G, suggesting that these two SNPs may not be in perfect LD, as previously assumed. Additional individuals with c.1236G>A, but not c.1129-5923C>G, were identified in the Children's Mercy Data Warehouse and the All of Us Research Program version 7 cohort substantiating incomplete SNP linkage. Consequently, testing only c.1236G>A can generate false-positive results in some cases and lead to suboptimal dosing that may negatively impact patient therapy and prospect of survival. Our data show that DPYD genotyping should include the functional variant c.1129-5923C>G, and not the c.1236G>A proxy, to accurately predict DPD activity.
Topics: Child; Humans; Dihydrouracil Dehydrogenase (NADP); Haplotypes; Antimetabolites, Antineoplastic; Pharmacogenomic Testing; Population Health; Genotype
PubMed: 38129972
DOI: 10.1111/cts.13699 -
Psychiatry Research Feb 2021We evaluated the clinical validity of a combinatorial pharmacogenomic test and single-gene Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines against...
Clinical validation of combinatorial pharmacogenomic testing and single-gene guidelines in predicting psychotropic medication blood levels and clinical outcomes in patients with depression.
We evaluated the clinical validity of a combinatorial pharmacogenomic test and single-gene Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines against patient outcomes and medication blood levels to assess their ability to inform prescribing in major depressive disorder (MDD). This is a secondary analysis of the Genomics Used to Improve DEpression Decisions (GUIDED) randomized-controlled trial, which included patients with a diagnosis of MDD, and ≥1 prior medication failure. The ability to predict increased/decreased medication metabolism was validated against blood levels at screening (adjusted for age, sex, smoking status). The ability of predicted gene-drug interactions (pharmacogenomic test) or therapeutic recommendations (single-gene guidelines) to predict patient outcomes was validated against week 8 outcomes (17-item Hamilton Depression Rating Scale; symptom improvement, response, remission). Analyses were performed for patients taking any eligible medication (outcomes N=1,022, blood levels N=1,034) and the subset taking medications with single-gene guidelines (outcomes N=584, blood levels N=372). The combinatorial pharmacogenomic test was the only significant predictor of patient outcomes. Both the combinatorial pharmacogenomic test and single-gene guidelines were significant predictors of blood levels for all medications when evaluated separately; however, only the combinatorial pharmacogenomic test remained significant when both were included in the multivariate model. There were no substantial differences when all medications were evaluated or for the subset with single-gene guidelines. Overall, this evaluation of clinical validity demonstrates that the combinatorial pharmacogenomic test was a superior predictor of patient outcomes and medication blood levels when compared with guidelines based on individual genes.
Topics: Adult; Depressive Disorder, Major; Genomics; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Pharmacogenetics; Pharmacogenomic Testing; Predictive Value of Tests; Psychotropic Drugs; Reproducibility of Results; Treatment Outcome
PubMed: 33360967
DOI: 10.1016/j.psychres.2020.113649 -
Anesthesia and Analgesia Nov 2022
Topics: Pharmacogenetics; Perioperative Medicine; Feasibility Studies; Pharmacogenomic Testing; Precision Medicine
PubMed: 36269983
DOI: 10.1213/ANE.0000000000006054 -
Deutsche Medizinische Wochenschrift... Jan 2021
Topics: Drug Therapy; Humans; Internal Medicine; Pharmacogenomic Testing; Polypharmacy; Precision Medicine
PubMed: 33395720
DOI: 10.1055/a-0952-9813 -
The Journal of Clinical Psychiatry Dec 2019
Topics: Antidepressive Agents; Humans; Pharmacogenomic Testing; Treatment Outcome
PubMed: 31846245
DOI: 10.4088/JCP.19com13119 -
British Journal of Clinical Pharmacology Mar 2021Pre-emptive pharmacogenomic (PGx) testing is potentially an efficient approach to improve drug safety and efficacy but the target population to test is unclear.
BACKGROUND
Pre-emptive pharmacogenomic (PGx) testing is potentially an efficient approach to improve drug safety and efficacy but the target population to test is unclear.
OBJECTIVES
We aim to describe the prescription pattern of PGx drugs among adult medical outpatients.
METHODS
We estimated the 5-year cumulative incidence (CI) for receiving three groups of PGx drugs using competing risks analysis: (i) all PGx drugs, (ii) PGx drugs with guidelines and (iii) PGx drugs with serious clinical effects. Comparisons of CIs were also done by patient characteristics using Gray's test.
RESULTS
The 5-year CIs of receiving any new PGx drug, PGx drug with guidelines and serious clinical effects were 42.6%, 37.3% and 13.7%, respectively. The 5-year CI of receiving any new PGx drug was higher for patients >40 years old (43.6% vs ≤40 years old 36.0%, P < 2.2 × 10 ), Malays and Indians (50.3% and 49.8% vs Chinese 31.1%, P < 2.2 × 10 ), those who attended one of the following four specialties at the index visit compared to other specialties (infectious diseases [46.2% vs 42.6%, P = 2.9 × 10 ], psychiatry [48.3% vs 42.3%, P = 7.4 × 10 ], renal [49.8% vs 40.9%, P < 2.2 × 10 ], and rheumatology and immunology [54.8% vs 41.7%, P < 2.2 × 10 ]) and those prescribed ≥5 drugs at index visit (51.7% vs 0-4 drugs 41.7%, P < 2.2 × 10 ).
CONCLUSIONS
Medical outpatients have a substantial probability of benefiting from pre-emptive PGx testing and this is higher in certain subgroups of patients.
Topics: Adult; Humans; Outpatients; Pharmacogenetics; Pharmacogenomic Testing; Prescriptions; Psychiatry
PubMed: 32559336
DOI: 10.1111/bcp.14439 -
Clinical and Translational Science Nov 2021Personal genomic educational testing (PGET) has been suggested as a strategy to improve student learning for pharmacogenomics (PGx), but no randomized studies have... (Randomized Controlled Trial)
Randomized Controlled Trial
Personal genomic educational testing (PGET) has been suggested as a strategy to improve student learning for pharmacogenomics (PGx), but no randomized studies have evaluated PGET's educational benefit. We investigated the effect of PGET on student knowledge, comfort, and attitudes related to PGx in a nonblinded, randomized controlled trial. Consenting participants were randomized to receive PGET or no PGET (NPGET) during 4 subsequent years of a PGx course. All participants completed a pre-survey and post-survey designed to assess (1) PGx knowledge, (2) comfort with PGx patient education and clinical skills, and (3) attitudes toward PGx. Instructors were blinded to PGET assignment. The Wilcoxon Rank Sum test was used to compare pre-survey and post-survey PGx knowledge, comfort, and attitudes. No differences in baseline characteristics were observed between PGET (n = 117) and NPGET (n = 116) participants. Among all participants, significant improvement was observed in PGx knowledge (mean 57% vs. 39% correct responses; p < 0.001) with similar results for student comfort and attitudes. Change in pre/post-PGx knowledge, comfort, and attitudes were not significantly different between PGET and NPGET groups (mean 19.5% vs. 16.7% knowledge improvement, respectively; p = 0.41). Similar results were observed for PGET participants carrying a highly actionable PGx variant versus PGET participants without an actionable variant. Significant improvement in Likert scale responses were observed in PGET versus NPGET for questions that assessed student engagement (p = 0.020) and reinforcement of course concepts (p = 0.006). Although some evidence of improved engagement and participation was observed, the results of this study suggest that PGET does not directly improve student PGx knowledge, comfort, and attitudes.
Topics: Adult; Curriculum; Education, Pharmacy; Female; Genotyping Techniques; Humans; Male; Pharmacogenomic Testing; Surveys and Questionnaires; Young Adult
PubMed: 34431601
DOI: 10.1111/cts.13121 -
Journal of the American Pharmacists... 2021To demonstrate the successful use of pharmacogenomic testing to specifically tailor antifungal treatment to the phenotype of a patient with human immunodeficiency virus...
OBJECTIVES
To demonstrate the successful use of pharmacogenomic testing to specifically tailor antifungal treatment to the phenotype of a patient with human immunodeficiency virus (HIV) and disseminated histoplasmosis who had clinical progression while on itraconazole and subsequently had insufficient therapeutic drug levels of voriconazole.
CASE SUMMARY
We present the case of a patient with HIV and disseminated histoplasmosis with a persistently elevated serum Histoplasma capsulatum antigen and subtherapeutic levels of voriconazole. Pharmacogenomic testing revealed he was a CYP2C19 rapid metabolizer, thus explaining his persistent, subtherapeutic levels of voriconazole and prompting a change in therapy.
PRACTICE IMPLICATIONS
Our case illustrates the importance of pharmacogenomic testing as a tool to evaluate subtherapeutic itraconazole or voriconazole levels, especially in patients with failed clinical or Histoplasmosis Ag response despite reporting full adherence to prescribed therapy.
Topics: HIV; HIV Infections; Histoplasma; Histoplasmosis; Humans; Male; Pharmacogenomic Testing
PubMed: 33583749
DOI: 10.1016/j.japh.2021.01.021 -
Pharmacogenetics and Genomics May 2017Pharmacogenomics seeks to improve prescribing by reducing drug inefficacy/toxicity. However, views of patients during pharmacogenomic-guided care are largely unknown. We...
OBJECTIVE
Pharmacogenomics seeks to improve prescribing by reducing drug inefficacy/toxicity. However, views of patients during pharmacogenomic-guided care are largely unknown. We sought to understand the attitudes and perceptions of patients in an institutional implementation project and hypothesized that views would differ on the basis of experience with pharmacogenomic-guided care.
METHODS
Two focus groups were conducted - one group included patients who had previously been subjected to broad pharmacogenomic genotyping with results available to physicians (pharmacogenomic group), whereas the other had not been offered genotyping (traditional care). Five domains were explored: (i) experiences with medications/side effects, (ii) understanding of pharmacogenomics, (iii) impact of pharmacogenomics on relationships with healthcare professionals, (iv) scenarios involving pharmacogenomic-guided prescribing, and (v) responses to pharmacogenomic education materials.
RESULTS
Nine pharmacogenomic and 13 traditional care participants were included. Participants in both groups agreed that pharmacogenomics could inform prescribing and help identify problem prescriptions, but expressed concerns over insurance coverage and employment discrimination. Both groups diverged on who should be permitted to access pharmacogenomic results, with some preferring access only for providers with a longstanding relationship, whereas others argued for open access. Notably, traditional care participants showed greater skepticism about how results might be used. Case scenarios and tested educational materials elicited strong desires on the part of patients for physicians to engage participants when considering pharmacogenomic-based prescribing and to utilize shared decision-making.
CONCLUSION
Participants experiencing pharmacogenomic-guided care were more receptive toward pharmacogenomic information being used than traditional care participants. As key stakeholders in implementation, addressing patients' concerns will be important to successfully facilitate clinical dissemination.
Topics: Adult; Aged; Decision Making; Female; Humans; Male; Middle Aged; Patient Acceptance of Health Care; Pharmacogenomic Testing; Precision Medicine
PubMed: 28267054
DOI: 10.1097/FPC.0000000000000275