12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2021/01/16

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Impact of Previous Genetic Counseling and Objective Numeracy on Accurate Interpretation of a Pharmacogenetics Test Report.

Public Health Genomics. 2021 Jan 14;:1-7

Authors: Drelles K, Pilarski R, Manickam K, Shoben AB, Toland AE

Abstract
INTRODUCTION: Pharmacogenetic (PGx) testing can be useful for providing information about a patient's drug response by increasing drug efficacy and decreasing the incidence of adverse drug events. While PGx tests were previously only offered to patients under healthcare provider supervision, they are now available as direct to consumer (DTC) tests. This study aimed to assess how accurately individuals from the general population were able to interpret a sample PGx test report and if accuracy differed based on individuals' numeracy or prior genetic counseling (GC).
METHODS: We surveyed 293 individuals from the general population, ascertained through ResearchMatch. The survey included questions about PGx test interpretation, numeracy, and genetic literacy.
RESULTS: In our cohort, numeracy level impacted PGx result interpretation, with those of high numeracy performing statistically significantly better on both the table format and graphical format (p value = 0.002 and p value <0.001, respectively) and genetic knowledge questions (p value <0.001) than those with low/average numeracy. In addition, previous GC did not impact test interpretation or genetic knowledge, but the number of individuals with prior GC was small (n = 26).
DISCUSSION/CONCLUSION: We found that numeracy had a significant impact on correct interpretation of PGx test reports. Because many individuals in the USA have low numeracy levels, it is extremely important that patients do not make their own medication management decision based on the test results and that they consult with their physicians about their PGx testing. The importance of consultation and discussion with providers about results should be emphasized on the test report.

PMID: 33445171 [PubMed - as supplied by publisher]

Effect of Hydrolyzable Tannins on Glucose-Transporter Expression and Their Bioavailability in Pig Small-Intestinal 3D Cell Model.

Molecules. 2021 Jan 11;26(2):

Authors: Brus M, Frangež R, Gorenjak M, Kotnik P, Knez Ž, Škorjanc D

Abstract
Intestinal transepithelial transport of glucose is mediated by glucose transporters, and affects postprandial blood-glucose levels. This study investigates the effect of wood extracts rich in hydrolyzable tannins (HTs) that originated from sweet chestnut (Castanea sativa Mill.) and oak (Quercus petraea) on the expression of glucose transporter genes and the uptake of glucose and HT constituents in a 3D porcine-small-intestine epithelial-cell model. The viability of epithelial cells CLAB and PSI exposed to different HTs was determined using alamarBlue®. qPCR was used to analyze the gene expression of SGLT1, GLUT2, GLUT4, and POLR2A. Glucose uptake was confirmed by assay, and LC-MS/ MS was used for the analysis of HT bioavailability. HTs at 37 µg/mL were found to adversely affect cell viability and downregulate POLR2A expression. HT from wood extract Tanex at concentrations of 4 µg/mL upregulated the expression of GLUT2, as well as glucose uptake at 1 µg/mL. The time-dependent passage of gallic acid through enterocytes was influenced by all wood extracts compared to gallic acid itself as a control. These results suggest that HTs could modulate glucose uptake and gallic acid passage in the 3D cell model.

PMID: 33440878 [PubMed - in process]

Pharmacogenetics of Direct Oral Anticoagulants: A Systematic Review.

J Pers Med. 2021 Jan 11;11(1):

Authors: Raymond J, Imbert L, Cousin T, Duflot T, Varin R, Wils J, Lamoureux F

Abstract
Dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban are direct oral anticoagulants (DOACs). Their inter-individual variability in pharmacodynamics and pharmacokinetics (transport and metabolism) is high, and could result from genetic polymorphisms. As recommended by the French Network of Pharmacogenetics (RNPGx), the management of some treatments in cardiovascular diseases (as antiplatelet agents, oral vitamin K antagonists, and statins) can rely on genetic testing in order to improve healthcare by reducing therapeutic resistance or toxicity. This paper is a review of association studies between single nucleotide polymorphisms (SNPs) and systemic exposure variation of DOACs. Most of the results presented here have a lot to do with some SNPs of CES1 (rs2244613, rs8192935, and rs71647871) and ABCB1 (rs1128503, rs2032582, rs1045642, and rs4148738) genes, and dabigatran, rivaroxaban, and apixaban. Regarding edoxaban and betrixaban, as well as SNPs in the CYP3A4 and CYP3A5 genes, literature is scarce, and further studies are needed.

PMID: 33440670 [PubMed]

Component resolved diagnosis by recombinant allergens in patients with allergies to inhalants.

J Biol Regul Homeost Agents. 2020 Sep-Oct,;34(5):1729-1737

Authors: Di Spigna G, Ladogana P, Covelli B, Ricciardone M, Salzano S, Spalletti Cernia D, Mormile I, Varriale G, Catapano O, Spadaro G, Mormile M, Postiglione L

Abstract
Molecular characterization of IgE reactivity of specific individual components of allergenic extracts is now possible due to the technology of recombinant allergens derived from studies of molecular biology of allergic pathology. The identification of the immunoreactivity to single allergenic components in allergic subjects allows to specifically define her/his allergic profile and obtain the so-termed Component Resolved Diagnosis (CRD). Molecular allergens can be classified into those that induce the respiratory allergic reactivity and those that identify the food-related allergic pathology. It is also essential to identify those molecular allergens whose immunoreactivity is able to connect the two clinical conditions: respiratory symptoms and food allergy symptoms. The present study was conducted on 50 patients with a clinical history of hypersensitivity to pollen and/or allergy and positivity to Skin Prick Test. The sera were analyzed in our laboratories and the panel of recombinant allergens was applied in the case of positivity of the specific IgE. Of the 50 patients enrolled, 31 were selected as positive to 4 main pan-allergen Bet v1, Par j2, Art v1 and Phl p1; among these, 14 subjects showed one allergen-specific IgE towards natural extracts of tested foods even in absence of clinical history. CRD allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in: a) resolving genuine vs cross-reactive sensitization in poly-sensitized patients, b) assessing, in selected cases, the risk of severe, systemic vs mild, local reactions in food allergy, and c) identifying patients and triggering allergens for specific immunotherapy (ITS). In light of our results, we believe that the transition from a diagnostic based on the use of allergenic extracts to another one based on the use of single allergenic molecules that is able to define the specific allergenic profile of each patient, seems to be able to revolutionize the allergy diagnosis.

PMID: 33143407 [PubMed - indexed for MEDLINE]

11 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2021/01/14

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Characterization of CYP2D6 drugs as substrates of human organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs).

Br J Pharmacol. 2021 Jan 12;:

Authors: Neul C, Hofmann U, Schaeffeler E, Winter S, Klein K, Giacomini KM, Eichelbaum M, Schwab M, Nies AT

Abstract
BACKGROUND AND PURPOSE: The metabolic activity of cytochrome P450 (CYP) 2D6 is highly variable and CYP2D6 genotypes insufficiently explain the extensive and intermediate metabolic phenotypes, thus limiting the prediction of drug response and/or adverse drug reactions. Since CYP2D6 prototypic substrates are positively charged, the aim of this study was to evaluate the organic cation membrane transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs) as potential contributors to the variability of CYP2D6 hydroxylation of the CYP2D6 drugs debrisoquine, dextromethorphan, diphenhydramine, perhexiline and sparteine.
EXPERIMENTAL APPROACH: OCT1/SLC22A1-, OCT2/SLC22A2-, OCT3/SLC22A3-, MATE1/SLC47A1- and MATE2K/SLC47A2-overexpressing cell lines were used to investigate the transport of the selected agents. Individuals from a study cohort, well-defined with respect to CYP2D6 genotype and sparteine pharmacokinetics, were genotyped for the common OCT1 variants rs12208357 (OCT1-R61C), rs34130495 (OCT1-G401S), rs202220802 (OCT1-Met420del), rs34059508 (OCT1-G465R), OCT2 variant rs316019 (OCT2-A270S) and MATE1 variant rs2289669. Sparteine pharmacokinetics was stratified according to CYP2D6 and OCT1, OCT2 or MATE1 genotype.
KEY RESULTS: OCTs and MATE1 transport sparteine and debrisoquine with high affinity in vitro, but OCT- and MATE1-dependent transport of dextromethorphan, diphenhydramine and perhexiline was not detected. Sparteine and debrisoquine transport in vitro depends on OCT1 genotype, however, sparteine pharmacokinetics is independent from OCT1 genotype.
CONCLUSIONS AND IMPLICATIONS: Some, but not all drugs, that are substrates of CYP2D6 are also substrates of OCTs and MATE1 suggesting that the enzyme and transporters have overlapping specificities. Variability in sparteine hydroxylation in extensive and intermediate metabolizers cannot be explained by OCT1 genetic variants indicating presence of other factors. Dose-dependent toxicities of dextromethorphan, diphenhydramine and perhexiline appear to be independent from OCTs and MATEs.

PMID: 33434947 [PubMed - as supplied by publisher]

Race specific comparisons of antihypertensive and metabolic effects of hydrochlorothiazide and chlorthalidone.

Am J Med. 2021 Jan 09;:

Authors: Chekka LMS, Chapman AB, Gums JG, Cooper-DeHoff RM, Johnson DADPDJA

Abstract
BACKGROUND: Chlorthalidone is recommended over hydrochlorothiazide (HCTZ) as the preferred thiazide, but the supporting evidence is not robust at routinely used doses, or in whites versus blacks, in whom differences in response to thiazides are well known. We compare the efficacy and safety of HCTZ and chlorthalidone as first-line therapies for white and black hypertensive patients.
METHODS: We compared treatment related outcomes between the HCTZ arm (12.5mg for 2-3 weeks; 25mg for additional 6 weeks) of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR, n=376) and chlorthalidone arm (15mg for 2 weeks; 25mg for additional 6 weeks) of PEAR-2 (n=326) clinical trials, in 17-65 year-old mild-moderate uncomplicated hypertensive whites and blacks.
RESULTS: Mean systolic/diastolic blood pressure (SBP/DBP) reduction with HCTZ vs chlorthalidone: 8±8/4±5 vs 12±9/7±5 mmHg in whites (p<10-6 SBP and DBP); 12±10/7±6 vs 15±10/9±6 in blacks (p=0.008 SBP, p=0.054 DBP). Treatment with HCTZ vs CTD in whites resulted in significantly fewer patients acheiving target-BP (<140/90 mmHg) (44% vs 57%, p=0.018) or clinical response rate (≥10 mmHg DBP reduction); and significantly higher non-response rate (<6 mmHg DBP reduction); but no significant differences in rates among blacks (e.g. target-BP rate: 56% vs 63%, p=0.31). Chlorthalidone treatment led to significantly lower rates of hypokalemia and hyperuricemia in whites and blacks, vs HCTZ, and significantly lower odds of requiring potassium supplementation among blacks (OR=0.16, 95% CI=0.07-0.37, p=3.4e-7).
CONCLUSION: Compared to HCTZ, chlorthalidone showed greater blood pressure lowering and adverse metabolic effects in whites, but similar blood pressure lowering and greater adverse effects in blacks; suggesting the recent guideline recommendations to choose chlorthalidone over HCTZ may not be warranted in blacks.

PMID: 33434556 [PubMed - as supplied by publisher]

Nonadherence to inhaled corticosteroids: A characteristic of the pediatric obese-asthma phenotype?

Pediatr Pulmonol. 2021 Jan 12;:

Authors: Orriëns LB, Vijverberg SJH, Maitland-van der Zee AH, Longo C

Abstract
BACKGROUND: Children with excess weight and asthma tend to respond less well to inhaled corticosteroids (ICS) than children with normal weight, potentially resulting in nonadherence to ICS.
OBJECTIVES: To assess whether excess weight (body mass index ≥85th percentile) was associated with general, unintentional, and intentional nonadherence to ICS in children with asthma.
METHODS: We analyzed data from 566 children aged 4-13 years with asthma, who used ICS as maintenance therapy, from the cross-sectional Pharmacogenetics of Asthma medication in Children: Medication with Anti-inflammatory effects study. General nonadherence was measured objectively with the proportion of days covered (<50%) and subjectively with the parent-reported Medication Adherence Rating Scale (MARS <21) reflecting parent-reported nonadherent behavior. Unintentional and intentional nonadherence were defined as forgetting to take medication and deliberately changing or skipping doses, respectively, from specific items of the MARS. We performed logistic regression analyses, stratifying estimates by asthma severity and age group.
RESULTS: Excess weight was associated with a trend towards increased odds of parent-reported nonadherent behavior (odds ratio [OR]: 1.54; 95% confidence interval [CI]: 0.84-2.81) and objectively measured general nonadherence, but only in moderate-to-severe asthma (OR: 1.71; 95% CI: 0.84-3.48). The odds of intentional, but not unintentional, nonadherence seemed to be greater in children with excess weight than normal weight (OR: 1.94; 95% CI: 0.94-4.01), and the association appeared to be stronger in younger (OR: 2.17; 95% CI 1.00-4.73) versus older children (OR: 1.18; 95% CI: 0.36-3.94).
CONCLUSIONS: Excess weight was associated with general nonadherence to ICS, but only in children with moderate-to-severe asthma, and nonadherent behavior, which seemed to be intentional.

PMID: 33434419 [PubMed - as supplied by publisher]

LncRNA linc00312 suppresses radiotherapy resistance by targeting DNA-PKcs and impairing DNA damage repair in nasopharyngeal carcinoma.

Cell Death Dis. 2021 Jan 04;12(1):69

Authors: Guo Z, Wang YH, Xu H, Yuan CS, Zhou HH, Huang WH, Wang H, Zhang W

Abstract
Radioresistance is the main obstacle in the clinical management of nasopharyngeal carcinoma (NPC). linc00312 is deregulated in a number of human cancers, including NPC. However, the detailed functions and underlying mechanisms of linc00312 in regulating radiosensitivity of NPC remains unknown. In this study, cox regression analysis was used to assess the association between linc00312 and NPC patients' survival after radiotherapy. Our results reveal that linc00312 is significantly down-regulated in NPC tissues and patients with higher expression of linc00312 are significantly associated with longer overall survival and better short-term radiotherapy efficacy. Overexpression of linc00312 could increase the sensitivity of NPC cells to ionizing radiation, as indicated by clonogenic survival assay, comet assay, and flow cytometry. Mechanistically, RNA pull down and RNA immunoprecipitation were performed to investigate the binding proteins of linc00312. linc00312 directly binds to DNA-PKcs, hinders the recruitment of DNA-PKcs to Ku80, and inhibits phosphorylation of AKT-DNA-PKcs axis, therefore inhibiting the DNA damage signal sensation and transduction in the NHEJ repair pathway. In addition, linc00312 impairs DNA repair and cell cycle control by suppressing MRN-ATM-CHK2 signal and ATR-CHK1 signal. In summary, we identified DNA-PKcs as the binding protein of linc00312 and revealed a novel mechanism of linc00312 in the DNA damage response, providing evidence for a potential therapeutic strategy in NPC.

PMID: 33431817 [PubMed - in process]

Epithelial-Mesenchymal Transition and MicroRNAs in Colorectal Cancer Chemoresistance to FOLFOX.

Pharmaceutics. 2021 Jan 08;13(1):

Authors: Escalante PI, Quiñones LA, Contreras HR

Abstract
The FOLFOX scheme, based on the association of 5-fluorouracil and oxaliplatin, is the most frequently indicated chemotherapy scheme for patients diagnosed with metastatic colorectal cancer. Nevertheless, development of chemoresistance is one of the major challenges associated with this disease. It has been reported that epithelial-mesenchymal transition (EMT) is implicated in microRNA-driven modulation of tumor cells response to 5-fluorouracil and oxaliplatin. Moreover, from pharmacogenomic research, it is known that overexpression of genes encoding dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), the DNA repair enzymes ERCC1, ERCC2, and XRCC1, and the phase 2 enzyme GSTP1 impair the response to FOLFOX. It has been observed that EMT is associated with overexpression of DPYD, TYMS, ERCC1, and GSTP1. In this review, we investigated the role of miRNAs as EMT promotors in tumor cells, and its potential effect on the upregulation of DPYD, TYMS, MTHFR, ERCC1, ERCC2, XRCC1, and GSTP1 expression, which would lead to resistance of CRC tumor cells to 5-fluorouracil and oxaliplatin. This constitutes a potential mechanism of epigenetic regulation involved in late-onset of acquired resistance in mCRC patients under FOLFOX chemotherapy. Expression of these biomarker microRNAs could serve as tools for personalized medicine, and as potential therapeutic targets in the future.

PMID: 33429840 [PubMed]

In Vivo Metabolic Profiles of Panax notoginseng Saponins Mediated by Gut Microbiota in Rats.

J Agric Food Chem. 2020 Jun 24;68(25):6835-6844

Authors: Guo YP, Shao L, Chen MY, Qiao RF, Zhang W, Yuan JB, Huang WH

Abstract
Panax notoginseng saponins (PNSs) are the major health-beneficial components of P. notoginseng with very low oral bioavailability, which could be biotransformed by gut microbiota in vitro. However, in vivo biotransformation of PNS mediated by gut microbiota is not well known. This study aimed to characterize the in vivo metabolic profiles of PNS mediated by gut microbiota. The saponins and yielded metabolites in rat feces were identified and relatively quantified by ultra-performance liquid chromatography tandem/quadrupole time-of-flight mass spectrometry. Seventy-three PNS metabolites had been identified in the normal control group, but only 11 PNS metabolites were determined in the pseudo germ-free (GF) group. In addition, the main biotransformation pathway of PNS metabolism was hydrolytic and dehydration reactions. The results indicated that a significant metabolic difference was observed between the normal control group and pseudo GF group, while gut microbiota played a profound role in the biotransformation of PNS in vivo.

PMID: 32449854 [PubMed - indexed for MEDLINE]

23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2021/01/12

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2021/01/12

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Quantitative and Qualitative Analysis of Blood-based Liquid Biopsies to Inform Clinical Decision-making in Prostate Cancer.

Eur Urol. 2021 Jan 06;:

Authors: Casanova-Salas I, Athie A, Boutros PC, Del Re M, Miyamoto DT, Pienta KJ, Posadas EM, Sowalsky AG, Stenzl A, Wyatt AW, Mateo J

Abstract
CONTEXT: Genomic stratification can impact prostate cancer (PC) care through diagnostic, prognostic, and predictive biomarkers that aid in clinical decision-making. The temporal and spatial genomic heterogeneity of PC together with the challenges of acquiring metastatic tissue biopsies hinder implementation of tissue-based molecular profiling in routine clinical practice. Blood-based liquid biopsies are an attractive, minimally invasive alternative.
OBJECTIVE: To review the clinical value of blood-based liquid biopsy assays in PC and identify potential applications to accelerate the development of precision medicine.
EVIDENCE ACQUISITION: A systematic review of PubMed/MEDLINE was performed to identify relevant literature on blood-based circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs) in PC.
EVIDENCE SYNTHESIS: Liquid biopsy has emerged as a practical tool to profile tumor dynamics over time, elucidating features that evolve (genome, epigenome, transcriptome, and proteome) with tumor progression. Liquid biopsy tests encompass analysis of DNA, RNA, and proteins that can be detected in CTCs, ctDNA, or EVs. Blood-based liquid biopsies have demonstrated promise in the context of localized tumors (diagnostic signatures, risk stratification, and disease monitoring) and advanced disease (response/resistance biomarkers and prognostic markers).
CONCLUSIONS: Liquid biopsies have value as a source of prognostic, predictive, and response biomarkers in PC. Most clinical applications have been developed in the advanced metastatic setting, where CTC and ctDNA yields are significantly higher. However, standardization of assays and analytical/clinical validation is necessary prior to clinical implementation.
PATIENT SUMMARY: Traces of tumors can be isolated from blood samples from patients with prostate cancer either as whole cells or as DNA fragments. These traces provide information on tumor features. These minimally invasive tests can guide diagnosis and treatment selection.

PMID: 33422353 [PubMed - as supplied by publisher]

Contribution of rare genetic variants to drug response in absence epilepsy.

Epilepsy Res. 2021 Jan 04;170:106537

Authors: Myers KA, Bennett MF, Grinton BE, Dabscheck G, Chan EK, Bello-Espinosa LE, Sadleir LG, D'Alfonso S, Schneider AL, Damiano JA, Hildebrand MS, Bahlo M, Berkovic SF, Buchhalter J, Scheffer IE

Abstract
OBJECTIVE: We investigated the possible significance of rare genetic variants to response to valproic acid (VPA) and ethosuximide (ETX) in patients with absence epilepsy. Our primary hypothesis was that rare CACNA1H variants are more frequent in ETX-non-responsive patients compared to ETX-responsive. Our secondary hypothesis was that rare variants in GABA-receptor genes are more frequent in VPA-non-responsive patients compared to VPA-responsive.
METHODS: We recruited patients with absence epilepsy treated with both VPA and ETX, and performed whole exome sequencing in order to investigate the potential role of rare variants in CACNA1H, other voltage-gated calcium channel (VGCC) genes, or GABA-receptor genes in predicting response to ETX or VPA.
RESULTS: Sixty-two patients were included; 12 were ETX-responsive, 14 VPA-responsive, and 36 did not have a clear positive response to either medication. We did not find significant enrichment inCACNA1H rare variants in ETX-responsive patients (odds ratio 3.43; 0.43-27.65; p = 0.20), nor was there enrichment for other VGCC genes. No significant enrichment of GABA-receptor gene rare variants was seen for VPA-non-responsive patients versus VPA-responsive. We found enrichment of rare GABA-receptor variants in our absence cohort compared to controls (odds ratio 3.82; 1.68-8.69). There was no difference in frequency of CACNA1H rs61734410 and CACNA1I rs3747178 polymorphisms between ETX-responsive and ETX-non-responsive groups; these polymorphisms have previously been reported to predict lack of response to ETX in absence epilepsy.
SIGNIFICANCE: We conclude that if CACNA1H rare variants predict lack of response to ETX, a larger sample is necessary to test this with sufficient power. Increased GABA-receptor gene rare variant frequency in absence epilepsy patients who fail initial anti-seizure therapy suggests subtle GABA receptor dysfunction may contribute to the underlying pathophysiology.

PMID: 33421703 [PubMed - as supplied by publisher]

A hybrid implementation-effectiveness randomized trial of CYP2D6-guided postoperative pain management.

Genet Med. 2021 Jan 08;:

Authors: Thomas CD, Parvataneni HK, Gray CF, Deen JT, Prieto HA, Pulido LF, Elsey AR, Elwood EN, Starostik P, Gong Y, Fillingim RB, Johnson JA, Cavallari LH

Abstract
PURPOSE: Cytochrome P450 2D6 (CYP2D6) genotype-guided opioid prescribing is limited. The purpose of this type 2 hybrid implementation-effectiveness trial was to evaluate the feasibility of clinically implementing CYP2D6-guided postsurgical pain management and determine that such an approach did not worsen pain control.
METHODS: Adults undergoing total joint arthroplasty were randomized 2:1 to genotype-guided or usual pain management. For participants in the genotype-guided arm with a CYP2D6 poor (PM), intermediate (IM), or ultrarapid (UM) metabolizer phenotype, recommendations were to avoid hydrocodone, tramadol, codeine, and oxycodone. The primary endpoints were feasibility metrics and opioid use; pain intensity was a secondary endpoint. Effectiveness outcomes were collected 2 weeks postsurgery.
RESULTS: Of 282 patients approached, 260 (92%) agreed to participate. In the genotype-guided arm, 20% had a high-risk (IM/PM/UM) phenotype, of whom 72% received an alternative opioid versus 0% of usual care participants (p < 0.001). In an exploratory analysis, there was less opioid consumption (200 [104-280] vs. 230 [133-350] morphine milligram equivalents; p = 0.047) and similar pain intensity (2.6 ± 0.8 vs. 2.5 ± 0.7; p = 0.638) in the genotype-guided vs. usual care arm, respectively.
CONCLUSION: Implementing CYP2D6 to guide postoperative pain management is feasible and may lead to lower opioid use without compromising pain control.

PMID: 33420349 [PubMed - as supplied by publisher]

Patients dispensed medications with actionable pharmacogenomic biomarkers: rates and characteristics.

Genet Med. 2021 Jan 08;:

Authors: Liu D, Olson KL, Manzi SF, Mandl KD

Abstract
PURPOSE: Pharmacogenomic biomarkers are increasingly listed on medication labels and authoritative guidelines but pharmacogenomic-guided prescribing is not yet common. Our objective was to assess the potential for incorporating knowledge of patients' genomic characteristics into prescribing practices.
METHODS: We performed a retrospective analysis of claims data for 2,096,971 beneficiaries with pharmacy coverage from a national, commercial health insurance plan between January 2017 and December 2019. Children between 0 and 17 years comprised 21% of the cohort. Adults were age 18 to 64. Medications with actionable pharmacogenomic biomarkers (MAPBs) were identified using public information from the US Food and Drug Administration (FDA), Clinical Pharmacogenomics Implementation Consortium (CPIC), and PharmGKB.
RESULTS: MAPBs were dispensed to 63% of the adults and 29% of the children in the cohort. Most frequently dispensed were ibuprofen, ondansetron, codeine, and oxycodone. Most common were medications with CYP2D6, G6PD, or CYPC19 pharmacogenomic biomarkers. Ten percent of the cohort were codispensed more than one MAPB for at least 30 days.
CONCLUSION: The number of people who might benefit from pharmacogenomic-guided prescribing is substantial. Future work should address obstacles to integrating genomic data into prescriber workflows, complex factors contributing to the magnitude of benefit, and the clinical availability of reliable on-demand or pre-emptive pharmacogenomic testing.

PMID: 33420348 [PubMed - as supplied by publisher]

Pharmacogenetics Update on Biologic Therapy in Psoriasis.

Medicina (Kaunas). 2020 Dec 20;56(12):

Authors: Muñoz-Aceituno E, Martos-Cabrera L, Ovejero-Benito MC, Reolid A, Abad-Santos F, Daudén E

Abstract
Background and objectives: Psoriasis is a chronic immune-mediated skin disease caused by several complex factors, both environmental and genetic, many of which are still not fully understood. Nowadays, several groups of biological drugs are being used for psoriasis treatment. Although these therapies are very effective, they show significant variability in efficacy among individuals. Therefore, there is a need for biomarkers to predict treatment outcomes in order to guide personalized therapeutic decisions. Pharmacogenetics is the study of variations in DNA sequences related to drug response. Materials and Methods: In this article, we review pharmacogenetics studies on the treatment of moderate-to-severe psoriasis focusing on anti-interleukin (IL) 12/23 (ustekinumab) and anti-IL17 drugs (secukinumab and ixekizumab), as well as recent studies concerning anti-TNF drugs. Results: Several polymorphisms have been studied over the years in reference to anti-TNF drugs; some of the most recent studies included the performance of a genome-wide association study (GWAS) and pharmacogenetics studies focused on the optimization of a treatment regimen. Various polymorphisms in different genes have been related to ustekinumab response; among them, the most commonly studied is the HLA-C*06:02 allele. Conclusions: Although not confirmed in some studies, most studies have shown that patients carrying this allele present a significantly higher response rate to ustekinumab. Some polymorphisms have been studied in patients treated with anti-IL17 drugs, mostly related to secukinumab; however, up to now, no association has been found between any of these polymorphisms and response. Nevertheless, further studies involving larger cohorts are needed in order to confirm these results before the implementation of this biomarker in clinical practice.

PMID: 33419370 [PubMed - as supplied by publisher]

Dose-dependent effects of antipsychotics on efficacy and adverse effects in schizophrenia.

Behav Brain Res. 2021 Jan 05;:113098

Authors: Yoshida K, Takeuchi H

Abstract
BACKGROUND: Antipsychotics are a cornerstone of pharmacological treatment of schizophrenia. Improved understanding of the dose-response relationship of antipsychotics in terms of efficacy, adverse effects, and mortality can help to optimize the pharmacological treatment of schizophrenia.
METHODS: This narrative literature review summarizes current evidence on the relationship of antipsychotic dose with efficacy, adverse effects, and mortality in patients with schizophrenia.
RESULTS: The efficacy of antipsychotics generally appeared to be highly dose-dependent in the acute phase of schizophrenia, with each antipsychotic having a specific dose-response curve. The presence or absence of dose-dependency and its extent varied according to the type of adverse effect. Parkinsonism, hyperprolactinemia, weight gain, and neurocognitive impairment appeared to be dose-related. The following adverse effects might be at least somewhat dose-dependent: akathisia, tardive dyskinesia, osteoporosis, sexual dysfunction, diabetes mellitus, myocardial infarction, stroke, thromboembolism, QT interval prolongation, anticholinergic adverse effects, somnolence, pneumonia, hip fracture, and neuroleptic malignant syndrome. In contrast, antipsychotic dose appeared to have no relationship with dyslipidemia, seizure, sialorrhea, neutropenia, and agranulocytosis. It was unclear whether the antipsychotic dose was correlated with the risk of hypotension due to a lack of data. Although a higher lifetime cumulative antipsychotic dose might contribute to higher mortality, it is still difficult to conclude whether mortality increases in a dose-dependent manner.
CONCLUSION: These findings could help clinicians to optimize antipsychotic treatment in patients with schizophrenia by balancing risks and benefits in clinical practice. However, further investigations with larger sample sizes and more robust study designs that focus on each antipsychotic agent are needed.

PMID: 33417992 [PubMed - as supplied by publisher]