Front Pharmacol. 2023 Aug 31;14:1274075. doi: 10.3389/fphar.2023.1274075. eCollection 2023.

ABSTRACT

[This corrects the article DOI: 10.3389/fphar.2023.1178421.].

PMID:37719864 | PMC:PMC10502220 | DOI:10.3389/fphar.2023.1274075

Asian Biomed (Res Rev News). 2023 Sep 17;17(2):84-92. doi: 10.2478/abm-2023-0048. eCollection 2023 Apr.

ABSTRACT

BACKGROUND: The cytochrome P450 (CYP450) family is well known as a major group of drug metabolizing enzymes. The polymorphism of CYP450 genes is the main factor having an impact on the interindividual difference in drug response, including drug efficacy and drug safety. The single nucleotide polymorphism (SNPs) of Vietnamese Kinh has been widely studied, but information about the copy number variations (CNVs) of other CYP450 genes is still unknown.

OBJECTIVE: To identify the CNV variability of CYP450 in 154 healthy unrelated Kinh Vietnamese, except eCYP2D6, which was previously reported.

METHODS: Multiplex Ligation-Dependent Probe Amplification (MLPA) was applied for determination of copy number of 10 CYP450 genes. Later, PCR or quantitative PCR (qPCR) was used to confirm the detected CNVs in randomly chosen subjects.

RESULTS: Of the 154 subjects, along with CYP2D6, 4 other CYP450 genes showed CNVs including duplications (CYP1B1), deletions (CYP2A6 and CYP2C9), and both duplications and deletions (CYP2E1). Among these, CYP2A6 exhibited the greatest frequency of CNVs compared with other CYP450, in which CYP2A6Del accounted for 11%. Meanwhile, allele CYP2E1Del showed the lowest frequency with only 0.3%.

CONCLUSIONS: The present study provides new insight into CYP450 CNVs in the Kinh Vietnamese cohort. Our data have contributed to genetic profiling of CYP450 CNVs in Vietnam, which would be helpful for facilitating implementation of pharmacogenetics in drug dosing adjustment in Vietnam.

PMID:37719322 | PMC:PMC10505059 | DOI:10.2478/abm-2023-0048

Br J Clin Pharmacol. 2023 Sep 15. doi: 10.1111/bcp.15909. Online ahead of print.

ABSTRACT

AIMS: This study aimed to provide up-to-date information on pediatric population pharmacokinetics (PopPK) models of tacrolimus and to identify factors influencing tacrolimus pharmacokinetic variability.

METHODS: Systematic searches in the Web of Science, PubMed, Scopus, Science Direct, Cochrane, EMBASE databases, and reference lists of articles were conducted from inception to March 2023. All PopPK studies of tacrolimus using nonlinear mixed-effect modeling in pediatric solid organ transplant patients were included.

RESULTS: Of the 21 studies reviewed, 62% developed from liver transplant recipients and 33% from kidney transplant recipients. Most studies used a one-compartment model to describe tacrolimus pharmacokinetics. Body weight was a significant predictor for tacrolimus volume of distribution (Vd/F). The estimated Vd/F for one-compartment models ranged from 20 to 1890 l, whereas the peripheral volume of distribution (Vp/F) for two-compartment models was between 290 and 1520 l. Body weight, days post-transplant, CYP3A5 genotype, or hematocrit were frequently reported as significant predictors of tacrolimus clearance. The estimated apparent clearance values range between 0.12 and 2.18 L/h/kg, with inter-individual variability from 13.5% to 110.0%. Only 29% of the studies assessed the generalizability of the models with external validation.

CONCLUSION: This review highlights the potential factors, modeling approaches, and validation methods that impact tacrolimus pharmacokinetics in a pediatric population. The clinician could predict tacrolimus clearance based on body weight, CYP3A5 genotype, days post-transplant, or hematocrit. Further research is required to determine the relationship between pharmacogenetics and tacrolimus pharmacodynamics in pediatric patients and confirm the applicability of nonlinear kinetics in this population.

PMID:37714740 | DOI:10.1111/bcp.15909

Am J Pharm Educ. 2023 Sep;87(9):100077. doi: 10.1016/j.ajpe.2023.100077. Epub 2023 May 10.

ABSTRACT

OBJECTIVE: Incorporating diversity, equity, inclusion, and anti-racism principles into clinical and didactic education is essential because each influence cognitive and affective attitudes in pharmacy practice. Educators must learn from the past to enlighten the future. For example, race is a social construct, not a biological construct. However, it persistently acts as a surrogate for determining medical diagnoses and treatment.

FINDINGS: Precision medicine and pharmacogenomics can serve as a basis for deconstructing social constructs surrounding race and other social determinants of health.

SUMMARY: In this review, the authors highlight why using race in health education will lead to less-than-optimal clinical decisions and discuss best practices for incorporating diversity, equity, inclusion, and anti-racism into health education from a pharmacogenomic-based perspective.

PMID:37714655 | DOI:10.1016/j.ajpe.2023.100077

ESMO Open. 2023 Sep 13;8(5):101628. doi: 10.1016/j.esmoop.2023.101628. Online ahead of print.

ABSTRACT

BACKGROUND: Testing for epidermal growth factor receptor (EGFR) mutations is an essential recommendation in guidelines for metastatic non-squamous non-small-cell lung cancer, and is considered mandatory in European countries. However, in practice, challenges are often faced when carrying out routine biomarker testing, including access to testing, inadequate tissue samples and long turnaround times (TATs).

MATERIALS AND METHODS: To evaluate the real-world EGFR testing practices of European pathology laboratories, an online survey was set up and validated by the Pulmonary Pathology Working Group of the European Society of Pathology and distributed to 64 expert testing laboratories. The retrospective survey focussed on laboratory organisation and daily EGFR testing practice of pathologists and molecular biologists between 2018 and 2021.

RESULTS: TATs varied greatly both between and within countries. These discrepancies may be partly due to reflex testing practices, as 20.8% of laboratories carried out EGFR testing only at the request of the clinician. Many laboratories across Europe still favour single-test sequencing as a primary method of EGFR mutation identification; 32.7% indicated that they only used targeted techniques and 45.1% used single-gene testing followed by next-generation sequencing (NGS), depending on the case. Reported testing rates were consistent over time with no significant decrease in the number of EGFR tests carried out in 2020, despite the increased pressure faced by testing facilities during the COVID-19 pandemic. ISO 15189 accreditation was reported by 42.0% of molecular biology laboratories for single-test sequencing, and by 42.3% for NGS. 92.5% of laboratories indicated they regularly participate in an external quality assessment scheme.

CONCLUSIONS: These results highlight the strong heterogeneity of EGFR testing that still occurs within thoracic pathology and molecular biology laboratories across Europe. Even among expert testing facilities there is variability in testing capabilities, TAT, reflex testing practice and laboratory accreditation, stressing the need to harmonise reimbursement technologies and decision-making algorithms in Europe.

PMID:37713929 | DOI:10.1016/j.esmoop.2023.101628

Anal Chem. 2023 Sep 15. doi: 10.1021/acs.analchem.3c01668. Online ahead of print.

ABSTRACT

The detection of single nucleotide polymorphisms (SNPs) is of increasing importance in many areas including clinical diagnostics, patient stratification for pharmacogenomics, and advanced forensic analysis. In the work reported, we apply a semiautomated system for solid-phase electrochemical melting curve analysis (éMCA) for the identification of the allele present at a specific SNP site associated with an increased risk of bone fracture and predisposition to osteoporosis. Asymmetric isothermal recombinase polymerase amplification using ferrocene labeled forward primers was employed to generate single stranded redox labeled amplicons. In a first approach to demonstrate the proof of concept of combining asymmetric RPA with solid-phase éMCA, a simplified system housing a multielectrode array within a polymeric microsystem, sandwiched between two aluminum plates of a heater device, was used. Sample manipulation through the microfluidic channel was controlled by a syringe pump, and an external Ag/AgCl reference electrode was employed. Individual electrodes of the array were functionalized with four different oligonucleotide probes, each probe equivalent in design with the exception of the middle nucleotide. The isothermally generated amplicons were allowed to hybridize to the surface-tethered probes and subsequently subjected to a controlled temperature ramp, and the melting of the duplex was monitored electrochemically. A clear difference between the fully complementary and a single mismatch was observed. Having demonstrated the proof-of-concept, a device for automated éMCA with increased flexibility to house diverse electrode arrays with internal quasi-gold reference electrodes, higher resolution, and broader melting temperature range was developed and exploited for the detection of SNP hetero/homozygosity. Using the optimized conditions, the system was applied to the identification of the allele present at an osteoporosis associated SNP site, rs2741856, in 10 real fingerprick/venous blood samples, with results validated using Sanger sequencing.

PMID:37713191 | DOI:10.1021/acs.analchem.3c01668

J Clin Invest. 2023 Sep 15;133(18):e173932. doi: 10.1172/JCI173932.

NO ABSTRACT

PMID:37712423 | DOI:10.1172/JCI173932

Am J Hypertens. 2023 Sep 15:hpad084. doi: 10.1093/ajh/hpad084. Online ahead of print.

ABSTRACT

BACKGROUND: Apparent treatment-resistant hypertension (aTRH) is defined as uncontrolled blood pressure (BP) despite using ≥3 antihypertensive classes or controlled BP while using ≥4 antihypertensive classes. Patients with aTRH have a higher risk for adverse cardiovascular outcomes compared to patients with controlled hypertension (HTN). Although there have been prior reports on the prevalence, characteristics, and predictors of aTRH, these have been broadly derived from smaller datasets, randomized controlled trials, or closed healthcare systems.

METHODS: We extracted patients with HTN defined by ICD 9 and 10 codes during 1/1/2015-12/31/2018, from two large electronic health record databases: the OneFlorida Data Trust (n=223,384) and Research Action for Health Network (REACHnet) (n=175,229). We applied our previously validated aTRH and stable controlled HTN computable phenotype algorithms and performed univariate and multivariate analyses to identify the prevalence, characteristics, and predictors of aTRH in these populations.

RESULTS: The prevalence of aTRH among patients with HTN in OneFlorida (16.7%) and REACHnet (11.3%) was similar to prior reports. Both populations had a significantly higher proportion of Black patients with aTRH compared to those with stable controlled HTN. aTRH in both populations shared similar significant predictors, including Black race, diabetes, heart failure, chronic kidney disease, cardiomegaly, and higher body mass index. In both populations, aTRH was significantly associated with similar comorbidities, when compared with stable controlled HTN.

CONCLUSIONS: In two large, diverse real-world populations, we observed similar comorbidities and predictors of aTRH as prior studies. In the future, these results may be used to improve healthcare professionals' understanding of aTRH predictors and associated comorbidities.

PMID:37712350 | DOI:10.1093/ajh/hpad084

Pharmacogenomics. 2023 Sep 15. doi: 10.2217/pgs-2023-0122. Online ahead of print.

ABSTRACT

A woman with ocular hypertension suffered from severe bradycardia, hypotension and syncope attacks in temporal relation with ophthalmic timolol application. Topically applied timolol is nasally absorbed and has been shown to reach potentially relevant systemic concentrations. Timolol is mainly metabolized by CYP2D6, which exhibits interindividual metabolic capacity due to genetic variations. A reactive pharmacogenetic panel test identified the patient as a CYP2D6 homozygous *4 allele carrier, which has been associated with a poor metabolizer phenotype and lacking enzyme activity. Thus, the adverse drug reactions possibly resulted from increased systemic timolol exposure. This case report highlights that pharmacogenetic panel testing can contribute to safe and effective pharmacotherapy, even for topically applied drugs.

PMID:37712172 | DOI:10.2217/pgs-2023-0122

Pharmacogenomics. 2023 Sep 15. doi: 10.2217/pgs-2023-0084. Online ahead of print.

ABSTRACT

Introduction: As the most distressing complication of sickle cell disease (SCD), pain is marked by considerable heterogenicity. In this study we explored the potential association of alcohol dehydrogenase 7 gene (ADH7) polymorphism rs971074 with sickle cell pain. Methods: We analyzed clinical phenotypes and the rs971074 single-nucleotide polymorphism in ADH7 by MassARRAY-iPlex analysis in a cohort of SCD patients. Results: The synonymous rs971074 was significantly associated with both acute and chronic pain in SCD. Patients with the minor T allele(s) recorded significantly more crisis episodes and severe chronic pain symptoms. Conclusion: Our study has identified the rs971074 minor T allele as a genetic biomarker potentially influencing acute and chronic pain. These findings may ultimately help inform strategies to develop precision pain therapies in SCD.

PMID:37712142 | DOI:10.2217/pgs-2023-0084

Front Pharmacol. 2023 Aug 29;14:1277561. doi: 10.3389/fphar.2023.1277561. eCollection 2023.

NO ABSTRACT

PMID:37711174 | PMC:PMC10497968 | DOI:10.3389/fphar.2023.1277561

Diabetes Ther. 2023 Sep 14. doi: 10.1007/s13300-023-01463-9. Online ahead of print.

ABSTRACT

BACKGROUND: Type 2 diabetes mellitus (T2D) is commonly associated with an increasing complexity of multimorbidity. While some progress has been made in identifying genetic and non-genetic risk factors for T2D, understanding the longitudinal clinical history of individuals before/after T2D diagnosis may provide additional insights.

METHODS: In this study, we utilised longitudinal data from the DARE (Diabetes Alliance for Research in England) study to examine the trajectory of clinical conditions in individuals with and without T2D. Data from 1932 individuals (T2D n = 1196 vs. matched non-T2D controls n = 736) were extracted and subjected to trajectory analysis over a period of up to 50 years (25 years pre-diagnosis/25 years post-diagnosis). We also analysed the cumulative proportion of people with diagnosed coronary artery disease (CAD) in their general practice (GP) record with an analysis of lower respiratory tract infection (RTI) as a comparator group.

RESULTS: The mean age of diagnosis of T2D was 52.6 (95% confidence interval 52.0-53.4) years. In the years leading up to T2D diagnosis, individuals who eventually received a T2D diagnosis consistently exhibited a considerable increase in several clinical phenotypes. Additionally, immediately prior to T2D diagnosis, a significantly greater prevalence of hypertension (35%)/RTI (34%)/heart conditions (17%)/eye, nose, throat infection (19%) and asthma (12%) were observed. The corresponding trajectory of each of these conditions was much less dramatic in the matched controls. Post-T2D diagnosis, proportions of T2D individuals exhibiting hypertension/chronic kidney disease/retinopathy/infections climbed rapidly before plateauing. At the last follow-up by quintile of disadvantage, the proportion (%) of people with diagnosed CAD was 6.4% for quintile 1 (least disadvantaged) and 11% for quintile 5 (F = 3.4, p = 0.01 for the difference between quintiles).

CONCLUSION: These findings provide novel insights into the onset/natural progression of T2D, suggesting an early phase of inflammation-related disease activity before any clinical diagnosis of T2D is made. Measures that reduce social inequality have the potential in the longer term to reduce the social gradient in health outcomes reported here.

PMID:37707702 | DOI:10.1007/s13300-023-01463-9

Histopathology. 2023 Sep 14. doi: 10.1111/his.15040. Online ahead of print.

ABSTRACT

AIMS: Malignant tumours of the lacrimal apparatus are rare and frequently show a poor prognosis, with no clear therapeutic standards. Characterisation of the genetic landscape of these rare tumours is sparse, and therefore therapeutics generally follow those of their common salivary gland counterparts. To further clarify the pathophysiology and discover potential therapeutic targets, we investigated the genetic landscape of eight tumours of the lacrimal apparatus.

METHODS AND RESULTS: DNA and RNA sequencing were performed to identify genetic mutations and gene fusions. Immunohistochemistry, fluorescence in-situ hybridisation and reverse transcription-polymerase chain reaction followed by Sanger sequencing were performed to confirm the identified molecular alterations. Genetic alterations were detected in six tumours. Among five adenoid cystic carcinomas (ACC), four had confirmed alterations of MYB or MYBL1 genes, including a MYB::NFIB fusion, a MYBL1::NFIB fusion, a MYB amplification and a novel NFIB::THSD7B fusion. Mutations in genes encoding epigenetic modifiers, as well as NOTCH1, FGFR2 and ATM mutations, were also identified in ACCs. A carcinoma ex pleomorphic adenoma showed TP53 and CIC mutations and an amplification of ERBB2. A transitional cell carcinoma was associated with HPV16 infection. No genetic alteration was found for one adenocarcinoma, not otherwise specified.

CONCLUSIONS: Our study highlights the variety of molecular alterations associated with lacrimal system tumours and emphasises the importance of molecular testing in these tumours, which can reveal potentially targetable mutations. Our results also reinforce the hypothesis of a common physiopathology of all ACCs, regardless of their primary location.

PMID:37706251 | DOI:10.1111/his.15040

Pharmacogenomics. 2023 Sep 14. doi: 10.2217/pgs-2023-0111. Online ahead of print.

ABSTRACT

Background: ALK rearrangements account for around 5% of non-small-cell lung cancers. Aim: This study surveys physicians on the potential efficacy of a mobile application in improving the management of ALK-rearranged non-small-cell lung cancer, through knowledge, treatment adherence and real-time adverse events reporting. Materials & methods: A total of 118 physicians from 11 countries in the Middle East participated. Results & conclusion: Results indicate 94% support for enhancing team communication via an application, and 93% believe real-time adverse events reporting improves the quality of care. Participants found an ALK-rearrangement patient-physicians forum valuable for communication improvement. Motivations for application use included treatment planning (73%), care enhancement (60%) and contributing to publications (40%).

PMID:37706248 | DOI:10.2217/pgs-2023-0111

Pharmacogenomics. 2023 Sep 14. doi: 10.2217/pgs-2023-0095. Online ahead of print.

ABSTRACT

Background: HLA-B*58:01 is strongly associated with allopurinol-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in Vietnam. This study assessed the cost-effectiveness of this testing to prevent SJS/TEN. Methods: A model was developed to compare three strategies: no screening, use allopurinol; HLA-B*58:01 screening; and no screening, use probenecid. A willingness-to-pay of three-times gross domestic product per capita was used. Results: Compared with 'no screening, use allopurinol', 'screening' increased quality-adjusted life-years by 0.0069 with the incremental cost of Vietnam dong (VND) 14,283,633 (US$617), yielding an incremental cost-effectiveness ratio of VND 2,070,459,122 (US$89,398) per quality-adjusted life-year. Therefore, 'screening' was unlikely to be cost-effective under the current willingness-to-pay. Testing's cost-effectiveness may change with targeted high-risk patients, reimbursed febuxostat or lower probenecid prices. Conclusion: The implementation of nationwide HLAB*58:01 testing before the use of allopurinol is not cost-effective, according to this analysis. This may be due to the lack of quality data on the effectiveness of testing and costing data in the Vietnamese population.

PMID:37706247 | DOI:10.2217/pgs-2023-0095

J Pharm Bioallied Sci. 2023 Jul-Sep;15(3):101-106. doi: 10.4103/jpbs.jpbs_313_23. Epub 2023 Aug 15.

ABSTRACT

BACKGROUND: Clinical pharmacogenetics is a rapidly growing field that focuses on the study of genetic variations and their impact on drug metabolism, efficacy, and safety. Angiotensin II receptor blockers (ARBs) are commonly used to treat hypertension in Iraq but not all patients respond equally to these drugs.

AIM: This article aims to review the current evidence on the clinical pharmacogenetics of ARBs in Iraq and its implications for personalized medicine.

MATERIALS AND METHODS: We conducted a literature review of studies on the genetic variations that affect the response to ARBs in Iraq. We also reviewed the prevalence of these genetic variants in the Iraqi population and discussed the potential clinical implications for personalized medicine.

RESULTS: The most studied genetic variations associated with ARB response in Iraq are the angiotensin-converting enzyme gene insertion/deletion polymorphism and the angiotensin II type 1 receptor gene A1166C polymorphism. The angiotensin-converting enzyme gene insertion/deletion polymorphism is associated with variability in response to ARBs, while the angiotensin II type 1 receptor A1166C polymorphism is associated with an increased risk of cardiovascular events in patients treated with ARBs. The prevalence of these genetic variants in the Iraqi population varies widely depending on the region and ethnic group.

CONCLUSION: The clinical pharmacogenetics of ARBs in Iraq suggests that pharmacogenetic testing could improve the selection and dosing of ARBs in Iraqi patients, leading to better patient outcomes and cost-effective healthcare.

PMID:37705854 | PMC:PMC10496849 | DOI:10.4103/jpbs.jpbs_313_23

Clin Transl Sci. 2023 Sep 13. doi: 10.1111/cts.13634. Online ahead of print.

ABSTRACT

Given the high prevalence of pain in older adults and current trends in opioid prescribing, inclusion of genetic information in risk prediction tools may improve opioid risk assessment. Our objectives were to (1) determine the feasibility of recruiting socioeconomically disadvantaged and racially diverse middle aged and older adult populations for a study seeking to identify risk factors for opioid-related falls and other serious adverse effects and (2) explore potential associations between the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (CIP-RIOSORD) risk class and other patient factors with falls and serious opioid adverse effects. This was an observational study of 44 participants discharged home from the emergency department with an opioid prescription for acute pain and followed for 30 days. We found pain interference may predict opioid-related falls or serious adverse effects within older, opioid-treated patients. If validated, pain interference may prove to be a beneficial marker for risk stratification of older adults initiated on opioids for acute pain.

PMID:37705211 | DOI:10.1111/cts.13634

Pediatr Blood Cancer. 2023 Sep 13:e30669. doi: 10.1002/pbc.30669. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Significantly discrepant survival rates have been documented in single disease childhood cancer cohorts in South Africa; those from higher socioeconomic groups were shown to have a significantly lower risk of death than those from less affluent households. This study aimed to determine the impact of socioeconomic status (SES) on childhood cancer survival using pooled South African data.

METHODS: Five databases spanning January 2000 to December 2021 were interrogated. SES status was assigned based on a public sector annual household income classification. H0 households (formally unemployed) received free healthcare. H1, H2 and H3 (annual income > United States Dollar [USD] 19,000) households paid for healthcare relative to their income. The Spearman test assessed correlations between SES and disease stage in patients with solid tumours. Hazard ratios were determined using Cox regression modelling. The Kaplan-Meier procedure estimated overall survival (OS).

RESULTS: A total of 1598 children were eligible for analysis; 1269 had a solid tumour with a negative correlation between SES and stage (Spearman rho = -.178; p < .001). Patients with solid tumours and lower SES showed proportionately higher numbers of stage III and IV disease (p < .01). This proportion decreased with higher SES categories. In the multivariate analyses adjusted for sex, age, tumour type and stage, higher SES was associated with lower mortality risk (p < .001), indicating that the impact of SES on survival was in excess of any effect that could be explained by lower stage disease alone. There was a strong positive correlation between race and SES (Fisher's exact tests, p < .001) across all groups and all SES strata. Five-year OS was 85.3% in children from H3 households versus 46.3% in children from H0 households (p < .001).

CONCLUSION: SES significantly impacts childhood cancer survival for children with solid tumours in South Africa. SES is a robust surrogate for race in South Africa as a prognostic metric of disease outcome in childhood cancer. Advocacy to increase social support for impoverished patients is essential to achieve equitable improvements in outcomes treated with standardised national treatment guidelines.

PMID:37705154 | DOI:10.1002/pbc.30669

Pediatr Clin North Am. 2023 Oct;70(5):995-1011. doi: 10.1016/j.pcl.2023.05.010. Epub 2023 Jul 3.

ABSTRACT

Pharmacogenomics, where genomic information is used to tailor medication management, is a strategy to maximize drug efficacy and minimize toxicity. Although pediatric evidence is less robust than for adults, medications influenced by pharmacogenomics are prescribed to children and adolescents. Evidence-based guidelines and drug label annotations are available from the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Pharmacogenomics Knowledgebase (PharmGKB). Some pediatric health care facilities use pharmacogenomics to provide dosing recommendations to pediatricians. Herein, we use a case-based approach to illustrate the use of pharmacogenomic data in pediatric clinical care and provide resources for finding and using pharmacogenomic guidelines.

PMID:37704356 | DOI:10.1016/j.pcl.2023.05.010

Pharmacogenomics. 2023 Sep 13. doi: 10.2217/pgs-2023-0099. Online ahead of print.

ABSTRACT

Background: Polymorphisms in the CYP2C9, VKORC1, MDR1 and APOE genes may impact warfarin dose. Aim: To investigate the influence of sociodemographic and clinical factors and polymorphisms *1, *2 and *3 for CYP2C9, -1639G>A for VKORC1, 3435C>T for MDR1, and ϵ2, ϵ3 and ϵ4 for APOE genes on the mean weekly warfarin maintenance dose in adults. Methods: This cross-sectional study recruited a calculated sample of 315 patients in three anticoagulation clinics in Brazil. A model containing the variables significantly associated with warfarin dose was estimated. Results: The mean age of patients was 64.1 ± 13.1 years, with 173 (54.9%) women. Age, use of amiodarone, genotype VKORC1 GA, genotype VKORC1 AA, genotypes CYP2C9*1/*2 or *1/*3 and genotypes CYP2C9*2/*2 or *2/*3 or *3/*3 were associated with a reduced warfarin dose. Conclusion: This study pointed out factors that could impact the management of oral anticoagulation.

PMID:37702085 | DOI:10.2217/pgs-2023-0099