Psychiatr Danub. 2024 Sep;36(Suppl 2):428-431.

NO ABSTRACT

PMID:39378510

Psychiatr Danub. 2024 Sep;36(Suppl 2):338-341.

ABSTRACT

Response rate to treatment is generally not as high as expected in psychiatric disorders. The lack of clinical improvement under a well-conducted treatment, that complies with guidelines, may be the consequence of genetic abnormalities that impact the metabolizing pathways of the drug. Genetic polymorphism of metabolizing enzymes is frequent in the population and has been proven to have a clinical impact. It may also be the consequence of environmental or organic factors that interact with the pharmacokinetic pathways (absorption, distribution, metabolizing, excretion) of the drug. These intrinsic and extrinsic factors will lead to inter- and intraindividual fluctuations in plasma drug concentrations. Therapeutic drug monitoring permits to measure plasma drug concentrations in order to adapt psychopharmacotherapy individually. In some cases, it can be coupled to pharmacogenetic testings. This review presents recent literature and guidelines on the subject. Eventually, there is a focus made on the French-speaking part of Belgium where neither therapeutic drug monitoring, nor pharmacogenetics testing, are used frequently in clinical practice. Some challenges are to be addressed to implement these techniques in Belgium.

PMID:39378493

Curr Drug Metab. 2024 Oct 4. doi: 10.2174/0113892002323910240924145310. Online ahead of print.

ABSTRACT

Drug metabolizing enzymes play a crucial role in the pharmacokinetics and pharmacodynamics of therapeutic drugs, influencing their efficacy and safety. This review explores the impact of genetic polymorphisms in drug-metabolizing genes on drug response within Arab populations. We examine the genetic diversity specific to Arab countries, focusing on the variations in key drug-metabolizing enzymes such as CYP450, GST, and UGT families. The review highlights recent research on polymorphisms in these genes and their implications for drug metabolism, including variations in allele frequencies and their effects on therapeutic outcomes. Additionally, the paper discusses how these genetic variations contribute to the variability in drug response and adverse drug reactions among individuals in Arab populations. By synthesizing current findings, this review aims to provide a comprehensive understanding of the pharmacogenetic landscape in Arab countries and offer insights into personalized medicine approaches tailored to genetic profiles. The findings underscore the importance of incorporating pharmacogenetic data into clinical practice to enhance drug efficacy and minimize adverse effects, ultimately paving the way for more effective and individualized treatment strategies in the region.

PMID:39377381 | DOI:10.2174/0113892002323910240924145310

Explor Res Clin Soc Pharm. 2024 Sep 12;16:100508. doi: 10.1016/j.rcsop.2024.100508. eCollection 2024 Dec.

ABSTRACT

BACKGROUND: Community pharmacists are essential to pharmacogenomics implementation because they can help trainers, clinical advisors, and other medical professionals understand the importance of pharmacogenomics and encourage them to use it in their practice. This study is to evaluate the community pharmacists' understanding, attitudes, and perceptions of pharmacogenomics in the United Arab Emirates (UAE).

METHODS: Professionals employed at community pharmacies in Abu Dhabi, Dubai, and the Northern Emirates participated in a cross-sectional study design. From July 2023 to February 2024, five pharmacy students in their last year conducted the survey. The study team employed a structured questionnaire to collect data in addition to conducting in-person interviews. The study questionnaire comprised three distinct sections namely, demographic information, knowledge of pharmacogenomics concepts, and perceptions regarding pharmacogenomics.

RESULTS: A total of 586 pharmacists enrolled in the study. The average knowledge score regarding pharmacogenomics was 75.1 % with a 95 % confidence interval (CI) of [72.4 %, 77.7 %]. The average attitude score toward pharmacogenomics was 67.5 % with a 95 % CI of [66.3 %, 68.7 %]. Better pharmacogenomics knowledge among several groups: independent pharmacies (OR 1.7; 95 % CI 1.2-2.4), Pharmacists in Charge (OR 1.4; 95 % CI 1.3-2.02), pharmacists with 11-15 years of experience (OR 2.1; 95 % CI 1.4-4.2), graduates from international universities (OR 4.6; 95 % CI 1.6-12.9), and those who received training on pharmacogenomics (OR 11.9; 95 % CI 3.3-14.5). Similarly, better attitude scores were observed among independent pharmacies (OR 1.5; 95 % CI 1.1-2.1), Pharmacists in Charge (OR 1.5; 95 % CI 1.07-2.1), pharmacists with 16-20 years of experience (OR 2.1; 95 % CI 1.16-3.7), graduates regional universities (OR 1.47; 95 % CI 1.05-2.1), and those who received training on pharmacogenomics (OR 4.8; 95 % CI 3.2-7.3).

CONCLUSION: The positive attitudes toward pharmacogenomics that we found in our research indicate that community pharmacists in the United Arab Emirates are beginning to realize the potential advantages of pharmacogenomics in terms of improving patient care. Policies ensuring the privacy and confidentiality of genetic information are also necessary in considering concerns about the availability of genetic test results to insurance companies and potential employers.

PMID:39376795 | PMC:PMC11456781 | DOI:10.1016/j.rcsop.2024.100508

Pharmacogenomics J. 2024 Oct 7;24(6):31. doi: 10.1038/s41397-024-00352-z.

ABSTRACT

Our study investigated the impact of genetic variations on metformin glycemic response in a cohort from the Rotterdam Study, comprising 14,926 individuals followed for up to 27 years. Among 1285 metformin users of European ancestry, using linear mixed models, we analyzed the association of single nucleotide polymorphisms (SNPs) and a Polygenic Risk Score (PRS) with glycemic response, measured by changes in metformin dosage or HbA1c levels. While individual genetic variants showed no significant association, rs622342 on SLC2A1 correlated with increased glycemic response only in metformin monotherapy patients (β = -2.09, P-value < 0.001). The collective effect of variants, as represented by PRS, weakly correlated with changes in metformin dosage (β = 0.023, P-value = 0.027). Synergistic interaction was observed between rs7124355 and rs8192675. Our findings suggest that while higher PRS correlates with increased metformin dosage, its modest effect size limits clinical utility, emphasizing the need for future research in diverse populations to refine genetic risk models.

PMID:39375343 | DOI:10.1038/s41397-024-00352-z

J Mol Neurosci. 2024 Oct 7;74(4):94. doi: 10.1007/s12031-024-02271-x.

ABSTRACT

Neurofibromatosis type 1 (NF1) is a prevalent autosomal dominant disorder caused by mutations in the NF1 gene, leading to multisystem disorders. Given the critical role of cysteine residues in protein stability and function, we aimed to identify key NF1 mutations affecting cysteine residues that significantly contribute to neurofibromatosis pathology. To identify the most critical mutations in the NF1 gene that contribute to the pathology of neurofibromatosis, we employed a sophisticated computational pipeline specifically designed to detect significant mutations affecting the NF1 gene. Our approach involved an exhaustive search of databases such as the Human Gene Mutation Database (HGMD), UniProt, and ClinVar for information on missense mutations associated with NF1. Our search yielded a total of 204 unique cysteine missense mutations. We then employed in silico prediction tools, including PredictSNP, iStable, and Align GVGD, to assess the impact of these mutations. Among the mutations, C379R, R1000C, and C1016Y stood out due to their deleterious effects on the biophysical properties of the neurofibromin protein, significantly destabilizing its structure. These mutations were subjected to further phenotyping analysis using SNPeffect 4.0, which predicted disturbances in the protein's chaperone binding sites and overall structural stability. Furthermore, to directly visualize the impact of these mutations on protein structure, we utilized AlphaFold3 to simulate both the wild-type and mutant NF1 structures, revealing the significant effects of the R1000C mutation on the protein's conformation. In conclusion, the identification of these mutations can play a pivotal role in advancing the field of precision medicine and aid in the development of effective drugs for associated diseases.

PMID:39373898 | PMC:PMC11458684 | DOI:10.1007/s12031-024-02271-x

J Dermatol. 2024 Oct 7. doi: 10.1111/1346-8138.17449. Online ahead of print.

ABSTRACT

Inflammatory diseases that are driven by several pro-inflammatory cytokines has resulted in in the development of targeted therapies across different disease settings. Interleukin (IL)-36 cytokines have been implicated in several inflammatory diseases. In this review we describe the scientific evidence surrounding the use of the IL-36 receptor (IL-36R)-targeting antibody, spesolimab, in IL-36-mediated skin diseases: generalized pustular psoriasis (GPP), palmoplantar pustulosis (PPP), hidradenitis suppurativa, and Netherton syndrome (NS). Spesolimab, a high affinity, specific, humanized, antagonistic immunoglobulin G1 antibody, targets the IL-36R at a binding site distinct from its agonists, IL-36α/β/γ, and at least one endogenous antagonist, IL-36R antagonist. In vitro and in vivo data for spesolimab show effective inhibition of IL-36R-mediated signaling pathways, and six Phase I studies in healthy volunteers presented a favorable safety and pharmacokinetic (PK) profile, leading to the development of a clinical trial program to evaluate spesolimab in the treatment of IL-36R-mediated diseases. Six studies (including an expanded access program) have evaluated the efficacy, safety, PKs, and pharmacogenomics of spesolimab in patients with GPP flares. Spesolimab treatment of GPP flares resulted in rapid and sustained improvements in pustular and skin clearance, and clinically significant improvements in patient-reported symptoms and quality of life. Spesolimab also significantly reduces the risk of GPP flares and flare occurrence, preventing disease worsening and has a favorable safety profile. There have been three trials of spesolimab in PPP; further evaluation is needed to better define those patients who might benefit from the treatment. A trial of spesolimab in NS is ongoing, while other spesolimab trials suggest that IL-36 may only play a secondary role in the pathogenesis of atopic dermatitis. In conclusion, research into spesolimab has provided much needed insight into the role of IL-36 in the human immune system and the mechanism behind IL-36-mediated inflammatory diseases. Spesolimab provides an efficacious targeted treatment for GPP, a disease with a high unmet medical need.

PMID:39373152 | DOI:10.1111/1346-8138.17449

SAGE Open Med Case Rep. 2024 Sep 21;12:2050313X241283262. doi: 10.1177/2050313X241283262. eCollection 2024.

ABSTRACT

The management of schizoaffective disorder bipolar type often involves a combination of pharmacotherapy and psychotherapy. Clozapine, an effective antipsychotic for treatment-resistant schizophrenia, and oxcarbazepine, a mood stabilizer, is a commonly prescribed medication. We present a case report of a 56-year-old male with schizoaffective disorder bipolar type who experienced subtherapeutic clozapine levels despite dose adjustments, leading to deteriorating symptoms. Oxcarbazepine, a weak CYP450 inducer, likely contributed to the subtherapeutic levels. Additionally, the pharmacogenetic analysis revealed a CYP1A2 *1F/*1F genotype, indicating normal activity with a potential for decreased serum levels and adverse events in the presence of inducers. The patient was eventually stabilized on a regimen of lithium, paliperidone, and quetiapine, avoiding oxcarbazepine. This case highlights the importance of considering individual patient factors, including pharmacogenetics when managing treatment-resistant patients. Monitoring serum clozapine levels and assessing enzyme activity before initiating therapy may help optimize treatment outcomes and minimize adverse events.

PMID:39371390 | PMC:PMC11456182 | DOI:10.1177/2050313X241283262

Prog Neuropsychopharmacol Biol Psychiatry. 2024 Oct 5;136:111154. doi: 10.1016/j.pnpbp.2024.111154. Online ahead of print.

ABSTRACT

Major Depressive Disorder (MDD) is one of the most prevalent neurobiological disorders globally. Antidepressant medications are the first-line treatment for managing symptoms. However, over time, pharmacotherapy has been linked to several challenges, primarily due to the wide array of side effects that often reduce patient adherence to treatment. The literature suggests that these side effects may be influenced by polymorphisms in genes related to the pharmacokinetics and pharmacodynamics of antidepressants. Thus, this systematic review aimed to identify studies that investigated the association between genetic variants and side effects resulting from antidepressant treatment in individuals with MDD. Original articles indexed in the electronic databases Cochrane Library, EMBASE, MEDLINE via PubMed, and Scopus were identified. A total of 55 studies were included in the review, and data regarding the outcomes of interest were extracted. Due to the exploratory nature of the review, a narrative/descriptive synthesis of the results was performed. The risk of bias was evaluated using the Joanna Briggs Institute's tools, tailored to the design of each study. Polymorphisms in 35 genes were statistically associated with the development of side effects. A subsequent Protein-Protein Interaction Network analysis helped elucidate the key biological pathways involved in antidepressant side effects, with a view toward exploring the potential application of pharmacogenetic markers in clinical practice.

PMID:39369809 | DOI:10.1016/j.pnpbp.2024.111154

Arh Hig Rada Toksikol. 2024 Sep 29;75(3):211-216. doi: 10.2478/aiht-2024-75-3846. eCollection 2024 Sep 1.

ABSTRACT

The aim of this study was to investigate the extent of second-hand smoke exposure in younger population visiting nightclubs in Croatia by comparing the levels of nicotine and its main metabolites cotinine and trans-3'-hydroxycotinine (3HC) in urine samples taken from 22 participants before and after spending about three hours in a nightclub, stratified by smoking status (smokers and non-smokers). The samples were prepared by liquid-liquid extraction and analysed with gas chromatography-mass spectrometry. The presence of nicotine, cotinine, and 3HC was confirmed in all urine samples. Their median concentrations significantly differed between the two measurements in non-smokers. Our findings show that even a three-hour exposure to second-hand smoke can significantly increase the levels of nicotine and its metabolites in urine, which are indicative of exposure to other, harmful tobacco smoke substances. They also call for raising awareness of the health risks of exposure to second-hand smoke in the general population and among individuals who frequent nightclubs in particular.

PMID:39369327 | PMC:PMC11456220 | DOI:10.2478/aiht-2024-75-3846

Muscle Nerve. 2024 Oct 5. doi: 10.1002/mus.28275. Online ahead of print.

ABSTRACT

INTRODUCTION/AIMS: Changes in body composition in patients with spinal muscular atrophy (SMA) can cause endocrine abnormalities that are insufficiently studied in adults. We aimed to assess the endocrine profile in a cohort of adults with SMA. Second, we compared body composition and endocrine profiles between nonambulatory and ambulatory patients and between different types of SMA.

METHODS: The cross-sectional study included 29 SMA patients (18 [62.1%] males and 11 [37.9%] females) of median age 44 (IQR 30-51.5) years with type 2, 3, or 4. Body composition was measured by bioimpedance. Morning blood samples were drawn for glycated hemoglobin (HbA1c), lipid profile, testosterone, cortisol, and insulin-like growth factor-1 (IGF-1). Blood glucose, insulin, and beta-hydroxybutyrate (BHB) were measured during a 75 g oral glucose tolerance test. The homeostatic model assessment for insulin resistance index was calculated.

RESULTS: In total, 75.9% of patients had increased fat mass (FM), with 51.7% having an increase despite normal body mass index. Ambulation was the most important discriminating factor of body composition. 93.1% of patients had metabolic abnormalities, including hyperglycemia, insulin resistance, and dyslipidemia. Increased BHB, a marker of ketosis, was present in more than a third of patients. Functional hypogonadism was present in half of male patients. Testosterone and IGF-1 negatively correlated with FM.

DISCUSSION: Adult patients with SMA had abnormal body composition and highly prevalent metabolic disturbances that might increase cardiometabolic risk. Because treatments have modified the course of SMA, it is important to investigate whether these observations translate into clinically relevant outcomes.

PMID:39367693 | DOI:10.1002/mus.28275

Lancet Public Health. 2024 Oct;9(10):e729-e744. doi: 10.1016/S2468-2667(24)00166-X.

ABSTRACT

BACKGROUND: Smoking is the leading behavioural risk factor for mortality globally, accounting for more than 175 million deaths and nearly 4·30 billion years of life lost (YLLs) from 1990 to 2021. The pace of decline in smoking prevalence has slowed in recent years for many countries, and although strategies have recently been proposed to achieve tobacco-free generations, none have been implemented to date. Assessing what could happen if current trends in smoking prevalence persist, and what could happen if additional smoking prevalence reductions occur, is important for communicating the effect of potential smoking policies.

METHODS: In this analysis, we use the Institute for Health Metrics and Evaluation's Future Health Scenarios platform to forecast the effects of three smoking prevalence scenarios on all-cause and cause-specific YLLs and life expectancy at birth until 2050. YLLs were computed for each scenario using the Global Burden of Disease Study 2021 reference life table and forecasts of cause-specific mortality under each scenario. The reference scenario forecasts what could occur if past smoking prevalence and other risk factor trends continue, the Tobacco Smoking Elimination as of 2023 (Elimination-2023) scenario quantifies the maximum potential future health benefits from assuming zero percent smoking prevalence from 2023 onwards, whereas the Tobacco Smoking Elimination by 2050 (Elimination-2050) scenario provides estimates for countries considering policies to steadily reduce smoking prevalence to 5%. Together, these scenarios underscore the magnitude of health benefits that could be reached by 2050 if countries take decisive action to eliminate smoking. The 95% uncertainty interval (UI) of estimates is based on the 2·5th and 97·5th percentile of draws that were carried through the multistage computational framework.

FINDINGS: Global age-standardised smoking prevalence was estimated to be 28·5% (95% UI 27·9-29·1) among males and 5·96% (5·76-6·21) among females in 2022. In the reference scenario, smoking prevalence declined by 25·9% (25·2-26·6) among males, and 30·0% (26·1-32·1) among females from 2022 to 2050. Under this scenario, we forecast a cumulative 29·3 billion (95% UI 26·8-32·4) overall YLLs among males and 22·2 billion (20·1-24·6) YLLs among females over this period. Life expectancy at birth under this scenario would increase from 73·6 years (95% UI 72·8-74·4) in 2022 to 78·3 years (75·9-80·3) in 2050. Under our Elimination-2023 scenario, we forecast 2·04 billion (95% UI 1·90-2·21) fewer cumulative YLLs by 2050 compared with the reference scenario, and life expectancy at birth would increase to 77·6 years (95% UI 75·1-79·6) among males and 81·0 years (78·5-83·1) among females. Under our Elimination-2050 scenario, we forecast 735 million (675-808) and 141 million (131-154) cumulative YLLs would be avoided among males and females, respectively. Life expectancy in 2050 would increase to 77·1 years (95% UI 74·6-79·0) among males and 80·8 years (78·3-82·9) among females.

INTERPRETATION: Existing tobacco policies must be maintained if smoking prevalence is to continue to decline as forecast by the reference scenario. In addition, substantial smoking-attributable burden can be avoided by accelerating the pace of smoking elimination. Implementation of new tobacco control policies are crucial in avoiding additional smoking-attributable burden in the coming decades and to ensure that the gains won over the past three decades are not lost.

FUNDING: Bloomberg Philanthropies and the Bill & Melinda Gates Foundation.

PMID:39366729 | PMC:PMC11447278 | DOI:10.1016/S2468-2667(24)00166-X

J Appl Lab Med. 2024 Oct 4:jfae105. doi: 10.1093/jalm/jfae105. Online ahead of print.

NO ABSTRACT

PMID:39365749 | DOI:10.1093/jalm/jfae105

Clin Transl Oncol. 2024 Oct 4. doi: 10.1007/s12094-024-03652-9. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Despite that incorporating antiangiogenic in combination with immune-checkpoint inhibitors as the standard first-line treatment for advanced clear cell renal cell cancer (ccRCC) yields promising outcomes, these regimens often lead to significant toxicity. However, a subgroup of patients has shown responsiveness to VEGFR tyrosine-kinase inhibitors (TKIs) in monotherapy, leading to the question of whether employing combination therapies can significantly enhance overall survival in all patients over monotherapy. Thus, we aim to identify gene expression signatures that can predict TKI response within subpopulations that might benefit from single-agent therapies, to minimize unnecessary exposure to combination therapies and their associated toxicities, as well as to discover new potential therapeutic targets to improve ccRCC treatment. Based on prior data, the androgen receptor (AR) might meet both conditions.

PATIENTS AND METHODS: We evaluated the association between AR expression, assessed through NanoString® technology-derived mRNA counts, and the clinical outcomes of 98 ccRCC patients treated with first-line antiangiogenics and determined its association with other genes implicated in ccRCC tumorigenesis.

RESULTS: Higher AR-expression correlates significantly with better prognosis and survival based on the MSKCC risk score, and longer PFS. Furthermore, we have identified a gene set signature associated with AR-overexpression and several genes involved in angiogenesis and transcriptional targets of the hypoxia-inducible factor, a cornerstone of ccRCC.

CONCLUSIONS: AR-overexpression and its association with other genes could favor a transcriptomic signature set to aid in identifying patients suitable for TKI in monotherapy, rather than aggressive combinations, enhancing thus, precision and personalized therapeutic decisions.

PMID:39365364 | DOI:10.1007/s12094-024-03652-9

Funct Integr Genomics. 2024 Oct 4;24(5):182. doi: 10.1007/s10142-024-01462-4.

ABSTRACT

This review analyzes the application of machine learning (ML) in oncological pharmacogenomics, focusing on customizing chemotherapy treatments. It explores how ML can analyze extensive genomic, proteomic, and other omics datasets to identify genetic patterns associated with drug responses. This, in turn, facilitates personalized therapies that are more effective and have fewer side effects. Recent studies have emphasized ML's revolutionary role of ML in personalized oncology treatment by identifying genetic variability and understanding cancer pharmacodynamics. Integrating ML with electronic health records and clinical data shows promise in refining chemotherapy recommendations by considering the complex influencing factors. Although standard chemotherapy depends on population-based doses and treatment regimens, customized techniques use genetic information to tailor treatments for specific patients, potentially enhancing efficacy and reducing adverse effects.However, challenges, such as model interpretability, data quality, transparency, ethical issues related to data privacy, and health disparities, remain. Machine learning has been used to transform oncological pharmacogenomics by enabling personalized chemotherapy treatments. This review highlights ML's potential of ML to enhance treatment effectiveness and minimize side effects through detailed genetic analysis. It also addresses ongoing challenges including improved model interpretability, data quality, and ethical considerations. The review concludes by emphasizing the importance of rigorous clinical trials and interdisciplinary collaboration in the ethical implementation of ML-driven personalized medicine, paving the way for improved outcomes in cancer patients and marking a new frontier in cancer treatment.

PMID:39365298 | DOI:10.1007/s10142-024-01462-4

Eur Heart J Cardiovasc Pharmacother. 2024 Oct 4;10(6):479-480. doi: 10.1093/ehjcvp/pvae061.

NO ABSTRACT

PMID:39364572 | DOI:10.1093/ehjcvp/pvae061

Clin Pharmacol Ther. 2024 Oct;116(4):885-889. doi: 10.1002/cpt.3404.

NO ABSTRACT

PMID:39363446 | DOI:10.1002/cpt.3404

Nat Genet. 2024 Oct 3. doi: 10.1038/s41588-024-01913-5. Online ahead of print.

ABSTRACT

Human genetic variants are associated with many traits through largely unknown mechanisms. Here, combining approximately 260,000 Japanese study participants, a Japanese-specific genotype reference panel and statistical fine-mapping, we identified 4,423 significant loci across 63 quantitative traits, among which 601 were new, and 9,406 putatively causal variants. New associations included Japanese-specific coding, splicing and noncoding variants, exemplified by a damaging missense variant rs730881101 in TNNT2 associated with lower heart function and increased risk for heart failure (P = 1.4 × 10-15 and odds ratio = 4.5, 95% confidence interval = 3.1-6.5). Putative causal noncoding variants were supported by state-of-art in silico functional assays and had comparable effect sizes to coding variants. A plausible example of new mechanisms of causal variants is an enrichment of causal variants in 3' untranslated regions (UTRs), including the Japanese-specific rs13306436 in IL6 associated with pro-inflammatory traits and protection against tuberculosis. We experimentally showed that transcripts with rs13306436 are resistant to mRNA degradation by regnase-1, an RNA-binding protein. Our study provides a list of fine-mapped causal variants to be tested for functionality and underscores the importance of sequencing, genotyping and association efforts in diverse populations.

PMID:39363016 | DOI:10.1038/s41588-024-01913-5

Pharmacogenomics. 2024 Oct 3:1-11. doi: 10.1080/14622416.2024.2406213. Online ahead of print.

ABSTRACT

Aim: To evaluate the feasibility and impact of using CYP2C19 genotype to guide selection of antiplatelet therapy in patients undergoing intracranial aneurysm treatment with a flow diversion stent in a real-world clinical setting.Patients & methods: A single-center, retrospective, observational cohort study was conducted in 112 patients undergoing intracranial aneurysm repair with flow-diversion stenting from 2014 to 2021. Data were abstracted from health records. The frequency of clopidogrel or alternative therapy (ticagrelor or prasugrel) use was compared across CYP2C19 status (intermediate or poor metabolizer [IM/PM] vs. normal, rapid, or ultrarapid metabolizer [NM/RM/UM]).Results: In the study population, CYP2C19 genotype testing was performed on 110 (98.2%) patients; of these, 106 (97.2%) had results available prior to the stent procedure and 28 (25.5%) were IM/PMs. Alternative therapy was used more frequently in IM/PMs compared with NM/RM/UMs (57.1 vs. 8.5%, respectively, p < 0.0001). The frequency of thromboembolic events over 12 months did not significantly differ across clopidogrel-treated IM/PMs, clopidogrel-treated NM/RM/UMs and patients on alternative therapy (p = 0.352); although, event numbers were low.Conclusion: A pre-emptive CYP2C19 genotyping strategy to guide antiplatelet therapy selection in intracranial aneurysm repair patients is feasible in a real-world clinical setting. Larger studies are needed to assess the impact on clinical outcomes.

PMID:39360670 | DOI:10.1080/14622416.2024.2406213

Pharmacogenomics J. 2024 Oct 2;24(5):30. doi: 10.1038/s41397-024-00350-1.

ABSTRACT

Clinical and economic outcomes from a pharmacogenomics-enriched comprehensive medication management program were evaluated over 26 months in a self-insured U.S. employee population (n = 452 participants; n = 1500 controls) using propensity matched pre-post design with adjusted negative binomial and linear regression models. After adjusting for baseline covariates, program participation was associated with 39% fewer inpatient (p = 0.05) and 39% fewer emergency department (p = 0.002) visits, and with 21% more outpatient visits (p < 0.001) in the follow-up period compared to the control group. Results show pharmacogenomics-enriched comprehensive medication management can favorably impact healthcare utilization in a self-insured employer population by reducing emergency department and inpatient visits and can offer the potential for cost savings. Self-insured employers may consider implementing pharmacogenomics-enriched comprehensive medication management to improve the healthcare of their employees.

PMID:39358335 | PMC:PMC11446811 | DOI:10.1038/s41397-024-00350-1