Eur Psychiatry. 2022 Oct 25:1-19. doi: 10.1192/j.eurpsy.2022.2333. Online ahead of print.

NO ABSTRACT

PMID:36281033 | DOI:10.1192/j.eurpsy.2022.2333

Nat Commun. 2022 Oct 24;13(1):6323. doi: 10.1038/s41467-022-33144-9.

ABSTRACT

Statins, a family of FDA-approved cholesterol-lowering drugs that inhibit the rate-limiting enzyme of the mevalonate metabolic pathway, have demonstrated anticancer activity. Evidence shows that dipyridamole potentiates statin-induced cancer cell death by blocking a restorative feedback loop triggered by statin treatment. Leveraging this knowledge, we develop an integrative pharmacogenomics pipeline to identify compounds similar to dipyridamole at the level of drug structure, cell sensitivity and molecular perturbation. To overcome the complex polypharmacology of dipyridamole, we focus our pharmacogenomics pipeline on mevalonate pathway genes, which we name mevalonate drug-network fusion (MVA-DNF). We validate top-ranked compounds, nelfinavir and honokiol, and identify that low expression of the canonical epithelial cell marker, E-cadherin, is associated with statin-compound synergy. Analysis of remaining prioritized hits led to the validation of additional compounds, clotrimazole and vemurafenib. Thus, our computational pharmacogenomic approach identifies actionable compounds with pathway-specific activities.

PMID:36280687 | DOI:10.1038/s41467-022-33144-9

Biomed Pharmacother. 2022 Oct 21;156:113899. doi: 10.1016/j.biopha.2022.113899. Online ahead of print.

ABSTRACT

Cannabinoid derivates have been largely used for different medical purpose. In the literature, several methods capable of separating THC and its principles metabolites are described, although Δ8- and Δ9-THC separation has not been completely achieved. THC metabolism has not been fully understood and metabolites plasma distribution in healthy and pathological patients remains to further deepen. The aim of this study was the validation of UHPLC-MS/MS method for the quantification of 10 cannabinoids in human plasma, as important tool for improving clinical efficacy of cannabis administration. Obtained results were in accordance with recommendations of ICH Harmonised Guideline for bioanalytical method validation, showing a good linearity, optimal accuracy as well as satisfactory results in terms of intra-day and inter-day precision and matrix effect. Furthermore, blood sampling study was performed to investigate the better collection method. Optimal separation of Δ-9-tetrahydrocannabinol (Δ9-THC), Δ8-tetrahydrocannabinol (Δ8-THC) was obtained. The present method showed optimal linearity and satisfactory results in terms of specificity and selectivity. Recovery was between 92.0% and 96.5% for all analytes. The matrix-effect showed good performance; no carry over was observed. Cannabinoid metabolites present in higher plasma concentrations were: 11-Hydroxy-Δ9-tetrahydrocannabinol, 11-Nor-9carboxy-Δ9-tetrahydrocannabinol and THC-COOH-glucuronide. Method performance makes it suitable for routine purposes and a potential tool for therapeutic ranges definition. The present work will be used to test several samples in a long-term clinical study, paving the way for further future works.

PMID:36279720 | DOI:10.1016/j.biopha.2022.113899

Pharmacogenomics J. 2022 Oct 22. doi: 10.1038/s41397-022-00295-3. Online ahead of print.

ABSTRACT

The study aimed to conduct a meta-analysis of studies comparing pharmacogenetically guided dosing of antidepressants with empiric standard of care. Publications referring to genotype-guided antidepressant therapy were identified via PubMed, Google Scholar, Scopus, Web of Science, Embase, and Cochrane databases from the inception of the databases to 2021. In addition, bibliographies of all articles were manually searched for additional references not identified in primary searches. Studies comparing clinical outcomes between two groups of patients who received antidepressant treatment were included in meta-analysis. Analysis of the data revealed statistically significant differences between the experimental group receiving pharmacogenetically guided dosing and the empirically treated controls. Specifically, genotype-guided treatment significantly improved response and remission of patients after both eight and twelve weeks of therapy, whereas no effect on the development of adverse drug reactions was observed. This meta-analysis indicates that the use of preemptive genotyping to guide dosing of antidepressants might increase treatment efficacy.

PMID:36273107 | DOI:10.1038/s41397-022-00295-3

Clin Transl Sci. 2022 Oct 21. doi: 10.1111/cts.13396. Online ahead of print.

ABSTRACT

This study conducted a pairwise comparison of antihypertensive and metabolic effects of hydrochlorothiazide (HCTZ) and chlorthalidone (CTD) at 25 mg/day in the same individuals to address the clinical dilemma on preferred thiazide for hypertension (HTN) management. We included 15 African American (AA) and 35 European American (EA) patients with HTN treated with HCTZ and CTD as part of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) and PEAR-2 trials, respectively. Mean reduction in systolic/diastolic blood pressure (SBP/DBP) with HCTZ versus CTD was 8/5 versus 16/8 mmHg among EA patients (p < 1.0e-5 SBP, p = 0.002 DBP) and 11/8 versus 20/11 mmHg among AA patients (p = 0.03 SBP, p = 0.22 DBP). While CTD showed clinically meaningful benefit over HCTZ in two-thirds of participants with respect to SBP reduction and half of EA patients with respect to DBP reduction, a majority of AA patients (53%) showed similar DBP reduction with both thiazides. Sixty percent of AA patients and 29% of EA patients attained blood pressure (BP) <140/90 mmHg with both thiazides. Mean potassium (K+) reduction was greater with CTD compared to HCTZ both in EA patients (mean difference = 0.35, p = 0.0002) and AA patients (0.49, p = 0.043). While 31% of AA patients developed severe hypokalemia on CTD, <5% of others developed severe hypokalemia. Although 46% of AA patients on CTD required K+ supplementation, only 6%-11% of others required supplementation. Overall, in the majority of EA patients, CTD was superior to HCTZ, whereas among AA patients, it was superior in a minority, and was associated with significant potassium-related risk, suggesting that guideline preferences for CTD over HCTZ are reasonable in EA patients but may be less reasonable in AA patients, particularly if the target is <140/90 mmHg.

PMID:36271676 | DOI:10.1111/cts.13396

Biomed Pharmacother. 2022 Nov;155:113787. doi: 10.1016/j.biopha.2022.113787. Epub 2022 Oct 6.

ABSTRACT

Tumor-infiltrating immune cells (TIICs) play a critical role in breast cancer (BC) prognosis, but little is known regarding the efficacy of endocrine therapy in patients with ER-positive BC with diverse immunological phenotypes. To investigate whether TIICs affect survival after endocrine therapy in patients with different BC molecular subtypes, data were gathered from six studies totaling 1900 samples. CIBERSORTx was used to analyze the invasion of 22 immune cell subpopulations using a bulk gene expression profile. The relationships of immune-related metagenes and immune cell subsets with survival (distant metastasis-free survival, relapse-free survival, and overall survival) were studied using Cox regression models with cell proportions modeled in quartiles. The immune score and IGHG3 and LCK gene activity were linked to a better prognosis. Among the immune cells, monocytes, resting CD4+ memory T cells and plasma cells were correlated with prolonged survival, while neutrophils, Tregs, M0 macrophages, and M2 macrophages were associated with an unfavorable prognosis. Similar effects were reported for the luminal A subtype. In the luminal B subtype, γδ T cells and eosinophils were favorable prognostic factors. Covariate-adjusted multivariate Cox regression analysis revealed that high proportions of resting CD4+ memory T cells and resting dendritic cells were correlated with a good prognosis. Meanwhile, neutrophils were associated with an unfavorable prognosis. Understanding how monocytes and macrophages interact in the tumor microenvironment may be a promising study focus. Comprehensive research on the cellular immune response in tumors could help facilitate the development of new treatments.

PMID:36271565 | DOI:10.1016/j.biopha.2022.113787

Pharm Res. 2022 Oct 21. doi: 10.1007/s11095-022-03407-7. Online ahead of print.

ABSTRACT

PURPOSE: Voriconazole is an essential antifungal drug whose complex pharmacokinetics with high interindividual variability impedes effective and safe therapy. By application of the minimally-invasive sampling technique microdialysis, interstitial space fluid (ISF) concentrations of VRC and its potentially toxic N-oxide metabolite (NO) were assessed to evaluate target-site exposure for further elucidating VRC pharmacokinetics.

METHODS: Plasma and ISF samples of a clinical trial with an approved VRC dosing regimen were analyzed for VRC and NO concentrations. Concentration-time profiles, exposure assessed as area-under-the-curve (AUC) and metabolic ratios of four healthy adults in plasma and ISF were evaluated regarding the impact of multiple dosing and CYP2C19 genotype.

RESULTS: VRC and NO revealed distribution into ISF with AUC values being ≤2.82- and 17.7-fold lower compared to plasma, respectively. Intraindividual variability of metabolic ratios was largest after the first VRC dose administration while interindividual variability increased with multiple dosing. The CYP2C19 genotype influenced interindividual differences with a maximum 6- and 24-fold larger AUCNO/AUCVRC ratio between the intermediate and rapid metabolizer in plasma and ISF, respectively. VRC metabolism was saturated/auto-inhibited indicated by substantially decreasing metabolic concentration ratios with increasing VRC concentrations and after multiple dosing.

CONCLUSION: The feasibility of the simultaneous microdialysis of VRC and NO in vivo was demonstrated and provided new quantitative insights by leveraging distribution and metabolism processes of VRC in humans. The exploratory analysis suggested substantial dissimilarities of VRC and NO pharmacokinetics in plasma and ISF. Ultimately, a thorough understanding of target-site pharmacokinetics might contribute to the optimization of personalized VRC dosing regimens.

PMID:36271205 | DOI:10.1007/s11095-022-03407-7

Support Care Cancer. 2022 Oct 21. doi: 10.1007/s00520-022-07404-9. Online ahead of print.

ABSTRACT

Studies suggest wide heterogeneity in pain management response. Improved methods of pain pharmacotherapy are urgently needed to improve clinical response and safety profile of analgesics. The study or application of how genetics influence response to medications is called pharmacogenomics (PGx). PGx testing is a tool that may support more precise selection and dosing of pain medicines. PGx guidelines exist for drug-gene interactions with high levels of evidence and can be applied in clinical practice for more precise care in patients with cancer. The Clinical Pharmacogenetics Implementation Consortium (CPIC) is a publicly funded international consortium of experts who curate published PGx data and create peer-reviewed guidelines on how to translate PGx results into actionable prescribing decisions. Given the immense need to improve pain management, it is important to increase awareness and consider application of CPIC guidelines to pain management strategies. This commentary concisely describes how PGx can be used to aid in more precise applications of pain pharmacotherapy based on the CPIC guidelines.

PMID:36271058 | DOI:10.1007/s00520-022-07404-9

Am J Pharm Educ. 2022 Oct 21:8899. doi: 10.5688/ajpe8899. Online ahead of print.

ABSTRACT

Objective: To describe the development and assessment of an integrated virtual escape room in a cardiology course.Methods: A virtual escape room was developed to reinforce therapeutics, pharmacology, pharmacokinetics, medicinal chemistry, pharmacogenomics, and calculations related to cardiology in an integrated pharmacy course and was completed by two student cohorts. Groups of 4-5 students had 40 minutes to complete virtual escape room puzzles, and each puzzle had to be solved correctly prior to advancing. After completion of the activity, learners met with facilitators to debrief. Students completed pre- and post-surveys to assess knowledge changes and perceptions of the experience.Results: One hundred and twenty-six second-year PharmD students completed the escape room, and 79% (n=55) and 93% (n=52) of students completed pre- and post-surveys for the 2020 and 2021 cohorts, respectively. McNemar's paired test indicates a statistically significant improvement in student knowledge on pre- and post-survey knowledge questions (M=43.1, SD=22.6; M=74.1, SD=19.6, and M=52.0, SD=15.8; M=67.1, SD=19.2 for 2020 and 2021, respectively). Most students in both cohorts (88%) agreed that logistics of the escape rooms were amenable to learning and applying information, and 86% enjoyed working through puzzles.Implications: The virtual escape room was well-received by students and served as an effective tool for reinforcing and integrating cardiology concepts. The virtual nature of the activity makes it practical and easily replicable to implement at other institutions, which can benefit from using the format, logistics and materials described in this study to decrease faculty workload and costs associated with implementing this educational technique.

PMID:36270662 | DOI:10.5688/ajpe8899

Annu Rev Pharmacol Toxicol. 2022 Oct 21. doi: 10.1146/annurev-pharmtox-091222-022612. Online ahead of print.

ABSTRACT

Investigations in pharmacology and toxicology range from molecular studies to clinical care. Studies in basic and clinical pharmacology and in preclinical and clinical toxicology are all essential in bringing new knowledge and new drugs into clinical use. The 30 reviews in Volume 63 of the Annual Review of Pharmacology and Toxicology explore topics across this spectrum. Examples include "Zebrafish as a Mainstream Model for In Vivo Systems Pharmacology and Toxicology" and "Artificial Intelligence and Machine Learning for Lead-to-Candidate Decision-Making and Beyond." Other reviews discuss components important for drug discovery and development and the use of pharmaceuticals in a variety of diseases. Air pollution continues to increase globally; accordingly, "Air Pollution-Related Neurotoxicity Across the Life Span" is a timely and forward-thinking review. Volume 63 also explores the use of contemporary technologies such as electronic health records, pharmacogenetics, and new drug delivery systems that help enhance and improve the utility of new therapies. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 63 is January 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID:36270297 | DOI:10.1146/annurev-pharmtox-091222-022612

Anesth Analg. 2022 Nov 1;135(5):926-928. doi: 10.1213/ANE.0000000000006054. Epub 2022 Oct 21.

NO ABSTRACT

PMID:36269983 | DOI:10.1213/ANE.0000000000006054

OMICS. 2022 Oct 21. doi: 10.1089/omi.2022.0105. Online ahead of print.

ABSTRACT

The current pandemic has markedly shifted the focus of the global research and development ecosystem toward infectious agents such as SARS-CoV-2, the causative agent for COVID-19. A case in point is the chronic liver disease associated with hepatitis B virus (HBV) infection that continues to be a leading cause of severe liver disease and death globally. The burden of HBV infection is highest in the World Health Organization designated western Pacific and Africa regions. Tenofovir disoproxil fumarate (TDF) is a nucleoside analogue used in treatment of HBV infection but carries a potential for kidney toxicity. TDF is not metabolized by the cytochrome P450 enzymes and, therefore, its clearance in the proximal tubule of the renal nephron is controlled mostly by membrane transport proteins. Clinical pharmacogenomics of TDF with a focus on drug transporters, discussed in this perspective article, offers a timely example where resource-limited countries and regions of the world with high prevalence of HBV can strengthen the collective efforts to fight both COVID-19 and liver diseases impacting public health. We argue that precision/personalized medicine is invaluable to guide this line of research inquiry. In all, our experience in Ghana tells us that it is important not to forget the burden of chronic diseases while advancing research on infectious diseases such as COVID-19. For the long game with COVID-19, we need to address the public health burden of infectious agents and chronic diseases in tandem.

PMID:36269614 | DOI:10.1089/omi.2022.0105

Expert Rev Mol Diagn. 2022 Oct 21. doi: 10.1080/14737159.2022.2139602. Online ahead of print.

NO ABSTRACT

PMID:36268756 | DOI:10.1080/14737159.2022.2139602

Pharmacogenomics. 2022 Oct 21. doi: 10.2217/pgs-2022-0113. Online ahead of print.

ABSTRACT

Aim: We sought to identify the variants that could predict the risk of nivolumab-induced immune-related adverse events (irAEs) in patients with cancer. Patients & methods: We enrolled 622 Japanese patients and carried out a genome-wide association study. The associations for 507 single nucleotide polymorphisms (SNPs) showing p < 0.001 were further investigated using an independent cohort. Results: In the combined analysis, possible associations were found for a total of 90 SNPs. Although no SNPs were identified to be significantly associated with nivolumab-induced irAEs, the SNP most strongly associated with nivolumab-induced irAEs was rs469490. Conclusion: This study is an important hypothesis-generating study to guide future studies in larger and/or other ethnic cohorts.

PMID:36268685 | DOI:10.2217/pgs-2022-0113

Ann Transl Med. 2022 Sep;10(18):983. doi: 10.21037/atm-22-3976.

ABSTRACT

BACKGROUND: Microvascular angina (MVA) is a group of clinical manifestations of angina pectoris or angina-like chest pain, positive exercise test, and exclusion of epicardial coronary artery spasm, wherein coronary angiography (CAG) does not present obvious epicardial vascular stenosis. Shexiang Tongxin dropping pill (STDP) has the effect of benefiting the Qi and opening the blood vessels, activating blood circulation, and resolving blood stasis. We explored the mechanism of STDP against MVA by network pharmacology and molecular docking.

METHODS: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), literature search, SwissTargetPrediction database, and high-throughput experiment- and reference-guided database of traditional Chinese medicine (HERB) were applied to identify the active ingredients and targets of STDP. The MVA targets were searched in the databases of GeneCards, Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB), DisGeNET, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). The common targets of STDP and MVA were screened. The software RStudio 4.1.3 was used to analyze the enrichment of these targets using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Protein-protein interaction (PPI) network analysis of the common targets was performed using the Search Tool for the Retrieval of Interacting Genes/Genomes (STRING) database. The cytoHubba plug-in of Cytoscape 3.9.1 software was employed to analyze the PPI network and obtain the core targets. Molecular docking was performed to verify the relationship between the core compounds and proteins with AutoDock Tools 1.5.7 and Pymol 2.4.0.

RESULTS: We identified 93 effective components of STDP, 310 potential targets, 981 MVA targets, and 138 intersectional targets. The potential anti-MVA mechanism of STDP may involve the advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications; lipids and atherosclerosis; fluid shear stress; atherosclerosis; the tumor necrosis factor (TNF), interleukin (IL)-17, hypoxia-inducible factor (HIF)-1, and C-type lectin receptor signaling pathways. Further, STDP mainly acts on its targets IL-6, AKT1, STAT3, JUN, and IL-1β to against MVA.

CONCLUSIONS: The STDP may exert its therapeutic effects through processes, such as anti-inflammation, promotion of smooth muscle cell proliferation and differentiation, lipid metabolism, immunomodulation, and regulation of cellular autophagy.

PMID:36267750 | PMC:PMC9577736 | DOI:10.21037/atm-22-3976

Pharmacogenomics J. 2022 Oct 20. doi: 10.1038/s41397-022-00293-5. Online ahead of print.

ABSTRACT

Using concentration-time data from the NEAT001/ARNS143 study (single sample at week 4 and 24), we determined raltegravir pharmacokinetic parameters using nonlinear mixed effects modelling (NONMEM v.7.3; 602 samples from 349 patients) and investigated the influence of demographics and SNPs (SLC22A6 and UGT1A1) on raltegravir pharmacokinetics and pharmacodynamics. Demographics and SNPs did not influence raltegravir pharmacokinetics and no significant pharmacokinetic/pharmacodynamic relationships were observed. At week 96, UGT1A1*28/*28 was associated with lower virological failure (p = 0.012), even after adjusting for baseline CD4 count (p = 0.048), but not when adjusted for baseline HIV-1 viral load (p = 0.082) or both (p = 0.089). This is the first study to our knowledge to assess the influence of SNPs on raltegravir pharmacodynamics. The lack of a pharmacokinetic/pharmacodynamic relationship is potentially an artefact of raltegravir's characteristic high inter and intra-patient variability and also suggesting single time point sampling schedules are inadequate to thoroughly assess the influence of SNPs on raltegravir pharmacokinetics.

PMID:36266537 | DOI:10.1038/s41397-022-00293-5

Pulm Pharmacol Ther. 2022 Oct 17:102172. doi: 10.1016/j.pupt.2022.102172. Online ahead of print.

ABSTRACT

COVID-19 medicines, such as molnupiravir are beginning to emerge for public health and clinical practice. On the other hand, drugs display marked variability in their efficacy and safety. Hence, COVID-19 medicines, as with all drugs, will be subject to the age-old maxim "one size prescription does not fit all". In this context, pharmacogenomics is the study of genome-by-drug interactions and offers insights on mechanisms of patient-to-patient and between-population variations in drug efficacy and safety. Pharmacogenomics information is crucial to tailoring the patients' prescriptions to achieve COVID-19 preventive and therapeutic interventions that take into account the host biology, patients' genome, and variable environmental exposures that collectively influence drug efficacy and safety. This expert review critically evaluates and summarizes the pharmacogenomics and personalized medicine aspects of the emerging COVID-19 drugs, and other selected drug interventions deployed to date. Here, we aim to sort out the hope, hype, and reality and suggest that there are veritable prospects to advance COVID-19 medicines for public health benefits, provided that pharmacogenomics is considered and implemented adequately. Pharmacogenomics is an integral part of rational and evidence-based medical practice. Scientists, health care professionals, pharmacists, pharmacovigilance practitioners, and importantly, patients stand to benefit by expanding the current pandemic response toolbox by the science of pharmacogenomics, and its applications in COVID-19 medicines and clinical trials.

PMID:36265833 | DOI:10.1016/j.pupt.2022.102172

Br J Clin Pharmacol. 2022 Oct 20. doi: 10.1111/bcp.15573. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Moore`s law predicts the doubling of complexity of integrated circuits every two years; Kryder's corollary assumes a doubling of data storage every thirteen months. With the increasing volume of legislation, pharmacovigilance systems today are inherently complex, and the emphasis has shifted from reactive (responding to emerging risks), to planned, active, risk-proportionate approaches operating throughout the lifecycle of medicines.

EXPERIMENTAL APPROACH: Exploration of the drivers for increasing complexity of pharmacovigilance systems, focusing on regulatory environment, data management, and evaluation.

KEY RESULTS: Evaluation of post-marketing data plays an increasingly important role in pharmacovigilance. There is great interest on the part of all stakeholders in optimizing the use of these data. Innovative approaches, including pharmacogenetics and passive measures (sensors), will lead to increased complexity and volumes of data, and inevitably to an increase in the volume of case reports. There is a multiplicity of regulations and guidelines on how to manage these data, with an inherent lack of harmonization.

CONCLUSION AND IMPLICATIONS: We summarize the current characterization of safety data types, sources, and the classification of these data. Using this benchmark, we discuss the future requirements of an effective pharmacovigilance ecosystem, keeping the principle of parsimony in mind. In this complex, continuously and rapidly changing environment, there is a need for a return to simplicity and pragmatism. The application of Ockam's razor could help to support the rapid provision of new, affordable medicines with a positive benefit to risk profile.

PMID:36264908 | DOI:10.1111/bcp.15573

Pharmacotherapy. 2022 Oct 20. doi: 10.1002/phar.2736. Online ahead of print.

ABSTRACT

AIMS: East Asians have a higher risk of bleeding than Europeans when treated with ticagrelor. This study aimed to explore genetic indicators related to the high bleeding propensity in East Asian patients with acute coronary syndrome (ACS) using ticagrelor.

METHODS: Between March 2018 and July 2021, 208 patients with ACS were administered ticagrelor and underwent genetic testing. These patients were enrolled and followed up for bleeding events for 12 months. Single nucleotide polymorphisms (SNPs) were detected using whole-exome sequencing. SNPs significantly associated with cumulative bleeding events within 1-, 6-, and 12-month follow-up were selected (p <0.01). Among these, SNPs showing a difference of ≥2 fold in their distribution frequency among East Asians and Europeans were selected.

RESULTS: Among all patients, 96.60% received ticagrelor plus aspirin or cilostazol, and 42.3% suffered from bleeding events during 12-month follow-up. Further, 22 SNPs of 15 genes were found to have a significant association with cumulative bleeding events within 1-, 6-, and 12-month follow-up. Among these SNPs, FIG4 rs2295837 (A>T) variant had the strongest association with bleeding events within 1 month (p = 1.28 × 10-4 ), with an increased risk of bleeding in T allele carriers (odds ratio [OR]: 3.07, 95% confidence interval [CI]: 1.68-5.63). PROK2 rs3796224 (C>T) variant was most strongly associated with cumulative bleeding events within 6 months (p = 4.57 × 10-4 ) with an increased risk of bleeding in T allele carriers (OR: 2.16, 95% CI: 1.20-3.89). Moreover, HRNR rs6662450 (C>T) variant showed the strongest relation with cumulative bleeding events within 12 months (p = 4.86 × 10-4 ) with a reduced risk of bleeding in T allele carriers (OR: 0.48, 95% CI: 0.24-0.95).

CONCLUSIONS: Fifteen genes, including PROK2, HRNR, and FIG4, were potential biomarkers of high bleeding propensity in East Asian patients with ACS using ticagrelor.

PMID:36263704 | DOI:10.1002/phar.2736

Clin Psychopharmacol Neurosci. 2022 Nov 30;20(4):762-767. doi: 10.9758/cpn.2022.20.4.762.

ABSTRACT

OBJECTIVE: Psychiatric symptoms and mental disorders are common after Coronavirus Disease-19 (COVID-19). Some drugs used to treat acute COVID-19 have psychiatric side effects. We assessed the psychiatric symptoms and mental disorders of patients treated for acute COVID-19 with hydroxychloroquine (HCQ), interleukin-6 receptor antagonists (anti-IL-6), and corticoids (CTC).

METHODS: We evaluated 177 patients in a day hospital 4 months after acute infection.

RESULTS: In a multivariate analysis, HCQ was associated with significant anxiety symptoms (odds ratio [OR] = 5.9, 95% confidence interval [95% CI] = 1.8-20.0, p = 0.003) and mental disorders (OR = 4.1, 95% CI = 1.2-13.9, p = 0.02). In a bivariate analysis with propensity matched cohorts, HCQ was associated with significant anxiety symptoms (9 patients [50.0%] with significant symptoms in the HCQ group versus 15 [20.1%] in the control group, OR = 3.8, 95% CI = 1.3-11.3, p = 0.01). Anti-IL-6 and CTC were not associated with significant psychiatric symptoms or mental disorders.

CONCLUSION: We recommend monitoring psychiatric symptoms, especially anxiety, in patients treated with HCQ during COVID-19 infection. Further studies with larger samples and prospective assessments are needed to confirm our results.

PMID:36263650 | DOI:10.9758/cpn.2022.20.4.762