Rheum Dis Clin North Am. 2022 Feb;48(1):305-330. doi: 10.1016/j.rdc.2021.09.010.

ABSTRACT

Despite an increase in the number of available therapeutics, many children with rheumatic disease continue to experience active inflammatory disease and treatment failure. One reason for treatment failure is the lack of dosing paradigms to account for the wide between-patient variability in drug pharmacokinetics because of developmental changes or genetic polymorphisms that effect drug absorption, distribution, metabolism, and elimination. This review highlights several strategies to optimize dosing for biologic and nonbiologic disease-modifying antirheumatic drugs, including therapeutic drug monitoring, pharmacogenomics, and the use of pharmacokinetic/pharmacodynamic modeling.

PMID:34798954 | DOI:10.1016/j.rdc.2021.09.010

BMC Genom Data. 2021 Nov 19;22(1):51. doi: 10.1186/s12863-021-00999-8.

ABSTRACT

BACKGROUND: The variation of drug responses and target does among individuals is mostly determined by genes. With the development of pharmacogenetics and pharmacogenomics, the differences in drug response between different races seem to be mainly caused by the genetic diversity of pharmacodynamics and pharmacokinetics genes. Very important pharmacogenetic (VIP) variants mean that genes or variants play important and vital roles in drug response, which have been listed in pharmacogenomics databases, such as Pharmacogenomics Knowledge Base (PharmGKB). The information of Chinese ethnic minorities such as the Wa ethnic group is scarce. This study aimed to uncover the significantly different loci in the Wa population in Yunnan Province of China from the perspective of pharmacogenomics, to provide a theoretical basis for the future medication guidance, and to ultimately achieve the best treatment in the future.

RESULTS: In this study, we recruited 200 unrelated healthy Wa adults from the Yunnan province of China, selected 52 VIP variants from the PharmGKB for genotyping. We also compared the genotype frequency and allele distribution of VIP variants between Wa population and the other 26 populations from the 1000 Genomes Project ( http://www.1000Genomes.org/ ). Next, χ2 test was used to determine the significant points between these populations. The study results showed that compared with the other 26 population groups, five variants rs776746 (CYP3A5), rs4291 (ACE), rs3093105 (CYP4F2), rs1051298 (SLC19A1), and rs1065852 (CYP2D6) had higher frequencies in the Wa population. The genotype frequencies rs4291-TA, rs3093105-CA, rs1051298-AG and rs1065852-GA were higher than those of the other populations, and the allele distributions of rs4291-T and rs3093105-C were significantly different. Additionally, the difference between the Wa ethnic group and East Asian populations, such as CDX, CHB, and CHS, was the smallest.

CONCLUSIONS: Our research results show that there is a significant difference in the distribution of VIP variants between the Wa ethnic group and the other 26 populations. The study results will have an effect on supplementing the pharmacogenomics information for the Wa population and providing a theoretical basis for individualised medication for the Wa population.

PMID:34798807 | DOI:10.1186/s12863-021-00999-8

PLoS One. 2021 Nov 19;16(11):e0260431. doi: 10.1371/journal.pone.0260431. eCollection 2021.

ABSTRACT

BACKGROUND: Regular visit to psychiatric clinic is essential for successful treatment of any psychiatric condition including attention-deficit/hyperactivity disorder (AD/HD). However, cancellation of outpatient appointments in patients with AD/HD, which represents a significant medical loss, has not been systematically investigated to our knowledge.

METHODS: A systematic chart review was conducted for patients visiting the Shimada Ryoiku medical Center for Challenged Children in Japan at the age of ≤15 years from January to December 2013. The primary outcome measure was the cancellation rate, defined as the number of missed visits divided by the number of scheduled visits. The cancellation rates during 24 months after the first visit were compared between outpatients with AD/HD and other psychiatric disorders, including pervasive developmental disorders (PDD), and developmental coordination disorders and/or communication disorders (DCD-CD). A generalized linear model with binomial distribution was used to examine factors associated with cancellation rates exclusively in the AD/HD group.

RESULTS: We included 589 patients (mean ± SD age, 5.6 ± 3.4 years; 432 males) in the analysis. The cancellation rate in patients with AD/HD was 12.3% (95% confidence interval [CI]: 10.0-15.1), which was significantly higher than in those with PDD (5.6%, 95% CI: 3.8-8.3) and DCD-CD (5.3%, 95% CI: 3.6-7.8). Prescriptions of osmotic-release oral system-methylphenidate (OROS-MPH) and antipsychotics were associated with fewer cancellations in AD/HD patients (odds ratios: 0.61, 95% CI: 0.39-0.95 and 0.49, 95% CI: 0.25-0.95, respectively), although these significances did not find in the subgroup analysis including only patients with ≥ 6 years old.

CONCLUSIONS: Patients with AD/HD were more likely to miss appointments compared to those with other psychiatric disorders. The impact of AD/HD medications as well as potential psychiatric symptoms of their parents or caregivers on appointment cancellations needs to be evaluated in more detail in future investigations.

PMID:34797891 | DOI:10.1371/journal.pone.0260431

Medicine (Baltimore). 2021 Nov 19;100(46):e27858. doi: 10.1097/MD.0000000000027858.

ABSTRACT

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder, and methylphenidate (MPH) is considered one of the first-line medicine for ADHD. Unfortunately, this medication is only effective for some children with ADHD. This meta-analysis was conducted to evaluate whether noradrenergic gene polymorphisms impact the efficacy of MPH in children with ADHD.

METHODS: Candidate gene studies published in English until March 1, 2020, were identified through literature searches on PubMed, Web of Science, and Embase. Data were pooled from individual clinical trials considering MPH pharmacogenomics. According to the heterogeneity, the odds ratio and mean differences were calculated by applying fixed-effects or random-effects models.

RESULTS: This meta-analysis includes 15 studies and 1382 patients. Four polymorphisms of the NET gene (rs5569, rs28386840, rs2242446, rs3785143) and 2 polymorphisms of the α2A-adrenergic receptor gene (ADRA2A) gene (MspI and DraI) were selected for the analysis. In the pooled data from all studies, T allele carriers of the rs28386840 polymorphism were significantly more likely to respond to MPH (P < .001, ORTcarriers = 2.051, 95% confidence interval [CI]:1.316, 3.197) and showed a relationship with significantly greater hyperactive-impulsive symptoms improvement (P < .001, mean difference:1.70, 95% CI:0.24, 3.16). None of the ADRA2A polymorphisms correlated significantly with MPH response as a whole. However, G allele carriers of the MspI polymorphism showed a relationship with significantly inattention symptoms improvement (P < .001, mean difference:0.31, 95% CI: 0.15, 0.47).

CONCLUSION: Our meta-analysis results indicate that the noradrenergic gene polymorphisms may impact MPH response. The NET rs28386840 is linked to improved MPH response in ADHD children. And the ADRA2A MspI is associated with inattention symptom improvements. Further investigations with larger samples will be needed to confirm these results.Registration: PROSPERO (no. CRD42021265830).

PMID:34797323 | DOI:10.1097/MD.0000000000027858

J Oncol Pharm Pract. 2021 Nov 19:10781552211049144. doi: 10.1177/10781552211049144. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate if dihydropyrimidine dehydrogenase phenotyping has added value when combined with DPYD genotyping in predicting fluoropyrimidine-related toxicity.

METHODS: Retrospective cohort study in which treatment and toxicity data were collected of 228 patients genotyped for four DPYD variants and phenotyped using an ex vivo peripheral blood mononuclear cell assay.

RESULTS: Severe toxicity occurred in 25% of patients with a variant and normal dihydropyrimidine dehydrogenase activity, in 21% of patients without a variant and with decreased dihydropyrimidine dehydrogenase activity, and in 29% of patients without a variant and with normal dihydropyrimidine dehydrogenase activity (controls). The majority of patients with a variant or a decreased dihydropyrimidine dehydrogenase activity received an initial dose reduction (68% and 53% vs 19% in controls) and had a lower mean dose intensity (75% and 81% vs 91% in controls). Fifty percent of patients with a variant and decreased enzyme activity experienced severe toxicity, despite the lowest initial dose and whole treatment dose intensity. They also experienced more grade 4/5 toxicities.

CONCLUSIONS: Our results indicate that a combined genotype-phenotype approach could be useful to identify patients at increased risk for fluoropyrimidine-associated toxicity (e.g. patients with a variant and decreased dihydropyrimidine dehydrogenase activity). Because the group sizes are too small to demonstrate statistically significant differences, this warrants further research in a prospective study in a larger cohort.

PMID:34797200 | DOI:10.1177/10781552211049144

Probl Sotsialnoi Gig Zdravookhranenniiai Istor Med. 2021 Aug;29(Special Issue):1258-1263. doi: 10.32687/0869-866X-2021-29-s2-1258-1263.

ABSTRACT

PURPOSE: To investigate the possibilities of pharmacoeconomic and pharmacogenetic factors monitoring to assess the effectiveness of treatment of a cardiological profile patients as a part of the implementation of a personalized approach.

MATERIAL AND METHODS: 200 patients with arterial hypertension and CHD were examined. Pharmacotherapy was analyzed. ABC/VEN and DDD analysis, pharmacoeconomic analysis were applied. Genetic analysis of the polymorphism of the genes CYP2D6*4 and CYP2D6*10 encoding the subfamily of the cytochrome isoenzyme Р-450 was carried out. An original monitoring method was used to assess the effect of pharmacoeconomic and pharmacogenetic factors on the performance of cardiac care.

RESULTS: When conducting a pharmacoeconomic analysis of cases of cardiac care, it was found that the costs of drug therapy are significant and take over 10% of the total costs. However, its effectiveness is insufficient in 58% of cases in inpatient and 37% in outpatient care. The analysis showed that there is an inverse mean correlation between gene polymorphism and clinical performance of cardiac care (r = -0.62) and a direct strong correlation between polypharmacy in pharmacotherapy, not accounting for interdrug interaction and clinical performance (r = 0.89).

PMID:34792874 | DOI:10.32687/0869-866X-2021-29-s2-1258-1263

Pharmacopsychiatry. 2021 Nov 18. doi: 10.1055/a-1681-2047. Online ahead of print.

ABSTRACT

OBJECTIVES: Partial response to pharmacotherapy is common in major depressive disorder (MDD) and many patients require alternative pharmacotherapy or augmentation, including adjunctive L-methylfolate. Given that L-methylfolate augmentation is rarely included in major clinical practice guidelines, we sought to systematically review evidence for L-methylfolate augmentation in adults with MDD and to examine its efficacy meta-analytically.

METHODS: We systematically searched PubMed for articles up to December 31, 2020, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Included studies were published in peer-reviewed, English-language journals and examined L-methylfolate adjunctive therapy in depressive disorders or its effect on antidepressant response. A fixed- and random-effects meta-analysis and risk of bias assessment using the Cochrane Risk of Bias Tool were conducted.

RESULTS: Qualitative assessment of nine articles (N=6,707 patients) suggests that adjunctive L-methylfolate improved antidepressant response. In the meta-analysis of categorical Hamilton Rating Scale for Depression-17 response, (three studies, N=483) adjunctive L-methylfolate was associated with a small effect versus antidepressant monotherapy (relative risk: 1.25, 95% confidence interval [CI]=1.08 to 1.46, p=0.004). A meta-analysis of four studies (N=507) using a continuous measure of depressive symptoms showed a similar effect of adjunctive L-methylfolate (standardized mean difference=- 0.38, 95% CI=- 0.59 to-0.17, p=0.0003).

CONCLUSION: Adjunctive L-methylfolate may have modest efficacy in antidepressant-treated adults with MDD.

PMID:34794190 | DOI:10.1055/a-1681-2047

Bioinformatics. 2021 Nov 18:btab783. doi: 10.1093/bioinformatics/btab783. Online ahead of print.

ABSTRACT

MOTIVATION: Identifying sample mix-ups in biobanks is essential to allow the repurposing of genetic data for clinical pharmacogenetics. Pharmacogenetic advice based on the genetic information of another individual is potentially harmful. Existing methods for identifying mix-ups are limited to datasets in which additional omics data (e.g., gene expression) is available. Cohorts lacking such data can only use sex, which can reveal only half of the mix-ups. Here, we describe Idéfix, a method for the identification of accidental sample mix-ups in biobanks using polygenic scores.

RESULTS: In the Lifelines population-based biobank we calculated polygenic scores (PGSs) for 25 traits for 32,786 participants. Idéfix then compares the actual phenotypes to PGSs and uses the relative discordance that is expected for mix-ups, compared to correct samples. In a simulation, using induced mix-ups, Idéfix reaches an AUC of 0.90 using 25 polygenic scores and sex. This is a substantial improvement over using only sex, which has an AUC of 0.75. Subsequent simulations present Idéfix's potential in varying datasets with more powerful PGSs. This suggests its performance will likely improve, when more highly powered GWASs for commonly measured traits will become available. Idéfix can be used to identify a set of high-quality participants for whom it is very unlikely that they reflect sample mix-ups, and for these participants we can use genetic data for clinical purposes, such as pharmacogenetic profiles. For instance, in Lifelines we can select 34.4% of participants, reducing the sample mix-up rate from 0.15% to 0.01%.

AVAILABILITY: Idéfix is freely available at https://github.com/molgenis/systemsgenetics/wiki/Idefix.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:34792549 | DOI:10.1093/bioinformatics/btab783

Pharmacogenomics. 2021 Nov 18. doi: 10.2217/pgs.10.77e1. Online ahead of print.

NO ABSTRACT

PMID:34792412 | DOI:10.2217/pgs.10.77e1

Curr Drug Saf. 2021 Nov 18. doi: 10.2174/157488631602211118122907. Online ahead of print.

ABSTRACT

BACKGROUND: Phenytoin is the most commonly reported aromatic Anti-Epileptic Drug (AED) to cause Cutaneous Adverse Drug Reactions (CADRs). Cutaneous adverse drug reactions may be immune or non-immune mediated. It has been observed that predisposition is multifactorial and that gene mutations alone cannot be the cause.

OBJECTIVES: In this study, we investigated the patient, disease, and drug-related risk factors associated with phenytoin-induced cutaneous adverse drug reactions in South Indian epileptic patients.

METHODOLOGY: This study was conducted as a single-center prospective case-control study over a period of 13 months. The Fisher's exact test and multivariate binary logistic regression analysis were used to test the association of single and multiple variables, respectively.

RESULTS: This study comprised 26 patients with phenytoin-induced cutaneous adverse drug reactions (PHT-CARDs) and 32 phenytoin-tolerant controls with a mean age of 40.60±18.15 and 36.21±14.71 years, respectively. Among 26 phenytoin-induced cutaneous adverse drug reactions, 76.92% cases were mild-moderate reactions and 23.07% were severe. The onset latency period of these reactions ranged from 7-42 days. The multivariate analysis showed that multiple AEDs (OR =18.62, 95% CI 4.28-80.87, p=<.001) and comorbidities (OR= 5.98, 95% CI 1.33-26.78, p=.01) are risk factors for PHT-CADRs. PHT-SCARs were shown to be associated with previous allergy history (OR= 31, % CI 2.40-398.8, p=.008).

CONCLUSION: The risk factors found to be associated with CARDs in South Indian Epileptic patients are multiple AEDs, comorbidities, and past allergic history. Therefore, physicians and other associated health care professionals should closely monitor the patients when phenytoin is employed.

PMID:34792004 | DOI:10.2174/157488631602211118122907

Addiction. 2021 Nov 17. doi: 10.1111/add.15742. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: CYP2B6, a genetically variable enzyme, converts bupropion to its active metabolite hydroxybupropion. CYP2B6 activity and bupropion-aided cessation differ between women and men. The aim of this study was to determine whether genetically normal (vs. reduced) CYP2B6 activity increases bupropion-aided cessation in African American smokers via higher hydroxybupropion concentration, and whether this differs by sex.

DESIGN AND SETTING: Secondary analysis of a smoking cessation clinical trial (NCT00666978).

PARTICIPANTS/CASES: African American light-smokers (≤10 cigarettes/day).

INTERVENTIONS: Participants were treated with bupropion for 7 weeks.

MEASUREMENTS: Participants with detectable bupropion and/or hydroxybupropion concentrations were divided into normal (n=64) and reduced (n=109) CYP2B6 activity groups based on the presence of reduced-function CYP2B6*6 and CYP2B6*18 alleles. Biochemically-verified smoking cessation was assessed at week 3, end-of-treatment (7 weeks), and follow-up (26 weeks).

FINDINGS: Normal (vs. reduced) CYP2B6 activity was associated with increased cessation at week 7, which was mediated by higher hydroxybupropion concentration (odds ratio (OR)=1.25, 95% confidence interval (CI)=1.03, 1.78); this mediation effect persisted at week 26 (OR=1.23, 95% CI=1.02, 1.70). The mediation effect was similar in women (n=116; OR=1.33, 95% CI=1.01, 2.30) and men (n=57; OR=1.33, 95% CI=0.92, 3.87). Moreover, sex did not appear to moderate the mediation effect, although this should be tested in a larger sample.

CONCLUSIONS: In African American light-smokers with verified early bupropion use, genetically normal CYP2B6 activity appears to be indirectly associated with greater smoking cessation success in a relationship mediated by higher hydroxybupropion concentration. The mediating effect of higher hydroxybupropion concentration on smoking cessation persists beyond the active treatment phase and does not appear to differ by sex.

PMID:34791718 | DOI:10.1111/add.15742

Int J Mol Med. 2022 Jan;49(1):9. doi: 10.3892/ijmm.2021.5064. Epub 2021 Nov 18.

ABSTRACT

RNA modifications have recently become the focus of attention due to their extensive regulatory effects in a vast array of cellular networks and signaling pathways. Just as epigenetics is responsible for the imprinting of environmental conditions on a genetic level, epitranscriptomics follows the same principle at the RNA level, but in a more dynamic and sensitive manner. Nevertheless, its impact in the field of cardiovascular disease (CVD) remains largely unexplored. CVD and its associated pathologies remain the leading cause of death in Western populations due to the limited regenerative capacity of the heart. As such, maintenance of cardiac homeostasis is paramount for its physiological function and its capacity to respond to environmental stimuli. In this context, epitranscriptomic modifications offer a novel and promising therapeutic avenue, based on the fine‑tuning of regulatory cascades, necessary for cardiac function. This review aimed to provide an overview of the most recent findings of key epitranscriptomic modifications in both coding and non‑coding RNAs. Additionally, the methods used for their detection and important associations with genetic variations in the context of CVD were summarized. Current knowledge on cardiac epitranscriptomics, albeit limited still, indicates that the impact of epitranscriptomic editing in the heart, in both physiological and pathological conditions, holds untapped potential for the development of novel targeted therapeutic approaches in a dynamic manner.

PMID:34791505 | DOI:10.3892/ijmm.2021.5064

Front Pharmacol. 2021 Nov 1;12:753845. doi: 10.3389/fphar.2021.753845. eCollection 2021.

ABSTRACT

Background: Understanding the prescription pattern of medications in a population can help reveal the potential usage scenarios, including off-label prescriptions, and the need for precision medicine implementation. Therefore, the aim of this study was to assess the prescription pattern and off-label use of antipsychotics in the Qatari population. Methods: We performed a cross-sectional study of Qatari patients who received antipsychotic prescriptions from the major healthcare providers in the country during the 2-year period between June 2018 and May 2020. The number of patients, prescriptions dispensed, and clinical indications were collected and statistical analysis using chi-square test was conducted. Results: Among the 9,349 Qatari patients prescribed with antipsychotics during the study period, the majority were female (57%; p < 0.001) and were in the age categories 20-39 and 30-39 years (both 22%; p < 0.001). Among the 35,938 antipsychotic prescriptions dispensed, second-generation antipsychotics were the most highly prescribed (59%), specifically, quetiapine (16%) and olanzapine (12%), but the first-generation antipsychotic prochlorperazine (13%) was also highly prescribed. Most of the indications of antipsychotics (69%) were for off-label use such as for controlling chronic diseases, sleeping disorders, benign paroxysmal positional vertigo and irritable bowel syndrome. Conclusion: Non-mental health and off-label prescriptions of several antipsychotics were observed. Integration of this data with pharmacogenomic and clinical outcome data will help in determining the course of action for implementing personalized and precision medicine in the country and beyond.

PMID:34790126 | PMC:PMC8591163 | DOI:10.3389/fphar.2021.753845

Ann Rheum Dis. 2021 Nov 17:annrheumdis-2021-220578. doi: 10.1136/annrheumdis-2021-220578. Online ahead of print.

ABSTRACT

OBJECTIVES: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, delayed hypersensitivity reaction (DHR). We observed DRESS to inhibitors of interleukin 1 (IL-1) or IL-6 in a small group of patients with Still's disease with atypical lung disease. We sought to characterise features of patients with Still's disease with DRESS compared with drug-tolerant Still's controls. We analysed human leucocyte antigen (HLA) alleles for association to inhibitor-related DHR, including in a small Kawasaki disease (KD) cohort.

METHODS: In a case/control study, we collected a multicentre series of patients with Still's disease with features of inhibitor-related DRESS (n=66) and drug-tolerant Still's controls (n=65). We retrospectively analysed clinical data from all Still's subjects and typed 94/131 for HLA. European Still's-DRESS cases were ancestry matched to International Childhood Arthritis Genetics Consortium paediatric Still's cases (n=550) and compared for HLA allele frequencies. HLA association also was analysed using Still's-DRESS cases (n=64) compared with drug-tolerant Still's controls (n=30). KD subjects (n=19) were similarly studied.

RESULTS: Still's-DRESS features included eosinophilia (89%), AST-ALT elevation (75%) and non-evanescent rash (95%; 88% involving face). Macrophage activation syndrome during treatment was frequent in Still's-DRESS (64%) versus drug-tolerant Still's (3%; p=1.2×10-14). We found striking enrichment for HLA-DRB1*15 haplotypes in Still's-DRESS cases versus INCHARGE Still's controls (p=7.5×10-13) and versus self-identified, ancestry-matched Still's controls (p=6.3×10-10). In the KD cohort, DRB1*15:01 was present only in those with suspected anakinra reactions.

CONCLUSIONS: DRESS-type reactions occur among patients treated with IL-1/IL-6 inhibitors and strongly associate with common HLA-DRB1*15 haplotypes. Consideration of preprescription HLA typing and vigilance for serious reactions to these drugs are warranted.

PMID:34789453 | DOI:10.1136/annrheumdis-2021-220578

Chem Res Toxicol. 2021 Nov 17. doi: 10.1021/acs.chemrestox.1c00300. Online ahead of print.

ABSTRACT

Methimazole (MMI) is a widely used antithyroid drug, but it can cause hepatotoxicity by unknown mechanisms. Previous studies showed that the hepatic metabolism of MMI produces N-methylthiourea, leading to liver damage. However, the specific enzyme responsible for the production of the toxic metabolite N-methylthiourea is still unclear. In this study, we screened cytochromes P450 (CYPs) in N-methylthiourea production from MMI. CYP2A6 was identified as the key enzyme in catalyzing MMI metabolism to produce N-methylthiourea. When mice were pretreated with a CYP2A6 inhibitor, formation of N-methylthiourea from MMI was remarkably reduced. Consistently, the CYP2A6 inhibitor prevented MMI-induced hepatotoxicity. These results demonstrated that CYP2A6 is essential in MMI bioactivation and hepatotoxicity.

PMID:34788025 | DOI:10.1021/acs.chemrestox.1c00300

West J Emerg Med. 2021 Sep 23;22(6):1347-1354. doi: 10.5811/westjem.2021.5.51248.

ABSTRACT

INTRODUCTION: Emergency departments (ED) use many medications with a range of therapeutic efficacy and potential significant side effects, and many medications have dosage adjustment recommendations based on the patient's specific genotype. How frequently medications with such pharmaco-genetic recommendations are used in United States (US) EDs has not been studied.

METHODS: We conducted a cross-sectional analysis of the 2010-2015 National Hospital Ambulatory Medical Care Survey (NHAMCS). We reported the proportion of ED visits in which at least one medication with Clinical Pharmacogenetics Implementation Consortium (CPIC) recommendation of Level A or B evidence was ordered. Secondary comparisons included distributions and 95% confidence intervals of age, gender, race/ethnicity, ED disposition, geographical region, immediacy, and insurance status between all ED visits and those involving a CPIC medication.

RESULTS: From 165,155 entries representing 805,726,000 US ED visits in the 2010-2015 NHAMCS, 148,243,000 ED visits (18.4%) led to orders of CPIC medications. The most common CPIC medication was tramadol (6.3%). Visits involving CPIC medications had higher proportions of patients who were female, had private insurance and self-pay, and were discharged from the ED. They also involved lower proportions of patients with Medicare and Medicaid.

CONCLUSION: Almost one fifth of US ED visits involve a medication with a pharmacogenetic recommendation that may impact the efficacy and toxicity for individual patients. While direct application of genotyping is still in development, it is important for emergency care providers to understand and support this technology given its potential to improve individualized, patient-centered care.

PMID:34787561 | DOI:10.5811/westjem.2021.5.51248

Pharmacogenomics. 2021 Nov 17. doi: 10.2217/pgs-2021-0110. Online ahead of print.

ABSTRACT

Pharmacogenomics clinical decision support (PGx-CDS) is an important tool to incorporate PGx information into existing clinical workflows and facilitate PGx clinical translation. However, due to the lack of a computable formalization to represent the primary PGx knowledge, the complexity of genomics information and the lag of current commercial electronic health record (EHR) system for precision medicine, it is difficult to develop computerized PGx-CDS. Therefore, we explored a novel approach to build an information system, named the Pharmacogenomics Clinical Translation Platform (PCTP), for PGx clinical implementation. The PCTP can represent, store, and manage the primary PGx knowledge in a structured and computable format. Moreover, it has the potential to provide various PGx-CDS services and simplify the integration of PGx-CDS into EHRs.

PMID:34787504 | DOI:10.2217/pgs-2021-0110

Pharmacogenomics. 2021 Nov 17. doi: 10.2217/pgs-2021-0113. Online ahead of print.

ABSTRACT

Aim: To explore possible differences in genome-wide methylation between schizophrenia patients who consume various antipsychotics. Methods: We compared DNA methylation in leukocytes between the following cohorts: clozapine (n = 19) versus risperidone (n = 19), clozapine (n = 12) versus olanzapine (n = 12), clozapine (n = 9) versus quetiapine (n = 9) and clozapine (n = 33) versus healthy controls (n = 33). Subjects were matched for age, sex, ethnicity, smoking status and leukocyte proportions. Results: No single CpG site reached genome-wide significance for clozapine versus risperidone/olanzapine/quetiapine. For clozapine versus quetiapine, one significantly differentially methylated region was found - ch5: 176797920-176798049 (fwer = 0.075). Clozapine versus healthy controls yielded thousands of significantly differentially methylated CpG sites. Conclusions: Establishing antipsychotic induced genome-wide methylation patterns will further elucidate the biological and clinical effects of antipsychotic administration.

PMID:34787483 | DOI:10.2217/pgs-2021-0113

Eur J Trauma Emerg Surg. 2021 Nov 16. doi: 10.1007/s00068-021-01817-7. Online ahead of print.

ABSTRACT

PURPOSE: Trauma is the leading cause of death before the age of 45 in the United States. Precision medicine (PM) is the most advanced scientific form of medical practice and seeks to gather data from the genome, environmental interactions, and lifestyles. Relating to trauma, PM promises to significantly advance our understanding of the factors that contribute to the physiologic response to injury.

METHODS: We review the status of PM-driven trauma care. Semantic-based methods were used to gather data on genetic/epigenetic variability previously linked to the principal causes of trauma-related outcomes. Data were curated to include human investigations involving genomics/epigenomics with clinical relevance identifiable early after injury.

RESULTS: Most studies relevant to genomic/epigenomic differences in trauma are specific to traumatic brain injury and injury-related sepsis. Genomic/epigenomic differences rarely encompass other relevant factors, such as coagulability and pharmacogenomics. Few studies describe clinical use of genomics/epigenomics for therapeutic intervention in trauma care, and even fewer attempt to incorporate real-time genomic/epigenomic information to precisely guide clinical decision-making.

CONCLUSION: Considering that genomics/epigenomics, environmental exposures, and lifestyles are most likely to be of significant medical relevance in advancing the field of trauma, the lack of application of concepts and methodologies from PM to trauma education, research, practice, and community wellness is underwhelming. We suggest that significant effort be given to incorporate the tools of what is becoming the "new medicine".

PMID:34786598 | DOI:10.1007/s00068-021-01817-7

Biomark Med. 2021 Nov 17. doi: 10.2217/bmm-2021-0348. Online ahead of print.

ABSTRACT

Aim: miRNAs are potential biomarkers of several diseases. This review aimed to identify the miRNAs that could serve as biomarkers of COVID-19. Materials & methods: A literature search of nine databases was carried out for studies published before 13 June 2021 that described dysregulated miRNAs in cells or animals infected by SARS-CoV-2 or in patients with COVID-19. Two independent reviewers selected the studies and extracted data; disagreements were resolved by a third reviewer. Results: Twenty studies were included in this scoping review; results suggested that miR-21-5p, miR-146a, miR-126-3p, miR-144 and miR-155 are the most important dysregulated miRNAs that could serve as biomarkers for diagnosing and indicating the severity of COVID-19. miRNAs appear to play key roles in viral replication, proliferation of infected cells, immune response, inflammation and cardiovascular dysfunction. Conclusion: This review provides insights into the role of miRNAs as biomarkers in COVID-19 and the current status and future directions for research in this field.

PMID:34784802 | DOI:10.2217/bmm-2021-0348