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International Journal of Molecular... Mar 2023The term severe mental illness (SMI) encompasses those psychiatric disorders exerting the highest clinical burden and socio-economic impact on the affected individuals... (Review)
Review
The term severe mental illness (SMI) encompasses those psychiatric disorders exerting the highest clinical burden and socio-economic impact on the affected individuals and their communities. Pharmacogenomic (PGx) approaches hold great promise in personalizing treatment selection and clinical outcomes, possibly reducing the burden of SMI. Here, we sought to review the literature in the field, focusing on PGx testing and particularly on pharmacokinetic markers. We performed a systematic review on PUBMED/Medline, Web of Science, and Scopus. The last search was performed on the 17 September 2022, and further augmented with a comprehensive pearl-growing strategy. In total, 1979 records were screened, and after duplicate removal, 587 unique records were screened by at least 2 independent reviewers. Ultimately, forty-two articles were included in the qualitative analysis, eleven randomized controlled trials and thirty-one nonrandomized studies. The observed lack of standardization in PGx tests, population selection, and tested outcomes limit the overall interpretation of the available evidence. A growing body of evidence suggests that PGx testing might be cost-effective in specific settings and may modestly improve clinical outcomes. More efforts need to be directed toward improving PGx standardization, knowledge for all stakeholders, and clinical practice guidelines for screening recommendations.
Topics: Humans; Mental Disorders; Pharmacogenetics
PubMed: 36902205
DOI: 10.3390/ijms24054776 -
American Journal of Pharmaceutical... Mar 2024Poor knowledge and confidence in pharmacogenomics are key barriers to implementation. Education of future health care professionals is required to enhance appropriate... (Review)
Review
OBJECTIVES
Poor knowledge and confidence in pharmacogenomics are key barriers to implementation. Education of future health care professionals is required to enhance appropriate use of pharmacogenomics; however, the optimal education approach is unclear. This systematic scoping review evaluates pharmacogenomic educational interventions to improve knowledge and confidence.
FINDINGS
A total of 24 studies were included. Most (90%) studies delivered pharmacogenomic education to pharmacy students and consisted of didactic lectures and workshops with case studies. To supplement case studies, self or class aggregated (52%, 12 of 23), mock (43%, 10 of 23) or faculty member provided (4%, 1 of 23) pharmacogenomic data were used in the case scenarios. All studies used quantitative methods, including student assessments and scaled surveys to assess the impact of the educational intervention on knowledge and/or confidence in pharmacogenomics. On average, the educational interventions improved knowledge acquisition by 21%, confidence in pharmacogenomic data interpretation by 37%, confidence in communication of pharmacogenomic information to patients by 41% and to health care professionals by 44%. Improvement in communication with other health care professionals was greater in students involved in interprofessional learning compared to self-pharmacogenomic testing.
SUMMARY
The measures used to determine the effect of educational interventions on student knowledge and confidence varied. Innovative pedagogy, specifically interactive case-based learning and simulation such as interprofessional learning, enhances the knowledge and confidence of students in pharmacogenomics. Course-embedded self-pharmacogenomic testing may offer a supplementary, interactive component to case-based learning by using real-life reports as the foundation of knowledge and confidence acquisition.
Topics: Humans; Pharmacogenetics; Education, Pharmacy; Learning; Health Personnel; Students, Pharmacy
PubMed: 38331197
DOI: 10.1016/j.ajpe.2024.100668 -
Journal of Personalized Medicine Aug 2022Polygenic models have emerged as promising prediction tools for the prediction of complex traits. Currently, the majority of polygenic models are developed in the... (Review)
Review
Polygenic models have emerged as promising prediction tools for the prediction of complex traits. Currently, the majority of polygenic models are developed in the context of predicting disease risk, but polygenic models may also prove useful in predicting drug outcomes. This study sought to understand how polygenic models incorporating pharmacogenetic variants are being used in the prediction of drug outcomes. A systematic review was conducted with the aim of gaining insights into the methods used to construct polygenic models, as well as their performance in drug outcome prediction. The search uncovered 89 papers that incorporated pharmacogenetic variants in the development of polygenic models. It was found that the most common polygenic models were constructed for drug dosing predictions in anticoagulant therapies ( = 27). While nearly all studies found a significant association with their polygenic model and the investigated drug outcome (93.3%), less than half (47.2%) compared the performance of the polygenic model against clinical predictors, and even fewer (40.4%) sought to validate model predictions in an independent cohort. Additionally, the heterogeneity of reported performance measures makes the comparison of models across studies challenging. These findings highlight key considerations for future work in developing polygenic models in pharmacogenomic research.
PubMed: 36143179
DOI: 10.3390/jpm12091394 -
Pharmaceutics Mar 2022Acute myeloid leukemia (AML) is a heterogeneous disease characterized by remarkable toxicity and great variability in response to treatment. Plenteous pharmacogenetic... (Review)
Review
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by remarkable toxicity and great variability in response to treatment. Plenteous pharmacogenetic studies have already been published for classical therapies, such as cytarabine or anthracyclines, but such studies remain scarce for newer drugs. There is evidence of the relevance of polymorphisms in response to treatment, although most studies have limitations in terms of cohort size or standardization of results. The different responses associated with genetic variability include both increased drug efficacy and toxicity and decreased response or resistance to treatment. A broad pharmacogenetic understanding may be useful in the design of dosing strategies and treatment guidelines. The aim of this study is to perform a review of the available publications and evidence related to the pharmacogenetics of AML, compiling those studies that may be useful in optimizing drug administration.
PubMed: 35335935
DOI: 10.3390/pharmaceutics14030559 -
Epilepsy & Behavior : E&B May 2021Epilepsy is one of the most prevalent neurologic conditions, affecting almost 70 million people worldwide. In the United States, 1.3 million women with epilepsy (WWE)... (Review)
Review
Epilepsy is one of the most prevalent neurologic conditions, affecting almost 70 million people worldwide. In the United States, 1.3 million women with epilepsy (WWE) are in their active reproductive years. Women with epilepsy (WWE) face gender-specific challenges such as pregnancy, seizure exacerbation with hormonal pattern fluctuations, contraception, fertility, and menopause. Precision medicine, which applies state-of-the art molecular profiling to diagnostic, prognostic, and therapeutic problems, has the potential to advance the care of WWE by precisely tailoring individualized management to each patient's needs. For example, antiseizure medications (ASMs) are among the most common teratogens prescribed to women of childbearing potential. Teratogens act in a dose-dependent manner on a susceptible genotype. However, the genotypes at risk for ASM-induced teratogenic deficits are unknown. Here we summarize current challenging issues for WWE, review the state-of-art tools for clinical precision medicine approaches, perform a systematic review of pharmacogenomic approaches in management for WWE, and discuss potential future directions in this field. We envision a future in which precision medicine enables a new practice style that puts focus on early detection, prediction, and targeted therapies for WWE.
Topics: Anticonvulsants; Contraception; Epilepsy; Female; Humans; Precision Medicine; Pregnancy; Pregnancy Complications
PubMed: 33774354
DOI: 10.1016/j.yebeh.2021.107928 -
Addiction Science & Clinical Practice Nov 2021Patients with opioid use disorder (OUD) display an interindividual variability in their response to medications for opioid use disorder (MOUD). A genetic basis may... (Review)
Review
BACKGROUND
Patients with opioid use disorder (OUD) display an interindividual variability in their response to medications for opioid use disorder (MOUD). A genetic basis may explain the variability in this response. However, no consensus has been reached regarding which genetic variants significantly contribute to MOUD outcomes.
OBJECTIVES
This systematic review aims to summarize genome-wide significant findings on MOUD outcomes and critically appraise the quality of the studies involved.
METHODS
Databases searched from inception until August 21st, 2020 include: MEDLINE, Web of Science, EMBASE, CINAHL and Pre-CINAHL, GWAS Catalog and GWAS Central. The included studies had to be GWASs that assessed MOUD in an OUD population. All studies were screened in duplicate. The quality of the included studies was scored and assessed using the Q-Genie tool. Quantitative analysis, as planned in the protocol, was not feasible, so the studies were analyzed qualitatively.
RESULTS
Our search identified 7292 studies. Five studies meeting the eligibility criteria were included. However, only three studies reported results that met our significance threshold of p ≤ 1.0 × 10. In total, 43 genetic variants were identified. Variants corresponding to CNIH3 were reported to be associated with daily heroin injection in Europeans, OPRM1, TRIB2, and ZNF146 with methadone dose in African Americans, EYS with methadone dose in Europeans, and SPON1 and intergenic regions in chromosomes 9 and 3 with plasma concentrations of S-methadone, R-methadone, and R-EDDP, respectively, in Han Chinese.
LIMITATIONS
The limitations of this study include not being able to synthesize the data in a quantitative way and a conservative eligibility and data collection model.
CONCLUSION
The results from this systematic review will aid in highlighting significant genetic variants that can be replicated in future OUD pharmacogenetics research to ascertain their role in patient-specific MOUD outcomes. Systematic review registration number CRD42020169121.
Topics: Buprenorphine; Calcium-Calmodulin-Dependent Protein Kinases; Eye Proteins; Genome-Wide Association Study; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Polymorphism, Single Nucleotide
PubMed: 34838141
DOI: 10.1186/s13722-021-00278-y -
Reviews in Medical Virology Sep 2022The aim of this systematic review and network meta-analysis is to evaluate the comparative effectiveness of N95, surgical/medical and non-medical facemasks as personal... (Meta-Analysis)
Meta-Analysis Review
Comparative effectiveness of N95, surgical or medical, and non-medical facemasks in protection against respiratory virus infection: A systematic review and network meta-analysis.
The aim of this systematic review and network meta-analysis is to evaluate the comparative effectiveness of N95, surgical/medical and non-medical facemasks as personal protective equipment against respiratory virus infection. The study incorporated 35 published and unpublished randomized controlled trials and observational studies investigating specific mask effectiveness against influenza virus, SARS-CoV, MERS-CoV and SARS-CoV-2. We searched PubMed, Google Scholar and medRxiv databases for studies published up to 5 February 2021 (PROSPERO registration: CRD42020214729). The primary outcome of interest was the rate of respiratory viral infection. The quality of evidence was estimated using the GRADE approach. High compliance to mask-wearing conferred a significantly better protection (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.23-0.82) than low compliance. N95 or equivalent masks were the most effective in providing protection against coronavirus infections (OR, 0.30; CI, 0.20-0.44) consistently across subgroup analyses of causative viruses and clinical settings. Evidence supporting the use of medical or surgical masks against influenza or coronavirus infections (SARS, MERS and COVID-19) was weak. Our study confirmed that the use of facemasks provides protection against respiratory viral infections in general; however, the effectiveness may vary according to the type of facemask used. Our findings encourage the use of N95 respirators or their equivalents (e.g., P2) for best personal protection in healthcare settings until more evidence on surgical and medical masks is accrued. This study highlights a substantial lack of evidence on the comparative effectiveness of mask types in community settings.
Topics: COVID-19; Humans; Masks; Network Meta-Analysis; Respiratory Tract Infections; SARS-CoV-2
PubMed: 35218279
DOI: 10.1002/rmv.2336 -
BMC Medicine Oct 2020Novel biological and precision therapies and their associated predictive biomarker tests offer opportunities for increased tumor response, reduced adverse effects, and... (Meta-Analysis)
Meta-Analysis
Are there socio-economic inequalities in utilization of predictive biomarker tests and biological and precision therapies for cancer? A systematic review and meta-analysis.
BACKGROUND
Novel biological and precision therapies and their associated predictive biomarker tests offer opportunities for increased tumor response, reduced adverse effects, and improved survival. This systematic review determined if there are socio-economic inequalities in utilization of predictive biomarker tests and/or biological and precision cancer therapies.
METHODS
MEDLINE, Embase, Scopus, CINAHL, Web of Science, PubMed, and PsycINFO were searched for peer-reviewed studies, published in English between January 1998 and December 2019. Observational studies reporting utilization data for predictive biomarker tests and/or cancer biological and precision therapies by a measure of socio-economic status (SES) were eligible. Data was extracted from eligible studies. A modified ISPOR checklist for retrospective database studies was used to assess study quality. Meta-analyses were undertaken using a random-effects model, with sub-group analyses by cancer site and drug class. Unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed for each study. Pooled utilization ORs for low versus high socio-economic groups were calculated for test and therapy receipt.
RESULTS
Among 10,722 citations screened, 62 papers (58 studies; 8 test utilization studies, 37 therapy utilization studies, 3 studies on testing and therapy, 10 studies without denominator populations or which only reported mean socio-economic status) met the inclusion criteria. Studies reported on 7 cancers, 5 predictive biomarkers tests, and 11 biological and precision therapies. Thirty-eight studies (including 1,036,125 patients) were eligible for inclusion in meta-analyses. Low socio-economic status was associated with modestly lower predictive biomarker test utilization (OR 0.86, 95% CI 0.71-1.05; 10 studies) and significantly lower biological and precision therapy utilization (OR 0.83, 95% CI 0.75-0.91; 30 studies). Associations with therapy utilization were stronger in lung cancer (OR 0.71, 95% CI 0.51-1.00; 6 studies), than breast cancer (OR 0.93, 95% CI 0.78-1.10; 8 studies). The mean study quality score was 6.9/10.
CONCLUSIONS
These novel results indicate that there are socio-economic inequalities in predictive biomarker tests and biological and precision therapy utilization. This requires further investigation to prevent differences in outcomes due to inequalities in treatment with biological and precision therapies.
Topics: Biomarkers, Tumor; Female; Humans; Immunotherapy; Male; Neoplasms; Precision Medicine; Retrospective Studies; Socioeconomic Factors
PubMed: 33092592
DOI: 10.1186/s12916-020-01753-0 -
Psychiatry Research Mar 2023Pharmacogenomic (PGx) testing may increase the probability of remission and response in patients with major depressive disorder (MDD) undergoing pharmacotherapy. Given... (Meta-Analysis)
Meta-Analysis
Pharmacogenomic (PGx) testing may increase the probability of remission and response in patients with major depressive disorder (MDD) undergoing pharmacotherapy. Given the potential implications of these outcomes and recent proliferation of PGx studies, we conducted a systematic review to evaluate the effectiveness of PGx testing on clinical outcomes in patients with MDD as compared to treatment as usual (TAU). MEDLINE, Embase, PsycInfo, and CENTRAL were searched for English-language articles from 2000 to 2021 for randomized controlled trials (RCTs) comparing PGx-guided treatment vs. TAU in patients with MDD. Meta-analyses were conducted in R. Ten RCTs were included: eight reported remission and seven reported response. The best available evidence suggests that PGx-guided care for moderate-to-severe adult depression is more likely to result in remission and response than TAU (both risk ratios significant). However, there are limitations in the evidence base, including high risk of bias and inconsistency between trials. Despite the consequent very low certainty in the magnitude of effect, there is confidence in the direction. Though modest, the beneficial effects of PGx for adults with moderate-severe MDD could - as a result of the scope and scale of the condition and its impacts - have important ramifications for patients and the health system.
Topics: Adult; Humans; Antidepressive Agents; Depression; Depressive Disorder, Major; Pharmacogenetics; Treatment Outcome
PubMed: 36780865
DOI: 10.1016/j.psychres.2023.115102 -
British Journal of Clinical Pharmacology Sep 2019Antithyroid drug (ATD)-induced agranulocytosis is a life-threatening adverse drug reaction. Previous studies suggested that HLA genotypes may play an important role in... (Meta-Analysis)
Meta-Analysis
AIMS
Antithyroid drug (ATD)-induced agranulocytosis is a life-threatening adverse drug reaction. Previous studies suggested that HLA genotypes may play an important role in ATD-induced agranulocytosis. To examine the associations between HLA genotypes and ATD-induced agranulocytosis, we conducted a systematic review and meta-analysis of pharmacogenomics studies.
METHODS
We searched the MEDLINE, Embase and CENTRAL databases on 16 June 2018 for case-control studies on the associations between HLA genotypes with ATD-induced agranulocytosis. The Newcastle-Ottawa scale was used to evaluate the risk of bias of included studies. We conducted random-effects model meta-analysis to obtain pooled odds ratios (ORs) with 95% confidence intervals (CIs) to determine the associations between HLA genotypes and ATD-induced agranulocytosis.
RESULTS
We included 5 studies with 142 ATD-induced agranulocytosis cases, 1529 matched ATD-tolerant controls and 5945 healthy controls. The risk of bias of included studies was generally low. ATD-induced agranulocytosis was associated with HLA-B*27:05 (OR 10.97; 95% CI 0.75-159.99), HLA-B*38:02 (OR 19.85; 95% CI 7.94-49.57) and HLA-DRB1*08:03 (OR 5.29; 95% CI 3.44-8.14). After excluding propylthiouracil, the associations of ATD-induced agranulocytosis with HLA-B*27:05 and HLA-B*38:02 were strengthened (OR being 20.61 (95% CI 5.21-81.58) and 40.59 (95% CI 13.24-124.47), respectively). The associations of ATD-induced agranulocytosis with HLA-B*27:05, HLA-B*38:02 and HLA-DRB1*08:03 remained significant when compared to population controls (OR being 7.37 (95% CI 3.86-14.07), 36.43 (95% CI 12.80-103.70) and 5.42 (95% CI 2.36-12.47), respectively). HLA-B*27:05, HLA-B*38:02, and HLA-DRB1*08:03 alleles were associated with ATD-induced agranulocytosis, especially in carbimazole/methimazole-induced agranulocytosis.
CONCLUSIONS
HLA-B*27:05, HLA-B*38:02 and HLA-DRB1*08:03 alleles were associated with ATD-induced agranulocytosis, especially in carbimazole/methimazole-induced agranulocytosis.
Topics: Agranulocytosis; Alleles; Antithyroid Agents; Graves Disease; HLA Antigens; Humans
PubMed: 31108563
DOI: 10.1111/bcp.13989