Individualized psychiatric care: integration of therapeutic drug monitoring, pharmacogenomics, and biomarkers.

Personalized treatment optimization considers individual clinical, genetic, and environmental factors influencing drug efficacy and tolerability. As evidence accumulates, these approaches may become increasingly integrated into standard psychiatric care, potentially transforming the treatment landscape for mental health disorders. While personalized treatment optimization shows promise in enhancing therapeutic outcomes and minimizing adverse effects, further research is needed to establish its clinical utility and cost-effectiveness across various psychiatric disorders.

A Study Of the effect of Sex on drug dosing, concentrations, and pharmacogenomics in the Montreal Heart Institute Hospital Cohort (SOS-PGx): methodology and research progress.

Background: Women are underrepresented in drug development trials and there is no sex-tailored drug regimen for most medications. It has been repeatedly shown that women have more adverse drug reactions than men for several medications. These differences could be explained by higher dose-adjusted drug concentrations in women.

Polymorphisms within genes encoding Ikaros family proteins IKZF1 and IKZF3 in multiple myeloma patients treated with thalidomide.

Background: Multiple myeloma (MM) is a hematological malignancy characterized by the presence of abnormal plasma cells. It is associated with anemia, bone lesions and renal dysfunction. Immunomodulatory drugs (IMiDs) are commonly used in MM treatment.

Genetic variation on dolutegravir pharmacokinetics and relation to safety and efficacy outcomes: a systematic review.

Background: Dolutegravir (DTG) is an antiviral agent used for the treatment of HIV, however, there is uncertainty over the influence of genetic variation on DTG exposure, and whether it has clinical implications for the efficacy or toxicity in different populations. This systematic review aims to create an overview of the impact of pharmacogenomics (PGx) on DTG exposure, efficacy, and toxicity.

Methods: Publications up to 14 November 2023 were searched and articles were selected on the following criteria: original research articles providing data on people with HIV, data on PGx and either PK or PD or both PD and PGx.

A genotype-guided prediction model for the incidence of persistent acute kidney injury following lung transplantation.

Background: This study aimed to develop a nomogram for predicting persistent renal dysfunction in acute kidney injury (AKI) following lung transplantation (LTx).

Method: A total of 229 LTx patients were enrolled, and genotyping for 153 single nucleotide polymorphisms (SNPs) was performed. The cohort was randomly divided into training (n = 183) and validation (n = 46) sets in an 8:2 ratio.

Leveraging artificial intelligence and machine learning to accelerate discovery of disease-modifying therapies in type 1 diabetes.

Progress in developing therapies for the maintenance of endogenous insulin secretion in, or the prevention of, type 1 diabetes has been hindered by limited animal models, the length and cost of clinical trials, difficulties in identifying individuals who will progress faster to a clinical diagnosis of type 1 diabetes, and heterogeneous clinical responses in intervention trials. Classic placebo-controlled intervention trials often include monotherapies, broad participant populations and extended follow-up periods focused on clinical endpoints. While this approach remains the 'gold standard' of clinical research, efforts are underway to implement new approaches harnessing the power of artificial intelligence and machine learning to accelerate drug discovery and efficacy testing.

Bridging genomics' greatest challenge: The diversity gap.

Achieving diverse representation in biomedical data is critical for healthcare equity. Failure to do so perpetuates health disparities and exacerbates biases that may harm patients with underrepresented ancestral backgrounds. We present a quantitative assessment of representation in datasets used across human genomics, including genome-wide association studies (GWASs), pharmacogenomics, clinical trials, and direct-to-consumer (DTC) genetic testing.

Pharmacogenomic profiling of the South Korean population: Insights and implications for personalized medicine.

Adverse drug reactions (ADRs) pose substantial public health issues, necessitating population-specific characterization due to variations in pharmacogenes. This study delineates the pharmacogenomic (PGx) landscape of the South Korean (SKR) population, focusing on 21 core pharmacogenes. Whole genome sequencing (WGS) was conducted on 396 individuals, including 99 healthy volunteers, 95 patients with chronic diseases, 81 with colon cancer, 81 with breast cancer, and 40 with gastric cancer, to identify genotype-specific drug dosing recommendations.

Lack of Association between BDNF rs6265 and Multiple Sclerosis: A Case-Control Study.

Background And Objectives: Data on the association between BDNF rs6265 and multiple sclerosis (MS) are scarce and heterogeneous.

Materials And Methods: We undertook a case-control study design. Newly diagnosed individuals with MS based on the 2017 revision of the McDonald criteria were recruited from the Neurology Department of the General University Hospital of Larissa.

A review of precision medicine in developing pharmaceutical products: Perspectives and opportunities.

Over the next decade, Precision Medicine (PM) is poised to become the standard of care in pharmaceutical therapy, necessitating a fundamental transformation in the design and development of innovative custom-made drug products. To date, a comprehensive review linking PM with practical personalized drug formulations is missing. This review attempts to provide an overview of state-of-the-art formulation approaches capable of translating PM evaluation and resulting recommendations (clinical research) into tailored drug products (non-clinical research) for real-world patients.

Pharmacogenetics of dabigatran and apixaban in association with gastrointestinal bleeding.

Objectives: To determine whether selected single nucleotide polymorphisms (SNPs) of genes encoding proteins responsible for the activation, transport, or metabolism of dabigatran and apixaban might be associated with a risk of gastrointestinal bleeding in a cohort of adult patients treated with these drugs. No previous study has focused specifically on the association with gastrointestinal bleeding.

Materials And Methods: Ninety-one patients treated with dabigatran or apixaban were genotyped for selected polymorphisms.

Clinical Actionability of the NUDT15 *4 (p.R139H) Allele and Its Association With Hispanic Ethnicity.

Nudix hydrolase 15 (NUDT15) deficiency is strongly associated with thiopurine-induced myelosuppression. Currently, testing for NUDT15 deficiency is based on the genotyping of the most frequent and clinically characterized no-function variants, that is, *2, *3 and *9. The Hispanic/Latino-predominant variant NUDT15 *4 (p.

Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma.

Background: Underlying immunological mechanisms in children with moderate-to-severe asthma are complex and unclear. We aimed to investigate the association between blood inflammatory parameters and asthma burden in children with moderate-to-severe asthma.

Methods: Blood inflammatory parameters (eosinophil and neutrophil counts and inflammatory mediators using multiplex immunoassay technology) were measured in children (6-17 years) with moderate-to-severe asthma from the SysPharmPediA cohort across four European countries.

Prevalence Estimates of Cytochrome P450 Phenoconversion in Youth Receiving Pharmacotherapy for Mental Health Conditions.

Pharmacogenetics-predicted drug metabolism may not match clinically observed metabolism due to a phenomenon known as phenoconversion. Phenoconversion can occur when an inhibitor or inducer of a drug-metabolizing enzyme is present. Although estimates of phenoconversion in adult populations are available, prevalence estimates in youth populations are limited.

mirSNPs as Potential Colorectal Cancer Biomarkers: A Systematic Review.

Colorectal cancer (CRC) is the third most common neoplasm in the world and the second with the highest mortality rate. Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes known as mirSNPs may be related to dysregulated miRNA expression in several neoplasms. This systematic review aims to investigate studies that investigate SNPs located in regions of miRNA genes that influence their expression and are associated with CRC, as well as their potential as biomarkers for the disease, based on the available literature.

Decoding Neurodegeneration: A Review of Molecular Mechanisms and Therapeutic Advances in Alzheimer's, Parkinson's, and ALS.

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, ALS, and Huntington's, remain formidable challenges in medicine, with their relentless progression and limited therapeutic options. These diseases arise from a web of molecular disturbances-misfolded proteins, chronic neuroinflammation, mitochondrial dysfunction, and genetic mutations-that slowly dismantle neuronal integrity. Yet, recent scientific breakthroughs are opening new paths to intervene in these once-intractable conditions.

Radiogenomics Pilot Study: Association Between Radiomics and Single Nucleotide Polymorphism-Based Microarray Copy Number Variation in Diagnosing Renal Oncocytoma and Chromophobe Renal Cell Carcinoma.

RO and ChRCC are kidney tumours with overlapping characteristics, making differentiation between them challenging. The objective of this research is to create a radiogenomics map by correlating radiomic features to molecular phenotypes in ChRCC and RO, using resection as the gold standard. Fourteen patients (6 RO and 8 ChRCC) were included in the prospective study.

Combined Therapeutic Strategies Based on the Inhibition of Non-Oncogene Addiction to Improve Tumor Response in EGFR- and KRAS-Mutant Non-Small-Cell Lung Cancer.

Background: Oncogene-driven NSCLC is usually treated with targeted therapies using tyrosine kinase inhibitors (TKIs) to inhibit oncogene downstream signaling pathways, affecting tumor survival and proliferation. EGFR- and KRAS-mutant NSCLCs are the most represented subtypes, and they are treated in clinical practice with oncogene-targeting drugs in the first and second line, respectively. Unfortunately, the development of oncogene-independent resistant clones limits TKI efficacy.

Clinical Pharmacogenetic Testing and Application: 2024 Updated Guidelines by the Korean Society of Laboratory Medicine.

In the era of precision medicine, pharmacogenetics has substantial potential for addressing inter-individual variability in drug responses. Although pharmacogenetics has been a research focus for many years, resulting in the establishment of several formal guidelines, its clinical implementation remains limited to several gene-drug combinations in most countries, including Korea. The main causes of delayed implementation are technical challenges in genotyping and knowledge gaps among healthcare providers; therefore, clinical laboratories play a critical role in the timely implementation of pharmacogenetics.

Clostridium Scindens Protects Against Vancomycin-Induced Cholestasis and Liver Fibrosis by Activating Intestinal FXR-FGF15/19 Signaling.

Primary sclerosing cholangitis (PSC) is characterized by abnormal bile acid metabolites and altered gut microbiota, with no effective treatments available. Vancomycin, a glycopeptide antibiotic, has emerged as a promising candidate. However, the mechanism by which vancomycin impacts the progression of PSC remains unknown.

Effects of pharmacogenomics-guided treatment on medication adherence and the antidepressant switching rate in major depressive disorder.

Background: In the treatment of depression, medication plays a crucial role. However, insufficient patient adherence to medication often results in unsatisfactory treatment outcomes, increasing both the recurrence and rehospitalization rates of depression, and consequently imposing a greater economic burden on the healthcare system.

Objectives: Our objective was to examine the impact of pharmacogenomic testing on medication adherence and antidepressant switching rates among individuals diagnosed with depression.

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between SLCO1B1 and statins and CYP2C9 and sulfonylureas.

Aligned with the mission of the Dutch Pharmacogenetics Working Group (DPWG) to promote the implementation of pharmacogenetics (PGx), this guideline is specifically designed to optimize pharmacotherapy of cholesterol lowering medication (statins) and glucose lowering medication (sulfonylureas). The SLCO1B1 c.521 T > C variant reduces the activity of the SLCO1B1 transporter involved in statin transport out of the blood into the liver.

Diagnostic Challenges in Malignant Hyperthermia and Anesthesia-Induced Rhabdomyolysis: A Case Study.

BACKGROUND Malignant hyperthermia (MH) and anesthesia-induced rhabdomyolysis (AIR) are rare, yet life-threatening complications that need prompt therapeutic actions and logistic preparedness for treatment success. Both conditions are triggered by general anesthetics, particularly volatiles and depolarizing muscle relaxants. In comparison with MH, which is an inherited pharmacogenomic disease of calcium channel receptor subpopulation and arises only after trigger exposure, AIR has been described mostly in patients with muscular dystrophies.

Implementation of Integrated Clinical Pharmacogenomics Testing at an Academic Medical Center.

Background: Pharmacogenomics has demonstrated benefits for clinical care, including a reduction in adverse events and cost savings. However, barriers in expanded implementation of pharmacogenomics testing include prolonged turnaround times and integration of results into the electronic health record with clinical decision support. A clinical workflow was developed and implemented to facilitate in-house result generation and incorporation into the electronic health record at a large academic medical center.