Search Results (147)

Personalized psychiatry represents an innovative therapeutic approach that integrates biological, genetic, and clinical data to optimize the treatment of mental disorders. Laboratory diagnostics play a fundamental role in this process by providing precise biomarkers that characterize pathophysiological mechanisms such as neuroinflammatory processes, oxidative stress, dysfunction of the Hypothalamic–Pituitary–Adrenal (HPA) axis, as well as disturbances in neuroplasticity and neurodegeneration. This article discusses the use of advanced analytical techniques, such as immunoenzymatic assays for pro-inflammatory cytokines (Interleukin-1β- IL-1β; Interleukin-6-IL-6; Interleukin-18-IL-18; and Tumor Necrosis Factor- α - TNF-α). It also emphasizes the role of pharmacogenomic diagnostics in the individualization of psychotropic therapy. Interdisciplinary collaboration between laboratory diagnosticians and clinicians supports the potential for multidimensional analysis of biomarker data in a clinical context, which supports precise patient profiling and monitoring of treatment responses. Despite progress, there are limitations, such as the lack of standardization in measurement methods, insufficient biomarker validation, and limited availability of tests in clinical practice. Development prospects include the integration of multi-marker panels, the use of point-of-care diagnostics, and the implementation of artificial intelligence tools for the analysis of multidimensional data. As a result, laboratory diagnostics are becoming an integral element of personalized psychiatry, enabling a better understanding of the neurobiology of mental disorders and the implementation of more effective therapeutic strategies. Full article

Hypomagnesaemia, a common complication ranging from 20% to over 90%, depending on the diagnostic criteria and population studied, significantly contributes to adverse outcomes, including new-onset diabetes after transplantation, cardiovascular complications, neurological dysfunction and increased infection risk. A total serum magnesium below 0.70 mmol/L is commonly used to define deficiency. In kidney transplant recipients, calcineurin inhibitors downregulate TRPM6 in the distal nephron, leading to early and persistent hypomagnesaemia with links to adverse metabolic and cardiovascular outcomes. Arrhythmia risk rises steeply at total magnesium of <0.50 mmol/L, while neuromuscular irritability and neuropsychiatric symptoms may appear at levels below 0.70 mmol/L. Severe manifestations, such as seizures or tetany, usually occur at ≤0.50 mmol/L and coma at <0.30 mmol/L. Normal ionised magnesium is typically ~0.48–0.65 mmol/L; transplant-specific intervention thresholds remain unvalidated. This narrative review addresses critical diagnostic gaps and explores emerging therapeutic strategies. It highlights three areas: the diagnostic accuracy of ionised magnesium over total magnesium, the critical role of pharmacogenomics in individualising immunosuppression to mitigate tacrolimus-induced hypomagnesaemia and the promising link between gut microbiome modulation and magnesium homeostasis. The implications of these insights are profound: enabling more precise diagnosis and personalised management, reducing the incidence and severity of hypomagnesaemia-related complications, and ultimately supporting more precise diagnosis and personalised management; prospective validation in transplant cohorts is required before outcome claims can be made. This review exposes current diagnostic and therapeutic limitations, advocating for more precise and personalised strategies to address this critical electrolyte imbalance. Identifying hypomagnesaemia as a mechanistically complex and clinically undertreated complication, this review proposes a thematic roadmap that serves as a scientific and clinical framework for advancing personalised electrolyte care in renal transplantation. It is emphasised that while these approaches appear promising, most remain under-evaluated or hypothesis-generating. Addressing hypomagnesaemia through validated thresholds, new research is required to test novel diagnostics and personalised strategies to improve patient and graft outcomes. Full article

Background: Carbamazepine (CBZ) is associated with severe cutaneous adverse reactions in individuals carrying the HLA-B*15:02 allele, which is prevalent in Asian populations. Genetic screening before the initiation of CBZ is recommended, yet screening is not always undertaken. Objectives: To determine the effect of implementing computerized physician order entry (CPOE) reminders on the screening rates of HLA-B*15:02 before CBZ prescription. Methods: We conducted a retrospective analysis of 1611 patients who were prescribed CBZ between 2012 and 2023 in a regional hospital in Taiwan. The intervention involved integrating automated HLA-B*15:02 screening reminders into the CPOE system in outpatient settings. Patients were divided into an outpatient (intervention) group and an inpatient (control) group, and their data were analyzed before and after the intervention. Screening rates were compared using Fisher’s exact test, and subgroup analyses were conducted on the basis of age group and physician specialty. Results: After the intervention, the outpatient group exhibited an increase in screening rate from 23.7% to 55.6% (p < 0.001). However, no significant change was observed in the inpatient group. Subgroup analysis revealed major improvements among neurologists and patients aged 41–80 years in outpatient settings. Conclusions: Implementing CPOE reminders substantially improves rates of screening for HLA-B*15:02 in outpatient settings, indicating the effectiveness of informatic interventions in enhancing adherence to pharmacogenomic guidelines. Extending such interventions to inpatient settings may further mitigate the risk of CBZ-induced severe cutaneous adverse reactions. Full article

Pharmacogenomics (PGx) has emerged as a powerful tool to personalize drug selection and dosing based on a patient’s genetic profile. However, there are a range of challenges that impede uptake in current clinical practice. For example, clinicians often express frustration with commercially available PGx panel tests, which fail to consistently include all key actionable PGx genes (according to the Clinical Pharmacogenetics Implementation Consortium (CPIC), Food and Drug Administration (FDA) PGx guidelines, or The Dutch Pharmacogenetics Working Group (DPWG) guidelines) and instead are too long with clinically unimportant information (unvalidated genotypes). Additionally, the lack of EMR integration, clinician education and awareness of the benefits of PGx impedes uptake. This paper examines key challenges identified in clinical practice and proposes future directions, focusing on limiting PGx reports to essential data, providing point-of-prescription alerts, and establishing reimbursement pathways that encourage adoption. Future directions include leveraging large language models, integrating point-of-prescription alerts and phenoconversion calculators into the electronic medical record, increasing the genomic diversity of PGx study populations, and streamlining coverage by payers. Full article

Background: Pharmacogenomics (PGx), a pivotal branch of personalized medicine, studies how genetic variations influence drug responses. Despite its transformative potential, the adoption of PGx in Indian clinical practice faces challenges, such as the lack of population-specific data, evidence-based guidelines, and complexities in interpreting genomic reports. Comprehensive datasets tailored to Indian patients are essential to facilitate the integration of PGx into clinical settings. Methodology: The study collates pharmacogenomic data from multiple sources, including essential drugs listed by the World Health Organization (WHO), drugs used in neonatal intensive care units (NICUs), minimum sets of alleles recommended by the Association for Molecular Pathology (AMP), and catalogs the allele frequencies from the IndiGenomes database to address gaps in actionable PGx for the Indian population. Curated datasets were used to identify pharmacogenomic variants relevant to clinical practice. Results: Overall, 24 prime genes are essential for the outcomes of 57 drugs. In adults, 18 genes influence the metabolism of 44 drugs whereas, in pediatric populations, genotypes of 18 genes significantly impact the metabolism of 18 drugs. Two over-the-counter drugs with actionable PGx variants were identified: ibuprofen and omeprazole. These findings emphasize the clinical relevance of PGx for commonly used drugs, underscoring the need for population-specific data. Conclusions: As the data of several Indian human genome projects become available, an overarching need exists to establish and regulate the dynamic actionable PGx in Indian clinical practice. This will facilitate the integration of pharmacogenomic data into healthcare, enabling effective and personalized drug therapies. Full article

Background: As more healthcare institutions consider providing preemptive pharmacogenomic (PGx) testing to greater numbers of their patients, it will be important to consider the potential concerns patients may have about the generation of preemptive PGx information. To date, few studies have examined the nature and incidence of patient concerns about preemptive PGx testing. Methods: We conducted a longitudinal survey study of 5000 patients receiving preemptive PGx testing in the Mayo Clinic RIGHT study. We assessed patient concerns regarding issues of data confidentiality, cost implications, comprehension of results, and potential disruption of pre-existing medication regimens. Participants were surveyed before and after they received PGx results from the RIGHT study. Results: We achieved 92.8% and 74.4% response rates on the pre- and post-results surveys, respectively. Participants had low levels of concern about PGx testing overall. However, 25.5% of participants were “quite/extremely concerned” about insurance implications, and 30.1% were “quite/extremely” concerned about increased out-of-pocket costs for prescription medications that might result from PGx testing. These same concerns were significantly reduced on the post-results survey. Patients who initially expressed concerns regarding their ability to understand PGx results were more likely to report having difficulty understanding results on the post-results survey. Conclusions: Our findings suggest that as healthcare institutions look to increase preemptive PGx screening, attention should be given to potential concerns patients may have around such testing. Educational interventions aimed at supporting patient understanding of PGx results and addressing potential concerns will be important elements of a successful PGx program. Full article

Background: Cephalosporins are considered safe antibiotics. However, serious hematological abnormalities may occur, although rarely, after their therapeutic use. Case Presentation: We present a case of pancytopenia in a 72-year-old female patient treated with ceftriaxone for a urinary tract infection. After five days of therapy, pancytopenia was observed. Other causes were excluded through extensive diagnostic evaluation, including immunological tests, viral serologies, bone marrow aspiration, and peripheral blood smear. The patient’s clinical condition significantly improved following the discontinuation of ceftriaxone and the administration of granulocyte colony-stimulating factor (G-CSF). Bone marrow findings revealed hypocellularity without malignant infiltration, and peripheral smear showed no dysplasia, blasts, or hemolysis. Conclusions: This case demonstrates that ceftriaxone, although widely regarded as a safe antibiotic, can induce rare but serious hematologic complications such as pancytopenia. A high index of suspicion is required when patients on antibiotic therapy develop unexplained cytopenias. Detailed medication history, exclusion of other causes, and prompt discontinuation of the suspected drug are essential. The patient’s favorable outcome supports the likelihood of an idiosyncratic, immune-mediated mechanism. Future research should explore pharmacogenomic screening in patients at increased risk, particularly involving HLA variants. Full article

Background: Pharmacogenetics (PGx) is the science of assessing how genetic variation affects drug efficacy, tolerability, and safety. While PGx is an emerging discipline which is becoming standard of care, many providers have misunderstandings about its utility. This is even more of a problem for patients, who may perceive that there is a single drug that is “right” for them. The primary objective of this study was to evaluate consumer comprehension of a newly developed patient-facing PGx report. Methods: In this study, we adapted a commercial pharmacogenetic test (Genomind Professional PGx) into a report intended to be more comprehensible to the consumer. The initial translation of the clinical terminology used in the PGx report, into lay terminology was conducted by PharmDs and PhDs who have collectively provided over 20,000 PGx consults to date. These reports were then evaluated with readability scoring software to ensure each translation’s complexity remained ≤8th-grade reading level. A total of 107 participants were recruited to conduct the initial analysis with a goal of achieving a 90% comprehension rate using the Genomind consumer comprehension survey. These participants were also given a modified Minnesota Assessment of Pharmacogenomic Literacy (MAPL™) both before and after the Genomind comprehension survey to assess overall PGx literacy. Results: Ninety-eight (98) out of 107 research participants scored one or zero questions incorrectly, translating to >90% comprehension score on the Genomind consumer comprehension survey. These participants also demonstrated a significant increase in overall pharmacogenetic literacy, as assessed by MAPL after viewing the consumer report and survey. Conclusions: This study found that translating pharmacogenetic test results into lay language may provide individuals with a greater understanding of how their DNA may impact prescribed medications. Full article

Epidermal growth factor receptor 2 (ERBB2/HER2) is a critical biomarker in gastric cancer management, but the clinical implications of specific ERBB2 mutations remain poorly characterized. Methods/Results: We investigated the ERBB2 R678Q mutation, utilizing the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, which involved the analysis of 3116 gastric/gastroesophageal junction adenocarcinomas. ERBB2 mutations were identified in 130 cases, with R678Q present in 40 patients. These patients exhibited significantly lower response rates to oxaliplatin-based regimens compared to ERBB2 wild-type cases (19.0% vs. 38.0%, p = 0.03), while other ERBB2 mutations demonstrated no such resistance. No significant differences in the response were observed to the ramucirumab or nivolumab regimens. Conclusions: Our findings suggest that the ERBB2 R678Q mutation may predict a poor response to oxaliplatin-based therapy. This study provides real-world evidence supporting the potential clinical relevance of this specific ERBB2 mutation in treatment decision making for gastric cancer. Full article

Background: Sources and evidence cited to inform payer coverage decisions on pharmacogenomic (PGx) testing in psychiatry are presently underexplored. Methods: We conducted a qualitative and quantitative assessment of publicly available coverage policies from 14 US payers, examining the number and both the type and source of citations across policies and coverage decisions. Payers were classified as for-profit or mutual fund versus non-profit or government, and their coverage decisions were categorized as either coverage (limited or specified) or no coverage. Results: Among 32 unique sources cited, peer-reviewed literature as a single source was most frequently cited across all policies. Of 207 peer-reviewed papers cited across all policies, 40% (n = 83) were psychiatry-specific real-world evidence (RWE) studies. No statistically significant relationships were observed when comparing variance in the number of citations per policy by payer type (p = 0.22) or coverage decision (p = 0.75; unadjusted variance of 61.25 and an adjusted variance of 60.98 for both comparisons). For-profit or mutual fund payers and/or payers providing no coverage cited systematic reviews and non-randomized controlled cohort RWE studies most often. Non-profit or government payers and/or payers providing coverage cited case series or case-control RWE studies most often. Six psychiatry-specific RWE studies and contributions from 13 distinct sources were often cited, regardless of payer type or coverage decision. Conclusions: RWE, among several sources, are cited in many forms and to varying degrees among payers providing coverage decisions for PGx testing in psychiatry, with coverage determinations being largely based on how certain payers interpret evidence on the clinical value of testing. Full article

Background/Objectives: Pharmacogenomic screening plays a crucial role in optimizing chemotherapy outcomes and minimizing toxicity. Characterizing the baseline distribution of genetic variants in specific populations is essential to inform the prioritization of drug–gene combinations for clinical implementation. The objective of this study was to investigate the distribution of pharmacogenetic variants in 36 genes related to the fluoropyrimidine (FP) pathway among healthy Omani individuals, forming a foundation for future studies in cancer patients receiving FP-based chemotherapy. Methods: Ninety-eight healthy Omani participants aged ≥18 years were recruited at the Sultan Qaboos Comprehensive Cancer Care and Research Center. Whole-blood samples were collected, and genomic DNA was extracted. Targeted next-generation sequencing was performed using a custom Ion AmpliSeq panel covering coding exons and splice-site regions of 36 genes involved in FP metabolism and response. Results: A total of 999 variants were detected across the 36 genes, with 63.3% being heterozygous. The ABCC4 gene had the highest mutation frequency (76 mutations), while DHFR and SMUG1 had the lowest (<10 mutations). In DPYD, four functionally significant variants were found at frequencies ranging from 1 to 8.2% of the population. Missense mutations were also observed in MTHFR and UGT1A1. Three actionable variants in DPYD and MTHFR, associated with 5-fluorouracil and/or capecitabine response, were identified. Additionally, 27 novel single-nucleotide polymorphisms of unknown clinical significance were detected. Conclusions: This study reveals key pharmacogenetic variants in the Omani population, underscoring the importance of integrating pharmacogenomic testing into routine care to support safer, more personalized chemotherapy in the region. Full article

Background: Pharmacogenomics (PGx) is the future of healthcare and implementation is being driven by increasing evidence. Understanding the workflow in a PGx clinic provides insight into the development and implementation of PGx services. It considers the patient’s perspective, the role of the interprofessional team and the pivotal input of the pharmacist. Objectives: The purpose of this study was to describe the clinical workflow followed in selected PGx clinics. Methods: Four different sites that offer PGx clinical services (United States of America) were included. Qualitative data were collected through semi-structured interviews and observations providing valuable insights into the workflow followed in both community-based and hospital-based PGx clinics. Results: Although each setting differed, the processes were similar with setting-specific workflows and barriers. This study highlights the role of the pharmacist and the interprofessional team, the resources used for interpretation of PGx test results and the importance of patient and healthcare education. Conclusions: Understanding the workflow and the role of the interprofessional team in PGx is essential to ensure successful implementation and sustainable precision medicine practices in resource-limited settings. Full article

Background/Objectives: Pharmacogenomics is an emerging field in precision medicine that aims to improve patient outcomes by tailoring drug selection and dosage to an individual’s genetic makeup. However, patients in rural communities often cannot take advantage of specialized services such as pharmacogenomics due to various barriers that limit access to healthcare. This article aims to identify the barriers to implementing pharmacogenomic initiatives in rural communities and assess strategies for integrating pharmacogenomics into rural healthcare systems. Methods: This article describes the qualitative research that was conducted using semi-structured interviews with various stakeholders in addition to explaining how strategic frameworks were used to synthesize secondary research. Results: The findings of this article indicated mixed awareness of pharmacogenomics as an option amongst stakeholders, highlighting the need for targeted outreach and education intervention. Solutions such as mail-in testing and telemedicine were determined to be feasible solutions to address various geographical and logistical barriers that exist for rural patients. This article determines that successful strategies will leverage existing infrastructure and prioritize patient care, workflow integration, and adoption. Conclusions: Making pharmacogenomics a viable option for rural patients will take a multi-faceted approach that combines outreach, education, and innovative delivery models to overcome the multiple barriers facing rural communities. Full article

Pharmacogenomics, the study of how genetic variations influence drug response, has become integral to cancer treatment as personalized medicine evolves. This review aims to explore key pharmacogenomic biomarkers relevant to cancer therapy and their clinical implications, providing an updated and comprehensive perspective on how genetic variations impact drug metabolism, efficacy, and toxicity in oncology. Genetic heterogeneity among oncology patients significantly impacts drug efficacy and toxicity, emphasizing the importance of incorporating pharmacogenomic testing into clinical practice. Genes such as CYP2D6, DPYD, UGT1A1, TPMT, EGFR, KRAS, and BRCA1/2 play pivotal roles in influencing the metabolism, efficacy, and adverse effects of various chemotherapeutic agents, targeted therapies, and immunotherapies. For example, CYP2D6 polymorphisms affect tamoxifen metabolism in breast cancer, while DPYD variants can result in severe toxicities in patients receiving fluoropyrimidines. Mutations in EGFR and KRAS have significant implications for the use of targeted therapies in lung and colorectal cancers, respectively. Additionally, BRCA1/2 mutations predict the efficacy of PARP inhibitors in breast and ovarian cancer. Ongoing research in polygenic risk scores, liquid biopsies, gene–drug interaction networks, and immunogenomics promises to further refine pharmacogenomic applications, improving patient outcomes and reducing treatment-related adverse events. This review also discusses the challenges and future directions in pharmacogenomics, including the integration of computational models and CRISPR-based gene editing to better understand gene–drug interactions and resistance mechanisms. The clinical implementation of pharmacogenomics has the potential to optimize cancer treatment by tailoring therapies to an individual’s genetic profile, ultimately enhancing therapeutic efficacy and minimizing toxicity. Full article

Background: In the United States, approximately 1 in 5 children experience comorbidities with mental illness, including depression and anxiety, which lead to poor general health outcomes. Adolescents with substance use disorders exhibit high rates of co-occurring mental illness, with over 60% meeting diagnostic criteria for another psychiatric condition in community-based treatment programs. Comorbidities are influenced by both genetic (DNA antecedents) and environmental (epigenetic) factors. Given the significant impact of psychiatric comorbidities on individuals’ lives, this study aims to uncover common mechanisms through a Genome-Wide Association Study (GWAS) meta-meta-analysis. Methods: GWAS datasets were obtained for each comorbid phenotype, followed by a GWAS meta-meta-analysis using a significance threshold of p < 5E−8 to validate the rationale behind combining all GWAS phenotypes. The combined and refined dataset was subjected to bioinformatic analyses, including Protein–Protein Interactions and Systems Biology. Pharmacogenomics (PGx) annotations for all potential genes with at least one PGx were tested, and the genes identified were combined with the Genetic Addiction Risk Severity (GARS) test, which included 10 genes and eleven Single Nucleotide Polymorphisms (SNPs). The STRING-MODEL was employed to discover novel networks and Protein–Drug interactions. Results: Autism Spectrum Disorder (ASD) was identified as the top manifestation derived from the known comorbid interaction of anxiety, depression, and attention deficit hyperactivity disorder (ADHD). The STRING-MODEL and Protein–Drug interaction analysis revealed a novel network associated with these psychiatric comorbidities. The findings suggest that these interactions are linked to the need to induce “dopamine homeostasis” as a therapeutic outcome. Conclusions: This study provides a reliable genetic and epigenetic map that could assist healthcare professionals in the therapeutic care of patients presenting with multiple psychiatric manifestations, including anxiety, depression, and ADHD. The results highlight the importance of targeting dopamine homeostasis in managing ASD linked to these comorbidities. These insights may guide future pharmacogenomic interventions to improve clinical outcomes in affected individuals. Full article