Search Results (1,172)

Pharmaceutical care provides the conceptual foundation for integrating pharmacogenetics into everyday pharmacy practice. Defined by Hepler and Strand as “the responsible provision of drug therapy for the purpose of achieving specific outcomes that improve a patient’s quality of life”, pharmaceutical care emphasizes a patient-centered approach in which the pharmacist collaborates with the patient, physician, and other healthcare professionals to design, implement, and monitor individualized therapeutic plans. In this context, pharmacogenetics can be regarded as an extension of pharmaceutical care: while the traditional model relies on monitoring patient outcomes and adherence, PGx adds a genetic dimension that allows treatment to be optimized from the very beginning. The pharmacist’s role therefore evolves from not only ensuring safe and effective use of medicines, but also interpreting genetic test results, supporting adherence to genetically guided therapy, and educating patients about the implications of their personal genetic profile. The introduction of pharmacogenetics testing as one of the potential services offered by community pharmacies is a promising proposition that may revolutionize the approach to drug therapy. Pharmacogenetics, a subset of pharmacogenomics, focuses on the study of DNA sequence variations that influence response to drugs. Thanks to advances in the field of genomics, it has become possible to study the genetic basis of variability in drug response. The identification of alleles responsible for the rapid or slow metabolism of xenobiotics has ushered in a new era in pharmacology. The aim of this interdisciplinary field, combining genetics and pharmacology, is to adapt treatment to a specific patient based on the analysis of their genome and gene polymorphism. Throughout the world, pharmacogenetics is gaining importance as a tool for personalizing medicine. In countries such as the United States, Canada, and the United Kingdom, programs integrating pharmacogenetics with healthcare are being developed. Clinical trials and the implementation of genetic tests into medical practice allow for better matching of medications and reducing the risk of side effects. Pharmacists will play a key role in integrating pharmacogenetics into healthcare. As specialists in the field of pharmacotherapy, they will support physicians in interpreting the results of genetic tests and adapting drug therapy to the individual needs of the patient. Additionally, pharmacists can educate patients and healthcare professionals about the benefits of pharmacogenetics and monitor the effects and safety of medications. Their involvement in the process of personalization of treatment may contribute to improving the effectiveness and safety of pharmacological therapies. Full article

Background: Tildrakizumab, an anti-IL-23p19 monoclonal antibody, has demonstrated efficacy in clinical trials, but real-world evidence remains crucial for confirming its profile in diverse populations. Methods: We have conducted a multicenter, retrospective observational study within the Spanish Psoriasis Group (GPS). This study updates previous findings with a larger sample size (n = 372) and longer follow-up. We assessed absolute Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), and the Dermatology Life Quality Index (DLQI) improvements, as well as safety, in patients with moderate-to-severe plaque psoriasis. Results: The cohort included a large population of patients with a high prevalence of comorbidities and prior biologic exposure. Effectiveness was high, with a significant proportion of patients achieving PASI < 1. Compared to recent real-world data, our cohort demonstrates superior complete clearance rates (PASI < 1) and includes a comprehensive DLQI assessment. Notably, 79 patients were aged ≥65 years, confirming the drug’s utility in the elderly. Safety was consistent with previous reports, with no new signals detected. Conclusions: Tildrakizumab shows robust effectiveness and safety in a complex, bio-experienced real-world population. The lack of clinical predictors of response suggests a need for future pharmacogenetic exploration. Full article

Background/Objectives: In several contexts, Dried Sample Spot Devices (DSSDs) offer a convenient and safe alternative for sampling, storage, and shipment, allowing the transport and storage of biological samples at room temperature, reducing shipment costs and improving access to diagnostics in faraway sites. This can be pivotal for the use of the therapeutic drug monitoring of anti-HIV treatment: therefore, this study aimed to develop and validate a UHPLC–MS/MS method for the simultaneous quantification of 12 antiretroviral drugs, including the recently introduced long-acting agents, in Dry Plasma Spots (DPSs). Methods: First, 100 µL of plasma sample and 100 µL of internal standard solution were spotted on each DSSD. After complete drying, DPSs were added with an acidifying solution (ammonium acetate buffer pH 4), and then, each sample underwent extraction with hexane-dichloromethane 50:50 (v/v). After tumbling, the organic phase was evaporated and reconstituted for injection. An Acquity UPLC HSS T3 1.8 µm, 2.1 × 150 mm column at 50 °C enabled separation, performed using H₂O + F.A. 0.05% (phase A) and ACN + F.A. 0.05% (phase B) as the mobile phase in gradient elution mode, for a total run time of 15 min. Results: The method was validated over the clinically relevant concentration ranges. For all quality control levels, accuracies ranged from 98.2% to 114.1%, and intra-day and inter-day RSD values ranged from 2.7% to 9.7% and 5.2% to 13.9%, respectively. All analytes demonstrated satisfactory short- and long-term stability in DPSs, confirming the suitability of shipment and storage at room temperature. Conclusions: The method demonstrated robustness and reproducibility in accordance with FDA and EMA guidelines. It ensures satisfactory accuracy and rapid analysis, supporting its application in clinical practice, including for monitoring the newest long-acting drugs. Full article

Major depressive disorder (MDD) affects over 330 million people globally, yet up to 30% of patients fail initial pharmacotherapy due to genetic variability in drug metabolism. This narrative review synthesizes evidence on pharmacogenomic (PGx) guided approaches for MDD, emphasizing their integration with POC diagnostics and engineering solutions. Approximately 40–50% of patients carry actionable variants in CYP2C19 or CYP2D6, which govern the metabolism of selective serotonin reuptake inhibitors. Landmark trials (GUIDED, PRIME Care, GAPP-MDD) and meta-analyses demonstrate that PGx-informed prescribing modestly but significantly improves remission and response rates, particularly in treatment-resistant depression. Established guidelines from CPIC and the Dutch Pharmacogenetics Working Group provide actionable recommendations for CYP2D6 and CYP2C19 phenotypes. Emerging POC platforms, including Genomadix Cube and Genedrive, now deliver CYP2C19 results within one hour, supporting rapid clinical decisions. However, psychiatric-specific implementation data remain limited compared to cardiology; current POC devices lack multi-gene capabilities, and most studies underrepresent diverse populations. Persistent barriers include variable reimbursement, limited clinician education, and fragmented electronic health record integration. Future directions include pre-emptive genotyping, expanded multi-gene panels, and embedded clinical decision support. With continued engineering innovation and rigorous validation, PGx-guided care holds promise for reducing the trial-and-error burden and advancing precision psychiatry. Full article

Introduction: Major Depressive Disorder (MDD) has been increasingly associated with inflammatory dysregulation, particularly involving tumor necrosis factor-alpha (TNF-α). Genetic polymorphisms within the TNFA promoter region have been investigated as potential modulators of depressive susceptibility, symptom expression, treatment response, and inflammatory comorbidity. However, findings remain inconsistent across populations and clinical contexts. Methods: This systematic review adhered to PRISMA 2020 guidelines and was registered in PROSPERO (CRD420251242724). Observational and interventional studies evaluating associations between TNFA polymorphisms—specifically rs1800629 (−308 G/A), rs1799724 (−857 C/T), and rs1799964 (−1031 T/C)—and MDD-related outcomes in adults were included. Data extraction and methodological quality assessment were performed independently using an adapted GRIPS framework. Results: Eleven studies met the inclusion criteria, with eight investigating MDD without cardiovascular comorbidity and three assessing cardiovascular populations. Across diverse cohorts, rs1800629 and rs1799724 did not demonstrate consistent associations with MDD susceptibility. Although isolated population-specific findings were reported, genotype and allele distributions were generally comparable between cases and controls. Rs1799724 was associated with symptom dimensions and altered TNF-α expression in two cohorts. Rs1799964 was not linked to disease occurrence but showed potential association with antidepressant response and adverse cardiovascular outcomes in patients with chronic heart failure and comorbid depression. Overall, findings were heterogeneous and influenced by population characteristics, sample size, and clinical context. Conclusions: Current evidence does not support a robust etiological role for TNFA promoter polymorphisms in major depressive disorder. These variants may exert context-dependent modulatory effects on symptom expression, treatment response, or inflammatory-cardiovascular interactions rather than serving as primary susceptibility determinants. Larger, ethnically diverse studies integrating genetic, inflammatory, and clinical data are required to clarify the contribution of inflammatory genetic variability in depressive disorders. Full article

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, underscoring the need to better define the molecular mechanisms that govern cardiovascular homeostasis and disease progression. Among post-transcriptional regulators, microRNAs have emerged as important modulators of endothelial function, vascular smooth muscle cell plasticity, cardiomyocyte integrity, and cardiac fibroblast activity. This narrative review examines how microRNAs orchestrate molecular networks linking cellular homeostasis to inflammation, oxidative stress, mitochondrial dysfunction, apoptosis, fibrosis, angiogenesis, and pathological remodeling across major cardiovascular cell types. It further discusses how these regulatory programs are reflected in specific cardiovascular diseases, including atherosclerosis, hypertension, acute myocardial infarction, heart failure, and arrhythmias. In addition, the review addresses the growing relevance of circulating and extracellular vesicle-associated microRNAs as candidate biomarkers for diagnosis, prognosis, and disease monitoring, as well as their therapeutic potential through mimics, inhibitors, antagomirs, and emerging delivery systems. Finally, current translation barriers are considered, including methodological heterogeneity, limited tissue specificity, delivery challenges, safety concerns, and the need for large-scale clinical validation. Overall, microRNAs are presented as integrative regulators connecting cardiovascular cell biology with disease mechanisms and clinical applications. Full article

Personalized Medicine has been a central aspiration of medical practice and has guided the direction of medical advances from ancient times to the present. This narrative review highlights some of the most significant past advances and present practices, discusses issues currently limiting Personalized Medicine and proposes activities necessary for Personalized Medicine to have a promising future. Throughout history, Personalized Medicine has developed along with the evolution of science and societal concepts. Notable advances paralleled the growth in what an individual person is and how experimental science can apply to medical practice. In the twentieth century, the study of inborn errors of metabolism and pharmacogenetics broadened the horizons of what Personalized Medicine could be. Presently, Personalized Medicine is challenged by different perspectives on its scope, by the various clinical scientific activities which can inadvertently or by misinterpretation serve to depersonalize medicine, and by the difficulties involved in integrating the massive amount of available scientific data to optimize medical practice centered on the individual. The conditions necessary for Personalized Medicine to have a promising future include developing broader, deeper, and more dynamic knowledge of disease processes, new methods to identify anomalous, singular disease-contributing characteristics in individuals, and improving data quality in research and medical practice. Advancing Personalized Medicine requires developing new perspectives for research, healthcare education, medical practice, and healthcare governance, as well as deploying medical advances at scale across populations. Full article

The ATP-binding cassette subfamily G member 2 (ABCG2), also known as breast cancer resistance protein (BCRP), is an efflux transporter expressed in key pharmacokinetic tissues and biological barriers. It regulates exposure to many endogenous compounds, drugs, and environmental toxins. Genetic variability in ABCG2 has been recognised as an important contributor to interindividual variability in drug response, especially in terms of efficacy and toxicity. This narrative review summarises current knowledge on the clinical relevance of ABCG2 genetic variants, with a focus on their effects on pharmacokinetics, adverse drug reactions and drug–drug–gene interactions, as well as their potential implementation in personalised therapy. A literature search was performed in PubMed, Scopus and the Clinical Pharmacogenomics Database (ClinPGx), with an emphasis on clinically relevant studies and available pharmacogenomic guidelines. The most investigated ABCG2 variant, c.421C>A (rs2231142; p.Gln141Lys), is consistently associated with reduced transporter activity and increased systemic exposure to several substrate drugs, including statins, allopurinol and anticancer agents, which may influence both treatment response and the risk of toxicity. Although growing evidence supports the clinical relevance of ABCG2 genotyping, its routine implementation remains limited. Integration of ABCG2 variability into polygenic models and clinical decision-support tools may further improve individualised treatment, particularly in patients with multimorbidity and polypharmacy. Full article

Introduction: Caffeine is the most widely consumed psychoactive stimulant worldwide and acts primarily through antagonism of adenosine A1 and A2A receptors, thereby reducing sleep pressure and promoting wakefulness. Although its alerting and performance-enhancing effects are well established, its influence on sleep-related electroencephalography (EEG) has been investigated across diverse paradigms with substantial methodological heterogeneity. This systematic and mechanistic review aimed to synthesize human evidence on how caffeine affects sleep architecture, quantitative sleep EEG, and neurophysiological markers of sleep homeostasis, and to interpret these findings within current models of adenosine-mediated sleep–wake regulation. Materials and Methods: A systematic search of PubMed/MEDLINE, Web of Science, Scopus, Embase, PsycINFO, ResearchGate, and Google Scholar was conducted for studies published between January 1980 and January 2026, with the final search performed on 10 January 2026. Eligible studies were original human investigations examining caffeine exposure or administration and reporting sleep-related EEG outcomes, including polysomnographic sleep staging, spectral EEG analyses, or other EEG-derived sleep metrics. Two reviewers independently screened records and assessed eligibility, with disagreements resolved by consensus. Data on study design, participant characteristics, caffeine interventions, EEG methodology, and outcomes were extracted using a predefined form. Risk of bias was evaluated using the RoB 2 and ROBINS-I tools. Owing to marked heterogeneity across studies, findings were synthesized narratively within a mechanistic interpretive framework. Results: Thirty-two studies were included. Across highly heterogeneous paradigms—including acute bedtime or evening dosing, daytime or repeated caffeine use before nocturnal sleep, administration during prolonged wakefulness followed by recovery sleep, withdrawal protocols, and ambulatory/home EEG monitoring—the most consistent finding was suppression of low-frequency NREM EEG activity, particularly slow-wave activity and the lowest delta frequencies. Caffeine frequently increased faster EEG activity, including sigma/spindle and beta ranges, producing a lighter, more aroused, and more wake-like sleep EEG profile. These effects were especially prominent during early-night NREM sleep and in recovery sleep after sleep deprivation, where caffeine attenuated the expected homeostatic rebound in low-frequency power. REM-related effects were less consistent, but some studies reported delayed REM timing and subtler alterations in REM EEG. Emerging evidence further suggests that caffeine increases EEG complexity and shifts sleep dynamics toward a more excitation-dominant state. Several studies indicated that quantitative EEG measures were more sensitive than conventional sleep-stage variables in detecting caffeine-related sleep disruption. Dose, timing, habitual caffeine use, withdrawal state, age, circadian context, and adenosinergic genetic variation, particularly involving ADORA2A, moderated the magnitude of effects. We also highlighted the connection between current results and sports and sports science. Conclusions: Caffeine reliably alters the neurophysiological architecture of human sleep in a direction consistent with reduced sleep depth and weakened homeostatic recovery. The overall evidence supports a mechanistic model centered on adenosine receptor antagonism, attenuation of sleep-pressure build-up and expression, and a shift toward greater cortical arousal during sleep. Sleep EEG appears to be a sensitive marker of these effects, often revealing physiological disruption even when conventional sleep architecture changes are modest. Future research should prioritize larger and more diverse samples, pharmacokinetic and pharmacogenetic characterization, and ecologically valid high-resolution sleep monitoring to clarify the real-world and functional consequences of caffeine-induced EEG changes. Full article

Background: Schizophrenia in adolescence disrupts neurodevelopment and long-term functioning. While symptom reduction remains a primary treatment goal, quality of life (QoL) represents a critical, patient-centered outcome. Pharmacogenetic variability, particularly in CYP2D6 metabolism of second-generation antipsychotics, may influence tolerability and subjective well-being beyond symptom control. Materials and Methods: Forty-seven adolescents (aged 14–18 years) diagnosed with schizophrenia (DSM-5) were followed in routine clinical care. CYP2D6 genotyping classified patients as normal metabolizers (NM, n = 27) or reduced-function metabolizers (RFM, including intermediate/poor, n = 20). Symptom severity was assessed with PANSS, QoL was assessed with the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q), and adverse effects (hyperprolactinemia, extrapyramidal symptoms, sedation, metabolic changes) were monitored. Non-parametric tests and multiple linear regression were applied. Results: At 12 months, RFM patients showed significantly higher PANSS scores, markedly more adverse reactions (95% vs. 48.1%), and lower PQ-LES-Q total and domain scores (all p < 0.0001) compared to NM patients. A regression analysis identified the metabolizer status (β = −0.410, p = 0.001), extrapyramidal symptoms (β = −0.248, p = 0.003), sedation (β = −0.193, p = 0.029), and hyperprolactinemia (β = −0.190, p = 0.012) as independent predictors of a reduced QoL, explaining 84% of the variance. The residual symptom severity was not independently associated. Conclusions: In adolescent schizophrenia, the CYP2D6-reduced metabolizer status is the strongest independent predictor of long-term QoL impairment, associated primarily through a substantially higher burden of treatment-related adverse effects (metabolic, endocrine, neurological, and sedative) rather than through persistence of psychotic symptoms alone. These findings support early pharmacogenetic testing to guide individualized dosing and improve tolerability and patient-reported outcomes. Full article

Background/Objectives: Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that is critical for intestinal immune homeostasis. Despite its therapeutic potential, systemic delivery of IL-10 has failed in clinical trials for inflammatory bowel disease (IBD), largely due to its poor localization and short half-life. Methods: We present a proof-of-concept study demonstrating that hydrodynamic delivery of a naked plasmid bearing the human IL-10 gene to ex vivo human colonic segments from Crohn’s disease patients results in localized IL-10 expression and modulation of inflammatory mediators. Results: Compared to venous administration, arterial delivery yielded significantly higher IL-10 mRNA and protein levels, as well as decreased IL-6 and TNF-α expression. Furthermore, nanoparticle tracing confirmed efficient tissue penetration via the arterial route. Conclusions: These findings establish arterial hydrodynamic delivery as a feasible, non-viral strategy for targeted gene therapy in IBD. Full article

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Beyond established risk factors such as smoking and exposure to pollutants increasing evidence emphasizes the role of oxidative stress (OS) in COPD pathophysiology. OS contributes to chronic inflammation, to the progression of the disease and affects both lung function and exacerbations, which opens a rationale for the use of antioxidant and redox-modulating substances in the treatment of the disease. Although numerous substances with antioxidant capacity have been evaluated in randomized clinical trials (RCTs), their clinical relevance remains uncertain. Therefore, a systematic review was conducted to evaluate the effects of these therapies in COPD. Also, a meta-analysis to evaluate the effects on exacerbations was performed. Nineteen RCTs meet the eligibility criteria and were included in the study. Quantitative analyses were performed using random-effects models. N-acetylcysteine-based interventions were associated with a significant reduction in exacerbation risk (risk ratio 0.80; 95% confidence interval 0.66–0.98), corresponding to a 20% relative reduction. No study reported serious adverse effects. These findings suggest that antioxidant-based strategies may have clinically meaningful benefits in COPD. However, larger, more robust RCTs are required to confirm these results and establish optimal therapeutic strategies. Full article

Background/Objectives: Pharmacogenomics (PGx) enables personalized therapy by identifying genetic variants that influence drug response. Despite the advantages of next-generation sequencing (NGS), few clinically validated, guideline-aligned panels comprehensively detect common, rare, and structurally complex pharmacogenetic variants. Methods: We developed and analytically validated Action PharmaKitDx, a targeted NGS panel covering 335 pharmacogenes, including all priority genes recommended by CPIC, DPWG, and CPNDS. Performance was assessed using Coriell HapMap and GeT-RM reference materials across multiple library preparation workflows and Illumina platforms. Clinical feasibility was evaluated in 41 patient samples from diverse specialties. Results were compared with established reference methods, including PCR-based assays, STR analysis, Sanger sequencing, and whole-exome sequencing. Results: Analytical validation: More than 99% of target bases achieved ≥30× coverage. Analytical accuracy, sensitivity, specificity, and positive predictive value exceeded 99.3%, with repeatability and reproducibility >99.7%. Concordance with GeT-RM haplotypes reached 98% after star-allele harmonization. The panel accurately detected complex variants, including CYP2D6 copy-number changes and hybrid alleles. Clinical validation: Full concordance with prior genotyping was observed in clinical samples. Beyond the initial testing indication, each sample harbored a mean of six actionable variants (range 2–10). Thirty-six rare (minor allele frequency <1%) potentially actionable variants were additionally identified. Conclusions: Action PharmaKitDx demonstrates high analytical performance and broad clinical applicability, supporting its implementation as a scalable solution for comprehensive pharmacogenetic testing and precision prescribing. Full article

Purpose: Bortezomib (BTZ) is widely used in multiple myeloma (MM), but its toxicity shows marked interindividual variability. This study aimed to identify pharmacogenetic and clinical factors associated with BTZ-related adverse drug reactions (ADRs). Methods: A retrospective and prospective observational study was conducted in 127 MM patients treated with BTZ-based regimens. Polymorphisms in CYP enzymes and ABCB1 were genotyped using qPCR. Associations between genetic variants, treatment response, and ADRs were assessed using univariate and multivariate analyses with Benjamini–Hochberg correction. Results: ADRs occurred in 98.4% of patients, most commonly gastrointestinal toxicity (49%), general toxicity (46%), and peripheral neuropathy (39%). Women showed higher rates of gastrointestinal toxicity and non-peripheral neurotoxicity. Multivariate analysis identified the ABCB1 C1236T A/G genotype as protective against gastrointestinal toxicity, while the CYP3A4 intermediate metabolizer phenotype was associated with increased psychiatric toxicity. TP53 mutations were independently associated with hematologic and renal toxicity. Kaplan–Meier analysis showed earlier onset of peripheral neuropathy and respiratory toxicity in CYP3A4 intermediate and poor metabolizers. Conclusions: Genetic variation in ABCB1 and CYP3A4, together with clinical factors such as TP53 mutation and sex, may contribute to interindividual variability in BTZ safety in MM. These findings should be considered exploratory given the sample size and require confirmation in larger cohorts. Nonetheless, they suggest a potential role for pharmacogenomics in supporting future approaches to treatment personalization. Full article

Background: Psoriasis is a chronic immune-mediated inflammatory disease with a strong genetic basis, driven in part by the dysregulation of the IL-23/Th17 signaling axis. Variants in the IL23R and IL12B genes have been associated with psoriasis susceptibility; however, data from Eastern European populations remains scarce. Objective: We aimed to evaluate the link between IL23R rs11209026 and IL12B rs3213094 polymorphisms and psoriasis susceptibility in a multi-center, Romanian cohort. Methods: We performed a multi-center case–control study including adult patients with clinically and histopathologically confirmed moderate-to-severe psoriasis undergoing biological therapy and controls without autoimmune or chronic inflammatory diseases. Genotyping was performed using TaqMan SNP assays. Associations were analyzed under a dominant genetic model. Results: A significant association was observed between IL23R rs11209026 polymorphism and psoriasis susceptibility. Carriers of the A allele (AA+GA) showed reduced odds of psoriasis compared with the GG homozygotes, emphasizing the protective effect of this specific variant. No significant association was identified for IL12B rs3213094 polymorphism. Conclusions: Our findings support the protective association of IL23R rs11209026 A allele with psoriasis in a Romanian Eastern European population and emphasize the importance of the IL-23 pathway in disease pathogenesis. Alcohol consumption was independently associated with increased risk of psoriasis. Further studies are justified to explore potential pharmacogenetic implications. Full article