Sexual healthGuojun Liang, Hao Huang, Haokui Wang, Qiong Liu, Yang Song
BACKGROUND: Flibanserin, a centrally acting 5-HT1A agonist and 5-HT2A antagonist, is the first approved therapy for acquired, generalized hypoactive sexual desire disorder in premenopausal women. Despite its clinical availability, post-marketing data on real-world safety remain limited. METHODS: A retrospective pharmacovigilance analysis was conducted using the US Food and Drug Administration Adverse Event Reporting System from 2016 to 2025. Duplicate removal, data harmonization and standardized MedDRA coding were applied. Only reports in which flibanserin was designated as the primary suspect drug were included. Disproportionality analyses using proportional reporting ratio, reporting odds ratio, information component and empirical Bayes geometric mean algorithms identified flibanserin-associated safety signals. Sensitivity analyses were conducted according to recorded concomitant medication status. RESULTS: A total of 1702 adverse event reports were identified, with 95% involving women. Most events were non-serious and occurred within the first week of therapy (median onset: 3 days). Prominent signals were nervous system and psychiatric disorders, notably somnolence, dizziness, insomnia and fatigue. Additional signals included hypotension, orthostatic hypotension and product use in unapproved populations, suggesting off-label exposure. Central nervous system-related signals remained directionally consistent in flibanserin-only and concomitant-medication cohorts, whereas hypotension was prominent among reports with recorded concomitant medications. CONCLUSIONS: Flibanserin's real-world safety profile is largely consistent with preapproval data, dominated by early-onset, reversible central nervous system reactions linked to its serotonergic mechanism. However, persistent hypotension and off-label or product-use-related reports underscore the need for continued pharmacovigilance, clinician education, and strict adherence to Risk Evaluation and Mitigation Strategy requirements to maintain an optimal benefit-risk balance.
Journal of the American College of Clinical Pharmacy : JACCPJohn P Bomkamp, Benjamin V Craft, Holly Nuest, Matthew Bjornstad, Jennifer Slavens
BACKGROUND: Pharmacist-driven microbiology review programs have been thoroughly described in the emergency department setting. However, there is limited evidence for programs in outpatient settings, especially for urgent care settings. The purpose of this study is to evaluate a pharmacist-driven urgent care microbiology review program to determine the impact of its implementation. METHODS: This retrospective cohort study evaluated urgent care patients who did not receive appropriate treatment based on urine, wound, or respiratory culture, or select sexually transmitted infection testing. A pharmacist-driven microbiology review program at two urgent cares was compared to 11 other urgent cares using only physician/advanced practice provider (APP) review of microbiology results. The primary end point was the time to appropriate treatment in hours from finalized result to prescription of appropriate treatment. Secondary end points included time to appropriate treatment in calendar days and unplanned 30-day revisit rate. RESULTS: A total of 400 patients were included in this study (pharmacist-driven, n = 200; physician/APP, n = 200). Time to appropriate treatment in hours was 11 h in the pharmacist-driven cohort and 13 h in the physician/APP cohort (p = 0.047). Unplanned 30-day revisit rate was similar between the two groups (pharmacist-driven 14% versus physician/APP 12.5%, p = 0.658). CONCLUSION: A pharmacist-driven urgent care microbiology review program achieved a similar time to appropriate antimicrobial treatment compared with a physician/APP process while maintaining comparable clinical outcomes.
Journal of the American College of Clinical Pharmacy : JACCPAngela Mercado, Jacob M Noble, Adriane N Irwin, Melissa E Badowski, Nitish Bangalore, Gina Caliendo, David C M Chan, Zachary J Dumont, Christine M Groth, Mais …
Key performance indicators (KPIs) are quantifiable measures that describe critical success factors of an organization. Their vital role in ensuring the delivery of quality health care services necessitates the development of KPIs relevant to inpatient clinical pharmacy practice. This opinion paper from the American College of Clinical Pharmacy (ACCP) Clinical Administration Practice and Research Network (CADM PRN) describes the rationale, methodology, and outcomes of a consensus process to identify a focused set of inpatient/acute care clinical pharmacy KPIs. Leveraging a modified Delphi approach, the CADM PRN convened an Expert Panel of clinical pharmacy leader members to build a consensus-driven set of KPIs reflecting clinical, operational, patient-centered, and financial contributions of clinical pharmacists in the inpatient/acute care setting. From a previous ACCP White Paper, a total of 15 KPIs were identified across four domains: (1) clinical practice and patient safety, (2) clinical outcomes and readmissions, (3) medication education and patient engagement, and (4) financial and operational value. The CADM PRN posits that the establishment and implementation of standardized KPIs are essential for measuring and demonstrating the value of clinical pharmacy services in modern health care, offers pragmatic, consensus-based KPIs for evaluating clinical pharmacy services supporting resource justification, and advancing the visibility and impact of pharmacists in acute care practice. As hospitals shift toward value-based care, robust KPI frameworks will be critical for optimizing patient outcomes, supporting financial sustainability, and justifying appropriate staffing. Future efforts should focus on pilot testing, addressing implementation barriers, and achieving broader acceptance for KPIs across the profession.
Journal of the American College of Clinical Pharmacy : JACCPHannah Webb, John G Gums
Music-based interventions (MBIs) have emerged as a promising, nonpharmacologic approach to improving patient care across a variety of clinical settings. This narrative review examines the current evidence describing the mechanistic basis through which music engages biological pathways relevant to clinical pharmacy practice, and the clinical evidence supporting MBIs as adjuncts to pharmacotherapy across clinical outcomes. From this evidence, the review proposes a framework through which MBIs may be integrated into clinical practice that comprises: (1) patient selection, (2) MBI selection, and (3) outcome monitoring. The review does not constitute formal practice guidance, as pharmacy-specific clinical protocols and implementation models remain active areas of research. Additionally, the review synthesizes emerging evidence supporting MBIs as a clinical pharmacy workforce well-being strategy. Collectively, these findings highlight the potential for MBIs to serve as an innovative adjunct to traditional pharmacotherapy that aligns with the clinical pharmacist's existing responsibilities for medication optimization, deprescribing, and holistic, patient-centered care.
Pharmacology research & perspectivesBjörn Ericsson, Ulf Lindahl, Johanna Villén, Marmar Nekoro, Helena Ramström, Björn Wettermark
During the past two decades, it has become evident that pharmaceuticals is an emerging environmental problem. In this study, we present the experiences from two Swedish Drug & Therapeutics Committees (DTCs) on how they integrate environmental considerations into their formularies and continuous professional education activities. A cross sectional study was performed describing activities to promote sustainable prescribing conducted during two decades by the DTCs in the Swedish regions of Gävleborg and Västernorrland, along with trends in sales of diclofenac and fluoroquinolones between 2000 and 2024. The two DTCs integrate environmental considerations in their formularies and continuous professional education activities. Further acitivities include monitoring of prescribing, dialogue with water suppliers and pharmacies, as well as information and communication to the general public. The total utilization of diclofenac for systemic use peaked with 127 kg in Gävleborg and 137 kg in Västernorrland in 2011, after which the amounts declined. The topical formulations were mainly sold as over-the-counter and increased until 2016, when it started to decline. The amounts of ciprofloxacin and norfloxacin increased until 2012 when they started to decline. This case study from two Swedish regions illustrates how environmental considerations can be incorporated into the DTC's mission to promote rational and responsible medication use. We believe it may be valuable for different stakeholders to show potential ways in how to promote a more sustainable use of medicines.
Basic & clinical pharmacology & toxicologyRonja Levomäki, Päivi Hirvensalo, Aleksi Tornio, Anne M Filppula
The 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor rosuvastatin is a substrate of breast cancer resistance protein (BCRP). BCRP inhibition increases rosuvastatin plasma concentrations and may result in concentration-dependent muscle toxicity, at worst rhabdomyolysis. We investigated if concomitant use of rosuvastatin and drugs identified as in vitro BCRP inhibitors shows an increased number of rhabdomyolysis events based on pharmacovigilance data. From reports in the US Food and Drug Administration Adverse Event Reporting System for patients using rosuvastatin, we formed interaction (rosuvastatin with inhibitor) and non-interaction (rosuvastatin without inhibitor) groups for 71 BCRP inhibitors. These groups were further divided into subgroups with or without rhabdomyolysis. For each inhibitor, we calculated reporting odds ratio (ROR) and 95% confidence intervals (CIs). We identified 9777 individual rosuvastatin-related reports during 2013-2023, including 815 rhabdomyolysis reports. Of the 71 inhibitors, 19 had enough reports for analysis. Significantly increased RORs were obtained for the clinical BCRP inhibitors febuxostat (ROR 2.47, 95% CI 1.38-4.43) and ticagrelor (ROR 4.15, 95% CI 3.32-5.20). Amiodarone, erlotinib and rifampicin showed significantly increased RORs. Our findings support known interactions involving febuxostat and ticagrelor and suggest that also other BCRP inhibitors may increase the risk of rosuvastatin-induced rhabdomyolysis.
This study aimed to examine sex-disaggregated adverse event signals associated with growth impairment in pediatric patients, utilizing data from the FDA adverse event reporting system, with a particular focus on growth hormone and related therapeutic agents. A disproportionality analysis was performed on FDA adverse event reporting system data spanning 2004 Q1 to 2025 Q1. The analysis encompassed 3281 growth impairment-related reports, disaggregated by gender, employing Reporting Odds Ratios (ROR) and proportional reporting ratios for signal detection, with temporal patterns assessed via Weibull distribution modeling. Significant sex-disaggregated disparities in safety signals were identified. Somatropin exhibited a stronger association with growth impairment in females (ROR 76.85, 95% CI 65.52-90.15) than in males (ROR 37.31, 95% CI 32.99-42.20). Deflazacort showed a male-exclusive signal (ROR 58.25, 95% CI 41.27-82.21), while imatinib displayed a higher risk in females (ROR 15.55, 95% CI 11.29-21.42) compared to males (ROR 4.17, 95% CI 2.91-5.99). Temporal analysis revealed an early-failure pattern, with 50.6% of events occurring within 180 days. These findings generate the hypothesis that sex-disaggregated pharmacovigilance in pediatrics, particularly for growth-modulating therapies, may reveal differential reporting patterns. Should these signals be validated in controlled prospective studies, they could inform the development of customized monitoring frameworks and dosing strategies aimed at potentially mitigating risks in hypothesized high-risk subgroups.
MedicineGuanbo Xie, Huili Weng, Jingxian Yu, Liqun Chi
Zuranolone and Brexanolone are Food and Drug Administration-approved novel agents for postpartum depression, yet real-world post-marketing safety data for the two drugs remain insufficient. This study aimed to systematically characterize their adverse event (AE) profiles via two authoritative pharmacovigilance databases, namely the Food and Drug Administration Adverse Event Reporting System (FAERS) and VigiAccess. FAERS data from Q1 2019 to Q3 2025 and VigiAccess data updated to November 2025 were extracted. Reporting odds ratio and proportional reporting ratio were adopted to screen and compare AE signals of the two drugs. A total of 631 primary suspect (PS) drug reports for Zuranolone and 102 for Brexanolone were extracted from FAERS, whereas 863 Zuranolone and 227 Brexanolone reports were obtained from VigiAccess. At the system organ class level, AEs associated with Zuranolone involved 22 SOCs in FAERS and 24 SOCs in VigiAccess, with the top three SOCs sorted by reported cases as follows: Nervous system disorders, Psychiatric disorders, and General disorders and administration site conditions (FAERS); Nervous system disorders, General disorders and administration site conditions, and Psychiatric disorders (VigiAccess). For Brexanolone, AEs retrieved from FAERS involved 16 SOCs, compared with 21 SOCs in VigiAccess; the top three SOCs by the number of reported cases were Injury, poisoning and procedural complications, General disorders and administration site conditions, and Psychiatric disorders. After signal screening in the FAERS database, a total of 78 positive signals (involving 9 SOCs) were identified for Zuranolone, whereas 10 positive signals (involving 4 SOCs) were detected for Brexanolone. Four SOCs were commonly implicated in the positive AE signals of both drugs, with the most commonly reported AEs including gait disturbance, exposure via breast milk, fatigue, and therapy cessation. Additionally, compared to Brexanolone, 5 SOCs were uniquely associated with Zuranolone, with the most commonly reported AEs such as vertigo, vision blurred, muscle twitching, somnolence, and loss of personal independence in daily activities. Zuranolone's AEs mainly involved nervous system disorders and Psychiatric disorders, while Brexanolone's primarily included Injury, poisoning and procedural complications, and Psychiatric disorders. This study would provide more safety reference data for the clinical use of two drugs.
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal ObstetriciansDaisuke Kikuchi, Taku Obara, Aoi Noda, Takamasa Sakai, Chiemi Ogura, Keiko Minato, Ami Murata, Naoko Matsuda, Kouji Okada, Atsuko Tominaga, Yuriko Murai
INTRODUCTION: Ritodrine hydrochloride has been widely used in Japan to treat threatened preterm labor, often beyond the internationally recommended short-term duration. Accumulating evidence has demonstrated limited benefits and raised safety concerns regarding prolonged ritodrine administration, and a declining trend in its use has been documented through 2021. However, prescribing trends following the March 2021 revision of the ritodrine package insert remain unclear. Here, we investigated recent nationwide trends in ritodrine prescriptions among pregnant women in Japan from 2015 to 2024, with particular focus on trends after 2021, and examined differences according to route of administration and healthcare setting. METHODS: Administrative data on pregnant Japanese women who visited acute-care Diagnosis Procedure Combination (DPC) hospitals between January 1, 2015, and December 31, 2024, were used in this study. The analysis focused on ritodrine products marketed in Japan. The prevalence of ritodrine prescriptions was analyzed, and temporal trends were assessed using the Cochran-Armitage trend test. Stratified analyses were performed according to age group, hospital bed capacity, and hospital type. RESULTS: Among hospitalized pregnant women, the prevalence of oral ritodrine prescriptions decreased from 22.0% to 17.2% (absolute decrease of 4.8 percentage points, p < 0.001) during the study period (2015-2024), whereas that of injectable ritodrine prescriptions decreased from 37.6% to 25.0% (absolute decrease of 12.6 percentage points, p < 0.001). Among pregnant outpatients, the prevalence of oral ritodrine prescriptions decreased from 58.5% to 34.5% (absolute decrease of 24.0 percentage points, p < 0.001), whereas that of injectable ritodrine prescriptions increased slightly from 0.42% to 0.46% (absolute increase of 0.04 percentage points, p = 0.01), although outpatient injectable ritodrine prescribing remained below 1% throughout the study period. The decline was more pronounced for oral ritodrine prescriptions than for injectable ritodrine prescriptions. CONCLUSION: Ritodrine prescriptions among pregnant women in Japan decreased between 2015 and 2024 for both oral and injectable formulations in hospitalized settings and for oral formulations in outpatient settings. The decline continued after the 2021 package insert revision, suggesting ongoing changes in prescribing practices related to prolonged ritodrine use.
The Journal of dermatological treatmentFilip Rob, Alena Machovcová, Marie Jandová, Martin Tichý, Yveta Vantuchová, Miroslav Nečas, Martina Kojanová, Petra Cetkovská, Jana Třešňák Hercogová, Spyridon…
INTRODUCTION: Switching biologics for psoriasis is common; however, data on switching to alternative treatments after failure of IL-23 inhibitors are limited. METHODS: A retrospective analysis was conducted to extract efficacy and drug survival data from the BIOREP registry from January 2015 to June 2025. The analysis included all patients with psoriasis who were switched from an IL-23 inhibitor to an IL-17 inhibitor during this period and had at least one follow-up visit recorded. RESULTS: A total of 102 patients were switched from an IL-23 inhibitor to an IL-17 inhibitor, with 92 (90.2%) of these switches occurring due to insufficient efficacy. In these 92 patients, PASI-75 was achieved in 82.6% after 3 months and in 73.5% after 12 months. Absolute PASI ≤ 1 was achieved by 66.3% of patients after 3 months and 52.9% after 12 months. Patients treated with bimekizumab had the highest probability of meeting both efficacy parameters, particularly an absolute PASI ≤ 1 after 3 months. The overall survival probability was 79.5% after 12 months and 68.1% after 24 months. CONCLUSION: For patients with an inadequate response to IL-23 inhibitors, switching to IL-17 inhibitors offers adequate efficacy in reaching current therapeutic goals during the first year of treatment.
Saudi medical journalAbdulrahman G Alharbi, Abdulrahman A Aljabri
The integration of artificial intelligence (AI) into pharmaceutical care represents a paradigm shift in healthcare delivery, offering unprecedented opportunities to revolutionize medication management, accelerate drug development, and enhance patient outcomes. This comprehensive review synthesized evidence from global literature (2021-2025) examining AI applications across drug discovery and development, clinical trials optimization, medication therapy management, and pharmacy operations. The AI demonstrated prediction accuracies of 86-98% in drug discovery, 80% improvement in clinical trial recruitment efficiency, and 32.7% increase in medication adherence over standard care. The global AI drug discovery market, valued at $1.5 billion (2023), is projected to reach $11.8 billion by 2030, reflecting substantial industry investment. However, implementation challenges persist including data quality concerns (30% accuracy in some datasets), regulatory compliance issues, and algorithmic bias (8-12% performance variations across demographics). Successful implementation requires coordinated efforts across technological development, regulatory frameworks, healthcare professional training, and continuous validation protocols addressing technical, organizational, and ethical dimensions simultaneously.
Sleep problems, particularly insomnia, are common among children and adolescents, and may have been exacerbated during the COVID-19 pandemic. However, long-term trends in pediatric hypnotic prescribing and changes associated with the pandemic remain poorly characterized. Using the JMDC Claims Database, we conducted an observational study of children and adolescents aged 2-18 years in Japan between January 2014 and December 2023 to examine hypnotic prescribing by age, sex, and pharmacological class and changes following the April 2020 COVID-19-related state of emergency. The proportion of children and adolescents prescribed hypnotics increased from 0.4% (2800 of 673,141) in 2014 to 1.0% (23,977 of 2,401,028) in 2023, with larger increases among adolescents and females. Prescribing of benzodiazepines and benzodiazepine receptor agonists decreased, whereas prescribing of melatonin receptor agonists and orexin receptor antagonists increased. Interrupted time-series analysis showed a significant increase in the slope after April 2020, whereas the immediate level change was not statistically significant. The post-state-of-emergency slope change was 3.64 (95% CI, 2.69 to 4.58; P < 0.001) prescriptions per 100,000 population per month. In sensitivity analyses excluding melatonin, post-state-of-emergency increases were attenuated overall and persisted mainly among adolescents. Pediatric hypnotic prescribing in Japan increased over the past decade, with distinct age-, sex-, and pharmacological class-specific patterns. Although prescription rates accelerated after April 2020, increases were already evident before the COVID-19 pandemic. Continued increases suggest that pre-existing trends and newly available pharmacological options, in addition to pandemic-related changes, may have contributed to the upward trend, particularly among adolescents and females.
Future healthcare journalAnmar Al-Taie, Ahmed Shaheen Abdullah, Oritsetimeyin Arueyingho
PURPOSE: Artificial intelligence (AI) is increasingly being integrated into healthcare systems, offering new opportunities to enhance the safety, efficiency and effectiveness of clinical pharmacy services. This scoping review aimed to systematically map the current applications of AI in clinical pharmacy practice and to identify the medication-management functions supported by these technologies. METHODS: A literature search was conducted following PRISMA-ScR guidelines, covering studies published between 2010 and 2025 in databases such as PubMed, Web of Science and Scopus. Included studies focused on the application of AI in clinical pharmacy services within hospital and community settings. Studies were screened at the title, abstract and full-text levels, followed by data extraction and synthesis. Eligible studies were required to be peer-reviewed, written in English, and to include relevant keywords exploring the intersection of artificial intelligence and pharmacy practice. RESULTS: A total of 36 publications were included in the final assessment and analysis. Most studies focused on AI applications for the detection of drug interactions and adverse drug effects (n = 12, 33.3%), followed by studies for medication errors and potentially inappropriate medications (n = 11, 30.6%). Machine learning techniques, including natural language processing and deep learning, were the most commonly used AI technologies. CONCLUSIONS: The development of AI-powered applications and tools for clinical pharmacy services is a promising approach. However, significant efforts, in collaboration with relevant stakeholders, are needed to explore how these AI technologies can add value to clinical pharmacy services in both community and hospital settings.
Journal of medical economicsCelia Oreja-Guevara, Lamberto Landete, Miguel Ángel Rodriguez Sagrado, Isabel Moya, Bleric Alcala Revilla, Heidi DelosSantos Real, Maria Luz Bernat Pinto, Gera…
AIMS: With the expanding range of disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS), clinicians face increasing complexity in defining optimal treatment sequences and timing of therapy switches. In this study, we adapted an earlier computer-assisted model to optimize therapeutic decisions and identify preferred treatment pathways, based on expert opinion and observations from clinical practice in Spain. MATERIALS AND METHODS: The original model was updated to integrate magnetic resonance imaging (MRI) activity data and define reaching an Expanded Disability Status Scale (EDSS) score of 3 - indicating moderate disability without ambulation impairment - as a criterion for switching treatment. Matrices were designed to model options when switching DMTs, triggered by either a lack of effectiveness or safety concerns. Change in DMT was based on a set of composite criteria (encompassing contributions from relapses, disability worsening, MRI activity, costs, and quality of life) according to the disease activity level. A maximum of three DMTs could be administered within the 8-year time horizon evaluated. RESULTS: The revised model identified high efficacy treatment, in particular cladribine tablets as the preferred initial DMT for patients with RRMS with mild or moderate disease activity. Of these patients with mild and moderate disease activity, most were switched to ofatumumab (79.4%) and ocrelizumab (75.9%), respectively, when disease progression occurred. Patients with high disease activity mostly received natalizumab if they were John Cunningham virus (JCV)-negative, or ocrelizumab if they were JCV-positive. LIMITATIONS: The model is informed by a Spain-based healthcare expert panel and has been evaluated using a simulated cohort of 10,000 patients with RRMS. CONCLUSION: This computational model helps to inform clinicians towards making optimal treatment decisions for RRMS, and identified high-efficacy DMTs as the preferred model-based option for all levels of disease activity, supporting early and effective control of disease activity in real-world clinical practice.
International journal of medical informaticsAna Carolina Jacoby, Mell Amisa Matsuda, Carine Raquel Blatt, Sílvio César Cazella
BACKGROUND: Pharmacovigilance is dedicated to the identification, evaluation, and prevention of adverse effects associated with the use of medicines after their commercialization. In this context, data mining techniques have been widely employed for the detection of safety signals. Although machine learning algorithms show potential to identify complex patterns and improve the prediction of adverse drug reactions, their application in pharmacovigilance databases remains limited. OBJECTIVE: To map the computational approaches used in pharmacovigilance, to identify the prevalence of traditional statistical methods and data mining techniques, and to assess the role of machine learning algorithms. METHODS: This scoping review followed PRISMA‑ScR guidelines (protocol registered on OSF: https://doi.org/10.17605/OSF.IO/KZJDT). We searched PubMed, Scopus, Embase, and Web of Science for English primary studies published from 2015 to July 2025 that applied data mining techniques to pharmacovigilance databases. Data extraction used a standardized form. RESULTS: The search identified 1,468 records, of which 162 studies were included after screening and eligibility assessment. Traditional disproportionality methods, such as Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR), were used in 87.7% of the studies, whereas 12.3% applied machine learning or deep learning techniques, mainly in classification tasks, with logistic regression being the most frequently employed algorithm. The most investigated drugs included immune checkpoint inhibitors, such as nivolumab, pembrolizumab, atezolizumab, and durvalumab. The most studied therapeutic classes were antineoplastic agents, immunosuppressants, and psycholeptics. CONCLUSION: Signal detection in pharmacovigilance remains predominantly based on classical statistical methods. Progress in the field is still constrained by the slow incorporation of advanced machine learning techniques and the limited public availability of datasets used in analyses.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research AssociationHayden Farquhar
Dietary supplements are consumed by over half of US adults, yet post-market safety surveillance remains limited. We applied four disproportionality methods (PRR, ROR, GPS, BCPNN), CUSUM temporal detection, and demographic stratification to 48,840 dietary supplement adverse event reports from the FDA CAERS database (2004-2025). Analysis was conducted at the product-name level, not the ingredient level, and the signals reported below are product-name-level signals to be interpreted as flags for further investigation rather than confirmed ingredient-specific risks. Of 4779 product-adverse event pairs, 3017 (63.1%) were detected by three or more methods. After variant-name consolidation of the most heavily fragmented products (Section 4.4 and Supplementary Material 4), this resolves to an estimated 1800-2200 distinct product-level signals. Kratom dominated the critical risk tier, with Kratom-Death ranked highest (PRR 19.7, N = 178). Hepatotoxicity signals clustered in herbal/botanical and weight loss products. Herbal/botanical supplements carried the highest serious outcome rate among classifiable products (78.0%; adjusted OR 2.08, 95% CI 1.53-2.84); the 54% "Other"-category share, however, limits the generalisability of category-specific estimates to all supplements within each nominal category. CUSUM detected 451 temporally emerging signals including preliminary hepatic enzyme elevations for AG1 and Nutrafol (2023-2025). Of consensus signals, 97.3% survived false discovery rate correction; 81% of established international supplement safety signals were recovered. These findings support regulatory prioritisation of herbal/botanical and weight loss supplement categories and identify emerging signals warranting continued monitoring.
International journal of medical informaticsAudrey Dintilhac, Laura Lohan, Marion Laureau, Damien Perier, Philippe Cestac, Blandine Juillard-Condat, Cyril Breuker
INTRODUCTION: Adverse drug events (ADEs) constitute a major clinical and economic burden in Europe. While hospital pharmacy activities improve prescription safety, pharmacists cannot review all orders in time and must prioritize high-risk patients. Rule-based clinical decision support systems (CDSS) offer an additional preventive strategy but often generate excessive, low-relevance alerts. OBJECTIVE: To develop rules for detecting iatrogenic risk in accordance with methodological standards reported in the literature, using ADEs identified in a prospective cohort of adult patients admitted to the emergency department of a French healthcare institution (2,600-bed tertiary care center). METHODS: ADEs were identified through a structured medication history interview conducted by a trained clinical pharmacist upon the patient's admission to the emergency department. To focus on the most critical situations, drug classes defined at the fourth level of the Anatomical Therapeutic Chemical (ATC) classification system (ATC4) and associated with the highest risk were identified by considering prescription frequency, ADE occurrence, and ADE severity. For each selected ATC level 4 class, logistic regression models were used to assess the association between ADE probability and specific explanatory factors. These factors were then operationalized into rules designed to detect iatrogenic risk. RESULTS: A total of 245 ATC4 classes were involved in at least one ADE. Among these, 22 classes were identified as high iatrogenic risk, accounting for approximately 50% of prescriptions leading to an ADE, with vitamin K antagonists and heparins showing the highest risk. Regression analyses resulted in 58 distinct rules: 31 (53.4%) combined prescription data with at least one laboratory parameter, 8 (13.8%) incorporated demographic variables (age or sex), and 19 (32.8%) were based solely on medication prescription data. CONCLUSION: The clinical and pharmaceutical relevance of the proposed rules must be further evaluated to reduce excessive alert generation, which may lead to disengagement from both pharmacists and prescribers. The institutional health data warehouse could provide an appropriate environment for this evaluation.
Exploratory research in clinical and social pharmacyRoshan Giri, Rohit Agrawal, Sabin Raj Lamichhane, Rachana Mahatara
OBJECTIVES: The global shift toward patient-centered clinical pharmacy services is governed by Good Pharmacy Practice (GPP) standards. However, implementing these in low-middle income countries (LMICs) remains challenging due to resource and infrastructure constraints. This study aimed to implement GPP standards at a central tertiary hospital using the Plan-Do-Study-Act (PDSA) cycle. METHODS: A prospective, interventional quality improvement study was conducted at a tertiary care central hospital over five months. Intervention included functional decentralization of services, development of 21 Standard Operating Procedure (SOPs) using the ALCOA+ framework, and staff training. Four longitudinal audits were performed using an expanded 125-indicator Department of Drug Administration (DDA) checklist. Root cause analysis (RCA) via the "5 Whys" technique addressed implementation barriers. RESULTS: Overall median GPP compliance increased from 57.1% (IQR: 25.0%-77.8%) to 100.0% (IQR: 100.0%-100.0%) by final audit (p < 0.0001). High-compliance domains rose from 17.6% to 88.2%. The Hodges-Lehmann estimator indicated a median improvement of 43.7% (95% CI: 22.2% - 62.5%). Qualitative analysis revealed that documentation gaps were rooted in ergonomic friction rather than incompetence; relocating logbooks to dispensing counters resolved these issues. A ceiling effect was observed in store management (91.7% compliance) due to fixed architectural constraints. CONCLUSION: The PDSA model is an effective framework for driving rapid quality improvement in resource-limited pharmacy settings. Success was achieved not only through procedural changes but by transitioning staff culture from a "money-driven" mindset to "professional ownership". This study provides a scalable roadmap for GPP implementation and suggests that national audit tools should adopt tier-specific indicators for tertiary facilities.
SeizureSamuel Oliveira de Amorim, Nathan Fellipe Cardoso da Silva, Matheus da Silva Ferreira, Cid Soares, Felipe Henrique Lima Pereira, Rayan Moura Patrik Naim, Vitór…
BACKGROUND: Oxcarbazepine (OXC) is widely used in focal epilepsy but is frequently limited by tolerability issues, particularly neurovestibular and sedative adverse events. Switching to eslicarbazepine acetate (ESL) has emerged in clinical practice as a pragmatic strategy to improve tolerability, although the available evidence remains fragmented and predominantly observational. MATERIAL AND METHODS: We conducted a systematic review and single-arm meta-analysis of studies reporting outcomes after switching from OXC to ESL in patients with focal epilepsy. PubMed, Embase, Scopus, Cochrane Library, and Web of Science were searched from inception to December 2025. Random-effects models were used to estimate pooled proportions for effectiveness and tolerability outcomes. Heterogeneity was assessed using the I² statistic. RESULTS: Seven studies comprising 312 patients were included. Pooled treatment retention was 74.0% (95% CI: 45.9-90.5; I²=79.2%). Resolution of OXC-related adverse events was observed in 53.1% of patients (95% CI: 12.3-90.1; I²=87.3%), although estimates showed substantial variability across studies. Somnolence improvement was reported in 28.2% (95% CI: 4.3-77.4%). The pooled response rate (≥50% seizure reduction) was 22.1% (95% CI: 6.4-53.9), while seizure freedom was achieved in 14.2% (95% CI: 4.5-37.2). Treatment discontinuation occurred in 15.0% of patients (95% CI: 7.2-28.6). CONCLUSION: Switching from OXC to ESL may represent a pragmatic strategy for patients with OXC-related intolerance, particularly when treatment retention and tolerability are prioritized. However, the observational nature of the available evidence, together with substantial heterogeneity and wide confidence intervals, limits the precision and generalizability of pooled estimates.