J Cardiothorac Surg. 2025 May 22;20(1):234. doi: 10.1186/s13019-025-03486-8.

ABSTRACT

BACKGROUND: Ascorbic acid is an essential cofactor of catecholamine synthesis that increases capillary bed density and improves microcirculation perfusion. We hypothesized early ascorbic acid administration in cardiothoracic surgery would preserve the microcirculatory integrity and minimize postoperative vasoplegia.

METHODS: This was a single-arm pilot feasibility study of adults undergoing septal myectomy combined with valve intervention or alone using cardiopulmonary bypass. Intravenous ascorbic acid 1,500 mg was administered before and immediately following cardiopulmonary bypass and every 6 h after for 12 doses. Three historical controls were identified and matched to each trial participant on age, gender, body mass index, preoperative ejection fraction, surgery performed, and time on cardiopulmonary bypass. The feasibility endpoint was a composite of successful and timely 1) ascorbic acid administration, 2) laboratory assessment, and 3) microcirculation measurements across the perioperative phases of care. Clinical endpoints included vasoplegia incidence, acute kidney injury, and lengths of stay compared to controls.

RESULTS: Fifteen patients were enrolled and compared to 45 historically matched controls. Participants' median baseline plasma ascorbic acid concentration was 0.5 (0.3, 0.9) mg/dL. Four (27%) patients had suboptimal concentrations. Eleven participants (75%) did not meet the feasibility composite endpoint due to the inability of microcirculation measurement. Incidence of vasoplegia and acute kidney injury, vasopressor duration, and lengths of stay were similar between participants and historical controls. No drug-related adverse events were noted.

CONCLUSIONS: Timely microcirculation measurements were challenging in the complex cardiothoracic surgery environment. Compared to historical controls, no meaningful differences in clinical endpoints were noted with ascorbic acid treatment. The utility of ascorbic acid on post-cardiopulmonary bypass vasoplegia remains unclear.

TRIAL REGISTRATION: ClinicalTrials.gov (NCT03744702, registered on November 14, 2018).

PMID:40400032 | DOI:10.1186/s13019-025-03486-8

BMJ Open. 2025 May 21;15(5):e088512. doi: 10.1136/bmjopen-2024-088512.

ABSTRACT

OBJECTIVE: Drug-induced ischaemic colitis is a significant adverse event (AE) in clinical practice. This study aimed to recognise the top drugs associated with the risk of ischaemic colitis based on the FDA Adverse Event Reporting System (FAERS) database.

DESIGN: A cross-sectional design.

SETTING: All data retrieved from the FAERS database from the first quarter of 2004 to the fourth quarter of 2023.

PARTICIPANTS: A total of 5664 drug-induced ischaemic colitis AEs eligible for screening.

PRIMARY AND SECONDARY OUTCOME MEASURES: The Medical Dictionary for Regulatory Activities was used to identify ischaemic colitis (code: 10009895) cases. Disproportionality analysis for drug-associated ischaemic colitis signals.

RESULTS: Drug-induced ischaemic colitis AEs were more prevalent in females (60.12%) and individuals aged ≥65 years (34.25%). The common outcomes were hospitalisation (46.85%) and death (9.73%). Disproportionality analysis identified 91 ischaemic colitis signals and the top 30 drugs mainly involved in the gastrointestinal and nervous systems. The top five drugs with the highest reported OR, proportional reporting ratio, information component and the empirical Bayesian geometric mean, were alosetron, tegaserod, osmoprep, naratriptan and kayexalate. Additionally, 20 of the top 30 drugs did not have ischaemic colitis risk indicated in the package insert.

CONCLUSIONS: This study identified key drugs associated with ischaemic colitis, particularly alosetron, tegaserod, osmoprep, naratriptan and kayexalate. Notably, two-thirds of these drugs lacked ischaemic colitis warnings in their package inserts. These findings underscore the need for greater clinical vigilance, improved regulatory oversight and further research to clarify underlying mechanisms and support safer medication use.

PMID:40398943 | DOI:10.1136/bmjopen-2024-088512

Biochim Biophys Acta Mol Basis Dis. 2025 May 19:167913. doi: 10.1016/j.bbadis.2025.167913. Online ahead of print.

ABSTRACT

Mammalian target of rapamycin (mTOR) signaling constitutes a crucial intracellular signaling pathway indispensable for regulating a variety of pathophysiological processes, including cancers. Intriguingly, the inhibition of mTOR can reverse the adverse effects induced by chemotherapy drugs; however, the fundamental mechanism underlying this phenomenon remains unclear. In this study, we demonstrate that mTOR signaling blockade can mitigate etoposide- or cisplatin-induced intestinal injury in mice. The mTOR inhibitor AZD8055 can inhibit chemotherapy drug-induced normal cell pyroptosis, as manifested by a decreased proportion of PI-positive cells, attenuated intestinal cell swelling, and reduced release of lactate dehydrogenase (LDH) and high mobility group box-1 protein (HMGB1). We further determined that mTOR inhibition suppressed the cleavage of caspase-3 and gasdermin E (GSDME), suggesting the inhibition of the caspase3/GSDME signaling pathway. We also discovered that AZD8055 can impede chemotherapy drug-induced alterations in mitochondrial membrane potential, reactive oxygen species generation, and DNA damage in intestinal cells, which are the key upstream events for activating caspase-3. Correspondingly, data from in vivo mouse models also demonstrated that AZD8055 effectively curtailed intestinal DNA damage and inflammation induced by chemotherapy drugs. Importantly, although AZD8055 counteracts the side effects of chemotherapy drugs, it does not substantially affect their anti-tumor activity. Our study proposes the potential application of mTOR inhibitors as chemoprotective agents, presenting a means to prolong the duration of chemotherapy drug use and optimize the chemotherapeutic regimen.

PMID:40398827 | DOI:10.1016/j.bbadis.2025.167913

BMC Psychiatry. 2025 May 20;25(1):509. doi: 10.1186/s12888-025-06983-1.

ABSTRACT

BACKGROUND: Treating depression in children and adolescents has always been a challenge in clinical pharmacotherapy. Vortioxetine, as a new type of antidepressant, is considered to have the potential for use in the treatment of depression in children and adolescents. This study aimed to evaluate the usage of vortioxetine and its efficacy and tolerability in children and adolescents with major depressive disorder in a real-world study.

METHODS: A retrospective survey of vortioxetine treatment was conducted at a Class A tertiary mental health hospital. Data regarding the demographic and clinical characteristics were collected among children and adolescents with major depressive disorder from electronic medical record system.

RESULTS: The study included a total of 253 depressive patients, comprising 96 males and 157 females, who were prescribed vortioxetine at any time during the research period. One hundred and twenty-three patients (43.62%) received vortioxetine treatment at the initial visit. Of the total patients, 27 (10.67%) reported side effect, such as nausea, vomiting, dizziness, palpitations, diarrhea, drowsiness, and itching. Additionally, 20 (7.91%) discontinued medical treatment due to adverse effect. No significant difference was found between males and females in drug-related adverse events (X2 = 0.56, P = 0.454). Furthermore, 96 (37.94%) reported relief from their symptoms in all patients, with a significant difference observed between males and females in reporting symptom relief (X2 = 3.934, P = 0.047). But this difference disappeared in patients who took vortioxetine alone and those who took it for more than three months.

CONCLUSION: There exists a certain proportion of children and adolescents suffering from depression who are prescribed vortioxetine in an off-label manner in psychiatric clinics. Vortioxetine demonstrates well tolerability in clinical practice. However, the proportion of self-report symptom alleviation is comparatively unsatisfactory. Furthermore, gender appears influence on self-report symptom relief.

PMID:40394553 | DOI:10.1186/s12888-025-06983-1

JACC Clin Electrophysiol. 2025 Apr 16:S2405-500X(25)00272-5. doi: 10.1016/j.jacep.2025.04.015. Online ahead of print.

ABSTRACT

BACKGROUND: Vagal responses (VR) are frequently observed during pulmonary vein isolation (PVI) with pulsed field ablation (PFA). Our aim was to compare the effectiveness of two different anticholinergic (AC) medications, namely Glycopyrrolate (GLY) or Atropine (ATP), for VR prophylaxis in patients undergoing PVI via a pentaspline PFA catheter.

METHODS: Consecutive AF patients undergoing first-time PVI with PFA were prospectively enrolled at four centres between April 2023 and March 2024. Intravenous GLY 0.2mg [Group GLY] or Atropine 1mg [Group ATP] were administered prophylactically before transseptal access. Clinically relevant VRs included sinus bradycardia (<40 beats/min), asystole (>6 sec), atrioventricular block (AVB), need for temporary backup pacing. The incidence of periprocedural VRs was compared with that of patients without prophylactic AC drug administration (Group noAC). Drug-related adverse events were compared between the two anticholinergic drugs.

RESULTS: We enrolled 240 (61±12 years, 60.0% males) patients (GLY:80 patients; ATP: 80 patients; noAC: 80 patients). Intraprocedural VRs were observed in 65 (27.1%) patients. GLY and ATP effectively reduced overall VRs (GLY: 7.5% vs. ATP: 11.3% vs. noAC:62.5%; p<0.001), asystole (GLY: 1.3% vs. ATP: 2.5% vs. noAC: 33.8%; p<0.001), and need for temporary backup pacing (GLY: 1.3% vs. ATP: 5.0% vs. noAC: 23.8%; p<0.001). The risk of overall drug-related adverse events (8.8% vs 0%; p=0.007) and drug-induced AF (5% vs 0%; p=0.043) was significantly higher with ATP.

CONCLUSIONS: Prophylactic AC drug administration effectively prevented clinically relevant VRs in patients undergoing PVI with PFA. Both AC drugs were equally highly effective, but ATP showed a significantly higher rate of drug-induced adverse events.

PMID:40392662 | DOI:10.1016/j.jacep.2025.04.015

Urolithiasis. 2025 May 20;53(1):95. doi: 10.1007/s00240-025-01760-x.

ABSTRACT

This study was designed to assess the safety and efficacy of Silodosin as a medical expulsive therapy following shockwave lithotripsy (SWL) in paediatric patients with renal stones. In this prospective randomized controlled study conducted at Tanta University Hospital from January 2022 to March 2024, thirty children with a single de novo radiopaque renal pelvic stone less than 2 cm scheduled for SWL were randomized into two equal groups. Group A (n = 15) received Silodosin 4 mg once daily after the first SWL session, and Group B (n = 15) received a matching placebo. The first dose was administered on the night of the initial SWL session and continued until stone-free status was confirmed, for a maximum of 4 weeks. The stone expulsion time was set as a primary outcome, while the secondary outcomes were one-session stone-free rate (SFR), postoperative pain scores, and Silodosin related adverse events. The results showed that the mean stone expulsion time in group A (11.4 ± 1.8 days) was significantly shorter compared to group B (16.4 ± 1.6 days; P < 0.0001). One-session SFR was 86.6% in Silodosin group compared to 73.3% in Placebo group (P = 0.6). Pain visual analogue scores were significantly lower in group A (2.31 ± 1.75) than in group B (5.08 ± 2.43; P = 0.003). No severe drug-related adverse effects were reported in either group. In conclusion, Silodosin appears to be a safe and effective adjunct to SWL in paediatric patients, significantly reducing stone expulsion time and postoperative pain. Larger studies are needed to confirm these findings.

PMID:40392272 | DOI:10.1007/s00240-025-01760-x

Hum Vaccin Immunother. 2025 Dec;21(1):2506294. doi: 10.1080/21645515.2025.2506294. Epub 2025 May 20.

ABSTRACT

This study aims to evaluate the immunogenicity and safety of hepatitis A vaccine administered with one or two doses among adults. Participants aged 18 y and above were recruited, with blood samples collected prior to vaccination for anti-HAV antibodies screening. All participants received a single dose of hepatitis A vaccine. Participants who tested negative for anti-HAV antibodies before vaccination were randomly assigned to four groups to receive the second dose at different intervals. Blood samples were collected for antibody testing. Adverse events were reported within 28 d after each vaccination for safety assessment. A total of 1,042 participants were included in study analysis. The seroprevalence of anti-HAV antibodies was 52.56%, with the lowest seroprevalence observed among adults aged 36-40 y. The overall seroconversion rate 1 month after the first dose of hep A vaccine was 67.68%. For participants in group A, the second dose was administered at a 6-month interval, both the seropositivity and seroconversion rates reached 100%, with a GMC of 3602.44 IU/L 1 months after the second vaccination. Difference of GMCs had no statistical significance across age groups. The incidence of adverse reactions (ARs) within 28 d after second vaccination in group A was 3.85%. No serious adverse events (SAEs) related to vaccination were reported. This interim analysis highlights the susceptibility of adults to hepatitis A virus (HAV). One or two doses of hepatitis A vaccine demonstrated good immunogenicity and safety in adults.

PMID:40391688 | DOI:10.1080/21645515.2025.2506294

Health Sci Rep. 2025 May 19;8(5):e70835. doi: 10.1002/hsr2.70835. eCollection 2025 May.

ABSTRACT

BACKGROUND AND AIMS: Children with congenital heart disease (CHD) often require complex pharmacotherapy for symptom management and complication prevention. However, their unique physiological profiles increase vulnerability to drug-related side effects. This study aimed to identify specialists' perspectives on drug-related side effects and associated risk factors in pediatric CHD patients.

METHODS: A cross-sectional study was conducted in 2024 involving 20 pediatric cardiologists and pediatric cardiology fellows. Data were collected using two 5-point Likert scale questionnaires assessing commonly prescribed drugs, observed side effects, and associated risk factors in pediatric CHD patients. Data were analyzed using student's t-tests and descriptive statistics.

RESULTS: According to the findings, the most frequent side effects linked to common medications were hypokalemia (Furosemide; 4.5 ± 0.69), apnea (Prostaglandin E1; 4.5 ± 0.62), and bradycardia (Sotalol; 4.41 ± 0.51). Dosage and polypharmacy emerged as major risk factors, particularly for drugs like Digoxin and Heparin. Younger age, underlying health conditions, and specific drug combinations also increased the risk of side effects. The t-test revealed significant associations between participants' demographics (sex, age, and work experience) and their perceptions of drug-related side effects and risk factors.

CONCLUSIONS: The findings emphasize the need for a personalized approach to pharmacotherapy in pediatric CHD patients, requiring careful drug selection, dose optimization, and enhanced monitoring strategies. Drug-related side effects highlight the importance of implementing clinical decision support systems, routine therapeutic drug monitoring, and individualized dosing adjustments to mitigate risks. Future research should prioritize longitudinal studies to establish causality relationships, optimize treatment protocols, and improve medication safety in this vulnerable population.

PMID:40391269 | PMC:PMC12086803 | DOI:10.1002/hsr2.70835

Clin Transl Sci. 2025 May;18(5):e70253. doi: 10.1111/cts.70253.

ABSTRACT

Evaluating clinical relevance of potential drug-drug interactions is significant for managing safety risks. However, current approaches to the evaluation lack data on rare but serious adverse events. This study aims to develop an approach to assessing clinical relevance of potential drug-drug interactions that induce rare and serious adverse events, and test its performance. In the development, three key dimensions for evaluating clinical relevance were synthesized based on a literature review. A systematic five-step approach was proposed through designated dimensions and discussions within the research team. Subsequently, the approach was applied to patients with depression to validate its ability of demonstrating the dimensions, and exacting data on rare but serious adverse events. The test results showed varying signal intensities among different drug combinations in relation to adverse events including serotonin syndrome, long QT syndrome, and Torsade de Pointes. Advanced age was identified as a confounding factor for the QT prolongation signal. These findings operationalize Dimension one: Probabilities and risk factors for the occurrence of rare and serious adverse events. Besides, in the test, fatality occurred in 22.01% of the cases having drug-triggered QT prolongation. Advancing age was associated with the fatality (odds ratio = 1.03, 95% confidence interval = 1.01-1.07). The findings manifested Dimension two: Magnitude of adverse events and associated factors. Dimension three was achieved by findings of median time-to-onset of fatal serotonin syndrome and QT prolongation, which was one and 8 days, respectively. In summary, the proposed approach demonstrates effects in assessing the clinical relevance of potential drug-drug interactions.

PMID:40390272 | DOI:10.1111/cts.70253

EMBO Mol Med. 2025 May 19. doi: 10.1038/s44321-025-00249-9. Online ahead of print.

ABSTRACT

Mutations in PIK3R1 have recently been identified in patients with overgrowth syndromes and complex vascular malformations. PIK3R1 encodes p85α which acts as the regulatory subunit of the lipid kinase PI3Kα. PIK3R1 mutations result in the excessive activation of the AKT/mTOR pathway. Currently, there are no approved treatments specifically dedicated to patients with PIK3R1 mutations, and medical care primarily focuses on managing symptoms. In this study, we identified three patients, including two children, who had mosaic somatic PIK3R1 mutations affecting the iSH2 domain, along with severe associated symptoms that were unsuccessfully treated with rapamycin. We conducted in vitro experiments to investigate the impact of these mutations, including a double PIK3R1 mutation in cis observed in one patient. Our findings revealed that p85α mutants in the iSH2 domain showed sensitivity to alpelisib, a pharmacological inhibitor of PI3Kα. Based on these findings, we received authorization to administer alpelisib to all three patients. Following drug introduction, patients rapidly demonstrated clinical improvement, pain, fatigue and inflammatory flares were attenuated. Magnetic Resonance Imaging showed a mean decrease of 22.67% in the volume of vascular malformations over twelve months of treatment with alpelisib. No drug-related adverse events were reported during the course of the study. In conclusion, this study provides support for the use of PI3Kα inhibition as a promising therapeutic approach for individuals with PIK3R1-related anomalies.

PMID:40389643 | DOI:10.1038/s44321-025-00249-9

Sci Rep. 2025 May 19;15(1):17301. doi: 10.1038/s41598-025-02359-3.

ABSTRACT

Through an in-depth analysis of ertapenem-associated adverse events (AEs) in the FDA Adverse Event Reporting System (FAERS) database, this study provides a reference for monitoring and safety management of ertapenem. Data from the FAERS database from Q1 2004 to Q1 2024 were analyzed via four nonproportional analysis techniques, including the reporting odds ratio (ROR). Gender, age, and sensitivity analyses were conducted for a more detailed assessment of ertapenem-associated signals. A total of 2,931 reports with ertapenem as the primary suspected drug were collected, covering 27 system organ classes (SOCs). The two SOCs with the strongest signals were nervous system disorders and psychiatric disorders, with overall stronger signals in individuals aged ≥ 65 years. The most frequently reported AEs were confusional state (n = 265) and convulsions (n = 214). Among the strongest signals were oropharyngeal edema (ROR = 191.05, 95% CI: 60.76-601.35) and granulomatous dermatitis (ROR = 150.49, 95% CI: 55.9-405.15). Eleven AEs not listed on the FDA label were identified. The top 20 AEs were predominantly associated with nervous system and psychiatric disorders, with a median time to onset ranging from 3.5 to 8.5 days. This study highlights the neuropsychiatric risks of ertapenem, providing strong evidence for its safety assessment and emphasizing the need for monitoring and individualized management in high-risk patients. Ertapenem, FAERS, Adverse events, Drug safety, Disproportionality analysis.

PMID:40389541 | DOI:10.1038/s41598-025-02359-3

Clin Transl Sci. 2025 May;18(5):e70222. doi: 10.1111/cts.70222.

ABSTRACT

Rational prescribing in geriatrics represents an important ethical as well as socio-economic issue. The aim of this project was to analyze the drug-related problems (DRPs) among the Czech nursing home residents and increase public awareness of further possible employment of clinical pharmacists in social care. The project was designed as a multicenter observational study. A total of 16 nursing homes and 800 participants with an average age of 84.6 ± 7.3 years were included in the study. Of them, a DRP was noted in 93.3% of people. The total amount of DRPs identified was 2215, which means an average of 2.8 ± 1.6 DRPs per patient. The most common DRPs identified were 'overtreatment' (19.5%), 'undertreatment' (12.8%), inappropriate dose (10.6%), recommendations for laboratory monitoring (10.4%) and adverse effects (10.3%). Of different drug classes, BZDs (OR 16.6, 95% CI 1.0-270.2), PPIs (OR 2.5, 95% CI 1.1-5.6) and NSAIDs (OR 4.4, 95% CI 1.1-18.3) were identified to be most commonly associated with DRPs. The risk of DRP identification clearly increased with the number of drugs used, with seven drugs demonstrated as the best cut-off for predicting DRP identification (AUC 0.842, sensitivity 0.602; specificity 0.796). 'SENIOR' project has confirmed a high rate of excessive polypharmacy among nursing home residents in the Czech republic resulting in high risk of potential and manifested DRPs. The project emphasized the role of clinical pharmacists in optimizing safety and effectiveness of treatment among older nursing home residents.

PMID:40388195 | DOI:10.1111/cts.70222

Clin Res Cardiol. 2025 May 19. doi: 10.1007/s00392-025-02637-0. Online ahead of print.

ABSTRACT

AIMS: Concerns exist about the safety of amiodarone and dronedarone. We assessed the long-term outcome of both drugs for early rhythm control (ERC) in the EAST-AFNET 4 trial.

METHODS AND RESULTS: Patients randomized for ERC and treated with amiodarone or dronedarone were compared to other ERC-therapies. Patients receiving amiodarone or dronedarone at initial therapy (n = 653/1395) were older with more comorbidities and less paroxysmal atrial fibrillation (AF, 29%) compared to patients never receiving amiodarone or dronedarone (Amiodarone/Dronedaronenever, 43% paroxysmal AF). Patients treated with amiodarone had more often heart failure (HF, 42%) and persistent AF (40%) compared to patients treated with dronedarone (16% HF, 15% persistent AF) and Amiodarone/Dronedaronenever (25% HF, 22% persistent AF). 115/398 amiodarone-treated patients (6.7/100 patient-years) and 51/255 dronedarone-treated patients (4.2/100 patient-years) experienced a primary efficacy outcome (cardiovascular death, stroke, HF-hospitalization or acute coronary syndrome), while 98/398 (5.3/100 patient-years) and 43/255 (3.4/100 patient-years) experienced a primary safety outcome (death, stroke or serious adverse events related to rhythm-control therapy). Serious adverse events related to drug therapy were similar for amiodarone (1.4/100 patient-years), dronedarone (1.2/100 patient-years), and other ERC (0.8/100 patient-years). Dronedarone (hazard ratio (HR) 0.5; CI 0.28-0.91), age (HR 1.05; CI 1.03-1.07), coronary artery disease (HR 1.84; CI 1.38-2.46) and stable HF (HR 1.66; CI 1.28-2.16) were associated with efficacy outcome upon multivariate Cox regression. Age (HR 1.07; CI 1.05-1.09) and left ventricular hypertrophy (HR 1.94; CI 1.13-3.32) were associated with safety outcome.

CONCLUSION: Early rhythm control using amiodarone or dronedarone rarely led to drug-related serious adverse events in EAST-AFNET 4.

CLINICAL TRIAL REGISTRATION: ISRCTN04708680, NCT01288352, EudraCT2010-021258-20.

PMID:40387892 | DOI:10.1007/s00392-025-02637-0

Stem Cells Transl Med. 2025 May 19;14(5):szaf018. doi: 10.1093/stcltm/szaf018.

ABSTRACT

This study investigated the safety and efficacy of MR-MC-01, a mesenchymal stem cell therapy derived from human embryonic stem cells, in patients with interstitial cystitis (IC), particularly those with Hunner lesions unresponsive to pentosan polysulfate sodium (PPS). Conducted as a prospective, randomized, double-blind, placebo-controlled phase I/IIa clinical trial, it enrolled 22 patients, with six completing phase I and 16 participating in phase IIa. Phase I tested 2 doses (2.0 × 107 and 5.0 × 107 cells) to determine the maximum tolerated dose (MTD), revealing no dose-limiting toxicities and only mild adverse events such as transient hemorrhage and bladder pain. In phase IIa, 12 participants received the MTD of 5.0 × 107 cells, and 4 received placebo. Significant reductions in interstitial cystitis questionnaire (ICQ) and pain urgency frequency (PUF) scores were observed in the treatment group. Improvements were noted in nocturnal voiding frequency and Hunner lesion size, with 8 patients showing either a reduction or complete resolution of lesions after 6 months. The global response assessment (GRA) reported moderate to marked improvement in 41.67% of treated patients versus 25% in the placebo group. MR-MC-01 demonstrated no serious drug-related adverse events, highlighting its favorable safety profile. These findings suggest that MR-MC-01 not only alleviates symptoms but also promotes structural recovery in IC, making it a promising treatment option. Further large-scale, long-term studies are warranted to confirm these results and optimize therapeutic protocols. (Identifier: NCT04610359).

PMID:40387787 | DOI:10.1093/stcltm/szaf018

Exp Biol Med (Maywood). 2025 May 2;250:10374. doi: 10.3389/ebm.2025.10374. eCollection 2025.

ABSTRACT

Adverse drug events are harms associated with drug use, whether the drug is used correctly or incorrectly. Identifying adverse drug events is vital in pharmacovigilance to safeguard public health. Drug safety surveillance can be performed using unstructured data. A comprehensive and accurate list of drug names is essential for effective identification of adverse drug events. While there are numerous sources for drug names, RxNorm is widely recognized as a leading resource. However, its effectiveness for unstructured data analysis in drug safety surveillance has not been thoroughly assessed. To address this, we evaluated the drug names in RxNorm for their suitability in unstructured data analysis and developed a refined set of drug names. Initially, we removed duplicates, the names exceeding 199 characters, and those that only describe administrative details. Drug names with four or fewer characters were analyzed using 18,000 drug-related PubMed abstracts to remove names which rarely appear in unstructured data. The remaining names, which ranged from five to 199 characters, were further refined to exclude those that could lead to inaccurate drug counts in unstructured data analysis. We compared the efficiency and accuracy of the refined set with the original RxNorm set by testing both on the 18,000 drug-related PubMed abstracts. The results showed a decrease in both computational cost and the number of false drug names identified. Further analysis of the removed names revealed that most originated from only one of the 14 sources. Our findings suggest that the refined set can enhance drug identification in unstructured data analysis, thereby improving pharmacovigilance.

PMID:40386037 | PMC:PMC12083459 | DOI:10.3389/ebm.2025.10374

Cureus. 2025 Apr 18;17(4):e82530. doi: 10.7759/cureus.82530. eCollection 2025 Apr.

ABSTRACT

We report a case of a 64-year-old man with advanced non-small cell lung cancer (NSCLC) who developed peritoneal metastasis during systemic treatment. Initially diagnosed with lung adenocarcinoma with pleural dissemination and bone metastases, he received carboplatin, pemetrexed, and pembrolizumab, followed by docetaxel due to clinical progression. While primary lung lesions responded to docetaxel, the patient developed new-onset abdominal pain and ascites. Radiologic findings suggested peritoneal thickening, raising suspicion for either docetaxel-induced toxicity or disease progression. Given the rarity of peritoneal metastasis in NSCLC and concurrent treatment response elsewhere, drug-induced complications were initially considered. However, worsening symptoms and further imaging prompted cytological evaluation of ascitic fluid, which confirmed metastatic adenocarcinoma consistent with lung origin. This case highlights the diagnostic challenge of distinguishing treatment-related adverse events from disease progression, especially in patients presenting with nonspecific abdominal symptoms during therapy. Clinicians should maintain a high index of suspicion for uncommon metastatic sites when new symptoms arise, even in the setting of apparent response at the primary site.

PMID:40385873 | PMC:PMC12085952 | DOI:10.7759/cureus.82530

Ther Adv Drug Saf. 2025 May 16;16:20420986251339358. doi: 10.1177/20420986251339358. eCollection 2025.

ABSTRACT

BACKGROUND: Drug-drug interactions (DDI) are an important cause of adverse drug reactions (ADRs). Could large language models (LLMs) serve as valuable tools for pharmacovigilance specialists in detecting DDIs that lead to ADR notifications?

OBJECTIVE: To compare the performance of three LLMs (ChatGPT, Gemini, and Claude) in detecting and explaining clinically significant DDIs that have led to an ADR.

DESIGN: Observational cross-sectional study.

METHODS: We used the French National Pharmacovigilance Database to randomly extract Individual Case Safety Reports (ICSRs) of ADRs with DDI (positive controls) and ICSRs of ADRs without DDI (negative controls) registered in 2022. Interaction cases were classified by difficulty level (level-1 DDI being the easiest and level-2 DDI being the most difficult). We give each LLM (ChatGPT, Gemini, and Claude) the same prompt and case summary. Sensitivity, specificity, and F-measure were calculated for each LLM in detecting DDIs in the case summaries.

RESULTS: We assessed 82 ICSRs with DDIs and 22 ICSRs without DDIs. Among ICSRs with DDIs, 37 involved level-1 DDIs, and 45 involved level-2 DDIs. Correct responses were more frequent for level-1 DDIs than for level-2 DDIs. Regardless of difficulty level, ChatGPT detected 99% of DDI cases, and Claude and Gemini detected 95%. The percentage of correct answers to all DDI-related questions was 66% for ChatGPT, 68% for Claude, and 33% for Gemini. ChatGPT and Claude produced comparable results and outperformed Gemini (F-measure between 0.83 and 0.85 for ChatGPT and Claude and 0.63-0.68 for Gemini) to detect drugs involved in DDI. All exhibited low specificity (ChatGPT 0.68, Claude 0.64, and Gemini 0.36) and reported nonexistent DDIs for negative controls.

CONCLUSION: LLMs can detect DDIs leading to pharmacovigilance cases, but cannot reliably exclude DDIs in cases without interactions. Pharmacologists are crucial for assessing whether a DDI is implicated in an ADR.

PMID:40385316 | PMC:PMC12084699 | DOI:10.1177/20420986251339358

Trop Med Int Health. 2025 May 19. doi: 10.1111/tmi.14123. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine, in a randomised placebo-controlled trial, if cutaneous adverse reactions during treatment (CARDT) with Benznidazole occur as often as with Nifurtimox, and whether the dose and duration of treatment change that frequency.

METHODS: We conducted the EQUITY trial (NCT02369978), allocating Trypanosoma cruzi seropositive adults with no apparent clinical disease to a 120-day, blinded treatment with Benznidazole, Nifurtimox, or Placebo (ratio 2:2:1). Active treatment groups included either 60-day conventional-dose (60CD) regimens (Benznidazole 300 mg/day or Nifurtimox 480 mg/day, followed or preceded by, 60 days of placebo) or 120-day half-dose (120HD) regimens (Benznidazole 150 mg/day or Nifurtimox 240 mg/day). CARDT had blinded adjudication as moderate to severe during the follow-up visits.

RESULTS: Among 307 participants, 42 CARDT (17.1%, 95% confidence interval [CI] 12.6-22.4) occurred in 246 receiving active treatment, compared to two CARDT (3.3%, 95% CI 0.0-11.3) in 61 participants receiving placebo. In 122 patients treated with Benznidazole, there were 31 CARDT (25.4%, including eight severe), compared to 11 CARDT (8.9%, including four severe) in 124 individuals treated with Nifurtimox (p < 0.001). Among the 125 participants assigned to the 120HD regimen, there were 26 CARDT (20.8%, including six severe), compared to 16 CARDT (13.2%, including six severe) among 121 in the 60CD group (p = 0.005). The agent-regime interaction was not significant (p = 0.443). Eleven participants (25%) with CARDT did not complete their treatment.

CONCLUSION: CARDT occurred more frequently with Benznidazole treatment, particularly with longer exposure despite the half-dose regimen. Clinicians should consider these differences when discussing treatment options with patients receiving nitro derivative agents.

PMID:40384408 | DOI:10.1111/tmi.14123

Am J Ophthalmol. 2025 May 16:S0002-9394(25)00239-9. doi: 10.1016/j.ajo.2025.05.007. Online ahead of print.

ABSTRACT

PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are important therapeutic options for type 2 diabetes and obesity; however, concerns about ophthalmic safety persist. This study examined associations between GLP-1 RAs and ocular adverse events (AEs).

DESIGN: Global observational pharmacovigilance study.

METHODS: We searched the US FAERS database (via OpenVigil 2.1) and WHO's VigiBase (via VigiAccess) for optic nerve and retinal AEs associated with semaglutide and tirzepatide, covering the period from their respective approval dates-December 2017 for semaglutide and May 2022 for tirzepatide-through September 2024. In FAERS, all other drugs were compared, while in VigiBase, metformin, empagliflozin, dulaglutide, and insulin served as controls. Disproportionality metrics included reporting odds ratios (RORs) with 95% confidence intervals.

RESULTS: Semaglutide and tirzepatide accounted for 76,444 cases (0.59%) in FAERS (n=12,936,341) and 118,639 cases (0.34%) in VigiBase (n>35,000,000). Semaglutide showed significantly higher odds of ischemic optic neuropathy (ION) (FAERS: ROR=11.12, 95%CI=8.15-15.16; VigiBase: ROR=68.58, 95%CI=16.75-280.67), diabetic retinopathy (DR) (FAERS: ROR=17.28, 95%CI=13.62-21.91; VigiBase: ROR=7.81, 95%CI=5.60-10.90), as well as retinal/vitreous detachment, retinal/vitreous hemorrhage, and retinal tear (FAERS: ROR=2.44-5.89, 95%CI=1.70-8.97, all p<0.001, IC025=0.49, compared to all other drugs. VigiBase: ROR=5.49-20.91, 95%CI=2.71-90.11, all p≤0.0001, IC025≥0.53, compared to metformin). Unique to VigiBase were macular edema (ROR=3.87, 95%CI=1.89-7.92), macular hole (ROR=20.90, 95%CI=2.65-165.01), and papilledema (ROR=6.97, 95%CI=2.53-19.17) (all p≤0.004, IC025≥0.27, compared to metformin). Sensitivity analyses using empagliflozin and dulaglutide revealed significant associations with ION and DR, while vitreous detachment and hemorrhage were significant when compared to dulaglutide. Additionally, when insulin was used as a comparator, semaglutide showed a higher ROR for ION (ROR=9.84, 95%CI=4.25-22.81, P<0.0001, IC025=0.42). However, tirzepatide was only significantly associated with DR in FAERS.

CONCLUSIONS: Given the widespread use of semaglutide, its association with ocular AEs highlight the need for global pharmacovigilance and post-marketing surveillance.

PMID:40383360 | DOI:10.1016/j.ajo.2025.05.007

Stud Health Technol Inform. 2025 May 15;327:1255-1259. doi: 10.3233/SHTI250599.

ABSTRACT

Pharmacist interventions significantly reduce medication errors and improve drug-therapy safety, with IT-supported workflows, including Clinical Decision Support Systems (CDSS), enhancing real-time decision-making. To address challenges in Germany's federated hospital system, the INTERPOLAR study platform integrates real-world data into routine care workflows. Developed under the Medical Informatics Initiative (MII), the platform leverages a CDS Toolchain with FHIR-based data items, predefined triggers, real-time feedback, and a robust data security framework. The platform supports diverse study designs, aligning technical capabilities with clinical workflows through process mapping and requirements engineering. A centralized health data warehouse enables large-scale analysis while ensuring GDPR compliance. Initial results demonstrate harmonized documentation, improved detection of drug-related problems (DRPs), and efficiency gains via automation. Current studies include medication adherence, ADEs, and pharmacist intervention impacts. By embedding IT-supported workflows into routine care, INTERPOLAR provides a scalable, federated solution for drug-therapy safety research, contributing to global pharmacovigilance and advancing evidence-based medicine.

PMID:40380703 | DOI:10.3233/SHTI250599