J Vitreoretin Dis. 2025 Feb 27:24741264251322213. doi: 10.1177/24741264251322213. Online ahead of print.

ABSTRACT

Purpose: To evaluate the early real-world clinical outcomes regarding the safety and efficacy after administration of a ranibizumab biosimilar (Ranieyes). Methods: This multicenter retrospective uncontrolled observational study incorporated data from 7 centers in India. All patients were treated with at least 1 intravitreal injection of 0.5 mg of ranibizumab biosimilar between July 2022 and July 2023 for various indications. Results: A total of 474 ranibizumab biosimilar injections were given in 268 eyes of 254 patients. Indications were diabetic macular edema (DME) (n = 112), macular neovascularization (MNV) (n = 92), retinal vein occlusion (RVO) (n = 54), cystoid macular edema (n = 4), and proliferative diabetic retinopathy with vitreous hemorrhage (n = 6). The mean logMAR BCVA (±SD) improved significantly from baseline to the last follow-up as follows: DME cases, from 0.77 ± 0.37 (Snellen equivalent, 6/36) to 0.43 ± 0.25 (6/15) (z = -8.0; r = -0.8); MNV cases, from 0.95 ± 0.53 (6/60) to 0.59 ± 0.42 (6/24) (z = -7.1; r = -0.8); RVO cases, from 0.83 ± 0.40 (6/45) to 0.44 ± 0.32 (6/15) (z = -5.5; r = -0.8) (all P < .001). All groups also had significant improvement in the central subfield thickness (all P < .001). No site reported drug-related adverse events (eg, inflammation, vasculitis, systemic adverse effects). Conclusions: The preliminary real-world data from this limited early series suggest that Ranieyes has clinical efficacy and is safe as a ranibizumab biosimilar across the approved indications.

PMID:40028177 | PMC:PMC11869221 | DOI:10.1177/24741264251322213

Cureus. 2025 Jan 29;17(1):e78185. doi: 10.7759/cureus.78185. eCollection 2025 Jan.

ABSTRACT

Introduction A combination of ipilimumab/nivolumab has demonstrated a median overall survival (mOS) of 71.9 months in advanced melanoma, establishing it as the standard first-line (1L) therapy. However, the approval of this combination by the Portuguese Regulatory Authority occurred 76 months after its approval by the European Authority, leaving tyrosine kinase inhibitors as the only 1L option available for the BRAF-mutated melanoma population. Our study aims to evaluate real-world data from patients with advanced melanoma and assess the potential prognostic impact of the delayed availability of ipilimumab/nivolumab combination therapy on this population. Methods This was an observational, retrospective cohort study conducted at a Portuguese Comprehensive Cancer Center. The study included adult patients with melanoma who received innovative therapies in the 1L between May 2016 and December 2021 and who would meet the criteria for treatment with ipilimumab/nivolumab. The primary outcome measure was mOS; secondary outcome measures included median progression-free survival (mPFS), objective response rate (ORR), and safety data. Results Our study included 172 patients, of which 50% were male, and 32.6% (n = 56) had BRAF-mutated melanoma. In 1L setting, 70.9% received anti-programmed cell death protein 1 (anti-PD-1) monotherapy, while the rest were treated with targeted therapies. The median follow-up time was 57 months. Patients treated with anti-PD-1 had ORR of 36.0%, mPFS of seven months (95% CI 2.9-11.1), and mOS of 19 months (95% CI 7.5-30.4). Among patients treated with targeted therapies, the ORR was 56.0%, mPFS seven months (95% CI 5.1-8.9), and mOS 14 months (95% CI 5.9-22.1). In our population, 10% presented grade 3 or higher adverse events, with no drug-related deaths reported. Conclusion These findings underscore significant disparities in access to innovative therapies in Portugal, which may have adversely impacted patients' outcomes. The delay raises ethical concerns regarding equity in healthcare access and highlights the need for policy measures to expedite the approval and availability of life-extending treatments.

PMID:40027067 | PMC:PMC11870778 | DOI:10.7759/cureus.78185

Respir Med Case Rep. 2025 Feb 10;54:102179. doi: 10.1016/j.rmcr.2025.102179. eCollection 2025.

ABSTRACT

Pembrolizumab is an immune checkpoint inhibitor (ICI) of programmed cell death-1 category, used for treating various types of cancer. ICIs can sometimes result in immune-related adverse events. Allergic bronchopulmonary mycosis (ABPM) induced by ICI has rarely been reported. We hereby report the case of an 83-year-old woman who experienced non-Aspergillus ABPM with eosinophilia induced by pembrolizumab that had been prescribed for treating bladder cancer. Steroid monotherapy with prednisone was successful and pembrolizumab could be resumed. Through the present case report, we urge the clinicians to be aware of the potential risk of ABPM as a T-helper type 2-associated immune-related adverse event.

PMID:40026847 | PMC:PMC11871464 | DOI:10.1016/j.rmcr.2025.102179

Antimicrob Steward Healthc Epidemiol. 2025 Feb 17;5(1):e53. doi: 10.1017/ash.2025.24. eCollection 2025.

ABSTRACT

OBJECTIVE: To compare the clinical outcomes of patients with lower limb osteomyelitis (LLOM) and negative methicillin-resistant Staphylococcus aureus (MRSA) cultures treated with anti-MRSA therapy (AMT) versus those treated with no-anti-MRSA therapy (NAMT).

DESIGN: Retrospective cohort study.

PATIENTS: Hospitalized adult (≥18 yr of age) patients admitted to multiple tertiary referral centers in a single healthcare system between April 1, 2017 and April 1, 2023, with LLOM and planned intravenous antibiotics for at least four weeks.

METHODS: Electronic medical records were queried for demographic information, admission dates, treatment strategies, imaging and culture results, and discharge diagnoses. Descriptive statistics measured baseline characteristics, imaging, and culture results.

RESULTS: Out of 473 patients, 64 met the inclusion criteria and 409 were excluded. Of the 64 patients, 26 (40%) had AMT and 38 (59%) had NAMT. A larger but statistically insignificant portion of patients in the NAMT cohort failed therapy (23% AMT vs 32% NAMT, P = 0.325). However, hospital readmission for LLOM within 180 days of antibiotic completion (46.2% vs 47%, P = 0.92), hospital length of stay (median (IQR): 6 (5-9) d vs 7 (5-12.5) d, P = 0.285), incidence of new renal replacement therapy initiation (0% vs 2.6%, P = 0.594), creatinine kinase levels (0 vs 2.6%, P = 0.594), and drug-induced immune thrombocytopenia (0% vs 5.3% P = 0.349) were comparable between the two cohorts.

CONCLUSIONS: Treatment failure rates and adverse events did not differ significantly among patients with LLOM treated with AMT or NAMT. Further investigation of determinants of clinical failures in LLOM may help optimize overall treatment.

PMID:40026767 | PMC:PMC11869046 | DOI:10.1017/ash.2025.24

J Brown Hosp Med. 2024 Oct 1;3(4):21-24. doi: 10.56305/001c.122729. eCollection 2024.

ABSTRACT

Turmeric and its active compound, curcumin, has gained popularity as an herbal supplement due to its anti-inflammatory properties. However, the lack of standardized regulation for herbal supplements raises concerns about potential side effects and toxicity. This case report presents a 53-year-old woman with Behçet disease who developed biopsy-proven drug-induced liver injury (DILI) after initiating a turmeric supplement, with resolution of laboratory abnormalities after a positive supplement de-challenge. This case highlights the importance of noting herbal supplementation during medication reconciliation and underscores the need for rigorous regulatory oversight to ensure the safety of such products.

PMID:40026546 | PMC:PMC11864403 | DOI:10.56305/001c.122729

Cardiovasc Ther. 2025 Feb 21;2025:5711316. doi: 10.1155/cdr/5711316. eCollection 2025.

ABSTRACT

Background: Cardiovascular diseases (CVDs) encompass a group of diseases that affect the heart and/or blood vessels, making them the leading cause of global mortality. In our study, we performed proteome-wide Mendelian randomization (MR) and colocalization analyses to identify novel therapeutic protein targets for CVDs and evaluate the potential drug-related protein side effects. Methods: We conducted a comprehensive proteome-wide MR study to assess the causal relationship between plasma proteins and the risk of CVDs. Summary-level data for 4907 circulating protein levels were extracted from a large-scale protein quantitative trait loci (pQTL) study involving 35,559 individuals. Additionally, genome-wide association study (GWAS) data for CVDs were extracted from the UK Biobank and the Finnish database. Colocalization analysis was utilized to identify causal variants shared between plasma proteins and CVDs. Finally, we conducted a comprehensive phenome-wide association study (PheWAS) using the R10 version of the Finnish database. This study was aimed at examining the potential drug-related protein side effects in the treatment of CVDs. A total of 2408 phenotypes were included in the analysis, categorized into 44 groups. Results: The research findings indicate the following associations: (1) In coronary artery disease (CAD), the plasma proteins A4GNT, COL6A3, KLC1, CALB2, KPNA2, MSMP, and ADH1B showed a positive causal relationship (p-fdr < 0.05). LAYN and GCKR exhibited a negative causal relationship (p-fdr < 0.05). (2) In chronic heart failure (CHF), PLG demonstrated a positive causal relationship (p-fdr < 0.05), while AZGP1 displayed a negative causal relationship (p-fdr < 0.05). (3) In ischemic stroke (IS), ALDH2 exhibited a positive causal relationship (p-fdr < 0.05), while PELO showed a negative causal relationship (p-fdr < 0.05). (4) In Type 2 diabetes (T2DM), the plasma proteins MCL1, SVEP1, PIP4K2A, RFK, HEXIM2, ALDH2, RAB1A, APOE, ANGPTL4, JAG1, FGFR1, and MLN demonstrated a positive causal relationship (p-fdr < 0.05). PTPN9, SNUPN, VAT1, COMT, CCL27, BMP7, and MSMP displayed a negative causal relationship (p-fdr < 0.05). Colocalization analysis conclusively identified that AZGP1, ALDH2, APOE, JAG1, MCL1, PTPN9, PIP4K2A, SNUPN, and RAB1A share a single causal variant with CVDs (PPH3 + PPH4 > 0.8). Further phenotype-wide association studies have shown some potential side effects of these nine targets (p-fdr < 0.05). Conclusions: This study identifies plasma proteins with significant causal associations with CVDs, providing a more comprehensive understanding of potential therapeutic targets. These findings contribute to our knowledge of the underlying mechanisms and offer insights into potential avenues for treatment.

PMID:40026415 | PMC:PMC11870767 | DOI:10.1155/cdr/5711316

Drug Saf. 2025 Mar 1. doi: 10.1007/s40264-025-01536-7. Online ahead of print.

ABSTRACT

BACKGROUND: The Pharmacovigilance Risk Assessment Committee (PRAC) plays a central role in the European Union's pharmacovigilance system, evaluating drug safety through several procedures and activities. Despite its central role, few studies have quantitatively investigated the PRAC's activities from a system's perspective.

OBJECTIVE: This study aims to map PRAC's evaluation of safety signals and concerns using antidiabetic products as a case. It characterises the drugs and adverse events involved, analyses the PRAC-led regulatory procedures where the safety signals and concerns were evaluated, and provides a comprehensive review of PRAC meeting minutes.

METHODS: From PRAC meeting minutes, we retrieved information on all antidiabetic drug-related adverse events discussed from 2012 to 2022. We identified drug-adverse event evaluations based on the discussion content. These were described by drug classes, System Organ Classes, PRAC procedures, and the evaluation outcomes corresponding to recommendations for regulatory actions. We also analysed the sequence of PRAC-led procedures and activities addressing drug-adverse event pairs across meeting minutes.

RESULTS: A total of 321 drug-adverse event pairs were identified, with 14 pairs associated with drug classes. Second-generation antidiabetic agents, including sodium-glucose transport protein-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase 4 inhibitors, were the most frequently discussed. Of these, 62 pairs underwent multiple evaluations, resulting in a total of 413 evaluations. In 48% of evaluations, no regulatory action was required. Most evaluations (97%) were concluded in a single procedure, and 66% were concluded in one meeting. Periodic safety update reports accounted for 54% of drug-adverse event evaluations and updates to product information were the most frequent outcome. Signal assessment and prioritisation procedures, while less common, resulted in more diverse recommendations for regulatory action. Referrals were infrequent (N = 5) and were often triggered by the signal assessment and prioritisation procedure.

CONCLUSIONS: Periodic safety update reports are the primary source for PRAC evaluations of safety signals although they are not intended for notification of new urgent safety information. Compared with periodic safety update reports, the signal assessment and prioritisation procedure evaluates fewer signals but leads to a wider range of regulatory actions, from risk minimisation measures to referrals. This difference may be attributed to the fact that signals detected in periodic safety update reports are not intended for urgent safety issues, these should be assessed through the signal assessment and prioritisation procedure, as the latter involves real-time signal management, whereas the periodic safety update reports are conducted at predefined intervals.

PMID:40024970 | DOI:10.1007/s40264-025-01536-7

Wiad Lek. 2024;78(1):187-196. doi: 10.36740/WLek/197143.

ABSTRACT

OBJECTIVE: Aim: To investigate how and why antidepressant side effects occur, in order to use them effectively in clinical practice.

PATIENTS AND METHODS: Materials and Methods: We have studied modern literary sources on the topic of side effects of antidepressant and presented in the form of a literature review in this article. Electronic Scopus and Pubmed databases were searched for articles on the studied topic. The review included original articles, research, and official recommendations from medical associations.

CONCLUSION: Conclusions: Side effects of antidepressants can reduce treatment adherence and delay recovery. Therefore, it is extremely important to consider possible side effects when choosing a therapy. While there is no perfect antidepressant that works quickly and is completely free of side effects, newer antidepressants are safer, better tolerated, and associated with lower rates of treatment failure. Most side effects occur as a consequence of the basic mechanism of action of the drugs. Therefore, it is important to understand the neurobiology of side effects, their frequency and risks, ways to prevent them or use them to your advantage resources.

PMID:40023872 | DOI:10.36740/WLek/197143

J Pharmacol Exp Ther. 2025 Feb;392(2):100023. doi: 10.1124/jpet.124.002184. Epub 2024 Nov 22.

ABSTRACT

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) established S7B and E14 guidelines in 2005 to prevent drug-induced torsade de pointes (TdP), effectively preventing the development of high-risk drugs. However, those guidelines hampered the development of some potentially valuable drug candidates despite not being proven to be proarrhythmic. In response, comprehensive in vitro proarrhythmia assay and exposure-response modeling were proposed in 2013 to reinforce proarrhythmic risk assessment. In 2022, the ICH released E14/S7B questions and answers (stage 1), emphasizing a "double negative" nonclinical scenario for low-risk compounds. For "non-double negative" compounds, new questions and answers are expected to be enacted as stage 2 shortly, in which more detailed recommendations for proarrhythmia models and proarrhythmic surrogate markers will be provided. This review details the onset mechanisms of drug-induced TdP, including IKr inhibition, pharmacokinetic factors, autonomic regulation, and reduced repolarization reserve. It also explores the utility of proarrhythmic surrogate markers (J-Tpeak, Tpeak-Tend, and terminal repolarization period) besides QT interval. Finally, it presents various in silico, in vitro, ex vivo, and in vivo models for proarrhythmic risk prediction, such as comprehensive in vitro proarrhythmia assay in silico model, induced pluripotent stem cell-derived cardiomyocyte sheet, Langendorff-perfused heart preparation, chronic atrioventricular block animals (dogs, monkeys, pigs, and rabbits), acute atrioventricular block rabbits, methoxamine-sensitized rabbits, and genetically engineered rabbits for specific long QT syndromes. Those models along with the surrogate markers can play important roles in quantifying TdP risk of new compounds, impacting late-phase clinical design and regulatory decision-making, and preventing adverse events on postmarketing clinical use. SIGNIFICANCE STATEMENT: Since ICH S7B/E14 guidelines hampered the development of some potentially valuable compounds with unproven proarrhythmic risk, comprehensive in vitro proarrhythmia assay and exposure-response modeling were proposed in 2013 to reinforce proarrhythmic risk assessment of new compounds. In 2022, the ICH released questions and answers (stage 1), emphasizing a "double negative" nonclinical scenario for low-risk compounds, and new questions and answers (stage 2) for "non-double negative" compounds are expected. This review delves into proarrhythmic mechanisms with surrogate markers and explores various models for proarrhythmic risk prediction.

PMID:40023597 | DOI:10.1124/jpet.124.002184

Eur J Pharmacol. 2025 Feb 26:177431. doi: 10.1016/j.ejphar.2025.177431. Online ahead of print.

ABSTRACT

Safe and effective pharmacotherapy not only requires biomedical and pharmacological knowledge, but also insight into the patient's perspective. Although factors such as personal beliefs, acceptance of side effects or medicine costs influence pharmacotherapy, these non-clinical factors are not extensively discussed within the health professions education (HPE) curricula. Incorporating patient-perspective into pharmacology could therefore help minimize drug-related problems in patients. As videos provide a holistic depiction of the patient's life, using patient videos, instead of commonly used, paper-based case studies, could be suitable to reach this objective. Here we aim to study effectiveness of patient videos as a tool for teaching HPE students on the value of patient's perspective in pharmacology and pharmacotherapy. An interactive lecture on pharmacokinetics was developed for first-year bachelor medical and pharmacy undergraduate students. The educational intervention included watching a patient video, followed by focused exercises and plenary discussions on various pharmacological and patient-perspective related topics. The lecture concluded with students filling up a questionnaire with both open-ended questions and Likert-scale based statements. Besides learning about pharmacological principles (e.g. clinical relevance of pharmacokinetics), students additionally learnt about other prescribing-related topics (e.g. therapy failure, shared decision making) and were able to identify skills required of healthcare professionals, beyond those connected directly to pharmacotherapy (e.g. empathy, listening). The study identifies patient videos as a highly suitable educational tool. Not only do videos teach about the various pharmacological principles, but they also add an extra dimension to pharmacology teaching and learning and can easily be integrated into existing teaching modalities.

PMID:40020985 | DOI:10.1016/j.ejphar.2025.177431

J Indian Soc Periodontol. 2024 Jul-Aug;28(4):494-498. doi: 10.4103/jisp.jisp_147_23. Epub 2025 Jan 6.

ABSTRACT

Drug-induced gingival enlargement often occurs due to patient's lack of awareness about the side effects of prescribed medications. This case report details an unusual instance of massive drug-induced gingival overgrowth in a 50-year-old female, successfully managed through a multidisciplinary approach, including surgical intervention and prosthetic rehabilitation. The surgical treatment involved multiple extractions and the excision of excessive tissue. Both arches healed completely after surgery, and the patient underwent prosthetic rehabilitation, with no signs of recurrence. Effective management of such cases relies on patient counseling and appropriate drug substitution. Increasing awareness about the side effects of certain medications and the connection between systemic and oral health is crucial to prevent such cases of gingival enlargement.

PMID:40018719 | PMC:PMC11864326 | DOI:10.4103/jisp.jisp_147_23

Malawi Med J. 2024 Oct 16;36(3):163-169. doi: 10.4314/mmj.v36i3.2. eCollection 2024 Oct.

ABSTRACT

BACKGROUND: Spontaneous reporting of adverse drug reaction (ADRs) is low in Malawi. We assessed the impact of training intervention on knowledge, attitudes, and practices of health care professionals (HCPs) in pharmacovigilance (PV).

METHODS: We employed a mixed-methods study design. A questionnaire was administered among HCPs who were trained in PV, followed by face-face interviews. We further extracted individual case safety reports which were submitted to the local databasewithin a period of six months prior and after the PV training. Quantitative data was analyzed using STATA 14.1. Paired t-test was used to assess the differences in PV knowledge among HCPs before and after the training. For qualitative data, we manually derived key themes from the participant's responses.

RESULTS: Overall, the mean knowledge score was significantly improved across all the participants from a mean of 56% (95% CI 53% to 58%) to 66% (95% CI 64% to 69%) after the training, p< 0.001. There was a 2.8-fold increase in the number of participants who were able to detect an ADR after the training and a 1.8-fold increase in the percentage of reporting the detected ADRs after the training. Participants expressed preference of a paper-based reporting system to other reporting tools. However, they outlined several challenges to the system which discourages HCPs from reporting ADRs, such as lack of feedback, unavailability of reporting forms and delay to transmit data to the national centre.

CONCLUSION: The survey found that in-service training for HCPs improves KAP of PV and reporting rates of ADRs. We recommend widening of the training and introducing PV courses in undergraduate programs for health care workers in Malawi.

PMID:40018398 | PMC:PMC11862858 | DOI:10.4314/mmj.v36i3.2

Eur J Med Res. 2025 Feb 27;30(1):143. doi: 10.1186/s40001-025-02406-9.

ABSTRACT

BACKGROUND: Overactive bladder (OAB) syndrome has a significant impact on quality of life, and vibegron has emerged as a therapeutic option. This study aims to evaluate the safety profile of vibegron in a disproportionality analysis by analyzing adverse event (AE) reports from the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

METHODS: We conducted a retrospective analysis of the FAERS database from January 2021 to September 2023. After duplicate removal and thorough screening, 1137 vibegron-related AE reports were identified. We analyzed these reports for demographic and clinical characteristics, signal detection at the system organ class (SOC) level, and specific AEs.

RESULTS: Females comprised a higher percentage (67.72%) of AE reports compared to males. The elderly population (age > 64 years) accounted for 15.84% of the cases. The majority (95.69%) of the reports originated from the USA. Signal detection revealed significant findings across 19 organ systems with notable SOCs, including renal and urinary disorders (ROR = 7.72, 95%CI 6.83-8.72), gastrointestinal disorders (ROR = 1.38, 95%CI 1.21-1.58), and respiratory, thoracic, and mediastinal disorders (ROR = 1.21, 95%CI 1.01-1.45). In addition, several unexpected AEs were identified, such as dry mouth, hot flush, constipation, and increased blood pressure.

CONCLUSIONS: This study provides comprehensive insights into vibegron's safety profile, revealing both known and unexpected AEs. The findings highlight the need for careful patient selection and monitoring, especially among females and the elderly. The results advocate for ongoing pharmacovigilance and further research to ensure vibegron's safe and effective use in OAB treatment.

PMID:40016845 | DOI:10.1186/s40001-025-02406-9

Eur J Hosp Pharm. 2025 Feb 26:ejhpharm-2024-004444. doi: 10.1136/ejhpharm-2024-004444. Online ahead of print.

ABSTRACT

BACKGROUND: Medical errors pose significant risks to patient safety and public health. Automated unit dose drug dispensing systems (UDDSs) have emerged as valuable tools to reduce medication errors while optimising economic and logistical resources.

OBJECTIVES: This systematic review aims to evaluate studies specifically focused on the impact of automated UDDSs in reducing medication errors and streamlining processes.

METHODS: A literature search was performed on PubMed, Scopus, and Web of Science, focusing on peer-reviewed articles published between 2019 and 2024. The search, concluded on 24 September 2024, included studies conducted in inpatient hospital settings that assessed automated UDDS effects on medication errors, therapy management and inventory control. Outcomes examined included effects on patient safety, cost-effectiveness and inventory management. Results were synthesised qualitatively.

RESULTS: From 3346 references, four studies met the inclusion criteria: a cost-effectiveness analysis, an uncontrolled before-and-after study, and two observational studies. UDDS improved medication processes, reducing drug-related problems, medication handling and dispensing time by 50% per patient per day. Integrated with barcode scanning, UDDS lowered medication administration errors (MAEs) from 19.5% to 15.8% and harmful MAEs from 3.0% to 0.3%. Overall, medication errors dropped by 45-70%, enhancing safety and reducing manual handling risks. UDDS demonstrated cost-effectiveness by significantly reducing MAEs. The study estimated a reduction in MAEs, with a cost-effectiveness ratio of €17.69 per avoided MAE. For potentially harmful MAEs, the cost-effectiveness ratio was estimated at €30.23 per avoided error. These findings suggest substantial long-term savings potential, though the exact magnitude may vary depending on hospital size and implementation specifics CONCLUSIONS: Automated UDDSs improve patient safety by significantly reducing medication errors and delivering cost savings through better inventory management. Challenges such as high initial costs and workflow adjustments can be mitigated through gradual implementation and staff training. Further integration with other healthcare technologies, such as barcoding, real-time tracking, artificial intelligence (AI)-driven error prevention tools and fully automated restocking systems could enhance UDDS benefits and further support hospital processes.

PMID:40015720 | DOI:10.1136/ejhpharm-2024-004444

J Clin Psychopharmacol. 2025 Mar-Apr 01;45(2):111-115. doi: 10.1097/JCP.0000000000001962.

ABSTRACT

PURPOSE: Women have historically been underrepresented in second-generation antipsychotic (SGA) clinical trials, accounting for less than 35% of participants, which raises concerns about the generalizability of the safety profile for these medications.

METHODS: The US adverse event reporting system was queried for the dates January 1, 2019, to July 8, 2024, to examine the following 6 SGAs: aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone. Reports were excluded if patients were under 18 years old, contained an unknown age or gender, or were duplicated. Five adverse events were examined: Torsades de pointes (TdP), neuroleptic malignant syndrome (NMS), tardive dyskinesia (TD), agranulocytosis (AG), and cerebrovascular adverse events (CVAE). Counts of these events were noted, and reporting odds ratios (ROR) were calculated.

RESULTS: The total study cohort was 87,356 reports, consisting of aripiprazole (n = 10,715, 12.2%), clozapine (n = 25,096, 28.7%), olanzapine (n = 11,587, 13.3%), quetiapine (n = 28,746, 32.9%), risperidone (n = 10,467, 12%), and ziprasidone (n = 745, 0.9%). The cohort's mean age was 48.6 ± 18.5 years and comprised 42,584 females (48.7%). Most cases were reported by healthcare professionals (74,836, 85.7%). A total of 3,754 reports contained at least 1 of the 5 adverse events. The RORs among females compared to males for TdP (5.55, 95% confidence interval [CI] = 3.78-8.47), NMS (0.59, 95% CI = 0.53-0.65), TD (0.88, 95% CI = 0.76-1.02), AG (0.59, 95% CI = 0.51-0.70), and CVAE (1.12, 95% CI = 0.89-1.41) were observed. Females had a significantly higher odds of hospitalization or death with TdP compared to males (ROR = 3.09, 95% CI = 1.36-7.01).

CONCLUSIONS: Our findings suggest higher odds of TdP and worse TdP-associated outcomes among females exposed to SGAs compared to males. Further studies are needed to confirm these preliminary findings.

PMID:40014466 | DOI:10.1097/JCP.0000000000001962

Epilepsia Open. 2025 Feb 27. doi: 10.1002/epi4.70016. Online ahead of print.

ABSTRACT

OBJECTIVE: The STANDLOW trial investigated whether first-line antiseizure monotherapy with low doses has a similar efficacy to standard doses, but with fewer adverse events, improved quality of life, and reduced costs for the National Health System.

METHODS: Multicenter, randomized, parallel-arm, single-blind, non-inferiority trial, comparing low dose versus standard dose of antiseizure medications (carbamazepine, levetiracetam, valproate, zonisamide, oxcarbazepine, topiramate, lamotrigine, gabapentin, lacosamide) in adults with newly diagnosed focal epilepsy.

RESULTS: The intention-to-treat (ITT) population consisted of 58 randomized patients, 29 in the low dose arm and 29 in the standard dose arm, 27 (46.6%) females and 31 (53.4%) males, with an age between 18 and 87 years (median 54.9, IQR 32-71). The seizure type was focal impaired awareness seizures in 44 (75.9%) and focal aware seizures in 14 (24.1%). Etiology was unknown in 43 (74.1%) and structural in 15 (25.9%). At study entry, EEG was epileptiform in 28 (48.2%) and seizure frequency was low (≤2 seizures/month) in 41 (70.7%). The estimated relapse proportions at 12 months were 47% for the low dose and 48% for the standard dose, with a difference of 1% (95% CI: -30%; 27%). At the end of the study visit (12 months of follow-up, or immediately after seizure relapse or study withdrawal for other reasons, whichever came first), no differences in the number or severity of adverse events or quality of life measures were observed between the two treatment groups. The total drug-related costs over the entire study period were lower in the low dose arm (median per participant 253 € versus 475 € in the standard dose arm).

SIGNIFICANCE: Although the efficacy of low doses versus standard doses appeared similar, non-inferiority could not be demonstrated due to slow recruitment and premature termination of the trial. Although statistically inconclusive, our findings suggest that a low dose of antiseizure medications may be considered as a first-line option in adult patients with a new diagnosis of focal epilepsy of unknown etiology and low seizure frequency.

PLAIN LANGUAGE SUMMARY: This study aimed to see if low doses of anti-seizure medications (ASMs) could be as effective as standard doses in treating adults with newly diagnosed epilepsy. Subjects were assigned to receive either a low or standard dose of ASMs. 58 adults participated. Both low and standard doses seemed to have a similar effect on controlling seizures. The study was stopped early due to slow enrollment, making it difficult to definitively prove that low doses were non-inferior to standard doses. Low doses of ASMs might be a reasonable option for adults with newly diagnosed epilepsy with no clear cause and few seizures.

PMID:40013886 | DOI:10.1002/epi4.70016

Turk J Surg. 2025 Feb 27;41(1):105-107. doi: 10.47717/turkjsurg.2022.5489.

ABSTRACT

Everolimus is one of the immunosuppressive drugs used in solid organ transplantation. Many side effects have been described for these immunosuppressive drugs, similar to other drugs in this category. The purpose of this case presentation is to draw attention to drug-induced pneumonitis, which is a rare and life-threatening side effect of everolimus. A nineteen-year-old female patient who received liver transplantation for toxic hepatitis was admitted to our institute with cough and dyspnea. Everolimus had been started in conjunction with tacrolimus therapy 6 months prior to admission. Her chest imaging were consistent with pneumonitis. Markers of infection and cultures were all negative. After discontinuation of everolimus, symptoms and radiological findings resolved. The adverse effects of the drug should be kept in mind while investigating possible infectious agents in liver transplant recipients who are prone to opportunistic infections.

PMID:40012361 | DOI:10.47717/turkjsurg.2022.5489

Acta Med Okayama. 2025 Feb;79(1):31-37. doi: 10.18926/AMO/68356.

ABSTRACT

We retrospectively analyzed the safety of the use of articaine, an amide-type local anesthetic, in Japanese dental patients (n=300) treated in Thailand in 2015-2017. The dosage, adverse events (AEs) caused by local anesthesia, and treatment efficacy were examined. Articaine, which is safe for patients with liver impairments due to its unique metabolism, has not been thoroughly tested in Japan for doses above 5.1 mL. Eighty of the present patients had undergone root canal treatment (RCT), 71 underwent tooth extraction, and 149 underwent implant-related surgery. More than three articaine cartridges were used in 41 patients, and no AEs occurred in these cases. The only AE occurred in a 52-year-old woman who was treated with three cartridges and presented with what appeared to be hyperventilation syndrome; she later recovered and received her dental treatment as scheduled. Most treatments were completed with three or fewer cartridges, suggesting that this number is generally sufficient. Our findings, particularly the low AE risk even with doses exceeding three cartridges, support the potential applicability of the overseas recommended maximum dose of articaine (7 mg/kg) in Japanese patients. This conclusion is significant for advancing dental anesthetic practices and ensuring patient safety and treatment efficacy in Japan.

PMID:40012157 | DOI:10.18926/AMO/68356

Drug Discov Ther. 2025 Mar 6;19(1):10-21. doi: 10.5582/ddt.2024.01090. Epub 2025 Feb 26.

ABSTRACT

Recently, increased attention has been paid to the consideration of individual characteristics, including sex and age, in the context of medication use and adverse events. However, the characteristics and patterns of adverse events reported in the Japanese Adverse Drug Event Report (JADER) database stratified by sex and age have not yet been clarified. This study aimed to clarify the characteristics and patterns of adverse event reports in the JADER database over a 20-year period (April 2004-March 2024). Data were stratified into 20 groups based on sex and age (aged 0-9 years, 10-19 years, 20-29 years, 30-39 years, 40-49 years, 50-59 years, 60-69 years, 70-79 years, 80-89 years, and ≥90 years). The female/male ratio of adverse event reports in JADER was 0.95. The largest group comprised males in their 70s. Adjusting for the proportion of adverse event reports in each group according to the demographic composition in 2015 highlighted that the reporting rates of adverse events were higher in people aged ≥70 years and that females aged 20-49 years reported more adverse events than males. Medical history, causative drugs, and adverse events reported to JADER were characterized by combinations of sex and age. Our results provide additional insights into the interpretation of previous studies using JADER. In addition, the results of this study will help understand the characteristics of adverse event reports contained in JADER and conduct appropriate subgroup and sensitivity analyses.

PMID:40010736 | DOI:10.5582/ddt.2024.01090

Eur J Cancer. 2025 Feb 15;219:115304. doi: 10.1016/j.ejca.2025.115304. Online ahead of print.

ABSTRACT

AIM: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer (LACC), but recurrence rates remain high. This multicenter phase-3 randomized trial (GOTIC-002) evaluated the efficacy of low-dose oral tegafur-uracil (UFT) as maintenance chemotherapy following curative CCRT for LACC.

METHODS: Between 2010 and 2018, 351 patients with stage Ib2-IVa cervical cancer were enrolled. After achieving complete or partial remission post-CCRT, patients were randomized 1:1 into observation (arm O) or UFT maintenance therapy (arm UFT). UFT doses were 300-400 mg/day based on body surface area for 2 years, disease progression or adverse effects occurred. The primary endpoint was progression-free survival (PFS), with overall survival (OS) and safety as secondary endpoints.

RESULTS: Patient characteristics were similar between the groups (n = 178 in arm O, n = 173 in arm UFT). During a median follow-up of 3 years, median PFS was not reached in either group. 5-year PFS rates were similar between them (arm O: 61.3 %, arm UFT: 62.0 %, hazard ratio: 0.92, P = .634). 5-year OS rates were also comparable (77.6 % vs 76.1 %, hazard ratio: 1.04, P = .869). Compliance with UFT ranged from 87.8 % to 98.8 %. Although adverse events were more frequent in arm UFT (93.5 % vs 73.9 %, odds ratio: 5.05), most were mild or moderate. Despite its tolerability, UFT did not improve PFS or OS.

CONCLUSIONS: These findings suggest the need to reconsider maintenance therapy strategies after CCRT for potentially shifting away from cytotoxic chemotherapy towards alternative methods to enhance survival outcomes in patients with LACC.

PMID:40010135 | DOI:10.1016/j.ejca.2025.115304