Sci Rep. 2025 Mar 12;15(1):8597. doi: 10.1038/s41598-025-92330-z.

ABSTRACT

This study aims to explore potential adverse events (AEs) related to Dupilumab using data from the US FDA Adverse Event Reporting System (FAERS) database. The FAERS database from Q2 2017 to Q4 2023 was mined for AEs related to Dupilumab. The types of AEs reported, along with gender, age distribution, and severity, were evaluated. Signal detection methods including Reporting Odds Ratio, Proportional Reporting Ratio, Bayesian Confidence Propagation Neural Network, and Empirical Bayesian Geometric Mean were used. A total of 11,547,571 AE reports were collected, with 5335 reports suspected of being related to Dupilumab, identifying 307 Preferred Terms involving 27 System Organ Classes. Reports from female patients outnumbered males (56.08% vs. 34.65%). Patients aged 45-65 years reported the most events (21.34%). The number of reports increased significantly in 2023 (34.25%) compared to 2017 (0.42%), with the highest reporting rate from the US (98.07%). Common AEs included Pruritus, Product use in unapproved indication, and Rash, with Product dose omission issue indicating widespread misuse of Dupilumab. High signal strength AEs included Rebound atopic dermatitis, Rebound eczema, Dermatitis atopic, and Dry skin; injection site AEs like Injection site dryness and eczema; new potential AEs such as Dry eye, Eye pruritus, Ocular hyperaemia, Eye irritation, Conjunctivitis, Vision blurred, and Sleep disorder. This study reveals various potential AEs associated with Dupilumab, including newly identified risks. Future research needs to delve deeper into the safety of Dupilumab to better guide its clinical application.

PMID:40074775 | DOI:10.1038/s41598-025-92330-z

Daru. 2025 Mar 12;33(1):13. doi: 10.1007/s40199-025-00559-w.

ABSTRACT

INTRODUCTION: Leukocytoclastic vasculitis (LCV) is a small-vessel inflammatory condition that can rarely occur as an adverse drug reaction (ADR). Vancomycin-induced LCV is an uncommon but potentially serious complication, particularly in patients with pre-existing renal impairment.

REASON FOR THE REPORT: This case report describes a patient with end-stage renal disease (ESRD) who developed LCV following vancomycin therapy for a catheter-related infection. The report emphasizes the diagnostic challenges and the importance of prompt and appropriate management of this ADR. A 53-year-old male with ESRD developed skin lesions and systemic symptoms after receiving vancomycin for catheter-related infection. The diagnosis of LCV was confirmed through a skin biopsy. Discontinuation of vancomycin with initiation of mycophenolate mofetil and prednisolone resulted in significant improvement in the patient's condition.

OUTCOME: The presented case underlines the recognition of vancomycin-induced LCV, especially in the vulnerable population of patients with ESRD. It emphasizes the need for a high degree of suspicion of drug-related adverse events and early diagnosis and management to achieve good outcomes.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:40072667 | DOI:10.1007/s40199-025-00559-w

Asian J Psychiatr. 2025 Feb 22;106:104409. doi: 10.1016/j.ajp.2025.104409. Online ahead of print.

ABSTRACT

INTRODUCTION: Late-life depression (LLD) is a significant yet often under-recognized health concern. While selective serotonin reuptake inhibitors (SSRIs) are widely used, their adverse effects remain a challenge. Vortioxetine, a multimodal antidepressant, has gained attention for its potentially better tolerability. However, data on its safety in older adults are limited. This meta-analysis assessed the safety and tolerability of Vortioxetine compared to serotonin reuptake inhibitors in LLD.

METHODS: A systematic search of PubMed, EMBASE, and Cochrane Central identified randomized controlled trials (RCTs) evaluating Vortioxetine's safety in ≥ 60-year-old patients. Primary outcomes included adverse events and withdrawal rates. Statistical analyses were conducted using Review Manager.

RESULTS: Three studies, involving 714 patients were included. There were no statistical differences between groups for nausea (RR 0.54; 95 % CI 0.22, 1.34; p = 0.18; I2 =75 %), diarrhea (RR 0.92; 95 % CI 0.20, 4.13; p = 0.91; I2 =59 %), constipation (RR 0.54; 95 % CI 0.28,1.02; p = 0.06; I2 =0 %) and loss of appetite (RR 1.00; 95 % CI 0.25, 4.05; p = 1.00; I2 =40 %). The total number of dropouts after randomization did not show a statistical significance with Vortioxetine use (RR 1.10; CI 95 % 0.82, 1.48; p = 0.52; I2 = 0 %), nor did the number of withdrawals (RR 1.09, CI 95 % 0.77, 1.55; p = 0.64; I2 = 0 %).

CONCLUSION: This meta-analysis suggests Vortioxetine is safe for LLD, with no significant increase in adverse effects. While reassuring, these findings emphasize the need for careful evaluation, as Vortioxetine showed no clear tolerability advantage over other serotonin reuptake inhibitors.

PMID:40073578 | DOI:10.1016/j.ajp.2025.104409

Endocr Oncol. 2025 Feb 26;5(1):e240060. doi: 10.1530/EO-24-0060. eCollection 2025 Jan.

ABSTRACT

Medullary thyroid cancer (MTC) is a rare subtype of thyroid cancer originating from parafollicular C-cells of the thyroid. Tyrosine kinase inhibitors are used to treat patients with advanced MTC. Selpercatinib is a highly selective RET inhibitor used in the treatment of advanced RET-mutated MTC, having shown higher potency and fewer side effects compared to multikinase inhibitors in clinical trials. As a relatively new drug, its toxicity profile continues to be characterised. This report describes a case of severe acute hypocalcaemia in a 64-year-old male with advanced MTC treated with selpercatinib. The patient, who had stable hypoparathyroidism, experienced acute hypocalcaemia (corrected calcium 1.4 mmol/L) 2 weeks after initiating selpercatinib, requiring hospitalisation for calcium supplementation and monitoring. Selpercatinib was temporarily withheld and later reintroduced at a lower dose, successfully preventing recurrence of hypocalcaemia. Investigations excluded other common or important causes of hypocalcaemia, which led us to conclude that this could be a drug-related adverse event. This case highlights the need for careful monitoring of electrolyte disturbances in patients on selpercatinib, particularly those with pre-existing hypoparathyroidism. Although rare, the development of hypocalcaemia with RET inhibitors may necessitate dose interruptions and adjustments. Our experience has also illustrated that re-challenge with selpercatinib is feasible with appropriate management strategies.

PMID:40070601 | PMC:PMC11896645 | DOI:10.1530/EO-24-0060

Crit Care. 2025 Mar 11;29(1):108. doi: 10.1186/s13054-025-05331-9.

ABSTRACT

BACKGROUND: Delirium and postoperative cognitive dysfunction (POCD) are common complications post-cardiac surgery, yet no specific medical intervention is currently recommended for prevention. This study aimed to evaluate the efficacy of gastrodin infusion in preventing delirium and POCD in critically ill patients following cardiac surgery.

MATERIAL AND METHODS: A double-blind, randomized, placebo-controlled trial was conducted on patients aged 18-75, scheduled for coronary artery bypass grafting (CABG) surgery, with or without valve replacement. Participants were randomized in a 1:1 ratio to receive gastrodin infusion 600 mg twice daily or placebo from the day of surgery until the postoperative day (POD) 6. The co-primary outcomes were the incidences of delirium and POCD, assessed from ICU admission until POD 7 and at 1 and 3 months postoperatively. This study was registered with the Chinese Clinical Trials Registry (ChiCTR1800020414).

RESULTS: Of 160 randomized participants, 155 were analyzed (77 gastrodin, 78 placebo) according to a modified intention to treat principle. The incidence of postoperative delirium was 19.5% in the gastrodin group and 35.9% in the placebo group, with a significant relative risk of 0.54 (95% CI 0.32-0.93, p = 0.022). The incidence of in-hospital POCD was 2.9% and 4.0% in the placebo and gastrodin groups, respectively. The odds of hospital discharge were significantly greater in the gastrodin group (subhazard ratio, 1.20; 95% CI 1.00-1.84; p = 0.049). Adverse events occurred in 9.1% (7/77) of patients administered gastrodin and 14.1% (11/78) of patients administered the placebo, with none being drug-related.

CONCLUSION: Gastrodin infusion significantly reduced postoperative delirium and improved discharge outcomes in patients undergoing CABG, but larger studies are needed to confirm its efficacy in preventing delirium.

PMID:40069830 | DOI:10.1186/s13054-025-05331-9

Sci Data. 2025 Mar 11;12(1):424. doi: 10.1038/s41597-025-04718-1.

ABSTRACT

Adverse drug events (ADEs) are a major safety issue in clinical trials. Thus, predicting ADEs is key to developing safer medications and enhancing patient outcomes. To support this effort, we introduce CT-ADE, a dataset for multilabel ADE prediction in monopharmacy treatments. CT-ADE encompasses 2,497 drugs and 168,984 drug-ADE pairs from clinical trial results, annotated using the MedDRA ontology. Unlike existing resources, CT-ADE integrates treatment and target population data, enabling comparative analyses under varying conditions, such as dosage, administration route, and demographics. In addition, CT-ADE systematically collects all ADEs in the study population, including positive and negative cases. To provide a baseline for ADE prediction performance using the CT-ADE dataset, we conducted analyses using large language models (LLMs). The best LLM achieved an F1-score of 56%, with models incorporating treatment and patient information outperforming by 21%-38% those relying solely on the chemical structure. These findings underscore the importance of contextual information in ADE prediction and establish CT-ADE as a robust resource for safety risk assessment in pharmaceutical research and development.

PMID:40069213 | DOI:10.1038/s41597-025-04718-1

BDJ Open. 2025 Mar 11;11(1):24. doi: 10.1038/s41405-024-00291-8.

ABSTRACT

BACKGROUND: Drug-associated gingival disorders can negatively impact on oral health. This study aimed to utilize the United States Food and Drug Administration Adverse Event Reporting System (USFDA AERS) to comprehensively assess the associations between medications and specific gingival disorders.

METHODS: Data were extracted from the USFDA AERS from 2004-2024 using Preferred Terms for eight gingival disorders. Reports were deduplicated and disproportionality analysis was conducted using frequentist and Bayesian approaches to detect potential signals. Volcano plots were generated for each gum disorder to identify the drugs with the strongest signals based on the statistical significance and magnitude of association.

RESULTS: A total of 11,465 reports were included. Several anti-osteoporotic drugs, anti-thrombotics, calcium channel blockers and immunosuppressants showed significant associations with multiple gingival disorders. Phenytoin was linked to hypertrophy and bleeding. Stomatological preparations were associated with discoloration and bleeding. Emergent signals were identified with finasteride, COVID-19 vaccine, and levothyroxine with gum disorders.

CONCLUSION: This study highlights the need for increased awareness of oral side effects amongst healthcare providers. Future research should explore the mechanisms of drug-induced gingival disorders and develop interdisciplinary management strategies to enhance oral health in patients on long-term medications.

PMID:40069171 | DOI:10.1038/s41405-024-00291-8

JMIR Cancer. 2025 Mar 11;11:e69663. doi: 10.2196/69663.

ABSTRACT

BACKGROUND: Androgen receptor axis-targeting reagents (ARATs) have become key drugs for patients with castration-resistant prostate cancer (CRPC). ARATs are taken long term in outpatient settings, and effective adverse event (AE) monitoring can help prolong treatment duration for patients with CRPC. Despite the importance of monitoring, few studies have identified which AEs can be captured and assessed in community pharmacies, where pharmacists in Japan dispense medications, provide counseling, and monitor potential AEs for outpatients prescribed ARATs. Therefore, we anticipated that a named entity recognition (NER) system might be used to extract AEs recorded in pharmaceutical care records generated by community pharmacists.

OBJECTIVE: This study aimed to evaluate whether an NER system can effectively and systematically identify AEs in outpatients undergoing ARAT therapy by reviewing pharmaceutical care records generated by community pharmacists, focusing on assessment notes, which often contain detailed records of AEs. Additionally, the study sought to determine whether outpatient pharmacotherapy monitoring can be enhanced by using NER to systematically collect AEs from pharmaceutical care records.

METHODS: We used an NER system based on the widely used Japanese medical term extraction system MedNER-CR-JA, which uses Bidirectional Encoder Representations from Transformers (BERT). To evaluate its performance for pharmaceutical care records by community pharmacists, the NER system was first applied to 1008 assessment notes in records related to anticancer drug prescriptions. Three pharmaceutically proficient researchers compared the results with the annotated notes assigned symptom tags according to annotation guidelines and evaluated the performance of the NER system on the assessment notes in the pharmaceutical care records. The system was then applied to 2193 assessment notes for patients prescribed ARATs.

RESULTS: The F1-score for exact matches of all symptom tags between the NER system and annotators was 0.72, confirming the NER system has sufficient performance for application to pharmaceutical care records. The NER system automatically assigned 1900 symptom tags for the 2193 assessment notes from patients prescribed ARATs; 623 tags (32.8%) were positive symptom tags (symptoms present), while 1067 tags (56.2%) were negative symptom tags (symptoms absent). Positive symptom tags included ARAT-related AEs such as "pain," "skin disorders," "fatigue," and "gastrointestinal symptoms." Many other symptoms were classified as serious AEs. Furthermore, differences in symptom tag profiles reflecting pharmacists' AE monitoring were observed between androgen synthesis inhibition and androgen receptor signaling inhibition.

CONCLUSIONS: The NER system successfully extracted AEs from pharmaceutical care records of patients prescribed ARATs, demonstrating its potential to systematically track the presence and absence of AEs in outpatients. Based on the analysis of a large volume of pharmaceutical medical records using the NER system, community pharmacists not only detect potential AEs but also actively monitor the absence of severe AEs, offering valuable insights for the continuous improvement of patient safety management.

PMID:40068144 | DOI:10.2196/69663

JAMA Netw Open. 2025 Mar 3;8(3):e250814. doi: 10.1001/jamanetworkopen.2025.0814.

ABSTRACT

IMPORTANCE: Given that older adults are at high risk for adverse drug events (ADEs), many geriatric medication programs have aimed to optimize safe ordering, prescribing, and deprescribing practices.

OBJECTIVE: To identify emergency department (ED)-based geriatric medication programs that are associated with reductions in potentially inappropriate medications (PIMs) and ADEs.

DATA SOURCES: A systematic search of Scopus, Embase, PubMed, PsycInfo, ProQuest Central, CINAHL, AgeLine, and Cochrane Library was conducted on February 14, 2024, with no date limits applied.

STUDY SELECTION: Randomized clinical trials or observational studies focused on ED-based geriatric (aged ≥65 years) medication programs that provide ED clinician support to avoid PIMs and reduce ADEs.

DATA EXTRACTION AND SYNTHESIS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for abstracting data and the Cochrane risk-of-bias tool were used to assess data quality and validity. Abstract screening and full-text review were independently conducted by 2 reviewers, with a third reviewer acting as an adjudicator.

MAIN OUTCOMES AND MEASURES: Process (ordering, prescribing, and deprescribing PIM rates) and clinical (ADE, health care utilization, and falls) outcomes.

RESULTS: The search strategy identified 3665 unique studies, 98 were assessed for eligibility in full-text review, and 25 studies, with 44 640 participants, were included: 9 clinical pharmacist reviews (with 28 360 participants), 1 geriatrician teleconsultation (with 50 participants), 8 clinician educational interventions (with 5888 participants), 4 computerized clinical decision support systems (CDSS; with 9462 participants), and 3 fall risk-increasing drug (FRID) reviews (with 880 participants). Clinical pharmacist review was not associated with decreased hospital admission or length of stay, but 2 studies showed a 32% reduction in PIMs from deprescribing (odds ratio [OR], 0.68 [95% CI, 0.50-0.92]; P = .01). One study also found that ED geriatrician teleconsultation was associated with enhanced deprescribing of PIMs. Three clinician educational intervention studies showed a 19% reduction in PIM prescribing (OR, 0.81 [95% CI, 0.68-0.96]; P = .02). Two computerized CDSS studies showed a 40% reduction in PIM ordering (OR, 0.60 [95% CI, 0.48-0.74]; P < .001). FRID reviews were not associated with reduced time to first fall or fall recurrence at 12 months.

CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of ED-based geriatric medication safety programs, a multidisciplinary team, including clinical pharmacists and/or geriatricians, was associated with improved PIM deprescribing. Furthermore, computerized CDSS, alone or in combination with ED clinician education, was associated with enhanced geriatric ordering and prescribing practices. These findings will inform the Geriatric ED Guidelines version 2.0 update.

PMID:40067297 | DOI:10.1001/jamanetworkopen.2025.0814

Respirol Case Rep. 2025 Mar 10;13(3):e70147. doi: 10.1002/rcr2.70147. eCollection 2025 Mar.

ABSTRACT

Dasatinib, a second-generation tyrosine kinase inhibitor used for treating chronic myeloid leukaemia (CML), is associated with rare but significant adverse effects, including pulmonary arterial hypertension. This condition is thought to result from endothelial dysfunction and vascular remodelling linked to Src kinase inhibition. Symptoms such as progressive dyspnoea and fatigue may appear months or years after starting therapy, emphasising the need for long-term vigilance. We present the case of a 55-year-old female with CML who developed severe pre-capillary pulmonary hypertension after prolonged dasatinib use. Diagnosis was confirmed via echocardiography and right heart catheterisation, with other causes excluded. Following dasatinib discontinuation, initiation of targeted PAH therapy, and replacement with imatinib, the patient showed significant clinical and haemodynamic improvement.

PMID:40065794 | PMC:PMC11893177 | DOI:10.1002/rcr2.70147

J Clin Hypertens (Greenwich). 2025 Mar;27(3):e70029. doi: 10.1111/jch.70029.

ABSTRACT

Hypertension exerts a significant global disease burden, adversely affecting the well-being of billions. Alarmingly, drug-related hypertension remains an area that has not been comprehensively investigated. Therefore, this study is designed to utilize the adverse event reports (AERs) from the US Food and Drug Administration's Adverse Event Reporting System (FAERS) to more comprehensively identify drugs that may potentially lead to hypertension. Specifically, a total of 207 233 AERs were extracted from FAERS, spanning the time period from 2004 to 2024. Based on these reports, this study presented the top 40 drugs most frequently reported to be associated with post-administration hypertension in different genders. Furthermore, we employed four disproportionality analysis methods, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM), to pinpoint the top three drugs with strongest signals in relation to hypertension across different age and gender subgroups. Some drugs, such as rofecoxib, lenvatinib, and celecoxib, were found to appear on both the frequency and signal strength lists. These results contribute to a more comprehensive understanding of the cardiovascular safety profiles of pharmacological agents, suggesting the necessity of blood pressure monitoring following administration.

PMID:40065662 | DOI:10.1111/jch.70029

MedComm (2020). 2025 Mar 6;6(3):e70124. doi: 10.1002/mco2.70124. eCollection 2025 Mar.

ABSTRACT

This multicenter study aimed to investigate the efficacy and safety of PD-1/PD-L1 inhibitors plus chemotherapy (ICI-Chemo group) versus chemotherapy alone (Chemo group) for patients with cancer of unknown primary (CUP) in the first-line setting. We included patients with unfavorable CUP across four medical centers in China. Between January 2014 and December 2023, 117 patients were enrolled: 46 patients in the ICI-Chemo group and 71 patients in the Chemo group. After a median follow-up of 28.1 months, the ICI-Chemo group exhibited a significant improvement over the Chemo group in median PFS (9.10 months vs. 6.37 months; hazard ratio [HR] 0.46; 95% CI: 0.30-0.71; p < 0.001) and OS (35.67 months vs. 10.2 months; HR 0.37; 95% CI: 0.22-0.64; p < 0.001). Similarly, among patients who received TP (taxane plus platinum)-based chemotherapies, OS and PFS benefits were observed in the ICI-Chemo group. The objective response rate was higher in the ICI-Chemo group than in the Chemo group (54.35% vs. 22.53%, p < 0.001). Grade 3 or higher drug-related adverse events occurred in 11 patients (23.91%) in the ICI-Chemo group and 28 patients (39.44%) in the Chemo group. Thus, PD-1/PD-L1 inhibitors plus chemotherapy could be the preferred first-line treatment for patients with unfavorable CUP, providing improved efficacy and manageable toxicity.

PMID:40060196 | PMC:PMC11885889 | DOI:10.1002/mco2.70124

Sci Rep. 2025 Mar 9;15(1):8148. doi: 10.1038/s41598-025-92605-5.

ABSTRACT

For individuals with amyotrophic lateral sclerosis (ALS), intravenous edaravone is approved as a disease-modifying medication; yet, there have been many reports of adverse events (AEs). We examined the AEs associated with edaravone in this study using actual data from the FDA's (Food and Drug Administration) adverse event reporting system (FAERS). By extracting large-scale data from the FAERS database, this study used the signals of edaravone-associated AEs were quantified using the multiitem gamma Poisson shrinker (MGPS) method based on disproportionality, the Bayesian confidence propagation neural network (BCPNN), the reporting odds ratio (ROR), and the proportional reporting ratio (PRR). In the FAERS database, this study extracted data between April 2017 and March 2024, and edaravone was identified as the "primary suspect (PS)" in 2,986 AE reports. AEs associated with edaravone specifically targeted 27 system organ types (SOCs). Unexpectedly serious AEs that weren't mentioned in the drug insert, include abnormal hepatic function, catheter site thrombosis, pain, cerebral hemorrhage, infection, cerebral infarction, poor venous access, disseminated intravascular coagulation, vein collapse and cerebral venous sinus thrombosis. Our research found possible signals of new AEs that may offer substantial backing for clinical surveillance and edaravone risk assessment, but further research and validation are needed, especially for those AE that may occur in actual usage scenarios but are not yet explicitly described in the instruction.

PMID:40059194 | DOI:10.1038/s41598-025-92605-5

Hum Vaccin Immunother. 2025 Dec;21(1):2471225. doi: 10.1080/21645515.2025.2471225. Epub 2025 Mar 9.

ABSTRACT

Fear of side effects is the main motive for vaccine refusal. However, before the COVID-19 pandemic, little attention had been paid to the actual experience of adverse events and its relationship with vaccine hesitancy. This scoping review aimed to analyze the impact of VH on EAE and vice versa. We reviewed 55 articles. Most of the studies focused on COVID-19 vaccination and employed cross-sectional surveys with self-reported indicators. These studies identified significant correlations between EAE and VH. Social cognitive models shed some light on the influence of EAE on VH, while the converse is usually explained by the nocebo effect that predominately accounts for the converse. This emerging research field is hampered by significant inconsistencies in theoretical explanations, assessments of the relationship, and measurements of these two phenomena. A more comprehensive consideration of individual experience, both objective and subjective, would help develop more effective vaccine communication strategies and improve pharmacological surveillance.

PMID:40058398 | DOI:10.1080/21645515.2025.2471225

Age Ageing. 2025 Mar 3;54(3):afaf019. doi: 10.1093/ageing/afaf019.

ABSTRACT

The adoption of technology, particularly for monitoring the effects of medications in residential aged care (nursing home), has been slow. Ageing populations have led to increased demand for residential aged care globally, resulting in a growing imperative to implement technological solutions to meet the complex healthcare and medication needs of older people in residential aged care. This commentary explores the potential for and the challenges associated with implementing technological interventions within residential aged care to improve monitoring of medication effects. Drawing on insights from two implementation trials, specifically the Reducing Medicine-induced Deterioration and Adverse Reactions and A Digitally Enabled Pharmacist Service to detecT medicine harms in residential aged care, we discuss the unique challenges and opportunities arising from the real-world applications of digital technologies for medication safety in aged care.

PMID:40057985 | DOI:10.1093/ageing/afaf019

J Allergy Clin Immunol Pract. 2025 Mar 7:S2213-2198(25)00208-9. doi: 10.1016/j.jaip.2025.02.035. Online ahead of print.

ABSTRACT

BACKGROUND: Long-acting bronchodilators can improve the control of asthma when added to inhaled corticosteroids. However, the cardiovascular safety of these drugs in patients with asthma has not been comprehensively evaluated. Notably, growing evidence has indicated a positive association between asthma and cardiovascular disease.

OBJECTIVE: To evaluate the cardiovascular safety of adding long-acting bronchodilators in patients with asthma.

METHODS: After a comprehensive search in PubMed, Embase, Cochrane Library, and Web of Science, we included randomized controlled trials that assessed the cardiovascular safety of long-acting bronchodilators in patients with asthma. The primary outcome was a comparison of the incidence of total cardiovascular adverse events (AEs). Secondary outcomes included drug-related AEs, AEs leading to discontinuation, serious AEs, and fatal AEs.

RESULTS: A total of 22 trials with 62,915 patients were included. The use of long-acting bronchodilators significantly increased the incidence of cardiovascular AEs leading to discontinuation (incidence rate ratio = 3.05; 95% CI, 1.07-8.48). The incidence of total cardiovascular AEs, drug-related AEs, serious AEs, and fatal AEs was higher in patients treated with long-acting bronchodilators, but the differences were not significant. The certainty of evidence was low for comparations of total cardiovascular AEs and fatal AEs. The certainty of evidence was very low for comparisons of drug-related AEs, AEs leading to discontinuation, and serious AEs.

CONCLUSIONS: The incidence of cardiovascular AEs was low in patients with asthma. Only the risk of AEs leading to discontinuation was significantly increased compared with those not exposed to long-acting bronchodilators. More studies are required to confirm these findings considering the potential reporting bias.

PMID:40057190 | DOI:10.1016/j.jaip.2025.02.035

Int J Neuropsychopharmacol. 2025 Mar 8:pyaf015. doi: 10.1093/ijnp/pyaf015. Online ahead of print.

ABSTRACT

Since the 1950s, understanding of antipsychotic activity in schizophrenia has been largely grounded in the dopamine hypothesis. Most antipsychotics approved for schizophrenia interact with D2 dopamine receptors as an important part of their mechanism of action. While antipsychotics blocking D2 dopamine receptors can be effective for positive symptoms of schizophrenia, none are approved by regulatory authorities for predominant negative or cognitive symptoms. Moreover, many of these agents induce a range of problematic side effects related to D2 dopamine receptor blockade (e.g., drug-induced parkinsonism, akathisia, tardive dyskinesia, hyperprolactinemia and related sexual side effects, sedation). This has prompted the search for novel mechanisms with improved efficacy and tolerability based on evidence supporting involvement of other neurotransmitter systems in schizophrenia pathophysiology, including acetylcholine, gamma-aminobutyric acid, and glutamate. Among these options, targeting muscarinic receptors emerged as a promising treatment strategy. In September 2024, the U.S. Food and Drug Administration approved xanomeline and trospium chloride for treatment of adults with schizophrenia based on results from three 5-week, randomized, double-blind, placebo-controlled trials and two 52 week open-label trials. In the placebo-controlled trials, xanomeline/trospium reduced symptoms of schizophrenia, was generally well tolerated, and was not associated with clinically meaningful motor symptoms, hyperprolactinemia, sexual side effects, or weight gain compared with placebo. The long-term safety of xanomeline/trospium was also confirmed in two 52-week, open-label trials. This paper reviews the preclinical and clinical rationale for muscarinic receptor activation as a treatment for schizophrenia and the efficacy, safety, and tolerability profile of xanomeline/trospium.

PMID:40056428 | DOI:10.1093/ijnp/pyaf015

BMC Gastroenterol. 2025 Mar 7;25(1):148. doi: 10.1186/s12876-025-03732-2.

ABSTRACT

OBJECTIVE: With the rising incidence of MASLD, extensive drug research has been conducted in clinical trials. The study examined the design principles and research objectives of MASLD therapeutics, in order to offer guidance to clinical trial participants and decision makers.

METHODS: By searching the clinical research trial data registered on clinicaltrials.gov platform, 1209 interventional clinical trials were screened. These trials were subsequently evaluated based on clinical stage, trial design, intervention modalities, outcome metrics, and other pertinent factors.

RESULTS: A total of 1,209 trials were included, of which 199 were registered from 2000 to 2012 (16.46%) and 1010 were registered from 2013 to 2024 (83.54%), reflecting the growing body of research on MASLD. Regarding the intervention model type, single-group designs were employed in 232 (19.19%) trials, and parallel designs were employed in 873(72.21%). A total of 13 trials were early phase 1 (1.08%), 152 (12.57%) were phase 1, 34 (2.81%) were phase 1/phase 2, 301 were phase 2 (24.90%), 19 (1.57%) were phase 2/phase 3, 72 (5.96%) were phase 3, and 84 (6.95%) were phase 4. Within these trials, the three primary clinical outcomes for drug interventions were hepatic histological improvement, hepatic fat content and adverse events. Furthermore, 140 drug interventional trials with results for therapeutic purposes (This accounted for 88.61% of the 158 drug interventional trials with results) primarily aimed to improve MASLD through mechanisms such as metabolic and energy balance, inflammatory and immunomodulatory, and lipid reduction, targeting primarily PPAR, FXR, ACC and GLP-1.

CONCLUSION: This study suggests the basic characteristics of global MASLD clinical trial design, and the current global interventional clinical trials are mainly focused on drug-related treatments, and drugs to improve inflammation and metabolism are still the first choice for MASLD drug intervention studies.

PMID:40055604 | DOI:10.1186/s12876-025-03732-2

Lancet HIV. 2025 Mar;12(3):e191-e200. doi: 10.1016/S2352-3018(24)00344-8.

ABSTRACT

BACKGROUND: Long-acting cabotegravir and long-acting rilpivirine constitute a completely intramuscular antiretroviral therapy (ART) regimen for adults with HIV. We aimed to assess the safety, antiviral activity, and pharmacokinetics of oral cabotegravir and rilpivirine followed by a combination of long-acting cabotegravir and long-acting rilpivirine in virologically suppressed adolescents with HIV.

METHODS: The IMPAACT 2017/MOCHA study is a phase 1/2, multicentre, open-label, non-comparative, dose-finding trial being conducted at 18 sites across Botswana, South Africa, Thailand, Uganda, and the USA. In cohort 2 of this study, adolescents (aged 12-18 years; weight ≥35 kg) with HIV and no serious comorbidities who were receiving stable combination ART with confirmed virological suppression and had either previously enrolled in the first cohort or had not previously participated in the study were eligible for inclusion. Participants stopped their background combination ART and received oral cabotegravir 30 mg once daily and oral rilpivirine 25 mg once daily orally for 4-6 weeks, followed by long-acting injectable cabotegravir 600 mg (3 mL) and long-acting injectable rilpivirine 900 mg (3 mL) intramuscularly at weeks 4 and 8, and every 8 weeks thereafter. The primary outcome was safety, including all adverse events, at week 24. Primary safety outcome measures were summarised as frequencies, percentages, and exact Clopper-Pearson 95% CIs in the evaluable analysis population, which included participants who were treated exclusively with the regimen and either completed all scheduled treatments or experienced severe adverse events, permanently discontinued the treatment, or died, whichever occurred first; and in the all-treated analysis population, which included all participants who received at least one dose of any study product. This study is registered with ClinicalTrials.gov (NCT3497676) and is ongoing.

FINDINGS: Between July 26, 2021, and Aug 27, 2022, 44 (80·0%) of 55 adolescents who participated in cohort 1 and 100 (87·0%) of 115 screened study-naive adolescents were enrolled in cohort 2. 74 (51·4%) participants were female and 70 (48·6%) were male. Overall, 15 (10·8% [95% CI 6·2-17·2]) of all 139 participants in the evaluable analysis population had at least one adverse event of grade 3 or above by week 24. Among 142 participants who received at least one injection, 43 (30%) experienced at least one injection site reaction (ISR). All 106 ISRs were either grade 1 (98 [92·5%]) or grade 2 (eight [7·5%]), and 97 (91·5%) resolved within 7 days. No participant experienced a drug-related serious adverse event or prematurely discontinued treatment due to a drug-related adverse event.

INTERPRETATION: Long-acting injectable cabotegravir and long-acting injectable rilpivirine, administered to adolescents at recommended adult dosages every 8 weeks, showed no unanticipated safety concerns in the 24 weeks following administration.

FUNDING: National Institutes of Health, ViiV Healthcare, and Johnson & Johnson.

PMID:40049924 | DOI:10.1016/S2352-3018(24)00344-8

J Nucl Med. 2025 Mar 6:jnumed.124.268872. doi: 10.2967/jnumed.124.268872. Online ahead of print.

ABSTRACT

A first-in-human phase I clinical study aimed to assess the safety profile, radiation dosimetry, and biodistribution of a potential cardiac PET myocardial perfusion imaging tracer, [18F]SYN2 (18F-labeled acridine derivative), in healthy subjects. Methods: [18F]SYN2 intravenous administration with PET imaging was performed on healthy volunteers, and sequential whole-body imaging was performed over 4 h. Blood and urine samples were collected for up to 240 min. Safety follow-up visits took place at 2, 5, and 14 d after the administration. Results: Ten subjects (8 women and 2 men) completed all study procedures. The mean age was 38.1 ± 8.8 y, and the mean body mass index was 22.7 ± 3.0 kg/m2 The mean administered dose of radioactivity was 258 MBq (range, 246-272 MBq). There were no drug-related adverse events, and the tracer was well tolerated in all subjects. The mean whole-body effective radiation dose for [18F]SYN2 was 0.0195 mSv/MBq. The tracer was rapidly taken up by the myocardial wall and cleared from plasma, leading to good image quality within minutes of tracer injection. Conclusion: On the basis of the safety profile, radiation dosimetry, and biodistribution of [18F]SYN2, it appears to be a promising agent for clinical PET myocardial perfusion imaging and to warrant further clinical studies.

PMID:40049745 | DOI:10.2967/jnumed.124.268872