JAMA Netw Open. 2025 Mar 3;8(3):e252668. doi: 10.1001/jamanetworkopen.2025.2668.

ABSTRACT

IMPORTANCE: The use of immune checkpoint inhibitors (ICIs) is increasing. Little is known about the frequency of late-onset immune-related adverse events (irAEs) and the patient-specific risk factors associated with their development.

OBJECTIVES: To assess the incidence of persistent or de novo late-onset irAEs requiring hospitalization and identify patient factors associated with risk of late-onset irAEs.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational cohort study conducted from January 2011 to October 2022 included patients who received ICIs and were hospitalized with irAEs at an academic medical center. Exclusion criteria included ICI therapy outside of the hospital system and no irAE diagnosis during admission. Data were analyzed from November 15, 2022, to January 8, 2025.

EXPOSURE: Late-onset irAEs.

MAIN OUTCOMES AND MEASURES: The main study outcomes were (1) incidence of irAE hospitalization at 0 to 6 months (early), more than 6 to 12 months (intermediate), and more than 12 months (late) after ICI initiation and (2) patient factors associated with risk of late-onset irAEs.

RESULTS: Among the 795 patients hospitalized with irAEs, the median age was 67.3 years (IQR, 58.3-74.8 years); 476 (59.9%) were male. Most patients (n = 517 [65.0%]) received anti-programmed death ligand 1 (PD-L1) and anti-programmed cell death 1 monotherapy, with the most common indications being melanoma (n = 335 [42.1%]) and lung cancer (n = 167 [21.0%]). The median time from start of ICI therapy to hospital admission was 2.7 months (IQR, 1.2-6.1 months), with 14.7% of patients (n = 117 of 795) presenting 6 to 12 months after initial ICI exposure and 10.8% of patients (86 of 795) presenting more than 12 months after initial exposure. The irAEs most likely to present late included those involving the kidney (10 of 32 [31.3%]) and hematologic (5 of 23 [21.7%]) organ systems. In univariate analysis, ICI type was significantly associated with the timing of hospital admission for irAEs; of the 517 patients receiving anti-PD-L1-based therapy, 13.5% (n = 70) presented late compared with 5.4% (9 of 167) receiving dual therapy with anti-cytotoxic T-lymphocyte-associated protein 4 (P < .001). Patients receiving perioperative ICI therapy were significantly more likely to be admitted at the intermediate interval (16 of 68 [23.5%]) compared with those with metastatic disease (87 of 678 [12.8%]) (P = .03). Timing of irAE was also significantly associated with active ICI exposure; among the patients presenting late, 7.4% (48 of 651) had received ICI therapy within the last 60 days compared with 26.4% (38 of 144) who had not had recent ICI exposure (P < .001).

CONCLUSIONS AND RELEVANCE: The findings of this retrospective observational cohort study suggest that late irAEs are possible, with a subset of patients presenting years after the start of ICI therapy. Clinicians must remain vigilant for irAEs regardless of elapsed time from ICI therapy, especially as patients live longer and ICIs become more widely used. Future investigations are needed to better understand the risk factors for late-onset irAEs and the distinct immunologic pathways that underlie such events.

PMID:40146104 | DOI:10.1001/jamanetworkopen.2025.2668

Pharmaceuticals (Basel). 2025 Feb 23;18(3):307. doi: 10.3390/ph18030307.

ABSTRACT

Background/Objectives: Transarterial chemoembolization (TACE) is a widely accepted and minimally invasive treatment for primary and metastatic liver cancer. Performing TACE with drug-eluting beads helps obtain a greater drug concentration in the target lesion, significantly reducing systemic drug leakage, liver toxicity, and adverse events. The aim of this study is to describe the safety and feasibility of TACE performed with BioPearlTM, the first biodegradable drug-eluting microspheres. Methods: This was a retrospective observational study on 13 consecutive patients affected by hepatocellular carcinoma (HCC) treated with doxorubicin-loaded-BioPearlTM-TACE. Data on safety, feasibility, and tumor response were collected. Results: One intra-procedural catheter blockage was registered, as well as two post-treatment bilomas that required additional treatment. No severe general drug-related side effects were detected at the follow-up. The 1-month overall disease control was 90.9%, with six complete responses. Conclusions: Data suggest that chemoembolization with BioPearlTM is feasible and safe for the treatment of HCC as indicated by good tolerability.

PMID:40143086 | DOI:10.3390/ph18030307

BJC Rep. 2025 Mar 26;3(1):17. doi: 10.1038/s44276-025-00133-6.

ABSTRACT

BACKGROUND: Single-agent MEK1/2 inhibition has been disappointing in clinical trials targeting RAS mutant (MT) cancers, probably due to upstream receptor activation, resulting in resistance. We previously found that dual c-MET/MEK1/2 inhibition attenuated RASMT colorectal cancer (CRC) xenograft growth. In this study, we assessed safety of MEK1/2 inhibitor PD-0325901 with c-MET inhibitor crizotinib and determined the optimal biological doses for subsequent clinical trials.

METHODS: In this dose-escalation phase I trial, patients with advanced solid tumours received PD-0325901 with crizotinib, using a rolling-6 design to determine the maximum tolerable dose (MTD) and safety/tolerability. Blood samples for pharmacokinetics and skin biopsies were collected.

RESULTS: Twenty-five patients were recruited in 4 cohorts up to doses of crizotinib 200 mg B.D continuously with PD-0325901 8 mg B.D, days 1-21 every 28 days. One in six patients exhibited a dose-limiting toxicity at this dose level. Drug-related adverse events were in keeping with single-agent toxicity profiles. The best clinical response was stable disease in seven patients (29%).

CONCLUSIONS: PD-0325901/crizotinib can be given together at pharmacologically-active doses. The MTD for PD-0325901/crizotinib was 8 mg B.D (days 1-21) and 200 mg B.D continuously in a 28-days cycle. The combination was further explored with an alternate MEK1/2 inhibitor in RASMT CRC patients.

EUDRACT-NUMBER: 2014-000463-40.

PMID:40140597 | DOI:10.1038/s44276-025-00133-6

Sci Rep. 2025 Mar 26;15(1):10384. doi: 10.1038/s41598-025-94947-6.

ABSTRACT

OBJECTIVE: To analyze and compare the incidence of adverse events (AEs) associated with different administration routes of colistin, with the aim of providing a reference for its safe and effective clinical use.

METHODS: Adverse event (AE) reports related to colistin were retrieved from the FDA Adverse Event Reporting System (FAERS) database. The reporting trends were analyzed, and the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) for colistin-associated AEs were calculated. A comparative analysis was conducted to examine the occurrence of AEs under different administration routes of colistin.

RESULTS: A total of 13,043 AE reports were extracted from the FAERS database. Further analysis of 176 key AEs associated with colistin indicated a significant increase in the number of reports after 2021. The year and country of the reports showed heterogeneity across different administration routes. Intravenous (IV) administration of colistin was associated with the highest proportion of AEs, and heterogeneity was also observed in the types of AEs reported for inhaled and oral (PO) administration routes.

CONCLUSION: Compared to inhaled and PO administration routes, IV administration of colistin is more likely to result in AEs such as nephrotoxicity and drug ineffectiveness. Additionally, there are significant differences in the types of AEs associated with colistin across different administration routes.

PMID:40140483 | DOI:10.1038/s41598-025-94947-6

Therapie. 2025 Mar 4:S0040-5957(25)00039-3. doi: 10.1016/j.therap.2025.02.011. Online ahead of print.

ABSTRACT

INTRODUCTION: Dentists, in their practice, bear responsibility for the benefits and the risks associated with the medications they prescribe. Their code of ethics grants them the freedom to prescribe while encouraging them to limit their interventions to what is strictly necessary for the quality and effectiveness of care. Furthermore, dentists also face ontological adverse effects resulting from medications they did not personally prescribe. A study based on the analysis of cases recorded over ten years in the national pharmacovigilance database (BNPV) is relevant for assessing the current state of pharmacovigilance reports submitted by dentists.

METHODS: We conducted a retrospective analysis of the cases recorded in the BNPV, reported by dentists between 01/01/2013 and 31/12/2023.

RESULTS: Over 10 years, 509 reports were recorded, representing 0.06% of all registered cases. These reports were divided into three main groups. Among the 509 declarations, 24.8% were cases associated with medications used in the field of dentistry, such as anti-inflammatory drugs, antibiotics, local anaesthetics, and local antiseptics. In total, 35.2% were cases of odontological adverse effects, such as jaw osteonecrosis, gingival hypertrophy, and oral ulcers. Finally, 28.3% of the cases involved reports of adverse effects related to coronavirus disease 2019 (COVID-19) vaccination, which began in late December 2020.

CONCLUSION: The low rate of pharmacovigilance reports by dentists in France over the past ten years highlights an issue of underreporting of adverse effects in dental practice. Recent literature emphasizes the importance of pharmacovigilance reporting in the field of dentistry, particularly concerning odontological effects.

PMID:40140295 | DOI:10.1016/j.therap.2025.02.011

Drug Ther Bull. 2025 Mar 26:dtb-2025-000012. doi: 10.1136/dtb.2025.000012. Online ahead of print.

ABSTRACT

The BNF is jointly published by the Royal Pharmaceutical Society and BMJ. BNF is published in print twice a year and interim updates are issued and published monthly in the digital versions. The following summary provides a brief description of some recent key changes that have been made to BNF content.

PMID:40139730 | DOI:10.1136/dtb.2025.000012

Curr Oncol. 2025 Feb 27;32(3):140. doi: 10.3390/curroncol32030140.

ABSTRACT

The advent of immune checkpoint inhibitors (ICIs) has significantly transformed cancer treatment outcomes. However, these therapies can induce immune-related adverse events (irAEs) that may affect any organ system, sometimes requiring specialized expertise. As ICIs are increasingly used across various tumor types and in earlier treatment settings, not all practitioners have the necessary support network to handle complex irAEs. To address this gap, we collaborated with ONCOassist, a leading app for oncology professionals, to establish the first virtual Canadian Community of Practice (CoP) focused on irAEs. The CoP facilitates continuous learning and improves patient care among Canadian clinicians treating patients with immunotherapy by providing a platform for knowledge exchange and peer-to-peer support. This article outlines the development and growth of the CoP on irAEs, highlighting both successes and challenges. As of May 2024, over a year since its inception, the CoP on irAEs has attracted almost 130 Canadian oncology healthcare professionals, and peer-to-peer interactions and engagement continue to increase. To ensure its long-term sustainability, we plan to evolve and adapt the CoP to meet the needs of the oncology community and address clinical challenges associated with new therapies.

PMID:40136344 | DOI:10.3390/curroncol32030140

Front Pharmacol. 2025 Mar 11;16:1508276. doi: 10.3389/fphar.2025.1508276. eCollection 2025.

ABSTRACT

BACKGROUND: Effective therapies for pulmonary fibrosis caused by coronavirus disease (COVID-19) and other etiologies are lacking. Our previous studies demonstrated that Fuzheng Huayu tablet (FZHY), a traditional Chinese medicine known for its anti-liver fibrotic properties, can improve lung function in patients with chronic obstructive pulmonary disease and attenuate bleomycin-induced pulmonary fibrosis in rats.

PURPOSE: This study aimed to evaluate the efficacy and safety of FZHY in post-COVID-19 pulmonary fibrosis.

METHODS: A multi-center, randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the efficacy of a 24-week treatment with FZHY, combined with vitamin C and respiratory function rehabilitation, for treating pulmonary fibrosis in discharged convalescent COVID-19 patients. The primary outcome was the regression rate of pulmonary fibrosis assessed by the high-resolution computed tomography scores and lung function improvement (forced vital capacity [FVC], forced expiratory volume in one second [FEV1], and FEV1/FVC) after 24 weeks. Secondary outcomes included the 6-min walk distance, improvement in pulmonary inflammation, clinical symptoms, and quality of life.

RESULTS: This study included 142 patients, who were randomized to the FZHY (n = 72) and placebo groups (n = 70). By week 24, the regression rates of pulmonary fibrosis in the FZHY and placebo groups were 71.2% and 49.2%, respectively (p = 0.01). Limited spirometry data revealed higher FEV1/FVC in the FZHY group than in the placebo group at week 8 ([87.7 ± 7.2] % vs. [82.7 ± 6.9] %; p = 0.018). The regression rates in pulmonary inflammation in the FZHY and placebo groups were 83.8% and 68.8%, respectively (p = 0.04). At week 4, the increase in 6-min walking distance was greater in the FZHY group than in the placebo group ([41.4 ± 64.1] m vs. [21.8 ± 50.3] m; p = 0.05). However, no significant differences were observed between the groups in the improvement rate of clinical symptoms, quality of life-BREF, patient health questionnaire-9, or generalized anxiety disorder-7 scores (p > 0.05). No drug-related adverse events were reported in the FZHY group.

CONCLUSION: FZHY attenuates post-COVID-19 pulmonary fibrosis, with good safety profiles.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04279197, identifier NCT04279197.

PMID:40135237 | PMC:PMC11933019 | DOI:10.3389/fphar.2025.1508276

Case Rep Anesthesiol. 2025 Mar 18;2025:1303993. doi: 10.1155/cria/1303993. eCollection 2025.

ABSTRACT

Acute liver injury can be precipitated by several factors perioperatively. One of the rare factors identified intraoperatively is the use of sevoflurane, an inhalational anesthetic agent which can cause significant acute hepatotoxicity. The report presents a case of acute liver injury followed by graft loss in a patient who underwent kidney transplantation. The patient developed several complications which resulted in graft loss. Close postoperative monitoring of patients following kidney transplantation is crucial. The case supports the current literature describing sevoflurane as a hepatotoxic agent. Medication side effects should be closely monitored both intraoperatively and postoperatively in those with renal dysfunction.

PMID:40134944 | PMC:PMC11936524 | DOI:10.1155/cria/1303993

Sci Rep. 2025 Mar 26;15(1):10359. doi: 10.1038/s41598-025-95021-x.

ABSTRACT

To use the FDA Adverse Event Reporting System (FAERS) database to identify drugs associated with orthostatic hypotension. Adverse event reports of orthostatic hypotension from Q1 2004 to Q3 2024 were obtained from the FAERS and JADER databases. We employed algorithms such as the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) for signal detection. JADER database was used to validate the findings from FAERS analysis. We identified 15,737 adverse events associated with orthostatic hypotension, involving 15,480 patients for analysis. The patient demographic included 6,745 males (43.5%) and 7,248 females (46.8%), with the largest group comprising adults over 65 years (7,654 cases, 49.4%). The three drugs with the highest ROR risk signals were terazosin [ROR (95% CI): 153.96 (124.57-190.28)], rasagiline [ROR (95% CI): 37.46 (29.99-46.78)], and doxazosin [ROR (95% CI): 37.06 (31.32-43.86)]. Apomorphine, abalopatine and levodopa were associated with the shortest onset time of orthostatic hypotension. Most of the signal detection results from the FAERS database were verified in the JADER database. Drugs associated with orthostatic hypertension still focused on cardiovascular and nervous system drugs. This study employed the FAERS database to identify 33 drugs that may be potentially linked to orthostatic hypotension. Medical workers should remain vigilant regarding the risk of these drugs causing orthostatic hypotension.

PMID:40133436 | DOI:10.1038/s41598-025-95021-x

J Med Internet Res. 2025 Mar 25;27:e65872. doi: 10.2196/65872.

ABSTRACT

BACKGROUND: Torsades de pointes (TdP) is a rare yet potentially fatal cardiac arrhythmia that is often drug-induced. Drug-drug interactions (DDIs) are a major risk factor for TdP development, but the specific drug combinations that increase this risk have not been extensively studied.

OBJECTIVE: This study aims to identify clinically significant, high-priority DDIs to provide a foundation to minimize the risk of TdP and effectively manage DDI risks in the future.

METHODS: We used the following 4 frequency statistical models to detect DDI signals using the Food and Drug Administration Adverse Event Reporting System (FAERS) database: Ω shrinkage measure, combination risk ratio, chi-square statistic, and additive model. The adverse event of interest was TdP, and the drugs targeted were all registered and classified as "suspect," "interacting," or "concomitant drugs" in FAERS. The DDI signals were identified and evaluated using the Lexicomp and Drugs.com databases, supplemented with real-world data from the literature.

RESULTS: As of September 2023, this study included 4313 TdP cases, with 721 drugs and 4230 drug combinations that were reported for at least 3 cases. The Ω shrinkage measure model demonstrated the most conservative signal detection, whereas the chi-square statistic model exhibited the closest similarity in signal detection tendency to the Ω shrinkage measure model. The κ value was 0.972 (95% CI 0.942-1.002), and the Ppositive and Pnegative values were 0.987 and 0.985, respectively. We detected 2158 combinations using the 4 frequency statistical models, of which 241 combinations were indexed by Drugs.com or Lexicomp and 105 were indexed by both. The most commonly interacting drugs were amiodarone, citalopram, quetiapine, ondansetron, ciprofloxacin, methadone, escitalopram, sotalol, and voriconazole. The most common combinations were citalopram and quetiapine, amiodarone and ciprofloxacin, amiodarone and escitalopram, amiodarone and fluoxetine, ciprofloxacin and sotalol, and amiodarone and citalopram. Although 38 DDIs were indexed by Drugs.com and Lexicomp, they were not detected by any of the 4 models.

CONCLUSIONS: Clinical evidence on DDIs is limited, and not all combinations of heart rate-corrected QT interval (QTc)-prolonging drugs result in TdP, even when involving high-risk drugs or those with known risk of TdP. This study provides a comprehensive real-world overview of drug-induced TdP, delimiting both clinically significant DDIs and negative DDIs, providing valuable insights into the safety profiles of various drugs, and informing the optimization of clinical practice.

PMID:40132181 | DOI:10.2196/65872

PLoS One. 2025 Mar 24;20(3):e0309849. doi: 10.1371/journal.pone.0309849. eCollection 2025.

ABSTRACT

BACKGROUND: Finasteride is commonly utilized in clinical practice for treating androgenetic alopecia, but real-world data regarding the long-term safety of its 0adverse events(AEs) remains incomplete, necessitating ongoing supplementation. This study aims to evaluate the AEs associated with finasteride use, based on data from the US Food and Drug Administration Adverse Event Reporting System (FAERS), to contribute to its safety assessment.

METHODS: We reviewed AE reports associated with finasteride from the US Food and Drug Administration Adverse Event Reporting System database, covering the period from the first quarter of 2004 to the first quarter of 2024. We assessed the safety of finasteride medication and AEs using four proportional disproportionality analyses: reported odds ratio (ROR), proportionate reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPN), and Multi-Item Gamma Poisson Shrinkage (MGPS). These methods were used to evaluate whether there is a significant association between finasteride drug use and AEs. To investigate potential safety issues related to drug use, we further analyzed the similarities and differences in the onset time and AEs by sex, as well as the similarities and differences in AEs by age.

RESULTS: A total of 11,557 AE reports in which finasteride was the primary suspected drug were analysed. The majority of patients were male (86.04%) and a significant proportion were young adults aged 18-45 years (27.22%). A total of 73 different AEs were categorised into 7 system organ classes (SOCs), with common AEs including erectile dysfunction and sexual dysfunction. In addition, we identified previously unlisted AEs, including Peyronie's disease and post-5α reductase inhibitor syndrome. Of the reported AEs, 102 occurred in men and 7 in women, with depression and anxiety being significant AEs observed in both sexes. When analysed by age group, there were 17 AEs in patients aged ≤ 18 years, 157 in patients aged 18-65 years and 133 in patients aged ≥ 65 years. Common AEs in all age groups included erectile dysfunction, decreased libido, depression, suicidal ideation, psychotic disturbances and attention disorders. The median time to onset of all AEs was 61 days, with the majority occurring within the first month of treatment. Notably, a significant number of AEs persisted beyond one year of treatment.

CONCLUSION: The results of our study uncovered both known and novel AEs associated with finasteride medication. Some of these AEs were identical to the specification, and some of them signaled AEs that were not demonstrated in the specification. In addition, some AEs showed variations based on sex and age in our study. Consequently, our findings offer valuable insights for future research on the safety of finasteride medication and are anticipated to enhance its safe use in clinical practice.

PMID:40127098 | DOI:10.1371/journal.pone.0309849

Skin Health Dis. 2025 Feb 14;5(1):70-74. doi: 10.1093/skinhd/vzae023. eCollection 2025 Feb.

ABSTRACT

Immune checkpoint inhibitors are a class of drugs used in cancer treatment that promote the immune system's response by blocking the inhibitor signals from tumour cells, such as programmed cell death protein 1/programmed death ligand 1 and cytotoxic T-lymphocyte associated protein 4. Despite their clinical benefit, these monoclonal antibodies unspecifically activate the immune system and can lead to the development of 'immune-related adverse events'. Cutaneous toxicities are the most frequent immune-related adverse events, reported in approximately 30-50% of patients treated with immunotherapy; the most common dermatological toxicities are represented by rash, vitiligo, pruritus and lichenoid reactions. Usually, these reactions are mild and it is not necessary to suspend immunotherapy. Potentially life-threatening skin toxicities, such as immunobullous eruption, are rare and may appear in approximately 1% of patients. In this report we describe a case of bullous pemphigoid, the most frequent bullous disease, that developed after treatment with pembrolizumab for a metastatic melanoma. The diagnosis, first suspected by the referring clinic, was confirmed by performing serology and biopsy with direct immunofluorescence. The patient was first treated with high doses of systemic corticosteroids, without suspending the immunotherapy treatment. Subsequently, due to the continuous relapses, we decided to suspend pembrolizumab and systemic corticosteroid and to begin off-label treatment with dupilumab. The following case gives cause for reflection about the management of a drug-induced disease in an immunocompromised patient, while exploring the therapeutic options.

PMID:40125009 | PMC:PMC11924371 | DOI:10.1093/skinhd/vzae023

Ann Gastroenterol. 2025 Mar-Apr;38(2):174-181. doi: 10.20524/aog.2025.0944. Epub 2025 Feb 25.

ABSTRACT

BACKGROUND: Patients' and gastroenterologists' views on the relative importance of treatment outcomes and medication attributes for ulcerative colitis (UC) may differ. We aimed to explore which treatment outcomes and medication attributes are considered important by both for therapeutic decisions.

METHODS: Eight gastroenterologists and 23 patients with UC in Greece participated in semi-structured interviews and focus groups, respectively. The focus groups and interviews were audio-recorded, transcribed and coded, utilizing thematic analysis until data saturation was achieved.

RESULTS: Themes that were discussed included the impact of UC on daily life, UC-related outcomes, drug-related attributes and the patient-doctor relationship. Within these themes, disparities between the perspectives of gastroenterologists and patients were evident on 2 main issues. Gastroenterologists prioritized clinical remission and emphasized long-term objectives, such as mucosal healing, while patients focused on shorter-term outcomes, such as the early and sustained relief of symptoms. Regarding medication attributes, important factors for patients were primarily those that impacted their daily life, such as route of administration, dosage and the need for hospital visits. In contrast, gastroenterologists were more concerned about potential adverse events and non-responsiveness to treatment. There was a consensus regarding the importance of shared decision-making for UC management, emphasized by both patients and clinicians.

CONCLUSIONS: Gastroenterologists mostly prioritize objective measures of remission, while patients mainly focus on factors related to their quality of life and overall well-being. Enhancing communication regarding different goals and expectations may strengthen the physician-patient relationship, ultimately resulting in better shared therapeutic decision-making.

PMID:40124436 | PMC:PMC11928895 | DOI:10.20524/aog.2025.0944

Pharmacoepidemiol Drug Saf. 2025 Mar;34(3):e70135. doi: 10.1002/pds.70135.

ABSTRACT

BACKGROUND: Direct Healthcare Professional Communications (DHPCs) are an important risk minimisation measure. Their effect has been shown to be variable and has been measured using different outcomes and study populations. Depending on the content of the message, the optimal outcome to measure a direct effect of the DHPC can differ. This systematic review investigates whether the effects of DHPCs differ according to the use of proximal outcomes and the inclusion of the targeted population.

METHODS: EMBASE and MEDLINE were searched for European DHPC effectiveness studies performed up to April 6, 2022, evaluating the impact of DHPCs issued from 2008. Outcomes and their impact were extracted, together with a classification of the message. The outcomes were categorised as knowledge/awareness, self-reported behaviour (prescribing/monitoring), prescribing of medication (including dosage changes), monitoring, or adverse events/other health outcomes, including hospitalisation. The outcomes closest to the message of the DHPC were defined as proximal. Outcomes were coded 1 when effective and 0 if not. If multiple outcomes were reported in a study, a composite outcome was created ranging from 0 to 1. Chi-square or Fisher exact tests were performed.

RESULTS: From 7063 (scientific) publications identified in our literature search, 60 publications evaluating 31 different DHPCs were selected for our review. As publications could study multiple messages with an outcome, from the 60 scientific publications, 103 outcomes were generated for the messages, of which 30 had a high impact on the composite outcome, with the proportion of analyses with a significant association between 0.75 and 1. When taking the target population into account, some messages were studied in more than one population, resulting in 115 outcomes, of which 33 had a high impact, that is, a composite outcome between 0.75 and 1.

CONCLUSION: Neither the use of proximal outcomes nor the restriction of the analysis to the targeted population significantly influenced the impact observed of the DHPC. These results stress the need for improving drug safety communication.

PMID:40122533 | DOI:10.1002/pds.70135

Geriatr Gerontol Int. 2025 Mar 21. doi: 10.1111/ggi.70035. Online ahead of print.

ABSTRACT

AIM: The use of potentially inappropriate medications (PIMs) in older adults can increase the risk of drug-related adverse events. We aimed to examine the associations between PIMs, frailty, and each frailty component in community-dwelling older women.

METHODS: This cross-sectional study included participants aged ≥65 years from a prospective cohort of older Japanese women. Frailty was classified using the Japanese version of Fried's Frailty Criteria, comprising five components. PIMs were identified using a screening tool for Japanese among regular prescription medications collected from participants' prescription notebooks. Multivariable logistic regression models adjusted for age and comorbidities were used to examine the association between PIMs (0, 1, 2, ≥3), frailty, and each component. The possible interactions between age groups (65-74 and ≥75 years) and PIMs were investigated. Age-stratified analyses were also performed.

RESULTS: We analyzed 530 older women (median age [interquartile range], 71 [68, 75] years) with a frailty prevalence of 5.5%. Three or more PIMs were associated with frailty and weight loss (adjusted odds ratio [95% confidence interval], 3.80 [1.23, 11.80], 2.53 [1.15, 5.39]). In age-stratified analyses, ≥3 PIMs were associated with weight loss (8.39 [1.79, 48.98]) in women aged ≥75 years, whereas 1 or 2 PIMs were associated with frailty (4.52 [1.17, 19.08]) or weakness (3.13 [1.22, 7.78]) in those aged 65-74 years.

CONCLUSIONS: Our results may suggest that the number of PIM prescriptions is associated with frailty and frailty components in older women. Longitudinal studies are required to clarify the causality between the number of PIMs and frailty. Geriatr Gerontol Int 2025; ••: ••-••.

PMID:40119543 | DOI:10.1111/ggi.70035

JMIR Res Protoc. 2025 Mar 21;14:e65789. doi: 10.2196/65789.

ABSTRACT

BACKGROUND: Pudilan Xiaoyan oral liquid (PDL) is a proprietary Chinese medicine preparation widely used for upper respiratory tract infection, known for its significant therapeutic effects. However, the safety profiles reported in several observational studies vary, and these studies primarily focus on efficacy rather than specifically addressing safety concerns, thus representing inadequate safety monitoring.

OBJECTIVE: This study aimed to investigate the incidence of adverse drug reactions (ADRs) associated with PDL and explore the factors contributing to these reactions.

METHODS: The study is a prospective, observational, multicenter, hospital-based surveillance study. A total of 17 hospitals from China are involved. The study is expected to enroll a large sample of 10,000 patients aged between 18 and 80 years with upper respiratory tract infection who were prescribed PDL. The patients' data, including demographics, medical history, diagnostic information, medication details, adverse events, and laboratory test results, will be monitored. The occurrence of ADRs will be recorded. The primary outcome is the incidence of ADR. Secondary outcomes are the ratio of patients whose body temperature return to the normal range (cases of body temperature normalization and the duration for achieving normal body temperature within a 3-day period will be documented) and changes in liver and kidney function (occurrence of drug-induced liver injury and acute kidney injury). Descriptive analyses will be performed for the primary and secondary outcomes. A cohort, nested, case-control study design will be used. If one patient has an ADR, then 4 patients without ADRs will be matched as the control group according to gender, age within 5 years, drug batch, and other factors, at a ratio of 1∶4 to compare the symptoms related to ADRs. The differences of ADR incidence among the possible influencing factors will be compared separately to find the factors with large differences. Then, synthetic minority oversampling technique and group least absolute shrinkage and selection operator methods will be used to identify factors influencing the occurrence of ADRs. Finally, propensity scoring methods will be used to control for confounding variables. The progress of each subcenter will be closely monitored, and the incidence of ADR will be systematically calculated. Furthermore, the characteristics and influencing factors of ADR will be analyzed, along with an investigation into its geographical distribution.

RESULTS: The study began on July 17, 2019. Due to the limited number of eligible patients, missed follow-ups, and the huge clinical burden caused by public health events in 2019, the final case will be enrolled on August 30, 2025.

CONCLUSIONS: This study will obtain safety results of PDL in the real world and provide guidance on the clinical safety of traditional Chinese medicine formulations.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04031651; https://clinicaltrials.gov/study/NCT04031651.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/65789.

PMID:40117581 | DOI:10.2196/65789

Eur J Clin Pharmacol. 2025 Mar 21. doi: 10.1007/s00228-025-03821-x. Online ahead of print.

ABSTRACT

PURPOSE: Direct oral anticoagulants (DOACs) are used to prevent and treat thromboembolic events in adults. We aimed to investigate whether pharmacogenomic variation contributes to the risk of bleeding during DOAC treatment.

METHODS: Cases were recruited from reports of bleeding sent to the Swedish Medical Products Agency (n = 129, 60% men, 93% Swedish, 89% on factor Xa inhibitors) and compared with population controls (n = 4891) and a subset matched for exposure to DOACs (n = 353). We performed a genome-wide association study, with analyses of candidate single nucleotide polymorphisms (SNPs) and candidate gene set analyses.

RESULTS: Forty-four cases had major, 37 minor, and 48 clinically relevant non-major (CRNM) bleeding. When cases were compared with matched controls, BAIAP2L2 rs142001534 was significantly associated with any bleeding and major/CRNM bleeding (P = 4.66 × 10-8 and P = 3.28 × 10-8, respectively). The candidate SNP CYP3A5 rs776746 was significantly associated with major and major/CRNM bleeding (P = 0.00020 and P = 0.00025, respectively), and ABCG2 rs2231142 was nominally associated with any bleeding (P = 0.01499). Rare coding variants in the candidate gene VWF were significantly associated with any bleeding (P = 0.00296).

CONCLUSION: BAIAP2L2, CYP3A5, ABCG2, and VWF may be associated with bleeding in DOAC-treated patients. The risk estimates of the candidate variants in CYP3A5 and ABCG2 were in the same direction as in previous studies. The Von Willebrand Factor gene (VWF) is linked to hereditary bleeding disorders, while there is no previous evidence of bleeding associated with BAIAP2L2.

PMID:40116934 | DOI:10.1007/s00228-025-03821-x

HIV Med. 2025 Mar 21. doi: 10.1111/hiv.70018. Online ahead of print.

ABSTRACT

INTRODUCTION: Black and Hispanic/Latine people are disproportionately affected by HIV-1 and may have a greater risk of comorbidities than non-Black and non-Hispanic/Latine people with HIV. However, they have historically been underrepresented in HIV clinical studies. We aimed to assess the efficacy and safety of first-line antiretroviral therapy with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) over 5 years in Black and Hispanic/Latine people with HIV.

METHODS: We present two post hoc pooled analyses of participants who received B/F/TAF up to week 240 in studies 1489 (NCT02607930) and 1490 (NCT02607956). Outcomes were compared between self-identified Black and non-Black participants and between Hispanic/Latine and non-Hispanic/Latine participants, including baseline characteristics, proportion with HIV-1 RNA <50 copies/mL, change in CD4 cell count, adherence, changes in metabolic parameters, and treatment-emergent adverse events.

RESULTS: Overall, 211 Black, 421 non-Black, 155 Hispanic/Latine, and 477 non-Hispanic/Latine participants received B/F/TAF up to week 240. At baseline, median ages were 30-34 years, and 84%-91% were male at birth. At week 240, high proportions of Black (97%), non-Black (99%), Hispanic/Latine (100%), and non-Hispanic/Latine (98%) participants had HIV-1 RNA <50 copies/mL. Black people with HIV were more likely than non-Black people with HIV to have low (<85%) adherence (11% vs. 5%; p = 0.0074). Changes in CD4 count, metabolic and renal parameters, and treatment-emergent hypertension and diabetes were generally similar between Black and non-Black and Hispanic/Latine and non-Hispanic/Latine participants. A smaller proportion of Black than non-Black people with HIV experienced study drug-related treatment-emergent adverse events (20% vs. 32%; p = 0.0026).

CONCLUSIONS: These results demonstrate the durability and long-term safety of B/F/TAF in Black and Hispanic/Latine people with HIV.

PMID:40116337 | DOI:10.1111/hiv.70018

Rev Cuid. 2024 Oct 11;15(3):e3612. doi: 10.15649/cuidarte.3612. eCollection 2024 Sep-Dec.

ABSTRACT

INTRODUCTION: Different non-pharmacological interventions have been studied to manage symptoms derived from chemotherapy, but their effectiveness is unknown.

OBJECTIVE: To describe non-pharmacological interventions for managing symptoms secondary to antineoplastic chemotherapy in adults.

MATERIALS AND METHODS: Systematic review of analytical experimental and observational studies (2021 to 2023). The studies were selected, and data was extracted in parallel. Discrepancies were resolved with a third reviewer. The risk of bias was assessed using the Risk of Bias (RoB) tool and The Newcastle-Ottawa Scale (NOS). The literature was synthesized descriptively based on prioritized outcomes.

RESULTS: The prioritized outcomes were neutropenia, pain, neuropathy, nausea, vomiting, alopecia, anorexia, and sleep disorders. Out of 7520 references found, 62 were included for analysis. Acupressure showed a possible effect in controlling symptoms such as nausea and vomiting. The intervention with cold on the scalp showed differences in the stages of alopecia severity. Other interventions showed heterogeneity.

DISCUSSION: Non-pharmacological interventions have been widely described in observational and experimental studies in the control of side effects of chemotherapy; however, there is homogeneity and a high risk of bias.

CONCLUSION: Acupressure, muscle massage, music therapy, foot baths, and other interventions have been studied for nausea, vomiting, sleep disorders, neutropenia, alopecia, anorexia, pain, and neuropathy as secondary symptoms prioritized by patients. It is necessary to standardize both the interventions and how measure the outcomes.

PMID:40115309 | PMC:PMC11922587 | DOI:10.15649/cuidarte.3612