Hum Vaccin Immunother. 2025 Dec;21(1):2424611. doi: 10.1080/21645515.2024.2424611. Epub 2025 Jan 6.

ABSTRACT

Programmed cell death-1 (PD-1) inhibitors and programmed cell death ligand 1 (PD-L1) inhibitors are considered effective alternatives for the primary treatment of recurrent metastatic cancers. However, they can induce various adverse events affecting multiple organ systems, potentially diminishing patients' quality of life, and even leading to treatment interruptions. Adverse events related to PD-1/PD-L1 inhibitors differ from those associated with CTLA-4 inhibitors and are more commonly observed in the treatment of solid tumors. This study aimed to address the knowledge gap regarding adverse events related to PD-1/PD-L1 inhibitors. A visual bibliometric network was constructed using VOSviewer, CiteSpace, R software, and the Web of Science Core Collection (WoSCC) to quantitatively analyze this research field. Future research directions were also explored. The USA ranked first in publication count and total citations. Over time, publication types transitioned from case reports to clinical trials. Research on for nivolumab was the most prevalent. The spectrum of cancers treated by PD-1/PD-L1 inhibitors expanded beyond melanoma and lung cancer to include renal cell carcinoma, esophageal cancer, and others. Common adverse events included pneumonitis, myasthenia gravis, and vitiligo. There was a significant increase in multi-phase clinical trials and studies related to biomarkers. This study offers valuable insights for potential collaborators and institutions, highlighting trends in the study of adverse events related to PD-1/PD-L1 inhibitors. The management of these adverse events has become more refined and standardized. Biomarker research and multi-phase clinical trials are likely to be key areas of focus in future studies.

PMID:39757956 | DOI:10.1080/21645515.2024.2424611

AIDS. 2024 Nov 14. doi: 10.1097/QAD.0000000000004065. Online ahead of print.

ABSTRACT

OBJECTIVE: Elevated blood pressure (BP), even at prehypertensive levels, increases cardiovascular disease risk among people with HIV (PWH); yet international guidelines in low-income countries recommend treatment initiation at BP at least 140/90 mmHg. We determined the efficacy, feasibility, and acceptability of treating prehypertension in PWH in Haiti.

DESIGN: An unblinded randomized clinical trial (enrolled April 2021-March 2022) with 12-month follow-up.

SETTING: GHESKIO Centres, Port-au-Prince, Haiti.

PARTICIPANTS: Two hundred fifty adults with HIV with prehypertension (SBP 120-138 or DBP 80-89) not on medication, aged 18-65 years, virally suppressed, and without pregnancy, diabetes, or kidney disease.

INTERVENTION: Participants were randomized to treatment (amlodipine 5 mg) or control (no amlodipine unless two BP ≥140/90 mmHg).

MAIN OUTCOME MEASURE: Primary outcome was mean change in SBP between intervention versus control groups from enrollment to 12 months.

RESULTS: Among 250 adults, median age was 49 years, 40.8% were women. Baseline median BP was 129/78 mmHg intervention versus 128/77 mmHg control. After 12 months, the difference in mean change between study groups for SBP was -5.9 mmHg [95% confidence interval (95% CI) -8.8 to -3.0] and for DBP was -5.5 mmHg (95% CI -7.9 to -3.2). At 12 months, 5.6% intervention and 23.0% control participants developed incident hypertension (hazard ratio 0.18; 95% CI 0.07-0.47). There were no differences in viral load suppression at 12 months or drug-related serious adverse events. Intervention acceptability was high among providers and participants in qualitative interviews.

CONCLUSION: In PWH in a resource-poor setting, prehypertension treatment was feasible, acceptable, and effective in reducing mean SBP and incident hypertension.

REGISTRATION: Clinicaltrials.gov NCT04692467.

PMID:39761592 | DOI:10.1097/QAD.0000000000004065

J Med Internet Res. 2025 Jan 6;27:e66220. doi: 10.2196/66220.

ABSTRACT

BACKGROUND: The increasing use of social media to share lived and living experiences of substance use presents a unique opportunity to obtain information on side effects, use patterns, and opinions on novel psychoactive substances. However, due to the large volume of data, obtaining useful insights through natural language processing technologies such as large language models is challenging.

OBJECTIVE: This paper aims to develop a retrieval-augmented generation (RAG) architecture for medical question answering pertaining to clinicians' queries on emerging issues associated with health-related topics, using user-generated medical information on social media.

METHODS: We proposed a two-layer RAG framework for query-focused answer generation and evaluated a proof of concept for the framework in the context of query-focused summary generation from social media forums, focusing on emerging drug-related information. Our modular framework generates individual summaries followed by an aggregated summary to answer medical queries from large amounts of user-generated social media data in an efficient manner. We compared the performance of a quantized large language model (Nous-Hermes-2-7B-DPO), deployable in low-resource settings, with GPT-4. For this proof-of-concept study, we used user-generated data from Reddit to answer clinicians' questions on the use of xylazine and ketamine.

RESULTS: Our framework achieves comparable median scores in terms of relevance, length, hallucination, coverage, and coherence when evaluated using GPT-4 and Nous-Hermes-2-7B-DPO, evaluated for 20 queries with 76 samples. There was no statistically significant difference between GPT-4 and Nous-Hermes-2-7B-DPO for coverage (Mann-Whitney U=733.0; n1=37; n2=39; P=.89 two-tailed), coherence (U=670.0; n1=37; n2=39; P=.49 two-tailed), relevance (U=662.0; n1=37; n2=39; P=.15 two-tailed), length (U=672.0; n1=37; n2=39; P=.55 two-tailed), and hallucination (U=859.0; n1=37; n2=39; P=.01 two-tailed). A statistically significant difference was noted for the Coleman-Liau Index (U=307.5; n1=20; n2=16; P<.001 two-tailed).

CONCLUSIONS: Our RAG framework can effectively answer medical questions about targeted topics and can be deployed in resource-constrained settings.

PMID:39761554 | DOI:10.2196/66220

Front Immunol. 2024 Dec 20;15:1470660. doi: 10.3389/fimmu.2024.1470660. eCollection 2024.

ABSTRACT

IMPORTANCE: Identifying environmental factors that contribute to disease onset/activity in PV stands to improve clinical outcomes and patient quality of life by strategies aimed at reducing specific disease promoting exposures and promoting personalized clinical management strategies.

OBJECTIVE: To evaluate the association between hydroxychloroquine use and the development of pemphigus using population level, publicly available, FDA-generated data.

DESIGN: Observational, retrospective, case-control, pharmacovigilance analysis.

SETTING: Population based.

PARTICIPANTS: Individuals who either independently or via their healthcare provider submitted a voluntary report of a drug related adverse event to the FDA from Q4 of 2003 to Q2 of 2023.

EXPOSURE: Cases were identified by the presence of adverse events described by the MedDRA preferred term (PT) of "pemphigus" (10034280) and then sorted based on exposure to the drug of interest, hydroxychloroquine, or lack thereof.

MAIN OUTCOMES AND MEASURES: Frequency of hydroxychloroquine exposure among those individuals who reported an adverse event of pemphigus to the FDA; quantification of the reporting odds ratio (ROR).

RESULTS: We identified a total of 2,548 reports that included the adverse event pemphigus; among these, 1,545 (n=706 (41.92%) age 18-64, n=1 age 65-85 years, and n=977 (58.02%) with no age specified; n=1,366 (81.12%) females, n=4 (0.24%) males, and n=314 (18.65%) with no gender specified) included exposure to hydroxychloroquine (ROR, 282.647; 95% CI, 260.951-306.148). We then stratified those reports that included the combination of pemphigus and hydroxychloroquine by gender and found that while the association between the exposure and adverse event remained significant across genders, the magnitude of the effect sizes differed significantly (p<0.001), being over 100-fold greater among females (ROR, 378.7; 95% CI, 339.0-423.1) compared to males (ROR, 3.6; 95% CI, 1.4-9.8).

CONCLUSIONS AND RELEVANCE: The frequency of reports containing the combination of the adverse event pemphigus and exposure to the drug hydroxychloroquine was disproportionately elevated across all genders in the years since the start of the COVID-19 pandemic. The disproportionately elevated frequency of reports of the combination of pemphigus and hydroxychloroquine supports an association between the two, corroborates previous case-report based evidence for such an association, suggests that hydroxychloroquine represents a possible trigger factor for the development of pemphigus, and paves the way for future research that is capable of establishing causality.

PMID:39759530 | PMC:PMC11695399 | DOI:10.3389/fimmu.2024.1470660

Ther Adv Drug Saf. 2025 Jan 2;16:20420986241311231. doi: 10.1177/20420986241311231. eCollection 2025.

ABSTRACT

BACKGROUND: Clarithromycin is a widely used antibiotic, but its safety profile, particularly in different age groups, remains inadequately explored.

OBJECTIVES: This study aims to characterize and illustrate the features of clarithromycin-related adverse events (AEs) across different age groups using the FDA Adverse Event Reporting System (FAERS) database, providing a reference for the clinical detection, prevention, and management of AEs in various age groups.

DESIGN: A disproportionality analysis was performed using data from the FAERS database. The study included all AE reports related to clarithromycin, stratified by age groups.

METHODS: Disproportionality analysis was conducted using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multiple gamma Poisson shrinkers. Statistical analyses included descriptive statistics and Chi-square tests.

RESULTS: A total of 7319 reports of clarithromycin AEs were retrieved from the FAERS database. Vomiting, diarrhea, drug interactions, and drug interactions were reported most frequently in the age groups 0-17, 18-44, 45-64, and ⩾65 years, respectively. Abnormal product taste, taste disorder, and medication errors related to drug interactions specified in the package insert were the strongest signals in the age groups 0-17, 18-44, 45-64, and ⩾65 years, respectively. A total of 41 Preferred Terms signals were not explicitly included in the clarithromycin package insert and were mainly associated with psychiatric disorders, skin and subcutaneous tissue disorders, and gastrointestinal disorders, among others. Specific signals for age differences were identified, with 18 signals being age-specific, including 3 in children and 15 in elderly individuals.

CONCLUSION: The safety profile of clarithromycin varies across age groups. In children, it is mainly associated with vomiting, hypersensitivity, and dyspnea, while in adults, psychiatric AEs are more common. In the elderly, clarithromycin should be used cautiously, with attention to drug interactions.

PMID:39758824 | PMC:PMC11696969 | DOI:10.1177/20420986241311231

J Diabetes Metab Disord. 2025 Jan 2;24(1):33. doi: 10.1007/s40200-024-01552-x. eCollection 2025 Jun.

ABSTRACT

OBJECTIVES: Glucagon-like peptide 1 (GLP-1) receptor agonists have recently proven to be an effective treatment for type 2 diabetes mellitus (T2DM). However, these drugs are also known to carry a significant risk of drug-induced pancreatitis. The purpose of this study is to determine whether or not GLP-1-associated pancreatitis risk is dose-dependent. That is, we aim to determine whether the risk of developing pancreatitis increases with the administered dose of GLP-1 agonist or not.

METHODS: We conduct a retrospective case control study using data taken from the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) database. Participants are included if they reported an adverse effect of GLP-1 agonist and reported the cumulative dose of drug administered. We measure the odds ratio of developing pancreatitis between patients who have taken a large cumulative dose of GLP-1 agonist and those with a low cumulative dose of GLP-1 agonist. The odds ratio of different GLP-1 agonists are combined via a random effects model.

RESULTS: Patients with a high cumulative dose of GLP-1 agonist are associated with a higher risk of developing drug-induced pancreatitis associated with GLP-1 agonists, indicated by a statistically significant odds ratio. Furthermore, the odds ratio increases as the cumulative dose increases.

CONCLUSIONS: GLP-1 agonists are associated with significant pancreatitis risk which increases with larger cumulative doses.

PMID:39758806 | PMC:PMC11695654 | DOI:10.1007/s40200-024-01552-x

Ann Med. 2025 Dec;57(1):2449589. doi: 10.1080/07853890.2025.2449589. Epub 2025 Jan 6.

ABSTRACT

BACKGROUND/OBJECTIVE: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease that typically occurs in childhood/infancy and is associated with complications like extracutaneous atopic morbidity. Providing systemic treatment for pediatric AD patients with unmet comprehensive medical needs remains challenging. We present a cohort study describing the efficacy and safety of dupilumab combined with topical calcineurin inhibitors (TCI) in children with moderate-to-severe atopic dermatitis under the age of 6 years.

METHODS: A retrospective cohort study was conducted at a single center to analyze the use of dupilumab in combination with topical calcineurin inhibitors (TCI) in children aged 6 years and under moderate-to-severe AD that was inadequately controlled with topical therapy.

RESULTS: Overall, 23 preschool children (mean [SD] age, 4.78 [1.278] years); 10 boys (43.5%) and 13 girls (56.5%) received 300 mg dupilumab every four weeks and TCI. The primary outcome, the average Eczema Area and Severity Index (EASI) percentage reduction from baseline, was -70.85%. Significant improvement was also observed in secondary outcomes: caregiver-reported Peak Pruritus numerical rating scale (P-NRS) (-77.73%), Body Surface Area (BSA) (-62.11%), and Investigators Global Assessment (IGA) (-36.23%) at week 16. A 1-2 grade decrease in IGA after 16 weeks of treatment was achieved by 91.3% of patients. There was a significant improvement in P-NRS and EASI scores from baseline to week 16. Injection-site reaction (one patient) and facial redness (two patients) were recorded. No severe drug-related adverse events were observed.

CONCLUSION: This study demonstrated that the combination of dupilumab and TCIs improved symptoms and quality of life in preschoolers with moderate-to-severe AD.

PMID:39757933 | DOI:10.1080/07853890.2025.2449589

Biol Pharm Bull. 2025;48(1):1-5. doi: 10.1248/bpb.b24-00509.

ABSTRACT

As unexpected adverse events and successful drug repositioning have shown, drug effects are complex and include aspects not recognized by developers. How can we understand these unrecognized drug effects? Drug effects can be numerized by encompassing biological responses to drugs. For instance, the transcriptome data of cultured cells and toxicopathological images of mice treated with a compound represent the effects of the compound in vitro and in vivo, respectively. As a next step, we focused on pattern recognition, a data science framework to extract essentially important low-dimensional latent variables from high-dimensional observed data such as latent variable models. Latent variables are low-dimensional, allowing us to visualize drug effects in an easily recognizable form, such as a radar chart. This bird's-eye view of drug effects enables us to compare them with existing knowledge, potentially articulating the effects of drugs as the known knowns and known unknowns. We believe that the three-step strategy of numerization, visualization, and articulation will allow us to understand drug effects comprehensively, and we are currently verifying this approach. In this review, we will introduce these candidate studies and hope to share our interest in "pattern recognition of biological responses," the pillar of our group.

PMID:39756864 | DOI:10.1248/bpb.b24-00509

J Nippon Med Sch. 2024;91(6):567-573. doi: 10.1272/jnms.JNMS.2024_91-605.

ABSTRACT

In patients not infected by HIV, Pneumocystis jirovecii pneumonia (PCP) is characterized by rapid disease progression, difficulty in confirming the diagnosis, and poor prognosis. PCP has also been reported in immunocompromised patients receiving chemotherapy, most often for hematologic tumors, although some patients receiving treatment for breast cancer have been affected. Dose-dense chemotherapy (DDC) which is performed with shorter dosing intervals than standard chemotherapy and is now widely used in clinical practice. However, adverse events have been reported, including infections associated with decreased immune status. PCP infection is considerably more challenging to diagnose and treat than bacterial or viral infections. Furthermore, organizing pneumonia (OP), a pulmonary lesion of PCP, is infrequent and requires caution on the part of clinicians, as protozoan infections require different forms of treatment. Although we initially suspected bacterial, viral, and drug-induced pneumonia in our patient and started treatment with antibiotics, antifungals, and prednisolone, the final diagnosis was OP. The pulmonary lesion of PCP was treated with systemic corticosteroids, leading to recovery. There have been no similar reports of PCP during chemotherapy for malignant disease; however, the possibility of OP should be considered during chemotherapy. Herein, we report a case of PCP during preoperative DDC for advanced breast cancer.

PMID:39756946 | DOI:10.1272/jnms.JNMS.2024_91-605

Am J Sports Med. 2025 Jan 5:3635465241252435. doi: 10.1177/03635465241252435. Online ahead of print.

ABSTRACT

BACKGROUND: Selective androgen receptor modulators (SARMs) are small-molecule compounds that exert agonist and antagonist effects on androgen receptors in a tissue-specific fashion. Because of their performance-enhancing implications, SARMs are increasingly abused by athletes. To date, SARMs have no Food and Drug Administration approved use, and recent case reports associate the use of SARMs with deleterious effects such as drug-induced liver injury, myocarditis, and tendon rupture.

PURPOSE: (1) To provide a comprehensive synthesis of the literature pertaining to SARMs from a sports medicine perspective and (2) to provide a better understanding of the clinical effects, treatment protocols, prevalence, and potential contamination associated with athlete-consumed SARMs.

STUDY DESIGN: Systematic review; Level of evidence, 4.

METHODS: A systematic review of the English-language literature from PubMed, Cochrane, and Embase databases was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Articles relevant to SARM clinical outcomes, elimination profiles, contamination, safety profiles, prevalence, and doping control were included.

RESULTS: A total of 72 articles from 2003 to 2022 were identified for inclusion. The prevalence of SARM use among athletes is estimated to be 1% to 3%. SARM preclinical and clinical studies reported significant increases in lean body mass and side effects-including bone remodeling, testosterone suppression, and kidney, liver, and prostate enlargement. Thirteen case reports described 15 cases of SARM abuse. All described patients were men, with a median age of 32 years (range, 19-52 years), more than half were identified as athletes (8/15), and all ingested SARMs orally for a mean course of 8 weeks. Five patients described in the case reports explicitly denied "illicit drug use," implying patients may believe their use to be legal. Athletes most commonly purchased SARMs online, and most of these compounds have been shown to be contaminated with other substances, contributing to adverse effects. Athletes reported consuming SARMs at much higher doses than clinically studied, which may increase the risk of the reported side effects, such as liver injury, impaired insulin sensitivity, cardiovascular events, and tendon damage.

CONCLUSION: The results of this systematic review serve to educate sports medicine clinicians and researchers on how to better identify, diagnose, and treat athlete SARM abuse. SARM use is associated with increased muscle mass, hepatotoxicity, cardiotoxicity, tendon damage, and androgenic side effects throughout the body-including prostate enlargement and serum testosterone suppression. Identifying and treating SARM abuse requires taking a thorough substance and supplement use history with open communication, providing literature-supported patient education, negotiating SARM discontinuation, and performing multidisciplinary treatment of adverse events. Athlete SARM abuse is increasingly widespread and unsafe, and public health oversight bodies should advocate for regulation of these gray-market compounds.

PMID:39755947 | DOI:10.1177/03635465241252435

J Cardiothorac Surg. 2025 Jan 4;20(1):8. doi: 10.1186/s13019-024-03237-1.

ABSTRACT

OBJECTIVE: The prevalence and characteristics of drug-related problems (DRPs) in the cardiovascular surgery unit have not been adequately explored, leaving a gap in our understanding of this critical issue. This study aimed to address this gap by determining the prevalence, characteristics of DRPs and identifying factors associated with their occurrence.

METHODS: During a non-consecutive 48-month study period, a retrospective analysis was conducted to investigate DRPs and the interventions carried out by pharmacists for patients undergoing cardiovascular surgery. The study collected data on patient demographics, clinical characteristics, and pharmacist interventions.

RESULTS: A comprehensive data analysis revealed 671 DRPs among the 623 hospitalized patients, averaging 1.08 DRPs per patient. The most prevalent type of DRPs observed was "Unnecessary drug-treatment P3.2", accounting for 56.18% (377/671). The primary cause of DRPs was drug selection (C1), followed by dose selection (C3). Pharmacists proposed 1,628 interventions, averaging 2.43 interventions per DRP and 2.61 interventions per patient. Most interventions were accepted and fully implemented by physicians or patients, resulting in 537 (80.03%) of the total DRPs resolved. Furthermore, binary logistic regression analysis demonstrated that the frequency of DRPs was correlated with age, the length of hospitalization, diagnosis of valvular disease, presence of infectious desease and the number of different types of drugs used by the patients.

CONCLUSIONS: DRPs are a prevalent issue within the cardiovascular surgery unit, mainly due to drug selection. Clinical pharmacists' presence has proven effective in mitigating and preventing DRPs, thus optimizing medication therapy.

PMID:39755659 | PMC:PMC11699638 | DOI:10.1186/s13019-024-03237-1

Cancer Chemother Pharmacol. 2025 Jan 4;95(1):17. doi: 10.1007/s00280-024-04721-0.

ABSTRACT

As development of new oncology small molecule therapies is focused mainly on molecularly targeted agents, the dose selection paradigm has shifted from the maximum tolerated dose (MTD)-based approach traditionally utilized with cytotoxic drugs towards determining an optimal dose with long-term tolerability while maintaining efficacy. To assess overall tolerability in recently approved oncology small molecules, we surveyed 54 compounds approved by the FDA since March 2017 with respect to dose intensity, dose modifications, and treatment emergent adverse events (TEAEs). Of the 54 new molecular entities surveyed, only 15 were approved at a label dose equal to the MTD (Label Dose = MTD). Compared to compounds where the label dose was less than the MTD, compounds where the Label Dose = MTD reported overall lower dose intensity and higher dose modifications due to adverse events, though treatment discontinuations due to adverse events were similar. A post-marketing requirement (PMR) for dose optimization was issued for 7 compounds in the dataset, of which 3 were at the Label Dose = MTD. None of these 7 compounds reported a positive exposure-response relationship in efficacy and only 4 reported an exposure-response in safety events. Overall, dose intensity was lower, and incidence of dose modifications, discontinuations, and Grade ≥ 3 TEAEs were higher in compounds issued a PMR vs. the latter. This analysis suggests that while recently approved oncology small molecules have a reasonable relative dose intensity (RDI), the higher incidence of Grade ≥ 3 TEAEs and dose modifications where Label Dose = MTD highlight the continuing need for dose optimization while developing oncology therapeutics.

PMID:39754626 | PMC:PMC11700039 | DOI:10.1007/s00280-024-04721-0

Mov Disord Clin Pract. 2025 Jan 4. doi: 10.1002/mdc3.14327. Online ahead of print.

ABSTRACT

BACKGROUND: Dystonia may respond to VMAT2 inhibition.

OBJECTIVES: Providing pilot data on the safety, tolerability, and efficacy of deutetrabenazine in non dopa-responsive dystonia.

METHODS: Deutetrabenazine was titrated by adults with isolated dystonia. Primary study endpoints included the proportion who maintained the individual, maximum tolerated dose for 6 weeks, and how many titrated to 48 mg/day. Secondary endpoints included rates of QTc prolongation/arrhythmias, suicidality, excessive daytime sleepiness, cognitive decline, and drug-induced parkinsonism. Exploratory endpoints for clinical efficacy were assessed.

RESULTS: Among 15 participants, four (26.7%) withdrew early and six (40%) titrated to 48 mg/day. Common adverse events included fatigue and diarrhea. Secondary safety endpoints did not change significantly, but MDS-UPDRS III scores worsened by ≥3 points in seven participants (46.7%). PGI-C and the blinded CGI-C and GDS improved in three women with blepharospasm.

CONCLUSIONS: Most participants tolerated deutetrabenazine for 6 weeks, and those with blepharospasm may have benefitted from its use.

PMID:39754397 | DOI:10.1002/mdc3.14327

Reg Anesth Pain Med. 2025 Jan 2:rapm-2024-106014. doi: 10.1136/rapm-2024-106014. Online ahead of print.

ABSTRACT

BACKGROUND/IMPORTANCE: Opioids continue to play a key role in managing acute postoperative pain, but their use contributes to adverse outcomes. Buprenorphine may offer effective analgesia with a superior safety profile.

OBJECTIVE: To compare the efficacy and safety of buprenorphine with other opioids for acute postoperative pain management in adults.

EVIDENCE REVIEW: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched from inception to February 2024. Randomized controlled trials comparing buprenorphine with other opioids for acute postoperative pain management in adults were included. Of 2421 records identified, 58 studies met inclusion criteria. Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analysis was performed using Stata/BE V.18. The primary outcome was pain intensity. Secondary outcomes included rescue analgesia use, duration of analgesia, and adverse effects.

FINDINGS: Analysis of 41 comparisons (2587 participants) showed buprenorphine significantly reduced pain intensity compared with all other opioids (Hedges's g=-0.36, 95% CI=-0.59 to -0.14, p<0.001, 95% prediction interval (PI)=-1.70 to 0.97). This effect persisted when compared with full agonist opioid (FAO) alone (standardized mean difference -0.34, 95% CI=-0.59 to -0.10, p<0.001, 95% PI=-1.76 to 1.07). Patients receiving buprenorphine were less likely to require rescue analgesia (OR=0.40, 95% CI=0.26 to 0.63, p<0.001, 95% PI=0.12 to 1.36). Mean duration of analgesia was 8.5 hours (SD 1.84). There were no significant differences in other adverse effects including nausea and respiratory depression. Inconsistency was significant for pain intensity (I2=86.28%, 95% CI=81.55% to 88.99%) and moderate for rescue analgesia (I2=38.93%, 95% CI=1.44% to 64.37%). Risk of bias was low in 19 studies, with some concerns in 37 studies, and high in two studies.

CONCLUSIONS: Buprenorphine demonstrated superior efficacy in managing acute postoperative pain compared with FAOs, with a favorable safety profile and longer duration of action. These findings support the use of buprenorphine as a first-line opioid analgesic for acute postoperative pain management requiring opioid analgesia, potentially reducing opioid-related harm in the postoperative period.

PROSPERO REGISTRATION NUMBER: CRD42023447715.

PMID:39753290 | DOI:10.1136/rapm-2024-106014

Inflammopharmacology. 2025 Jan 3. doi: 10.1007/s10787-024-01611-y. Online ahead of print.

ABSTRACT

Clove oil obtained from Syzygium aromaticum (L.) is traditionally employed to treat inflammation associated with rheumatism, gastric disorders, and as an analgesic. Chemo-herbal combinations are known to have potent anti-inflammatory and analgesic effects, while mitigating the drug related side effects. The purpose of this study was to evaluate anti-inflammatory, analgesic and antipyretic effects of a combination of flurbiprofen and clove oil in a micro-emulsion (FCM) form using various in vivo models. Micro-emulsion of flurbiprofen and clove oil (FCM) was prepared following reported protocols and three different dose combinations (25, 12.5 and 6.25 mg/kg) were evaluated in carrageenan and histamine-induced acute inflammation, CFA-induced arthritis, yeast-induced pyrexia, and acetic acid-induced writhing models. qPCR studies were conducted to explore the possible mechanism of action. GC-MS of clove oil was performed to explore its chemical composition. FCM 25 mg/kg treated group exhibited significantly better (p < 0.05) effects compared to clove oil (CM) and flurbiprofen (FBR) (25 mg/kg) treated groups in both acute and chronic models. Histopathological study of joints showed a reduction in infiltration of inflammatory cells, bone erosion, and tissue oedema in FCM (25 mg/kg) treated group as compared to other treatment groups. Significant up-regulation in mRNA expression of anti-inflammatory (IL-4, IL-10) and down-regulation of pro-inflammatory genes (NF-κB, IL-6, TNF-α, IL-1β and COX-2) was observed in all the FCM-treated groups but, 25 mg/kg-treated group showed comparatively better results. Gross macroscopic examination of stomach sections also showed relatively less deleterious effects of test treatments (CM and FCM) as compared with FBR treated group. Serum levels of liver enzymes (alanine aminotransferase (ALT), and alkaline phosphatase (ALP)), blood urea nitrogen (BUN) and creatinine were also found to be normal as compared to FBR and tween-water (TW) treated groups. GC-MS of clove oil revealed that it was rich in eugenol contents. This study reveals that a combination of flurbiprofen and clove oil in a micro-emulsion form could be a promising approach to enhance therapeutic actions and to mitigate synthetic drugs related side effects in clinical settings. It might implicate a synergistic action on the modulation of inflammatory genes expression. Further research is warranted to explore the full potential of this combination in treating various inflammatory conditions.

PMID:39752039 | DOI:10.1007/s10787-024-01611-y

Expert Opin Drug Saf. 2025 Jan 3. doi: 10.1080/14740338.2024.2446430. Online ahead of print.

ABSTRACT

BACKGROUND: Dry eye syndrome (DES) has become a significant public health issue, impacting quality of life. Meibomian Gland Dysfunction (MGD) is a primary contributor to DES, and its etiology includes diverse factors. Given the potential for drug-induced MGD, comprehensive investigation into this association is crucial.

RESEARCH DESIGN AND METHODS: This study aims to identify and analyze signals associated with drug-induced MGD risk, enhancing drug safety evaluation. Data from the FDA Adverse Event Reporting System (FAERS) from January 2004 to September 2023 were analyzed using statistical algorithms, including the Ratio of Odds Ratios (ROR) and Proportional Reporting Ratio (PRR), to detect potential adverse reaction signals. Drugs associated with MGD were categorized across therapeutic classes.

RESULTS: Analysis of 289 cases reporting MGD as an adverse reaction revealed an average patient age of 51.69 years, with 65.44% female. The annual number of MGD reports has increased since the establishment of FAERS database, peaking in 2023, mainly from the United States and European countries. Disproportionate analysis of 148 drugs identified 9 associated with MGD adverse events, including ophthalmology, oncology, immunomodulation, dermatology, and urogenital system.

CONCLUSION: This study provides real-world data from the identification of drugs potentially inducing MGD and offers a comprehensive approach to exploring MGD-related drug safety. Our findings support the development of pharmacovigilance strategies for drug-induced ocular conditions and contribute to optimized drug management in clinical practice.

PMID:39749737 | DOI:10.1080/14740338.2024.2446430

Sci Rep. 2025 Jan 2;15(1):278. doi: 10.1038/s41598-024-75421-1.

ABSTRACT

This study aims to mine and analyze adverse events (AEs) of Vedolizumab based on the FAERS database to better understand its safety and potential risks in the real world. Data from the second quarter of 2014 to the third quarter of 2023 were collected, employing various signal mining methods such as Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). The study gathered 14,753,012 reports of AEs, of which 46,726 were related to Vedolizumab. Signal mining identified 401 Preferred Terms (PTs) involving 27 System Organ Classes (SOCs). There was an increasing trend in the number of reports, with a slightly higher proportion of reports from women compared to men, and the primary reporting group was adults, especially those aged between 18 and 65 years. New potential AE signals were identified, such as a higher incidence of Pregnancy, Haematochezia, and Clostridium difficile infection. Although less frequent, strong signals were noted for Incisional hernia, Intestinal fistula infection, Anastomotic complication, Drug metabolising enzyme increased, Gingival graft, Intestinal anastomosis complication, Anorectal infection, Perineal rash, and Abdominal hernia obstructive. Despite the positive prospects of Vedolizumab in the treatment of inflammatory bowel diseases, the AEs related to its use identified in this study, particularly the newly identified potential risks, suggest that even targeted therapies can have systemic effects beyond expectations.

PMID:39747183 | DOI:10.1038/s41598-024-75421-1

Obstet Gynecol. 2025 Jan 2. doi: 10.1097/AOG.0000000000005812. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the efficacy and safety of fezolinetant and elinzanetant for vasomotor symptoms in menopausal women.

DATA SOURCES: MEDLINE, EMBASE, and Cochrane databases were systematically searched until August 22, 2024. Because the Cochrane Library included all the identified randomized controlled trials (RCTs), it was unnecessary to search ClinicalTrials.gov. The following words made up the search strategy, which was applied to the three databases: fezolinetant, elinzanetant, vasomotor symptoms, and menopause.

METHODS OF STUDY SELECTION: Only RCTs comparing fezolinetant and elinzanetant with placebo for vasomotor symptoms in menopausal women were included.

TABULATION, INTEGRATION, AND RESULTS: We extracted the number of patients, mean age, body mass index (BMI), and number of patients who underwent oophorectomy. Data were examined with the Mantel-Haenszel method and 95% CIs. Heterogeneity was assessed with I2 statistics. R 4.3.2 was used for statistical analysis. Seven RCTs with 4,087 patients were included in the analysis. Fezolinetant and elinzanetant were associated with diminished vasomotor symptom frequency: fezolinetant 30 mg (mean difference 2.16, 95% CI, 1.54-2.79, I2=0%), fezolinetant 45 mg (mean difference 2.54, 95% CI, 1.86-3.21, I2=0%), and elinzanetant 120 mg (mean difference 2.99, 95% CI, 1.74-4.23, I2=0%). Both drugs also showed a decrease in vasomotor symptom severity: fezolinetant 30 mg (mean difference 0.20, 95% CI, 0.09-0.33, I2=0%), fezolinetant 45 mg (mean difference 0.24, 95% CI, 0.13-0.34, I2=0%), and elinzanetant 120 mg (mean difference 0.36, 95% CI, 0.26-0.46, I2=0%). Elinzanetant 120 mg showed a significant improvement in sleep quality (mean difference 4.65, 95% CI, 3.73-5.56, I2=0%). Elinzanetant 120 mg was associated with the occurrence of drug-related adverse events (11.70% vs 20.75%, risk ratio [RR] 0.57, 95% CI, 0.39-0.82, I2=19%) and headache (2.54% vs 8.0%, RR 0.32, 95% CI, 0.16-0.64, I2=0%).

CONCLUSION: In this meta-analysis, consistent results suggest that fezolinetant and elinzanetant are associated with beneficial outcomes in menopausal women with vasomotor symptoms. Elinzanetant provided a larger effect size in vasomotor symptom frequency and severity reduction and greatly improved sleep quality compared with fezolinetant.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023469952.

PMID:39746208 | DOI:10.1097/AOG.0000000000005812

J Manag Care Spec Pharm. 2025 Jan;31(1):96-100. doi: 10.18553/jmcp.2025.31.1.96.

ABSTRACT

The majority of a health plan's performance and designated Star Rating is related to medication-related behavior, eg, medication adherence, medication review, and reconciliation, that are intricately related to adverse drug events (ADEs). Altered pharmacodynamics and pharmacokinetics owing to aging make older adults more vulnerable to ADEs like falls, fractures, hospitalizations, and mortality. Prevention of avoidable risk factors such as medication burden can help maintain quality of life. Studies of multiple populations have established drug burden index (DBI), a dose-dependent measure of anticholinergic and sedative burden, to be strongly associated with worsening vertigo, dizziness, and balance, which all predicate falls. The mean difference in DBI greater than 0.1 provides greater predictive power for adverse events, such as falls and 30-day readmission rates. Inclusion of a DBI delta metric especially on an electronic medical record has the potential to reduce fall incidence and associated health outcomes such as hospitalizations and death; this presents an opportunity to improve Centers for Medicare & Medicaid Services Star Ratings by using meaningful tools to foster engagement among informed and active Medicare beneficiaries. We believe this information is extremely relevant in real-world decision-making for health care professionals, specifically when the changes are dynamic and happen very quickly. Moreover, managed care organizations are now dedicated to eliciting a deeper understanding and mitigation of social inequalities in medication use and consequences. Among the proposed solutions includes tailoring prescription utilization management tools with DBI to decrease avoidable incidences of complications and unintended costs. Understanding the dynamic relationship between medication exposures causing ADEs and associated health care utilization and costs to third-party payments remains vital because in the United States, approximately one-third of hospital admissions in older adults occur because of ADEs. This can be achieved by emphasizing equitable therapy and tailoring quality initiatives that minimize racial disparities and avoidable costs that affect the financial burden of these patients. Importantly, this approach becomes even more critical as health care systems increasingly emphasize star ratings, which reflect the quality of care delivered to patients. By prioritizing DBI metrics in these ratings, we can ensure that care is not only clinically effective but also equitable and focused on improving patients' overall well-being. Lastly, as the future directions, the timely application of advanced technologies like artificial intelligence and machine learning in analyzing DBI metrics could enhance our ability to predict the value of DBI adjustments and their correlation with falls and other unintended ADEs. These real-world technologies can process vast amounts of data quickly and accurately, identifying patterns and potential risks that might otherwise go unnoticed.

PMID:39745841 | DOI:10.18553/jmcp.2025.31.1.96

Pharm Dev Technol. 2025 Jan 2:1-17. doi: 10.1080/10837450.2024.2448619. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aims to develop a dual-ligand-modified targeted drug delivery system by integrating photosensitizers and chemotherapeutic drugs to enhance anti-glioma effects. The system is designed to overcome the blood-brain barrier (BBB) that hinders effective drug delivery, increase drug accumulation in glioma cells, and thereby enhance therapeutic efficacy.

METHODS: Liposomes were prepared using the film dispersion-ammonium sulfate gradient technique, co-loading the photosensitizer indocyanine green (ICG) and the chemotherapeutic drug mitoxantrone (MTO). The conjugation of BTP-7 and BR2 to the liposome surface was achieved using an organic phase reaction method. The stability, dispersibility, particle size, and potential of the modified liposomes were tested. Their ability to penetrate the BBB and accumulate in glioma was evaluated in BBB models and cellular uptake studies. Additionally, the anti-tumor activity of this combination approach was assessed.

RESULTS: The resulting liposomes demonstrated significant stability and dispersibility, with an average particle size of 142.3 ± 1.8 nm and a potential of -17.6 mV. BBB model and cellular uptake studies indicated that BTP-7/BR2-ICG/MTO-LP could not only penetrate the BBB but also accumulate in glioma, leading to glioma cell necrosis. The anti-tumor activity evaluation showed that this combination approach exhibited a strong tumor-suppressing effect.

CONCLUSION: The dual-ligand-modified liposomes developed in this study can penetrate the blood-brain barrier and achieve targeted drug delivery in glioma therapy. The combination of BTP-7 and BR2 not only enhances the carrier's penetration ability but also increases intracellular drug accumulation, thereby improving therapeutic efficacy. This novel therapeutic approach, which combines chemotherapy and photothermal response via dual-ligand-modified liposomes delivered to the tumor site, demonstrates the potential to reduce drug-related side effects and improve treatment outcomes.

PMID:39745268 | DOI:10.1080/10837450.2024.2448619