Fundamental & Clinical Pharmacology最新文献

{"title":"Gabapentinoids and Neuropathic Pain: Evaluation of the Quality of Randomised Controlled Trials: An Umbrella Review","authors":"Humbert de Freminville,&nbsp;Laura Lucatelli,&nbsp;Marc Chanelière,&nbsp;Guillaume Grenet,&nbsp;Sabine Mainbourg,&nbsp;Rémy Boussageon","doi":"10.1111/fcp.70052","DOIUrl":"https://doi.org/10.1111/fcp.70052","url":null,"abstract":"<div>\u0000 \u0000 <p>Neuropathic pain remains a complex condition to manage. While current literature provides best practice guidelines for the use of gabapentinoids in this indication, these recommendations are primarily based on randomised clinical trials (RCTs) and meta-analyses of varying methodological quality. To support evidence-based prescribing, we conducted an evaluation of the overall confidence in meta-analytic findings on the efficacy of gabapentinoid in adults. A systematic review of the meta-analyses of RCTs retrieved from the MEDLINE (PubMed) database was performed. The methodological quality of these meta-analyses was assessed using the AMSTAR 2 tool (A MeaSurement Tool to Assess systematic Reviews) and compared when available with the quality of evidence determined by the GRADE approach. Among the 16 included meta-analyses, 14 were rated as having ‘critically low’ quality, one as ‘low’ and one as ‘moderate’ according to AMSTAR 2. GRADE and AMSTAR 2 assessments were both available for six meta-analyses, but only one yielded a concordant result. According to AMSTAR 2, the highest-quality meta-analysis was the one published in the Cochrane Database of Systematic Reviews and concluded that more participants had substantial benefit (at least 50% pain relief or patient global impression change very much improved) with gabapentin at 1200 mg daily or greater than with placebo (in postherpetic neuralgia: RR = 1.8 [95% CI 1.5 to 2.1] and in painful diabetic neuropathy: RR = 1.9 [95% CI 1.5 to 2.3]). One limitation of this work is the inconsistent use of the term neuropathic pain, which may be defined differently across studies.</p>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145739879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Residual Effects of Acute and Subchronic Zolpidem Treatments on Attentional Processes in Aged Female Rats","authors":"Marianne Leger,&nbsp;Michel Boulouard,&nbsp;Christophe Liet,&nbsp;Ben Grayson,&nbsp;Michael Harte,&nbsp;Joanna C. Neill,&nbsp;Marie-Laure Bocca,&nbsp;Véronique Lelong-Boulouard","doi":"10.1111/fcp.70067","DOIUrl":"https://doi.org/10.1111/fcp.70067","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rational</h3>\u0000 \u0000 <p>Zolpidem, a hypnotic Z-drug commonly prescribed to promote sleep, is predominantly used over the age of 50. In this elderly population, adverse behavioral disturbances, impaired driving performance, and an increased risk of falls have been frequently reported. These concerns have raised questions about the residual adverse effects of zolpidem in older adults, particularly on cognitive processes such as executive and attentional functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aimed to investigate the residual effects of zolpidem on attentional performance following either acute or subchronic administration in aged rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A zolpidem dose of 3 mg/kg and a 3-h postadministration time point were selected based on pharmacokinetic data from the literature and a dose–response analysis of its locomotor effects in the open-field test. Attentional performance was then assessed in aged female rats treated with either saline or zolpidem (acutely or for 7 days), using the 5-choice continuous performance task (5C-CPT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Acute zolpidem administration significantly reduced the percentage of correct responses, increased correct response latency, and showed a trend toward more omissions, indicative of impaired attentional performance and psychomotor slowing. These effects were not further observed after subchronic treatment, suggesting a potential tolerance over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings highlight a critical period of vulnerability following the initiation of zolpidem treatment, during which residual cognitive impairments may emerge. Such effects may compromise complex tasks requiring sustained attention and processing speed, such as driving, especially in older adults.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145719648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking the NETSARC+ National Sarcoma Database With the SNDS to Evaluate Adjuvant and/or Neoadjuvant Therapy: Report on the Linkage Process and Result (Health Data Hub's DEEPSARC Pilot Project)","authors":"Erwan Drezen,&nbsp;André Happe,&nbsp;Vincent Thevenet,&nbsp;Nicolas Penel,&nbsp;François Gouin,&nbsp;François Le Loarer,&nbsp;Gonzague Du Bouexic De Pinieux,&nbsp;Hugo Crochet,&nbsp;Claire Chemin Airiau,&nbsp;Françoise Ducimetiere,&nbsp;Simone Mathoulin Pelissier,&nbsp;Jean-Yves Blay,&nbsp;Emmanuel Oger","doi":"10.1111/fcp.70066","DOIUrl":"https://doi.org/10.1111/fcp.70066","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>DEEPSARC, one of the first projects running on the Health Data Hub, aimed to identify real-life treatment regimens that could improve overall survival. The project is based on matching the national database of the sarcoma reference network with the SNDS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>We aimed to report a transparent description of the linking process and its results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The sarcoma database encompasses 33 548 patients matching the selection criteria divided into three subsets: 13507 patients with a complete dataset gathering clinical and pathological data; 5844 patients with clinical data alone; and 14 197 patients with pathological data alone. As no ICD-10 code reliably identifies patients with sarcoma, the subpopulation extracted from the SNDS was extended to 3 million patients who underwent surgery for their cancer. An indirect record linkage process used a combination (called a signature) of so-called chaining variables to uniquely identify a pair of patients from each of the bases. Two metrics (signature robustness and overall quality) were calculated for ease of interpretation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The overall matching rate of 73.1% (24 539 pairs out of 33 548 observations), reaching 90.5% in the intersection of the sarcomas databases (with extended data, 12 225 pairs out of 13 507 observations).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>An optimized and transparent process led to a moderate matching rate but enhanced the confidence in true matching. Representativeness is an issue related to the missing data pattern across the three NETSARC databases. For instance, an individual present only in the RREPS database has a greater probability of not being linked.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Antipyretic Effects of Toll-Like Receptor 4 Signal Inhibitors in Male Rats","authors":"Tuğçe Nomenoğlu,&nbsp;İbrahim Mert Yüksel,&nbsp;Soner Mamuk,&nbsp;Eyüp Sabri Akarsu","doi":"10.1111/fcp.70059","DOIUrl":"10.1111/fcp.70059","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pattern recognition receptors (PRR) are responsible for detecting pathogens and danger signals in organisms. Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS) and some danger-associated molecular patterns (DAMPs). Activation of this receptor initiates sickness behavior. Fever is a hallmark of this process.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>We hypothesized that TLR4 signal inhibitors may have antipyretic activity. We evaluated the effect of TLR4 signal inhibitors on LPS or carrageenan-induced fever in male Wistar rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Core body temperature was measured via telemetric implants. Fever was induced by injection of LPS (<i>E. coli</i> O111:B4, 250 μg/kg, sc) or carrageenan (50 mg/kg, sc). For TLR4 signal inhibition, LPS from <i>Rhodobacter sphaeroides</i> (LPS-RS), IAXO-102, or naltrexone was used. Intracardiac blood samples were collected for measurement of interleukin-6 (IL-6), an endogenous pyrogen cytokine in plasma, by ELISA during the initial phase of LPS-induced fever.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>LPS-RS pretreatment (25 or 100 μg/kg, sc) did not inhibit LPS-induced fever and plasma IL-6 elevation. Other alternative TLR4 signal inhibitors, such as IAXO-102 (3 mg/kg, sc) or naltrexone (10 mg/kg, sc), also failed to abolish LPS-induced fever. An intriguing finding is that LPS-RS or naltrexone inhibited the fever caused by carrageenan.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Data show that TLR4 signal inhibitors have differential antipyretic activity on fever suggesting that some alternative or complementary mechanisms might be operational for LPS-induced fever. Data also suggest that TLR4 signal inhibitors may be an alternative as a possible treatment option for DAMP-mediated clinical pathologies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145714143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of Intrathecal Lidocaine Combined With Guanfacine or Dexmedetomidine on Nociceptive and Motor Blockade in Rats","authors":"An-Kuo Chou,&nbsp;Chong-Chi Chiu,&nbsp;Yu-Wen Chen,&nbsp;Ching-Hsia Hung,&nbsp;Jhi-Joung Wang","doi":"10.1111/fcp.70057","DOIUrl":"10.1111/fcp.70057","url":null,"abstract":"<div>\u0000 \u0000 <p>The aim of this study was to examine the effects of intrathecal lidocaine combined with guanfacine or dexmedetomidine on nociceptive and motor blockade, in comparison to clonidine. Using a rat model of intrathecal injection, we evaluated the effects of lidocaine combined with guanfacine, dexmedetomidine, or clonidine on nociceptive and motor blockade. The dose-dependent effects of guanfacine on spinal nociceptive and motor blockade were compared to those of lidocaine, a well-known local anesthetic. Guanfacine (0.46 μmol/kg, 3 mM), dexmedetomidine (0.02 μmol/kg, 0.1 mM), or clonidine (1.52 μmol/kg, 10 mM) alone produced no spinal nociceptive or motor blockade. Co-administration of guanfacine (0.46 μmol/kg) or dexmedetomidine (0.02 μmol/kg) with lidocaine (3.14 or 8.38 μmol/kg) prolonged the duration of spinal blockade, an effect attenuated by yohimbine (0.76 μmol/kg), which alone produced no spinal nociceptive or motor blockade. In contrast, the addition of clonidine (1.52 μmol/kg) did not enhance the duration of lidocaine-induced spinal blockade. Guanfacine produced a dose-dependent spinal blockade of both nociceptive and motor functions. The potency ranking (ED₅₀, 50% effective dose) of spinal blockade showed that guanfacine and lidocaine were equal. Guanfacine resulted in a markedly longer spinal block duration than lidocaine at equivalent anesthetic doses (ED₂₅, ED₅₀, and ED₇₅). In summary, co-administration of subeffective doses of guanfacine or dexmedetomidine with lidocaine prolonged the duration of spinal blockade, likely involving α2-adrenergic receptors, whereas subeffective doses of clonidine did not. Guanfacine produced dose-dependent spinal blockade and was equipotent to lidocaine. At equianesthetic doses, guanfacine produced a longer duration of blockade than lidocaine.</p>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145563538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treprostinil Iontophoresis in Diabetic Foot Ulcers: A Single Ascending Dose Safety Study","authors":"Alicia Guigui,&nbsp;Enkeledja Hodaj,&nbsp;Marie Muller,&nbsp;Françoise Stanke-Labesque,&nbsp;Sophie Blaise,&nbsp;Jean-Luc Cracowski,&nbsp;Matthieu Roustit","doi":"10.1111/fcp.70054","DOIUrl":"10.1111/fcp.70054","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetic foot ulcers (DFUs) represent a serious public health problem associated with significant morbidity and health costs. Despite optimal etiologic treatment and local care, amputation is frequent, stressing the need for new treatments. The benefit of systemic administration of vasodilators, such as prostacyclin analogues, has proven efficacy in other types of skin ulcers, but it is counterbalanced by potentially serious vasodilation-induced, concentration-dependent, adverse effects. Experimental data has shown the feasibility of local administration of treprostinil on the wound using iontophoresis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We aimed to assess the safety of the local iontophoretic administration of treprostinil in patients with DFU through a single ascending dose safety study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a prospective single ascending dose phase I study. Patients received a single dose of treprostinil applied via iontophoresis at a current density of 0.2 mA/cm² for 30 min. Local and systemic adverse effects were monitored, and plasma treprostinil concentrations were measured over an 8-h follow-up period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Four patients were included, and received single doses of 0.025, 0.05, 0.1, and 0.25 mg/L at 0.2 mA/cm² during 30 min, and were followed-up for 8 h. All patients did not present any significant adverse effect. Plasma concentration was below &lt; 1.8 ng/mL 8 h after the administration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results suggest that iontophoresis of treprostinil is a safe procedure at 0.25 mg/mL, without systemic adverse effect, suggesting its potential as a targeted treatment for DFUs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12627982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145549057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Remodeling, Tissue Fibrosis, and Clinical Translation","authors":"Yves Fromes","doi":"10.1111/fcp.70055","DOIUrl":"10.1111/fcp.70055","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the Immune System Effects of Desloratadine on Lipopolysaccharide-Stimulated Mammalian Macrophage Cells","authors":"Batuhan Yurtseven,&nbsp;Ömer Mete Başkan,&nbsp;Esra Aydemir,&nbsp;Furkan Ayaz","doi":"10.1111/fcp.70056","DOIUrl":"10.1111/fcp.70056","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neuroimmune interactions are central to inflammatory and neurological disorders. Desloratadine (DES), a second-generation H₁ antihistamine, has been suggested to exert immunomodulatory effects, yet its impact on innate immune cells remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>J774.2 macrophages were treated with DES (1–10 μg/mL) ± lipopolysaccharide (LPS, 1 μg/mL). Cytokine secretion (IL-6, TNF-α, IL-12p40, GM-CSF) was measured by ELISA, and cell viability was assessed using Trypan Blue exclusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DES induced a dose-dependent suppression of TNF-α, with significant inhibition at higher concentrations, and reduced IL-12p40 at 10 μg/mL. IL-6 showed a modest, nonsignificant decrease, whereas GM-CSF was increased, indicating a pro-inflammatory effect on macrophage activation. No cytotoxicity was detected at any dose.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>DES selectively modulates macrophage responses, strongly inhibiting TNF-α and IL-12p40 while enhancing GM-CSF, reflecting a dual anti- and pro-inflammatory profile. These findings support further investigation of DES in neuroinflammatory and immune-mediated conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Direct Oral Anticoagulant Uptake on Hospitalizations for Stroke/Transient Ischemic Attack, Intracranial Hemorrhage, and Gastrointestinal Bleeding in Individuals With Atrial Fibrillation: A Population-Based Study","authors":"Tony Antoniou,&nbsp;Daniel McCormack,&nbsp;Tianru Wang,&nbsp;Mina Tadrous,&nbsp;Tara Gomes","doi":"10.1111/fcp.70051","DOIUrl":"10.1111/fcp.70051","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Direct-acting oral anticoagulants (DOACs) have largely replaced warfarin for stroke prevention in patients with atrial fibrillation, yet their population-level impact on health outcomes and costs remains unclear. We examined whether the widespread uptake of DOACs was associated with changes in hospitalization rates and costs for stroke/transient ischemic attack (TIA), intracranial hemorrhage (ICH), and gastrointestinal bleeding among individuals with atrial fibrillation receiving publicly funded anticoagulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a population-based ecological time series study using administrative health data from Ontario, Canada, between 2003 and 2021. We used segmented negative binomial regression and generalized additive models to estimate immediate and post-DOAC uptake trends in hospitalization rates and costs following increased use of DOACs in 2012.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 12,134 hospitalizations for ICH, 59 946 for gastrointestinal bleeding, and 40 724 for stroke/TIA among anticoagulated individuals with atrial fibrillation. Following DOAC uptake, ICH rates (rate ratio [RR]: 0.88; 95% CI: 0.86–0.90) and costs (RR: 0.74; 95% CI: 0.62–0.88) declined immediately, with continued quarterly declines. Gastrointestinal bleeding rates increased initially (RR: 1.17; 95% CI: 1.14–1.20) and declined over time (RR per quarter: 0.99; 95% CI: 0.99–0.99). Gastrointestinal bleeding-related costs did not change significantly. Stroke/TIA rates remained stable, but hospitalization costs declined ($366 per 1000 individuals per quarter; 95% CI: −$562 to −$170).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>DOAC uptake was associated with reduced ICH rates and costs and an initial increase but subsequent decline in gastrointestinal bleeding rates. Despite stable stroke rates, reduced costs suggest potential long-term economic benefits. Our findings support the real-world effectiveness and safety of DOACs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex and Age Differences in Suspected Bleeding Reporting With Acetyl Salicylic Acid: A Descriptive Study in the Global Pharmacovigilance Database, Vigibase","authors":"Jean-Louis Montastruc,&nbsp;Alessandra Bura-Rivière","doi":"10.1111/fcp.70053","DOIUrl":"10.1111/fcp.70053","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The present study was performed to investigate putative sex differences in the reporting of acetyl salicylic acid (ASA)–related bleeding in the global pharmacovigilance database.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using Vigibase, the global pharmacovigilance database, all bleeding reports with ASA between January 1, 2008, and December 31, 2021, in adults were included. The main bleeding locations with ASA were compared in men versus women. A secondary objective was to analyze possible age differences. Results are presented as reporting odds ratios (RORs) with their 95% confidence interval.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 29 034 bleeding with ASA, the most frequent were gastrointestinal (41.2%), neurological (21.3%), and nasal (13.6%). Higher ROR values were found in men for all bleeding in general (ROR = 1.56 [1.51–1.61]) but also for gastrointestinal, neurological, nasal, and renal locations. Similar trends were found for “serious” reports (except for gastrointestinal bleeding). Neurological fatal reports were more frequently reported in men. These sex differences were also found in all the age categories. Higher ROR values were found in patients from 65 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The risk of total, “serious,” and fatal bleeding reporting with ASA was higher in men than in women and after 65 years. Similar conclusions can be made for the most frequent locations of ASA-associated bleeding: gastrointestinal followed by neurological and nasal ones.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}