European Journal of Clinical Pharmacology最新文献

{"title":"Attitudes, barriers, and facilitators toward tools supporting appropriate prescribing among healthcare professionals: a cross-sectional study.","authors":"Monia Donati, Valentina Giunchi, Giulia Grillini, Marco Domenicali, Maria Lia Lunardelli, Veronica Pasini, Susy Milandri, Monica Mussoni, Fabio Pieraccini, Elisa Sangiorgi, Emanuel Raschi, Valentina Colonnello, Carlotta Lunghi, Elisabetta Poluzzi","doi":"10.1007/s00228-025-03852-4","DOIUrl":"10.1007/s00228-025-03852-4","url":null,"abstract":"<p><strong>Purpose: </strong>Potentially inappropriate prescriptions are associated with an increased risk of drug-drug interactions, adverse events, and unfavorable clinical outcomes, especially in older adults. Although different tools to improve appropriate prescribing have been developed to support healthcare professionals, their application and the barriers to their use remain insufficiently explored. This study aimed to assess Italian healthcare professionals' knowledge of these tools and identify obstacles to their adoption.</p><p><strong>Methods: </strong>The study used a purposefully designed questionnaire to assess knowledge, adoption, and barriers related to appropriateness tools. The tools included were identified through a literature review and subsequently refined via expert consensus. Open-ended responses were analyzed using a conventional content analysis approach, and the analyses focused on differences across professional groups.</p><p><strong>Results: </strong>The survey collected 657 responses from pharmacists (35%), nurses (26%), general practitioners (22%), geriatricians/internists (9%), and other physicians (8%). The Beers and STOPP/START criteria were used by 38% and 34% of participants, respectively, with geriatricians and other physicians being the primary users. Additionally, 34% of participants reported using specific software integrated into their institutional computer systems. Among 294 respondents identifying barriers to appropriate prescribing, the most common were lack of time (14%), lack of knowledge (10%), and accessibility/costs of digital tools (8%). Key facilitators included specific training (38%), integrated software/apps (29%), and more time with patients (11%).</p><p><strong>Conclusions: </strong>The adoption of tools supporting appropriate prescribing remains limited among healthcare professionals in Italy, with significant differences among professionals. Policymakers and healthcare institutions should focus on education, interprofessional collaboration, and user-friendly digital solutions to improve prescribing process and patient safety.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1155-1165"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disproportionality analysis of serotonin syndrome associated with selective serotonin reuptake inhibitors: a pharmacovigilance analysis.","authors":"Taelim Choi, Jeongseon Oh, Jaehyeong Cho, Jaeyu Park, Tae Hyeon Kim, Jiseung Kang, André Hajek, Jaewon Kim, Selin Woo, Yerin Hwang, Dong Keon Yon","doi":"10.1007/s00228-025-03856-0","DOIUrl":"10.1007/s00228-025-03856-0","url":null,"abstract":"<p><strong>Purpose: </strong>The incidence and risk of serotonin syndrome associated with selective serotonin reuptake inhibitors (SSRIs) have increased. However, large-scale studies investigating this relationship remain limited. Therefore, this study aims to evaluate the signal detection between six SSRIs and serotonin syndrome, rank their relative risks, and propose practical preventive strategies.</p><p><strong>Methods: </strong>This study utilized the global pharmacovigilance database, which systematically compiles adverse drug reaction reports from over 140 countries. The analysis focused on individuals diagnosed with serotonin syndrome associated with SSRIs, classified under the Anatomical Therapeutic Chemical code 'N06AB' and categorized into six types. A disproportionality analysis was conducted using the information component (IC) with IC_0.25 and the reporting odds ratio (ROR) with 95% confidence interval (CI) to assess the signal detection between serotonin syndrome and SSRIs.</p><p><strong>Results: </strong>Among 35 million reports, 24,674 reports of serotonin syndrome were identified from 1968 to 2024, including 4,035 associated with SSRIs. Sertraline (24.46%) was the most frequently implicated SSRI. All SSRIs indicated a significant signal detection with serotonin syndrome, with citalopram exhibited the highest signal (ROR: 77.29 [95% CI, 71.63-83.40]; IC: 6.13 [IC₀₂₅, 6.01]). Hyperthermia and neurological manifestations were the most prevalent. The median time to onset was one day. Recovery rate was 62.21%, and mortality was 0.25%.</p><p><strong>Conclusion: </strong>The findings underscore the potential signal detection between SSRIs and serotonin syndrome. Results also highlight the need to strengthen prevention and management to mitigate associated risks, while long-term studies on serotonin syndrome are essential for improving patient safety and optimizing treatment.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1167-1175"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on disproportionality in the detection of potential signals between quetiapine and diabetic ketoacidosis.","authors":"Haiya Liang, Dandan Mao, Yan Zhao, Rongjing Zhou","doi":"10.1007/s00228-025-03895-7","DOIUrl":"https://doi.org/10.1007/s00228-025-03895-7","url":null,"abstract":"<p><strong>Purpose: </strong>Quetiapine is an atypical second-generation antipsychotic. Diabetic ketoacidosis (DKA) is an acute metabolic complication, most commonly encountered in type 1 diabetes, and it can be life-threatening if not treated promptly. This study aimed to assess quetiapine-associated DKA using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.</p><p><strong>Methods: </strong>We performed a retrospective investigation on the FAERS from the first quarter of 2004 to the second quarter of 2024 using the reporting odds ratio (ROR) and proportional reporting ratio (PRR) from the disproportionality analysis. According to the Medical Dictionary for Regulatory Activities (MedDRA) 26.1, preferred terms (PTs) of reports on adverse drug reactions (ADRs) were classified using System Organ Classification (SOC), and filtered based on hyperglycemia and new-onset diabetes mellitus in the Standardized MedDRA Query (SMQ).</p><p><strong>Results: </strong>We collected 65,536 ADR reports with quetiapine as the primary suspected drug, including 27 system organ classifications. There were 3,046 cases related to DKA, predominantly from the United States, with a slightly higher proportion of females (51.31%) than males (45.63%). The most common severe ADR outcome (539 cases, 17.70%) was hospitalization-initial or prolonged, followed by death (333 cases, 10.93%). Additionally, compared to the other three second-generation antipsychotics (clozapine, olanzapine, and risperidone), quetiapine exhibited a stronger association with DKA (ROR = 31.05, ROR025 = 29.87).</p><p><strong>Conclusion: </strong>Quetiapine could be associated with DKA; therefore, physicians should be aware of this potentially fatal adverse event. Studies are needed to investigate the matter further.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term results of a multidisciplinary medication optimization program for older adults including primary care and hospital team.","authors":"Camille Guerin, Romain Leguillon, Albane Cherel, Lucie Valembois, Gwladys Brochard, Mélissa Pierre, Antoine Bourderont, Bérénice Gaillot, Claire Bernardeau, Céline Vaesken, Ines Tebourski, Pablo Descatoire, Guillaume Saint-Lorant, Cédric Villain, Alexandre Meurant","doi":"10.1007/s00228-025-03889-5","DOIUrl":"https://doi.org/10.1007/s00228-025-03889-5","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic optimization and deprescribing in older adults face multiple barriers, whereas drug-related hospitalization increased from 3.6% to 8.5% between 2006 and 2018. The OPTIMEDOC program aims to optimize older adults' prescriptions through clinical medication review conducted by a multidisciplinary team including clinical pharmacist, geriatrician, and general practitioner (GP). This collaboration between primary care and hospital team aims to enable appropriate and sustainable prescriptions.</p><p><strong>Purpose: </strong>This study aimed to assess the implementation of therapeutic optimizations at least 6 months after the intervention. The secondary objective was to document the most frequently deprescribed and newly introduced medications and their long-term implementation rate.</p><p><strong>Methods: </strong>This observational study was conducted in a university hospital, including patients who benefited from the OPTIMEDOC program from April 2022 to April 2024. The primary outcome was the long-term implementation rate of recommendations. The secondary outcome was a description of the optimized drugs according to ATC2 classes.</p><p><strong>Results: </strong>Among 1580 validated therapeutic recommendations for 143 patients included with an average age of 86.4 years old, 1473 were followed up (93.2%). Of these, 1017 were successfully implemented over 1 year (69.0%). Specifically, 81.8% of deprescriptions, 58.3% of introductions, and 70.5% of modifications were implemented. Although vaccine introductions were the most frequently recommended (n = 222), only 41% were implemented. Regarding deprescribing, psycholeptics, psychoanaleptics, and drugs for acid-related disorders had a long-term implementation rate of over 75%.</p><p><strong>Conclusion: </strong>These results validate the OPTIMEDOC program as an effective strategy for sustainable therapeutic optimization, especially for deprescribing. Engaging community pharmacists could further enhance the implementation of therapeutic recommendations.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Barriers and solutions for the European prescribing exam: a qualitative world café study.","authors":"Erik M Donker, Joost D Piët, David J Brinkman, Milan C Richir, Paraskevi Papaioannidou, Robert Likic, Emilio J Sanz, Thierry Christiaens, João N Costa, Fabrizio De Ponti, Milo Gatti, Ylva Böttiger, Cornelis Kramers, Michiel A van Agtmael, Jelle Tichelaar","doi":"10.1007/s00228-025-03886-8","DOIUrl":"https://doi.org/10.1007/s00228-025-03886-8","url":null,"abstract":"<p><strong>Purpose: </strong>To harmonize and modernize clinical pharmacology and therapeutics (CPT) education across Europe, we developed the European Prescribing Exam. Before its introduction into medical degree programs, it is crucial to understand the potential barriers to its implementation and ways to overcome them. Therefore, the aim of this study was to identify barriers and potential solutions to the implementation of the European Prescribing Exam.</p><p><strong>Methods: </strong>This qualitative World Café (WC) study involved CPT teachers who participated in a 2-day event focused on the European Prescribing Exam. There were five tables in the WC, each dedicated to a different topic of implementation: (1) organization, (2) technical aspects, (3) content, (4) rollout logistics, and (5) politics. Participants rotated randomly between the tables every 20 min. During each round, they were encouraged to identify barriers and solutions, which were then discussed. The rounds continued until data saturation was reached. Findings were summarized at the end of the WC. We used inductive thematic analysis using a semantic approach to analyze the data.</p><p><strong>Results: </strong>In total, 26 CPT teachers (female: n = 14) from 19 medical schools in 15 European countries participated. After four rounds, 86 potential barriers and 86 solutions were identified. Most barriers were related to the topics \"Content\" (n = 22), \"Organization\" (n = 20), and \"Technical aspects\" (n = 18). Thematic analysis identified 11 themes, three of which were overarching, meaning they applied to multiple topics. The most significant themes included barriers related to curricula, motivation, information technology, and relevance.</p><p><strong>Conclusion: </strong>This study shows that organizing and implementing the European Prescribing Exam will be challenging. However, participants proposed potential solutions for nearly all barriers, which suggest that the implementation of the European Prescribing Exam is feasible.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tool use isn't enough-outcomes matter.","authors":"Muhammad Zahir Shah, Azka Mustaan","doi":"10.1007/s00228-025-03887-7","DOIUrl":"https://doi.org/10.1007/s00228-025-03887-7","url":null,"abstract":"","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"External validation of population pharmacokinetic models of oxcarbazepine active metabolite in Chinese children with epilepsy.","authors":"Ruoyun Wu, Xintian Li, Yujie Wu, Zhigang Zhao, Weixing Feng, Shenghui Mei","doi":"10.1007/s00228-025-03875-x","DOIUrl":"https://doi.org/10.1007/s00228-025-03875-x","url":null,"abstract":"<p><strong>Objective: </strong>To assess the predictive performance of published population pharmacokinetic models of the oxcarbazepine (OXC) active metabolite, 10, 11-dihydro-10-monohydroxycarbazepine (MHD), using external data sets in Chinese children with epilepsy.</p><p><strong>Method: </strong>A total of 231 concentrations from 185 Chinese children with epilepsy were used for external validation. PubMed, Embase, and Web of Science were searched for published PPK models of OXC active metabolite MHD in children. Seven models were searched and labeled A to G based on the year of publication. Prediction error, visual predictive check, and normal prediction distribution error tests were employed to assess the model's extrapolation performance. The Bayesian prediction method was applied to ascertain the influence of prior concentrations on the model's predictive performance.</p><p><strong>Result: </strong>A total of seven MHD PPK models were retrieved. Models A, D, E, and G exhibited good predictive performance in prediction-based diagnostics and visual predictive checks. The normalized predictive distribution error test shows that none of the models is suitable to describe our data. Bayesian prediction significantly improved the prediction performance of all the models with one prior observation.</p><p><strong>Conclusion: </strong>The published MHD PPK models showed extensive variation in predictive performance when extrapolated in Chinese children with epilepsy. Bayesian forecasting substantially improved the predictive performance of the model and might facilitate the customization of OXC dosing.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From adoption to impact: linking prescribing tools to clinical outcomes-authors' response.","authors":"Monia Donati, Carlotta Lunghi, Giulia Grillini, Marco Domenicali, Maria Lia Lunardelli, Veronica Pasini, Susy Milandri, Monica Mussoni, Fabio Pieraccini, Elisa Sangiorgi, Emanuel Raschi, Valentina Colonnello, Elisabetta Poluzzi","doi":"10.1007/s00228-025-03888-6","DOIUrl":"https://doi.org/10.1007/s00228-025-03888-6","url":null,"abstract":"","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Possible increased risks of cholecystitis in patients with idiopathic pulmonary fibrosis treated with nintedanib.","authors":"Catherine Kiani, Alexandre Bleinc, Theodora Bejan-Angoulvant, Marion Teulier, Sylvain Marchand-Adam","doi":"10.1007/s00228-025-03867-x","DOIUrl":"https://doi.org/10.1007/s00228-025-03867-x","url":null,"abstract":"","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacogenetics and pharmacometabolomics predictors of clozapine and norclozapine pharmacokinetic exposure in healthy volunteers.","authors":"Orwa Albitar, Mohd Rahimi Muda, Siti Maisharah Sheikh Ghadzi, Dzul Azri Mohamed Noor, Baharudin Ibrahim, Chin-Hoe Teh, Mohammed Ahmed Akkaif, Fatimatuzzahra' Abd Aziz","doi":"10.1007/s00228-025-03884-w","DOIUrl":"https://doi.org/10.1007/s00228-025-03884-w","url":null,"abstract":"<p><strong>Purpose: </strong>Clozapine is the only effective medication for unresponsive schizophrenia. However, it has a complicated dose-concentration relationship. The present study aimed to investigate the role of some genetic polymorphisms and metabolic profiles in addressing the variability in clozapine and norclozapine concentrations.</p><p><strong>Methods: </strong>A single dose of 12.5 mg clozapine was administered to 33 healthy volunteers, from whom 270 samples were collected at 30 min, 1, 2, 3, 5, and 8 h. The concentrations of clozapine and norclozapine were determined using HPLC-UV. CYP1A2 -163 C>A, ABCB1 3435 C>T, and ABCB1 2677 G>T genetic polymorphisms were investigated using allele-specific polymerase chain reaction and restriction fragment length polymorphism, and the metabolic profiles were identified using proton nuclear magnetic resonance (¹H NMR).</p><p><strong>Results: </strong>Clozapine concentrations and area under the curve (AUC) were higher, and the clearance was 38.3% (95% confidence intervals (95% CI), 4.5-72.2%) lower in the CYP1A2 -163 AA genotype, while clozapine initial concentrations were lower in the ABCB1 2677 GG genotype. In a multiple regression analysis, glucose (p-value, 0.009) was significantly associated with the norclozapine to clozapine AUC (N:C) ratio.</p><p><strong>Conclusions: </strong>Variabilities in clozapine pharmacokinetics were accounted for using genetic polymorphisms and metabolic profiles. Clozapine concentrations in CYP1A2 -163 C>A polymorphism should be cautiously interpreted considering the smoking status. Altered glucose levels, besides being an adverse effect of clozapine, may also be indirectly associated with variability in CYP1A2 activity as indicated by the N:C ratio to be confirmed in larger and controlled trials.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}