Therapeutic Advances in Drug Safety最新文献

{"title":"Implementation of electronic distribution of Direct Healthcare Professional Communications by the Danish Medicines Agency: a survey study of physicians' experiences and preferences.","authors":"Per Sindahl, Mathias Møllebæk, Helga Gardarsdottir, Marie Louise De Bruin, Christine Erikstrup Hallgreen, Marianne Hald Clemmensen","doi":"10.1177/20420986251333911","DOIUrl":"10.1177/20420986251333911","url":null,"abstract":"<p><strong>Background: </strong>The efficient distribution of Direct Healthcare Professional Communications (DHPCs) is crucial for ensuring healthcare providers promptly receive important new safety information.</p><p><strong>Objectives: </strong>This study aimed to evaluate the implementation of the electronic distribution of DHPCs by the Danish Medicines Agency (DKMA) and to assess how future safety communication can be improved.</p><p><strong>Design: </strong>We conducted a web-based cross-sectional survey among Danish physicians using a self-administered questionnaire.</p><p><strong>Methods: </strong>DKMA sends DHPCs to healthcare professionals via an electronic mailbox called e-Boks which is linked to the unique personal identifier. To evaluate DKMA's distribution of DHPCs, participants were asked about awareness, frequency and barriers of reading, preferred distribution channel and overall satisfaction. To further identify potential improvements, respondents were asked about general preferences regarding sender and channels of safety information in addition to which information sources they use to keep up-to-date.</p><p><strong>Results: </strong>A total of 2238 physicians completed the survey corresponding to a response rate of 26% based on the total target population. The total awareness was 81%. Compared to previous research, awareness of GPs increased from 66% to 82%, and the percentage of GPs who rarely or never read DHPCs decreased from 33% to 20%. In addition, our study revealed a preference for receiving DHPCs electronically through e-Boks as opposed to workplace-delivered postal letters, and a preference for the DKMA over pharmaceutical companies as the sender of DHPCs. One-third of the respondents were either 'dissatisfied' or 'very dissatisfied' with the current solution. A professional mailbox and point-of-care alerts when prescribing may complement the primary distribution channel to strengthen the uptake. Additionally, existing information sources already frequented by the target group may be used to communicate safety information.</p><p><strong>Conclusion: </strong>The DKMA's electronic distribution of DHPCs suggests an improvement and may serve as inspiration for other agencies. However, the considerable dissatisfaction calls for further improvements.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"16 ","pages":"20420986251333911"},"PeriodicalIF":3.4,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143687","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":"Can large language models detect drug-drug interactions leading to adverse drug reactions?","authors":"Justine Sicard, François Montastruc, Coline Achalme, Annie Pierre Jonville-Bera, Paul Songue, Marina Babin, Thomas Soeiro, Pauline Schiro, Claire de Canecaude, Romain Barus","doi":"10.1177/20420986251339358","DOIUrl":"10.1177/20420986251339358","url":null,"abstract":"<p><strong>Background: </strong>Drug-drug interactions (DDI) are an important cause of adverse drug reactions (ADRs). Could large language models (LLMs) serve as valuable tools for pharmacovigilance specialists in detecting DDIs that lead to ADR notifications?</p><p><strong>Objective: </strong>To compare the performance of three LLMs (ChatGPT, Gemini, and Claude) in detecting and explaining clinically significant DDIs that have led to an ADR.</p><p><strong>Design: </strong>Observational cross-sectional study.</p><p><strong>Methods: </strong>We used the French National Pharmacovigilance Database to randomly extract Individual Case Safety Reports (ICSRs) of ADRs with DDI (positive controls) and ICSRs of ADRs without DDI (negative controls) registered in 2022. Interaction cases were classified by difficulty level (level-1 DDI being the easiest and level-2 DDI being the most difficult). We give each LLM (ChatGPT, Gemini, and Claude) the same prompt and case summary. Sensitivity, specificity, and <i>F</i>-measure were calculated for each LLM in detecting DDIs in the case summaries.</p><p><strong>Results: </strong>We assessed 82 ICSRs with DDIs and 22 ICSRs without DDIs. Among ICSRs with DDIs, 37 involved level-1 DDIs, and 45 involved level-2 DDIs. Correct responses were more frequent for level-1 DDIs than for level-2 DDIs. Regardless of difficulty level, ChatGPT detected 99% of DDI cases, and Claude and Gemini detected 95%. The percentage of correct answers to all DDI-related questions was 66% for ChatGPT, 68% for Claude, and 33% for Gemini. ChatGPT and Claude produced comparable results and outperformed Gemini (<i>F</i>-measure between 0.83 and 0.85 for ChatGPT and Claude and 0.63-0.68 for Gemini) to detect drugs involved in DDI. All exhibited low specificity (ChatGPT 0.68, Claude 0.64, and Gemini 0.36) and reported nonexistent DDIs for negative controls.</p><p><strong>Conclusion: </strong>LLMs can detect DDIs leading to pharmacovigilance cases, but cannot reliably exclude DDIs in cases without interactions. Pharmacologists are crucial for assessing whether a DDI is implicated in an ADR.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"16 ","pages":"20420986251339358"},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094923","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":"Drug-induced fever in post-surgical patients: a systematic review of case reports.","authors":"Fatemeh Afra, Mona Aboutalebzadeh, Soheila Tayefeh, Sepide Javankiani, Bita Shahrami, Amir Ahmad Arabzadeh","doi":"10.1177/20420986251335825","DOIUrl":"https://doi.org/10.1177/20420986251335825","url":null,"abstract":"<p><strong>Background: </strong>Fever is a common postoperative complication, typically caused by aseptic inflammation or infection. However, drug-induced fever (DIF) is an underdiagnosed etiology that should be considered in the differential diagnosis, especially in patients receiving complex medication regimens post-surgery.</p><p><strong>Objectives: </strong>This systematic review aims to assess the current literature on DIF in post-surgical patients to improve diagnostic accuracy and patient care.</p><p><strong>Design: </strong>Systematic review of case reports and case series.</p><p><strong>Data sources and methods: </strong>This systematic review was conducted following the PRISMA 2020 guidelines. We included case reports and series involving post-surgical patients with fever linked to drug administration. Studies were retrieved from the PubMed, Scopus, Embase, and Web of Science databases, as well as gray literature sources. Quality and bias were assessed using the Joanna Briggs Institute (JBI) critical appraisal tools.</p><p><strong>Results: </strong>A total of 16 studies (14 case reports and 2 case series) involving 23 patients were included. The most frequently implicated drugs were propofol, morphine, and cephalosporins. Fever onset ranged from immediate postoperative to several days later, with varied patterns, including intermittent, remittent, and continuous fever. The majority of patients recovered after drug discontinuation, although two cases resulted in death.</p><p><strong>Conclusion: </strong>DIF is one of the causes of postoperative fever. Early identification and cessation of the offending drug are crucial for resolving the fever and preventing severe complications. Clinicians must remain vigilant in diagnosing DIF to improve patient outcomes post-surgery.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"16 ","pages":"20420986251335825"},"PeriodicalIF":3.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019906","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":"Pharmacovigilance analysis of small bowel bleeding associated with NSAIDs.","authors":"Ying-Han Deng, Meiting Jiang, Yun Chen, Hong-Bin Chen","doi":"10.1177/20420986251318848","DOIUrl":"https://doi.org/10.1177/20420986251318848","url":null,"abstract":"<p><strong>Background: </strong>Currently, the factors influencing small bowel bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs) remain unclear.</p><p><strong>Objectives: </strong>This study aimed to assess NSAID-associated small bowel bleeding and evaluate the impact of other drugs on it through a pharmacovigilance study, thereby providing valuable insights for clinical practice.</p><p><strong>Design: </strong>Data on NSAID-associated small bowel bleeding were retrospectively extracted from two public adverse drug reaction databases-the Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) and the Japan Pharmaceuticals and Medical Devices Agency's Adverse Drug Event Reporting (JADER)-from 2004 to 2023 for further analysis.</p><p><strong>Methods: </strong>The reporting odds ratio (ROR), a pharmacovigilance technique, was employed to identify signals of adverse reactions, and the Chi-square test was utilized to assess differences between groups.</p><p><strong>Results: </strong>Multiple NSAIDs associated with small bowel bleeding were identified in both databases. In the drug combination analysis, no significant differences in the risk of small bowel bleeding were found between NSAIDs combined with proton pump inhibitors (PPIs) and NSAIDs alone in FAERS (all <i>p</i> > 0.05). Decreasing risks were found when multiple NSAIDs were combined with rebamipide or probiotics compared to NSAIDs alone in JADER (<i>p</i> < 0.05 and ROR  < 1). In subgroup analyses of age and sex, older adults and males who used aspirin showed higher risk signals in both databases (all <i>p</i> < 0.05 and ROR  > 1).</p><p><strong>Conclusion: </strong>PPIs did not show a significant impact on NSAIDs-associated small bowel bleeding, while rebamipide and probiotics may exhibited a preventive effect against NSAIDs-associated small bowel bleeding. Older adults and males constituted risk factors for aspirin-associated small bowel bleeding.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"16 ","pages":"20420986251318848"},"PeriodicalIF":3.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050154","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":"Semaglutide: a gendered phenomenon-women's increased vulnerability to adverse drug reactions in the global weight loss trend.","authors":"Eleonora Castellana, Maria Rachele Chiappetta","doi":"10.1177/20420986251332737","DOIUrl":"https://doi.org/10.1177/20420986251332737","url":null,"abstract":"","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"16 ","pages":"20420986251332737"},"PeriodicalIF":3.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061866","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":"Pharmacovigilance study on the reporting frequency of atrial fibrillation with immune checkpoint inhibitors: insights from FDA Adverse Event Reporting System.","authors":"Nunzia Balzano, Annamaria Mascolo, Donatella Ruggiero, Concetta Rafaniello, Giuseppe Paolisso, Francesco Rossi, Annalisa Capuano","doi":"10.1177/20420986241312497","DOIUrl":"https://doi.org/10.1177/20420986241312497","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are linked with immune-related adverse events (irAEs), including cardiac events.</p><p><strong>Objective: </strong>This study aims to assess the reporting frequency of atrial fibrillation with ICIs using data from the Food and Drug Administration Adverse Event Reporting System (FAERS).</p><p><strong>Design: </strong>It is an observational, retrospective, pharmacovigilance study.</p><p><strong>Methods: </strong>Individual Case Safety Reports (ICSRs) were retrieved from FAERS up to September 24, 2024. Cases reporting one or more ICIs (atezolizumab, avelumab, cemiplimab, dostarlimab, durvalumab, ipilimumab, nivolumab, pembrolizumab, and tremelimumab) and atrial fibrillation were selected. Disproportionality analyses were performed by applying the reporting odds ratio (ROR) and the Informational Component (IC) with a 95% confidence interval (95% CI).</p><p><strong>Results: </strong>A total of 1228 ICSRs were retrieved, of which 218 (17.75%) were related to combinations of ICIs. Most ICSRs (<i>N</i> = 812; 66.1%) referred to male patients and the age group most represented was ⩾65 years (<i>N</i> = 772; 62.9%). Atrial fibrillation was serious in 99.3% (<i>N</i> = 1220) of cases and had a fatal outcome (<i>N</i> = 248; 20.3%). Atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab were associated with a statistically significant higher reporting frequency of atrial fibrillation compared to all other drugs (ROR: 1.90, IC: 0.91; ROR: 1.94, IC: 0.92; ROR: 1.52, IC: 0.60; ROR: 1.30, IC: 0.38; ROR: 1.66, IC: 0.72, respectively). The anti-CTLA-4 ipilimumab showed a statistically significant lower reporting frequency of atrial fibrillation compared to all other drugs (ROR: 0.69, IC: -0.53) and to all other ICIs (ROR: 0.45, IC: -1.02). Moreover, anti-PD-L1 (ROR: 2.60, IC: 0.47) and anti-PD-1 (ROR: 2.12, IC: 0.16) were associated with a higher reporting of atrial fibrillation compared to anti-CTLA-4.</p><p><strong>Conclusion: </strong>ICI-induced atrial fibrillation was serious and had severe outcomes. The anti-CTLA-4 showed a lower likelihood of reporting atrial fibrillation, while higher reporting was found with anti-PD-1 and anti-PD-L1. Further studies are needed to confirm this safety aspect.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"16 ","pages":"20420986241312497"},"PeriodicalIF":3.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011629","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":"Mydriasis mediated by local anesthetics: an unexpected adverse event or new therapeutic indication?","authors":"Homero Contreras-Salinas, Janet Cristina Vázquez-Beltrán, María Soledad Romero-López, Oscar Olvera-Montaño, Lourdes Yolotzin Rodríguez-Herrera","doi":"10.1177/20420986251332740","DOIUrl":"https://doi.org/10.1177/20420986251332740","url":null,"abstract":"<p><p>The increasing off-label use of medications needs a robust pharmacovigilance system. This is particularly crucial given the abundance of scientific data that can be harnessed to ensure a product's safety. Our review focuses on the off-label use of local anesthetics, a common practice in topical and intracameral applications. However, the occurrence of mydriasis, as indicated in the monographs/summaries of product characteristics, is an unexpected adverse event. Our aim is to provide a comprehensive understanding of mydriasis caused by local anesthetics, both as an unexpected adverse event and as an off-label use, to reinforce the importance of pharmacovigilance practices. We conducted a comprehensive search in Medline/PubMed and Google Scholar from two distinct perspectives: examining the occurrence of mydriasis with the use of local anesthetic as an adverse event and as an off-label use. Our search yielded 14 articles that reported mydriasis as an unexpected adverse event with the use of anesthetics, with dental procedures being a significant contributor to this type of event. Also, we identified eight articles that explored the off-label use of local anesthetics to induce mydriasis, with the most common method of drug administration being intracameral injection. These findings underscore the importance of our research in understanding the unexpected adverse event of mydriasis and the potential for off-label use of local anesthetics. They also highlight the need for continued involvement and vigilance in this area, as our understanding of these phenomena continues to evolve and further investigation is crucial. The use of local anesthetics for mydriasis holds significant promise, particularly in ophthalmological surgeries. This approach could potentially mitigate the adverse events associated with conventional mydriatics, offering a more efficient and safer alternative. Furthermore, using a single medication for akinesia, anesthesia, and mydriasis could significantly enhance the efficiency and convenience of surgical procedures. On the other hand, it is crucial to extend the knowledge of the mydriasis-anesthesia association through risk minimization activities (e.g., the inclusion of monographs/summary of product characteristics) to communicate the risk of mydriasis with the use of local anesthetics.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"16 ","pages":"20420986251332740"},"PeriodicalIF":3.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039344","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":"Perspective review: Will generative AI make common data models obsolete in future analyses of distributed data networks?","authors":"Jeffery L Painter, Darmendra Ramcharran, Andrew Bate","doi":"10.1177/20420986251332743","DOIUrl":"https://doi.org/10.1177/20420986251332743","url":null,"abstract":"<p><p>Integrating real-world healthcare data is challenging due to diverse formats and terminologies, making standardization resource-intensive. While Common Data Models (CDMs) facilitate interoperability, they often cause information loss, exhibit semantic inconsistencies, and are labor-intensive to implement and update. We explore how generative artificial intelligence (GenAI), especially large language models (LLMs), could make CDMs obsolete in quantitative healthcare data analysis by interpreting natural language queries and generating code, enabling direct interaction with raw data. Knowledge graphs (KGs) standardize relationships and semantics across heterogeneous data, preserving integrity. This perspective review proposes a fourth generation of distributed data network analysis, building on previous generations categorized by their approach to data standardization and utilization. It emphasizes the potential of GenAI to overcome the limitations CDMs with GenAI-enabled access, KGs, and automatic code generation. A data commons may further enhance this capability, and KGs may well be needed to enable effective GenAI. Addressing privacy, security, and governance is critical; any new method must ensure protections comparable to CDM-based models. Our approach would aim to enable efficient, real-time analyses across diverse datasets and enhance patient safety. We recommend prioritizing research to assess how GenAI can transform quantitative healthcare data analysis by overcoming current limitations.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"16 ","pages":"20420986251332743"},"PeriodicalIF":3.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027155","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":"Real-world evidence on the association of novel antidiabetic medication use with cancer risk and protective effects: a systematic review and network meta-analysis.","authors":"Ahmed S Kenawy, Yi-Shao Liu, Ayobami Aiyeolemi, Godwin Okoye, Chanhyun Park","doi":"10.1177/20420986251335214","DOIUrl":"https://doi.org/10.1177/20420986251335214","url":null,"abstract":"<p><strong>Background: </strong>Novel antidiabetic medications (SGLT-2 inhibitors, DPP-4 inhibitors, and GLP-1 agonists) are commonly used worldwide; however, the available research lacks definitive conclusions on their protective effects or potential risks on cancer.</p><p><strong>Objectives: </strong>Compared to other antidiabetics, our systematic review and network meta-analysis (NMA) aims to use real-world studies to assess the potential cancer risks or protective effects of these novel antidiabetics.</p><p><strong>Methods: </strong>We comprehensively searched PubMed, CINAHL, and Web of Science from their inception until November 30, 2023. We included observational studies examining at least one novel antidiabetics in the systematic review. The novel antidiabetics include sodium-glucose cotransporter-2 inhibitors (SGLT-2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), and glucagon-like peptide-1 agonists (GLP-1a).</p><p><strong>Design: </strong>We focused on cohort studies that provided data on cancer incidence and sample size in the NMA. Using NetMetaXL^®, the random effects model with informative priors was used in the NMA to estimate the pooled odds ratio (OR) with 95% credible intervals (CrI).</p><p><strong>Results: </strong>The systematic review included 62 studies, of which 22 met the inclusion criteria for the NMA. SGLT-2i users had lower overall cancer risk compared to sulfonylureas (OR: 0.54; 95% CrI: 0.40-0.74, low certainty), GLP-1a (OR: 0.70; 95% CrI: 0.53-0.92, low certainty), and DPP-4i users (OR: 0.72; 95% CrI: 0.57-0.92, very low certainty). DPP-4i users also had a lower cancer risk than sulfonylureas users (OR: 0.76; 95% CrI: 0.60-0.96, low certainty). No other statistically significant ORs were found in other direct comparisons.</p><p><strong>Conclusion: </strong>SGLT-2i users have a lower risk of developing cancers than sulfonylureas, GLP-1a, and DPP-4i users. These results may improve patient safety by guiding future clinical practice and medication choices. Future studies should investigate the mechanisms behind these observed associations.</p><p><strong>Trial registration: </strong>This NMA was registered in PROSPERO (CRD42023469941).</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"16 ","pages":"20420986251335214"},"PeriodicalIF":3.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024077","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":"The 90% effective dose of ciprofol and propofol with S-ketamine for painless abortion: a randomized, double-blind, sequential dose-finding trial.","authors":"Qiang Tao, Qiao Shi, Tao Xu, Shanshan Ye","doi":"10.1177/20420986251328673","DOIUrl":"10.1177/20420986251328673","url":null,"abstract":"<p><strong>Background: </strong>Unlike the propofol-opioids combination, a single dose of S-ketamine with propofol achieves the same anesthetic effects while effectively minimizing adverse reactions in painless abortion. Ciprofol, a novel analog of propofol, has distinct advantages, its application in painless abortion is underexplored.</p><p><strong>Objectives: </strong>To investigate a 90% effective dose (ED₉₀) of ciprofol and propofol with S-ketamine for painless abortion.</p><p><strong>Design: </strong>This prospective biased coin up-and-down (BCUD) sequential dose-finding study aimed to estimate the ED₉₀ of ciprofol when administered with 0.15 mg/kg S-ketamine in painless abortion while comparing adverse effects incidence with the ED₉₀ of propofol when combined with the same dose of S-ketamine.</p><p><strong>Methods: </strong>Eighty patients were recruited and randomly allocated to either ciprofol or propofol groups, with initial doses of 0.375 mg/kg and 1.5 mg/kg, respectively. The dose for the subsequent patient in the study was based on the response of the preceding patient, following the BCUD design. The study estimated the ED₉₀ using isotonic regression. Secondary outcomes, including the incidence of injection pain, vital signs, and adverse events, were recorded and compared between the two groups.</p><p><strong>Results: </strong>The ED₉₀ of ciprofol with 0.15 mg/kg S-ketamine was 0.498 mg/kg (95% confidence interval: 0.498-0.510), while the ED₉₀ of propofol with 0.15 mg/kg S-ketamine was 1.99 mg/kg (95% confidence interval: 1.98-2.16). Patients in the ciprofol group had a lower incidence of respiratory pause (7.5% vs 52.5%; <i>p</i> < 0.001). Other adverse events and recovery time were comparable between groups.</p><p><strong>Conclusion: </strong>Compared to propofol and S-ketamine combination, ciprofol and S-ketamine are equally effective with reduced respiratory depression. Thus, clinicians should consider a dose of 0.5 mg/kg ciprofol with 0.15 mg/kg S-ketamine for painless abortion.</p><p><strong>Trial registration: </strong>http://www.chictr.org.cn; ChiCTR2400086522; July 5, 2024.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"16 ","pages":"20420986251328673"},"PeriodicalIF":3.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731741","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}