Therapeutic Advances in Drug Safety最新文献

{"title":"Determinants of COVID-19 vaccine-induced myocarditis","authors":"Jessica Rose, Nicolas Hulscher, Peter A McCullough","doi":"10.1177/20420986241226566","DOIUrl":"https://doi.org/10.1177/20420986241226566","url":null,"abstract":"Following the roll-out of the Pfizer-BioNTech BNT162b2, Moderna mRNA-1273, and Janssen Ad26.COV2.S coronavirus disease 2019 (COVID-19) injections in the United States, millions of individuals have reported adverse events (AEs) using the vaccine adverse events reports system (VAERS). The objective of this analysis is to describe the myocarditis data in VAERS and the COVID-19 vaccines as potential determinants of myocarditis. We used VAERS data to examine the frequency of reporting myocarditis since the beginning of the mass vaccination campaign and compared this with historical values in VAERS and COVID-19 vaccine administration data from the Our World in Data database. We examined myocarditis reports in VAERS in the context of sex, age, and dose. Statistical analysis was done using the Student’s t-test to determine statistically significant differences between ages among myocarditis adverse events (AEs) and the chi-square test to determine relationships between categorical variables with statistical significance. We found the number of myocarditis reports in VAERS after COVID-19 vaccination in 2021 was 223 times higher than the average of all vaccines combined for the past 30 years. This represented a 2500% increase in the absolute number of reports in the first year of the campaign when comparing historical values prior to 2021. Demographic data revealed that myocarditis occurred most in youths (50%) and males (69%). A total of 76% of cases resulted in emergency care and hospitalization. Of the total myocarditis reports, 92 individuals died (3%). Myocarditis was more likely after dose 2 ( p < 0.00001) and individuals less than 30 years of age were more likely than individuals older than 30 to acquire myocarditis ( p < 0.00001). COVID-19 vaccination is strongly associated with a serious adverse safety signal of myocarditis, particularly in children and young adults resulting in hospitalization and death. Further investigation into the underlying mechanisms of COVID-19 vaccine-induced myocarditis is imperative to create effective mitigation strategies and ensure the safety of COVID-19 vaccination programs across populations.","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139635443","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":"Drug-induced interstitial lung disease: a real-world pharmacovigilance study of the FDA Adverse Event Reporting System from 2004 to 2021","authors":"Tingting Jiang, Hui Su, Jing Xu, Chen Li, Ni Zhang, Yanping Li, Yuanlin Wu, Rui Ni, Yue Ming, Zi-wei Li, Li Li, Yao Liu","doi":"10.1177/20420986231224227","DOIUrl":"https://doi.org/10.1177/20420986231224227","url":null,"abstract":"Drug-induced interstitial lung disease (DILD) is an increasingly common cause of morbidity and mortality. However, due to the lack of specificity, DILD detection remains an unsolved public health challenge. For the first time, we aimed to examine DILD reports submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to identify demographic characteristics and top drugs associated with DILD at a group level (including age, sex, drug class, and country stratification) and individual drug level. A retrospective analysis of the FAERS database was examined by disproportionality analysis. We reviewed the FAERS database from 2004 to 2021, using search terms ‘interstitial lung disease’ and sorting cases by generic drug name. The reporting odds ratio, proportional reporting ratio, and Bayesian confidence propagation neural network were calculated as the measure of strength of association. There were 32,821 DILD reports in the FAERS. After excluding reports without age, sex, or country data according to the specific measurement, the median age of patients was 68 (interquartile range: 59), 54.77% were male, and 46.00% of reports came from Japan. The top drug classes related to DILD in the FAERS were antineoplastic, followed by cardiovascular and antirheumatic agents, in varying order in different sexes. Fam-trastuzumab deruxtecan-nxki, ramucirumab, and eribulin were the top three drugs with the highest strength of association. We also found some drugs without DILD in the labels, such as amiodarone, temsirolimus, and ursodiol. There are significant differences in DILD reports in various countries. For example, the United States and France reported more cardiovascular agents, whereas Canada reported more antirheumatic agents. We found the top drugs and drug classes that were associated with DILD in the FAERS, which provides a real-world window for different ages, sexes, and countries to formulate precise pharmacovigilance policies.","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139637784","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":"The 7th European Pharmacovigilance Congress: speaker abstracts","authors":"M. Sardella, Lucia Costanzo, Ilaria Grisoni, Marcela Fialova","doi":"10.1177/20420986231225509","DOIUrl":"https://doi.org/10.1177/20420986231225509","url":null,"abstract":"","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140519331","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":"Direct oral anticoagulant use in hospitalized patients with atrial fibrillation across body mass index categories: design and rationale for a retrospective cohort study","authors":"F. Shaikh, Rochelle Wynne, Ronald L. Castelino, Sally C. Inglis, Patricia M. Davidson, Caleb Ferguson","doi":"10.1177/20420986241227014","DOIUrl":"https://doi.org/10.1177/20420986241227014","url":null,"abstract":"Atrial fibrillation (AF) and obesity are common conditions globally; yet, there remains suboptimal pharmacological management contributing to high rates of hospitalization in patients with AF. The altered pathophysiology of both obese and underweight individuals may influence the pharmacology of medications, including those used to manage AF. This, in turn, increases the risk of adverse events and impacts patient risk for stroke and rehospitalization. Despite the well-established complications of obesity, research investigating the relationship between obesity and AF is scant. The primary aim of this study is to describe cardiovascular-related hospitalization in AF patients according to BMI categories. A secondary aim is to describe anticoagulant and antiarrhythmic prescribing practice patterns in patients with AF, according to the BMI category. A retrospective, exploratory descriptive observational cohort study, using routinely collected electronic medical record data from five public hospitals within a single health district, with a population dominantly that is culturally and linguistically diverse, and has a low socioeconomic status. Data extraction will include a 24-month period (January 2017 to December 2018) with a 12-month follow-up. All adult (⩾18 years) patients at discharge diagnosed with AF, prescribed any oral anticoagulant and/or oral rate/rhythm control agent, will be eligible for inclusion. Ethics approval from the health district and the University of Wollongong has been granted. Findings will seek to demonstrate associations between management strategies and patient outcomes, as well as describe patterns of acute care management from prescribers. These data will be used to inform and generate hypotheses for large-scale studies examining the impact of body weight on anticoagulation prescribing at national and global scales.","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139636334","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":"Association of thrombopoietin-related drugs with thromboembolic events: Mendelian randomization and a real-world study","authors":"Cuilv Liang, Qiying Chen, Yin Zhang","doi":"10.1177/20420986231224236","DOIUrl":"https://doi.org/10.1177/20420986231224236","url":null,"abstract":"Studies have shown conflicting results when using thrombopoietin-related drugs (TPORD) for thromboembolic events (TEEs). Our study aimed to explore the correlation between TPORDs and TEEs. Drug-targeted Mendelian randomization (MR) and multivariate MR (MVMR) analysis were used to explore the causal relationship between TPORDs and TEEs such as venous thromboembolism (VTE), deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI) and ischemic stroke (STR). At the same time, a real-world study was conducted by extracting adverse events (AEs) from the FDA Adverse Event Reporting System database included in AERSMine to further validate our findings. In drug-target MR, TPORDs were associated with VTE (OR = 1.193, 95% confidence interval (CI): 1.001–1.423, p = 0.049], DVT (OR = 1.321, 95% CI: 1.027–1.700, p = 0.030), MI (OR = 1.216, 95% CI: 1.010–1.464, p = 0.039), STR (OR = 1.224, 95% CI: 1.021–1.468, p = 0.029). VTE/DVT/STR remained stable in MVMR (VTE: OR = 1.3, 95% CI: 1.187–1.422, p < 0.001; DVT: OR = 1.465,95% CI:1.285–1.671, p < 0.001; STR: OR = 1.119, 95% CI: 1.018–1.229, p = 0.019) and real-world studies [lower bound of proportional reporting ratio (ROR) greater than 1]. The significance of myocardial infarction disappeared in MVMR (OR = 0.996, 95% CI: 0.894–1.109, p = 0.942) and in real-world studies (lower ROR lower than 1). There was no evidence of a causal relationship between TPORD and PE (OR = 1.244, 95% CI: 0.969-1.597, p = 0.087), but it generated a signal from a real-world study (lower bound of ROR greater than 1). This study suggests that TPORDs may be associated with an increased risk of TEEs, particularly AEs leading to VTE/DVT/STR. In addition, the relationship between TPORDs and PE/MI is debatable and requires more research.","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139639494","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":"Physiologically based pharmacokinetic modeling of candesartan to predict the exposure in hepatic and renal impairment and elderly populations.","authors":"Lingfeng Guo, Xinyu Zhu, Lei Zhang, Yichao Xu","doi":"10.1177/20420986231220222","DOIUrl":"10.1177/20420986231220222","url":null,"abstract":"<p><strong>Background: </strong>Candesartan cilexetil is a widely used angiotensin II receptor blocker with minimal adverse effects and high tolerability for the treatment of hypertension. Candesartan is administered orally as the prodrug candesartan cilexetil, which is wholly and swiftly converted to the active metabolite candesartan by carboxylesterase during absorption in the intestinal tract. In populations with renal or hepatic impairment, candesartan's pharmacokinetic (PK) behavior may be altered, necessitating dosage adjustments.</p><p><strong>Objectives: </strong>This study was conducted to examine how the physiologically based PK (PBPK) model characterizes the PKs of candesartan in adult and geriatric populations and to predict the PKs of candesartan in elderly populations with renal and hepatic impairment.</p><p><strong>Design: </strong>After developing PBPK models using the reported physicochemical properties of candesartan and clinical data, these models were validated using data from clinical investigations involving various dose ranges.</p><p><strong>Methods: </strong>Comparing predicted and observed blood concentration data and PK parameters was used to assess the fit performance of the models.</p><p><strong>Results: </strong>Doses should be reduced to approximately 94% of Chinese healthy adults for the Chinese healthy elderly population; approximately 92%, 68%, and 64% of that of the Chinese healthy adult dose in elderly populations with mild, moderate, and severe renal impairment, respectively; and approximately 72%, 71%, and 52% of that of the Chinese healthy adult dose in elderly populations with Child-Pugh-A, Child-Pugh-B, and Child-Pugh-C hepatic impairment, respectively.</p><p><strong>Conclusion: </strong>The results suggest that the PBPK model of candesartan can be utilized to optimize dosage regimens for special populations.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10752084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075104","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":"Evaluation of four machine learning models for signal detection.","authors":"Daniel G Dauner, Eleazar Leal, Terrence J Adam, Rui Zhang, Joel F Farley","doi":"10.1177/20420986231219472","DOIUrl":"10.1177/20420986231219472","url":null,"abstract":"<p><strong>Background: </strong>Logistic regression-based signal detection algorithms have benefits over disproportionality analysis due to their ability to handle potential confounders and masking factors. Feature exploration and developing alternative machine learning algorithms can further strengthen signal detection.</p><p><strong>Objectives: </strong>Our objective was to compare the signal detection performance of logistic regression, gradient-boosted trees, random forest and support vector machine models utilizing Food and Drug Administration adverse event reporting system data.</p><p><strong>Design: </strong>Cross-sectional study.</p><p><strong>Methods: </strong>The quarterly data extract files from 1 October 2017 through 31 December 2020 were downloaded. Due to an imbalanced outcome, two training sets were used: one stratified on the outcome variable and another using Synthetic Minority Oversampling Technique (SMOTE). A crude model and a model with tuned hyperparameters were developed for each algorithm. Model performance was compared against a reference set using accuracy, precision, F1 score, recall, the receiver operating characteristic area under the curve (ROCAUC), and the precision-recall curve area under the curve (PRCAUC).</p><p><strong>Results: </strong>Models trained on the balanced training set had higher accuracy, F1 score and recall compared to models trained on the SMOTE training set. When using the balanced training set, logistic regression, gradient-boosted trees, random forest and support vector machine models obtained similar performance evaluation metrics. The gradient-boosted trees hyperparameter tuned model had the highest ROCAUC (0.646) and the random forest crude model had the highest PRCAUC (0.839) when using the balanced training set.</p><p><strong>Conclusion: </strong>All models trained on the balanced training set performed similarly. Logistic regression models had higher accuracy, precision and recall. Logistic regression, random forest and gradient-boosted trees hyperparameter tuned models had a PRCAUC ⩾ 0.8. All models had an ROCAUC ⩾ 0.5. Including both disproportionality analysis results and additional case report information in models resulted in higher performance evaluation metrics than disproportionality analysis alone.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10752114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075103","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":"Acceptability of a cross-sectoral hospital pharmacist intervention for patients in transition between hospital and general practice: a mixed methods study.","authors":"Charlotte Arp Sørensen, Linda Jeffery, Klaus Roelsgaard, Solveig Gram, Jannik Falhof, Philipp Harbig, Charlotte Olesen","doi":"10.1177/20420986231213714","DOIUrl":"https://doi.org/10.1177/20420986231213714","url":null,"abstract":"<p><strong>Background and objective: </strong>Drug-related problems (DRPs) are often seen when a patient is transitioning from one healthcare sector to another, for example, when a patient moves from the hospital to a General Practice (GP) setting. This transition creates an opportunity for information on medication changes and follow-up plans to be lost. A cross-sectoral hospital pharmacist intervention was developed and pilot-tested in a large GP clinic. The intervention included medication history, medication reconciliation, medication review, follow-up telephone calls, identification of possible DRPs and communication with the GP. It is unknown whether the intervention is transferable to other GP clinics. The aim of the study was to explore similarities and differences between GP clinics in descriptive data and intervention acceptability.</p><p><strong>Methods: </strong>A convergent mixed methods study design was used. The intervention was tested in four GP clinics with differing characteristics. Quantitative data on the GP clinics, patients and pharmacist activities were collected. Qualitative data on the acceptability were collected through focus group interviews with general practitioners, nurses and pharmacists. The Theoretical Framework of Acceptability was used.</p><p><strong>Results: </strong>Overall, the intervention was found acceptable and relevant by all. There were differences between the GP clinics in terms of size, daily physician work form and their use of pharmacists for <i>ad hoc</i> tasks. There were similarities in patient characteristics across GP clinics. Therefore, the intervention was found equally relevant for all of the clinics. Shared employment with unique access to health records in both sectors was important in the identification and resolution of DRPs. Economy was a barrier for further implementation.</p><p><strong>Conclusions: </strong>The intervention was found acceptable and relevant by all; therefore, it was considered transferable to other GP clinics. Hospital pharmacists were perceived to be relevant healthcare professionals to be utilized in GP, in hospitals and in the cross-sectoral transition of patients.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10725152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138799858","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":"Understanding, readiness, and response of healthcare professionals in combating falsified medical products in Eritrea: a population-based survey.","authors":"Yodit Fitsum, Azania Werede, Abubeker Mahmud Saleh, Eyasu H Tesfamariam, Francis Magombo, Freminatos Misghina, Hermella Yemane, Iyassu Bahta, Liya Abraham, Merhawi Bahta, Merhawi Debesai, Meron Tesfagaber, Michael Ghirmai, Sirak Tesfamariam, Mulugeta Russom","doi":"10.1177/20420986231213713","DOIUrl":"10.1177/20420986231213713","url":null,"abstract":"<p><strong>Background: </strong>The circulation of falsified medical products is a global threat and is expected to be higher in low- and middle-income countries.</p><p><strong>Objective: </strong>This study was conducted to assess the understanding, readiness, and response of Eritrea's healthcare professionals (HCPs), and identify potential areas of intervention to combat circulation of falsified medical products.</p><p><strong>Design: </strong>This was a nationwide population-based cross-sectional survey, conducted in December 2021.</p><p><strong>Methods: </strong>This study enrolled representative samples of HCPs working in public and private health facilities. Two-stage stratified cluster sampling was used to select study participants and data were collected through face-to-face interviews. Descriptive statistics, Mann-Whitney <i>U</i> test, Kruskal-Wallis test along with their post hoc tests, Jonckheere-Terpstra, and logistic regression analyses were performed as appropriate.</p><p><strong>Results: </strong>The study enrolled 707 HCPs, and 96.6% were successfully surveyed. The majority of the participants (62.5%) encountered products with suspected quality defects and 63.8% claimed that they had reported the incident(s) at least once. About 85% reported that complaints should be submitted to the Eritrean Pharmacovigilance Centre and 74.0% indicated that it should be reported at the earliest time possible even if the reporter lacks details. The standard reporting form for suspected product quality issues was correctly recognized by 13.8%. Overall, the median knowledge and attitude scores were found to be 9 out of 17 (interquartile range, IQR: 4.0) and 30 out of 35 (IQR: 4.0), respectively. Not knowing how to report (55.6%) and what to report (34.9%), no/delayed feedback from the regulatory authority (30.0%), and unavailability of reporting forms (29.0%) were the frequently reported barriers to reporting. In addition, profession (<i>p</i> = 0.027), no/delayed feedback (adjusted odds ratio [AOR]: 4.70; 95% CI: 2.17-10.18; <i>p</i> < 0.001), and not knowing how to report (AOR: 0.12; 95% CI: 0.05-0.28; <i>p</i> < 0.001) were found to be determinants of reporting suspected product quality defects.</p><p><strong>Conclusion: </strong>The readiness and response of Eritrea's HCPs in detecting and reporting falsified medical products seems promising, although a significant knowledge gap was observed.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10725142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138800007","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":"Modified Dixon sequential method to determine the effective dose of alfentanil compounded with propofol for day-case hysteroscopy.","authors":"Chenyang Xu, Rui Peng, Xiali Qian, Shanwu Feng, Hongmei Yuan","doi":"10.1177/20420986231214992","DOIUrl":"https://doi.org/10.1177/20420986231214992","url":null,"abstract":"<p><strong>Background: </strong>Propofol combined with alfentanil is suitable for intravenous anesthesia for day-case hysteroscopy.</p><p><strong>Objective: </strong>To investigate the median effective dose (ED₅₀) and 95% effective dose (ED₉₅) of alfentanil compounded with propofol for day-case hysteroscopy.</p><p><strong>Design: </strong>In all, 29 patients who volunteered for painless hysteroscopy in 2022 were recruited. 1.5 mg/kg propofol was given as a sedative to all patients. The trial was conducted using the modified Dixon sequential method, with an initial dose of 10 μg/kg of alfentanil, and the subject's alfentanil dose depended on whether the prior hysteroscopy had failed, which was defined as inadequate cervical dilatation and hysteroscope placement with the patient exhibiting body movement, frowning, or a MOAA/S score >1. If the hysteroscopy failed (i.e. a positive response), the subsequent subject's alfentanil dosage was raised, and conversely (i.e. a negative response), the dose was decreased, with the adjacent dose ratio always being 1:1.2. The formal test begins with the first crossover wave and lasts until seven crossover waves materialize.</p><p><strong>Methods: </strong>The probit method was used to calculate the ED₅₀, ED₉₅, and corresponding 95% confidence intervals (CIs) of alfentanil compounded with propofol for hysteroscopy.</p><p><strong>Results: </strong>The ED₅₀ and ED₉₅ of alfentanil combined with propofol for day-case hysteroscopy were 5.701 (95% CI: 3.841-7.069) μg/kg and 8.817 (95% CI: 7.307-20.868) μg/kg, respectively.</p><p><strong>Conclusion: </strong>Alfentanil at 8.817 μg/kg in conjunction with propofol is a successful and safe approach for day-case painless hysteroscopy.</p><p><strong>Trial registration: </strong>The trial registry name: Modified sequential method to determine the half-effective dose of alfentanil compounded with propofol for ambulatory hysteroscopy. The URL of registration is https://www.chictr.org.cn/showproj.html?proj=171786, where the full trial protocol can be accessed. Registration number: ChiCTR2200061619.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10702409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138799831","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}