The use of cefoperazone/sulbactam (CPZ/SAM) could commonly cause vitamin K-dependent coagulation disorders and even hemorrhage sometimes. However, there is a lack of prediction tools estimating the risk for this. This study aimed at developing and internally validating a model for predicting CPZ/SAM-associated coagulation disorders in Chinese inpatients. A case-control study was conducted in 11,092 adult inpatients admitted to a Chinese general hospital between 2020 and 2021 and treated with CPZ/SAM. Patients with CPZ/SAM-associated coagulation disorders were identified through the Adverse Drug Events Active Surveillance and Assessment System-II and subsequent manual evaluation. Controls were selected from eligible patients who didn’t develop coagulation disorders after CPZ/SAM therapy, with a 1:1 propensity score matching. The final predictors were obtained by univariable and multivariable logistic regression analyses. Internal validation and calibration for the model were performed using 1000 bootstrap resamplings. 258 patients were identified as CPZ/SAM-associated coagulation disorders in 2184 patients eligible for inclusions and exclusions and the incidence was 11.8

This study aimed to analyze the incidence, clinical characteristics, and risk factors of moxifloxacin-related arrhythmias and electrocardiographic alterations in hospitalized patients using real-world data. Concurrently, a nomogram was established and validated to provide a practical tool for prediction. Retrospective automatic monitoring of inpatients using moxifloxacin was performed in a Chinese hospital from January 1, 2017, to December 31, 2021, to obtain the incidence of drug-induced arrhythmias and electrocardiographic alterations. Propensity score matching was conducted to balance confounders and analyze clinical characteristics. Based on the risk and protective factors identified through logistic regression analysis, a prediction nomogram was developed and internally validated using the Bootstrap method. Arrhythmias and electrocardiographic alterations occurred in 265 of 21,711 cases taking moxifloxacin, with an incidence of 1.2%. Independent risk factors included medication duration (odds ratio [OR] 1.211, 95% confidence interval [CI] 1.156-1.270), concomitant use of meropenem (OR 4.977, 95% CI 2.568-9.644), aspartate aminotransferase >40 U/L (OR 3.728, 95% CI 1.800-7.721), glucose >6.1 mmol/L (OR 2.377, 95% CI 1.531-3.690), and abnormally elevated level of amino-terminal brain natriuretic peptide precursor (OR 2.908, 95% CI 1.640-5.156). Concomitant use of cardioprotective drugs (OR 0.430, 95% CI 0.220-0.841) was a protective factor. The nomogram showed good differentiation and calibration, with enhanced clinical benefit. The incidence of moxifloxacin-related arrhythmias and electrocardiographic alterations is in the range of common. The nomogram proves valuable in predicting the risk in the moxifloxacin-administered population, offering significant clinical applications.

Abstract Background and aim: Long-term use of cefoperazone/sulbactam (CPZ/SAM) may lead to vitamin K-dependent coagulation dysfunction which is significantly associated with increased risks of major bleeding and death. However, there is a lack of prediction models estimating the risk for this adverse drug reaction. This study aimed at developing and internally validating a risk prediction model for coagulation-related adverse reactions in Chinese inpatients treated with CPZ/SAM. Methods: A case-control study was conducted in 11,092 adult inpatients admitted to our hospital from 2020 to 2021. We selected patients reporting coagulation-related adverse reactions through the Adverse Drug Events Active Surveillance and Assessment System-2 developed by our team. The final predictors were obtained by using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm. The prediction model was visualized as a static nomogram and a web-based dynamic nomogram. Internal validation and calibration were performed using bootstrap enhanced procedure with 1000 resampling. Results: We found 215 coagulation-related adverse reactions (5.1%) in 4212 patients treated with CPZ/SAM. A final population of 208 cases and 624 controls was considered for model development and validation. Malnutrition, renal insufficiency, parenteral nutrition, longer treatment duration and red blood cell count were identified as final predictors. There is a nonlinear relationship between treatment duration and coagulation disorder. The model shows good discrimination and calibration, with the validated area under the receiver operating characteristic curve (AUROC)being 0.739 (0.699-0.779), p for Hosmer-lemeshow more than 0.05 and Brier score being 0.152. The decision curve analysis reveals that the net benefit of the model is higher, compared with the hypothesis that coagulopathy occurs in all patients with medication or no coagulopathy occurs. Conclusions: The nomogram model quantifies the risk for coagulation-related adverse reactions in Chinese inpatients treated with CPZ/SAM, supporting individual assessment and interventions to mitigate the risk.

Objective The purpose of this study was to analyze the occurrence characteristics, clinical manifestations, medication distribution, and incidence of drug-induced arrhythmias in a real-world inpatient population. Methods According to the inclusion and exclusion criteria as well as the ADR evaluation criteria, we retrospectively evaluated hospitalized patients in 2019 using the arrhythmia module of the Adverse Drug Event Active Surveillance and Assessment System-II (ADE-ASAS-II). A detailed analysis was performed on the demographic data, ADR manifestations, and medication distribution of 2097 patients with drug-induced arrhythmias and QT interval prolongation. Results Of the 167,546 hospitalized patients, there were 1809 cases of drug-induced arrhythmias, with an incidence of 1.08%. The ADRs in 45.35% of positive patients occurred within 3 days after medication administration, and 46.73% of the patients were 65 years old or older. The predominant ADRs identified in this study were extrasystole, tachycardia, and QT interval prolongation, of which the incidence was 0.20%. Levofloxacin was the most involved drug, and levofloxacin-associated rates of incidence of arrhythmia and QT interval prolongation were 1.24% and 0.44%, respectively. The risk factors for drug-induced arrhythmias were male sex, advanced age, emaciation, obesity, and underlying illnesses such as cardiovascular diseases, diabetes mellitus, cerebrovascular diseases, and hepatic and renal inadequacy ( P < 0.05). Conclusion The incidence of drug-induced arrhythmias was in the range of common, while QTc interval prolongation was occasional. It is necessary to pay attention to patients with risk factors.

Objective To investigate the incidence and risk factors of adverse events related to liver injury induced by triazole antifungal agents in inpatients. Methods Based on the active Surveillance and Intelligent Assessment alert System of Adverse Drug Events in medical institutions（ADE-ASAS）, all eligible inpatients who received triazole antifungal injective preparation from January 2010 to June 2021 were retrospectively studied and divided into voriconazole, fluconazole and itraconazole groups, and the incidence and risk factors of liver injury in each group were analyzed. Results A total of 555 positive cases were included, and the overall incidence of adverse events of liver injury was 5.31%, among which, the incidence of voriconazole, fluconazole and itraconazole were 6.53%, 4.52% and 4.53%, respectively. The risk factors for adverse events of liver injury caused by voriconazole were hematopoietic stem cell transplantation, hypoalbuminemia, high baseline of total bilirubin（TB） and combined use of alkylation agents.the risk factors of fluconazole-induced liver injury adverse events were hematopoietic stem cell transplantation, hypoalbuminemia, high baseline of TB, surgical treatment. The risk factors of liver injury induced by itraconazole included hematopoietic stem cell transplantation and hypoalbuminemia. Conclusion Triazole antifungal drug-related liver injury is a common adverse drug reaction. When triazole antifungal agents are used clinically, the liver function of patients undergoing hematopoietic stem cell transplantation or surgical treatment during hospitalization, as well as patients with hypoalbuminemia, high baseline of TB and combined use of alkylating agents should be closely monitored.

Objective To determine the clinical characteristics and influence factors of thrombocytopenia associated with lobaplatin for injection in hospitalized population, and to provide reference for clinical safe and rational drug use. Methods Based on the adverse drug event active surveillance and assessment system（ADE-ASAS）, inpatients receiving lobaplatin for injection（10mg） in our hospital from January 1st, 2012 to December 31st, 2019 were retrospectively analyzed the occurrence and characteristics of thrombocytopenia. Propensity score matching（PSM） method was used to select the control group to determine the relevant influence factors. Results Among the 4899 inpatients receiving lobaplatin for injection, 360（7.35%） had thrombocytopenia. Logistic regression model analysis showed that the influencing factors of thrombocytopenia associated with lobaplatin for injection mainly included previous lobaplatin administration history（OR: 2.967; 95%CI: 1.676 ～ 5.250）, combined use of pirubicin（OR: 3.634; 95% CI: 1.355 ～ 9.750） and platelet base value（OR: 0.955; 95% CI: 0.947 ～ 0.962）. Conclusion ADE-ASAS can accurately and efficiently collect the real world data of large sample target drug users. Thrombocytopenia associated with lobaplatin for injection is a common adverse drug reaction. Attention should be paid to patients with clinical use of lobaplatin for injection in the past, the combination of antitumor antibiotics, especially anthracycline drugs such as pirubicin, and platelet count monitoring.

目的 了解住院人群中氟比洛芬酯相关急性肾损伤的发生率、临床特征和危险因素.方法 依托医疗机构药物不良事件主动监测与智能评估警示系统(ADE-ASAS),回顾性监测解放军总医院2010年12月1日至2020年11月30日所有使用氟比洛芬酯的住院患者,并进行病例对照研究,分析氟比洛芬酯所致急性肾损伤的发生率、临床特征和危险因素.结果 116097例使用氟比洛芬酯的住院患者中,急性肾损伤阳性病例815例,发生率0.70％.因果关联性评价结果以可能最多见,692例(84.91％).阳性病例的严重程度分期以1期为主,449例(55.00％);转归结果主要是好转,556例(68.22％);住院科室以肝胆外科为主,575例(70.55％).合并贫血(OR=2.30;95％CI:1.80～2.94)、较低基线肾小球滤过率(OR=1.01;95％CI:1.01～1.02)、联用利尿剂(OR=3.80;95％CI:3.01～4.81)发生急性肾损伤的风险较高.结论 氟比洛芬酯相关急性肾损伤的发生率为偶见;对合并贫血、较低基线肾小球滤过率以及联用利尿剂的患者,临床应用该药时应注意监测.

目的 对比分析住院患者中两性霉素B及其脂质体致急性肾损伤(AKI)的发生特点和临床特征,为临床安全合理用药提供参考.方法 基于医疗机构药物不良事件主动监测与智能评估警示系统(ADE-ASAS)回顾性监测解放军总医院2010年1月1日—2020年1月1日所有使用两性霉素B普通制剂(AmB-D)和脂质体制剂(L-AmB)的住院患者,并根据给药途径将AmB-D分为静脉途径及其他途径2个亚组进行分析,经系统报警、双人盲评、专家审核最终确认AmB-D及L-AmB致AKI阳 性病例.结果 AmB-D及L-AmB用药患者分别为2139例次及717例次,AmB-D静脉途径、其他途径及L-AmB致AKI阳性病例分别为53例次(6.92％)、45例次(3.28％)及27例次(3.77％),发生率差异有统计学意义(P＜0.01).AmB-D静脉途径致AKI中位发生时间4(2～6)d,其他途径为3(2～6)d,L-AmB为5(3～6)d,均以1期AKI为主(分别占77.4％,73.3％,55.6％).2种剂型都以血液科及血液系统疾病患者发生AKI占比最高.静脉用药后血清肌酐(SCr)及峰值SCr均以L-AmB略高于AmB-D.结论 ADE-ASAS能够精准高效获取真实世界用药安全数据;静脉使用AmB-D致AKI的发生率高于其他途径,同时高于L-AmB;临床应用中均应监测重点科室用药人群肾功能变化,尤其是用药后3～5 d的SCr水平.

目的 挖掘并分析含氮双膦酸盐（N-BPs）类药物相关药品不良事件（ADE）信号。方法 采用报告比值比（ROR）法和英国药品和健康产品管理局（MHRA）综合法，对美国食品药品管理局不良事件报告系统（FAERS）2004年第1季度至2021年第2季度品主要怀疑药品为N-BPs的ADE报告进行分析并挖掘风险信号。结果 研究共获得N-BPs相关报告55 604份，ADE 773 235例，生成有效信号2534个，主要涉及各种肌肉骨骼及结缔组织疾病、胃肠系统疾病、感染及侵染类疾病等；患病人群以女性（76.28%）、45岁以上中老年（75.82%）为主；研究发现大量说明书中未提及的ADE，其中例数较多或结局较严重的ADE包括椎间盘病变、牙齿及口腔软组织损伤、恶性肿瘤、间质性肺疾病等。结论 N-BPs相关ADE多，结局严重，累及器官系统较广，新的ADE的发现可为临床安全用药及相关真实世界研究提供一定参考。

目的:依托临床ADE主动监测与智能评估警示系统-Ⅱ(ADE-ASAS-Ⅱ)构建住院人群癫痫发作自动监测模块,为癫痫发作大样本真实世界研究提供高效的数据挖掘工具.方法:搜集指南、文献、自发报告中与癫痫相关的描述词为初始关键词集,通过预实验对初始关键词集进行初筛分类,利用文本分类技术与决策树建立报警规则,利用ADE-ASAS-Ⅱ的自定义功能与屏蔽功能对模块进行调试,确定模块最佳设置.扩大监测样本量对模块进行验证,对阳性病例的人口学特征及发作原因进行统计描述.结果:以5557例经人工审查的住院患者为测试数据,对模块进行反复调试后,最终确定决策树各分支报警关键词共37个,标题屏蔽关键词12个,模块阳性预测值(PPV)为13.86％,召回率(R)为100.00％.监测我院2021年5月共14549例在院患者,通过纳排甄别得到90例癫痫发作患者,PPV为14.59％,发生率为0.62％,其中急性症状性癫痫发作53例,以强直阵挛发作为主,发作原因以神经系统肿瘤手术最为常见.结论:基于ADE-ASAS-Ⅱ建立的癫痫发作主动监测模块,可以高效、全面、快速的获取住院人群中的目标病例,能够为癫痫发作大样本真实世界研究提供可靠的文本数据挖掘工具.

目的:了解应用贝伐珠单抗的住院患者药源性尿蛋白阳性的情况,计算其真实世界发生率并探究风险因素.方法:借助医疗机构药物不良事件主动监测与智能评估警示系统-Ⅱ(ADE-ASAS-Ⅱ),回顾性监测某三甲医院2018年1月1日-2019年12月31日所有使用贝伐珠单抗的住院患者电子病历信息,确定阳性病例后,应用个案控制匹配1:1匹配对照组,通过条件逻辑回归识别相关风险因素.结果:1932例用药患者中,出现贝伐珠单抗相关尿蛋白阳性353例,发生率为18.27％,其中三级及以上尿蛋白阳性的发生率为4.04％.相关风险因素有合并肾脏疾病(OR=7.238,95％CI:1.512～34.655),单次使用剂量＞5mg·kg-1(OR=2.055,95％CI:1.359～3.108),使用贝伐珠单抗周期数＞10(OR=2.950,95％CI:1.136～7.692),用药前尿糖阳性(OR=2.458,95％CI:1.112～5.434)和收缩压基值偏高(OR=1.714,95％CI:1.073～2.738).结论:临床使用贝伐珠单抗时,对合并肾脏疾病、患高血压、糖尿病及高剂量、多疗程化疗的住院患者应加强监测,出现蛋白尿后及时干预以避免更严重后果.

目的:在临床ADE主动监测与智能评估警示系统-Ⅱ(ADE-ASAS-Ⅱ)中建立药源性心律失常自动监测模块,探究药物与心律失常的关系,为临床合理用药提供参考.方法:建立心律失常模块的关键词词集,采用文本分类技术识别提取上述词集,优化报警规则;扩大监测样本量,对阳性患者的性别、年龄、相关药物等数据进行分析以验证模块.结果:最终确定关键词28个,模块最佳设置条件的阳性预测值(PPV)为10.82％,召回率(R)为99.18％.利用该模块监测患者33007例,其中阳性622例,发生率1.88％,PPV 7.88％.65岁及以上患者占比50.32％;涉及药物共64类、133种,以喹诺酮类抗菌药物、钙通道阻滞剂、抗真菌药物为主;药源性心律失常类型多样,主要是期外收缩、心动过速、QTc间期延长.结论:本研究构建的药源性心律失常自动监测模块,可以高效、精准、快速获取真实世界大样本用药人群中的目标病例.监测结果显示住院人群发生药源性心律失常属于常见,相关患者的年龄分布、药物类别、类型分类等与有关研究结果基本一致.

目的 了解大样本真实世界中住院患者使用贝伐珠单抗出现血小板减少的情况,计算发生率并探究风险因素.方法 借助医疗机构药物不良事件主动监测与智能评估警示系统-II(ADE-ASAS-II),回顾性监测某院2010年1月1日至2020年12月31日所有使用贝伐珠单抗的住院患者电子病历信息,确定阳性病例后,应用倾向性评分1:1匹配对照组,通过二元逻辑回归识别相关风险因素.结果 4864例使用贝伐珠单抗的住院患者中有455例在用药后出现血小板减少,发生率为10.00％.血小板基值<150×109·L-1(OR=11.896,95％CI:8.270～17.111),白细胞基值偏低(OR=1.801,95％CI:1.213～2.675),红细胞基值偏低(OR=1.561,95％CI:1.085～2.246),肿瘤分期(TNM分期)为Ⅳ期(OR=1.814,95％CI:1.059～3.107),总化疗次数≥10次(OR=2.537,95％CI:1.675～3.842),联用紫杉醇、铂类(OR=2.658,95％CI:1.267～5.578)为应用贝伐珠单抗后出现血小板减少的风险因素;联用铂类、培美曲塞方案(OR=0.289,95％CI:0.147～0.568)为应用贝伐珠单抗后出现血小板减少的保护因素.结论 临床使用贝伐珠单抗时,对具有血小板基值偏低、多疗程、与紫杉醇和铂类联合治疗等相关风险因素的住院患者应予以严密关注.

目的 了解抗肿瘤血管生成类药品不良反应(ADR)发生特点.方法 回顾性分析我中心ADR数据库中2008-2019所有抗肿瘤血管生成类的药品相关ADR自发报告,对患者年龄、性别、怀疑药品、累及系统/器官损害、临床表现、ADR发生时间、关联性评价及转归等情况进行统计分析.结果 共纳入972例ADR报告,累及系统/器官达18个.其中严重ADR报告262例,占26.95％.在972例ADR报告中,患者男女比例为1.93:1,年龄以≥45岁为最多,占83.02％;引发ADR最多的前5种药品为阿帕替尼(31.69％)、贝伐珠单抗(20.16％)、索拉非尼(18.00％)、重组人血管内皮生长抑素(14.30％)、安罗替尼(8.95％).严重ADR以高血压、血小板减少、肝功能异常和手足综合征较为多见.结论 抗肿瘤血管生成类药品所致ADR累及部位广泛,有必要进行重点品种的主动监测.

目的:了解非甾体抗炎药(NSAIDs)相关不良反应(ADRs)的发生情况及特点,为临床提供参考.方法:采用回顾性研究方法,调取2008～2019年解放军药品不良反应监测中心ADR数据库中所有NSAIDs相关ADRs自发报告,对其中5 597例有效自发报告中的患者性别、年龄,可疑NSAIDs分类、给药途径,以及ADRs类型、诱导期和累及系统/器官等进行统计分析,比较不同性别患者各个年龄段的构成比差异.结果:5 597例NSAIDs相关自发报告中,新的一般的ADR报告404例,严重的ADR报告428例,新的严重的ADR报告47例.ADRs报告中男性2 965例(52.97％),女性2 632例(47.03％);年龄1～116(56.53±19.37)岁,大于60岁年龄段构成比最高;40岁以下年龄段男性多于女性,＞40岁年龄段女性多于男性(P＜0.01);且各年龄段男女构成比差异均有统计学意义(P＜0.001).5 597例ADRs涉及NSAIDs十大类别,给药途径以静脉给药为主;ADR诱导期≤1 h例数最多;累及多个系统/器官,以胃肠系统损害(26.02％)和皮肤及皮肤附件损害(23.05％)为多见;严重ADR构成比最高为肝胆系统损害(17.67％);例数最多的品种为氟比洛芬酯,共686例(12.26％),相关严重ADR主要为肝功能异常等.结论:临床使用中应重视NSAIDs安全性问题,及时识别并处理ADR;有必要开展氟比洛芬酯相关用药风险评价研究.

目的:了解铂类抗肿瘤药相关严重药品不良反应(ADR)的发生情况和特点,挖掘相关风险信号,为临床用药提供参考.方法:调取我中心ADR数据库中铂类抗肿瘤药相关严重ADR报告,对患者一般情况、累及系统器官、涉及ADR名称等信息进行回顾性分析.运用多种数据挖掘方法,获取铂类抗肿瘤药相关严重ADR的风险信号.结果:2008年1月～2020年6月铂类抗肿瘤药相关严重ADR报告共1 374例,男女比例为1.26:1,累及系统器官以血液系统疾病(骨髓抑制)为最多,构成比达到55.75％,涉及87种临床表现.共有20个"药品-系统器官/ADR名称"组合在4种数据挖掘方法中均生成风险信号,其中奥沙利铂相关信号数量最多.结论:风险信号挖掘结果与已知的铂类ADR信息基本一致,临床使用铂类抗肿瘤药应加强警戒并采取相应防范措施,规避严重ADR的发生.

目的:了解药源性心律失常的发生规律及特点,为临床安全用药提供参考.方法:采用回顾性研究方法,提取我中心药品不良反应数据库中2008-2019年药源性心律失常的自发报告,剔除信息不全和无效报告后对报告一般情况、患者基本信息、药物类别、给药途径、心律失常类型、ADR治疗和转归等情况进行统计分析.利用Logistic回归分析方法筛选相关风险因素.结果:1 439例药源性心律失常报告中,患者平均年龄为(55.17±21.20)岁,以45-64岁占比最高(35.72％);共涉及19类、387种药物,排名前5位的药物是右美托咪定(24.15％)、莫西沙星(16.18％)、重组人白介素-11(11.11％)、沙丁胺醇(10.39％)、胺碘酮(7.73％);心律失常类型多样,以心动过速(56.46％)和心动过缓(19.63％)为主.与非QT/QTc间期延长组相比,年龄＞65岁(P = 0.007)及患有心脑血管疾病(P=0.016)是QT/QTc间期延长患者的独立危险因素;治疗药物以抗心律失常药和抗过敏药为主.结论:莫西沙星和胺碘酮可导致多种类型的心律失常,重组人白介素-11以诱发心房颤动为主,右美托咪定主要为心动过缓,临床应加强用药监护;老年人和原患心脑血管疾病是药物导致QT/QTc间期延长的高风险因素,临床应予以重点关注;有必要开展重点品种主动监测研究,为临床提供用药参考.

目的:了解新型冠状病毒肺炎(COVID-19)疫苗相关不良事件的发生情况和特点,为预防接种和科学研究提供参考.方法:调取2020年1月1日 –2021年2月26日期间美国疫苗不良事件报告系统中COVID-19疫苗相关报告,对受种者一般情况、接种剂次、发生时间、临床症状等信息进行回顾性分析.结果:18184例COVID-19疫苗相关不良事件报告中,严重报告3521例(19.36％);男女比例为1:3.26;14194例(78.06％)发生于第1剂次接种后;13675例(75.20％)发生于接种后2天之内;共涉及3092种(89694例次)临床症状,主要表现为头痛、疲劳、发热等.916例死亡报告中有767例(83.73％)为65岁及以上受种者,631例(68.89％)发生于第1剂次接种后.结论:预防接种应重点关注老年受种者;持续开展疫苗安全性监测,有助于减少疫苗犹豫、提高接种率,最终有效控制COVID-19疫情.