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

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 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.

目的:探讨伏立康唑注射制剂原研药与仿制药在住院人群中相关急性肾损伤(AKI)的发生率及危险因素.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),回顾性自动监测某中心自2010年1月–2021年6月间使用伏立康唑注射制剂原研药与仿制药的所有住院患者,对相关AKI的发生率及特征进行分析,探究危险因素.结果:原研药相关AKI的发生率为2.58％(70/2717),仿制药相关AKI的发生率为1.51％(35/2322),原研药组的严重AKI占比高于仿制组(28.57％vs 17.14％);两组中阳性病例的中位年龄均高于总体人群.相关风险因素分析显示,联合使用≥3种肾毒性药物及白蛋白<30 g·L-1在原研药与仿制药组均有统计学意义,原研药相关AKI的风险因素还有血红蛋白≤90 g·L-1.结论:伏立康唑原研药与仿制药相关AKI发生率及风险因素的差异可能与辅料相关,但用药目标差异的影响有待证实;对住院期间合并低白蛋白、联合使用多种肾毒性药物、贫血的老年患者,临床应用该药时应注意监测其肾功能.

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.

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.