Yu Yuncui, Nie Xiaolu, Song Ziyang, Xie Yuefeng, Zhang Xuan, Du Zhaoyang, Wei Ran, Fan Duanfang, Liu Yiwei, Zhao Qiuye, Peng Xiaoxia, Jia Lulu, Wang Xiaoling
Clinical Research Center, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.
Center for Clinical Epidemiology and Evidence-Based Medicine, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.
Front Pediatr. 2020 Apr 16;8:171. doi: 10.3389/fped.2020.00171. eCollection 2020.
This study proposes a quantitative 2-stage procedure to detect potential drug-induced liver injury (DILI) signals in pediatric inpatients using an data warehouse of electronic health records (EHRs). Eight years of medical data from a constructed database were used. A two-stage procedure was adopted: (i) stage 1: the drugs suspected of inducing DILI were selected and (ii) stage 2: the associations between the drugs and DILI were identified in a retrospective cohort study. 1,196 drugs were filtered initially and 12 drugs were further potentially identified as suspect drugs inducing DILI. Eleven drugs (fluconazole, omeprazole, sulfamethoxazole, vancomycin, granulocyte colony-stimulating factor (G-CSF), acetaminophen, nifedipine, fusidine, oseltamivir, nystatin and meropenem) were showed to be associated with DILI. Of these, two drugs, nystatin [odds ratio[OR]=1.39, 95%CI:1.10-1.75] and G-CSF (OR = 1.91, 95%CI:1.55-2.35), were found to be new potential signals in adults and children. Three drugs [nifedipine [OR = 1.77, 95%CI:1.26-2.46], fusidine [OR = 1.43, 95%CI:1.08-1.86], and oseltamivi r [OR = 1.64, 95%CI:1.23-2.18]] were demonstrated to be new signals in pediatrics. The other drug-DILI associations had been confirmed in previous studies. A quantitative algorithm to detect potential signals of DILI has been described. Our work promotes the application of EHR data in pharmacovigilance and provides candidate drugs for further causality assessment studies.
本研究提出了一种定量两阶段程序,以利用电子健康记录(EHR)数据仓库检测儿科住院患者中潜在的药物性肝损伤(DILI)信号。使用了来自一个构建数据库的八年医疗数据。采用了两阶段程序:(i)第一阶段:选择怀疑引起DILI的药物;(ii)第二阶段:在一项回顾性队列研究中确定药物与DILI之间的关联。最初筛选出1196种药物,进一步潜在确定有12种药物为引起DILI的可疑药物。11种药物(氟康唑、奥美拉唑、磺胺甲恶唑、万古霉素、粒细胞集落刺激因子(G-CSF)、对乙酰氨基酚、硝苯地平、夫西地酸、奥司他韦、制霉菌素和美罗培南)显示与DILI有关。其中,两种药物,制霉菌素[比值比(OR)=1.39,95%置信区间:1.10-1.75]和G-CSF(OR = 1.91,95%置信区间:1.55-2.35),被发现是成人和儿童中的新潜在信号。三种药物[硝苯地平[OR = 1.77,95%置信区间:1.26-2.46]、夫西地酸[OR = 1.43,95%置信区间:1.08-1.86]和奥司他韦[OR = 1.64,95%置信区间:1.23-2.18]]被证明是儿科中的新信号。其他药物与DILI的关联在先前研究中已得到证实。描述了一种检测DILI潜在信号的定量算法。我们的工作促进了EHR数据在药物警戒中的应用,并为进一步的因果关系评估研究提供了候选药物。