Nie Xiaolu, Yu Yuncui, Jia Lulu, Zhao Houyu, Chen Zhenping, Zhang Liqiang, Cheng Xiaoling, Lyu Yaqi, Cao Wang, Wang Xiaoling, Peng Xiaoxia
Center for Clinical Epidemiology and Evidence-based Medicine, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
Front Pharmacol. 2022 Jul 20;13:935627. doi: 10.3389/fphar.2022.935627. eCollection 2022.
Drug-induced coagulopathy (DIC) is a severe adverse reaction and has become a significantly increased clinical problem in children. It is crucial to the detection of the DIC safety signal for drug post-marketing scientific supervision purposes. Therefore, this study aimed to detect potential signals for DIC in children using the routine electronic medical record (EMR) data. This study extracted EMR data from Beijing Children's Hospital between 2009 and 2020. A two-stage modeling method was developed to detect the signal of DIC. We calculated the crude incidence by mining cases of coagulopathy to select the potential suspected drugs; then, propensity score-matched retrospective cohorts of specific screened drugs from the first stage were constructed and estimated the odds ratio (OR) and 95% confidence interval (CI) using conditional logistic regression models. The current literature evidence was used to assess the novelty of the signal. In the study, from a total of 340 drugs, 22 drugs were initially screened as potentially inducing coagulopathy. In total, we identified 19 positive DIC associations. Of these, potential DIC risk of omeprazole (OR: 2.23, 95% CI: 1.88-2.65), chlorpheniramine (OR:3.04, 95% CI:2.56-3.60), and salbutamol sulfate (OR:1.36, 95% CI:1.07-1.73) were three new DIC signals in both children and adults. Twelve associations between coagulopathy and drugs, meropenem (OR: 3.38, 95% CI: 2.72-4.20), cefoperazone sulbactam (OR: 2.80, 95% CI: 2.30-3.41), fluconazole (OR: 2.11, 95% CI: 1.71-2.59), voriconazole (OR: 2.82, 95% CI: 2.20-3.61), ambroxol hydrochloride (OR: 2.12, 95% CI: 1.74-2.58), furosemide (OR: 2.36, 95% CI: 2.08-2.67), iodixanol (OR: 2.21, 95% CI: 1.72-2.85), cefamandole (OR: 1.82, 95% CI: 1.56-2.13), ceftizoxime (OR: 1.95, 95% CI: 1.44-2.63), ceftriaxone (OR: 1.95, 95% CI: 1.44-2.63), latamoxef sodium (OR: 1.76, 95% CI: 1.49-2.07), and sulfamethoxazole (OR: 1.29, 95% CI: 1.01-1.64), were considered as new signals in children. The two-stage algorithm developed in our study to detect safety signals of DIC found nineteen signals of DIC, including twelve new signals in a pediatric population. However, these safety signals of DIC need to be confirmed by further studies based on population study and mechanism research.
药物性凝血病（DIC）是一种严重的不良反应，在儿童中已成为一个显著增加的临床问题。对于药物上市后科学监管而言，检测DIC安全信号至关重要。因此，本研究旨在利用常规电子病历（EMR）数据检测儿童DIC的潜在信号。本研究提取了2009年至2020年北京儿童医院的EMR数据。开发了一种两阶段建模方法来检测DIC信号。我们通过挖掘凝血病病例计算粗发病率，以选择潜在的可疑药物；然后，构建第一阶段特定筛选药物的倾向评分匹配回顾性队列，并使用条件逻辑回归模型估计比值比（OR）和95%置信区间（CI）。利用当前的文献证据评估信号的新颖性。在该研究中，从总共340种药物中，最初筛选出22种药物可能诱发凝血病。我们总共确定了19个DIC阳性关联。其中，奥美拉唑（OR：2.23，95%CI：1.88 - 2.65）、氯苯那敏（OR：3.04，95%CI：2.56 - 3.60）和硫酸沙丁胺醇（OR：1.36，95%CI：1.07 - 1.73）的潜在DIC风险在儿童和成人中均为三个新的DIC信号。凝血病与美罗培南（OR：3.38，95%CI：2.72 - 4.20）、头孢哌酮舒巴坦（OR：2.80，95%CI：2.30 - 3.41）、氟康唑（OR：2.11，95%CI：1.71 - 2.59）、伏立康唑（OR：2.82，95%CI：2.20 - 3.61）、盐酸氨溴索（OR：2.12，95%CI：1.74 - 2.58）、呋塞米（OR：2.36，95%CI：2.08 - 2.67）、碘克沙醇（OR：2.21，95%CI：1.72 - 2.85）、头孢孟多（OR：1.82，95%CI：1.56 - 2.13）、头孢唑肟（OR：1.95，95%CI：1.44 - 2.63）、头孢曲松（OR：1.95，95%CI：1.44 - 2.63）、拉氧头孢钠（OR：1.76，95%CI：1.49 - 2.07）和磺胺甲恶唑（OR：1.29，95%CI：1.01 - 1.64）之间的十二个关联被视为儿童中的新信号。我们研究中开发的用于检测DIC安全信号的两阶段算法发现了19个DIC信号，包括儿科人群中的12个新信号。然而，这些DIC安全信号需要基于人群研究和机制研究的进一步研究来证实。
