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药物不良反应分析-全国主动监测网络:加拿大药物安全数据库的药物基因组学网络。

Analyses of Adverse Drug Reactions-Nationwide Active Surveillance Network: Canadian Pharmacogenomics Network for Drug Safety Database.

机构信息

Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.

British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada.

出版信息

J Clin Pharmacol. 2019 Mar;59(3):356-363. doi: 10.1002/jcph.1336. Epub 2018 Nov 19.

DOI:10.1002/jcph.1336
PMID:30452777
Abstract

Adverse drug reactions (ADRs) are a major problem in modern medicine, representing up to the fourth-highest cause of mortality. Pharmacogenomic tests are 1 of the most promising methods to tackle the challenge of ADRs. The objective of this study was to analyze the clinical and demographic information of the pan-Canadian active surveillance network, Canadian Pharmacogenomics Network for Drug Safety (CPNDS). Information entered into the database by trained active surveillors between May 15, 2005 and May 9, 2017 was collected and analyzed. Specific data included for analysis were number of ADR reports, reports of drug use without ADRs, date of onset of ADR, suspected drugs, concomitant drugs, and fatal ADR cases. The CPNDS database consisted of 93,974 reports of medication use, including 10,475 reports of ADRs, of which 72.6% occurred in pediatric patients (≤21 years old). Self-reported ancestries were predominantly Europe (38.2%), Canada (9.6%), and East Asia (4.9%). The 5 most frequent ADRs were cutaneous ADRs, peripheral neuropathy, cardiotoxicity, central nervous system toxicity, and ototoxicity. The 5 drugs most commonly suspected to cause ADRs were methotrexate, vincristine, doxorubicin, cisplatin, and L-asparaginase. The CPNDS database is a valuable resource to identify clinical and genomic predictors of ADRs. The database also highlights our candidate ADRs for pharmacogenomic discovery research to identify additional ADR biomarkers. Additionally, the database provides information that can be used for developing strategies to prevent ADRs and raises awareness of ADRs among Canadian healthcare professionals.

摘要

药物不良反应(ADR)是现代医学面临的主要问题,是导致死亡的第四大主要原因。药物基因组学检测是应对 ADR 挑战的最有前途的方法之一。本研究的目的是分析加拿大药物安全基因组网络(CPNDS)全加主动监测网络的临床和人口统计学信息。该数据库于 2005 年 5 月 15 日至 2017 年 5 月 9 日期间由训练有素的主动监测人员输入信息,收集并分析。分析中包含的具体数据包括 ADR 报告数量、无 ADR 药物使用报告、ADR 发病日期、可疑药物、伴随药物和致命 ADR 病例。CPNDS 数据库包含 93974 份药物使用报告,其中 10475 份报告为 ADR,其中 72.6%发生在儿科患者(≤21 岁)。自我报告的祖先是欧洲(38.2%)、加拿大(9.6%)和东亚(4.9%)。最常见的 5 种 ADR 是皮肤 ADR、周围神经病变、心脏毒性、中枢神经系统毒性和耳毒性。最常怀疑引起 ADR 的 5 种药物是甲氨蝶呤、长春新碱、阿霉素、顺铂和 L-天冬酰胺酶。CPNDS 数据库是识别 ADR 临床和基因组预测因子的有价值资源。该数据库还突出了我们的候选 ADR,用于药物基因组发现研究,以确定其他 ADR 生物标志物。此外,该数据库提供了可用于制定预防 ADR 策略和提高加拿大医疗保健专业人员对 ADR 认识的信息。

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