Predicting medical consequences of novel fentanyl analog overdose using the Toxicology Investigators Consortium (TOXIC)

这份R01提案的目的是加深我们对#年药物过量死亡的主要原因的认识 今日美国：新型精神活性合成阿片类药物，其中大部分是芬太尼类似物。使用 全国向急诊科提交的患者登记，新型芬太尼类似物过量将 在流行病学、分析确认、临床风险因素和治疗需求方面进行研究，由 独一无二的合格的多学科团队，在该领域有着广泛的合作记录。 美国阿片类药物流行的范围正在扩大，药物过量死亡人数从1999-2015年间几乎增加了两倍。2015年，美国吸毒过量死亡人数首次超过5万人(52,404人)，其中33,091人 (63.1%)涉及阿片类药物。2016年，服药过量死亡人数继续增加，达到63,600人。阿片类药物过量成本 2015年，美国人的收入为5,040亿美元(占国内生产总值的2.8%)，是2013年估计的6倍。 仅去年一年，全国范围内因阿片类药物过量而前往急诊科就诊的人数就增加了27%。 通过减少处方阿片类药物的可获得性和滥用潜力来缓解这一趋势的战略已经 紧随其后的是非法阿片类药物使用的增加。虽然最初非法阿片类药物过量占主导地位 都是海洛因暴露的结果，全球毒品贸易的变化面貌引入了合成阿片类药物 芬太尼类似物进入毒品供应，在那里它们现在估计已经超过海洛因成为 药物过量死亡的主要原因。 利用全国近70家医院中心对患者进行床边评估，超过1万名服药过量患者 已经参加了首席调查员先前的研究，从而使这项提议具有了势头和可行性。 我们的具体目标有四个方面：(1)推导和验证以下不良健康后果的临床预测指标： 芬太尼类似物过量；(2)通过最先进的毒理学试验确认芬太尼类似物暴露； (3)调查芬太尼类似物过量的治疗利用、持续时间和差异；及(4) 评估经分析证实的芬太尼类似物过量的流行病学。 为了实现这些具体目标，我们将前瞻性地在全国范围内对患者进行抽样。我们将实施 向公众和公共卫生实体迅速传播关于以下物质不良影响的警报和信息 芬太尼类似物。在拟议的研究完成后，药物滥用领域将显著 使美国阿片类药物流行的数千名受害者受益。

The purpose of this R01 proposal is to deepen our knowledge of the primary cause of drug overdose deaths in the U.S. today: novel psychoactive synthetic opioids, the majority of which are fentanyl analogues. Using a nationwide registry of patients who present to emergency departments, novel fentanyl analogue overdose will be studied in terms of its epidemiology, analytical confirmation, clinical risk factors, and treatment needs, by a uniquely qualified multidisciplinary team with an extensive track record of collaboration in the field. The scope of the U.S. opioid epidemic is broadening, with drug overdose deaths nearly tripling from 1999-2015. For the first time ever, in 2015 U.S. drug overdose deaths surpassed 50,000 (52,404), of which 33,091 (63.1%) involved an opioid. Overdose deaths continued to increase in 2016 to 63,600. Opioid overdoses cost Americans $504 billion in 2015 (2.8% of gross domestic product), up from six times the prior estimates in 2013. There was a 27% increase in nationwide Emergency Department visits for opioid overdoses last year alone. Strategies to mitigate this trend by decreasing the availability and abuse potential of prescription opioids have been followed by an increase in illicit opioid use. While initially the predominance of illicit opioid overdoses were a result of heroin exposure, the changing face of global drug commerce introduced synthetic opioid fentanyl analogues into the drug supply, where they are now estimated to have surpassed heroin as the primary cause of drug overdose deaths. Using nearly 70 hospital centers nationwide with bedside evaluation of patients, over 10,000 overdose patients have been enrolled in the Principal Investigator’s prior study giving this proposal momentum and feasibility. Our specific aims are four-fold: (1) To derive and validate clinical predictors of adverse health consequences of fentanyl analogue overdose; (2) To confirm fentanyl analogue exposure via state-of-the-art toxicology testing; (3) To investigate treatment utilization, duration, and disparities for fentanyl analogue overdose; and (4) To assess epidemiology of analytically-confirmed fentanyl analogue overdose. To achieve these Specific Aims, we will prospectively enroll a national sampling of patients. We will implement the rapid dissemination of alerts and information to the public and public health entities on adverse effects of fentanyl analogues. At the completion of the proposed research, the field of drug abuse will be significantly advanced to the benefit of thousands of victims of the U.S. opioid epidemic.