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

本R 01提案的目的是加深我们对药物过量死亡的主要原因的了解， 今日美国：新型精神活性合成阿片类药物，其中大多数是芬太尼类似物。使用 在全国范围内登记到急诊室的患者中，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， 具有独特资格的多学科团队，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年到2015年增加了近两倍。2015年，美国药物过量死亡人数首次超过50，000人（52，404人），其中33，091人 (63.1%）涉及阿片类药物。2016年，过量死亡人数继续增加至63，600人。阿片类药物过量费用 2015年，美国人的收入为5040亿美元（占国内生产总值的2.8%），高于2013年先前估计的六倍。 仅去年一年，全国范围内因阿片类药物过量而前往急诊室的人数就增加了27%。 通过减少处方类阿片的供应和滥用可能性来减缓这一趋势的战略有 其次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， 由于接触海洛因，全球毒品贸易的面貌不断变化， 芬太尼类似物进入毒品供应，现在估计它们已经超过海洛因， 药物过量死亡的主要原因。 利用全国近70个医院中心对患者进行床边评估， 已入组主要研究者的既往研究，从而为该提案提供动力和可行性。 我们的具体目标有四个方面：（1）推导和验证不良健康后果的临床预测因子， 芬太尼类似物过量;（2）通过最先进的毒理学测试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;以及（4） 评估经分析确认的芬太尼类似物过量的流行病学。 为了实现这些特定目标，我们将前瞻性地招募全国患者样本。落实 向公众和公共卫生实体迅速传播关于 芬太尼类似物。在拟议的研究完成后，药物滥用领域将大大 美国阿片类药物流行病的数千名受害者的利益。

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.