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

摘要和项目摘要 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 多中心网络，向急诊科提出新型芬太尼类似物过量的患者 将从分析确认、临床风险因素、治疗需求和区域趋势方面进行研究。 国际和平研究所组建了一支多学科团队，在该领域有着广泛的协作记录。 美国阿片类药物流行的范围正在扩大，药物过量死亡人数比 1999-2015年。2015年，美国吸毒过量死亡人数首次超过5万人(52404人)，其中 33,091例(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 2015年，吸毒过量给美国人造成了5040亿美元的损失(占国内生产总值的2.8%)，高于之前的6倍 2013年的估计数字。全国范围内因阿片类药物过量而前往急诊科就诊的人数增加了27% 仅去年一年。通过减少可获得性和滥用可能性来缓解这一趋势的策略 在处方阿片类药物之后，非法阿片类药物的使用有所增加。虽然最初的优势是 非法阿片类药物过量是海洛因暴露的结果，全球毒品贸易的变化面貌引入 合成阿片类芬太尼类似物进入药物供应，在那里他们现在估计已经超过 海洛因是吸毒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10,000例过量用药 患者已经参加了首席调查员之前的研究，这给了这项提议的势头和 可行性。 我们的具体目标有三个：(1)确认和表征芬太尼类似物过量在新的 前瞻性队列；(2)评估芬太尼的后遗症、治疗需求和资源利用 模拟过量；以及(3)趋势和地理位置分析确认的芬太尼类似物过量 跨多中心网络。 为了实现这些具体目标，我们将前瞻性地招募新的多中心患者队列。我们 将在以下时间向公众和公共卫生实体快速传播警报和信息 芬太尼类似物的不良反应。在拟议的研究完成后，药物滥用领域将 大大进步，以便能够预测美国数千名受害者的医疗后果。 阿片类药物泛滥。

ABSTRACT AND PROJECT SUMMARY 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 multicenter network, patients who present to emergency departments with novel fentanyl analogue overdose will be studied in terms of analytical confirmation, clinical risk factors, treatment needs, and regional trends. The PI has assembled a 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 three-fold: (1) To confirm and characterize fentanyl analogue overdoses in a new prospective cohort; (2) To evaluate sequelae, treatment needs, and resource utilization following fentanyl analogue overdoses; and (3) To trend and geolocate analytically confirmed fentanyl analogue overdoses across a multicenter network. To achieve these Specific Aims, we will prospectively enroll a new multicenter cohort 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 allow prediction of medical consequences for thousands of victims of the U.S. opioid epidemic.