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

使用毒理学研究联盟 (TOXIC) 预测新型芬太尼类似物过量服用的医疗后果

• 批准号: 10546762
• 负责人: Alex Francis Manini
• 金额: $ 50万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10546762
• 关键词: Accident and Emergency department; Address; Admission activity; Adverse effects; Affect; American; Biological; Caring; Cessation of life; Characteristics; Chronology; Clinical; Clinical Data; Clinical Management; Cocaine; Collaborations; Commerce; Critical Care; Data; Diagnosis; Disease Outbreaks; Dose; Drug abuse; Drug usage; Emergency Care; Emergency Department evaluation; Emergency Department patient; Emergency department visit; Enrollment; Epidemic; Epidemiology; Evaluation; Factor Analysis; Fentanyl; Forensic Medicine; Health; Heroin; Hospitals; Incidence; Individual; Ingestion; Knowledge; Laboratory Markers; Length of Stay; Liquid Chromatography; Mechanical ventilation; Medical; Medical Records; Molecular; Morphine; Naloxone; National Institute of Drug Abuse; Opioid; Outcome; Overdose; Patient Self-Report; Patients; Pattern; Periodicity; Pharmaceutical Preparations; Poison; Population; Prevalence; Principal Investigator; Property; Prospective cohort; Public Health; Reporting; Research; Research Personnel; Resources; Risk Factors; Sampling; Standardization; Suicide; System; Testing; Time; Time trend; Toxicology; Visit; abuse liability; analog; analytic epidemiology; base; cathinone; clinical effect; clinical predictors; clinical risk; cohort; cost; data streams; demographics; design; drug of abuse; heroin overdose; illicit opioid; improved; multidisciplinary; novel; opioid epidemic; opioid mortality; opioid overdose; opioid use; organ injury; overdose death; patient registry; prescription opioid; prospective; psychostimulant; regional difference; screening; sedative; sex; stem; substance use; synthetic cannabinoid; synthetic opioid; tandem mass spectrometry; time of flight mass spectrometry; trend; trend analysis

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.

该R01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 今天的美国：新型的精神活性合成OioIds，其中大多数是芬太尼类似物。使用 出席急诊科的患者注册表，新型的芬太尼类似物过量会 根据其流行病学，分析确认，临床风险因素和治疗需求的研究 具有独特资格的多学科团队，具有该领域合作的广泛记录。 美国阿片类药物流行的范围正在扩大，药物过量死亡几乎在1999 - 2015年之间几乎增加了三倍。有史以来第一次，2015年美国药物过量死亡人数超过50,000（52,404），其中33,091 （63.1％）涉及阿片类药物。 2016年过量死亡人数继续增加到63,600。阿片类药物过量成本 2015年，美国人的5004亿美元（占国内生产总值的2.8％），高于2013年先前的估计值的六倍。 仅去年一年，全国范围内就阿片类药物过量的急诊室就诊增长了27％。 通过减少处方阿片类药物的可用性和滥用潜力来减轻这种趋势的策略 紧随其后的是非法使用阿片类药物。虽然最初是非法阿片类药物过量的占主导地位 是海洛因暴露的结果，全球毒品贸易的不断变化引入了合成的Ooid 芬太尼类似物进入药物供应，现在估计它们已超过海洛因作为 药物过量死亡的主要原因。 在全国范围内使用近70个医院中心对患者进行床头评估，超过10,000例过量患者 已入学了首席研究者的先前研究，这给了这一提议的势头和可行性。 我们的具体目的是四倍：（1）得出并验证临床预测因素 芬太尼类似物过量； （2）通过最新的毒理学测试确认芬太尼模拟暴露； （3）研究芬太尼类似物过量的治疗利用，持续时间和差异； （4）到 评估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，我们可能会招募患者的全国样本。我们将实施 对公共和公共卫生实体的警报和信息的迅速传播有关的不利影响 芬太尼类似物。拟议研究完成时，药物滥用领域将大大显着 美国阿片类药物流行病的成千上万受害者受益。