Evaluation of a Veterinary Ethylene Glycol Qualitative Assay in Human Subjects wi

兽医乙二醇定性测定对人类受试者的评估

• 批准号: 7978770
• 负责人: Michael David Schwartz
• 金额: $ 6.46万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7978770
• 关键词: Acetone; Animals; Antidotes; Antifreeze; Area; Biological Assay; Case-Control Studies; Cessation of life; Clinical; Clinical Management; Collection; Controlled Clinical Trials; Data; Delaware; Detection; Diagnosis; Enrollment; Ethanol; Ethylene Glycols; Etiology; Evaluation; Exposure to; Gas Chromatography; Gold; Hemodialysis; Hospitals; Hour; Human; Isopropanol; Kidney Failure; Laboratories; Mass Spectrum Analysis; Medical; Metabolic acidosis; Methanol; Morbidity - disease rate; Patients; Pilot Projects; Poison; Poison Control Centers; Poisoning; Predictive Value; Reporting; Research Personnel; Sampling; Screening procedure; Sensitivity and Specificity; Serum; Source; Specificity; Testing; Time; Veterinarians; Veterinary Medicine; base; case control; clinically relevant; data sharing; diagnosis standard; ethylene glycol; exposed human population; fomepizole; gamma hydroxybutyrate; hospital laboratories; human subject; mortality; prevent; prospective; public health relevance; salicylate; statistics

DESCRIPTION (provided by applicant): Ethylene glycol (EG; CAS No. 107-21-1) is the toxic chemical found in automotive antifreeze. Ethylene glycol is a frequently encountered etiology of human poisoning and causes significant morbidity and mortality. In 2002, 5816 calls to US Poison Control Centers involved human exposure to ethylene glycol. The medical management of presumed ethylene glycol poisoning involves a significant delay of several hours while waiting for confirmatory testing for EG in a serum sample; this testing is available only at reference laboratories. As the same time, an expensive antidote (fomepizole; 4-methylpirazole; AntazolTM, Paladin Labs, Delaware US) and/or invasive empirical treatment (hemodialysis) must be started to prevent renal failure, worsening metabolic acidosis and death. While a reliable and validated qualitative ethylene glycol test kit (EGT, PRN Phramacal, Pensacola, FL) exists for use in veterinary medicine, the clinical management of EG poisoning in humans is not as advanced. Thus, EG poisoning diagnosis is hampered by the absence of a readily available screening test in nearly all hospital laboratories. The veterinary EGT has demonstrated efficacy in a small convenience sample of known EG positive serum samples. In that study (n=24), the EGT had 100% sensitivity and high specificity over a clinically relevant range of EG serum concentrations (27-281 mg/dl). No interference was observed in samples positive for methanol or ethanol. We propose an un-blinded, prospective, case-control study of the clinical utility of the veterinary EG test kit to detect ethylene glycol in human serum samples from known poisoning cases compared to unmatched controls. EGT kit results will be compared against criterion standard testing with gas chromatography/mass spectroscopy performed in duplicate at two independent reference laboratories. We will assess the EGT detection limit in human serum and the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of the platform, as well as any evidence of interfering substances (ethanol, acetone, lactate, methanol, salicylate) leading to false positive or false negative results. If successful, this pilot study will provide preliminary data which will enable pursuit of a much larger, multi-centered, prospective, case controlled clinical trial, of the utility of the EGT kit. PUBLIC HEALTH RELEVANCE: Ethylene glycol is a fairly common occurrence and delay in diagnosis and treatment is a source of significant morbidity and mortality. Gas chromatography/mass spectroscopy (GC/MS), the current gold standard for the diagnosis of EG poisoning, is unfortunately not widely clinically available and confirmation of poisoning takes anywhere between 12 and 24 hours to be completed. Veterinarians have been using a qualitative EG assay in animals that ingest EG which is rapid, inexpensive, and easy to perform; our study will assess the utility of this bioassay in humans with clinical and laboratory suspicion of EG poisoning.

说明（申请人提供）：乙二醇（EG; CAS No. 107-21-1）是汽车防冻液中的有毒化学物质。乙二醇是一种常见的人类中毒的病因，并导致显著的发病率和死亡率。2002年，美国中毒控制中心接到5816个与人体接触乙二醇有关的电话。假定乙二醇中毒的医疗处理涉及在等待血清样本中EG的确认性检测时明显延迟数小时；这项测试只能在参考实验室进行。与此同时，必须开始使用昂贵的解毒剂（福美唑、4-甲基吡唑、安他唑tm， Paladin Labs, Delaware US）和/或侵入性经验治疗（血液透析），以防止肾功能衰竭、代谢性酸中毒恶化和死亡。虽然存在可靠且经过验证的定性乙二醇检测试剂盒（EGT, PRN Phramacal, Pensacola， FL）用于兽药，但人类EG中毒的临床管理并不先进。因此，EG中毒的诊断由于几乎所有医院实验室缺乏现成的筛查试验而受到阻碍。兽医用EGT已在已知EG阳性血清样本中证明了其有效性。在该研究中（n=24）， EGT在临床相关的EG血清浓度范围（27-281 mg/dl）内具有100%的敏感性和高特异性。在甲醇或乙醇阳性样品中未观察到干扰。我们建议进行一项非盲法、前瞻性、病例对照研究，研究兽医EG检测试剂盒的临床应用，以检测已知中毒病例的人类血清样本中的乙二醇，并与未匹配的对照组进行比较。EGT试剂盒结果将与在两个独立参考实验室进行的气相色谱/质谱两份标准测试进行比较。我们将评估EGT在人血清中的检测限以及平台的敏感性、特异性、阳性预测值（PPV）、阴性预测值（NPV），以及是否存在干扰物质（乙醇、丙酮、乳酸、甲醇、水杨酸盐）导致假阳性或假阴性结果的证据。如果成功，这项试点研究将提供初步数据，这将有助于开展更大规模的、多中心的、前瞻性的、病例对照的EGT试剂盒临床试验。