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

描述（由申请人提供）：乙二醇（EG; CAS编号107-21-1）是在汽车防冻剂中发现的有毒化学品。乙二醇是一种常见的人类中毒病因，并导致显著的发病率和死亡率。2002年，美国毒物控制中心接到的5816个电话涉及人体接触乙二醇。假定乙二醇中毒的医疗管理涉及到在等待血清样本中EG的确认性检测时的几个小时的显著延迟;该检测仅在参考实验室提供。同时，必须开始昂贵的解毒剂（福美吡唑; 4-甲基吡唑; AntazolTM，Paladin Labs，特拉华州US）和/或侵入性经验治疗（血液透析），以预防肾衰竭、代谢性酸中毒恶化和死亡。虽然存在可靠且经验证的定性乙二醇检测试剂盒（EGT，PRN Phramacal，彭萨科拉，佛罗里达州）可用于兽药，但人类EG中毒的临床管理并不先进。因此，EG中毒的诊断是阻碍了缺乏一个现成的筛选测试，在几乎所有的医院实验室。兽用EGT已在已知EG阳性血清样本的少量便利样本中证明了有效性。在该研究（n=24）中，EGT在临床相关的EG血清浓度范围（27-281 mg/dl）内具有100%的灵敏度和高特异性。在甲醇或乙醇阳性样品中未观察到干扰。我们提出了一个非盲的，前瞻性的，病例对照研究的临床实用性的兽医EG检测试剂盒检测乙二醇在人类血清样本中已知的中毒情况相比，不匹配的控制。将EGT试剂盒结果与在两个独立参考实验室进行的气相色谱/质谱标准检测进行比较，一式两份。我们将评估人血清中的EGT检测限和平台的灵敏度、特异性、阳性预测值（PPV）、阴性预测值（NPV），以及导致假阳性或假阴性结果的干扰物质（乙醇、丙酮、乳酸盐、甲醇、水杨酸盐）的任何证据。如果成功，该初步研究将提供初步数据，这将使追求更大的，多中心的，前瞻性的，病例对照的临床试验，EGT套件的效用。 公共卫生相关性：乙二醇是一种相当常见的事件，诊断和治疗的延误是显著发病率和死亡率的来源。气相色谱/质谱（GC/MS）是目前诊断EG中毒的金标准，但不幸的是，在临床上并不广泛使用，中毒的确认需要12至24小时才能完成。兽医一直在使用一种定性的EG测定动物摄入EG，这是快速，廉价，易于执行;我们的研究将评估这种生物测定在人类的临床和实验室怀疑EG中毒的效用。

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.