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

描述(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物质。乙二醇是一种常见的人体中毒病原学，可导致严重的发病率和死亡率。2002年，5816个致电美国毒物控制中心的电话涉及人类接触乙二醇。推定乙二醇中毒的医疗处理在等待血清样本中的乙二醇确证检测时需要几个小时的显著延迟；这种检测只有在参考实验室才能得到。与此同时，必须开始一种昂贵的解毒剂(福美唑；4-甲基吡拉唑；美国特拉华州Paladin Labs的AntazolTM)和/或侵入性经验性治疗(血液透析)，以防止肾功能衰竭、恶化的代谢性酸中毒和死亡。虽然有可靠和有效的乙二醇定性试剂盒(EGT、PRN Phramacal、Pensacola、FL)用于兽医，但人类EG中毒的临床治疗并不先进。因此，由于几乎所有医院实验室都没有现成的筛查试验，EG中毒的诊断受到了阻碍。兽医EGT已在已知EG阳性血清样本中的一小部分方便样本中证明了有效性。在这项研究中(n=24)，EGT在临床相关的EG血清浓度范围内(27-281 mg/dl)具有100%的敏感性和高度的特异性。甲醇或乙醇阳性样品中未观察到干扰。我们提出了一项非盲法、前瞻性、病例对照研究，比较兽医EG检测试剂盒在检测已知中毒病例和不匹配对照的人血清样本中乙二醇的临床实用性。EGT试剂盒结果将与在两个独立的参考实验室进行的一式两份的气相色谱/质谱仪标准测试进行比较。我们将评估人血清中EGT的检测限，以及该平台的敏感性、特异性、阳性预测值(PPV)、阴性预测值(NPV)，以及任何干扰物质(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，这项先导性研究将提供初步数据，这将使寻求EGT试剂盒的实用性的更大规模、多中心、前瞻性、病例对照的临床试验成为可能。 与公共卫生相关：乙二醇病相当常见，诊断和治疗的延误是严重发病率和死亡率的来源。不幸的是，目前诊断EG中毒的金标准--气相色谱/质谱仪(GC/MS)并未广泛应用于临床，中毒的确认需要12至24小时才能完成。兽医一直在摄取EG的动物身上使用定性EG测试，这种方法快速、廉价且易于操作；我们的研究将评估这种生物测试在临床和实验室怀疑EG中毒的人类中的实用性。

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.