Analytical Performance/Clinical Utility Of Laboratory Te

实验室技术的分析性能/临床实用性

• 批准号: 7332041
• 负责人: Gyorgy Csako
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7332041
• 关键词: Analytical; Performance; Clinical; Utility; Laboratory

Atherothrombosis is a multifactorial disease and risk factors for atherothrombosis are now estimated to be in the hundreds. In addition to classical risk factors like serum lipids (total cholesterol and triglycerides), lipoproteins, apolipoproteins, and a variety of inflammatory molecules such as C-reactive protein, serum amyloid A, and hemostatic factors have been also considered for risk and/or require management. For thrombosis prevention, the effectiveness and safety of warfarin require maintaining an international normalized ratio within the therapeutic range. In a retrospective study, we attempted to identify predictors of nontherapeutic international normalized ratio results in 350 ambulatory care patients from a broad geographic region. Possible predictors (gender, age, body weight, body mass index, height, race, tobacco use, alcohol use, warfarin dose, therapeutic indication, regimen intensity, international normalized ratio monitoring frequency/category, interacting medications, adverse events) were assessed with logistic regression models. Subset analysis involved 146 patients concurrently monitored with capillary whole blood INR (CoaguChek). As measured on venous specimens, 52% (182/350) of the patients had subtherapeutic international normalized ratio results and 13% (44/350) had supratherapeutic international normalized ratio results despite frequent (< or =4 wk) monitoring in 75% of the patients. Due to the small sample size, supratherapeutic international normalized ratio results could not be further analyzed. Of 19 predictors tested, only daily warfarin dose (p < 0.02) and regimen intensity (p < 0.03) were significant independent and additive predictors of subtherapeutic results. Patients on the high-intensity regimen (international normalized ratio 2.5-3.5) and receiving warfarin < or =6 mg/day had >50% risk of having subtherapeutic international normalized ratio results. Subtherapeutic CoaguChek results were independent predictors of subtherapeutic venipuncture international normalized ratio results in the subset (p = 0.001). We concluded that, in the absence of readily identifiable predictors, only higher warfarin dosing and/or more frequent monitoring (possibly with point-of-care/home monitoring devices) may minimize the time that international normalized ratio are subtherapeutic, especially in patients receiving low-dose and/or high-intensity anticoagulation therapy. In a collaborative study, the potential benefit of granulocyte colony-stimulating factor administration to coronary artery disease patients was evaluated. It was suggested that cytokine mobilization of progenitor cells from bone marrow may promote myocardial neovascularization with relief of ischemia. After administration of granulocyte colony-stimulating factor, indices of platelet and coagulation activation were not changed, but C-reactive protein increased from 4.5 +/- 1.3 mg/L to 8.6 +/- 1.3 mg/L (p = 0.017). Further, granulocyte colony-stimulating factor mobilized cells with endothelial progenitor potential from bone marrow, but without objective evidence of cardiac benefit and with the potential for adverse outcomes in some patients. In another collaborative study, the effect of parenteral L-arginine supplementation was studied in a canine model of sepsis. Septic shock has been alternatively viewed as an L-arginine-deficient state or as a syndrome caused by excess nitric oxide, an end-product of L-arginine metabolism. In the canine sepsis model employed, the main measurements were hemodynamics, plasma arginine and ornithine, serum nitrate/nitrite, laboratory studies for organ injury, and survival. Two different doses of L-arginine both similarly increased mortality (p=0.02), and worsened shock (p=0.001 for reduced mean arterial pressure), suggesting that supplemental parenteral L-arginine, at doses above standard dietary practices, should be avoided in critically ill patients with septic shock.

动脉粥样硬化血栓形成是一种多因素疾病，目前估计动脉粥样硬化血栓形成的危险因素有数百种。除了经典的风险因素如血清脂质（总胆固醇和甘油三酯），脂蛋白、载脂蛋白和各种炎症分子如C反应蛋白、血清淀粉样蛋白A和止血因子也被认为是风险和/或需要管理。为了预防血栓形成，华法林的有效性和安全性需要在治疗范围内维持国际标准化比值。在一项回顾性研究中，我们试图确定来自广泛地理区域的350例门诊患者的非治疗性国际标准化比值结果的预测因素。使用logistic回归模型评估可能的预测因素（性别、年龄、体重、体重指数、身高、种族、吸烟、饮酒、华法林剂量、治疗适应症、方案强度、国际标准化比率监测频率/类别、相互作用药物、不良事件）。亚组分析涉及146例同时监测毛细血管全血INR（CoaguChek）的患者。通过静脉标本测量，52%（182/350）患者的国际标准化比值结果低于治疗水平，13%（44/350）患者的国际标准化比值结果高于治疗水平，尽管75%的患者进行了频繁（≤ 4周）监测。由于样本量较小，无法进一步分析超治疗国际标准化比值结果。在19个预测因子中，只有华法林日剂量（p < 0.02）和方案强度（p < 0.03）是亚治疗结果的显著独立和附加预测因子。接受高强度方案（国际标准化比值2.5-3.5）和华法林≤ 6 mg/d的患者出现亚治疗国际标准化比值结果的风险>50%。亚治疗CoaguChek结果是亚治疗静脉穿刺国际标准化比率结果的独立预测因子（p = 0.001）。我们的结论是，在缺乏容易识别的预测因素的情况下，只有更高的华法林剂量和/或更频繁的监测（可能使用床旁/家庭监测设备）可以最大限度地减少国际标准化比值处于亚治疗水平的时间，特别是在接受低剂量和/或高强度抗凝治疗的患者中。 在一项合作研究中，评价了粒细胞集落刺激因子给药对冠心病患者的潜在益处。提示细胞因子动员骨髓祖细胞可促进心肌血管新生，缓解缺血。粒细胞集落刺激因子给药后，血小板和凝血活化指数无变化，但C反应蛋白从4.5 +/- 1.3 mg/L升高至8.6 +/- 1.3 mg/L（p = 0.017）。此外，粒细胞集落刺激因子从骨髓中动员了具有内皮祖细胞潜能的细胞，但没有客观证据表明对心脏有益，并且在某些患者中有可能产生不良后果。 在另一项合作研究中，在脓毒症犬模型中研究了肠外L-精氨酸补充的作用。脓毒性休克被认为是L-精氨酸缺乏状态或由过量的一氧化氮（L-精氨酸代谢的终产物）引起的综合征。在所采用的犬脓毒症模型中，主要测量是血流动力学、血浆精氨酸和鸟氨酸、血清硝酸盐/亚硝酸盐、器官损伤的实验室研究和存活率。两种不同剂量的L-精氨酸均相似地增加死亡率（p=0.02），并使休克恶化（平均动脉压降低，p=0.001），这表明在脓毒性休克的危重患者中应避免以高于标准饮食实践的剂量补充肠外L-精氨酸。