University of Guelph, Department of Population Medicine, Guelph, ON N1G 2W1, Canada.
University of Guelph, Department of Population Medicine, Guelph, ON N1G 2W1, Canada.
Prev Vet Med. 2016 Aug 1;130:18-32. doi: 10.1016/j.prevetmed.2016.06.002. Epub 2016 Jun 2.
Several rapid tests for use on farm have been validated for the detection of hyperketonemia (HK) in dairy cattle, however the reported sensitivity and specificity of each method varies and no single study has compared them all. Meta-analysis of diagnostic test accuracy is becoming more common in human medical literature but there are few veterinary examples. The objective of this work was to perform a systematic review and meta-analysis to determine the point-of-care testing method with the highest combined sensitivity and specificity, the optimal threshold for each method, and to identify gaps in the literature. A comprehensive literature search resulted in 5196 references. After removing duplicates and performing relevance screening, 23 studies were included for the qualitative synthesis and 18 for the meta-analysis. The three index tests evaluated in the meta-analysis were: the Precision Xtra(®) handheld device measuring beta-hydroxybutyrate (BHB) concentration in whole blood, and Ketostix(®) and KetoTest(®) semi-quantitative strips measuring the concentration of acetoacetate in urine and BHB in milk, respectively. The diagnostic accuracy of the 3 index tests relative to the reference standard measurement of BHB in serum or whole blood between 1.0-1.4mmol/L was compared using the hierarchical summary receiver operator characteristic (HSROC) method. Subgroup analysis was conducted for each index test to examine the accuracy at different thresholds. The impact of the reference standard threshold, the reference standard method, the prevalence of HK in the population, the primary study source and risk of bias of the primary study was explored using meta-regression. The Precision Xtra(®) device had the highest summary sensitivity in whole blood BHB at 1.2mmol/L, 94.8% (CI95%: 92.6-97.0), and specificity, 97.5% (CI95%: 96.9-98.1). The threshold employed (1.2-1.4mmol/L) did not impact the diagnostic accuracy of the test. The Ketostix(®) and KetoTest(®) strips had the highest summary sensitivity and specificity when the trace and weak positive thresholds were used, respectively. Controlling for the source of publication, HK prevalence and reference standard employed did not impact the estimated sensitivity and specificity of the tests. Including only peer-reviewed studies reduced the number of primary studies evaluating the Precision Xtra(®) by 43% and Ketostix(®) by 33%. Diagnosing HK with blood, urine or milk are valid options, however, the diagnostic inaccuracy of urine and milk should be considered when making economic and treatment decisions.
已经有几种用于农场的快速检测方法被验证可用于检测奶牛的酮血症（HK），然而，每种方法的报告灵敏度和特异性都有所不同，没有单一的研究对它们进行了比较。在人类医学文献中，诊断测试准确性的荟萃分析越来越常见，但兽医领域的例子却很少。这项工作的目的是进行系统评价和荟萃分析，以确定具有最高综合灵敏度和特异性的即时检测方法，确定每种方法的最佳阈值，并确定文献中的空白。全面的文献检索产生了 5196 篇参考文献。在去除重复项并进行相关性筛选后，有 23 项研究被纳入定性综合分析，18 项研究被纳入荟萃分析。荟萃分析中评估了三种索引测试：Precision Xtra®手持式设备测量全血中的β-羟丁酸（BHB）浓度，以及 Ketostix®和 KetoTest®半定量条带分别测量尿液中的乙酰乙酸和乳中的 BHB 浓度。使用分层综合接收者操作特征（HSROC）方法比较了这 3 种索引测试相对于血清或全血中 1.0-1.4mmol/L 的 BHB 参考标准测量值的诊断准确性。使用亚组分析检查了不同阈值下每种索引测试的准确性。使用元回归探索了参考标准阈值、参考标准方法、人群中 HK 的患病率、主要研究来源和主要研究的偏倚风险对 Precision Xtra®设备的影响。在全血 BHB 中，Precision Xtra(®)设备在 1.2mmol/L 时具有最高的综合敏感性，为 94.8%（95%CI：92.6-97.0），特异性为 97.5%（95%CI：96.9-98.1）。所使用的阈值（1.2-1.4mmol/L）并未影响测试的诊断准确性。当使用痕量和弱阳性阈值时，Ketostix®和 KetoTest®条带具有最高的综合敏感性和特异性。控制出版物来源、HK 患病率和参考标准后，并未影响测试的估计敏感性和特异性。仅纳入同行评审研究将评估 Precision Xtra(®)的主要研究数量减少了 43%，将评估 Ketostix(®)的主要研究数量减少了 33%。使用血液、尿液或牛奶诊断 HK 是有效的选择，但在做出经济和治疗决策时应考虑尿液和牛奶的诊断不准确性。
