title: A systematic review and meta-analysis of the diagnostic accuracy of point-of-care tests for the detection of hyperketonemia in dairy cows.
abstract: 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.
authors.affiliation: University of Guelph, Department of Population Medicine, Guelph, ON N1G 2W1, Canada. Electronic address: etatone@uoguelph.ca.
authors.forename: Elise H
authors.initials: EH
authors.lastname: Tatone
authors.affiliation: University of Guelph, Department of Population Medicine, Guelph, ON N1G 2W1, Canada.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Gordon
authors.affiliation: University of Guelph, Department of Population Medicine, Guelph, ON N1G 2W1, Canada.
authors.forename: Jessie
authors.initials: J
authors.lastname: Hubbs
authors.affiliation: University of Guelph, Department of Population Medicine, Guelph, ON N1G 2W1, Canada.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: LeBlanc
authors.affiliation: University of Guelph, Animal and Poultry Sciences, Guelph, ON N1G 2W1, Canada.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: DeVries
authors.affiliation: University of Guelph, Department of Population Medicine, Guelph, ON N1G 2W1, Canada.
authors.forename: Todd F
authors.initials: TF
authors.lastname: Duffield
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood / Q000652:urine; D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000097:blood / Q000175:diagnosis* / Q000652:urine; D003955:Diagnostic Tests, Routine / Q000379:methods / Q000592:standards / Q000662:veterinary*; D005260:Female; D007662:Ketosis / Q000175:diagnosis / Q000662:veterinary*; D008892:Milk / Q000737:chemistry; D019095:Point-of-Care Systems; D012680:Sensitivity and Specificity
chemical_list: D020155:3-Hydroxybutyric Acid
keywords: Dairy cattle; Diagnostic test accuracy; Ketosis; Meta-analysis