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Assessment of diagnostic and prognostic accuracyRepresentative spectrum?Acceptable reference standard?Acceptable delay between tests?Partial verification avoided?Differential verification avoided?Incorporation avoided?Yes (high quality)UnclearNo (low quality)Reference standard results blinded?Index test results blinded?0% 25% 50% 75% 100%FIGURE 15 Methodological quality summary of diagnostic studies of H-FABP.definition. Although most studies had an acceptable reference standard by these criteria, it is debatablewhether the troponin assays and threshold used represented best current practice in some cases.Analysis of diagnostic studies of myoglobinFigure 23 shows the results of meta-analysis of studies of myoglobin. The summary estimates of sensitivityand specificity were 62% (35–83%) and 83% (35–98%), respectively.Description of diagnostic studies of other biomarkersWe identified 10 diagnostic studies 46,47,51,55–57,65,71,80,81 of other biomarkers. Table 15 shows the populationcharacteristics and Table 16 shows the index and reference standard test characteristics. The prevalenceof MI was lower than the studies of troponin, H-FABP and myoglobin, and varied from 5% to 29%. Themedian time from symptom onset to sampling varied from 2 to 4.5 hours. Most of the studies used amodern troponin assay with an acceptable threshold for the reference standard.Quality assessment of diagnostic studies of other biomarkersFigure 24 shows the quality assessments for studies of other biomarkers, whereas Figure 25 shows themethodological quality summary.Analysis of diagnostic studies of other biomarkersThe studies reported four analyses of MPO, 55,57,65,81 two each of BNP, 55,56 CD40L, 46,55 copeptin 71,80 andCRP, 51,55 and one each of MMP9, 55 NT-pro-BNP 55 and PAPP-A. 46 No two analyses evaluated the samebiomarker at the same threshold. The data were therefore insufficient for meaningful meta-analysis.Sensitivity and specificity of each biomarker in each analysis are reported in Table 17. Overall, diagnosticaccuracy was modest. Sensitivity exceeding 0.8 was achieved only at the expense of specificity. None ofthese analyses suggests that the biomarker in question could be used as a single test for early diagnosisof MI.Diagnostic studies of biomarkers in combination with troponinNine studies 48,55,57,67,70,71,76,77,80 reported 11 analyses of the sensitivity and specificity of biomarkers incombination with troponin, compared with troponin alone. These are outlined in Table 18. We did notundertake meta-analysis because no combination was evaluated in more than two studies. In most cases,40NIHR Journals Library
DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1Study TP FP FN TN Sensitivity Specificity Sensitivity SpecificityBody 2011 57 97 63 32 513 0.76 (0.68 to 0.82) 0.89 (0.86 to 0.91)Di Serio 2005 63 16 4 0 10 0.89 (0.76 to 0.97) 0.74 (0.51 to 0.90)Garcia-Valdecasas 2011 49 53 50 12 50 0.82 (0.72 to 0.89) 0.52 (0.42 to 0.61)Haltern 2010 67 27 21 4 42 0.85 (0.73 to 0.93) 0.68 (0.56 to 0.78)Hjortshoj 2010 68 31 6 6 64 0.82 (0.71 to 0.91) 0.90 (0.82 to 0.96)Ilva 2009 50 84 19 39 151 0.70 (0.62 to 0.77) 0.89 (0.83 to 0.93)McCann 2008 76 150 85 48 132 0.76 (0.70 to 0.82) 0.62 (0.55 to 0.68)Mion 2007 77 35 6 7 84 0.82 (0.71 to 0.91) 0.92 (0.86 to 0.96)Pooled effect 0.81 (0.72 to 0.89) 0.80 (0.64 to 0.90)Predictive effect 0.81 (0.50 to 0.95) 0.80 (0.26 to 0.98)0 0.2 0.4 0.6 0.8 1.00 0.2 0.4 0.6 0.8 1.0FIGURE 16 Meta-analysis of quantitative H-FABP assays.Study TP FP FN TN Sensitivity Specificity Sensitivity SpecificityCete 2010 58 30 0 43 151 0.41 (0.30 to 0.53) 0.99 (0.98 to 1.00)Charpentier 2010 59 21 20 78 558 0.23 (0.15 to 0.32) 0.97 (0.95 to 0.98)Ecollan 2007 64 48 3 7 50 0.86 (0.75 to 0.93) 0.94 (0.86 to 0.98)LeFevre 2007 72 19 5 17 34 0.55 (0.39 to 0.70) 0.89 (0.77 to 0.96)Li 2010 73 106 10 8 103 0.92 (0.86 to 0.96) 0.91 (0.85 to 0.95)Liao 2009 74 45 14 9 6 0.84 (0.73 to 0.92) 0.36 (0.17 to 0.58)Mad 2007 75 34 12 18 43 0.66 (0.53 to 0.78) 0.80 (0.68 to 0.88)Naroo 2009 78 75 21 24 671 0.75 (0.66 to 0.83) 0.97 (0.95 to 0.98)Valle 2007 82 89 33 59 238 0.61 (0.53 to 0.68) 0.88 (0.84 to 0.92)Pooled effect 0.68 (0.46 to 0.84) 0.92 (0.77 to 0.98)Predictive effect 0.68 (0.11 to 0.97) 0.92 (0.20 to 1.00)0 0.2 0.4 0.6 0.8 1.00 0.2 0.4 0.6 0.8 1.0FIGURE 17 Meta-analysis of qualitative H-FABP assays.© Queen’s Printer and Controller of HMSO 2013. This work was produced by Goodacre et al. under the terms of a commissioning contract issued by the Secretary of Statefor Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journalsprovided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should beaddressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton SciencePark, Southampton SO16 7NS, UK.41
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Health Technology AssessmentVOLUME
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DOI: 10.3310/hta17010 Health Techno
Page 10 and 11: ContentsAppendix 5 Expected discoun
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Page 22 and 23: BackgroundTABLE 1 Hospital admissio
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Discussionspecificity were 62% (95%
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Discussionneed for revascularisatio
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Discussionchanges in sensitivity an
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Discussionuncertainty about these p
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Discussiontroponin assays have bett
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ConclusionsSuggested research prior
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Appendix 144. heart-type fatty acid
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Appendix 1135. interleukin 33.mp. (
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Appendix 9Clinical diagnosis of NST
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Appendix 9respectively. Exercise EC
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Appendix 93. Two reviewers will mak
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Appendix 9The methodology used in t
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Appendix 9ES (Information Resources
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Appendix 923. Westwood ME, Whiting
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