Likelihood Ratio Approach and Clinical Interpretation of Laboratory Tests

Fierz, Walter; Bossuyt, Xavier

doi:10.3389/fimmu.2021.655262

Cited by 34 publications

(25 citation statements)

References 47 publications

(51 reference statements)

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“…Generally, an LR >10 is considered to support a diagnosis and an LR <0.1 to rule out a diagnosis 34. It is important that laboratory professionals and clinicians become more familiar with the concept of LRs and that they develop an intuitive feeling for the clinical relevance of an LR 18. There is increasing awareness that efforts should be undertaken to harmonise interpretation of RF and ACPA test results.…”

Section: Discussionmentioning

confidence: 99%

“…The aim of this international multicentre study is to harmonise interpretation of commonly used commercially available RF and ACPA assays. In order to overcome differences in the arbitrary units of the different assays, we applied the concept of likelihood ratio (LR), which is a unit-independent method to express test results 16–18. The LR is defined as the fraction of patients with a particular test result divided by the fraction of controls with the same test result.…”

Section: Introductionmentioning

confidence: 99%

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Multicentre study to improve clinical interpretation of rheumatoid factor and anti-citrullinated protein/peptide antibodies test results

et al. 2022

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BackgroundRheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) are important biomarkers for diagnosis of rheumatoid arthritis (RA). However, there is poor harmonisation of RF and ACPA assays. The aim of this study was to refine RF and ACPA interpretation across commercial assays.Materials and methodsSix total RF isotype-non-specific assays, 3 RF IgM isotype-specific assays and 9 ACPA immunoglobulin G assays of 13 different companies were evaluated using 398 diagnostic samples from patients with RA and 1073 disease controls.ResultsUsing cut-offs proposed by the manufacturer, there was a large variability in diagnostic sensitivity and specificity between assays. Thresholds of antibody levels were determined based on predefined specificities and used to define test result intervals. Test result interval-specific likelihood ratios (LRs) were concordant across the different RF and ACPA assays. For all assays, the LR for RA increased with increasing antibody level. Higher LRs were found for ACPA than for RF. ACPA levels associated with LRs >80 were found in a substantial fraction (>22%) of patients with RA.ConclusionDefining thresholds for antibody levels and assigning test result interval-specific LRs allows alignment of clinical interpretation for all RF and ACPA assays.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multicentre study to improve clinical interpretation of rheumatoid factor and anti-citrullinated protein/peptide antibodies test results

et al. 2022

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“…Additionally, cut-off points and positive and negative predictive values were calculated along with overall assay accuracy. The cut-off point for each analyte was chosen based on the highest likelihood ratio in the sensitivity vs. 1-specificity plot, considering a higher sensitivity than higher specificity values, in order to obtain assays that provide a higher likelihood of reliability for the respective sensitivity for each analyte [ 24 ]. In addition, a two-tailed Pearson r correlation matrix was carried using Prism 9 software (GraphPad).…”

Section: Methodsmentioning

confidence: 99%

Renal and Inflammatory Proteins as Biomarkers of Diabetic Kidney Disease and Lupus Nephritis

Johnson

Keane

Vaccari

2022

Oxidative Medicine and Cellular Longevity

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Current methods for differentiation of kidney disease types are unspecific and may be invasive. Thus, there is a need for development of new biomarkers of kidney disorders that are specific and less invasive. In this study, we analyzed serum samples of diabetic kidney disease (DKD) and lupus nephritis (LN) patients to identify biomarkers of these two disorders. Serum samples were analyzed by Simple Plex assays. We calculated the area under the curve (AUC) as well as receiver operating characteristics (ROC) to obtain the sensitivity and specificity and other biomarker-related variables of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin- (IL-) 18, Lipocalin-2/NGAL, epidermal growth factor (EGF), u-Plasminogen Activator (uPA), and C-reactive protein (CRP) as potential biomarkers. Protein levels of ASC, IL-18, EGF, and Lipocalin-2/NGAL were higher in DKD and LN patients when compared to controls, whereas only uPA was elevated in DKD patients and CRP in LN patients. As determined by the AUC, of the six analytes studied, EGF ( AUC = 0.9935 ), Lipocalin-2/NGAL (0.9554), ASC (0.7666), and uPA (0.7522) are reliable biomarkers of DKD, whereas EGF (1.000), Lipocalin-2/NGAL (0.9412), uPA (0.7443), and IL-18 (0.7384) are more reliable for LN. The biomarkers analyzed can differentiate between healthy and affected individuals. However, there was no difference between the levels of these biomarkers in DKD vs LN. Thus, although these biomarkers cannot be used to categorize patients between DKD and LN, they are useful as biomarkers of renal pathology.

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“…Receiver operating characteristics (ROC) were calculated to obtain the area under the curve (AUC) in order to obtain cut-off points and the respective specificity, sensitivity and likelihood ratio. The cut-off point for each analyte was chosen based on the highest likelihood ratio in the sensitivity vs. 1-specificity plot, favoring a higher sensitivity than specificity values, to obtain assays with a higher likelihood of reliability for each analyte [81]. Positive and negative predictive values were also calculated along with overall assay accuracy.…”

Section: Statistical and Biomarker Analysismentioning

confidence: 99%

Inflammatory Biomarkers of Traumatic Brain Injury

et al. 2022

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Traumatic brain injury (TBI) has a complex pathology in which the initial injury releases damage associated proteins that exacerbate the neuroinflammatory response during the chronic secondary injury period. One of the major pathological players in the inflammatory response after TBI is the inflammasome. Increased levels of inflammasome proteins during the acute phase after TBI are associated with worse functional outcomes. Previous studies reveal that the level of inflammasome proteins in biological fluids may be used as promising new biomarkers for the determination of TBI functional outcomes. In this study, we provide further evidence that inflammatory cytokines and inflammasome proteins in serum may be used to determine injury severity and predict pathological outcomes. In this study, we analyzed blood serum from TBI patients and respective controls utilizing Simple Plex inflammasome and V-PLEX inflammatory cytokine assays. We performed statistical analyses to determine which proteins were significantly elevated in TBI individuals. The receiver operating characteristics (ROC) were determined to obtain the area under the curve (AUC) to establish the potential fit as a biomarker. Potential biomarkers were then compared to documented patient Glasgow coma scale scores via a correlation matrix and a multivariate linear regression to determine how respective biomarkers are related to the injury severity and pathological outcome. Inflammasome proteins and inflammatory cytokines were elevated after TBI, and the apoptosis-associated speck like protein containing a caspase recruitment domain (ASC), interleukin (IL)-18, tumor necrosis factor (TNF)-α, IL-4 and IL-6 were the most reliable biomarkers. Additionally, levels of these proteins were correlated with known clinical indicators of pathological outcome, such as the Glasgow coma scale (GCS). Our results show that inflammatory cytokines and inflammasome proteins are promising biomarkers for determining pathological outcomes after TBI. Additionally, levels of biomarkers could potentially be utilized to determine a patient’s injury severity and subsequent pathological outcome. These findings show that inflammation-associated proteins in the blood are reliable biomarkers of injury severity that can also be used to assess the functional outcomes of TBI patients.

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Likelihood Ratio Approach and Clinical Interpretation of Laboratory Tests

Cited by 34 publications

References 47 publications

Multicentre study to improve clinical interpretation of rheumatoid factor and anti-citrullinated protein/peptide antibodies test results

Multicentre study to improve clinical interpretation of rheumatoid factor and anti-citrullinated protein/peptide antibodies test results

Renal and Inflammatory Proteins as Biomarkers of Diabetic Kidney Disease and Lupus Nephritis

Inflammatory Biomarkers of Traumatic Brain Injury

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