Diagnostic tests are commonly evaluated using sensitivity, specificity, predictive values, likelihood ratios, and receiver operating characteristic (ROC) curve analysis. Although essential, these measures do not fully answer two practical questions frequently raised in clinical medicine: how often a test makes mistakes, and whether those mistakes are predominantly false positive or false negative. This article introduces two complementary measures that address these questions: the number needed to misdiagnose (NNM), which expresses the frequency of diagnostic error in intuitive clinical terms, and the misdiagnosis direction index (MDI), which indicates whether errors are mainly false positive or false negative. A weighted MDI is also introduced for unequal clinical harms of errors. Together with conventional indices such as Youden's index, these measures provide a broader framework for interpreting diagnostic performance.
Introduction: For measurands with a low index of individuality (II), delta check is crucial. If delta percentage change (DPC) values in different patients consecutively exceed the reference change value (RCV), it may indicate an analytical problem. Similarly to moving sum (MovSuM), percentage of DPCs exceeding RCV can be used as a quality control model by comparing it with a certain threshold. This study aimed to develop a novel patient-based quality control (PBQC) model using delta checks and evaluate its performance. Materials and methods: The study was performed at Gazi University Biochemistry Laboratory. The model was tested on creatinine (measured on Advia Chemistry Systems using the alkaline picrate method), with pooled-CVa = 2.5%, CVi = 4.7%, and RCV = 19%. If DPC > RCV, it was counted as a violation, i.e. failed delta check (FDC). The percentage of violations was calculated for every 20 consecutive patients with previous results over the past year. Similarly to MovSuM, when a new result is added, moving percentage of failed delta checks (MPFDC) removes the oldest data and calculates the percentage of violations continuously. Moving percentage of failed delta checks thresholds determined as 35%/30% (for positive/negative direction). After excluding dialysis patients and patients without previous results, and previous results measured with different systems, we applied truncation (truncation limits: < 27 and > 362 μmol/L). The remaining 5484 results were divided into 55 batches. Results: After applying positive and negative errors of 15%, median number of patients affected before error detection (MNPed) was 34 and 29, respectively. Median time until error detection was 18 minutes. Sensitivity and specificity were 96% and 86%, respectively. Conclusions: Moving percentage of failed delta checks, a novel RCV-based PBQC model, has high sensitivity and rapid error detection, suitable for measurands with low II.
The International Normalized Ratio (INR), introduced by the World Health Organization in 1983, is central to vitamin K antagonist (VKA) therapy monitoring. However, thromboplastin standardization alone does not ensure harmonized prothrombin time (PT)/INR results. Residual variability arises throughout the testing continuum. In this narrative review, we examine the principal sources of residual PT/INR non-equivalence across the “vein-to-report” pathway. Particular attention is devoted to clinical settings in which the assumptions underlying INR calibration are only partially satisfied, including advanced liver disease and exposure to direct oral anticoagulants. We further discuss postanalytical factors, such as determination of the mean normal prothrombin time and system-specific verification of the International Sensitivity Index, as well as quality assurance strategies, including the use of commutable external quality assessment materials and patient-based real-time quality control. Prothrombin time/INR harmonization requires integrating preanalytical practices, recognizing reagent-instrument dependencies, and quality strategies reflecting real-world testing conditions.
Introduction: We aimed to compare total serum vitamin B12 measurements across four immunoassay platforms, establish method-specific reference intervals, evaluate the clinical impact of a uniform deficiency cut-off, and assess associations between total vitamin B12 and holotranscobalaMaterials and methods: Residual serum samples from 220 apparently healthy adults undergoing routine health check-ups were analyzed. Total vitamin B12 was measured on Beckman, Abbott, Siemens, and Roche platforms. Beckman analyses used the updated Access Vitamin B12 II calibrator introduced in December 2024. Holotranscobalamin was measured on the Abbott system. Reference intervals were derived using non-parametric methods according to CLSI EP28-A3c guidelines. Method comparison was performed using Passing-Bablok regression and concordance correlation coefficients (CCC), and associations between total vitamin B12 and holoTC were assessed using Spearman correlation analysis. Results: Total vitamin B12 concentrations differed significantly across platforms, with moderate to good agreement (CCC: 0.81-0.91). Study-derived lower reference limits (LRLs) varied substantially between assays and differed from manufacturer-provided values, most prominently for the Beckman platform. Application of a fixed deficiency cut-off of 148 pmol/L resulted in marked method-dependent differences in deficiency classification. Correlations between total vitamin B12 and holoTC were low to moderate across analytical platforms. Conclusions: Serum vitamin B12 results vary across platforms, causing method-dependent LRLs and inconsistent classification with uniform cutoffs, underscoring the need for method-specific interpretation and improved harmonization. Low-to-moderate correlations reflect that holoTC and total vitamin B12 represent different components of vitamin B12 status and that total vitamin B12 assays differ by platform in reflecting the active fraction.
Guillain-Barré syndrome (GBS) is a leading cause of acquired acute neuromuscular paralysis and is an immune-mediated disorder of the peripheral nervous system (PNS). Accumulating evidence indi-cates that GBS is often preceded by infectious events that trigger autoimmune responses through mechanisms such as molecular mimicry and autoantibody production. Campylobacter jejuni remains the most common bacterial agent, but viral pathogens also contribute to the development of GBS. This review summarizes the current evidence regarding viruses as triggers of GBS, including herpes-viruses, hepatotropic viruses (A, B, C, and E), human immunodeficiency virus, Zika virus, influenza virus, varicella-zoster virus, and the coronavirus SARS-CoV-2. Emphasis is placed on laboratory test results related to viral GBS, including antiganglioside antibodies, serological markers of recent in-fection, molecular diagnostic methods, and cerebrospinal fluid analysis. From the standpoint of la-boratory medicine, both the clinical diagnosis and the distinction of GBS subtypes can be supported by the identification of recent viral infections and the detection of immunological biomarkers. How-ever, cross-reactivity, extended antibody persistence, and inadequate assay standardization frequently make it difficult to interpret laboratory test results. In patients with probable viral GBS, this review shows the diagnostic significance and limitations of routine laboratory testing. It also highlights the significance of close coordination between laboratory professionals and clinicians.
