Driving consistency: CEPI-Centralized Laboratory Network's conversion factor initiative for SARS-CoV-2 clinical assays used for efficacy assessment of COVID vaccines.

To date, thousands of SARS-CoV-2 samples from many vaccine developers have been tested within the CEPI-Centralized Laboratory Network. To convert data from each clinical assay to international standard units, the WHO international standard and the CEPI standard generated by the Medicines and Healthcare products Regulatory Agency were run in multiple facilities to determine the conversion factor for each assay. Reporting results in international units advances global understanding of SARS-CoV-2 immunity and vaccine efficacy, enhancing the quality, reliability, and utility of clinical assay data.

A Novel Approach for Routinely Assessing Laboratory Sigma Metrics for a Broad Range of Automated Assays.

BACKGROUND: Sigma metrics have been adapted for the clinical laboratory to incorporate observed accuracy, precision, and total error allowed. The higher the Sigma level for a process, the better performance that process has. A limitation of studies assessing Sigma metrics is that they are performed on a small number of well-controlled systems. METHODS: An algorithm was developed to extract QC data and derive the Sigma metric for 115 analytes from sites connected to the QuidelOrtho E-Connectivity® database. The median of these results was then used to derive the Sigma metric for each assay. RESULTS: In this analysis, 79 out of 115 (68.7%) of the assays assessed achieved 6 Sigma or better and 98 out of 115 (85.2%) achieved 5 Sigma or better. CONCLUSIONS: This study has demonstrated a methodology that can be used to condense Sigma metrics from hundreds of analyzers into a single metric of assay quality. Because these analyzers are running in working laboratories from around the world, this analysis can serve as a baseline for understanding the assay performance achieved in the presence of variabilities such as lab-to-lab, instrument-to-instrument, material handling, environmental conditions, and reagent lot. The significant number of assays demonstrating high Sigma levels did so despite this variation. The ability of the methods reported here to include hundreds of analyzers represents a novel approach for assessing Sigma metrics in clinical laboratories.

Harmonizing the post-analytical phase: focus on the laboratory report.

The final, post-analytical, phase of laboratory testing is increasingly recognized as a fundamental step in maximizing quality and effectiveness of laboratory information. There is a need to close the loop of the total testing cycle by improving upon the laboratory report, and its notification to users. The harmonization of the post-analytical phase is somewhat complicated, mainly because it calls for communication that involves parties speaking different languages, including laboratorians, physicians, information technology specialists, and patients. Recently, increasing interest has been expressed in integrated diagnostics, defined as convergence of imaging, pathology, and laboratory tests with advanced information technology (IT). In particular, a common laboratory, radiology and pathology diagnostic reporting system that integrates text, sentinel images and molecular diagnostic data to an integrated, coherent interpretation enhances management decisions and improves quality of care.

Lessons from Theranos - Restructuring Biomedical Innovation.

After raising more than $700 million, Elizabeth Holmes, the founder and chief executive officer of a healthcare startup once valued at $10 billion, was found guilty on four charges of defrauding investors. Founded in 2003, Theranos Inc. was a privately held corporation that aimed to disrupt the diagnostics industry with rapid, direct-to-consumer laboratory testing using only "a drop of blood" and the company's patented Nanotainer technology. By exploiting gaps in regulatory policy, Theranos brought its panel of laboratory tests to patients without pre-market review or validation from peer-reviewed scientific research. Investigations into Theranos' dubious operations and inaccurate test results exposed the failed venture which had squandered millions of dollars. Theranos affected the lives and health of patients further disrupting an already tenuous relationship between healthcare and the public - the importance of which cannot be understated in the setting of the COVID-19 pandemic. As medical systems address a national public health crisis and pervasive structural inequities, we must align stakeholder incentives between industry and academic biomedical innovation to rebuild trust with our patients.

External quality assessment of COVID-19 real time reverse transcription PCR laboratories in India.

Sudden emergence and rapid spread of COVID-19 created an inevitable need for expansion of the COVID-19 laboratory testing network across the world. The strategy to test-track-treat was advocated for quick detection and containment of the disease. Being the second most populous country in the world, India was challenged to make COVID-19 testing available and accessible in all parts of the country. The molecular laboratory testing network was augmented expeditiously, and number of laboratories was increased from one in January 2020 to 2951 till mid-September, 2021. This rapid expansion warranted the need to have inbuilt systems of quality control/ quality assurance. In addition to the ongoing inter-laboratory quality control (ILQC), India implemented an External Quality Assurance Program (EQAP) with assistance from World Health Organization (WHO) and Royal College of Pathologists, Australasia. Out of the 953 open system rRTPCR laboratories in both public and private sector who participated in the first round of EQAP, 891(93.4%) laboratories obtained a passing score of > = 80%. The satisfactory performance of Indian COVID-19 testing laboratories has boosted the confidence of the public and policy makers in the quality of testing. ILQC and EQAP need to continue to ensure adherence of the testing laboratories to the desired quality standards.

Diagnostic value of different interleukins and procalcitonin in critically ill patients admitted with suspected sepsis.

BACKGROUND: : Many biomarkers have now been studied such as C-reactive Protein (CRP), procalcitonin (PCT), etc., and are widely used for the diagnosis of sepsis in clinical practice which may determine the appropriate antibiotic treatment. A flowcytometric cytokine bead array (CBA) assay has now been used to determine multiple interleukins (IL), simultaneously. The aim of this study was to determine the cytokine (IL2, IL4, IL6, IL10, TNFα, INFγ, and IL17) profiles of interleukins in plasma of sepsis patients by using multiplex Flowcytometric CBA array assay. MATERIALS AND METHOD: s: A total of 99 consecutive patients admitted with the suspected sepsis were studied. PCT concentrations were measured by using the enzyme-linked fluorescent immunoassay (ELFA) technique and flow cytometry-based BD™ CBA Cytokine Kit was used to evaluate levels of 7 cytokines [IL-2, IL-4, IL-6, IL-10, Tumour Necrosis Factor (TNF), Interferon- γ (IFN-γ), and IL-17A]. RESULTS: Microbiologically defined infection (MDI) demonstrated a positive culture report in 79/99 (79.7%) of patients. The IL6 [1873.7 (4-5000)] and IL10 [(154.7 (0-1764)] levels were significantly higher in septic patients than those in the negative MDI IL6 [901 (4-5000)] and IL10 [110.4 (4-1372)] levels. The AUROC value of IL6 [0.66 (0.53-0.79)] was found to be the highest among all followed by IL10 [0.65 (0.51-0.79)], IFNγ [0.63 (0.51-0.77)], PCT [0.61 (0.48-0.75)], and TNFα [0.55 (0.42-0.69)]. CONCLUSION: Our study suggests that that IL6 is substantially more economical and can reduce the investigation cost to half as compared with the procalcitonin assay.

Prevalence of Latent Tuberculosis Infection Among Healthy Young Children and Adolescents and a Two-step Approach for the Diagnosis of Tuberculosis Infection in Chengdu, China.

BACKGROUND: China has a high burden of tuberculosis and latent tuberculosis infection (LTBI). The aim of this study was to estimate the prevalence of LTBI among healthy young children and adolescents and test a 2-step approach to explore the threshold for the diagnosis of tuberculosis infection in Chengdu, China. METHODS: Healthy preschool children and school-going children in Chengdu, Sichuan Province, were screened for LTBI using the tuberculin skin test (TST). Preschool children with TST ≥ 5 mm also underwent interferon-γ release assay (IGRA) to explore the threshold of this 2-step approach. RESULTS: In total, 5667 healthy young children and adolescents completed TST test between July 2020 and January 2021 and were included in the present analysis. The age of the participants ranged from 2.4 to 18 years (median 7.25 ± 4.514 years), of which 2093 (36.9%) were younger than 5 years. The overall prevalence of LTBI was 6.37% and 6.64% in children younger than 5 years old. Fourteen of the 341 preschool children with TST ≥5 mm were interferon-γ release assay positive, of which 4 showed a TST result of 5-10 mm, and 6 preschool children received preventive treatment for LTBI. CONCLUSIONS: Healthy young children and adolescents should also be considered as important target populations for LTBI screening. TST can be recommended for first-line screening as part of a 2-step approach for LTBI screening using a positive threshold of 5 mm.

A Critical Review on the Standardization and Quality Assessment of Nonfunctional Laboratory Tests Frequently Used to Identify Inborn Errors of Immunity.

Inborn errors of immunity (IEI), which were previously termed primary immunodeficiency diseases, represent a large and growing heterogeneous group of diseases that are mostly monogenic. In addition to increased susceptibility to infections, other clinical phenotypes have recently been associated with IEI, such as autoimmune disorders, severe allergies, autoinflammatory disorders, benign lymphoproliferative diseases, and malignant manifestations. The IUIS 2019 classification comprises 430 distinct defects that, although rare individually, represent a group affecting a significant number of patients, with an overall prevalence of 1:1,200-2,000 in the general population. Early IEI diagnosis is critical for appropriate therapy and genetic counseling, however, this process is deeply dependent on accurate laboratory tests. Despite the striking importance of laboratory data for clinical immunologists, several IEI-relevant immunoassays still lack standardization, including standardized protocols, reference materials, and external quality assessment programs. Moreover, well-established reference values mostly remain to be determined, especially for early ages, when the most severe conditions manifest and diagnosis is critical for patient survival. In this article, we intend to approach the issue of standardization and quality control of the nonfunctional diagnostic tests used for IEI, focusing on those frequently utilized in clinical practice. Herein, we will focus on discussing the issues of nonfunctional immunoassays (flow cytometry, enzyme-linked immunosorbent assays, and turbidimetry/nephelometry, among others), as defined by the pure quantification of proteins or cell subsets without cell activation or cell culture-based methods.

[Step by step - A diagnostic approach to bleeding disorders]. / Abklärung erhöhter Blutungsneigung ­ Schritt für Schritt.

The main symptom of hemorrhagic diathesis is an increased bleeding tendency. Due to the subjectivity of various features of the bleeding history, unclarity of the family history, and an individualization of the extent of diagnostic the evaluation of a suspected bleeding disorder represents a challenging endeavour in hematology. Hemorrhagic diathesis can be divided into the following sub-categories: disorders in primary hemostasis (e. g. von Willebrand disease, different causes of thrombocytopenia), secondary hemostasis (e. g. hemophilia A and B, Vitamin K deficiency) and fibrinolysis, and in connective tissue or vascular formation. This article reviews available diagnostic methods for bleeding disorders, from structured patient history to highly specialized laboratory diagnosis.

Combining Multiple Assays Improves Detection and Serotyping of Foot-and-Mouth Disease Virus. A Practical Example with Field Samples from East Africa.

Multiple serotypes and topotypes of foot-and-mouth disease virus (FMDV) circulate in endemic areas, posing considerable impacts locally. In addition, introductions into new areas are of great concern. Indeed, in recent years, multiple FMDV outbreaks, caused by topotypes that have escaped from their original areas, have been recorded in various parts of the world. In both cases, rapid and accurate diagnosis, including the identification of the serotype and topotype causing the given outbreaks, plays an important role in the implementation of the most effective and appropriate measures to control the spread of the disease. In the present study, we describe the performance of a range of diagnostic and typing tools for FMDV on a panel of vesicular samples collected in northern Tanzania (East Africa, EA) during 2012-2018. Specifically, we tested these samples with a real-time RT-PCR targeting 3D sequence for pan-FMDV detection; an FMDV monoclonal antibody-based antigen (Ag) detection and serotyping ELISA kit; virus isolation (VI) on LFBKαVß6 cell line; and a panel of four topotype-specific real-time RT-PCRs, specifically tailored for circulating strains in EA. The 3D real-time RT-PCR showed the highest diagnostic sensitivity, but it lacked typing capacity. Ag-ELISA detected and typed FMDV in 71% of sample homogenates, while VI combined with Ag-ELISA for typing showed an efficiency of 82%. The panel of topotype-specific real-time RT-PCRs identified and typed FMDV in 93% of samples. However, the SAT1 real-time RT-PCR had the highest (20%) failure rate. Briefly, topotype-specific real-time RT-PCRs had the highest serotyping capacity for EA FMDVs, although four assays were required, while the Ag-ELISA, which was less sensitive, was the most user-friendly, hence suitable for any laboratory level. In conclusion, when the four compared tests were used in combination, both the diagnostic and serotyping performances approached 100%.

Comparison of seven heterophile antibody assays for laboratory diagnosis of infectious mononucleosis in pediatric patients.

Heterophile antibody assays have been used to aid the diagnosis of infectious mononucleosis caused by the Epstein-Barr virus. Seven commercially available assays currently widely utilized in clinical laboratories were compared in this study. Variable performance characteristics and assay times are observed, and these pieces of data may assist clinical laboratories in assay selection and result interpretation.