18 research outputs found
Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality
APS calculator: A data-driven tool for setting outcome-based analytical performance specifications for measurement uncertainty using specific clinical requirements and population data
According to ISO 15189:2022, analytical performance specifications (APS) should relate to intended clinical use and impact on patient care. Therefore, we aimed to develop a web application for laboratory professionals to calculate APS based on a simulation of the impact of measurement uncertainty (MU) on the outcome using the chosen decision limits, agreement thresholds, and data of the population of interest. We developed the "APS Calculator"allowing users to upload and select data of concern, specify decision limits and agreement thresholds, and conduct simulations to determine APS for MU. The simulation involved categorizing original measurand concentrations, generating measured (simulated) results by introducing different degrees of MU, and recategorizing measured concentrations based on clinical decision limits and acceptable clinical misclassification rates. The agreements between original and simulated result categories were assessed, and values that met or exceeded user-specified agreement thresholds that set goals for the between-category agreement were considered acceptable. The application generates contour plots of agreement rates and corresponding MU values. We tested the application using National Health and Nutrition Examination Survey data, with decision limits from relevant guidelines. We determined APS for MU of six measurands (blood total hemoglobin, plasma fasting glucose, serum total and high-density lipoprotein cholesterol, triglycerides, and total folate) to demonstrate the potential of the application to generate APS. The developed data-driven web application offers a flexible tool for laboratory professionals to calculate APS for MU using their chosen decision limits and agreement thresholds, and the data of the population of interest
An approach for determining allowable between reagent lot variation
Clinicians trust medical laboratories to provide reliable results on
which they rely for clinical decisions. Laboratories fulfil their
responsibility for accurate and consistent results by utilizing an
arsenal of approaches, ranging from validation and verification
experiments to daily quality control procedures. All these procedures
verify, on different moments, that the results of a certain examination
procedure have analytical performance characteristics (APC) that meet
analytical performance specifications (APS) set for a particular
intended use. The APC can in part be determined by estimating the
measurement uncertainty component under conditions of within-laboratory
precision (u (Rw)), which comprises all components influencing the
measurement uncertainty of random sources. To maintain the adequacy of
their measurement procedures, laboratories need to distinguish aspects
that are manageable vs. those that are not. One of the aspects that may
influence u (Rw) is the momentary significant bias caused by shifts in
reagent and/or calibrator lots, which, when accepted or unnoticed,
become a factor of the APC. In this paper, we postulate a model for
allocating a part of allowable u (Rw) to between-reagent lot variation,
based on the need for long-term consistency of the measurement
variability for that specific measurand. The allocation manages the
ratio between short-term and long-term variation and indicates
laboratories when to reject or correct certain variations due to reagent
lots
Improving the laboratory result release process in the light of ISO 15189:2012 standard
The ISO 15189:2012 standard section 5.9.1 requires laboratories to
review results before release, considering quality control, previous
results, and clinical information, if any, and to issue documented
procedures about it. While laboratory result reporting is generally
regarded as part of the post-analytical phase, the result release
process requires a general view of the total examination process.
Reviewing test results may follow with troubleshooting and test
repetition, including reanalyzing an individual sample or resampling. A
systematic understanding of the result release may help laboratory
professionals carry out appropriate test repetition and ensure the
plausibility of laboratory results. In this paper, we addressed the
crucial steps in the result release process, including evaluation of
sample quality, critical result notification, result reporting, and
recommendations for the management of the result release, considering
quality control alerts, instrument flags, warning messages, and
interference indexes. Error detection tools and plausibility checks
mentioned in the present paper can support the daily practice of results
release
Comparison of three methods for determining anti-thyrotropin receptor antibodies (TRAb) for diagnosis of Gravesâ disease: a clinical validation
Gravesâ disease is secondary to the presence of anti-thyrotropin receptor antibodies (TRAb), which stimulate thyroid hormones. TRab determination is crucial for etiological diagnosis. The objectives of this study were (i)Â to compare two methods for determining TRab by chemoluminiscence vs. standard TRACE-immunofluorescence; (ii) to determine the diagnostic validity of the three methods
ComparaciĂłn de tres mĂ©todos para la medida de la concentraciĂłn de anticuerpos anti-receptor de tirotropina (TRAb) en el diagnĂłstico de la enfermedad de Graves. ValidaciĂłn clĂnica
La enfermedad de Graves (EG) es una enfermedad secundaria a la presencia de autoanticuerpos anti-receptor de TSH (TRAb) que estimulan la producción de hormonas tiroideas. La medida de la concentración de TRAb es crucial para su diagnóstico etiológico. Los objetivos de este estudio fueron 1. Comparar dos métodos de medida de TRAb por quimioluminiscencia con el método habitual del laboratorio (TRACE-inmunofluorescencia). 2. Determinar la validez diagnóstica de los tres métodos
Recommendation for the review of biological reference intervals in medical laboratories (vol 54, pg 1893, 2016)
This document is based on the original recommendation of the Expert
Panel on the Theory of Reference Values of the International Federation
of Clinical Chemistry and Laboratory Medicine (IFCC), updated guidelines
were recently published under the auspices of the IFCC and the Clinical
and Laboratory Standards Institute (CLSI). This document summarizes
proposals for recommendations on: (i) The terminology, which is often
confusing, noticeably concerning the terms of reference limits and
decision limits. (ii) The method for the determination of reference
limits according to the original procedure and the conditions, which
should be used. (iii) A simple procedure allowing the medical
laboratories to fulfill the requirements of the regulation and
standards. The updated document proposes to verify that published
reference limits are applicable to the laboratory involved. Finally, the
strengths and limits of the revised recommendations (especially the
selection of the reference population, the maintenance of the analytical
quality, the choice of the statistical method used.) will be briefly
discussed
Improving the laboratory result release process in the light of ISO 15189:2012 standard
The ISO 15189:2012 standard section 5.9.1 requires laboratories to review results before release, considering quality control, previous results, and clinical information, if any, and to issue documented procedures about it. While laboratory result reporting is generally regarded as part of the post-analytical phase, the result release process requires a general view of the total examination process. Reviewing test results may follow with troubleshooting and test repetition, including reanalyzing an individual sample or resampling. A systematic understanding of the result release may help laboratory professionals carry out appropriate test repetition and ensure the plausibility of laboratory results. In this paper, we addressed the crucial steps in the result release process, including evaluation of sample quality, critical result notification, result reporting, and recommendations for the management of the result release, considering quality control alerts, instrument flags, warning messages, and interference indexes. Error detection tools and plausibility checks mentioned in the present paper can support the daily practice of results release