Recommendations for Setting a Criterion and Assessing Commutability of Sample Materials Used in External Quality Assessment/Proficiency Testing Schemes.

It is important for external quality assessment materials (EQAMs) to be commutable with clinical samples; i.e., they should behave like clinical samples when measured using end-user clinical laboratory in vitro diagnostic medical devices (IVD-MDs). Using commutable EQAMs makes it possible to evaluate metrological traceability and/or equivalence of results between IVD-MDs. The criterion for assessing commutability of an EQAM between 2 IVD-MDs is that its result should be within the prediction interval limits based on the statistical distribution of the clinical sample results from the 2 IVD-MDs being compared. The width of the prediction interval is, among other things, dependent on the analytical performance characteristics of the IVD-MDs. A presupposition for using this criterion is that the differences in nonselectivity between the 2 IVD-MDs being compared are acceptable. An acceptable difference in nonselectivity should be small relative to the analytical performance specifications used in the external quality assessment scheme. The acceptable difference in nonselectivity is used to modify the prediction interval criterion for commutability assessment. The present report provides recommendations on how to establish a criterion for acceptable commutability for EQAMS, establish the difference in nonselectivity that can be accepted between IVD-MDs, and perform a commutability assessment. The report also contains examples for performing a commutability assessment of EQAMs.

Endometrial microbiome: sampling, assessment, and possible impact on embryo implantation.

There is growing interest on the potential clinical relevance of the endometrial microbiome. However, insufficient attention has been given to the methodology of sampling. To minimize contamination, we advocate the use of the double-lumen catheters commonly employed for the embryo transfer. Endometrial fluid samples obtained from 53 women scheduled for IVF were studied for microbiome characterization. Control samples from the vagina of these same women were concomitantly obtained. Samples were analysed by V3-V4-V6 regions of 16S rRNA gene sequencing with Next Generation Sequencing technique. Endometrial Lactobacillus-dominant cases were uncommon compared to previous evidence, being observed in only 4 (8%) women. Taxonomy markedly differed between the endometrial and vaginal microbiomes composition. The most common bacterial genera coincided in only 4 (8%) women. The comparison between women who did and did not subsequently become pregnant failed to identify any microorganism associated with the success of the procedure. However, the endometrial biodiversity resulted higher among pregnant women. Shannon's Equitability index in pregnant and non pregnant women was 0.76 [0.57-0.87] and 0.55 [0.51-0.64], respectively (p = 0.002). In conclusion, the use of embryo transfer catheters for testing the endometrial microbiome is promising. The scant concordance with vaginal samples supports the validity of this approach. Moreover, our study highlighted a possible beneficial role of a higher biodiversity on endometrial receptivity.

The assessment of high sensitivity cardiac troponin in patients with COVID-19: A multicenter study.

BACKGROUND: Recent studies have shown that patients diagnosed with coronarivus disease 2019 (COVID-19) and also with previous cardiovascular diseases have a higher mortality due to worsening heart disease. At the same time, patients without previous cardiovascular disease may also have cardiac complications. The aim of this multicenter study was to assess high sensitivity cardiac troponin T (hs-cTnT) in patients with COVID-19 and to evaluate the incidence of myocardial injury. METHODS: In this multicenter study we enrolled 543 patients, 57.8% males, median age 63 years (range 18-99) from three selected hospitals: University Hospital Tor Vergata in Rome, Fondazione IRCCS Ca 'Granda Ospedale Maggiore Policlinico, in Milan, S Chiara Hospital in Trento. We measured hs-cTnT in all patients to assess myocardial injury and correlations with patient's age, symptoms and disease course. RESULTS: The data showed that, among the 543 patients studied, 257 patients (47.3%) had hs-cTnT values higher than the upper reference limit (URL) of 14 ng/L. Patients with high hs-cTnT had more frequently fever (p < 0.01) and respiratory symptoms (p < 0.01), compared to the group with hs-cTnT values below URL. The results showed also that patients with hs-cTnT above URL had a higher frequency of previous cardiovascular disease (p < 0.01) as well as of hypertension (p < 0.01). Instead, among 231 patients with no previous cardiovascular disease, 81 (31.5%) had hs-cTnT values above the URL. Finally. the majority of the patients with high hs-cTnT were admitted to the intensive care unit (p < 0.01). CONCLUSION: Our data suggest the assessment of high sensitivity cardiac troponin in patients with COVID-19 for early diagnosis of cardiac involvement.

Triage process for the assessment of coronavirus disease 2019-positive patients with cancer: The ONCOVID prospective study.

BACKGROUND: Patients with cancer are considered at high risk for the novel respiratory illness coronavirus disease 2019 (COVID-19). General measures to keep COVID-19-free cancer divisions have been adopted worldwide. The objective of this study was to evaluate the efficacy of triage to identify COVID-19 among patients with cancer. METHODS: From March 20 to April 17, 2020, data were collected from patients who were treated or followed at the authors' institution in a prospective clinical trial. The primary endpoint was to estimate the cumulative incidence of COVID-19-positive patients who were identified using a triage process through the aid of medical and patient questionnaires. Based on a diagnostic algorithm, patients with suspect symptoms underwent an infectious disease specialist's evaluation and a COVID-19 swab. Serologic tests were proposed for patients who had symptoms or altered laboratory tests that did not fall into the diagnostic algorithm but were suspicious for COVID-19. RESULTS: Overall, 562 patients were enrolled. Six patients (1%) were diagnosed with COVID-19, of whom 4 (67%) had the disease detected through telehealth triage, and 2 patients (33%) without suspect symptoms at triage had the disease detected later. Seventy-one patients (13%) had suspect symptoms and/or altered laboratory tests that were not included in the diagnostic algorithm and, of these, 47 patients (73%) underwent testing for severe acute respiratory syndrome coronavirus 2 antibody: 6 (13%) were positive for IgG (n = 5) or for both IgM and IgG (n = 1), and antibody tests were negative in the remaining 41 patients. CONCLUSIONS: The triage process had a positive effect on the detection of COVID-19 in patients with cancer. Telehealth triage was helpful in detecting suspect patients and to keep a COVID-19-free cancer center. The overall incidence of COVID-19 diagnosis (1%) and antibody positivity (13%) in patients with suspect symptoms was similar to that observed in the general population.

Commutability Assessment of Candidate Reference Materials for Pancreatic α-Amylase.

BACKGROUND: Measurement standardization of the catalytic concentration of α-amylase in serum is based on 3 pillars: the primary reference measurement procedure (PRMP), reference laboratories, and suitable certified reference materials (CRMs). Commutability is a prerequisite when using a CRM for calibration and trueness control of routine methods or for value transfer from the PRMP to end-user calibrators of routine methods through a calibration hierarchy. METHODS: We performed a commutability study with 30 serum pools and 5 candidate reference materials (RMs) for pancreatic α-amylase using an automated version of the PRMP and 5 different routine methods. Four candidate RMs had an artificial matrix, each with a different composition, and 1 candidate RM was based on human serum. Data were analyzed according to a linear regression analysis with prediction interval as described in the Clinical and Laboratory Standards Institute guideline EP30-A and a difference in bias analysis as described in the recommendations of the IFCC Working Group on Commutability. RESULTS: The commutability profile of the 4 candidate RMs with an artificial matrix was variable. Only 1 candidate RM, with human serum albumin in the matrix, showed a good profile like that of the candidate RM based on serum. The comparison of both commutability assessment approaches indicated some differences because of inconclusive results for the difference in bias approach, suggesting a large uncertainty on the commutability assessment. CONCLUSIONS: A CRM for pancreatic amylase in an artificial matrix can be commutable for routine methods using the same substrate as the PRMP, but the matrix composition is crucial.

Comparative performance assessment of point-of-care testing devices for measuring glucose and ketones at the patient bedside.

Point-of-care (POC) testing devices for monitoring glucose and ketones can play a key role in the management of dysglycemia in hospitalized diabetes patients. The accuracy of glucose devices can be influenced by biochemical changes that commonly occur in critically ill hospital patients and by the medication prescribed. Little is known about the influence of these factors on ketone POC measurements. The aim of this study was to assess the analytical performance of POC hospital whole-blood glucose and ketone meters and the extent of glucose interference factors on the design and accuracy of ketone results. StatStrip glucose/ketone, Optium FreeStyle glucose/ketone, and Accu-Chek Performa glucose were also assessed and results compared to a central laboratory reference method. The analytical evaluation was performed according to Clinical and Laboratory Standards Institute (CLSI) protocols for precision, linearity, method comparison, and interference. The interferences assessed included acetoacetate, acetaminophen, ascorbic acid, galactose, maltose, uric acid, and sodium. The accuracies of both Optium ketone and glucose measurements were significantly influenced by varying levels of hematocrit and ascorbic acid. StatStrip ketone and glucose measurements were unaffected by the interferences tested with exception of ascorbic acid, which reduced the higher level ketone value. The accuracy of Accu-Chek glucose measurements was affected by hematocrit, by ascorbic acid, and significantly by galactose. The method correlation assessment indicated differences between the meters in compliance to ISO 15197 and CLSI 12-A3 performance criteria. Combined POC glucose/ketone methods are now available. The use of these devices in a hospital setting requires careful consideration with regard to the selection of instruments not sensitive to hematocrit variation and presence of interfering substances.

The role of External Quality Assessment Schemes in monitoring and improving the standardization process.

This paper examines the evolution of External Quality Assessment Schemes (EQAS), focusing on the need for target values based on reference methods and control material commutability. Although the key role of EQAS in the standardization process has been clear from the start, it has never been totally implemented, mainly due to the lack of commutable materials. Costs, the difficulty to assign reference method values, and the non-availability of field methods able to provide results traceable to the reference measurement system have also played an important role. Using commutable materials with target values assigned by reference methods, EQAS can define and verify the uncertainty of test results produced by analytical methods. EQAS may also improve standardization, proposing rules for the post-analytical phase (uniform units of measurement, description of measurands, rounding off and number of decimal places to report). Only the described EQAS may become a reliable indicator of the status of the standardization process. Improvements will only take place if stakeholders (governments and international organizations, scientific societies, manufacturers and specialists in laboratory medicine) act in a coordinated way to take corrective action every time EQAS clearly indicates a suboptimal situation.

Comparison of the results from two different External Quality Assessment Schemes supports the utility of robust quality specifications.

BACKGROUND: The definition of quality goals to evaluate the performance of laboratories participating in External Quality Assessment Schemes (EQAS) is currently not homogeneous. The aim of the work was to verify the applicability of quality goals based on biological variation comparing the results from two different EQAS. METHODS: We evaluated the performance of the laboratories participating in two Italian EQAS, presenting similar characteristics in terms of number of participants, type of EQA-samples, and program organization. The results were obtained during 2007 for 27 components in the regional scheme of Lombardy (RGL) and in the national scheme of Prolarit (PRL). The percentage total error of single measurements was calculated for each reported EQA value. The total error values at the 68th percentile, at selected critical concentration values, were compared with maximum tolerable error derived from biological variation. RESULTS: The performance of laboratories participating in the RGL scheme was significantly better. The frequency of satisfactory performance at, respectively, minimum, desirable and optimum levels was 98%, 80% and 59% in the RGL scheme, and 73%, 56% and 22% in the PRL scheme. CONCLUSIONS: Due to the different performance shown in the two programs, objective analytical goals based on biological variability constitute the optimal solution.

Reference intervals for serum creatinine concentrations: assessment of available data for global application.

BACKGROUND: Reference intervals for serum creatinine remain relevant despite the current emphasis on the use of the estimated glomerular filtration rate for assessing renal function. Many studies on creatinine reference values have been published in the last 20 years. Using criteria derived from published IFCC documents, we sought to identify universally applicable reference intervals for creatinine via a systematic review of the literature. METHODS: Studies were selected for inclusion in the systematic review only if the following criteria were met: (a) reference individuals were selected using an "a priori" selection scheme, (b) preanalytical conditions were adequately described; (c) traceability of the produced results to the isotope dilution-mass spectrometry (IDMS) reference method was demonstrated experimentally, and (d) the collected data received adequate statistical treatment. RESULTS: Of 37 reports dealing specifically with serum creatinine reference values, only 1 report with pediatric data and 5 reports with adult data met these criteria. The primary reason for exclusion of most papers was an inadequate demonstration of measurement traceability. Based on the data of the selected studies, we have collated recommended reference intervals for white adults and children. CONCLUSION: Laboratories using methods producing traceable results to IDMS can apply the selected reference intervals for serum creatinine in evaluating white individuals.