Coming in Hot: A quality improvement approach to improving care of febrile infants.

Background and Objectives: Significant practice variation exists in managing young infants with fever. Quality improvement strategies can aid in risk stratification and standardization of best care practices, along with a reduction of unnecessary interventions. The aim of this initiative was to safely reduce unnecessary admissions, antibiotics, and lumbar punctures (LPs) by 10% in low-risk, febrile infants aged 29 to 90 days presenting to the emergency department (ED) over a 12-month period. Methods: Using the Model for Improvement, a multidisciplinary team developed a multipronged intervention: an updated clinical decision tool (CDT), procalcitonin (PCT) adoption, education, a feedback tool, and best practice advisory (BPA) banner. Outcome measures included the proportion of low-risk infants that were admitted, received antibiotics, and had LPs. Process measures were adherence to the CDT and percentage of PCT ordered. Missed bacterial infections and return visits were balancing measures. The analysis was completed using descriptive statistics and statistical process control methods. Results: Five hundred and sixteen patients less than 90 days of age were included in the study, with 403 patients in the 29- to 90-day old subset of primary interest. In the low-risk group, a reduction in hospital admissions from a mean of 24.1% to 12.0% and a reduction in antibiotics from a mean of 15.2% to 1.3% was achieved. The mean proportion of LPs performed decreased in the intervention period from 7.5% to 1.8%, but special cause variation was not detected. Adherence to the CDT increased from 70.4% to 90.9% and PCT was ordered in 92.3% of cases. The proportion of missed bacterial infections was 0.3% at baseline and 0.5% in the intervention period while return visits were 6.7% at baseline and 5.0% in the intervention period. Conclusions: The implementation of a quality improvement strategy, including an updated evidence-based CDT for young infant fever incorporating PCT, safely reduced unnecessary care in low-risk, febrile infants aged 29 to 90 days in the ED. Purpose: To develop and implement a multipronged improvement strategy including an evidence-based CDT utilizing PCT to maximize value of care delivered to well-appearing, febrile infants presenting to EDs.

Age-specific reference intervals for routine biochemical parameters in healthy neonates, infants, and young children in Iran.

Age and sex need to be considered in the establishment of reference intervals (RIs), especially in early life when there are dynamic physiological changes. Since data for important biomarkers in healthy neonates and infants are limited, particularly in Iranian populations, we have determined age-specific RIs for 7 laboratory biochemical parameters. This cross-sectional study comprised a total of 344 paediatric participants (males: 158, females: 186) between the ages of 3 days and 30 months (mean age: 12.91 ± 7.15 months). Serum levels of creatinine, urea, uric acid, calcium, phosphate, vitamin D and high-sensitivity C-reactive protein (hs-CRP) were measured using an Alpha classic-AT plus auto-analyser. We determined age-specific RIs using CLSI Ep28-A3 and C28-A3 guidelines. No sex partitioning was required for any of the biomarkers. Age partitioning was required for kidney function tests and phosphate. The serum concentration of urea and creatinine increased with age, while phosphate and uric acid decreased with age. Age partitioning was not required for serum calcium, vitamin D, and hs-CRP, which remained relatively constant throughout the age range. Age-specific RIs for 7 routine biochemical markers were determined to address critical gaps in RIs in early life to help improve clinical interpretation of blood test results in young children, including neonates. Established age partitions demonstrate the biochemical changes that take place during child growth and development. These novel data will ultimately better disease management in the Iranian paediatric population and can be of value to clinical and hospital laboratories with similar populations.

Reference Interval Harmonization: Harnessing the Power of Big Data Analytics to Derive Common Reference Intervals across Populations and Testing Platforms.

BACKGROUND: Harmonization in laboratory medicine is essential for consistent and accurate clinical decision-making. There is significant and unwarranted variation in reference intervals (RIs) used by laboratories for assays with established analytical traceability. The Canadian Society of Clinical Chemists (CSCC) Working Group on Reference Interval Harmonization (hRI-WG) aims to establish harmonized RIs (hRIs) for laboratory tests and support implementation. METHODS: Harnessing the power of big data, laboratory results were collected across populations and testing platforms to derive common adult RIs for 16 biochemical markers. A novel comprehensive approach was established, including: (a) analysis of big data from community laboratories across Canada; (b) statistical evaluation of age, sex, and analytical differences; (c) derivation of hRIs using the refineR method; and (d) verification of proposed hRIs across 9 laboratories with different instrumentation using serum and plasma samples collected from healthy Canadian adults. RESULTS: Harmonized RIs were calculated for all assays using the refineR method, except free thyroxine. Derived hRIs met proposed verification criterion across 9 laboratories and 5 manufacturers for alkaline phosphatase, albumin (bromocresol green), chloride, lactate dehydrogenase, magnesium, phosphate, potassium (serum), and total protein (serum). Further investigation is needed for some analytes due to failure to meet verification criteria in one or more laboratories (albumin [bromocresol purple], calcium, total carbon dioxide, total bilirubin, and sodium) or concern regarding excessively wide hRIs (alanine aminotransferase, creatinine, and thyroid stimulating hormone). CONCLUSIONS: We report a novel data-driven approach for RI harmonization. Findings support feasibility of RI harmonization for several analytes; however, some presented challenges, highlighting limitations that need to be considered in harmonization and big data analytics.

Mining the Gap: Deriving Pregnancy Reference Intervals for Hematology Parameters Using Clinical Datasets.

BACKGROUND: Physiological changes during pregnancy invalidate use of general population reference intervals (RIs) for pregnant people. The complete blood count (CBC) is commonly ordered during pregnancy, but few studies have established pregnancy RIs suitable for contemporary Canadian mothers. Prospective RI studies are challenging to perform during pregnancy while retrospective techniques fall short as pregnancy and health status are not readily available in the laboratory information system (LIS). This study derived pregnancy RIs retrospectively using LIS data linked to provincial perinatal registry data. METHODS: A 5-year healthy pregnancy cohort was defined from the British Columbia Perinatal Data Registry and linked to laboratory data from two laboratories. CBC and differential RIs were calculated using direct and indirect approaches. Impacts of maternal and pregnancy characteristics, such as age, body mass index, and ethnicity, on laboratory values were also assessed. RESULTS: The cohort contained 143 106 unique term singleton pregnancies, linked to >972 000 CBC results. RIs were calculated by trimester and gestational week. Result trends throughout gestation aligned with previous reports in the literature, although differences in exact RI limits were seen for many tests. Trimester-specific bins may not be appropriate for several CBC parameters that change rapidly within trimesters, including red blood cells (RBCs), some leukocyte parameters, and platelet counts. CONCLUSIONS: Combining information from comprehensive clinical databases with LIS data provides a robust and reliable means for deriving pregnancy RIs. The present analysis also illustrates limitations of using conventional trimester bins during pregnancy, supporting use of gestational age or empirically derived bins for defining CBC normal values during pregnancy.

Central role of laboratory medicine in public health and patient care.

Clinical laboratories play a vital role in the healthcare system. Objective medical data provided by clinical laboratories supports approximately 60-70% of clinical decisions, however, evidence supporting this claim is poorly documented and laboratories still lack visibility, despite their indisputable impact on patient care and public health. The International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on Outcome Studies in Laboratory Medicine (TF-OSLM) was recently developed to support directed research evaluating the role of laboratory medicine on clinical outcomes. Establishing and documenting this evidence is key to enhance visibility of the field in the eye of the public and other healthcare professionals together with optimizing patient outcomes and health care system operations. In this review, we discuss four areas that exemplify the contribution of laboratory medicine directly to patient care. This includes high-sensitivity cardiac troponin (hs-cTn) and N-terminal pro-B-type natriuretic peptide/B-type natriuretic peptides (NT-proBNP/BNP) for the diagnosis and prognosis of myocardial infarction and heart failure, respectively, and procalcitonin for the management of sepsis and antibiotic stewardship. Emerging markers of traumatic brain injury and the role of laboratory medicine in the fight against the COVID-19 pandemic are discussed along with an introduction to plans of IFCC TF-OSLM.

LMS-based continuous reference percentiles for 14 laboratory parameters in the CALIPER cohort of healthy children and adolescents.

OBJECTIVES: Marked physiological changes in growth and development present challenges in defining pediatric reference intervals for biomarkers of health and disease. Lambda, Mu, and Sigma (LMS)-based statistical modeling provides a continuous normal distribution by negating skewness and variation, and is commonly used to establish growth charts. Such LMS reference curves are suggested to enhance laboratory test result interpretation. The current study establishes LMS-based continuous reference percentiles for 14 biomarkers in the CALIPER cohort of healthy children and adolescents. METHODS: Data from healthy children and adolescents aged 1-<19 years were used to establish continuous reference percentiles using a novel LMS-based statistical method, including 2.5th, 25th, 50th, 75th, and 97.5th percentiles. The LMS approach applies a Box-Cox data transformation and summarizes continuous distributions by age via three curves: skewness (Lambda), median (Mu), and coefficient of variation (Sigma). RESULTS: LMS-based percentiles and z-scores were generated for 14 common pediatric biomarkers that demonstrate dynamic concentration patterns with age (e.g., alkaline phosphatase) and/or wherein the magnitude of difference from the population mean may be clinically relevant (e.g., triglycerides). The LMS model captured age- and sex-specific distributions accurately and was not substantially influenced by outlying points. CONCLUSIONS: This is the first study to establish LMS-based continuous reference percentiles for biochemical markers in a healthy Canadian pediatric population. The current LMS-based approach builds upon previous continuous reference interval models by providing graded percentiles to improve test result interpretation, particularly with repeated measures over time. This method may assist in facilitating a patient-centered approach to laboratory medicine.

Pediatric reference interval verification for 16 biochemical markers on the Alinity ci system in the CALIPER cohort of healthy children and adolescents.

OBJECTIVES: Special chemistry parameters are useful in the diagnosis and management of inherited disorders, liver disease, and immunopathology. Evidence-based pediatric reference intervals (RIs) are required for appropriate clinical decision-making and need to be verified as new assays are developed. This study aimed to evaluate the applicability of pediatric RIs established for biochemical markers on the ARCHITECT for use on newer Alinity assays. METHODS: An initial method validation was completed for 16 assays, including precision, linearity, and method comparison. Sera collected from approximately 100 healthy children and adolescents as part of the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) were also analyzed on the Alinity c system. Percentage of results within established ARCHITECT RIs were calculated and considered verified if ≥90 % fell within established limits. New RIs were established for three electrolytes, glucose, and lactate wherein no data were previously reported. RESULTS: Of the 11 assays for which CALIPER pediatric RIs were previously established on ARCHITECT assays, 10 met the verification criteria. Alpha-1-antitrypsin did not meet verification criterion and a new RI was established. For the other 5 assays, de novo RIs were derived following analysis of 139-168 samples from healthy children and adolescents. None required age- and sex-partitioning. CONCLUSIONS: Herein, pediatric RIs were verified or established for 16 chemistry markers in the CALIPER cohort on Alinity assays. Findings support excellent concordance between ARCHITECT and Alinity assays with one exception (alpha-1-antitrypsin) as well as robustness of age- and sex-specific patterns originally reported by CALIPER in healthy Canadian children and adolescents.

Pediatric reference interval verification for 17 specialized immunoassays and cancer markers on the Abbott Alinity i system in the CALIPER cohort of healthy children and adolescents.

OBJECTIVES: Clinical laboratory investigation of autoimmune, metabolic, and oncologic disorders in children and adolescents relies on appropriateness of reference intervals (RIs). The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) previously established comprehensive pediatric RIs for specialized immunoassays on the Abbott ARCHITECT system. Herein, we aim to verify performance on new Alinity i assays by evaluating sera collected from healthy children as per Clinical and Laboratory Standards Institute (CLSI) EP-28A3C guidelines. METHODS: Precision, linearity, and method comparison experiments were completed for 17 specialized Alinity immunoassays, including cancer antigens, autoimmune peptides, and hormones. Sera collected from healthy children and adolescents (birth-18 years, n=100) were evaluated. CLSI-based verification was completed using previously established CALIPER RIs for ARCHITECT assays as the reference. RESULTS: Of 17 specialized immunoassays assays, only anti-cyclic citrullinated peptides (anti-CCP) did not meet acceptable verification criterion (i.e., ≥90% of results within ARCHITECT reference CI). Anti-thyroglobulin, anti-thyroid peroxidase, and carcinoembryonic antigen did not require age-specific consideration beyond one year of age, with 63, 91, and 80% of samples equalling the limit of detection, respectively. Estimates were separated by sex for relevant assays (e.g., sex hormone binding globulin, total and free prostate specific antigen). CONCLUSIONS: Findings support transferability of pediatric RIs on ARCHITECT system to the Alinity system for 16 specialized immunoassays in the CALIPER cohort and will be a useful resource for pediatric clinical laboratories using Alinity assays. Further work is needed to establish evidence-based interpretative recommendations for anti-CCP and continue to evaluate pediatric RI acceptability for newly available assay technologies.

Highly sensitive tandem mass spectrometric measurement of serum estradiol without derivatization and pediatric reference intervals in children and adolescents.

OBJECTIVES: Monitoring estradiol (E2) is important for determining the onset of pubertal development as well as in the evaluation of girls with precocious puberty. However, E2 measurement remains an analytical challenge in children, who have lower circulating levels. We developed and evaluated a simple and sensitive LC-MS/MS procedure for serum E2 quantification in pediatric populations and established age- and sex-specific pediatric reference intervals. METHODS: Residual patient serum samples were used to evaluate the analytical performance of our in-house LC-MS/MS E2 assay. The evaluation included accuracy, precision, linearity, functional sensitivity (LLoQ), and method comparison. Age- and sex-specific pediatric E2 reference intervals were also established from a cohort of 405 healthy children (birth to 18 years) recruited with informed consent. Age- and sex-specific differences were assessed, and outliers were removed. Reference intervals were established using the robust method. RESULTS: The assay imprecision was <5.3 %. Assay linearity ranged from 13.7 to 1923.3 pmol/L. The LLoQ corresponding to a CV of 20 % was determined to be 8.9 pmol/L. Bland-Altman analysis revealed a mean bias of 29.3 pmol/L or 9.1 % between our LC-MS/MS E2 assay and an external reference laboratory measuring E2 by LC-MS/MS. CONCLUSIONS: Our LC-MS/MS E2 assay shows acceptable accuracy, precision, functional sensitivity (LLoQ), and linearity for E2 quantification. Our LC-MS/MS E2 assay also showed good agreement with an external reference laboratory measuring E2 by LC-MS/MS. In addition, using CALIPER samples, we established robust age- and sex-specific pediatric E2 reference intervals to improve accuracy of test result interpretation and clinical decision making.

Age-specific reference intervals for liver function tests in healthy neonates, infants, and young children in Iran.

BACKGROUND: The reference intervals (RIs) for liver function tests (LFTs) were determined in Iranian children for the first time. METHODS: A total of 344 healthy pediatrics aged 3 days to 30 months old were recruited. Serum levels of ALT, AST, ALP, direct bilirubin, and total bilirubin were measured. RIs were determined using CLSI Ep28-A3 guidelines. RESULTS: All analytes demonstrated age-specific differences except AST. ALT and ALP demonstrated significantly elevated levels in infants 0 to <5 months relative to the remainder of the age range. Direct and total bilirubin demonstrated markedly elevated levels in early life with mean of 0.28 mg/dL and 1.64 mg/dL observed for direct and total bilirubin, respectively, decreasing by ~50% in the adjacent partition. CONCLUSION: These novel data will help improve the clinical interpretation of biochemical test results in young Iranian neonates and children and can be of value to clinical laboratories with similar populations.

Physiological and metabolic adaptations in pregnancy: importance of trimester-specific reference intervals to investigate maternal health and complications.

Diagnosis, prognostication, and monitoring of maternal health throughout pregnancy relies on laboratory testing, including but not limited to key markers of thyroid, hepatic, cardiac, hematology, and renal function. Dynamic physiological processes during gestation significantly influence the maternal biochemistry that supports both the mother and fetus. Resultant changes in blood biochemistry alter the expected values of common laboratory tests. However, the importance of pregnancy-specific reference intervals for laboratory test result interpretation and appropriate monitoring of maternal health and complications is underappreciated. Most clinical laboratories continue to use non-pregnant adult reference intervals for laboratory test interpretation in pregnancy. The current review summarizes and critically evaluates the available literature regarding physiological and metabolic adaptations in pregnancy and their influence on common biomarkers of health and disease. The main laboratory parameters discussed include thyroid, hepatic, metabolic, renal, hematology, inflammatory, and cardiac markers. Considering the available data, further studies are urgently needed to establish trimester-specific reference intervals in healthy pregnant women on updated analytical platforms. Without such data, the standard of clinical laboratory service in pregnancy remains compromised and affects the quality of maternal-fetal healthcare.

Determination of pediatric reference limits for 10 commonly measured autoantibodies.

OBJECTIVES: The objective of this study was to establish pediatric reference limits for autoimmune disease markers in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents to support their interpretation and clinical decision making. The CALIPER is a national study of healthy children aiming to close gaps in pediatric laboratory medicine by establishing a robust database of pediatric reference intervals for pediatric disease biomarkers (caliperdatabase.org). METHODS: Healthy children and adolescents (n=123, aged 1-19) were recruited to CALIPER with informed consent. Serum autoantibody testing conducted on the BIO-FLASH analyzer (Werfen, Barcelona, Spain) included anti-dsDNA IgG, anti-Sm IgG, anti-RNP IgG, anti-SSB/La IgG, anti-Ro60 IgG, anti-Ro52 IgG, anti-cardiolipin IgG, anti-MPO IgG, anti-PR3 IgG, and anti-tTG IgA. Pediatric reference limits representing 95th, 97.5th, and 99th percentiles were calculated using the non-parametric rank method according to Clinical Laboratory Standards Institute C28-A3 guidelines. RESULTS: The proportion of samples with results above the lower limit of the analytical measuring range were: anti-cardiolipin IgG 90%, anti-dsDNA 22%, anti-Sm 13%, anti-RNP 0.8%, anti-SSB/La 0%, anti-Ro60 0%, anti-Ro52 0%, anti-MPO 25%, anti-PR3 9%, and anti-tTG IgA 28%. Pediatric reference limits and associated 90% confidence intervals were established for all 10 markers. All autoantibodies could be described by one age range except for anti-cardiolipin IgG and anti-MPO. A sex-specific difference was identified for anti-tTG IgA. CONCLUSIONS: Robust pediatric reference limits for 10 commonly clinically utilized autoimmune markers established herein will allow for improved laboratory assessment and clinical decision making in pediatric patients using the BIO-FLASH assay platform worldwide.

Age and sex-specific reference intervals for prooxidant-antioxidant balance, anti-heat-shock protein 27 (anti-hsp27), and routine laboratory tests in the middle-aged adult population.

INTRODUCTION: We aimed to define specific reference intervals (RIs) for 11 biomarkers including inflammatory and oxidative stress biomarkers, liver, and renal function tests in a healthy Iranian adult population for the first time. METHODS: CLSI Ep28-A3 guidelines were then used to calculate accurate age- and sex- as well as body mass index (BMI)-specific RIs. RESULTS: RIs for studied biomarkers showed no significant age and sex-specific differences, except for uric acid, which had higher concentrations in men when compared to women. Additionally, after partitioning the participants based on the BMI with a cutoff point of 25 kg/m2 , only the levels of hs-CRP were positively associated with higher BMI (RI for BMI>25: 0.51-7.85 mg/L and for BMI<25: 0.40-4.46 mg/L). RI for PAB and anti-hsp-27 were reported 4.69-155.36 HK and 0.01-0.70 OD in men and women aged 35-65 years old. CONCLUSION: Partitioning by sex and BMI was only required for uric acid and hs-CRP, respectively, while other biomarkers required no partitioning. These results can be expected to valuably contribute to improve laboratory test result interpretation in adults for improved monitoring of various diseases in the Iranian population.

Pathophysiology of COVID-19: Mechanisms Underlying Disease Severity and Progression.

The global epidemiology of coronavirus disease 2019 (COVID-19) suggests a wide spectrum of clinical severity, ranging from asymptomatic to fatal. Although the clinical and laboratory characteristics of COVID-19 patients have been well characterized, the pathophysiological mechanisms underlying disease severity and progression remain unclear. This review highlights key mechanisms that have been proposed to contribute to COVID-19 progression from viral entry to multisystem organ failure, as well as the central role of the immune response in successful viral clearance or progression to death.

Cardiac Biomarkers in Pediatrics: An Undervalued Resource.

BACKGROUND: The clinical use of common cardiac biomarkers, such as brain natriuretic peptides and troponins, has traditionally been limited to adult populations in the assessment of heart failure and acute coronary syndrome, respectively. While many have discounted the value of these markers in pediatric populations, emerging evidence suggests they may be useful in the diagnosis and prognostication of many cardiac and noncardiac pathologies in neonates, children, and adolescents, and an increasing number of pediatric hospitals are routinely measuring cardiac markers in their clinical practice. CONTENT: This review summarizes and critically evaluates the current literature regarding the application of cardiac biomarkers for clinical decision-making in the pediatric population. Main potential clinical indications discussed herein include primary cardiac disease, immune-related conditions, and noncardiac disease. Important diagnostic and interpretative challenges are also described in relation to each potential indication. SUMMARY: Despite a general lack of clinical awareness regarding the value of cardiac biomarkers in pediatrics, there is increasing literature to support their application in various contexts. Cardiac biomarkers should be considered an undervalued resource in the pediatric population with potential value in the diagnosis and prognosis of myocarditis, congenital heart disease, and heart failure, as well as in the assessment of severity and cardiac involvement in immune-related and other systemic conditions. While interpretation remains challenging in pediatrics due to the age- and sex-specific dynamics occurring throughout growth and development, this should not prevent their application. Future research should focus on defining evidence-based cut-offs for specific indications using the most up-to-date assays.

Pediatric reference interval verification for endocrine and fertility hormone assays on the Abbott Alinity system.

OBJECTIVES: The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has developed an extensive database of reference intervals (RIs) for several biomarkers on various analytical systems. In this study, pediatric RIs were verified for key immunoassays on the Abbott Alinity system based on the analysis of healthy children samples and comparison to comprehensive RIs previously established for Abbott ARCHITECT assays. METHODS: Analytical performance of Alinity immunoassays was first assessed. Subsequently, 100 serum samples from healthy children recruited with informed consent were analyzed for 16 Alinity immunoassays. The percentage of test results falling within published CALIPER ARCHITECT reference and confidence limits was determined. If ≥ 90% of test results fell within the confidence limits, they were considered verified based on CLSI guidelines. If <90% of test results fell within the confidence limits, additional samples were analyzed and new Alinity RIs were established. RESULTS: Of the 16 immunoassays assessed, 13 met the criteria for verification with test results from ≥ 90% of healthy serum samples falling within the published ARCHITECT confidence limits. New CALIPER RIs were established for free thyroxine and prolactin on the Alinity system. Estradiol required special considerations in early life. CONCLUSIONS: Our data demonstrate excellent concordance between ARCHITECT and Alinity immunoassays, as well as the robustness of previously established CALIPER RIs for most immunoassays, eliminating the need for de novo RI studies for most parameters. Availability of pediatric RIs for immunoassays on the Alinity system will assist clinical laboratories using this new platform and contribute to improved clinical decision-making.

Pediatric reference intervals for endocrine markers and fertility hormones in healthy children and adolescents on the Siemens Healthineers Atellica immunoassay system.

OBJECTIVES: Rapid development in childhood and adolescence combined with lack of immunoassay standardization necessitates the establishment of age-, sex-, and assay-specific reference intervals for immunochemical markers. This study established reference intervals for 11 immunoassays on the new Siemens Healthineers Atellica® IM Analyzer in the healthy CALIPER cohort. METHODS: A total of 600 healthy participants (birth to 18 years) were recruited from the community, and serum samples were collected with informed consent. After sample analysis, age- and sex-specific differences were assessed, and outliers were removed. Reference intervals were established using the robust method (40-<120 participants) or nonparametric method (≥120 participants). RESULTS: Of the 11 immunoassays studied, nine required age partitioning (i.e., dehydroepiandrosterone-sulfate, estradiol, ferritin, folate, follicle-stimulating hormone, luteinizing hormone, progesterone, testosterone, vitamin B12), and seven required sex partitioning. Free thyroxine and thyroid-stimulating hormone demonstrated no significant age- and/or sex-specific differences. CONCLUSIONS: Overall, the age- and sex-specific trends observed closely mirrored those previously reported by CALIPER on other platforms as well as other internationally recognized studies. However, established lower and upper limits demonstrated some discrepancies between published values from healthy cohorts on alternate analytical systems, highlighting differences between manufacturers and the need for platform-specific reference intervals for informed pediatric clinical decision-making.

Pediatric reference interval verification for common biochemical assays on the Abbott Alinity system.

OBJECTIVES: The quality of clinical laboratory service depends on quality laboratory operations and accurate test result interpretation based on reference intervals (RIs). As new analytical systems continue to be developed and improved, previously established RIs must be verified. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has established comprehensive RIs for many biomarkers on several analytical systems. Here, published CALIPER RIs for 28 chemistry assays on the Abbott ARCHITECT were assessed for verification on the newer Alinity system. METHODS: An analytical validation was first completed to assess assay performance. CALIPER serum samples (100) were analyzed for 28 chemistry assays on the Alinity system. The percentage of results falling within published pediatric ARCHITECT reference and confidence limits was determined for each analyte. Based on Clinical and Laboratory Standards Institute (CLSI) guidelines, if ≥90% of test results fell within confidence limits of ARCHITECT assay RIs, they were considered verified. RESULTS: Of the 28 assays assessed, 26 met the criteria for verification. Reference values for calcium and magnesium did not meet the criteria for verification with 87% and 35% falling within previously established ARCHITECT confidence limits, respectively. However, both assays could be verified using pediatric RIs provided in the Abbott Alinity package insert. CONCLUSIONS: In this study, CALIPER ARCHITECT RIs were verified on the Alinity system for several chemistry assays. These data demonstrate excellent concordance for most assays between the Abbott ARCHITECT and Alinity systems and will assist in the implementation of the Alinity system in pediatric healthcare institutions.

IFCC interim guidelines on rapid point-of-care antigen testing for SARS-CoV-2 detection in asymptomatic and symptomatic individuals.

With an almost unremittent progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections all around the world, there is a compelling need to introduce rapid, reliable, and high-throughput testing to allow appropriate clinical management and/or timely isolation of infected individuals. Although nucleic acid amplification testing (NAAT) remains the gold standard for detecting and theoretically quantifying SARS-CoV-2 mRNA in various specimen types, antigen assays may be considered a suitable alternative, under specific circumstances. Rapid antigen tests are meant to detect viral antigen proteins in biological specimens (e.g. nasal, nasopharyngeal, saliva), to indicate current SARS-CoV-2 infection. The available assay methodology includes rapid chromatographic immunoassays, used at the point-of-care, which carries some advantages and drawbacks compared to more conventional, instrumentation-based, laboratory immunoassays. Therefore, this document by the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) Taskforce on COVID-19 aims to summarize available data on the performance of currently available SARS-CoV-2 antigen rapid detection tests (Ag-RDTs), providing interim guidance on clinical indications and target populations, assay selection, and evaluation, test interpretation and limitations, as well as on pre-analytical considerations. This document is hence mainly aimed to assist laboratory and regulated health professionals in selecting, validating, and implementing regulatory approved Ag-RDTs.

Reference intervals for hemoglobin and mean corpuscular volume in an ethnically diverse community sample of Canadian children 2 to 36 months.

OBJECTIVE: To establish reference intervals for hemoglobin and mean corpuscular volume (MCV) in an ethnically diverse community sample of Canadian children 36 months and younger. METHODS: We collected blood samples from young children at scheduled primary care health supervision visits at 2 weeks, 2, 4, 6, 9, 12, 15, 18, 24, and 36 months of age. Samples were analyzed on the Sysmex XN-9000 Hematology Analyzer. We followed the Clinical and Laboratory Standards Institute guidelines in our analysis. Data were partitioned by sex and also combined. We considered large age partitions (3 and 6 months) as well as monthly partitions. Reference intervals (lower and upper limits) and 90% confidence intervals were calculated. RESULTS: Data from 2106 children were included. The age range was 2 weeks to 36 months, 46% were female, 48% were European and 23% were of mixed ethnicity. For hemoglobin, from 2 to 36 months of age, we found a wide reference interval and the 90% confidence intervals indicated little difference across age groups or according to sex. For MCV, from 2 to 7 months of age there was considerable decrease in the reference interval, which was lowest during the second year of life, followed by a slight increase in the last months of the third year of life. CONCLUSION: These findings suggest adoption of a single hemoglobin reference interval for children 2-36 months of age. Further studies in children under 4 months of age are needed. TRIAL REGISTRATION: TARGet Kids! cohort is registered at ClinicalTrials.gov. www.clinicaltrials.gov . Identifier: NCT01869530 .