Establishing quality indicators for point of care glucose testing: recommendations from the Canadian Society for Clinical Chemists Point of Care Testing and Quality Indicators Special Interest Groups.

OBJECTIVES: Monitoring quality indicators (QIs) is an important part of laboratory quality assurance (QA). Here, the Canadian Society of Clinical Chemists (CSCC) Point of Care Testing (POCT) and QI Special Interest Groups describe a process for establishing and monitoring QIs for POCT glucose testing. METHODS: Key, error prone steps in the POCT glucose testing process were collaboratively mapped out, followed by risk assessment for each step. Steps with the highest risk and ability to detect a non-conformance were chosen for follow-up. These were positive patient identification (PPID) and repeat of critically high glucose measurements. Participating sites were asked to submit aggregate data for these indicators from their site(s) for a one-month period. The PPID QI was also included as part of a national QI monitoring program for which fifty-seven sites submitted data. RESULTS: The percentage of POCT glucose tests performed without valid PPID ranged from 0-87%. Sites without Admission-Discharge-Transfer (ADT) connectivity to POCT meters were among those with the highest percentage of POCT glucose tests performed without valid PPID. The percentage repeated critically high glucose measurements ranged from 0-50%, indicating low compliance with this recommendation. A high rate of discordance was also noted when critically high POCT glucose measurements were repeated, demonstrating the importance of repeat testing prior to insulin administration. CONCLUSIONS: Here, a process for establishing these QIs is described, with preliminary data for two QIs chosen from this process. The findings demonstrate the importance of QIs for identification and comparative performance monitoring of non-conformances to improve POCT quality.

Multicenter Postimplementation Assessment of the Positive Predictive Value of SARS-CoV-2 Antigen-Based Point-of-Care Tests Used for Screening of Asymptomatic Continuing Care Staff.

Frequent screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among asymptomatic populations using antigen-based point-of-care tests (APOCTs) is occurring globally with limited clinical performance data. The positive predictive value (PPV) of two APOCTs used in the asymptomatic screening of SARS-CoV-2 among health care workers (HCWs) at continuing care (CC) sites across AB, Canada, was evaluated. Between 22 February and 2 May 2021, CC sites implemented SARS-CoV-2 voluntary screening of their asymptomatic HCWs. On-site testing with Abbott Panbio or BD Veritor occurred on a weekly or twice-weekly basis. Positive APOCTs were confirmed with a real-time reverse transcriptase PCR (rRT-PCR) reference method. A total of 71,847 APOCTs (17,689 Veritor and 54,158 Panbio) were performed among 369 CC sites. Eighty-seven (0.12%) APOCTs were positive, of which 39 (0.05%) were confirmed as true positives using rRT-PCR. Use of the Veritor and Panbio resulted in 76.6% and 30.0% false-positive detection, respectively (P < 0.001). This corresponded to PPVs of 23.4 and 70.0% for the Veritor and Panbio, respectively. Frequent screening of SARS-CoV-2 among asymptomatic HCWs in CC, using APOCTs, resulted in a very low detection rate and a high rate of detection of false positives. Careful assessment of the risks versus benefits of APOCT programs and the prevalence of infection in this population needs to be thoroughly considered before implementation.

Clinical performance of the Abbott Panbio with nasopharyngeal, throat, and saliva swabs among symptomatic individuals with COVID-19.

SARS-CoV-2 antigen tests used at the point-of-care, such as the Abbott Panbio, have great potential to help combat the COVID-19 pandemic. The Panbio is Health Canada approved for the detection of SARS-CoV-2 in symptomatic individuals within the first 7 days of COVID-19 symptom onset(s). Symptomatic adults recently diagnosed with COVID-19 in the community were recruited into the study. Paired nasopharyngeal (NP), throat, and saliva swabs were collected, with one paired swab tested immediately with the Panbio, and the other transported in universal transport media and tested using real-time reverse-transcriptase polymerase chain reaction (RT-PCR). We also prospectively evaluated results from assessment centers within the community. For those individuals, an NP swab was collected for Panbio testing and paired with RT-PCR results from parallel NP or throat swabs. One hundred and forty-five individuals were included in the study. Collection of throat and saliva was stopped early due to poorer performance (throat sensitivity 57.7%, n=61, and saliva sensitivity 2.6%, n=41). NP swab sensitivity was 87.7% [n=145, 95% confidence interval (CI) 81.0-92.7%]. There were 1641 symptomatic individuals tested by Panbio in assessment centers with 268/1641 (16.3%) positive for SARS-CoV-2. There were 37 false negatives and 2 false positives, corresponding to a sensitivity and specificity of 86.1% [95% CI 81.3-90.0%] and 99.9% [95% CI 99.5-100.0%], respectively. The Panbio test reliably detects most cases of SARS-CoV-2 from adults in the community setting presenting within 7 days of symptom onset using nasopharyngeal swabs. Throat and saliva swabs are not reliable specimens for the Panbio.

Canadian Society of Clinical Chemists Harmonized Pediatric Lipid Reporting Recommendations for Clinical Laboratories.

Detecting dyslipidemia early is important because atherosclerosis originates in childhood and early treatment can improve outcomes. In 2022, the Canadian Cardiovascular Society (CCS) and Canadian Pediatric Cardiology Association (CPCA) published a clinical practice update to detect, evaluate, and manage pediatric dyslipidemia. However, guidance on its translation into clinical laboratories is lacking. The Canadian Society of Clinical Chemists Working Group on Reference Interval Harmonization Lipid Team aims to assist guideline implementation and promote harmonized pediatric lipid reporting across Canada. The 2022 CCS/CPCA clinical practice update, 2011 National Heart, Lung, and Blood Institute integrated guidelines, and new data analysis (Canadian pediatric reference values from the Canadian Laboratory Initiative on Pediatric Reference Intervals [CALIPER] and retrospective patient data from large community laboratories) were incorporated to develop 5 key recommendations. These include recommendations to: (1) offer nonfasting and fasting lipid testing; (2) offer a lipid panel including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and triglycerides, with apolipoprotein B and lipoprotein(a) available as individually orderable tests; (3) flag total cholesterol, LDL-C, and non-HDL-C results ≥ 95th percentile, and HDL-C results < 10th percentile, as recommended by CCS/CPCA/National Heart, Lung, and Blood Institute and validated by CALIPER, and flag apolipoprotein B and nonfasting triglyceride results ≥ 95th percentile on the basis of CALIPER, and do not flag Lp(a) results but mention the adult cutoff in the interpretive comments; (4) implement interpretive comments listed in the current report; and (5) implement the National Institutes of Health LDL-C equation. The Canadian Society of Clinical Chemists Working Group on Reference Interval Harmonization Lipid Team will support clinical laboratories to implement these recommendations using knowledge translation strategies. Harmonizing pediatric lipid reporting across Canadian clinical laboratories will optimize clinical decision-making and improve cardiovascular risk management in youth.

Prospective population-level validation of the Abbott ID NOW severe acute respiratory syndrome coronavirus 2 device implemented in multiple settings for testing asymptomatic and symptomatic individuals.

OBJECTIVE: Diagnostic evaluation of the ID NOW coronavirus disease 2019 (COVID-19) assay in various real-world settings among symptomatic and asymptomatic individuals. METHODS: Depending on the setting, the ID NOW testing was performed using oropharyngeal swabs (OPSs) taken from patients with symptoms suggestive of COVID-19, asymptomatic close contacts, or asymptomatic individuals as part of outbreak point prevalence screening. From January to April 2021, a select number of sites switched from using OPS to combined oropharyngeal and nasal swab (O + NS) for ID NOW testing. For every individual tested, two swabs were collected by a health care worker: one swab (OPS or O + NS) for ID NOW testing and a separate swab (OPS or nasopharyngeal swab) for RT-PCR. RESULTS: A total of 129 112 paired samples were analysed (16 061 RT-PCR positive). Of these, 81 697 samples were from 42 COVID-19 community collection sites, 16 924 samples were from 69 rural hospitals, 1927 samples were from nine emergency shelters and addiction treatment facilities, 23 802 samples were from six mobile units that responded to 356 community outbreaks, and 4762 O + NS swabs were collected from three community collection sites and one emergency shelter. The ID NOW assay sensitivity was the highest among symptomatic individuals presenting to community collection sites (92.5%; 95% CI, 92.0-93.0%) and the lowest for asymptomatic individuals associated with community outbreaks (73.9%; 95% CI, 69.8-77.7%). Specificity was >99% in all populations tested. DISCUSSION: The sensitivity of ID NOW severe acute respiratory syndrome coronavirus 2 testing is the highest when used in symptomatic community populations not seeking medical care. Sensitivity and positive predictive value drop by approximately 10% when tested on asymptomatic populations. Using combined oropharyngeal and nasal swabs did not improve the performance of ID NOW assay.

Evaluation of the ID NOW among symptomatic individuals during the Omicron wave.

Introduction. Starting in December, 2020, the ID NOW was implemented throughout the province of Alberta, Canada (population 4.4 million) in various settings.Gap statement. ID NOW's test performance with SARS-CoV-2 Omicron variant BA.1 is unknown.Aim. To assess the ID NOW performance among symptomatic individuals during the BA.1 Omicron wave and compare it to previous SARS-CoV-2 variant waves.Methodology. The ID NOW was assessed in two locations among symptomatic individuals: rural hospitals and community assessment centres (AC) during the period 5-18 January 2022. Starting 5 January, Omicron represented >95 % of variants detected in our population. For every individual tested, two swabs were collected: one for ID NOW testing and the other for either reverse-transcriptase polymerase chain reaction (RT-PCR) confirmation of negative ID NOW results or for variant testing of positive ID NOW results.Results. A total of 3041 paired samples were analysed (1139 RT-PCR positive). From this, 1873 samples were from 42 COVID-19 AC and 1168 from 69 rural hospitals. ID NOW sensitivity for symptomatic individuals presenting to community AC and rural hospitals was 96.0 % [95 % confidence interval (CI) 94.5-97.3 %, n=830 RT-PCR positive], and 91.6 % (95 % CI 87.9-94.4 %, n=309 RT-PCR positive), respectively. SARS-CoV-2 positivity rate was very high for both populations (44.3 % at AC, 26.5 % in hospital).Conclusions. Sensitivity of ID NOW SARS-CoV-2, compared to RT-PCR, is very high during the BA.1 Omicron wave, and is significantly higher when compared to previous SARS-CoV-2 variant waves.

Low partial pressure of oxygen causes significant and unrecognized under-recovery of glucose on blood gas analyzers.

BACKGROUND: Blood gas analyzers employing glucose-oxidase biosensors under-recover glucose when pO2 is low. The manufacturer of the GEM®Premier™ series of analyzers introduced an algorithm to detect specimens at risk of low pO2 interference. We investigated the reliability of this algorithm. METHODS: Whole blood specimens were tested by GEM®Premier™ 4000 (GEM 4000) and 5000 (GEM 5000). Specimens with an incalculable ("incalc") error code for glucose result or that had a glucose ≥ 20 mmol/L were retested on a second analyzer of the same type within 5 min over the course of 30 months in 5 hospitals in Calgary, Alberta. Discordant retests were defined as either: 1) paired numeric results with a difference >10 %, or 2) an "incalc" code that yielded a numeric result upon retesting. Glucose recovery in relation to pO2 level was assessed by comparing specimens experimentally depleted of pO2 between GEM 5000 and a laboratory analyzer (Siemens Vista®). RESULTS: Of 1,776 glucose tests repeated on the GEM 5000 or 1,544 on GEM 4000, 10% were discordant. GEM 5000 produced twice as many discordant numeric retests versus the GEM 4000 [5.9% (98/1,651) vs 2.7% (38/1,391)]. The majority of "incalc" error codes repeated with a numeric glucose result on both GEM analyzers [(79.7% (122/153) vs 75.2% (94/125)]. Among specimens experimentally depleted of pO2, the GEM 5000 under-recovered glucose by up to 30% compared to the Siemens Vista and were not flagged by an "incalc" code. CONCLUSIONS: The algorithm in the GEM®PremierTM series of analyzers that flags specimens at risk for glucose under-recovery due to low pO2 does not reliably detect specimens at risk for glucose under-recovery.

Closing the gaps in pediatric laboratory reference intervals: a CALIPER database of 40 biochemical markers in a healthy and multiethnic population of children.

BACKGROUND: Pediatric healthcare is critically dependent on the availability of accurate and precise laboratory biomarkers of pediatric disease, and on the availability of reference intervals to allow appropriate clinical interpretation. The development and growth of children profoundly influence normal circulating concentrations of biochemical markers and thus the respective reference intervals. There are currently substantial gaps in our knowledge of the influences of age, sex, and ethnicity on reference intervals. We report a comprehensive covariate-stratified reference interval database established from a healthy, nonhospitalized, and multiethnic pediatric population. METHODS: Healthy children and adolescents (n = 2188, newborn to 18 years of age) were recruited from a multiethnic population with informed parental consent and were assessed from completed questionnaires and according to defined exclusion criteria. Whole-blood samples were collected for establishing age- and sex-stratified reference intervals for 40 serum biochemical markers (serum chemistry, enzymes, lipids, proteins) on the Abbott ARCHITECT c8000 analyzer. RESULTS: Reference intervals were generated according to CLSI C28-A3 statistical guidelines. Caucasians, East Asians, and South Asian participants were evaluated with respect to the influence of ethnicity, and statistically significant differences were observed for 7 specific biomarkers. CONCLUSIONS: The establishment of a new comprehensive database of pediatric reference intervals is part of the Canadian Laboratory Initiative in Pediatric Reference Intervals (CALIPER). It should assist laboratorians and pediatricians in interpreting test results more accurately and thereby lead to improved diagnosis of childhood diseases and reduced patient risk. The database will also be of global benefit once reference intervals are validated in transference studies with other analytical platforms and local populations, as recommended by the CLSI.

Point of care molecular and antigen detection tests for COVID-19: current status and future prospects.

INTRODUCTION: Detection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been critical to support and management of the COVID-19 pandemic. Point of care testing (POCT) for SARS-CoV-2 has been a widely used tool for detection of SARS-CoV-2. AREAS COVERED: POCT nucleic acid amplification tests (NAATs) and rapid antigen tests (RATs) have been the most readily used POCT for SARS-CoV-2. Here, current knowledge on the utility of POCT NAATs and RATs for SARS-CoV-2 are reviewed and discussed alongside aspects of quality assurance factors that must be considered for successful and safe implementation of POCT. EXPERT OPINION: Use cases for implementation of POCT must be evidence based, regardless of the test used. A quality assurance framework must be in place to ensure accuracy and safety of POCT.

Canadian Society of Clinical Chemists Harmonized Clinical Laboratory Lipid Reporting Recommendations on the Basis of the 2021 Canadian Cardiovascular Society Lipid Guidelines.

There is limited guidance on laboratory reporting and interpretation of lipids and lipoproteins used in cardiovascular risk stratification. This contributes to inconsistencies in lipid reporting across clinical laboratories. Recently, the Canadian Cardiovascular Society (CCS) published the 2021 CCS guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. A subcommittee of the Working Group on Reference Interval Harmonization of the Canadian Society of Clinical Chemists has developed harmonized lipid reporting recommendations that are aligned with the 2021 CCS guidelines, to improve the standardization of lipid assessment and clinical decision-making. The proposed harmonized lipid reporting recommendations were critically reviewed by a broad range of laboratory and clinical experts across Canada. Feedback from approximately 30 expert reviewers was reviewed by the Working Group on Reference Interval Harmonization lipid subcommittee, and consensus decisions were incorporated into the 2021 harmonized lipid reporting recommendations. In this position statement, we provide 6 recommendations for laboratory reporting of lipid parameters. These recommendations include implementing the new National Institutes of Health equation to replace the Friedewald equation for calculating low-density lipoprotein cholesterol, offering lipoprotein (a), either as an in-house or send-out test, and using assays that report lipoprotein (a) in molar units (nmol/L). We also developed a harmonized lipid reporting format with interpretive comments that includes flagging results based on screening patients using treatment decision thresholds in a primary prevention setting. Overall, harmonized lipid reporting will help bridge the gap between clinical guideline recommendations and clinical laboratory reporting and interpretation, and will improve cardiovascular risk assessment across Canada.

A Snapshot of Lipid-Reporting Practices in Canadian Clinical Laboratories: An Urgent Need for Harmonisation.

To effectively implement the Canadian Cardiovascular Society (CCS) guidelines for dyslipidemia management into clinical laboratories, clear recommendations for lipid reporting are essential. In this study, the Canadian Society of Clinical Chemists Working Group on Reference Interval Harmonisation surveyed Canadian laboratories on adult lipid reporting practices to set a foundation for the development and implementation of harmonised lipid reporting across Canada. Key aspects of the survey asked laboratories: what reporting parameters were in place to assess lipid results; what interpretative comments were provided; whether nonfasting lipids were permitted and, if so, what strategy was used to document fasting status; and whether there was interest in implementing a harmonised lipid report. A total of 101 laboratories were represented by 24 respondents, as many responses were submitted by laboratory networks that included more than 1 laboratory. There was at least 1 response from 9 Canadian provinces and representation across 5 testing platforms. Upper and lower limits for lipid parameters and referenced source of limits varied substantially across laboratories, with only 56% of laboratories (9 respondents) referencing the 2016 CCS guidelines. Eighty-six percent of laboratories (19 respondents) report nonfasting lipids, although the method of documenting nonfasting status varied. Overall, 36% of laboratories (8 respondents) reported interest in implementing a harmonised lipid report. Assessment of current lipid-reporting practices supports the need for harmonised lipid reporting across Canada. Development of a harmonised lipid report for the adult population, consistent with up-to-date Canadian guidelines, will improve continuity of lipid test interpretation across Canada and improve clinical decision making.

Identifying sources of error and selecting quality indicators for point of care testing.

OBJECTIVES: Point of Care Testing (POCT) is a rapidly expanding area of clinical laboratory testing and quality assurance is an important area of focus. Quality indicators (QIs) are a quality management system tool that monitors aspects of the testing process to help meet the challenges associated with maintaining high quality patient safety given the growth in POCT. Alberta aims to formalize the development and use of QIs for POCT. DESIGN: and Methods: Potential QIs were identified by reviewing both the current standards and guidelines for QIs in POCT, and the research regarding quality and sources of error in POCT. Quality practices and potential sources of error in POCT were identified by: 1) a Canadian national survey on POCT, and 2) direct observation in two local POCT programs. RESULTS: A proposed selection of QIs in POCT were identified by incorporating the results from these investigations, while considering the unique characteristics of POCT. These QIs monitor the preanalytical, analytical, and post-analytical phases of testing, and support processes. CONCLUSIONS: As POCT volumes and test menu expands, QIs will be a vital tool in monitoring error and maintaining high quality of results. Adoption of formal QIs will support continuous quality improvement and improved patient care.

Quality assurance practices for point of care testing programs: Recommendations by the Canadian society of clinical chemists point of care testing interest group.

Point of Care Testing (POCT) refers to clinical laboratory testing performed outside the central laboratory, nearer to the patient and sometimes at the patient bedside. The testing is usually performed by clinical staff, such as physicians or nurses, who are not laboratory trained. This document was developed by the POCT Interest group of the Canadian Society of Clinical Chemists (CSCC) as practical guidance for quality assurance practices related to POCT performed in hospital and outside hospital environments. The aspects of quality assurance addressed in this document include: (1) device selection, (2) initial device verification, (3) ongoing device verification, (4) ongoing quality assurance including reagent and quality control (QC) lot changes, and (5) quality management including operator and document management.

A meta-analysis of leptin reference ranges in the healthy paediatric prepubertal population.

OBJECTIVE: The initial discovery of leptin (1994) has given rise to a substantial number of published studies. This study aimed at identifying the published data on the reference ranges of total, free and bound leptin concentration in the healthy prepubertal population. METHODS: A search was conducted on original English language studies published from 1994 to 2005 in the following databases: PubMed (n = 58), EMBASE (n = 4), Biological Abstracts (n = 2) and Science Finder Scholar (n = 66). A cited reference search was completed in Science Citation Index on studies with a leptin range. A meta-analysis was completed on included studies containing a dataset and a sample size for a leptin concentration range and/or mean+/-standard deviation for a healthy prepubertal population. Preanalytical and analytical variations were examined. Preanalytical variables included aspects such as fasting state and gender, while analytical variation comprised the type of leptin assay methodology. RESULTS: Twelve studies met the inclusion criteria. One study examined free leptin; 11 studies examined total concentration. No studies reported leptin reference ranges established by Clinical and Laboratory Standards Institute (CLSI) criteria, although four studies reported specific study leptin ranges. The methodology of enzyme-linked immunosorbent assay demonstrated a wider leptin range than radio immunoassay (0.56-36.35 vs. 1.01-12.21 ng/mL). Males had a significantly lower mean leptin concentration than females (P = 0.0006); obese children had a higher concentration than non-obese (P = 0.0001). CONCLUSION: No studies have established CLSI-based leptin reference ranges in prepubertal healthy children and there is a wide variation in the published leptin concentrations. These differences suggest that caution should be used in the interpretation and comparison between studies.

Urine protein detection by dipstick: No interference from alkalinity or specific gravity.

Tetrabromphenol blue dye based methods are used to detect proteinuria using urinalysis dipsticks. Manufacturers have claimed that alkalinity leads to false positive proteinuria, and that high specific gravity leads to false negative protein results. However, published reports describing this phenomenon remain equivocal. This study aimed to determine whether pH and/or specific gravity affect protein detection in patient urine using three different tetrabromophenol blue dye-based dipsticks. Patient urine pools were divided into individual aliquots with varied pH or specific gravity, and measured for protein in triplicate using iChem 10SG, iChem Velocity, and Multistix 8SG dipsticks. The pH experiment involved progressive alkalinization of urine aliquots with either 1M NaOH, Na2CO3, or NaHCO3; pH was recorded by electrode. The specific gravity experiment involved mixing aliquots with NaCl and spiking with human albumin. Urine electrolytes and total CO2 were measured (Roche cobas 8000). Fresh patient urines (N = 35) were analyzed for physiological urine pH and total CO2. Urine protein results were not affected by NaOH alkalinization up to pH 10.9. False positive protein occurred at pH 9.9 and >97 mmol/L total CO2 (Na2CO3 alkalization; P < .05). Moreover, false positive protein occurred at pH 7.6 when total CO2 exceeded 137 mmol/L (NaHCO3 alkalization; P < .05). Fresh patient urines did not exceed pH 8.5 or 86 mmol/L total CO2. NaCl elevated specific gravity and caused false negative protein detection when urine ionic strength was >1100 mmol/L (P < .05). Tetrabromphenol blue dipsticks provide robust detection of proteinuria when human urine is within physiological pH, total CO2 and ionic strength.

Statin Prescriptions for High-Risk Patients Are Increased by Laboratory-Initiated Framingham Risk Scores: A Quality-Improvement Initiative.

Low rates of cardiovascular preventive therapy with statin medications is a significant public health problem in Canada. There is a pressing need for public health interventions to increase the use of statin medications, especially among high-risk patients. In this article, we present the results of a quality assurance pilot program to provide laboratory-reported Framingham Risk Score (FRS) to physicians. This work was performed in a mixed urban and rural setting in southern Alberta. We provided FRSs and, for high-risk patients, statin treatment recommendations in conjunction with laboratory lipid panel requests. Adhesive labels were supplied to primary care physicians, and space was provided for information necessary for the calculation of the FRS by a laboratory information system. In total, 16 physicians from 4 different clinics participated in the pilot program. Data were collected from October 25, 2014-November 5, 2015, during which time 1266 patients had FRSs from the laboratory. Three hundred twenty-four individuals were identified as high risk for coronary heart disease (≥ 20% 10-year risk) and received a recommendation for treatment with a statin medication in the laboratory result report. These individuals had a 26% relative and a 6.4% absolute increase in statin prescriptions compared with before the pilot program. The laboratory-based provision of FRSs with statin treatment recommendations for high-risk individuals has the potential to significantly increase the use of statin drugs.

National Survey of Adult and Pediatric Reference Intervals in Clinical Laboratories across Canada: A Report of the CSCC Working Group on Reference Interval Harmonization.

OBJECTIVE: Reference intervals are widely used decision-making tools in laboratory medicine, serving as health-associated standards to interpret laboratory test results. Numerous studies have shown wide variation in reference intervals, even between laboratories using assays from the same manufacturer. Lack of consistency in either sample measurement or reference intervals across laboratories challenges the expectation of standardized patient care regardless of testing location. Here, we present data from a national survey conducted by the Canadian Society of Clinical Chemists (CSCC) Reference Interval Harmonization (hRI) Working Group that examines variation in laboratory reference sample measurements, as well as pediatric and adult reference intervals currently used in clinical practice across Canada. DESIGN AND METHODS: Data on reference intervals currently used by 37 laboratories were collected through a national survey to examine the variation in reference intervals for seven common laboratory tests. Additionally, 40 clinical laboratories participated in a baseline assessment by measuring six analytes in a reference sample. RESULTS: Of the seven analytes examined, alanine aminotransferase (ALT), alkaline phosphatase (ALP), and creatinine reference intervals were most variable. As expected, reference interval variation was more substantial in the pediatric population and varied between laboratories using the same instrumentation. Reference sample results differed between laboratories, particularly for ALT and free thyroxine (FT4). Reference interval variation was greater than test result variation for the majority of analytes. CONCLUSION: It is evident that there is a critical lack of harmonization in laboratory reference intervals, particularly for the pediatric population. Furthermore, the observed variation in reference intervals across instruments cannot be explained by the bias between the results obtained on instruments by different manufacturers.

Leptin: a potential biomarker for childhood obesity?

Leptin, a hormone made by adipocytes, is an important circulating signal for the regulation of body weight. A review of the scientific literature (PubMed Search 1994 to 2005) for studies examining the relationship among leptin, pediatric obesity and the impact of exercise intervention programmes on leptin concentrations are summarized. The potential utility of leptin as a biomarker for identifying children at risk of obesity is discussed. This literature review demonstrated that (1) leptin directly interacts with the hypothalamus for energy balance regulation; (2) the measurement of free, bound and total leptin as well as soluble leptin receptor concentration are critical for our understanding of obesity in children; and (3) leptin concentration may be an important factor for determining intervention programme responsiveness in pediatric obesity.

Erroneous HbA1c results in a patient with elevated HbC and HbF.

BACKGROUND: HbA1c is used in the diagnosis and monitoring of diabetes mellitus (DM). Interference from hemoglobin variants is a well-described phenomenon, particularly with HPLC-based methods. While immunoassays may generate more reliable HbA1c results in the presence of some variants, these methods are susceptible to negative interference from high concentrations of HbF. We report a case where an accurate HbA1c result could not be obtained by any available method due to the presence of a compound hemoglobinopathy. METHODS: HbA1c was measured by HPLC, immunoassay, and capillary electrophoresis. Hemoglobinopathy investigation consisted of a CBC, hemoglobin fractionation by HPLC and electrophoresis, and molecular analysis. RESULTS: HbA1c analysis by HPLC and capillary electrophoresis gave no result. Analysis by immunoassay yielded HbA1c results of 5.9% (Siemens DCA 2000+) and 5.1% (Roche Integra), which were inconsistent with other markers of glycemic control. Hemoglobinopathy investigation showed HbC with the hereditary persistence of fetal hemoglobin-2 Ghana deletion. CONCLUSION: Reliable HbA1c results may be unobtainable in the presence of some hemoglobinopathies. HPLC and capillary electrophoresis alerted the laboratory to the presence of an unusual hemoglobinopathy. Immunoassays generated falsely low results without warning, which could lead to missed diagnoses and under treatment of patients with DM.