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.

Transformation of Sequential Hospital and Outpatient Laboratory Data into Between-Day Reference Change Values.

BACKGROUND: Serial differences between intrapatient consecutive measurements can be transformed into Taylor series of variation vs time with the intersection at time = 0 (y0) equal to the total variation (analytical + biological + preanalytical). With small preanalytical variation, y0, expressed as a percentage of the mean, is equal to the variable component of the reference change value (RCV) calculation: (CVA2 + CVI2)1/2. METHODS: We determined the between-day RCV of patient data for 17 analytes and compared them to healthy participants' RCVs. We analyzed 653 consecutive days of Dartmouth-Hitchcock Roche Modular general chemistry data (4.2 million results: 60% inpatient, 40% outpatient). The serial patient values of 17 analytes were transformed into 95% 2-sided RCV (RCVAlternate), and 3 sets of RCVhealthy were calculated from 3 Roche Modular analyzers' quality control summaries and CVI derived from biological variation (BV) studies using healthy participants. RESULTS: The RCVAlternate values are similar to RCVhealthy derived from known components of variation. For sodium, chloride, bicarbonate calcium, magnesium, phosphate, alanine aminotransferase, albumin, and total protein, the RCVs are equivalent. As expected, increased variation was found for glucose, aspartate aminotransferase, creatinine, and potassium. Direct bilirubin and urea demonstrated lower variation. CONCLUSIONS: Our RCVAlternate values integrate known and unknown components of analytic, biologic, and preanalytic variation, and depict the variations observed by clinical teams that make medical decisions based on the test values. The RCVAlternate values are similar to the RCVhealthy values derived from known components of variation and suggest further studies to better understand the results being generated on actual patients tested in typical laboratory environments.

Average of Patient Deltas: Patient-Based Quality Control Utilizing the Mean Within-Patient Analyte Variation.

BACKGROUND: Because traditional QC is discontinuous, laboratories use additional strategies to detect systematic error. One strategy, the delta check, is best suited to detect large systematic error. The moving average (MA) monitors the mean patient analyte value but cannot equitably detect systematic error in skewed distributions. Our study combines delta check and MA to develop an average of deltas (AoD) strategy that monitors the mean delta of consecutive, intrapatient results. METHODS: Arrays of the differences (delta) between paired patient results collected within 20-28 h of each other were generated from historical data. AoD protocols were developed using a simulated annealing algorithm in MatLab (Mathworks) to select the number of patient delta values to average and truncation limits to eliminate large deltas. We simulated systematic error by adding bias to arrays for plasma albumin, alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, bicarbonate, bilirubin (total and direct), calcium, chloride, creatinine, lipase, sodium, phosphorus, potassium, total protein, and magnesium. The average number of deltas to detection (ANDED) was then calculated in response to induced systematic error. RESULTS: ANDED varied by combination of assay and AoD protocol. Errors in albumin, lipase, and total protein were detected with a mean of 6 delta pairs. The highest ANDED was calcium, with a positive 0.6-mg/dL shift detected with an ANDED of 75. However, a negative 0.6-mg/dL calcium shift was detected with an ANDED of 25. CONCLUSIONS: AoD detects systematic error with relatively few paired patient samples and is a patient-based QC technique that will enhance error detection.

Urinary metal concentrations among female welders.

As part of a Canada-wide study of women entering non-traditional trades [Women's Health in Apprenticeship Trades-Metalworkers and Electricians (WHAT-ME)], we examined spot urine samples from women welders in Alberta to determine whether urinary metal concentrations exceeded those of the general population, to compare levels to previously published urinary concentrations in male welders and to examine the relationship with welding tasks. Women mailed-in urine samples collected close to the time of completing a detailed exposure questionnaire, including welding tasks on their most recent day welding at work. Of 53 welders working in their trade, 45 had urinary creatinine >0.3-≤3.0g l(-1) and were included in analyses. Seven metals were examined for which both population and male welder urinary concentrations were available: cadmium, chromium, cobalt, copper, manganese, nickel, and zinc. Principal component analysis was used to extract three components from natural log transformed creatinine-corrected metal concentrations. Of the 45 women, 17 reported more than one main task. Overall two thirds worked in fabrication, a third on pipe welding, and smaller numbers on repair, in construction or other tasks: manual metal arc welding was reported by 62%, semi-automatic arc welding by 47%, and arc welding with a tungsten electrode by 15%. In multiple regression analyses, little relation was found between urinary metals and task or type of welding, except for cadmium where lower levels were seen in those reporting semi-automatic manual welding (after adjustment for age and smoking). The proportion of women welders exceeding the selected general population 95th percentile was high for manganese (96%) and chromium (29%). Urinary metal concentrations were similar to those reported for male welders with only manganese, with a geometric mean in women of 1.91 µg g(-1) creatinine, and perhaps copper (11.8 µg g(-1) creatinine), consistently lower in male welders. Although not evident from the task analysis reported here, differences in exposure by sex may be explained by type of welding or by other work practices. A closely comparable cohort of male welders would be necessary to examine this hypothesis more fully.

Serum testosterone levels and clinical outcomes in male hemodialysis patients.

BACKGROUND: Studies linking low serum testosterone concentration to adverse clinical outcomes in hemodialysis patients have been relatively small. We investigated the role of testosterone in adverse outcomes and quality of life in an incident cohort of male Canadian hemodialysis patients. STUDY DESIGN: A prospectively designed multicenter observational study using data from the Canadian Kidney Disease Cohort Study (CKDCS). SETTING & PARTICIPANTS: Male patients initiating hemodialysis therapy since February 14, 2005, in 3 Canadian centers serving ethnically diverse populations were studied (N = 623). PREDICTOR: Serum testosterone levels using the International Society of Andrology, International Society for the Study of the Aging Male, and European Association of Urology cutoffs (low, <231 ng/dL; borderline, 231-346 ng/dL; normal, >346 ng/dL). OUTCOMES: All-cause mortality, fatal and nonfatal cardiovascular (CV) events, and Health Utility Index (HUI)-assessed health-related quality of life. MEASUREMENTS: Participants completed a structured interview on demographics and medical history and an HUI questionnaire (version 3). Routine laboratory test results captured into the study database, and serum testosterone measured within 3 months after initiation of the baseline hemodialysis session. RESULTS: During a median follow-up of 20 (range, 1-81) months, 166 (27%) died and 98 (20%) had a CV event. Mean serum testosterone level was 234.1 ± 146.1 (SD) ng/dL. Higher serum testosterone levels were associated with significantly decreased unadjusted risk of death (HR per 10-ng/dL increase, 0.58; 95% CI, 0.37-0.90). There was a statistically significant trend for higher all-cause mortality with low serum testosterone levels in adjusted analyses (P < 0.001). Higher levels of log-transformed testosterone were associated with significantly higher HUI scores (P for trend <0.001), and low levels of serum testosterone were associated significantly with lower HUI scores (P for trend <0.001). Although there was a significant trend in the unadjusted risk of CV events among participants with low serum testosterone levels (P < 0.001), the risk was no longer significant after adjustment for age. There was no significant interaction with age and serum testosterone level tested as continuous variables (P = 0.07). LIMITATIONS: A short follow-up period and serum testosterone measured on a single occasion. CONCLUSIONS: Low serum testosterone concentration may be a modifiable risk factor for adverse outcomes and poor quality of life in male hemodialysis patients. This hypothesis should be tested in randomized controlled trials.

Reference intervals of complete blood count constituents are highly correlated to waist circumference: should obese patients have their own "normal values?".

Body mass index (BMI), the prevalent indicator of obesity, is not easily grasped by patients nor physicians. Waist circumference (WC) is correlated to obesity, is better understood and has a stronger relationship to the metabolic syndrome. We compiled WC, complete blood count (CBC) parameters as well as other pertinent data of 6766 25-55-year-old US volunteers sampled in the US National Health and Nutrition Examination Survey, in the years 2005-2010. To determine reference intervals of typical US patients visiting their clinician, we used minimal exclusion criteria. We compiled hemoglobin, red blood cell count, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration, mean cell hemoglobin (MCH), red cell distribution width (RDW), platelet count, mean platelet volume, and counts of white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, and basophils. In addition, we also compiled serum C reactive protein and serum iron. The three major US races were studied and reference interval diagrams were constructed for each CBC parameter plotted against WC. WBC count, RDW, lymphocyte, neutrophil, and red blood cell count increase with WC. Conversely, serum iron and MCH and MCV decrease. These relationships may be related to insulin resistance and chronic activation of the immune system and the resulting low-grade inflammatory state. WC is a strong predictor for many CBC parameters, suggesting that WC should be taken into account when evaluating blood count results. Clinicians who take care of obese patients should be aware of altered hematology and investigate and treat accordingly.

Tighter precision target required for lactate testing in patients with lactic acidosis.

BACKGROUND: Allowable analytic errors are generally based on biologic variation in normal, healthy subjects. Some analytes like blood lactate have low concentrations in healthy individuals and resultant allowable variation is large when expressed as a coefficient of variation (CV). In Ricós' compendium of biologic variation, the relative pooled intra-individual lactate variation (si) averages 27% and the desirable imprecision becomes 13.5%. We derived biologic variability (sb) from consecutive patient data and demonstrate that sb of lactate is significantly lower. METHODS: A data repository provided lactate results measured over 18 months in the General Systems intensive care unit (ICU) at the University of Alberta Hospital in Edmonton, Canada. In total 54,000 lactate measurements were made on two point-of-care Radiometer 800 blood gas systems operated by Respiratory Therapy. The standard deviations of duplicates (SDD) were tabulated for the intra-patient lactates that were separated by 0-1, 1-2...up to 16 h. The graphs of SDD vs. time interval were approximately linear; the y-intercept provided by the linear regression represents the sum of sb and short-term analytic variation (sa):y0=(sa²+sb²)½. The short-term sa was determined from imprecisions provided by Radiometer and confirmed with onsite controls. The derivation of sb was performed for multiple patient ranges of lactate. RESULTS: The relative desirable lactate imprecision for patients with lactic acidosis is about half that of normal individuals. CONCLUSIONS: As such, evaluations of lactate measurements must use tighter allowable error limits.

ICSH guidance for internal quality control policy for blood cell counters.

This paper is a description of the ICSH guidance for internal quality control (IQC) policy for blood cell counters. It follows from and links to a separate ICSH review for such policies and practices. The ICSH has gathered information regarding the current state of practice through review of published guidance from regulatory bodies, a questionnaire to six major cell counter manufacturers and a survey issued to 191 diagnostic laboratories in four countries (China, the Republic of Ireland, Spain, and the United Kingdom) on their IQC practice and approach to the use of commercial IQC materials. This has revealed diversity both in guidance and in practice around the world. There is diversity in guidance from regulatory organizations in regard to IQC methods each recommends, clinical levels to use and frequency to run commercial controls, and finally recommended sources of commercial control materials. The diversity in practice among clinical laboratories spans the areas of IQC methods used, derivation of target values, and action limits used with commercial control materials, and frequency of running commercial controls materials. These findings and their implications for IQC Practice are addressed in this guidance document, which proposes a harmonized approach to address the issues faced by diagnostic laboratories.

ICSH review of internal quality control policy for blood cell counters.

INTRODUCTION: This paper is a report of an ICSH review of policies and practices for internal quality control (IQC) policy for haematology cell counters among regulatory bodies, cell counter manufacturers and diagnostic laboratories. It includes a discussion of the study findings and links to separate ICSH guidance for such policies and practices. The application of internal quality control (IQC) methods is an essential pre-requisite for all clinical laboratory testing including the blood count (Full Blood Count, FBC, or Complete Blood Count, CBC). METHODS: The ICSH has gathered information regarding the current state of practice through review of published guidance from regulatory bodies, a questionnaire to six major cell counter manufacturers (Abbott Diagnostics, Beckman Coulter, Horiba Medical Diagnostic Instruments & Systems, Mindray Medical International, Siemens Healthcare Diagnostics and Sysmex Corporation) and a survey issued to 191 diagnostic laboratories in four countries (China, Republic of Ireland, Spain and the United Kingdom) on their IQC practice and approach to use of commercial IQC materials. RESULTS: This has revealed diversity both in guidance and in practice around the world. There is diversity in guidance from regulatory organizations in regard to IQC methods each recommends, clinical levels to use and frequency to run commercial controls, and finally recommended sources of commercial controls. The diversity in practice among clinical laboratories spans the areas of IQC methods used, derivation of target values and action limits used with control materials, and frequency of running commercial controls materials. CONCLUSIONS: These findings and their implications for IQC Practice are discussed in this paper. They are used to inform a separate guidance document, which proposes a harmonized approach to address the issues faced by diagnostic laboratories.

Retrospective analysis of intra-patient laboratory variation demonstrates that the BD Vacutainer® Barricor™ blood collection tube reduces troponin variation.

OBJECTIVE: The BD Vacutainer® Barricor™ plasma blood collection tube uses a mechanical separator during centrifugation to separate plasma from the cellular elements of blood. Compared to use of plasma separator tubes (PST™) with gel, Barricor™ produces a cleaner sample with less residual cellular content. We sought to determine if Barricor™ reduces pre-analytical error compared to PST™. DESIGN & METHODS: We used a model previously published that utilizes serial differences between intra-patient measurements transformed into a Taylor series of variation vs time with the y-intercept equal to the sum of short-term analytic variation, preanalytic variation and biologic variation. The intra-patient variation of chloride, sodium, potassium, and troponin-T (hs-TnT) obtained from the Emergency Department of a large tertiary care center sampled with PST™ (May 2015-April 2018, n = 59,762 specimens) or Barricor™ (May 2018-May 2021, n = 61,512 specimens) was evaluated. All specimens were analyzed on either Roche Modular or Cobas® instruments. For each analyte, pairs of intra-patient results were tabulated and separated by 1 h intervals. The average between-pair variations were then regressed against time. We also determined the number of intra-patient outliers using the reference change value for each analyte. RESULTS: The Barricor™ hs-TnT y-intercept (-0.0132) was significantly lower than the PST™ intercept (0.9109; p = 0.022). This was also true for chloride (y-intercept = 1.0067 in Barricor™ and 1.3431 in PST™, p = 0.037). The percentage of hs-TnT outliers was significantly lower in Barricor™ (8.32 %) vs PST™ (12.2 %; p < 0.001). CONCLUSION: The analytical and biological variations are assumed to be steady over the study periods; we ascribe the difference in the y-intercept to the preanalytical effect of the Barricor™ tube reducing platelets and other cellular debris.

Towards more complete specifications for acceptable analytical performance - a plea for error grid analysis.

Abstract We examine limitations of common analytical performance specifications for quantitative assays. Specifications can be either clinical or regulatory. Problems with current specifications include specifying limits for only 95% of the results, having only one set of limits that demarcate no harm from minor harm, using incomplete models for total error, not accounting for the potential of user error, and not supplying sufficient protocol requirements. Error grids are recommended to address these problems as error grids account for 100% of the data and stratify errors into different severity categories. Total error estimation from a method comparison can be used to estimate the inner region of an error grid, but the outer region needs to be addressed using risk management techniques. The risk management steps, foreign to many in laboratory medicine, are outlined.

Design and implementation of the Canadian Kidney Disease Cohort Study (CKDCS): A prospective observational study of incident hemodialysis patients.

BACKGROUND: Many nephrology observational studies use renal registries, which have well known limitations. The Canadian Kidney Disease Cohort Study (CKDCS) is a large prospective observational study of patients commencing hemodialysis in five Canadian centers. This study focuses on delineating potentially reversible determinants of adverse outcomes that occur in patients receiving dialysis for end-stage renal disease (ESRD). METHODS/DESIGN: The CKDCS collects information on risk factors and outcomes, and stores specimens (blood, dialysate, hair and fingernails) at baseline and in long-term follow-up. Such specimens will permit measurements of biochemical markers, proteomic and genetic parameters (proteins and DNA) not measured in routine care. To avoid selection bias, all consenting incident hemodialysis patients at participating centers are enrolled, the large sample size (target of 1500 patients), large number of exposures, and high event rates will permit the exploration of multiple potential research questions. PRELIMINARY RESULTS: Data on the baseline characteristics from the first 1074 subjects showed that the average age of patients was 62 (range; 50-73) years. The leading cause of ESRD was diabetic nephropathy (41.9%), and the majority of the patients were white (80.0%). Only 18.7% of the subjects received dialysis in a satellite unit, and over 80% lived within a 50 km radius of the nearest nephrologist's practice. DISCUSSION: The prospective design, detailed clinical information, and stored biological specimens provide a wealth of information with potential to greatly enhance our understanding of risk factors for adverse outcomes in dialysis patients. The scientific value of the stored patient tissue will grow as new genetic and biochemical markers are discovered in the future.

The use of serial patient blood gas, electrolyte and glucose results to derive biologic variation: a new tool to assess the acceptability of intensive care unit testing.

BACKGROUND: Most estimates of biologic variation (s(b)) are based on periodically acquiring and storing specimens, followed by analysis within a single analytic run. We demonstrate for many intensive care unit (ICU) tests, only patient results need be statistically analyzed to provide reliable estimates of s(b). METHODS: Over 11 months, approximately 28,000 blood gas measurements (including electrolyte panels and glucose) were performed on one of two Radiometer ABL800 FLEX analyzers (Radiometer, Copenhagen, Denmark) from 1676 ICU patients. We tabulated the measurements of paired intra-patient blood samples drawn within 24 h of each other. After removal of outliers, we calculated the standard deviations of duplicates (SDD) of the intra-patient pairs grouped in 2-h intervals: 0-2 h, 2-4 h, 4-6 h, … 20-22 h and 22-24 h. The SDDs were then regressed against the time intervals of 2-14 h; extrapolation to zero time represents the sum of s(b) and short-term analytic variation (s(a)). RESULTS: Substitution of experimentally derived analytic error permitted the calculation of coefficient of variation (biologic) (CV(b)) (100 s(b)/mean): pH, 0.3%; pCO(2), 5.7%; pO(2), 13%; Na(+), 0.6%; K(+), 4.8%; Cl(-), 0.8%; HCO(3)(-), 3.2%; iCa(++), 2.4%; and glucose, 10.3%. The CV(b) of the electrolytes very closely matches the lowest estimates obtained in the usual manner. CONCLUSIONS: Derivation of the ratio of biologic to analytic variation indicates that the ABL800 is extremely suitable for ICU testing. This analysis should be extended to other point of care instrument systems.

Five-Year Two-Center Retrospective Comparison of Central Laboratory Glucose to GEM 4000 and ABL 800 Blood Glucose: Demonstrating the (In)adequacy of Blood Gas Glucose.

PURPOSE: To evaluate the glucose assays of two blood gas analyzers (BGAs) in intensive care unit (ICU) patients by comparing ICU BGA glucoses to central laboratory (CL) glucoses of almost simultaneously drawn specimens. METHODS: Data repositories provided five years of ICU BGA glucoses and contemporaneously drawn CL glucoses from a Calgary, Alberta ICU equipped with IL GEM 4000 and CL Roche Cobas 8000-C702, and an Edmonton, Alberta ICU equipped with Radiometer ABL 800 and CL Beckman-Coulter DxC. Blood glucose analyzer and CL glucose differences were evaluated if they were both drawn either within ±15 or ±5 minutes. Glucose differences were assessed graphically and quantitatively with simple run charts and the surveillance error grid (SEG) and quantitatively with the 2016 Food and Drug Administration guidance document, with ISO 15197 and SEG statistical summaries. As the GEM glucose exhibits diurnal variation, CL-arterial blood gas (ABG) differences were evaluated according to time of day. RESULTS: Compared to the GEM glucoses measured between 0200 and 0800, the run charts of (GEM-CL) glucose demonstrate significant outliers between 0800 and 0200 which are identified as moderate to severe clinical outliers by SEG analysis (P < .002 and P < .0005 for 5- and 15-minute intervals). Over the entire 24-hour period, the rates of moderate to severe glucose clinical outliers are 3.5/1000 (GEM) and 0.6/1000 glucoses (ABL), respectively, using the 15-minute interval (P < .0001). DISCUSSION: The GEM ABG glucose is associated with a higher frequency of moderate to severe glucose clinical outliers, especially between 0800 and 0200, increased CL testing and higher average patient glucoses.

Barricor blood collection tubes are equivalent to PST for a variety of chemistry and immunoassay analytes except for lactate dehydrogenase.

INTRODUCTION: The BD Barricor tube uses a novel mechanical separator designed to eliminate gel artifacts, decrease cellular contamination, and improve stability. Here, we evaluated the Barricor tube as a possible replacement for PST using Beckman Coulter analyzers under both optimal, alternative, and suboptimal centrifugation conditions based on BD recommendations. METHODS: Paired PST and Barricor samples were collected from 4 local hospitals and processed based on site-specific preanalytical systems involving automated or manual centrifugation. Centrifugation conditions ranged from 1912 ×g for 10 min (suboptimal), 2060 g for 10 min (alternative), and 4000 ×g for 3 or 10 min (optimal). Tube volume (4.5 vs. 5.5 ml) was also assessed. Forty-three chemistry and immunochemistry analytes were measured on Beckman Coulter DxC and DxI analyzers. RESULTS: Using an automated preanlaytical system with suboptimal spin conditions, no bias between PST and Barricor was observed for all analytes tested except lactate dehydrogenase (LD). Further investigation revealed significant increase in LD when Barricor was spun for 10 min at 1912, 2060 and 4000 ×g, ranging from +7.4-19.4% vs. PST across the entire measurement interval (87-493 U/l). Smaller tube volume was also associated with higher LD. Differences in LD occurred despite no change in other hemolysis markers such as potassium, phosphate, and AST. CONCLUSIONS: LD is most sensitive to varying centrifugation conditions (time and speed) in Barricor tubes. We recommend that BD centrifugation protocols should be closely evaluated to determine if Barricor is equivalent to PST under local preanalytical configurations.

Analytical Concordance of Diverse Point-of-Care and Central Laboratory Troponin I Assays.

BACKGROUND: Cardiac troponin I (cTnI) 99th percentile cutoffs, used in the diagnosis of acute myocardial infarction, are not standardized across cTnI assays. We compared 3 point-of-care (POC) and 1 central laboratory contemporary cTnI assays against the Abbott high-sensitivity (hs) cTnI to evaluate the analytical concordance and the feasibility of using a single cutoff value for all assays. METHODS: Fresh blood samples collected from 102 inpatients in the coronary care unit were measured on central laboratory instruments (Beckman Coulter DxI AccuTnI+3 TnI, Abbott Architect hs-TnI) and cTnI POC analyzers (Alere Triage Troponin I, Radiometer AQT90, Abbott i-STAT). Agreement and correlation between the contemporary cTnI assays and hs-cTnI assay were assessed using regression analysis. Proportional bias was assessed using Bland-Altman plots. Concordance between the contemporary cTnI and hs-cTnI assays was determined by diagnostic contingency tables at specific cutoffs. RESULTS: Most POC cTnI assays had excellent correlation with the Abbott hs-cTnI method (r 2 = 0.955-0.970) except for Alere Triage (r 2 = 0.617), while proportional bias is evident between all cTnI assays. Overall concordance between POC contemporary cTnI assays and hs-cTnI assay was 80% to 90% at their respective 99th percentile cutoffs. The concordance increased to 90% to 95% when a fixed cutoff of 0.03 to 0.05 ng/mL was used across the assays. CONCLUSIONS: This study demonstrates poor analytical concordance between cTnI assays at the 99th percentile and supports the notion of a single clinical decision limit for cTnI and consequently standardization of diagnostic protocols despite the analytical differences among these assays.

Accuracy of the CoaguChek XS for point-of-care international normalized ratio (INR) measurement in children requiring warfarin.

Point-of-care INR (POC INR) meters can provide a safe and effective method for monitoring oral vitamin K antagonists (VKAs) in children. Stollery Children's Hospital has a large POC INR meter loan program for children requiring oral VKAs. Our protocol requires that POC INR results be compared to the standard laboratory INR for each child on several consecutive tests to ensure accuracy of CoaguChek XS (Roche Diagnostics, Basel Switzerland) meter. It was the objective of the study to determine the accuracy of the CoaguChek XS by comparing whole blood INR results from the CoaguChek XS to plasma INR results from the standard laboratory in children. POC INR meter validations were performed on plasma samples from two time points from 62 children receiving warfarin by drawing a venous blood sample for laboratory prothrombin (PT)-INR measurements and simultaneous INR determinations using the POC-INR meter. Agreement between CoaguChek XS INR and laboratory INR was assessed using Bland-Altman plots. Bland-Altman's 95% limits of agreement were 0.11 (-0.20; 0.42) and 0.13 (-0.22; 0.48) at the two time points, respectively. In conclusion, the CoaguChek XS meter appraisal generates an accurate and precise INR measure in children when compared to laboratory INR test results.

Application of 3-D Delta check graphs to HbA1c quality control and HbA1c utilization.

Delta checking is a laboratory information system (LIS)-based tool that detects patient and laboratory quality control errors. By using hemoglobin A1c (HbA1c) data, we developed a novel approach to summarizing and presenting patient Delta values to address limitations of current Delta check algorithms. Delta values were calculated from intrapatient pairs of HbA1c (n = 55,327) measured during 2 years in a single referral or a university hospital laboratory. Three-dimensional Delta-time (DeltaT) and percentile limit graphs were constructed. Cumulative distribution function analysis was used to explore clinical utilization. The DeltaT graphs showed that HbA1c Delta values increase asymmetrically over time. Although the 2.5 to 97.5 and 5.0 to 95.0 percentile Delta check limits were similar for both sites, the referral laboratory's 0.5 to 99.5 percentile limits were wider. For acute patient care environments, we recommend limits of -3.5% and 1.8% for measurements between 0 and 60 days and -4.0% and 2.0% for measurements between 60 and 120 days. For the outpatient environment, we recommend limits of -4.2% and 2.1% and 5.0% and 2.5% for measurements between 0 and 60 days and 60 and 120 days, respectively.Delta checking can be significantly improved with customization of limits set by population and interobservation period. Because LIS systems are incapable of these customizations, customers must become advocates for these modifications.