George S. Cembrowski

Alberta Health Services · Laboratory Medicine and Pathology

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™ reduce...

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 variabl...

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 combine...

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...

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 B...

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...

Objectives In our study of the accuracy of blood gas/electrolyte analyzers, we have re-discovered that the the anion gap calculation (Na – Cl – HCO3) is an excellent indicator of electrolyte measurement inaccuracy. Calculations that incorporate component measurements will exhibit propagation of errors; inaccurate systems will demonstrate increased...

Objectives Not infrequently, patient laboratory printouts suggest followup tests. In reviewing the report of a 46 year old British Columbia female’s ferritin of 86 ug/L, we were puzzled by the comment: ‘Possible Iron Deficiency’ for ferritins between 50 and 100 ug/L based on 2010 guidelines. This comment medicalizes the patient and she thinks she h...

Objectives The GEM 4000 (Instrumentation Laboratory, Bedford, MA) is a point-of-care analyzer, primarily used in a critical care setting to measure blood gases, glucose, electrolytes, and hemoglobin. Previous studies have shown that the instrument demonstrates increased imprecision compared to similar analyzers for iCa, electrolytes, and blood gase...

Introduction: Lactic acidosis represents the pathologic accumulation of lactate and hydrogen ions. It is important to efficiently diagnose lactic acidosis as delayed treatment will lead to poor patient outcomes. As plasma lactate levels may not be rapidly available, some physicians may use elevated anion gaps to test for the need to measure lactat...

Objectives: BD Canada recently released a blood collection tube with a novel mechanical separator called the Barricor. We evaluated this tube as an alternate sample type for cardiac troponin I (cTnI) testing using the Beckman Coulter AccuTnI+3 assay. Design and methods: 3014 paired patient specimens (Barricor, plasma separator tube or PST) were...

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 measurem...

Abstract Introduction Myocardial infarction (MI) is the death of cardiac muscle in the setting of severe ischemia (lack of oxygen and nutrient supply). Assay of serum troponin I (TnI) is the biochemical gold standard for detecting MI. With the development of high sensitivity assays, TnI is being detected in milder conditions such as reversible t...

Background: Within- and/or between-instrument variation may falsely indicate patient trends or obscure real trends. We employ a methodology that transforms sequential intra-patient results into estimates of biologic and analytic variation. We previously derived realistic biologic variation (sb) of blood gas (BG) and hematology analytes. We extend...

One of the most frequent questions asked by the new clinical chemist is, “How do I set up the quality control for a particular analyzer?” Two new documents described below will readily help both the neophyte and practicing chemist. The practice of quality control in the clinical laboratory has been evolving in fits and starts. Unfortunately, today'...

Widespread and successful implementation of any glucose measurement system in a hospital point-of-care (POC) program requires a number of features in addition to accurate and reliable analytical performance. Such features include, but are not limited to, a system's glucose-hematocrit dependence, durability, information technology capabilities, and...

Xu et al1 published an article entitled “Limiting the Testing of AST: A Diagnostically Nonspecific Enzyme,” in which the authors claimed that only aspartate aminotransferase (AST) could be measured when alanine aminotransferase (ALT) exceeds a predetermined limit, and so a substantial health care budget could be saved. That is a great idea. However...

Introduction: Most estimates of biologic variation (sb ) are based on periodically acquiring and storing specimens from reference subjects, followed by analysis within a tightly controlled analytic run. We demonstrate that reliable estimates of sb can be derived for virtually all constituents of the CBC from previously obtained paired patient resu...

The MyStar Extra self-monitoring blood glucose (SMBG) system provides moving estimates of the patient's hemoglobin A1c (HbA1c). There is a treasure trove of highly accurate glucose data available from highly accurate SMBG, CGM and FGM along with highly accurate HPLC HbA1c. If Nathan's criteria are used to select subjects whose glucoses can be corre...

Annually, millions of pairs of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) tests are ordered. These enzymes are highly correlated, and ALT is far more specific diagnostically than AST. To reduce AST testing, we suggest measuring AST only when ALT exceeds a predetermined limit. We derived the proportions of elevated ASTs that...

The optimal means of pre-operative risk stratification in patients with atrial fibrillation (AF) is uncertain. To examine the accuracy of AF thromboembolic risk models (the CHADS2 , CHA2 DS2 -VASc, and R2 CHADS2 scores) for predicting 30 day stroke and/or all-cause mortality after non-cardiac surgery in patients with preoperative AF, and to compare...

The hematology analyzers of today provide more reproducible analyses compared with those of a few decades ago, necessitating an evolution in hematology quality practices. The improved performance allows use of simple quality control rules. This improved performance also renders the repeat analysis of critical value specimens non value added. Some o...

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 publishe...

Traditional glucose error grids provide error limits for glucose meters. These criteria help to assess the meter's suitability to prevent acute injury. We present a rationale for an error grid that provides a different set of error limits to help prevent chronic injury in diabetes. For example, glucose values in the no treatment zone of a tradition...

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 to 55 year ol...

To investigate the rates and causality of adverse event(s) (AE) associated with natural health product (NHP) use, prescription drug use and concurrent NHP-drug use through active surveillance in community pharmacies. Cross-sectional study of screened patients. 10 community pharmacies across Alberta and British Columbia, Canada from 14 January to 30...

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 in...

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. A prospectively designed multicenter observational study using data from...

If initial lipid screening requires just the knowledge of the Framingham risk score, patients need not fast.  the 12 hour fast should remain mandatory when:  significant hyperlipidemia is discovered  cholesterol reducing therapy is indicated  serial, calculated LDL-cholesterol , levels need to be assessed for treatment efficacy. Abstract Introd...

Many self-monitoring of blood glucose (SMBG) systems have generated artefactually increased glucose results in low-hematocrit patients (e.g., intensive care unit and renal failure patients); conversely, these devices could produce artefactually decreased glucose results in high-hematocrit patients (e.g., neonates). The introduction of hematocrit-in...

Background Many consumers use natural health products (NHPs) concurrently with prescription medications. As NHP-related harms are under-reported through passive surveillance, the safety of concurrent NHP-drug use remains unknown. To conduct active surveillance in participating community pharmacies to identify adverse events related to concurrent NH...

Case summaries for all detailed patient interviews. (DOCX)

MHPD Memo (February 23, 2012) supporting Health Canada passive surveillance cost data. (PDF)

Cvijovic et al. 2011 Unpublished manuscript supporting Case 1. (DOC)

Purpose To investigate the adverse event (AE) rates associated with natural health product (NHP) use, prescription drug use and concurrent NHPs-drug use through active surveillance in community pharmacies in Alberta and British Columbia, Canada. Methods Participating pharmacists and pharmacy technicians screened consecutive individuals picking up p...

The Coalition for Clinical Research—Self-Monitoring of Blood Glucose Scientific Board convened a meeting in San Francisco, CA, July 20–21, 2011, to discuss the current practice of self-monitoring of blood glucose (SMBG) in non-insulin-treated (NIT) type 2 diabetes mellitus (T2DM). Twelve physician panel members from academia, practice, and governme...

HbA(1c) has been recently recommended as the primary diagnostic test for diabetes. This study evaluated the positive predictive value (PPV) and negative predictive value (NPV) of HbA(1c) against the oral glucose tolerance test (OGTT) in three locations. Three years of data with concurrent OGTT and HbA(1c) tests were extracted from Laboratory Inform...

Dr. Cembrowski provides an analysis of an article by Harrison and colleagues in this issue of Journal of Diabetes Science and Technology in which the authors describe the evaluation of a new device for self-monitoring of blood glucose, the Bayer CONTOUR® blood glucose monitoring system.

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 to...

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...

Diverse approaches have been used to assure the analytical quality of automated hematology; as such, there is great variation in their error detection capabilities. We summarize the intralaboratory performance of a cohort of Sysmex XE-2100's running e-Check hematology quality control (QC). The imprecisions of a median performing (50th percentile im...

Background: The measurement of umbilical arterial and venous blood pH is a minimum medico legal standard used to rule out prolonged asphyxia which can result in neonatal brain damage. There is a continuous stream of postnatal investigations that generally support the measurement of more cord blood analytes including lactate, bicarbonate, base exces...

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). Over 11 months, approximately 28,000 blood gas m...

The recently published findings of the Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR)1 trial have dramatically changed clinician attitudes toward the achievement of euglycemia in intensive care unit (ICU) patients (1). In defending the proof-of-concept studies that validated the efficacy of n...

Healthy African Americans are known to have reduced white blood cell counts (WBC) and absolute neutrophil counts (ANC) compared with European Americans, with little agreement about the levels in reference intervals. The objective is to establish race-specific reference intervals for WBC and ANC using US National Health and Nutrition Examination Sur...

Glucose performance is reviewed in the context of total error, which includes error from all sources, not just analytical. Many standards require less than 100% of results to be within specific tolerance limits. Analytical error represents the difference between tested glucose and reference method glucose. Medical errors include analytical errors w...

Hemoglobin A1c (HbA1c) values are influenced by analytical interferences such as HbF and hemoglobin variants and clinical factors such as increased red cell turnover. Although less well-known, demographic factors such as race, age, and sex also influence HbA1c values. The HbA1c reference range should be homogenous in the United States based on the...

Temperature and humidity have been reported to influence the results of whole blood glucose (WBG) measurements. To determine whether patient WBG values were affected by seasonal variation, we conducted a retrospective analysis of 3 years' worth of weekly averages of patient WBG in five Edmonton hospitals. In all five hospitals, the winter WBG avera...

There are several reports from locations in the northern hemisphere of seasonal variation in hemoglobin A1c (HbA1c) levels with higher values noted in the cooler months. The variation has been attributed to holiday seasons, temperature differences, and changes in diet. This article describes the seasonal variation in both hemispheres and in a count...

The volume of hemoglobin A1c (HbA1c) testing has increased dramatically over the past decade and few studies have attempted to determine how the test is used. The goals of this study were to evaluate the frequency of HbA1c testing in regional populations to assess the extent of screening for diabetes and to determine if the HbA1c testing intervals...

The quality of the HbA1c assay is inversely proportional to the variation of the assay. Most published measures of HbA1c variation are limited by the data collection period, the statistical treatment of outliers, and even the noncommutability of the products used to generate the variation measurements. We have used an alternate approach to derive H...

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...

Recent evidence emphasizes the importance of maintaining normoglycemia in critically ill patients to reduce morbidity and mortality. Different analytical methods of varying accuracy exist for obtaining and measuring blood glucose in critically ill patients. The purpose of this study was to determine if there were differences in blood glucose values...

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...

Background and objectives. It is essential that candidates for kidney donation be carefully screened to ensure safety of donation and monitored following unilateral nephrectomy as previous experience has demonstrated loss of kidney function of up to 50% following donation. The low-molecular-weight protein cystatin C (cysC) has been introduced as an...

Analytic imprecision is used to assess the acceptability of HbA(1c) methods performed on a single analyzer. When multiple analyzers are used interchangeably in a laboratory, the analytic imprecision is usually increased and can obscure the detection of a genuine HbA(1c) trend or result in an artefactual patient trend. We have estimated the imprecis...

A patient presented with severe acidosis and a point-of-care lactate measurement of 42 mmol/L. Mesenteric ischemia was suspected, with a potential need for laparotomy; however, plasma lactate measurements were below 4 mmol/L. Ethylene glycol ingestion was subsequently diagnosed. We therefore wished to determine why discrepancies in lactate measurem...