Christensen Ng

Diagnosing Diabetes Mellitus: Performance of Hemoglobin A1c Point-of-Care Instruments in General Practice Offices

BACKGROUND Hemoglobin A1c (Hb A1c) measurement by hospital laboratory instruments, but not by point-of-care (POC) instruments, has been recommended for use to diagnose diabetes mellitus. We evaluated results from 13 Hb A1c external quality assurance (EQA) surveys over a 6-year period in Norway, from both POC instruments used in general practice (GP) offices and instruments in hospital laboratories, against the analytical quality specifications recommended for use of Hb A1c to diagnose diabetes mellitus. METHODS All GP offices (n = 1288) and hospital laboratories (n = 52) measuring Hb A1c in Norway participated in the EQA survey. The percentage of participants that performed measurements within the quality specifications was calculated. Pooled within-laboratory CVs were estimated for the Afinion, DCA 2000, DCA 2000+, DCA Vantage(TM), and Nycocard Hb A1c Reader instruments and for hospital laboratory instruments. RESULTS Between 60% to 90% of Afinion and DCA users and hospital laboratories performed Hb A1c measurements within the quality specifications for both trueness (6.0%) and imprecision (CV ≤2.0%) at 2 levels in each EQA survey. The pooled within-laboratory CVs for the Afinion and DCA instruments and hospital laboratories were below the recommended limit of 2.0% for most of the surveys. CONCLUSIONS A large proportion of GP offices using Afinion and DCA POC instruments to measure Hb A1c fulfill the analytical quality specifications for diagnosing diabetes mellitus, and these instruments demonstrate analytical quality comparable to that of hospital laboratory instruments. When GP offices participate in a stringent quality assurance program and generate Hb A1c measurements that meet analytical quality specifications, these measurements can be recommended for use to diagnose diabetes mellitus.

External quality assessment of prothrombin time: The split‐sample model compared with external quality assessment with commercial control material

Objective. CoaguChek S is a point‐of‐care, whole‐blood, prothrombin time monitor. The purpose of this study was to compare two different methods for external quality assessments of CoaguChek S. Material and methods. In the traditional external quality assessment scheme, commercial control material was sent to office laboratories and the results were compared with a method‐specific target value. In the alternative external quality assessment (the split‐sample survey) patient samples were analyzed on CoaguChek S at office laboratories, and venous blood samples from the same patients were analyzed at a hospital laboratory using an assigned comparison method. To obtain comparable performance criteria for the two methods, the limits for “good”, “acceptable” and “poor” performance evaluation in the split‐sample survey had to be expanded because of uncertainties in preanalytical factors and the comparison method. Results. In the traditional external quality assessment the total imprecision (between‐office and within‐office) was 8.0 % at the low level (1.6 INR (International Normalized Ratio)) and 10.5 % at the therapeutic level (3.4 INR). In the split‐sample survey the total imprecision was 12.3 % at the low level (2.1 INR) and 10.7 % at the high level (3.0 INR). Seventy‐five percent of the participating office laboratories were characterized as “good” with the traditional external quality assessments, whereas the corresponding number was 73 % using the split‐sample model. Conclusions. Available commercial control material for CoaguChek S is different from patient samples. This study demonstrates that split‐sample survey is achievable, and is an acceptable alternative to traditional external quality assessment for point‐of‐care prothrombin time monitors where appropriate control material is difficult to obtain.

Stool porphyrins determined by high pressure liquid chromatography and by fractional hydrochloric acid—ether extraction

When stool copro- and protoporphyrin were quantitated by spectrophotometry, after fractional hydrochloric acid-ether extraction, up to 30% of the protoporphyrins were recovered in the coproporphyrin extract. In disorders with elevated stool protoporphyrin excretion (e.g. erythropoietic protoporphyria), this method therefore may give falsely elevated coproporphyrin values. When the stool porphyrins were determined by high pressure liquid chromatography there was no carry-over of protoporphyrin to coproporphyrin. The recoveries were 82 and 87%, and the coefficients of variation 5.6 and 3.1% for proto- and coproporphyrin, respectively. Moreover, in specimens containing a more complex mixture of porphyrins, a complete separation of the C2-C8 porphyrins and porphyrin isomers was obtained in a single run. High pressure liquid chromatography should therefore be considered the method of choice to obtain a quantitative profile of stool porphyrins in the routine laboratory.

The Importance of Reagent Lot Registration in External Quality Assurance/Proficiency Testing Schemes

BACKGROUND Providers of external quality assurance (EQA)/proficiency testing schemes have traditionally focused on evaluation of measurement procedures and participant performance and little attention has been given to reagent lot variation. The aim of the present study was to show the importance of reagent lot registration and evaluation in EQA schemes. METHODS Results from the Noklus (Norwegian Quality Improvement of Primary Care Laboratories) urine albumin/creatinine ratio (ACR) and prothrombin time international normalized ratio (INR) point-of-care EQA schemes from 2009-2015 were used as examples in this study. RESULTS The between-participant CV for Afinion ACR increased from 6%-7% to 11% in 3 consecutive surveys. This increase was caused by differences between albumin reagent lots that were also observed when fresh urine samples were used. For the INR scheme, the CoaguChek INR results increased with the production date of the reagent lots, with reagent lot medians increasing from 2.0 to 2.5 INR and from 2.7 to 3.3 INR (from the oldest to the newest reagent lot) for 2 control levels, respectively. These differences in lot medians were not observed when native patient samples were used. CONCLUSIONS Presenting results from different reagent lots in EQA feedback reports can give helpful information to the participants that may explain their deviant EQA results. Information regarding whether the reagent lot differences found in the schemes can affect patient samples is important and should be communicated to the participants as well as to the manufacturers. EQA providers should consider registering and evaluating results from reagent lots.

How to deal with semi-quantitative tests? Application of an ordinal scale model to measurements of urine glucose

Abstract Background: The interpretation of semi-quantitative methods has always been difficult, because the different kitmanufacturers use varying concentration values and there is a considerable overlap between kit-defined concentrations within the same kit (Kit: ‘Ready-to-use’ measuring system specific for each manufacturers product). Material: More than 2000 private practitioners and laboratories participated in three external quality control surveys on urine-glucose performed with a total of six control materials with known concentrations. Method: The ordinal scale model for evaluation of dichotomous methods based on rankit transformation of fractions of positive results (Petersen et al. Scand J Clin Lab Invest 2008;68:298–311) has been extended and modified to handle semi-quantitative data. Here, the percentages of results larger than the kit-concentration is calculated for each control sample and applied as a dichotomous method. Thereafter, these percentages are separated into all the defined kit-concentrations. Results: A total of eight kits had more than 50 measurements on at least four control materials which made them eligible for the calculations of logarithmic mean and standard deviation and thereby geometric mean and coefficient of variation for each of the kit-concentrations of each kit. Based on these parameters, the true concentration for selected percentages of each kit-concentration could be estimated. Moreover, the percentages of the different kit-concentrations could be calculated for each known true concentration. Conclusions: The present model is a powerful tool for improved characterization of semi-quantitative kits, which makes it possible to evaluate and validate kits and to optimize external quality control.

Point-of-care urine albumin in general practice offices: effect of participation in an external quality assurance scheme.

Abstract Background: The Norwegian Quality Improvement of Primary Care Laboratories (Noklus) offers external quality assurance (EQA) schemes (EQASs) for urine albumin (UA) annually. This study analyzed the EQA results to determine how the analytical quality of UA analysis in general practice (GP) offices developed between 1998 (n=473) and 2012 (n=1160). Methods: Two EQA urine samples were distributed yearly to the participants by mail. The participants measured the UA of each sample and returned the results together with information about their instrument, the profession and number of employees at the office, frequency of internal quality control (IQC), and number of analyses per month. In the feedback report, they received an assessment of their analytical performance. Results: The number of years that the GP office had participated in Noklus was inversely related to the percentage of “poor” results for quantitative but not semiquantitative instruments. The analytical quality improved for participants using quantitative instruments who received an initial assessment of “poor” and who subsequently changed their instrument. Participants using reagents that had expired or were within 3 months of the expiration date performed worse than those using reagents that were expiring in more than 3 months. Conclusions: Continuous participation in the Noklus program improved the performance of quantitative UA analyses at GP offices. This is probably in part attributable to the complete Noklus quality system, whereby in addition to participating in EQAS, participants are visited by laboratory consultants who examine their procedures and provide practical advice and education regarding the use of different instruments.

Response to Kitchen et al.'s External quality assessment of prothrombin time: The split‐sample model compared to external quality assessment with commercial control material

First of all, we thank Kitchen et al. [1] for commenting on our manuscript [2], and also the Editor of SJCLI for this opportunity to respond and extend the discussion of these interesting matters. Kitchen et al. point out that we used only one hospital laboratory in the comparison in our split-sample survey. This was done deliberately. In our study, we describe a model in which all the participants are compared with only one hospital laboratory in order to avoid the problem of systematic differences between methods and the use of different thromboplastins and technologies. In the absence of a reference method, we chose a hospital using the method most commonly used in Norwegian hospitals for measuring PT INR (Prothrombin Time International Normalized Ratio), and that performed well on our EQAS (External Quality Assessment) for hospital laboratories with fresh frozen plasma. If a split-sample survey is to be offered as part of the EQA programme at NOKLUS (Norwegian Quality Improvement of Primary Care Laboratories), we would probably use the same model as described in the manuscript. All the participants (office laboratories, patients self-testing) would use only one hospital laboratory assigned to be the comparison method, and not the local hospitals. The analytical quality of the assigned hospital would naturally be crucial. In Norway, all hospital methods are calibrated by the same calibrators from EQUALIS (External Quality Assurance in Laboratory Medicine in Sweden) and are traceable to the reference thromboplastin RBT/90 from the World Health Organization (WHO).

Evaluation of Serum Separator Tubes as a Mail Transport Device in Primary Health Care

Serum separator tubes were evaluated as a serum separator system and a mail transport device. Using conventional tubes as controls, 26 serum constituents were examined. The samples were mailed from three different general practitioners to a central laboratory. Thirteen constituents had concentrations that were significantly different from the concentration in the conventional tubes. When medically important coefficients of variations were taken into account, however, the changes of only two constituents (potassium and cobalamin) were regarded as important.