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BACKGROUNDThe European Federation of Clinical Chemistry and Laboratory Medicine European Biological Variation Study (EuBIVAS) has been established to deliver rigorously determined data describing biological variation (BV) of clinically important measurands. Here, EuBIVAS-based BV estimates of serum electrolytes, lipids, urea, uric acid, total protein, total bilirubin, direct bilirubin, and glucose, as well as their associated analytical performance specifications (APSs), are presented.METHODSamples were drawn from 91 healthy individuals (38 male, 53 female; age range, 21–69 years) for 10 consecutive weeks at 6 European laboratories. Samples were stored at −80 °C before duplicate analysis of all samples on an ADVIA 2400 (Siemens Healthineers). Outlier and homogeneity analyses were performed, followed by CV-ANOVA on trend-corrected data, when relevant, to determine BV estimates with CIs.RESULTSThe within-subject BV (CVI) estimates of all measurands, except for urea and LDL cholesterol, were lower than estimates available in an online BV database, with differences being most pronounced for HDL cholesterol, glucose, and direct bilirubin. Significant differences in CVI for men and women/women CONCLUSIONSThe EuBIVAS, which is fully compliant with the recently published Biological Variation Data Critical Appraisal Checklist, has produced well-characterized, high-quality BV estimates utilizing a stringent experimental protocol. These new reference data deliver revised and more exacting APS and reference change values for commonly used clinically important measurands, thus having direct relevance to diagnostics manufacturers, service providers, clinical users, and ultimately patients.

BACKGROUND Concern has been raised about the quality of available biological variation (BV) estimates and the effect of their application in clinical practice. A European Federation of Clinical Chemistry and Laboratory Medicine Task and Finish Group has addressed this issue. The aim of this report is to (a) describe the Biological Variation Data Critical Appraisal Checklist (BIVAC), which verifies whether publications have included all essential elements that may impact the veracity of associated BV estimates, (b) use the BIVAC to critically appraise existing BV publications on enzymes, lipids, kidney, and diabetes-related measurands, and (c) apply metaanalysis to deliver a global within-subject BV (CVI) estimate for alanine aminotransferase (ALT). METHODS In the BIVAC, publications were rated as A, B, C, or D, indicating descending compliance for 14 BIVAC quality items, focusing on study design, methodology, and statistical handling. A D grade indicated that associated BV estimates should not be applied in clinical practice. Systematic searches were applied to identify BV studies for 28 different measurands. RESULTS In total, 128 publications were identified, providing 935 different BV estimates. Nine percent achieved D scores. Outlier analysis and variance homogeneity testing were scored as C in >60% of 847 cases. Metaanalysis delivered a CVI estimate for ALT of 15.4%. CONCLUSIONS Application of BIVAC to BV publications identified deficiencies in required study detail and delivery, especially for statistical analysis. Those deficiencies impact the veracity of BV estimates. BV data from BIVAC-compliant studies can be combined to deliver robust global estimates for safe clinical application.

Introduction: Technological innovation requires the laboratories to ensure that modifications or incorporations of new techniques do not alter the quality of their results. In an ISO 15189 accredited laboratory, flexible scope accreditation facilitates the inclusion of these changes prior to accreditation body evaluation. A strategy to perform the validation of a biochemistry analyzer in an accredited laboratory having a flexible scope is shown. Materials and methods: A validation procedure including the evaluation of imprecision and bias of two Dimension Vista analysers 1500 was conducted. Comparability of patient results between one of them and the lately replaced Dimension RxL Max was evaluated. All studies followed the respective Clinical and Laboratory Standards Institute (CLSI) protocols. 30 chemistry assays were studied. Coefficients of variation, percent bias and total error were calculated for all tests and biological variation was considered as acceptance criteria. Quality control material and patient samples were used as test materials. Interchangeability of the results was established by processing forty patients’ samples in both devices. Results: 27 of the 30 studied parameters met allowable performance criteria. Sodium, chloride and magnesium did not fulfil acceptance criteria. Evidence of interchangeability of patient results was obtained for all parameters except magnesium, NT-proBNP, cTroponin I and C-reactive protein. Conclusions: A laboratory having a well structured and documented validation procedure can opt to get a flexible scope of accreditation. In addition, performing these activities prior to use on patient samples may evidence technical issues which must be corrected to minimize their impact on patient results.

Background: The Commission of Analytical Quality and the Committee of External Quality Programs of Spanish Society of Laboratory Medicine (SEQC) in collaboration with the Dutch Foundation for the Quality organized the first national category 1 External Quality Assessment Programs (EQAP) pilot study. The aim is to evaluate the standardization of serum creatinine measurements in the Spanish laboratories through a category 1 external quality assurance program with commutable material and reference method assigned values. Methods: A total of 87 Spanish laboratories were involved in this program in 2015. Each day a sample control was measured by duplicate during 6 consecutive days. Percentage deviations and coefficients of variation obtained were compared with quality specifications derived from biological variation. Results: A total of 1044 creatinine results were obtained. Laboratories were coded in 11 different method-traceability combinations. Only enzymatic methods get all results within the acceptability limits. Discussion: To participate in a category 1 EQAP is a valuable tool to assess the standardization degree in our country; a big effort should be made to promote laboratories to change their procedures and to use enzymatic creatinine methods, in order to achieve a satisfactory standardization degree for this important analyte.

This paper, prepared by the EFLM Task and Finish Group on Allocation of laboratory tests to different models for performance specifications (TFG-DM), is dealing with criteria for allocating measurands to the different models for analytical performance specifications (APS) recognized in the 1st EFLM Strategic Conference Consensus Statement. Model 1, based on the effect of APS on clinical outcome, is the model of choice for measurands that have a central role in the decision-making of a specific disease or clinical situation and where cut-off/decision limits are established for either diagnosing, screening or monitoring. Total cholesterol, glucose, HbA1c, serum albumin and cardiac troponins represent practical examples. Model 2 is based on components of biological variation and should be applied to measurands that do not have a central role in a specific disease or clinical situation, but where the concentration of the measurand is in a steady state. This is best achieved for measurands under strict homeostatic control in order to preserve their concentrations in the body fluid of interest, but it can also be applied to other measurands that are in a steady state in biological fluids. In this case, it is expected that the “noise” produced by the measurement procedure will not significantly alter the signal provided by the concentration of the measurand. This model especially applies to electrolytes and minerals in blood plasma (sodium, potassium, chloride, bicarbonate, calcium, magnesium, inorganic phosphate) and to creatinine, cystatin C, uric acid and total protein in plasma. Model 3, based on state-of-the-art of the measurement, should be used for all the measurands that cannot be included in models 1 or 2.

Background: Biological variation (BV) data have many fundamental applications in laboratory medicine. At the 1st Strategic Conference of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) the reliability and limitations of current BV data were discussed. The EFLM Working Group on Biological Variation is working to increase the quality of BV data by developing a European project to establish a biobank of samples from healthy subjects to be used to produce high quality BV data. Methods: The project involved six European laboratories (Milan, Italy; Bergen, Norway; Madrid, Spain; Padua, Italy; Istanbul, Turkey; Assen, The Netherlands). Blood samples were collected from 97 volunteers (44 men, aged 20–60 years; 43 women, aged 20–50 years; 10 women, aged 55–69 years). Initial subject inclusion required that participants completed an enrolment questionnaire to verify their health status. The volunteers provided blood specimens once per week for 10 weeks. A short questionnaire was completed and some laboratory tests were performed at each sampling consisting of blood collected under controlled conditions to provide serum, K2EDTA-plasma and citrated-plasma samples. Results: Samples from six out of the 97 enroled subjects were discarded as a consequence of abnormal laboratory measurements. A biobank of 18,000 aliquots was established consisting of 120 aliquots of serum, 40 of EDTA-plasma, and 40 of citrated-plasma from each subject. The samples were stored at –80 °C. Conclusions: A biobank of well-characterised samples collected under controlled conditions has been established delivering a European resource to enable production of contemporary BV data.

Point-of-care testing (POCT) refers to laboratory diagnostic testing determined outside the clinical laboratory, in a setting near where the patient is being treated. Blood gas analysis is relevant in chronic obstructive pulmonary disease (COPD) management. Despite its potential benefits of POCT, there are few studies that have assessed its operational and economic impact. The aim of our study is to determine the overall cost per process of COPD outpatient care when the blood gas measurement was performed in a pulmonologist office or in clinical laboratory. A prospective study of 112 outpatients, stages III to IV COPD, was carried out. They undergo an arterial blood gas measurement that was performed both in pulmonology office as POCT and in Departament of Laboratory Medicine. We analyzed the cost of the process based on whether the process was conducted in the pulmonology office or in the laboratory. The median turnaround time elapsed from specimen collection to receiving the blood gas report for the pulmonary office and for the laboratory were 1 and 79 min, respectively. If we consider only the costs related to human and material resources for conducting the blood gas measurement, the costs came to 3.47€ per measurement for the pulmonology office and 1.35€ in the clinical laboratory. However, when considering all issues involved, from the blood gas analysis request by the doctor to the indication (or not) for LTOT, the overall cost by process for the 112 patients in each unit was €16,769.89 and €22,260.97, respectively. This represents a difference of 24.7%. We conclude that there is an overall cost per process in the pulmonary office that is 24.7% lower than that of the clinical laboratory.

The ongoing Ebola virus outbreak in several countries in West Africa was considered by the World Health Organisation (WHO) as a public health emergency of international concern. Healthcare providers must be prepared by organising specific procedures in our hospitals based on recommendations from national and international healthcare organisations. Two aims should be considered: appropriate medical care for patients with suspected or confirmed disease must be ensured, as must measures to prevent transmission to healthcare workers. The clinical laboratory plays an important role and must define and establish its own procedures in accordance with clinicians and integrated into those of the institution, starting with the definition of the organisation model in the laboratory to achieve those goals. In this review we present our experience based on the care of three patients with confirmed cases. We hope it will help other colleagues to plan for Ebola.

The aims of this study are: 1) to use the data included in the biological variation (BV) database to address the usability of BV estimates; and 2) to use different examples from the authors' laboratories to illustrate the use and the usefulness of BV data in laboratory medicine. The BV database is an essential tool for laboratory management. Examples of application of data derived from BV are given in this paper, such as analytical performance specifications that have been included in various quality control software designed to optimize operative rules; also they have been incorporated as acceptability limits in external quality assurance reports. BV data from pathological status are of utmost interest for monitoring patients and differences between the intra-individual coefficients of variation (CVI) estimated from healthy and patients are shown. However, for a number of analytes there are limited data available and for many there are no data, consequently new studies should be encouraged at an international level. In addition, developing international criteria to evaluate publications dealing with the estimation of BV components would be of the utmost interest. We are ready and willing to collaborate with such worthy initiatives. The first EFLM strategic conference on analytical performance specifications is an excellent opportunity for debating these ideas.

Numerical data on the components of biological variation (BV) have many uses in laboratory medicine, including in the setting of analytical quality specifications, generation of reference change values and assessment of the utility of conventional reference values.Generation of a series of up-to-date comprehensive database of components of BV was initiated in 1997, integrating the more relevant information found in publications concerning BV. A scoring system was designed to evaluate the robustness of the data included. The database has been updated every 2 years, made available on the Internet and derived analytical quality specifications for imprecision, bias and total allowable error included in the tabulation of data.Our aim here is to document, in detail, the methodology we used to evaluate the reliability of the included data compiled from the published literature. To date, our approach has not been explicitly documented, although the principles have been presented at many symposia, courses and conferences.

Introduction Arterial blood gas analysis is relevant in chronic obstructive pulmonary disease (COPD) management. The aim of this study was to evaluate whether the use of a blood gas analyzer in pulmonology departments improves the clinical, operational and economic outcomes when compared with clinical laboratory measurements. Patients and methods It is an observational prospective study. 112 patients were selected. After specimen collection, the measurement was performed both in pulmonology office as point-of-care and in laboratory. We evaluated clinical outcomes (modification of the indication of long-term oxygen therapy (LTOT) according to results, changes in blood gas analysis results, relationship of the partial pressure of oxygen (PaO 2 ) obtained in the medical visit and velocity of change of the PaO 2 , influence of total haemoglobin concentration and the change in PaO 2 ), operational outcomes (turnaround time (TAT) from specimen collection to receiving the blood gas analysis report) and economic outcomes (overall cost per process of patient care). Results There were discrepancies in the indication of LTOT in 13.4% of patients. All parameters showed changes. PaO 2 levels showed changes in 2 ways, though they frequently increase over time. The correlation was not good in the other two clinical outcomes. The median TATs in pulmonology office were 1 min versus 79 in laboratory, with 52 min for specimen preparation and transport and 17 min for TAT intralaboratory. The overall cost for the 112 patients in pulmonology office and laboratory was 16,769.89€ and 22,260.97€ respectively. Conclusions The use of a blood gas analyzer in a pulmonology office improves clinical, operational and economic outcomes when compared with clinical laboratory.

Introduction In the modern healthcare service, patients receive care in multiple hospitals and healthcare settings. Therefore, harmonization of results from different methods and instruments, both between and within laboratories, is of the utmost importance. The present pilot study aims to test the use of a Category 1 EQA scheme across four European countries by assessing the current level of equivalence of test results. Method This work was led by the Dutch External Quality Assurance Scheme SKML and involved 28 laboratories from three regions in the UK, Spain and Portugal, and 120 laboratories from The Netherlands. A set of six commutable samples, targeted with reference methods, were circulated and 18 biochemistry analytes were tested. Results and conclusions The Total Error (TE) score, defined as the probability (%) that results are within the Total Error Acceptable (TE A ) limits, for the eighteen analytes was calculated. Our data show that there is a need for further harmonization of laboratory data, in particular for electrolytes (calcium, chloride, magnesium, sodium), enzymes (ALT, amylase, AST, LDH), lipids (HDL-cholesterol), and for substrates (creatinine, total protein). Lack of performance consistency between instruments was seen for most analytes. The lack of harmonization is still present despite manufacturer claims of established traceability.

La Paz is a large university hospital that covers a population of more than 800,000 habitants. In 1998, there were 6 blood gases analyzers outside the laboratory and 4 in the emergency laboratory belonging to 4 different manufacturers. Devices installed in critical care units were controlled directly by nonlaboratory health care personnel. As proposed by the board of directors, we decided to take over the leadership and coordination of an already existing point-of-care testing (POCT) project and to broaden it to other critical care units. A POCT director and coordinator were named. As a first step, 11 devices for blood gases, electrolytes, and metabolites were installed and connected to a data management system and controlled from the emergency laboratory. In 2002, the project increased, including 4 POCT units more, with another 4 added in 2006. Currently, there are 17 devices outside the emergency laboratory, 3 in the stat laboratory, and 1 in a peripheral laboratory. A specific training program is designed for the operators. More than 1200 operators have received the initial training in the current period. In 2002, a multidisciplinary POCT committee was created, and at the end of 2006, the committee decided to incorporate a personal identification protocol. In conclusion, since established, the project’s 2 main objectives have been attained: to assure the quality of the test results and to reduce the turnaround time. Some other clear advantages of the project are the unifying of the technology for the same test and having a unique

The measurement of ammonia is a standard request for patients hospitalised in critical care units and is of considerable usefulness in managing hepatic impairment for monitoring the onset of encephalopathy, particularly in paediatric units.1 However, its measurement presents difficulties for the laboratory due to preanalytical and analytical issues. There are multiple preanalytical issues that can cause false increases in ammonia in the sample due to deterioration phenomena related to protein catabolism. The sample's stability limit is 1 h, and the sample needs to be kept refrigerated and sealed throughout the process, including pre-centrifugation, to avoid external contamination and evaporation.2 The most extensively used laboratory methodology in laboratories is enzymatic determination (glutamate dehydrogenase (GLDH)). Interference from various factors has been reported, including products resulting from hepatic damage. Haemolysis also causes a false increase in ammonia, although it is not clear whether this increase is due to the release of intracellular content or to some other mechanism. It is therefore recommended that a sample blank be employed.3 In the laboratory, we perform the ammonia measurement in lithium-heparin plasma, using the enzymatic method (without a sample blank or reagent blank), which uses GLDH and a stabilised hydroxymethylglutaryl-CoA reductase (NADPH) analogue (Dimension Vista 1500, Siemens HD, Tarrytown, New York, USA). There has been a recent change in the formulation of the reagent, with a reduction in the limit of detection from 25 to 10 µmol/L. New reagent has a microbial source of the enzyme (GLDH), …

Introduction Current external quality assurance schemes have been classified into six categories, according to their ability to verify the degree of standardization of the participating measurement procedures. SKML (Netherlands) is a Category 1 EQA scheme (commutable EQA materials with values assigned by reference methods), whereas SEQC (Spain) is a Category 5 scheme (replicate analyses of non-commutable materials with no values assigned by reference methods). Aim The results obtained by a group of Spanish laboratories participating in a pilot study organized by SKML are examined, with the aim of pointing out the improvements over our current scheme that a Category 1 program could provide. Method Imprecision and bias are calculated for each analyte and laboratory, and compared with quality specifications derived from biological variation. Results Of the 26 analytes studied, 9 had results comparable with those from reference methods, and 10 analytes did not have comparable results. The remaining 7 analytes measured did not have available reference method values, and in these cases, comparison with the peer group showed comparable results. The reasons for disagreement in the second group can be summarized as: use of non-standard methods (IFCC without exogenous pyridoxal phosphate for AST and ALT, Jaffe kinetic at low-normal creatinine concentrations and with eGFR); non-commutability of the reference material used to assign values to the routine calibrator (calcium, magnesium and sodium); use of reference materials without established commutability instead of reference methods for AST and GGT, and lack of a systematic effort by manufacturers to harmonize results. Conclusions Results obtained in this work demonstrate the important role of external quality assurance programs using commutable materials with values assigned by reference methods to correctly monitor the standardization of laboratory tests with consequent minimization of risk to patients.

Permeability test with sugars (PTS) as a non-invasive diagnostic tool is of special interest in pediatric patients. This study evaluated the relationship between PTS and antigliadin antibodies (AA) with the intestinal biopsy and studied whether an altered expired hydrogen test (EHT) could interfere in this relation in celiac patients. Thirty children (13 girls, 17 boys) with diagnosis of celiac disease (ESPGAN criteria) were divided into three groups according to this histopathology: Group A (n = 23) normal biopsy; Group B (n = 7) biopsy grade III or IV; Group C (n = 25) controls. The intestinal permeability test showed significative differences (p0.01) of Group B (0.159 +/- 0.03) with Group A (0.048 +/- 0.005) and with the control Group C (0.039 +/- 0.002). The cut-off for the Youden maximum index (0.75) was 0.092 and ROC SE 0.87 +/- 0.7. The results of the AA were related to those of the PTS. The variance analysis showed that the results of the expired hydrogen test do not interfere statistically on the good correlation of PTS with the histology. The PTS is a good indicator of the status of intestinal mucosa. There is a good correlation between PTS and AA in celiac children. A pathological expired hydrogen test seems not to interfere with the correlation found between PTS and histological damage in our series.

The Ves-MaticR system (VS) for evaluating erythrocyte sedimentation rate (ESR) is compared to Westergren method. A good correlation between both methods is obtained in spite of small differences observed; the accuracy of the VS is also studied. Concerning the time variation, a small reduction of the ESR in the first seven hours is observed, being significant at 24 hours. The most important advantages of the VS are the near complete disappearance of the contamination risk, the reduction of the time employed in setting up, sedimentation and reading, and the reliability.

ISO 22870 lists specific requirements for the quality and competence of point-of-care testing (POCT), which are intended for medical laboratories in conjunction with ISO 15189. POCT characteristics include the availability of a large number of devices 24 h/day, a variety of analytical methods, clinical settings inside and outside the hospital, and general non-laboratory staff. ISO 22870 accreditation for adequate POCT management therefore poses a challenge for laboratory medicine, which is charged with leading and coordinating POCT with a multidisciplinary committee. La Paz University Hospital has a complex multitest and multisite network that has been accredited since 2017. In our experience, the particularly crucial areas for POCT accreditation are method performance verification, internal and external quality assurance, staff training and competency, and continuous improvement. ISO 22870 and ISO 15189 accreditation have led us to improve numerous areas regarding the total testing process and, consequently, our patients' results.

This report shows, that the major factors involved were histological damage of the mucosa and the etiological diagnosis. Other factors (bacterial overgrowth, malnutrition, etc.), added to the previous referred, increase the oligosaccharidases alteration, yielding statistically significant values referring to healthy subjects. The oligosaccharidases activity were significantly decreased to referring to healthy subjects (p less than 0.001) in the IC1.o and 2.o that have not histological damage, in the DGR, IPLV and coeliac disease with AS of the mucosa and in the SPG that present APM. On the other hand, the analytical methodology with its different biochemical basis could evidence very various values and there is always important to remark the reference normal values in each laboratory.