[Show abstract][Hide abstract] ABSTRACT: At least one in 10 patients experience adverse events while receiving hospital care. Many of the errors are related to laboratory diagnostics. Efforts to reduce laboratory errors over recent decades have primarily focused on the measurement process while pre- and post-analytical errors including errors in sampling, reporting and decision-making have received much less attention. Proper sampling and additives to the samples are essential. Tubes and additives are identified not only in writing on the tubes but also by the colour of the tube closures. Unfortunately these colours have not been standardised, running the risk of error when tubes from one manufacturer are replaced by the tubes from another manufacturer that use different colour coding. EFLM therefore supports the worldwide harmonisation of the colour coding for blood collection tube closures and labels in order to reduce the risk of pre-analytical errors and improve the patient safety.
Clinical Chemistry and Laboratory Medicine 10/2014; · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract The availability of so-called high-sensitivity troponin assays (hsTn) has scored a compelling goal for laboratory medicine, allowing the safe clinical application of international recommendations for the definition of acute myocardial infarction (AMI). However, the introduction of hsTn has not been welcomed by clinicians, claiming an increase in false-positive results. Here we critically trace back the steps following the introduction of hsTn by referring to the 5-year practical experience in our academic hospital and to suitable information available in the literature. In agreement with published data, we found that hsTn introduction was associated with an increased number of AMI diagnoses, whereas the test volume, the revascularization rate, and the proportion of cases with negative angiography findings remained virtually unchanged. Fast-track protocols for ruling out AMI have been further optimized to recommend sampling at presentation and after 3 h only. We focus on a cost-effective use of hsTn that can account for all clinical variables increasing the pre-test probability in order to ensure that tests are ordered only for patients at medium to high risk for acute coronary syndrome (ACS). To guide interpretation of results, hsTn typical release patterns suggestive for AMI should be identified by evaluating the significance of concentration changes. hsTn have markedly shortened the time to rule out or rule in AMI and has the potential to improve the prognostic assessment of critical patients in clinical contexts different from ACS.
Clinical chemistry and laboratory medicine : CCLM / FESCC. 10/2014;
[Show abstract][Hide abstract] ABSTRACT: Among the newly proposed biomarkers for ovarian cancer, serum human epididymis protein 4 (HE4) shows the greatest potential for clinical use. However, systematic appraisals of its biological characteristics are not available. This study sought to critically revise the available literature on biological and lifestyle factors affecting HE4 concentrations in serum to understand their possible influence on the marker interpretation.
[Show abstract][Hide abstract] ABSTRACT: Abstract Background: An increased focus on the biological behaviour of serum biomarkers for ovarian cancer, i.e., carbohydrate antigen 125 (CA-125) and human epididymis protein 4 (HE4), has been advocated to improve their clinical use. Due to the paucity and poor design of available studies evaluating biological variation (BV) of CA-125 and the lack of BV data for HE4, in this study we evaluated BV of both biomarkers. Methods: Monthly we obtained serum samples from 14 pre- (PreM) and 14 post-menopausal (PostM) healthy women for 4 consecutive months. Once all samples were available, they were analysed in a single run in duplicate for CA-125 and HE4 on Roche Modular system. Data were analysed by ANOVA. Results: For both biomarkers no difference in median concentrations was found between PreM and PostM. For CA-125 the intra-individual CV (CVI) was not different between groups (9.1% in both). For HE4 CVI was higher in PreM (12.1%) than in PostM (6.5%) (p<0.001). Between-subject CVs were 10.6% for CA-125 and 16.4% for HE4, with no influence by the fertility status. Both biomarkers showed high individuality meaning that the use of population-based reference limits may have limited value for their interpretation. Reference change values were 26% for CA-125 (all), 34% for HE4 PreM and 18% for HE4 PostM. Conclusions: Monitoring longitudinal changes in serum concentrations of ovarian cancer biomarkers over time is probably better than using single threshold rules. According to differences in BV due to the hormonal status, one should differently interpret HE4 changes in PreM and PostM.
Clinical Chemistry and Laboratory Medicine 05/2014; · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Glycated hemoglobin (HbA1c) plays a key role in diagnosing diabetes and monitoring the glycemic state. To guarantee the reliability of its measurement at the global level, the IFCC has defined a reference measurement system, based on the definition of the measurand as hemoglobin molecules having a special hexapeptide in common, which is the stable adduct of glucose to the N-terminal valine of the hemoglobin β-chain. In addition to the traceability of HbA1c results to the reference system, the establishment of analytical goals to make HbA1c measurements clinically reliable becomes crucial. However, allowable goals will depend on the assay specificity (i.e., selectivity) and, consequently, on units in which HbA1c results are expressed [mmol/mol for IFCC-aligned systems or % for National Glycohemoglobin Standardization Program (NGSP) converted numbers]. In this regard, analytical goals derived from biological variability studies in which the determination of HbA1c has been carried out by an assay providing the same selectivity for the measurand as defined by the IFCC are recommended. Only these targets should be used for evaluating the performance of commercial assays traceable to the IFCC system and of clinical laboratories using them through appropriately structured quality assessment schemes. Analytical systems following different calibration hierarchies (e.g., the NGSP-aligned assays) will require different analytical goals, possibly derived from clinical outcome data.
Clinical Chemistry and Laboratory Medicine 05/2014; 52(5):759. · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Determination of serum soluble transferrin receptor (sTfR) has been proposed to identify iron-deficiency anemia (IDA) in patients affected by concurrent inflammatory disease that may spuriously increases ferritin concentration. The aim of this study was to critically review the available literature to assess the diagnostic efficacy of sTfR in complicated anemia. The criteria for study selection were: enrolment of patients with complicated anemia; bone marrow examination used as diagnostic gold standard for IDA; evaluation of sTfR vs. ferritin and binary data presentation. Six published studies met the criteria. However, small size and wide heterogeneity of the studies did not allow us to conduct a meta-analysys. sTfR was overall more sensitive, even though it was evident that the ferritin sensitivity was influenced by selected cut-offs. Well-designed studies are still needed to define the added value, if any, of sTfR to ferritin for IDA detection in complicated anemia.
Clinica chimica acta; international journal of clinical chemistry 02/2014; · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract In our hospital, we are currently working to manage the appropriateness of vitamin B12 (B12) testing. Unfortunately, the classic evidence-based approach is unhelpful in this process and meta-analyzing data on the accuracy of this marker for cobalamin deficiency detection is misleading due to the lack of reference diagnostic methods. The approach currently proposed by the Health Technology Assessment (HTA) enables us to tackle the issue of B12 requests as a "healthcare" problem by considering the position of stakeholders involved in ordering, performing, interpreting the test, and receiving its results. Clinical expectations, methodological issues, and ethical aspects concerning the performance of the test can aid us in providing more guidance on the use of this marker. By building such structured information, hemodialysis patients and pregnant women have emerged as those groups preferentially requiring B12 testing, as it may potentially improve the clinical outcome. To avoid misinterpretation of B12 results more care should be taken in considering its biochemical and biological features, as well as the analytical issues. Spurious values obtained by current automated immunoassays may reflect suboptimal pre-analytical steps as well as known interfering conditions. Furthermore, the harmonization of results by available methods is still a far-reaching goal and the approach to interpret an individual's results should be improved. Tracing a roadmap for B12 testing by exploiting the HTA model to balance the stakeholders' claims and maximizing the patient's outcome may help to manage the marker demand.
Clinical Chemistry and Laboratory Medicine 12/2013; · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To be accurate and equivalent, laboratory results should be traceable to higher-order references. Furthermore, their analytical performance should fulfil acceptable measurement uncertainty criteria defined to fit the intended clinical use. With this aim, In Vitro Diagnostics (IVD) manufacturers should define a calibration hierarchy to assign traceable values to their system calibrators and to fulfil during this process uncertainty limits for calibrators, which should represent a proportion of the uncertainty budget allowed for laboratory results. It is important that end-users may know and verify how manufacturers have implemented the traceability of their calibrators and estimated the corresponding uncertainty. However, full information about traceability and combined uncertainty of calibrators is currently not available. Important tools for IVD traceability surveillance are the verification by laboratories of the consistency of declared performance during daily operations performed in accordance with the manufacturer's instructions and the organization of appropriately structured External Quality Assessment (EQA) programs. The former activity should be accomplished by analyzing system control materials and confirming that current measurements are in the manufacturer's established control range. With regard to EQA, it is mandatory that target values for materials are assigned with reference procedures by accredited laboratories, that materials are commutable and a clinically allowable inaccuracy for participant's results is defined.
Clinica chimica acta; international journal of clinical chemistry 11/2013; · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The major source of errors producing unreliable laboratory test results is the pre-analytical phase with hemolysis accounting for approximately half of them and being the leading cause of unsuitable blood specimens. Hemolysis may produce interference in many laboratory tests by a variety of biological and analytical mechanisms. Consequently, laboratories need to systematically detect and reliably quantify hemolysis in every collected sample by means of objective and consistent technical tools that assess sample integrity. This is currently done by automated estimation of hemolysis index (HI), available on almost all clinical chemistry platforms, making the hemolysis detection reliable and reportable patient test results more accurate. Despite these advantages, a degree of variability still affects the HI estimate and more efforts should be placed on harmonization of this index. The harmonization of HI results from different analytical systems should be the immediate goal, but the scope of harmonization should go beyond analytical steps to include other aspects, such as HI decision thresholds, criteria for result interpretation and application in clinical practice as well as report formats. With regard to this, relevant issues to overcome remain the objective definition of a maximum allowable bias for hemolysis interference based on the clinical application of the measurements and the management of unsuitable samples. Particularly, for the latter a recommended harmonized approach is required when not reporting numerical results of unsuitable samples with significantly increased HI and replacing the test result with a specific comment highlighting hemolysis of the sample.
Clinica chimica acta; international journal of clinical chemistry 10/2013; · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Creatinine determination in serum is a key indicator of kidney glomerular function. A reference measurement system for its standardization is available and virtually all IVD manufacturers have aligned their assays to this system. In this study, we verified the impact of these standardization efforts on the results of an Italian EQAS involving about 430 laboratories.
We considered data obtained during 2006, 2010 and 2011 schemes of EQAS Prolarit for control materials with target values assigned by a traceable method (enzymatic assay calibrated against the NIST SRM 967).
The results showed a good alignment at concentrations ~170 μmol/L, with 2011 results - except for one method group - well inside the desirable bias (±4%). At higher concentrations, whereas the bias was small in 2010, for some groups using alkaline-picrate (AP) methods it became significantly negative in 2011. The performance seems to worsen when measuring physiologic concentrations, where a significant positive bias (up to ~20%) is shown by most of the AP-based analytical systems. With few exceptions, no evident improvement in individual assay bias was noted from pre- (2006) to post-standardization (2011) periods. The enzymatic method groups were the only always presenting an acceptable bias at all creatinine concentrations, also showing the lowest between-laboratory variability.
our data seem to indicate that the standardization efforts are still having effects lower than expected. Even taking into consideration that some of the bias may derive from non commutability problems, most of the current "standardized" AP-based methods, at the lower creatinine concentrations, seem to present accuracy problems. This inaccuracy can adversely impact the estimation of GFR by equations and the evaluation of kidney function in pediatrics.
Clinica chimica acta; international journal of clinical chemistry 10/2013; · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The lack of interchangeable results in current practice among clinical laboratories has underpinned greater attention to standardization and harmonization projects. Although the focus was mainly on the standardization and harmonization of measurement procedures and their results, the scope of harmonization goes beyond method and analytical results: it includes all other aspects of laboratory testing, including terminology and units, report formats, reference limits and decision thresholds, as well as test profiles and criteria for the interpretation of results. In particular, as evidence collected in last decades demonstrates that pre-pre- and post-post-analytical steps are more vulnerable to errors, harmonization initiatives should be performed to improve procedures and processes at the laboratory-clinical interface. Managing upstream demand, down-stream interpretation of laboratory results, and subsequent appropriate action through close relationships between laboratorians and clinicians remains a crucial issue of the laboratory testing process. Therefore, initiatives to improve test demand management from one hand and to harmonize procedures to improve physicians acknowledgment of laboratory data and their interpretation from the other hand are needed in order to assure quality and safety in the total testing process.
Clinica chimica acta; international journal of clinical chemistry 10/2013; · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The National Institute for Health and Clinical Excellence (NICE) guidelines have sparked hot debate regarding the role of carbohydrate antigen 125 (CA-125) for ovarian cancer (OC) detection. Recent literature and evidence calls into question the use of CA-125 in diagnostic algorithms, given the better performance of human epididymis protein 4 (HE4) vs. CA-125 to rule OC. This is an important consideration since combined measurements are not cost-effective. The quality of this evidence is, however, threatened by important gaps related to study design, enrolled populations and analytical issues. For instance, despite the clinical need to prioritize the evaluation of biomarker performance in early stage tumours, sound evidence on this cannot be provided. In addition, results should be cautiously interpreted due to wide differences in the type of employed assays and in adopted diagnostic thresholds for HE4. Comparability among results obtained by different commercially available HE4 assays, together with an objective establishment of analytical goals is essential for the optimal clinical application of this marker.
Annals of Clinical Biochemistry 09/2013; · 1.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Harmonization in laboratory testing is more far-reaching than merely analytical harmonization. It includes all aspects of the total testing process from the "pre-pre-analytical" phase through analysis to the "post-post-analytical" phase. Harmonizing the pre-analytical phase requires use of standardized operating procedures for correct test selection, sample collection and handling, while standardized test terminology, and units and traceability to ISO standard 17511 are required to ensure equivalency of measurement results. Use of harmonized reference intervals and decision limits for analytes where platforms share allowable bias requirements will reduce inaccurate clinical interpretation and unnecessary laboratory testing. In the post-analytical phase, harmonized procedures for the management of critical laboratory test results are required to improve service quality and ensure patient safety. Monitoring of the outcomes of harmonization activities is through surveillance by external quality assessment schemes that use commutable materials and auditing of the "pre-pre-analytical" and "post-post-analytical" phases. Successful implementation of harmonization in laboratory testing requires input by all stakeholders, including the clinical laboratory community, diagnostics industry, clinicians, professional societies, IT providers, consumer advocate groups and governmental bodies.
Clinica chimica acta; international journal of clinical chemistry 08/2013; · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: ST-elevation and non ST-elevation myocardial infarction (STEMI, NSTEMI) are considered two distinct pathophysiologic entities. We evaluated cardiac troponin I (cTnI) release in STEMI and NSTEMI using a "contemporary" (CV>10 to 20% at the 99th percentile concentration) cTnI assay for patients undergoing early percutaneous coronary intervention (PCI). DESIGN AND METHODS: 856 patients with suspected Acute Coronary Syndrome consecutively admitted to Emergency Department 225 STEMI and 135 NSTEMI were selected according to: 1) early (≤4 h from admission) and successful PCI; 2) cTnI measurements at ED presentation and within 24h. The influence of MI type on cTnI concentrations at baseline and after PCI as well as the velocity of cTnI [cTnI V= absolute increase (after log conversion of cTnI measurements)/delay between the two measurements] was studied by multiple regression analysis, adjusting for patient parameters. RESULTS: A statistically significant interaction between MI type and time from symptoms was reported on cTnI concentrations (p<0.0001): STEMI and NSTEMI differed for cTnI releases at admission and after revascularisation. Higher cTnI V in STEMI was detectable in patients admitted within 6 h from symptoms. Baseline cTnI concentrations were lower in patients with history of coronary artery disease (CAD) and increased with aging (p<0.0001). In the elderly (>75 years) the cTnI V was significantly increased. CONCLUSION: STEMI and NSTEMI patients have different patterns and dynamics of cTnI release influenced by the interaction with time from symptoms, by aging and history of CAD.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Human growth hormone (hGH) is measured for the diagnosis of secretion disorders. These measurements fall under the EU Directive 98/79/EC on in vitro diagnostic medical devices requiring traceability of commercial calibrator values to higher-order reference materials or procedures. External quality assessment schemes show large discrepancies between results from different methods, even though most methods provide results traceable to the recommended International Standard (IS 98/574). The aim of this study was to investigate possible causes for these discrepancies.METHODS: We investigated the commutability and recovery of hGH in reconstituted IS 98/574. We tested different reconstitution protocols and used 4 different serum matrices for spiking. These IS preparations were measured together with serum samples. We quantified hGH by 5 different methods in 4 different laboratories.RESULTS: Results from the different methods correlated well for the serum samples. Mean discrepancies between results from different methods were ≤20%. None of the IS preparations was commutable for all the method comparisons. The recovery of hGH in preparations of IS 98/574 depended on the reconstitution protocol (>10-fold differences) and background matrix (relative differences ≤17% for different serum matrices).CONCLUSIONS: The use of different protocols for reconstitution and spiking of hGH reference preparations affects quantification by immunoassays, potentially leading to a bias between commercial methods, despite the use of calibrators with values claimed to be traceable to the same higher-order reference material.