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High quality laboratory results are critical for patient management. However, poor sample quality can impact these results and patient safety. To ensure reliable and accurate results laboratories must be aware of each analyte's stability under various storage conditions and matrices to guarantee correct and dependable outcomes. This knowledge allows laboratories to define the allowable delay between sample collection and centrifugation/analysis for all analytes to guarantee appropriate results quality and interpretation. The EFLM Working Group for the Preanalytical Phase (WG-PRE) therefore established a 4-step plan to tackle this issue, aiming to standardize and harmonize stability studies for improved comparison and meta-analysis. The plan included the development of checklists and how-to guides for performing and reporting stability studies as well as a central resource of stability data. This manuscript deals with the issue of evaluating publications and incorporating them into a central resource. To evaluate stability studies, the CRESS checklist was used to structure 20 sections used to judge the quality of studies. Each section has 4 levels of quality, with scores converted to numerical values and weighted based on expert opinion. Based on this, a final score ranging from A to D was determined. The procedure was then tested on six manuscripts and checked for agreement between expert judgements. The results demonstrated that the proposed evaluation process is a useful tool to distinguish between best in class manuscripts and those of lower quality. The EFLM WG-PRE strongly believes that the provided recommendations and checklists will help improving stability studies both in quality and standardisation., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Aim: Blood Sampling Guidelines have been developed to target European emergency medicine-related professionals involved in the blood sampling process (e.g. physicians, nurses, phlebotomists working in the ED), as well as laboratory physicians and other related professionals. The guidelines population focus on adult patients. The development of these blood sampling guidelines for the ED setting is based on the collaboration of three European scientific societies that have a role to play in the preanalytical phase process: EuSEN, EFLM, and EUSEM. The elaboration of the questions was done using the PICO procedure, literature search and appraisal was based on the GRADE methodology. The final recommendations were reviewed by an international multidisciplinary external review group., Results: The document includes the elaborated recommendations for the selected sixteen questions. Three in pre-sampling, eight regarding sampling, three post-sampling, and two focus on quality assurance. In general, the quality of the evidence is very low, and the strength of the recommendation in all the questions has been rated as weak. The working group in four questions elaborate the recommendations, based mainly on group experience, rating as good practice., Conclusions: The multidisciplinary working group was considered one of the major contributors to this guideline. The lack of quality information highlights the need for research in this area of the patient care process. The peculiarities of the emergency medical areas need specific considerations to minimise the possibility of errors in the preanalytical phase., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: Knowledge of the stability of analytes in clinical specimens is a prerequisite for proper transport and preservation of samples to avoid laboratory errors. The new version of ISO 15189:2022 and the European directive 2017/746 increase the requirements on this topic for manufacturers and laboratories. Within the project to generate a stability database of European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group Preanalytical Phase (WG-PRE), the need to standardise and improve the quality of published stability studies has been detected, being a manifest deficit the absence of international guidelines for the performance of stability studies on clinical specimens., Methods: These recommendations have been developed and summarised by consensus of the WG-PRE and are intended primarily to improve the quality of sample stability claims included in information for users provided by assay supplier companies, according to the requirements of the new European regulations and standards for accreditation., Results: This document provides general recommendations for the performance of stability studies, oriented to the estimation of instability equations in the usual working conditions, allowing flexible adaptation of the maximum permissible error specifications to obtain stability limits adapted to the intended use., Conclusions: We present this recommendation based on the opinions of the EFLM WG-PRE group for the standardisation and improvement of stability studies, with the intention to improve the quality of the studies and the transferability of their results to laboratories., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Context.—: Underuse of laboratory testing has been previously investigated in preselected populations, such as documented malpractice claims. However, these numbers might not reflect real-life situations., Objective.—: To evaluate the underuse and misuse of laboratory follow-up testing in a real-life hospital patient population with microcytic anemia, using laboratory results ordered during routine patient care., Design.—: From all patients in whom a microcytic anemia was detected during routine diagnostics in 2018, all available laboratory data were collected and screened for appropriateness of diagnostic workup of iron deficiency and thalassemia. Subgroup analysis was performed for patient groups with mean corpuscular volume values 75 to 79 μm3 (group 1), 65 to 74 μm3 (group 2), and <65 μm3 (group 3)., Results.—: A total of 2244 patients with microcytic anemia were identified. Follow-up testing for iron deficiency was not performed in 761 cases (34%). For inconclusive ferritin levels due to elevated C-reactive protein results (n = 336), reticulocyte hemoglobin content or soluble transferrin receptor levels were missing in 86 cases (26%). In patients with suspected thalassemia (n = 127), follow-up testing for hemoglobin variants was not performed in 70 cases (55%). Subgroup analysis showed that the frequency of underuse of iron status as well as thalassemia/hemoglobinopathy testing decreased from group 1 to group 3. When considering relevant preexisting anemia diagnoses, laboratory tests were underused in 904 cases (40.3%)., Conclusions.—: Because 40% (n = 904) of the patients with microcytic anemia were potentially not followed up correctly, laboratory specialists are advised to act by implementing demand management strategies in collaboration with clinicians to overcome underuse of laboratory tests and to improve patient safety., (© 2023 College of American Pathologists.)

Objectives: Clinical decision-making in emergency medicine is under constant pressure from demand and performance requirements, with blood tests being a fundamental part of this. However, the preanalytical process has received little attention. Therefore, this study aimed to investigate the quality of preanalytical phase processes in European emergency departments (EDs) from the perspectives of the three main providers: clinicians, nurses, and laboratory specialists., Methods: This online survey, distributed among European EDs and laboratories, was supported by the European Society for Emergency Nursing (EUSEN), European Society for Emergency Medicine (EuSEM), and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM). The size of the centres, the European region, the responder's profession and the country's economic condition were used as co-variables., Results: We included 376 responses from all ED-related professions from 306 European centres. In 66.9% of all ED visits, at least one blood test was performed. Tests were requested mostly by nurses (44.6%) using electronic Order/Entry systems (65.4%). Only a minority (19%) reported not using laboratory quality indicators (QIs). Most responders defined the TAT starting point "when the laboratory receives the sample" (66.1%), defining the goal to be "less than 60 min" (69.9%), but only 42.4% of the centres estimated achieving this goal., Conclusions: Our survey illustrates the current situation on preanalytical blood sample processing in European EDs from the clinical and laboratory perspectives. The results emphasise the importance of the IT infrastructure and QI usage in this process and highlight some differences between European regions., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Purpose: In infections of the Central Nervous System (iCNS), rapid identification of causing pathogens is crucial for survival and to avoid long-term sequelae. Targeted therapy may reduce side effects and development of antibiotic resistance. New molecular-based syndromic tests such as the "meningitis/encephalitis panel" (MEP) allow accelerated pathogen identification from cerebrospinal fluid. We conducted a clinical study to evaluate the MEP's efficacy in paediatric patients., Methods: Cohort study in a unique clinical setting by comparing the outcome data of two neighbouring Children's Hospitals in Germany which are comparable in size, catchment area and equipment but differ regarding availability of the MEP: study centre 1 (SC1): yes; SC2: no. The study population included 213 paediatric patients with a suspected iCNS (SC1: 106; SC2: 107), with comparable age, CRP at admission and frequency of intensive care. The primary outcome was total use of antibiotics., Results: Total antibiotic use per patient was numerically lower in SC1 than in SC2 (SC1: median 2.83 days; SC2 3.67 days; p = 0.671). Multiple linear regression analysis did not show a relevant association between MEP-availability and total antibiotic use (ß = 0.1, 95% confidence interval [-1.46; +1.67], p = 0.897). In the subcohort with suspected meningoencephalitis (SC1: 18, SC2: 17), duration of acyclovir treatment was shorter in SC1 than in SC2 (median 1.3 days vs. 2.7 days, descriptive p = 0.0397)., Conclusions: The add-on use of the MEP in paediatric patients with suspected iCNS was associated with a non-significant reduction in total antibiotic use, and with a reduced exposure to acyclovir in treated patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Recommendations on the optimal preservation of 24 h urine for the metabolic work-up in urolithiasis patients are very heterogeneous. In case two such tests with different storage condition recommendations are being analysed, multiple collections would be needed, challenging especially elderly and very young patients. We therefore aimed to evaluate the stability of urine constituents under different storage conditions., Material and Methods: We collected urine samples from ten healthy volunteers and prepared aliquots to be stored either at room temperature or 4 °C. Some aliquots were preserved using hydrochloric acid prior to storage, some thereafter, some using the BD Urine preservation tube and some were not preserved at all. Storage duration was 0, 24, 48 or 72 h. In all samples calcium, magnesium, phosphorus, creatinine, oxalate, citrate and uric acid were measured and compared to the according reference sample., Results: We could not find any significant deviation for any of the analytes and preanalytical treatment conditions compared to the associated reference sample., Conclusion: Preservation of 24 h urine for the metabolic evaluation in stone formers might not be necessary for sample storage up to 72 h., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: Although laboratory result presentation may lead to information overload and subsequent missed or delayed diagnosis, little has been done in the past to improve this post-analytical issue. We aimed to investigate the efficiency, efficacy and user satisfaction of alternative report formats., Methods: We redesigned cumulative (sparkline format) and single reports (improved tabular and z-log format) and tested these on 46 physicians, nurses and medical students in comparison to the classical tabular formats, by asking standardized questions on general items on the reports as well as on suspected diagnosis and follow-up treatment or diagnostics., Results: Efficacy remained at a very high level both in the new formats as well as in the classical formats. We found no significant difference in any of the groups. Efficiency improved in all groups when using the sparkline cumulative format and marginally when showing the improved tabular format. When asking medical questions, efficiency and efficacy remained similar between report formats and groups. All alternative reports were subjectively more attractive to the majority of participants., Conclusions: Showing cumulative reports as a graphical display led to faster detection of general information on the report with the same level of correctness. Considering the familiarity bias of the classical single report formats, the borderline-significant improvement of the alternative tabular format and the non-inferiority of the z-log format, suggests that single reports might benefit from some improvements derived from basic information design., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Risk factors for disease progression and severity of SARS-CoV-2 infections require an understanding of acute and long-term virological and immunological dynamics. Fifty-one RT-PCR positive COVID-19 outpatients were recruited between May and December 2020 in Munich, Germany, and followed up at multiple defined timepoints for up to one year. RT-PCR and viral culture were performed and seroresponses measured. Participants were classified applying the WHO clinical progression scale. Short symptom to test time (median 5.0 days; p = 0.0016) and high viral loads (VL; median maximum VL: 3∙10 8 copies/mL; p = 0.0015) were indicative for viral culture positivity. Participants with WHO grade 3 at baseline had significantly higher VLs compared to those with WHO 1 and 2 (p = 0.01). VLs dropped fast within 1 week of symptom onset. Maximum VLs were positively correlated with the magnitude of Ro-N-Ig seroresponse (p = 0.022). Our results describe the dynamics of VLs and antibodies to SARS-CoV-2 in mild to moderate cases that can support public health measures during the ongoing global pandemic., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Since the beginning of laboratory medicine, the main focus was to provide high quality analytics. Over time the importance of the extra-analytical phases and their contribution to the overall quality became evident. However, as the initial preanalytical processes take place outside of the laboratory and mostly without its supervision, all professions participating in these process steps, from test selection to sample collection and transport, need to engage accordingly. Focusing solely on intra-laboratory processes will not be sufficient to achieve the best possible preanalytical quality. The Working Group for the Preanalytical Phase (WG-PRE) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has provided several recommendations, opinion papers and scientific evidence over the past years, aiming to standardize the preanalytical phase across Europe. One of its strategies to reach this goal are educational efforts. As such, the WG-PRE has organized five conferences in the past decade with the sole focus on preanalytical quality. This year's conference mainly aims to depict the views of different professions on preanalytical processes in order to acquire common ground as basis for further improvements. This article summarizes the content of this 6th preanalytical conference., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

In laboratory medicine, much effort has been put into analytical quality in the past decades, making this medical profession one of the most standardized with the lowest rates of error. However, even the best analytical quality cannot compensate for errors or low quality in the pre or postanalytical phase of the total testing process. Guidelines for data reporting focus solely on defined data elements, which have to be provided alongside the analytical test results. No guidelines on how to format laboratory reports exist. The habit of reporting as much diagnostic data as possible, including supplemental information, may lead to an information overload. Considering the multiple tasks physicians have to do simultaneously, unfiltered data presentation may contribute to patient risk, as important information may be overlooked, or juxtaposition errors may occur. As laboratories should aim to answer clinical questions, rather than providing sole analytical results, optimizing formatting options may help improve the effectiveness and efficiency of medical decision-making. In this narrative review, we focus on the underappreciated topic of laboratory result reporting. We present published literature, focusing on the impact of laboratory result report formatting on medical decisions as well as approaches, potential benefits, and limitations for alternative report formats. We discuss influencing variables such as, for example, the type of patient (e.g. acute versus chronic), the medical specialty of the recipient of the report, the display of reference intervals, the medium or platform on which the laboratory report is presented (printed paper, within electronic health record systems, on handheld devices, etc.), the context in which the report is viewed in, and difficulties in formatting single versus cumulative reports. Evidence on this topic, especially experimental studies, is scarce. When considering the medical impact, it is of utmost importance that laboratories focus not only on the analytical aspects but on the total testing process. The achievement of high analytical quality may be of minor value if essential results get lost in overload or scattering of information by using a non-formatted tabular design. More experimental studies to define guidelines and to standardize effective and efficient reporting are most definitely needed.

Purpose: The recent COVID-19 pandemic has resulted in an increasing overload of the medical system. Healthcare workers (HCW) in radiology departments are exposed to a high infection risk similar to HCWs in the ICU or dedicated COVID wards. The goal of our paper is to evaluate the prevalence of IgG antibody against SARS-CoV-2 among radiology HCWs in two different hospitals and regions in Germany with a low and high COVID-19 prevalence and to compare it to the prevalence in other clinical personnel. Additionally, we assessed the number of radiological procedures performed in patients with a positive PCR test (C+) followed by a short review of the risk for nosocomial infections of radiology HCWs., Materials and Methods: During the first COVID-19 wave between March and July 2020, we evaluated a region with one of the highest COVID-19 rates (776-1570/100 000) in Germany (Hospital A). Additionally, we assessed Hospital B in a region with a low prevalence (65/100 000). We tested the serum prevalence of SARS-CoV-2 IgG antibodies among the whole staff with a subgroup analysis for radiology in both hospitals. We calculated the total number of different radiological procedures performed in C+ patients., Results: In Hospital A 594 PCR-proven C+ patients were treated resulting in 2723 radiological procedures. 24 % (n = 6) of the radiology technicians and 13.35 (n = 2) of radiologists had a positive IgG test. The rates were similar to positive rates in HCWs in COVID-19 wards and ICUs within the hospital. The most frequently performed procedures in C+ patients were chest X-rays (3.17/patient) and CT examinations (1.15/patient). In Hospital B 50 C+ patients were treated, resulting in 64 radiological procedures. None of the HCWs tested IgG positive. The most frequently performed examinations were also chest X-rays (1.04/patient) and CT (0.2/patient)., Conclusion: HCWs in radiology have a high occupational infection risk similar to that of HCWs in ICUs and dedicated COVID wards., Key Points: · The risk of acquiring COVID-19 increases with the amount of contact with infected individuals.. · The occupational risk of a SARS-CoV-2 infection for radiology staff is similar to that of nurses and physicians in COVID wards.. · Hygiene concepts and medical resources have to be adapted for further COVID outbreaks.. · Reporting of an occupational disease can be considered in the case of seropositive staff.., Citation Format: · Finkenzeller T, Lenhart S, Reinwald M et al. Risk to Radiology Staff for Occupational COVID-19 Infection in a High-Risk and a Low-Risk Region in Germany: Lessons from the "First Wave". Fortschr Röntgenstr 2021; 193: 537 - 543., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

The International Organization for Standardization (ISO) 15189:2012 standard aims to improve quality in medical laboratories through standardization of all key elements in the total testing process, including the pre-analytical phase. It is hence essential that accreditation bodies, assessing laboratories against ISO15189:2012, pay sufficient attention to auditing pre-analytical activities. However, there are significant differences in how technical auditors interpret the pre-analytical requirements described in ISO15189:2012. In this consensus document, the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for Pre-analytical Phase (WG-PRE) sets out to review pre-analytical requirements contained in ISO15189:2012 and provide guidance for laboratories on how to meet these requirements. The target audience for this consensus document is laboratory professionals who wish to improve the quality of the pre-analytical phase in their laboratory. For each of the ISO requirements described in ISO15189:2012, members of EFLM WG-PRE agreed by consensus on minimal recommendations and best-in-class solutions. The minimal consensus recommendation was defined as the minimal specification which laboratories should implement in their quality management system to adequately address the pre-analytical requirement described in ISO15189:2012. The best-in-class solution describes the current state-of-the-art in fulfilling a particular pre-analytical requirement in ISO15189:2012. We fully acknowledge that not every laboratory has the means to implement these best-in-class solutions, but we hope to challenge laboratories in critically evaluating and improving their current procedures by providing this expanded guidance., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: Biotin >20 ng/mL may interfere with the Elecsys ® Troponin T-high sensitive assay (cTnT-hs; Roche Diagnostics International Ltd). We evaluated the performance of an updated assay, cTnT-hs*, which was designed to reduce biotin interference., Methods: cTnT-hs* assay performance was assessed using up to two applications (18 min/9 min) on three analyzers (cobas e 411/cobas e 601/cobas e 801). Biotin interference was determined by measuring recovery in an 11-sample series dilution with biotin ranging from 0-3600 ng/mL. Repeatability/reproducibility were evaluated in five serum sample pools (n=75 each). Method comparisons tested: cTnT-hs* vs. cTnT-hs (18 min/cobas e 601); cTnT-hs* assay 18 vs. 9 min (cobas e 601); cTnT-hs* (18 min) on cobas e 601 vs. cobas e 411 and cobas e 601 vs. cobas e 801. Concordance at the 99th percentile decision limit between cTnT-hs* and cTnT-hs (9 min/cobas e 601) was calculated using 300 lithium-heparin plasma samples and a 14 ng/L assay cutoff., Results: cTnT-hs* assay (18 min/cobas e 601) recovery was ≥96% for biotin ≤1250 ng/mL. Across all applications/analyzers, coefficients of variation for repeatability/reproducibility with the cTnT-hs* assay were <5% in most serum sample pools (mean cardiac troponin T: 8.528-9484 ng/L). High correlation (Pearson's r=1.000) was demonstrated for all method comparisons. Concordance at the 99th percentile decision limit was high between the cTnT-hs* and cTnT-hs assays., Conclusions: The updated cTnT-hs* assay may provide greater tolerance to biotin interference, and shows good analytical and clinical agreement/concordance with the previous cTnT-hs assay., (© 2021 Alexander von Meyer et al., published by De Gruyter, Berlin/Boston.)

Objectives An accurate knowledge of blood collection times is crucial for verifying the stability of laboratory analytes. We therefore aimed to (i) assess if and how this information is collected throughout Europe and (ii) provide a list of potentially available solutions. Methods A survey was issued by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group on Preanalytical Phase (WG-PRE) in 2017, aiming to collect data on preanalytical process management, including sampling time documentation, in European laboratories. A preceding pilot survey was disseminated in Austria in 2016. Additionally, preanalytical experts were surveyed on their local setting on this topic. Finally, the current scientific literature was reviewed on established possibilities of sampling time collection. Results A total number of 85 responses was collected from the pilot survey, whilst 1347 responses from 37 European countries were obtained from the final survey. A minority (i.e. ~13%) of responders to the latter declared they are unaware of the exact sampling time. The corresponding rate in Austria was ~70% in the pilot and ~30% in the final survey, respectively. Answers from 17 preanalytical experts from 16 countries revealed that sampling time collection seems to be better documented for out- than for in-patients. Eight different solutions for sample time documentation are presented. Conclusions The sample collection time seems to be documented very heterogeneously across Europe, or not at all. Here we provide some solutions to this issue and believe that laboratories should urgently aim to implement one of these.

To ensure that clinical laboratories produce results that are both accurate and of clinical utility it is essential that only samples of adequate quality are analysed. Although various studies and databases assessing the stability of analytes in different settings do exist, guidance on how to perform and report stability studies is lacking. This results in studies that often do not report essential information, thus compromising transferability of the data. The aim of this manuscript is to describe the Checklist for Reporting Stability Studies (CRESS) against which future studies should be reported to ensure standardisation of reporting and easy assessment of transferability of studies to other healthcare settings. The EFLM WG-PRE (European Federation of Clinical Chemistry and Laboratory Medicine Working Group for the Preanalytical Phase) produced the CRESS checklist following a detailed literature review and extensive discussions resulting in consensus agreement. The checklist consists of 20 items covering all the aspects that should be considered when producing a report on a stability study including details of what should be included for each item and a rationale as to why. Adherence to the CRESS checklist will ensure that studies are reported in a transparent and replicable way. This will allow other laboratories to assess whether published data meet the stability criteria required in their own particular healthcare scenario. The EFLM WG-PRE encourage researchers and authors to use the CRESS checklist as a guide to planning stability studies and to produce standardised reporting of future stability studies.

Introduction: The appropriate use of laboratory diagnostics is increasingly at stake. The aim of this study was to depict some paradigmatic examples of under- and overutilization, as well as possible solutions across Europe., Methods: We collected six examples from five European countries where a rise or decline of orders for specific laboratory parameters was observed after organizational changes but without evidence of changes in patient collective characteristics as source of this variation., Results: The collected examples were the following: 1-Germany) Switch from a Brain-Natriuretic-Peptide assay to NT-pro Brain-Natriuretic-Peptide assay, resulting in a 374% increase in these analytics; 2-Spain) Implementation of a gatekeeping strategy in tumor marker diagnostics, resulting in a 15-61% reduction of these diagnostics; 3-Croatia) Stepwise elimination of creatine-kinase-MB assay from the laboratory portfolio; 4-UK) Removal of γ-glutamyl transferase from a "liver function" profile, resulting in 82% reduction of orders; 5-Austria) Implementation of a new device for rapid Influenza-RNA detection, resulting in a 450% increase of Influenza testing; 6-Spain) Insourcing of 1,25-(OH) 2 -Vitamin D measurements, leading to a 378% increase of these analyses., Conclusion: The six paradigmatic examples described in this manuscript show that availability of laboratory resources may considerably catalyze the demand, thus underscoring that inappropriate use of laboratory resources may be commonplace in routine laboratories all across Europe and most probably beyond. They also demonstrate that the application of simple strategies may assist in overcoming this issue. We believe that laboratory specialists need to refocus on the extra-analytical parts of the testing process and engage more in interdisciplinary patient-care., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Although the importance of guaranteeing a high level of preanalytical quality in routine diagnostic testing has already been largely acknowledged over the past decades, minor emphasis is currently being placed on the fact that accurate performance and standardization of many preanalytical activities are also necessary prerogatives of clinical trials. Reliable evidence exists that clear indications on how to manage the different preanalytical steps are currently lacking in many clinical trials protocols, nor have detailed authoritative documents been published or endorsed on this matter to the best of our knowledge. To fill this gap, the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for Preanalytical Phase (WG-PRE) will provide here a specific checklist for preventing preanalytical diagnostic errors in clinical trials (PREDICT), especially focused on covering the most important preanalytical aspects of blood sample management in clinical studies, and thus encompassing test selection, patient preparation, sample collection, management and storage, sample transportation, as well as specimen retrieval before testing. The WG-PRE members sincerely hope that these recommendations will provide a useful contribution for increasing the success rate in clinical trials.

Background Published evidence on the risk of additive carryover during phlebotomy remains elusive. We aimed to assess potential carryover of citrated and heparinized blood and the relative volume needed to bias clinical chemistry and coagulation tests. Methods We simulated standardized phlebotomies to quantify the risk of carryover of citrate and heparin additives in distilled water, using sodium and lithium as surrogates. We also investigated the effects of contamination of heparinized blood samples with increasing volumes of citrated blood and pure citrate on measurements of sodium, potassium, chloride, magnesium, total and ionized calcium and phosphate. Likewise, we studied the effects of contamination of citrated blood samples with increasing volumes of heparinized blood on heparin (anti-Xa) activity, lithium, activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). We interpreted these results based on measurement deviations beyond analytical, biological and clinical significance. Results Standardized phlebotomy simulations revealed no significant differences in concentration of surrogate markers. Clinically significant alterations were observed after contamination of heparinized blood samples with volumes of citrated blood beyond 5-50 μL for ionized calcium and beyond 100-1000 μL for sodium, chloride and total calcium. Investigations of pure citrate carryover revealed similar results at somewhat lower volumes. Heparinized blood carryover showed clinically significant interference of coagulation testing at volumes beyond 5-100 μL. Conclusions Our results suggest that during a standardized phlebotomy, heparin or citrate contamination is highly unlikely. However, smaller volumes are sufficient to severely alter test results when deviating from phlebotomy guidelines.

The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase (WG-PRE) was originally established in 2013, with the main aims of (i) promoting the importance of quality in the preanalytical phase of the testing process, (ii) establishing best practices and providing guidance for critical activities in the preanalytical phase, (iii) developing and disseminating European surveys for exploring practices concerning preanalytical issues, (iv) organizing meetings, workshops, webinars or specific training courses on preanalytical issues. As education is a core activity of the WG-PRE, a series of European conferences have been organized every second year across Europe. This collective article summarizes the leading concepts expressed during the lectures of the fifth EFLM Preanalytical Conference "Preanalytical Challenges - Time for solutions", held in Zagreb, 22-23 March, 2019. The topics covered include sample stability, preanalytical challenges in hematology testing, feces analysis, bio-banking, liquid profiling, mass spectrometry, next generation sequencing, laboratory automation, the importance of knowing and measuring the exact sampling time, technology aids in managing inappropriate utilization of laboratory resources, management of hemolyzed samples and preanalytical quality indicators.

Introduction: No guideline currently exists on how to detect or document haemolysis, icterus or lipemia (HIL) in blood samples, nor on subsequent use of this information. The EFLM WG-PRE has performed a survey for assessing current practices of European laboratories in HIL monitoring. This second part of two coherent articles is focused on HIL., Materials and Methods: An online survey, containing 39 questions on preanalytical issues, was disseminated among EFLM member countries. Seventeen questions exclusively focused on assessment, management and follow-up actions of HIL in routine blood samples., Results: Overall, 1405 valid responses from 37 countries were received. A total of 1160 (86%) of all responders stating to analyse blood samples - monitored HIL. HIL was mostly checked in clinical chemistry samples and less frequently in those received for coagulation, therapeutic drug monitoring and serology/infectious disease testing. HIL detection by automatic HIL indices or visual inspection, along with haemolysis cut-offs definition, varied widely among responders. A quarter of responders performing automated HIL checks used internal quality controls. In haemolytic/icteric/lipemic samples, most responders (70%) only rejected HIL-sensitive parameters, whilst about 20% released all test results with general comments. Other responders did not analysed but rejected the entire sample, while some released all tests, without comments. Overall, 26% responders who monitored HIL were using this information for monitoring phlebotomy or sample transport quality., Conclusion: Strategies for monitoring and treating haemolytic, icteric or lipemic samples are quite heterogeneous in Europe. The WG-PRE will use these insights for developing and providing recommendations aimed at harmonizing strategies across Europe., Competing Interests: Potential conflict of interest: None declared.

Introduction: Compared to other activities of the testing process, the preanalytical phase is plagued by a lower degree of standardization, which makes it more vulnerable to errors. With the aim of providing guidelines and recommendations, the EFLM WG-PRE issued a survey across European medical laboratories, to gather information on local preanalytical practices. This is part one of two coherent articles, which covers all practices on monitoring preanalytical quality except haemolysis, icterus and lipemia (HIL)., Materials and Methods: An online survey, containing 39 questions dealing with a broad spectrum of preanalytical issues, was disseminated to EFLM member countries. The survey included questions on willingness of laboratories to engage in preanalytical issues., Results: Overall, 1405 valid responses were received from 37 countries. 1265 (94%) responders declared to monitor preanalytical errors. Assessment, documentation and further use of this information varied widely among respondents and partially among countries. Many responders were interested in a preanalytical online platform, holding information on various aspects of the preanalytical phase (N = 1177; 87%), in a guideline for measurement and evaluation of preanalytical variables (N = 1235; 92%), and in preanalytical e-learning programs or webinars (N = 1125; 84%). Fewer responders were interested in, or already participating in, preanalytical EQA programs (N = 951; 71%)., Conclusion: Although substantial heterogeneity was found across European laboratories on preanalytical phase monitoring, the interest in preanalytical issues was high. A large majority of participants indicated an interest in new guidelines regarding preanalytical variables and learning activities. This important data will be used by the WG-PRE for providing recommendations on the most critical issues., Competing Interests: Potential conflict of interest: None declared.

This document provides a joint recommendation for venous blood sampling of the European federation of clinical chemistry and laboratory medicine (EFLM) Working Group for preanalytical phase (WG-PRE) and Latin American working group for preanalytical phase (WG-PRE-LATAM) of the Latin America confederation of clinical biochemistry (COLABIOCLI). It offers guidance on the requirements for ensuring that blood collection is a safe and patient-centered procedure and provides practical guidance on how to successfully overcome potential barriers and obstacles to its widespread implementation. The target audience for this recommendation are healthcare staff members directly involved in blood collection. This recommendation applies to the use of a closed blood collection system and does not provide guidance for the blood collection with an open needle and syringe and catheter collections. Moreover, this document neither addresses patient consent, test ordering, sample handling and transport nor collection from children and unconscious patients. The recommended procedure is based on the best available evidence. Each step was graded using a system that scores the quality of the evidence and the strength of the recommendation. The process of grading was done at several face-to-face meetings involving the same mixture of stakeholders stated previously. The main parts of this recommendation are: 1) Pre-sampling procedures, 2) Sampling procedure, 3) Post-sampling procedures and 4) Implementation. A first draft of the recommendation was circulated to EFLM members for public consultation. WG-PRE-LATAM was also invited to comment the document. A revised version has been sent for voting on to all EFLM and COLABIOCLI members and has been officially endorsed by 33/40 EFLM and 21/21 COLABIOCLI members. We encourage professionals throughout Europe and Latin America to adopt and implement this recommendation to improve the quality of blood collection practices and increase patient and workers safety.

Following an ordered clinical chemistry plasma/serum test, ideally the venous blood specimen is adequately collected at a health care facility, then swiftly transported to and readily handled, analyzed and sometimes interpreted at a clinical chemistry laboratory followed by a report of the test result to the ordering physician to finally handle the result. However, often there are practical as well as sample quality reasons for short- or long-term storage of samples before and after analysis. If there are specific storage needs, the preanalytical handling practices are specified in the laboratory's specimen collection instructions for the ordered test analyte. Biobanking of specimens over a very long time prior to analysis includes an often neglected preanalytical challenge for preserved quality of the blood specimen and also involves administrative and additional practical handling aspects (specified in a standard operating procedure - SOP) when demands and considerations from academic, industry, research organizations and authorities are included. This short review highlights some preanalytical aspects of plasma/serum short- and long- term storage that must be considered by clinicians, laboratory staff as well as the researchers.

Background The inappropriate use of laboratory resources, due to excessive number of tests not really necessary for patient care or by failure to order the appropriate diagnostic test, may lead to wrong, missed or delayed diagnosis, thus potentially jeopardizing patient safety. It is estimated that 5-95% of tests are currently used inappropriately, depending on the appropriateness criteria, thus significantly contributing to the potential of generating medical errors, the third leading cause of death in the US. Content In this review, we discuss the reasons as well as the medical and financial consequences of inappropriate utilization of laboratory tests. We then provide demand management (DM) tools as a means for overcoming this issue and also discuss their benefits, challenges, limitations and requirements for successful implementation. Summary and outlook When based on current evidence, adapted to local conditions and developed in close collaboration with clinicians, DM is a reasonable strategy for progressing toward better management of over- and underuse of laboratory resources.

Several lines of evidence now confirm that the vast majority of errors in laboratory medicine occur in the extra-analytical phases of the total testing processing, especially in the preanalytical phase. Most importantly, the collection of unsuitable specimens for testing (either due to inappropriate volume or quality) is by far the most frequent source of all laboratory errors, thus calling for urgent strategies for improving blood sample quality and managing data potentially generated measuring unsuitable specimens. A comprehensive overview of scientific literature leads us to conclude that hemolyzed samples are the most frequent cause of specimen non-conformity in clinical laboratories (40-70%), followed by insufficient or inappropriate sample volume (10-20%), biological samples collected in the wrong container (5-15%) and undue clotting (5-10%). Less frequent causes of impaired sample quality include contamination by infusion fluids (i.e. most often saline or glucose solutions), cross-contamination of blood tubes additives, inappropriate sample storage conditions or repeated freezing-thawing cycles. Therefore, this article is aimed to summarize the current evidence about the most frequent types of unsuitable blood samples, along with tentative recommendations on how to prevent or manage these preanalytical non-conformities.

This document provides a joint recommendation for venous blood sampling of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for Preanalytical Phase (WG-PRE) and Latin American Working Group for Preanalytical Phase (WG-PRE-LATAM) of the Latin America Confederation of Clinical Biochemistry (COLABIOCLI). It offers guidance on the requirements for ensuring that blood collection is a safe and patient-centered procedure and provides practical guidance on how to successfully overcome potential barriers and obstacles to its widespread implementation. The target audience for this recommendation are healthcare staff members directly involved in blood collection. This recommendation applies to the use of a closed blood collection system and does not provide guidance for the blood collection with an open needle and syringe and catheter collections. Moreover, this document neither addresses patient consent, test ordering, sample handling and transport nor collection from children and unconscious patients. The recommended procedure is based on the best available evidence. Each step was graded using a system that scores the quality of the evidence and the strength of the recommendation. The process of grading was done at several face-to-face meetings involving the same mixture of stakeholders stated previously. The main parts of this recommendation are: 1) Pre-sampling procedures, 2) Sampling procedure, 3) Post-sampling procedures and 4) Implementation. A first draft of the recommendation was circulated to EFLM members for public consultation. WG-PRE-LATAM was also invited to comment the document. A revised version has been sent for voting on to all EFLM and COLABIOCLI members and has been officially endorsed by 33/40 EFLM and 21/21 COLABIOCLI members. We encourage professionals throughout Europe and Latin America to adopt and implement this recommendation to improve the quality of blood collection practices and increase patient and workers safety.

The presence of interfering substances like free hemoglobin, bilirubin or lipids compromises sample quality and potentially affects laboratory analysis and test results. Recently, the use of serum indices for objectively assessing sample quality has become commonplace and many preanalytical platforms, as well as clinical chemistry and coagulation analyzers, are now equipped with this analytical feature. Nevertheless, some important drawbacks remain in this practice, mainly pertaining the measurement procedure, the approach for reporting interference data, the definition of objective thresholds of interference after which test results may be biased, and the lack of harmonized practices for describing how interference cut-offs have been identified. Therefore, this document aims to discuss these important caveats and propose some reliable solutions that may be adopted by manufacturers for increasing worldwide harmonization of serum indices., (Copyright © 2018. Published by Elsevier B.V.)

Automatic assessment of hemoglobin (H), lipaemia (L) and icterus (I) in serum or plasma (HIL indices) is the mainstay for evaluating sample quality. We planned this study to verify whether in-house prepared internal quality control (IQC) materials may be suitable for quality assurance of HIL indices. Pools containing different values of each of the three HIL indices were prepared from routine plasma samples, divided in aliquots and frozen at -20°C. Stability of frozen materials was assessed by thawing one aliquot of each pool after different days of freezing (1, 4, 8, 15, 22 and 29), and by measuring HIL indices on baseline fresh samples and frozen-thawed aliquots with Roche Cobas c702. Five fresh liquid IQCs materials were also measured at the same time points. Intra-assay and inter-assay imprecision of HIL indices calculated with commercial IQC materials ranged between 1.1-2.0% and 1.6-3.3%, respectively. When target values of HIL indices were calculated using frozen-thawed aliquots, the inter-assay imprecision of in-house prepared materials was optimal, even better than that of commercial liquid IQCs (H-index, 0.8% versus 1.6%; L-index, 2.2% versus 2.5%; I-index, 0.8% versus 3.3%). In conclusion, in-house prepared IQC materials are cost-effective alternatives to commercial liquid IQCs for HIL quality assurance., Competing Interests: The authors have declared that no competing interests exist.

We suggest here a pragmatic approach for managing results of clinical chemistry testing in hemolyzed samples collected from adults/older children, attempting to balance the need to produce quality laboratory data with clinical urgency of releasing test results. Automatic measurement of the hemolysis index (H-index) in serum or plasma is highly advisable, whilst low-quality assessment of this test remains less good than a visual inspection. Regarding its practical use, when the H-index value does not generate an analytically significant bias, results can be released, whilst when the value is associated with analyte variation in a range between analytically and clinically significant bias (i.e. variation does not exceed the reference change value [RCV]), results of hemolysis-sensitive tests can be released in association with a comment describing the direction in which data are potentially altered, suggesting the need to collect another sample. When the H-index is associated with analyte variation exceeding clinically significant bias (i.e. variation exceeds the RCV), results of hemolysis-sensitive tests should be suppressed and replaced with a comment that biased results cannot be released because the sample is preanalytically compromised and advising the recollection of another sample. If H-index values reach an even higher critical cut-off (i.e. H-index corresponding to a cell-free hemoglobin concentration ≥10 g/L), all laboratory data may be unreliable and should hence be suppressed and replaced with a comment that all data cannot be released because the sample is grossly hemolyzed, also suggesting the recollection of another sample. Due to inaccuracy and imprecision, the use of corrective formulas for adjusting data of hemolysis-sensitive tests is discouraged.

Background: Inappropriate utilization of laboratory resources is an increasing concern especially in high-throughput facilities. Until now, no reliable information has been published addressing to which extent laboratory results are actually used for clinical decision-making. Therefore, we aimed to close this gap using a novel retrospective approach including a survey of clinicians and nurses., Methods: We retrospectively evaluated the number of re-orders for potassium (K), lactate dehydrogenase (LD), aspartate-aminotransferase (AST), activated partial thromboplastin-time (APTT) and prothrombin-time/INR (PT/INR), after the initial order had to be cancelled due to preanalytical non-conformities. We analyzed subgroups regarding time to re-order, ward and sample priority (urgent vs. routine). Subsequently, we surveyed clinicians and nurses, asking for their estimate of the amount of failed re-orders as well as for possible reasons., Results: From initially cancelled tests, only ~20% of K, LD, AST and ~30% of APTT and PT/INR tests were re-ordered within 24 h. 70% of the investigated clinical chemistry and 60% of coagulation tests were re-ordered one week after cancellation or not at all. Survey participants quite accurately estimated these numbers. Routine laboratory panels, short stay of out-patients, obsolete test results and avoiding additional phlebotomies were the main reasons for not re-ordering cancelled tests., Conclusions: Overall, 60-70% of test results in the investigated assays ordered in a high throughput laboratory are potentially inappropriate or of doubtful clinically importance. Although clinicians and nurses are aware of this situation, it is the duty of laboratory specialists to overcome overutilization in close collaboration with all involved healthcare workers., (Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Hemolytic samples are one of the most challenging preanalytical issues in laboratory medicine. Even causes leading to hemolytic specimen are various, including phlebotomy practices. Respective educational interventions as well as the reduction of the number of people involved in blood collections are claimed to influence the sample quality for the better. In our hospital 70 junior doctors were in charge of routine phlebotomy until 2012, when this task was shifted to 874 nurses, including a preceding training in phlebotomy and preanalytics. Our aim was to evaluate the impact of this training effect and the increase of people involved on sample quality., Methods: The hemolysis index (HI) of 43,875 samples was measured before (n=21,512) and after (n=22,363) the switch of blood collection responsibilities. Differences in overall hemolysis rates and the amount of plasma samples with a concentration of free hemoglobin (fHb) above 0.5 g/L and 1 g/L were calculated., Results: Overall HI as well as the percentage of samples with an fHb concentration >0.5 g/L decreased after the responsibility for phlebotomy changed. The rate of samples with an fHb concentration >1 g/L remained unchanged., Conclusions: Hemolysis rates were reduced upon passing phlebotomy tasks from untrained physicians on to a trained nursing staff. We therefore conclude that the number of people performing phlebotomy seems to play a minor role, compared to the effect of a standardized training. However, whether a reduction in the number of people involved in blood collection could lead to further improvement of sample quality, remains to be investigated in future studies.