External quality assessment of serum indices: Spanish SEQC-ML program.

OBJECTIVES: Serum indices included in clinical chemistry instruments are widely used by laboratories to assess the quality of samples. Instruments that report quantitative results allow an evaluation of their diagnostic performance in a similar way to other biochemical tests. The Spanish Society of Laboratory Medicine (SEQC-ML) launched a monthly External Quality program of serum indices in 2018 using three lyophilized materials of simultaneous annual distribution. We present the results of the first three years of the program. METHODS: The use of four different quality control materials with different concentrations in three alternate months allows an annual evaluation of the participant's accuracy. Assigned values are established by consensus among homogeneous groups, considering necessary at least 10 participants for a comparison at instrument level. The average percentage difference results per instrument allow the assessment of bias among groups. RESULTS: The imprecision of the three indices ranges between 3 and 9%, with no major differences among instruments. Significant differences were observed in all indices among instruments with more than 10 participants (Roche Cobas, Abbott Architect, Abbott Alinity and Siemens Advia). The 90th percentile of the distribution of percentage differences was used as the analytical performance specification (APS). An improvement in performance was observed in the first three years of the program, probably due to the learning curve effect. In 2020, APS of 7.8, 12.2 and 9.7% were proposed for hemolytic, icteric and lipemic indices, respectively. CONCLUSIONS: Serum indices have a great impact on the quality and the reliability of laboratory test results. Participation in proficiency testing programs for serum indices is helpful to encourage harmonization among providers and laboratories.

Physical and mental health effects of repeated short walks in a blue space environment: A randomised crossover study.

INTRODUCTION: Blue spaces may benefit mental health and promote physical activity, although the evidence is still scarce. And benefits on physical health are less consistent. The objective of this randomized crossover study was to assess psychological and cardiovascular responses to blue spaces' exposure. METHODS: A sample of 59 healthy adult office workers was randomly assigned to a different environment (i.e. blue space, urban space, and control site) on 4 days each week, for 3 weeks. For 20 min per day, they either walked along a blue or an urban space or rested at a control site. Before, during and/or after the exposure, we measured self-reported well-being and mood, blood pressure, and heart rate variability parameters. For well-being, we also assessed the duration of these potential effects over time (at least 4 h after exposure). RESULTS: We found significantly improved well-being and mood responses immediately after walking in the blue space compared with walking in the urban space or when resting in the control site. Cardiovascular responses showed increased activity of the sympathetic nervous system, both during and after walking along the blue and urban spaces. However, cardiovascular responses measured after the walks, showed no statistically significant differences between the blue and the urban space environments. CONCLUSIONS: Short walks in blue spaces can benefit both well-being and mood. However, we did not observe a positive effect of blue spaces for any of the cardiovascular outcomes assessed in this study.

Reaching consensus on communication of critical laboratory results using a collective intelligence method.

BACKGROUND: There is no consensus in the literature about what analytes or values should be informed as critical results and how they should be communicated. The main aim of this project is to establish consensual standards of critical results for the laboratories participating in the study. Among the project's secondary objectives, establishing consensual procedures for communication can be highlighted. METHODS: Consensus was reached among all participating laboratories establishing the basis for the construction of the initial model put forward for consensus in conjunction with the clinicians. A real-time Delphi, methodology "health consensus" (HC), with motivating and participative questions was applied. The physician was expected to choose a numeric value within a scale designed for each analyte. RESULTS: The medians of critical results obtained represent the consensus on critical results for outpatient and inpatient care. Both in primary care and in hospital care a high degree of consensus was observed for critical values proposed in the analysis of creatinine, digoxin, phosphorus, glucose, international normalized ratio (INR), leukocytes, magnesium, neutrophils, chloride, sodium, calcium and lithium. For the rest of critical results the degree of consensus obtained was "medium high". The results obtained showed that in 72% of cases the consensual critical value coincided with the medians initially proposed by the laboratories. CONCLUSIONS: The real-time Delphi has allowed obtaining consensual standards for communication of critical results among the laboratories participating in the study, which can serve as a basis for other organizations.

Laboratory sample stability. Is it possible to define a consensus stability function? An example of five blood magnitudes.

BACKGROUND: The stability limit of an analyte in a biological sample can be defined as the time required until a measured property acquires a bias higher than a defined specification. Many studies assessing stability and presenting recommendations of stability limits are available, but differences among them are frequent. The aim of this study was to classify and to grade a set of bibliographic studies on the stability of five common blood measurands and subsequently generate a consensus stability function. METHODS: First, a bibliographic search was made for stability studies for five analytes in blood: alanine aminotransferase (ALT), glucose, phosphorus, potassium and prostate specific antigen (PSA). The quality of every study was evaluated using an in-house grading tool. Second, the different conditions of stability were uniformly defined and the percent deviation (PD%) over time for each analyte and condition were scattered while unifying studies with similar conditions. RESULTS: From the 37 articles considered as valid, up to 130 experiments were evaluated and 629 PD% data were included (106 for ALT, 180 for glucose, 113 for phosphorus, 145 for potassium and 85 for PSA). Consensus stability equations were established for glucose, potassium, phosphorus and PSA, but not for ALT. CONCLUSIONS: Time is the main variable affecting stability in medical laboratory samples. Bibliographic studies differ in recommedations of stability limits mainly because of different specifications for maximum allowable error. Definition of a consensus stability function in specific conditions can help laboratories define stability limits using their own quality specifications.

Spanish Preanalytical Quality Monitoring Program (SEQC), an overview of 12 years' experience.

BACKGROUND: Preanalytical variables, such as sample collection, handling and transport, may affect patient results. Preanalytical phase quality monitoring should be established in order to minimize laboratory errors and improve patient safety. METHODS: A retrospective study (2001-2013) of the results obtained through the Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC) External quality assessment (preanalytical phase) was performed to summarize data regarding the main factors affecting preanalytical phase quality. Our aim was to compare data from 2006 to 2013 with a previously published manuscript assessing the 2001-2005 period. RESULTS: A significant decrease in rejection rates was observed both for blood and urine samples. For serum samples, the most frequent rejection causes in the first period were non-received samples (37.5%), hemolysis (29.3%) and clotted samples (14.4%). Conversely, in the second period, hemolysis was the main rejection cause (36.2%), followed by non-received samples (34.5%) and clotted samples (11.1%). For urine samples, the main rejection cause overall was a non-received sample (up to 86.1% of cases in the second period, and 81.6% in the first). For blood samples with anticoagulant, the number of rejections also decreased. While plasma-citrate-ESR still showed the highest percentages of rejections (0.980% vs. 1.473%, p<0.001), the lowest corresponded to whole-blood EDTA (0.296% vs. 0.381%, p<0.001). CONCLUSIONS: For the majority of sample types, a decrease in preanalytical errors was confirmed. Improvements in organization, implementation of standardized procedures in the preanalytical phase, and participation in a Spanish external quality assessment scheme may have notably contributed to error reduction in this phase.

Harmonization in hemolysis detection and prevention. A working group of the Catalonian Health Institute (ICS) experience.

BACKGROUND: Hemolysis is the main cause of non-quality samples in clinical laboratories, producing the highest percentage of rejections in the external assurance programs of preanalytical quality. The objective was to: 1) study the agreement between the detection methods and quantification of hemolysis; 2) establish comparable hemolysis interference limits for a series of tests and analytical methods; and 3) study the preanalytical variables which most influence hemolysis production. METHODS: Different hemoglobin concentration standards were prepared using the reference method. Agreement was studied between automated methods [hemolytic indexes (HI)] and reference method, as well as the interference according to hemolysis degree in various biochemical tests was measured. Preanalytical variables which could influence hemolysis production were studied: type of extraction, type of tubes, transport time, temperature and centrifugation conditions. RESULTS: Good agreement was obtained between hemoglobin concentrations measured using the reference method and HI, for the most of studied analyzers, particularly those giving quantitative HI. The hemolysis interference cut-off points obtained for the majority of tests studied (except LDH, K) are dependent on the method/analyzer utilized. Furthermore, discrepancies have been observed between interference limits recommended by the manufacturer. The preanalytical variables which produce a lower percentage of hemolysis rejections were: centrifugation at the extraction site, the use of lower volume tubes and a transport time under 15 min at room temperature. CONCLUSIONS: The setting of interference limits (cut-off) for each used test/method, and the study of preanalytical variability will assist to the results harmonization for this quality indicator.

Current status of verification practices in clinical biochemistry in Spain.

BACKGROUND: Verification uses logical algorithms to detect potential errors before laboratory results are released to the clinician. Even though verification is one of the main processes in all laboratories, there is a lack of standardization mainly in the algorithms used and the criteria and verification limits applied. A survey in clinical laboratories in Spain was conducted in order to assess the verification process, particularly the use of autoverification. METHODS: Questionnaires were sent to the laboratories involved in the External Quality Assurance Program organized by the Spanish Society of Clinical Biochemistry and Molecular Pathology. Seven common biochemical parameters were included (glucose, cholesterol, triglycerides, creatinine, potassium, calcium, and alanine aminotransferase). RESULTS: Completed questionnaires were received from 85 laboratories. Nearly all the laboratories reported using the following seven verification criteria: internal quality control, instrument warnings, sample deterioration, reference limits, clinical data, concordance between parameters, and verification of results. The use of all verification criteria varied according to the type of verification (automatic, technical, or medical). Verification limits for these parameters are similar to biological reference ranges. Delta Check was used in 24% of laboratories. Most laboratories (64%) reported using autoverification systems. Autoverification use was related to laboratory size, ownership, and type of laboratory information system, but amount of use (percentage of test autoverified) was not related to laboratory size. CONCLUSIONS: A total of 36% of Spanish laboratories do not use autoverification, despite the general implementation of laboratory information systems, most of them, with autoverification ability. Criteria and rules for seven routine biochemical tests were obtained.

Sociodemographic, lifestyle, and environmental determinants of vitamin D levels in pregnant women in Spain.

INTRODUCTION: Vitamin D deficiency (<20 ng/mL circulating levels) is a worldwide public health concern and pregnant women are especially vulnerable, affecting the health of the mother and the fetus. This study aims to evaluate the sociodemographic, lifestyle, and environmental determinants associated with circulating vitamin D levels in Spanish pregnant women. METHODS: We used data from the Spanish INMA ("Infancia y Medio Ambiente") prospective birth cohort study from the regions of Gipuzkoa, Sabadell, and Valencia. 25-hydroxyvitamin D3 (25(OH)D3) was measured in plasma collected in the first trimester of pregnancy. Information on 108 determinants was gathered: 13 sociodemographic, 48 lifestyle including diet, smoking and physical activity, and 47 environmental variables, representing the urban and the chemical exposome. Association of the determinants with maternal 25(OH)D3 levels was estimated in single- and multiple-exposure models. Machine learning techniques were used to predict 25(OH)D3 levels below sufficiency (30 ng/mL). RESULTS: The prevalence of < 30 ng/mL 25(OH)D3 levels was 51 %. In the single-exposure analysis, older age, higher socioeconomic status, taking vitamin D, B12 and other sup*plementation, and higher humidity, atmospheric pressure and UV rays were associated with higher levels of 25(OH)D3 (IQR increase of age: 1.2 [95 % CI: 0.6, 1.8] ng/mL 25(OH)D3). In the multiple-exposures model, most of these associations remained and others were revealed. Higher body mass index, PM2.5 and high deprivation area were associated with lower 25(OH)D3 levels (i.e., Quartile 4 of PM2.5 vs Q1: -3.6 [95 % CI: -5.6, -1.5] ng/mL of 25(OH)D3). History of allergy and asthma, being multiparous, intake of vegetable fat, vitamin B6, alcohol consumption and molybdenum were associated with higher levels. The machine learning classification model confirmed some of these associations. CONCLUSIONS: This comprehensive study shows that younger age, higher body mass index, higher deprived areas, higher air pollution and lower UV rays and humidity are associated with lower 25(OH)D3 levels.

Evaluation of 18 quality indicators from the external quality assurance preanalytical programme of the Spanish Society of Laboratory Medicine (SEQCML).

Objectives: Most errors in laboratory medicine occur in the pre- and post-analytical phases of the total testing process (TTP). In 2014, the Spanish Society of Laboratory Medicine (SEQCML) started the current Preanalytical Phase EQA Programme, with the objective of providing a tool for the improvement of the preanalytical phase. The aim of this study was to review the evolution of quality indicators (QI) and the comparability of established performance specifications (PS) with other EQA programmes. Methods: In the SEQCML programme, participants were asked to register rejections of the main specimens and the causes for rejections. Data collected from 2014 to 2017, and then reviewed biennially (2018-2019), was used to calculate the percentiles; p25, p50, p75, and p90 for every round, and their means were set as PS. These PS were compared with the results of other programmes. Results: The evolution of QI results for 2018-2019 period showed general maintenance or improvement, e.g., a significant decrease in the number of serum samples with a haemolytic index ≥0.5 g/L, except for EDTA and citrate samples handle, maybe for an improvement in detection. The comparison with PS for the QI of the IFCC Working Group "Laboratory Errors and Patient Safety" and the Key Incident Management and Monitoring System (KIMMS) programme of the RCPA showed comparable results, supporting the validity of the established specifications. Conclusions: The PS obtained are a helpful tool for benchmarking and to identify processes of the preanalytical phase whose improvement should be set as a priority.

Influence of study model, baseline catalytic concentrations and analytical system on the stability of serum alanine aminotransferase.

Objectives: The stability of the analytes most commonly used in routine clinical practice has been the subject of intensive research, with varying and even conflicting results. Such is the case of alanine aminotransferase (ALT). The purpose of this study was to determine the stability of serum ALT according to different variables. Methods: A multicentric study was conducted in eight laboratories using serum samples with known initial catalytic concentrations of ALT within four different ranges, namely: <50 U/L (<0.83 µkat/L), 50-200 U/L (0.83-3.33 µkat/L), 200-400 U/L (3.33-6.67 µkat/L) and >400 U/L (>6.67 µkat/L). Samples were stored for seven days at two different temperatures using four experimental models and four laboratory analytical platforms. The respective stability equations were calculated by linear regression. A multivariate model was used to assess the influence of different variables. Results: Catalytic concentrations of ALT decreased gradually over time. Temperature (-4%/day at room temperature vs. -1%/day under refrigeration) and the analytical platform had a significant impact, with Architect (Abbott) showing the greatest instability. Initial catalytic concentrations of ALT only had a slight impact on stability, whereas the experimental model had no impact at all. Conclusions: The constant decrease in serum ALT is reduced when refrigerated. Scarcely studied variables were found to have a significant impact on ALT stability. This observation, added to a considerable inter-individual variability, makes larger studies necessary for the definition of stability equations.

Corrigendum to: Preanalytical issues related to routine and diagnostic glucose tests: Results from a survey in Spain.

[This corrects the article DOI: 10.11613/BM.2020.010704.].

Preanalytical issues related to routine and diagnostic glucose tests: Results from a survey in Spain.

INTRODUCTION: Diabetes mellitus (DM) is one of the most prevalent diseases worldwide. The objective of this study was to find out under what preanalytical conditions routine and diagnostic glucose tests are performed across Spanish laboratories; and also what criteria are used for DM diagnosis. MATERIALS AND METHODS: An online survey was performed by the Commission on Quality Assurance in the Extra-Analytical Phase of the Spanish Society of Laboratory Medicine (SEQC-ML). Access to the questionnaire was available on the home page of the SEQC-ML website during the period April-July 2018. Data analysis was conducted with the IBM SPSS© Statistics (version 20.0) program. RESULTS: A total of 96 valid surveys were obtained. Most laboratories were in public ownership, serving hospital and primary care patients, with high and medium workloads, and a predominance of mixed routine-urgent glucose testing. Serum tubes were the most used for routine glucose analysis (92%) and DM diagnosis (54%); followed by lithium-heparin plasma tubes (62%), intended primarily for urgent glucose testing; point-of-care testing devices were used by 37%; and plasma tubes with a glycolysis inhibitor, mainly sodium fluoride, by 19%. Laboratories used the cut-off values and criteria recognized worldwide for DM diagnosis in adults and glucose-impaired tolerance, but diverged in terms of fasting plasma glucose and gestational DM criteria. CONCLUSION: Preanalytical processing of routine and DM diagnostic glucose testing in Spain does not allow a significant, non-quantified influence of glycolysis on the results to be ruled out. Possible adverse consequences include a delay in diagnosis and possible under-treatment.

Cystathionine beta synthase as a risk factor for Alzheimer disease.

One of the known risk factors for developing Alzheimer disease (AD) is hyperhomocysteinemia. The latter may result from mutations of the genes coding for three key enzymes involved in homocysteine metabolism (methylenetetrahydrofolate reductase [MTHFR], methionine synthase [MS], and cystathionine beta-synthase [CBS]). Although MTHFR and MS polymorphisms have been shown to be positively associated with AD in some populations, the relationship of the CBS gene with AD remains undefined. In order to evaluate whether AD is associated with CBS gene changes leading to decreased CBS activity and homocysteine accumulation, we genotyped the CBS 844ins68 mutation and VNTR polymorphisms of the CBS gene in 206 AD patients and 186 age-matched controls. A slight increase in both 844ins68 mutation and VNTR allele 19 frequencies was detected in the whole AD patient group, compared with controls. The division of AD patients and controls into three age-at-onset/age dependent subgroups (<65 years, 65-74 years, > 75 years) revealed that the 844ins68 mutation and VNTR allele 19 are independent risk factors for AD development in subjects aged 75 years or more.