Evaluation of Coefficients of Variation for Clinical Chemistry Tests Based on Internal Quality Control Data Across 5,425 Laboratories in China From 2013 to 2022.

Background: Clinical chemistry tests are most widely used in clinical laboratories, and diverse measurement systems for these analyses are available in China. We evaluated the imprecision of clinical chemistry measurement systems based on internal QC (IQC) data. Methods: IQC data for 27 general chemistry analytes were collected in February each year from 2013 to 2022. Four performance specifications were used to calculate pass rates for CVs of IQC data in 2022. Boxplots were drawn to analyze trends of CVs, and differences in CVs among different groups were assessed using the Mann-Whitney U-test or Kruskal-Wallis test. Results: The number of participating laboratories increased significantly from 1,777 in 2013 to 5,425 in 2022. CVs significantly decreased for all 27 analytes, except creatine kinase and lipase. Triglycerides, total bilirubin, direct bilirubin, iron, and γ-glutamyl transferase achieved pass rates >80% for all goals. Nine analytes with pass rates <80% based on 1/3 allowable total error were further analyzed; the results indicated that closed systems exhibited lower CVs than open systems for all analytes, except total protein. For all nine analytes, differences were significant between tertiary hospitals and non-tertiary hospitals and between accredited and non-accredited laboratories. Conclusions: The CVs of IQC data for clinical chemistry have seen a continuous overall improvement in China. However, there is ample room for imprecision improvement for several analytes, with stricter performance specifications.

In-house standards derived from doping peptides: Enzymatic and serum stability and degradation profile of GHRP and GHRH-related peptides.

Matrix effect and sample pretreatment significantly affect the percentage recovery of peptides in biological matrices, affecting the method robustness and accuracy. To counteract this effect, an internal standard (IS) is used; however, in most cases this is not available, which limits the analytical method. It is important to identify short peptides that can be used as ISs in the quantification of peptides in biological matrices. In this study, doping peptides GHRP-4, GHRP-5, GHRP-6, Sermorelin (1-11), Sermorelin (13-20) and Sermorelin (22-29) were synthesized using solid-phase peptide synthesis. Treatment with human blood, trypsin and chymotrypsin was used to determine the stability of the peptides. Products were evaluated using the high-performance liquid chromatography-diode array detector (HPLC-DAD) method. The analytical methodology and sample pretreatment were effective for the analysis of these molecules. A unique profile related to protein binding and enzymatic stability of each peptide was established. GHRP-4, GHRP-6 and Sermorelin (22-29) can be considered as in-house ISs as they were stable to enzyme and blood treatment and can be used for the quantification of peptides in biological samples. Peptides GHRP-6 and Sermorelin (22-29) were used to analyse a dimeric peptide (26 [F] LfcinB (20-30)2 ) in four different matrices to test these peptides as in-house IS.

Clinical chemistry laboratory test overuse in a cardiology clinic: a single-center study.

Diagnostic laboratory tests are frequently overused in healthcare entities, leading to an increased strain on laboratory resources, additional workload, and wastage of resources. Continuous monitoring of test ordering behavior is crucial to evaluate clinical necessity. This cross-sectional study aimed to estimate the necessity of ordering clinical chemistry tests in the cardiology clinic of a tertiary center in Saudi Arabia. We retrieved medical records of patients diagnosed with cardiovascular problems admitted at the cardiology clinic in 2020. The frequency and percentages of the ordered tests were calculated upon admission and follow-up, and the difference between necessary and unnecessary tests was compared for each category. Test ordering assessment included cardiac, renal, and liver functions, blood gases, thyroid and diabetic profile, iron indices, hormones, water and electrolytes, and inflammatory markers. The results showed a large number of clinical chemistry tests ordered without clinical necessity. While the number of necessary tests was significantly higher than that of unnecessary tests, 21% of the tests ordered between June-December 2021 at the center were unnecessary. Further studies are necessary to identify driving factors and develop strategies to reduce the overutilization of diagnostic laboratory tests in clinical practice. Eliminating this phenomenon will reduce the risk of unnecessary medical interventions and associated costs, improve patient outcomes, and reduce the overall burden on the healthcare system.

Quality improvement of outpatient clinical chemistry tests through a novel middleware-laboratory information system solution.

OBJECTIVES: Rapid and accurate laboratory tests are essential to support clinical decision-making. Despite the various efforts to control quality in the laboratory, our outpatient chemistry turnaround time (TAT) has deteriorated since 2018. Moreover, these difficulties have accelerated further due to the COVID-19 pandemic. Therefore, we aimed to improve laboratory work efficiency by identifying and eliminating the causes of reduced laboratory work efficiency. DESIGN & METHODS: We surveyed to identify tasks that reduce work efficiency. Based on our survey, a new-concept of work assistance middleware linked to laboratory information system (LIS) was developed. The middleware supports test end-time prediction, automatic real-time TAT monitoring, and urgent test requests so that medical technologists can focus on their chemistry tests. The developed middleware was used for 6 months in laboratory and outpatient clinics, and its effectiveness was evaluated. RESULTS: The median TAT for outpatient chemistry tests was reduced by 6.6 min, from 72.4 min to 65.8 min. And not only did the maximum TAT for the sample decrease from 353 min to 214 min, but the proportion of samples exceeding the TAT target (120 min) also decreased by 77%; from 2.00% in 2010 (1,905 out of 94,989 samples) to 0.46% in 2021 (453 out of 98,117 samples). 2,199 samples were urgently requested through middleware, and they were processed about 15% faster than other samples, effectively performing urgent tests. The test end-time prediction showed an error of 8.6 min in the evaluation using the MAE (Mean Absolute Error) index. CONCLUSIONS: Through this study, the quality and efficiency of the laboratory were improved, and while reducing the workload of medical staff, it contributed to enhancing patient safety and satisfaction.

Hemolysis interference on clinical chemistry tests analyzed on DxC 700 AU (Beckman Coulter®) and kaliemia rendering algorithm / Interférence de l'hémolyse sur les examens de biochimie clinique analysés sur DxC 700 AU (Beckman Coulter®) et algorithme de rendu de la kaliémie

The influence of hemolysis was evaluated for 26 clinical chemistry parameters on DxC 700AU (Beckman Coulter®). Ten sample pools were prepared and separated into six aliquots. These aliquots were overloaded with hemolysis in increasing amounts to reach levels equivalent to the maximum hemolysis thresholds H1 (+), H2 (++), H3 (+++) and H4 (++++). Each aliquot is compared to its reference aliquot (not hemolyzed) and a ratio is calculated for each parameter. We proposed that there was a significant difference if, for a given analyte and threshold, more than 20% of the ratios are above the total acceptable limit variability. A significant difference was found for TGP, TGO, cholesterol, creatine kinase (CPK), lactate deshydrogenase (LDH), phosphorus and potassium at H1 (+), chlorine, iron, γ-glutamyltransferase (GGT), and magnesium at H2 (++), amylase and alkaline phosphatase (PAL) at H3 (++++), and prealbumin at H4 (++++). No interference was found until H4 included for uric acid, calcium, creatinine, lipase, glucose, HDL-cholesterol, triglycerides, urea, sodium and immunoglobulins A, G and M. The overestimation of kalemia was calculated as a function of hemolysis, ranging from 0.28 mM +/­0.047 (upper H1 threshold) to 1.37 mM +/­0.126 (upper H4 threshold). Its estimation makes it possible to propose a result rendering algorithm of kalemia according to the hemolysis index. Evaluation of the automates hemolysis indexes is highly recommended for each laboratory. It can allow for some critical parameters the establishment of a decision tree facilitating the result rendering, after clinicobiological consultation.

L'influence de l'hémolyse a été évaluée pour 26 paramètres biochimiques sur l'analyseur DxC 700 AU (Beckman Coulter®). Dix pools d'échantillons ont été préparés et séparés en six aliquots surchargés en hémolysat selon une quantité croissante d'hémoglobine pour atteindre des niveaux équivalents aux seuils maximums d'hémolyse de l'automate H1(+), H2(++), H3(+++) et H4 (++++). Chaque aliquot est comparé à son aliquot de référence (sans hémolysat) et un ratio est calculé pour chaque paramètre. Nous proposons une différence significative si, pour un analyte et un seuil donné, plus de 20 % des ratios sont supérieurs à la variabilité limite totale acceptable (VLTA). Une différence significative est retrouvée pour ALAT, ASAT, cholestérol, créatine kinase (CPK), lactate deshydrogenase (LDH), phosphore et potassium dès H1, chlore, fer, γ--glutamyltransferase (GGT), et magnésium pour H2, amylase et phosphatase alcaline (PAL) pour H3, et préalbumine pour H4. Aucune interférence n'a été retrouvée jusqu'à H4 inclus pour acide urique, calcium, créatinine, lipase, glucose, HDL-cholestérol, triglycérides, urée, sodium et immunoglobulines A, G et M. La surestimation de la kaliémie a été calculée en fonction de l'hémolyse : elle varie de 0,28 mM ± 0,047 (seuil supérieur de H1) à 1,37 mM ± 0,126 (seuil supérieur de H4). Son estimation permet proposer un algorithme de rendu de résultat de la kaliémie selon l'index d'hémolyse. L'évaluation des index d'hémolyses de l'automate est, pour chaque laboratoire, fortement recommandée. Elle peut permettre, pour certains paramètres critiques, la mise en place d'un arbre décisionnel facilitant le rendu de résultat, après concertation clinicobiologique.

Comparison between polynomial regression and weighted least squares regression analysis for verification of analytical measurement range.

OBJECTIVES: Recently, the linearity evaluation protocol by the Clinical & Laboratory Standards Institute (CLSI) has been revised from EP6-A to EP6-ED2, with the statistical method of interpreting linearity evaluation data being changed from polynomial regression to weighted least squares linear regression (WLS). We analyzed and compared the analytical measurement range (AMR) verification results according to the present and prior linearity evaluation guidelines. METHODS: The verification of AMR of clinical chemistry tests was performed using five samples with two replicates in three different laboratories. After analyzing the same evaluation data in each laboratory by the polynomial regression analysis and WLS methods, results were compared to determine whether linearity was verified across the five sample concentrations. In addition, whether the 90% confidence interval of deviation from linearity by WLS was included in the allowable deviation from linearity (ADL) was compared. RESULTS: A linearity of 42.3-56.8% of the chemistry items was verified by polynomial regression analysis in three laboratories. For analysis of the same data by WLS, a linearity of 63.5-78.3% of the test items was verified where the deviation from linearity of all five samples was within the ADL criteria, and the cases where the 90% confidence interval of all deviation from linearity overlapped the ADL was 78.8-91.3%. CONCLUSIONS: Interpreting AMR verification data by the WLS method according to the newly revised CLSI document EP6-ED2 could reduce laboratory workload, enabling efficient laboratory practice.

Analytical validation of 39 clinical chemistry tests and 17 immunoassays on the Alinity analytical system.

The aim of this study was to perform the analytical validation of Alinity c and i analyzers (Abbott Laboratories, Chicago, IL, USA) for 39 clinical chemistry tests and 17 immunoassays. Precision was evaluated at least at two concentration levels for 5 days in quintuplicate, following CLSI EP15-A3. Method comparison included parallel analysis of leftover routine samples on Alinity analyzers and the previously used Cobas c501 and e601 (Roche Diagnostics, Mannheim, Germany). Linearity was tested by preparing sequential sample dilutions with high analyte concentration, following the CLSI EP6 document. For clinical chemistry tests, within-run coefficients of variation (CV) were up to 6.0% (beta-2-microglobulin), while between-run CVs up to 5.4% (immunoglobulin M). Among immunoassays, the highest within-run CV was obtained for vitamin B12 (6.9%), while between-run for CA 19-9 (4.3%). Complete agreement with Roche analyzers was observed for 16 (41%) clinical chemistry assays and 6 (35%) immunoassays. Half of all evaluated assays did not meet the desirable biological variation criteria for bias, being especially exceeded for alpha1-antitrypsin, apolipoprotein A1, ceruloplasmin, complement C3 and C4, hemoglobin A1c, lipoprotein (a) and myoglobin, as well as some tumor markers (CA 125, CEA, fPSA, AFP, and ferritin), hormones (cortisol, DHEA-S, insulin) and vitamins (25-OHD). Linearity in the tested ranges was confirmed. Overall, this study revealed that precision criteria derived from manufacturer's claims were not satisfied for all assays while comparison study for some assays yielded differences that imply the need for additional assay evaluation prior to introduction into routine practice.

Comparison of Five Common Analyzers in the Measurement of Chemistry Analytes in an Authentic Cohort of Body Fluid Specimens.

OBJECTIVES: Interpretation of body fluid (BF) results is based on published studies and clinical guidelines. The aim of this study is to determine whether the assays from five common commercial vendors produce similar results in BFs for 12 analytes in a BF cohort. METHODS: BFs (n = 25) and serum (n = 5) were analyzed on five instruments (Roche cobas c501, Ortho 5600, Beckman AU5800 and DXI800, Siemens Vista 1500, and Abbott Architect c8000) to measure albumin, amylase, total bilirubin, cholesterol, creatinine, glucose, lactate dehydrogenase (LDH), lipase, total protein, triglycerides, urea nitrogen, and carcinoembryonic antigen. Deming regression and Bland-Altman analysis were used for method comparison to Roche. RESULTS: Results were significantly different from Roche for LDH and lipase on Ortho and lipase on Siemens but similar for both BFs and serum. BF differences were larger than serum differences when measuring creatinine, glucose, and urea nitrogen on Ortho and glucose on Siemens. CONCLUSIONS: Five instruments used to perform BF testing produce results that are not significantly different except for lipase and LDH measurements. Bias of similar magnitude observed in both BF and serum should not affect interpretation. Further investigations into Ortho and Siemens measuring glucose and Ortho measuring creatinine and urea nitrogen are warranted.

Combined strategy of knowledge-based rule selection and historical data percentile-based range determination to improve an autoverification system for clinical chemistry test results.

BACKGROUND: Current autoverification, which is only knowledge-based, has low efficiency. Regular historical data analysis may improve autoverification range determination. We attempted to enhance autoverification by selecting autoverification rules by knowledge and ranges from historical data. This new system was compared with the original knowledge-based system. METHODS: New types of rules, extreme values, and consistency checks were added and the autoverification workflow was rearranged to construct a framework. Criteria for creating rules for extreme value ranges, limit checks, consistency checks, and delta checks were determined by analyzing historical Zhongshan laboratory data. The new system's effectiveness was evaluated using pooled data from 20 centers. Efficiency improvement was assessed by a multicenter process. RESULTS: Effectiveness was evaluated by the true positive rate, true negative rate, and overall consistency rate, as compared to manual verification, which were 77.55%, 78.53%, and 78.3%, respectively for the new system. The original overall consistency rate was 56.2%. The new pass rates, indicating efficiency, were increased by 19%-51% among hospitals. Further customization using individualized data increased this rate. CONCLUSIONS: The improved system showed a comparable effectiveness and markedly increased efficiency. This transferable system could be further improved and popularized by utilizing historical data from each hospital.

Evaluation of the clinical chemistry tests analytical performance with Sigma Metric by using different quality specifications - Comparison of analyser actual performance with manufacturer data.

INTRODUCTION: The interest in quality management tools/methodologies is gradually increasing to ensure quality and accurate results in line with international standards in clinical laboratories. Six Sigma stands apart from other methodologies with its total quality management system approach. However, the lack of standardization in tolerance limits restricts the advantages for the process. Our study aimed both to evaluate the applicability of analytical quality goals with Roche Cobas c 702 analyser and to determine achievable goals specific to the analyser used. MATERIALS AND METHODS: The study examined under two main headings as Sigmalaboratory and Sigmaanalyser. Sigmalaboratory was calculated using internal and external quality control data by using Roche Cobas c 702 analyser for 21 routine biochemistry parameters and, Sigmaanalyser calculation was based on the manufacturer data presented in the package inserts of the reagents used in our laboratory during the study. Sigma values were calculated with the six sigma formula. RESULTS: Considering the total number of targets achieved, Sigmaanalyser performed best by meeting all CLIA goals, while Sigmalaboratory showed the lowest performance relative to biological variation (BV) desirable goals. CONCLUSIONS: The balance between the applicability and analytical assurance of "goal-setting models" should be well established. Even if the package insert data provided by the manufacturer were used in our study, it was observed that almost a quarter of the evaluated analytes failed to achieve even "acceptable" level performance according to BV-based goals. Therefore, "state-of-the-art" goals for the Six Sigma methodology are considered to be more reasonable, achievable, and compatible with today's technologies.

Dynamic Tests in Pituitary Endocrinology: Pitfalls in Interpretation during Aging.

Aging and age-related diseases represent hot topics of current research. Progressive damage in morphology and function of cells and tissue characterizes the normal process of aging that is influenced by both genetic and environmental factors. The ability of each individual to adapt to these stressors defines the type of aging and the onset of age-related diseases (i.e., metabolic syndrome, inflammatory disorders, cancer, and neurodegenerative diseases). The endocrine system plays a critical role in this process because of its complex relationships with brain, immune system, and skeletal muscle; thus, alterations in hormonal networks occur during aging to maintain homeostasis, with consequent under- or overactivity of specific hypothalamic-pituitary-peripheral hormone axes. On the other hand, the increase in life expectancy has led to increasing incidence of age-related diseases, including endocrine disorders, which may prompt assessment of endocrine function in aging individuals. In this context, there is growing awareness that natural changes of endocrine physiology and physiopathology occurring with increasing age may necessitate age-driven diagnostic cutoffs requiring validation in the elderly. This review aims to analyze the available literature on the hormone response to the most important dynamic tests currently used in the clinical practice for the screening of anterior pituitary-related diseases to underline pitfalls in interpretation during aging.

Periodic Comparability Verification and Within-Laboratory Harmonization of Clinical Chemistry Laboratory Results at a Large Healthcare Center With Multiple Instruments.

BACKGROUND: Results from laboratories using multiple instruments should be standardized or harmonized and comparability-verified for consistent quality control. We developed a simple frequent comparability verification methodology applicable to large healthcare centers using multiple clinical chemistry instruments from different manufacturers. METHODS: Comparability of five clinical chemistry instruments (Beckman Coulter AU5800, Abbott Architect Ci16000, two Siemens Vista 1500, and Ortho Vitros 5600) was evaluated from 2015 to 2019 for 12 clinical chemistry measurements. Pooled residual patient samples were used for weekly verifications. Results from any instrument exceeding the allowable verification range versus the results from the comparative instrument (AU5800) were reported to clinicians after being multiplied by conversion factors that were determined via a linear regression equation obtained from simplified comparison. RESULTS: Over the five-year study period, 432 weekly inter-instrument comparability verification results were obtained. Approximately 58% of results were converted due to non-comparable verification. Expected average absolute percent bias and percentage of non-comparable results for non-converted and converted results after conversion action were much lower than those for data measured before conversion action. The inter-instrument CV for both non-converted and converted results after conversion action was much lower than that for measured data before conversion action for all analytes. CONCLUSIONS: We maintained within-laboratory comparability of clinical chemistry tests from multiple instruments for five years using frequent low-labor periodic comparability verification methods from pooled residual sera. This methodology is applicable to large testing facilities using multiple instruments.

Establishment of dry chemistry based reference intervals of renal function test parameters for the adult population of Kaski District, Nepal.

BACKGROUND: Reference intervals (RIs) for clinical chemistry test parameters are specific to the method of measurement and population under service. However, there has been no locally available dry chemistry based RIs for the Nepalese population. Thus, the present study aimed to establish dry chemistry based RIs for sodium, potassium, urea, and creatinine specific to adult populations of Kaski districts, Nepal METHODS: This was a cross-sectional study conducted at the Manipal Teaching Hospital, Pokhara, Kaski, Nepal on 360 healthy adult participants aged 18-65 years. The test parameters under study were analyzed using a fully automated OCD Vitros 350 dry chemistry analyzer following the protocols provided by the reagent kit manufacturer. The RIs were estimated using reference limits at 2.5th and 97.5th percentiles. The normal distribution of the data was tested by Kolmogorov-Smirnov, and Shapiro-Wilk tests. The differences between males and females RIs were compared by the Mann-Whitney test while age-specific RIs for each sex was compared by One-Way-ANOVA and Dunnett's Multiple Comparisons Tests. All the data were managed and analyzed using MS Excel and SPSS version 20. RESULTS: The RIs of urea, creatinine, sodium, and potassium specific to the adult population of Kaski district, Nepal are as follows: urea: 4.20-13.70 mmol/L (males: 4.70-13.99; females: 4.20-13.23); creatinine: 44.20-106.10 µmol/L (males: 48.82-106.10; females: 35.40-83.78); sodium 135-146 mmol/L (males: 135-146; females: 135-146) and potassium 3.60-5.10 mmol/L (males: 3.54-5.0; females: 3.60-5.10). These RIs were found to be different from currently used RIs provided by the reagent manufacturer. RIs of all the test parameters were significantly influenced by the age of the study participants. However, only the RIs of urea, creatinine, and potassium were significantly influenced by sex. CONCLUSIONS: The present study has for the first time established dry chemistry based RIs for selected renal function test parameters specific to the adult population of Kaski district, Nepal. This result will aid the clinician in minimizing the errors in result interpretation and making a precise clinical decision.

Application of Sigma metrics in the quality control strategies of immunology and protein analytes.

BACKGROUND: Six Sigma (6σ) is an efficient laboratory management method. We aimed to analyze the performance of immunology and protein analytes in terms of Six Sigma. METHODS: Assays were evaluated for these 10 immunology and protein analytes: Immunoglobulin G (IgG), Immunoglobulin A (IgA), Immunoglobulin M (IgM), Complement 3 (C3), Complement 4 (C4), Prealbumin (PA), Rheumatoid factor (RF), Anti streptolysin O (ASO), C-reactive protein (CRP), and Cystatin C (Cys C). The Sigma values were evaluated based on bias, four different allowable total error (TEa) and coefficient of variation (CV) at QC materials levels 1 and 2 in 2020. Sigma Method Decision Charts were established. Improvement measures of analytes with poor performance were recommended according to the quality goal index (QGI), and appropriate quality control rules were given according to the Sigma values. RESULTS: While using the TEaNCCL , 90% analytes had a world-class performance with σ>6, Cys C showed marginal performance with σ<4. While using minimum, desirable, and optimal biological variation of TEa, only three (IgG, IgM, and CRP), one (CRP), and one (CRP) analytes reached 6σ level, respectively. Based on σNCCL that is calculated from TEaNCCL , Sigma Method Decision Charts were constructed. For Cys C, five multi-rules (13s /22s /R4s /41s /6X , N = 6, R = 1, Batch length: 45) were adopted for QC management. The remaining analytes required only one QC rule (13s , N = 2, R = 1, Batch length: 1000). Cys C need to improve precision (QGI = 0.12). CONCLUSIONS: The laboratories should choose appropriate TEa goals and make judicious use of Sigma metrics as a quality improvement tool.

A nomogram based on clinicopathological features and serological indicators predicting breast pathologic complete response of neoadjuvant chemotherapy in breast cancer.

A single tumor marker is not enough to predict the breast pathologic complete response (bpCR) after neoadjuvant chemotherapy (NAC) in breast cancer patients. We aimed to establish a nomogram based on multiple clinicopathological features and routine serological indicators to predict bpCR after NAC in breast cancer patients. Data on clinical factors and laboratory indices of 130 breast cancer patients who underwent NAC and surgery in First Affiliated Hospital of Xi'an Jiaotong University from July 2017 to July 2019 were collected. Multivariable logistic regression analysis identified 11 independent indicators: body mass index, carbohydrate antigen 125, total protein, blood urea nitrogen, cystatin C, serum potassium, serum phosphorus, platelet distribution width, activated partial thromboplastin time, thrombin time, and hepatitis B surface antibodies. The nomogram was established based on these indicators. The 1000 bootstrap resampling internal verification calibration curve and the GiViTI calibration belt showed that the model was well calibrated. The Brier score of 0.095 indicated that the nomogram had a high accuracy. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was 0.941 (95% confidence interval: 0.900-0.982) showed good discrimination of the model. In conclusion, this nomogram showed high accuracy and specificity and did not increase the economic burden of patients, thereby having a high clinical application value.

Association and genetic overlap between clinical chemistry tests and migraine.

INTRODUCTION: In this paper, we studied several serum clinical chemistry tests of cardiovascular disease (CVD), iron deficiency anemia, liver and kidney disorders in migraine. METHODS: We first explored the association of 22 clinical chemistry tests with migraine risk in 697 migraine patients and 2722 controls. To validate and interpret association findings, cross-trait genetic analyses were conducted utilising genome-wide association study (GWAS) data comprising 23,986 to 452,264 individuals. RESULTS: Significant associations with migraine risk were identified for biomarkers of CVD risk, iron deficiency and liver dysfunction (odds ratios = 0.86-1.21; 1 × 10-4 < p < 3 × 10-2). Results from cross-trait genetic analyses corroborate the significant biomarker associations and indicate their relationship with migraine is more consistent with biological pleiotropy than causality. For example, association and genetic overlap between a lower level of HDL-C and increased migraine risk are due to shared biology rather than a causal relationship. Furthermore, additional genetic analyses revealed shared genetics among migraine, the clinical chemistry tests, and heart problems and iron deficiency anemia, but not liver disease. CONCLUSIONS: These findings highlight common biological mechanisms underlying migraine, heart problems and iron deficiency anemia and provide support for their investigation in the development of novel therapeutic and dietary interventions.

Body fluid matrix effect evaluation on the Hitachi Labospect 008 system.

BACKGROUND: Non-standard body fluids (NSBFs) can provide essential clinical information otherwise unobtainable with conventional biological specimens. However, as most commercial chemistry reagents are only validated for serum, plasma, and urine by manufacturers, individual laboratories have to validate testing with NSBF to comply with regulatory standards. However, the heightened level of oversight and uncertainty of validation requirements to comply with regulatory standards pose a significant challenge for NSBF testing in clinical laboratories. METHODS: 28 combinations of high-volume chemistry tests requested on NSBF with established clinical utility were selected from retrospective data analysis. Specimens were analyzed with both closed and open channel chemistry reagents on a LABOSPECT 008AS platform (Hitachi High-Tech Co., Tokyo, Japan). Recovery studies were performed using a high concentration serum sample and 5 clinical NSBF samples at varying concentrations for each analyte. Acceptable performance limits were defined as 100 ± 10% of expected recovery. RESULTS: The average percent recovery ranged from 94.5% to 106.6% depending on the analyte/NSBF combination evaluated, and for each of the 28 combinations, the average percent recovery was within the predefined acceptable limits of ± 10%. CONCLUSIONS: The recovery results from this study on the LABOSPECT 008AS platform demonstrates that any systematic matrix interference of high-volume chemistry testing on NSBF samples is well within the defined limits of acceptability. This work also demonstrates recovery studies performed by an individual laboratory are practial and it is feasible to demonstrate compliance with regulatory requirements for accuracy of chemistry testing on NSBF samples.

Point-of-care faecal calprotectin testing in patients with paediatric inflammatory bowel disease during the COVID-19 pandemic.

OBJECTIVES: Following the disruption of normal paediatric inflammatory bowel disease (IBD) services during the peak of the COVID-19 pandemic, we prospectively audited the first-time use of home faecal calprotectin testing. We aimed to provide an alternative to laboratory tests and to assess the value of home testing as part of our regular services going forward. METHODS: Home test kits as well as accompanying user instructions were made available to our patients with paediatric IBD that required faecal calprotectin test between 17 April and 12 August 2020. Once the user completed the test, results were automatically uploaded to the result portal and clinical staff were alerted. A user feedback questionnaire was sent to users that had completed the home test. RESULTS: Of the 54 patients, 41 (76%) aged between 4.7 and 18.1 years used the home test. A total of 45 home tests were done, one of which produced an invalid result. The decision to modify management was made in 12 (29%) of the patients, while 14 (34%) had no changes made and 15 (37%) required further assessment. Twenty (48.8%) responded to the questionnaire and 85% stated that they preferred the home test to the laboratory testing method. CONCLUSIONS: Home calprotectin tests were useful in guiding clinical management during a time when laboratory testing was less available. They may offer benefits as part of routine paediatric IBD monitoring to help target appointments and reduce unnecessary hospital attendances in the future.

Establishment of reference intervals of clinical chemistry analytes for the adult population in Egypt.

BACKGROUND: This is the first Egyptian nationwide study for derivation of reference intervals (RIs) for 34 major chemistry analytes. It was conducted as a part of the global initiative by the IFCC Committee on Reference Intervals and Decision Limits (C-RIDL) for establishing country-specific RIs based on a harmonized protocol. METHODS: 691 apparently healthy volunteers aged ≥18 years were recruited from multiple regions in Egypt. Serum specimens were analyzed in two centers. The harmonization and standardization of test results were achieved by measuring value-assigned serum panel provided by C-RIDL. The RIs were calculated by parametric method. Sources of variation of reference values (RVs) were evaluated by multiple regression analysis. The need for partitioning by sex, age, and region was judged primarily by standard deviation ratio (SDR). RESULTS: Gender-specific RIs were required for six analytes including total bilirubin (TBil), aspartate and alanine aminotransferase (AST, ALT). Seven analytes required age-partitioning including glucose and low-density lipoprotein cholesterol (LDL-C). Regional differences were observed between northern and southern Egypt for direct bilirubin, glucose, and high-density-lipoprotein cholesterol (HDL-C) with all their RVs lower in southern Egypt. Compared with other collaborating countries, the features of Egyptian RVs were lower HDL-C and TBil and higher TG and C-reactive protein. In addition, BMI showed weak association with most of nutritional markers. These features were shared with two other Middle Eastern countries: Saudi Arabia and Turkey. CONCLUSION: The standardized RIs established by this study can be used as common Egyptian RI, except for a few analytes that showed regional differences. Despite high prevalence of obesity among Egyptians, their RVs of nutritional markers are less sensitive to increased BMI, compared to other collaborating countries.

Evaluation of toxic effects induced by repeated exposure to Cylindrospermopsin in rats using a 28-day feeding study.

Cylindrospermopsin (CYN) is a toxin with a world-wide increasing occurrence. It can induce toxic effects both in humans and the environment, and toxicity studies are needed to complete its toxicological profile. In this sense, in vivo oral toxicity studies with pure CYN are scarce. The aim of this work was to perform a repeated dose 28-day oral study in rats following the OECD guideline 407 to provide information on health hazard likely to arise from this kind of exposure. Male and female Sprague-Dawley rats were dosed with 18.75, 37.5 and 75 µg CYN/kg b.w./day. After the study period, no clinical signs or mortality and no significant differences in final body weight, body weight gain and total feed intake in both sexes were observed. Only in females some biochemical parameters (triglycerides (TRIG) levels and aspartate aminotransferase (AST) activity) as well as changes in the weight of organs (absolute liver weight values, relative kidney/body weight ratios or relative liver weight/brain weight ratios) were altered, but without toxicological relevance. Histopathological analysis revealed a very mild affectation of liver and kidney in rats. These results suggest the need to perform longer oral toxicity studies to define the potential consequences of long term CYN exposure.