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.

Osteomalacia Prevalence, Biochemical Profile, and Histology in Patients with Low-Energy Hip Fractures Over the Age of 45.

Our objective was to determine the prevalence of osteomalacia in low-energy hip fracture patients over the age of 45, based on biochemical and histological measures. This cross-sectional study included 72 patients over 45 with low-energy mechanism hip fractures. Samples of fasting venous blood were taken for hemograms and serum biochemistry analyses. Bicortical biopsies of the iliac crest were obtained, processed, and evaluated by an expert pathologist for osteomalacia. Biochemical osteomalacia (b-OM) is defined according to a distinct criterion. A low level of serum calcium, phosphorus, albumin, and 25OHD was found in 43.1, 16.7, 73.6, and 59.7% of patients, respectively. 50.0% of patients had high serum alkaline phosphatase (ALP) levels. b-OM was found in 30 (41.7%), and no significant association was found with PTH, Cr, Alb, age, sex, fracture type, side of the trauma, and season were not associated with osteomalacia. Osteomalacia was diagnosed on histopathological analysis in 19/72 (26.7%), and 54/72 (75.0%) of all cases fulfilled b-OM criteria. In the histologic evaluation, osteoid seam width, osteoid surface, and osteoid volume were 28.5 µm, 25.6, and 12.1%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the biochemical test for detecting osteomalacia were 73.6, 64.2, 42.4, 87.2, and 66.7%, respectively. Up to 30% of elderly patients with low-energy hip fractures are affected by osteomalacia. A biochemical screening along with a bone biopsy and histopathologic evaluation may be logical in a high-risk population for osteomalacia diagnosis.

Comparison of the accuracy of the Friedewald, Martin, and Sampson formulas to estimate very low levels of low-density lipoprotein cholesterol.

INTRODUCTION: The Martin (MF) and Sampson (SF) formulas have shown greater accuracy for low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL compared to the Friedewald formula (FF); however, some disagreement is maintained. Non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (ApoB) are alternatives to assessing cardiovascular risk in patients with very low LDL-C. The objective was to evaluate the accuracy of FF, MF, and SF formulas to estimate LDL-C < 70 mg/dL vs. directly measured LDL-C (LDLd-C) and to compare non-HDL-C and Apo-B levels between the groups of patients with concordant vs. discordant LDL-C. MATERIAL AND METHODS: This was a prospective clinical study with measurements of lipid profile and LDLd-C in 214 patients with triglycerides < 400 mg/dL. For each formula, the estimated LDL-C was compared with the LDLd-C, and the correlation, the median difference, and the discordance rate were evaluated. Non-HDL-C and Apo-B levels were compared between the groups with concordant and discordant LDL-C. RESULTS: The estimated LDL-C was < 70 mg/dL in 130 (60.7%) patients by FF, 109 (50.9%) by MF, and 113 (52.8%) by SF. The strongest correlation was found between LDLd-C and Sampson estimated LDL-C (LDLs-C) (R2 = 0.778), followed by Friedewald-estimated LDL-C (LDLf-C) (R2 = 0.680) and Martin estimated LDL-C (LDLm-C) (R2 = 0.652). Estimated LDL-C < 70 mg/dL was lower than LDLd-C, with the largest median absolute difference (25-75th) of -15 (-19 to -10) with FF. For estimated LDL-C < 70 mg/dL, the discordant rate was 43.8%, 38.1%, and 35.1%, reaching for 62.3%, 50.9%, and 50% when LDL-C < 55 mg/dL by FF, SF, and MF, respectively. Patients in the discordant group presented significantly higher levels of non-HDL-C and ApoB for all 3 formulas (p < 0.001). CONCLUSION: FF was the most inaccurate formula to estimate very low LDL-C. Despite MF and SF showing better results, their frequency in underestimating LDL-C was still considerable. In patients with falsely low estimated LDL-C, apoB and non-HDL-C were significantly higher, reflecting its true high atherogenic burden.

Ratiometric electrochemical OR gate assay for NSCLC-derived exosomes.

Non-small cell lung cancer (NSCLC) is the most common pathological type of LC and ranks as the leading cause of cancer deaths. Circulating exosomes have emerged as a valuable biomarker for the diagnosis of NSCLC, while the performance of current electrochemical assays for exosome detection is constrained by unsatisfactory sensitivity and specificity. Here we integrated a ratiometric biosensor with an OR logic gate to form an assay for surface protein profiling of exosomes from clinical serum samples. By using the specific aptamers for recognition of clinically validated biomarkers (EpCAM and CEA), the assay enabled ultrasensitive detection of trace levels of NSCLC-derived exosomes in complex serum samples (15.1 particles µL-1 within a linear range of 102-108 particles µL-1). The assay outperformed the analysis of six serum biomarkers for the accurate diagnosis, staging, and prognosis of NSCLC, displaying a diagnostic sensitivity of 93.3% even at an early stage (Stage I). The assay provides an advanced tool for exosome quantification and facilitates exosome-based liquid biopsies for cancer management in clinics.

A Tale of Two Approaches.

OBJECTIVES: To summarize and assess the literature on the performances of methods beyond the Friedewald formula (FF) used in routine practice to determine low-density lipoprotein cholesterol (LDL-C). METHODS: A literature review was performed by searching the PubMed database. Many peer-reviewed articles were assessed. RESULTS: The examined methods included direct homogeneous LDL-C assays, the FF, mathematical equations derived from the FF, the Martin-Hopkins equation (MHE), and the Sampson equation. Direct homogeneous assays perform inconsistently across manufacturers and disease status, whereas most FF-derived methods exhibit variable levels of performance across populations. The MHE consistently outperforms the FF but cannot be applied in the setting of severe hypertriglyceridemia. The Sampson equation shows promise against both the FF and MHE, especially in severe hypertriglyceridemia, but data are still limited on its validation in various settings, including disease and therapeutic states. CONCLUSIONS: There is still no consensus on a universal best method to estimate LDL-C in routine practice. Further studies are needed to assess the performance of the Sampson equation.

A method for measuring the experimental resolution of laboratory assays (clinical biochemical, blood count, immunological, and qPCR) to evaluate analytical performance.

BACKGROUND: The measurement method for experimental resolution and related data to evaluate analytical performance is poorly explored in clinical research. We established a method to measure the experimental resolution of clinical tests, including biochemical tests, automatic hematology analyzer methods, immunoassays, chemical experiments, and qPCR, to evaluate their analytical performance. METHODS: Serially diluted samples in equal proportions were measured, and correlation analysis was performed between the relative concentration and the measured value. Results were accepted for p ≤ 0.01 of the correlation coefficient. The minimum concentration gradient (eg, 10%) was defined as the experimental resolution. For this method, the smaller the value, the higher the experimental resolution and the better the analytical performance. RESULTS: The experimental resolution of the most common biochemical indices reached 10%, with some even reaching 1%. The results of most counting experiments showed experimental resolution up to 10%, whereas the experimental resolution of the classical chemical assays reached 1%. Unexpectedly, the experimental resolution of more sensitive assays, such as immunoassays was only 25% when using the manual method and 10% for qPCR. CONCLUSION: This study established a method for measuring the experimental resolution of laboratory assays and provides a new index for evaluating the reliability of methods in clinical laboratories.

Establishment of a new protein C detection system based on chromogenic substrate assay and its clinical diagnostic value for deep vein thrombosis.

BACKGROUND: Deficiency of protein C (PC) affects the balance between blood coagulation and fibrinolysis in the human body. Chromogenic-based assay is recommended as the preferred screening method for detecting PC deficiency. We established a PC detection system based on the chromogenic substrate assay. METHODS: First, a kit for the determination of PC activity in plasma was elaborately developed and its reaction parameters on XL-3200c were explored. Then, we evaluated its performance and collected specimens to compare the test results obtained with those of the Siemens detection system. Finally, the clinical diagnostic efficacy of this detection system for deep vein thrombosis (DVT) was assessed. RESULTS: Optimum conditions for PC detection were 0.25-0.1 U/ml protein C activator Protac® and 2.5-1 mM Pefachrome® PCa5297. The composition and concentration ranges of buffer substances and stabilizers in the kit were also explored. Satisfactory results were observed in performance evaluation. The test results of the newly built detection system were highly correlated with those of the Siemens detection system (R2  = 0.9771 in the control group and R2  = 0.9776 in the DVT group), and Bland-Altman plots also showed high consistency between the two detection systems. In addition, the area under the curve (AUC) of the newly built PC detection system for DVT was 0.888, indicating this system could effectively improve the diagnostic sensitivity and specificity for DVT. CONCLUSION: In this study, a sensitive, wide linear range and reliable PC activity detection system were established.

Simultaneous point-of-care testing of blood lipid profile and glucose: Performance evaluation of the GCare Lipid Analyzer.

BACKGROUND: Point-of-care (POC) testing provides quick results and includes tests for blood glucose and lipid profiles. We evaluated the newly developed POC device, the GCare Lipid Analyzer, which is used to measure glucose, total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) levels. METHODS: Venous and capillary blood samples were collected from patients who visited Korea University Guro Hospital. The results obtained using the GCare Lipid Analyzer were compared with those obtained using the TBA 2000FR chemistry analyzer and YSI 2300 STAT Plus analyzer. The glucose system evaluation process was based on the International Organization for Standardization 15197:2013 guidelines. RESULTS: The correlation coefficients (R) for TC, TG, and HDL-C were 0.965, 0.969, and 0.943 in capillary blood and 0.969, 0.990, and 0.956 in venous blood, respectively. The total errors for TC, TG, and HDL-C of the lipid profile using venous blood were all acceptable at 6.6%, 9.3%, and 11.6%, respectively. For glucose concentrations <100 mg/dl, 96.1% of the measured glucose levels were within ±15 mg/dl in venous samples and 100% were within ±15 mg/dl in capillary samples. For glucose concentrations ≥100 mg/dl, 100% and 99.5% of the measured glucose levels were within 15% for venous and capillary blood, respectively. CONCLUSION: The performance of the GCare Lipid Analyzer is acceptable for both blood glucose and lipid profile testing, indicating that it is reliable for use in patients with diabetic dyslipidemia.

Variation in the Measurement of Anti-Müllerian Hormone - What Are the Laboratory Issues?

Anti-Müllerian Hormone (AMH) is a 140 kDa homodimeric glycoprotein consisting of two identical subunits linked by disulphide bonds and is synthesised by the testes and ovaries. Its clinical applications are prediction of ovarian response and gonadotropin dose selection upon in vitro fertilization. In males, AMH is used to investigate sexual developmental disorders and gonadal function. AMH is commonly assayed by enzyme-linked immunosorbent assay or automated immunoassay formats that show variation between methods. This review applies fundamental chemical pathology concepts to explain the observed analytical variation of AMH measurement. We examine the lack of standardisation between AMH assays, the impact of antibody design on variable measurements, consider the analytical detection of AMH isoforms, review analytical interference in AMH measurement, and briefly assess systematic bias between AMH assays. The improved attempt at standardising AMH measurement by the recent approval of a WHO Reference Reagent offers promise for harmonising immunoassay results and establishing consensus medical cut-off points for AMH in disease. Standardisation, however, will need to redress the issue of poor commutability of standard reference material and further assign a standard reference procedure to quantify AMH standard reference material. The improvement of the analytical phase of AMH testing will support harmonised method development and patient care.

Comparison and optimization of various moving patient-based real-time quality control procedures for serum sodium.

BACKGROUND: Patient-based real-time quality control (PBRTQC) is a valuable tool for monitoring the performance of testing processes. We aimed to compare and optimize various PBRTQC procedures for serum sodium. METHODS: In a computer simulation, artificial errors were added to 680,000 real patients' results. The characteristics of error detection of various algorithms-moving average, moving median, moving SD and moving proportion of normal results including different control limits (CLs)-were assessed on their ability to detect critical errors early. RESULTS: The moving average and moving median were sensitive to system error, and the moving SD tended to detect random error. P3SD (moving proportion of normal results, CLs based on mean and SD of proportion of normal results) demonstrated excellent performance for both system error and random error. The increase of block sizes (N) leads to the delay of error detection and the decrease of false rejection, except for QC procedures with minimum and maximum as CLs. CLs calculation with "0.1% false alarm rate" had more effective performance than that set false alarm to zero (minimum and maximum as CLs). The impact of truncation on QC performance depended on truncation limits, algorithms and the types of error. The significant improvement in QC performance due to truncation was only found in moving SD. CONCLUSION: "P3SD ,N = 50, without truncation" and "moving SD, N = 25, set 0.1% false alarm as CLs and set 1% outliers exclusion as truncation limits" were recommended as the optimized procedures for serum sodium to monitor system error and random error, respectively.

Common Pitfalls in the Interpretation of Endocrine Tests.

Endocrine tests are the cornerstone of diagnosing multiple diseases that primary care physicians are frequently faced with. Some of these tests can be affected by situations that affect the proper interpretation, leading to incorrect diagnoses and unnecessary treatment, such as the interference of biotin with thyroid function test, falsely elevated prolactin values in presence of macroprolactinemia or falsely normal due to the "hook effect" in macroprolactinomas. Recognizing these situations is essential for the clinician to make an adequate interpretation of these tests as well as an accurate diagnosis that guarantees the best outcomes for the patient.

Analytical and clinical evaluation of a novel assay for measurement of interleukin 6 in human whole blood samples.

BACKGROUND: Interleukin 6 assays are useful in early detection of infections and risk stratification of critically ill patients, so an assay with a short turnaround-time and near-patient use is preferred. This study evaluated the performance of a new interleukin 6 assay, Pylon IL-6 assay, and explored its potential use in near-patient settings. METHODS: We carried out imprecision, linearity and comparison studies using serum and plasma samples according to CLSI EP guidelines. The stability of whole blood samples during storage was assessed. Furthermore, whole blood samples from pediatric patients with suspected infection were measured to evaluate the assay's diagnostic performance. RESULTS: The within-run CVs and total CVs of Pylon IL-6 assay were determined as 1.8% and 3.0% at 159.3 pg/ml and 3.5% and 4.7% at 8009.9 pg/ml, respectively. The method showed linearity between 1.5 and 42,854 pg/ml. The results of serum samples measured by Pylon assays correlated to those measured by Roche assays, as well as to those of matched whole blood samples measured by Pylon assays. IL-6 in whole blood was found stable for ~8 h at room temperature. Pylon IL-6 results of whole blood samples from 179 pediatric patients with suspected infection showed an AUC of 0.842 in diagnosis of bacterial infection. The turnaround time of Pylon IL-6 assay was only 1 h when using whole blood samples. CONCLUSION: The new assay demonstrated performance comparable to those performed on clinical laboratory instruments and can be used in near-patient settings with whole blood to reduce turnaround times.

Establishing paediatric reference intervals for thyroid function tests in Croatian population on the Abbott Architect i2000.

INTRODUCTION: Evaluation of thyroid function is often requested and therefore defining paediatric reference intervals (RIs) is of vital importance. Currently, there is a distinct lack of paediatric RIs for thyroid function tests in Croatia. Thus, we established RIs for thyroid stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3) and free thyroxine (FT4) in the Croatian paediatric population. MATERIALS AND METHODS: Reference intervals were calculated from 397 apparently healthy children, aged from 2 days to < 19 years. Serum samples were analysed for thyroid function tests on the Abbott Architect i2000. Age- and sex-specific 95% RIs with 90% confidence intervals were established according to Clinical and Laboratory Standards Institute guidelines. To express the magnitude of sex and age variation, standard deviation ratio (SDR) was calculated using two-level nested ANOVA. The criterion for considering partitioning reference values was set to SDR > 0.3. RESULTS: All thyroid function tests required age partitioning, confirmed by SDR above 0.3. There was no need for sex partitioning, confirmed by SDR below 0.3. Still, FT3 was partitioned due to visually noticeable sex related difference for the oldest group (12 years to < 19 years). CONCLUSION: This is the first study to establish RIs for thyroid function tests in the Croatian paediatric population. We propose RIs for widely used Abbott platform, thus giving laboratories method- and population-specific paediatric RIs for thyroid function tests that should improve clinical test interpretation.

Estimation of inter-laboratory reference change values from external quality assessment data.

INTRODUCTION: It is common for patients to switch between several healthcare providers. In this context, the long-term follow-up of medical conditions based on laboratory test results obtained from different laboratories is a challenge. The measurement uncertainty in an inter-laboratory context should also be considered in data mining research based on routine results from randomly selected laboratories. As a proof-of-concept study, we aimed at estimating the inter-laboratory reference change value (IL-RCV) for exemplary analytes from publicly available data on external quality assessment (EQA) and biological variation. MATERIALS AND METHODS: External quality assessment data of the Reference Institute for Bioanalytics (RfB, Bonn, Germany) for serum creatinine, calcium, aldosterone, PSA, and of whole blood HbA1c from campaigns sent out in 2019 were analysed. The median CVs of all EQA participants were calculated based on 8 samples from 4 EQA campaigns per analyte. Using intra-individual biological variation data from the EFLM database, positive and negative IL-RCV were estimated with a formula based on log transformation under the assumption that the analytes under examination have a skewed distribution. RESULTS: We estimated IL-RCVs for all exemplary analytes, ranging from 13.3% to 203% for the positive IL-RCV and - 11.8% to - 67.0% for the negative IL-RCV (serum calcium - serum aldosterone), respectively. CONCLUSION: External quality assessment data together with data on the biological variation - both freely available - allow the estimation of inter-laboratory RCVs. These differ substantially between different analytes and can help to assess the boundaries of interoperability in laboratory medicine.

Hyperlipidemia Influences the Accuracy of Glucometer-Measured Blood Glucose Concentrations in Genetically Diverse Mice.

BACKGROUND: Glucometers are widely used in animal research due to simplicity and ease of utilization, but their accuracy in blood glucose assessment for hyperlipidemic mice is unknown. METHODS: Here, we compared blood glucose levels measured by a glucometer with plasma glucose levels measured by a standard enzymatic assay for 325 genetically diverse F2 mice derived from LP and BALB/c (BALB) Apoe-/- mice. Non-fasting glucose levels were measured before initiation of a Western diet and after 11 weeks on the diet. RESULTS: On chow diet, lab-measured plasma glucose levels were 279.5 ± 42.6 mg/dl (mean ± SD), while blood glucose values measured by glucometer were 138.7 ± 16.6 mg/dl. The two measures had no correlation (R2 = 0.006, p = 0.167). On the Western diet, plasma glucose levels rose to 351.1 ± 121.6 mg/dl, while glucometer-measured blood glucose fell to 128.7 ± 27.9 mg/dl. The two measures showed a moderate correlation (R2 = 0.111, p = 3.1E-9). Lab-measured plasma glucose showed strong positive correlations with plasma triglyceride and non-high-density lipoprotein cholesterol levels, while glucometer-measured blood glucose showed an inverse correlation with non-high-density lipoprotein levels on the chow diet. CONCLUSIONS: Our results indicate that hyperlipidemia affects the accuracy of glucometers in measuring blood glucose levels of mice.

Age- and sex-associated differences in hematology and biochemistry parameters of Dunkin Hartley guinea pigs (Cavia porcellus).

The Dunkin Hartley is the most common guinea pig strain used in biomedical research, particularly for studies of asthma, allergy, infectious disease, reproduction, and osteoarthritis. Minimally invasive blood tests, such as complete blood counts and serum biochemistry profiles, are often collected for diagnostics and laboratory analyses. However, reference intervals for these assays have not yet been well-documented in this strain. The purpose of this study was to establish reference intervals for hematologic and biochemical parameters of Dunkin Hartley guinea pigs and determine age- and sex-related differences. Hematologic and biochemical parameters were retrospectively obtained from 145 male and 68 female guinea pigs between 2 and 15 months of age. All blood parameters were analyzed by a veterinary clinical pathology laboratory. Reference intervals were established according to the American Society for Veterinary Clinical Pathology guidelines. Age- and sex-related differences were determined using unpaired t-tests or nonparametric Mann-Whitney tests. Hematocrit, red blood cell distribution width, mean platelet volume, white blood cell count, heterophils, monocytes, eosinophils, glucose, blood urea nitrogen, creatinine, calcium, magnesium, total protein, albumin, globulin, cholesterol, aspartate aminotransferase, gamma glutamyl transferase, and bicarbonate increased with age. Mean corpuscular hemoglobin concentration, cellular hemoglobin concentration mean, platelets, lymphocytes, phosphorus, albumin/globulin ratio, alkaline phosphatase, anion gap, and calculated osmolality decreased with age. Males had higher hemoglobin, hematocrit, red blood cell count, mean corpuscular hemoglobin concentration, white blood cell count, heterophils, Foa-Kurloff cells, alanine aminotransferase, and bicarbonate and lower mean corpuscular volume, red blood cell distribution width, platelets, mean platelet volume, eosinophils, total protein, albumin, globulin, cholesterol, potassium, anion gap, calculated osmolality, and iron compared to females. Establishing age and sex differences in hematologic and biochemical parameters of Dunkin Hartley guinea pigs provides valuable insight into their physiology to better evaluate diagnostics and experimental results.

Optimized procedures for testing plasma metanephrines in patients on hemodialysis.

Diagnosis of pheochromocytomas and paragangliomas in patients receiving hemodialysis is troublesome. The aim of the study was to establish optimal conditions for blood sampling for mass spectrometric measurements of normetanephrine, metanephrine and 3-methoxytyramine in patients on hemodialysis and specific reference intervals for plasma metanephrines under the most optimal sampling conditions. Blood was sampled before and near the end of dialysis, including different sampling sites in 170 patients on hemodialysis. Plasma normetanephrine concentrations were lower (P < 0.0001) and metanephrine concentrations higher (P < 0.0001) in shunt than in venous blood, with no differences for 3-methoxytyramine. Normetanephrine, metanephrine and 3-methoxytyramine concentrations in shunt and venous blood were lower (P < 0.0001) near the end than before hemodialysis. Upper cut-offs for normetanephrine were 34% lower when the blood was drawn from the shunt and near the end of hemodialysis compared to blood drawn before hemodialysis. This study establishes optimal sampling conditions using blood from the dialysis shunt near the end of hemodialysis with optimal reference intervals for plasma metanephrines for the diagnosis of pheochromocytomas/paragangliomas among patients on hemodialysis.

Impact of managing affected results in haemolysed samples of an infant-maternity hospital using an unconventional approach.

BACKGROUND: The management of affected results in haemolysed samples (HS) is debated. In an infant-maternity setting, for reporting interfered test results, we provided the result itself, the degree of haemolysis (as free haemoglobin concentration), and a warning recommending sample recollection. We investigated the impact of this approach on sample quality and clinicians' decision-making. METHODS: Free haemoglobin was measured on Beckman Coulter AU680 as haemolytic index. We estimated the total HS number, the clinical wards more affected by HS, the most interfered analytes, and the retesting rate of interfered tests, by comparing data from Apr-Dec 2017, the period just after the introduction of the new policy, vs. Apr-Dec 2018. RESULTS: One year after the new report introduction, a significant HS decrease (5.8% vs. 7.8%, P < 0.001) was detected, together with a reduction of the frequency by which haemolysis affected results. The most affected wards, i.e., Paediatric and Neonatal Intensive Care Units, showed an improvement in sample quality (HS rate, 30.6% to 16.1%, P < 0.001, and 25.2% to 20.9%, P = 0.048, respectively). We noted a significant decrease in retesting after an alerted result for aspartate aminotransferase, magnesium, potassium, conjugated bilirubin, and lactate dehydrogenase. CONCLUSIONS: Our approach led to a HS decrease, suggesting that the provided report could be a driving force for improvement of phlebotomy quality, also helping clinicians in deciding if retesting is essential or not.

Utility of process capability indices in assessment of quality control processes at a clinical laboratory chain.

BACKGROUND: To evaluate the utility of the process capability indices Cp and Cpk for assessing the quality control processes at chain laboratory facilities. METHODS: In April 2020, the minimum Cp and Cpk values for 33 assays of a laboratory chain with 19 facilities were collected for further analysis and a total of 627 datasets (Cp and Cpk ) were compared. In addition, standard values for Cp and Cpk , defined as the lowest of the top 20%, were obtained for comparison and the indices were used to determine whether precision or trueness improvements were required for the corresponding assay. RESULTS: A total of 627 datasets of 33 assays from 19 laboratory facilities were collected for further analysis. Based on the Cp results, 329 (52.5%), 211 (33.7%), 65 (10.3%), and 22 (3.5%) were rated as excellent, good, marginal, and poor, respectively. While the corresponding results for Cpk were 300 (47.8%), 216 (34.4%), 79 (12.6%), and 32 (5.1%). In addition, it was noteworthy that eight (Cp criteria) and six assays (Cpk criteria) were rated as excellent or good at all 19 facilities. Comparison of the process capability indices at the Jinan KingMed Center with the standard values revealed that total protein, albumin, and urea showed trueness individual improvement, precision individual improvement, and precision common improvement, respectively, while the results of other assays were stable. CONCLUSION: Process capability indices are useful for evaluating the quality control procedures in laboratory facilities and can help improve the precision and trueness of laboratory tests.

Testing the limits: the diagnostic accuracy of reference change values.

Reference change values (RCVs) are used by the physician to judge whether a change in analyte concentration from one sample to the next may represent a clinically significant change. Published RCVs are usually given as fixed percentages of the analyte concentration in the first sample. The accuracy of published RCVs is not well known. We obtained public-use data from the US National Health and Nutrition Examination Survey (NHANES) 2001-2002 to study the distribution of changes in the concentration of eight commonly used analytes. Specimens were obtained on two occasions 7-47 days apart from 279 to 411 individuals with an analyte concentration within the reference interval in both samples. The analytes were albumin, calcium, cholesterol, phosphate, potassium, sodium, hemoglobin and thrombocytes. For each analyte, normal within-subject biological coefficient of variation from the EFLM Working Group on Biological Variation and the NHANES analytical coefficient of variation were used to calculate the 5 and 95 percentile RCVs. These RCVs were calculated as fixed percentages of the analyte concentrations in the first sample and compared to the empirical 5 and 95 percentiles. The sensitivity of the RCVs in detecting changes outside the empirical percentiles ranged from 0.35 for sodium to 0.80 for albumin. The specificity of the RCVs in detecting changes inside the empirical percentiles ranged from 0.85 for potassium to 0.97 for thrombocytes. Calculating RCVs as fixed percentages of the analyte concentration in the first sample lessened the diagnostic accuracy. RCVs given as a function of the first result would perform better.