Annals of Clinical Biochemistry最新文献

Background: Laboratory test results are crucial for clinical decisions, but errors at any stage can compromise patient safety. Despite technological advances and quality systems, laboratory processes remain vulnerable, necessitating structured risk assessment. Limited research exists on integrating Failure Mode and Effects Analysis (FMEA) with Sigma metrics. This study addresses these gaps through a comprehensive risk assessment in a NABL-accredited tertiary care hospital laboratory.

Methods: A retrospective observational study was conducted over 2.5 years. FMEA was used to identify errors across all phases of the total testing process. Quarterly error rates were calculated, converted to defects per million (DPM), and expressed as Sigma metrics. Risk Priority Numbers (RPN = severity × detectability × frequency) were scored quarterly to prioritize failures. The effect of corrective actions was evaluated by comparing pre- and post-intervention Sigma values.

Results: Across ten quarters (five pre- and five post-intervention), 23 error types were identified. The highest RPNs (>20) were observed for haemolysed samples, clotted samples, and non-intimation of critical values. Haemolysed samples declined from 0.97% to 0.49% (ARR 0.48%; RR 0.51; 95% CI 0.47-0.55; p < 0.0001). Clotted samples reduced from 0.24% to 0.06% (ARR 0.18%; RR 0.24; 95% CI 0.20-0.29; p < 0.0001). Non-intimation of critical values decreased from 2.63% to 2.18% (RR 0.83; 95% CI 0.70-0.99; p = 0.065).

Conclusion: Integrating FMEA with Sigma metrics provides a robust framework for identifying, prioritizing, and reducing laboratory errors. Continuous monitoring and corrective action are essential to sustain improvements in laboratory quality and patient safety.

Background: Conventional transcutaneous bilirubinometers often underestimate total bilirubin (TB) levels at high concentrations, limiting their clinical utility in cases of neonatal hyperbilirubinemia. We aimed to address this shortcoming by developing and testing a novel type of advanced transcutaneous bilirubinometer that may enhance the early identification of severe hyperbilirubinemia, potentially reducing the need for invasive testing and exchange transfusions.

Methods: We developed a novel transcutaneous bilirubinometer with adjustable light intensity and detection distances. Transcutaneous bilirubin (TcB) measurements were obtained using both the novel device and a conventional JM-105 bilirubinometer in 66 instances in 62 neonates (≥36 weeks gestation). TB values measured in patient blood samples were used as reference values for calculating correlations and error metrics (i.e., mean squared error [MSE] and mean absolute error [MAE]).

Results: The novel device showed strong correlation with TB values across all concentrations (R² = 0.96), including those ≥15 mg/dL (R² = 0.84), outperforming the JM-105 device (R² = 0.60 for TBs ≥15 mg/dL). The novel device also yielded lower MSE (1.53 vs. 2.95) and MAE values (1.00 vs. 1.39) than the JM-105.

Conclusions: Our novel transcutaneous bilirubinometer demonstrated improved accuracy at higher bilirubin concentrations compared with a conventional JM-105 device.

Objectives To evaluate the stability of commonly used biomarkers in whole blood under various storage conditions, in order to assess their suitability for home-based blood collection in remote care settings. Methods Whole blood samples were stored at 4-8 °C, 20-25 °C, and 37 °C for up to 72 hours. Six pooled samples and two healthy volunteer samples were aliquoted and analysed at four time points (T0, T24, T48, T72 hours). A panel of 47 routine chemistry and immunochemistry biomarkers was measured in all samples. Recoveries relative to T0 were compared to within subject coefficients of variation of the individual biomarkers. Results Most biomarkers remained stable at refrigerated and room temperature conditions up to 72 hours with a subset of biomarkers, mostly proteins and tumour markers also showing good to acceptable stability at 37 °C. Several biomarkers, including potassium, inorganic phosphate and iron, consistently fell outside acceptable limits under multiple conditions. Others, such as sodium, calcium, ferritin, aspartate aminotransferase and cytokeratin fragment 21-1, were unstable only at 37 °C . A few transient deviations were observed but these were not consistent over time. Conclusions Home-based blood sampling is feasible for a broad range of biomarkers, provided that heat exposure during transport is minimised. These findings are a first step in the further validation of selected analytes under real-world, capillary blood sampling conditions.

BackgroundTocilizumab co-administration and inflammatory conditions potentially alter the activity of cytochrome P450 (CYP) 3A4 by modulating the interleukin-6 (IL-6) signaling pathway in patients with rheumatoid arthritis (RA). This study aimed to evaluate the correlations of serum levels of tocilizumab with IL-6 and CYP3A activity in RA.MethodsRA patients (n = 35) with controllable disease activity using intravenous or subcutaneous tocilizumab were enrolled. Serum tocilizumab was monitored at the trough point after reaching steady-state. Serum levels of IL-6, its soluble receptor (sIL-6R), 4β-hydroxycholesterol (4β-OHC), and 25-hydroxyvitamin D (25-OHD) and CYP3A5 genotype were determined.ResultsThe RA patients had a wide variation of serum tocilizumab level (interquartile range, 9.8-24.6 µg/mL). Tocilizumab treatment led to abnormally high levels of serum IL-6 and sIL-6R. The serum level of tocilizumab was correlated with that of IL-6 but not sIL-6R. In the tocilizumab-treated RA patients, the median serum levels of 4β-OHC and 25-OHD were 36.7 and 17.7 ng/mL, respectively, and no correlations with the serum level of tocilizumab were observed. CYP3A5 genetic polymorphisms were not also associated with the serum level of 4β-OHC. RA patients with the CYP3A5*1 allele exhibited a correlation between serum levels of tocilizumab and 4β-OHC, while those with CYP3A5*3/*3 did not.ConclusionsTocilizumab treatment raised the serum IL-6 level in a concentration-dependent manner. In the RA patients with functional CYP3A5 protein, the serum tocilizumab level partially explained the interindividual variation in CYP3A activity.

BackgroundThe diagnosis of cystic fibrosis (CF) is challenging due to high quantity not sufficient (QNS) rates of sweat tests, leading to frequent retesting, increasing costs and adverse impacts on patient care. This study aimed to assess sweat test performance and implement a quality improvement project (QIP) to reduce QNS rates.MethodsA two-part retrospective audit was conducted. Part one spanned 2 years reviewing the two-tiered testing with sweat conductivity as a screening tool, followed by chloride testing. Part two evaluated the QNS rates over two 6-month periods, separated by a QIP, which involved technologist training, clinician education, patient preparation protocols and revised testing procedures.ResultsOver the 2-year period, 425 sweat tests were performed on 291 patients. Sweat conductivity testing demonstrated a lower QNS rate, 13% (31/238), compared to sweat chloride testing's 31% (33/105). High QNS rates were observed in younger infants and in malnourished or acutely ill patients. Post-QIP, the QNS rates for the total study population decreased by 5%, from an initial 30% to 25% in the sweat chloride cohort, while the acceptable QNS rate of 12% remained unchanged in the sweat conductivity cohort.ConclusionAchieving target QNS rates remains challenging, especially in younger infants, with improved QNS rates in older infants and children. Recommendations include limiting sweat testing to experienced technologists and ensuring patient readiness.

BackgroundCurrent coeliac disease (CD) NICE guidelines recommend testing IgA-endomysial antibodies (EMA) following a weak-positive IgA-tissue transglutaminase antibody (tTGA). Outside of patients with very high IgA-tTGA results, a positive IgA-EMA necessitates duodenal biopsy to confirm CD diagnosis, meaning a positive IgA-EMA does not alter the diagnostic pathway. Therefore, to be helpful, a negative IgA-EMA needs to reliably exclude CD.ObjectivesWe aimed to evaluate the negative predictive value (NPV) of IgA-EMA, following a weak-positive/positive IgA-tTGA, and to evaluate whether IgA-EMA result (positive or negative) affects duodenal biopsy rates.MethodsRetrospective patient cohort (n = 963) study of patients with IgA-EMA and IgA-tTGA testing, with or without evidence of duodenal biopsy. The NPV of IgA-EMA was assessed by comparison to duodenal biopsy. Duodenal biopsy rates were compared between patients with a positive/negative IgA-EMA (after positive/weak-positive IgA-tTGA).ResultsThe NPVs for CD of a negative IgA-EMA, in the context of a weak-positive or positive IgA-tTGA, were 41% and 0%, respectively (n = 45). There was a significant reduction in the proportion of patients who had a duodenal biopsy with a negative IgA-EMA (9.4%) compared to patients with a positive IgA-EMA (28.5%), following a positive/weak-positive IgA-tTGA (n = 963).ConclusionIgA-EMA does not reliably exclude CD following a positive/weak-positive IgA-tTGA result. Our data indicates that clinicians are utilizing a negative IgA-EMA, following a positive/weak-positive IgA-tTGA result, to inappropriately exclude CD. We recommend IgA-EMA be exclusively used in the context of a 'non-biopsy' approach to CD diagnosis, following a high positive IgA-tTGA, and that a negative IgA-EMA result should not be used to exclude CD in the context of a weak-positive/positive IgA-tTGA.

Background and objectivesSERPINA4 has been identified as a potential diagnostic biomarker for diabetic nephropathy (DN) in our previous research. This study aims to develop electrochemiluminescence immunoassay (ECLIA) methods for the detection of SERPINA4 and to establish a diagnostic model that incorporates additional indicators for DN.Materials and methodsAntibodies utilized in the ECLIA for the detection of SERPINA4 were labelled with ruthenium and biotin, respectively. The reliability of ECLIA was evaluated based on its linear range, precision, and hook effect. A total of 28 indicators were collected from 98 patients, including SERPINA4/UCr, diabetic retinopathy (DR), and duration of diabetes mellitus. A diagnostic model was developed employing Random Forest, Support Vector Machine (SVM), and Naive Bayes algorithms. The performance of the model was assessed using metrics such as area under the curve (AUC), precision, recall, and F1 score; ultimately selecting the best-performing model for final diagnosis.ResultThe ECLIA method established in this study for urinary SERPINA4 demonstrates a linearity range from 7.5 ng/mL to 16,000 ng/mL, with within-run precision (CV%) values of 0.25% and 3.78%. The diagnostic model developed using random forest exhibits optimal performance, achieving an AUC of 0.89, accuracy of 90%, sensitivity of 100%, and specificity of 70%. The top five variables ranked by importance are serum creatinine, microalbumin, SERPINA4/UCr ratio, systolic blood pressure, and total urine protein.ConclusionA method for the detection of urinary SERPINA4 using ECLIA has been successfully established. The combination of SERPINA4/UCr with other clinical indicators demonstrated strong performance in the diagnostic model developed through the random forest algorithm.

BackgroundThe six sigma model is widely used in laboratory quality management. For the first time, this study introduced total allowable error (TEa) from WS/T403-2024 and 'desirable' biological variation (BV) as dual quality goals to evaluate serum lipid analytes in six laboratories and develop individualized quality control (QC) strategies.MethodsWe collected internal quality control (IQC) and external quality assessment (EQA) data to calculate sigma values for each serum lipid analyte. Normalized sigma method decision charts were employed, and the Westgard sigma rule flow chart with batch size plus the quality goal index (QGI) guided individualized QC strategies and improvement plans.ResultsUnder the same quality goal, different QC concentrations produced varying sigma values. Sigma values also differed significantly between the two quality goals. When WS/T403-2024 was applied, all analytes except triglycerides (TGs) showed lower sigma values than under 'desirable' BV. Normalized sigma method decision charts effectively highlighted these differences. Based on the Westgard sigma rule flow chart with batch size and QGI, individualized QC strategies were created, and priority improvement measures were proposed for analytes with sigma values below six.ConclusionsThe six sigma model is a valuable tool for laboratory quality management, guiding laboratories to enhance the detection capabilities of serum lipid analytes through targeted QC strategies and improvement measures.

BackgroundModern analyzers employ the haemolysis index (HI) to identify interference in biochemical assays, yet manufacturer-defined HI thresholds may be inappropriate for true haemolysis effects, resulting in unnecessary sample rejections. This study aimed to validate these thresholds using non-simulated hemolyzed patient samples.MethodsPaired samples (hemolyzed primary and non-hemolyzed recollected) from 678 patients were analysed for haemolysis interference. Biochemical analytes and serum indices were measured using a Roche Cobas^® 8000 analyzer. Haemolysis effects on test results and lipaemia index (LI) were assessed. HI thresholds were derived from reference change value (RCV) limits and regression of HI versus percentage bias, then compared to the conventional 10% deviation criterion and Roche-defined cut-offs.ResultsSamples exhibited predominantly moderate haemolysis (72.3%, HI: 101-300). Strong HI correlations were observed for lactate dehydrogenase (51% change per 100-unit HI, R² = 0.6524, P < .0001), potassium (14% per 100-unit HI, R² = 0.5630, P < .0001), and sodium (-0.6% per 100-unit HI, R² = 0.5414, P < .0001). Elevated biases exceeded the RCV for these analytes, plus ammonia, aspartate aminotransferase, creatine kinase, γ-glutamyltransferase, and bilirubin-direct, whereas sodium showed a clinically significant reduction at heavy haemolysis (HI 560). RCV-derived thresholds exhibited comparable or higher than 10% change and Roche cut-offs. The elevated LI in hemolyzed samples with HI greater than 100 decreased significantly after recollection.ConclusionsPatient-based haemolysis data indicated that biases for most analytes remain within clinically acceptable limits, suggesting the manufacturer's HI thresholds may overestimate interference, supporting lab-validated, RCV-based cut-offs enhance clinical relevance and decrease unnecessary sample rejection.