Quantification of serum free light chains (FLCs) is essential for the diagnosis and monitoring of plasma cell disorders. This study evaluated the analytical performance of a novel avian IgY-based particle-enhanced turbidimetric immunoassay (PETIA) for measuring free kappa (κ) and lambda (λ) light chains in serum and plasma. The assay was evaluated on the Cobas Pro c503 (Roche Diagnostics, Basel, Switzerland) and Abbott Architect c4000 (Abbott Laboratories, Abbott Park, IL) platforms using samples from patients with monoclonal components and healthy donors. Performance characteristics included precision, limit of quantification (LoQ), linearity, interference, measuring interval, reagent stability, high-dose hook effect, method comparison with the Diazyme FLC assay, and reference interval verification in 70 healthy individuals. Within-run precision was acceptable at clinically relevant concentrations. Functional LoQs (15% CV) were 1.94 mg/L for κ and 3.74 mg/L for λ. Linearity was demonstrated on the Abbott platform, with no significant interference from haemolysis, lipaemia or bilirubin. Reagents were stable for 38 days on-board, and no hook effect was observed at very high FLC concentrations. Method comparison showed strong correlation with the Diazyme assay (κ: r = 0.953; λ: r = 0.881) and substantial agreement for κ/λ ratios (Cohen's κ = 0.64). Verified reference intervals aligned with established standards. The IgY-based PETIA provides precise, interference-resistant measurement of free κ and λ light chains across a wide dynamic range, supporting its suitability for routine clinical use.
Standard operating procedures (SOPs) are foundational to quality assurance in ISO-accredited clinical laboratories, but manual SOP development is labor-intensive and prone to error. With the emergence of large language models (LLMs), such as ChatGPT-5, there is growing interest in their potential to generate compliant, context-specific laboratory documentation. To test a regulatory-aligned, clause-based evaluation framework for assessing whether ChatGPT-5 can generate context-aware, fit-for-purpose SOP drafts within a real ISO-aligned laboratory environment. In a single-site, paired proof-of-concept study, 10 high-priority SOPs were generated using ChatGPT-5 and compared with matched SOPs written by experienced laboratory professionals. AI prompts were enriched with laboratory-specific inputs (e.g. operator manuals, reagent inserts and LIS codes). SOPs were evaluated using a seven-domain ISO/CLSI-aligned rubric, a laboratory-specificity audit, clause-mapping checklists, content validity indexing and usability testing by junior staff. Inter-rater reliability and paired non-parametric statistics were applied. AI-assisted SOPs demonstrated higher median quality scores, more complete ISO clause referencing, improved traceability and stronger lifecycle conformity compared with manual SOPs. Drafting time was reduced by approximately 91%. Expert reviewers showed excellent agreement (ICC = 0.91), and content validity indices exceeded established thresholds. Junior staff rated AI-assisted SOPs as clearer and more independently usable. Context-anchored prompts improved laboratory-specific relevance. This study demonstrates a replicable, clause-based framework for evaluating AI-assisted SOP generation within a regulated laboratory context. While findings support the feasibility of AI as a documentation co-author under expert oversight, external multi-center validation is required before broader regulatory or clinical adoption.
Background: Urinalysis is a fundamental diagnostic tool, yet its reliability is heavily dependent on the pre-analytical phase. International guidelines recommend processing within two hours. This study evaluates the stability of urinary sediment elements over 72 h using BD Vacutainer® UAP preservative tubes. Methods: A total of 150 urinary specimens were collected into BD Vacutainer® UAP tubes (containing chlorhexidine, ethyl paraben, and sodium propionate). Samples were analyzed at 0, 24, 48, and 72 h using the Sysmex UF-5000 fluorescence flow cytometer at room temperature. Stability was assessed using Cohen's Kappa (κ) statistics, with κ > 0.80 defined as the threshold for good clinical agreement. Results: Cellular elements showed stability up to 24 h, but significant time-dependent degradation after 24 h. White Blood Cells were the most labile, showing a 36.7% loss of detectability at 48 h (κ = 0.62). Red Blood Cells (RBCs) and transitional cells exhibited a critical inflection point at 48 h with a 22.7% loss (κ = 0.77). In contrast, squamous epithelial cells and casts (cellular and non-cellular) remained highly stable up to 72 h (κ ≥ 0.97). Non-cellular analytes, including bacteria, crystals, yeasts, and spermatozoa, showed absolute stability (0% loss, κ = 1.00) throughout the entire 72-hour period. Conclusions: The use of BD Vacutainer® UAP tubes successfully mitigates osmotic lysis and alkaline degradation, extending the reliable analytical window up to 24 h.
BACKGROUND:Discovered in 1938, haptoglobin is a liver-produced α2-glycoprotein that binds free hemoglobin, mitigating its toxic effects, and serves as a biomarker for hemolysis. The current study, under the HAPPI Kids initiative, aimed to define paediatric reference intervals for haptoglobin through the collection of samples from healthy children and neonates, with the overall aim to improve diagnostic accuracy in young patients. METHODS:Blood was collected from 335 children aged 30 days to 18 years and 20 neonates from February 2015 through December 2016. Samples were analysed on 3 automated analysers: a) Roche Cobas c501/c502, b) Roche Cobas c701, and c) Beckman Coulter Unicel DXL 600/800. RESULTS:Age and sex specific haptoglobin reference ranges were reported with a 95% confidence interval. CONCLUSION:We report continuous age-specific reference intervals for serum haptoglobin in neonates and children. The data suggests that haptoglobin levels have limited clinical value in children under 13-15 years, as they are often naturally low and may fall below the assay detection threshold.
BACKGROUND:The Enhanced Liver Fibrosis (ELF) score, which combines aminoterminal peptide of type III procollagen (PIIINP), hyaluronic acid (HA) and tissue inhibitor of metalloproteinases-1 (TIMP-1), is a clinically relevant tool for assessing liver fibrosis. This study examines the effect of preanalytical factors on the measurement of PIIINP, HA, TIMP-1 and the ELF score. METHODS:Serum pools spanning the measurement range of ELF biomarkers were spiked with increasing concentrations of hemolysate. Additionally, blood samples from 30 donors were centrifuged at 0-, 4-, 8-, and 24-hours post-collection. The influence of these factors was assessed by calculating the percentage difference in measured concentrations compared to baseline, and the underlying mechanisms were investigated. RESULTS:PIIINP showed significant susceptibility to hemolysis, with a 10% reduction in analyte concentration already at 0.5 g/L free hemoglobin. HA and TIMP-1 remained stable even at 10 g/L, and the ELF score up to 4 g/L. The effect on PIIINP cannot be explained by proteolytic activity, or assay components, but may be linked to direct effects of hemoglobin on the PIIINP molecule. Pre-centrifugation delays up to 8 h had minimal impact on PIIINP and HA measurements, whereas TIMP-1 concentrations fluctuated dramatically already after 4 h, but this had a negligible impact on the ELF score. CONCLUSION:Hemolysis significantly interferes with PIIINP measurement, and centrifugation delays particularly affect TIMP-1 measurement in serum, whereas the ELF-score remains robust. These findings highlight the need for thorough investigation of preanalytical factors of an assay alongside the manufacturer's instruction.
Phosphatidylethanol (PEth) in whole blood and carbohydrate-deficient transferrin (CDT) in serum are routinely used alcohol biomarkers of repeated high intake and harmful drinking over the preceding weeks to month. The study compared 27,293 paired measurements of PEth (PEth 16:0/18:1) and CDT (%disialotransferrin) from occupational health care testing in Sweden. PEth concentrations ranged <0.01-9.0 µmol/L (mean 0.09, median 0.36), and CDT values ranged <0.5-19.1% (mean 1.78, median 1.40). The values were significantly correlated (R = 0.64, p < 0.0001) but with substantial individual variability. Clinical classification was concordant in most cases, 66% being negative for both and 16% being positive for both at routine cutoffs (PEth >0.30 µmol/L; CDT ≥2.0%). However, PEth alone was positive in 15% and CDT alone in ∼3%. PEth identified 90% of all positive cases (i.e. by PEth and/or CDT) compared with 57% for CDT, while 47% were positive for both. Increasing the PEth cutoff to >0.50 µmol/L reduced positivity to 66%, whereas lowering the CDT cutoff to ≥1.7% increased positivity to 90%. The prevalence of positive test results increased with age. For CDT, men showed higher positivity across all age groups, while PEth scored higher for men only in those aged <30 years. In routine hospital testing (>64,000 test per biomarker), the monthly average and proportion of positive PEth values correlated with population-level alcohol consumption showing peaks during summer holidays and after Christmas-New Year, whereas no correlation was observed for CDT. In conclusion, differences between PEth and CDT are largely driven by cutoff-dependent classification rather than discordant biomarker behavior.
In large datasets, conventional t-tests may identify statistically significant but practically trivial differences because statistical significance increases with sample size. A log-adjusted t-statistic, defined as an empirical sample-size-aware modification of the classical t-statistic, was evaluated to reduce this oversensitivity. Performance was assessed by Monte Carlo simulations of two-sample comparisons across sample sizes from 10 to 50,000 and effect sizes from δ = 0 to 1.0, and by application to a real clinical laboratory dataset comprising 464,145 participants. In simulations, the log10(Df)-adjusted statistic showed null rejection rates close to 0.05 across sample sizes, whereas the classical t-test became increasingly oversized at very large n. The adjustment was more conservative for small effects (δ = 0.2-0.4) while high rejection rates were retained for larger effects (δ = 0.6-1.0). In the real-data analysis, several sex differences that were highly significant by the classical t-test had small effect sizes and yielded reference p-values above the conventional 0.05 threshold after adjustment; platelet count (Cohen's d = 0.13) changed from p < 10-300 to reference p = 0.052, and potassium (d = 0.05) from p = 10-51 to reference p = 0.104. In contrast, larger effects such as hematocrit (d = 0.83) and HDL cholesterol (d = 0.77) continued to yield reference p-values below that threshold. These reference p-values were compared with the conventional α = 0.05 threshold for illustrative purposes only and were not intended to imply formal Type I error control. These findings suggest that the log-adjusted t-statistic may serve as a useful empirical decision aid for interpreting large clinical laboratory datasets by attenuating sample-size-driven significance while preserving detection of substantively meaningful effects.
Thyroid hormones (THs) modulate male reproductive function, but their graded associations with multidimensional semen parameters remain poorly defined. This stratified analysis investigated TH levels and semen quality in 5142 infertile men (20-45 years). Serum concentrations of free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4) and thyroid-stimulating hormone (TSH) were measured and stratified into quartiles (Q1-Q4). Comprehensive semen analysis included conventional, kinematic and morphological parameters. Multivariable logistic regression was used to assess the risk of specific semen abnormalities. Key findings revealed hormone-specific, graded associations: lower FT3 (Q1-Q2) and TT3 (Q1-Q2) levels were independently associated with increased risk of oligozoospermia (adjusted odds ratios [aORs] ranging from 1.434 to 1.785), while moderate FT3 (Q3) and FT4 (Q3) levels conferred protection against asthenozoospermia (aORs: 0.740 and 0.664, respectively). For teratozoospermia, lower TT3 (Q1) increased risk (aOR: 1.219), whereas moderate FT4 (Q2) was protective (aOR: 0.705). Interestingly, men in the lowest TSH quartile (Q1) exhibited a lower risk of both oligozoospermia and asthenozoospermia. Beyond conventional parameters, FT3 and TT4 demonstrated the most extensive associations with detailed motility, morphology and kinematic measures, including progressive motility, head/tail defects and multiple velocity parameters. These findings suggest that TH levels exhibit graded associations with semen quality in infertile men, with specific strata - even within conventional reference ranges - serving as independent risk factors for distinct semen abnormalities. The observed hormone-specific signatures support the potential integration of comprehensive thyroid profiling into male infertility evaluation, enabling refined risk stratification and personalized clinical management.
In diagnostic medicine, a likelihood ratio (LR) is the probability of getting a specific test result if diseased, divided by the probability of getting the same test result if not diseased. The clinician may use the LR to revise the probability of disease. For quantitative test results there is a distribution of likelihood ratios. Grouping quantitative test results into a few (2-10) intervals and calculating LRs for those intervals leads to loss of information. We argue that LR for a specific diagnostic test result can be estimated by any statistical procedure capable of estimating the probability of disease as a function of the quantitative test result. Using real-life data, we show that logistic regression with fractional polynomials, or nonparametric regression, may be preferred over ordinary logistic regression.
OBJECTIVE:To evaluate the feasibility of using Sebia Capillarys HbA1c mode for quantifying hemoglobin fractions in patients with known sickle cell disease to reduce turnaround time. METHODS:Hemoglobin fractions were analyzed in 58 samples from patients with previously diagnosed sickle cell disease using the Sebia Capillarys 2 FP HbA1c mode (A1c mode) and Sebia Capillarys 2 FP, HEMOGLOBIN(E) mode (Hb mode). Method comparison was performed using Bland-Altman and linear regression analyses. Precision was determined by repeated analysis of internal control material and patient samples, while linearity was studied by serial dilution of a sample containing HbS with a sample without HbS. RESULTS:The A1c mode showed good agreement with the Hb mode for quantification of HbA, HbS, and HbF fractions, with small biases of 1.44%, -1.66%, and 0.-02% respectively. Good linearity was demonstrated for HbS and HbA quantification (R2=0.9995). CONCLUSION:The A1c mode is appropriate for quick measurement of hemoglobin fractions in patients with known sickle cell disease, allowing for improved turnaround times in clinical settings. Due to occasional peak shifts and peak mislabeling by the software, a flow chart is included to guide proper A1c mode electropherogram interpretation.
This study aimed to identify early predictors of severe acute pancreatitis (SAP). Additionally, we examined whether admission laboratory parameters improve the prognostic performance of established severity scoring systems in patients presenting to the emergency department. A prospective observational cohort study was conducted in the ED of a tertiary care hospital between 15 September 2023 and 15 September 2024. A total of 208 adult patients diagnosed with AP were enrolled. Demographic characteristics, clinical findings, laboratory parameters, imaging results, complications, and outcomes were recorded. Variables associated with SAP were examined using univariate analysis followed by backward stepwise multivariate logistic regression. Predictive accuracy was assessed using receiver operating characteristic (ROC) analysis. Of the 208 patients, 52.4% were female, and the median age was 57 years (IQR: 41-68.8). SAP occurred in 11.1% of cases. In multivariate analysis, both the BISAP score (OR: 4.398; 95% CI: 2.205-8.775; p < 0.001) and admission glucose level (OR: 1.009; 95% CI: 1.003-1.016; p = 0.007) were independent predictors of SAP. A combined model incorporating BISAP and glucose demonstrated very good discriminative performance (AUC: 0.889; 95% CI: 0.850-0.972), with 87% sensitivity and 70.3% specificity. BISAP alone also showed strong predictive ability (AUC: 0.833; 95% CI: 0.727-0.938). A glucose-enhanced BISAP model provides a practical and highly accurate early risk-stratification tool for predicting severe disease among ED patients with AP. Incorporating admission glucose into BISAP may support timelier clinical decision-making and improve early management strategies.
BACKGROUND:Autoantibodies against the TSH receptor (TRAb) mediate hyperthyroidism in Graves' disease (GD). While 3rd-generation competitive immunoassays are the standard screening tool, the performance of accessible, sandwich ELISA-based TSI remains understudied in specific populations. This study evaluated the diagnostic utility of a sandwich TSI ELISA compared to a competitive TRAb ELISA in Iraqi patients with untreated hyperthyroidism. METHODS:A case-control study on 60 newly diagnosed, untreated GD patients and 30 age-matched healthy controls. Serum samples were analyzed using a competitive inhibition ELISA for TRAb and a double-antigen sandwich ELISA for TSI. Clinical severity and disease duration were compared between concordant and discordant groups. RESULTS:The competitive TRAb assay showed a superior performance (Sensitivity 90.0%, Specificity 86.7%, AUC = 0.95) compared to the TSI sandwich ELISA (Sensitivity 70.0%, Specificity 76.7%, AUC = 0.62). Diagnostic discordance was observed in 30% of patients who tested positive for TRAb but negative for TSI. The sub-analysis revealed that these discordant patients did not differ in biochemical severity from those detected by both assays. However, the discordant group presented with a shorter median duration of symptoms (1 vs. 3 months, p = 0.053). CONCLUSION:The competitive TRAb ELISA significantly outperformed the sandwich TSI ELISA. The observed discordance does not seem to be related to disease severity. We hypothesize that this discordance may result from the sandwich assay's limited ability to detect low-affinity or polyclonal antibodies, which are often present in early Graves' disease. Thus, the competitive TRAb assay remains the more robust and reliable primary screening tool.
Blood collection tubes significantly impact laboratory test accuracy, yet supply chain vulnerabilities of imported tubes necessitate evaluating domestic alternatives. This study compared the analytical performance of Ampulab and BD Vacutainer tubes. Paired blood samples were collected from 44 adult volunteers into Ampulab and BD Vacutainer tubes. Sixty-five analytes across clinical chemistry, immunology, hematology, and coagulation panels were analyzed using established platforms. Statistical comparisons included Passing-Bablok regression, Bland-Altman analysis, Wilcoxon signed-rank tests, and bias estimation against desirable biological variation thresholds. Most analytes showed acceptable agreement between the two tube types. Lactate dehydrogenase showed greater variability, exceeding the desirable bias (-4.37% vs. 3.1%), whereas chloride demonstrated a marginal deviation (-0.43% vs. 0.4%) with absolute differences remaining within 1-2 mmol/L. Prostate-specific antigen exhibited a bias above the desirable threshold at low concentrations but showed good regression agreement overall. Several hematology parameters, including white blood cells, mean corpuscular volume, and neutrophils, showed statistically significant differences; however, all remained within acceptable bias limits. Coagulation analytes demonstrated strong analytical agreement, but fibrin degradation product (FDP) showed greater variability without established performance criteria, indicating a need for further validation. Ampulab tubes demonstrated analytical performance comparable to BD Vacutainer tubes for most parameters tested. Serum separator and EDTA tubes are suitable for routine clinical use. Sodium citrate tubes require further validation for fibrinogen and FDP. These findings support the implementation of Ampulab tubes in clinical laboratories, with targeted verification recommended for selected analytes.
This study aimed to establish age- and gender-specific reference intervals for thyroid function tests-fT3 (pmol/L), fT4 (pmol/L), and TSH (μIU/L)-in both pediatric and adult populations, and for anti-TPO (kIU/L) only in adults. It also compared partitioned and continuous modeling approaches to determine the most appropriate method for clinical interpretation. In this retrospective observational study, laboratory data from individuals who visited Sivas Cumhuriyet University Hospital between 2017 and 2022 were analyzed. Partitioned reference intervals were determined using the refineR method. Continuous reference intervals were modeled using Generalized Additive Models for Location, Scale, and Shape (GAMLSS), including LMS (Box-Cox Normal), LMST (Box-Cox t), and LMSP (Box-Cox Power Exponential) distributions. Model selection was based on Generalized Akaike Information Criterion (GAIC) values, and gender differences were evaluated using parametric and non-parametric tests. In pediatric subjects, hormone distributions largely overlapped between sexes during early childhood, whereas significant gender differences in fT3 appeared after approximately age 12 (p < 0.001). In adults, males generally showed higher fT3 concentrations than females, while sex differences in fT4 were less consistent across ages. TSH levels showed minimal gender-related variation in both pediatric and adult groups. According to GAIC values, the LMSP model provided the best fit for thyroid function parameters in both pediatric and adult datasets. Continuous reference interval modeling captured gradual age-related changes and provided a flexible framework for evaluating thyroid function.
Misinterpretation of diurnal variation in thyroid hormones and thyroid stimulating hormone (TSH) could have a significant impact on diagnostic interpretation. However, the circadian rhythm of plasma thyroxine (T4) and triiodothyronine (T3) is unclarified. The aim of this study was to assess the clinical relevance of diurnal variation in thyroid hormones and TSH. Blood samples from 24 healthy Caucasian males were drawn every third hour for 24 h in a controlled environment. Diurnal variation of TSH and total/free peripheral thyroid hormones was evaluated by cosinor rhythmometry. Data was fitted with both ordinary least squares regression and mixed-effects models. Cosinor analysis showed statistically significant diurnal variation of TSH (p < 0.001), which displayed the lowest levels in the early afternoon and peaked at 2 am. During 24 h, the average within subject coefficient of variation of TSH was 31%, whereas for the peripheral thyroid hormones it was between 4-7%. All thyroid parameters exhibited large between-participant differences in individual mesor values. Extending the model to account for these individual differences in biological set-point - a mixed-effects cosinor analysis - all thyroid parameters showed statistically significant diurnal variation (p < 0.001), except free T3 (p = 0.056). Total T3 displayed a diurnal profile almost synchronized with TSH, albeit with a small temporal lag, while free/total T4 oscillated opposite to TSH with a peak around mid-day and nadir at night. In conclusion, thyroid parameters in this study exhibited significant diurnal variation, particularly TSH. These physiological fluctuations should be considered when diagnosing thyroid diseases.
To investigate the combined predictive value of plasma trimethylamine N-oxide (TMAO) and white matter lesions (WMLs) burden for 90-day prognosis after endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) with large vessel occlusion (AIS-LVO). This retrospective study included 202 AIS-LVO patients from six centers who achieved successful recanalization after EVT between February 2023 and October 2024. Patients were categorized into good (mRS ≤ 3, n = 89) and poor prognosis (mRS > 3, n = 113) groups based on 90-day modified Rankin Scale (mRS). Univariate and multivariable logistic regression analyses were performed to identify independent predictors of poor prognosis. Receiver operating characteristic (ROC) curves evaluated the predictive performance of combined TMAO and WML scores. DeLong's test confirmed that combining TMAO with the Aharon Peretz score improves the predictive value for poor outcomes over traditional risk factors (NIHSS score and age). The poor prognosis group exhibited significantly higher age, TMAO levels, creatinine, Aharon Peretz scores and NIHSS compared to the good prognosis group (p < 0.05). Multivariable analysis identified TMAO (OR = 2.854, 95%CI: 1.693-4.812), and Aharon Peretz score (OR = 1.881, 95%CI: 1.384-2.558) as new independent predictors (p < 0.05). The combination of TMAO and Aharon Peretz scores predicted poor prognosis with an AUC of 0.786 (95%CI: 0.723-0.848). TMAO and Aharon Peretz scores are independent risk factors for poor short-term prognosis after EVT in patients with AIS. The combination of TMAO and Aharon Peretz scores more accurately predicts the occurrence of short-term poor prognosis after EVT in patients with AIS.
This study evaluted the Sysmex XR-9000 hematology analyzer in a clinical setting, comparing it with the XN-9100 system using patient samples from routine laboratory. The evaluation followed CLSI H26-A2 and ICSH guidelines, incorporating state-of-the-art (SOTA) and EFLM biological variation criteria. The XR-9000 met LLoQ criteria for leukocyte and platelet counts using the White cell Differential channel by Fluorescence (WDF) and platelet fluorescence (PLT-F) channels, with CV% below 7% for WBC at 0.1 x109/L and platelets at 1.5 x109/L. Linearity was excellent across all parameters (r2 > 0.99) and imprecision reported by the manufacturer was verified. For Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), and Mean Corpuscular Hemoglobin Concentration (MCHC), CV% values reached 0.7%, 1.3%, and 1.7%, respectively, exceeding EFLM criteria of 0.4%, 0.3%, and 0.5%. The low concentration controls for neutrophils counts (NEUT) and platelets exceeded SOTA limits of 2.5% and 3%, respectively, with CV% up to 3.6% and 4.1%. Clinically relevant levels for platelets, hemoglobin, and NEUT showed acceptable imprecision with CV% <5, ≤1.3, and <9, respectively. Accuracy testing confirmed agreement with manufacturer's controls and an EQA program, with immature granulocytes as the only exception due to its level falling below LLoQ. Method comparison between the XR-9000 and XN-9100 systems demonstrated strong agreement, with minor discrepancies in MCHC, basophils count (BASO), and platelets. In conclusion, the XR-9000 demonstrated reliable performance across key metrics, meeting clinical requirements for accurate diagnosis and monitoring in hematology.
Measurement of plasma melatonin is important in studies of sleep disorders and neurodegenerative diseases and is also increasingly associated with cardiometabolic diseases and cancer. There is currently an increase in the usage of melatonin in the population. However, commercially available and reliable melatonin assays are lacking. Here we present a rapid and simple LC-MS/MS-based method for plasma melatonin in a clinical laboratory. The method demonstrates a limit of detection of 5 ng/L and inter-assay imprecision < 16%. This newly developed LC-MS/MS method was applied to 216 plasma samples collected from 24 men as part of The Bispebjerg study of diurnal variation. The results showed increased melatonin concentrations during the nighttime and fitted well to a diurnal rhythm curve (p < 0.0001). The LC-MS/MS assay correlated significantly with commercial RIA (p < 0.03) but demonstrated a substantial bias. We conclude that our simple LC-MS/MS method can detect biologically relevant changes in plasma melatonin and may enable insight into circadian biology in humans. We propose that the observed differences between melatonin assays could be clarified by the distribution of reference plasma melatonin material and that additional studies are needed to fully understand the minimum circulating levels of melatonin in the daytime.
Routine inpatient biochemical testing is often repeated without clinical indication. This quality improvement project aimed to reduce low-value biochemical testing in a Danish cardiology ward, targeting a 5% reduction within 6 months and sustainment for 12 months, without adverse changes in length of stay, discharges after noon, or 30-day readmissions. In a quality improvement project using the Model for Improvement and conducted through Plan-Do-Study-Act cycles, a multidisciplinary team implemented the following interventions: (i)targeted education for physicians and nurses e.g. clarifying of ordering responsibility; (ii)refinement of default biochemical profiles by removing non-essential tests (e.g. leukocyte count with differential, urea, hemoglobin) and curbing premature orders placed before the minimum re-testing interval; and (III)a centrally placed feedback dashboard. The primary outcome was the number of biochemical tests, adjusted for hours of hospitalization and caseload. Secondary outcomes were the proportion of results outside reference intervals and re‑testing intervals for common biochemical tests. Safety balancing measures were length of stay, discharges after noon, and 30-day readmissions. The pre-intervention period ran from February 27th, 2022, to February 26th, 2023, post-intervention period from March 5th, 2023, to February 2nd, 2025. After biochemical profile refinement in June 2023, median number of biochemical tests decreased 54% (hours of hospitalization adjusted) and 48% (caseload adjusted). The proportion of test results outside reference ranges increased 21%. Re-testing intervals lengthened for hemoglobin and troponin-I. Balancing measures showed no adverse signals, and effects persisted into February 2025. A pragmatic, simple bundle halved routine biochemical tests and increased diagnostic yield without measurable harm.
Pneumatic transportation systems (PTS) are used for sample transportation to ensure faster turn-around-times. This transportation form can however cause preanalytical changes in the samples, especially haemolysis, and it must therefore be controlled and surveyed. In order to elucidate the use and quality control (QC) of PTS in the Nordic countries, a survey was conducted in 2018 and 2024. A questionnaire was constructed using Webropol based on the CLSI document H18-A4 on handling and processing of blood specimens. It was distributed electronically in 2018 to all Nordic biochemistry laboratories through the National societies of clinical biochemistry. Due to Covid-19, the results were unfortunately not handled timely, and a follow-up questionnaire was therefore distributed in 2024. In 2018, 85 laboratories replied, while 30 laboratories replied in 2024. In 2018, 24% of the transportation lines ended either directly on the analysis track or in a bulk sorter connected to the track, while in 2024, 59% ended directly on the analysis track. In 2018, 69% had validated their PTS, mostly using haemolysis index (32%), while in 2024, 88% had validated their PTS with 87% using haemolysis index. In 2024, only 10% used internal QC for their PTS, while just 24% had entered an external quality assessment program, which was unavailable in 2018. Despite a promising development in PTS validation and quality control, several necessary actions are needed when samples are delivered via PTS. The Nordic preanalytical scientific working group has listed recommendations that should be adopted to ensure sample quality.
