Volume 44, Issue 1

Measurement uncertainty is a parameter that is associated with the dispersion of measurements. Assessment of the measurement uncertainty is recommended in qualitative analyses in clinical laboratories; however, the measurement uncertainty of qualitative tests has been neglected despite the introduction of many adequate methods. We herein provide an overview of three reasonable statistical methods for quantifying the measurement uncertainties of qualitative assays, namely Bayes’ theorem, the normal distribution method, and the information theoretic approach. Unlike in quantitative analysis, the measurement uncertainty of qualitative analysis is expressed using a conditional probability, likelihood ratio, and entropy. With the necessary theoretical background, the practical applications for clinical laboratories are also provided using statistical calculations. Using statistical approaches, we hope that our review will contribute to the use of measurement uncertainty in qualitative analyses in the clinical laboratory environment.

Background Vitamin B12 deficiency is still an important nutritional problem worldwide. There is no consensus on the reference intervals (RIs) for vitamin B12. In order to establish vitamin B12 RIs, we used the database obtained from a primary healthcare organization and estimated region-specific intervals. Methods Vitamin B12 results were collected from our laboratory information system (LIS) between January 2014 and July 2014. We excluded the results of the individuals who had megaloblastic and microcytic anemia. After outlier detection and exclusion, we estimated the RIs of the “1–12, 13–18, 19–64 and 65 +” age groups according to the International Federation of Clinical Chemistry (IFCC) method. Statistical differences were examined between groups. Results The reference limits and 90% confidence intervals (CIs) (n = 14,748, 3790 male, age: 1–96; 10,958 female, age: 1–115) were estimated with 90% CIs as 106 (104–107)–393 (391–395) pmol/L. We also estimated the reference limits of the “1–12, 13–18, 19–64 and 65 +” age groups to be 127–459, 108–398, 106–384 and 104–426 pmol/L, respectively. There was no difference between genders in all age groups. Conclusions Both the lower and upper limits of the estimated RIs were found to be lower than the reference limits recommended by the manufacturer. Our findings revealed that the RIs of vitamin B12 should be given for the “1–12, 13–18, 19–64 and 65 +” age groups separately. The big data obtained from laboratories should be used for the determination of its population health status. As our population is composed of outpatients, the estimated vitamin B12 RIs may establish the basic information for the examination of our population for vitamin B12 deficiency.

Background Serum sodium concentration could be spuriously reduced by excess glucose or lipid; thus, hyponatremia should be reassessed before reporting in order to exclude the possibility of pseudohyponatremia. Methods In this study, we used the calculation of corrected serum sodium concentration in hyperglycemic or lipemic samples and evaluated its effect on the reduction in frequency of reports on pseudohyponatremia. We retrospectively analyzed 1-year data from the laboratory information system. Results From August 2017 to July 2018, hyponatremia was initially noted in 30,465 results, of which 6614 results reported hyperglycemia. Corrected sodium concentrations were calculated using the results with glucose >170 mg/dL or lipemia index ≥3. The reported frequency of hyponatremia before and after correction of sodium concentration was reduced by 42.9%. Moreover, only 51.9% of the patients with severe hyponatremia had “true” severe hyponatremia. After applying the formula, the degree of hyponatremia was unchanged in only 45.8% of the total results. Conclusions Our report on the corrected sodium concentration reduced the frequency of pseudohyponatremia in hyperglycemic samples. Calculation of corrected sodium concentration is a useful tool to help clinicians establish appropriate care and treatment plans. Further prospective study is required to validate to our system in a real clinical practice.

Background This study aimed to investigate the implications of antinuclear antibodies (ANAs) in juvenile idiopathic arthritis (JIA), the association with uveitis and the favorable evolution of the disease. Methods We followed 45 pediatric patients suffering from JIA, according to the International League of Associations for Rheumatology (ILAR), for a period of 2 years. ANAs were followed through immunofluorescence methods using a high-performance immunofluorescence automatic Helios device. Results A total of 15 of the ANA-positive patients presented an oligoarticular form of the disease, eight of them presented a polyarticular form of the disease and two of them presented a systemic form. The most severe forms have associated iridocyclitis. ANA-positive patients presented an earlier onset of disease in comparison with ANA-negative ones. ANA-positive patients from different ILAR categories had similar characteristics of the disease such as onset age (earlier), higher prevalence in females and the presence of asymmetric arthritis or iridocyclitis. Conclusions ANA may be an important marker for JIA and association with iridocyclitis. Following ANA titer in evolution might be a criterion for assessing the evolution of the disease. The association between positive ANA, oligoarticular JIA, iridocyclitis and a 2- to 4-year-old onset is common.

Background Escherichia coli accounts for 70–95% of community-acquired urinary tract infections (UTIs). Recently, there has been an increase in the prevalence of extended-spectrum β-lactamase (ESBL) in the community which required an accurate identification for better management. Therefore, the current study was performed to determine the antimicrobial resistance pattern, investigate ESBL phenotypes and genotypes ( blaCTX-M , bla TEM and bla SHV genes) and determine the phylogenetic groups among ESBL-positive isolates from outpatients. Methods One hundred and eighty-three positive urine samples were collected from 4450 outpatient clinic attendees. Antibiotic susceptibility was determined and ESBL phenotype screening was carried out using disk diffusion agar and combination disk techniques, respectively. The assessment of the presence of the blaCTX-M , bla TEM and blaSHV genes and phylogenetic grouping were performed using the polymerase chain reaction (PCR) method. Results Out of 183 E. coli isolates, 59 (32.2%) showed a positive ESBL phenotype. The prevalence of ESBL-producing E. coli was higher in males (57.4%). Fifty-seven of the ESBL-producing strains carried at least one of the β-lactamase genes ( bla CTX-M , bla TEM , bla SHV ). Phylotyping of multi-drug resistant isolates indicated that the isolates belonged to B2, A and D phylogroups. Analysis of resistance patterns among these phylogroups revealed that 74.4%, 55.3% and 29.7% of the isolates in the B2 group were resistant to trimethoprim-sulfamethoxazole, ciprofloxacin and gentamicin, respectively. Most of the strains in the phylogroup B2 carried the bla CTX-M gene. Conclusions All the ESBL-producing isolates were placed in one of the four phylogenetic groups. The presence of CTX-M and resistance to quinolones were more frequent in B2 strains than in non-B2 strains.

Background The aim of this study was to compare the estimated glomerular filtration rate (eGFR) from serum creatinine (eGFRcrea) and cystatin C (eGFRcys) in patients with elevated serum trough levels of gentamicin before the next planned dose during treatment in the intensive care unit (ICU). Methods This was a retrospective observational study. Patients who stayed in an ICU, received a once-daily dose of gentamicin, and who had results from all serum gentamicin trough levels, eGFRcrea and eGFRcys analyses were included in the study. Overdosed patients were defined as those with serum gentamicin trough levels above 1 mg/L before the next dose. Gentamicin was measured by a particle-enhanced turbidimetric immunoassay (PETIA). Creatinine and cystatin C were measured by standardized methods. Results The median age (range) was lower in all patients with gentamicin concentration measurements than in overdosed patients (67 [19–96] vs. 75 [48–99] years, respectively; p < 0.0001). The median interquartile range (IQR) of the eGFRcrea was higher than that of the eGFRcys in overdosed patients (60 [44–79] mL/min/1.73 m 2 vs. 41 [29–58] mL/min/1.73 m 2 , respectively; p < 0.0001). The median IQR of the eGFRcrea was higher than that of the eGFRcys in controls (87 [78–98] mL/min/1.73 m 2 vs. 66 [54–93] mL/min/1.73 m 2 , respectively; p < 0.0001). Conclusions Overdosed patients had both a lower eGFRcrea and eGFRcys than controls. Elderly patients are the most commonly overdosed patients. We recommend measuring cystatin C and calculating the eGFRcys and combined equation (eGFRcrea + cys) in ICU patients over 65 years of age, which would enable improved gentamicin dosage adjustments.

Background It is meaningful to quantify some neurotransmitters in cerebrospinal fluid (CSF) for pathology and clinical diagnosis. The objective of this study was to develop a rapid and reliable method for detecting 5-hydroxyindole ethanol (5-HTOL), 5-hydroxyindole acetic acid (5-HIAA), 5-hydroxytryptophan (5-HTP) and 5-hydroxytryptamine (5-HT) in CSF by gas chromatography-mass spectrometry (GC-MS), and explore the clinical significance of the levels of these neurotransmitters in CSF from acute lymphoblastic leukemia (ALL). Methods The levels of 5-HTOL, 5-HIAA, 5-HTP and 5-HT in CSF from children with ALL and a control (CON) group were examined by the proposed GC-MS method. Results The GC-MS method showed good sensitivity and accuracy. 5-HT and 5-HIAA contents in the ALL group were significantly lower than those in the CON group (p < 0.01), while there was no significant difference in 5-HTP and 5-HTOL contents between the two groups (p > 0.05). Conclusions This sensitive and reliable method could be used in studies focusing on clinical pathogenesis of ALL.

Background A meta-analysis of previously performed evaluation studies of nucleic acid amplification testing (NAT) approaches for the screening for and differentiation of Plasmodium spp. using identical samples was performed to comparatively assess their suitability for the routine diagnostic setting. Methods Three commercial NATs for malaria (one loop-mediated isothermal amplification [LAMP] assay, two real-time polymerase chain reactions [PCRs]) and one in-house real-time PCR were comparatively assessed with a collection of 1020 well-characterized ethylenediaminetetraacetic acid (EDTA) blood samples from patients with suspected or confirmed malaria. Results Altogether 765 (75%) concordantly negative and 223 (21.9%) concordantly positive results of the four molecular tests were obtained, while discordant results were seen in 32 (3.1%) instances. For genus-specific assays, the observed sensitivity and specificity ranges were 96.4%–98.4% and 99.6%–99.9%, and for species-specific assays, 94.0%–97.6% and 99.6%–100%, respectively. Falsely negative molecular test results comprised microscopically negative samples, samples at the microscopic detection threshold and quantitatively less abundant species in mixed infections. Conclusions Excellent test characteristics of all assessed assays with only minor differences encourage molecular malaria screening with genus- and species-specific NAT with discrepancies only within the borderline range of their detection thresholds.

This is the first report of glycated haemoglobin (Hb) eluting in zone 10 on capillary zone electrophoresis (CZE). In an index case, the aberrant peak was picked up during routine haemoglobinopathy testing using CZE. Mass spectrometry (MS) revealed this aberrant peak to be glycated Hb. Prompted by this initial case, a study was undertaken and the results showed that there was a strong positive linear relationship (R 2  = 0.774; ρ = 0.88) between the level of glycated Hb peak eluting in zone 10 and the HbA 1c value. Furthermore, all samples with an HbA 1c of 54 mmol/mol or greater had an HbA 1c peak eluting in zone 10.