Age- and ethnicity-related reference intervals for serum vitamin B12.

BACKGROUND: Age and ethnicity are known to influence serum vitamin B12 (B12) concentration, yet universal reference intervals (RIs) are typically applied by laboratories. Both lower and upper RI limits for B12 are clinically relevant. Low values suggest deficiency leading to anemia and/or neurological impairment, while high values are not always an innocuous consequence of high B12 intake but are associated with some cancers, autoimmune, liver, and renal diseases. This work aimed to establish age- and ethnicity-related RIs for B12 using a modified indirect method based on Hoffmann's approach. METHODS: A total of 72,091 anonymized B12 results (Jan 2018-Nov 2019) were analyzed from an ethnically-diverse South-East London general practice patient population. Patients belonged to five ethnic groups: Asian, Black, White, Mixed, or Other. Multiple records for the same patient and results with missing ethnicity were excluded from the analysis of adult RIs. B12 analyses were performed using ARCHITECT® (Abbott Diagnostics). RESULTS: B12 was significantly higher in Black compared with Asian and White adults. There were no differences in B12 between Asian and White adults. Children (all ethnicities) between 2 and 5 years old had the highest B12. Because of the small number of children (up to the age of 13) in each ethnic-related age category, all ethnic groups were combined to obtain age-related RIs. The children's RIs ranged from 159 to 1025 pmol/L for 0-1-year-olds to 276-1102 pmol/L for 2-5-year-olds. The RIs for Black and White/Asian people >13 years of age were 166-805 pmol/L and 134-511 pmol/L respectively. CONCLUSIONS: The application of age- and ethnicity-appropriate RIs into diagnostic practice will provide a more accurate evaluation of B12 status when using the B12 test alone or in combination with other markers.

Automated Processing and Evaluation of Anti-Nuclear Antibody Indirect Immunofluorescence Testing.

Indirect immunofluorescence (IIF) is considered by the American College of Rheumatology (ACR) and the international consensus on ANA patterns (ICAP) the gold standard for the screening of anti-nuclear antibodies (ANA). As conventional IIF is labor intensive, time-consuming, subjective, and poorly standardized, there have been ongoing efforts to improve the standardization of reagents and to develop automated platforms for assay incubation, microscopy, and evaluation. In this study, the workflow and performance characteristics of a fully automated ANA IIF system (Sprinter XL, EUROPattern Suite, IFA 40: HEp-20-10 cells) were compared to a manual approach using visual microscopy with a filter device for single-well titration and to technologist reading. The Sprinter/EUROPattern system enabled the processing of large daily workload cohorts in less than 8 h and the reduction of labor hands-on time by more than 4 h. Regarding the discrimination of positive from negative samples, the overall agreement of the EUROPattern software with technologist reading was higher (95.6%) than when compared to the current method (89.4%). Moreover, the software was consistent with technologist reading in 80.6-97.5% of patterns and 71.0-93.8% of titers. In conclusion, the Sprinter/EUROPattern system provides substantial labor savings and good concordance with technologist ANA IIF microscopy, thus increasing standardization, laboratory efficiency, and removing subjectivity.

Prevalence of isolated non-albumin proteinuria in the US population tested for both, urine total protein and urine albumin: An unexpected discovery.

BACKGROUND: Isolated non-albumin proteinuria (NAP) is a condition when urine total protein concentrations are elevated without elevation of urine albumin. The prevalence of NAP in the US population tested for both, urine total protein and albumin was assessed in this study. METHODS: The database of a US nationwide laboratory network was queried for test results when random urine albumin was ordered together with urine total protein and also when timed 24-hour urine albumin was ordered together with urine total protein. The total prevalence of NAP in the US population tested for both, urine total protein and albumin was calculated for patient groups having normal and low-normal urine albumin (random and timed) with elevated and severely increased urine total protein (random and timed). Also, the prevalence of NAP was calculated for patients with normal urine albumin to assess the probability of missing proteinuria if only urine albumin is measured. RESULTS: The prevalence of NAP in the random samples group was 10.1% (15.2% for females and 4.7% for males). Among patients with normal random albumin, there were 20.0% (27.3% of females and 10.7% of males) patients with NAP. The prevalence of NAP in the timed samples group was 24.6% (29.8% for females and 18.5% for males). Among patients with normal timed urine albumin, there were 36.2% (40.0% of females and 30.8% of males) patients with NAP. There was a strong positive association with female gender and NAP in most patients groups. CONCLUSIONS: Testing for only urine (micro)albumin can miss up to 40% of females and 30.8% of males with gross proteinuria.

Changing the paradigm of laboratory quality control through implementation of real-time test results monitoring: For patients by patients.

OBJECTIVES: To develop and implement a quality control protocol using real-time patient data with immediate failure analysis and prevention of releasing results that exceed the allowable total error. DESIGN AND METHODS: Patient data are analyzed in real time using algorithms that incorporate moving medians and moving means for selected chemistry analytes. Simulation software was developed to determine optimal algorithms, establish error limits, and number of patient results for calculation of a single cumulative datum point. Algorithms for moving median (MovMed) and mean (MovMen) were chosen and validated for each analyte. Error limits (TEa) were established using biological and analytical variation with a goal of greater than 90% error detection rate during simulation runs. Middleware software was developed to prohibit the release of patient results upon error detection. RESULTS: A block size of 50 was determined to be the optimal number of patient results used in cumulative calculations. The application of MovMed and MovMen algorithms achieved 0% false rejection for 24 out of 28 tests (85.7%) during the simulation phase. Four tests had a false rejection rate ranging from 0.2 to 1.0%. Error detection rates of 100% were achieved for 16 out of 28 tests (57.1%). Twelve tests had error detection rates ranging from 94.5 to 99.8%. Traditional QC material utilization was reduced by approximately 75-85% and repeat analysis was reduced by approximately 50%. CONCLUSIONS: We successfully developed and implemented a real-time quality control protocol using patient results with true error detection and without release of erroneous results.

Reference intervals data mining: no longer a probability paper method.

OBJECTIVES: To describe the application of a data-mining statistical algorithm for calculation of clinical laboratory tests reference intervals. METHODS: Reference intervals for eight different analytes and different age and sex groups (a total of 11 separate reference intervals) for tests that are unlikely to be ordered during routine screening of disease-free populations were calculated using the modified algorithm for data mining of test results stored in the laboratory database and compared with published peer-reviewed studies that used direct sampling. The selection of analytes was based on the predefined criteria that include comparability of analytical methods with a statistically significant number of observations. RESULTS: Of the 11 calculated reference intervals, having upper and lower limits for each, 21 of 22 reference interval limits were not statistically different from the reference studies. CONCLUSIONS: The presented statistical algorithm is shown to be an accurate and practical tool for reference interval calculations.

Patient results and laboratory test accuracy.

PURPOSE: Traditional quality control materials used for monitoring the clinical laboratory test accuracy might be non-commutable with patient samples and may not detect systematic errors. The aim of this paper is to describe a method to monitor inter-instrument bias using result distributions that are independent of the control's commutability. DESIGN/METHODOLOGY/APPROACH: Serum calcium data collected within a laboratory network were assessed. A reference interval was calculated using a computerized, indirect Hoffmann's algorithm using all data across a laboratory network without excluding any results. Results outside the reference interval were considered as the zero-bias distribution. Three allowable bias levels were then calculated to determine the corresponding shift in abnormal results for each bias level in both directions from the zero-bias distribution. The observed result distributions in three laboratories within the network were compared for bias performance after one year of the reference interval study. FINDINGS: Performance levels for bias were: minimum allowable < 1.27 percent; desirable < 0.85 percent; and optimal < 0.42 percent. Zero bias result distribution above and below the reference interval for calcium was 3.92 percent and 2.53 percent respectively. All three laboratories performed within the desirable allowable bias level. ORIGINALITY/VALUE: Bias-monitoring process using patient result distributions allows managers to: assess systematic error between laboratory instruments; improve laboratory quality control; and strengthen patient risk management.