Performance characteristics of the ARCHITECT Active-B12 (Holotranscobalamin) assay.

BACKGROUND: Vitamin B12 (cobalamin) is a necessary cofactor in methionine and succinyl-CoA metabolism. Studies estimate the deficiency prevalence as high as 30% in the elderly population. Ten to thirty percent of circulating cobalamin is bound to transcobalamin (holotranscobalamin, holoTC) which can readily enter cells and is therefore considered the bioactive form. The objective of our study was to evaluate the analytical performance of a high-throughput, automated holoTC assay (ARCHITECT i2000(SR) Active-B12 (Holotranscobalamin)) and compare it to other available methods. METHODS: Manufacturer-specified limits of blank (LoB), detection (LoD), and quantitation (LoQ), imprecision, interference, and linearity were evaluated for the ARCHITECT HoloTC assay. Residual de-identified serum samples were used to compare the ARCHITECT HoloTC assay with the automated AxSYM Active-B12 (Holotranscobalamin) assay (Abbott Diagnostics) and the manual Active-B12 (Holotranscobalamin) Enzyme Immunoassay (EIA) (Axis-Shield Diagnostics, Dundee, Scotland, UK). RESULTS: Manufacturer's claims of LoB, LoD, LoQ, imprecision, interference, and linearity to the highest point tested (113.4 pmol/L) were verified for the ARCHITECT HoloTC assay. Method comparison of the ARCHITECT HoloTC to the AxSYM HoloTC produced the following Deming regression statistics: (ARCHITECT(HoloTc)) = 0.941 (AxSYM(HoloTC)) + 1.2 pmol/L, S(y/x) = 6.4, r = 0.947 (n = 98). Comparison to the Active-B12 EIA produced: (ARCHITECT(HoloTC)) = 1.105 (EIA(Active-B12)) - 6.8 pmol/L, S(y/x) = 11.0, r = 0.950 (n = 221). CONCLUSIONS: This assay performed acceptably for LoB, LoD, LoQ, imprecision, interference, linearity and method comparison to the predicate device (AxSYM). An additional comparison to a manual Active-B12 EIA method performed similarly, with minor exceptions. This study determined that the ARCHITECT HoloTC assay is suitable for routine clinical use, which provides a high-throughput alternative for automated testing of this emerging marker of cobalamin deficiency.

Incomplete reporting of manual therapy interventions and a lack of clinician and setting diversity in clinical trials for neck pain limits replication and real-world translation. A scoping review.

INTRODUCTION: Neck pain is a leading cause of disability, and manual therapy (MT) is a common intervention used across disciplines and settings to treat it. While there is consistent support for MT in managing neck pain, questions remain about the feasibility of incorporating MT from research into clinical practice. The purpose of this scoping review was to assess the adequacy of MT intervention descriptions and the variability in clinician and setting for MT delivery in trials for neck pain. METHODS: Medline (via PubMed), CINAHL, PEDRo, and the Cochrane Central Registry for Controlled Trials were searched for clinical trials published from January 2010 to November 2021. A 11-item tool modified from the Consensus on Exercise Reporting Template was used to assess appropriateness of intervention reporting. Clinicians, subclassifications of neck pain, and clinical settings were also extracted. RESULTS: 113 trials were included. A low percentage of studies provided the recommended level of detail in the description of how MT was delivered (4.4%), while 39.0% included no description at all. Just over half of trials included clinician's qualifications (58.4%), dose of MT (59.3%), and occurrence of adverse events (55.8%). The proportion of trials with clinicians delivering MT were physical therapists (77.9%), chiropractors (10.6%), and osteopaths (2.7%). DISCUSSION/CONCLUSION: These results reveal incomplete reporting of essential treatment parameters, and a lack of clinician diversity. To foster reproducibility, researchers should report detailed descriptions of MT interventions. Future research should incorporate a variety of MT practitioners to improve generalizability.

The influence of pain-related comorbidities on pain intensity and pain-related psychological distress in patients presenting with musculoskeletal pain.

BACKGROUND: Musculoskeletal pain (MSP) is the largest contributor to chronic pain and frequently occurs alongside other medical comorbidities. OBJECTIVE: Explore the relationships between the presence of pain-related comorbidities, pain intensity, and pain-related psychological distress in patients with MSP. METHODS: A longitudinal assessment of individuals 18-90 years old in the Midwestern United States beginning a new episode of physical therapy for MSP. Electronic medical records were assessed the full year prior for care-seeking of diagnoses for pain-related comorbidities (anxiety, metabolic disorder, chronic pain, depression, nicotine dependence, post-traumatic stress disorder, sleep apnea, and sleep insomnia). Pain intensity and pain-related psychological distress (Optimal Screening for Prediction of Referral and Outcome - Yellow Flags tool) were captured during the physical therapy evaluation. Generalized linear models were used to assess the association between pain intensity, psychological distress, and pain-related co-morbidities. Models were adjusted for variables shown in the literature to influence pain. RESULTS: 532 participants were included in the cohort (56.4% female; median age of 59 years, Interquartile Range [IQR]:47, 69). Comorbid depression (beta coefficient (ß) = 0.7; 95%CI: 0.2, 1.2), spine versus lower extremity pain ((ß = 0.6; 95%CI: 0.1, 1.1), and prior surgery (ß = 0.8, 95%CI: 0.3, 1.4) were associated with higher pain intensity scores. No pain-related comorbidities were associated with pain-related psychological distress (yellow flag count or number of domains). Female sex was associated with less pain-related psychological distress (ß = -0.2, 95%CI: -0.3, -0.02). CONCLUSIONS: Depression was associated with greater pain intensity. No comorbidities were able to account for the extent of pain-related psychological distress.

Pediatric reference intervals for random urine calcium, phosphorus and total protein.

The aim of this study was to establish age appropriate reference intervals for calcium (Ca), phosphorus (P) and total protein (UTP) in random urine samples. All analytes were measured using the Roche MODULAR P analyzer and normalized to creatinine (Cr). Our study cohort consisted of 674 boys and 728 girls between 7 and 17 years old (y.o.), which allowed us to determine the central 95% reference intervals with 90% confidence intervals by non-parametric analysis partitioned by both gender and 2-year age intervals for each analyte [i.e. boys in age group 7-9 years (7-9 boys); girls in age group 7-9 years (7-9 girls), etc.]. Results for the upper limits of the central 95% reference interval were: for Ca/Cr, 0.27 (16,17 y.o.) to 0.46 mg/mg (7-9 y.o.) for the girls and 0.26 (16,17 y.o.) to 0.43 mg/mg (7-9 y.o.) for the boys; for P/Cr, 0.85 (16,17 y.o.) to 1.44 mg/mg (7-9 y.o.) for the girls and 0.87 (16,17 y.o.) to 1.68 mg/mg (7-9 y.o.) for the boys; for UTP/Cr, 0.30 (7-9 y.o.) to 0.34 mg/mg (10-12 y.o.) for the girls and 0.19 (16,17, y.o.) to 0.26 mg/mg (13-15 y.o.) for the boys. Upper reference limits decreased with increasing age, and age was a statistically significant variable for all analytes. Eight separate age- and gender-specific reference intervals are proposed per analyte.

Effects of hemoglobin (Hb) E and HbD traits on measurements of glycated Hb (HbA1c) by 23 methods.

BACKGROUND: Glycohemoglobin (GHB), reported as hemoglobin (Hb) A(1c), is a marker of long-term glycemic control in patients with diabetes and is directly related to risk for diabetic complications. HbE and HbD are the second and fourth most common Hb variants worldwide. We investigated the accuracy of HbA(1c) measurement in the presence of HbE and/or HbD traits. METHODS: We evaluated 23 HbA(1c) methods; 9 were immunoassay methods, 10 were ion-exchange HPLC methods, and 4 were capillary electrophoresis, affinity chromatography, or enzymatic methods. An overall test of coincidence of 2 least-squares linear regression lines was performed to determine whether the presence of HbE or HbD traits caused a statistically significant difference from HbAA results relative to the boronate affinity HPLC comparative method. Deming regression analysis was performed to determine whether the presence of these traits produced a clinically significant effect on HbA(1c) results with the use of +/-10% relative bias at 6% and 9% HbA(1c) as evaluation limits. RESULTS: Statistically significant differences were found in more than half of the methods tested. Only 22% and 13% showed clinically significant interference for HbE and HbD traits, respectively. CONCLUSIONS: Some current HbA(1c) methods show clinically significant interferences with samples containing HbE or HbD traits. To avoid reporting of inaccurate results, ion-exchange chromatograms must be carefully examined to identify possible interference from these Hb variants. For some methods, manufacturers' instructions do not provide adequate information for making correct decisions about reporting results.

Effects of hemoglobin C and S traits on the results of 14 commercial glycated hemoglobin assays.

Glycated hemoglobin is widely used in the management of diabetes mellitus. At least 300,000 Americans with diabetes mellitus have the hemoglobin (Hb) C or S trait. The accuracy of HbA1c methods can be adversely affected by the presence of these traits. We evaluated the effects of HbC and HbS traits on the results of 14 commercial HbA1c methods that use boronate affinity, enzymatic, immunoassay, and ion exchange methods. Whole blood samples from people homozygous for HbA or heterozygous for HbC or HbS were analyzed for HbA1c. Results for each sample type were compared with those from the CLC 330 comparative method (Primus Diagnostics, Kansas City, MO). After correcting for calibration bias by comparing results from the homozygous HbA group, method bias attributable to the presence of HbC or HbS trait was evaluated with a clinically significant difference being more than 10% (ie, 0.6% at 6% HbA1c). One immunoassay method exhibited clinically significant differences owing to the presence of HbC and HbS traits.

Alpha-fetoprotein in pericardial, peritoneal, and pleural fluids: A body fluid matrix evaluation.

OBJECTIVES: Alpha-fetoprotein (AFP) measurement in pericardial, peritoneal (ascites), and pleural fluids is sometimes requested by clinicians as supportive evidence in the evaluation of suspected malignancy. As commercially available, Food and Drug Administration (FDA)-cleared AFP assays are not validated for these fluid types, laboratories must complete additional validation studies to comply with regulatory requirements for body fluid testing. The objective of this study was therefore to conduct a matrix evaluation for these body fluid types using the Beckman Access AFP assay on the UniCel DxI 800 immunoassay system. DESIGN AND METHODS: Using an Institutional Review Board (IRB) approved protocol, previously collected pericardial fluid, peritoneal fluid, pleural fluid, and serum specimens were de-identified and frozen at -20 °C prior to matrix evaluation experiments. Spiked recovery, mixed recovery/linearity, and precision studies were conducted. RESULTS: In spiked and mixed recovery studies, the average percent (%) recovery was within predefined acceptable limits (±15%) for all three body fluids. Linearity was observed over the analytical measurement range (AMR) for all three body fluids (slope, intercept, systematic error): pericardial 0.988, -0.1, 6.1%; peritoneal 0.986, 0.0, 4.1%; and pleural 1.016, 0.0, 1.6%. Imprecision was ≤6.0% CV for all three body fluids at both high and low AFP concentrations. CONCLUSIONS: Matrix interference with AFP testing was not observed for pericardial, peritoneal, or pleural fluids on the Beckman UniCel DxI 800 system.

Adrenal steroid concentrations in children seven to seventeen years of age.

During puberty, serum steroid concentrations change dramatically. The objective of this study was to determine the adrenal steroid concentrations in children from 7 to 17 years of age. Tanner stage was determined in each child by physical examination. 11-Deoxycortisol, pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone and testosterone were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Androstenedione and dehydroepiandrosterone sulfate were measured by immunoassay. The median and central 95% of the steroid concentrations were determined for age, gender, and Tanner stage. Except for 11-deoxycortisol, all of the steroids exhibited an increase in concentration after age 7-9 years in both boys and girls. 11-Deoxycortisol, which is made exclusively in the adrenal cortex, declined with age and Tanner stage. This suggests that a rise in gonadal function and decreased efficiency of 11beta-hydroxylase with age may contribute to an increase in the remaining steroids. Testosterone concentrations increased more dramatically in boys, but increases were seen with each Tanner stage in girls.

Performance characteristics of six IMMULITE 2000 TORCH assays.

TORCH is an acronym for Toxoplasma gondii (Toxo), other microorganisms (eg, syphilis), rubella virus (RV), cytomegalovirus (CMV), and herpes simplex virus (HSV) that are associated with congenital abnormalities from maternal infection. We evaluated linearity, imprecision, and comparison with commercially available methods of the IMMULITE 2000 (Diagnostic Products, Los Angeles, CA) Toxo IgG, Toxo IgM, RV IgG, RV IgM, CMV IgG, and HSV IgG assays. Linearity and imprecision results were acceptable. The IMMULITE 2000 assays show good concordance with other commercially available methods except for Toxo IgM and RV IgM. Toxo IgM showed better concordance with a consensus of 3 of 4 (Access, Beckman Coulter, Fullerton, CA; IMMULITE 2000; Platelia, Bio-Rad Laboratories Diagnostics Group, Redmond, WA; and Vidas, bioMerieux, Hazelwood, MO) assays than with Access alone. The RV IgM assay showed better concordance with the Zeus method than with the Diamedix method (Diamedix, Miami, FL). The IMMULITE 2000 TORCH assays studied show acceptable performance and are suitable for routine clinical use. Some commercial assays for Toxo IgM and RV IgM show rather poor concordance.

Performance characteristics of seven automated CA 125 assays.

Cancer antigen 125 (CA 125) is a high-molecular-mass glycoprotein that is used as a tumor marker to monitor disease progression and response to therapy and in early detection of recurrence after treatment for ovarian cancer. The Access 2 (Beckman Coulter, Brea, CA), ADVIA Centaur (Bayer Diagnostics, Tarrytown, NY), ARCHITECT i2000 (Abbott Diagnostics, Abbott Park, IL), AxSYM (Abbott Diagnostics), Elecsys 2010 (Roche Diagnostics, Indianapolis, IN), IMMULITE 2000 (Diagnostic Products, Los Angeles, CA), and VITROS ECi (Ortho Clinical Diagnostics, Raritan, NJ) assays for CA 125 were evaluated for detection limit, dilution linearity, imprecision, correlation, and reference intervals. The maximum average deviation from target recoveries for dilution linearity studies ranged from 3.7% for the ADVIA Centaur to 18.2% for the IMMULITE 2000. Imprecision studies yielded total coefficients of variation of 2.0% to 8.3% at CA 125 concentrations of 35 and 114 U/mL (35 and 114 kU/L). Method comparison studies revealed good agreement with the VITROS ECi comparison method, with slopes ranging between 0.88 to 1.19 and correlation coefficients of more than 0.95. All methods show acceptable performance characteristics and generally compare well. However, for some samples, substantial differences exist between methods, necessitating parallel testing when introducing a new method.

Performance characteristics of an HPLC assay for urinary albumin.

Microalbuminuria is a marker of diabetic nephropathy and cardiovascular risk. Immunoassays underestimate the amount of intact albumin present in urine. The purpose of this study was to evaluate a new urinary albumin assay that uses size exclusion high-performance liquid chromatography (HPLC). We determined the limit of detection, linearity, imprecision, a comparison with an immunoturbidimetric assay, and pediatric and adult reference intervals. The limit of detection was 3.4 mg/L. The assay was linear from 4 to 240 mg/L. Total imprecision was less than 10% from 16 to 206 mg/L. Comparison of the albumin/creatinine ratio by HPLC with an immunoturbidimetric method showed positive proportional bias, which decreased with increasing concentrations of albumin. Nonparametric reference intervals were 22 to 250 mg/g for girls, 20 to 130 mg/g for boys, 14 to 62 mg/g for women, and 10 to 37 mg/g for men. This HPLC assay for urinary albumin shows acceptable performance and quantifies albumin species that are not detected by immunoassay. Separate reference intervals for children and adults seem necessary.

Performance characteristics of four automated natriuretic peptide assays.

Measurement of circulating B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) can identify patients with heart failure and guide therapy. The limit of detection, linearity, imprecision, method comparison, analytic concordance, and reference intervals of the Access 2 BNP (Biosite, San Diego, CA), ADVIA Centaur BNP (Bayer Diagnostics, Tarrytown, NY), AxSYM BNP (Abbott Diagnostics, Abbott Park, IL), and E170 NT-proBNP (Roche Diagnostics, Indianapolis, IN) methods were evaluated. The Triage meter BNP assay (Biosite) was the comparison method. Imprecision testing showed total coefficients of variation of 4.1%, 4.4%, 5.5%, and 0.8% for the Access 2, ADVIA Centaur, AxSYM, and E170, respectively. Relative to the Triage meter, method comparison revealed a slope of 0.96 and r = 0.95, a slope of 0.77 and r = 0.92, a slope of 1.13 and r = 0.94, and a slope of 8.8 and r = 0.80 for the Access 2, ADVIA Centaur, AxSYM, and E170, respectively. Overall analytic concordance values with the Triage meter were 95.9%, 92.9%, 92.4%, and 84.3% for the Access 2, ADVIA Centaur, AxSYM, and E170, respectively. All automated natriuretic peptide methods showed acceptable analytic performance.

Performance characteristics of the IMMULITE 2000 insulin-like growth factor binding protein-3 assay.

BACKGROUND: Insulin-like growth factor binding protein-3 (IGFBP-3) is the chief binding protein for insulin-like growth factors 1 and 2 (IGF-1 and IGF-2). Serum concentrations of IGFBP-3 are regulated by growth hormone (GH) and IGF-1 levels. Serum IGFBP-3 measurements are useful for diagnostic evaluations of short stature in children and acromegaly. METHODS: A IGFBP-3 assay for the IMMULITE 2000 analyzer was evaluated for limit of detection, linearity, intra- and interassay imprecision, comparison to another commercially available assay, interference studies, and an adult reference interval. RESULTS: The limit of detection was 0.006 mg/l. The assay was linear from 0.01 to 15.1 mg/l. The total interassay imprecision was <6% for IGFBP-3 concentrations of 1.1 and 4.4 mg/l. Comparison with a Nichols RIA method showed comparable results. Deming regression analysis gave a slope of 1.02+/-0.02, an intercept of 0.24+/-0.07, and a Sy/x of 0.33 (r=0.98) over the range tested (0.4 to 10.3 mg/l). Interference was <10% for all levels of bilirubin, triglyceride, and hemoglobin tested. The nonparametric reference interval for adults 26 to 61 years was 2.9 to 6.5 ng/ml. CONCLUSIONS: The IMMULITE 2000 IGFBP-3 assay shows acceptable performance and is suitable for routine clinical use.

Liver function testing on the Abaxis Piccolo Xpress: Use in Ebola virus disease protocols.

BACKGROUND: Laboratories that choose a point-of-care approach for liver function testing in patients undergoing evaluation for Ebola virus disease (EVD) have few options to choose from. The primary objective of this study was to conduct a performance characterization of a Clinical Laboratory Improvement Amendments (CLIA)-waived liver function panel on the Abaxis Piccolo® Xpress chemistry analyzer. The secondary objectives were to evaluate multiple specimen types, characterize whole blood specimen stability, and validate disposable exact transfer pipettes. Our final objective was to assess instrument airflow from a biosafety perspective. METHODS: An instrument performance characterization, including precision, linearity, accuracy, reference interval verification, and specimen type evaluation was conducted using Liver Panel Plus reagent discs on the Piccolo® Xpress. RESULTS: All assays demonstrated acceptable linearity (slopes, 0.938-1.061; observed error, 0.8-6.3%). Assay precision was 0.0-3.6% (%CV; within-day studies) and 0.9-5.6% (between-day studies). Method comparison experiments (versus Roche cobas c502/c702 chemistry analyzers) showed excellent correlation for most assays, although a few notable differences were observed (Piccolo versus Roche): alkaline phosphatase, -18.6%; amylase, -29.0%; total bilirubin, +0.3mg/dl. Pre-programmed reference intervals were verified except for the alkaline phosphatase (male and female) and alanine aminotransferase (female), which had greater than 10% of results fall below the programmed ranges. Piccolo instrument results were largely consistent across specimen types tested (lithium-heparin whole blood, lithium-heparin plasma, and serum), although some statistical differences were observed for aspartate aminotransferase, gamma glutamyltransferase, and total protein. Whole blood time course studies demonstrated that some analytes (albumin, amylase, and total protein) showed remarkable stability, while others (such as aspartate aminotransferase) showed a slight trend toward decreased activity over time. Exact volume transfer pipettes provided an effective disposable option for disc loading. Finally, airflow studies suggested that, in the context of EVD protocols, instrument placement in a biosafety level (BSL) 2 cabinet or greater is justified. CONCLUSIONS: Given its analytical performance and ease of operation, the Piccolo Xpress was transferred to a BSL-2 cabinet in our BSL-3 suite for use in our hospital's diagnostic protocol for providing liver function testing in patients undergoing evaluation for EVD.

Body fluid matrix evaluation on a Roche cobas 8000 system.

OBJECTIVES: Chemical analysis of body fluids is commonly requested by physicians. Because most commercial FDA-cleared clinical laboratory assays are not validated by diagnostic manufacturers for "non-serum" and "non-plasma" specimens, laboratories may need to complete additional validation studies to comply with regulatory requirements regarding body fluid testing. The objective of this report is to perform recovery studies to evaluate potential body fluid matrix interferences for commonly requested chemistry analytes. DESIGN AND METHODS: Using an IRB-approved protocol, previously collected clinical body fluid specimens (biliary/hepatic, cerebrospinal, dialysate, drain, pancreatic, pericardial, peritoneal, pleural, synovial, and vitreous) were de-identified and frozen (-20°C) until experiments were performed. Recovery studies (spiking with high concentration serum, control, and/or calibrator) were conducted using 10% spiking solution by volume; n=5 specimens per analyte/body fluid investigated. Specimens were tested on a Roche cobas 8000 system (c502, c702, e602, and ISE modules). RESULTS: In all 80 analyte/body fluid combinations investigated (including amylase, total bilirubin, urea nitrogen, carbohydrate antigen 19-9, carcinoembryonic antigen, cholesterol, chloride, creatinine, glucose, potassium, lactate dehydrogenase, lipase, rheumatoid factor, sodium, total protein, triglycerides, and uric acid), the average percent recovery was within predefined acceptable limits (less than ±10% from the calculated ideal recovery). CONCLUSIONS: The present study provides evidence against the presence of any systematic matrix interference in the analyte/body fluid combinations investigated on the Roche cobas 8000 system. Such findings support the utility of ongoing body fluid validation initiatives conducted to maintain compliance with regulatory requirements.

Performance characteristics of four immunonephelometric assays for the quantitative determination of IgA and IgM in cerebrospinal fluid.

Measurement of IgA and IgM in cerebrospinal fluid (CSF) can be useful in the diagnosis of multiple sclerosis and other central nervous system disorders. The Dade Behring (Deerfield, IL) N Latex IgA and N Latex IgM tests on the BN II System and Beckman Coulter (Brea, CA) low-concentration IgA and IgM tests on the IMMAGE Immunochemistry System were evaluated for linearity, imprecision, method comparison, and reference interval verification. Both IgA methods were linear from 1.4 to at least 50 mg/L. Both IgM methods were linear from 0.14 to more than 6 mg/L. The total imprecision of the BN II IgA and IgM methods and the IMMAGE IgA method was less than 10%. The imprecision of the IMMAGE IgM method was 10.2% at 0.49 mg/L and less than 5% at higher IgM concentrations. Method comparison studies indicated that IgA and IgM methods on both instruments showed good comparability. Reference interval studies demonstrated that both methods had similar reference intervals that agreed with published values of less than 6 mg/L for IgA and less than 1.3 mg/L for IgM. Methods for quantifying IgA and IgM in CSF on the BN II and IMMAGE nephelometers perform well and give comparable results.

Comparison of five automated serum and whole blood folate assays.

Serum and whole blood folate measurements are used to establish folate deficiency. Most methods used in clinical laboratories are automated, nonistopic methods that use folate-binding protein. Linearity, imprecision, and method comparison studies, including serum and whole blood hemolysates, were performed with the Access, Advia Centaur, ARCHITECT i2000, Elecsys 2010, and IMMULITE 2000 methods. The QuantaPhase II radioassay served as the comparison method. (Proprietary information is given in the text.) The Access and IMMULITE 2000 methods had higher systematic errors in linearity studies than the other 3 methods. The imprecision of all methods was acceptable (coefficient of variation, < 10%) even at low folate concentrations with the exception of the Elecsys 2010 (coefficient of variation, 16%). Method comparison studies using serum samples revealed calibration differences between the Access and Elecsys 2010 methods and the comparison method. Method comparison studies using whole blood samples showed poorer agreement between each of the automated methods and the comparison method than was seen with serum samples. The ARCHITECT i2000 folate assay demonstrated the best analytic performance. The poor agreement seen with whole blood hemolysates likely is due to calibration differences and differences in hemolysate preparation conditions.

Performance characteristics of eight estradiol immunoassays.

Measurement of estradiol is useful in assisted reproduction, evaluation of infertility, menopause, and male feminization. The analytic performance of 8 estradiol immunoassays was evaluated. The imprecision and accuracy of the Access, ADVIA Centaur, ARCHITECT i2000, AutoDELFIA, Elecsys 2010, IMMULITE 2000, and Vitros ECi estradiol assays (see text for proprietary information) were evaluated by using an isotope dilution-gas chromatography-mass spectrometry (ID-GC-MS) reference method. The coefficient of variation (CV) ranged from 6.9% on the Elecsys 2010 to 42.6% on the ADVIA Centaur at an estradiol concentration of 18 pg/mL (66 pmol/L), with the ARCHITECT i2000 assay in development and the Vitros ECi having a CV below 10% at this estradiol concentration. Agreement between the automated assays and ID-GC-MS was variable, with slopes ranging from 0.87 to 1.20. The Access, ARCHITECT i2000 in development, and the IMMULITE 2000 were the most accurate, with slopes of 0.99, 0.98, and 1.03, respectively. These findings indicate that the ARCHITECT i2000 estradiol assay in development had the best precision and accuracy of the assays evaluated for measurement of serum estradiol concentrations.

Performance characteristics of the IMMUNLITE 2000 erythropoietin assay.

BACKGROUND: Erythropoietin (EPO) is a glycoprotein hormone produced by specialized cells in the kidney that acts as the primary regulator of erythropoiesis. Serum EPO measurements are useful for diagnostic evaluations of anemia and polycythemia. METHODS: The IMMULITE 2000 is an automated random access immunoassay analyzer for the central laboratory. The limit of detection (LOD), linearity, imprecision, comparison to another commercially available assay, and reference interval of a new EPO assay for this analyzer were assessed. RESULTS: The LOD was 0.2 U/l. The assay was linear within an allowable systematic error of 10% over the range tested (2-178 U/l). The total imprecision of the new assay was <7% for concentrations from 15.8 to 68.4 U/l. Comparison with the Advantage EPO assay method showed comparable results. Deming regression analysis gave a slope of 1.13+/-0.02, an intercept of -1.09+/-0.97, and a S(y/x) of 7.1 (r=0.99) over the range tested (2-200 U/l). CONCLUSIONS: The IMMULITE 2000 EPO assay shows acceptable performance and is suitable for routine clinical use.

Performance characteristics of an automated high-sensitivity C-reactive protein assay on the Dimension RXL analyzer.

BACKGROUND: C-reactive protein (CRP) is a nonspecific marker of inflammation that can be used as a marker for atherosclerotic risk. This application requires increased precision at low CRP concentrations compared to traditional assays. METHODS: The Dimension RXL is an automated chemistry analyzer for central laboratory use. The limit of detection, limit of quantification, linearity and imprecision of a high-sensitivity CRP assay developed for it were assessed. Method comparison studies were performed using samples both inside and outside the reference interval. The presence of a prozone effect was also evaluated. RESULTS: The limit of detection was 0.7 mg/l. The method was linear from 2 to 60 mg/l and from 1 to 60 mg/l using systematic error limits of 10% and 20%, respectively. The total imprecision was <10% for CRP concentrations above 1.5 mg/l. No prozone effect was seen at a CRP concentration of 450 mg/l, the highest concentration tested. Using samples from 212 apparently healthy adults, the Dimension RXL method demonstrated good concordance with the BN II high-sensitivity CRP method for samples in the highest quartile. It also compared well using samples with elevated CRP concentrations. CONCLUSIONS: The Dimension RXL high-sensitivity CRP method may be adequate for atherosclerotic risk prediction in clinical practice if accurate and precise measurement is only required for the highest quartile. However, the total error of this method for CRP concentrations <3 mg/l appears too large for accurate assignment to lower risk groups.