Analysis of patient results distributions to reevaluate a reference range change for calcium, after a change in assay reagents on the Roche Cobas c500 analyzer

Introduction: A change in reagents for calcium (Ca) on the Roche Cobas c500 used in our laboratory analyzer took place in 2013. The previous reference range (8.5-10.5 mg/dL) was replaced with that from the manufacturer\u27s study (8.6-10.0 mg/dL), based on correlation of results between the new and old assays. As a matter of quality assurance, we undertook a post-assay-change reevaluation of the reference range change, using a method based on that of Bhattacharya [1]. In short, the method relies on the assumption that the reference range is a normal distribution, which assumption enables this distribution to be isolated mathematically from within all-comers patient distribution data that are not normally distributed

Drug Interaction Study Of Apixaban With Cyclosporine Or Tacrolimus: Results From A Phase 1, Randomized, Open-Label, Crossover Study In Healthy Volunteers

BACKGROUND Solid organ transplant recipients commonly require anticoagulation. Apixaban (APX) is principally metabolized by CYP3A4, undergoes direct intestinal excretion, and is a substrate to P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) transporters. We examined the potential drug interaction between cyclosporine (CsA) and tacrolimus (Tac) [combined inhibitors of CYP3A4, P-gp and, BCRP] with APX.https://jdc.jefferson.edu/petposters/1005/thumbnail.jp

Assessment of utility of daily patient results averages as adjunct quality control in a weekday-only satellite chemistry laboratory

ABSTRACT Background: Our department operates a weekday-only (8AM-5PM) satellite laboratory in an infusion center with a menu of 18 chemistry tests on a Roche c501 analyzer. We examined whether daily patient results averages (PRA) in this setting might be useful as a patient-based quality control (PBQC) adjunct to standard daily liquid quality control (LQC) measurements. First, we evaluated the reproducibility (coefficient of variation, CV) of daily PRAs for each analyte, and compared these to CVs of LQC. Second, for select analytes found to have relatively low PRA CVs, we evaluated the extent to which use of daily PRA measurements could improve detection of analytical errors when combined with LQC. Methods: Patient results data for approximately one month (21 weekdays) were obtained from the Sunquest laboratory information system. For calculation of patient results averages (PRA), qualifying results were restricted to those within the reference range for each analyte. PRA and standard deviation (S) of PRA across 21 days was calculated for each analyte. Coefficients of variation for PRA (CV-PRA) were compared to those observed for standard liquid quality control (LQC) measurements (CV-LQC). For those analytes for which CV-PRA was less than CV-LQC, we evaluated the potential advantage of addition of PRA to daily LQC. For each analyte, a presumed PRA shift was determined such that probability of detection (P) was 0.5 when using LQC alone (viz., using high LQC and low LQC measurements), according to criterion that at least one 1-2S deviation from mean was obtained. For this same PRA shift, P = 0.5 for LQC alone was compared to P obtained for LQC + PRA (viz., using high LQC, low LQC, and PRA measurements), according to the same criterion. Results: Across 21 days, the number of results per day per assay ranged from 23 ±4 (uric acid) to 75 ±21 (electrolytes). Qualifying results (results within the reference range) ranged from 70 ± 6 % (LDH) to 99 ± 1 % (Cl). Seven analytes had CV-PRA \u3c CV-LQC (analyte, CV%): albumin, 1.25%; Ca, 0.67%; Cl, 0.62%; CO2, 1.13%; creatinine, 3.44%; K, 1.14%; Na, 0.65%. The remainder did not meet this criterion: ALP, 3.7%; ALT, 5.2%; AST, 5.1%; BUN, 4.6%; glucose, 1.4%; LDH, 2.0%; Mg, 1.4%; P, 2.5%; protein, 0.9%; TBIL, 6.1%; uric acid, 4.3%. Among the seven analytes for which CV-PRA \u3c CV-LQC, probability (P) of shift detection by LQC for circumstances as described in Methods (LQC P = 0.5) was increased substantially by inclusion of PRA (analyte, shift in analyte concentration, P): CO2, ±1.07 mmol/L, 0.97; creatinine, ±0.099 mg/dL, 0.93; albumin, ±0.126 g/dL, 0.85; Ca, ±0.14 mg/dL, 0.80; K, ±0.097 mmol/L, 0.76; Cl, ±1.24 mmol/L, 0.74; Na, ±1.48 mmol/L, 0.68. Conclusions: For 7 analytes, daily PRA demonstrated CVs less than those for LQC. For these analytes, calculations demonstrated that daily PRA can increase probability of detection of small results shifts when used as an adjunct to LQC. Daily PRA is a simple and essentially cost-free form of PBQC that may be useful for certain analytes in part-time laboratory settings

Quantitation of hemoglobins using Sebia Capillarys-2 capillary electrophoresis (CE) for A1c: Comparison to results using CE for hemoglobins

Background: Measurement of A1c using the Sebia Capillarys-2 capillary electrophoresis (A1c CE) involves relative quantitative measurements of peaks for hemoglobins A1c, A, A2. We examined correlation of A1c CE results with results of CE analysis for hemoglobins (Hb CE) for homozygous A and S-trait patients. We specifically examined whether abnormalities in A2 or the A/S ratio by A1c CE alone would reasonably be the basis for recommendation of red cell indices for evaluation of possible thalassemia. Methods: Selection of patients was from results for A1c CE, exhibiting either a normal pattern or a pattern consistent with S-trait. We then examined correlation of results of quantitation for A, S and A2 between A1c CE and Hb CE. Results: %A2 by A1c CE (y) had high correlation with %A2 by Hb CE (x): y = 0.88 x; r = 0.948. %A2 in S-trait patients was right-shifted in comparison to normals by 0.5%. For S-trait patients, the A/S ratio by A1c CE (y) had high correlation with the A/S ratio by Hb CE (x): y = 1.02 x; r = 0.995. Conclusions: Given high correlation of results between A1c CE and Hb CE, patent elevation of A2 by A1c CE for either normal or S-trait patients is a reasonable basis for recommendation of red cell indices for evaluation of possible beta thalassemia. For S-trait patients, patent abnormality in the A/S ratio by A1c CE is a reasonable basis for recommendation of red cell indices for evaluation of possible alpha or beta thalassemia

Incidence rates of critical low glucoses (\u3c40 mg/dL) by POCT before and after new policies for treatment of clinically significant hypoglycemia (\u3c54 mg/dL): A comparison between two hospitals

Glucose \u3c54 mg/dL was recently defined as Clinically Significant Hypoglycemia (CSH, American Diabetes Association, Standards of Medical Care in Diabetes, 2017). In January 2018, our hospitals instituted a callback policy for inpatient CSH from the central laboratory, and instituted a new nursing procedure for response to CSH. We examined whether the new policies had affected the incidence rate of low glucose critical values (CRITICAL, \u3c40 mg/dL) among POCT glucose measurements. This was investigated for two hospitals within our system: A, a 950-bed academic medical center hospital, and B, a 200-bed community hospital.https://jdc.jefferson.edu/pacbposters/1016/thumbnail.jp

Distribution of serum concentrations reported for macroenzyme aspartate aminotransferase (macro-AST)

Background: The presence of macroenzyme (M) is often the explanation of an isolated elevation of aspartate aminotransferase (AST). Where M is identified, it is reasonable for the clinician to ask where an individual patient's result fits in with known concentrations of M. In this context, we conducted a survey of literature to examine the distribution of reported serum concentrations of macro-AST. We also analyzed the distribution data to examine whether elevations were consistent with simple alteration of circulatory half-life (t1/2) of M relative to normal AST. Methods: Distributions of M were compiled from the literature. These distributions were compared to predictions based on fixed changes in t1/2 applied to the reference interval for AST. Results: There was a bimodal distribution of literature values for M (n =51), comprised roughly of populations A (M 200 U/L; 40% of total). The two distributions were reasonably well characterized by a simple projection to the right of the reference interval for AST according to increased t1/2 (A: t1/2 =3.3 days; B: t1/2 =19.8 days) relative to AST (t1/2 =0.7 days). Conclusions: Knowledge of distributions for M may be useful in discussion with clinicians regarding significance of M for individual patients. Distributions for M were consistent with the simplest explanation for elevated AST due strictly to an extended circulatory lifetime for M. Caveats to analysis, however, include selection within literature data mainly for patients with various co-morbidities. Keywords: Macroenzyme, Aspartate amino transferase, Immunoglobulins, Mathematical mode

Non-linearity within the primary measurement range of a lipase assay as the cause of a gap in the interpatient lipase results distribution.

OBJECTIVES: Interpatient distribution data for lipase (Roche Cobas® assay) showed an unexpected data gap, where no results were reported. This gap occurred beginning at a point just above the assay\u27s primary measurement range (i.e., above the cutoff (300U/L) for automated repeat-on-dilution). Calculation or other errors within the automated dilution process were ruled out. Linearity of assay results was investigated. DESIGN AND METHODS: Linearity of experimental sample dilution series data was assessed by correlation coefficient, intercept, and constancy of slope. RESULTS: Dilution experiment data demonstrated a discontinuity of results between 300 and 400U/L consistent with the observed gap in patient data. Although data within the presumed linear range of the assay had a high linear correlation coefficient (r2\u3e0.99), a non-zero intercept and progressively variable slope were inconsistent with linearity. Although the assay was assessed as linear by the College of American Pathology linearity survey, survey data also demonstrated non-linearity for this assay when analyzed for slopes and intercept. CONCLUSIONS: Non-linearity in the presumed linear range of an assay can produce gaps in patient data above a repeat-on-dilution cutoff. As in this instance, CAP linearity surveys may not identify certain forms of non-linearity