Reference Intervals Generated by Electronic Medical Record Data Mining with Clinical Exclusions: Age-Specific Intervals for Thyroid-Stimulating Hormone from 33038 Euthyroid Patients.

BACKGROUND: Serum thyroid-stimulating hormone (TSH) reference intervals are dependent on population characteristics, including prevalent thyroid disease and iodine status. Studies in the US have demonstrated increasing TSH levels with age, and the American Thyroid Association recommends higher TSH goals for older patients taking thyroid supplementation, but few laboratories offer age-specific reference intervals for TSH. Our objective was to establish TSH reference ranges in our racially diverse population in northern California. METHODS: Data mining of electronic medical records was used with the a posteriori approach to select a euthyroid reference population for TSH reference intervals. A report gathered all TSH results from 2 weeks from >1 year in the past, excluding results from patients with thyroid-related disease or medication use at any time before or after the TSH test. RESULTS: The reference population numbered 33038 and consisted of approximately 44% of the total TSH results reported in the selected time periods. The population identified as 46.5% white, 18.3% Asian, 17.0% Hispanic/Latino, 8.0% black/African American, and 10.3% other or unknown. These data demonstrate an increase in the median and 97.5 percentile of TSH levels with increasing age in adults. No clinically significant difference was seen between female and male individuals or between the self-identified races, except for lower TSH levels in the black/African American population. CONCLUSIONS: The a posteriori approach using data mining for disease-specific criteria proved to be an efficient method for obtaining a large healthy reference population. Age-specific TSH reference ranges could prevent inappropriate diagnoses of subclinical hypothyroidism in older patients.

Effect of Several Negative Rounds of Human Papillomavirus and Cytology Co-testing on Safety Against Cervical Cancer: An Observational Cohort Study.

Background: Current U.S. cervical cancer screening and management guidelines do not consider previous screening history, because data on multiple-round human papillomavirus (HPV) and cytology "co-testing" have been unavailable. Objective: To measure cervical cancer risk in routine practice after successive negative screening co-tests at 3-year intervals. Design: Observational cohort study. Setting: Integrated health care system (Kaiser Permanente Northern California, Oakland, California). Patients: 990 013 women who had 1 or more co-tests from 2003 to 2014. Measurements: 3- and 5-year cumulative detection of (risk for) cervical intraepithelial neoplasia grade 3, adenocarcinoma in situ, and cervical cancer (≥CIN3) in women with different numbers of negative co-tests, overall and within subgroups defined by previous co-test results or baseline age. Results: Five-year ≥CIN3 risks decreased after each successive negative co-test screening round (0.098%, 0.052%, and 0.035%). Five-year ≥CIN3 risks for an HPV-negative co-test, regardless of the cytology result, nearly matched the performance (reassurance) of a negative co-test for each successive round of screening (0.114%, 0.061%, and 0.041%). By comparison, ≥CIN3 risks for the cytology-negative co-test, regardless of the HPV result, also decreased with each successive round, but 3-year risks were as high as 5-year risks after an HPV-negative co-test (0.199%, 0.065%, and 0.043%). No interval cervical cancer cases were diagnosed after the second negative co-test. Independently, ≥CIN3 risks decreased with age. Length of previous screening interval did not influence future ≥CIN3 risks. Limitation: Interval-censored observational data. Conclusion: After 1 or more negative cervical co-tests (or HPV tests), longer screening intervals (every 5 years or more) might be feasible and safe. Primary Funding Source: National Cancer Institute Intramural Research Program.

Challenges in harmonizing integrated healthcare network laboratories: multi-center evaluation of the hCG5 assay.

BACKGROUND: Beckman Coulter recently introduced a new hCG assay manufactured for the Access 2 and DxI platforms. This assay is the first to use the 5th International Standard (5th IS) as its primary calibration material. Clinical laboratories are required to validate the method performance before testing and reporting patient results. METHODS: Beckman Coulter Access 2 instruments (n=41) across Kaiser Permanente Northern California were evaluated for their performance characteristics using the hCG5 reagent. Precision, linearity, dilution verification, and patient sample comparisons were performed on each instrument. RESULTS: The assay was linear up to 1350IU/L. Intra-day and inter-day precision ranged from 1.0%-3.3% and 1.8-7.3%, respectively, for the low QC material (mean concentration 4.6IU/L). Percent bias between the previous assay (hCG2) and the hCG5 assay was 3.2 to 22.7% for hCG concentrations <1000IU/L and -2.9 to 30% for concentrations >1000IU/L. On board and manual dilutions agreed within 15% following proper adjustment of the instrument dilution factor. CONCLUSIONS: Achieving Access 2 inter-instrument agreement on specimens needing dilutions (hCG>1350IU/L) requires validation of the on board dilution factor. Laboratories should use QC material above the linear range to monitor instrument dilution accuracy and precision.

Challenges in harmonizing integrated healthcare network laboratories: Multi-center evaluation of the AccuTnI+3 troponin assay.

BACKGROUND: Beckman Coulter has recently introduced a new troponin assay manufactured for the Access2 and DxI platforms, releasing it under the name AccuTnI+3. Clinical laboratories are required to validate method performance before testing and reporting patient results. METHODS: Beckman Coulter Access 2 instruments (n=42) across Kaiser Permanente Northern California were evaluated for their performance characteristics using the AccuTnI+3 reagent. Precision, linearity, and patient sample comparisons were performed on each instrument. Limit of the blank (LOB), limit of detection (LOD), limit of quantitation (LOQ), serum plasma comparisons, and specimen stability were evaluated using a single instrument. RESULTS: The assay was linear from 0-100,000ng/L. The LOB, LOD and LOQ were determined to be 5, 8 and 20ng/L, respectively. Interday precision on the low QC (mean concentration 41ng/L) ranged from 3.0% to 14.2%. The bias observed between the former assay (AccuTnI) and the AccuTnI+3 was comparable to the inter-instrument bias for either assay. Non-uniform distribution was observed in the precision and inter-instrument/inter-assay comparisons among the instruments evaluated. CONCLUSIONS: The AccuTnI and AccuTnI+3 troponin assays are equivalent across the analytical measuring range. There was no significant difference at the medical decision point. No changes in patient results are anticipated. However, the assay-independent inter-instrument bias observed is an important consideration for harmonization efforts.