Effect of Using an Age-adjusted D-dimer to Assess for Pulmonary Embolism in Community Emergency Departments.

BACKGROUND: The objective of this study was to evaluate the effect of changing the laboratory-reported D-dimer reference intervals to age-adjusted reference intervals on the use of advanced chest imaging and 30-day adverse events among emergency department (ED) encounters. METHODS: A retrospective interrupted time-series analysis of ED encounters for patients > 50 years evaluated for suspected pulmonary embolism (PE) from April 2014 to April 2016. The primary outcome was use of advanced diagnostic imaging, and the secondary outcome was 30-day mortality or PE diagnosis. Secondary analyses also quantified delayed PE diagnoses pre- and postintervention. A generalized estimating equation segmented logistic regression model, adjusting for patient and facility characteristics, was used to determine changes in odds of diagnostic imaging and 30-day mortality or PE diagnoses. RESULTS: A total of 10,534 (5,153 pre- and 5,381 postimplementation) ED encounters were included. Advanced imaging was obtained in 35.9% of pre- versus 33% of postimplementation encounters. Age-adjusted D-dimer (AADD) showed a small and nonsignificant decrease in month-to-month trends of advanced chest imaging postimplementation (odds ratio [OR] = 0.98, 95% confidence interval [CI] = 0.96 to 1.00). Use of advanced imaging in patients with D-dimer values lower than 500 ng/mL fibrinogen-equivalent units (FEU) was similar in the preintervention (5.8%) and postintervention (6.8%) periods. However, imaging was obtained in 30% of patients postintervention with a D-dimer result less than AADD reference interval , but more than the historical 500 ng/mL FEU reference interval. Implementing an AADD threshold demonstrated no change in the rate of 30-day adverse events (missed PE or mortality). CONCLUSION: Changing the laboratory-reported D-dimer reference intervals for evaluation of PE was not associated with reduction in advanced chest imaging and did not increase 30-day adverse events. However, there was substantial noncompliance with the age-adjusted reference intervals in the postintervention period likely blunting the impact of this intervention.

Age-Dependent Hemoglobin A1c Therapeutic Targets Reduce Diabetic Medication Changes in the Elderly.

OBJECTIVE: To assess whether implementation of age-dependent therapeutic targets for high hemoglobin A1c (HbA1c) changed clinicians' ordering of diabetes medications for older adults. BACKGROUND: In 2016, Kaiser Permanente Southern California (KPSC) changed the therapeutic targets for alerting clinicians about high HbA1c results in the electronic health record, KP HealthConnect (KPHC). Previously, all HbA1c results ≥7.0 percent were flagged as high in adult patients with diabetes. Starting in 2016, HbA1c therapeutic targets were relaxed to <7.5 percent for patients age 65 to 75, and to <8.0 percent for patients over age 75 to reduce treatment intensity and adverse events. METHODS: This retrospective analysis used logistic regression models to calculate the change in odds of a medication change following an HbA1c result after age-dependent HbA1c flags were introduced. RESULTS: The odds of medication change decreased among patients whose HbA1c targets were relaxed: Odds Ratio (OR) 0.72 (95 percent CI 0.67-0.76) for patients age 65-75 and HbA1c 7.0 percent-7.5 percent; OR 0.72 (95 percent CI 0.65-0.80) for patients over age 75 and HbA1c 7.0 percent-7.5 percent; and OR 0.67 (95 percent CI 0.61-0.75) for patients over age 75 and HbA1c 7.5 percent-8.0 percent. In the age and HbA1c ranges for which the alerts did not change, the odds of medication change generally increased or stayed the same. There was little evidence of medication de-intensification in any group. CONCLUSIONS: These findings suggest that the change in therapeutic targets was associated with a reduction in medication intensification among older adults with diabetes.

Accuracy-Based Vitamin D Survey: Six Years of Quality Improvement Guided by Proficiency Testing.

CONTEXT.­: The goal of the College of American Pathologists Accuracy-Based Proficiency Testing Program is to promote the quality, standardization, and harmonization of clinical laboratory results through proficiency testing specimens that are free from matrix effects, have target values that are traceable to reference methods, and that probe the limitations of current methods. OBJECTIVE.­: To summarize the first 6 years of the Accuracy-Based Vitamin D Survey and highlight key insights from the data generated as it relates to assay performance. DESIGN.­: Accuracy-based challenges were created by using pooled human serum samples. Certain samples were derived from participants in an institutional review board-approved protocol in which vitamin D-deficient participants were treated with ergocalciferol (vitamin D2). Reference targets for the survey were set by the Centers for Disease Control and Prevention using isotope-dilution liquid chromatography-tandem mass spectrometry. Each method was compared with the reference method procedure over the course of the program (n = 43 proficiency testing samples). RESULTS.­: Linear regression versus the reference method procedure revealed proportional biases across the methods, ranging from 0.0% to 16.7%. Pearson correlation coefficients (r2) ranged from 0.902 to 0.996. Results were influenced by the concentration of 25-hydroxyvitamin D2 as well as the C-3 epimer of 25-hydroxyvitamin D3. During the 6 years, 2 manufacturers altered their assays to match the reference method procedure more closely. CONCLUSIONS.­: There is considerable bias, both proportional bias and sample-specific matrix effects, affecting many assays. This ongoing accuracy-based proficiency testing program for vitamin D will provide the data needed for laboratories and manufacturers to improve their assays and thereby patient care.

Trends in Prostate-specific Antigen Screening, Prostate Biopsies, Urology Visits, and Prostate Cancer Treatments From 2000 to 2012.

OBJECTIVE: To determine whether the rates of prostate-specific antigen (PSA) screening, related biopsies and subsequent prostate cancer utilization decreased between 2000 and 2012 in a large, managed care organization. METHODS: Male members of Kaiser Permanente Southern California who were aged ≥40 years and had no history of prostate cancer (N = 15,326) were passively followed through electronic health plan files from January 1, 2000, through December 31, 2012 (N = 1,539,469). The rates of PSA testing, elevated PSA tests, prostate biopsies, prostate cancer treatment (surgery and radiation), and urology visits were calculated per year among eligible men and stratified by age group. RESULTS: A 59% decrease in PSA screening occurred among men aged ≥75 years beginning in 2008, followed by 49% in ages 65-74, 20% in ages 50-64, and 33% in ages 40-49 years in 2009. However, the number of elevated PSA tests remained largely unchanged in all groups except in men aged ≥75 years (45% decrease). Prostate biopsy rates and urology visits remained consistent among elderly men. CONCLUSION: Among men in this managed care setting, although there was a sharp decline in PSA testing among men aged ≥75 years after 2008, prostate biopsy rates remained constant, and subsequent prostate cancer treatment remained highest among men in this age group. These results suggest that the guidelines recommending against PSA and the subsequent provider-targeted interventions implemented in this system resulted in decreased screening across age groups and potentially led to more discriminant screening among those aged ≥75 years.

Multilectin affinity chromatography for characterization of multiple glycoprotein biomarker candidates in serum from breast cancer patients.

BACKGROUND: Glycoproteins are often associated with cancer and are important in serum studies, for which glycosylation is a common posttranslational modification. METHODS: We used multilectin affinity chromatography (M-LAC) to isolate glycoproteins from the sera of breast cancer patients and controls. The proteins were identified by HPLC-tandem mass spectrometry (MS/MS) analysis of the corresponding tryptic digests. We used the FuncAssociate Gene Ontology program for association analysis of the identified proteins. Biomarker candidates in these groups were comparatively quantitated by use of peak area measurements, with inclusion of an internal standard. We analyzed data for concordance within the ontology association groups for vector of change with the development of breast cancer. RESULTS: Detection of the known low-concentration biomarker HER-2 (8-24 mug/L) enabled us to establish a dynamic range of 10(6), relative to the amount of albumin, for the depletion step. We then used ELISA to confirm this range. Proteins associated with lipid transport and metabolism, cell growth and maintenance, ion homeostasis, and protease inhibition were found to be differentially regulated in serum from women with breast cancer compared with serum from women without breast cancer. CONCLUSIONS: M-LAC for isolation of the serum glycoproteome, coupled with liquid chromatography-MS/MS and the use of gene ontology associations, can be used to characterize large panels of candidate markers, which can then be evaluated in a particular patient population.

Total long-term within-laboratory precision of cortisol, ferritin, thyroxine, free thyroxine, and thyroid-stimulating hormone assays based on a College of American Pathologists fresh frozen serum study: do available methods meet medical needs for precision?

CONTEXT: It is important that the total long-term precision of laboratory methods meet the medical needs of the patients being served. OBJECTIVES: To determine the long-term within- and between-laboratory variation of cortisol, ferritin, thyroxine, free thyroxine, and thyroid-stimulating hormone measurements using commonly available methods and to determine if these variations are within accepted medical needs. DESIGN: Two vials of pooled frozen serum were mailed 6 months apart to laboratories participating in 2 separate College of American Pathologists surveys. The data from those laboratories that analyzed an analyte in both surveys were used to determine for each method the total variance and the within- and between-laboratory components. SETTING: The study included the A mailing of the 2003 College of American Pathologists Ligand Survey and the C mailing of the Chemistry Survey. MAIN OUTCOME MEASURES: For each analyte, total variance was partitioned into within- and between-laboratory components for each analytic method. The within-laboratory variations were then compared with imprecision criteria based on biological variation. PARTICIPANTS: The laboratories that reported results on the same analyte using the same method in both surveys. RESULTS: For each analyte, the median of the long-term within-laboratory variances of each peer group was 78% to 95% of its total-survey variance, and the median long-term within-laboratory coefficients of variation varied from 5.1% to 7.6%. The number of methods that met within-laboratory imprecision goals based on biological criteria were 5 of 5 for cortisol; 5 of 7 for ferritin; 0 of 7 for thyroxine and free thyroxine; and 8 of 8 for thyroid-stimulating hormone. CONCLUSIONS: For all analytes tested, the total within-laboratory component of variance was the major source of variability in this study. In addition, there are several methods, especially for thyroxine and free thyroxine, that may not meet analytic goals in terms of their imprecision.