Bryant, Sandra C.

BackgroundThe cold agglutinin (CAGG) titer is offered at our institution to aid in diagnosing cold agglutinin disease (CAD). Our goal was to create a seasonally adjusted reference range using prospective samples and compare it to a reference range generated retrospectively.Study Design and MethodsProspective CAGG titer testing was performed on healthy blood donors. Retrospective electronic analysis was performed on patients in two groups defined by current and historical testing methods. Blood donor testing was performed in January and July to determine if seasonal variation existed. Retrospective patients with conditions associated with CAD were excluded from analysis. Additional prospective CAGG testing using reference range program volunteers was performed to verify blood donor and patient result differences.ResultsTiters from the blood donor and patient cohorts had no age association (p > 0.44). Titers from those same cohorts did not show winter/summer variation (p > 0.11). No sex association was found with titer reference ranges in the blood donor and historical patient cohort. A sex association was found with titers in the current method patient cohort (male 64 to 512 and female ≤64; p < 0.0001). Blood donor CAGG titer lower 95% reference range was not more than 4 while historical and current patient cohorts ranges were not more than 32 and not more than 64, respectively. Reference range volunteers confirmed the narrow reference range in healthy individuals when compared to patients and blood donors.ConclusionProspective blood donor CAGG titers were lower than retrospective patient cohorts. This may be due to blood donors representing a healthier population than the patient cohorts.

BACKGROUND Maintaining consistency of results over time is a challenge in laboratory medicine. Lot-to-lot reagent changes are a major threat to consistency of results. METHODS For the period October 2007 through July 2012, we reviewed lot validation data for each new lot of insulin-like growth factor 1 (IGF-1) reagents (Siemens Healthcare Diagnostics) at Mayo Clinic, Rochester, MN, and the University of Virginia, Charlottesville, VA. Analyses of discarded patient samples were used for comparison of lots. For the same period, we determined the distributions of reported patient results for each lot of reagents at the 2 institutions. RESULTS Lot-to-lot validation studies identified no reagent lot as significantly different from the preceding lot. By contrast, significant lot-to-lot changes were seen in the means and medians of 105 668 reported patient IGF-I results during the period. The frequency of increased results increased nearly 2-fold to a high of 17%, without detectable changes in the underlying patient demographics. Retrospective statistical analysis indicated that lot-to-lot comparison protocols were underpowered and that validation studies for this assay required testing &gt;100 samples to achieve 90% power to detect reagent lots that would significantly alter the distributions of patient results. CONCLUSIONS The number of test samples required for adequate lot-to-lot validation protocols is high and may be prohibitively large, especially for low-volume or complex assays. Monitoring of the distributions of patient results has the potential to detect lot-to-lot inconsistencies relatively quickly. We recommend that manufacturers implement remote monitoring of patient results from analyzers in multiple institutions to allow rapid identification of between-lot result inconsistency.

This descriptive population study of 307 public high school students, ages 15 to 17 years, was performed to establish reference ranges for orthostatic changes in heart rate and blood pressure in adolescents, and to identify influential variables. Noninvasive measurements of blood pressure and heart rate were obtained. Reference ranges for orthostatic heart rate change in this population at 2 minutes were –2 to +41 beats per minute and at 5 minutes were –1 to +48 beats per minute. Orthostatic blood pressure changes were within the adult range for 98% of adolescents tested. One-third of participants experienced orthostatic symptoms during testing. In conclusion, this study shows that orthostatic symptoms and large orthostatic heart rate changes occur in adolescents. This suggests that the current orthostatic heart rate criterion aiding the diagnosis of adult orthostatic intolerance syndromes is likely not appropriate for adolescents and should be reevaluated.

Abstract Background: Natriuretic peptide concentrations in adults require age- and sex-specific reference intervals for optimal interpretation. Females have higher natriuretic peptide concentrations, and hypotheses suggest that estrogen may be responsible. This study sought to determine the influence of hormone modulation on N-terminal probrain natriuretic peptide (NT-proBNP) by using a pediatric cohort. Children/adolescents typically have rapid hormone changes during puberty, making them an ideal group to study. Methods: We selected 759 specimens (303 male, 456 female; ages 2 months to 18 years, mean 13 years) obtained from the Mayo Clinic Pediatric Residual Specimen Bank. We measured NT-proBNP, sex hormone–binding globulin (SHBG), estradiol, and testosterone by immunoassays or LC-MS/MS and calculated free testosterone. We performed univariate and multivariate analyses to investigate the significance of NT-proBNP with each hormone. Results: Reference values demonstrated a sex difference and sequential age differences in females. Univariate modeling of the hormones with NT-proBNP revealed an independent inverse association of NT-proBNP with testosterone, a direct association with SHBG, and no significant association with estradiol. Multivariate modeling confirmed a strong association of testosterone and SHBG with NT-proBNP. Correlation of hormones with NT-proBNP retained greater significance than either age or sex. Conclusions: In pediatric patients, NT-proBNP is independently associated with both testosterone and SHBG hormone concentrations. Measurements of testosterone are inversely associated with NT-proBNP, and estrogens are marginally associated with NT-proBNP in males but not females, suggesting that androgens and not estrogens modulate sex differences notable in natriuretic peptides. Children and adolescents may require an objective assessment of hormones if optimal interpretation of natriuretic peptide concentrations is desired or the concentrations are confounded. .

Background. Statin Choice is a decision aid about taking statins. The optimal mode of delivering Statin Choice (or any other decision aid) in clinical practice is unknown. Methods. To investigate the effect of mode of delivery on decision aid efficacy, the authors further explored the results of a concealed 2 × 2 factorial clustered randomized trial enrolling 21 endocrinologists and 98 diabetes patients and randomizing them to 1) receive either the decision aid or pamphlet about cholesterol, and 2) have these delivered either during the office visit (by the clinician) or before the visit (by a researcher). We estimated between-group differences and their 95% confidence intervals (CI) for acceptability of information delivery (1—7), knowledge about statins and coronary risk (0—9), and decisional conflict about statin use (0—100) assessed immediately after the visit. Follow-up was 99%. Results. The relative efficacy of the decision aid v. pamphlet interacted with the mode of delivery. Compared with the pamphlet, patients whose clinicians delivered the decision aid during the office visit showed significant improvements in knowledge (difference of 1.6 of 9 questions, CI 0.3, 2.8) and nonsignificant trends toward finding the decision aid more acceptable (odds ratio 3.1, CI 0.9, 11.2) and having less decisional conflict (difference of 7 of 100 points, CI - 4, 18) than when a researcher delivered the decision aid just before the office visit. Conclusions. Delivery of decision aids by clinicians during the visit improves knowledge and shows a trend toward better acceptability and less decisional conflict.

Background . Clinicians often use validated risk models to guide treatment decisions for cardiovascular risk reduction. The most common risk models for predicting cardiovascular risk are the UKPDS, Framingham, and Archimedes models. In this article, the authors propose a model to optimize the selection of patients for statin therapy of hypercholesterolemia, for patients with type 2 diabetes, using each of the risk models. For each model, they evaluate the role of age, gender, and metabolic state on the optimal start time for statins. Method . Using clinical data from the Mayo Clinic electronic medical record, the authors construct a Markov decision process model with health states composed of cardiovascular events and metabolic factors such as total cholesterol and high-density lipoproteins. They use it to evaluate the optimal start time of statin treatment for different combinations of cardiovascular risk models and patient attributes. Results . The authors find that treatment decisions depend on the cardiovascular risk model used and the age, gender, and metabolic state of the patient. Using the UKPDS risk model to estimate the probability of coronary heart disease and stroke events, they find that all white male patients should eventually start statin therapy; however, using Framingham and Archimedes models in place of UKPDS, they find that for male patients at lower risk, it is never optimal to initiate statins. For white female patients, the authors also find some patients for whom it is never optimal to initiate statins. Assuming that age 40 is the earliest possible start time, the authors find that the earliest optimal start times for UKPDS, Framingham, and Archimedes are 50, 46, and 40, respectively, for women. For men, the earliest optimal start times are 40, 40, and 40, respectively. Conclusions . In addition to age, gender, and metabolic state, the choice of cardiovascular risk model influences the apparent optimal time for starting statins in patients with diabetes.

Abstract Background: The International Staging System for multiple myeloma has increased the importance of accurate measurement of serum albumin. Two common albumin assays, bromcresol green (BCG) and agarose gel protein electrophoresis (PEL), frequently yield discordant results, creating confusion regarding which assay is superior for use in myeloma. Methods: We measured albumin by BCG on a Roche Modular system, by PEL with a Helena SPIFE SPE Vis agarose gel, and by immunonephelometry performed on a Dade Behring BNII nephelometer. BCG and PEL were used to measure albumin in 5777 patient samples, and all 3 methods were used in an additional 252 samples. The clinical impact was assessed on 698 myeloma patient samples. Results: For sera with zero/low monoclonal immunoglobulin protein (M)-spike (0 to &lt;15 g/L), results for both BCG and PEL correlated well to nephelometry, although median PEL results were 8 g/L lower than corresponding BCG measurements. Correlation between PEL and nephelometry or BCG diminished with increasing M-spike, with PEL eventually overestimating albumin compared with both other assays. IgG and IgA M-spikes showed significantly different effects on albumin discordance. For 35% of myeloma patients, discrepancy between BCG and PEL had a potentially clinically significant effect on staging, but no difference in group survival was found. Conclusions: Both BCG and PEL correlate well to nephelometry in sera with zero/low M-spikes. In the presence of larger M-spikes, PEL correlates poorly to nephelometry or BCG, whereas BCG compares well with nephelometry regardless of M-spike. Thus, albumin measurement can be performed reliably in myeloma patient sera by use of inexpensive, automated BCG assays.

OBJECTIVE—The aim of this study was to determine personal characteristics and preferences that affect decision making (decisional attributes) in patients with diabetes. In particular, we were interested in relating these attributes to the choice of using aspirin to reduce cardiovascular risk. RESEARCH DESIGN AND METHODS—We conducted a cross-sectional survey (70% response rate) of 206 diabetic patients (median age, 63 years; 42% women; 91% completed high school; median HbA1c, 8%) attending a tertiary care diabetes clinic. Patients answered a 42-question survey exploring decisional attributes. Medical records provided the source of clinical information. We evaluated sociodemographic, clinical, and decisional predictors of aspirin use. We also conducted a multivariable analysis with aspirin use as a dependent variable. RESULTS—Sixty-seven percent of patients surveyed used aspirin. Patients using aspirin were at higher risk of cardiovascular disease (odds ratio 1.4, 95% CI 1.0–2.1), knew more about the benefits of aspirin (1.9, 1.4–2.6) and less about the risks of aspirin (1.4, 1.2–1.8), and were more certain about using aspirin (0.5, 0.3–0.8) than patients not using aspirin. Patients using aspirin placed a higher value on preventing cardiovascular events than on avoiding the side effects of aspirin. Patients perceived that their diabetes provider and the American Diabetes Association had greater influence on their decision to use aspirin than family members or other patients with diabetes. CONCLUSIONS—The decisional attributes of patients with diabetes are associated with aspirin use. Decisional attributes may be the target of research and interventions to reduce underutilization to levels consistent with patient preferences.