Differential Viral Dynamics by Sex and Body Mass Index During Acute SARS-CoV-2 Infection: Results from a Longitudinal Cohort Study.

BACKGROUND: There is evidence of an association of severe COVID-19 outcomes with increased body mass index (BMI) and male sex. However, few studies have examined the interaction between sex and BMI on SARS-CoV-2 viral dynamics. METHODS: Participants conducted RT-PCR testing every 24-48 hours over a 15-day period. Sex and BMI were self-reported, and Ct values from E-gene were used to quantify viral load. Three distinct outcomes were examined using mixed effects generalized linear models, linear models, and logistic models, respectively: all Ct values (Model 1); nadir Ct value (model 2); and strongly detectable infection (at least one Ct value ≤28 during their infection) (Model 3). An interaction term between BMI and sex was included, and inverse logit transformations were applied to quantify the differences by BMI and sex using marginal predictions. RESULTS: In total, 7,988 participants enrolled in this study, and 439 participants (Model 1) and 309 (Model 2 and 3) were eligible for these analyses. Among males, increasing BMI was associated with lower Ct values in a dose-response fashion. For participants with BMIs greater than 29, males had significantly lower Ct values and nadir Ct values than females. In total, 67.8% of males and 55.3% of females recorded a strongly detectable infection; increasing proportions of men had Ct values <28 with BMIs of 35 and 40. CONCLUSIONS: We observed sex-based dimorphism in relation to BMI and COVID-19 viral load. Further investigation is needed to determine the cause, clinical impact, and transmission implications of this sex-differential effect of BMI on viral load.

Performance of Rapid Antigen Tests to Detect Symptomatic and Asymptomatic SARS-CoV-2 Infection : A Prospective Cohort Study.

BACKGROUND: The performance of rapid antigen tests (Ag-RDTs) for screening asymptomatic and symptomatic persons for SARS-CoV-2 is not well established. OBJECTIVE: To evaluate the performance of Ag-RDTs for detection of SARS-CoV-2 among symptomatic and asymptomatic participants. DESIGN: This prospective cohort study enrolled participants between October 2021 and January 2022. Participants completed Ag-RDTs and reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 every 48 hours for 15 days. SETTING: Participants were enrolled digitally throughout the mainland United States. They self-collected anterior nasal swabs for Ag-RDTs and RT-PCR testing. Nasal swabs for RT-PCR were shipped to a central laboratory, whereas Ag-RDTs were done at home. PARTICIPANTS: Of 7361 participants in the study, 5353 who were asymptomatic and negative for SARS-CoV-2 on study day 1 were eligible. In total, 154 participants had at least 1 positive RT-PCR result. MEASUREMENTS: The sensitivity of Ag-RDTs was measured on the basis of testing once (same-day), twice (after 48 hours), and thrice (after a total of 96 hours). The analysis was repeated for different days past index PCR positivity (DPIPPs) to approximate real-world scenarios where testing initiation may not always coincide with DPIPP 0. Results were stratified by symptom status. RESULTS: Among 154 participants who tested positive for SARS-CoV-2, 97 were asymptomatic and 57 had symptoms at infection onset. Serial testing with Ag-RDTs twice 48 hours apart resulted in an aggregated sensitivity of 93.4% (95% CI, 90.4% to 95.9%) among symptomatic participants on DPIPPs 0 to 6. When singleton positive results were excluded, the aggregated sensitivity on DPIPPs 0 to 6 for 2-time serial testing among asymptomatic participants was lower at 62.7% (CI, 57.0% to 70.5%), but it improved to 79.0% (CI, 70.1% to 87.4%) with testing 3 times at 48-hour intervals. LIMITATION: Participants tested every 48 hours; therefore, these data cannot support conclusions about serial testing intervals shorter than 48 hours. CONCLUSION: The performance of Ag-RDTs was optimized when asymptomatic participants tested 3 times at 48-hour intervals and when symptomatic participants tested 2 times separated by 48 hours. PRIMARY FUNDING SOURCE: National Institutes of Health RADx Tech program.

Design and implementation of a digital site-less clinical study of serial rapid antigen testing to identify asymptomatic SARS-CoV-2 infection.

Background: Rapid antigen detection tests (Ag-RDT) for SARS-CoV-2 with emergency use authorization generally include a condition of authorization to evaluate the test's performance in asymptomatic individuals when used serially. We aim to describe a novel study design that was used to generate regulatory-quality data to evaluate the serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals. Methods: This prospective cohort study used a siteless, digital approach to assess longitudinal performance of Ag-RDT. Individuals over 2 years old from across the USA with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Participants throughout the mainland USA were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported. Key Results: A total of 7361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 US states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide. Conclusions: The digital site-less approach employed in the "Test Us At Home" study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19 and can be adapted across research disciplines to optimize study enrollment and accessibility.

Finding a Needle in a Haystack: Design and Implementation of a Digital Site-less Clinical Study of Serial Rapid Antigen Testing to Identify Asymptomatic SARS-CoV-2 Infection.

Background: Rapid antigen tests (Ag-RDT) for SARS-CoV-2 with Emergency Use Authorization generally include a condition of authorization to evaluate the test's performance in asymptomatic individuals when used serially. Objective: To describe a novel study design to generate regulatory-quality data to evaluate serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals. Design: Prospective cohort study using a decentralized approach. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Setting: Participants throughout the mainland United States were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Ag-RDTs were completed at home, and molecular comparators were shipped to a central laboratory. Participants: Individuals over 2 years old from across the U.S. with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Measurements: Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported. Key Results: A total of 7,361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 U.S. states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide. Limitations: New, complex workflows required significant operational and data team support. Conclusions: The digital site-less approach employed in the 'Test Us At Home' study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19, and can be adapted across research disciplines to optimize study enrollment and accessibility.

Performance of Rapid Antigen Tests to Detect Symptomatic and Asymptomatic SARS-CoV-2 Infection.

Background: Performance of rapid antigen tests for SARS-CoV-2 (Ag-RDT) varies over the course of an infection, and their performance in screening for SARS-CoV-2 is not well established. We aimed to evaluate performance of Ag-RDT for detection of SARS-CoV-2 for symptomatic and asymptomatic participants. Methods: Participants >2 years old across the United States enrolled in the study between October 2021 and February 2022. Participants completed Ag-RDT and molecular testing (RT-PCR) for SARS-CoV-2 every 48 hours for 15 days. This analysis was limited to participants who were asymptomatic and tested negative on their first day of study participation. Onset of infection was defined as the day of first positive RT-PCR result. Sensitivity of Ag-RDT was measured based on testing once, twice (after 48-hours), and thrice (after 96 hours). Analysis was repeated for different Days Post Index PCR Positivity (DPIPP) and stratified based on symptom-status. Results: In total, 5,609 of 7,361 participants were eligible for this analysis. Among 154 participants who tested positive for SARS-CoV-2, 97 were asymptomatic and 57 had symptoms at infection onset. Serial testing with Ag-RDT twice 48-hours apart resulted in an aggregated sensitivity of 93.4% (95% CI: 89.1-96.1%) among symptomatic participants on DPIPP 0-6. Excluding singleton positives, aggregated sensitivity on DPIPP 0-6 for two-time serial-testing among asymptomatic participants was lower at 62.7% (54.7-70.0%) but improved to 79.0% (71.0-85.3%) with testing three times at 48-hour intervals. Discussion: Performance of Ag-RDT was optimized when asymptomatic participants tested three-times at 48-hour intervals and when symptomatic participants tested two-times separated by 48-hours.

Utility of Whole Blood Real-Time PCR Testing for the Diagnosis of Early Lyme Disease.

OBJECTIVES: Whole blood real-time polymerase chain reaction (WB-RTPCR) detection of Borrelia burgdorferi is not currently recommended for diagnosing Lyme disease. This study aims to elucidate the utility of WB-RTPCR as a diagnostic aid for early Lyme disease (ELD), defined as either positive PCR or positive immunoglobulin M with negative immunoglobulin G immunoblot. METHODS: A retrospective analysis was performed on 33,199 blood specimens evaluated concurrently by WB-RTPCR and antibody-capture serology (ACEIA) methods (group A). Fifty-six pairs of specimens from a separate data set were retrospectively identified and analyzed at initial and follow-up time points to monitor for seroconversion (group B). Also, a separate data set of 2,526 specimens concurrently assessed by molecular and modified two-tiered enzyme-linked immunosorbent assay serology methods was analyzed (group C). RESULTS: Group A yielded 1,379 specimens consistent with ELD when tested by ACEIA and WB-RTPCR. In total, 131 (9.5% of positive results) were identified by WB-RTPCR, with negative serology. Group C identified 358 samples compatible with ELD, with 31 (8.7% of positive results) identified by RTPCR alone. CONCLUSIONS: When used concurrently with serologic testing, WB-RTPCR testing increases diagnostic sensitivity in cases of ELD.

A Comparison of Lyme Serological Testing Platforms with a Panel of Clinically Characterized Samples from Various Stages of Lyme Disease.

BACKGROUND: In 2019, the CDC updated serology testing guidelines for Lyme disease diagnosis to include alternative modified two-tiered testing that replaces the western blots of standard testing with an additional ELISA. Antibody-capture serological assays have also been used as an aid for Lyme diagnosis. A panel of clinically characterized samples from the CDC was tested to compare modified two-tiered testing to the standard two-tiered algorithm and an antibody capture immunoassay. METHODS: A CDC panel of 92 samples comprised a range of samples including early Lyme, Lyme neuroborreliosis, Lyme arthritis, infections by other pathogens, and healthy controls. The panel was tested on a standard two-tiered platform by the CDC, the ZEUS Borrelia Test System for modified two-tiered testing, and a lab-developed antibody-capture serological assay. Sensitivity and specificity results from each assay were compared to determine significance. RESULTS: The antibody-capture assay demonstrated increased sensitivity but decreased specificity compared to the modified and standard two-tiered platforms. There was no statistical difference found between the modified and standard two-tiered platforms. CONCLUSIONS: Improved sensitivity of antibody-capture when testing early Lyme disease samples is offset by decreased specificity, especially with syphilis-positive samples. Modified two-tiered testing is similar to standard two-tiered methods while also being more scalable and simpler to interpret.

Association between liver and chronic kidney disease on hemoglobin A1c concentrations.

INTRODUCTION: HbA1c is the gold standard for measuring long-range glycemic control in patients with type-2 diabetes mellitus. Conditions such as CKD or LD can lead to spurious HbA1c test results. There is conflicting literature about the relationship between HbA1c, LD, and CKD. METHODS: Results for HbA1c concentrations were retrieved from 2015- to 2019. We evaluated over 2,500 test results with LD and 20,000 results with CKD compared to over 21,000 test results without LD, iron deficiency anemia, or CKD. Patients were classified as having LD if they had high ALT and AST concentrations and classified as CKD, if they have abnormal serum creatinine and BUN or low eGFR based on age-based reference ranges. Kruskal-Wallis statistical analyses method was used to test whether the two populations followed the same distribution and significance. RESULTS: The median HbA1c concentration was 5.8% (40 mmol/l) among LD classified patients in both males and females vs. 5.4% (36 mmol/l) (P < 0.001) for females and 5.6% (38 mmol/l) (P < 0.001) for males without LD. A significant difference in median HbA1c concentrations were also observed between CKD samples (female: 5.7% (39 mmol/l), male: 6.0% (42 mmol/l)) and non-CKD samples (female: 5.4% (36 mmol/l), male: 5.6% (38 mmol/l)) (P < 0.001). Depending on the population's CKD stage, median concentrations of % HbA1c are increased from stage-1 through stage-4 and fell in Stage-5. CONCLUSION: Patients with high AST and ALT concentrations or CKD can have increased HbA1c concentrations compared to normal patients. When using HbA1c concentrations to monitor diabetes, healthcare professionals should consider LD or CKD status before making any therapeutic decisions.

Large-scale retrospective analyses of the effect of iron deficiency anemia on hemoglobin A1c concentrations.

INTRODUCTION: HbA1c is a reliable biomarker for diagnosing and prognosis of diabetes, but many clinical scenarios and interfering factors can affect the test results. Any conditions that affect red cell turnover, such as iron-deficiency anemia (IDA), can lead to spurious HbA1c results. Reports on how IDA affects HbA1c concentrations are contradictory, and to understand better the association between HbA1c concentrations and IDA, we conducted a large-scale retrospective study. METHODS: Test results for HbA1c concentrations were retrieved from the years 2015-2019. We evaluated over 12,000 patients with IDA and 21,000 patients without IDA. Patients were classified as having IDA if samples with below the age-based ranges for serum iron, ferritin, or transferrin iron saturation and above age-based ranges for transferrin iron-binding capacity or transferrin concentrations. Kruskal-Wallis statistical analyses method was used to test whether the two samples follow the same distribution and significance. RESULTS: The median HbA1c concentration was 5.7% among IDA classified patients and 5.4% among normal samples (P < 0.001) for females. For males, the median HbA1c concentration was 6.0% among IDA classified patients and 5.6% among normal samples (P < 0.001). CONCLUSION: Patients classified as IDA can have increased HbA1c concentrations than patients without IDA. Clinicians should consider IDA status before making therapeutic decisions based on HbA1c concentrations.

Seroprevalence of SARS-CoV-2-Specific IgG Antibodies Among Adults Living in Connecticut: Post-Infection Prevalence (PIP) Study.

BACKGROUND: A seroprevalence study can estimate the percentage of people with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in the general population; however, most existing reports have used a convenience sample, which may bias their estimates. METHODS: We sought a representative sample of Connecticut residents, ages ≥18 years and residing in noncongregate settings, who completed a survey between June 4 and June 23, 2020, and underwent serology testing for SARS-CoV-2-specific immunoglobulin G (IgG) antibodies between June 10 and July 29, 2020. We also oversampled non-Hispanic black and Hispanic subpopulations. We estimated the seroprevalence of SARS-CoV-2-specific IgG antibodies and the prevalence of symptomatic illness and self-reported adherence to risk-mitigation behaviors among this population. RESULTS: Of the 567 respondents (mean age 50 [± 17] years; 53% women; 75% non-Hispanic white individuals) included at the state level, 23 respondents tested positive for SARS-CoV-2-specific antibodies, resulting in weighted seroprevalence of 4.0 (90% confidence interval [CI] 2.0-6.0). The weighted seroprevalence for the oversampled non-Hispanic black and Hispanic populations was 6.4% (90% CI 0.9-11.9) and 19.9% (90% CI 13.2-26.6), respectively. The majority of respondents at the state level reported following risk-mitigation behaviors: 73% avoided public places, 75% avoided gatherings of families or friends, and 97% wore a facemask, at least part of the time. CONCLUSIONS: These estimates indicate that the vast majority of people in Connecticut lack antibodies against SARS-CoV-2, and there is variation by race and ethnicity. There is a need for continued adherence to risk-mitigation behaviors among Connecticut residents to prevent resurgence of COVID-19 in this region.

Retrospective Analysis of Point-of-Care and Laboratory-Based Hemoglobin A1c Testing.

BACKGROUND: Glycemic control is essential to diabetic management, and hemoglobin A1c (Hb A1c) has long been used for this purpose. Though laboratory-based testing is standard, point-of-care (POC) systems provide rapid results in clinic, allowing more timely patient management. A negative bias with POC testing has been observed, and our aim is to further characterize these discrepancies at our institution. METHODS: A medical record search identified patients who underwent laboratory-based and/or POC Hb A1c testing (DCA Vantage™) at our medical center from July 2015 to April 2016. Patients who underwent both tests within 30 days were grouped by age, sex, and test interval (same day, <1 day, ≤15 days, or ≤30 days). Mean laboratory-based and POC values were compared using the paired t-test. Correlation statistics were determined using the Deming regression. RESULTS: In total, 40503 data points were gathered from the database, comprising 28555 laboratory-based Hb A1c tests and 11948 POC-based Hb A1c tests. A total of 28292 unique patients were identified, of which 493 underwent both tests within 30 days. While DCA and laboratory-based testing was highly correlated, there was a mean negative bias of 0.18% with POC testing. Bias was greater for women [0.17% higher (95% CI, 0.063%-0.284%), P = 0.002] and children aged 0-13 years [0.52% higher (95% CI, 0.141%-0.891%), P = 0.007]. CONCLUSIONS: There is a consistent negative bias with POC testing, most pronounced in the female and pediatric populations. Further studies will determine what variables contribute to this discrepancy and how clinical management is modified. POC testing using the DCA Vantage should be interpreted cautiously.

Comparison of Point-of-Care Activated Clotting Time Methods in Different Clinical Settings in a Large Academic Medical Center.

OBJECTIVES: This study is a comparative analysis of measured activated clotting time (ACT) values by use of 5 different point-of-care (POC) ACT methods spanning the range detected during different clinical procedures at our institution. METHODS: We determined the correlation, imprecision, and differences in measured ACT values with use of 4 POC ACT methods compared with a reference ACT method in 41 venous whole blood samples collected from 25 adult patients undergoing interventional procedures. The POC ACT methods evaluated included the i-STAT with kaolin activator in prewarm mode, i-STAT with Celite activator in prewarm and nonprewarm modes, ACTPlus, and HMSPlus, which was designated the reference method. Each venous whole blood patient sample was tested in duplicate on each POC ACT test system (total n = 410 ACT measurements). Analyses of imprecision and differences in measured ACT values were stratified by moderate (100-299 s) and high (≥300 s) ACT ranges. RESULTS: In this study population, measured ACT values ranged from 100-835 s with use of the HMSPlus. All methods demonstrated good correlation (r ≥ 0.95) in ACT values compared to the reference method. Imprecision varied by method with ranges of 1.7%-2.7% CV in the moderate ACT range and 2.5%-4.8% CV in the high ACT range. ACTPlus and i-STAT-Celite-prewarm methods exhibited proportional differences in measured ACT values whereas the i-STAT-Celite-nonprewarm and i-STAT-kaolin-prewarm demonstrated constant differences in measured ACT values compared to HMSPlus. CONCLUSIONS: ACT values correlate well between POC methods. Imprecision and difference profiles vary by method; notably, imprecision exceeds systematic differences in the high ACT range and contributes to intermethod differences that are limitations worthy of consideration when contemplating a change in ACT methods.

Utilization of assay performance characteristics to estimate hemoglobin A1c result reliability.

BACKGROUND: Allowable total error (TE(a)) goals for hemoglobin (Hb) A(1c) require minimal assay imprecision and bias and implementation of a robust QC monitoring program. Here, we compare the combined influence on the risk of reporting unreliable results of TE(a) goals, a routine QC practice, and assay performance characteristics of 6 Hb A(1c) instruments across 4 academic medical centers. METHODS: The CLSI protocols EP-5 and EP-9 were applied to investigate Hb A(1c) result imprecision and bias on the Variant II Turbo and Variant II (Bio-Rad), G8 (Tosoh), Capillarys 2 Flex Piercing (Sebia), COBAS Integra 800 (Roche), and DCA Vantage (Siemens). Patient-weighted σ values and the risk of reporting unreliable Hb A(1c) results were determined for each assay at TE(a) specifications of 5%, 6%, and 7%. RESULTS: A large range of patient-weighted σ values spanning 0.5 orders of magnitude at a 6% TE(a) was observed. Although imprecision for all instruments was <3%, bias impacted the majority of the σ changes observed. Estimates for reporting unreliable results varied almost 500-fold based on analytical performance alone. CONCLUSIONS: Considerable differences in the probability of reporting unreliable Hb A(1c) results between different NGSP (formerly the National Glycohemoglobin Standardization Program)-certified platforms were observed. At a 6% TE(a), our study indicates all but the Capillarys 2 Flex Piercing requires that the maximum affordable QC be run. Risk estimates for individual laboratories' Hb A(1c) methods can be used to assess QC practices and residual risk of an unreliable Hb A(1c) result.

Reducing analytical variation between point-of-care and laboratory HbA1c testing.

BACKGROUND: Point-of-care (POC) HbA1c testing allows for timely treatment changes, improved glycemic control, and patient and provider satisfaction. Substantial variation between POC and laboratory HbA1c results has been reported. At our university hospital diabetes clinic, we observed significant negative bias in HbA1c with the DCA Vantage (Siemens Healthcare Diagnostics, Tarrytown, NY, USA) compared with the Tosoh G8 HPLC laboratory analyzer (Tosoh Bioscience, San Francisco, CA, USA). This led us to systematically analyze the bias with the goal of recalibrating the DCA to minimize bias. METHODS: We analyzed 45 patient samples, with HbA1c ranging between 5% and 10.8%, concurrently on two DCA analyzers and on the Tosoh G8 machine. The bias for each sample was the difference between the value on the DCA and the Tosoh G8 analyzer. Based on regression equations derived from the data, a correction factor for each DCA analyzer was calculated. The analyzers were recalibrated and retested for bias. RESULTS: At baseline, the mean bias (range) was -0.5229 (+0.1 to -1.3) for Analyzer 1 and -0.5348 (0.0 to -1.6) for Analyzer 2. After recalibration, the mean bias (range) was 0.000 (+0.6 to -0.6) and 0.0003 (+0.5 to -0.5) for Analyzers 1 and 2, respectively, and the systematic negative bias seen prior to the calibration was almost eliminated. CONCLUSIONS: We recommend periodic recalibration of POC analyzers to eliminate systematic unidirectional bias and to harmonize results between the POC and central laboratory analyzers within a healthcare system. Calibration may need to be repeated with any change in the reagent lot.

Detection of macro-creatine kinase and macroamylase by polyethylene glycol precipitation and ultrafiltration methods.

BACKGROUND: Macroenzymes may cause elevations in serum enzyme activity. Macroenzymes are not common; however their detection is important because they cause diagnostic confusion and therapeutic errors. METHODS: We analyzed 2 of the most prevalent macroenzymes in the literature, macro-creatine kinase (macro-CK) and macroamylase, using 2 methods for detection, polyethylene glycol (PEG) precipitation and ultrafiltration (UF). Enzyme measurements were made using a Roche Modular Analytics P analyzer. Imprecision was assessed using quality control material. We evaluated 125 samples from apparently healthy subjects to establish reference intervals. For macro-CK comparison, 94 samples with activities >200 U/l were analyzed with both PEG precipitation and UF and compared to electrophoresis. PEG precipitation and UF were compared for macroamylase detection using 130 samples with amylase activities >110 U/l. RESULTS: UF was more precise and demonstrated narrower reference intervals for both analytes. PEG precipitation and UF were able to detect true cases of macro-CK with overall agreement with electrophoresis of 79.8% and 80.9%, respectively. Both methods detected the same number of 'positive' macroamylase samples; however PEG precipitation resulted in a greater number of 'indeterminate' cases. CONCLUSION: This is the first report where UF has been shown useful for the detection of both macro-CK and macroamylase.

Analytical validation of an HPLC assay for urinary albumin.

BACKGROUND: Microalbuminuria is the earliest clinical finding for renal disease. Diabetic individuals often produce modified forms of albumin, perhaps due to impaired lysosomal processing, that are undetectable by common immunoassays but accurately measured by HPLC. METHODS: We evaluated the performance of a commercially available, FDA-approved HPLC assay (AusAm Biotechnologies, NY) and compare results to our immunoturbidimetric assay (ITA, Beckman-Coulter, CA) using random urine specimens from 32 nondiabetic and 60 type 1 and 2 diabetic subjects. RESULTS: The HPLC assay was linear to 963 mg/l with a limit of detection of 6.1 mg/l. Within-run and between-run precision was <2% and 7-10%, respectively. Unpreserved urine was stable for at least 3 days at room temperature and 10 days at 4 degrees C. In both diabetic and nondiabetic subjects urinary albumin concentrations were higher by HPLC than by ITA, and many more diabetic and nondiabetic individuals were classified as microalbuminuric by HPLC than by ITA. The HPLC assay showed acceptable performance; however, because urinary albumin concentrations are higher in apparently healthy nondiabetic as well as diabetic subjects, different cutpoints will be necessary to accurately differentiate microalbuminuria. CONCLUSIONS: Prospective studies are necessary to determine whether the HPLC assay can effectively detect microalbuminuria earlier than current assays without a concomitant increase in the false positive rate.

Accuracy evaluation of a new glucometer with automated hematocrit measurement and correction.

BACKGROUND: Blood glucose meters are widely used in point of care testing, however, many studies have shown inaccuracies in the glucose measurement due to a number of factors. The present study evaluated the accuracy of a new glucometer capable of simultaneous measurement of patient's hematocrit with algorithmic adjustment of glucose result. This meter was compared with a reference method and 2 other existing meters widely used in the market. METHODS: Venous whole blood samples from healthy volunteers were pooled and reconstituted to produce 5 different hematocrit (30-60%) concentrations. Each hematocrit specimen was spiked to produce 4 different glucose (50-500 mg/dl) concentrations. RESULTS: Hematocrit measured by the new meter correlated well with the reference method. Mean percentage error differences, compared to the reference method, showed obvious differences between existing meters across the wide hematocrit range at various glucose concentrations. The new meter showed a steady and consistent glucose concentrations compared to the reference method. CONCLUSION: The new glucometer, which simultaneously measures hematocrit and performs automated correction for the hematocrit effect, provides a glucose result with improved accuracy. Its measurement of hematocrit from the same blood sample will eliminate the need for additional collection of blood or measurement using another method.

Gadolinium magnetic resonance contrast agents produce analytic interference in multiple serum assays.

Gadolinium magnetic resonance contrast agents are known to interfere with some clinical chemistry tests, particularly colorimetric assays for serum calcium. We studied the effects of 4 agents, gadodiamide, gadoversetamide, gadopentetate dimeglumine, and gadoteridol, for interference with multiple serum assays. Gadodiamide and gadoversetamide produced clinically significant negative interference with colorimetric assays for serum angiotensin-converting enzyme, calcium, and zinc. These agents produced clinically significant positive interference in magnesium and total iron binding capacity assays and both positive and negative interference in iron assays. Gadopentetate dimeglumine produced a negative interference with iron assays, and gadopentetate dimeglumine and gadoteridol produced negative interference with a colorimetric zinc assay. Caution should be exercised when using colorimetric assays for angiotensin-converting enzyme, calcium, iron, magnesium, total iron binding capacity, and zinc in serum samples from patients who have recently received magnetic resonance contrast agents. In general, gadodiamide and gadoversetamide are more likely to produce a clinically significant interference than gadopentetate dimeglumine and gadoteridol. Likewise, certain analytic methods are more prone to interference, while others not affected.