European Multicenter Study on Analytical Performance of Veris HIV-1 Assay.

The analytical performance of the Veris HIV-1 assay for use on the new, fully automated Beckman Coulter DxN Veris molecular diagnostics system was evaluated at 10 European virology laboratories. The precision, analytical sensitivity, performance with negative samples, linearity, and performance with HIV-1 groups/subtypes were evaluated. The precision for the 1-ml assay showed a standard deviation (SD) of 0.14 log10 copies/ml or less and a coefficient of variation (CV) of ≤6.1% for each level tested. The 0.175-ml assay showed an SD of 0.17 log10 copies/ml or less and a CV of ≤5.2% for each level tested. The analytical sensitivities determined by probit analysis were 19.3 copies/ml for the 1-ml assay and 126 copies/ml for the 0.175-ml assay. The performance with 1,357 negative samples demonstrated 99.2% with not detected results. Linearity using patient samples was shown from 1.54 to 6.93 log10 copies/ml. The assay performed well, detecting and showing linearity with all HIV-1 genotypes tested. The Veris HIV-1 assay demonstrated analytical performance comparable to that of currently marketed HIV-1 assays. (DxN Veris products are Conformité Européenne [CE]-marked in vitro diagnostic products. The DxN Veris product line has not been submitted to the U.S. FDA and is not available in the U.S. market. The DxN Veris molecular diagnostics system is also known as the Veris MDx molecular diagnostics system and the Veris MDx system.).

European Multicenter Study on Analytical Performance of DxN Veris System HCV Assay.

The analytical performance of the Veris HCV Assay for use on the new and fully automated Beckman Coulter DxN Veris Molecular Diagnostics System (DxN Veris System) was evaluated at 10 European virology laboratories. Precision, analytical sensitivity, specificity, and performance with negative samples, linearity, and performance with hepatitis C virus (HCV) genotypes were evaluated. Precision for all sites showed a standard deviation (SD) of 0.22 log10 IU/ml or lower for each level tested. Analytical sensitivity determined by probit analysis was between 6.2 and 9.0 IU/ml. Specificity on 94 unique patient samples was 100%, and performance with 1,089 negative samples demonstrated 100% not-detected results. Linearity using patient samples was shown from 1.34 to 6.94 log10 IU/ml. The assay demonstrated linearity upon dilution with all HCV genotypes. The Veris HCV Assay demonstrated an analytical performance comparable to that of currently marketed HCV assays when tested across multiple European sites.

Absolute and relative changes (delta) in troponin I for early diagnosis of myocardial infarction: Results of a prospective multicenter trial.

OBJECTIVES: We investigated absolute and relative cardiac troponin I (TnI) delta changes, optimal sampling protocols, and decision thresholds for early diagnosis of myocardial infarction (MI). Serial cardiac biomarker values demonstrating a rise and/or fall define MI diagnosis; however the magnitude of change, timing, and diagnostic accuracy of absolute versus relative (percentage) deltas remains unsettled. METHODS: We prospectively measured TnI (AccuTnI+3™, Beckman Coulter) at serial time intervals in 1929 subjects with chest pain or equivalent symptoms of acute coronary syndrome at 14 medical centers. Diagnosis was adjudicated by an independent central committee. RESULTS: Elevated TnI above a threshold of 0.03ng/mL demonstrated significant diagnostic efficacy (AUC 0.96). For patients with TnI<0.03ng/mL and symptom onset≥8h, 99.1% (NPV) were diagnosed with conditions other than MI. Absolute delta performed significantly better than relative delta at 1-3h (AUC 0.84 vs 0.69), 3-6h (0.85 vs 0.73), and 6-9h (0.91 vs 0.79). Current recommendations propose ≥20% delta within 3-6h; however, results were optimized using an absolute delta of 0.01 or 0.02ng/mL. Sensitivity results for absolute delta at 1-3h and 3-6h (75.8%, 78.3%) were superior to relative delta (48.0%, 61.3%). NPV (rule out) was 99.6% when baseline TnI<0.03ng/mL and absolute delta TnI<0.01ng/mL. CONCLUSIONS: Absolute delta performed significantly better than relative delta at all time intervals. Baseline TnI and absolute delta may be used in conjunction to estimate probability of MI. Consensus recommendations are supported for sampling on admission and 3h later, repeated at 6h in patients when clinical suspicion remains high.

Diagnostic performance of cardiac Troponin I for early rule-in and rule-out of acute myocardial infarction: Results of a prospective multicenter trial.

OBJECTIVES: To compare emergency department TnI serial sampling intervals, determine optimal diagnostic thresholds, and report representative diagnostic performance characteristics for early rule-in and rule-out of MI. METHODS: We prospectively measured TnI (AccuTnI+3™, Beckman Coulter) at serial time intervals in 1929 subjects with chest pain or equivalent ischemic symptoms suggestive of acute coronary syndromes at 14 medical centers. Diagnosis was adjudicated by an independent central committee. RESULTS: TnI ≥0.03ng/mL provided 96.0% sensitivity and 89.4% specificity at 1-3h after admission, and 94.9% sensitivity and 86.7% specificity at 3-6h. NPV (rule-out, non-MI) was 99.5% at 1-3h, and 99.0% at 3-6h when TnI is <0.03ng/mL. NPV was 99.1% when TnI is <0.03ng/mL and time of symptom onset is ≥8h. Approximately 50-58% (PPV) of patients with TnI ≥0.03ng/mL were diagnosed with MI, depending upon time from onset or admission; PPVs emphasize the importance of serial samples and delta TnI (rising or falling pattern) when low cutoffs are used. Nevertheless, even a single elevated TnI value increased the risk of MI. As TnI values rose, the probability of MI increased. Values ≥0.20ng/mL were associated with nearly 90% probability of MI. CONCLUSIONS: We report a large multicenter prospective adjudicated trial assessing troponin for early rule-in and rule-out using the Universal Definition of MI and conducted in primary care hospital-associated emergency departments. Our study demonstrates high diagnostic accuracy at early observation times, and reinforces consensus recommendations for sampling on admission and 3h later, repeated at 6h when clinical suspicion remains high.

Prospective evaluation of pregnancy-associated plasma protein-a and outcomes in patients with acute coronary syndromes.

OBJECTIVES: This study sought to investigate whether pregnancy-associated plasma protein-A (PAPP-A) is useful for risk assessment in non-ST-segment elevation acute coronary syndrome (NSTE-ACS). BACKGROUND: PAPP-A is a high molecular weight, zinc-binding metalloproteinase that is associated with vulnerable plaque and may be a predictor of cardiovascular disease and mortality. METHODS: We measured PAPP-A at baseline in 3,782 patients with non NSTE-ACS randomized to ranolazine or placebo in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes) trial and followed for an average of 1 year. A cut point of 6.0 µIU/ml was chosen from pilot work in this cohort. RESULTS: PAPP-A >6.0 µIU/ml at presentation was associated with higher rates of cardiovascular death (CVD) or myocardial infarction (MI) at 30 days (7.4% vs. 3.7%, hazard ratio [HR]: 2.01; 95% confidence interval [CI]: 1.43 to 2.82; p < 0.001) and at 1 year (14.9% vs. 9.7%, HR: 1.63; 95% CI: 1.29 to 2.05; p < 0.001). PAPP-A was also associated with higher rates of CVD (HR: 1.94; 95% CI: 1.07 to 3.52, p = 0.027) and myocardial infarction (HR: 1.82; 95% CI: 1.22 to 2.71, p = 0.003) individually at 30 days. There was no difference in the risk associated with PAPP-A stratified by baseline cardiac troponin I [Accu-TnI >0.04 µg/l], p interaction = 0.87). After adjustment for cardiac troponin I, ST-segment deviation, age, sex, diabetes, smoking, hypertension, and coronary artery disease, PAPP-A was independently associated with CVD/myocardial infarction at 30 days (adjusted HR: 1.62, 95% CI: 1.15 to 2.29; p = 0.006) and 1 year (adjusted HR: 1.35, 95% CI: 1.07 to 1.71; p = 0.012). PAPP-A also improved the net reclassification for CVD/MI (p = 0.003). There was no significant interaction with ranolazine. CONCLUSIONS: PAPP-A was independently associated with recurrent cardiovascular events in patients with NSTE-ACS. This finding supports PAPP-A as a candidate prognostic marker in patients with ACS and supports investigation of its therapeutic implications.