A Multicenter Evaluation of a Nongel Mechanical Separator Plasma Blood Collection Tube for Testing of Selected Therapeutic Drugs.

BACKGROUND: Some therapeutic drugs are unstable during sample storage in gel tubes. BD Vacutainer® Barricor™ Plasma Blood Collection Tube with nongel separator was compared with plasma gel tubes, BD Vacutainer PST™, PST II, and BD Vacutainer Serum Tube for acetaminophen, salicylate, digoxin, carbamazepine, phenytoin, valproic acid, and vancomycin during sample storage for up to 7 days. METHODS: Seven hospital sites enrolled 705 participants who were taking at least one selected drug. The study tubes were collected and tested at initial time (0 h), after 48 h of storage at room temperature and on day 7 (after additional 5 days of refrigerated storage). The performance of BD Barricor tube was evaluated for each drug by comparing BD Barricor samples with samples from the other tubes at 0 h from the same participant; stability was evaluated by comparing test results from the same tube at 0 h, 48 h, and 7 days. RESULTS: At 0 h, BD Barricor showed clinically equivalent results for selected therapeutic drugs compared with the other tubes, except phenytoin in BD PST. Phenytoin samples ≥20 µg/mL in BD PST had 10-12% lower values than samples in BD Barricor. During sample storage, all selected drugs remained stable for 7 days in BD Barricor and in serum aliquots. In BD PST, all drugs remained stable except phenytoin and carbamazepine and in BD PST II except for phenytoin. CONCLUSION: The BD Barricor Tube is effective for the collection and storage of plasma blood samples for therapeutic drug monitoring without sample aliquoting.

Analytical and Clinical Performance Evaluation of the Elecsys HIV combi PT Assay on the cobas e 602 Analyzer for the Diagnosis of Human Immunodeficiency Virus.

OBJECTIVES: We evaluated the performance of the Elecsys HIV combi PT assay on the cobas e 602 analyzer for diagnosing human immunodeficiency virus (HIV; part of the US Food and Drug Administration [FDA] submission). METHODS: The HIV combi PT and reference (ARCHITECT HIV Ag/Ab Combo) assays were assessed at four independent clinical laboratories/one reference laboratory (United States; July 2014 to November 2015). Clinical performance was evaluated using four reagent lots. Analytical performance was evaluated per Clinical and Laboratory Standards Institute EP05-A3 guidelines. Serum/plasma samples from 18 clinical sites/vendors (United States and outside the United States) were tested. RESULTS: Sensitivity (95% confidence interval [CI]) in HIV-1 antibody-positive individuals (United States and outside the United States; n = 1,460) was 100.00% (99.75%-100.00%). Specificity was 99.94% (95% CI, 99.85%-99.98%) in low-risk individuals (United States; n = 6,843), 98.19% (95% CI, 96.93%-99.04%) in high-risk individuals (United States and outside the United States; n = 758), and 97.43% (95% CI, 95.32%-98.76%) in pregnant women (United States and outside the United States; n = 440). Analytical performance was acceptable. CONCLUSIONS: We demonstrate the robustness of the FDA-approved Elecsys HIV combi PT assay on the cobas e 602 analyzer for HIV testing in the United States.

Evaluation of Pain and Specimen Quality by Use of a Novel 25-Gauge Blood Collection Set With Ultra-Thin Wall Cannula and 5-Bevel Tip Design.

BACKGROUND: Phlebotomy has significant impact on overall patient satisfaction. Smaller gauge needles, such as a 25 gauge, may lessen patient discomfort but increase hemolysis and tube-filling times. Our studies evaluated the effect of a 5-bevel, 25-gauge blood collection set (BCS) with ultra-thin wall cannula [BD Vacutainer® UltraTouch™ Push Button BCS (UltraTouch)] on patient pain and anxiety compared with two 3-bevel, thin-wall, 23-gauge BCSs [BD Vacutainer® Safety-Lok™ (Safety-Lok) and Greiner Bio-One Vacuette® (Vacuette)]. Our studies also evaluated the 25-gauge UltraTouch for sample quality and tube filling compared with the 3-bevel, thin-wall, 23-gauge BD Vacutainer Push Button BCS. METHODS: We conducted 2 studies with 214 subjects to compare pain and anxiety regarding future phlebotomy with the 3 aforementioned devices. Another study with 52 subjects assessed hemolysis in specimens collected with the UltraTouch and Push Button BCS; bench testing evaluated tube-filling times with these devices. A questionnaire captured pain upon needle insertion, overall pain, and anxiety regarding future phlebotomy. Hemolysis was evaluated visually, by Hemolysis Index and hemolysis-sensitive indicators potassium (K) and lactate dehydrogenase (LDH). RESULTS: A statistically significant decrease was noted for overall pain with UltraTouch compared with Vacuette and with insertion pain compared with Safety-Lok. There was no significant difference in anxiety regarding future phlebotomy. No increase was observed in Hemolysis Index, K or LDH. Tube-filling times were comparable for each device. CONCLUSIONS: The 25-gauge UltraTouch provided less overall pain compared with the 23-gauge Vacuette, less pain upon needle insertion than the 23-gauge Safety-Lok, and no compromise in specimen quality or flow rate.

Comparison of 13 Commercially Available Cardiac Troponin Assays in a Multicenter North American Study.

BACKGROUND: We examined the concordance of 13 commercial cardiac troponin (cTn) assays [point-of-care, high-sensitivity (hs), and conventional] using samples distributed across a continuum of results. METHODS: cTnI (11 assays) and cTnT (2 assays) were measured in 191 samples from 128 volunteers. cTn assays included Abbott (iSTAT, STAT, and hs), Alere (Cardio 3), Beckman (AccuTnI+3), Pathfast (cTnI-II), Ortho (Vitros), Siemens (LOCI, cTnI-Ultra, Xpand, Stratus CS), and Roche [4th Generation (Gen), hs]. Manufacturer-derived 99th percentile cutoffs were used to classify results as positive or negative. Alternative 99th percentile cutoffs were tested for some assays. Correlation was assessed using Passing-Bablok linear regression, bias was examined using Bland-Altman difference plots, and concordance/discordance of each method comparison was determined using the McNemar method. RESULTS: Regression slopes ranged from 0.63 to 1.87, y-intercepts from 0.00 to 0.03 ng/mL, and r values from 0.93 to 0.99. The cTnT methods had a slope of 0.93, y-intercept of 0.02 ng/mL, and r value of 0.99. For the cTnI assays, positive, negative, and overall concordance was 76.2%-100%, 66.0%-100%, and 82.9%-98.4%, respectively. Overall concordance between the 4th Gen cTnT and hsTnT assays was 88.9%. A total of 30 of the 78 method comparisons showed significant differences in classification of samples (P <0.001); the iSTAT showed 10, hsTnT showed 9, AccuTnI+3 showed 5, Xpand showed 5, and Stratus CS showed 1. Using alternative 99th percentile cutoffs to those listed by manufacturers lowered the method discordance by 6-fold, from 30 to 5 (all involved iSTAT). CONCLUSIONS: These data provide insight into characteristics of cTn methods and will assist the healthcare community in setting expectations for relationships among commercial cTn assays.

Infection preventionists and laboratorians: Case studies on successful collaboration.

Efforts to reduce the incidence of hospital-acquired infection (HAI) remain a significant focus for health care facilities, particularly in this era of drug-resistant organisms. With as many as 1 in every 25 hospitalized patients acquiring an infection, the need to minimize the risk of HAIs is widely recognized as critical. Advances in the fields of biomedical technology, microbiology, pharmacology, and infection control and prevention, among others, have played a tremendous role in these efforts. However, evidence suggests that a key element in this battle against HAIs is missing: collaboration and communication between these groups in health care facilities-particularly in microbiology and infection prevention. The need for collaboration between infection preventionists (IPs) and laboratorians has been addressed in the literature; however, a survey conducted by the APIC and the American Society for Microbiology demonstrated that both IPs and laboratorians feel they lack the tools to engage in this collaboration. This article addresses strategies for a working partnership between IPs and laboratorians and reports 3 case studies on successful collaborations at major medical centers.

Analytical characteristics of a biomarker-based risk assessment test for acute kidney injury (AKI).

BACKGROUND: Acute kidney injury (AKI) is associated with increased mortality, morbidity, hospital length of stay, and costs. A quantitative urine test is available to assess the risk of developing AKI by measuring the concentrations of two protein biomarkers, TIMP-2 and IGFBP-7. The NephroCheck Test combines these concentrations into an AKIRisk Score. The purpose of this study is to characterize the analytical performance characteristics of the AKIRisk Score. METHODS: Linearity and analytical sensitivity were evaluated by following Clinical Laboratory Standards Institute (CLSI) EP06-A and EP17-A, respectively. Precision was evaluated by testing clinical samples and examining the repeatability of test results. Potential interference was evaluated for endogenous and exogenous substances. Sample stability was examined at room temperature and at 2-8°C, as well as the effect of sample centrifugation temperature on test results. RESULTS: The AKIRisk Score exhibits approximately 10% coefficient of variation (CV) at the recommended cutoff value of 0.3 and the limit of quantitation (LoQ) was 0.002. Only albumin, bilirubin (conjugated), and methylene blue interfered with test results, at concentrations exceeding 1250 mg/L, 72 mg/L, and 0.49 mg/L, respectively. AKIRisk Score results were stable for 6h at room temperature, 24h refrigerated, and not impacted by sample centrifugation temperature. CONCLUSIONS: Our studies demonstrate that the AKIRisk Score has robust analytical performance, good precision, minimal analytical interference, acceptable sensitivity, and excellent sample stability.

Reference intervals of urinary acute kidney injury (AKI) markers [IGFBP7]∙[TIMP2] in apparently healthy subjects and chronic comorbid subjects without AKI.

BACKGROUND: Insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) have demonstrated significantly improved diagnostic performance in assessing risk for acute kidney injury (AKI) compared with existing biomarkers. We present the findings of a multi-site trial to determine the reference intervals for these biomarkers in apparently healthy adults and those with stable chronic morbid conditions without AKI. METHODS: A urine specimen was collected from apparently healthy subjects (N=378) and subjects with at least one stable chronic morbidity (N=372). Specimens were kept frozen until analysis with the NephroCheck® Test (Astute Medical). The test is comprised of fluorescence immunoassays for IGFBP7 and TIMP-2 and is used with the Astute140® Meter which quantifies the concentration of each biomarker. The meter multiplies the concentrations of IGFBP7 and TIMP-2 and displays the result as a numerical value ([IGFBP7]∙[TIMP-2]) expressed in (ng/ml)(2)/1000 which is called the AKIRisk™ Score. RESULTS: The reference intervals (inner 95%) for [IGFBP7]∙[TIMP-2] in all subjects (N=750), apparently healthy subjects, and subjects with stable chronic morbidities were 0.04-2.22, 0.04-2.25, and 0.05-2.20 (ng/ml)(2)/1000 respectively. There was no statistical difference between reference intervals for apparently healthy and chronic stable morbid cohorts (p=0.42). CONCLUSIONS: Our investigation showed that urine [IGFBP7]∙[TIMP-2] values were not elevated in patients with stable chronic morbidities who did not have AKI.

Demographic data for urinary Acute Kidney Injury (AKI) marker [IGFBP7]·[TIMP2] reference range determinations.

This data in brief describes characteristics of chronic stable comorbid patients who were included in reference range studies of [IGFBP7]·[TIMP-2] "Reference Intervals of Urinary Acute Kidney Injury (AKI) Markers [IGFBP7]·[TIMP2] in Apparently Healthy Subjects and Chronic Comorbid Subjects without AKI" [1]. In order to determine the specificity of [IGFBP7]·[TIMP-2] for identifying patients at risk of developing AKI we studied a cohort with nine broad classification of disease who did not have AKI. Details regarding the population that was targeted for inclusion in the study are also described. Finally, we present data on the inclusion criteria for the healthy subjects used in this investigation to determine the reference range.

A primer on on-demand polymerase chain reaction technology.

Efforts to reduce health care-associated infections (HAIs) have grown in both scale and sophistication over the past few decades; however, the increasing threat of antimicrobial resistance and the impact of new legislation regarding HAIs on health care economics make the fight against them all the more urgent. On-demand polymerase chain reaction (PCR) technology has proven to be a highly effective weapon in this fight, offering the ability to accurately and efficiently identify disease-causing pathogens such that targeted and directed therapy can be initiated at the point of care. As a result, on-demand PCR technology has far-reaching influences on HAI rates, health care outcomes, hospital length of stay, isolation days, patient satisfaction, antibiotic stewardship, and health care economics. The basics of on-demand PCR technology and its potential to impact health care have not been widely incorporated into health care education and enrichment programs for many of those involved in infection control and prevention, however. This article serves as a primer on on-demand PCR technology and its ramifications.

Derivation and validation of cutoffs for clinical use of cell cycle arrest biomarkers.

BACKGROUND: Acute kidney injury (AKI) remains a deadly condition. Tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein (IGFBP)7 are two recently discovered urinary biomarkers for AKI. We now report on the development, and diagnostic accuracy of two clinical cutoffs for a test using these markers. METHODS: We derived cutoffs based on sensitivity and specificity for prediction of Kidney Disease: Improving Global Outcomes Stages 2-3 AKI within 12 h using data from a previously published multicenter cohort (Sapphire). Next, we verified these cutoffs in a new study (Opal) enrolling 154 critically ill adults from six sites in the USA. RESULTS: One hundred subjects (14%) in Sapphire and 27 (18%) in Opal met the primary end point. The results of the Opal study replicated those of Sapphire. Relative risk (95% CI) in both studies for subjects testing at ≤0.3 versus >0.3-2 were 4.7 (1.5-16) and 4.4 (2.5-8.7), or 12 (4.2-40) and 18 (10-37) for ≤0.3 versus >2. For the 0.3 cutoff, sensitivity was 89% in both studies, and specificity 50 and 53%. For 2.0, sensitivity was 42 and 44%, and specificity 95 and 90%. CONCLUSIONS: Urinary [TIMP-2]•[IGFBP7] values of 0.3 or greater identify patients at high risk and those >2 at highest risk for AKI and provide new information to support clinical decision-making. CLINICAL TRIALS REGISTRATION: Clintrials.gov # NCT01209169 (Sapphire) and NCT01846884 (Opal).

Meta-analysis of ischemia-modified albumin to rule out acute coronary syndromes in the emergency department.

BACKGROUND: Because of possible adverse outcomes, many of the >6 million annual emergency department (ED) patients with suspected acute coronary syndromes (ACS) undergo extensive evaluations. To minimize medical errors, chest pain evaluations are structured to identify accurately nearly 100% of patients with ACS. This is at a cost of negative evaluation rates that can exceed 90%. Ischemia-modified albumin (IMA), a serum biomarker with a high negative predictive value (NPV) at ED presentation, may exclude ACS. Our objective was to perform a meta-analysis of IMA use for ACS risk stratification. METHODS: By computer literature search and communication with authors of unpublished information, all IMA data were considered. This analysis included studies if they reported IMA results from an ED presentation for suspected ACS. We defined a negative triple prediction test (TPT) as a nondiagnostic electrocardiogram, negative troponin, and negative IMA. RESULTS: Eight studies of >1800 patients met the entry criteria. The TPT sensitivity and NPV for acute ACS were 94.4% and 97.1% and, for longer-term outcomes, were 89.2% and 94.5%, respectively. CONCLUSIONS: A negative TPT of a nondiagnostic electrocardiogram, negative troponin, and negative IMA has a high NPV for excluding ACS in the ED.

Multicenter evaluation of an automated assay for troponin I.

BACKGROUND: Cardiac troponin I (cTnI) is a powerful tool to aid in the diagnosis of myocardial infarction and cardiac muscle damage. We describe an assay that overcomes problems of early assays that were often affected by cTnI degradation, assay interference, poor sensitivity, and imprecision. METHODS: The analytical performance of the Access AccuTnI assay (Beckman Coulter) was evaluated at five institutions. Controls, zero calibrator, and diluted patient samples were used to determine precision, detection limit, functional sensitivity, and linearity. The 97.5 and 99 percentiles of a reference population were determined. Common interferents and heterophilic patient samples were tested. Equimolarity was determined by assaying samples with various ratios of free and complexed cTnI. Matched samples drawn into serum, EDTA, lithium heparin, and sodium heparin sample tubes were compared. RESULTS: Total imprecision (CVs) was 4.0-8.8% between 0.40 and 31 microg/L cTnI. The detection limit was <0.01 microg/L. The 97.5 percentile upper reference limit (URL) was 0.03 microg/L (CV = 20%), and the 99 percentile URL was 0.04 microg/L (CV = 14%). Total CVs of 10% and 20% were seen at and above 0.06 and 0.03 microg/L, respectively. The assay was linear to >60 microg/L and not affected by common assay interferents. An equimolar response was observed with free, complexed, phosphorylated, and dephosphorylated forms of cTnI. Results were 4% lower in serum and 14% lower in EDTA plasma than in lithium heparin plasma (P <0.01), independent of cTnI concentration. CONCLUSION: AccuTnI is a sensitive and precise assay for the measurement of cTnI.