Comparative Analyses of Three Point-of-Care Urine Drug Test Devices' Performance Characteristics for Use in Ambulatory Clinic Settings.

BACKGROUND: Urine drug testing (UDT) is a standard practice used for monitoring controlled and illicit substances in ambulatory care patients. Point-of-care (POC) UDTs are useful tools that allow for drug identification within minutes, providing rapid and objective diagnostic assistance for clinicians. The objective of this study was to evaluate the performance characteristics of 3 different POC UDT devices compared to reference methods. METHODS: A total of 106 residual urine specimens were collected to evaluate the 3 POC UDT devices: the Profile®-V MEDTOX Scan® drugs of abuse test, Quidel Triage® TOX Drug screen, and Quidel Triage Rapid OXY-BUP-MDMA panel. Device performance was assessed by their ability to identify drug classes/compounds compared to manufacturer and reference method (mass spectrometry) cutoffs. RESULTS: The results from quantitative mass spectrometry showed that 77% (84/106) of the samples were positive for one or more drugs. Each device had variable performance across each drug class. Overall, the specificity of the Profile-V MEDTOX Scan test was 90.1%, while the Quidel Triage TOX Drug Screen and Rapid OXY-BUP-MDMA devices had specificities of 89.0% and 50.0% using their respective manufacturer-stated cutoffs. Overall sensitivity was determined to be 98.6%, 97.0%, and 100% for the Profile-V MEDTOX Scan, Quidel Triage TOX Drug Screen, and Rapid OXY-BUP-MDMA, respectively. CONCLUSIONS: Of the 3 POC UDT devices evaluated, the Profile-V MEDTOX Scan demonstrated the best overall sensitivity and specificity compared to reference methods. False positive and negative results are possible with UDTs, ultimately the best device may depend on patient population and drugs of interest.

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.

Urinary fluticasone propionate-17beta-carboxylic acid to assess asthma therapy adherence.

Although the National Asthma Education and Prevention Program Expert Panel Report 3 recommends referral to specialists to address adherence, guidelines do not provide a tool to determine nonadherence. This study was designed to prospectively evaluate the characteristics of urinary analysis of fluticasone propionate-17beta-carboxylic acid (FP17betaCA) as a test to verify if a specific patient has not taken fluticasone propionate (FP) within 16-24 hours. Urine of asthmatic subjects was prospectively analyzed 16-24 hours after witnessed administration of orally inhaled FP using liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis; limit of quantitation was 10.3 pg/mL. Results were compared with those from asthmatic subjects not receiving inhaled FP. Thirty asthmatic subjects receiving inhaled FP (2 oral inhalations of FP at 110 micrograms each or 1 oral inhalation twice daily of fluticasone and salmeterol in fixed combination at 250/50 micrograms for 1 week) were compared with 30 asthmatic subjects not receiving FP. FP17betaCA was detected in the urine of 30 of 30 asthmatic subjects receiving FP (median, interquartile range [IQR; 413.5, 212.8-1230.0] range 12.4-3290.0 pg/mL [corrected for urine creatinine: median, IQR {576.2, 188.1-1306.6} range 6.3-5425.9 ng/g Cr]) and was undetectable in 30 of 30 subjects not receiving inhaled FP. The sensitivity and specificity of LC-MS/MS to detect FP17betaCA in urine were 100% (95% exact binomial confidence interval, 88-100) and 100% (95% exact binomial confidence interval, 88-100), respectively. Analysis of FP17betaCA in urine provides a sensitive method that may be used to verify that a specific patient may not have administered FP within a 16- to 24-hour window before testing.

Liquid chromatography-tandem mass spectrometry analysis of urinary fluticasone propionate-17beta-carboxylic acid for monitoring compliance with inhaled-fluticasone propionate therapy.

BACKGROUND: Inhaled corticosteroids including fluticasone propionate (FP) are the most effective treatment for persistent-asthma. Noncompliance ranging from 20% to 80% of treated patients is associated with substantial health care costs, morbidity and fatalities. A noninvasive test to assess FP treatment compliance is needed. The major metabolite of FP is FP-17beta-carboxylic acid (FP17betaCA) and is excreted in urine. This study demonstrates the development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay to measure FP17betaCA in urine and evaluation of FP17betaCA urinary elimination. EXPERIMENTAL: Fluorometholone was used as the internal standard. After acetonitrile precipitation, samples were extracted with dichloromethane, washed and dried. Reconstituted extract (60 microL) was subjected to reversed-phase chromatography and positive-ion mode LC-MS/MS analysis. Assay precision, linearity, recovery and sample stability were determined. Elimination evaluation included measurement of FP17betaCA in urine collected daily from human subjects before (day 1), during treatment (days 2-5; dose FP-110 microg 2 puffs/day), and following cessation of FP therapy (days 6-14; n=4). RESULTS: Linear range of the FP17betaCA assay was 10.3-9510pg/mL. Limit of quantitation (LOQ) was 10.3 pg/mL and recovery ranged from 85.8% to 111.9%. Inter-assay CVs were 7.4-12.0% for FP17betaCA concentrations of 11.1-5117 pg/mL. Urine FP17betaCA was absent in subjects prior to FP therapy, detectable (180-1991 ng FP17betaCA/g creatinine) throughout the dosing period and reached below the LOQ at 6 days after therapy cessation. CONCLUSIONS: Measurement of FP17betaCA by LC-MS/MS has acceptable analytical performance for clinical use. These data support the clinical utility of measuring FP17betaCA in urine to monitor patient compliance with FP therapy.

Comparison of three whole blood creatinine methods for estimation of glomerular filtration rate before radiographic contrast administration.

We compared the clinical concordance of estimated glomerular filtration rate (eGFR) based on 3 whole blood creatinine assays with the eGFR calculated from a reference plasma creatinine assay. Whole blood creatinine on the Radiometer ABL800 FLEX (Radiometer A/S, Bronshoj, Denmark) demonstrated the best correlation and concordance to plasma creatinine/eGFR compared with the i-STAT (i-STAT, East Windsor, NJ) and StatSensor (Nova Biomedical, Waltham, MA). The i-STAT had better sensitivity (compared with Radiometer) but poorer specificity for prediction of plasma eGFR less than 60 mL/min/1.73 m(2). The StatSensor demonstrated lower concordance of whole blood to plasma eGFR but offered a slope and an intercept offset feature that partially compensates for this effect. The optimal device for use in rapid determination of eGFR from whole blood creatinine may depend on whether it is more important in a given practice to optimize sensitivity, specificity, or overall concordance for determining plasma eGFR less than 60 mL/min/1.73 m(2).

Comparative analysis of fecal fat quantitation via nuclear magnetic resonance spectroscopy (1H NMR) and gravimetry.

BACKGROUND: Fecal-fat is typically measured by extracting lipid from homogenized feces with subsequent gravimetric/titrimetric analyses that are time-consuming and involve toxic solvents. Accordingly, an efficient and more safe method to quantitate fecal-fat is needed. The present objective was to adapt CEM SmartTrac technology (i.e. (1)H NMR) to rapidly (< 5 min) quantitate fecal-fat and compare (1)H NMR and gravimetric performance characteristics. METHODS: (1)H NMR and gravimetric measurements of stool-fat were conducted using excess stool samples (72 h collection; n=107) homogenized to semi-liquid consistency prior to analyses. RESULTS: The (1)H NMR method demonstrated acceptable linearity (R(2)=0.9999) and recovery (mean=105%) with imprecision (intra-assay CV=1.2-6.5%; inter-assay CV=1.8-5.8%) comparable to or better than gravimetry (intra-assay CV=1.0-17.2%; inter-assay CV=3.8-6.5%). Excellent correlation between fecal-fat quantitation by (1)H NMR and gravimetry (n=107; R(2)=0.983; y=1.0173x-0.6859) was exhibited; moreover, (1)H NMR demonstrated good sensitivity (92.3%), specificity (94.5%), negative-predictive value (92.9%) and positive-predictive value (94.1%) for malabsorption using the reference cut-off of < or = 7 g fat/24 h. CONCLUSIONS: These data demonstrate that (1)H NMR permits rapid and safe quantitation of fecal-fat while maintaining acceptable performance characteristics, thereby supporting the utility of (1)H NMR as an alternative method to gravimetry for fecal-fat quantitation.

Human rhinovirus induces robust IP-10 release by monocytic cells, which is independent of viral replication but linked to type I interferon receptor ligation and STAT1 activation.

Human rhinovirus (HRV)-induced respiratory infections are associated with elevated levels of IFN-gamma-inducible protein 10 (IP-10), which is an enhancer of T lymphocyte chemotaxis and correlates with symptom severity and T lymphocyte number. Increased IP-10 expression is exhibited by airway epithelial cells following ex vivo HRV challenge and requires intracellular viral replication; however, there are conflicting reports regarding the necessity of type I IFN receptor ligation for IP-10 expression. Furthermore, the involvement of resident airway immune cells, predominantly bronchoalveolar macrophages, in contributing to HRV-stimulated IP-10 elaboration remains unclear. In this regard, our findings demonstrate that ex vivo exposure of human peripheral blood monocytes and bronchoalveolar macrophages (monocytic cells) to native or replication-defective HRV serotype 16 (HRV16) resulted in similarly robust levels of IP-10 release, which occurred in a time- and dose-dependent manner. Furthermore, HRV16 induced a significant increase in type I IFN (IFN-alpha) release and STAT1 phosphorylation in monocytes. Neutralization of the type I IFN receptor and inhibition of JAK or p38 kinase activity strongly attenuated HRV16-stimulated STAT1 phosphorylation and IP-10 release. Thus, this work supports a model, wherein HRV16-induced IP-10 release by monocytic cells is modulated via autocrine/paracrine action of type I IFNs and subsequent JAK/STAT pathway activity. Our findings demonstrating robust activation of monocytic cells in response to native and/or replication-defective HRV16 challenge represent the first evidence indicating a mechanistic disparity in the activation of macrophages when compared with epithelial cells and suggest that macrophages likely contribute to cytokine elaboration following HRV challenge in vivo.