Evaluation of the rapid Quidel Sofia Lyme fluorescent immunoassay as a first-tier test in a modified 2-tier testing algorithm for Lyme disease: A comparison with the Zeus ELISA Borrelia VlsE1/pepC10 lgG/IgM assay followed by the Zeus monovalent IgM/IgG confirmatory assay.

OBJECTIVES: Recently modified 2-tier testing (MTTT) algorithms using 2 enzyme immunoassays (EIAs) as opposed to an EIA followed by immunoblot have been approved by the US Food and Drug Administration (FDA) for the screening and confirmation of Lyme disease. The Quidel Sofia Lyme fluorescent immunoassay is a rapid lateral-flow method that can be performed in real time, permitting on-demand testing. We evaluated the performance of the Sofia assay as a first-tier test in an MTTT algorithm. METHODS: We compared the Sofia Lyme test with the Zeus ELISA Borrelia VlsE1/pepC10 lgG/IgM test, followed by the Zeus monovalent IgM/IgG EIA as the confirmatory test. RESULTS: When used as a first-tier test compared with a standard Zeus MTTT assay, the positive percentage agreement was 91.4%% (95% CI, 77.6%-97.0%). The negative percentage agreement was 100% (95% CI, 94.0%-100%). The overall agreement was 98.3% (95% CI, 94.2%-99.4%). κ = 0.945, indicating "almost perfect agreement." CONCLUSIONS: The Sofia Lyme test performs well compared with an FDA-approved MTTT.

Detection and localization of early- and late-stage cancers using platelet RNA.

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I-IV cancer patients and in half of 352 stage I-III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.

Laboratory Blood-Based Testing for Non-Lyme Disease Tick-Borne Infections at a National Reference Laboratory.

OBJECTIVES: We evaluated trends in non-Lyme disease tick-borne disease (NLTBI) testing at a national reference laboratory. METHODS: Testing data performed at Quest Diagnostics during 2010 to 2016 were analyzed nationally and at the state level. RESULTS: Testing and positivity for most NLTBIs increased dramatically from 2010 through 2016 based on testing from a large reference laboratory. The number of positive cases, though not as stringent as criteria for public health reporting, generally exceeds that reported by the Centers for Disease Control and Prevention. The frequency of NLTBI in the US is seasonal but testing activity and positive test results are observed throughout all months of the year. Positive results for NLTBI testing mostly originated from a limited number of states, indicating the geographic concentration and distribution of NLTBIs reported in this study. CONCLUSIONS: This report provides an important complementary source of data to best understand trends in and spread of NLTBI.

Laboratory Blood-Based Testing for Lyme Disease at a National Reference Laboratory.

OBJECTIVES: We evaluated trends in Lyme disease (LD) testing at a national reference laboratory. METHODS: LD screening enzyme immunoassay and Western blot testing data performed at Quest Diagnostics during 2010 to 2016 were analyzed nationally and at the state level. RESULTS: Overall, 593,800 (11.3%) results were positive of 5,255,636 tests. There was an increase in the rate of positivity over the last 2 years of the study and an increase in the number of positive tests in 2016. Positive tests were observed in all 50 states and the District of Columbia. New York had the most positive tests, whereas Connecticut had the highest positivity rate when normalized to state populations. Some states with historically low rates of LD (eg, Texas, Florida, and California) showed significant increases in testing and positivity rates over time. CONCLUSIONS: LD testing and positivity have increased in recent years, including in states not historically associated with the disease.

Laboratory Testing for Tick-Borne Infections in a Large Northeastern Academic Medical Center: An 11-Year Experience.

OBJECTIVES: We evaluated changes in the testing menu, volume, and positivity rates for tick-borne illnesses in a New England medical center over an 11-year time frame. METHODS: Testing data were obtained by a retrospective review utilizing searchable data from a laboratory information system archive. RESULTS: Testing for tick-borne infections (TBI) increased 5.3-fold over an 11-year time period and the number of positive test results increased threefold. Annual rates for Lyme serology positivity varied from 14% to 29% and for western blot confirmation from 26% to 48%. Test volumes and the number of positive results increased for all TBI endemic to our region. CONCLUSIONS: Our results confirm national trends suggesting increasing rates of TBI and substantially increased testing. This may reflect a greater incidence of TBI in our region and/or increased awareness of these infections.

Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets.

Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA-sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources.

Total and ionized magnesium testing in the surgical intensive care unit - Opportunities for improved laboratory and pharmacy utilization.

PURPOSE: Ionized fraction (iMg) is the physiologically active form of magnesium (Mg); total Mg may not accurately reflect iMg status. Erroneously "low" Mg levels may result in unnecessary repetitive testing. MATERIALS AND METHODS: From 11/2015 to 01/2016, patients ordered for Mg from a pilot ICU also had iMg tested. Weighted kappa statistic was used to assess agreement between Mg categories (low, normal, high). Predictors of unnecessary repeated Mg testing and repletion using data were explored through logistic regression models using GEE techniques to account for repeated measurements in both bivariate and multivariable analyses. RESULTS: There were 470Mg/iMg paired measurements from 173 patients. The weighted kappa statistic was 0.35 (95%CI 0.27-0.43) indicating poor agreement in assessment of magnesium status. Of the 34Mg samples reported as "low", only 6 (18%) were considered "low" using concurrent iMg testing. In the multivariable models, history of atrial fibrillation (aOR=1.61, 95%CI 1.16-2.21, p=0.004) and concomitant metoclopramide (aOR=1.71, 95%CI 1.03-2.81, p=0.036) were significant predictors of unnecessary repeat Mg testing. CONCLUSIONS: In the surgical ICU, categorical agreement (low, normal, high) was poor between Mg and iMg. Over 80% of "low" total Mg values are erroneous and may result in unnecessary additional measurements and repletion.

Elevated admission N-terminal pro-brain natriuretic peptide level predicts the development of atrial fibrillation in general surgical intensive care unit patients.

BACKGROUND: New onset atrial fibrillation (AF) in critically ill surgical patients is associated with significant morbidity and increased mortality. N-terminal pro-B type natriuretic peptide (NT-proBNP) is released by cardiomyocytes in response to stress and may predict AF development after surgery. We hypothesized that elevated NT-proBNP level at surgical intensive care unit (ICU) admission predicts AF development in a general surgical and trauma population. METHODS: From July to October 2015, NT-proBNP concentrations were measured at ICU admission. Abnormal NT-proBNP concentrations were defined by age-adjusted cut-offs. We examined the relationship between the development of AF and demographics, clinical variables, and NT-proBNP level using univariate analysis and a multivariable logistic regression model. RESULTS: Three hundred eighty-seven subjects were included in the cohort, none of whom were in AF at ICU admission. The median age was 63 years (52-73 years), and 40.3% were women. The risk of developing AF was higher for abnormal versus normal NT-proBNP (22% vs. 4%; p < 0.0001). Using optimal derived cutoffs (regardless of age), the risk of developing AF was 2% for NT-proBNP less than 600 ng/L, 15% for NT-proBNP of 600 ng/L to 1,999 ng/L, and 27% for NT-proBNP of 2,000 ng/L or greater. Multiple logistic regression analysis identified three independent predictors for new-onset AF: age, older than 70 years (odds ratio [OR], 3.7, 95% confidence interval [CI], 1.5-9.3), history of AF (OR, 25.3; 95% CI, 9.6-67.0), and NT-proBNP of 600 or greater (OR, 4.3; 95% CI, 1.3-14.2). When none or only one predictor was present, AF incidence was less than 1%. When all three predictors were present, AF incidence was 66%. For subjects 70 years or older but no history of AF, AF incidence was 12.8% when NT-proBNP was 600 or greater compared with 0% when NT-proBNP was less than 600. For subjects younger than 70 years with a history of AF, AF incidence was 44.4% when NT-proBNP was 600 or higher compared to 0% when NT-proBNP was less than 600. CONCLUSION: Elevated NT-proBNP at ICU admission in general surgical and trauma patients is predictive of AF development in the first 3 ICU days. Addition of NT-proBNP measurement to known risk factors can improve predictive power and identify patients who might potentially benefit from evidence-based prophylactic treatment for AF.

Can a Point-of-Care Troponin I Assay be as Good as a Central Laboratory Assay? A MIDAS Investigation.

BACKGROUND: We aimed to compare the diagnostic accuracy of the Alere Triage Cardio3 Tropinin I (TnI) assay (Alere, Inc., USA) and the PathFast cTnI-II (Mitsubishi Chemical Medience Corporation, Japan) against the central laboratory assay Singulex Erenna TnI assay (Singulex, USA). METHODS: Using the Markers in the Diagnosis of Acute Coronary Syndromes (MIDAS) study population, we evaluated the ability of three different assays to identify patients with acute myocardial infarction (AMI). The MIDAS dataset, described elsewhere, is a prospective multicenter dataset of emergency department (ED) patients with suspected acute coronary syndrome (ACS) and a planned objective myocardial perfusion evaluation. Myocardial infarction (MI) was diagnosed by central adjudication. RESULTS: The C-statistic with 95% confidence intervals (CI) for diagnosing MI by using a common population (n=241) was 0.95 (0.91-0.99), 0.95 (0.91-0.99), and 0.93 (0.89-0.97) for the Triage, Singulex, and PathFast assays, respectively. Of samples with detectable troponin, the absolute values had high Pearson (R(P)) and Spearman (R(S)) correlations and were R(P)=0.94 and R(S)=0.94 for Triage vs Singulex, R(P)=0.93 and R(S)=0.85 for Triage vs PathFast, and R(P)=0.89 and R(S)=0.73 for PathFast vs Singulex. CONCLUSIONS: In a single comparative population of ED patients with suspected ACS, the Triage Cardio3 TnI, PathFast, and Singulex TnI assays provided similar diagnostic performance for MI.

Implementation of point-of-care testing in an ambulatory practice of an academic medical center.

OBJECTIVES: Point-of-care laboratory testing (POCT) offers reduced turnaround time and may promote improved operational efficiency. Few studies have been reported that document improvements from implementing POCT in primary care. METHODS: We measured metrics of practice efficiency in a primary care practice before and after implementation of POCT, including the total number of tests ordered, letters and phone calls to patients, and revisits due to abnormal test results. We performed a cost and revenue analysis. RESULTS: Following implementation of POCT, there was a 21% decrease in tests ordered per patient (P < .0001); a decrease in follow-up phone calls and letters by 89% and 85%, respectively (P < .0001 and P < .0001); and a 61% decrease in patient revisits (P = .0002). Estimated testing revenues exceeded expenses by $6.62 per patient, and potential cost savings from improved efficiency were $24.64 per patient. CONCLUSIONS: POCT can significantly improve clinical operations with cost reductions through improved practice efficiency.

The practice of clinical pathology: a quantitative description of laboratory director activities at a large academic medical center.

OBJECTIVES: The scope of activities performed by clinical laboratory directors is sometimes unfamiliar to other physicians or hospital administrators. Consequently, hospital leadership may undervalue the role and assume that many director level activities could be delegated to a professional manager. In this study, we sought to define the activities of academic laboratory directors, and to determine which activities require doctorate level medical or scientific expertise. METHODS: We performed an audit of laboratory director activities at a large academic medical center by reviewing electronic calendars and other available records from the preceding 12 consecutive months. For episodic activities, the directors estimated the average number of hours devoted over the 1-year period. RESULTS: On average, directors worked 54.9 hours per week and performed at least some service work 47.7 weeks per year. Administrative duties accounted for the greatest proportion of effort (47.1%), followed by clinical activities (33.1%) and academic activities (19.8%). Among administrative duties, those that required doctorate level medical or scientific expertise comprised 60.3% of the total administrative effort, whereas the remaining 39.7% (18.7% of total activity) could be performed by a professional manager.. CONCLUSIONS: Although the activities of clinical laboratory directors have been described elsewhere, this is the first study detailing the effort allocated to these various activities in quantitative terms. The study demonstrated that less than 20% of an academic laboratory director's effort involves administrative activities that could potentially be performed by a professional manager lacking doctorate level medical or scientific expertise.

Detection of influenza A and B viruses with the Sofia analyzer: a novel, rapid immunofluorescence-based in vitro diagnostic device.

This report describes the clinical evaluation of a novel fluorescent immunoassay (FIA), Sofia Influenza A+B FIA (Quidel, San Diego, CA), for the rapid detection and differentiation of influenza A and B viruses. A total of 2,047 subjects provided nasal swabs and nasopharyngeal swabs or aspirates. The overall sensitivity and specificity for influenza A virus vs virus culture were 94% and 95%, respectively, and for influenza B virus were 89% and 96%, respectively. Fourteen hundred and sixty-one specimens were available for testing with reverse transcriptase-polymerase chain reaction (RT-PCR). The sensitivity of the Sofia Influenza A+B FIA for detecting influenza A and B viruses compared with the RT-PCR method was 78% and 86%, respectively. A high percentage of the positive specimens had low cycle threshold values, and almost all of these were positive with the Sofia test. This high level of sensitivity demonstrates that the Sofia influenza A+B FIA could improve the usefulness of rapid influenza virus testing.

Evaluation of rapid point-of-care creatinine testing in the radiology service of a large academic medical center: impact on clinical operations and patient disposition.

BACKGROUND: Measurement of creatinine and calculation of the estimated glomerular filtration rate (eGFR) are widely employed to identify patients with chronic kidney disease who are at risk for contrast induced acute kidney injury and nephrogenic systemic fibrosis. However, patients may present for radiologic studies without a recent creatinine/eGFR necessitating cancelation of the study or performance of the scan without contrast. Both of these approaches are suboptimal. METHODS: We implemented a rapid whole blood point-of-care (POCT) creatinine test (iSTAT, Abbott Point-of-Care) in our radiology department and assessed the impact on clinical operations. RESULTS: Over a 7-month period a total of 3087 creatinine tests were performed. Overall 5.3% of patients presenting for scans (441/month) did not have a recent eGFR. An audit of 1 month of creatinine/eGFR values showed that 74% were normal permitting the scan to be performed without further consideration. Of the abnormal values 74% were performed with contrast and 26% without. Of note 78% of patients with an abnormal eGFR had a normal creatinine value. The cost of the POC test was $10.06 compared to a cost of $5.32 (including phlebotomy) for a creatinine performed in the central laboratory. The added incremental cost for the POC test was therefore $4.74. CONCLUSIONS: Determining the cost effectiveness of the rapid test is extremely challenging because the analysis would need to take many complex factors into consideration including the effect on workflow in the radiology department, the clinical impact of more timely scans, the clinical and financial consequences of performing scans with or without contrast and the impact on revenues complicated by differential reimbursement rates and payor mix. However, given the benefits of the test on radiology operations and on the quality and timeliness of care it appears that the POCT test is cost effective and improves clinical operations.

Evaluation of first-draw whole blood, point-of-care cardiac markers in the context of the universal definition of myocardial infarction: a comparison of a multimarker panel to troponin alone and to testing in the central laboratory.

CONTEXT: Previous studies evaluating point-of-care testing (POCT) for cardiac biomarkers did not use current recommendations for troponin cutoff values or recognize the recent universal definition of acute myocardial infarction. Traditionally, achieving optimal sensitivity for the detection of myocardial injury on initial presentation required combining cardiac troponin and/or creatine kinase isoenzyme MB with an early marker, usually myoglobin. In recent years, the performance of central laboratory combining cardiac troponin assays has improved significantly, potentially obviating the need for a multimarker panel to achieve optimum sensitivity. OBJECTIVE: To compare 2 commonly used POCT strategies to a fourth generation, central laboratory cardiac troponin T assay on first-draw specimens from patients being evaluated for acute myocardial infarction in the emergency department. The 2 strategies included a traditional POCT multimarker panel and a newer POCT method using cardiac troponin I alone. DESIGN: Blood specimens from 204 patients presenting to the emergency department with signs and/or symptoms of myocardial ischemia were measured on the 2 POCT systems and by a central laboratory method. The diagnosis for each patient was determined by retrospective chart review. RESULTS: The cardiac troponin T assasy alone was more sensitive for acute myocardial infarction than the multimarker POCT panel with equal or better specificity. When compared with a POCT troponin I, the cardiac troponin T was also more sensitive, but this difference was not significant. The POCT troponin I alone also had the same sensitivity as the multimarker panel. CONCLUSIONS: Testing for combining cardiac troponin alone using newer, commercially available, central laboratory or POCT assays performed with equal or greater sensitivity to acute myocardial infarction as the older, traditional, multimarker panel. In the near future, high-sensitivity, central laboratory troponins will be available for routine clinical use. As a result, the quality gap between central laboratories and older POCT methods will continue to widen, unless the performance of the POCT methods is improved.

Point of care testing in a large urban academic medical center: evolving test menu and clinical applications.

INTRODUCTION: There have been many reports describing individual POCT technologies but there are no recent studies describing the organizational scope and impact of a POCT program. METHODS: Our menu of POCT tests has increased to 26 and the test volume to 664,287 tests/year equivalent to 14.5% of the volume of the central core laboratory. POCT is performed in nearly all inpatient units and in a variety of outpatient settings. RESULTS: Cumulatively 84.6% of the test volume and most testing sites can be accounted for by 4 traditional tests (bedside glucose testing, fecal occult blood, dipstick urinalysis and activated clotting time). Most POCT tests are not performed because of a true medical necessity but rather to improve the efficiency of clinical operations. CONCLUSION: We are experiencing a significant increase in requests for new POCT tests. Unlike established high volume conventional POC tests, these new requests originate from specialized services seeking to improve the efficiency of clinical operations.

Perspectives on cost and outcomes for point-of-care testing.

Point-of-care testing (POCT) is usually more expensive on a unit-cost basis than testing performed in a central laboratory. It is difficult to manage POCT and to maintain regulatory compliance, especially in large institutions. However, some POCT technologies have improved patient outcomes (patient self-glucose monitoring in the home, tight glycemic control in intensive care settings) or hospital or emergency department operations (whole-blood cardiac-marker testing and D-dimer testing in emergency departments). In some cases, these outcomes result simply from making a new test available, rather than performing the test at the point of care. In most cases, the rapid turnaround time provided by POCT is the main factor that is ultimately responsible for the improvement in outcomes.

Implementation of a rapid whole blood D-dimer test in the emergency department of an urban academic medical center: impact on ED length of stay and ancillary test utilization.

Overcrowding and prolonged patient length-of-stay (LOS) in emergency departments (EDs) are growing problems. We evaluated the impact of implementing a rapid whole blood quantitative D-dimer test (Biosite Triage, Biosite Diagnostics, San Diego, CA) in our ED satellite laboratory on 252 patients before vs 211 patients after implementation. All patients also underwent testing with the existing central laboratory method (VIDAS D-dimer, bioMérieux, Durham, NC). D-dimer turnaround time (from blood draw to result) decreased approximately 79% (approximately 2 hours vs 25 minutes). The mean ED LOS declined from 8.46 to 7.14 hours (P = .016). Hospital admissions decreased 13.8%, ED discharges increased 7.3%, and the number of patients admitted for observation increased 6.4% (P = .005). No difference in the utilization of radiologic studies was observed (P = .86). At 3 months' follow-up, none of the after-implementation patients with negative D-dimer results were admitted for subsequent venous thromboembolic disease. The rapid D-dimer test was associated with a shorter ED LOS and fewer hospital admissions.

Comparison of conventional guaiac to four immunochemical methods for fecal occult blood testing: implications for clinical practice in hospital and outpatient settings.

BACKGROUND: Fecal occult blood testing (FOBT) is one method to screen for colorectal cancer and to assess for gastrointestinal bleeding in hospitalized patients. Differences in the analytical sensitivity among various methods may have significant clinical repercussions. METHODS: We evaluated the analytical performance of 5 different FOBT methods (standard guaiac-based method and four immunochemical methods) using patient samples and spiked stool specimens. RESULTS: The analytical sensitivity measured using spiked stool samples varied from <8 to 1500 ug hemoglobin/gram of stool. In some cases the results differed significantly from the manufacturers reported analytical sensitivity. Analysis of 71 stool samples measured by all 5 methods showed a discrepant result in 31 cases (43.7%). The rate of positive samples varied by method from 8.5% to 42.2%. CONCLUSIONS: These results demonstrate significant differences in the analytical performance among FOBT methods. Careful method validation and selection of a method with appropriate sensitivity is essential when choosing an FOBT method for colorectal cancer screening or for the assessment of gastrointestinal bleeding in the emergency department and hospital inpatients.

Cardiac biomarkers, electrolytes, and other analytes in collapsed marathon runners: implications for the evaluation of runners following competition.

We measured analytes in collapsed Boston Marathon runners to compare with changes in asymptomatic runners. Of collapsed runners at the 2007 marathon, 18.2% had a measurable cardiac troponin T (cTnT) value with a mean postrace level of 0.017 ng/mL (0.017 microg/L; SD, 0.02 ng/mL [0.02 microg/L]). Three subjects had cTnT values above the cutoff (0.10 ng/mL [0.10 microg/L]) typically used for the diagnosis of acute myocardial infarction. The mean and median N-terminal pro-B-type natriuretic peptide levels were 73 ng/L (SD, 77.3 ng/L) and 54.3 ng/L (interquartile range, 22.8-87.3 ng/L), respectively, in collapsed runners. Only 4.9% had values more than the age-specific normal value (<125 ng/L for subjects younger than 75 years). In collapsed subjects at the 2006 marathon, 18.0% had an abnormal sodium value, including 18 cases of hypernatremia and 7 cases of hyponatremia. The ionized calcium level was low in 49% of subjects, and the ionized magnesium level was low in 19.5% and elevated in 1 subject. The blood lactate level was elevated in 95% of subjects. The frequency of elevated postrace cTnT levels in collapsed athletes after endurance exercise is similar to that in asymptomatic runners. Other metabolic abnormalities, including hypernatremia, hyponatremia, low ionized calcium and magnesium levels, and lactic acidosis may contribute to muscle fatigue and collapse.

Implementation of point-of-care rapid urine testing for drugs of abuse in the emergency department of an academic medical center: impact on test utilization and ED length of stay.

We evaluated the impact of implementing a point-of-care (POC) rapid urine test panel for drugs of abuse on turnaround time (TAT), emergency department length of stay (LOS), and laboratory test utilization patterns. The mean TAT from sample collection to results reporting decreased by 69.4%, from 108 to 33 minutes, the mean LOS from 11.1 to 8.1 hours (27% P < .0001), and the median LOS from 8.0 to 7.0 hours (13% P = .0017). A method crossover between the POC and central laboratory methods revealed differences in sensitivity and specificity. Overall, there was no clear preference for either method. Differences in performance for individual drug classes were reconciled by providing interpretive comments with POC results. Following implementation, use of urine testing for drugs of abuse increased by 30%, which was offset by fewer requests for extended toxicology testing in the central laboratory and more selective ordering of toxicology tests not on the POC panel (alcohols and analgesics). The implementation of a POC urine test panel for drugs of abuse decreased LOS and TAT and essentially replaced central laboratory testing for drugs of abuse. Differences in sensitivity and specificity between POC and central laboratory results require provision of interpretive comments with results.