bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inaccurate First-Generation Testosterone Assays Are Influenced by Sex Hormone–Binding Globulin Concentrations
Authors: Heijboer Annemieke C , Savelkoul Edo , Kruit Adrian , Endert Erik , Blankenstein Marinus A 
Published: July 2018

Abstract

Background
The quality of testosterone assays has been a matter of debate for several years. Known limitations of testosterone immunoassays are the cross-reactivity with other steroids and a high variation in the low concentration range. We hypothesized that one of the additional limitations of testosterone immunoassays is an ineffective displacement of testosterone from its binding protein.

Methods
Thirty samples from women not using oral contraceptives (OAC), 30 samples from women using OAC, and 30 samples from pregnant women were used to measure testosterone by an isotope dilution (ID)-LC-MS/MS method and by 6 commercially available testosterone immunoassays (UniCel®, ARCHITECT®, Centaur®, Cobas®, Immulite®, and Liaison®). In addition, sex hormone–binding globulin (SHBG)4 was measured by immunoassay (ARCHITECT).

Results
The first-generation immunoassays (UniCel, Centaur, Immulite, and Liaison) showed inaccurate testosterone results in the method comparisons with the ID-LC-MS/MS method (R between 0.61 and 0.86) and for some assays (UniCel and Liaison) also a very poor standardization (slopes of 0.59 and 0.67, respectively). On average, SHBG concentrations were lowest in women not using OAC and highest in pregnant women, and overall ranged from 18.5 to 633 nmol/L. In the first-generation immunoassays, but not in the second-generation immunoassays, we observed an inverse relationship between SHBG concentrations and deviations in testosterone from the ID-LC-MS/MS results.

Conclusions
Widely used first-generation testosterone immunoassays are influenced by SHBG concentrations, which lead to inaccurate results in samples from patients with high or low SHBG concentrations, respectively. Laboratory specialists, clinicians, and researchers should be aware of this limitation in testosterone assays.
Novel Chemiluminescent Enzyme Immunoassays for Individual Quantification of 3 Endogenous Molecular Forms of Atrial Natriuretic Peptide in Human Plasma
Authors: Nagai-Okatani Chiaki , Kangawa Kenji , Takashio Seiji , Takahama Hiroyuki , Hayashi Tomohiro , Anzai Toshihisa , Minamino Naoto 
Published: July 2018

Abstract

Background
Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are cardiac peptide hormones with pivotal roles in maintaining cardiovascular homeostasis. BNP and its precursor fragment are accepted as gold standard markers for heart failure (HF). Human ANP is present in the atria of the heart and plasma as 3 endogenous molecular forms designated α-ANP, β-ANP, and proANP. A previous study indicated that the ratios of these 3 ANP forms are altered in the plasma of HF patients. The purpose of our study was to establish immunoassays for quantifying the individual ANP forms to collect clinical information.

Methods
We developed 3 plate-based chemiluminescent enzyme immunoassays (CLEIAs) for measuring total ANP (i.e., sum of α-ANP, β-ANP, and proANP), β-ANP, and proANP levels. To minimize background signals, we added single-step PEGylation targeting the immobilized antibody in the conventional plate-based sandwich CLEIA procedure.

Results
CLEIAs with PEGylation showed sensitivity, specificity, reproducibility, and accuracy satisfying clinical requirements. Two of the CLEIAs enabled direct measurement in plasma samples. During treatments, acute decompensated HF patients exhibited marked decreases in plasma β-ANP levels but moderate decreases in plasma proANP level. The plasma ratios of α-ANP/total ANP and proANP/total ANP in acute decompensated HF patients were maintained, whereas the β-ANP/total ANP ratio was significantly decreased at discharge.

Conclusions
The combination of the 3 CLEIAs enabled accurate quantification of α-ANP, β-ANP, and proANP, even in plasma samples, and indicated the potential of β-ANP and proANP as circulating biomarkers for HF, with different characteristics from that of BNP.
Analytical Performances of an Enzymatic Assay for the Measurement of Glycated Albumin
Authors: Testa Roberto , Guerra Elena , Bonfigli Anna Rita , Di Gaetano Nicola , Santini Gabriele , Ceriotti Ferruccio 
Published: July 2018

Abstract

Background
Short to intermediate integrated glycemic control is best determined by glycated albumin (GA). This assay is appropriate when interpretation of glycated hemoglobin (HbA1c) is critical because of hemoglobinopathies, severe anemias, or other factors that affect red blood lifespan as hemodialysis. We evaluated a new assay based on the enzymatic quantification of GA by ketoamine oxidase and an albumin-specific protease.

Methods
Limits of blank, detection, and quantification; precision; linearity; accuracy; interferences; correlation with HbA1c; and serum vs plasma study have been evaluated on ILab® systems.

Results
Limit of blank, detection, and quantification for GA (g/L) were, respectively, 0.26, 0.36, and 1.15. Repeatability and within-device precision CVs were lower than 2.11%, 1.61%, and 1.56% for GA (g/L), albumin (g/L), and GA%, respectively. Linearity for GA (g/L) and GA% was 1.2–36.8 and 5.5–92.2, respectively. Highest deviation from linearity was &lt;11% and recovery was higher than 90%. Accuracy against the certified ReCCS Japan Clinical Chemistry Reference Material (JCCRM) 611 was &lt;1%. Classical interfering substances had no significant impact. Correlation of GA% between ILab® Taurus and ADVIA system was y = 1.02[GA%]+0.25; R 2 = 0.994. No difference was found in the determination of GA% in serum vs plasma.

Conclusions
GA enzymatic assay is a reliable, fully automated method allowing accurate and precise determination of GA in a routine laboratory.
Practices and Perceived Value of Proficiency Testing in Clinical Laboratories
Authors: Earley Marie C , Astles J Rex , Breckenridge Karen 
Published: July 2018

Abstract

Background
Proficiency testing (PT) can have regulatory and nonregulatory uses, providing an effective tool for quality improvement. Clinical laboratories were surveyed to determine how they perceive PT and how they use PT results and materials to improve laboratory testing quality.

Methods
All laboratories certified to perform nonwaived testing under the CLIA regulations expected to perform required PT were invited to participate in the survey. We examined respondents' use of PT from 5 laboratory types: hospital, independent, public health, physician office, and “all other.” Respondents' awareness of resources about PT was also examined. Several questions allowed responses on a categorical scale.

Results
Varying proportions of the respondents (n = 769) used PT to identify problems in the preanalytic (48%), analytic (86%), and postanalytic (76%) phases of testing. Responses also showed that PT was important for demonstrating personnel competency (93%), inappropriate specimen handling (80%), incorrect result interpretation (84%), and other uses. Respondents purchased PT even when not required to do so (77%). Based on all responses, most considered PT worth the cost (65%).

Conclusions
Laboratories, regardless of type, have found ways of using leftover PT samples and the information from PT event summaries to help improve laboratory quality. Our findings suggest many laboratories are not taking full advantage of PT to improve testing quality. Additionally, the study suggests a need to improve awareness of resources about PT.
Retrospective Analysis of Point-of-Care and Laboratory-Based Hemoglobin A1c Testing
Authors: Clark Jennifer L , Rao Lokinendi V 
Published: July 2018

Abstract

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, &lt;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.
Near-Patient Thrombin Generation in Patients Undergoing Elective Cardiac Surgery
Authors: Moorlag Martijn , Schurgers Evelien , Krishnamoorthy Ganeshram , Bouwhuis Anne , Lindhout Theo , Kelchtermans Hilde , Lance Marcus D , de Laat Bas 
Published: July 2018

Abstract

Background
Measuring thrombin generation (TG) in plasma increasingly gained attention as a diagnostic tool in the field of thrombosis and hemostasis. To include the contribution of all blood cells, recently, the whole blood TG method was developed.

Methods
We changed the calculation method of the standard calibrated automated thrombography (CAT) to a method only taking into account the data until the peak of TG, thereby considerably reducing the time from blood draw to result. By redesigning the method, the blood volume per test was reduced to 15 μL.

Results
For all TG parameters, the interassay variation proved to be below 15%. The interindividual variation of all parameters was comparable to the CAT method. Thirty-three patients undergoing cardiothoracic surgery were included to investigate whether our assay correlates with postoperative blood loss. On dividing patients into severe and mild bleeders, significant differences between both groups were found for the peak endogenous thrombin potential (peakETP) and peak values determined by our near-patient device. Importantly, patients with a peakETP below the median experienced significantly more blood loss compared to those with a peakETP above the median. A similar division based on the peak as well as the body mass index of the patient yielded similar significant differences. A combination of the peakETP, the body mass index, and the lag time even resulted in a better predictor of blood loss compared to each parameter separately.

Conclusions
Our adapted whole blood TG assay can be used near patients and is indicative for the amount of blood loss post cardiothoracic surgery.
Comparison of the Alere i and BD Veritor Assays for the Rapid Detection of Influenza A and B Viruses
Authors: Berry Gregory J , Oladipo Olajumoke , Wittnebert Debbie , Loeffelholz Michael J , Petersen John R 
Published: July 2018

Abstract

Background
The use of point-of care testing (POCT) in patient management decisions is becoming increasingly common. Our goal was to evaluate the diagnostic performance of 2 commercially available rapid POCT devices for influenza viruses A and B: the Alere™ i Instrument (Alere, Scarborough) and the BD Veritor™ System (BD Diagnostics).

Methods
Paired nasopharyngeal swabs were collected from patients (18–71 years) presenting with influenza-like symptoms at 3 outpatient clinics. A total of 65 samples were obtained. The Alere i and BD Veritor were performed according to the manufacturers' instructions. Discordant results were resolved using real-time reverse transcription PCR (RT-PCR).

Results
In a head-to-head comparison involving symptomatic adult patients visiting outpatient clinics during the 2014–2015 and 2015–2016 influenza seasons, the Alere i and BD Veritor had 90.63% agreement in the detection of influenza A virus and a statistically significant observed κ coefficient of 0.754 (P &lt;0.0001). Discordant results between the Alere i and BD Veritor were further investigated using RT-PCR, showing that the BD Veritor missed 5 positive influenza A virus results (false negatives) and detected 1 false positive, while the Alere i results agreed with all RT-PCR results. There were no discordant results between the Alere i and BD Veritor in the detection of influenza B virus.

Conclusions
Our data suggest that the Alere i has higher sensitivity and specificity than the BD Veritor in the detection of influenza A virus. Both assays showed equal performance in the detection of influenza B virus.
Automated Sample Preparation Enables LC-MS/MS as a Routine Diagnostic Analysis for Serum Testosterone
Authors: Stone Judith A , van Staveren Dave R , Fitzerald Robert L 
Published: July 2018

Abstract

Background
The advantage of LC-MS/MS for analyzing serum testosterone in female, pediatric, and hypogonadal male patient samples is well accepted (J Clin Endocrinol Metab 2010;95:4542–8). However, many clinical laboratories still use testosterone immunoassays because of the technical challenges of LC-MS/MS (Clin Chem 2010;56:1234–44). Although LC-MS/MS has been shown to have better accuracy and specificity than immunoassay, better reproducibility has been more elusive because of the complexities of sample preparation (Clin Chem 2008;54:1290–7; Rev Endocr Metab Disord 2013;14:185–205).

Methods
We evaluated replacing automated immunoassay with LC-MS/MS for all testosterone analyses at the University of California San Diego Health System Center for Advanced Laboratory Medicine. We used a novel extraction media, AC Extraction Plate™ (AC Plate), from Tecan Schweiz with automated liquid handling for LC-MS/MS sample preparation. We modified the existing vendor application and validated the method for matrix effect, recovery, precision, trueness [accuracy relative to certified reference material (CRM)], specificity, reportable range, sample stability, and correlation with other methods.

Results
Method performance was excellent, with a reportable range of 4–1560 ng/dL (0.14–54.13 nmol/L), between-day CV &lt;6%, mean accuracy for CRM of &lt;4.0% bias, no interference from hemolysis, icterus, lipemia, serum separator tube gel, or common steroids/metabolites, and mean bias of 1.3% vs 4 other LC-MS/MS testosterone methods. A retrospective analysis of calibration stability suggests that sparse and/or historical calibration is feasible for routine use.

Conclusions
We conclude that automated extraction with the AC Plate and a focus on robustness during method development delivered ease of use and method performance consistent with adopting LC-MS/MS for all testosterone testing.
Validation of a Capillary Electrophoresis Assay for Monitoring Iodine Nutrition in Populations for Prevention of Iodine Deficiency: An Interlaboratory Method Comparison
Authors: de Macedo Adriana Nori , Macri Joseph , Hudecki Patricia L , Saoi Michelle , McQueen Matthew J , Britz-McKibbin Philip 
Published: July 2018

Abstract

Background
A capillary electrophoresis (CE) assay was recently introduced as a new method for monitoring iodine nutrition in large-scale epidemiological studies. However, further tests revealed unanticipated matrix-dependent interferences when analyzing submicromolar levels of iodide in human urine as the predominate ionic form of dietary iodine. Herein, we describe a rigorous validation study that was used to identify sources of bias and establish modifications to the original CE method to improve method accuracy.

Methods
An interlaboratory method comparison using CE with UV detection and inductively coupled plasma–mass spectrometry (ICP-MS) was performed to quantify urinary iodide concentrations (n = 71) independently at McMaster University and Hamilton General Hospital, as well as the CDC as part of their quality assurance program. A positive bias in the original CE method was indicated, and buffer conditions were subsequently optimized to overcome matrix interferences for reliable iodine status determination.

Results
Positive bias in CE was attributed to variable concentrations of sulfate, a major urinary anion interference with similar mobility to iodide under the conditions originally reported. By increasing the concentration of α-cyclodextrin in the background electrolyte, the CE method was able to tolerate urinary sulfate over its normal physiological range without loss in signal response for iodide. The optimized CE assay generated results that were consistent with ICP-MS using 2 different internal standards (187Re and 130Te) with a median bias under 10%.

Conclusions
CE offers a simple, selective, and cost-effective separation platform for surveillance of the iodine status of a population requiring only small volumes (&lt;10 μL) of biobanked urine specimens, which is comparable to previously validated screening methods currently used in global health initiatives for prevention of iodine deficiency disorders.
Opiate & Benzodiazepine Confirmations: To Hydrolyze or Not to Hydrolyze is the Question
Authors: Johnson-Davis Kamisha L 
Published: July 2018

Abstract

Background
Opiates/opioids and benzodiazepines are commonly prescribed drug therapies for acute and chronic pain. Urine drug testing is often employed to assess adherence to these mediations. Opioids and benzodiazepines are drug classes that undergo extensive metabolism through glucuronidation/sulfation. Conjugated glucuronide and sulfate drug metabolites can be difficult to detect by immunoassay and mass spectrometry methods. Consequently, false-negative or false-positive results can have a damaging impact on patient care. A common dilemma among drug-testing laboratories is whether to perform preanalytical hydrolysis to increase detection of drugs that are highly conjugated as metabolites.

Methods
The purpose of hydrolysis is to cleave the glucuronide or sulfate compounds to enhance analyte detection by increasing the parent drug concentration of those drugs that are primarily metabolized by glucuronidation or sulfation. Hydrolysis procedures can be performed by acid, base, or enzyme sources (β-glucuronidase).

Results
Preanalytical hydrolysis can improve the overall detection of most opioids and benzodiazepine drugs. However, the limitation of this procedure is that the process can be time-consuming and prolong the turnaround time to result. In addition, chemical hydrolysis has the potential to degrade opioid and benzodiazepine drugs, whereas incomplete hydrolysis and variable hydrolysis efficiencies can occur with an enzymatic approach.

Conclusions
Preanalytical hydrolysis can improve the sensitivity of drug detection for drug classes such as opiates/opioids and benzodiazepines, which are highly metabolized by glucuronidation and sulfation and should be implemented in analytical procedures to convert conjugated metabolites into the free (unbound) form.
New Bugs and New Drugs: Updates in Clinical Microbiology
Authors: Lainhart William , Yarbrough Melanie L , Jean Sophonie , Burnham Carey-Ann D 
Published: July 2018

AbstractBackgroundThe landscape of clinical microbiology laboratories is changing. As new technologies are introduced, we are better able to detect and identify pathogens and to recognize and characterize emerging antimicrobial resistance mechanisms.ContentIn this review, a selected cross-section of current hot topics in clinical microbiology is discussed. These topics include (a) diagnostics for urinary tract and sexually transmitted infections; (b) phenotypic and genotypic methods of detecting carbapenem resistance and discussion of newly approved anti-infective agents for these multi-drug resistant organisms; and (c) the significance, epidemiology, and identification of the emerging pathogens Mycobacterium chimaera and Candida auris.SummaryCommunication between clinical microbiologists and their clinical colleagues is imperative to convey the significance of emerging pathogens and resistance determinants, as well as the performance characteristics of new diagnostic methods. Additionally, as antimicrobial resistance is surging, it is important to comprehensively evaluate the resistance profiles of clinical isolates to facilitate antimicrobial stewardship and inform infection prevention measures. Although antimicrobial resistance is a global public health crisis, it is encouraging that new anti-infective agents are in the pipeline and being approved for use in patients.
Removing Cerebrospinal Fluid Antibody Orders from the Test Menu Results in a Dramatic Decrease in Order Volume
Authors: Beal Stacy G , Tremblay Elizabeth , Harris Neil , Rand Kenneth 
Published: July 2018

Abstract

Background
Antibody tests for Borrelia burgdorferi (agent of Lyme disease), Toxoplasma gondii, and cytomegalovirus in cerebrospinal fluid (CSF) are rarely useful. One reason for misutilization of laboratory tests is simply the convenience offered by a computerized physician order entry (CPOE) system.

Methods
The cytomegalovirus (CMV) antibodies-CSF, B. burgdorferi antibodies-CSF, and T. gondii antibodies-CSF orders were removed from the test menu. A provider could still order these tests using a miscellaneous order. We collected monthly volumes of test orders before and after the tests were removed from the CPOE.

Results
Orders for CSF antibody testing for B. burgdorferi, T. gondii, and CMV decreased by 91%, 93%, and 98%, respectively (P &lt; 0.01), after they were removed from the CPOE test menu. This result correlates to a savings of $50053.44 per year. Additionally, we did not see a paradoxical increase in CMV PCR or T. gondii PCR orders after the intervention.

Conclusions
Removal of test orders from the CPOE dramatically decreased test order volume, which led to substantial cost savings and availability of CSF for more useful tests. There was no compensatory increase in order volume for related tests, indicating that providers were not looking for alternate tests.