scholarly journals Evaluation of the Performance of the IMMY sona Aspergillus Galactomannan Lateral Flow Assay When Testing Serum To Aid in Diagnosis of Invasive Aspergillosis

2020 ◽  
Vol 58 (6) ◽  
Author(s):  
P. Lewis White ◽  
Jessica S. Price ◽  
Raquel Posso ◽  
Morgan Cutlan-Vaughan ◽  
Lorna Vale ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Roc Analysis ◽  
False Negative ◽  
Area Under The Curve ◽  
Invasive Fungal Disease ◽  
Lateral Flow ◽  
Optimal Threshold ◽  
Serum Samples ◽  
Simple Method ◽  
The Impact

ABSTRACT Management of invasive aspergillosis has been improved by biomarker assays, but limited accessibility and batch testing limit the impact. Lateral flow assays (LFA) are a simple method for use outside specialist centers, provided performance is acceptable. The objective of this study was to determine the performance of the recently released IMMY sona Aspergillus LFA when testing serum samples. The study took the form of a retrospective, anonymous case/control study comprising 179 serum samples from 136 patients with invasive fungal disease, previously documented using recently revised internationally accepted definitions. The LFA was performed following the manufacturer’s instructions using a cube reader to generate a galactomannan index (GMI). Performance parameters were determined, and receiver operator characteristic (ROC) analysis was used to identify an optimal threshold. Concordance with the Bio-Rad Aspergillus Ag assay (GM-EIA) was performed. At the recommended positivity threshold (GMI ≥ 0.5), LFA sensitivity and specificity were 96.9% (31/32) and 98% (98/100), respectively. ROC analysis confirmed the optimal threshold and generated an area under the curve of 0.9919. Qualitative agreement between LFA and GM-EIA was 89.0%, generating a Kappa statistic of 0.698, representing good agreement, with most discordance arising due to false-negative GM-EIA samples that were positive by LFA. The median GMI generated by the LFA was significantly greater than that generated by the GM-EIA. The IMMY sona Aspergillus LFA, when used with a cube reader, provides a rapid alternative to the well-established GM-EIA, potentially detecting more GM epitopes and enhancing sensitivity.

scholarly journals The evaluation of binary classification tasks in economical prediction

2010 ◽  
Vol 58 (6) ◽  
pp. 369-378
Author(s):  
Martin Pokorný
Keyword(s):  
False Positive ◽  
Roc Analysis ◽  
Binary Classification ◽  
False Negative ◽  
Optimal Threshold ◽  
False Negatives ◽  
Classifier Performance ◽  
False Negative Error ◽  
Classification Tasks ◽  
Error Costs

In the area of economical classification tasks, the accuracy maximization is often used to evaluate classifier performance. Accuracy maximization (or error rate minimization) suffers from the assumption of equal false positive and false negative error costs. Furthermore, accuracy is not able to express true classifier performance under skewed class distribution. Due to these limitations, the use of accuracy on real tasks is questionable. In a real binary classification task, the difference between the costs of false positive and false negative error is usually critical. To overcome this issue, the Receiver Ope­rating Characteristic (ROC) method in relation to decision-analytic principles can be used. One essential advantage of this method is the possibility of classifier performance visualization by means of a ROC graph. This paper presents concrete examples of binary classification, where the inadequacy of accuracy as the evaluation metric is shown, and on the same examples the ROC method is applied. From the set of possible classification models, the probabilistic classifier with continuous output is under consideration. Mainly two questions are solved. Firstly, the selection of the best classifier from a set of possible classifiers. For example, accuracy metric rates two classifiers almost equiva­lently (87.7 % and 89.3 %), whereas decision analysis (via costs minimization) or ROC analysis reveal differe­nt performance according to target conditions of unequal error costs of false positives and false negatives. Secondly, the setting of an optimal decision threshold at classifier’s output. For example, accuracy maximization finds the optimal threshold at classifier’s output in value of 0.597, but the optimal threshold respecting higher costs of false negatives is discovered by costs minimization or ROC analysis in a value substantially lower (0.477).

scholarly journals Impact of Mucositis on Absorption and Systemic Drug Exposure of Isavuconazole

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Laura L. Kovanda ◽  
Francisco M. Marty ◽  
Johan Maertens ◽  
Amit V. Desai ◽  
Christopher Lademacher ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Drug Exposure ◽  
Area Under The Curve ◽  
Invasive Fungal Disease ◽  
Oral Formulation ◽  
Water Soluble ◽  
Parameter Estimates ◽  
Two Phase ◽  
Population Pk ◽  
The Impact

ABSTRACT Isavuconazonium sulfate is the water-soluble prodrug of isavuconazole. Population analyses have demonstrated relatively predictable pharmacokinetic (PK) behavior in diverse patient populations. We evaluated the impact of mucositis on the oral isavuconazole exposure using population PK modeling. This study included patients treated in two phase 3 trials of isavuconazole, SECURE for treatment of invasive aspergillosis (IA) and other filamentous fungi and VITAL for patients with mucormycosis, invasive fungal disease (IFD) caused by other rare fungi, or IA and renal impairment. Mucositis was reported by site investigators and its impact on oral bioavailability was assessed. Use of the oral formulation was at the discretion of the investigator. Patients with plasma samples collected during the use of isavuconazonium sulfate were included in the construction of population PK model. Of 250 patients included, 56 patients had mucositis at therapy onset or as an adverse event during oral isavuconazole therapy. Levels of oral bioavailability were comparable, at 98.3% and 99.8%, respectively. The average drug exposures (average area under the curve [AUCave]) calculated from either the mean or median parameter estimates were not different between patients with and without mucositis. Mortality and overall clinical responses were similar between patients receiving oral therapy with and without mucositis. We found that isavuconazole exposures and clinical outcomes in this subset of patients with mucositis who were able to take oral isavuconazonium sulfate were comparable to those in patients without mucositis, despite the difference in oral bioavailability. Therefore, mucositis may not preclude use of the oral formulation of isavuconazonium sulfate.

scholarly journals A Blend of Chlorophytum Borivilianum and Velvet Bean Increases Serum Growth Hormone in Exercise-Trained Men

2011 ◽  
Vol 4 ◽  
pp. NMI.S8127 ◽  
Author(s):  
Rick J. Alleman ◽  
Robert E. Canale ◽  
Cameron G. McCarthy ◽  
Richard J. Bloomer
Keyword(s):  
Growth Hormone ◽  
Dietary Supplement ◽  
Area Under The Curve ◽  
Serum Samples ◽  
Velvet Bean ◽  
Serum Growth Hormone ◽  
Chlorophytum Borivilianum ◽  
Acute Ingestion ◽  
Health Related ◽  
The Impact

Background Several isolated ingredients have been proposed to increase growth hormone (GH) release, including Chlorophytum borivilianum and Velvet bean. A combination of these two ingredients has been packaged within an investigational dietary supplement. It was the purpose of the present investigation to determine the impact of acute ingestion of this supplement on circulating GH in healthy, exercise-trained men. Methods Fifteen men ingested the dietary supplement on two different days, separated by one week. Blood was collected from subjects before ingestion of the supplement and at 20, 40, 60, 80, 100, and 120 minutes post ingestion. GH was analyzed in serum samples using an ELISA method. Values for GH for each subject, at each collection time, were averaged over both test days and used in the main analysis. Results Serum GH increased over time, with higher values at 60 minutes (1.56 ± 0.65 ng mL-1; P = 0.04; +767%), 80 minutes (1.76 ± 0.69 ng · mL-1; P = 0.02; +878%), and 100 minutes (1.48 ± 0.62 ng · mL1; P = 0.05; +722%) compared to pre ingestion (0.18 ± 0.04 ng · mL-1). A great deal of subject variability existed in the area under the curve (AUC) for GH, with pooled values ranging from 0.49 to 61.2 ng · mL-1 · 2 hr-1. Conclusion Acute ingestion of an investigational dietary supplement containing the active ingredients Chlorophytum borivilianum and Velvet bean results in an increase in circulating GH in exercise-trained men. Additional placebo controlled investigations are needed to extend these findings. Moreover, studies are needed to determine if chronic use of such supplementation leads to favorable changes in health-related parameters associated with increased circulating GH.

scholarly journals Serum MALAT1 Assumes Signifying Capacity in Gastric Cancer Diagnosis.

2020 ◽  
Author(s):  
Keqian Zhang ◽  
Tianqi Mao ◽  
Zhicheng He ◽  
Xiaojiao Wu ◽  
Yu Peng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Roc Analysis ◽  
Operating Characteristic ◽  
Area Under The Curve ◽  
Diagnostic Value ◽  
Chain Reaction ◽  
Serum Samples ◽  
Chi Square ◽  
Chi Square Test ◽  
Polymerase Chain

Abstract Background: Gastric cancer (GC) represents one of the most serious cancers worldwide with the increasing mortality. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), a kind of lncRNAs, has been reported to be involved in the progression of cancers. This study aimed to assess serum expression pattern of MALAT1 and its clinical significance in diagnosis of GC.Methods: Serum specimens were collected from 120 GC patients and 58 healthy individuals. The expression profile of MALAT1 was examined using quantitative real-time polymerase chain reaction (qRT-PCR), and its association with clinical parameters was estimated by chi-square test. The diagnostic value of MALAT1 in GC was evaluated by the receiver operating characteristic (ROC) analysis.Results: Upregulated expression of MALTA1 was found in GC patients compared with the healthy controls (P<0.05). The overexpression of MALAT1 was positively correlated with lymph node metastasis (P=0.041) and TNM stage (P=0.005). An area under the curve (AUC) was 0.897 in ROC analysis, suggesting the high diagnostic value of MALAT1. Conclusion: The expression of MALAT1 was upregulated in GC serum samples, and its expression might serve as a potential diagnostic biomarker in patients with GC.

scholarly journals Bloodstream Infections Are an Improbable Cause of Positive Serum (1,3)-β-d-Glucan in Hematology Patients

2014 ◽  
Vol 21 (9) ◽  
pp. 1357-1359 ◽  
Author(s):  
E. Furfaro ◽  
M. Mikulska ◽  
V. Del Bono ◽  
F. Guolo ◽  
P. Minetto ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
False Positive ◽  
Bloodstream Infections ◽  
Invasive Fungal Disease ◽  
Fungal Disease ◽  
Serum Samples ◽  
Positive Serum

ABSTRACTNinety-one serum samples from 51 hematology patients with bacteremia infections were tested for (1,3)-β-d-glucan (BG). Eleven samples (15%) from 7 patients (14%) were positive for BG. Of these 7 patients with positive BG results, 4 (8%) had invasive aspergillosis and 3 (6%) had no invasive fungal disease. Bacteremia was an unlikely cause of the false-positive BG results.

scholarly journals Aspergillus Lateral Flow Assay with Digital Reader for the Diagnosis of COVID-19 Associated Pulmonary Aspergillosis (CAPA): A multicenter study

2021 ◽  
Author(s):  
Brice Autier ◽  
Juergen Prattes ◽  
P. Lewis White ◽  
Maricela Valerio ◽  
Marina Machado ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Multicenter Study ◽  
Area Under The Curve ◽  
Lavage Fluid ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
Sample Type ◽  
Serum Samples ◽  
Pulmonary Aspergillosis ◽  
Roc Area

This multicenter study evaluated the IMMY Aspergillus Galactomannan Lateral Flow Assay (LFA) with automated reader for diagnosis of pulmonary aspergillosis in patients with COVID-19 associated acute respiratory failure (ARF) requiring intensive care unit (ICU) admission between 03/2020 and 04/2021. A total of 196 respiratory samples and 148 serum samples (n=344) from 238 patients were retrospectively included, with a maximum of one of each sample type per patient. Cases were retrospectively classified for COVID-19 associated pulmonary aspergillosis (CAPA) status following the 2020 consensus criteria, with the exclusion of LFA results as a mycological criterion. At the 1.0 cutoff, sensitivity of LFA for CAPA (proven/probable/possible) was 52%, 80% and 81%, and specificity was 98%, 88% and 67%, for bronchoalveolar lavage fluid (BALF), non-directed bronchoalveolar lavage (NBL), and tracheal aspiration (TA), respectively. At the 0.5 manufacturer’s cutoff, sensitivity was 72%, 90% and 100%, and specificity was 79%, 83% and 44%, for BALF, NBL and TA, respectively. When combining all respiratory samples, the receiver operating characteristic (ROC) area under the curve (AUC) was 0.823, versus 0.754, 0.890 and 0.814 for BALF, NBL and TA, respectively. Sensitivity and specificity of serum LFA were 20% and 93%, respectively, at the 0.5 ODI cutoff. Overall, the Aspergillus Galactomannan LFA showed good performances for CAPA diagnosis, when used from respiratory samples at the 1.0 cutoff, while sensitivity from serum was limited, linked to weak invasiveness during CAPA. As some false positive results can occur, isolated results slightly above the recommended cutoff should lead to further mycological investigations.

scholarly journals Prospective Evaluation of the Turbidimetric β-D-Glucan Assay and 2 Lateral Flow Assays on Serum in Invasive Aspergillosis

2020 ◽  
Author(s):  
Toine Mercier ◽  
Ellen Guldentops ◽  
Katrien Lagrou ◽  
Johan Maertens
Keyword(s):  
Invasive Aspergillosis ◽  
Predictive Value ◽  
Diagnostic Performance ◽  
Lateral Flow ◽  
Added Value ◽  
Prospective Evaluation ◽  
Serum Samples ◽  
Flow Device ◽  
Lateral Flow Assays ◽  
Risk Patients

Abstract Background Invasive aspergillosis (IA) remains a potentially lethal disease and requires timely diagnosis and initiation of antifungal therapy. Recently, the IMMY lateral flow assay (LFA), the OLM Diagnostics lateral flow device (LFD), and the Wako turbidimetric β-d-glucan assay have been approved for use as a diagnostic aid. However, their performance in diagnosing IA on serum samples from at-risk patients and the added value to the existing detection of serum galactomannan remain to be investigated. Methods We prospectively collected serum samples from 239 hematology patients and evaluated the diagnostic performance of these 3 assays while using the 2019 EORTC/MSG definitions (study number S59863/S61797, NCT03004092). Results We identified 5 cases of proven IA, 36 cases of probable IA, and 188 controls. The LFA had the highest negative predictive value (NPV) and sensitivity (0.90 and 0.49, respectively) while galactomannan detection had the highest positive predictive value and specificity (0.93 and 0.99, respectively). Sensitivity was not significantly different between both tests. When used in combination, the highest NPV was seen in patients with a negative LFA and a negative β-d-glucan test. The sensitivity of the LFD was significantly lower than the LFA. After omitting serum galactomannan from the definitions to control for incorporation bias, the sensitivity of the LFA outperformed galactomannan detection (0.41 vs 0.31, P = .046). Conclusions The LFA is a fast and effective alternative to serum galactomannan detection for the diagnosis of IA and is especially useful for centers with low sample throughputs. The addition of the Wako β-D-glucan assay further improves the diagnostic performance.

scholarly journals An Evaluation of the Performance of the IMMY Aspergillus Galactomannan Enzyme-Linked Immunosorbent Assay When Testing Serum To Aid in the Diagnosis of Invasive Aspergillosis

2020 ◽  
Vol 58 (12) ◽  
Author(s):  
P. Lewis White ◽  
Jessica S. Price ◽  
Raquel Posso ◽  
Lorna Vale ◽  
Matthijs Backx
Keyword(s):  
Invasive Aspergillosis ◽  
Sensitivity And Specificity ◽  
Clinical Performance ◽  
Kappa Statistic ◽  
Invasive Fungal Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Characteristic Analysis ◽  
Serum Samples ◽  
Retrospective Case ◽  
And Control

ABSTRACT The objectives of this study were to evaluate the performance of the recently released IMMY Aspergillus galactomannan enzyme immunoassay (IMMY GM-EIA) when testing serum samples and to identify the optimal galactomannan index (GMI) positivity threshold for the diagnosis of invasive aspergillosis (IA). This was a retrospective case/control study, comprising 175 serum samples obtained from 131 patients, 35 of whom had probable or possible invasive fungal disease (IFD) as categorized using recently revised, internationally accepted definitions. The IMMY GM-EIA was performed following the manufacturer’s instructions. Performance parameters were determined and receiver operator characteristic analysis was used to identify an optimal GMI threshold. Concordance with the Bio-Rad Aspergillus Ag assay (Bio Rad GM-EIA) and IMMY sona Aspergillus lateral flow assay was assessed. The median GMIs generated by the IMMY GM-EIA for samples originating from probable IA/IFD cases (n = 31), possible IFD (n = 4), and control patients (n = 100) were 0.61, 0.11, and 0.14, respectively, and were comparable to those of the Bio-Rad GM-EIA (0.70, 0.04, and 0.04, respectively). Overall qualitative observed sample agreement between the IMMY GM-EIA and Bio-Rad GM-EIA was 94.7%, generating a kappa statistic of 0.820. At a GMI positivity threshold of ≥0.5, the IMMY GM-EIA had a sensitivity and specificity of 71% and 98%, respectively. Reducing the threshold to ≥0.27 generated sensitivity and specificity of 90% and 92%, respectively. The IMMY GM-EIA provides a comparable alternative to the Bio-Rad GM-EIA when testing serum samples. Further prospective, multicenter evaluations are required to confirm the optimal threshold and associated clinical performance.

scholarly journals Evaluation of Serum Cryptococcal Antigen Testing Using Two Novel Semiquantitative Lateral Flow Assays in Persons with Cryptococcal Antigenemia

2020 ◽  
Vol 58 (4) ◽  
Author(s):  
Caleb Skipper ◽  
Kiiza Tadeo ◽  
Emily Martyn ◽  
Elizabeth Nalintya ◽  
Radha Rajasingham ◽  
...  
Keyword(s):  
False Positive ◽  
Diagnostic Performance ◽  
False Negative ◽  
Lateral Flow ◽  
Reference Standard ◽  
Serum Samples ◽  
Cryptococcal Antigen ◽  
Negative Results ◽  
Lateral Flow Assays ◽  
Positive Results

ABSTRACT Early cryptococcal disease can be detected via circulating antigen in blood before fulminant meningitis develops, when early antifungal therapy improves survival. Two semiquantitative cryptococcal antigen (CrAg) lateral flow assays (LFAs) have been developed, but their diagnostic performance has not been defined. Cryopreserved serum samples from HIV-infected Ugandans obtained as part of a prospective CrAg-screening cohort were tested in duplicate for CrAg by the CrAgSQ (IMMY) and CryptoPS (Biosynex) lateral flow assays. Case-controlled diagnostic performance was measured using the FDA-approved CrAg LFA (IMMY) as a reference standard via McNemar’s test. Of 99 serum samples tested, 57 were CrAg positive (CrAg+) by the CrAg LFA reference standard. By CrAgSQ, 57 were read as positive, with 98% sensitivity (56/57; 95% confidence interval [CI], 0.91 to 0.99) and 98% specificity (41/42; 95% CI, 0.88 to 0.99) (McNemar’s, P = 0.99). The sample with a false-negative result by CrAgSQ (n = 1) had a titer of <1:5, while the sample with a false-positive result (n = 1) yielded a 1+ result. By CryptoPS, 52 samples were read as positive, with 88% sensitivity (50/57; 95% CI, 0.76 to 0.95) and 95% specificity (40/42; 95% CI, 0.84 to 0.99) (McNemar’s, P = 0.18). The CryptoPS false-negative results included samples with titers of <1:5 (n = 1), 1:5 (n = 5), and 1:20 (n = 1), while samples with false-positive results by CryptoPS (n = 2) yielded Positive results. The CryptoPS assay missed 35% (7/20) of samples with CrAg LFA titers of ≤1:20. The new semiquantitative CrAg LFAs allow rapid estimation of titer levels in easy-to-perform platforms. The CrAgSQ demonstrated better qualitative sensitivity and specificity than the CryptoPS compared to the reference standard. The exact grading of the CrAgSQ results has some subjectivity, with interreader variability; however, qualitative reads were generally concordant for both assays.

scholarly journals Alix: A Candidate Serum Biomarker of Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Yingni Sun ◽  
Jin Hua ◽  
Gen Chen ◽  
Jianjie Li ◽  
Jiateng Yang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Roc Analysis ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Serum Levels ◽  
The Elderly ◽  
Significant Negative Correlation ◽  
Serum Samples ◽  
Non Invasive

Alzheimer’s disease (AD) is the most common fatal neurodegenerative disease of the elderly worldwide. The identification of AD biomarkers will allow for earlier diagnosis and thus earlier intervention. The aim of this study was to find such biomarkers. It was observed that the expression of Alix was significantly decreased in brain tissues and serum samples from AD patients compared to the controls. A significant correlation between Alix levels and cognitive decline was observed (r = 0.80; p &lt; 0.001) as well as a significant negative correlation between Alix and Aβ40 in serum levels (r =−0.60, p &lt; 0.001). The receiver operating characteristic curve (ROC) analysis showed the area under the curve (AUC) of Alix was 0.80, and the optimal cut-off point of 199.5 pg/ml was selected with the highest sum of sensitivity and specificity. The diagnostic accuracy for serum Alix was 74%, with 76% sensitivity and 71% specificity respectively, which could differentiate AD from controls. In addition, the expression of Alix was found to be significantly decreased in AD compared to vascular dementia (VaD). ROC analysis between AD and VaD showed that the AUC was 0.777, which could be indicative of the role of serum Alix as a biomarker in the differential diagnosis between AD and VaD. Most surprisingly, the decreased expression of Alix was attenuated after the treatment of Memantine in different AD animal models. In conclusion, our results indicate the possibility of serum Alix as a novel and non-invasive biomarker for AD for the first time.

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