Performance of three automated SARS-CoV-2 antibody assays and relevance of orthogonal testing algorithms

AbstractObjectivesDevelopment and implementation of SARS-CoV-2 serologic assays gained momentum. Laboratories keep on investigating the performance of these assays. In this study, we compared three fully automated SARS-CoV-2 antibody assays.MethodsA total of 186 samples from 84 PCR-positive COVID-19 patients and 120 control samples taken before the SARS-CoV-2 pandemic were analyzed using commercial serologic assays from Roche, Siemens and DiaSorin. Time after the positive COVID-19 PCR result and onset of symptoms was retrieved from the medical record. An extended golden standard, using the result of all three assays was defined, judging if antibodies are present or absent in a sample. Diagnostic and screening sensitivity/specificity and positive/negative predictive value were calculated.ResultsDiagnostic sensitivity (ability to detect a COVID-19 positive patient) ≥14 days after positive PCR testing was 96.7% (95% CI 88.5–99.6%) for DiaSorin, 93.3% (95% CI 83.8–98.2%) for Roche and 100% (95% CI 94.0–100%) for Siemens. Lower diagnostic sensitivities were observed <14 days after onset of symptoms for all three assay. Diagnostic specificity (ability to detect a COVID-19 negative patient) was 95.0% (95% CI 89.4–98.1%) for DiaSorin, 99.2% (95% CI 95.4–99.9%) for Roche and 100% (95% CI 97.0–100%) for Siemens. The sensitivity/specificity for detecting antibodies (ability of detecting absence (specificity) or presence (sensitivity) of COVID-19 antibodies) was 92.4% (95% CI 86.4–96.3%)/94.9% (95% CI 90.5–97.6%) for DiaSorin, 97.7% (95% CI 93.5–99.5%)/97.1% (95% CI 93.5–99.1%) for Roche and 98.5% (95% CI 94.6–99.8)/97.1 (95% CI 93.5–99.1%) for Siemens.ConclusionsThis study revealed acceptable performance for all three assays. An orthogonal testing algorithm using the Siemens and Roche assay achieved the highest positive predictive values for antibody detection in low seroprevalence settings.

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Aksillere temperatuur vergelyk met timpaniese membraan temperatuur in kinders

Curationis ◽

10.4102/curationis.v23i3.701 ◽

2000 ◽

Vol 23 (3) ◽

Cited By ~ 1

Author(s):

G Greyling ◽

MJ Viljoen ◽

G Joubert

Keyword(s):

Screening Method ◽

Maximum Temperature ◽

Limits Of Agreement ◽

Axillary Temperature ◽

Predictive Values ◽

Tympanic Membrane Temperature ◽

Temperature Reading ◽

Golden Standard ◽

Acceptable Method ◽

Sensitivity Specificity

The purpose of the study was to measure the axillary temperature at three, six and nine minutes in a hundred children between the ages of one and twelve years who were selected in a non-random deliberate way, and to compare the measurements with the tympanic membrane temperature (golden standard) which was measured in the test persons at the same time. The results were described by sensitivity, specificity, limits of agreement, and predictive values. From some of the findings of the research it is apparent that the axillary temperature reading increased after measurement of three, six and nine minutes. A maximum temperature reading was reached after three minutes in only 9% of the test persons, in 25% after six minutes and in 66% after nine minutes. From the findings it is clear that the ranges that were used influenced the sensitivity of the measurements, and it would appear that the range 35,5°C to 37,2°C was the best range to measure pyrexia in the age group one to 12 years. The 9- minute measurement then had the highest sensitivity. However, the specificity of measurement in this range was lower. The conclusion was drawn that axillary temperature measurement is an acceptable method, with certain reservations, to use as screening method for pyrexia in emergency divisions or clinics.

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Effectiveness of a Two-Step Testing Algorithm for Reliable and Cost-Effective Detection of Clostridium difficile Infection in a Tertiary Care Hospital in Saudi Arabia

Medical Sciences ◽

10.3390/medsci7010006 ◽

2019 ◽

Vol 7 (1) ◽

pp. 6

Author(s):

Mohammed Qutub ◽

Prasanth Govindan ◽

Anupama Vattappillil

Keyword(s):

Clostridium Difficile ◽

Clostridium Difficile Infection ◽

Tertiary Care ◽

Care Hospital ◽

Predictive Values ◽

Stool Samples ◽

Step Algorithm ◽

Testing Algorithm ◽

Sensitivity Specificity ◽

Pcr Test

The aim of this study was to evaluate the effectiveness of a two-step algorithm for the detection of Clostridium difficile infection. Setting and Design: A two-step testing algorithm was evaluated for testing stool samples from patients suspected of Clostridium difficile infection (CDI). A total of 103 stool specimens were tested using the C. diff Quik Chek Complete enzyme immunoassay (EIA) test and the Xpert C. difficile PCR test. A two-step algorithm was implemented, and data from 3518 patient samples tested during a two-year period after implementation were analyzed to evaluate the effectiveness. The sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of the Quik Chek Complete EIA test were calculated using the Xpert C. difficile PCR test as a reference method. The sensitivity, specificity, PPV, and NPV of the Quik Chek Complete EIA test for C. difficile toxin were 46.7%, 100%, 100%, and 91%, respectively. The two-step algorithm, which combined the Quik Chek Complete EIA with Xpert C. difficile PCR, improved the sensitivity and also provided rapid detection. When algorithm-based testing was performed daily, there was a 66% reduction in turnaround time compared to batch testing using a lengthy ELISA procedure. Postimplementation data analysis showed that almost 89% of the samples could be reported immediately by initial screening with Quik Chek Complete EIA. Only 11% of the samples gave discrepant results and required PCR confirmation. According to our results, the two-step algorithm is an effective tool for the rapid and reliable detection of toxigenic C. difficile from stool samples.

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Validity Of Mothers’ Caries Screening Of Their Preschool Children And Its Relationship To Sociodemographic Backgrounds

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v16i2.1120 ◽

2017 ◽

Vol 16 (2) ◽

Author(s):

Syarifah Haizan Sayed Kamar ◽

Nasruddin Jaafar

Keyword(s):

Preschool Children ◽

Significant Relationship ◽

Household Income ◽

Educational Status ◽

Caries Detection ◽

Caries Prevalence ◽

Predictive Values ◽

Screening Sensitivity ◽

Sensitivity Specificity ◽

At Home

Introduction: Mothers can be trained to screen caries in their children. The aim of this study is to assess the validity of mothers’ caries screening of their preschool children. Materials and Methods: 81 volunteer mothers of four- and five-year-old preschool children, from four kindergartens in Pahang were included this study. All mothers were trained by a dentist to detect caries in preschoolers based on a simplified caries detection guideline by WHO (1997) in a three-hour course. Subsequently, all mothers screened their own children caries status at the workshop and 24 hour later, at home. The validity of the results was determined by comparing mothers’ to dentist’s findings; and calculating their sensitivity, specificity, positive predictive and negative predictive values at child and tooth levels. Results: Caries prevalence among the children was 88.9%, with mean dmft of 7.10 (sd 5.07). At the workshop, mothers’ screening sensitivity, specificity, positive predictive and negative predictive values at child level were 93.1%, 66.7%, 95.7%, 54.5%; and at tooth level were 76.6%, 94.0%, 90.4% and 87.8%, respectively. 24 hours post-workshop screening’s sensitivity, specificity, positive predictive and negative predictive values at tooth level were 76.1%, 93.7%, 90.7% and 87.9% respectively. The reliability of 24 hours post- workshop screening at tooth level was almost perfect (kappa=0.84). No significant relationship was reported between validity of screening and mothers' age, educational status, household income and area of residence. Conclusion(s): The validity of mothers’ screening in this sample was adequate in identifying caries in their preschool children, regardless of their sociodemographic backgrounds.

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Evaluation of characteristics of thyroid nodules on contrast-enhanced ultrasonography: a retrospective analysis of 252 cases

Medical Ultrasonography ◽

10.11152/mu-2252 ◽

2020 ◽

Vol 22 (2) ◽

pp. 164

Author(s):

Wen Luo ◽

Xiao Yang ◽

Jiani Yuan ◽

Lina Pang ◽

Peidi Zhang ◽

...

Keyword(s):

Retrospective Review ◽

Thyroid Nodules ◽

Contrast Enhanced Ultrasound ◽

Diagnostic Specificity ◽

Benign Lesions ◽

Predictive Values ◽

Contrast Enhanced ◽

Contrast Enhanced Ultrasonography ◽

Benign Nodules ◽

Sensitivity Specificity

Aim: This study investigated the enhancement patterns observed on contrast-enhanced ultrasound (CEUS) images for differentiating thyroid nodules.Material and methods: A retrospective review was conducted of CEUS cine loops of 252 nodules by two independent readers. Seven categories of enhancement patterns were identified: concentric hypoenhancement; heterogeneous hypoenhancement; hypoenhancement with sharp margin; homogeneous hyper/isoenhancement; hyper/isoenhancement with ring-like vascularity; island-like enhancement; and no perfusion. Associations between these patterns and the confirmed pathological/cytological outcomes (178 malignant, 74 benign) were analyzed and the sensitivity, specificity and positive predictive values (PPVs) determined. The agreement of the readers’ assessments was evaluated by Kappa value.Results: For malignant nodules, the predominant 3 patterns were: concentric hypoenhancement, heterogeneous hypoenhancement and homogeneous hyper/isoenhancement. For each of these, the diagnostic specificity was above 87% and the PPV more than 85%. Combining these patterns for malignancy the rates of sensitivity, specificity and PPV for reader 1 (reader 2) were 96.1% (98.9%), 71.6% (71.6%), and 89.1% (89.3%), respectively. For benign nodules, the predominant 4 patterns were: hypoenhancement with sharp margin; hyper/isoenhancement with ring-like vascularity; island-like enhancement; and no perfusion. The specificity for each was above 98% and the PPV more than 70%. Combining these patterns for benignity, the rates of sensitivity, specificity and PPV for reader 1 (reader 2) were 71.6% (71.6%), 96.1% (98.9%) and 88.3% (96.3%), respectively. The inter-reviewers agreement for classifying enhancement patterns was excellent (κ = 0.84, 95% CI: 0.79-0.89).Conclusions: Enhancement patterns of thyroid nodules on CEUS investigation, enable differentiation between malignant and benign lesions with good diagnostic sensitivity, specificity and PPV.

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Screening, Sensitivity, Specificity, and So Forth: A Second, Somewhat Skeptical, Sequel

Modern Health Science ◽

10.30560/mhs.v2n1p60 ◽

2019 ◽

Vol 2 (1) ◽

pp. p60 ◽

Cited By ~ 1

Author(s):

Robert Trevethan

Keyword(s):

Peripheral Artery Disease ◽

Previous Article ◽

Screening Tests ◽

Peripheral Artery ◽

Predictive Values ◽

Artery Disease ◽

Screening Sensitivity ◽

Sensitivity Specificity ◽

Gold Standards ◽

Conceptual Difficulties

This article is concerned with the sensitivity, specificity, predictive values, and other metrics associated with screening tests. It has direct origins in two previous articles. In this third article, the author of the first article writes about topics and issues that were addressed only minimally in his previous article and expands on topics raised by authors of the second article. In particular, attention is turned to wording and terminology that can be idiosyncratic and confusing with regard to screening versus diagnosis as well as to issues associated with reference (“gold”) standards and screening tests, and to the importance of cutpoints and prevalence in relation to metrics associated with screening tests. The primary aims are to help readers attain clarity about topics that they might have felt unsure about; gain reassurance about conceptual difficulties in the field that, once recognized for what they are, can become less problematic because it is possible to be confident about not being confident; and, where appropriate, adopt an appropriately skeptical attitude about screening tests and their associated metrics. Examples are drawn from the use of ankle–brachial and toe–brachial indices for identifying peripheral artery disease, although wider applicability is intended.

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Evaluation of commercially available high-throughput SARS-CoV-2 serological assays for serosurveillance and related applications

10.1101/2021.09.04.21262414 ◽

2021 ◽

Author(s):

Mars Stone ◽

Eduard Grebe ◽

Hasan Sulaeman ◽

Clara Di Germanio ◽

Honey Dave ◽

...

Keyword(s):

High Throughput ◽

High Sensitivity ◽

Antibody Responses ◽

Antibody Detection ◽

Laboratory Evaluation ◽

Assay Performance ◽

Testing Algorithm ◽

Sensitivity Specificity ◽

Intended Use

SARS-CoV-2 serosurveys can estimate cumulative incidence for monitoring epidemics but require characterization of employed serological assays performance to inform testing algorithm development and interpretation of results. We conducted a multi-laboratory evaluation of 21 commercial high-throughput SARS-CoV-2 serological assays using blinded panels of 1,000 highly-characterized blood-donor specimens. Assays demonstrated a range of sensitivities (96%-63%), specificities (99%-96%) and precision (IIC 0.55-0.99). Durability of antibody detection in longitudinal samples was dependent on assay format and immunoglobulin target, with anti-spike, direct, or total Ig assays demonstrating more stable, or increasing reactivity over time than anti-nucleocapsid, indirect, or IgG assays. Assays with high sensitivity, specificity and durable antibody detection are ideal for serosurveillance. Less sensitive assays demonstrating waning reactivity are appropriate for other applications, including characterizing antibody responses after infection and vaccination, and detection of anamnestic boosting by reinfections and vaccine breakthrough infections. Assay performance must be evaluated in the context of the intended use.

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Evaluation of aseptic loosening of knee prostheses by quantitative bone scintigraphy

Nuklearmedizin ◽

10.3413/nukmed-0123 ◽

2008 ◽

Vol 47 (04) ◽

pp. 163-166 ◽

Cited By ~ 6

Author(s):

D. Steiner ◽

S. Laurich ◽

R. Bauer ◽

J. Kordelle ◽

R. Klett

Keyword(s):

Aseptic Loosening ◽

Bone Scintigraphy ◽

Revision Surgery ◽

Predictive Value ◽

Knee Prostheses ◽

Treatment Regimes ◽

Golden Standard ◽

The Difference ◽

Sensitivity Specificity ◽

Asymptomatic Control

SummaryIn not infected knee prostheses bone scintigraphy is a possible method to diagnose mechanical loosening, and therefore, to affect treatment regimes in symptomatic patients. However, hitherto studies showed controversial results for the reliability of bone scintigraphy in diagnosing loosened knee prostheses by using asymptomatic control groups. Therefore, the aim of our study was to optimize the interpretation procedure and to evaluate the accuracy using results from revision surgery as standard. Methods: Retrospectively, we were able to examine the tibial component in 31 cemented prostheses. In this prostheses infection was excluded by histological or bacteriological examination during revision surgery. To quantify bone scintigraphy, we used medial and lateral tibial regions with a reference region from the contralateral femur. Results: To differentiate between loosened and intact prostheses we found a threshold of 5.0 for the maximum tibia to femur ratio of the both tibial regions and a threshold of 18% for the difference of the ratio of both tibial regions. Using these thresholds, values of 0.9, 1, 0.85, 1, and 0.94 were calculated for sensitivity, specificity, negative predictive value, positive predictive value, and accuracy, respectively. To get a sensitivity of 1, we found a lower threshold of 3.3 for the maximum tibia to femur ratio. Conclusion: Quantitative bone scintigraphy appears to be a reliable diagnostic tool for aseptic loosening of knee prostheses with thresholds evaluated by revision surgery results being the golden standard.

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Discriminating Malignancy in Thyroid Nodules: The Nomogram Versus the Kwak and ACR TI-RADS

Otolaryngology ◽

10.1177/0194599820939071 ◽

2020 ◽

Vol 163 (6) ◽

pp. 1156-1165

Author(s):

Juan Xiao ◽

Qiang Xiao ◽

Wei Cong ◽

Ting Li ◽

Shouluan Ding ◽

...

Keyword(s):

Thyroid Nodules ◽

Characteristic Curve ◽

Area Under The Curve ◽

Diagnostic Study ◽

Diagnostic Efficiency ◽

Training Set ◽

Multivariable Logistic Regression Model ◽

Predictive Values ◽

Validation Set ◽

Sensitivity Specificity

Objective To develop an easy-to-use nomogram for discrimination of malignant thyroid nodules and to compare diagnostic efficiency with the Kwak and American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS). Study Design Retrospective diagnostic study. Setting The Second Hospital of Shandong University. Subjects and Methods From March 2017 to April 2019, 792 patients with 1940 thyroid nodules were included into the training set; from May 2019 to December 2019, 174 patients with 389 nodules were included into the validation set. Multivariable logistic regression model was used to develop a nomogram for discriminating malignant nodules. To compare the diagnostic performance of the nomogram with the Kwak and ACR TI-RADS, the area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative predictive values were calculated. Results The nomogram consisted of 7 factors: composition, orientation, echogenicity, border, margin, extrathyroidal extension, and calcification. In the training set, for all nodules, the area under the curve (AUC) for the nomogram was 0.844, which was higher than the Kwak TI-RADS (0.826, P = .008) and the ACR TI-RADS (0.810, P < .001). For the 822 nodules >1 cm, the AUC of the nomogram was 0.891, which was higher than the Kwak TI-RADS (0.852, P < .001) and the ACR TI-RADS (0.853, P < .001). In the validation set, the AUC of the nomogram was also higher than the Kwak and ACR TI-RADS ( P < .05), each in the whole series and separately for nodules >1 or ≤1 cm. Conclusions When compared with the Kwak and ACR TI-RADS, the nomogram had a better performance in discriminating malignant thyroid nodules.

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The Impact of Narrow-band Imaging on the Pre- and Intra- operative Assessments of Neoplastic and Preneoplastic Laryngeal Lesions. A Systematic Review

International Archives of Otorhinolaryngology ◽

10.1055/s-0040-1719119 ◽

2020 ◽

Author(s):

Carmelo Saraniti ◽

Enzo Chianetta ◽

Giuseppe Greco ◽

Norhafiza Mat Lazim ◽

Barbara Verro

Keyword(s):

White Light ◽

Diagnostic Tool ◽

Narrow Band ◽

Narrow Band Imaging ◽

Resection Margins ◽

Predictive Values ◽

White Light Endoscopy ◽

Laryngeal Lesions ◽

Sensitivity Specificity ◽

The Impact

Introduction Narrow-band imaging is an endoscopic diagnostic tool that, focusing on superficial vascular changes, is useful to detect suspicious laryngeal lesions, enabling their complete excision with safe and tailored resection margins. Objectives To analyze the applications and benefits of narrow-band imaging in detecting premalignant and malignant laryngeal lesions through a comparison with white-light endoscopy. Data Synthesis A literature search was performed in the PubMed, Scopus and Web of Science databases using strict keywords. Then, two authors independently analyzed the articles, read the titles and abstracts, and read completely only the relevant studies according to certain eligibility criteria. In total, 14 articles have been included in the present review; the sensitivity, specificity, positive and negative predictive values, and accuracy of pre- and/or intraoperative narrow-band imaging were analyzed. The analysis showed that narrow-band imaging is better than white-light endoscopy in terms of sensitivity, specificity, positive and negative predictive values, and accuracy regarding the ability to identify cancer and/or precancerous laryngeal lesions. Moreover, the intraoperative performance of narrow-band imaging resulted more effective than the in-office performance. Conclusion Narrow-band imaging is an effective diagnostic tool to detect premalignant and malignant laryngeal lesions and to define proper resection margins. Moreover, narrow-band imaging is useful in cases of leukoplakia that may cover a possible malignant lesion and that cannot be easily assessed with white-light endoscopy. Finally, a shared, simple and practical classification of laryngeal lesions, such as that of the European Laryngological Society, is required to identify a shared lesion management strategy. Key Points

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Predicting youth diabetes risk using NHANES data and machine learning

Scientific Reports ◽

10.1038/s41598-021-90406-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nita Vangeepuram ◽

Bian Liu ◽

Po-hsiang Chiu ◽

Linhua Wang ◽

Gaurav Pandey

Keyword(s):

Machine Learning ◽

Large Scale ◽

Clinical Guideline ◽

Diabetes Risk ◽

Screening Tools ◽

Clinical Screening ◽

Predictive Values ◽

Screening Guideline ◽

Demographic Subgroups ◽

Sensitivity Specificity

AbstractPrediabetes and diabetes mellitus (preDM/DM) have become alarmingly prevalent among youth in recent years. However, simple questionnaire-based screening tools to reliably assess diabetes risk are only available for adults, not youth. As a first step in developing such a tool, we used a large-scale dataset from the National Health and Nutritional Examination Survey (NHANES) to examine the performance of a published pediatric clinical screening guideline in identifying youth with preDM/DM based on American Diabetes Association diagnostic biomarkers. We assessed the agreement between the clinical guideline and biomarker criteria using established evaluation measures (sensitivity, specificity, positive/negative predictive value, F-measure for the positive/negative preDM/DM classes, and Kappa). We also compared the performance of the guideline to those of machine learning (ML) based preDM/DM classifiers derived from the NHANES dataset. Approximately 29% of the 2858 youth in our study population had preDM/DM based on biomarker criteria. The clinical guideline had a sensitivity of 43.1% and specificity of 67.6%, positive/negative predictive values of 35.2%/74.5%, positive/negative F-measures of 38.8%/70.9%, and Kappa of 0.1 (95%CI: 0.06–0.14). The performance of the guideline varied across demographic subgroups. Some ML-based classifiers performed comparably to or better than the screening guideline, especially in identifying preDM/DM youth (p = 5.23 × 10−5).We demonstrated that a recommended pediatric clinical screening guideline did not perform well in identifying preDM/DM status among youth. Additional work is needed to develop a simple yet accurate screener for youth diabetes risk, potentially by using advanced ML methods and a wider range of clinical and behavioral health data.

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