scholarly journals A Bayesian method for synthesizing multiple diagnostic outcomes of COVID-19 tests

2021 ◽  
Vol 8 (9) ◽  
pp. 201867
Author(s):  
Lirong Cao ◽  
Shi Zhao ◽  
Qi Li ◽  
Lowell Ling ◽  
William K. K. Wu ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Web Application ◽  
Multiple Testing ◽  
Posterior Probability ◽  
Human Life ◽  
False Negative ◽  
Patient Treatment ◽  
Bayesian Posterior Probability ◽  
Free Access ◽  
Negative Results

The novel coronavirus disease 2019 (COVID-19) has spread worldwide and threatened human life. Diagnosis is crucial to contain the spread of SARS-CoV-2 infections and save lives. Diagnostic tests for COVID-19 have varying sensitivity and specificity, and the false-negative results would have substantial consequences to patient treatment and pandemic control. To detect all suspected infections, multiple testing is widely used. However, it may be challenging to build an assertion when the testing results are inconsistent. Considering the situation where there is more than one diagnostic outcome for each subject, we proposed a Bayesian probabilistic framework based on the sensitivity and specificity of each diagnostic method to synthesize a posterior probability of being infected by SARS-CoV-2. We demonstrated that the synthesized posterior outcome outperformed each individual testing outcome. A user-friendly web application was developed to implement our analytic framework with free access via http://www2.ccrb.cuhk.edu.hk/statgene/COVID_19/ . The web application enables the real-time display of the integrated outcome incorporating two or more tests and calculated based on Bayesian posterior probability. A simulation-based assessment demonstrated higher accuracy and precision of the Bayesian probabilistic model compared with a single-test outcome. The online tool developed in this study can assist physicians in making clinical evaluations by effectively integrating multiple COVID-19 tests.

scholarly journals Diagnostic Performance of Ankle-Brachial Pressure Index in Lower Extremity Arterial Disease

2021 ◽  
Vol 07 (03) ◽  
pp. e132-e137
Author(s):  
Mohammed Alagha ◽  
Thomas M. Aherne ◽  
Ahmed Hassanin ◽  
Adeel S. Zafar ◽  
Doireann P. Joyce ◽  
...  
Keyword(s):  
Lower Extremity ◽  
Sensitivity And Specificity ◽  
False Negative ◽  
Arterial Disease ◽  
Initial Assessment ◽  
Reference Standard ◽  
Lower Extremity Arterial Disease ◽  
Negative Results ◽  
Positive Results ◽  
Arterial Imaging

Abstract Introduction Ankle-brachial pressure indices (ABIs) continue to form the basis of diagnostics for lower extremity arterial disease (LEAD). However, there remains a paucity of data to support its accuracy. This study aims to evaluate its diagnostic sensitivity and specificity using established arterial-imaging modalities as a benchmark. Methods In this retrospective study, a regional, prospectively maintained, vascular laboratory database was interrogated to identify referred patients with arterial disease who underwent concomitant assessment with ABI and lower limb arterial duplex ultrasound (DUS). Duplex acted as the reference standard. Those who had peripheral computed tomography angiogram (CTA) within 3 months of initial assessment were included in a subgroup analysis to correlate ABI with CTA. The primary end point was the sensitivity and specificity of ABI compared with DUS as the reference standard. Results Concomitant assessment was performed in 438 limbs (250 patients) over a 27-month period. The ABI was normal (0.9 to 1.4) in 196 limbs (44.9%) and abnormal in the remaining 241 limbs (55.1%). False-positive results occurred in 83 out of 241 limbs (34.4%), and false-negative results occurred in 54 limbs out of 196 (27.5%). True-positive results were 158 out of 241 limbs (65.6%), whereas true-negative results were 142 out of 196 limbs (72.4%). ABI using DUS as a benchmark identified a sensitivity for peripheral artery disease of 72.3% and a specificity of 69.3%. Concomitant CTA imaging was available in 200 limbs. The sensitivity and specificity of ABI correlated with CTA were 65.5 and 68.8%, respectively. Conclusion ABIs have a moderate predictive value in the diagnosis of LEAD. Normal range outcomes cannot be taken to infer the absence of LEAD and, as such, further arterial imaging in the form of DUS or angiography should be strongly considered in those with suspected underlying disease requiring intervention. Further noninvasive tests such as exercise studies or pulse volume waveforms should be considered, if diagnostic uncertainty exists, in those requiring nonoperative intervention and risk factor control.

scholarly journals Evaluation of Recombinant Proteins of Burkholderia mallei for Serodiagnosis of Glanders

2012 ◽  
Vol 19 (8) ◽  
pp. 1193-1198 ◽  
Author(s):  
Vijai Pal ◽  
Subodh Kumar ◽  
Praveen Malik ◽  
Ganga Prasad Rai
Keyword(s):  
Sensitivity And Specificity ◽  
Recombinant Proteins ◽  
False Negative ◽  
Enzyme Linked Immunosorbent Assay ◽  
Burkholderia Mallei ◽  
Content Type ◽  
Whole Cells ◽  
Negative Results ◽  
Elisa Format ◽  
Low Sensitivity

ABSTRACTGlanders is a contagious disease caused by the Gram-negative bacillusBurkholderia mallei. The number of equine glanders outbreaks has increased steadily during the last decade. The disease must be reported to the Office International des Epizooties, Paris, France. Glanders serodiagnosis is hampered by the considerable number of false positives and negatives of the internationally prescribed tests. The major problem leading to the low sensitivity and specificity of the complement fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA) has been linked to the test antigens currently used, i.e., crude preparations of whole cells. False-positive results obtained from other diagnostic tests utilizing crude antigens lead to financial losses to animal owners, and false-negative results can turn a risk into a possible threat. In this study, we report on the identification of diagnostic targets using bioinformatics tools for serodiagnosis of glanders. The identified gene sequences were cloned and expressed as recombinant proteins. The purified recombinant proteins ofB. malleiwere used in an indirect ELISA format for serodiagnosis of glanders. Two recombinant proteins, 0375H and 0375TH, exhibited 100% sensitivity and specificity for glanders diagnosis. The proteins also did not cross-react with sera from patients with the closely related disease melioidosis. The results of this investigation highlight the potential of recombinant 0375H and 0375TH proteins in specific and sensitive diagnosis of glanders.

scholarly journals Towards Multitarget Testing in Molecular Microbiology

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Deborah Steensels ◽  
Anne Vankeerberghen ◽  
Hans De Beenhouwer
Keyword(s):  
False Negative ◽  
Lessons Learned ◽  
Patient Treatment ◽  
Culture Methods ◽  
Diagnostic Assays ◽  
Genome Variability ◽  
Negative Results ◽  
Conventional Culture ◽  
False Negative Results ◽  
Single Target

Advantages of PCR assays over more conventional culture-based diagnostics include significantly higher sensitivities and shorter turnaround times. They are particularly useful when patient treatment has already been initiated or for specimens that may contain microorganisms that are slow-growing, difficult to culture, or for which culture methods do not exist. However, due to genome variability, single target testing might lead to false-negative results. This paper focuses on examples from our own experiences and the literature to provide insight into the limitations of single target testing in molecular biology. Lessons learned from these experiences include the careful design of diagnostic assays, preferably multitargeted, the importance of investigating the incidence and epidemiology of infection in detail, the frequent participation in appropriate quality assurance schemes, and the importance of continuous attentiveness by investigators when confronted with inconsistent results. In conclusion, multitargeted testing in microbiological molecular assays should be a rule.

Pearls and Pitfalls of Interpretation in CT Colonography

2020 ◽  
Vol 71 (2) ◽  
pp. 140-148
Author(s):  
Michael Schonberger ◽  
Philippe Lefere ◽  
Abraham H. Dachman
Keyword(s):  
Computed Tomography ◽  
Sensitivity And Specificity ◽  
False Positive ◽  
Ct Colonography ◽  
False Negative ◽  
High Sensitivity ◽  
Negative Results ◽  
False Negative Results ◽  
The Common

The accuracy of computed tomography (CT) colonography (CTC) requires that the radiologist be well trained in the recognition of pitfalls of interpretation. In order to achieve a high sensitivity and specificity, the interpreting radiologist must be well versed in the causes of both false-positive and false-negative results. In this article, we review the common and uncommon pitfalls of interpretation in CTC.

scholarly journals Fluorometric detection of HIV-1 genome through use of an internal control, inosine-substituted primers, and microtiter plate format

1996 ◽  
Vol 42 (5) ◽  
pp. 696-703 ◽  
Author(s):  
B Gérard ◽  
C Peponnet ◽  
G Brunie ◽  
H Cavé ◽  
E Denamur ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Internal Control ◽  
False Negative ◽  
Enzymatic Reaction ◽  
Pcr Amplification ◽  
Microtiter Plate ◽  
Fluorometric Detection ◽  
Negative Results ◽  
False Negative Results ◽  
Hiv 1

Abstract We describe a PCR-based fluorometric assay for the detection of the HIV-1 genome. This technique consists of a reverse hybridization with oligonucleotide probes covalently coated onto a microtiter plate as a solid support. Several improvements to the PCR amplification and detection steps gave greater sensitivity and specificity for HIV-1 screening and resulted in a convenient and rapid technique. False-positive results were avoided by using uracyl DNA glycosylase. False-negative results from the presence of PCR inhibitors were detected by coamplifying an internal control with the viral sequence. False-negative results from viral genome variability were limited by using two pairs of primers and by incorporating inosine at the primer positions corresponding to viral polymorphic nucleotides. Furthermore, the hybridization buffer and enzymatic reaction were optimized to increase the assay's sensitivity. The sensitivity and specificity of the fluorometric detection were similar to those of radioisotopic oligonucleotide solution hybridization; however, hands-on time was reduced, and the use of radioactivity was eliminated. We have used this technique routinely on 115 samples and obtained 100% specificity and high sensitivity (only one false-negative result) according to viral culture and (or) serological status of the patients.

scholarly journals Performance of SARS-CoV-2 Serology tests: Are they good enough?

2020 ◽  
Author(s):  
Isabelle Piec ◽  
Emma English ◽  
M Annette Thomas ◽  
Samir Dervisevic ◽  
William D Fraser ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Respiratory Infections ◽  
Point Of Care ◽  
False Negative ◽  
Rapid Test ◽  
Diagnostic Sensitivity ◽  
Medical Community ◽  
Antibody Detection ◽  
Serological Tests ◽  
Negative Results

AbstractBackgroundIn the emergency of the SARS-CoV-2 pandemic, great efforts were made to quickly provide serology testing to the medical community however, these methods have been introduced into clinical practice without the complete validation usually required by the regulatory organizations.MethodsSARS-CoV-2 patient samples (n=43) were analysed alongside pre-pandemic control specimen (n=50), confirmed respiratory infections (n=50), inflammatory polyarthritis (n=22) and positive for thyroid stimulating immunoglobulin (n=30). Imprecision, diagnostic sensitivity and specificity and concordance were evaluated on IgG serologic assays from EuroImmun, Epitope Diagnostics (EDI), Abbott Diagnostics and DiaSorin and a rapid IgG/IgM test from Healgen.ResultsEDI and EuroImmun imprecision was 0.02-14.0% CV. Abbott and DiaSorin imprecision (CV) ranged from 5.2% - 8.1% and 8.2% - 9.6% respectively. Diagnostic sensitivity of the assays were 100% (CI: 80-100%) for Abbott, EDI and EuroImmun and 95% (CI: 73-100%) for DiaSorin at ≥14 days post PCR. Only the Abbott assay had a diagnostic specificity of 100% (CI: 91-100%). EuroImmun cross-reacted in 3 non-SARS-CoV-2 respiratory infections and 2 controls. The DiaSorin displayed more false negative results and cross-reacted in six cases across all conditions tested. EDI had one cross-reactive sample. The Healgen rapid test showed excellent sensitivity and specificity. Overall, concordance of the assays ranged from 76.1% to 97.9%.ConclusionsSerological tests for SARS-CoV-2 showed good analytical performance. The head-to-head analysis of samples revealed differences in results that may be linked to the use of nucleocapsid or spike proteins. The point of care device tested demonstrated adequate performance for antibody detection.

scholarly journals Droplet Digital PCR – A Superior Complementary Technique for SARS-CoV-2 Detection

2020 ◽  
pp. 12-15
Author(s):  
I. M. Hussaini ◽  
S. Gide ◽  
B. Musa ◽  
M. A. Sulaiman ◽  
A. Usman
Keyword(s):  
Sensitivity And Specificity ◽  
False Negative ◽  
Standard Technique ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Reference Standard ◽  
Rt Pcr ◽  
Negative Results ◽  
False Negative Results ◽  
Current Reference Standard

Accurate and timely SARS-CoV-2 detection in suspected persons is crucial in the fight against its spread. Many techniques have been developed to meet up with the continuously growing demand, however some of these techniques lack the required accuracy, sensitivity and specificity. The current reference standard technique for SARS-CoV-2 detection is RT-PCR, but studies have shown that false-negative results are inevitable and data can be non-reproducible when samples and primers are not appropriately verified and validated. Droplet digital PCR (ddPCR) is a newly introduced technique that performs precise nucleic acid quantification. Researchers have evaluated the efficacy of ddPCR and the technique has shown promising results even in specimens with low viral load. ddPCR has shown increased accuracy, precision, sensitivity and specificity. Furthermore, it is less affected by annealing and amplification inhibitors. This suggests that ddPCR can be used as a complementary detection technique especially in convalescent cases.

scholarly journals Performance of seven commercial automated assays for the detection of low levels of anti-Toxoplasma IgG in French immunocompromised patients

Parasite ◽  
2019 ◽  
Vol 26 ◽  
pp. 51 ◽  
Author(s):  
Tiphaine Douet ◽  
Catherine Armengol ◽  
Elena Charpentier ◽  
Pamela Chauvin ◽  
Sophie Cassaing ◽  
...  
Keyword(s):  
High Risk ◽  
Sensitivity And Specificity ◽  
False Negative ◽  
Tissue Cyst ◽  
Grey Zone ◽  
Immunocompromised Patients ◽  
Negative Results ◽  
Acute Infections ◽  
False Negative Results ◽  
Low Levels

Background: Immunocompromised patients are at high risk for the development of severe toxoplasmosis from tissue cyst reactivation, the most frequently, or from recently acquired acute infections. Knowledge of serologic status is therefore crucial. Screening for toxoplasmosis is sometimes performed while patients are already immunocompromised and have a low or even undetectable IgG titer by routine automated enzyme immunoassays. The aim of this study was to assess the sensitivity and specificity of seven reagents for the detection of low levels of IgG. Sera from 354 patients were collected and analysed. Results: Elecsys® offered the best analytic performances, superior to those of Architect® and Platelia®, which were superior to those of Access II® and TGS TA®. Vidas II® and Liaison II® reagents exhibited poor analytical performances in this cohort. For Elecsys®, Platelia® and Architect®, new thresholds for the grey zone and positive zone have been defined to improve the sensitivity of these reagents while maintaining excellent specificity. Conclusions: Commercialized assays for toxoplasmosis screening are not suitable for IgG low-level detection in patients without adapting the supplier thresholds to avoid false negative results and risk generalized toxoplasmosis.

scholarly journals Nucleic Acid and Immunological Diagnostics for SARS-CoV-2: Processes, Platforms and Pitfalls

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 866
Author(s):  
Avinash Premraj ◽  
Abi George Aleyas ◽  
Binita Nautiyal ◽  
Thaha J Rasool
Keyword(s):  
Sensitivity And Specificity ◽  
Early Stage ◽  
Control Strategies ◽  
False Negative ◽  
Primary Diagnosis ◽  
Test Methods ◽  
Molecular Technique ◽  
Negative Results ◽  
False Negative Results ◽  
Host Tissues

Accurate diagnosis at an early stage of infection is essential for the successful management of any contagious disease. The coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus is a pandemic that has affected 214 countries affecting more than 37.4 million people causing 1.07 million deaths as of the second week of October 2020. The primary diagnosis of the infection is done either by the molecular technique of RT-qPCR by detecting portions of the RNA of the viral genome or through immunodiagnostic tests by detecting the viral proteins or the antibodies produced by the host. As the demand for the test increased rapidly many naive manufacturers entered the market with novel kits and more and more laboratories also entered the diagnostic arena making the test result more error-prone. There are serious debates globally and regionally on the sensitivity and specificity of these tests and about the overall accuracy and reliability of the tests for decision making on control strategies. The significance of the test is also complexed by the presence of asymptomatic carriers, re-occurrence of infection in cured patients as well as by the varied incubation periods of the infection and shifting of the viral location in the host tissues. In this paper, we review the techniques available for SARS-CoV-2 diagnosis and probable factors that can reduce the sensitivity and specificity of the different test methods currently in vogue. We also provide a checklist of factors to be considered to avoid fallacious practices to reduce false positive and false negative results by the clinical laboratories.

False positivity in HER2 testing of breast cancer: novel paths for approaching an old dilemma

2013 ◽  
Vol 66 (11) ◽  
pp. 946-950 ◽  
Author(s):  
Cristiana Buzelin Nunes ◽  
Rafael Malagoli Rocha ◽  
Marcelo Araújo Buzelin ◽  
Débora Balabram ◽  
Fernanda de Souza Foureaux ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Specific Antibody ◽  
False Positive ◽  
In Situ Hybridisation ◽  
False Negative ◽  
Tissue Microarrays ◽  
Her2 Status ◽  
Kappa Statistics ◽  
Negative Results ◽  
Dual Colour

AimsVariability in determining HER2 status has been reported, especially, differences in sensitivity and specificity among commercially available antibodies, with false positive and false negative results. We compared the sensitivity and specificity of five anti-HER2 antibodies by immunohistochemistry (IHC), using the new dual colour brightfield in situ hybridisation (DDISH) as the gold standard, on invasive breast carcinomas (IBC) arrays.Material and methodsSerial sections from tissue microarrays (TMA) containing 200 preselected primary IBC were submitted to DDISH (VENTANA INFORM HER2 Dual ISH assay), and immunohistochemistry, using Dako A0485 and HercepTest (polyclonal), Novocastra CB11 (mouse monoclonal), NeoMarkers SP3 and Ventana 4B5 (rabbit monoclonal).ResultsFrom the initial 200 cases, 184 were assessed by DDISH and IHC. The concordance among the antibodies was considered very good (kappa statistics varied from 0.82 to 0.9). The overall concordance between IHC and DDISH ranged from 94.1% for CB11 to 96.6% for A0485. The antibodies A0485, HercepTest, SP3 and 4B5 were over 95% sensitive and specific. CB11 was the most specific antibody (97.1%). 60% (CB11) to 83.3% (SP3) of the 2+ cases showed no gene amplification by DDISH. False negative cases varied from 0.5% (A0485) to 3.8% (CB11) of the cases, and false positive from 1.6% (CB11) to 2.7% (HercepTest, SP3 and 4B5) of the 184 cases.ConclusionsThere was very good agreement among the five anti-HER2 antibodies. CB11 was the most specific antibody, but showed more false negative cases. A0485, SP3, 4B5 and HercepTest were highly sensitive and specific, but showed more false positive cases.

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