scholarly journals Diagnostic performance of rapid antigen tests (RATs) for SARS-CoV-2 and their efficacy in monitoring the infectiousness of COVID-19 patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
John G. Routsias ◽  
Maria Mavrouli ◽  
Panagiota Tsoplou ◽  
Kyriaki Dioikitopoulou ◽  
Athanasios Tsakris
Keyword(s):  
Diagnostic Performance ◽  
Limit Of Detection ◽  
High Sensitivity ◽  
Cost Effective ◽  
Clinical Samples ◽  
True Positive ◽  
Antigen Tests ◽  
The Cost ◽  
Very High ◽  
Test Result

AbstractThe most widely used test for the diagnosis of SARS-CoV-2 infection is a PCR test. PCR has very high sensitivity and is able to detect very low amounts of RNA. However, many individuals receiving a positive test result in a context of a PCR-based surveillance might be infected with SARS-CoV-2, but they are not contagious at the time of the test. The question arises regards if the cost effective, portable rapid antigen tests (RATs) have a better performance than PCR in identification of infectious individuals. In this direction, we examined the diagnostic performance of RATs from 14 different manufacturers in 400 clinical samples with known rRT-PCR cycles threshold (cT) and 50 control samples. Substantial variability was observed in the limit of detection (LOD) of different RATs (cT = 26.8–34.7). The fluorescence-based RAT exhibited a LOD of cT = 34.7. The use of the most effective RATs leads to true positive rates (sensitivities) of 99.1% and 90.9% for samples with cT ≤ 30 and cT ≤ 33, respectively, percentages that can guarantee a sensitivity high enough to identify contagious patients. RAT testing may also substantially reduce the quarantine period for infected individuals without compromising personal or public safety.

scholarly journals Confirming putative variants at ≤ 5% allele frequency using allele enrichment and Sanger sequencing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yan Helen Yan ◽  
Sherry X. Chen ◽  
Lauren Y. Cheng ◽  
Alyssa Y. Rodriguez ◽  
Rui Tang ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Limit Of Detection ◽  
High Sensitivity ◽  
Sequencing Errors ◽  
Whole Exome ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Fresh Frozen ◽  
The Cost ◽  
Allelic Fraction

AbstractWhole exome sequencing (WES) is used to identify mutations in a patient’s tumor DNA that are predictive of tumor behavior, including the likelihood of response or resistance to cancer therapy. WES has a mutation limit of detection (LoD) at variant allele frequencies (VAF) of 5%. Putative mutations called at ≤ 5% VAF are frequently due to sequencing errors, therefore reporting these subclonal mutations incurs risk of significant false positives. Here we performed ~ 1000 × WES on fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissue biopsy samples from a non-small cell lung cancer patient, and identified 226 putative mutations at between 0.5 and 5% VAF. Each variant was then tested using NuProbe NGSure, to confirm the original WES calls. NGSure utilizes Blocker Displacement Amplification to first enrich the allelic fraction of the mutation and then uses Sanger sequencing to determine mutation identity. Results showed that 52% of the 226 (117) putative variants were disconfirmed, among which 2% (5) putative variants were found to be misidentified in WES. In the 66 cancer-related variants, the disconfirmed rate was 82% (54/66). This data demonstrates Blocker Displacement Amplification allelic enrichment coupled with Sanger sequencing can be used to confirm putative mutations ≤ 5% VAF. By implementing this method, next-generation sequencing can reliably report low-level variants at a high sensitivity, without the cost of high sequencing depth.

scholarly journals Direct diagnostic testing of SARS-CoV-2 without the need for prior RNA extraction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shan Wei ◽  
Esther Kohl ◽  
Alexandre Djandji ◽  
Stephanie Morgan ◽  
Susan Whittier ◽  
...  
Keyword(s):  
Limit Of Detection ◽  
Point Of Care ◽  
Diagnostic Testing ◽  
Rna Extraction ◽  
Cost Effective ◽  
Clinical Samples ◽  
Nasopharyngeal Swab ◽  
Percentage Agreement ◽  
Testing Method ◽  
Viral Transport

AbstractThe COVID-19 pandemic has resulted in an urgent need for a rapid, point of care diagnostic testing that could be rapidly scaled on a worldwide level. We developed and tested a highly sensitive and robust assay based on reverse transcription loop mediated isothermal amplification (RT-LAMP) that uses readily available reagents and a simple heat block using contrived spike-in and actual clinical samples. RT-LAMP testing on RNA-spiked samples showed a limit of detection (LoD) of 2.5 copies/μl of viral transport media. RT-LAMP testing directly on clinical nasopharyngeal swab samples in viral transport media had an 85% positive percentage agreement (PPA) (17/20), and 100% negative percentage agreement (NPV) and delivered results in 30 min. Our optimized RT-LAMP based testing method is a scalable system that is sufficiently sensitive and robust to test for SARS-CoV-2 directly on clinical nasopharyngeal swab samples in viral transport media in 30 min at the point of care without the need for specialized or proprietary equipment or reagents. This cost-effective and efficient one-step testing method can be readily available for COVID-19 testing world-wide, especially in resource poor settings.

scholarly journals Addition of Flucytosine to Fluconazole for the Treatment of Cryptococcal Meningitis in Africa: A Multicountry Cost-effectiveness Analysis

2019 ◽  
Vol 70 (1) ◽  
pp. 26-29 ◽  
Author(s):  
Tinevimbo Shiri ◽  
Angela Loyse ◽  
Lawrence Mwenge ◽  
Tao Chen ◽  
Shabir Lakhi ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Cost Effectiveness ◽  
Cryptococcal Meningitis ◽  
Cost Effective ◽  
Immunodeficiency Virus ◽  
The Mean ◽  
The Cost ◽  
The Impact ◽  
Costing Analysis ◽  
Very High

Abstract Background Mortality from cryptococcal meningitis remains very high in Africa. In the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2 weeks of amphotericin-based regimens. However, many African settings treat with FLU monotherapy, and the cost-effectiveness of adding 5FC to FLU is uncertain. Methods The effectiveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian site. The effectiveness of FLU was derived from cohorts of consecutively enrolled patients, managed in respects other than drug therapy, as were participants in ACTA. FLU costs were derived from costs of FLU+5FC in ACTA, by subtracting 5FC drug and monitoring costs. The cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). A probabilistic sensitivity analysis assessed uncertainties and a bivariate deterministic sensitivity analysis examined the impact of varying mortality and 5FC drug costs on the ICER. Results The mean costs per patient were US $847 (95% confidence interval [CI] $776–927) for FLU+5FC, and US $628 (95% CI $557–709) for FLU. The 10-week mortality rate was 35.1% (95% CI 28.9–41.7%) with FLU+5FC and 53.8% (95% CI 43.1–64.1%) with FLU. At the current 5FC price of US $1.30 per 500 mg tablet, the ICER of 5FC+FLU versus FLU alone was US $65 (95% CI $28–208) per life-year saved. Reducing the 5FC cost to between US $0.80 and US $0.40 per 500 mg resulted in an ICER between US $44 and US $28 per life-year saved. Conclusions The addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and, if made available widely, could substantially reduce mortality rates among human immunodeficiency virus–infected persons in Africa.

scholarly journals SARS-CoV-2 Direct Detection Without RNA Isolation With Loop-Mediated Isothermal Amplification (LAMP) and CRISPR-Cas12

2021 ◽  
Vol 8 ◽  
Author(s):  
Alfredo Garcia-Venzor ◽  
Bertha Rueda-Zarazua ◽  
Eduardo Marquez-Garcia ◽  
Vilma Maldonado ◽  
Angelica Moncada-Morales ◽  
...  
Keyword(s):  
Limit Of Detection ◽  
Direct Detection ◽  
Direct Method ◽  
Rna Extraction ◽  
Rna Isolation ◽  
High Sensitivity ◽  
High Specificity ◽  
Isothermal Amplification ◽  
Clinical Samples ◽  
Loop Mediated Isothermal Amplification

As to date, more than 49 million confirmed cases of Coronavirus Disease 19 (COVID-19) have been reported worldwide. Current diagnostic protocols use qRT-PCR for viral RNA detection, which is expensive and requires sophisticated equipment, trained personnel and previous RNA extraction. For this reason, we need a faster, direct and more versatile detection method for better epidemiological management of the COVID-19 outbreak. In this work, we propose a direct method without RNA extraction, based on the Loop-mediated isothermal amplification (LAMP) and Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated protein (CRISPR-Cas12) technique that allows the fast detection of SARS-CoV-2 from patient samples with high sensitivity and specificity. We obtained a limit of detection of 16 copies/μL with high specificity and at an affordable cost. The diagnostic test readout can be done with a real-time PCR thermocycler or with the naked eye in a blue-light transilluminator. Our method has been evaluated on a small set of clinical samples with promising results.

scholarly journals Long-acting porcine sequence ACTH in the diagnosis of adrenal insufficiency: a cost-effective alternative to the ACTH1–24 test

2020 ◽  
Vol 182 (2) ◽  
pp. C5-C7
Author(s):  
Warrick J Inder
Keyword(s):  
Developing Countries ◽  
Adrenal Insufficiency ◽  
Diagnostic Performance ◽  
Cost Effective ◽  
Effective Alternative ◽  
Secondary Adrenal Insufficiency ◽  
Robust Test ◽  
Cost Effective Alternative ◽  
Long Acting ◽  
The Cost

While the ACTH1–24 test has some well-documented shortcomings, it is the most widely used test to diagnose primary and secondary adrenal insufficiency. However, this synthetic ACTH preparation is not readily available in some countries. Research from India has demonstrated that using a long-acting porcine sequence ACTH has similar diagnostic performance to ACTH1–24 at around 25% of the cost. This may allow access to a robust test for adrenal insufficiency to developing countries and potentially allow thousands of patients to be identified and appropriately treated.

scholarly journals Coupling multiplex pre-amplification and droplet digital PCR for longitudinal monitoring ofESR1andPIK3CAmutations from plasma cell-free DNA

2019 ◽  
Author(s):  
Huilan Yao ◽  
Grant Wu ◽  
Subhasree Das ◽  
Crystal MacKenzie ◽  
Hua Gao ◽  
...  
Keyword(s):  
Limit Of Detection ◽  
Hot Spot ◽  
Metastatic Breast ◽  
High Sensitivity ◽  
Cost Effective ◽  
Digital Pcr ◽  
Cost Effective Method ◽  
High Prevalence ◽  
High Concordance ◽  
Hotspot Mutations

AbstractHere we report on the development of a sensitive and cost-effective method to longitudinally trackESR1andPIK3CAmutations from cfDNA in patients with metastatic breast cancer (MBC) using a streamlined and de-centralized workflow. Hotspot mutations inESR1have been shown to cause resistance to aromatase inhibitor–based and anti-estrogenic therapies, whilePIK3CAmutations have high prevalence in MBC. As a result, their utility as circulating biomarkers to predict or monitor response in the clinical development of investigational compounds has been the focus of many studies. Six regions inESR1andPIK3CAgenes containing 20 hotspot mutations were pre-amplified, followed by optimized singleplex ddPCR assays to detect allele frequencies of individual mutations. Without pre-amplification, the limit of detection (LOD) and limit of linearity (LOL) of individual ddPCR assays were at 0.05-0.1% and 0.25% level, respectively. With pre-amplification, the LOD and LOL were slightly elevated at 0.1-0.25% and 0.25-0.5% levels, respectively. High concordance was achieved to the BEAMing assay (Sysmex Inostics) for mutation positive assays (r=0.98, P<0.0001). In conclusion, coupling pre-amplification and ddPCR assays allowed us for the detection of up to 20 hot spot mutations inESR1andPIK3CAwith high sensitivity and reproducibility.

Smart Healthcare

2018 ◽  
pp. 21-33
Author(s):  
R. Rajkumar
Keyword(s):  
Internet Of Things ◽  
Real Time ◽  
Cost Effective ◽  
Reliable System ◽  
Smart Healthcare ◽  
Cloud Server ◽  
Android App ◽  
The Cost ◽  
Very High ◽  
At Home

Internet of things is a revolutionary domain, when we use it for the wellness of people in a smart way. As of now, the cost to implement IoT-enabled services is very high. So, this chapter introduces a cost effective and a reliable system to monitor patients at home and in hospitals with the help of IoT. The monitored details of a person can be drawn at any time with the help of an android app, which can produce output at real-time. The processed data are stored in the UBIDOTS cloud server, and the patients' needs can be met in time as well lives saved during critical cases with the help of the system proposed in this chapter.

scholarly journals Proposal of De Novo Antigen Test for COVID-19: Ultrasensitive Detection of Spike Proteins of SARS-CoV-2

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 594 ◽  
Author(s):  
Yuta Kyosei ◽  
Mayuri Namba ◽  
Sou Yamura ◽  
Rikiya Takeuchi ◽  
Noriko Aoki ◽  
...  
Keyword(s):  
De Novo ◽  
Limit Of Detection ◽  
False Negative ◽  
Cost Effective ◽  
Detection Sensitivity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antigen Test ◽  
Virus Rna ◽  
Antigen Tests ◽  
Spike Proteins

Polymerase chain reaction (PCR)-based antigen tests are technically difficult, time-consuming, and expensive, and may produce false negative results requiring follow-up confirmation with computed tomography. The global coronavirus disease 2019 (COVID-19) pandemic has increased the demand for accurate, easy-to-use, rapid, and cost-effective antigen tests for clinical application. We propose a de novo antigen test for diagnosing COVID-19 using the combination of sandwich enzyme-linked immunosorbent assay and thio-nicotinamide adenine dinucleotide (thio-NAD) cycling. Our test takes advantage of the spike proteins specific to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The limit of detection of our test was 2.3 × 10−18 moles/assay. If the virus has ~25 spike proteins on its surface, our method should detect on the order of 10−20 moles of virus/assay, corresponding to ~104 copies of the virus RNA/assay. The detection sensitivity approaches that of PCR-based assays because the average virus RNA load used for PCR-based assays is ~105 copies per oro- or naso-pharyngeal swab specimen. To our knowledge, this is the first ultrasensitive antigen test for SARS-CoV-2 spike proteins that can be performed with an easy-to-use microplate reader. Sufficient sensitivity can be achieved within 10 min of thio-NAD cycling. Our antigen test allows for rapid, cost-effective, specific, ultrasensitive, and simultaneous multiple measurements of SARS-CoV-2, and has broad application for the diagnosis for COVID-19.

scholarly journals Routine blood cultures in the management of community acquired pneumonia; is it necessary?

2013 ◽  
Vol 1 (2) ◽  
pp. 54-57
Author(s):  
TM Ibrahim
Keyword(s):  
Case Fatality ◽  
Length Of Hospital Stay ◽  
Cost Effective ◽  
Antibiotic Use ◽  
Community Acquired Pneumonia ◽  
Blood Cultures ◽  
True Positive ◽  
It Use ◽  
The Cost

INTRODUCTION: The role of blood cultures (BCs) in the management of community acquired pneumonia (CAP) has generated a lot of controversy among clinicians in recent times. The main objectives of this audit were to determine if BC results impact the choice of antibiotics, and hospital outcomes in CAP. MATERIALS AND METHODS: This was a retrospective study of adults with CAP treated in the ED of Goulbourn Valley Base Hospital, Shepparton in Australia from November 2010 to November 2011. RESULTS: Two hundred and twenty five patients were treated for CAP during the period in review with a mean age of 67.09±19.82 yrs and male:female of 1.5:1. 277 sets of BCs were performed and only 2.2% of the cases had true positive BCs .87% of the total cost of performing these BCs was spent on those with negative cultres.15.1% of the cases had their antibiotics changed during their hospitalization but the results of the BCs had no impact on the antibiotic change. Even though not statistically significant true positive BCs was associated with prolong length of hospital stay (7.6 ± 9.39 days vs 4.89 ± 3.24 days, p=0.44), and duration of IV antibiotic use (4.8±3.27 days vs 3.58±1.97 days, p=0.39). But the case fatality rate was much lower in those with positive BCs, (0 vs 5.7%,p< 0.05). Tachycardia (>120.4±12.46 bpm), neutrophilia (15.0± 8.16 /ul), and high CRP (326.4±146.32 ug/l) were predictors of true positive BCs. CONCLUSIONS: Routine BCs in the management of CAP is not cost-effective with large portion of the cost spent on cultures that returned negative result .Therefore it use show be limited to those likely to return positive cultures. DOI: http://dx.doi.org/10.3126/ijim.v1i2.7408 Int J Infect Microbiol 2012;1(1):54-57

Diagnostic information as a commodity

1995 ◽  
Vol 41 (5) ◽  
pp. 781-784 ◽  
Author(s):  
H A Johnson
Keyword(s):  
Diagnostic Tests ◽  
Multiple Testing ◽  
Cost Effective ◽  
Diagnostic Procedures ◽  
Diagnostic Information ◽  
Unit Price ◽  
Screening Tests ◽  
The Cost ◽  
Effective Conditions ◽  
Test Result

Abstract In estimating the cost-effectiveness of diagnostic procedures, it is helpful to treat diagnostic information as a commodity with a unit price. The amount of useful information provided by a test result can be measured in binary units (bits), and the unit price of the information produced by the test result can be expressed in dollars per bit in much the same way that the price of gold is given in dollars per ounce. This allows comparison of the unit prices of various diagnostic tests, examination of the effect of multiple testing, and calculation of the most cost-effective conditions for screening tests.

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