Improving Detection Efficiency of SARS-CoV-2 Nucleic Acid Testing

BackgroundSARS-CoV-2 nucleic acid testing (NAT) has been routinely used for COVID-19 diagnosis during this pandemic; however, there have been concerns about its high false negative rate. We dissected its detection efficiency with a large COVID-19 cohort study.MethodsWe analyzed SARS-CoV-2 NAT positive rates of 4,275 specimens from 532 COVID-19 patients in Sichuan Province with different disease severities, statuses, and stages, as well as different types and numbers of specimens.ResultsThe total positive rate of the 4,275 specimens was 37.5%. Among seven specimen types, BALF generated a 77.8% positive rate, followed by URT specimens (38.5%), sputum (39.8%), and feces/rectal swabs (34.1%). Specimens from critical cases generated a 43.4% positive rate, which was significantly higher than that of other severities. With specimens from patients at stable status, the SARS-CoV-2 positive rate was 40.6%, which was significantly higher than that of improved status (17.1%), but lower than that of aggravated status (61.5%). Notably, the positive rate of specimens from COVID-19 patients varied significantly from 85 to 95% during 3 days before and after symptom onset, to 20% at around 18 days after symptom onset. In addition, the detection rate increased from 72.1% after testing one throat swab, to 93.2% after testing three consecutive respiratory specimens from each patient.ConclusionsSARS-CoV-2 NAT detection rates vary with patient disease severity and status, specimen type, number of specimens, and especially disease progression. Sampling as close to symptom onset as possible, and consecutively collecting more than one respiratory specimen could effectively improve SARS-CoV-2 NAT detection efficiency.

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Pathologic Assessment of Computerized Tomography Accuracy for the Evaluation of the Laryngeal Cartilaginous Frame Work in Laryngopharyngeal Carcinomas

Tumori Journal ◽

10.1177/030089168907500216 ◽

1989 ◽

Vol 75 (2) ◽

pp. 156-162 ◽

Cited By ~ 5

Author(s):

Sandro Sulfaro ◽

Francesco Querin ◽

Luigi Barzan ◽

Mario Lutman ◽

Roberto Comoretto ◽

...

Keyword(s):

Computerized Tomography ◽

False Positive ◽

False Positive Rate ◽

False Negative ◽

False Negative Rate ◽

Cartilage Destruction ◽

High False Negative Rate ◽

Positive Rate ◽

Pathologic Assessment ◽

Low Sensitivity

Sixty-six whole-organ sectioned laryngopharyngectomy specimens removed for cancer during a seven-year period were uniformly examined to determine the accuracy of preoperative high resolution computerized tomography (CT) for detection of cartilaginous involvement. Our results indicate that CT has a high overall specificity (88.2%) but a low sensitivity (47.1 %); we observed a high false-negative rate (26.5%) and a fairly low false-positive rate (5.9%). Massive cartilage destruction was easily assessed by CT, whereas both small macroscopic and microscopic neoplastic foci of cartilaginous invasion were missed on CT scans. Moreover, false-positive cases were mainly due to proximity of the tumor to the cartilage. Clinical implications of these results are discussed.

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Three-dimensional camera anthropometry to assess risk of cephalopelvic disproportion-related obstructed labour in Ethiopia

Interface Focus ◽

10.1098/rsfs.2019.0036 ◽

2019 ◽

Vol 9 (5) ◽

pp. 20190036 ◽

Cited By ~ 1

Author(s):

Lorenzo Tolentino ◽

Mahlet Yigeremu ◽

Sisay Teklu ◽

Shehab Attia ◽

Michael Weiler ◽

...

Keyword(s):

False Negative ◽

Three Dimensional ◽

False Negative Rate ◽

Detection Rates ◽

Cephalopelvic Disproportion ◽

Obstructed Labour ◽

Tape Measure ◽

Negative Rate ◽

Positive Rate ◽

Tape Measurement

Cephalopelvic disproportion (CPD)-related obstructed labour requires delivery via Caesarean section (C/S); however, in low-resource settings around the world, facilities with C/S capabilities are often far away. This paper reports three low-cost tools to assess the risk of CPD, well before labour, to provide adequate time for referral and planning for delivery. We performed tape measurement- and three-dimensional (3D) camera-based anthropometry, using two 3D cameras (Kinect and Structure) on primigravida, gestational age ≥ 36 weeks, from Addis Ababa, Ethiopia. Novel risk scores were developed and tested to identify models with the highest predicted area under the receiver-operator characteristic curve (AUC), detection rate (true positive rate at a 5% false-positive rate, FPR) and triage rate (true negative rate at a 0% false-negative rate). For tape measure, Kinect and Structure, the detection rates were 53%, 61% and 64% (at 5% FPR), the triage rates were 30%, 56% and 63%, and the AUCs were 0.871, 0.908 and 0.918, respectively. Detection rates were 77%, 80% and 84% at the maximum J -statistic, which corresponded to FPRs of 10%, 15% and 11%, respectively, for tape measure, Kinect and Structure. Thus, tape measurement anthropometry was a very good predictor and Kinect and Structure anthropometry were excellent predictors of CPD risk.

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Comparison of throat swabs and sputum specimens for viral nucleic acid detection in 52 cases of novel coronavirus (SARS-Cov-2) infected pneumonia (COVID-19)

10.1101/2020.02.21.20026187 ◽

2020 ◽

Cited By ~ 9

Author(s):

Chenyao Lin ◽

Jie Xiang ◽

Mingzhe Yan ◽

Hongze Li ◽

Shuang Huang ◽

...

Keyword(s):

Nucleic Acid ◽

Detection Efficiency ◽

Nucleic Acid Detection ◽

Sample Collection ◽

Pcr Assay ◽

Viral Nucleic Acid ◽

Detection Rates ◽

Qrt Pcr ◽

Positive Rate ◽

Novel Coronavirus

AbstractBackgroundIn December 2019, a novel coronavirus (SARS-CoV-2) infected pneumonia (COVID-19) occurred in Wuhan, China. Diagnostic test based on real-time reverse transcription polymerase chain reaction assay (qRT-PCR) was the main means of confirmation, and sample collection was mostly throat swabs, which was easy to miss the diagnosis. It is necessary to seek specimen types with higher detection efficiency and accuracy.MethodsPaired specimens of throat swabs and sputum were obtained from 54 cases, and RNA was extracted and tested for 2019-nCoV (equated with SARS-CoV-2) by qRT-PCR assay.ResultsThe positive rates of 2019-nCoV from sputum specimens and throat swabs were 76.9% and 44.2%, respectively. Sputum specimens showed a significantly higher positive rate than throat swabs in detecting viral nucleic acid using qRT-PCR assay (P=0.001).ConclusionsThe detection rates of 2019-nCoV from sputum specimens are significantly higher than throat swabs. We suggest that sputum would benefit for the detection of 2019-nCoV in patients who produce sputum. The results can facilitate the selection of specimens and increase the accuracy of diagnosis.

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A sequence-based method for predicting extant fold switchers that undergo α-helix β-strand transitions

10.1101/2021.01.14.426714 ◽

2021 ◽

Author(s):

Soumya Mishra ◽

Loren L. Looger ◽

Lauren L. Porter

Keyword(s):

Secondary Structure ◽

False Positive Rate ◽

False Negative ◽

False Negative Rate ◽

Data Bank ◽

Parent Protein ◽

High False Negative Rate ◽

Single Fold ◽

Positive Rate ◽

Α Helix

AbstractExtant fold-switching proteins remodel their secondary structures and change their functions in response to cellular stimuli, regulating biological processes and affecting human health. In spite of their biological importance, these proteins remain understudied. Few representative examples of fold switchers are available in the Protein Data Bank, and they are difficult to predict. In fact, all 96 experimentally validated examples of extant fold switchers were stumbled upon by chance. Thus, predictive methods are needed to expedite the process of discovering and characterizing more of these shapeshifting proteins. Previous approaches require a solved structure or all-atom simulations, greatly constraining their use. Here, we propose a high-throughput sequence-based method for predicting extant fold switchers that transition from α-helix in one conformation to β-strand in the other. This method leverages two previous observations: (1) α-helix <-> β-strand prediction discrepancies from JPred4 are a robust predictor of fold switching, and (2) the fold-switching regions (FSRs) of some extant fold switchers have different secondary structure propensities when expressed in isolation (isolated FSRs) than when expressed within the context of their parent protein (contextualized FSRs). Combining these two observations, we ran JPred4 on the sequences of isolated and contextualized FSRs from 14 known extant fold switchers and found α-helix <->β-strand prediction discrepancies in every case. To test the overall robustness of this finding, we randomly selected regions of proteins not expected to switch folds (single-fold proteins) and found significantly fewer α-helix <-> β-strand prediction discrepancies (p < 4.2*10−20, Kolmogorov-Smirnov test). Combining these discrepancies with the overall percentage of predicted secondary structure, we developed a classifier that often robustly identifies extant fold switchers (Matthews Correlation Coefficient of 0.70). Although this classifier had a high false negative rate (6/14), its false positive rate was very low (1/211), suggesting that it can be used to predict a subset of extant fold switchers from billions of available genomic sequences.

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Comparison of throat swabs and sputum specimens for viral nucleic acid detection in 52 cases of novel coronavirus (SARS-Cov-2)-infected pneumonia (COVID-19)

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-0187 ◽

2020 ◽

Vol 58 (7) ◽

pp. 1089-1094 ◽

Cited By ~ 44

Author(s):

Chenyao Lin ◽

Jie Xiang ◽

Mingzhe Yan ◽

Hongze Li ◽

Shuang Huang ◽

...

Keyword(s):

Nucleic Acid ◽

Detection Efficiency ◽

Diagnostic Value ◽

Nucleic Acid Detection ◽

Rt Pcr ◽

Pcr Assay ◽

Viral Nucleic Acid ◽

Detection Rates ◽

Positive Rate ◽

Novel Coronavirus

AbstractObjectivesIn December 2019, a novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, China. Laboratory-based diagnostic tests utilized real-time reverse transcriptase polymerase chain reaction (RT-PCR) on throat samples. This study evaluated the diagnostic value to analyzing throat and sputum samples in order to improve accuracy and detection efficiency.MethodsPaired specimens of throat swabs and sputum were obtained from 54 cases, and RNA was extracted and tested for 2019-nCoV (equated with SARS-CoV-2) by the RT-PCR assay.ResultsThe positive rates of 2019-nCoV from sputum specimens and throat swabs were 76.9% and 44.2%, respectively. Sputum specimens showed a significantly higher positive rate than throat swabs in detecting viral nucleic acid using the RT-PCR assay (p = 0.001).ConclusionsThe detection rates of 2019-nCoV from sputum specimens were significantly higher than those from throat swabs. We suggest that sputum would benefit for the detection of 2019-nCoV in patients who produce sputum. The results can facilitate the selection of specimens and increase the accuracy of diagnosis.

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Clinically Meaningful Change

Methodology ◽

10.1027/1614-2241/a000168 ◽

2019 ◽

Vol 15 (3) ◽

pp. 97-105

Author(s):

Rodrigo Ferrer ◽

Antonio Pardo

Keyword(s):

Effect Size ◽

False Negative ◽

False Negative Rate ◽

Point Of View ◽

Skewed Distribution ◽

Effect Sizes ◽

False Negatives ◽

Large Size ◽

Before And After ◽

Post Test

Abstract. In a recent paper, Ferrer and Pardo (2014) tested several distribution-based methods designed to assess when test scores obtained before and after an intervention reflect a statistically reliable change. However, we still do not know how these methods perform from the point of view of false negatives. For this purpose, we have simulated change scenarios (different effect sizes in a pre-post-test design) with distributions of different shapes and with different sample sizes. For each simulated scenario, we generated 1,000 samples. In each sample, we recorded the false-negative rate of the five distribution-based methods with the best performance from the point of view of the false positives. Our results have revealed unacceptable rates of false negatives even with effects of very large size, starting from 31.8% in an optimistic scenario (effect size of 2.0 and a normal distribution) to 99.9% in the worst scenario (effect size of 0.2 and a highly skewed distribution). Therefore, our results suggest that the widely used distribution-based methods must be applied with caution in a clinical context, because they need huge effect sizes to detect a true change. However, we made some considerations regarding the effect size and the cut-off points commonly used which allow us to be more precise in our estimates.

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TO010A NEW IMMUN-TOXICOLOGICAL TEST TO DETECT POLYSULFONE HYPERSENSITIVITY IN HEMODIALYSIS PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa141.to010 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Joachim Beige ◽

Ralph Wendt ◽

Despina Rüssmann ◽

Karl-Peter Ringel

Keyword(s):

False Negative ◽

False Negative Rate ◽

Lymphocyte Transformation ◽

Clinical Problem ◽

Lymphocyte Transformation Test ◽

Laboratory Research ◽

Humoral Immune ◽

Before And After ◽

Positive Results

Abstract Background and Aims Incompatibility of dialysis procedure due to hypersensitivity against dialyzer material which currently is mainly based on polysulfone and derivatives can not be assessed by routine laboratory tests. Although the frequency of such symptoms is suspected to be low (below 2%) such resembles an important clinical problem because dialysis procedures are frequently accompanied by symptoms of non-tolerability with reasons not being entirely clear while circulatory reasons are suspected to play a major role. Method To enlighten the role of polysulfone hypersensitivity, we adapted known standardized material immune-toxicological tests (lymphocyte transformation test, basophil degranulation test) to the specific conditions of dialysis and polysulfone material sensitivity. We developed a method of polysulfone micronisation and measured humoral immune response of isolated patient´s lymphocytes when incubated with polysulfone dispersion. Results 39 samples from 103 patients with suspected polysulfone hypersensitivity showed positive results for type 1 (n=19), type 4 (n=18) or both type (n=2) reactions. There were no significant differences in the level of stimulation measured for DI, SI and lymphogenesis before and after dialysis (average delta -0.4; -0.28; - 1.74, p = 0.71; 0.34; 0.37) and with different dialyzer materials (Tab. 1). Patients with pos. type 4 results (LTT and lymphogenesis) showed highly correlated results in either LTT or lymphogenesis test (Fig. 1, R=0.87, p<0.0001). 8 out of 8 samples from patients with repeated test on different PS showed positive results on either PS. One patient tested positive on PS showed no hypersensitivity with another non-PS (PMMA) material. Conclusion This is the first methodological report showing plausible in-vitro results of patients samples concerning polysulfone intolerance. On the first superficial view, a “false-negative” rate of 60% looks rather disappointing, because all samples derived from patients with suspicion of PS hypersensitivity. However, due to the clinical variability of intolerance symptoms and the high prevalence of any problems after HD initiation, mainly of circulatory origin after initiating extracorporeal circuit, this rate may obviously express the true frequency of isolated PS material hypersensitivity in suspected patients. Alternative pathophysiological pathways of material sensitivity like complement activation, remain to be elucidated and incorporated into a comprehensive future testing panel. Further clinical and laboratory research is needed to define true polysulfone hypersensitivity and to enlighten the field of hypothetic subclinical material incompatibility in patients with impaired dialysis tolerability.

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Pretherapeutic Imaging for Axillary Staging in Breast Cancer: A Systematic Review and Meta-Analysis of Ultrasound, MRI and FDG PET

Journal of Clinical Medicine ◽

10.3390/jcm10071543 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1543

Author(s):

Morwenn Le Boulc’h ◽

Julia Gilhodes ◽

Zara Steinmeyer ◽

Sébastien Molière ◽

Carole Mathelin

Keyword(s):

Systematic Review ◽

Sensitivity And Specificity ◽

Meta Analysis ◽

False Negative ◽

Significant Proportion ◽

False Negative Rate ◽

True Positive Rate ◽

Axillary Staging ◽

Positron Emission ◽

Positive Rate

Background: This systematic review aimed at comparing performances of ultrasonography (US), magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography (PET) for axillary staging, with a focus on micro- or micrometastases. Methods: A search for relevant studies published between January 2002 and March 2018 was conducted in MEDLINE database. Study quality was assessed using the QUality Assessment of Diagnostic Accuracy Studies checklist. Sensitivity and specificity were meta-analyzed using a bivariate random effects approach; Results: Across 62 studies (n = 10,374 patients), sensitivity and specificity to detect metastatic ALN were, respectively, 51% (95% CI: 43–59%) and 100% (95% CI: 99–100%) for US, 83% (95% CI: 72–91%) and 85% (95% CI: 72–92%) for MRI, and 49% (95% CI: 39–59%) and 94% (95% CI: 91–96%) for PET. Interestingly, US detects a significant proportion of macrometastases (false negative rate was 0.28 (0.22, 0.34) for more than 2 metastatic ALN and 0.96 (0.86, 0.99) for micrometastases). In contrast, PET tends to detect a significant proportion of micrometastases (true positive rate = 0.41 (0.29, 0.54)). Data are not available for MRI. Conclusions: In comparison with MRI and PET Fluorodeoxyglucose (FDG), US is an effective technique for axillary triage, especially to detect high metastatic burden without upstaging majority of micrometastases.

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Effects of Previous Surgery on the Detection of Sentinel Nodes in Women With Vulvar Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e31822dbe3c ◽

2011 ◽

Vol 21 (9) ◽

pp. 1679-1683 ◽

Cited By ~ 10

Author(s):

Tessa A. Ennik ◽

David G. Allen ◽

Ruud L.M. Bekkers ◽

Simon E. Hyde ◽

Peter T. Grant

Keyword(s):

Vulvar Cancer ◽

False Negative ◽

False Negative Rate ◽

Blue Dye ◽

Previous Surgery ◽

Detection Rates ◽

Reliable Technique ◽

Appearance Time ◽

Negative Rate ◽

Significant Difference

BackgroundThere is a growing interest to apply the sentinel node (SN) procedure in the treatment of vulvar cancer. Previous vulvar surgery might disrupt lymphatic patterns and thereby decrease SN detection rates, lengthen scintigraphic appearance time (SAT), and increase SN false-negative rate. The aims of this study were to evaluate the SN detection rates at the Mercy Hospital for Women in Melbourne and to investigate whether previous vulvar surgery affects SN detection rates, SAT, and SN false-negative rate.MethodsData on all patients with vulvar cancer who underwent an SN procedure (blue dye, technetium, or combined technique) from November 2000 to July 2010 were retrospectively collected.ResultsSixty-five SN procedures were performed. Overall detection rate was 94% per person and 80% per groin. Detection rates in the group of patients who underwent previous excision of the primary tumor were not lower compared with the group without previous surgery or with just an incisional biopsy. There was no statistical significant difference in SAT between the previous excision group and the other patients. None of the patients with a false-negative SN had undergone previous excision.ConclusionsResults indicate that previous excision of a primary vulvar malignancy does not decrease SN detection rates or increase SN false-negative rate. Therefore, the SN procedure appears to be a reliable technique in patients who have previously undergone vulvar surgery. Previous excision did not significantly lengthen SAT, but the sample size in this subgroup analysis was small.

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