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3.
PLoS One ; 15(9): e0239943, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32997724

RESUMO

We report on the results of a Covid-19 contact tracing app measurement study carried out on a standard design of European commuter tram. Our measurements indicate that in the tram there is little correlation between Bluetooth received signal strength and distance between handsets. We applied the detection rules used by the Italian, Swiss and German apps to our measurement data and also characterised the impact on performance of changes in the parameters used in these detection rules. We find that the Swiss and German detection rules trigger no exposure notifications on our data, while the Italian detection rule generates a true positive rate of 50% and a false positive rate of 50%. Our analysis indicates that the performance of such detection rules is similar to that of triggering notifications by randomly selecting from the participants in our experiments, regardless of proximity.


Assuntos
Busca de Comunicante/métodos , Notificação de Doenças/métodos , Aplicativos Móveis , Transportes , Betacoronavirus , Infecções por Coronavirus/transmissão , Reações Falso-Positivas , Humanos , Pandemias , Pneumonia Viral/transmissão
4.
F1000Res ; 9: 671, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32968484

RESUMO

Institutions such as hospitals and nursing or long-stay residential homes accommodate individuals at considerable risk of mortality should they acquire SARS-CoV-2 infection. In these settings, polymerase chain reaction tests play a central role in infection prevention and control. Here, we argue that both false negative and false positive tests are possible and that careful consideration of the prior probability of infection and of test characteristics are needed to prevent harm. We outline evidence suggesting that regular systematic testing of asymptomatic and pre-symptomatic individuals could play an important role in reducing transmission of SARS-CoV-2 within institutions. We discuss how such a programme might be organised, arguing that frequent testing and rapid reporting of results are particularly important. We highlight studies demonstrating that polymerase chain reaction testing of pooled samples can be undertaken with acceptable loss of sensitivity, and advocate such an approach where test capacity is limited. We provide an approach to calculating the most efficient pool size. Given the current limitations of tests for SARS-CoV-2 infection, physical distancing and meticulous infection prevention and control will remain essential in institutions caring for vulnerable people.


Assuntos
Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Reação em Cadeia da Polimerase , Betacoronavirus , Técnicas de Laboratório Clínico , Reações Falso-Negativas , Reações Falso-Positivas , Hospitais , Humanos , Casas de Saúde , Pandemias
6.
Am J Case Rep ; 21: e925931, 2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32980852

RESUMO

BACKGROUND The worldwide spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-COV-2) has created unprecedented situations for healthcare professionals and healthcare systems. Although infection with this virus is considered the main health problem currently, other diseases are still prevalent. CASE REPORT This report describes a 59-year-old man who presented with symptoms of dyspnea and fever that were attributed to Covid-19 infection. His clinical condition deteriorated and further examinations revealed a subjacent severe aortic regurgitation due to acute infective endocarditis. Surgical treatment was successful. CONCLUSIONS The results of diagnostic tests for Covid-19 should be re-evaluated whenever there are clinical mismatches or doubts, as false-positive Covid-19 test results can occur. Clinical interpretation should not be determined exclusively by the Covid-19 pandemic. This case report highlights the importance of using validated and approved serological and molecular testing to detect infection with SARS-CoV-2, and to repeat tests when there is doubt about presenting symptoms.


Assuntos
Insuficiência da Valva Aórtica/cirurgia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Diagnóstico Tardio , Endocardite/complicações , Endocardite/diagnóstico , Pneumonia Viral/diagnóstico , Anticorpos Antivirais/análise , Insuficiência da Valva Aórtica/complicações , Insuficiência da Valva Aórtica/diagnóstico , Procedimentos Cirúrgicos Cardíacos/métodos , Infecções por Coronavirus/complicações , Estado Terminal , Progressão da Doença , Dispneia/diagnóstico , Dispneia/etiologia , Endocardite/virologia , Reações Falso-Positivas , Febre/diagnóstico , Febre/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Medição de Risco , Resultado do Tratamento
7.
Cochrane Database Syst Rev ; 8: CD013705, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32845525

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting COVID-19 pandemic present important diagnostic challenges. Several diagnostic strategies are available to identify or rule out current infection, identify people in need of care escalation, or to test for past infection and immune response. Point-of-care antigen and molecular tests to detect current SARS-CoV-2 infection have the potential to allow earlier detection and isolation of confirmed cases compared to laboratory-based diagnostic methods, with the aim of reducing household and community transmission. OBJECTIVES: To assess the diagnostic accuracy of point-of-care antigen and molecular-based tests to determine if a person presenting in the community or in primary or secondary care has current SARS-CoV-2 infection. SEARCH METHODS: On 25 May 2020 we undertook electronic searches in the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. SELECTION CRITERIA: We included studies of people with suspected current SARS-CoV-2 infection, known to have, or not to have SARS-CoV-2 infection, or where tests were used to screen for infection. We included test accuracy studies of any design that evaluated antigen or molecular tests suitable for a point-of-care setting (minimal equipment, sample preparation, and biosafety requirements, with results available within two hours of sample collection). We included all reference standards to define the presence or absence of SARS-CoV-2 (including reverse transcription polymerase chain reaction (RT-PCR) tests and established clinical diagnostic criteria). DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies and resolved any disagreements by discussion with a third review author. One review author independently extracted study characteristics, which were checked by a second review author. Two review authors independently extracted 2x2 contingency table data and assessed risk of bias and applicability of the studies using the QUADAS-2 tool. We present sensitivity and specificity, with 95% confidence intervals (CIs), for each test using paired forest plots. We pooled data using the bivariate hierarchical model separately for antigen and molecular-based tests, with simplifications when few studies were available. We tabulated available data by test manufacturer. MAIN RESULTS: We included 22 publications reporting on a total of 18 study cohorts with 3198 unique samples, of which 1775 had confirmed SARS-CoV-2 infection. Ten studies took place in North America, two in South America, four in Europe, one in China and one was conducted internationally. We identified data for eight commercial tests (four antigen and four molecular) and one in-house antigen test. Five of the studies included were only available as preprints. We did not find any studies at low risk of bias for all quality domains and had concerns about applicability of results across all studies. We judged patient selection to be at high risk of bias in 50% of the studies because of deliberate over-sampling of samples with confirmed COVID-19 infection and unclear in seven out of 18 studies because of poor reporting. Sixteen (89%) studies used only a single, negative RT-PCR to confirm the absence of COVID-19 infection, risking missing infection. There was a lack of information on blinding of index test (n = 11), and around participant exclusions from analyses (n = 10). We did not observe differences in methodological quality between antigen and molecular test evaluations. Antigen tests Sensitivity varied considerably across studies (from 0% to 94%): the average sensitivity was 56.2% (95% CI 29.5 to 79.8%) and average specificity was 99.5% (95% CI 98.1% to 99.9%; based on 8 evaluations in 5 studies on 943 samples). Data for individual antigen tests were limited with no more than two studies for any test. Rapid molecular assays Sensitivity showed less variation compared to antigen tests (from 68% to 100%), average sensitivity was 95.2% (95% CI 86.7% to 98.3%) and specificity 98.9% (95% CI 97.3% to 99.5%) based on 13 evaluations in 11 studies of on 2255 samples. Predicted values based on a hypothetical cohort of 1000 people with suspected COVID-19 infection (with a prevalence of 10%) result in 105 positive test results including 10 false positives (positive predictive value 90%), and 895 negative results including 5 false negatives (negative predictive value 99%). Individual tests We calculated pooled results of individual tests for ID NOW (Abbott Laboratories) (5 evaluations) and Xpert Xpress (Cepheid Inc) (6 evaluations). Summary sensitivity for the Xpert Xpress assay (99.4%, 95% CI 98.0% to 99.8%) was 22.6 (95% CI 18.8 to 26.3) percentage points higher than that of ID NOW (76.8%, (95% CI 72.9% to 80.3%), whilst the specificity of Xpert Xpress (96.8%, 95% CI 90.6% to 99.0%) was marginally lower than ID NOW (99.6%, 95% CI 98.4% to 99.9%; a difference of -2.8% (95% CI -6.4 to 0.8)) AUTHORS' CONCLUSIONS: This review identifies early-stage evaluations of point-of-care tests for detecting SARS-CoV-2 infection, largely based on remnant laboratory samples. The findings currently have limited applicability, as we are uncertain whether tests will perform in the same way in clinical practice, and according to symptoms of COVID-19, duration of symptoms, or in asymptomatic people. Rapid tests have the potential to be used to inform triage of RT-PCR use, allowing earlier detection of those testing positive, but the evidence currently is not strong enough to determine how useful they are in clinical practice. Prospective and comparative evaluations of rapid tests for COVID-19 infection in clinically relevant settings are urgently needed. Studies should recruit consecutive series of eligible participants, including both those presenting for testing due to symptoms and asymptomatic people who may have come into contact with confirmed cases. Studies should clearly describe symptomatic status and document time from symptom onset or time since exposure. Point-of-care tests must be conducted on samples according to manufacturer instructions for use and be conducted at the point of care. Any future research study report should conform to the Standards for Reporting of Diagnostic Accuracy (STARD) guideline.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Antígenos Virais/análise , Infecções por Coronavirus/epidemiologia , Reações Falso-Negativas , Reações Falso-Positivas , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Sensibilidade e Especificidade
8.
J Clin Virol ; 130: 104549, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32763809

RESUMO

BACKGROUND: The global market for SARS-CoV-2-immunoassays is becoming ever more crowded with antibody-tests of various formats, targets and technologies, careful evaluation is crucial for understanding the implications of individual test results. Here, we evaluate the clinical performance of five automated immunoassays on a set of clinical samples. METHODS: Serum/plasma samples of 75 confirmed COVID-19 patients and 320 pre-pandemic serum samples of healthy blood donors were subjected to two IgG and three total antibody SARS-CoV-2-immunoassays. All test setups were automated workflows. RESULTS: Positivity of assays (onset of symptoms > 10 days) ranged between 68.4 % and 81.6 % (Diasorin 68.4 %, Euroimmun 70.3 %, Siemens 73.7 %, Roche 79.0 % and Wantai 81.6 %). All examined assays demonstrated high specificity of >99 % (Euroimmun, Diasorin: 99.1 %, Wantai: 99.4 %) but only two reached levels above 99.5 % (Roche: 99.7 %, Siemens 100 %). Interestingly, there was no overlap in false positive results between the assays. The strongest correlation of quantitative results was observed between the Diasorin and Euroimmun IgG tests (r2 = 0.76). Overall, we observed no difference in the distribution of test results between female and male patients (p-values: 0.18-0.87). A significant difference between severely versus critically ill patients was demonstrated for the Euroimmun, Diasorin, Wantai and Siemens assays (p-values:0.041). CONCLUSION: All assays showed good clinical performance. Our data confirm that orthogonal test strategies as recommended by the CDC can enhance clinical specificity. However, the suboptimal rates of test positivity found at time of hospitalization in this cohort underline the importance of molecular diagnostics to rule out/confirm active infection with SARS-CoV-2.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Testes Sorológicos/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Automação Laboratorial , Betacoronavirus , Técnicas de Laboratório Clínico , Estudos de Coortes , Infecções por Coronavirus/imunologia , Reações Falso-Positivas , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Sensibilidade e Especificidade , Adulto Jovem
9.
J Theor Biol ; 506: 110450, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-32814072

RESUMO

Pooling of samples can increase lab capacity when using Polymerase chain reaction (PCR) to detect diseases such as COVID-19. However, pool testing is typically performed via an adaptive testing strategy which requires a feedback loop in the lab and at least two PCR runs to confirm positive results. This can cost precious time. We discuss a non-adaptive testing method where each sample is distributed in a prescribed manner over several pools, and which yields reliable results after one round of testing. More precisely, assuming knowledge about the overall incidence rate, we calculate explicit error bounds on the number of false positives which scale favourably with pool size and sample multiplicity. This allows for hugely streamlined PCR testing and cuts in detection times for a large-scale testing scenario. A viable consequence of this method could be real-time screening of entire communities, frontline healthcare workers and international flight passengers, for example, using the PCR machines currently in operation.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Programas de Rastreamento/métodos , Pneumonia Viral/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Betacoronavirus/genética , Técnicas de Laboratório Clínico , Reações Falso-Positivas , Humanos , Programas de Rastreamento/normas , Pandemias , Fatores de Tempo
10.
Nat Commun ; 11(1): 4294, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32855423

RESUMO

The early detection and accurate histopathological diagnosis of gastric cancer increase the chances of successful treatment. The worldwide shortage of pathologists offers a unique opportunity for the use of artificial intelligence assistance systems to alleviate the workload and increase diagnostic accuracy. Here, we report a clinically applicable system developed at the Chinese PLA General Hospital, China, using a deep convolutional neural network trained with 2,123 pixel-level annotated H&E-stained whole slide images. The model achieves a sensitivity near 100% and an average specificity of 80.6% on a real-world test dataset with 3,212 whole slide images digitalized by three scanners. We show that the system could aid pathologists in improving diagnostic accuracy and preventing misdiagnoses. Moreover, we demonstrate that our system performs robustly with 1,582 whole slide images from two other medical centres. Our study suggests the feasibility and benefits of using histopathological artificial intelligence assistance systems in routine practice scenarios.


Assuntos
Aprendizado Profundo , Diagnóstico por Computador/métodos , Neoplasias Gástricas/patologia , Bases de Dados Factuais , Reações Falso-Positivas , Humanos , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação
11.
Afr J Prim Health Care Fam Med ; 12(1): e1-e3, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32787398

RESUMO

The use of SARS-CoV-2 rapid diagnostic test (RDT) kits by some African countries for screening has raised serious concerns over their role in malaria areas. Coupled with a lack of adequate personal protective equipment and the scarcity of knowledge on the possible interaction between malaria and COVID-19 both in terms of presentations and shared symptoms, this has left many frontline health workers with fears and anxieties. Several anecdotal reports have already raised questions pertaining to possible false-positive COVID-19 results in proven malaria cases by use of SARS-CoV-2 RDT kits with huge costs to already constrained budgets. The report raises concerns on the use of SARS-CoV-2 kits in malaria areas in terms of cost, to prompt research, allay fears and guide policy during this pandemic and beyond.


Assuntos
Infecções por Coronavirus/diagnóstico , Malária/diagnóstico , Pneumonia Viral/diagnóstico , África/epidemiologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/epidemiologia , Diagnóstico Diferencial , Reações Falso-Positivas , Humanos , Malária/epidemiologia , Programas de Rastreamento , Pandemias , Pneumonia Viral/epidemiologia , Kit de Reagentes para Diagnóstico/economia
12.
Nat Biotechnol ; 38(10): 1168-1173, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32733106

RESUMO

Detection of SARS-CoV-2 using RT-PCR and other advanced methods can achieve high accuracy. However, their application is limited in countries that lack sufficient resources to handle large-scale testing during the COVID-19 pandemic. Here, we describe a method to detect SARS-CoV-2 in nasal swabs using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and machine learning analysis. This approach uses equipment and expertise commonly found in clinical laboratories in developing countries. We obtained mass spectra from a total of 362 samples (211 SARS-CoV-2-positive and 151 negative by RT-PCR) without prior sample preparation from three different laboratories. We tested two feature selection methods and six machine learning approaches to identify the top performing analysis approaches and determine the accuracy of SARS-CoV-2 detection. The support vector machine model provided the highest accuracy (93.9%), with 7% false positives and 5% false negatives. Our results suggest that MALDI-MS and machine learning analysis can be used to reliably detect SARS-CoV-2 in nasal swab samples.


Assuntos
Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Algoritmos , Biotecnologia , Técnicas de Laboratório Clínico/estatística & dados numéricos , Infecções por Coronavirus/epidemiologia , Países em Desenvolvimento , Reações Falso-Negativas , Reações Falso-Positivas , Humanos , Aprendizado de Máquina , Mucosa Nasal/virologia , Pandemias , Pneumonia Viral/epidemiologia , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/estatística & dados numéricos , Máquina de Vetores de Suporte
13.
PLoS One ; 15(8): e0237580, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790740

RESUMO

BACKGROUND: HIV screening (i.e. antigen/antibody) tests are followed by a supplemental (i.e. antibody-only) if the screen is positive. Discrepant results can result from two scenarios: a false-positive screening test or acute HIV infection. These scenarios can be distinguished by a molecular HIV test, but due to contamination concerns, our laboratory recently implemented a policy requiring a second specimen dedicated for molecular HIV testing. Our objective was to (1) characterize the effect of this policy on the time-to-diagnosis for patients with discrepant screening and supplemental test results, and (2) explore "strength of positivity" as an interim predictor of screening test accuracy while awaiting confirmatory test results. METHODS: Data from our laboratory information system, electronic health record, and instrument logs were used to collate data for all HIV testing performed at Barnes-Jewish Hospital (BJH) between January 1, 2014 and October 18, 2017. RESULTS: Requiring a dedicated specimen for molecular testing significantly increased the time-to-diagnosis for patients with discrepant screening and supplemental HIV tests (p = 0.0084). This policy also contributed to loss-to-followup, with 0/35 discrepant cases lost-to-followup prior to policy implementation compared to 2/10 after implementation. However, by optimizing the signal-to-cutoff (S/CO) ratio of the screening test, we were able to more accurately distinguish false-positives from acute-HIV prior to molecular testing (sensitivity of 100%, specificity of 89%). CONCLUSIONS: We propose utilizing quantitative fourth-generation assay results (S/CO) ratios as a predictor of infection true positivity in situations where the screening assay is reactive but the supplemental test is negative and confirmatory molecular results are not immediately available.


Assuntos
Sorodiagnóstico da AIDS/normas , Anticorpos Anti-HIV/sangue , Antígenos HIV/imunologia , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Programas de Rastreamento/métodos , Algoritmos , Reações Falso-Positivas , Anticorpos Anti-HIV/imunologia , Infecções por HIV/sangue , Infecções por HIV/virologia , Humanos
14.
ACS Sens ; 5(8): 2283-2296, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32627534

RESUMO

The COVID-19 pandemic has created huge damage to society and brought panic around the world. Such panic can be ascribed to the seemingly deceptive features of COVID-19: Compared to other deadly viral outbreaks, it has medium transmission and mortality rates. As a result, the severity of the causative coronavirus, SARS-CoV-2, was deeply underestimated by society at the beginning of the COVID-19 outbreak. Based on this, in this review, we define the viruses with features similar to those of SARS-CoV-2 as the Panic Zone viruses. To contain those viruses, accurate and fast diagnosis followed by effective isolation and treatment of patients are pivotal at the early stage of virus breakouts. This is especially true when there is no cure or vaccine available for a transmissible disease, which is the case for the current COVID-19 pandemic. As of July 2020, more than 100 kits for COVID-19 diagnosis on the market have been surveyed in this review, while emerging sensing techniques for SARS-CoV-2 are also discussed. It is of critical importance to rationally use these kits for efficient management and control of the Panic Zone viruses. Therefore, we discuss guidelines to select diagnostic kits at different outbreak stages of the Panic Zone viruses, SARS-CoV-2 in particular. While it is of utmost importance to use nucleic acid based detection kits with low false negativity (high sensitivity) at the early stage of an outbreak, the low false positivity (high specificity) gains importance at later stages of the outbreak. When society is set to reopen from the lockdown stage of the COVID-19 pandemic, it becomes critical to have immunoassay based kits with high specificity to identify people who can safely return to society after their recovery from SARS-CoV-2 infections. Finally, since a massive attack from a viral pandemic requires a massive defense from the whole society, we urge both government and the private sector to research and develop affordable and reliable point-of-care testing (POCT) kits, which can be used massively by the general public (and therefore called massive POCT) to contain Panic Zone viruses in the future.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Kit de Reagentes para Diagnóstico/normas , Reações Falso-Negativas , Reações Falso-Positivas , Humanos , Imunoensaio/métodos , Imunoensaio/normas , Pandemias , Testes Imediatos
15.
Rev Soc Bras Med Trop ; 53: e20200351, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32638891

RESUMO

INTRODUCTION: Estimates of the number of individuals infected by severe acute respiratory syndrome coronavirus 2 are important for health planning and establishment of expectations regarding herd immunity. METHODS: Seven testing rounds of a serological survey were conducted at 1-week intervals between April 19 and May 31, 2020 in Teresina municipality. RESULTS Over the 7 weeks, serological positivity increased from 0.56% (95% confidence interval [CI]: 0.18%-1.30%) to 8.33% (95% CI: 6.61%-10.33%), representing 33-53 persons infected for each reported case. CONCLUSIONS: Serological screening may be an important tool for understanding the immunity of a population and planning community interventions.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Doenças Assintomáticas/epidemiologia , Brasil/epidemiologia , Intervalos de Confiança , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Reações Falso-Positivas , Humanos , Imunidade Coletiva , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Sensibilidade e Especificidade , Estudos Soroepidemiológicos
17.
BMC Bioinformatics ; 21(1): 271, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32605541

RESUMO

BACKGROUND: Systematic technical effects-also called batch effects-are a considerable challenge when analyzing DNA methylation (DNAm) microarray data, because they can lead to false results when confounded with the variable of interest. Methods to correct these batch effects are error-prone, as previous findings have shown. RESULTS: Here, we demonstrate how using the R function ComBat to correct simulated Infinium HumanMethylation450 BeadChip (450 K) and Infinium MethylationEPIC BeadChip Kit (EPIC) DNAm data can lead to a large number of false positive results under certain conditions. We further provide a detailed assessment of the consequences for the highly relevant problem of p-value inflation with subsequent false positive findings after application of the frequently used ComBat method. Using ComBat to correct for batch effects in randomly generated samples produced alarming numbers of false discovery rate (FDR) and Bonferroni-corrected (BF) false positive results in unbalanced as well as in balanced sample distributions in terms of the relation between the outcome of interest variable and the technical position of the sample during the probe measurement. Both sample size and number of batch factors (e.g. number of chips) were systematically simulated to assess the probability of false positive findings. The effect of sample size was simulated using n = 48 up to n = 768 randomly generated samples. Increasing the number of corrected factors led to an exponential increase in the number of false positive signals. Increasing the number of samples reduced, but did not completely prevent, this effect. CONCLUSIONS: Using the approach described, we demonstrate, that using ComBat for batch correction in DNAm data can lead to false positive results under certain conditions and sample distributions. Our results are thus contrary to previous publications, considering a balanced sample distribution as unproblematic when using ComBat. We do not claim completeness in terms of reporting all technical conditions and possible solutions of the occurring problems as we approach the problem from a clinician's perspective and not from that of a computer scientist. With our approach of simulating data, we provide readers with a simple method to assess the probability of false positive findings in DNAm microarray data analysis pipelines.


Assuntos
Metilação de DNA , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Ilhas de CpG , Reações Falso-Positivas , Humanos , Dispositivos Lab-On-A-Chip , Probabilidade , Tamanho da Amostra
20.
J Glaucoma ; 29(10): 989-991, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32675556

RESUMO

PURPOSE: The coronavirus (COVID-19) pandemic has had a profound impact on how glaucoma care is delivered, necessitating reduced clinic flow, social distancing, and use of face coverings by patients and staff. This case highlights the need to be aware of improperly fitted face masks as a cause of artifact on standard automated perimetry (SAP). CLINICAL PRESENTATION: A 32-year-old female underwent SAP with the 24-2 SITA Fast test of the Humphrey Field Analyzer wearing an ear-loop surgical face mask. At the end of testing, it was noted that the mask had ridden up the patient's face. Small amounts of condensate were noted on the perimeter lens. CLINICAL FINDINGS: SAP demonstrated good reliability indices but in both eyes, there was a marked reduction in sensitivity inferiorly. The glaucoma hemifield test was outside normal limits. It was ensured the upper border of the mask was well sealed with the loops secured around the ears and nasal strip of the mask pinched down. Visual fields were repeated and were found to be normal. CONCLUSIONS: Poorly fitting face masks represent a new cause of visual field artifact which may mimic pathologic field defects. Without careful attention during testing, the cause of such artifacts may not be apparent, especially as reliability indices may be normal. Adjustments to the fit of face masks may help prevent fogging or mask slippage and increase test reliability.


Assuntos
Artefatos , Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Glaucoma/diagnóstico , Máscaras/efeitos adversos , Doenças do Nervo Óptico/diagnóstico , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Testes de Campo Visual , Adulto , Reações Falso-Positivas , Feminino , Humanos , Pressão Intraocular , Valor Preditivo dos Testes , Campos Visuais/fisiologia
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