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1.
Ann R Coll Surg Engl ; 103(3): 203-207, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33645277

RESUMEN

INTRODUCTION: Patients with suspected appendicitis remain a diagnostic challenge. The aim of this study was to validate risk prediction models, and to investigate diagnostic accuracy of ultrasonography and computed tomography (CT) in adults undergoing appendicectomy. METHODS: A retrospective case review was performed of patients aged 16-45 years having an appendicectomy between January 2019 and January 2020 at a tertiary referral centre. Primary outcomes were the accuracy of a high risk appendicitis risk score and ultrasonography and CT imaging modalities compared with histological reports following appendicectomy. RESULTS: A total of 206 patients (52% female) were included in the study. Removal of a histologically normal appendix was equally likely in men and women (13.1% vs 11.2% respectively, relative risk: 1.17, 95% confidence interval: 0.56-2.44, p=0.674). A high risk appendicitis score correctly identified 84.0% (79/94) of cases in men and 85.9% (67/78) of cases in women. Ultrasonography was reported as equivocal in 85.7% (18/21) of low risk women and 59.0% (23/39) of high risk women. CT correctly detected or excluded appendicitis in 75.0% (6/8) of low risk women and 88.5% (23/26) of high risk women. CONCLUSIONS: This study suggests that risk prediction models may be useful in both women and men to identify appendicitis. Ultrasonography gave high rates of equivocal results and should not be relied on for the diagnosis of appendicitis. CT is a highly accurate diagnostic tool and could be considered in those at low risk where clinical suspicion remains to reduce negative appendicectomy rates.


Asunto(s)
Apendicitis/diagnóstico por imagen , Apéndice/patología , Reglas de Decisión Clínica , Adolescente , Adulto , Apendicectomía , Neoplasias del Apéndice/patología , Apendicitis/patología , Apendicitis/cirugía , Errores Diagnósticos , Reacciones Falso Positivas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/patología , Readmisión del Paciente , Estudios Retrospectivos , Factores Sexuales , Tomografía Computarizada por Rayos X , Ultrasonografía , Adulto Joven
2.
Antimicrob Resist Infect Control ; 10(1): 51, 2021 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-33750477

RESUMEN

The rapid spread of the coronavirus disease 2019 pandemic urged immense testing capacities as one cornerstone of infection control. Many institutions opened outpatient SARS-CoV-2 test centers to allow large number of tests in comparatively short time frames. With increasing positive test rates, concerns for a possible airborne or droplet contamination of specimens leading to false-positive results were raised. In our experimental series performed in a dedicated SARS-CoV-2 test center, 40 open collection tubes placed for defined time periods in proximity to individuals were found to be SARS-CoV-2 negative. These findings argue against false-positive SARS-CoV-2 results due to droplet or airborne contamination.


Asunto(s)
/métodos , Contaminación de Equipos/estadística & datos numéricos , Manejo de Especímenes/métodos , Reacciones Falso Positivas , Humanos , Material Particulado/análisis , Reacción en Cadena de la Polimerasa , /aislamiento & purificación
3.
Int J Mol Sci ; 22(4)2021 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-33669963

RESUMEN

Because Japanese cedar pollen (JCP) contains beta-1,3-d-glucan (BG), there is concern that its lingering presence in the atmosphere, especially during its scattering period, may cause false positives in the factor-G-based Limulus amebocyte lysate (LAL) assay used to test for deep mycosis (i.e., G-test). Hence, we examined whether the LAL assay would react positively with substances contained in JCP by using the G-test to measure JCP particles and extracts. BG was purified from the JCP extract on a BG-specific affinity column, and the percentage extractability was measured using three different BG-specific quantitative methods. The G-test detected 0.4 pg BG in a single JCP particle and 10 fg from a single particle in the extract. The percentage extractability of JCP-derived BG was not significantly different among the three quantitative methods. As the JCP particles should technically have been removed during serum separation, they should be less likely to be a direct false-positive factor. However, given that the LAL-assay-positive substances in the JCP extract were not distinguishable by the three BG-specific quantitative methods, we conclude that they may cause the background to rise. Therefore, in Japan false positives arising from JCP contamination should be considered when testing patients for deep mycosis.


Asunto(s)
Cryptomeria/inmunología , Micosis/diagnóstico , Polen/inmunología , Reacciones Falso Positivas , Concentración de Iones de Hidrógeno , Lectinas Tipo C/metabolismo , beta-Glucanos/metabolismo
4.
PLoS One ; 16(3): e0248920, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33765050

RESUMEN

BACKGROUND: Tests are scarce resources, especially in low and middle-income countries, and the optimization of testing programs during a pandemic is critical for the effectiveness of the disease control. Hence, we aim to use the combination of symptoms to build a predictive model as a screening tool to identify people and areas with a higher risk of SARS-CoV-2 infection to be prioritized for testing. MATERIALS AND METHODS: We performed a retrospective analysis of individuals registered in "Dados do Bem," a Brazilian app-based symptom tracker. We applied machine learning techniques and provided a SARS-CoV-2 infection risk map of Rio de Janeiro city. RESULTS: From April 28 to July 16, 2020, 337,435 individuals registered their symptoms through the app. Of these, 49,721 participants were tested for SARS-CoV-2 infection, being 5,888 (11.8%) positive. Among self-reported symptoms, loss of smell (OR[95%CI]: 4.6 [4.4-4.9]), fever (2.6 [2.5-2.8]), and shortness of breath (2.1 [1.6-2.7]) were independently associated with SARS-CoV-2 infection. Our final model obtained a competitive performance, with only 7% of false-negative users predicted as negatives (NPV = 0.93). The model was incorporated by the "Dados do Bem" app aiming to prioritize users for testing. We developed an external validation in the city of Rio de Janeiro. We found that the proportion of positive results increased significantly from 14.9% (before using our model) to 18.1% (after the model). CONCLUSIONS: Our results showed that the combination of symptoms might predict SARS-Cov-2 infection and, therefore, can be used as a tool by decision-makers to refine testing and disease control strategies.


Asunto(s)
/diagnóstico , Aprendizaje Automático , Adulto , Brasil , /virología , Disnea/etiología , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Fiebre/etiología , Humanos , Masculino , Persona de Mediana Edad , Aplicaciones Móviles , Sistema de Registros , Estudios Retrospectivos , Riesgo , Autoinforme
5.
Health Technol Assess ; 25(21): 1-68, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33764295

RESUMEN

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019. At the time of writing (October 2020), the number of cases of COVID-19 had been approaching 38 million and more than 1 million deaths were attributable to it. SARS-CoV-2 appears to be highly transmissible and could rapidly spread in hospital wards. OBJECTIVE: The work undertaken aimed to estimate the clinical effectiveness and cost-effectiveness of viral detection point-of-care tests for detecting SARS-CoV-2 compared with laboratory-based tests. A further objective was to assess occupancy levels in hospital areas, such as waiting bays, before allocation to an appropriate bay. PERSPECTIVE/SETTING: The perspective was that of the UK NHS in 2020. The setting was a hypothetical hospital with an accident and emergency department. METHODS: An individual patient model was constructed that simulated the spread of disease and mortality within the hospital and recorded occupancy levels. Thirty-two strategies involving different hypothetical SARS-CoV-2 tests were modelled. Recently published desirable and acceptable target product profiles for SARS-CoV-2 point-of-care tests were modelled. Incremental analyses were undertaken using both incremental cost-effectiveness ratios and net monetary benefits, and key patient outcomes, such as death and intensive care unit care, caused directly by COVID-19 were recorded. RESULTS: A SARS-CoV-2 point-of-care test with a desirable target product profile appears to have a relatively small number of infections, a low occupancy level within the waiting bays, and a high net monetary benefit. However, if hospital laboratory testing can produce results in 6 hours, then the benefits of point-of-care tests may be reduced. The acceptable target product profiles performed less well and had lower net monetary benefits than both a laboratory-based test with a 24-hour turnaround time and strategies using data from currently available SARS-CoV-2 point-of-care tests. The desirable and acceptable point-of-care test target product profiles had lower requirement for patients to be in waiting bays before being allocated to an appropriate bay than laboratory-based tests, which may be of high importance in some hospitals. Tests that appeared more cost-effective also had better patient outcomes. LIMITATIONS: There is considerable uncertainty in the values for key parameters within the model, although calibration was undertaken in an attempt to mitigate this. The example hospital simulated will also not match those of decision-makers deciding on the clinical effectiveness and cost-effectiveness of introducing SARS-CoV-2 point-of-care tests. Given these limitations, the results should be taken as indicative rather than definitive, particularly cost-effectiveness results when the relative cost per SARS-CoV-2 point-of-care test is uncertain. CONCLUSIONS: Should a SARS-CoV-2 point-of-care test with a desirable target product profile become available, this appears promising, particularly when the reduction on the requirements for waiting bays before allocation to a SARS-CoV-2-infected bay, or a non-SARS-CoV-2-infected bay, is considered. The results produced should be informative to decision-makers who can identify the results most pertinent to their specific circumstances. FUTURE WORK: More accurate results could be obtained when there is more certainty on the diagnostic accuracy of, and the reduction in time to test result associated with, SARS-CoV-2 point-of-care tests, and on the impact of these tests on occupancy of waiting bays and isolation bays. These parameters are currently uncertain. FUNDING: This report was commissioned by the National Institute for Health Research (NIHR) Evidence Synthesis programme as project number 132154. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 21. See the NIHR Journals Library website for further project information.


Asunto(s)
/diagnóstico , Servicio de Urgencia en Hospital/organización & administración , Admisión del Paciente , Pruebas en el Punto de Atención/economía , Pruebas en el Punto de Atención/normas , /epidemiología , Análisis Costo-Beneficio , Servicio de Urgencia en Hospital/economía , Servicio de Urgencia en Hospital/normas , Reacciones Falso Negativas , Reacciones Falso Positivas , Humanos , Medicina Estatal , Reino Unido
6.
Biomed Eng Online ; 20(1): 27, 2021 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-33743707

RESUMEN

BACKGROUND: Lung ultrasound (LUS) can be an important imaging tool for the diagnosis and assessment of lung involvement. Ultrasound sonograms have been confirmed to illustrate damage to a person's lungs, which means that the correct classification and scoring of a patient's sonogram can be used to assess lung involvement. METHODS: The purpose of this study was to establish a lung involvement assessment model based on deep learning. A novel multimodal channel and receptive field attention network combined with ResNeXt (MCRFNet) was proposed to classify sonograms, and the network can automatically fuse shallow features and determine the importance of different channels and respective fields. Finally, sonogram classes were transformed into scores to evaluate lung involvement from the initial diagnosis to rehabilitation. RESULTS AND CONCLUSION: Using multicenter and multimodal ultrasound data from 104 patients, the diagnostic model achieved 94.39% accuracy, 82.28% precision, 76.27% sensitivity, and 96.44% specificity. The lung involvement severity and the trend of COVID-19 pneumonia were evaluated quantitatively.


Asunto(s)
/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Neumonía/diagnóstico por imagen , Ultrasonografía , Algoritmos , Bases de Datos Factuales , Reacciones Falso Positivas , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Modelos Estadísticos , Redes Neurales de la Computación , Lenguajes de Programación , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Programas Informáticos
7.
J Infect Dev Ctries ; 15(2): 237-241, 2021 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-33690206

RESUMEN

INTRODUCTION: We aim to describe the performance of combined IgM and IgG point-of-care antibody test (POC-Ab) (Wondfo®) compared to real-time reverse transcriptase (rRT-PCR) (Allplex™ 2019-nCoV Assay) in detecting coronavirus disease 2019 (COVID-19). METHODOLOGY: We compared POC-Ab with rRT-PCR results among patients in a tertiary hospital from January to March 2020 in Bandung, Indonesia. We selected presumptive COVID-19 patients with positive rRT-PCR consecutively and 20 patients with negative rRT-PCR results were selected randomly from the same group of patients as controls. We described the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) with corresponding 95% confidence interval using serum and capillary blood samples. We also tested POC-Ab using non-COVID-19 (confirmed dengue and typhoid) patients' sera. RESULTS: Twenty-seven patients with positive rRT-PCR result and 20 negative controls were included (68.1% males, mean age 46 (SD: 15.4)). Using the serum, the sensitivity of the POC-Ab was 63.0% (42.4-80.6), specificity was 95.0% (75.1-99.9), PPV was 94.4% (72.7-99.8), NPV was 65.5% (45.7-82.1). A subset of 20 patients was tested using a capillary blood sample. The accuracy of the capillary blood sample is lower compared to serum (50.0% vs. 78.7%). None of the non-COVID-19 sera tested were reactive. CONCLUSIONS: POC-Ab for COVID-19 has a high specificity with no false-positive result in non-COVID-19 sera. Therefore, it can be used to guide diagnostic among symptomatic patients in resource limited settings. Given its low sensitivity, patients with high suspicion of COVID-19 but non-reactive result should be prioritized for rRT-PCR testing.


Asunto(s)
/métodos , Adulto , Anciano , /etiología , Reacciones Falso Positivas , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Indonesia , Masculino , Persona de Mediana Edad , Nasofaringe/virología , Sistemas de Atención de Punto , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Sensibilidad y Especificidad , Centros de Atención Terciaria
8.
Virol J ; 18(1): 54, 2021 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-33706767

RESUMEN

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic remains ongoing around the world, including in areas where dengue is endemic. Dengue and COVID-19, to some extent, have similar clinical and laboratory features, which can lead to misdiagnosis, delayed treatment and patient's isolation. The use of rapid diagnostic tests (RDT) is easy and convenient for fast diagnosis, however there may be issues with cross-reactivity with antibodies for other pathogens. METHODS: We assessed the possibility of cross-reactivity between SARS-CoV-2 and dengue antibodies by: (1) testing five brands of COVID-19 IgG / IgM RDTs on 60 RT-PCR-confirmed dengue samples; (2) testing 95 RT-PCR-confirmed COVID-19 samples on dengue RDT; and (3) testing samples positive for COVID-19 IgG and/or IgM on dengue RDT. RESULTS: We observed a high specificity across all five brands of COVID-19 RDTs, ranging from 98.3 to 100%. Out of the confirmed COVID-19 samples, one patient tested positive for dengue IgM only, another tested positive for dengue IgG only. One patient tested positive for dengue IgG, IgM, and NS1, suggesting a co-infection. In COVID-19 IgG and/or IgM samples, 6.3% of COVID-19 IgG-positive samples also tested positive for dengue IgG, while 21.1% of COVID-19 IgM-positive samples also tested positive for dengue IgG. CONCLUSION: Despite the high specificity of the COVID-19 RDT, we observed cross-reactions and false-positive results between dengue and COVID-19. Dengue and COVID-19 co-infection was also found. Health practitioners in dengue endemic areas should be careful when using antibody RDT for the diagnosis of dengue during the COVID-19 pandemic to avoid misdiagnosis.


Asunto(s)
Anticuerpos Antivirales/inmunología , Reacciones Cruzadas/inmunología , Virus del Dengue/inmunología , Dengue/diagnóstico , /inmunología , Adolescente , Adulto , Niño , Diagnóstico Diferencial , Pruebas Diagnósticas de Rutina , Reacciones Falso Positivas , Femenino , Humanos , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Indonesia , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Proteínas no Estructurales Virales/inmunología , Adulto Joven
9.
JAMA ; 325(10): 971-987, 2021 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-33687468

RESUMEN

Importance: Lung cancer is the leading cause of cancer-related death in the US. Objective: To review the evidence on screening for lung cancer with low-dose computed tomography (LDCT) to inform the US Preventive Services Task Force (USPSTF). Data Sources: MEDLINE, Cochrane Library, and trial registries through May 2019; references; experts; and literature surveillance through November 20, 2020. Study Selection: English-language studies of screening with LDCT, accuracy of LDCT, risk prediction models, or treatment for early-stage lung cancer. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings. Data were not pooled because of heterogeneity of populations and screening protocols. Main Outcomes and Measures: Lung cancer incidence, lung cancer mortality, all-cause mortality, test accuracy, and harms. Results: This review included 223 publications. Seven randomized clinical trials (RCTs) (N = 86 486) evaluated lung cancer screening with LDCT; the National Lung Screening Trial (NLST, N = 53 454) and Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON, N = 15 792) were the largest RCTs. Participants were more likely to benefit than the US screening-eligible population (eg, based on life expectancy). The NLST found a reduction in lung cancer mortality (incidence rate ratio [IRR], 0.85 [95% CI, 0.75-0.96]; number needed to screen [NNS] to prevent 1 lung cancer death, 323 over 6.5 years of follow-up) with 3 rounds of annual LDCT screening compared with chest radiograph for high-risk current and former smokers aged 55 to 74 years. NELSON found a reduction in lung cancer mortality (IRR, 0.75 [95% CI, 0.61-0.90]; NNS to prevent 1 lung cancer death of 130 over 10 years of follow-up) with 4 rounds of LDCT screening with increasing intervals compared with no screening for high-risk current and former smokers aged 50 to 74 years. Harms of screening included radiation-induced cancer, false-positive results leading to unnecessary tests and invasive procedures, overdiagnosis, incidental findings, and increases in distress. For every 1000 persons screened in the NLST, false-positive results led to 17 invasive procedures (number needed to harm, 59) and fewer than 1 person having a major complication. Overdiagnosis estimates varied greatly (0%-67% chance that a lung cancer was overdiagnosed). Incidental findings were common, and estimates varied widely (4.4%-40.7% of persons screened). Conclusions and Relevance: Screening high-risk persons with LDCT can reduce lung cancer mortality but also causes false-positive results leading to unnecessary tests and invasive procedures, overdiagnosis, incidental findings, increases in distress, and, rarely, radiation-induced cancers. Most studies reviewed did not use current nodule evaluation protocols, which might reduce false-positive results and invasive procedures for false-positive results.


Asunto(s)
Detección Precoz del Cáncer , Neoplasias Pulmonares/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Anciano , Anciano de 80 o más Años , Causas de Muerte , Detección Precoz del Cáncer/efectos adversos , Reacciones Falso Positivas , Humanos , Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/mortalidad , Uso Excesivo de los Servicios de Salud , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Factores de Riesgo , Sensibilidad y Especificidad , Fumar/efectos adversos , Procedimientos Innecesarios
10.
BMC Infect Dis ; 21(1): 288, 2021 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-33743628

RESUMEN

BACKGROUND: Many clinicians are aware that certain therapies administered to their patients can have downstream consequences in the form of clinical laboratory test interferences. This is particularly true of laboratory tests that depend on, or directly involve the use of, antibody-based methodology. Intravenously-administered immunoglobulin therapy is one such treatment that can in theory directly impact the results of particular tests in the area of viral serology. This study can help serve as a reference for clinicians researching the impact of intravenously-administered immunoglobulin therapy in the context of positive results that do not reflect the clinical background of the patient. CASE PRESENTATION: We describe a case whereby an intravenously-administered immunoglobulin therapy led to a series of clinical false positives in viral serology, inconsistent with the known patient history as well as recent laboratory results. The patient presented to hospital with petechiae-type bleeding rashes and was investigated for thrombocytopenia after initial blood investigations indicated very low platelets. Subsequent testing of the potential causes for low-platelet involved several viral serology investigations, including hepatitis, cytomegalovirus and human immunodeficiency virus. Initial testing indicated patient exhibited negative status for all viral antibodies and antigens (except immunity for hepatitis B surface antigen antibody). As part of the thrombocytopenia treatment, intravenously-administered immunoglobulin therapy was administered, and subsequent viral serology was ordered. These investigations indicated a positive status for several hepatitis antibodies as well as cytomegalovirus. CONCLUSIONS: This case study illustrates the potential for improper diagnosis of previous or ongoing infection status in patients administered IVIg therapy. Caution should be exercised particularly when interpreting results involving cytomegalovirus and hepatitis.


Asunto(s)
Anticuerpos Antivirales/sangre , Reacciones Falso Positivas , Inmunoglobulinas Intravenosas/uso terapéutico , Adulto , Citomegalovirus , Femenino , Anticuerpos Antihepatitis/sangre , Virus de Hepatitis , Humanos
11.
Cochrane Database Syst Rev ; 3: CD013705, 2021 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-33760236

RESUMEN

BACKGROUND: Accurate rapid diagnostic tests for SARS-CoV-2 infection could contribute to clinical and public health strategies to manage the COVID-19 pandemic. Point-of-care antigen and molecular tests to detect current infection could increase access to testing and early confirmation of cases, and expediate clinical and public health management decisions that may reduce transmission. OBJECTIVES: To assess the diagnostic accuracy of point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection. We consider accuracy separately in symptomatic and asymptomatic population groups. SEARCH METHODS: Electronic searches of the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) were undertaken on 30 Sept 2020. We checked repositories of COVID-19 publications and included independent evaluations from national reference laboratories, the Foundation for Innovative New Diagnostics and the Diagnostics Global Health website to 16 Nov 2020. We did not apply language restrictions. SELECTION CRITERIA: We included studies of people with either suspected SARS-CoV-2 infection, known SARS-CoV-2 infection or known absence of infection, or those who were being screened for infection. We included test accuracy studies of any design that evaluated commercially produced, rapid antigen or molecular tests suitable for a point-of-care setting (minimal equipment, sample preparation, and biosafety requirements, with results within two hours of sample collection). We included all reference standards that define the presence or absence of SARS-CoV-2 (including reverse transcription polymerase chain reaction (RT-PCR) tests and established diagnostic criteria). DATA COLLECTION AND ANALYSIS: Studies were screened independently in duplicate with disagreements resolved by discussion with a third author. Study characteristics were extracted by one author and checked by a second; extraction of study results and assessments of risk of bias and applicability (made using the QUADAS-2 tool) were undertaken independently in duplicate. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test and pooled data using the bivariate model separately for antigen and molecular-based tests. We tabulated results by test manufacturer and compliance with manufacturer instructions for use and according to symptom status. MAIN RESULTS: Seventy-eight study cohorts were included (described in 64 study reports, including 20 pre-prints), reporting results for 24,087 samples (7,415 with confirmed SARS-CoV-2). Studies were mainly from Europe (n = 39) or North America (n = 20), and evaluated 16 antigen and five molecular assays. We considered risk of bias to be high in 29 (50%) studies because of participant selection; in 66 (85%) because of weaknesses in the reference standard for absence of infection; and in 29 (45%) for participant flow and timing. Studies of antigen tests were of a higher methodological quality compared to studies of molecular tests, particularly regarding the risk of bias for participant selection and the index test. Characteristics of participants in 35 (45%) studies differed from those in whom the test was intended to be used and the delivery of the index test in 39 (50%) studies differed from the way in which the test was intended to be used. Nearly all studies (97%) defined the presence or absence of SARS-CoV-2 based on a single RT-PCR result, and none included participants meeting case definitions for probable COVID-19. Antigen tests Forty-eight studies reported 58 evaluations of antigen tests. Estimates of sensitivity varied considerably between studies. There were differences between symptomatic (72.0%, 95% CI 63.7% to 79.0%; 37 evaluations; 15530 samples, 4410 cases) and asymptomatic participants (58.1%, 95% CI 40.2% to 74.1%; 12 evaluations; 1581 samples, 295 cases). Average sensitivity was higher in the first week after symptom onset (78.3%, 95% CI 71.1% to 84.1%; 26 evaluations; 5769 samples, 2320 cases) than in the second week of symptoms (51.0%, 95% CI 40.8% to 61.0%; 22 evaluations; 935 samples, 692 cases). Sensitivity was high in those with cycle threshold (Ct) values on PCR ≤25 (94.5%, 95% CI 91.0% to 96.7%; 36 evaluations; 2613 cases) compared to those with Ct values >25 (40.7%, 95% CI 31.8% to 50.3%; 36 evaluations; 2632 cases). Sensitivity varied between brands. Using data from instructions for use (IFU) compliant evaluations in symptomatic participants, summary sensitivities ranged from 34.1% (95% CI 29.7% to 38.8%; Coris Bioconcept) to 88.1% (95% CI 84.2% to 91.1%; SD Biosensor STANDARD Q). Average specificities were high in symptomatic and asymptomatic participants, and for most brands (overall summary specificity 99.6%, 95% CI 99.0% to 99.8%). At 5% prevalence using data for the most sensitive assays in symptomatic people (SD Biosensor STANDARD Q and Abbott Panbio), positive predictive values (PPVs) of 84% to 90% mean that between 1 in 10 and 1 in 6 positive results will be a false positive, and between 1 in 4 and 1 in 8 cases will be missed. At 0.5% prevalence applying the same tests in asymptomatic people would result in PPVs of 11% to 28% meaning that between 7 in 10 and 9 in 10 positive results will be false positives, and between 1 in 2 and 1 in 3 cases will be missed. No studies assessed the accuracy of repeated lateral flow testing or self-testing. Rapid molecular assays Thirty studies reported 33 evaluations of five different rapid molecular tests. Sensitivities varied according to test brand. Most of the data relate to the ID NOW and Xpert Xpress assays. Using data from evaluations following the manufacturer's instructions for use, the average sensitivity of ID NOW was 73.0% (95% CI 66.8% to 78.4%) and average specificity 99.7% (95% CI 98.7% to 99.9%; 4 evaluations; 812 samples, 222 cases). For Xpert Xpress, the average sensitivity was 100% (95% CI 88.1% to 100%) and average specificity 97.2% (95% CI 89.4% to 99.3%; 2 evaluations; 100 samples, 29 cases). Insufficient data were available to investigate the effect of symptom status or time after symptom onset. AUTHORS' CONCLUSIONS: Antigen tests vary in sensitivity. In people with signs and symptoms of COVID-19, sensitivities are highest in the first week of illness when viral loads are higher. The assays shown to meet appropriate criteria, such as WHO's priority target product profiles for COVID-19 diagnostics ('acceptable' sensitivity ≥ 80% and specificity ≥ 97%), can be considered as a replacement for laboratory-based RT-PCR when immediate decisions about patient care must be made, or where RT-PCR cannot be delivered in a timely manner. Positive predictive values suggest that confirmatory testing of those with positive results may be considered in low prevalence settings. Due to the variable sensitivity of antigen tests, people who test negative may still be infected. Evidence for testing in asymptomatic cohorts was limited. Test accuracy studies cannot adequately assess the ability of antigen tests to differentiate those who are infectious and require isolation from those who pose no risk, as there is no reference standard for infectiousness. A small number of molecular tests showed high accuracy and may be suitable alternatives to RT-PCR. However, further evaluations of the tests in settings as they are intended to be used are required to fully establish performance in practice. Several important studies in asymptomatic individuals have been reported since the close of our search and will be incorporated at the next update of this review. Comparative studies of antigen tests in their intended use settings and according to test operator (including self-testing) are required.


Asunto(s)
Antígenos Virales/análisis , /diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Sistemas de Atención de Punto , /inmunología , Adulto , Infecciones Asintomáticas , Sesgo , Niño , Estudios de Cohortes , Reacciones Falso Negativas , Reacciones Falso Positivas , Humanos , Técnicas de Diagnóstico Molecular/normas , Valor Predictivo de las Pruebas , Estándares de Referencia , Sensibilidad y Especificidad
12.
Fukushima J Med Sci ; 67(1): 27-32, 2021 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-33642419

RESUMEN

Of the 47 prefectures in Japan, Iwate had the fewest cases of coronavirus disease 2019 (COVID-19), with the first diagnosis officially confirmed on July 28, 2020. A baseline serological survey of COVID-19 antibodies is essential to accurately evaluate an epidemic outbreak. The primary purpose of this study was to determine pre-epidemic prevalence of COVID-19 antibodies among healthcare workers, using two laboratory-based quantitative tests. In addition, a point-of-care (POC) qualitative test, rapid, simple, and convenient for primary care clinics, was compared with the laboratory-based tests. All antibody tests were performed on serum from 1,000 healthcare workers (mean age, 40 ± 11 years) in Iwate Prefectural Central Hospital, May 29-31, 2020. A COVID-19 case was defined as showing positive results in both laboratory-based quantitative tests. None of 1,000 samples had positive results in both of the laboratory immunoassays. The POC test showed positive results in 33 of 1,000 samples (3.3%) (95% confidence interval:2.19-4.41), but no samples were simultaneously positive in both laboratory-based tests. In conclusion, COVID-19 cases were not serologically confirmed by a baseline control study of healthcare workers at our hospital in late May, 2020. Moreover, the POC qualitative test may offer no advantage in areas with very low prevalence of COVID-19, due to higher false-positive reactions compared with laboratory-based quantitative immunoassays.


Asunto(s)
/diagnóstico , Personal de Salud , Adulto , Anticuerpos Antivirales/sangre , /estadística & datos numéricos , Epidemias , Reacciones Falso Positivas , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Pandemias , Pruebas en el Punto de Atención/estadística & datos numéricos , Estudios Seroepidemiológicos , Centros de Atención Terciaria , Factores de Tiempo
14.
J Glob Health ; 11: 05001, 2021 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-33604032

RESUMEN

Background: On 12 June 2020, Brazil reached the second position worldwide in the number of COVID-19 cases. Authorities increased the number of tests performed, including the identification of antibodies to SARS-CoV-2 (IgG, IgA, and IgM). There was an overflooding of the market with several tests, and the presence of possible false-positive results became a challenge. The purpose of this study was to describe the seroprevalence and immunoglobulin blood levels in a group of asymptomatic individuals using the reference levels provided by the manufacturer. Methods: Levels of IgG and IgA antibodies to SARS-CoV-2 were determined in blood serum by the same ELISA (enzyme-linked immunoassay) test. Patients must be free of symptoms. Results: From 20 to 22 May 2020, 938 individuals were tested. There were 441 (47%) men, age 53 years (interquartile range (IQR) = 39-63.2). The sample included 335 (35.7%) subjects aged ≥60 years old. Subjects with a positive test were 54 (5.8%) for IgG and 96 (10.2%) for IgA and 42 (4.5%) for both IgG and IgA. The prevalence of IgG and IgA positive test was not different in men and women and not different in individuals under 60 and over 60 years of age. Conversely, analysing only individuals with positive tests, the levels of IgG in positive subjects were significantly higher than those with an IgA positive test, 3.00 (IQR = 1.68-5.65), and 1.95 (IQR = 1.40-3.38), respectively; P = 0.017. Additionally, individuals with isolated IgA positive tests had significantly lower levels of IgA than those with both IgA and IgG positive tests: 1.95 (IQR = 1.60-2.40) and 3.15 (IQR = 2.20-3.90), respectively, P = 0.005. These latter data suggest that IgA shows a deviation of the distribution to the left in comparison to IgG distribution data. Indeed, many subjects reported as IgA positive had immunoglobulin levels slightly elevated. Conclusions: In conclusion, we strongly suggest caution in the interpretation of IgA test results. This recommendation is more important for those with positive IgA just above the reference level.


Asunto(s)
Anticuerpos Antivirales/sangre , Reacciones Falso Positivas , Inmunoglobulina A/sangre , /inmunología , Adulto , Brasil/epidemiología , Estudios Transversales , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Valores de Referencia , Estudios Seroepidemiológicos
15.
Diagn Microbiol Infect Dis ; 100(1): 115330, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33571860

RESUMEN

SARS-CoV-2 pandemic shows the importance of having efficient virus diagnosis, especially in groups of particular relevance such as health care professionals, without involving a large economic expense. This is a prevalence study carried out in 7400 health care professionals in a 1350-bed hospital in Madrid, Spain. Pools of 10 samples were performed, using the Xpert® Xpress SARS-CoV-2 test for the diagnosis from clinical samples of nasopharyngeal exudate. A previous study was performed to evaluate the effect of the dilution in terms of sensitivity. The estimated sensitivity was over 95%. A total of 740 pools were performed, with a final result of 218 health care professionals being positive. Using the pooling system, the reagent cost reduction to the institution was 75.3%. It can be concluded that the described sample pooling system is a useful and efficient tool in the diagnosis of SARS-CoV-2 in certain groups, assuming a cost reduction without reducing the sensitivity.


Asunto(s)
/métodos , Personal de Hospital/estadística & datos numéricos , Reacción en Cadena de la Polimerasa/métodos , /epidemiología , Reacciones Falso Positivas , Humanos , Nasofaringe/virología , Prevalencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , España/epidemiología , Manejo de Especímenes/métodos
16.
Diagn Microbiol Infect Dis ; 100(1): 115334, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33571862

RESUMEN

Several real-time RT-PCR assays have received Emergency Use Authorization from the United States Food and Drug Administration. The BD MAX™ SARS-CoV-2 assay, run by the BD MAX™ system, is a qualitative test that detects the SARS-CoV-2 specific nucleocapsid phosphoprotein gene regions, N1 and N2. The human RNase P gene is used as the endogenous nucleic acid extraction control. The Cepheid Xpert® Xpress SARS-CoV-2 assay, run by the GeneXpert system, detects the pan-sarbecovirus E gene and the N2 region of the N gene. We evaluated the performance characteristics of the BD and Cepheid assays using matched patient samples. We also analyzed comparative Ct values for both assays using 183 positive samples tested at this facility. In addition, we mitigated reporting false positive results without relying on interpretive software. We found that both systems showed comparable sensitivity. We found an approximately 3.5% false positive rate from the BD MAX™ system results.


Asunto(s)
/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , /genética , Reacciones Falso Positivas , Humanos , Fosfoproteínas/genética
17.
J Clin Neurosci ; 85: 36-40, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33581787

RESUMEN

BACKGROUND: Symptomatic carotid stenosis is responsible for 10% of all strokes. Currently, CT angiography (CTA) is the main diagnostic tool for carotid stenosis. It is frequently the only diagnostic test preceding recommendations for carotid angioplasty and stenting (CAS) or carotid endarterectomy (CEA). However, the specificity of CTA, especially in patients with 50-70% stenosis, was previously reported to be relatively low. Most studies testing the diagnostic accuracy of CTA were published more than a decade ago. Therefore, we aimed to test the diagnostic accuracy of CTA, performed with current available technology, compared with digital subtraction angiography (DSA) in patients with carotid stenosis. This study aims to characterize patients who were candidates for CAS/CEA based on CTA, but may not require it based on DSA. METHODS: Consecutive candidates for carotid interventions (CAS or CEA) following CTA were identified from prospectively maintained stroke center registries at two large academic centers. As part of our institutional practice all patients had a routine pre-procedural diagnostic DSA. In each patient, degree of carotid stenosis was compared between CTA and DSA. Patients with concordant degree of stenosis on DSA and CTA (true positive group) were compared to patients with a discordant degree of stenosis with less than 50% on DSA (false positive group). RESULTS: Out of 90 patients with significant stenosis on CTA, only 70 (78%) were found to have a significant stenosis on DSA. Severe plaque calcification was significantly more common in the false-positive group. In those patients whose CTA reported stenosis of ≥90%, we found a strong agreement between CTA and DSA (positive predictive value [PPV] - 0.9) for a significant stenosis (≥50%). Conversely, the correlation between CTA and DSA in patients with CTA reported 50-70% stenosis was poor (PPV - 0.29) (p < 0.001). CONCLUSIONS: Our results suggest that despite ongoing radiological progress, the specificity of CTA in accurately assessing carotid stenosis remains relatively low in patients with both moderate stenosis and heavily calcified plaques. Consequently, patients could possibly be referred for unnecessary CEA surgery and may become exposed to associated potential complications.


Asunto(s)
Angiografía de Substracción Digital/métodos , Estenosis Carotídea/diagnóstico por imagen , Angiografía por Tomografía Computarizada/métodos , Anciano , Reacciones Falso Positivas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas
18.
Am J Nurs ; 121(3): 13, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33624994
19.
Cochrane Database Syst Rev ; 2: CD009593, 2021 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-33616229

RESUMEN

BACKGROUND: Xpert MTB/RIF and Xpert MTB/RIF Ultra (Xpert Ultra) are World Health Organization (WHO)-recommended rapid tests that simultaneously detect tuberculosis and rifampicin resistance in people with signs and symptoms of tuberculosis. This review builds on our recent extensive Cochrane Review of Xpert MTB/RIF accuracy. OBJECTIVES: To compare the diagnostic accuracy of Xpert Ultra and Xpert MTB/RIF for the detection of pulmonary tuberculosis and detection of rifampicin resistance in adults with presumptive pulmonary tuberculosis. For pulmonary tuberculosis and rifampicin resistance, we also investigated potential sources of heterogeneity. We also summarized the frequency of Xpert Ultra trace-positive results, and estimated the accuracy of Xpert Ultra after repeat testing in those with trace-positive results. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, LILACS, Scopus, the WHO ICTRP, the ISRCTN registry, and ProQuest to 28 January 2020 with no language restriction. SELECTION CRITERIA: We included diagnostic accuracy studies using respiratory specimens in adults with presumptive pulmonary tuberculosis that directly compared the index tests. For pulmonary tuberculosis detection, the reference standards were culture and a composite reference standard. For rifampicin resistance, the reference standards were culture-based drug susceptibility testing and line probe assays. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data using a standardized form, including data by smear and HIV status. We assessed risk of bias using QUADAS-2 and QUADAS-C. We performed meta-analyses comparing pooled sensitivities and specificities, separately for pulmonary tuberculosis detection and rifampicin resistance detection, and separately by reference standard. Most analyses used a bivariate random-effects model. For tuberculosis detection, we estimated accuracy in studies in participants who were not selected based on prior microscopy testing or history of tuberculosis. We performed subgroup analyses by smear status, HIV status, and history of tuberculosis. We summarized Xpert Ultra trace results. MAIN RESULTS: We identified nine studies (3500 participants): seven had unselected participants (2834 participants). All compared Xpert Ultra and Xpert MTB/RIF for pulmonary tuberculosis detection; seven studies used a paired comparative accuracy design, and two studies used a randomized design. Five studies compared Xpert Ultra and Xpert MTB/RIF for rifampicin resistance detection; four studies used a paired design, and one study used a randomized design. Of the nine included studies, seven (78%) were mainly or exclusively in high tuberculosis burden countries. For pulmonary tuberculosis detection, most studies had low risk of bias in all domains. Pulmonary tuberculosis detection Xpert Ultra pooled sensitivity and specificity (95% credible interval) against culture were 90.9% (86.2 to 94.7) and 95.6% (93.0 to 97.4) (7 studies, 2834 participants; high-certainty evidence) versus Xpert MTB/RIF pooled sensitivity and specificity of 84.7% (78.6 to 89.9) and 98.4% (97.0 to 99.3) (7 studies, 2835 participants; high-certainty evidence). The difference in the accuracy of Xpert Ultra minus Xpert MTB/RIF was estimated at 6.3% (0.1 to 12.8) for sensitivity and -2.7% (-5.7 to -0.5) for specificity. If the point estimates for Xpert Ultra and Xpert MTB/RIF are applied to a hypothetical cohort of 1000 patients, where 10% of those presenting with symptoms have pulmonary tuberculosis, Xpert Ultra will miss 9 cases, and Xpert MTB/RIF will miss 15 cases. The number of people wrongly diagnosed with pulmonary tuberculosis would be 40 with Xpert Ultra and 14 with Xpert MTB/RIF. In smear-negative, culture-positive participants, pooled sensitivity was 77.5% (67.6 to 85.6) for Xpert Ultra versus 60.6% (48.4 to 71.7) for Xpert MTB/RIF; pooled specificity was 95.8% (92.9 to 97.7) for Xpert Ultra versus 98.8% (97.7 to 99.5) for Xpert MTB/RIF (6 studies). In people living with HIV, pooled sensitivity was 87.6% (75.4 to 94.1) for Xpert Ultra versus 74.9% (58.7 to 86.2) for Xpert MTB/RIF; pooled specificity was 92.8% (82.3 to 97.0) for Xpert Ultra versus 99.7% (98.6 to 100.0) for Xpert MTB/RIF (3 studies). In participants with a history of tuberculosis, pooled sensitivity was 84.2% (72.5 to 91.7) for Xpert Ultra versus 81.8% (68.7 to 90.0) for Xpert MTB/RIF; pooled specificity was 88.2% (70.5 to 96.6) for Xpert Ultra versus 97.4% (91.7 to 99.5) for Xpert MTB/RIF (4 studies). The proportion of Ultra trace-positive results ranged from 3.0% to 30.4%. Data were insufficient to estimate the accuracy of Xpert Ultra repeat testing in individuals with initial trace-positive results. Rifampicin resistance detection Pooled sensitivity and specificity were 94.9% (88.9 to 97.9) and 99.1% (97.7 to 99.8) (5 studies, 921 participants; high-certainty evidence) for Xpert Ultra versus 95.3% (90.0 to 98.1) and 98.8% (97.2 to 99.6) (5 studies, 930 participants; high-certainty evidence) for Xpert MTB/RIF. The difference in the accuracy of Xpert Ultra minus Xpert MTB/RIF was estimated at -0.3% (-6.9 to 5.7) for sensitivity and 0.3% (-1.2 to 2.0) for specificity. If the point estimates for Xpert Ultra and Xpert MTB/RIF are applied to a hypothetical cohort of 1000 patients, where 10% of those presenting with symptoms have rifampicin resistance, Xpert Ultra will miss 5 cases, and Xpert MTB/RIF will miss 5 cases. The number of people wrongly diagnosed with rifampicin resistance would be 8 with Xpert Ultra and 11 with Xpert MTB/RIF. We identified a higher number of rifampicin resistance indeterminate results with Xpert Ultra, pooled proportion 7.6% (2.4 to 21.0) compared to Xpert MTB/RIF pooled proportion 0.8% (0.2 to 2.4). The estimated difference in the pooled proportion of indeterminate rifampicin resistance results for Xpert Ultra versus Xpert MTB/RIF was 6.7% (1.4 to 20.1). AUTHORS' CONCLUSIONS: Xpert Ultra has higher sensitivity and lower specificity than Xpert MTB/RIF for pulmonary tuberculosis, especially in smear-negative participants and people living with HIV. Xpert Ultra specificity was lower than that of Xpert MTB/RIF in participants with a history of tuberculosis. The sensitivity and specificity trade-off would be expected to vary by setting. For detection of rifampicin resistance, Xpert Ultra and Xpert MTB/RIF had similar sensitivity and specificity. Ultra trace-positive results were common. Xpert Ultra and Xpert MTB/RIF provide accurate results and can allow rapid initiation of treatment for rifampicin-resistant and multidrug-resistant tuberculosis.


Asunto(s)
Antibióticos Antituberculosos , Farmacorresistencia Bacteriana , Mycobacterium tuberculosis , Rifampin , Tuberculosis Pulmonar , Antibióticos Antituberculosos/farmacología , Errores Diagnósticos , Tuberculosis Extensivamente Resistente a Drogas/diagnóstico , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Reacciones Falso Negativas , Reacciones Falso Positivas , Humanos , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/efectos de los fármacos , Rifampin/farmacología , Sensibilidad y Especificidad , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/tratamiento farmacológico
20.
BMJ ; 372: n214, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-33589468

RESUMEN

OBJECTIVE: To determine whether the sensitivity and specificity of SNP chips are adequate for detecting rare pathogenic variants in a clinically unselected population. DESIGN: Retrospective, population based diagnostic evaluation. PARTICIPANTS: 49 908 people recruited to the UK Biobank with SNP chip and next generation sequencing data, and an additional 21 people who purchased consumer genetic tests and shared their data online via the Personal Genome Project. MAIN OUTCOME MEASURES: Genotyping (that is, identification of the correct DNA base at a specific genomic location) using SNP chips versus sequencing, with results split by frequency of that genotype in the population. Rare pathogenic variants in the BRCA1 and BRCA2 genes were selected as an exemplar for detailed analysis of clinically actionable variants in the UK Biobank, and BRCA related cancers (breast, ovarian, prostate, and pancreatic) were assessed in participants through use of cancer registry data. RESULTS: Overall, genotyping using SNP chips performed well compared with sequencing; sensitivity, specificity, positive predictive value, and negative predictive value were all above 99% for 108 574 common variants directly genotyped on the SNP chips and sequenced in the UK Biobank. However, the likelihood of a true positive result decreased dramatically with decreasing variant frequency; for variants that are very rare in the population, with a frequency below 0.001% in UK Biobank, the positive predictive value was very low and only 16% of 4757 heterozygous genotypes from the SNP chips were confirmed with sequencing data. Results were similar for SNP chip data from the Personal Genome Project, and 20/21 individuals analysed had at least one false positive rare pathogenic variant that had been incorrectly genotyped. For pathogenic variants in the BRCA1 and BRCA2 genes, which are individually very rare, the overall performance metrics for the SNP chips versus sequencing in the UK Biobank were: sensitivity 34.6%, specificity 98.3%, positive predictive value 4.2%, and negative predictive value 99.9%. Rates of BRCA related cancers in UK Biobank participants with a positive SNP chip result were similar to those for age matched controls (odds ratio 1.31, 95% confidence interval 0.99 to 1.71) because the vast majority of variants were false positives, whereas sequence positive participants had a significantly increased risk (odds ratio 4.05, 2.72 to 6.03). CONCLUSIONS: SNP chips are extremely unreliable for genotyping very rare pathogenic variants and should not be used to guide health decisions without validation.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Secuenciación de Nucleótidos de Alto Rendimiento , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias Ováricas/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Neoplasias de la Próstata/diagnóstico , Adulto , Anciano , Neoplasias de la Mama/genética , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Genes BRCA1 , Genes BRCA2 , Pruebas Genéticas/métodos , Técnicas de Genotipaje , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Ováricas/genética , Neoplasias Pancreáticas/genética , Polimorfismo de Nucleótido Simple , Valor Predictivo de las Pruebas , Neoplasias de la Próstata/genética , Sistema de Registros , Estudios Retrospectivos , Análisis de Secuencia de ADN
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