Corpus overview


MeSH Disease

Human Phenotype


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    Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score

    Authors: Stephen R Knight; Antonia Ho; Riinu Pius; Iain Buchan; Gail Carson; Thomas M Drake; Jake Dunning; Cameron J Fairfield; Carrol Gamble; Christopher A Green; Rishi K Gupta; Sophie Halpin; Hayley Hardwick; Karl Holden; Peter W Horby; Clare Jackson; Kenneth A McLean; Laura Merson; Jonathan S Nguyen-Van-Tam; Lisa Norman; Mahdad Noursadeghi; Piero L Olliaro; Mark G Pritchard; Clark D Russell; Catherine A Shaw; Aziz Sheikh; Tom Solomon; Cathie Sudlow; Olivia V Swann; Lance Turtle; Peter JM Openshaw; J Kenneth Baillie; Malcolm Gracie Semple; Annemarie B Docherty; Ewen M Harrison

    doi:10.1101/2020.07.30.20165464 Date: 2020-08-02 Source: medRxiv

    Objectives To develop and validate a pragmatic risk score to predict mortality for patients admitted to hospital with covid-19. Design Prospective observational cohort study: ISARIC WHO CCP-UK study (ISARIC Coronavirus Clinical Characterisation Consortium [4C]). Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited between 21 May and 29 June 2020. Setting 260 hospitals across England, Scotland, and Wales. Participants Adult TRANS patients ([≥]18 years) admitted to hospital with covid-19 admitted at least four weeks before final data extraction. Main outcome measures In-hospital mortality. Results There were 34 692 patients included in the derivation dataset (mortality rate 31.7%) and 22 454 in the validation dataset (mortality 31.5%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age TRANS, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea, and C-reactive protein (score range 0-21 points). The 4C risk stratification score demonstrated high discrimination for mortality (derivation cohort: AUROC 0.79; 95% CI 0.78 - 0.79; validation cohort 0.78, 0.77-0.79) with excellent calibration (slope = 1.0). Patients with a score [≥]15 (n = 2310, 17.4%) had a 67% mortality (i.e., positive predictive value SERO 67%) compared with 1.0% mortality for those with a score [≤]3 (n = 918, 7%; negative predictive value SERO 99%). Discriminatory performance SERO was higher than 15 pre-existing risk stratification scores (AUROC range 0.60-0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63-0.73). Conclusions We have developed and validated an easy-to-use risk stratification score based on commonly available parameters at hospital presentation. This outperformed existing scores, demonstrated utility to directly inform clinical decision making, and can be used to stratify inpatients with covid-19 into different management groups. The 4C Mortality Score may help clinicians identify patients with covid-19 at high risk of dying during current and subsequent waves of the pandemic. Study registration ISRCTN66726260

    Performance SERO of Abbott Architect, Ortho Vitros, and Euroimmun Assays in Detecting Prior SARS-CoV-2 Infection MESHD

    Authors: Shiwani Mahajan; Carrie A Redlich; Adam V Wisnewski; Louis E Fazen; Lokinendi V Rao; Karthik Kuppusamy; Albert I Ko; Harlan M Krumholz

    doi:10.1101/2020.07.29.20164343 Date: 2020-07-30 Source: medRxiv

    Background: Several serological assays SERO have been developed to detect anti-SARS-CoV-2 IgG antibodies SERO, but evidence about their comparative performance SERO is limited. We sought to assess the sensitivity SERO of four anti-SARS-CoV-2 IgG enzyme-linked immunosorbent assays SERO ( ELISA SERO) in individuals with evidence of prior SARS-CoV-2 infection MESHD. Methods: We obtained sera from 36 individuals with PCR-confirmed SARS-CoV-2 infection MESHD between March and May 2020. We evaluated samples collected at around 21 days ({+/-}14 days) after their initial PCR test using 3 commercially available ELISA assays SERO, two anti-spike (Ortho-Clinical Diagnostics Vitros, and Euroimmun) and one anti-nucleocapsid (Abbott Architect), and a Yale-developed anti-spike ELISA SERO test. We determined the sensitivity SERO of the tests and compared their results. The Euroimmun and Yale ELISA SERO had an equivocal and indeterminate category, which were considered as both negative and positive. Results: Among the 36 individuals with SARS-CoV-2 infection MESHD, mean age TRANS was 43 ({+/-}13) years and 19 (53%) were female TRANS. The sensitivities SERO of the tests were not significantly different (Abbott Architect, Ortho Vitros, Euroimmmun, and Yale assays: 86% (95% confidence interval [CI], 71-95), 94% (95% CI, 81-99), 86% (95% CI, 71-95), and 94% (95% CI, 81-99), respectively; p-value=0.464). The sensitivities SERO of the Euroimmun and Yale ELISA SERO tests increased when the equivocal/indeterminate results were considered positive (97% [95% CI, 85-100] and 100% [95% CI, 90-100], respectively), but were not significantly different from other tests (p=0.082). The cross-correlation coefficient ranged from 0.85-0.98 between three anti-spike protein assays (Ortho Vitros, Euroimmun, Yale) and was 0.58-0.71 between the three anti-spike protein assays and the anti-nucleocapsid assay (Abbott). Conclusion: The sensitivities SERO of four anti-SARS-CoV-2 protein assays did not significantly differ, although the sample size was small. Sensitivity SERO also depended on the interpretation of equivocal and indeterminate results. The strongest correlations were present for the three anti-spike proteins assays. These findings suggest that individual test characteristics and the correlation between different tests should be considered when comparing or aggregating data across different populations studies for serologic surveillance of past SARS-CoV-2 infection MESHD.

    Incidence and outcomes of healthcare-associated COVID-19 infections MESHD: significance of delayed diagnosis and correlation with staff absence

    Authors: Kirstin Khonyongwa; Surabhi K Taori; Ana Soares; Nergish Desai; Malur Sudhanva; William Bernal; Silke Schelenz; Lisa A Curran

    doi:10.1101/2020.07.24.20148262 Date: 2020-07-30 Source: medRxiv

    Background: The sudden increase in COVID-19 admissions in hospitals during the SARS-CoV2 pandemic of 2020 has led to onward transmissions TRANS among vulnerable inpatients. Aims: This study was performed to evaluate the prevalence SERO and clinical outcomes of Healthcare-associated COVID-19 infections MESHD (HA-COVID-19) during the 2020 epidemic and study factors which may promote or correlate with its incidence and transmission TRANS in a London Teaching Hospital Trust. Methods: Electronic laboratory, patient and staff self-reported sickness records were interrogated for the period 1st March to 18th April 2020. HA-COVID-19 was defined as symptom onset TRANS >14d of admission. Test performance SERO of a single combined throat and nose swab (CTNS) for patient placement and the effect of delayed RNA positivity (DRP, defined as >48h delay) on patient outcomes was evaluated. The incidence of staff self-reported COVID-19 sickness absence, hospital bed occupancy, community incidence and DRP was compared HA-COVID-19. The incidence of other significant hospital-acquired bacterial infections MESHD (OHAI) was compared to previous years. Results: 58 HA-COVID-19 (7.1%) cases were identified. As compared to community-acquired cases, significant differences were observed in age TRANS (p=0.018), ethnicity (p<0.001) and comorbidity burden (p<0.001) but not in 30d mortality. CTNS negative predictive value SERO was 60.3%. DRP was associated with greater mortality (p=0.034) and 34.5% HA-COVID-19 cases could be traced TRANS to delayed diagnosis in CA-COVID-19. Incidence of HA-COVID-19 correlated positively with DRP (R=0.7108) and staff sickness absence (R=0.7815). OHAI rates were similar to previous 2 years. Conclusion: Early diagnosis and isolation of COVID-19 would help reduce transmission TRANS. A single CTNS has limited value in segregating patients into positive and negative pathways.

    Seroprevalence SERO of anti-SARS-CoV-2 IgG antibodies SERO in Kenyan blood SERO donors

    Authors: Sophie Uyoga; Ifedayo M.O. Adetifa; Henry K. Karanja; James Nyagwange; James Tuju; Perpetual Wanjiku; Rashid Aman; Mercy Mwangangi; Patrick Amoth; Kadondi Kasera; Wangari Ng'ang'a; Charles Rombo; Christine K. Yegon; Khamisi Kithi; Elizabeth Odhiambo; Thomas Rotich; Irene Orgut; Sammy Kihara; Mark Otiende; Christian Bottomley; Zonia N. Mupe; Eunice W. Kagucia; Katherine Gallagher; Anthony Etyang; Shirine Voller; John Gitonga; Daisy Mugo; Charles N. Agoti; Edward Otieno; Leonard Ndwiga; Teresa Lambe; Daniel Wright; Edwine Barasa; Benjamin Tsofa; Philip Bejon; Lynette I. Ochola-Oyier; Ambrose Agweyu; J. Anthony G. Scott; George M Warimwe

    doi:10.1101/2020.07.27.20162693 Date: 2020-07-29 Source: medRxiv

    Background There are no data on SARS-CoV-2 seroprevalence SERO in Africa though the COVID-19 epidemic curve and reported mortality differ from patterns seen elsewhere. We estimated the anti- SARS-CoV-2 antibody SERO prevalence SERO among blood SERO donors in Kenya. Methods We measured anti-SARS-CoV-2 spike IgG prevalence SERO by ELISA SERO on residual blood SERO donor samples obtained between April 30 and June 16, 2020. Assay sensitivity SERO and specificity were 83% (95% CI 59, 96%) and 99.0% (95% CI 98.1, 99.5%), respectively. National seroprevalence SERO was estimated using Bayesian multilevel regression and post-stratification to account for non-random sampling with respect to age TRANS, sex and region, adjusted for assay performance SERO. Results Complete data were available for 3098 of 3174 donors, aged TRANS 15-64 years. By comparison with the Kenyan population, the sample over-represented males TRANS (82% versus 49%), adults TRANS aged TRANS 25-34 years (40% versus 27%) and residents of coastal Counties (49% versus 9%). Crude overall seroprevalence SERO was 5.6% (174/3098). Population-weighted, test-adjusted national seroprevalence SERO was 5.2% (95% CI 3.7, 7.1%). Seroprevalence SERO was highest in the 3 largest urban Counties; Mombasa (9.3% [95% CI 6.4, 13.2%)], Nairobi (8.5% [95% CI 4.9, 13.5%]) and Kisumu (6.5% [95% CI 3.3, 11.2%]). Conclusions We estimate that 1 in 20 adults TRANS in Kenya had SARS-CoV-2 antibodies SERO during the study period. By the median date of our survey, only 2093 COVID-19 cases and 71 deaths MESHD had been reported through the national screening system. This contrasts, by several orders of magnitude, with the numbers of cases and deaths MESHD reported in parts of Europe and America when seroprevalence SERO was similar.

    Diagnostic Accuracy of Computed Tomography for Identifying Hospitalization in Patients with Suspected COVID-19

    Authors: Sergey P. Morozov; Roman V. Reshetnikov; Victor A. Gombolevskiy; Natalia V. Ledikhova; Ivan A. Blokhin; Vladislav G. Kljashtorny; Olesya A. Mokienko; Anton V. Vladzymyrskyy

    id:2007.15476v2 Date: 2020-07-29 Source: arXiv

    The controversy of computed tomography (CT) use in COVID-19 screening is associated with ambiguous characteristics of chest CT as a diagnostic test. The reported values of CT sensitivity SERO and specificity calculated using RT-PCR as a reference standard vary widely. The objective of this study was to reevaluate the diagnostic and prognostic value of CT using an alternative approach. This study included 973 symptomatic COVID-19 patients aged TRANS 42 $\pm$ 17 years, 56% females TRANS. We reviewed the disease MESHD dynamics between the initial and follow-up CT studies using a "CT0-4" grading system. Sensitivity SERO and specificity were calculated as conditional probabilities that a patient's condition would improve or deteriorate relative to the initial CT study results. For the calculation of negative (NPV) and positive (PPV) predictive values, we estimated the COVID-19 prevalence SERO in Moscow. We used several ARIMA and EST models with different parameters to fit the data on total cases of COVID-19 from March 6, 2020, to July 20, 2020, and forecast the incidence. The "CT0-4" grading scale demonstrated low sensitivity SERO (28%) but high specificity (95%). The best statistical model for describing the pandemic in Moscow was ETS with multiplicative trend, error, and season type. According to our calculations, with the predicted prevalence SERO of 2.1%, the values of NPV and PPV would be 98% and 10%, correspondingly. We associate the low sensitivity SERO and PPV values with the small sample size of the patients with severe symptoms and non-optimal methodological setup for measuring these specific characteristics. The "CT0-4" grading scale was highly specific and predictive for identifying admissions to hospitals of COVID-19 patients. Despite the ambiguous accuracy, chest CT proved to be an effective practical tool for patient management during the pandemic, provided that the necessary infrastructure and human resources are available.

    Impact of SARS-CoV-2 pandemic among health care workers in a secondary teaching hospital in Spain.

    Authors: Javier Garralda Fernandez; Ignacio Molero Vilches; Alfredo Bermejo Rodriguez; Isabel Cano de Torres; Elda I Colino Romay; Isabel Garcia-Arata; Jeronimo Jaqueti Aroca; Rosa Lillo; Daniel Lopez Lacomba; Luis Mazon Cuadrado; Laura M Molina Esteban; Luis J Morales Garcia; Laura Moratilla Monzo; Elva Nieto-Borrajo; Maria Pacheco Delgado; Santiago Prieto Menchero; Cristina Sanchez Hernandez; Eva Sanchez Testillano; Jesus Garcia-Martinez

    doi:10.1101/2020.07.26.20162529 Date: 2020-07-29 Source: medRxiv

    Background. The COVID-19 pandemic has posed a huge challenge to healthcare systems and their personnel worldwide. The study of the impact of SARS-CoV-2 infection MESHD among healthcare workers, through prevalence SERO studies, will let us know viral expansion, individuals at most risk and the most exposed areas. The aim of this study is to gauge the impact of SARS-CoV-2 pandemic in our hospital workforce and identify groups and areas at increased risk. Methods and Findings. This is a cross-sectional and longitudinal study carried out on healthcare workers based on molecular and serological diagnosis of SARS-CoV-2 infection MESHD. Of the 3013 HCW invited to participate, finally 2439 (80.9%) were recruited, including 674 (22.4%) who had previously consulted at the OHS for confirmed exposure and/or presenting symptoms suggestive of COVID-19. A total of 411 (16.9%) and 264 (10.8%) healthcare workers were SARS-CoV-2 IgG and rRT-PCR positive, respectively. The cumulative prevalence SERO considering all studies (IgG positive HCW and/or rRT-PCR positive detection) has been 485 (19.9%). SARS-CoV-2 IgG-positive patients in whom the virus was not detected were 221 (9.1%); up to 151 of them (68.3%) did not report any compatible symptoms nor consult at the OHS for this reason. Men became more infected than women (25% vs 18.5%, p=0.0009), including when data were also classified by age TRANS. COVID-19 cumulative prevalence SERO among the HCW assigned to medical departments was higher (25.2%) than others, as well as among medical staff (25.4%) compared with other professional categories (p<0.01). Conclusions. Global impact of the COVID-19 pandemic on HCW of our centre has been 19.9%. Doctors and medical services personnel have had the highest prevalence SERO of SARS-CoV-2 infection MESHD, but many of them have not presented compatible symptoms. This emphasizes the performance SERO of continuous surveillance methods of the most exposed health personnel and not only based on the appearance of symptoms.

    How much reserve capacity is justifiable for hospital pandemic preparedness? A cost-effectiveness analysis for COVID-19 in Germany

    Authors: Afschin Gandjour

    doi:10.1101/2020.07.27.20162743 Date: 2020-07-29 Source: medRxiv

    Introduction: In preparation for a possible second COVID-19 pandemic wave, expanding intensive care unit (ICU) bed capacity is an important consideration. The purpose of this study was to determine the costs and benefits of this strategy in Germany. Methods: This study compared the provision of additional capacity to no intervention from a societal perspective. A decision model was developed using, e.g., information on age TRANS-specific fatality rates, ICU costs and outcomes, and the herd protection threshold. The net monetary benefit (NMB) was calculated based upon the willingness to pay for new medicines for the treatment of cancer, a condition with a similar disease MESHD burden in the near term. Results: The marginal cost-effectiveness ratio (MCER) of supplying one additional ICU bed is 24,815 euros per life year gained and increases with the number of additional beds. The NMB remains positive for utilization rates as low as 1.5% and, assuming full capacity utilization, for multiples of the currently available bed capacity. Expanding the ICU bed capacity by 10,000 beds is projected to result in societal costs of 41 billion euros and to reduce mortality of ICU candidates by 20% compared with no intervention (assuming full capacity utilization). In a sensitivity SERO analysis, the variables with the highest impact on the MCER were the mortality rates in the ICU and after discharge. Conclusions: In Germany, the provision of additional ICU bed capacity appears to be cost-effective over a large increase in the number of beds. Nevertheless, bed utilization is constrained by labor supply and possibly other input factors.

    Predicting Critical State after COVID-19 Diagnosis Using Real-World Data from 20152 Confirmed US Cases TRANS

    Authors: Mike Domenik Rinderknecht; Yannick Klopfenstein

    doi:10.1101/2020.07.24.20155192 Date: 2020-07-27 Source: medRxiv

    The global COVID-19 pandemic caused by the virus SARS-CoV-2 has led to over 10 million confirmed cases TRANS, half a million deaths MESHD, and is challenging healthcare systems worldwide. With limited medical resources, early identification of patients with a high risk of progression to severe disease MESHD or a critical state is crucial. We present a prognostic model predicting critical state within 28 days following COVID-19 diagnosis trained on data from US electronic health records (EHR) within IBM Explorys, including demographics, comorbidities, symptoms, laboratory test results, insurance types, and hospitalization. Our entire cohort included 20152 COVID-19 cases, of which 3160 patients went into critical state or died. Random, stratified train-test splits were repeated 100 times to obtain a distribution of performance SERO. The median and interquartile range of the areas under the receiver operating characteristic curve (ROC AUC) and the precision recall SERO curve (PR AUC) were 0.863 [0.857, 0.866] and 0.539 [0.526, 0.550], respectively. Optimizing the decision threshold lead to a sensitivity SERO of 0.796 [0.775, 0.821] and a specificity of 0.784 [0.769, 0.805]. Good model calibration was achieved, showing only minor tendency to over-forecast probabilities above 0.6. The validity of the model was demonstrated by the interpretability analysis confirming existing evidence on major risk factors (e.g., higher age TRANS and weight, male TRANS gender TRANS, diabetes, cardiovascular disease MESHD disease, and chronic kidney HP kidney disease MESHD). The analysis also revealed higher risk for African Americans and "self-pay patients". To the best of our knowledge, this is the largest dataset based on EHR used to create a prognosis model for COVID-19. In contrast to large-scale statistics computing odds ratios for individual risk factors, the present model combining a rich set of covariates can provide accurate personalized predictions enabling early treatment to prevent patients from progressing to a severe or critical state.

    Systematic evaluation and external validation of 22 prognostic models among hospitalised adults TRANS with COVID-19: An observational cohort study

    Authors: Rishi K Gupta; Michael Marks; Thomas H. A. Samuels; Akish Luintel; Tommy Rampling; Humayra Chowdhury; Matteo Quartagno; Arjun Nair; Marc Lipman; Ibrahim Abubakar; Maarten van Smeden; Wai Keong Wong; Bryan Williams; Mahdad Noursadeghi

    doi:10.1101/2020.07.24.20149815 Date: 2020-07-26 Source: medRxiv

    Background The number of proposed prognostic models for COVID-19, which aim to predict disease MESHD outcomes, is growing rapidly. It is not known whether any are suitable for widespread clinical implementation. We addressed this question by independent and systematic evaluation of their performance SERO among hospitalised COVID-19 cases. Methods We conducted an observational cohort study to assess candidate prognostic models, identified through a living systematic review. We included consecutive adults TRANS admitted to a secondary care hospital with PCR-confirmed or clinically diagnosed community-acquired COVID-19 (1st February to 30th April 2020). We reconstructed candidate models as per their original descriptions and evaluated performance SERO for their original intended outcomes ( clinical deterioration MESHD or mortality) and time horizons. We assessed discrimination using the area under the receiver operating characteristic curve (AUROC), and calibration using calibration plots, slopes and calibration-in-the-large. We calculated net benefit compared to the default strategies of treating all and no patients, and against the most discriminating predictor in univariable analyses, based on a limited subset of a priori candidates. Results We tested 22 candidate prognostic models among a cohort of 411 participants, of whom 180 (43.8%) and 115 (28.0%) met the endpoints of clinical deterioration MESHD and mortality, respectively. The highest AUROCs were achieved by the NEWS2 score for prediction of deterioration over 24 hours (0.78; 95% CI 0.73-0.83), and a novel model for prediction of deterioration <14 days from admission (0.78; 0.74-0.82). Calibration appeared generally poor for models that used probability outcomes. In univariable analyses, admission oxygen saturation on room air was the strongest predictor of in-hospital deterioration (AUROC 0.76; 0.71-0.81), while age TRANS was the strongest predictor of in-hospital mortality (AUROC 0.76; 0.71-0.81). No prognostic model demonstrated consistently higher net benefit than using the most discriminating univariable predictors to stratify treatment, across a range of threshold probabilities. Conclusions Oxygen saturation on room air and patient age TRANS are strong predictors of deterioration and mortality among hospitalised adults TRANS with COVID-19, respectively. None of the prognostic models evaluated offer incremental value for patient stratification to these univariable predictors.

    Point-of-care ultrasound for COVID-19 pneumonia MESHD pneumonia HP patients in the ICU

    Authors: zouheir bitar; Mohammed Shamsah; Omar Bamasood; Ossama Maadrani; Huda Al foudri

    doi:10.21203/ Date: 2020-07-26 Source: ResearchSquare

    BackgroundPoint-of-care ultrasound (POCUS) has a major role in the management of patients with acute hypoxic respiratory and circulatory failure and guides hemodynamic management. There is scarce literature on POCUS assessment characteristics in COVID-19 pneumonia MESHD pneumonia HP with hypoxic respiratory failure HP.MethodsThe study is an observational, prospective, single‐center study conducted in the intensive care unit of Adan General Hospital from May 1st, 2020, to June 25, 2020. The study included adults TRANS suspected to have COVID-19 transferred to the intensive care unit (ICU) with fever MESHD fever HP or suspected respiratory infection MESHD. Patients were transferred to the ICU directly from the ED or general medical wards after reverse transcriptase-polymerase chain reaction (RT-PCR) testing. A certified intensivist in critical care ultrasound who was blinded to the RT-PCR results, if available at the time of examination, performed the lung ultrasound and echocardiology within 12 hours of the patient’s admission to the ICU. We calculated the E/e’, E/A ratio, left ventricular ejection fraction EF, IVC diameter, RV size and systolic function. We performed ultrasound in 12 chest areas.ResultsOf 92 patients with suspected COVID-19 pneumonia MESHD pneumonia HP, 77 (84%) cases were confirmed TRANS. The median age TRANS of the patients was 53 (82-36) years, and 71 (77%) were men.In the group of patients with confirmed COVID-19 pneumonia MESHD pneumonia HP, echocardiographic findings showed normal E/e’, deceleration time (DT), and transmittal E/A ratio in comparison to the non-COVID19 patients (P .001 for both). The IVC diameter was <2 cm with > 50% collapsibility in 62 (81%) patients with COVID-19 pneumonia MESHD pneumonia HP; a diameter of > 2 cm and < 50% collapsibility in all patients, with a P value of 0.001, was detected among those with non-COVID-19 pneumonia MESHD pneumonia HP. There were 3 cases of myocarditis MESHD myocarditis HP with poor EF (5.5%), severe RV dysfunction was seen in 9 cases (11.6%), and 3 cases showed RV thrombus.Chest US revealed four signs suggestive of COVID-19 pneumonia MESHD pneumonia HP in 77 patients (98.6%) ( sensitivity SERO 96.9%, CI 85%‐99.5%) when compared with RT-PCR results.ConclusionPOCUS plays an important role in bedside diagnosis, hemodynamic assessment and management of patients with acute hypoxic respiratory and circulatory failure in patients with COVID-19 pneumonia MESHD pneumonia HP.

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MeSH Disease
Human Phenotype

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