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1. Performance of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) biomarkers in predicting CT scan results and neurological outcomes in children with traumatic brain injury (BRAINI-2 paediatric study): protocol of a European prospective multicentre study

Author

Vincent Sapin, Javier de la Cruz, Alfonso Lagares, Odile Mejan, Vladislav Pavlov, François Dubos, Christèle Gras-Le-Guen, Anne Chauvire-Drouard, Fleur Lorton, María Antonia Poca, Thibault de Groc, Belén Rivero, Rocío Rodrigo, Peter Biberthaler, Noelia Montoya, Paula Duch, Aasma Sahuquillo, Pauline Scherdel, Markus Lehner, Lydie Abaléa, Aymeric Cantais, Véronique Chasle, Marie-Amélie Chêne, Béatrice De Pracontal, Alban Laspougeas, Ophélia Le Gentil, Hélène Liénard, Juliette Massot, Cédric Ménager, Sidney Passat, Nadia Savy, Gaelle Tourniaire, Serafín Alonso, Eva Andreu, Montserrat Feliu, Sandra Galve, Francisca Munar, Cristina Muro, Elena Vilardell, Iván Valverde, Sonia Cañadas, Sebastià González, Esther Lera, Olalla Rodríguez, Mónica Sancosmed, Núria Wörner, Pablo Martín Munarriz, Javier Saceda, and Hannah Luz

Subjects
Medicine
Abstract

Introduction In light of the burden of traumatic brain injury (TBI) in children and the excessive number of unnecessary CT scans still being performed, new strategies are needed to limit their use while minimising the risk of delayed diagnosis of intracranial lesions (ICLs). Identifying children at higher risk of poor outcomes would enable them to be better monitored. The use of the blood-based brain biomarkers glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) could help clinicians in this decision. The overall aim of this study is to provide new knowledge regarding GFAP and UCH-L1 in order to improve TBI management in the paediatric population.Methods and analysis We will conduct a European, prospective, multicentre study, the BRAINI-2 paediatric study, in 20 centres in France, Spain and Switzerland with an inclusion period of 30 months for a total of 2880 children and adolescents included. To assess the performance of GFAP and UCH-L1 used separately and in combination to predict ICLs on CT scans (primary objective), 630 children less than 18 years of age with mild TBI, defined by a Glasgow Coma Scale score of 13–15 and with a CT scan will be recruited. To evaluate the potential of GFAP and UCH-L1 in predicting the prognosis after TBI (secondary objective), a further 1720 children with mild TBI but no CT scan as well as 130 children with moderate or severe TBI will be recruited. Finally, to establish age-specific reference values for GFAP and UCH-L1 (secondary objective), we will include 400 children and adolescents with no history of TBI.Ethics and dissemination This study has received ethics approval in all participating countries. Results from our study will be disseminated in international peer-reviewed journals. All procedures were developed in order to assure data protection and confidentiality.Trial registration number NCT05413499.

Published
2024
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2. DeepBreath—automated detection of respiratory pathology from lung auscultation in 572 pediatric outpatients across 5 countries

Author

Julien Heitmann, Alban Glangetas, Jonathan Doenz, Juliane Dervaux, Deeksha M. Shama, Daniel Hinjos Garcia, Mohamed Rida Benissa, Aymeric Cantais, Alexandre Perez, Daniel Müller, Tatjana Chavdarova, Isabelle Ruchonnet-Metrailler, Johan N. Siebert, Laurence Lacroix, Martin Jaggi, Alain Gervaix, Mary-Anne Hartley, and with the Pneumoscope Study Group

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract The interpretation of lung auscultation is highly subjective and relies on non-specific nomenclature. Computer-aided analysis has the potential to better standardize and automate evaluation. We used 35.9 hours of auscultation audio from 572 pediatric outpatients to develop DeepBreath : a deep learning model identifying the audible signatures of acute respiratory illness in children. It comprises a convolutional neural network followed by a logistic regression classifier, aggregating estimates on recordings from eight thoracic sites into a single prediction at the patient-level. Patients were either healthy controls (29%) or had one of three acute respiratory illnesses (71%) including pneumonia, wheezing disorders (bronchitis/asthma), and bronchiolitis). To ensure objective estimates on model generalisability, DeepBreath is trained on patients from two countries (Switzerland, Brazil), and results are reported on an internal 5-fold cross-validation as well as externally validated (extval) on three other countries (Senegal, Cameroon, Morocco). DeepBreath differentiated healthy and pathological breathing with an Area Under the Receiver-Operator Characteristic (AUROC) of 0.93 (standard deviation [SD] ± 0.01 on internal validation). Similarly promising results were obtained for pneumonia (AUROC 0.75 ± 0.10), wheezing disorders (AUROC 0.91 ± 0.03), and bronchiolitis (AUROC 0.94 ± 0.02). Extval AUROCs were 0.89, 0.74, 0.74 and 0.87 respectively. All either matched or were significant improvements on a clinical baseline model using age and respiratory rate. Temporal attention showed clear alignment between model prediction and independently annotated respiratory cycles, providing evidence that DeepBreath extracts physiologically meaningful representations. DeepBreath provides a framework for interpretable deep learning to identify the objective audio signatures of respiratory pathology.

Published
2023
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3. Deep learning diagnostic and risk-stratification pattern detection for COVID-19 in digital lung auscultations: clinical protocol for a case–control and prospective cohort study

Author

Alban Glangetas, Mary-Anne Hartley, Aymeric Cantais, Delphine S. Courvoisier, David Rivollet, Deeksha M. Shama, Alexandre Perez, Hervé Spechbach, Véronique Trombert, Stéphane Bourquin, Martin Jaggi, Constance Barazzone-Argiroffo, Alain Gervaix, and Johan N. Siebert

Subjects
COVID-19, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Deep learning, Artificial intelligence, Respiratory sounds, Auscultation, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Lung auscultation is fundamental to the clinical diagnosis of respiratory disease. However, auscultation is a subjective practice and interpretations vary widely between users. The digitization of auscultation acquisition and interpretation is a particularly promising strategy for diagnosing and monitoring infectious diseases such as Coronavirus-19 disease (COVID-19) where automated analyses could help decentralise care and better inform decision-making in telemedicine. This protocol describes the standardised collection of lung auscultations in COVID-19 triage sites and a deep learning approach to diagnostic and prognostic modelling for future incorporation into an intelligent autonomous stethoscope benchmarked against human expert interpretation. Methods A total of 1000 consecutive, patients aged ≥ 16 years and meeting COVID-19 testing criteria will be recruited at screening sites and amongst inpatients of the internal medicine department at the Geneva University Hospitals, starting from October 2020. COVID-19 is diagnosed by RT-PCR on a nasopharyngeal swab and COVID-positive patients are followed up until outcome (i.e., discharge, hospitalisation, intubation and/or death). At inclusion, demographic and clinical data are collected, such as age, sex, medical history, and signs and symptoms of the current episode. Additionally, lung auscultation will be recorded with a digital stethoscope at 6 thoracic sites in each patient. A deep learning algorithm (DeepBreath) using a Convolutional Neural Network (CNN) and Support Vector Machine classifier will be trained on these audio recordings to derive an automated prediction of diagnostic (COVID positive vs negative) and risk stratification categories (mild to severe). The performance of this model will be compared to a human prediction baseline on a random subset of lung sounds, where blinded physicians are asked to classify the audios into the same categories. Discussion This approach has broad potential to standardise the evaluation of lung auscultation in COVID-19 at various levels of healthcare, especially in the context of decentralised triage and monitoring. Trial registration: PB_2016-00500, SwissEthics. Registered on 6 April 2020.

Published
2021
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4. Evaluating the Increased Burden of Cardiorespiratory Illness Visits to Adult Emergency Departments During Flu and Bronchiolitis Outbreaks in the Pediatric Population: Retrospective Multicentric Time Series Analysis

Author

Benoit Morel, Guillaume Bouleux, Alain Viallon, Maxime Maignan, Luc Provoost, Jean-Christophe Bernadac, Sarah Devidal, Sylvie Pillet, Aymeric Cantais, and Olivier Mory

Subjects
Public aspects of medicine, RA1-1270
Abstract

BackgroundCardiorespiratory decompensation (CRD) visits have a profound effect on adult emergency departments (EDs). Respiratory pathogens like respiratory syncytial virus (RSV) and influenza virus are common reasons for increased activity in pediatric EDs and are associated with CRD in the adult population. Given the seasonal aspects of such challenging pathology, it would be advantageous to predict their variations. ObjectiveThe goal of this study was to evaluate the increased burden of CRD in adult EDs during flu and bronchiolitis outbreaks in the pediatric population. MethodsAn ecological study was conducted, based on admissions to the adult ED of the Centre Hospitalier Universitaire (CHU) of Grenoble and Saint Etienne from June 29, 2015 to March 22, 2020. The outbreak periods for bronchiolitis and flu in the pediatric population were defined with a decision-making support tool, PREDAFLU, used in the pediatric ED. A Kruskal-Wallis variance analysis and a Spearman monotone dependency were performed in order to study the relationship between the number of adult ED admissions for the International Classification of Diseases (ICD)-10 codes related to cardiorespiratory diagnoses and the presence of an epidemic outbreak as defined with PREDAFLU. ResultsThe increase in visits to the adult ED for CRD and the bronchiolitis and flu outbreaks had a similar distribution pattern (CHU Saint Etienne: χ23=102.7, P

Published
2022
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5. Strategy using a new antigenic test for rapid diagnosis of Streptococcus pneumoniae infection in respiratory samples from children consulting at hospital

Author

Cyrille H. Haddar, Johan Joly, Anne Carricajo, Paul O. Verhoeven, Florence Grattard, Olivier Mory, Evelyne Begaud, Yves Germani, Aymeric Cantais, and Bruno Pozzetto

Subjects
Streptococcus pneumoniae, Respiratory infection, Rapid diagnostic test, PCR assay, Pneumonia, Child, Microbiology, QR1-502
Abstract

Abstract Background Despite vaccination programs, Streptococcus pneumoniae remains among the main microorganisms involved in bacterial pneumonia, notably in terms of severity. The prognosis of pneumococcal infections is conditioned in part by the precocity of the diagnosis. The aim of this study was to evaluate the impact of a Rapid Diagnostic Test (RDT) targeting cell wall polysaccharide of Streptococcus pneumoniae and performed directly in respiratory samples, on the strategy of diagnosis of respiratory pneumococcal infections in children. Results Upper-respiratory tract samples from 196 children consulting at hospital for respiratory infection were tested for detecting S. pneumoniae using a newly-designed RDT (PneumoResp, Biospeedia), a semi-quantitative culture and two PCR assays. If positive on fluidized undiluted specimen, the RDT was repeated on 1:100-diluted sample. The RDT was found highly specific when tested on non-S. pneumoniae strains. By comparison to culture and PCR assays, the RDT on undiluted secretions exhibited a sensitivity (Se) and negative predictive value (NPV) of more than 98%. By comparison to criteria of S. pneumoniae pneumonia combining typical symptoms, X-ray image, and culture ≥107 CFU/ml, the Se and NPV of RDT on diluted specimens were 100% in both cases. Conclusions In case of negative result, the excellent NPV of RDT on undiluted secretions allows excluding S. pneumoniae pneumonia. In case of positive result, the excellent sensitivity of RDT on diluted secretions for the diagnosis of S. pneumoniae pneumonia allows proposing a suitable antimicrobial treatment at day 0.

Published
2020
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6. Impact of Dextran-Sodium-Sulfate-Induced Enteritis on Murine Cytomegalovirus Reactivation

Author

Alexandre Jentzer, Sébastien Fauteux-Daniel, Paul Verhoeven, Aymeric Cantais, Melyssa Yaugel Novoa, Fabienne Jospin, Blandine Chanut, Nicolas Rochereau, Thomas Bourlet, Xavier Roblin, Bruno Pozzetto, and Sylvie Pillet

Subjects
murine cytomegalovirus, mouse model, viral reactivation, DSS-induced enteritis, Microbiology, QR1-502
Abstract

(1) Background: Ulcerative colitis (UC) is an inflammatory bowel disease that causes inflammation of the intestines, which participates in human cytomegalovirus (HCMV) reactivation from its latent reservoir. CMV-associated colitis plays a pejorative role in the clinical course of UC. We took advantage of a model of chemically induced enteritis to study the viral reactivation of murine CMV (MCMV) in the context of gut inflammation. (2) Methods: Seven-week-old BALB/c mice were infected by 3 × 103 plaque-forming units (PFU) of MCMV; 2.5% (w/v) DSS was administered in the drinking water from day (D) 30 to D37 post-infection to induce enteritis. (3) Results: MCMV DNA levels in the circulation decreased from D21 after infection until resolution of the acute infection. DSS administration resulted in weight loss, high disease activity index, elevated Nancy index shortening of the colon length and increase in fecal lipocalin. However, chemically induced enteritis had no impact on MCMV reactivation as determined by qPCR and immunohistochemistry of intestinal tissues. (4) Conclusions: Despite the persistence of MCMV in the digestive tissues after the acute phase of infection, the gut inflammation induced by DSS did not induce MCMV reactivation in intestinal tissues, thus failing to recapitulate inflammation-driven HCMV reactivation in human UC.

Published
2022
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7. Humoral immunity to SARS-CoV-2 and seasonal coronaviruses in children and adults in north-eastern France

Author

Tom Woudenberg, Stéphane Pelleau, François Anna, Mikael Attia, Françoise Donnadieu, Alain Gravet, Caroline Lohmann, Hélène Seraphin, Raphaël Guiheneuf, Catherine Delamare, Karl Stefic, Julien Marlet, Etienne Brochot, Sandrine Castelain, Olivier Augereau, Jean Sibilia, François Dubos, Damia Meddour, Christèle Gras-Le Guen, Marianne Coste-Burel, Berthe-Marie Imbert-Marcille, Anne Chauvire-Drouard, Cyril Schweitzer, Amélie Gatin, Sandra Lomazzi, Aline Joulié, Hervé HAAS, Aymeric Cantais, Frederique Bertholon, Marie-France Chinazzo-Vigouroux, Mohamed SI Abdallah, Laurence Arowas, Pierre Charneau, Bruno Hoen, Caroline Demeret, Sylvie Van Der Werf, Arnaud Fontanet, and Michael White

Subjects
SARS-CoV-2, COVID-19, seroprevalence, sero-epidemiology, seasonal coronaviruses, antibody response, Medicine, Medicine (General), R5-920
Abstract

Background: Children are underrepresented in the COVID-19 pandemic and often experience milder disease than adolescents and adults. Reduced severity is possibly due to recent and more frequent seasonal human coronaviruses (HCoV) infections. We assessed the seroprevalence of SARS-CoV-2 and seasonal HCoV specific antibodies in a large cohort in north-eastern France. Methods: In this cross-sectional seroprevalence study, serum samples were collected from children and adults requiring hospital admission for non-COVID-19 between February and August 2020. Antibody responses to SARS-CoV-2 and seasonal HCoV (229E, HKU1, NL63, OC43) were assessed using a bead-based multiplex assay, Luciferase-Linked ImmunoSorbent Assay, and a pseudotype neutralisation assay. Findings: In 2,408 individuals, seroprevalence of SARS-CoV-2-specific antibodies was 7-8% with three different immunoassays. Antibody levels to seasonal HCoV increased substantially up to the age of 10. Antibody responses in SARS-CoV-2 seropositive individuals were lowest in adults 18-30 years. In SARS-CoV-2 seronegative individuals, we observed cross-reactivity between antibodies to the four HCoV and SARS-CoV-2 Spike. In contrast to other antibodies to SARS-CoV-2, specific antibodies to sub-unit 2 of Spike (S2) in seronegative samples were highest in children. Upon infection with SARS-CoV-2, antibody levels to Spike of betacoronavirus OC43 increased across the whole age spectrum. No SARS-CoV-2 seropositive individuals with low levels of antibodies to seasonal HCoV were observed. Interpretation: Our findings underline significant cross-reactivity between antibodies to SARS-CoV-2 and seasonal HCoV, but provide no significant evidence for cross-protective immunity to SARS-CoV-2 infection due to a recent seasonal HCoV infection. In particular, across all age groups we did not observe SARS-CoV-2 infected individuals with low levels of antibodies to seasonal HCoV. Funding: This work was supported by the « URGENCE COVID-19 » fundraising campaign of Institut Pasteur, by the French Government's Investissement d'Avenir program, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (Grant No. ANR-10-LABX-62-IBEID), and by the REACTing (Research & Action Emerging Infectious Diseases), and by the RECOVER project funded by the European Union's Horizon 2020 research and innovation programme under grant agreement No. 101003589, and by a grant from LabEx IBEID (ANR-10-LABX-62-IBEID).

Published
2021
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8. Longitudinal Study of Viral and Bacterial Contamination of Hospital Pediatricians’ Mobile Phones

Author

Aymeric Cantais, Florence Grattard, Julie Gagnaire, Olivier Mory, Aurélie Plat, Manon Lleres-Vadeboin, Philippe Berthelot, Thomas Bourlet, Elisabeth Botelho-Nevers, Bruno Pozzetto, and Sylvie Pillet

Subjects
cell phones, infection control, cross infection, infectious disease outbreak, Biology (General), QH301-705.5
Abstract

Mobile phones (MPs) of healthcare workers (HCWs) may represent an important source of transmission of infectious agents. This longitudinal study documents the contamination of these tools. Ten MPs handled by senior pediatricians were sampled once a week during 23 weeks in three pediatric wards of the University Hospital of Saint-Etienne, France. Cultures were performed for bacteria and multiplex PCR assays for a panel of respiratory and enteric viruses. A questionnaire on hygiene habits regarding phoning and care was filled-in by pediatricians before and after the study. From a total of 230 samples, 145 (63%) were contaminated by at least one pathogen. The MPs from emergency departments were the most impacted. Viruses were detected in 179 samples; bacteria were isolated in 59 samples. Contamination increased during the winter epidemic peak. A cross-contamination by Paracoccus yeei between hands and MPs of different HCWs was demonstrated. The communication of the study results influenced the hygiene behaviors. This study highlights the contamination of MPs by pathogens that are resistant in the environment, and its sustainability along the winter season. The role of MPs as vectors of nosocomial infection needs to be better investigated.

Published
2020
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9. A very low prevalence of SARS‐CoV‐2 infection but a high prevalence of other respiratory virus infections in children admitted to paediatric emergency departments

Author

Juliette Viart, Ilka Engelmann, Flora Joannes, Christèle Gras‐Le Guen, Hervé Haas, Marie Chinazzo, Aymeric Cantais, Amélie Gatin, Camille Brehin, Ilyes Benhalima, Mahdi Ouafi, Alain Martinot, and François Dubos

Subjects
Male, SARS-CoV-2, COVID-19, General Medicine, Cohort Studies, Child, Preschool, Viruses, Pediatrics, Perinatology and Child Health, Prevalence, Humans, Female, Prospective Studies, Child, Emergency Service, Hospital
Abstract

To investigate the prevalence of infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses among children admitted to paediatric emergency departments (PEDs).From April to July 2020, a prospective, multicentre cohort study was conducted in the PEDs of eight French university hospitals. Regardless of the reason for admission, a nasopharyngeal swab sample from each child was screened using reverse transcription polymerase chain reaction tests for SARS-CoV-2 and other respiratory viruses. We determined the prevalence of SARS-CoV-2 and other respiratory viruses and identified risk factors associated with a positive test.Of the 924 included children (median [interquartile range] age: 4 years [1-9]; boys: 55%), 908 (98.3%) were tested for SARS-CoV-2. Only three samples were positive (0.3%; 95% confidence interval: 0.1-1) and none of these children had symptoms of coronavirus disease 2019. Of the 836 samples (90%) tested for other viruses, 129 (15.4%) were positive (primarily rhinovirus). Respiratory viruses were significantly more common in young children and in children with respiratory tract symptoms and fever.The prevalence of SARS-CoV-2 among children admitted to emergency departments was low. In contrast, and despite social distancing and other protective measures, the prevalence of other respiratory viruses detection was high.

Published
2022

10. Hyper inflammatory syndrome following COVID-19 mRNA vaccine in children: A national post-authorization pharmacovigilance study

Author

Naïm Ouldali, Haleh Bagheri, Francesco Salvo, Denise Antona, Antoine Pariente, Claire Leblanc, Martine Tebacher, Joëlle Micallef, Corinne Levy, Robert Cohen, Etienne Javouhey, Brigitte Bader-Meunier, Caroline Ovaert, Sylvain Renolleau, Veronique Hentgen, Isabelle Kone-Paut, Nina Deschamps, Loïc De Pontual, Xavier Iriart, Christelle Gras-Le Guen, François Angoulvant, Alexandre Belot, Aurelie Donzeau, Layal El Aridi, Sophie Lety, Bertrand Leboucher, Agnes Baur, Lucas Jeusset, Maelle Selegny, Cristian Fedorczuk, Marion Lajus, Philippe Bensaid, Yacine Laoudi, Charlotte Pons, Anne-Cécile Robert, Camille Beaucourt, Muriel Richard, Etienne Goisque, Olivier Brissaud, Pierre Segretin, Julie Molimard, Marie-Clothilde Orecel, Gregoire Benoit, Lucille Bongiovanni, Margaux Guerder, Robin Pouyau, Jean-Marie De Guillebon De Resnes, Ellia Mezgueldi, Fleur Cour-Andlauer, Come Horvat, Pierre Poinsot, Cecile Frachette, Antoine Ouziel, Yves Gillet, Catherine Barrey, Jacques Brouard, Florence Villedieu, Vathanaksambath Ro, Narcisse Elanga, Vincent Gajdos, Romain Basmaci, Hadile Mutar, Sébastien Rouget, Elodie Nattes, Isabelle Hau, Sandra Biscardi, Houmam El Jurdi, Camille Jung, Denis Semama, Frederic Huet, Anne-Marie Zoccarato, Mayssa Sarakbi, Guillaume Mortamet, Cécile Bost-Bru, Joachim Bassil, Caroline Vinit, Véronique Hentgen, Pascal Leroux, Valérie Bertrand, Caroline Parrod, Irina Craiu, Philippe Durand, Pierre Tissiere, Caroline Claude, Guillaume Morelle, Tamazoust Guiddir, Charlotte Borocco, Frédérique Delion, Camille Guillot, Stéphane Leteurtre, François Dubos, Mylene Jouancastay, Alain Martinot, Valentine Voeusler, Jeanne Languepin, Nathalie Garrec, Arnaud Chalvon Demersay, Aurélie Morand, Emmanuelle Bosdure, Noémie Vanel, Fabrice Ughetto, Fabrice Michel, Marie Caujolle, Renaud Blonde, Jacqueline Nguyen, Olivier Vignaud, Caroline Masserot-Lureau, François Gouraud, Carine Araujo, Tara Ingrao, Sanaa Naji, Mohammed Sehaba, Christine Roche, Aurelia Carbasse, Christophe Milesi, Mustapha Mazeghrane, Sandrine Haupt, Cyril Schweitzer, Benedicte Romefort, Elise Launay, Christèle Gras-Le Guen, Ahmed Ali, Nathalie Blot, Antoine Tran, Anne Rancurel, Mickael Afanetti, Sophie Odorico, Deborah Talmud, Anais Chosidow, Anne-Sophie Romain, Emmanuel Grimprel, Marie Pouletty, Jean Gaschignard, Olivier Corseri, Albert Faye, Isabelle Melki, Camille Ducrocq, Cherine Benzoïd, Johanna Lokmer, Stéphane Dauger, Maryline Chomton, Anna Deho, Fleur Lebourgeois, Fabrice Lesage, Florence Moulin, Laurent Dupic, Yael Pinhas, Agathe Debray, Martin Chalumeau, Véronique Abadie, Pierre Frange, Jeremie F Cohen, Slimane Allali, William Curtis, Zahra Belhadjer, Johanne Auriau, Mathilde Méot, Lucile Houyel, Damien Bonnet, Christophe Delacourt, Brigitte Bader Meunier, Pierre Quartier, Youssef Shaim, Laurence Baril, Samuel Crommelynck, Baptiste Jacquot, Philippe Blanc, Natacha Maledon, Blandine Robert, Camille Loeile, Clémence Cazau, Gauthier Loron, Simona Gaga, Cécile Vittot, Loubna El Nabhani, François Buisson, Muriel Prudent, Hugues Flodrops, Fadhila Mokraoui, Simon Escoda, Laurent Bonnemains, Sarah-Louisa Mahi, Clara Mertes, Joelle Terzic, Julie Helms, Charlotte Idier, Soraya Chenichene, Nicoleta Magdolena Ursulescu, Gladys Beaujour, Abdelhak Hakim, Alice Miquel, Agnès Rey, Arnaud Wiedermann, Anne Charbonneau, Agnès Veauvy-Juven, Alexandrine Ferry, Alexis Mandelcwajg, Alix Rousseau, Amandine Prenant, Anne-Laure Bourneuf, Anne Filleron, Audrey Robine, Arthur Félix, Aude Parizel, Aurélie Labarre, Aymeric Cantais, Barbara Ros, Basile Coulon, Blandine Biot, Bérengère Dalichoux, Benjamin Fournier, Benoit Cagnard, Blandine Vanel, David Brossier, Bruno Ménager, Bruno Ozanne, Carole Marie-Jeanne, Camille Bergerot, Camille Chavy, Camille Guidon, Candice Fabre, Caroline Galeotti, Catherine Baker, Claire Ballot-Schmit, Céline Belleau, Céline Charasse, Caroline Favel, Chadia Toumi, Charlène Ferrandiz, Charlotte Couturier, Charlotte Pouchoux, Maryline Chomton-Cailliez, Charlotte Kevorkian-Verguet, Clément Brunet, Céline Manteau, Clémence Mougey, Coline Santy, Coralie Fitament, Charlotte Petriat, Charlotte Rebelle, Cyril Charron, Maxime Dartus, David Toulorge, Cécile Guillou-Debuisson, Dorann Bartebin, Valérie Klein, E Broustal, E Desselas, Elodie Marteau, Emmanuelle Bouvrot, Elise Delacroix, Edeline Coinde, Loubna Elnabhani, Elsa Amouyal, Emilie Chaillou, Emeline Gabilly-Bernard, Emilie Ruiz, Emilie Thibault, Emilie Robin, Etienne Darrieux, Eva Blondel, Floriane Socchi, François Cazassus, Fanny Bajolle, Fatma Lacin, Fouad Madhi, Franck Zekre, François Guerin, Gerald Boussicault, Henri Ginies, Gnansounou Magloire, Guilhem Arnold, Ines Coulognon, Iona Sicard-Cras, Jean-Emmanuel Kahn, Jeanne Bordet, Jeanne-Lise Fausser, Jean-François Baleine, Josephine Brice, Julie Gendras, Kaan Pekin, Karine Norbert, Clément Karsenty, Léa Savary, Laurence Martinat, Léa Lesniewski, Lorelei Charbonnier, Louise Alexandre, Lucas Percheron, Marie Vincenti, Manon Lanzini, Margot Grisval, Marianne Mercy, Marie-Emilie Lampin, Marie Desgranges, Marie Duperril, Marie-Clothilde Orcel, Marion Audier, Marion Favier, Mathieu Carpentier, Mathilde Balcean, Mathilde Bonnet, Maurine Jouret, Marie Delattre, Michael Levy, Michael Valensi, Mickael Shum, Morgane Dumortier, Morgane Gelin, Morgane Nemmouchi, Morgane Williaume, M Sebaha, Nicoleta Genetay-Stanescu, Nathan Giroux, Nicolas Crassard, Neil Derridj, Noemie Lachaume, Oscar Werner, Olivier Guilluy, Olivier Richer, Olivier Tirel, Aurianne Pauvert, Paul Casha, Noémie Perez, Pauline Gras, Pierre-Louis Leger, Marion Pinchou, Pierre Mornand, Prisca Largo, Ramona-Christina Ibanez, Charlotte Roulland, Salam Hadah Albarazi, Said Bichali, Sarah Faton, Amandine Schott, Sébastien Walser, Severine Guillaume, Solene Vincent, Sophie Galene-Gromez, Stanislas Kozisek, Thierry Maugard, Thierry Blanc, Thierry Navarro, Thomas Lauvray, Tamas Kovacs, Valérie Launay, Véronique Despert, Victoria Lhostis, Virginie Gall, Xavier Micaelli, Yasmine Benadjaoud, Zied Matoussi, Hélène Géniaux, Anthony Facile, Tessa Pietri, Pascale Palassin, Sylvine Pinel, Laurent Chouchana, Delphine Callot, Charlène Boulay, Hôpital Robert Debré, CHU Sainte Justine [Montréal], Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Santé publique France - French National Public Health Agency [Saint-Maurice, France], Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, CHU Marseille, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHI Créteil, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Référence pour les Maladies Rhumatologiques Auto-Immunes et Systémiques [CHU Necker] (RAISE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital de la Timone [CHU - APHM] (TIMONE), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Evaluation thérapeutique et pharmacologie périnatale et pédiatrique (EA_7323), Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier de Versailles André Mignot (CHV), Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] (CeRéMAIA - Hôpital André Mignot), Hôpital Bicêtre, Université Paris-Saclay, CH de Saint-Malo [Broussais], Hôpital Jean Verdier [AP-HP], Institut de rythmologie et modélisation cardiaque [Pessac] (IHU Liryc), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant / National Referee Centre for Rheumatic and AutoImmune and Systemic Diseases in Children [Lyon] (RAISE), European Society for Paediatric Infectious Diseases, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPC), CHU Toulouse [Toulouse], Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), Centre de Référence pour les Maladies Rhumatologiques Auto-Immunes et Systémiques [Paris] (Institut IMAGINE/RAISE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Imagine [Paris Necker] (2I), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE)

Subjects
Oncology, [SDV]Life Sciences [q-bio], Health Policy, Multisystem inflammatory syndrome in children, Internal Medicine, COVID-19 mRNA vaccine, BNT162b2, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, SARS-COV-2, Hyper-inflammatory syndrome, Child
Abstract

International audience; BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is the most severe clinical entity associated with pediatric SARS-CoV-2 infection with a putative role of the spike protein into the immune system activation. Whether COVID-19 mRNA vaccine can induce this complication in children is unknown. We aimed to assess the risk of hyper-inflammatory syndrome following COVID-19 mRNA vaccine in children. METHODS: We conducted a post-authorization national population-based surveillance using the French enhanced pharmacovigilance surveillance system for COVID-19 vaccines. All cases of suspected hyper-inflammatory syndrome following COVID-19 mRNA vaccine in 12-17-year-old children between June 15(th), 2021 and January 1(st), 2022, were reported. Cases were reviewed according to WHO criteria for MIS-C. The reporting rate of this syndrome was compared to the MIS-C rate per 1,000,000 12-17-year-old children infected by SARS-CoV-2. FINDINGS: Up to January 2022, 8,113,058 COVID-19 mRNA vaccine doses were administered to 4,079,234 12-17-year-old children. Among them, 12 presented a hyper-inflammatory syndrome with multisystemic involvement. Main clinical features included male predominance (10/12, 83%), cardiac involvement (10/12, 83%), digestive symptoms (10/12, 83%), coagulopathy (7/12, 58%), cytolytic hepatitis (6/12, 50%), and shock (5/12, 42%). 4/12 (33%) required intensive care unit transfer, and 3/12 (25%) hemodynamic support. All cases recovered. In eight cases, no evidence of previous SARS-CoV-2 infection was found. The reporting rate was 1.5 (95%CI [0.8; 2.6]) per 1,000,000 doses injected, i.e. 2.9 (95%CI [1.5; 5.1]) per 1,000,000 12-17-year-old vaccinated children. As a comparison, 113 MIS-C (95%CI [95; 135]) occurred per 1,000,000 12-17-year-old children infected by SARS-CoV-2. INTERPRETATION: Very few cases of hyper-inflammatory syndrome with multi-organ involvement occurred following COVID-19 mRNA vaccine in 12-17-year-old children. The low reporting rate of this syndrome, compared to the rate of post-SARS-CoV-2 MIS-C in the same age-group, largely supports the vaccination in a context of an important circulation of SARS-CoV-2. FUNDING: ESPID Fellowship Award; Grandir-Fonds de Solidarité Pour L'enfance.

Published
2022

11. Deep learning diagnostic and risk-stratification pattern detection for COVID-19 in digital lung auscultations: clinical protocol for a case–control and prospective cohort study

Author

David Rivollet, Constance Barazzone-Argiroffo, Delphine S. Courvoisier, Véronique Trombert, Aymeric Cantais, Alexandre Perez, Deeksha M. Shama, Martin Jaggi, Mary-Anne Hartley, Stéphane Bourquin, Alban Glangetas, Hervé Spechbach, Johan N. Siebert, and Alain Gervaix

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Telemedicine, Artificial intelligence, Adolescent, Stethoscope, Context (language use), Risk Assessment, law.invention, Study Protocol, Young Adult, 03 medical and health sciences, COVID-19 Testing, 0302 clinical medicine, Clinical Protocols, law, Respiratory sounds, Clinical Decision Rules, medicine, Humans, pneumonia, Medical history, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Aged, Aged, 80 and over, lcsh:RC705-779, medicine.diagnostic_test, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, Deep learning, Auscultation, lcsh:Diseases of the respiratory system, Middle Aged, Prognosis, Triage, 030228 respiratory system, Case-Control Studies, Emergency medicine, Female, business, Algorithms
Abstract

Background Lung auscultation is fundamental to the clinical diagnosis of respiratory disease. However, auscultation is a subjective practice and interpretations vary widely between users. The digitization of auscultation acquisition and interpretation is a particularly promising strategy for diagnosing and monitoring infectious diseases such as Coronavirus-19 disease (COVID-19) where automated analyses could help decentralise care and better inform decision-making in telemedicine. This protocol describes the standardised collection of lung auscultations in COVID-19 triage sites and a deep learning approach to diagnostic and prognostic modelling for future incorporation into an intelligent autonomous stethoscope benchmarked against human expert interpretation. Methods A total of 1000 consecutive, patients aged ≥ 16 years and meeting COVID-19 testing criteria will be recruited at screening sites and amongst inpatients of the internal medicine department at the Geneva University Hospitals, starting from October 2020. COVID-19 is diagnosed by RT-PCR on a nasopharyngeal swab and COVID-positive patients are followed up until outcome (i.e., discharge, hospitalisation, intubation and/or death). At inclusion, demographic and clinical data are collected, such as age, sex, medical history, and signs and symptoms of the current episode. Additionally, lung auscultation will be recorded with a digital stethoscope at 6 thoracic sites in each patient. A deep learning algorithm (DeepBreath) using a Convolutional Neural Network (CNN) and Support Vector Machine classifier will be trained on these audio recordings to derive an automated prediction of diagnostic (COVID positive vs negative) and risk stratification categories (mild to severe). The performance of this model will be compared to a human prediction baseline on a random subset of lung sounds, where blinded physicians are asked to classify the audios into the same categories. Discussion This approach has broad potential to standardise the evaluation of lung auscultation in COVID-19 at various levels of healthcare, especially in the context of decentralised triage and monitoring. Trial registration: PB_2016-00500, SwissEthics. Registered on 6 April 2020.

Published
2021

12. Strategy using a new antigenic test for rapid diagnosis of Streptococcus pneumoniae infection in respiratory samples from children consulting at hospital

Author

E. Begaud, Cyrille H. Haddar, Aymeric Cantais, Johan Md Joly, Yves Germani, Paul O. Verhoeven, O. Mory, Florence Grattard, Bruno Pozzetto, and Anne Carricajo

Subjects
Microbiology (medical), Male, Microbiological Techniques, Adolescent, PCR assay, lcsh:QR1-502, Rapid diagnostic test, Biology, medicine.disease_cause, Microbiology, Sensitivity and Specificity, Pneumococcal Infections, lcsh:Microbiology, 03 medical and health sciences, 0302 clinical medicine, Respiratory infection, Streptococcus pneumoniae, parasitic diseases, medicine, Humans, 030212 general & internal medicine, Child, Respiratory Tract Infections, 0303 health sciences, Antigens, Bacterial, 030306 microbiology, Polysaccharides, Bacterial, Bacterial pneumonia, Infant, Newborn, Infant, Pneumonia, medicine.disease, Prognosis, respiratory tract diseases, Vaccination, Pneumococcal infections, Early Diagnosis, Parasitology, Child, Preschool, Female, Research Article
Abstract

Background Despite vaccination programs, Streptococcus pneumoniae remains among the main microorganisms involved in bacterial pneumonia, notably in terms of severity. The prognosis of pneumococcal infections is conditioned in part by the precocity of the diagnosis. The aim of this study was to evaluate the impact of a Rapid Diagnostic Test (RDT) targeting cell wall polysaccharide of Streptococcus pneumoniae and performed directly in respiratory samples, on the strategy of diagnosis of respiratory pneumococcal infections in children. Results Upper-respiratory tract samples from 196 children consulting at hospital for respiratory infection were tested for detecting S. pneumoniae using a newly-designed RDT (PneumoResp, Biospeedia), a semi-quantitative culture and two PCR assays. If positive on fluidized undiluted specimen, the RDT was repeated on 1:100-diluted sample. The RDT was found highly specific when tested on non-S. pneumoniae strains. By comparison to culture and PCR assays, the RDT on undiluted secretions exhibited a sensitivity (Se) and negative predictive value (NPV) of more than 98%. By comparison to criteria of S. pneumoniae pneumonia combining typical symptoms, X-ray image, and culture ≥107 CFU/ml, the Se and NPV of RDT on diluted specimens were 100% in both cases. Conclusions In case of negative result, the excellent NPV of RDT on undiluted secretions allows excluding S. pneumoniae pneumonia. In case of positive result, the excellent sensitivity of RDT on diluted secretions for the diagnosis of S. pneumoniae pneumonia allows proposing a suitable antimicrobial treatment at day 0.

Published
2020

13. Correction to 'Hyper inflammatory syndrome following COVID-19 mRNA vaccine in children: A national post-authorization pharmacovigilance study'

Author

Naïm Ouldali, Haleh Bagheri, Francesco Salvo, Denise Antona, Antoine Pariente, Claire Leblanc, Martine Tebacher, Joëlle Micallef, Corinne Levy, Robert Cohen, Etienne Javouhey, Brigitte Bader-Meunier, Caroline Ovaert, Sylvain Renolleau, Veronique Hentgen, Isabelle Kone-Paut, Nina Deschamps, Loïc De Pontual, Xavier Iriart, Christelle Gras-Le Guen, Francois Angoulvant, Alexandre Belot, Aurelie Donzeau, Layal El Aridi, Sophie Lety, Bertrand Leboucher, Agnes Baur, Lucas Jeusset, Maelle Selegny, Cristian Fedorczuk, Marion Lajus, Philippe Bensaid, Yacine Laoudi, Charlotte Pons, Anne-Cécile Robert, Camille Beaucourt, Muriel Richard, Etienne Goisque, Olivier Brissaud, Pierre Segretin, Julie Molimard, Marie-Clothilde Orecel, Gregoire Benoit, Lucille Bongiovanni, Margaux Guerder, Robin Pouyau, Jean-Marie De Guillebon De Resnes, Ellia Mezgueldi, Fleur Cour-Andlauer, Come Horvat, Pierre Poinsot, Cecile Frachette, Antoine Ouziel, Yves Gillet, Catherine Barrey, Jacques Brouard, Florence Villedieu, Vathanaksambath Ro, Narcisse Elanga, Vincent Gajdos, Romain Basmaci, Hadile Mutar, Sébastien Rouget, Elodie Nattes, Isabelle Hau, Sandra Biscardi, Houmam El Jurdi, Camille Jung, Denis Semama, Frederic Huet, Anne-Marie Zoccarato, Mayssa Sarakbi, Guillaume Mortamet, Cécile Bost-Bru, Joachim Bassil, Caroline Vinit, Véronique Hentgen, Pascal Leroux, Valérie Bertrand, Caroline Parrod, Irina Craiu, Philippe Durand, Pierre Tissiere, Caroline Claude, Guillaume Morelle, Tamazoust Guiddir, Charlotte Borocco, Frédérique Delion, Camille Guillot, Stéphane Leteurtre, François Dubos, Mylene Jouancastay, Alain Martinot, Valentine Voeusler, Jeanne Languepin, Nathalie Garrec, Arnaud Chalvon Demersay, Aurélie Morand, Emmanuelle Bosdure, Noémie Vanel, Fabrice Ughetto, Fabrice Michel, Marie Caujolle, Renaud Blonde, Jacqueline Nguyen, Olivier Vignaud, Caroline Masserot-Lureau, François Gouraud, Carine Araujo, Tara Ingrao, Sanaa Naji, Mohammed Sehaba, Christine Roche, Aurelia Carbasse, Christophe Milesi, Mustapha Mazeghrane, Sandrine Haupt, Cyril Schweitzer, Benedicte Romefort, Elise Launay, Christèle Gras-Le Guen, Ahmed Ali, Nathalie Blot, Antoine Tran, Anne Rancurel, Mickael Afanetti, Sophie Odorico, Deborah Talmud, Anais Chosidow, Anne-Sophie Romain, Emmanuel Grimprel, Marie Pouletty, Jean Gaschignard, Olivier Corseri, Albert Faye, Isabelle Melki, Camille Ducrocq, Cherine Benzoïd, Johanna Lokmer, Stéphane Dauger, Maryline Chomton, Anna Deho, Fleur Lebourgeois, Fabrice Lesage, Florence Moulin, Laurent Dupic, Yael Pinhas, Agathe Debray, Martin Chalumeau, Véronique Abadie, Pierre Frange, Jeremie F Cohen, Slimane Allali, William Curtis, Zahra Belhadjer, Johanne Auriau, Mathilde Méot, Lucile Houyel, Damien Bonnet, Christophe Delacourt, Brigitte Bader Meunier, Pierre Quartier, Youssef Shaim, Laurence Baril, Samuel Crommelynck, Baptiste Jacquot, Philippe Blanc, Natacha Maledon, Blandine Robert, Camille Loeile, Clémence Cazau, Gauthier Loron, Simona Gaga, Cécile Vittot, Loubna El Nabhani, François Buisson, Muriel Prudent, Hugues Flodrops, Fadhila Mokraoui, Simon Escoda, Laurent Bonnemains, Sarah-Louisa Mahi, Clara Mertes, Joelle Terzic, Julie Helms, Charlotte Idier, Soraya Chenichene, Nicoleta Magdolena Ursulescu, Gladys Beaujour, Abdelhak Hakim, Alice Miquel, Agnès Rey, Arnaud Wiedermann, Anne Charbonneau, Agnès Veauvy-Juven, Alexandrine Ferry, Alexis Mandelcwajg, Alix Rousseau, Amandine Prenant, Anne-Laure Bourneuf, Anne Filleron, Audrey Robine, Arthur Félix, Aude Parizel, Aurélie Labarre, Aymeric Cantais, Barbara Ros, Basile Coulon, Blandine Biot, Bérengère Dalichoux, Benjamin Fournier, Benoit Cagnard, Blandine Vanel, David Brossier, Bruno Ménager, Bruno Ozanne, Carole Marie-Jeanne, Camille Bergerot, Camille Chavy, Camille Guidon, Candice Fabre, Caroline Galeotti, Catherine Baker, Claire Ballot-Schmit, Céline Belleau, Céline Charasse, Caroline Favel, Chadia Toumi, Charlène Ferrandiz, Charlotte Couturier, Charlotte Pouchoux, Maryline Chomton-Cailliez, Charlotte Kevorkian-Verguet, Clément Brunet, Céline Manteau, Clémence Mougey, Coline Santy, Coralie Fitament, Charlotte Petriat, Charlotte Rebelle, Cyril Charron, Maxime Dartus, David Toulorge, Cécile Guillou-Debuisson, Dorann Bartebin, Valérie Klein, E Broustal, E. Desselas, Elodie Marteau, Emmanuelle Bouvrot, Elise Delacroix, Edeline Coinde, Loubna Elnabhani, Elsa Amouyal, Emilie Chaillou, Emeline Gabilly-Bernard, Emilie Ruiz, Emilie Thibault, Emilie Robin, Etienne Darrieux, Eva Blondel, Floriane Socchi, François Cazassus, Fanny Bajolle, Fatma Lacin, Fouad Madhi, Franck Zekre, François Guerin, Gerald Boussicault, Henri Ginies, Gnansounou Magloire, Guilhem Arnold, Ines Coulognon, Iona Sicard-Cras, Jean-Emmanuel Kahn, Jeanne Bordet, Jeanne-Lise Fausser, Jean-François Baleine, Josephine Brice, Julie Gendras, Kaan Pekin, Karine Norbert, Clément Karsenty, Léa Savary, Laurence Martinat, Léa Lesniewski, Lorelei Charbonnier, Louise Alexandre, Lucas Percheron, Marie Vincenti, Manon Lanzini, Margot Grisval, Marianne Mercy, Marie-Emilie Lampin, Marie Desgranges, Marie Duperril, Marie-Clothilde Orcel, Marion Audier, Marion Favier, Mathieu Carpentier, Mathilde Balcean, Mathilde Bonnet, Maurine Jouret, Marie Delattre, Michael Levy, Michael Valensi, Mickael Shum, Morgane Dumortier, Morgane Gelin, Morgane Nemmouchi, Morgane Williaume, M. Sebaha, Nicoleta Genetay-Stanescu, Nathan Giroux, Nicolas Crassard, Neil Derridj, Noemie Lachaume, Oscar Werner, Olivier Guilluy, Olivier Richer, Olivier Tirel, Aurianne Pauvert, Paul Casha, Noémie Perez, Pauline Gras, Pierre-Louis Leger, Marion Pinchou, Pierre Mornand, Prisca Largo, Ramona-Christina Ibanez, Charlotte Roulland, Salam Hadah Albarazi, Said Bichali, Sarah Faton, Amandine Schott, Sébastien Walser, Severine Guillaume, Solene Vincent, Sophie Galene-Gromez, Stanislas Kozisek, Thierry Maugard, Thierry Blanc, Thierry Navarro, Thomas Lauvray, Tamas Kovacs, Valérie Launay, Véronique Despert, Victoria Lhostis, Virginie Gall, Xavier Micaelli, Yasmine Benadjaoud, Zied Matoussi, Hélène Géniaux, Anthony Facile, Tessa Pietri, Pascale Palassin, Sylvine Pinel, Laurent Chouchana, Delphine Callot, and Charlène Boulay

Subjects
Oncology, Health Policy, Internal Medicine
Published
2022

14. Prospective evaluation of the point-of-care use of a rapid antigenic SARS-CoV-2 immunochromatographic test in a paediatric emergency department

Author

Quentin Ollier, Sylvie Pillet, Olivier Mory, Julie Gagnaire, Charlotte Thuiller, Nadine Annino, Amandine Gagneux-Brunon, Elisabeth Botelho-Nevers, Thomas Bourlet, Bruno Pozzetto, and Aymeric Cantais

Subjects
Microbiology (medical), SARS-CoV-2, Point-of-Care Systems, COVID-19, General Medicine, Sensitivity and Specificity, POCT, Infectious Diseases, COVID-19 Testing, Sensitivity, Paediatric, Humans, Original Article, Diagnosis test, Child, Emergency Service, Hospital
Abstract

Objectives This study aimed to evaluate the immunochromatographic coronavirus disease 2019 (COVID-19) speed antigen test (BioSpeedia, France) as an antigen point-of-care test (AgPOCT) to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at the paediatric emergency department of the University Hospital of Saint-Etienne in France. Methods Between 15 January and 28 May, 2021, children presenting with respiratory symptoms compatible with COVID-19 infection (symptomatic group) or those requiring hospitalization for any reason (asymptomatic group) were included prospectively and received a nasopharyngeal aspiration to carry out both AgPOCT and quantitative reverse transcription (RT) PCR (RT-qPCR) tests, with the latter being used as the reference standard, for the diagnosis of SARS-CoV-2 infection. Results Among the 1009 enrolled children, we obtained a result from both techniques for 990: 33 (3.3%) tested positive with AgPOCT and 46 (4.6%) with RT-qPCR. The overall sensitivity and specificity of the AgPOCT were 69.6% (95% confidence interval (CI), 54.3–82.3) and 99.9% (95% CI, 99.4–100), respectively, compared with the RT-qPCR. Sensitivity increased to 82.9% (95% CI, 66.4–93.4) in symptomatic children. The mean cycle threshold value was significantly lower in positive samples for AgPOCT than in negative samples in the overall population and in both the symptomatic and asymptomatic groups. Discussion The use of the COVID-19 speed antigen test at the bedside in the emergency department has satisfactory performance for diagnosing SARS-CoV-2 infection in symptomatic children.

Published
2021

15. Impact of bedside diagnosis of influenza in the paediatric emergency ward

Author

A. Giraud, A. Plat, A. Bourmaud, O. Mory, Aymeric Cantais, M. Costille, Bruno Pozzetto, Sylvie Pillet, Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet [Saint-Étienne] (UJM), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon

Subjects
Male, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Adolescent, medicine.drug_class, Cost-Benefit Analysis, [SDV]Life Sciences [q-bio], 030106 microbiology, Antibiotics, Sensitivity and Specificity, Hospitals, University, 03 medical and health sciences, 0302 clinical medicine, Nasopharynx, Influenza, Human, medicine, Humans, Antimicrobial stewardship, Prospective Studies, 030212 general & internal medicine, Medical prescription, Child, Prospective cohort study, Immunoassay, medicine.diagnostic_test, Lumbar puncture, business.industry, Infant, Newborn, Becton dickinson, Infant, General Medicine, Antimicrobial, 3. Good health, Influenza B virus, Infectious Diseases, Influenza A virus, Point-of-Care Testing, Child, Preschool, Emergency medicine, Etiology, Female, Emergency Service, Hospital, business
Abstract

Objectives This prospective study performed in the paediatric emergency department of the University Hospital of Saint-Etienne aimed to measure the impact of the 24/7 bedside use of the Veritor™ System (Becton Dickinson) on the reduction of supplementary investigations, hospital stay and antimicrobial use. Methods Influenza virus A and B antigens were detected with a rapid influenza digital immunoassay (DIA) on nasopharyngeal aspirates (NPAs) sampled from the children consulting at the paediatric emergency department between January and March 2016 for influenza-like illness. The same NPA was tested by immunofluorescence and/or molecular routine assays. Before performing the DIA, the clinician filled in a questionnaire listing the tests that he/she would have prescribed in the absence of the rapid testing. The prescription of complementary investigations, antimicrobial treatments and hospital stay were also compared to those of the 3 previous years. Results A total of 514 children with flu-like symptoms were included. The use of the DIA at bedside decreased the prescription of blood puncture by 47.9% (21.2% to 6.6%), of chest X-rays by 69.0% (33.3% to 10.3%), of lumbar puncture by 77.8% (7.0% to 1.6%), of urine culture by 79.2% (23.3% to 4.9%), of antibiotic treatments by 70.1% (16.9% to 5.1%), and of hospital stay by 25.0% (27.2% to 20.4%), resulting in a reduction of medical costs estimated to more than €69 000 in a season. Conclusions In addition to delivering a rapid aetiological diagnosis, this strategy saves medical costs and favours an antimicrobial stewardship strategy. However, further prospective studies are needed to confirm our findings.

Published
2019

16. Low rate of oseltamivir prescription among adults and children with confirmed influenza illness in France during the 2018-19 influenza season

Author

Sylvie Pillet, Elisabeth Botelho-Nevers, Aymeric Cantais, Alexandra Cizeron, Florian Saunier, and Amandine Gagneux-Brunon

Subjects
0301 basic medicine, Microbiology (medical), Adult, Oseltamivir, medicine.medical_specialty, medicine.drug_class, 030106 microbiology, Neuraminidase, Influenza season, Severe influenza, Antiviral Agents, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pregnancy, Internal medicine, Influenza, Human, Medicine, Humans, Pharmacology (medical), Zanamivir, 030212 general & internal medicine, Prospective Studies, Risk factor, Medical prescription, Enzyme Inhibitors, Child, Pharmacology, Neuraminidase inhibitor, business.industry, medicine.disease, Infectious Diseases, Prescriptions, chemistry, Observational study, Female, France, Seasons, business
Abstract

Background Oseltamivir shows effectiveness in reducing influenza-related symptoms, morbidity and mortality. Its prescription remains suboptimal. Objectives We aim to describe oseltamivir prescription in confirmed cases of influenza and to identify associated factors. Methods A prospective monocentric observational study was conducted between 1 December 2018 and 30 April 2019. All patients with a virologically confirmed influenza diagnosis were included. Factors associated with oseltamivir prescription were studied. Results Influenza was confirmed in 755 patients (483 children and 272 adults), of which 188 (25.1%) were hospitalized and 86 (11.4%) had signs of severity. Oseltamivir was prescribed for 452 patients (59.9%), more frequently in children than in adults [329/483 (68.1%) versus 123/272 (45.2%), P Conclusions Oseltamivir should be administered as early as possible, preferably within 24–48 h after illness onset, for the best benefits. It is, however, very important to promote the use of neuraminidase inhibitor (‘NAI’) treatment beyond 48 h in some specific patient populations.

Published
2020

17. The Impact of a Tablet App on Adherence to American Heart Association Guidelines During Simulated Pediatric Cardiopulmonary Resuscitation: Randomized Controlled Trial (Preprint)

Author

Johan N Siebert, Laurence Lacroix, Aymeric Cantais, Sergio Manzano, and Frederic Ehrler

Abstract

BACKGROUND Evidence-based best practices are the cornerstone to guide optimal cardiopulmonary arrest resuscitation care. Adherence to the American Heart Association (AHA) guidelines for cardiopulmonary resuscitation (CPR) optimizes the management of critically ill patients and increases their chances of survival after cardiac arrest. Despite advances in resuscitation science and survival improvement over the last decades, only approximately 38% of children survive to hospital discharge after in-hospital cardiac arrest and only 6%-20% after out-of-hospital cardiac arrest. OBJECTIVE We investigated whether a mobile app developed as a guide to support and drive CPR providers in real time through interactive pediatric advanced life support (PALS) algorithms would increase adherence to AHA guidelines and reduce the time to initiation of critical life-saving maneuvers compared to the use of PALS pocket reference cards. METHODS This study was a randomized controlled trial conducted during a simulation-based pediatric cardiac arrest scenario caused by pulseless ventricular tachycardia (pVT). A total of 26 pediatric residents were randomized into two groups. The primary outcome was the elapsed time in seconds in each allocation group from the onset of pVT to the first defibrillation attempt. Secondary outcomes were time elapsed to (1) initiation of chest compression, (2) subsequent defibrillation attempts, and (3) administration of drugs, including the time intervals between defibrillation attempts and drug doses, shock doses, and the number of shocks. All outcomes were assessed for deviation from AHA guidelines. RESULTS Mean time to the first defibrillation attempt (121.4 sec, 95% CI 105.3-137.5) was significantly reduced among residents using the app compared to those using PALS pocket cards (211.5 sec, 95% CI 162.5-260.6, PP=.001) when using the app following all CPR sequences of action in a stepwise fashion until return of spontaneous circulation. The pVT rhythm was recognized correctly in 51 out of 52 (98%) opportunities among residents using the app compared to only 19 out of 52 (37%) among those using PALS cards (PP=.005) when using the app. CONCLUSIONS Use of the mobile app was associated with a shorter time to first and subsequent defibrillation attempts, fewer medication and defibrillation dose errors, and improved adherence to AHA recommendations compared with the use of PALS pocket cards. CLINICALTRIAL According to ICMJE recommendations, a trial registration number was not required as the purpose of the study was to examine the effect of the intervention on healthcare providers.

Published
2020

18. Analytical performances of the BD Veritor™ System for the detection of respiratory syncytial virus and influenzaviruses A and B when used at bedside in the pediatric emergency department

Author

Bruno Pozzetto, Aymeric Cantais, Aurélie Plat, O. Mory, Antoine Giraud, Sylvie Pillet, Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), and Université Jean Monnet [Saint-Étienne] (UJM)

Subjects
0301 basic medicine, Pediatric emergency, Influenzavirus A, Male, medicine.medical_specialty, Adolescent, Influenzavirus B, Concordance, Point-of-Care Systems, [SDV]Life Sciences [q-bio], 030106 microbiology, Respiratory Syncytial Virus Infections, Biology, Sensitivity and Specificity, Virus, Chromatography, Affinity, 03 medical and health sciences, Virology, Internal medicine, Nasopharynx, Influenza, Human, medicine, Humans, Respiratory system, Child, Infant, Newborn, Infant, Gold standard (test), University hospital, medicine.disease, 3. Good health, 030104 developmental biology, Bronchiolitis, Fluorescent Antibody Technique, Direct, Child, Preschool, Respiratory Syncytial Virus, Human, Female, Emergency Service, Hospital
Abstract

This study aims to evaluate the analytical performance of the BD Veritor™ rapid diagnostic assays (RDTs) for respiratory syncytial virus (RSV) and influenzaviruses when performed 24/7 at bedside by nurses in the pediatric emergency department (PED). The study was performed between 14/10/2015 and 19/03/2016 on nasopharyngeal aspirates (NPAs) collected from children consulting at the PED of the University Hospital of Saint-Etienne for bronchiolitis (RSV detection) or flu-like syndrome (influenzaviruses A/B detection). NPAs were tested 24/7 at the PED with the RDT and then sent to the Infectious Agents Department for routine analyses, first by immunofluorescence assay (IFA), then by nucleic acid amplification test (NAAT) considered as the gold standard in case of discrepancy between RDT and IFA results. For RSV detection, 205 NPAs was analyzed; the overall concordance between RDT and routine assays was of 97.6% (200/205). The sensitivity (Se), specificity (Sp), negative predictive value (NPV) and positive predictive value (PPV) were of 97.6% (160/164), 97.6% (40/41), 90.9% (40/44) and 99.4% (160/161), respectively. A total of 419 NPA was tested for influenzaviruses. For influenzavirus A, the overall concordance was of 98.8% (414/419); Se, Sp, NPV and PPV were of 100% (41/41), 98.7% (373/378), 100% (373/373) and 89.1% (41/46), respectively. For influenzavirus B, the overall concordance was of 97.9% (410/419); Se, Sp, NPV and PPV were of 96.6% (172/178), 98.8% (238/241), 97.5% (238/244) and 98.3% (172/175), respectively. Due to their excellent performances and their easy handle by non-laboratory personnel, these RDTs can be warmly recommended as point of care assays at the PED.

Published
2019

19. Longitudinal Study of Viral and Bacterial Contamination of Hospital Pediatricians’ Mobile Phones

Author

Elisabeth Botelho-Nevers, Sylvie Pillet, Julie Gagnaire, Philippe Berthelot, Florence Grattard, Bruno Pozzetto, Manon Lleres-Vadeboin, Aymeric Cantais, Aurélie Plat, Thomas Bourlet, and O. Mory

Subjects
0301 basic medicine, Microbiology (medical), Longitudinal study, media_common.quotation_subject, 030106 microbiology, cell phones, Microbiology, Article, 03 medical and health sciences, 0302 clinical medicine, Hygiene, Virology, Environmental health, Infection control, Medicine, 030212 general & internal medicine, lcsh:QH301-705.5, media_common, Transmission (medicine), business.industry, infectious disease outbreak, Contamination, cross infection, University hospital, infection control, lcsh:Biology (General), PARACOCCUS YEEI, Winter season, business
Abstract

Mobile phones (MPs) of healthcare workers (HCWs) may represent an important source of transmission of infectious agents. This longitudinal study documents the contamination of these tools. Ten MPs handled by senior pediatricians were sampled once a week during 23 weeks in three pediatric wards of the University Hospital of Saint-Etienne, France. Cultures were performed for bacteria and multiplex PCR assays for a panel of respiratory and enteric viruses. A questionnaire on hygiene habits regarding phoning and care was filled-in by pediatricians before and after the study. From a total of 230 samples, 145 (63%) were contaminated by at least one pathogen. The MPs from emergency departments were the most impacted. Viruses were detected in 179 samples, bacteria were isolated in 59 samples. Contamination increased during the winter epidemic peak. A cross-contamination by Paracoccus yeei between hands and MPs of different HCWs was demonstrated. The communication of the study results influenced the hygiene behaviors. This study highlights the contamination of MPs by pathogens that are resistant in the environment, and its sustainability along the winter season. The role of MPs as vectors of nosocomial infection needs to be better investigated.

Published
2020

20. Emergency Department Admissions Overflow Modeling by a Clustering of Time Evolving Clinical Diagnoses

Author

Aymeric Cantais, O. Mory, Gregory Soler, Eric Marcon, Guillaume Bouleux, Sylvie Pillet, Décision et Information pour les Systèmes de Production (DISP), Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet [Saint-Étienne] (UJM), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), and Bouleux, Guillaume

Subjects
[INFO.INFO-AI] Computer Science [cs]/Artificial Intelligence [cs.AI], Respiratory diseases, Disease cluster, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Overcrowding, 03 medical and health sciences, 0302 clinical medicine, Medicine, Average length of stay, 030212 general & internal medicine, Medical diagnosis, Cardiac disorders, Cluster analysis, Hierarchical Clustering, [SDV.IB] Life Sciences [q-bio]/Bioengineering, business.industry, 030208 emergency & critical care medicine, Emergency department, medicine.disease, Influenza, 3. Good health, Patient flow, Hierarchical clustering, Diagnoses clustering, Patients flow, K-Means, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Medical emergency, business
Abstract

Emergency Departments (ED) of hospitals are greatly impacted by winter epidemics of respiratory diseases. To detect the underlying overcrowding, it is essential to study patient flow. In this paper we propose to model the admission flow corresponding to clinical diagnoses encoded with ICD-10 which are more likely linked with respiratory diseases. To achieve this, clustering algorithms are applied on time evolving diagnoses in the adult ED of Saint-Etienne and benchmarked regarding a time series of laboratory-confirmed influenza data. For both K-Means and Hierarchical algorithms, the cluster containing the laboratory-confirmed series is composed of ICD-10 codes of diagnoses representing respiratory diseases and diseases linked with cardiac disorders, showing that these diseases present similar variations overtime. The information contained in such a cluster makes it possible to plot the average number of arrivals of these diagnoses overtime and the average length of stay of the patients in the ED who only have one or several of these diagnoses. Such an acknowlegdement about its patient flow will allow an ED staff to detect the underlying overcrowding.

Published
2018

21. Epidemiology and microbiological investigations of community-acquired pneumonia in children admitted at the emergency department of a university hospital

Author

Paul O. Verhoeven, O. Mory, Hugues Patural, Sylvie Pillet, Julie Bonneau, Aymeric Cantais, and Bruno Pozzetto

Subjects
Male, Mycoplasma pneumoniae, Pediatrics, medicine.medical_specialty, Epidemiology, Viral pneumonia, viruses, Pneumonia, Viral, medicine.disease_cause, Article, Hospitals, University, Human metapneumovirus, Community-acquired pneumonia, Virology, Pneumonia, Bacterial, medicine, Humans, Children, Retrospective Studies, biology, business.industry, Community-acquired-pneumonia, biology.organism_classification, medicine.disease, Community-Acquired Infections, Pneumonia, PCR, Infectious Diseases, Molecular Diagnostic Techniques, Child, Preschool, Coinfection, Enterovirus, Female, France, Rhinovirus, Emergency Service, Hospital, business, Multiplex Polymerase Chain Reaction
Abstract

Highlights • Systematic antimicrobials are recommended in community-acquired pneumonia of child. • A large panel of bacteria and viruses was detected in 85 children exhibiting CAP. • More than 60% of children with CAP exhibited an exclusive viral infection. • A co-infection with at least 2 viruses was observed in >40% of the children. • Data suggest that the use of antimicrobials in child's CAP should be revisited., Background The management of children with community-acquired pneumonia (CAP) is largely influenced by the development of new molecular diagnostic tests that allow the simultaneous detection of a wide range of pathogens. Objectives Evaluation of a diagnostic approach including multiplex PCR assays for revisiting the epidemiology and etiology of CAP in children at hospital. Study design Children of all ages consulting at the Emergency Department of the University hospital of Saint-Etienne, France, during the 2012–2013 winter period were included. In addition to bacterial cultures, the following pathogens were detected using biplex commercially-available rt-PCR tests: adenovirus, respiratory syncytial virus, human metapneumovirus, bocavirus, rhinovirus/enterovirus, coronavirus, influenza viruses A and B, parainfluenza viruses, Mycoplasma pneumoniae and Chlamydophila pneumonia. Results From 85 patients with CAP, at least one pathogen was identified in 81 cases (95.3%), including 4 bacterial exclusive infections (4.7%), 53 viral exclusive infections (62.4%) and 24 mixed infections (28.2%). Coinfection by at least two viruses was observed in 37 cases (43.5%). Mean age was higher in the case of documented bacterial infection (P

Published
2014

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