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1. Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial

Author: Anatole Harrois, Florence Patin, Anaïs Razurel, Laure Allanic, Grégoire Martin de Frémont, Vincent Jachiet, Gonçalo Boleto, Eric D'Ortenzio, Xavier Mariette, Philippe Dieudé, Etienne Canouï, Z Julia, Nathalie Dournon, Jean-Sébastien Hulot, David Lebeaux, Eric Mariotte, Dorothee Vallois, Laurence Berard, Nicolas Gambier, Christiane Verny, Mathilde Le Marchand, Mitja Jevnikar, Jean-Jacques Mourad, Marjolaine Morgand, Bertrand Guidet, Alexandre Moores, Prissile Bakouboula, Frédéric Pène, Pascal Richette, Martine Meunier, Juliette Camuset, Stéphane Jauréguiberry, Lynda Chalal, Mamadou Salif Cisse, Marie-Hélène Legros, Yann Nguyen, Damien Roux, Robin Deleris, Maxence Decavele, Patrice Cacoub, Isabelle Dusanter, Patricia Senet, Nassim Mahtal, Raphael Borie, Philippe Benoit, Blandine Denis, Luca Semerano, Sebastien Abad, Marie Dubert, Marie Lachatre, Marine Livrozet, Nathan Ebstein, Lakhdar Mameri, Adrien Michon, Olivier Sanchez, Aurélien Guffroy, Pierre Dupland, Jérôme Pacanowski, Yasmina Ferfar, Tassadit Hadjam, Anne-Marie Roques, Celine Comparon, Solaya Chalal, A Soria, Isabelle Lehir, Anne Gysembergh-Houal, Stéphanie Alary, Valérie Dejean, Elena Kiouris, Estelle Henry, Sophie Diemunsch, Jonathan London, Fanny Charbonnier, Alexandre Demoule, Louise Bondeelle, Samira Saleh-Mghir, Lise Bernard, Brigitte Sabatier, Anne Jacolot, Aurelie Sautereau, Pierre Faye, Benjamin Fournier, Noémie Abisror, Awa Ndiaye, Ruben Benainous, Damien Sène, Emmanuelle Sacco, Isabelle Debrix, Gabriel Nisand, Régis Peffault de Latour, Anne Sophie Korganow, Kévin Cardet, Perrine Guillaume-Jugnot, Soumeya Hammal, B. Duchemann, Elena Fois, Jean-Benoit Arlet, Christine Broissand, Yaël Amara, Matheus Vieira, Sophie Caillat-Zucman, Madona Sakkal, Juliette Djadi-Prat, Jean-Louis Teboul, Hélène François, Stéphane Renaud, Sylviane Ravato, Alaki Thiemele, Gabrielle Archer, Alain Fourreau, David Boutboul, Arsène Mekinian, Antoine Gros, Morgane Faure, Anne Pattyn, Camille Petit-Hoang, Jessica Krause le Garrec, Antony Canellas, Jean-Michel Molina, Zakaria Ait Hamou, Eric Oksenhendler, Ilias Koumis, Marie-Aude Penet, Catherine Boussard, Vincent Fallet, Guillaume Geri, Loic Kassegne, Bernard Cholley, Lucie Biard, Elodie Perrodeau, Tomas Urbina, David Schmitz, johann Cailhol, Elise Morawiec, Audrey Phibel, Sophie Renet, Emmanuel Weiss, Faouzi Saliba, Kristina Beziriganyan, Abdellatif Tazi, Isabelle Peigney, Bertrand Dunogue, Rémy Gauzit, Damien Bergerot, Bob Heger, Ines Ben-Mabrouk, Jade Ghosn, Benjamin Planquette, Alexis Régent, François Weill, Yasmina Mekid, Rosa Da Silva, Victor Lancon, Marc Michel, Nadia Anguel, Anne Claire Desbois, François Danion, Brigitte Ranque, Mohamed Belloul, Nadège Lemarié, Amélie Cransac, Marine Nadal, Lalia Djaghout, Anne Tréhan, Samy Figueiredo, Hakim Meddah, Aurélie Clan Hew Wai, Julie Delemazure, Soraya Fellahi, Jacques-Eric Gottenberg, Matthieu Uzzan, Jean-Charles Duclos-Vallée, Tabassome Simon, Vanessa Rathouin, Yves Hansmann, Hélène Gros, Syllia Belazouz, Nathalie Marin, Camille Rolland-Debord, Edouard Lefèvre, Sophie-Rym Hamada, Tristan Martin, Annabelle Stoclin, Frédéric Duée, Helene Chambrin-Lauvray, Ramdane Meftali, Miguel Alejandro Vasquez-Ibarra, Isabelle Madeleine, Simon Valayer, Anne Adda, Marie-Thérèse Tremorin, Nicolas Meyer, Vixra Keo, Lara Zafrani, Caroline Semaille, Maxime Dougados, Olivier Olivier, Emeline Colomba, Florence Morin, Claire Rouzaud, Paul Michel Mertes, Claire Montlahuc, Anne Blanchard, Valérie Pourchet-Martinez, Constance Delaugerre, Nicolas Carlier, Jacques Cadranel, Nicolas Noel, Kahina Cheref, Bao Phung, Moez Jallouli, Ulrich Clarac, Marthe Rigal, Mireille Adda, Lionel Galicier, Fanny Domont, Lee S. Nguyen, Férial Berbour, Fanny Pommeret, Celine Dupré, Gaël Leprun, Jean-Luc Diehl, Laetitia Languille, Philippe Blanche, Abolfazl Mohebbi, Mathilde Noaillon, Olivier Collange, Paul Jaubert, Anne Daguenel-Nguyen, Sandrine Briois, Anne-Lise Pouliquen, Coralie Bloch Queyrat, Clément Jourdaine, Cédric Pierron, Geoffrey Rossi, Chloe McAvoy, Claire Courtin, Mathias Cornic, C Rioux, Christine Lemagner, Martin Dres, Emmanuelle Guillot, Marc Garnier, Safaa Nemlaghi, Guillaume Grailles, Yazdan Yazdanpanah, Veronique Joly, Thiziri Sadaoui, Marion Bouhris, Vincent Castelain, Muriel Fartoukh, Sébastien Cavelot, Sophie Ohlmann-Caillard, Valentina Isernia, Bruno Crestani, Thinhinane Bariz, Benjamin Chaigne, Emmanuel Andrès, Frédéric Blanc, Alain Wynckel, Louise-Laure Mariani, Yasmine Messaoudi, Naima Sguiouar, Amina Kebir, Asmaa Mamoune, Caroline Gaudefroy, Victoire De Lastours, Pierre Diemunsch, Etienne Lengliné, Claire Tantet, Julien Mayaux, Benjamin G. Chousterman, Arthur Pavot, Anne Rachline, Gwenaël Lorillon, Hassan Joumaa, Nicolas Lefebvre, Elodie Baudry, Nicolas Bonnet, Fanny Defrancq, Véronique Vigna, Yves Cohen, Amira Benattia, Martin Siguier, Sophie Georgin-Lavialle, Emmanuelle Bugnet, Lamiae Grimaldi, Olivia Daconceicao, Olivier Hermine, Mathieu Vautier, Florence Tubach, Marion Licois, Anaïs Codorniu, Fanny Alby-Laurent, Jérémie Zerbit, Aude Jacob, Benedicte Giroux-Leprieur, Carine Karachi, Laurent Cylly, Edouard Flamarion, Gladys Aratus, Charléne Jouve, Robin Dhote, Claire Davoine, Valentin Greigert, Gaelle Leroux, Cécile Kedzia, Guillaume Lefèvre, Catherine Metzger, Olivier Benveniste, Clairelyne Dupin, Marie-Alexandra Alyanakian, Mathieu Oberlin, Julien Poissy, Linda Gimeno, Adrien Contejean, Segolene Toquet, Jeanne CHAUFFiER, Mathieu Jozwiak, Laurent Savale, Virginie Zarrouk, Cécile Yelnik, Mandy Nizard, Mourad Djadel, F-Xavier Lescure, Agnes Maurer, Geoffroy Liégeon, Arthur Neuschwander, Hélène Lafoeste, Gaëtan Deslée, Frédéric De Blay, Claire Pernin, Cloé Comarmond, Anne Hutt, Ridha Belilita, Laurence Lecomte, Sophie-Caroline Sacleux, Nathalie Rozensztajn, Jean-Jacques Tudesq, Benjamin Terrier, Solène Fabre, Lelia Escaut, Eva Chatron, Emmanuelle Blin, Pauline Jouany, Sara Sambin, Chistophe Willekens, Nabil Raked, Jean-Simon Rech, Serge Bureau, Boris Bienvenu, Elisabeth Coupez, Tali-Anne Szwebel, Lydia Suarez, Chaouki Bouras, Kamyl Baghli, Emilia Stan, Valérie Camara-Clayette, Fanette Denies, Nathalie Menage, Paul Legendre, Axelle Fuentes, Oriane Puéchal, Charlotte Kaeuffer, Guillaume Becker, Clara Campos-Vega, Armand Mekontso-Dessaps, Pernelle Vauboin, Yurdagul Uzunhan, F Louni, Marie hélène Pari, Myriam Virlouvet, Nicolas Belaube, Hugues Cordel, Nathalie Chavarot, Olivier Sitbon, Jean-Daniel Lelievre, Matthieu Mahévas, Julie Smati, Olivier Clovet, Marc Bardou, Ada Clarke, Gilles Garcia, Anouk Walter-Petrich, Hala Semri, Vasco Honsel, Giovanna Melica, Pierre Mora, Olivier Fain, A Gervais, Marc Humbert, Yves Allenbach, Céline Verstuyft Verstuyft, Blandine Lehmann, Pascal Martel, Aida Zahrate-Ghoul, Karine Martin, Alexandre Bourgoin, Baptiste Duceau, Philippe Ravaud, Celine Wilpotte, Sylvie Le Gac, Michaël Darmont, Aurélie Durel Maurisse, Younes Keroumi, Aude Rigolet, Julie Chas, Pierre-Louis Tharaux, Caroline Morbieu, Valérie Paquet, Eric Vicaut, Pascaline Choinier, Samir Hamiria, Elsa Feredj, Frédéric Schlemmer, Gilles Pialoux, Zeina Louis, Marion Parisey, David Montani, Jean-Pierre Riveline, Jean-Marie Michot, Pascal Lim, Eliane Bertrand, Gaelle Clavere, Julie Jambon, Stéphane Brin, Saskia Flamand, Jeanne Meunier, Geoffroy Volle, Martin De Sarcus, Marie Vayssettes, Thomas Papo, Caroline Hauw-Berlemont, Gabriel Baron, Jeremy Arzoine, Loren Soyez-Herkert, Maria Pereira, Antoine Parrot, Johanna Oziel, Carole Burger, Eric Noll, Paul Vermes, Jeanne Goupil de Bouille, Xavier Monnet, Paul Crespin, Sarah Dalibey, Thierno Dieye, Renaud Felten, Jean-Philippe Bastard, Younes El Amine, Timothee Bironne, Damien Vanhoye, Amine Ghembaza, Laure Berton, Yvon Ruch, Thomas Volpe, Thomas Gorget, Jaouad Benhida, Julien Saussereau, Elodie Issorat, Virginie Elisee, Adrien Mirouse, Cecile Larcheveque, Laurène Deconinck, A. Dossier, Félix Ackermann, Greggory Ducrocq, Anne Bergeron, Laurence Annonay, Camille Knosp, Laurence Drouard, Adrien Joseph, Hilario Nunes, Hanane Fodil, Sabrine Ouamri, Belkacem Asselate, Julie Fillon, Dominique Dautel, Isabelle Brindele, Robin Charreteur, S Lariven, Elie Azoulay, Sami Kolta, Cédric Sublon, Florence Bellenfant, Melissa Clément, Lola-Jade Palmieri, Bruno Mourvillier, Ewa Kozaliewicz, Vincent Provitolo, Marie Lecronier, Julien Chabert, Matthieu Resche-Rigon, Stéphan Pavy, Naura Gamany, Dorothée Chopin, Aïcha Bah, Moustafa Benafla, Corinne Guerin, Pierre Tissieres, Nathalie Costedoat-Chalumeau, Nessima Yelles, Emmanuel Chatelus, Jean-Christophe Corvol, Luc Mouthon, Marie Gilbert, Matthieu Lemoine, Lucie Aunay, Candice Estellat, Laure Choupeaux, Dhiaa Meriem Hai, Bernard Goichot, Céline Louapre, Roza Rahli, Nathalie De Castro, Christian Richard, Malikhone Chansombat, Kamil Chitour, Joseph Emmerich, Elodie Drouet, Julien Pottecher, Eric Demonsant, Alexandra Beurton, Raphaël Porcher, Lauren Demerville, Amélie Servettaz, Annabelle Pourbaix, Philippe Manivet, Pierre-Grégoire Guinot, Nicolas Champtiaux, Caroline Pradon, Annick Tibi, Julien Le Marec, Nawal Derridj, Mohamad Zaidan, Eric Marquis, Mickael Henriques, Bruno Mégarbane, Aline Frazier, Ramon Junquera, Diane Le Pluart, Coralie Gernez, Yacine Boudali, Dimitri Fremont, Pierrick Le Borgne, Corinne Pernot, Mélanie Dehais, Claire Madelaine, Dominique Roulot, Georgina Maalouf, Constance Guillaud, Corine Nyanou, Karine Celli Lebras, Sophie Granville, Sabrina Brahmi, Catherine Le Bourlout, Hassan Tarhini, Asmaa Mabrouki, Hakim Tayebi, Sophie Ismael, Jonathan Marey, Sophie Bayer, Gabriel Steg, Antoine Fayol, Catherine Fauvaux, Delphine Feyeux, Côme Bureau, Alexandre Morel, Agathe Bounhiol, Alexandre Buffet, Souad Benarab, Luc Haudebourg, Pierre Le Guen, Damien Vimpere, Xavier Jaïs, Clotilde Le Tiec Le Tiec, Sophie Bulifon, Pélagie Thibaut, Alison Klasen, Claire Pacheco, Anne Godier, Marie Antignac, Domitille Molinari, Philippe Durand, Olivier Lambotte, Paul Henri Grisot, Anne Lise Jegu, Vincent Poindron, Ruxandra Burlacu, Denis Jesuthasan, Sarah Benghanem, Solen Kernéis, Antoine Bachelard, Jacques Duranteau, Karine Lacombe, Olivia Lenoir, Mathilde Vallet, Sara Virolle, Léa Resmini, Liem Binh Luong Nguyen, Marie Matignon, Céline Leplay, and Claire Aguilar
Subjects: medicine.medical_specialty, business.industry, Immunology, Hazard ratio, Absolute risk reduction, Articles, medicine.disease, law.invention, Clinical trial, Pneumonia, Sarilumab, Rheumatology, Randomized controlled trial, law, Internal medicine, Cohort, medicine, Immunology and Allergy, Adverse effect, business
Abstract: Summary Background Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov , NCT04324073 . Findings 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival. Funding Assistance publique—Hopitaux de Paris
Published: 2022

2. Discontinuing β-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial

Author: Aurélien Dinh, Jacques Ropers, Clara Duran, Benjamin Davido, Laurène Deconinck, Morgan Matt, Olivia Senard, Aurore Lagrange, Sabrina Makhloufi, Guillaume Mellon, Victoire de Lastours, Frédérique Bouchand, Emmanuel Mathieu, Jean-Emmanuel Kahn, Elisabeth Rouveix, Julie Grenet, Jennifer Dumoulin, Thierry Chinet, Marion Pépin, Véronique Delcey, Sylvain Diamantis, Daniel Benhamou, Virginie Vitrat, Marie-Christine Dombret, Bertrand Renaud, Christian Perronne, Yann-Erick Claessens, José Labarère, Jean-Pierre Bedos, Philippe Aegerter, Anne-Claude Crémieux, Julie ATTAL-BEHAR, Sébastien BEAUNE, Thierry CHINET, Tristan CUDENNEC, Marine DE LAROCHE, Albane DE THEZY, Jennifer DUMOULIN, Caroline DUPONT, Elise FERCOT, Violaine GIRAUT, Ségolène GREFFE, Julie GRENET, Caroline GUYOT, Jean-Emmanuel KAHN, Sylvie LABRUNE, Marie LACHATRE, Sophie MOULIAS, Charlotte NALINE, Marion PEPIN, Elisabeth ROUVEIX, Marine SAHUT-D'IZARN, Abel SEFSSAFI, Laurent TEILLET, Jean-Pierre BRU, Jacques GAILLAT, Vincent GAUTIER, Cécile JANSSEN, Leonardo PAGANI, Virginie VITRAT, Malika ABDERRAHMANE, Juliette CAMUSET, Catherine LEGALL, Pascale LONGUET-FLANDRES, Anne-Marie MENN, Victoire DE LASTOURS, Marie LECRONIER, Gwenolée PREVOST, Charles BURDET, Ouda DERRADJI, Lelia ESCAUT, Etienne HINGLAIS, Philippe LEBRAS, Edouard LEFEVRE, Mathilde NOAILLON, Pauline RABIER, Maurice RAPHAEL, Elina TEICHER, Christiane VERNY, Daniel VITTECOQ, Benjamin WYPLOSZ, Michèle BEN HAYOUN, Françoise BRUN-VEZINET, Enrique CASALINO, Christophe CHOQUET, Marie-Christine DOMBRET, Xavier DUVAL, Nadhira HOUHOU, Véronique JOLY, Xavier LESCURE, Manuela POGLIAGHI, Christophe RIOUX, Yazdan YAZDANPANAH, Elsa BARROS, Belinda BEGGA, Sébastien BOUKOBZA, Houria BOUREDJI, Imad CHOUAHI, Isabelle DELACROIX, Antoine FROISSART, Valérie GARRAIT, Elsa NGWEM, Catherine PHLIPPOTEAU, Sepehr SALEHABADI, Cécile TOPER, Florent VINAS, Marie AMSILLI, Olivier EPAULARD, Patricia PAVESE, Isabelle PIERRE, Jean-Paul STAHL, Jérôme AULAGNIER, Julie CELERIER, Roxana COJOCARIU, Emmanuel MATHIEU, Charlotte RACHLINE, Yoland SCHOINDRE, Thomas SENE, Christelle THIERRY, Caroline APARICIO, Véronique DELCEY, Amanda LOPES, Marjolaine MORGAND, Pierre SELLIER, Guy SIMONEAU, Catherine CHAKVETADZE, Sylvain DIAMANTIS, Arnaud GAUTHIER, Kaoutar JIDAR, Béatrice JOURDAIN, Jean-Francois BOITIAUX, Patrick DESCHAMPS, Edouard DEVAUD, Bruno PHILIPPE, Ruxandra-Oana CALIN, Tomasz CHROBOCZEK, Benjamin DAVIDO, Laurène DECONINCK, Pierre DE TRUCHIS, Aurore LAGRANGE, Sabrina MAKHLOUFI, Morgan MATT, Guillaume MELLON, Olivia SENARD, Daniel BENHAMOU, Claire CHAPUZET, Laure CHAUFFREY, Manuel ETIENNE, Luc-Marie JOLY, Bérengère OBSTOY, Mathieu SALAUN, Luc THIBERVILLE, Julie TILLON, Diane BOLLENS, Julie BOTTERO, Pauline CAMPA, Gäelle COSQUERIC, Bénédicte LEFEBVRE, Zineb OUAZENE, Jérôme PACANOWSKI, Dominique PATERON, Nadia VALIN, Caroline COMPAIN, Hugues CORDEL, Benoit DOUMENC, Elena FOIS, Nicolas GAMBIER, Marie-Aude KHUONG, Elisa PASQUALONI, and Marie POUPARD
Subjects: medicine.medical_specialty, education.field_of_study, business.industry, Pneumonia severity index, Incidence (epidemiology), Population, General Medicine, 030204 cardiovascular system & hematology, Amoxicillin, medicine.disease, Placebo, 03 medical and health sciences, Pneumonia, 0302 clinical medicine, Community-acquired pneumonia, Internal medicine, medicine, 030212 general & internal medicine, education, Adverse effect, business, medicine.drug
Abstract: Summary Background Shortening the duration of antibiotic therapy for patients admitted to hospital with community-acquired pneumonia should help reduce antibiotic consumption and thus bacterial resistance, adverse events, and related costs. We aimed to assess the need for an additional 5-day course of β-lactam therapy among patients with community-acquired pneumonia who were stable after 3 days of treatment. Methods We did this double-blind, randomised, placebo-controlled, non-inferiority trial (the Pneumonia Short Treatment [PTC]) in 16 centres in France. Adult patients (aged ≥18 years) admitted to hospital with moderately severe community-acquired pneumonia (defined as patients admitted to a non-critical care unit) and who met prespecified clinical stability criteria after 3 days of treatment with β-lactam therapy were randomly assigned (1:1) to receive β-lactam therapy (oral amoxicillin 1 g plus clavulanate 125 mg three times a day) or matched placebo for 5 extra days. Randomisation was done using a web-based system with permuted blocks with random sizes and stratified by randomisation site and Pneumonia Severity Index score. Participants, clinicians, and study staff were masked to treatment allocation. The primary outcome was cure 15 days after first antibiotic intake, defined by apyrexia (temperature ≤37·8°C), resolution or improvement of respiratory symptoms, and no additional antibiotic treatment for any cause. A non-inferiority margin of 10 percentage points was chosen. The primary outcome was assessed in all patients who were randomly assigned and received any treatment (intention-to-treat [ITT] population) and in all patients who received their assigned treatment (per-protocol population). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT01963442, and is now complete. Findings Between Dec 19, 2013, and Feb 1, 2018, 706 patients were assessed for eligibility, and after 3 days of β-lactam treatment, 310 eligible patients were randomly assigned to receive either placebo (n=157) or β-lactam treatment (n=153). Seven patients withdrew consent before taking any study drug, five in the placebo group and two in the β-lactam group. In the ITT population, median age was 73·0 years (IQR 57·0–84·0) and 123 (41%) of 303 participants were female. In the ITT analysis, cure at day 15 occurred in 117 (77%) of 152 participants in the placebo group and 102 (68%) of 151 participants in the β-lactam group (between-group difference of 9·42%, 95% CI −0·38 to 20·04), indicating non-inferiority. In the per-protocol analysis, 113 (78%) of 145 participants in the placebo treatment group and 100 (68%) of 146 participants in the β-lactam treatment group were cured at day 15 (difference of 9·44% [95% CI −0·15 to 20·34]), indicating non-inferiority. Incidence of adverse events was similar between the treatment groups (22 [14%] of 152 in the placebo group and 29 [19%] of 151 in the β-lactam group). The most common adverse events were digestive disorders, reported in 17 (11%) of 152 patients in the placebo group and 28 (19%) of 151 patients in the β-lactam group. By day 30, three (2%) patients had died in the placebo group (one due to bacteraemia due to Staphylococcus aureus, one due to cardiogenic shock after acute pulmonary oedema, and one due to heart failure associated with acute renal failure) and two (1%) in the β-lactam group (due to pneumonia recurrence and possible acute pulmonary oedema). Interpretation Among patients admitted to hospital with community-acquired pneumonia who met clinical stability criteria, discontinuing β-lactam treatment after 3 days was non-inferior to 8 days of treatment. These findings could allow substantial reduction of antibiotic consumption. Funding French Ministry of Health.
Published: 2021

3. Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Author: François-Xavier Lescure, Hitoshi Honda, Robert A Fowler, Jennifer Sloane Lazar, Genming Shi, Peter Wung, Naimish Patel, Owen Hagino, Ignacio J. Bazzalo, Marcelo M. Casas, Sebastián A. Nuñez, Yael Pere, Carlos M. Ibarrola, Marco A. Solis Aramayo, Maria C. Cuesta, Andrea E. Duarte, Pablo M. Gutierrez Fernandez, Maria A. Iannantuono, Erica A. Miyazaki, Javier P. Silvio, Dario G. Scublinsky, Alessandra Bales, Daniela Catarino, Elie Fiss, Sara Mohrbacher, Victor Sato, Antonio Baylao, Adilson Cavalcante, Francini Correa, Celso A. de Andrade, Juvencio Furtado, Nelson Ribeiro Filho, Valéria Telles, Leopoldo T. Trevelin, Ricardo Vipich, Rodrigo Boldo, Paula Borges, Suzana Lobo, Graziela Luckemeyer, Luana Machado, Maysa B. Alves, Ana C. Iglessias, Marianna M. Lago, Daniel W. Santos, Hugo Chapdelaine, Emilia L. Falcone, Rahima Jamal, Me-Linh Luong, Madeleine Durand, Stephane Doucet, François-Martin Carrier, Bryan A. Coburn, Lorenzo Del Sorbo, Sharon L. Walmsley, Sara Belga, Luke Y. Chen, Allison D. Mah, Theodore Steiner, Alissa J. Wright, J. Hajek, Neill Adhikari, Robert A. Fowler, Nick Daneman, Kosar A. Khwaja, Jason Shahin, Carolina Gonzalez, Rafael Silva, Marcelo Lindh, Gabriel Maluenda, Patricia Fernandez, Maite Oyonarte, Martin Lasso, Alexandre Boyer, Didier Bronnimann, Hoang-Nam Bui, Charles Cazanave, Helene Chaussade, Arnaud Desclaux, Mailys Ducours, Alexandre Duvignaud, Denis Malvy, Lisa Martin, Didier Neau, Duc Nguyen, Thierry Pistone, Gaetane Soubrane-Wirth, Julie Leitao, Clotilde Allavena, Charlotte Biron, Sabelline Bouchez, Benjamin Gaborit, Antoine Gregoire, Paul Le Turnier, Anne-Sophie Lecompte, Raphael Lecomte, Maeva Lefebvre, Francois Raffi, David Boutoille, Pascale H. Morineau, Romain Guéry, Emmanuel Chatelus, Nathalie Dumoussaud, Renaud Felten, Florina Luca, Bernard Goichot, Francis Schneider, Marie-Caroline Taquet, Matthieu Groh, Mathilde Roumier, Mathilde Neuville, Antoine Bachelard, Valentina Isernia, F-Xavier Lescure, Bao-Chau Phung, Anne Rachline, Aurelie Sautereau, Dorothee Vallois, Yves Bleher, Delphine Boucher, Clémentine Coudon, Jean Esnault, Thomas Guimard, Sophie Leautez-Nainville, Dominique Merrien, Marine Morrier, Pauline Motte-Vincent, Romain Gabeff, Hélène Leclerc, Céline Cozic, Romain Decours, Ronan Février, Gwenhael Colin, Sophie Abgrall, Dorothee Vignes, Raluca Sterpu, Mira Kuellmar, Melanie Meersch-Dini, Raphael Weiss, Alexander Zarbock, Christiane Antony, Marc Berger, Thorsten Brenner, Christian Taube, Frank Herbstreit, Sebastian Dolff, Margarethe Konik, Karsten Schmidt, Markus Zettler, Oliver Witzke, Boris Boell, Jorge Garcia Borrega, Philipp Koehler, Thomas Zander, Fabian Dusse, Othman Al-Sawaf, Philipp Köhler, Dennis Eichenauer, Matthias Kochanek, Alexander Shimabukuro-Vornhagen, Sibylle Mellinghoff, Annika Claßen, Jan-Michel Heger, Charlotte Meyer-Schwickerath, Paul Liedgens, Katrin Heindel, Ana Belkin, Asaf Biber, Mayan Gilboa, Itzchak Levy, Vladislav Litachevsky, Galia Rahav, Anat Finesod Wiedner, Tal Zilberman-Daniels, Yonatan Oster, Jacob Strahilevitz, Sigal Sviri, Elena M. Baldissera, Corrado Campochiaro, Giulio Cavalli, Lorenzo Dagna, Giacomo De Luca, Emanuel Della Torre, Alessandro Tomelleri, Davide Bernasconi De Luca, Amedeo F. Capetti, Massimo Coen, Maria V. Cossu, Massimo Galli, Andrea Giacomelli, Guido A. Gubertini, Stefano Rusconi, Giulia J. Burastero, Margherita Digaetano, Giovanni Guaraldi, Marianna Meschiari, Cristina Mussini, Cinzia Puzzolante, Sara Volpi, Marina Aiello, Alarico Ariani, Alfredo A. Chetta, Annalisa Frizzelli, Andrea Ticinesi, Domenico Tuttolomondo, Stefano Aliberti, Francesco B. Blasi, Marta F. Di Pasquale, Sofia Misuraca, Tommaso Pilocane, Edoardo Simonetta, Alessio M. Aghelmo, Claudio Angelini, Enrico Brunetta, Giorgio W. Canonica, Michele Ciccarelli, Sara Dal Farra, Maria De Santis, Sebastian Ferri, Marco Folci, Giacomo M. Guidelli, Enrico M. Heffler, Ferdinando Loiacono, Giacomo Malipiero, Giovanni Paoletti, Rosa Pedale, Francesca A. Puggioni, Francesca Racca, Aurora Zumbo, Morihiko Satou, Tatyana Lisun, Denis Protsenko, Nikolay Rubtsov, Irina Beloglazova, Daria Fomina, Mariana Lysenko, Sofia Serdotetskova, Vitali Firstov, Ivan Gordeev, Ilia Kokorin, Ksenia Komissarova, Nina Lapochkina, Elena Luchinkina, Valentin Malimon, Sevinch Mamedguseyinova, Ksenia Polubatonova, Natalia Suvorova, Jose Arribas, Alberto M. Borobia Perez, Fernando de la Calle Prieto, Juan Carlos Figueira, Rocio Motejano Sanchez, Marta Mora-Rillo, Concepcion Prados Sanchez, Javier Queiruga Parada, Francisco Fernandez Arnalich, Maria Guerro Barrientos, Alejandro Bendala Estrada, Aranzazu Caballero Marcos, Maria E. Garcia Leoni, Rita García-Martínez, Ana María Collado, Patricia Munoz Garcia, Ana Torres do Rego, María V. Villalba García, Almudena Burrillo, Maricela Valerio Minero, Paloma Gijon Vidaurreta, Sonsoles Infante Herrero, Elena Velilla, Marina Machado, Maria Olmedo, Blanca Pinilla, Benito Almirante Gragera, Maria de la Esperanza Cañas Ruano, Sofia Contreras Medina, Alejandro Cortés Herrera, Vicenç Falcó Ferrer, Ricard Ferrer Roca, Xavier Nuvials Casals, Esteve Ribera Pascuet, Paula Suanzes Diez, Pedro Rebollo Castro, Felipe Garcia Alcaide, Alejandro Soriano, Aina Oliver Caldes, Ana González Cordón, Celia Cardozo, Lorena De la Mora Cañizo, Romina Pena López, Sandra Chamorro, Clara Crespillo-Andujar, Rosa Escudero Sanchez, Jesús Fortún-Abete, Begoña Monge-Maillo, Ana Moreno Zamora, Francesca Norman, Matilde Sanchez Conde, Sergio Serrano Villar, Pilar Vizcarra, Lescure, F. -X., Honda, H., Fowler, R. A., Lazar, J. S., Shi, G., Wung, P., Patel, N., Hagino, O., Bazzalo, I. J., Casas, M. M., Nunez, S. A., Pere, Y., Ibarrola, C. M., Solis Aramayo, M. A., Cuesta, M. C., Duarte, A. E., Gutierrez Fernandez, P. M., Iannantuono, M. A., Miyazaki, E. A., Silvio, J. P., Scublinsky, D. G., Bales, A., Catarino, D., Fiss, E., Mohrbacher, S., Sato, V., Baylao, A., Cavalcante, A., Correa, F., de Andrade, C. A., Furtado, J., Ribeiro Filho, N., Telles, V., Trevelin, L. T., Vipich, R., Boldo, R., Borges, P., Lobo, S., Luckemeyer, G., Machado, L., Alves, M. B., Iglessias, A. C., Lago, M. M., Santos, D. W., Chapdelaine, H., Falcone, E. L., Jamal, R., Luong, M. -L., Durand, M., Doucet, S., Carrier, F. -M., Coburn, B. A., Del Sorbo, L., Walmsley, S. L., Belga, S., Chen, L. Y., Mah, A. D., Steiner, T., Wright, A. J., Hajek, J., Adhikari, N., Daneman, N., Khwaja, K. A., Shahin, J., Gonzalez, C., Silva, R., Lindh, M., Maluenda, G., Fernandez, P., Oyonarte, M., Lasso, M., Boyer, A., Bronnimann, D., Bui, H. -N., Cazanave, C., Chaussade, H., Desclaux, A., Ducours, M., Duvignaud, A., Malvy, D., Martin, L., Neau, D., Nguyen, D., Pistone, T., Soubrane-Wirth, G., Leitao, J., Allavena, C., Biron, C., Bouchez, S., Gaborit, B., Gregoire, A., Le Turnier, P., Lecompte, A. -S., Lecomte, R., Lefebvre, M., Raffi, F., Boutoille, D., Morineau, P. H., Guery, R., Chatelus, E., Dumoussaud, N., Felten, R., Luca, F., Goichot, B., Schneider, F., Taquet, M. -C., Groh, M., Roumier, M., Neuville, M., Bachelard, A., Isernia, V., Phung, B. -C., Rachline, A., Sautereau, A., Vallois, D., Bleher, Y., Boucher, D., Coudon, C., Esnault, J., Guimard, T., Leautez-Nainville, S., Merrien, D., Morrier, M., Motte-Vincent, P., Gabeff, R., Leclerc, H., Cozic, C., Decours, R., Fevrier, R., Colin, G., Abgrall, S., Vignes, D., Sterpu, R., Kuellmar, M., Meersch-Dini, M., Weiss, R., Zarbock, A., Antony, C., Berger, M., Brenner, T., Taube, C., Herbstreit, F., Dolff, S., Konik, M., Schmidt, K., Zettler, M., Witzke, O., Boell, B., Garcia Borrega, J., Koehler, P., Zander, T., Dusse, F., Al-Sawaf, O., Kohler, P., Eichenauer, D., Kochanek, M., Shimabukuro-Vornhagen, A., Mellinghoff, S., Classen, A., Heger, J. -M., Meyer-Schwickerath, C., Liedgens, P., Heindel, K., Belkin, A., Biber, A., Gilboa, M., Levy, I., Litachevsky, V., Rahav, G., Finesod Wiedner, A., Zilberman-Daniels, T., Oster, Y., Strahilevitz, J., Sviri, S., Baldissera, E. M., Campochiaro, C., Cavalli, G., Dagna, L., De Luca, Giacomo., Della Torre, E., Tomelleri, A., Bernasconi De Luca, D., Capetti, A. F., Coen, M., Cossu, M. V., Galli, M., Giacomelli, A., Gubertini, G. A., Rusconi, S., Burastero, G. J., Digaetano, M., Guaraldi, G., Meschiari, M., Mussini, C., Puzzolante, C., Volpi, S., Aiello, M., Ariani, A., Chetta, A. A., Frizzelli, A., Ticinesi, A., Tuttolomondo, D., Aliberti, S., Blasi, F. B., Di Pasquale, M. F., Misuraca, S., Pilocane, T., Simonetta, E., Aghelmo, A. M., Angelini, C., Brunetta, E., Canonica, G. W., Ciccarelli, M., Dal Farra, S., De Santis, M., Ferri, S., Folci, M., Guidelli, G. M., Heffler, E. M., Loiacono, F., Malipiero, G., Paoletti, G., Pedale, R., Puggioni, F. A., Racca, F., Zumbo, A., Satou, M., Lisun, T., Protsenko, D., Rubtsov, N., Beloglazova, I., Fomina, D., Lysenko, M., Serdotetskova, S., Firstov, V., Gordeev, I., Kokorin, I., Komissarova, K., Lapochkina, N., Luchinkina, E., Malimon, V., Mamedguseyinova, S., Polubatonova, K., Suvorova, N., Arribas, J., Borobia Perez, A. M., de la Calle Prieto, F., Figueira, J. C., Motejano Sanchez, R., Mora-Rillo, M., Prados Sanchez, C., Queiruga Parada, J., Fernandez Arnalich, F., Guerro Barrientos, M., Bendala Estrada, A., Caballero Marcos, A., Garcia Leoni, M. E., Garcia-Martinez, R., Collado, A. M., Munoz Garcia, P., Torres do Rego, A., Villalba Garcia, M. V., Burrillo, A., Valerio Minero, M., Gijon Vidaurreta, P., Infante Herrero, S., Velilla, E., Machado, M., Olmedo, M., Pinilla, B., Almirante Gragera, B., Canas Ruano, M. D. L. E., Contreras Medina, S., Cortes Herrera, A., Falco Ferrer, V., Ferrer Roca, R., Nuvials Casals, X., Ribera Pascuet, E., Suanzes Diez, P., Rebollo Castro, P., Garcia Alcaide, F., Soriano, A., Oliver Caldes, A., Gonzalez Cordon, A., Cardozo, C., De la Mora Canizo, L., Pena Lopez, R., Chamorro, S., Crespillo-Andujar, C., Escudero Sanchez, R., Fortun-Abete, J., Monge-Maillo, B., Moreno Zamora, A., Norman, F., Sanchez Conde, M., Serrano Villar, S., and Vizcarra, P.
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Critical Care, International Cooperation, Population, Antibodies, Monoclonal, Humanized, Placebo, Severity of Illness Index, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Intensive care, Severity of illness, medicine, Clinical endpoint, Humans, Immunologic Factors, 030212 general & internal medicine, Mortality, education, Respiratory Distress Syndrome, education.field_of_study, Dose-Response Relationship, Drug, SARS-CoV-2, business.industry, Hazard ratio, COVID-19, Articles, Middle Aged, Receptors, Interleukin-6, Sarilumab, Treatment Outcome, 030228 respiratory system, Female, Drug Monitoring, Cytokine Release Syndrome, business
Abstract: Summary Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding Sanofi and Regeneron Pharmaceuticals.
Published: 2021

4. Impact of the COVID-19 pandemic on the homeless: results from a retrospective closed cohort in France (March-May 2020)

Author: Yazdan Yazdanpanah, Armelle Pasquet-Cadre, Maï Le Teurnier, Marie Wicky-Thisse, Anthony Cousien, Maria Vargas Gomez, Maya Husain, Claire Rouzaud, Anne Rachline, Simon Rolland, Charlotte Charpentier, Valentine Marie Ferré, and Diane Descamps
Subjects: Adult, Male, 0301 basic medicine, Microbiology (medical), 030106 microbiology, Population, Serology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Seroepidemiologic Studies, Pandemic, Prevalence, medicine, Humans, Seroprevalence, 030212 general & internal medicine, Mortality, education, Retrospective Studies, education.field_of_study, business.industry, SARS-CoV-2, Incidence, Mortality rate, Vaccination, COVID-19, General Medicine, Middle Aged, medicine.disease, Comorbidity, body regions, Hospitalization, Research Note, Infectious Diseases, Ill-Housed Persons, Cohort, Female, France, Homeless, Homeless shelters, business, Demography
Abstract: Objectives To evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospitalization and fatality rates in residents of homeless shelters run by Samusocial of Paris. Methods We conducted a retrospective serological study between July and August 2020 on all residents and staff members of three homeless shelters run by Samusocial of Paris: two centres providing healthcare accommodation (HCA) and one a women's dormitory. We included all adults present in the shelters or who died of a proven SARS-CoV-2 infection during the first wave (March–May). SARS-CoV-2 antibodies were detected in serum samples using the SARS-CoV-2 IgG Architect (Abbott) test. Any participant with a positive PCR or serology was defined as a confirmed SARS-CoV-2 case. Results We included 100 residents and 83 staff members. The confirmed SARS-CoV-2 rate by PCR or serology was 72/100 (72.0%) for residents and 17/83 (20.5%) for staff members. Women accommodated in the dormitory had the highest infection rate (90.6%). The hospitalization rate in residents was 17/72 (23.6%) and the death rate 4/72 (5.6%). All hospitalizations and deaths occurred among HCA residents. Among the residents of HCA shelters, 34/68 (50%) presented at least two comorbidity factors associated with being at high risk for severe SARS-CoV-2 infection. Conclusion The SARS-CoV-2 infection rate was high in residents of these homeless shelters (10.6% seroprevalence in the Ile-de-France region during the first wave). Severe SARS-CoV-2 infection was highly associated with the prevalence of comorbidities. This population should be considered as a priority in vaccination campaigns and in access to individual housing units when at risk.
Published: 2021

5. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial

Author: Mathieu Vautier, Florence Tubach, Marion Licois, Estelle Henry, Marie-Alexandra Alyanakian, Julien Poissy, Solaya Chalal, Anne Gysembergh-Houal, Stéphanie Alary, Sophie Diemunsch, Jonathan London, Camille Petit-Hoang, Ruben Benainous, Catherine Metzger, Olivier Benveniste, Hala Semri, Charléne Jouve, Robin Dhote, johann Cailhol, Elise Morawiec, Kristina Beziriganyan, Mathieu Oberlin, Paul Legendre, Hélène François, Claire Davoine, F Louni, Myriam Virlouvet, Stéphane Renaud, Christiane Verny, Bertrand Guidet, Bob Heger, Lara Zafrani, Pierre-Louis Tharaux, Mandy Nizard, Adrien Contejean, Segolene Toquet, Ulrich Clarac, Sylviane Ravato, Gaëtan Deslée, Frédéric De Blay, Christian Richard, Raphaël Porcher, Malikhone Chansombat, Marie Lachatre, Ines Ben-Mabrouk, Matthieu Uzzan, Lauren Demerville, Amélie Servettaz, Annabelle Pourbaix, Philippe Manivet, Fanny Charbonnier, Pierre-Grégoire Guinot, Alexandre Demoule, Nicolas Champtiaux, Nicolas Belaube, Jean-Pierre Riveline, Kamil Chitour, Joseph Emmerich, Arthur Neuschwander, Mickael Henriques, Anne Hutt, Arthur Pavot, Anne Rachline, Elena Fois, Audrey Phibel, Xavier Monnet, Jean-Charles Duclos-Vallée, Félix Ackermann, Maria Pereira, Anne Sophie Korganow, Elodie Drouet, Tabassome Simon, Morgane Faure, Anne Pattyn, Aida Zahrate-Ghoul, Karine Martin, Jean-Jacques Tudesq, Gladys Aratus, Kévin Cardet, Julien Pottecher, Eric Demonsant, Arsène Mekinian, Rémy Gauzit, Julie Smati, Robin Deleris, Jean-Simon Rech, Boris Bienvenu, Nicolas Lefebvre, Elodie Baudry, Nicolas Bonnet, Alexis Régent, François Weill, Lalia Djaghout, Anne Tréhan, Isabelle Lehir, Elena Kiouris, Sophie Renet, Yasmina Mekid, Vanessa Rathouin, David Montani, Annick Tibi, Anne Blanchard, Fanette Denies, Nathalie Menage, Guillaume Becker, Valérie Camara-Clayette, Loic Kassegne, Nathalie Chavarot, Aurélie Clan Hew Wai, Jeremy Arzoine, Louise Bondeelle, Mohamad Zaidan, S Lariven, Laurent Cylly, Edouard Flamarion, Chaouki Bouras, Florence Bellenfant, Melissa Clément, Lola-Jade Palmieri, Marie hélène Pari, Lionel Galicier, Valérie Dejean, Delphine Feyeux, Naima Sguiouar, Anne Bergeron, Laurence Annonay, Anouk Walter-Petrich, Camille Knosp, Laurence Drouard, Thiziri Sadaoui, Julie Delemazure, Antoine Parrot, Carole Burger, Laurence Berard, Nicolas Gambier, Eric Marquis, Isabelle Madeleine, Gwenaël Lorillon, Matthieu Resche-Rigon, Yves Hansmann, Claire Rouzaud, Hélène Gros, Sophie Caillat-Zucman, Bernard Cholley, Celine Wilpotte, Chistophe Willekens, Lydia Suarez, Syllia Belazouz, Valérie Pourchet-Martinez, Dhiaa Meriem Hai, Olivier Collange, Paul Jaubert, Marie-Thérèse Tremorin, Nathalie Marin, Diane Le Pluart, Madona Sakkal, Juliette Djadi-Prat, Alexandre Morel, Agathe Bounhiol, Xavier Jaïs, Nicolas Meyer, Vixra Keo, Michaël Darmont, Benedicte Giroux-Leprieur, Anatole Harrois, Anne Adda, Yaël Amara, Fanny Pommeret, Antony Canellas, Matheus Vieira, Clotilde Le Tiec Le Tiec, Corinne Pernot, Bernard Goichot, Céline Louapre, Roza Rahli, Anne Jacolot, Anne Daguenel-Nguyen, Marie Dubert, Anaïs Razurel, Aurelie Sautereau, Mitja Jevnikar, Pierre Faye, Jeanne CHAUFFiER, Mathieu Jozwiak, Laurent Savale, Florence Patin, Kahina Cheref, Mélanie Dehais, Paul Michel Mertes, Caroline Morbieu, Valérie Paquet, Dominique Roulot, Giovanna Melica, Pauline Jouany, Frédéric Schlemmer, Blandine Lehmann, Pascal Martel, Tomas Urbina, Yazdan Yazdanpanah, Veronique Joly, Damien Bergerot, Claire Courtin, Benjamin Fournier, Guillaume Grailles, Asmaa Mamoune, Caroline Gaudefroy, Charlotte Kaeuffer, Bruno Crestani, Thinhinane Bariz, C Rioux, Karine Celli Lebras, Sophie Granville, Marion Bouhris, Hugues Cordel, Jean-Marie Michot, Mohamed Belloul, Nadège Lemarié, Philippe Dieudé, Sylvie Le Gac, Matthieu Mahévas, Pascal Richette, Anaïs Codorniu, Camille Rolland-Debord, Edouard Lefèvre, Sophie-Rym Hamada, Tristan Martin, Vincent Castelain, Aude Rigolet, Valentin Greigert, Gaelle Leroux, Simon Valayer, Eliane Bertrand, Eric Vicaut, Stéphane Brin, Jacques-Eric Gottenberg, Olivier Clovet, Marc Bardou, Muriel Fartoukh, Valentina Isernia, Ada Clarke, Bao Phung, Grégoire Martin de Frémont, Jeanne Meunier, Gonçalo Boleto, David Lebeaux, Hassan Tarhini, Asmaa Mabrouki, Pascaline Choinier, Etienne Canouï, Eric D'Ortenzio, Constance Guillaud, Corine Nyanou, Alexandre Moores, Linda Gimeno, Victoire De Lastours, F-Xavier Lescure, Claire Montlahuc, Sophie Georgin-Lavialle, A Soria, Xavier Mariette, Sophie Ismael, Prissile Bakouboula, Olivier Lambotte, Jérémie Zerbit, Aude Jacob, Z Julia, Nathalie Dournon, Marthe Rigal, Mireille Adda, Nathan Ebstein, Frédéric Duée, Helene Chambrin-Lauvray, Ramdane Meftali, Hélène Lafoeste, Coralie Bloch Queyrat, Sabrina Brahmi, Catherine Le Bourlout, Nicolas Noel, Emmanuelle Guillot, Hakim Tayebi, Sandrine Briois, Anne-Lise Pouliquen, Lakhdar Mameri, Sophie-Caroline Sacleux, Nathalie Rozensztajn, Lelia Escaut, Clément Jourdaine, Cédric Pierron, Marc Garnier, Yves Cohen, Abdellatif Tazi, Maxence Decavele, Paul Henri Grisot, Patrice Cacoub, Laure Allanic, Amira Benattia, Martin Siguier, Luca Semerano, Jean-Sébastien Hulot, Jean-Jacques Mourad, Sara Sambin, Miguel Alejandro Vasquez-Ibarra, Nabil Raked, Christine Lemagner, Martin Dres, Clara Campos-Vega, Tali-Anne Szwebel, Benjamin Chaigne, Emmanuel Andrès, Gabriel Steg, Frédéric Blanc, Isabelle Peigney, Catherine Fauvaux, Côme Bureau, Samira Saleh-Mghir, Julie Jambon, Pierre Dupland, Anne Lise Jegu, Mamadou Salif Cisse, Damien Roux, Moez Jallouli, Philippe Blanche, Sébastien Cavelot, Sophie Ohlmann-Caillard, Louise-Laure Mariani, Adrien Michon, Alain Wynckel, Saskia Flamand, Safaa Nemlaghi, Benjamin G. Chousterman, Geoffroy Volle, Cécile Kedzia, Fanny Domont, Lee S. Nguyen, Férial Berbour, Pierre Diemunsch, Celine Dupré, Etienne Lengliné, Claire Tantet, Gaël Leprun, Sara Virolle, Perrine Guillaume-Jugnot, Soumeya Hammal, B. Duchemann, Mathilde Le Marchand, Vincent Poindron, Victor Lancon, Ruxandra Burlacu, Guillaume Lefèvre, Kamyl Baghli, Emilia Stan, Yann Nguyen, Olivier Sanchez, Olivier Sitbon, Loren Soyez-Herkert, Fanny Defrancq, Véronique Vigna, Aurélien Guffroy, Martine Meunier, Pierre Mora, Léa Resmini, Liem Binh Luong Nguyen, Jean-Luc Diehl, Johanna Oziel, Emmanuelle Bugnet, Lamiae Grimaldi, Olivia Daconceicao, Marie Matignon, Mourad Djadel, Yasmine Messaoudi, Hassan Joumaa, Isabelle Dusanter, Sarah Benghanem, Julien Mayaux, Marc Michel, Claire Pernin, Antoine Gros, Nassim Mahtal, Philippe Benoit, Cloé Comarmond, Laurence Lecomte, Patricia Senet, Sebastien Abad, Jérôme Pacanowski, Céline Leplay, Claire Aguilar, Cédric Sublon, Jesuthasan Denis, Régis Peffault de Latour, Gabrielle Archer, Alain Fourreau, Emmanuelle Blin, Lise Bernard, Alexandra Beurton, Alexandre Buffet, Pierre Le Guen, Clairelyne Dupin, Olivier Fain, A Gervais, Marc Humbert, Yves Allenbach, Alexandre Bourgoin, Agnes Maurer, Eric Noll, Virginie Elisee, Adrien Mirouse, Cecile Larcheveque, Carine Karachi, Samy Figueiredo, Hakim Meddah, Greggory Ducrocq, Jeanne Goupil de Bouille, Awa Ndiaye, Jessica Krause le Garrec, Maxime Dougados, Yasmina Ferfar, Damien Vimpere, Olivier Olivier, Annabelle Stoclin, Jean-Louis Teboul, Ridha Belilita, Serge Bureau, Naura Gamany, Emeline Colomba, Baptiste Duceau, Philippe Ravaud, Corinne Guerin, Florence Morin, Pélagie Thibaut, Younes Keroumi, Julie Chas, Elisabeth Coupez, Laetitia Languille, Mathias Cornic, Jean-Michel Molina, Caroline Pradon, Alison Klasen, Zakaria Ait Hamou, Armand Mekontso-Dessaps, Yurdagul Uzunhan, Samir Hamiria, Anne Godier, Elsa Feredj, Nessima Yelles, Jean-Benoit Arlet, Christine Broissand, Belkacem Asselate, Jaouad Benhida, Julien Le Marec, Nawal Derridj, Laurène Deconinck, A. Dossier, Eric Oksenhendler, Eva Chatron, Lucie Aunay, Candice Estellat, Julie Fillon, Marie Antignac, Jade Ghosn, Ilias Koumis, David Schmitz, Domitille Molinari, Soraya Fellahi, Bruno Mégarbane, Aline Frazier, Ramon Junquera, Vincent Provitolo, Marie Lecronier, Dimitri Fremont, Pierrick Le Borgne, Emmanuel Weiss, Faouzi Saliba, Stéphan Pavy, Geoffrey Rossi, Chloe McAvoy, Eric Mariotte, Dorothee Vallois, Sabrine Ouamri, Pierre Tissieres, Luc Mouthon, Blandine Denis, Celine Comparon, Emmanuelle Sacco, Frédéric Pène, Marjolaine Morgand, Vasco Honsel, Laure Choupeaux, Bruno Mourvillier, Ewa Kozaliewicz, Marie-Hélène Legros, Isabelle Debrix, Gabriel Nisand, Julien Chabert, Juliette Camuset, Stéphane Jauréguiberry, Lynda Chalal, Marine Livrozet, Lucie Biard, Elodie Perrodeau, Brigitte Sabatier, Raphael Borie, Rosa Da Silva, Nathalie Costedoat-Chalumeau, Emmanuel Chatelus, Jean-Christophe Corvol, Nathalie De Castro, David Boutboul, Benjamin Planquette, Anne Claire Desbois, François Danion, Brigitte Ranque, Amélie Cransac, Marine Nadal, Coralie Gernez, Yacine Boudali, Claire Madelaine, Georgina Maalouf, Jonathan Marey, Sophie Bayer, Antoine Fayol, Souad Benarab, Luc Haudebourg, Sophie Bulifon, Claire Pacheco, Philippe Durand, Olivier Hermine, Fanny Alby-Laurent, Geoffroy Liégeon, Axelle Fuentes, Jean-Daniel Lelievre, Gilles Garcia, Céline Verstuyft Verstuyft, Marie-Aude Penet, Constance Delaugerre, Nicolas Carlier, Aurélie Durel Maurisse, Gilles Pialoux, Zeina Louis, Marion Parisey, Pascal Lim, Gaelle Clavere, Martin De Sarcus, Marie Vayssettes, Thomas Papo, Adrien Joseph, Hilario Nunes, Hanane Fodil, Solen Kernéis, Antoine Bachelard, Jacques Duranteau, Karine Lacombe, Olivia Lenoir, Mathilde Vallet, Isabelle Brindele, Robin Charreteur, Elie Azoulay, Dorothée Chopin, Aïcha Bah, Moustafa Benafla, Marie Gilbert, Matthieu Lemoine, Abolfazl Mohebbi, Mathilde Noaillon, Amina Kebir, Virginie Zarrouk, Cécile Yelnik, Benjamin Terrier, Solène Fabre, Paul Crespin, Sarah Dalibey, Thierno Dieye, Renaud Felten, Oriane Puéchal, Pernelle Vauboin, Caroline Hauw-Berlemont, Gabriel Baron, Paul Vermes, Yvon Ruch, Dominique Dautel, Tassadit Hadjam, Anne-Marie Roques, Jean-Philippe Bastard, Younes El Amine, Damien Sène, Alaki Thiemele, Catherine Boussard, Vincent Fallet, Timothee Bironne, Damien Vanhoye, Guillaume Geri, Amine Ghembaza, Bertrand Dunogue, Nadia Anguel, Laure Berton, Caroline Semaille, Thomas Volpe, Jacques Cadranel, Thomas Gorget, Julien Saussereau, Elodie Issorat, Sami Kolta, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Porcher, Raphaël
Subjects: Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 0302 clinical medicine, Randomized controlled trial, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, Hazard ratio, Articles, Middle Aged, Intensive care unit, Hospitals, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Hospitalization, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Treatment Outcome, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, France, medicine.drug, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Critical Care, Population, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, education, Critical Care Outcomes, Aged, Mechanical ventilation, Anakinra, SARS-CoV-2, business.industry, Comment, COVID-19, Bayes Theorem, Pneumonia, medicine.disease, Respiration, Artificial, COVID-19 Drug Treatment, Clinical trial, Interleukin 1 Receptor Antagonist Protein, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business, Interleukin-1
Abstract: International audience; Background: Patients with COVID-19 pneumonia have an excess of inflammation and increased concentrations of cytokines including interleukin-1 (IL-1). We aimed to determine whether anakinra, a recombinant human IL-1 receptor antagonist, could improve outcomes in patients in hospital with mild-to-moderate COVID-19 pneumonia.Methods: In this multicentre, open-label, Bayesian randomised clinical trial (CORIMUNO-ANA-1), nested within the CORIMUNO-19 cohort, we recruited patients from 16 University hospitals in France with mild-to-moderate COVID-19 pneumonia, severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time RT-PCR, requiring at least 3 L/min of oxygen by mask or nasal cannula but without ventilation assistance, a score of 5 on the WHO Clinical Progression Scale (WHO-CPS), and a C-reactive protein serum concentration of more than 25 mg/L not requiring admission to the intensive care unit at admission to hospital. Eligible patients were randomly assigned (1:1) using a web-based secure centralised system, stratified by centre and blocked with varying block sizes (randomly of size two or four), to either usual care plus anakinra (200 mg twice a day on days 1-3, 100 mg twice on day 4, 100 mg once on day 5) or usual care alone. Usual care was provided at the discretion of the site clinicians. The two coprimary outcomes were the proportion of patients who had died or needed non-invasive or mechanical ventilation by day 4 (ie, a score of >5 on the WHO-CPS) and survival without need for mechanical or non-invasive ventilation (including high-flow oxygen) at day 14. All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT04341584, and is now closed to accrual.Findings: Between April 8 and April 26, 2020, we screened 153 patients. The study was stopped early following the recommendation of the data and safety monitoring board, after the recruitment of 116 patients: 59 were assigned to the anakinra group, and 57 were assigned to the usual care group. Two patients in the usual care group withdrew consent and were not analysed. In the analysable population, the median age was 66 years (IQR 59 to 76) and 80 (70%) participants were men. In the anakinra group, 21 (36%) of 59 patients had a WHO-CPS score of more than 5 at day 4 versus 21 (38%) of 55 in the usual care group (median posterior absolute risk difference [ARD] -2·5%, 90% credible interval [CrI] -17·1 to 12·0), with a posterior probability of ARD of less than 0 (ie, anakinra better than usual care) of 61·2%. At day 14, 28 (47%; 95% CI 33 to 59) patients in the anakinra group and 28 (51%; 95% CI 36 to 62) in the usual care group needed ventilation or died, with a posterior probability of any efficacy of anakinra (hazard ratio [HR] being less than 1) of 54·5% (median posterior HR 0·97; 90% CrI 0·62 to 1·52). At day 90, 16 (27%) patients in the anakinra group and 15 (27%) in the usual care group had died. Serious adverse events occurred in 27 (46%) patients in the anakinra group and 21 (38%) in the usual care group (p=0·45).Interpretation: Anakinra did not improve outcomes in patients with mild-to-moderate COVID-19 pneumonia. Further studies are needed to assess the efficacy of anakinra in other selected groups of patients with more severe COVID-19.Funding: The Ministry of Health, Programme Hospitalier de Recherche Clinique, Foundation for Medical Research, and AP-HP Foundation.
Published: 2021
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6. Author Correction: Combined inhibition of MEK and nuclear ERK translocation has synergistic antitumor activity in melanoma cells

Author: Steven A. Rosenberg, Rony Seger, Rand Arafeh, Yardena Samuels, Naomi Gutkind, Galia Maik-Rachline, Karen Flores, and Alona Keren-Paz
Subjects: MAPK/ERK pathway, Proto-Oncogene Proteins B-raf, Cell Survival, MAP Kinase Signaling System, Nuclear Localization Signals, lcsh:Medicine, Chromosomal translocation, Antineoplastic Agents, Text mining, Cell Movement, Cell Line, Tumor, medicine, Biomarkers, Tumor, Humans, lcsh:Science, Author Correction, Extracellular Signal-Regulated MAP Kinases, Melanoma, Antitumor activity, Multidisciplinary, Chemistry, business.industry, lcsh:R, Drug Synergism, medicine.disease, 3. Good health, Protein Transport, Cancer research, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, lcsh:Q, Mitogen-Activated Protein Kinases, business, Peptides
Abstract: Genetic alterations in BRAF, NRAS and NF1 that activate the ERK cascade, account for over 80% of metastatic melanomas. However, ERK cascade inhibitors have been proven beneficial almost exclusively for BRAF mutant melanomas. One of the hallmarks of the ERK cascade is the nuclear translocation of ERK1/2, which is important mainly for the induction of proliferation. This translocation can be inhibited by the NTS-derived peptide (EPE) that blocks the ERK1/2-importin7 interaction, inhibits the nuclear translocation of ERK1/2, and arrests active ERK1/2 in the cytoplasm. In this study, we found that the EPE peptide significantly reduced the viability of not only BRAF, but also several NRAS and NF1 mutant melanomas. Importantly, combination of the EPE peptide and trametinib showed synergy in reducing the viability of some NRAS mutant melanomas, an effect driven by the partial preservation of negative feedback loops. The same combination significantly reduced the viability of other melanoma cells, including those resistant to mono-treatment with EPE peptide and ERK cascade inhibitors. Our study indicates that targeting the nuclear translocation of ERK1/2, in combination with MEK inhibitors can be used for the treatment of different mutant melanomas.
Published: 2019

7. Decreased darunavir concentrations during once-daily co-administration with maraviroc and raltegravir: OPTIPRIM-ANRS 147 trial

Author: Pressiat, Claire, Hirt, Déborah, Treluyer, Jean-Marc, Zheng, Yi, Morlat, Philippe, Naqvi, Alice, Tran, Laurent, Viard, Jean-Paul, Avettand-Fenoel, Véronique, Rouzioux, Christine, Meyer, Laurence, Cheret, Antoine, Hoen, B, Bourdeaux, C, Delfraissy, J, Goujard, C, Amri, I, Fourn, E, Quertainmont, Y, Môle, M, Rami, A, Durel, A, Diemer, M, Parrinello, M, Allègre, T, Lafeuillade, A, Hittinger, G, Lambry, V, Carrerre, M, Philip, G, Duvivier, C, Consigny, P, Charlier, C, Shoai, M, Touam, F, Pialoux, G, Slama, L, l'Yavanc, T, Mathurin, P, Adda, A, Berrebi, V, Salmon, D, Chakvetadze, E, Tassadit, T, Ousseima, E, Pietri, M, Levy, Y, Lascaux, A, Lelievre, J, Giovanna, M, Dominguez, S, Dumont, C, Katlama, C, Valentin, M, Seang, S, Schneider, L, Kiorza, N, Chermak, A, Ben Abdallah, S, Simon, A, Pichon, F, Pauchard, M, Molina, J, Lascoux, C, Ponscarme, D, Colin de Verdiere, N, Scemla, A, de Castro, N, Rachline, A, Garrait, V, Rozenbaum, W, Ferret, S, Balkan, S, Clavel, F, Tourdjman, M, Lafaurie, M, Aslan, A, Goguel, J, Thierry, S, de Lastours, V, Gallien, S, Pavie, J, Delgado, J, Mededji, C, Veron, R, Abel, S, Pierre-François, S, Baringhton, C, Chennebault, J, Vandamme, Y, Fialaire, P, Rehaiem, S, Rabier, V, Abgueguen, P, Vandenhende, M, Bernard, N, Lacoste, D, Michaux, C, Paccalin, F, Receveur, M, Caldato, S, Delaune, J, Ragnaud, J, Neau, D, Lacaze-Buzy, L, Livrozet, J, Jeanblanc, F, Makhloufi, D, Brunel Dalmas, F, Jourdain, J, Chiarello, P, Yeni, P, Phung, B, Rioux, C, Godard, C, Louni, F, El Alami Talbi, N, Catalano, G, Guiroy, F, Reynes, J, Jacquet, J, Fauchere, V, Merle, C, Lemoine, V, Loriette, M, Morquin, D, Makinson, A, Atoui, N, Tramoni, C, Raffi, F, Allavena, C, Bonnet, B, Bouchez, S, Feuillebois, N, Brunet-François, C, Reliquet, V, Mounoury, O, Morineau-Le-Houssine, P, Billaud, E, Brosseau, D, Hüe, H, Dellamonica, P, Vassallo, M, Leplatois, A, Durant, J, Joulié, A, Souala, F, Michelet, C, Arvieux, C, Tattevin, P, Leroy, H, Revest, M, Fily, F, Chapplain, J, Ratajczak, C, Gras, G, Bernard, L, Dailloux, J, Laplantine, V, Cuzin, L, Marchou, B, Larrigue, S, Chauveau, M, Balsarin, F, Obadia, M, Bonne, S, Huleux, T, Ajana, F, Alcaraz, I, Baclet, V, Melliez, H, Viget, N, de la Tribonniere, X, Aissi, E, Poissy, J, Ravaux, I, Vallon, A, Varan, M, May, T, Letranchant, L, Burty, C, Briaud, A, Wassoumbou, S, Stenzel, M, Bouillon, M, Debab, Y, Caron, F, Gueit, I, Chapuzet, C, Borsa Lebas, F, Etienne, M, Miailhes, P, Perpoint, T, Senechal, A, Schlienger, I, Cotte, L, Augustin Normand, C, Boibieux, A, Ferry, T, Corsini, N, Braun, E, Lippran, J, Biron, F, Chidiac, C, Pailhes, S, Lipman, J, Koffi, J, Thoirain, V, Brochier, C, Greder Belan, A, Therby, A, Monnier, S, Ruquet, M, Richier, L, Prevoteau Du Clary, F, Evaluation thérapeutique et pharmacologie périnatale et pédiatrique (EA_7323), Université Paris Descartes - Paris 5 (UPD5), 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), Service de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Service de Maladies Infectieuses [CHU Nice], Hôpital l'Archet - CHU de Nice, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Diagnostic et de Thérapeutique, Hôpital de l’Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Stratégies thérapeutiques contre l'infection VIH et les maladies virales associées [iPLesp] (THERAVIR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and CHU Pontchaillou [Rennes]
Subjects: Male, 0301 basic medicine, MESH: Raltegravir Potassium, [SDV]Life Sciences [q-bio], HIV Infections, Pharmacology, Maraviroc, MESH: HIV-1, Plasma, chemistry.chemical_compound, Pharmacology (medical), MESH: Anti-HIV Agents, MESH: Maraviroc, Darunavir, MESH: Darunavir, education.field_of_study, MESH: Middle Aged, MESH: HIV Infections, Middle Aged, Viral Load, Infectious Diseases, MESH: Young Adult, Female, MESH: Viral Load, Viral load, medicine.drug, Adult, Microbiology (medical), Anti-HIV Agents, 030106 microbiology, Population, Emtricitabine, Young Adult, 03 medical and health sciences, Pharmacokinetics, Raltegravir Potassium, medicine, Humans, education, MESH: Plasma, Models, Statistical, Ritonavir, MESH: Humans, business.industry, MESH: Adult, Raltegravir, MESH: Male, 030104 developmental biology, chemistry, HIV-1, MESH: Ritonavir, business, MESH: Female, MESH: Models, Statistical
Abstract: International audience; BackgroundThe OPTIPRIM-ANRS 147 trial compared intensive combination ART (darunavir/ritonavir, tenofovir disoproxil fumarate/emtricitabine, raltegravir and maraviroc) started early during primary HIV-1 infection with standard tritherapy with darunavir/ritonavir, tenofovir disoproxil fumarate and emtricitabine. From month 6 to 18, the percentage of viral load values
Published: 2018

8. RAF, MEK and ERK Inhibitors as Anti-Cancer Drugs: Intrinsic and Acquired Resistance as a Major Therapeutic Challenge

Author: Rony Seger, Galia Maik-Rachline, and Izel Cohen
Subjects: Drug, MAPK/ERK pathway, Gene isoform, Hyperactivation, business.industry, Melanoma, media_common.quotation_subject, Cancer, Drug resistance, medicine.disease, medicine, Cancer research, Signal transduction, business, media_common
Abstract: The ERK cascade regulates various cellular functions and is hyperactivated in more than 85% of cancers leading to dysregulated proliferation. This hyperactivation as well as oncogenic activating mutations in the different components of the cascade (mainly RAS, RAF and MEK) have inspired the development of several inhibitors targeting the different tiers of the cascade. As a result, clinically approved RAF and MEK inhibitors are used for targeted therapies of metastatic mutated BRAF melanoma. However, along with the impressive clinical results observed with many of these patients upon initial treatment, other patients do not respond to the drugs, and development of resistance in the sensitive group is unavoidable. Deciphering the molecular mechanisms underlying this intrinsic or acquired resistance is a necessity in order to enhance the treatment efficacy of the drugs used for ERK-addicted cancers. Several resistance mechanisms have been proposed up to date, which result from either preexisting mechanisms in some or all cells within the tumors or due to drug-induced mechanisms. These include (a) expression of drug-resistant RAF isoforms (b) molecular or genetic alterations of downstream components that reactivate the ERK cascade and (c) induction of upstream components and other signaling pathways that bypass the drug blockage. All these mechanisms eventually result in inducing reactivation of ERK or other survival-related pathways. Here we review the mechanisms underlying drug resistance and future efforts to develop activity-independent, resistance-escaped, more efficacious anti-tumor drugs.
Published: 2018

9. Surveillance of post-caesarean surgical site infections in a hospital with limited resources, Cambodia

Author: Sok Srun, Somary Nhem, Yin Sinath, An Thoun Seng, Amanda Daniel, Philippe Cavailler, Sophie Goyet, Za Reed, Anne Rachline, Mony Borin, Nora Chea, Meas Chea, Rodney Hoff, and Nima Asgari
Subjects: Adult, medicine.medical_specialty, Pediatrics, Adolescent, Erythromycin, Staphylococcus lugdunensis, Microbiology, Young Adult, Pregnancy, Virology, Internal medicine, Ampicillin, Hospital-acquired infection, medicine, Humans, Surgical Wound Infection, Infection control, Developing Countries, Bacteria, biology, Cesarean Section, business.industry, Incidence, Incidence (epidemiology), Clindamycin, Bacterial Infections, General Medicine, Middle Aged, Amoxicillin, medicine.disease, biology.organism_classification, Hospitals, Infectious Diseases, Epidemiological Monitoring, Female, Parasitology, Cambodia, business, medicine.drug
Abstract: Introduction: In Cambodia, we implemented a pilot surveillance of superficial surgical site infections (SSSI) following caesarean deliveries (CD) in a provincial hospital, to estimate their incidence, describe their clinical management, and determine their causative pathogens. Methodology: Between October 2010 and February 2011, all women admitted for CD were included in the surveillance. Their clinical condition was monitored for a post-operative period of 30 days, including two assessments performed by surgeons. Cases were clinically diagnosed by surgeons, with bacterial cultures performed. Results: Of the 222 patients admitted for CD, 176 (79.3%) were monitored for 30 days. Of these, 11 were diagnosed with a SSSI, giving an incidence rate of 6.25% (95% CI 3.2-10.9). Four of the cases (36.4%) were detected after hospital discharge. Length of hospitalization was significantly longer for the SSSI cases. All 222 patients were prescribed antibiotics. Ampicillin was administered intravenously to 98.6% of them, with subsequent oral amoxicillin given to 82.9%. Three of six pus samples collected were positive on culture: two with Staphylococcus aureus and one with Staphylococcus lugdunensis. One S.aureus was methicillin resistant (MRSA). The other was clindamycin and erythromycin resistant. Conclusion: Surveillance of health-care associated infections in a setting with limited resources is challenging but feasible. Effective post-discharge surveillance was essential for the estimation of the incidence rate of SSSI following caesarean deliveries. This surveillance led to a peer-review of medical practices.
Published: 2013

10. Early diagnosis of dengue disease severity in a resource-limited Asian country

Author: Veasna Duong, Moniboth Duch, Yee Sin Leo, Yuvatha Kdan, Ai Li Quake, Andrew A. Lover, Arnaud Tarantola, Philippe Buchy, Anne Rachline, Philippe Cavailler, Rekol Huy, Jeremy Brett, National University of Singapore (NUS), Unité d'Épidémiologie et de Santé Publique [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Tan Tock Seng Hospital, National Pediatric Hospital, University of Health Sciences – Cambodia, National Center of Parasitology (CNM), National Malaria Center [Phnom Penh], Unité de Virologie / Virology Unit [Phnom Penh], Sanofi Pasteur [Marcy-l'Étoile, France], and Funding for this study was provided by Sanofi-Pasteur. The funders had no role in the study design, data collection and data analysis. Decision to publish and preparation of the manuscript were made jointly by all the authors.
Subjects: 0301 basic medicine, Dengue Infection, medicine.medical_specialty, Pathology, Dengue Shock Syndrome, 030106 microbiology, 030231 tropical medicine, Dengue virus, medicine.disease_cause, Severe dengue, Dengue fever, 03 medical and health sciences, 0302 clinical medicine, Medical microbiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Severe Dengue, Leukopenia, business.industry, medicine.disease, Triage, 3. Good health, Infectious Diseases, Tropical medicine, Emergency medicine, Tourniquet test, Hemagglutination Inhibition, Dengue Hemorrhagic Fever, medicine.symptom, business, Research Article
Abstract: Background Dengue is endemic throughout Cambodia, a country faced with significant health and economic challenges. We undertook a clinical study at the National Paediatric Hospital in Phnom Penh to evaluate clinical diagnostic parameters for dengue and predictors of disease outcome. Methods Between September 2011 and January 2013, all consecutive inpatients aged between 1 and 15 years and presenting with suspected dengue were enrolled. They were clinically assessed using both the 1997 and 2009 WHO dengue classifications. Specimens were collected upon admission and discharge and tested for dengue at Institut Pasteur in Cambodia. Results A total of 701 patients were screened. Of these, 79 % were dengue-confirmed by laboratory testing, and 21 % tested dengue-negative. A positive tourniquet test, absence of upper respiratory symptoms, leukopenia, thrombocytopenia, and elevated liver transaminases were independent predictors for laboratory-confirmed dengue among the children. The presence of several warning signs on hospital admission was associated with a concurrent laboratory-confirmed diagnosis of severe disease outcome. Conclusions The presence of two or more warning signs was associated with a concurrent laboratory-confirmed diagnosis of severe dengue at hospital admission. Thus, a cumulative score combining simple clinical parameters and first-line laboratory findings could be used to accurately predict dengue virus infection in pediatric populations, optimizing triage in settings with limited laboratory resources. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1849-8) contains supplementary material, which is available to authorized users.
Published: 2016

11. Efficacy and safety of a switch to unboosted atazanavir in combination with nucleoside analogues in HIV-1-infected patients with virological suppression under antiretroviral therapy

Author: Paola Nasta, Caroline Lascoux-combes, Patrizia Lorenzini, Raphaël Porcher, Nadia Valin, Filippo Castelnuovo, Constance Delaugerre, Laura Albini, Carlo Torti, Anne Rachline, Jean-Michel Molina, Giampiero Carosi, Marco Franzetti, Stefano Rusconi, Jade Ghosn, José Medrano, Eugenia Quiros-Roldan, Juliette Pavie, Adriana Ammassari, Antonella Castagna, Pavie, Juliette, Porcher, Raphael, Torti, Carlo, NEAT Unboosted Atazanavir, Cohort, and Castagna, A
Subjects: Male, Pyridines, HIV Infections, medicine.disease_cause, Deoxycytidine, Gastroenterology, Cohort Studies, Abacavir, Antiretroviral Therapy, Highly Active, Emtricitabine, Pharmacology (medical), medicine.diagnostic_test, Hazard ratio, Lamivudine, Middle Aged, Viral Load, Infectious Diseases, Coinfection, RNA, Viral, Reverse Transcriptase Inhibitors, Drug Therapy, Combination, Female, Oligopeptides, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, Anti-HIV Agents, Hepatitis C virus, Atazanavir Sulfate, Organophosphonates, Internal medicine, medicine, Humans, Tenofovir, Aged, Retrospective Studies, Pharmacology, business.industry, Adenine, HIV Protease Inhibitors, medicine.disease, Virology, Dideoxynucleosides, CD4 Lymphocyte Count, Atazanavir, HIV-1, Lipid profile, business
Abstract: Limited data are available on the use of unboosted atazanavir in combination with nucleoside reverse transcriptase inhibitors (NRTIs) in treatment-experienced HIV-infected patients.We conducted a multicentre, retrospective study among patients with plasma HIV-1 RNA levels50 copies/mL under antiretroviral therapy who switched to unboosted atazanavir + NRTIs between January 2002 and December 2008. Virological failure during follow-up was defined as a confirmed plasma HIV-1 RNA level50 copies/mL. Baseline risk factors for virological failure were identified using Cox proportional hazards models.A total of 886 patients were analysed. At baseline, median age was 44 years, 71.5% were males and median CD4 cell count was 490 cells/mm(3). NRTIs used in combination with atazanavir were tenofovir, abacavir and emtricitabine/lamivudine in 36.9%, 44.1% and 94.4% of patients, respectively. Median follow-up was 21 months. The 3 year probability of virological failure was 20.1%. Only a history of virological failure under NRTIs [hazard ratio (HR) 1.63, P = 0.049] and under protease inhibitors (HR 2.04, P = 0.006) were significantly associated with the risk of virological failure. Among the 431 patients without a prior history of virological failure, the 3 year probability of virological failure was 11.3%, and only hepatitis C virus co-infection (HR 2.25, P = 0.026) and abacavir use (HR 0.43, P = 0.04) were associated with the risk of virological failure. Safety of the switch was satisfactory, with improvement of the lipid profile.In patients with virological suppression and no prior history of virological failure, a switch to unboosted atazanavir in combination with NRTIs is associated with a low probability of virological failure and a good safety profile.
Published: 2011

12. A descriptive, retrospective study of 567 accidental blood exposures in healthcare workers in three West African countries

Author: E. Bouvet, A. Rachline, M.B. Diallo, G. Brücker, P.S. Sow, C. Aka, S. Doumbia, E. Ehui, Arnaud Tarantola, and A. Koumaré
Subjects: Adult, Male, Microbiology (medical), medicine.medical_specialty, Pediatrics, Health Personnel, education, Blood-borne disease, Occupational medicine, Acquired immunodeficiency syndrome (AIDS), Surveys and Questionnaires, Intensive care, Health care, Blood-Borne Pathogens, medicine, Humans, Needlestick Injuries, Retrospective Studies, business.industry, Incidence, Public health, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, Africa, Western, Infectious Diseases, Emergency medicine, Female, Serostatus, business
Abstract: We conducted a multi-centre study in West African hospital wards to document accidental blood exposure (ABE) risks in these settings, and assessed the incidence of ABE in participating healthcare workers (HCWs) retrospectively. In total, 1241 HCWs participated in the survey from 43 hospital wards. Among them, 567 (45.7%) had sustained at least one ABE with an estimated incidence of 0.33 percutaneous injuries (PCIs) and 0.04 mucocutaneous contacts (MCCs)/HCW/year in medical or intensive care personnel and 1.8 PCIs/HCW/year in surgeons. The ABE was a needlestick in 454 (80.1%) of 567 cases, a cut in 19 cases (3.4%), a splash or contact with non-intact skin in 87 cases (15.3%), and was undocumented in seven cases (1.2%). The source patient's human immunodeficiency virus (HIV) serostatus was positive in 74 cases (13.1%), negative in 65 cases (11.5%), and unknown in 416 cases (73.4%). The ABE was not notified in the ward in 392 cases (69.1%). Healthcare structures can improve HCWs' safety and reduce the stigma against HIV-infected patients by improving access to training, information, primary prevention (ABE prevention equipment) and secondary prevention (postexposure prophylaxis) of occupational infection risks.
Published: 2005

13. Quality of travel health advice in a French travel medicine and vaccine center: a prospective observational study

Author: Samuel Ferret, Marie-Anne Bouldouyre, Juliette Pavie, Samia Hamane, Jean-Michel Molina, Nathalie Colin de Verdière, Nathalie De Castro, Diane Ponscarme, and Anne Rachline
Subjects: Adult, Male, medicine.medical_specialty, Paris, Asia, Consultants, Endemic Diseases, Hepatitis A vaccine, Yellow fever vaccine, Ambulatory Care Facilities, Antimalarials, Surveys and Questionnaires, parasitic diseases, Health care, Outcome Assessment, Health Care, Yellow Fever, medicine, Travel medicine, Humans, Prospective Studies, Practice Patterns, Physicians', Africa South of the Sahara, Decision Making, Computer-Assisted, Quality of Health Care, Travel, Vaccines, business.industry, Malaria prophylaxis, Vaccination, Hepatitis A, General Medicine, South America, medicine.disease, Malaria, Family medicine, Immunology, Female, Guideline Adherence, business, Travel Medicine, medicine.drug
Abstract: Background. The number of international trips undertaken by French citizens is rising and we wished to assess the appropriateness of advices given to travelers in a vaccine and travel medicine center in France. Methods. We conducted a 3-month prospective study in one center in Paris where prescriptions and advice to travelers are given by trained physicians in travel medicine who have access to a computerized decision support system (Edisan). A questionnaire was used to record trip characteristics, patients' demographics, and prescriptions. Main outcome measure was the adequacy of prescriptions for malaria prophylaxis, yellow fever, and hepatitis A vaccines to French guidelines. Results. A total of 730 subjects were enrolled in this study, with a median age of 28 years. Travel destinations were sub-Saharan Africa (58%), Asia (21%), and South America (18%). Among the 608 patients (83%) traveling to malaria-endemic areas, malaria prophylaxis was in accordance with guidelines in 578/608 patients (95.1%, 95% CI: 93–96.5), and doxycycline was the regimen of choice (48%). Inappropriate malaria prophylaxis was given to eight patients, one of whom developed plasmodium falciparum malaria. All 413 patients (100%, 95% CI: 99–100) traveling to yellow fever-endemic areas who needed vaccination were correctly vaccinated. However, three patients received yellow fever vaccination without indication. Also, 442 of 454 patients (97.4%, 95% CI: 95.4–98.5) eligible to receive hepatitis A vaccination were immunized. Conclusion. Appropriate advice for malaria prophylaxis, yellow fever, and hepatitis A vaccinations was provided in a travel medicine and vaccine center where trained physicians used a computerized decision support system. Even in this setting, however, errors can occur and professional practices should be regularly assessed to improve health care.
Published: 2012

14. Antiretroviral therapy initiation in France: adherence to national guidelines and outcome

Author: Vatthanaphone Latthaphasavang, Marie-Anne Bouldouyre, Jean-Michel Molina, Diane Ponscarme, Constance Delaugerre, Jean-Yves Mary, Anne Rachline, and Willy Rozenbaum
Subjects: Adult, Cyclopropanes, Male, medicine.medical_specialty, Efavirenz, Time Factors, Anti-HIV Agents, Immunology, Dermatology, Single Center, chemistry.chemical_compound, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Medicine, Humans, Protease inhibitor (pharmacology), Retrospective Studies, Acquired Immunodeficiency Syndrome, Ritonavir, business.industry, Retrospective cohort study, Middle Aged, Viral Load, medicine.disease, Antiretroviral therapy, Benzoxazines, CD4 Lymphocyte Count, Infectious Diseases, Treatment Outcome, chemistry, Alkynes, Practice Guidelines as Topic, Physical therapy, Reverse Transcriptase Inhibitors, Drug Therapy, Combination, Female, France, Guideline Adherence, business, Viral load, medicine.drug
Abstract: Objectives and Methods: Retrospective study of all patients who started antiretroviral therapy (ART) in 2007 in a single center in Paris, with baseline characteristics and 1-year outcome, to assess adherence to national guidelines. Results: We analyzed 118 patients. Time of ART initiation was in agreement with the guidelines for only 64 (54.2%) patients. Fifty patients (42%) started ART with AIDS or a CD4 count 3. In all, 62 (52%) and 47 patients (40%) received a combination of 2 nucleoside analogues with efavirenz (EFV) and 1 ritonavir-boosted protease inhibitor (PI/r), respectively. Treatment regimens were in accordance with the guidelines for 114 patients (97%). At 1 year, 16 patients (13.5%) were lost to follow-up, only 5 (4.9%) experienced HIV disease progression or death, but 19 (18.6%) required hospitalization. Antiretroviral therapy was changed in 21 patients (21%). Ten patients (8.4%) experienced virologic failure. Conclusion: Antiretroviral therapy was in agreement with guidelines for the choice of combination but was often initiated too late.
Published: 2011

15. Case report: Cure of chronic infection with hepatitis C virus after 6 weeks of peg-interferon and ribavirin in a patient co-infected with HIV

Author: Jean-Michel Molina, Pierre Palmer, Anne Rachline, and François Simon
Subjects: Male, Hepatitis C virus, Injections, Subcutaneous, Interferon alpha-2, medicine.disease_cause, Administration, Cutaneous, Antiviral Agents, Virus, Polyethylene Glycols, chemistry.chemical_compound, Pharmacotherapy, Interferon, Virology, Ribavirin, Medicine, Humans, AIDS-Related Opportunistic Infections, business.industry, virus diseases, Interferon-alpha, Hepatitis C, Hepatitis C, Chronic, Middle Aged, Viral Load, medicine.disease, digestive system diseases, Recombinant Proteins, Chronic infection, Infectious Diseases, Treatment Outcome, chemistry, HIV-1, Drug Therapy, Combination, business, Viral load, medicine.drug
Abstract: The recommended treatment duration of chronic hepatitis C virus (HCV) in patients infected with human immunodeficiency virus (HIV) is 48 weeks. This report describes a patient co-infected with HCV genotype 2 and HIV who discontinued HCV therapy after 6 weeks because of adverse events and had a sustained virologic response.
Published: 2010

16. Infection risks following accidental exposure to blood or body fluids in health care workers: a review of pathogens transmitted in published cases

Author: Dominique Abiteboul, Arnaud Tarantola, and Anne Rachline
Subjects: Risk, medicine.medical_specialty, Infection risk, Epidemiology, Health Personnel, Hcv transmission, Human immunodeficiency virus (HIV), medicine.disease_cause, Infections, Antiviral Agents, Article, Prion Diseases, Occupational Exposure, Health care, medicine, Blood-Borne Pathogens, Animals, Humans, Risk factor, Intensive care medicine, Needlestick Injuries, business.industry, Health Policy, Public Health, Environmental and Occupational Health, Hepatitis B, medicine.disease, Research Personnel, Surgery, Body Fluids, Accidental exposure, Infectious Diseases, Blood, Health Occupations, France, business, Developed country
Abstract: Hospital staff and all other human or veterinary health care workers, including laboratory, research, emergency service, or cleaning personnel are exposed to the risk of occupational infection following accidental exposure to blood or body fluids (BBF) contaminated with a virus, a bacteria, a parasite, or a yeast. The human immunodeficiency virus (HIV) or those of hepatitis B (HBV) or C (HCV) account for most of this risk in France and worldwide. Many other pathogens, however, have been responsible for occupational infections in health care workers following exposure to BBF, some with unfavorable prognosis. In developed countries, a growing number of workers are referred to clinicians responsible for the evaluation of occupational infection risks following accidental exposure. Although their principal task remains the evaluation of the risks of HIV, HBV, or HCV transmission and the possible usefulness of postexposure prophylaxis, these experts are also responsible for evaluating risks of occupational infection with other emergent or more rare pathogens and their possible timely prevention. The determinants of the risks of infection and the characteristics of described cases are discussed in this article.
Published: 2004

17. Major Hypertriglyceridemia in HIV-Infected Patients on Antiretroviral Therapy: A Role of the Personal and Family History

Author: L. Rollinat, Marie-Caroline Meyohas, P. Tangre, P. Benlian, A. Rachline, J. L. Meynard, P.-M. Girard, Marguerite Guiguet, and D. Bollens
Subjects: Adult, Male, Microbiology (medical), medicine.medical_specialty, Hepatitis C virus, HIV Infections, Disease, medicine.disease_cause, Body Mass Index, Risk Factors, Internal medicine, medicine, Humans, Family history, Risk factor, Medical History Taking, Life Style, Retrospective Studies, Hypertriglyceridemia, business.industry, General Medicine, Odds ratio, medicine.disease, Antiretroviral therapy, Confidence interval, Diet, Pedigree, Infectious Diseases, Anti-Retroviral Agents, Case-Control Studies, Immunology, Female, business
Abstract: Our aim was to identify factors predisposing HIV-infected patients on long-term antiretroviral therapy (ART) to major hypertriglyceridemia (HTG). We conducted a retrospective, casecontrol study involving 76 HIV-infected patients with HTG, defined by 12-hour fasting plasma triglyceride (TG) > 4.5 mmol/l on at least one occasion, and 150 HIV-infected matched control patients with TG consistently below 1.8 mmol/l. Patients coinfected by the hepatitis C virus appeared to be protected from HTG. In addition to known predisposing factors for HTG in HIV-infected patients (ART and immune/viral status), patients with a history of excess body weight were twice as likely to have HTG (odds ratio [OR] 2.8, 95% confidence interval [CI]: 1.1–6.9); HTG was also more frequent in patients who had a first-degree relative with cardiovascular disease (CVD) or a major risk factor for CVD (OR = 3.6, CI: 1.3–9.9). By identifying subgroups of highly predisposed patients, appropriate lifestyle and dietary measures could be recommended on ART initiation.
Published: 2004

18. Spatial epidemiology and climatic predictors of paediatric dengue infections captured via sentinel site surveillance, Phnom Penh Cambodia 2011–2012

Author: Rekol Huy, Veasna Duong, Sophie Goyet, Yee Sin Leo, Bunthin Y, Andrew A. Lover, Philippe Buchy, Chour Y Meng, Kdan Yuvatha, Anne Rachline, Ung Sophal, Philippe Cavailler, Duch Moniboth, Arnaud Tarantola, Ngan Chantha, Jeremy Brett, National University of Singapore (NUS), Unité de Virologie / Virology Unit [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Regional Emerging Diseases Intervention Centre (REDI), National Paediatric Hospital, Ministry of Health [Phnom Penh], Tan Tock Seng Hospital, Sanofi Pasteur [Marcy-l'Étoile, France], Unité d'Épidémiologie et de Santé Publique [Phnom Penh], Médecins Sans Frontières (MSF), Médecins Sans Frontières, Funding for this study was provided by Sanofi-Pasteur. The sponsors of the study were involved in study design and review of the manuscript, and the sponsors had no role in the data collection/analysis and the decision to publish was made jointly by all authors.
Subjects: Male, Pediatrics, Climate, MESH: Dengue, Dengue fever, Dengue, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, Epidemiology, Medicine, 030212 general & internal medicine, Prospective Studies, Child, Neighbourhood (mathematics), Small-Area Analysis, Spatial epidemiology, MESH: Climate, Hospitals, Pediatric, 3. Good health, Child, Preschool, Cohort, MESH: Sentinel Surveillance, Female, Cambodia, Research Article, MESH: Forecasting, medicine.medical_specialty, Adolescent, 030231 tropical medicine, Disease cluster, MESH: Hospitals, Pediatric, 03 medical and health sciences, MESH: Small-Area Analysis, Humans, MESH: Adolescent, MESH: Humans, Models, Statistical, business.industry, MESH: Cambodia, MESH: Child, Preschool, Public Health, Environmental and Occupational Health, medicine.disease, MESH: Male, MESH: Prospective Studies, Biostatistics, business, MESH: Female, Sentinel Surveillance, MESH: Models, Statistical, Demography, Forecasting
Abstract: International audience; BACKGROUND:Dengue is a major contributor to morbidity in children aged twelve and below throughout Cambodia; the 2012 epidemic season was the most severe in the country since 2007, with more than 42,000 reported (suspect or confirmed) cases.METHODS:We report basic epidemiological characteristics in a series of 701 patients at the National Paediatric Hospital in Cambodia, recruited during a prospective clinical study (2011-2012). To more fully explore this cohort, we examined climatic factors using multivariate negative binomial models and spatial clustering of cases using spatial scan statistics to place the clinical study within a larger epidemiological framework.RESULTS:We identify statistically significant spatial clusters at the urban village scale, and find that the key climatic predictors of increasing cases are weekly minimum temperature, median relative humidity, but find a negative association with rainfall maximum, all at lag times of 1-6 weeks, with significant effects extending to 10 weeks.CONCLUSIONS:Our results identify clustering of infections at the neighbourhood scale, suggesting points for targeted interventions, and we find that the complex interactions of vectors and climatic conditions in this setting may be best captured by rising minimum temperature, and median (as opposed to mean) relative humidity, with complex and limited effects from rainfall. These results suggest that real-time cluster detection during epidemics should be considered in Cambodia, and that improvements in weather data reporting could benefit national control programs by allow greater prioritization of limited health resources to both vulnerable populations and time periods of greatest risk. Finally, these results add to the increasing body of knowledge suggesting complex interactions between climate and dengue cases that require further targeted research
Published: 2014

19. Surveillance and training, not postexposure prophylaxis, are the basis for the prevention of occupational infection by blood-borne pathogens in developing countries

Author: Arnaud Tarantola and A. Rachline
Subjects: Microbiology (medical), medicine.medical_specialty, Infectious Diseases, business.industry, medicine, Blood-Borne Pathogens, Developing country, General Medicine, Intensive care medicine, business
Published: 2005

20. Back-calculation of the number of inoculated Plasmodium falciparum parasites in a documented case of needlestick malaria in a French nurse

Author: A. Rachline, A. Tarantola, and David C. Warhurst
Subjects: biology, business.industry, Inoculation, Public Health, Environmental and Occupational Health, Plasmodium falciparum, General Medicine, medicine.disease, biology.organism_classification, Virology, Back calculation, Infectious Diseases, medicine, Parasitology, business, Malaria
Published: 2003

21. Sensitivity of Five Rapid HIV Tests on Oral Fluid or Finger-Stick Whole Blood: A Real-Time Comparison in a Healthcare Setting

Author: Benedicte Loze, Anne Rachline, Willy Rozenbaum, Eric Laforgerie, Jean-Christophe Plantier, Sylvie Chevret, Jean-Michel Molina, Constance Delaugerre, Juliette Pavie, François Simon, and Laurence Niedbalski
Subjects: Adult, Male, medicine.medical_specialty, Saliva, Adolescent, Science, Human immunodeficiency virus (HIV), HIV Infections, HIV Antibodies, medicine.disease_cause, Sensitivity and Specificity, Fingers, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Infectious Diseases/Viral Infections, Blood plasma, Infectious Diseases/Sexually Transmitted Diseases, medicine, Humans, 030212 general & internal medicine, Young adult, Whole blood, 0303 health sciences, Multidisciplinary, biology, 030306 microbiology, business.industry, AIDS Serodiagnosis, Virology/Diagnosis, Middle Aged, Infectious Diseases/HIV Infection and AIDS, 3. Good health, Europe, Immunology, biology.protein, Medicine, Oral fluid, Female, Antibody, business, Viral load, Research Article
Abstract: BackgroundHealth authorities in several countries recently recommended the expansion of human immunodeficiency virus (HIV) antibody testing, including the use of rapid tests. Several HIV rapid tests are now licensed in Europe but their sensitivity on total blood and/or oral fluid in routine healthcare settings is not known.Methods and findings200 adults with documented HIV-1 (n=194) or HIV-2 infection (n=6) were prospectively screened with five HIV rapid tests using either oral fluid (OF) or finger-stick whole blood (FSB). The OraQuick Advance rapid HIV1/2 was first applied to OF and then to FSB, while the other tests were applied to FSB, in the following order: Vikia HIV 1/2, Determine HIV 1-2, Determine HIV-1/2 Ag/Ab Combo and INSTI HIV-1/HIV-2. Tests negative on FSB were repeated on paired serum samples. Twenty randomly selected HIV-seronegative subjects served as controls, and the results were read blindly. Most patients had HIV-1 subtype B infection (63.3%) and most were on antiretroviral therapy (68.5%). Sensitivity was 86.5%, 94.5%, 98.5%, 94.9%, 95.8% and 99% respectively, with OraQuick OF, OraQuick FSB, Vikia, Determine, Determine Ag/Ab Combo and INSTI (pConclusionWhen evaluated in a healthcare setting, rapid HIV tests were less sensitive on oral fluid than on finger-stick whole blood and less sensitive on finger-stick whole blood than on serum.
Published: 2010

22. Leucocytoclastic vasculitis and indinavir

Author: E. Bouvet, A. Rachline, Vincent Descamps, S. Lariven, and Maggy Grossin
Subjects: Leucocytoclastic vasculitis, biology, business.industry, Dermatology, biology.organism_classification, Virology, Indinavir, Immunopathology, Toxicity, Immunology, medicine, Protease inhibitor (pharmacology), Viral disease, Sida, business, medicine.drug
Published: 2000

23. 694 MDRD CREATININE CLEARANCE IS NOT ALTERED IN HIV-HBV CO-INFECTED PATIENTS WITH A NORMAL RENAL FUNCTION AND TREATED WITH TENOFOVIR (TDF)

Author: Patrick Miailhes, Jean-Michel Molina, Aldo Trylesinski, A. Rachline, Philippe Bonnard, Anders Boyd, J. L. Meynard, L. Taulera, Karine Lacombe, Laurent Cotte, and Pierre-Marie Girard
Subjects: medicine.medical_specialty, Normal renal function, Hepatology, Tenofovir, business.industry, Urology, medicine, Human immunodeficiency virus (HIV), Renal function, medicine.disease_cause, business, medicine.drug
Published: 2008

24. EFFECT OF ACUTE EXERCISE ON LYMPHOCYTE ENUMERATION IN HIV+ AFRICAN-AMERICAN FEMALES 904

Author: A Goldstein, Mary A Fletcher, J. Junco, Nancy G. Klimas, Arthur LaPerriere, C Talluto, Arlette C. Perry, P Majors, Neil Schneiderman, Gail Ironson, and G Maik-Rachline
Subjects: African american, medicine.anatomical_structure, business.industry, Lymphocyte, Immunology, Human immunodeficiency virus (HIV), medicine, Enumeration, Physical Therapy, Sports Therapy and Rehabilitation, Orthopedics and Sports Medicine, medicine.disease_cause, business, Virology
Published: 1997

25. LOWER THAN PREDICTED HEART RATE RESPONSE TO MAX VO2 TESTING IN HIV-1 DISEASE1174

Author: A Goldstein, Gail Ironson, Arlette C. Perry, Arthur LaPerriere, C Talluto, P Majors, Mary A Fletcher, G Maik-Rachline, Nancy G. Klimas, and Neil Schneiderman
Subjects: medicine.medical_specialty, business.industry, Internal medicine, Human immunodeficiency virus (HIV), Cardiology, Medicine, VO2 max, Physical Therapy, Sports Therapy and Rehabilitation, Orthopedics and Sports Medicine, business, medicine.disease_cause, Heart rate response
Published: 1997

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25 results on '"Rachline, A"'

1. Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial

2. Discontinuing β-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial

3. Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

4. Impact of the COVID-19 pandemic on the homeless: results from a retrospective closed cohort in France (March-May 2020)

5. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial

6. Author Correction: Combined inhibition of MEK and nuclear ERK translocation has synergistic antitumor activity in melanoma cells

7. Decreased darunavir concentrations during once-daily co-administration with maraviroc and raltegravir: OPTIPRIM-ANRS 147 trial

8. RAF, MEK and ERK Inhibitors as Anti-Cancer Drugs: Intrinsic and Acquired Resistance as a Major Therapeutic Challenge

9. Surveillance of post-caesarean surgical site infections in a hospital with limited resources, Cambodia

10. Early diagnosis of dengue disease severity in a resource-limited Asian country

11. Efficacy and safety of a switch to unboosted atazanavir in combination with nucleoside analogues in HIV-1-infected patients with virological suppression under antiretroviral therapy

12. A descriptive, retrospective study of 567 accidental blood exposures in healthcare workers in three West African countries

13. Quality of travel health advice in a French travel medicine and vaccine center: a prospective observational study

14. Antiretroviral therapy initiation in France: adherence to national guidelines and outcome

15. Case report: Cure of chronic infection with hepatitis C virus after 6 weeks of peg-interferon and ribavirin in a patient co-infected with HIV

16. Infection risks following accidental exposure to blood or body fluids in health care workers: a review of pathogens transmitted in published cases

17. Major Hypertriglyceridemia in HIV-Infected Patients on Antiretroviral Therapy: A Role of the Personal and Family History

18. Spatial epidemiology and climatic predictors of paediatric dengue infections captured via sentinel site surveillance, Phnom Penh Cambodia 2011–2012

19. Surveillance and training, not postexposure prophylaxis, are the basis for the prevention of occupational infection by blood-borne pathogens in developing countries

20. Back-calculation of the number of inoculated Plasmodium falciparum parasites in a documented case of needlestick malaria in a French nurse

21. Sensitivity of Five Rapid HIV Tests on Oral Fluid or Finger-Stick Whole Blood: A Real-Time Comparison in a Healthcare Setting

22. Leucocytoclastic vasculitis and indinavir

23. 694 MDRD CREATININE CLEARANCE IS NOT ALTERED IN HIV-HBV CO-INFECTED PATIENTS WITH A NORMAL RENAL FUNCTION AND TREATED WITH TENOFOVIR (TDF)

24. EFFECT OF ACUTE EXERCISE ON LYMPHOCYTE ENUMERATION IN HIV+ AFRICAN-AMERICAN FEMALES 904

25. LOWER THAN PREDICTED HEART RATE RESPONSE TO MAX VO2 TESTING IN HIV-1 DISEASE1174

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