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Baruch, Joaquin, Rojek, Amanda, Kartsonaki, Christiana, Vijayaraghavan, Bharath K. T.; Gonçalves, Bronner P.; Pritchard, Mark G.; Merson, Laura, Dunning, Jake, Hall, Matthew, Sigfrid, Louise, Citarella, Barbara W.; Murthy, Srinivas, Yeabah, Trokon O.; Olliaro, Piero, Abbas, Ali, Abdukahil, Sheryl Ann, Abdulkadir, Nurul Najmee, Abe, Ryuzo, Abel, Laurent, Absil, Lara, Acharya, Subhash, Acker, Andrew, Adam, Elisabeth, Adrião, Diana, Al Ageel, Saleh, Ahmed, Shakeel, Ainscough, Kate, Airlangga, Eka, Aisa, Tharwat, Hssain, Ali Ait, Tamlihat, Younes Ait, Akimoto, Takako, Akmal, Ernita, Al Qasim, Eman, Alalqam, Razi, Alberti, Angela, Al‐dabbous, Tala, Alegesan, Senthilkumar, Alegre, Cynthia, Alessi, Marta, Alex, Beatrice, Alexandre, Kévin, Al‐Fares, Abdulrahman, Alfoudri, Huda, Ali, Imran, Ali, Adam, Shah, Naseem Ali, Alidjnou, Kazali Enagnon, Aliudin, Jeffrey, Alkhafajee, Qabas, Allavena, Clotilde, Allou, Nathalie, Altaf, Aneela, Alves, João, Alves, Rita, Alves, João Melo, Amaral, Maria, Amira, Nur, Ampaw, Phoebe, Andini, Roberto, Andréjak, Claire, Angheben, Andrea, Angoulvant, François, Ansart, Séverine, Anthonidass, Sivanesen, Antonelli, Massimo, de Brito, Carlos Alexandre Antunes, Apriyana, Ardiyan, Arabi, Yaseen, Aragao, Irene, Araujo, Carolline, Arcadipane, Antonio, Archambault, Patrick, Arenz, Lukas, Arlet, Jean‐Benoît, Arora, Lovkesh, Arora, Rakesh, Artaud‐Macari, Elise, Aryal, Diptesh, Asensio, Angel, Ashraf, Muhammad, Asif, Namra, Asim, Mohammad, Assie, Jean Baptiste, Asyraf, Amirul, Atique, Anika, Attanyake, A. M. Udara Lakshan, Auchabie, Johann, Aumaitre, Hugues, Auvet, Adrien, Axelsen, Eyvind W.; Azemar, Laurène, Azoulay, Cecile, Bach, Benjamin, Bachelet, Delphine, Badr, Claudine, Bævre‐Jensen, Roar, Baig, Nadia, Baillie, J. Kenneth, Baird, J. Kevin, Bak, Erica, Bakakos, Agamemnon, Bakar, Nazreen Abu, Bal, Andriy, Balakrishnan, Mohanaprasanth, Balan, Valeria, Bani‐Sadr, Firouzé, Barbalho, Renata, Barbosa, Nicholas Yuri, Barclay, Wendy S.; Barnett, Saef Umar, Barnikel, Michaela, Barrasa, Helena, Barrelet, Audrey, Barrigoto, Cleide, Bartoli, Marie, Baruch, Joaquín, Bashir, Mustehan, Basmaci, Romain, Basri, Muhammad Fadhli Hassin, Battaglini, Denise, Bauer, Jules, Rincon, Diego Fernando Bautista, Dow, Denisse Bazan, Beane, Abigail, Bedossa, Alexandra, Bee, Ker Hong, Begum, Husna, Behilill, Sylvie, Beishuizen, Albertus, Beljantsev, Aleksandr, Bellemare, David, Beltrame, Anna, Beltrão, Beatriz Amorim, Beluze, Marine, Benech, Nicolas, Benjiman, Lionel Eric, Benkerrou, Dehbia, Bennett, Suzanne, Bento, Luís, Berdal, Jan‐Erik, Bergeaud, Delphine, Bergin, Hazel, Sobrino, José Luis Bernal, Bertoli, Giulia, Bertolino, Lorenzo, Bessis, Simon, Bevilcaqua, Sybille, Bezulier, Karine, Bhatt, Amar, Bhavsar, Krishna, Bianco, Claudia, Bidin, Farah Nadiah, Singh, Moirangthem Bikram, Humaid, Felwa Bin, Kamarudin, Mohd Nazlin Bin, Bissuel, François, Bitker, Laurent, Bitton, Jonathan, Blanco‐Schweizer, Pablo, Blier, Catherine, Bloos, Frank, Blot, Mathieu, Boccia, Filomena, Bodenes, Laetitia, Bogaarts, Alice, Bogaert, Debby, Boivin, Anne‐Hélène, Bolze, Pierre‐Adrien, Bompart, François, Bonfasius, Aurelius, Borges, Diogo, Borie, Raphaël, Bosse, Hans Martin, Botelho‐Nevers, Elisabeth, Bouadma, Lila, Bouchaud, Olivier, Bouchez, Sabelline, Bouhmani, Dounia, Bouhour, Damien, Bouiller, Kévin, Bouillet, Laurence, Bouisse, Camile, Boureau, Anne‐Sophie, Bourke, John, Bouscambert, Maude, Bousquet, Aurore, Bouziotis, Jason, Boxma, Bianca, Boyer‐Besseyre, Marielle, Boylan, Maria, Bozza, Fernando Augusto, Braconnier, Axelle, Braga, Cynthia, Brandenburger, Timo, Monteiro, Filipa Brás, Brazzi, Luca, Breen, Patrick, Breen, Dorothy, Breen, Patrick, Brickell, Kathy, Browne, Shaunagh, Browne, Alex, Brozzi, Nicolas, Brunvoll, Sonja Hjellegjerde, Brusse‐Keizer, Marjolein, Buchtele, Nina, Buesaquillo, Christian, Bugaeva, Polina, Buisson, Marielle, Buonsenso, Danilo, Burhan, Erlina, Burrell, Aidan, Bustos, Ingrid G.; Butnaru, Denis, Cabie, André, Cabral, Susana, Caceres, Eder, Cadoz, Cyril, Calligy, Kate, Calvache, Jose Andres, Camões, João, Campana, Valentine, Campbell, Paul, Campisi, Josie, Canepa, Cecilia, Cantero, Mireia, Caraux‐Paz, Pauline, Cárcel, Sheila, Cardellino, Chiara Simona, Cardoso, Sofia, Cardoso, Filipe, Cardoso, Filipa, Cardoso, Nelson, Carelli, Simone, Carlier, Nicolas, Carmoi, Thierry, Carney, Gayle, Carqueja, Inês, Carret, Marie‐Christine, Carrier, François Martin, Carroll, Ida, Carson, Gail, Casanova, Maire‐Laure, Cascão, Mariana, Casey, Siobhan, Casimiro, José, Cassandra, Bailey, Castañeda, Silvia, Castanheira, Nidyanara, Castor‐Alexandre, Guylaine, Castrillón, Henry, Castro, Ivo, Catarino, Ana, Catherine, François‐Xavier, Cattaneo, Paolo, Cavalin, Roberta, Cavalli, Giulio Giovanni, Cavayas, Alexandros, Ceccato, Adrian, Cervantes‐Gonzalez, Minerva, Chair, Anissa, Chakveatze, Catherine, Chan, Adrienne, Chand, Meera, Auger, Christelle Chantalat, Chapplain, Jean‐Marc, Chas, Julie, Chatterjee, Allegra, Chaudry, Mobin, Iñiguez, Jonathan Samuel Chávez, Chen, Anjellica, Chen, Yih‐Sharng, Cheng, Matthew Pellan, Cheret, Antoine, Chiarabini, Thibault, Chica, Julian, Chidambaram, Suresh Kumar, Tho, Leong Chin, Chirouze, Catherine, Chiumello, Davide, Cho, Sung‐Min, Cholley, Bernard, Chopin, Marie‐Charlotte, Chow, Ting Soo, Chow, Yock Ping, Chua, Jonathan, Chua, Hiu Jian, Cidade, Jose Pedro, Herreros, José Miguel Cisneros, Citarella, Barbara Wanjiru, Ciullo, Anna, Clarke, Jennifer, Clarke, Emma, Granado, Rolando Claure‐Del, Clohisey, Sara, Cobb, Perren J.; Codan, Cassidy, Cody, Caitriona, Coelho, Alexandra, Coles, Megan, Colin, Gwenhaël, Collins, Michael, Colombo, Sebastiano Maria, Combs, Pamela, Connor, Marie, Conrad, Anne, Contreras, Sofía, Conway, Elaine, Cooke, Graham S.; Copland, Mary, Cordel, Hugues, Corley, Amanda, Cornelis, Sabine, Cornet, Alexander Daniel, Corpuz, Arianne Joy, Cortegiani, Andrea, Corvaisier, Grégory, Costigan, Emma, Couffignal, Camille, Couffin‐Cadiergues, Sandrine, Courtois, Roxane, Cousse, Stéphanie, Cregan, Rachel, Croonen, Sabine, Crowl, Gloria, Crump, Jonathan, Cruz, Claudina, Bermúdez, Juan Luis Cruz, Rojo, Jaime Cruz, Csete, Marc, Cullen, Ailbhe, Cummings, Matthew, Curley, Gerard, Curlier, Elodie, Curran, Colleen, Custodio, Paula, da Silva Filipe, Ana, Da Silveira, Charlene, Dabaliz, Al‐Awwab, Dagens, Andrew, Dahl, John Arne, Dahly, Darren, Dalton, Heidi, Dalton, Jo, Daly, Seamus, Daneman, Nick, Daniel, Corinne, Dankwa, Emmanuelle A.; Dantas, Jorge, D'Aragon, Frédérick, de Loughry, Gillian, de Mendoza, Diego, De Montmollin, Etienne, de Oliveira França, Rafael Freitas, de Pinho Oliveira, Ana Isabel, De Rosa, Rosanna, De Rose, Cristina, de Silva, Thushan, de Vries, Peter, Deacon, Jillian, Dean, David, Debard, Alexa, Debray, Marie‐Pierre, DeCastro, Nathalie, Dechert, William, Deconninck, Lauren, Decours, Romain, Defous, Eve, Delacroix, Isabelle, Delaveuve, Eric, Delavigne, Karen, Delfos, Nathalie M.; Deligiannis, Ionna, Dell'Amore, Andrea, Delmas, Christelle, Delobel, Pierre, Delsing, Corine, Demonchy, Elisa, Denis, Emmanuelle, Deplanque, Dominique, Depuydt, Pieter, Desai, Mehul, Descamps, Diane, Desvallées, Mathilde, Dewayanti, Santi, Dhanger, Pathik, Diallo, Alpha, Diamantis, Sylvain, Dias, André, Diaz, Juan Jose, Diaz, Priscila, Diaz, Rodrigo, Didier, Kévin, Diehl, Jean‐Luc, Dieperink, Wim, Dimet, Jérôme, Dinot, Vincent, Diop, Fara, Diouf, Alphonsine, Dishon, Yael, Djossou, Félix, Docherty, Annemarie B.; Doherty, Helen, Dondorp, Arjen M.; Donnelly, Maria, Donnelly, Christl A.; Donohue, Sean, Donohue, Yoann, Donohue, Chloe, Doran, Peter, Dorival, Céline, D'Ortenzio, Eric, Douglas, James Joshua, Douma, Renee, Dournon, Nathalie, Downer, Triona, Downey, Joanne, Downing, Mark, Drake, Tom, Driscoll, Aoife, Dryden, Murray, Fonseca, Claudio Duarte, Dubee, Vincent, Dubos, François, Ducancelle, Alexandre, Duculan, Toni, Dudman, Susanne, Duggal, Abhijit, Dunand, Paul, Dunning, Jake, Duplaix, Mathilde, Durante‐Mangoni, Emanuele, Durham, Lucian, Dussol, Bertrand, Duthoit, Juliette, Duval, Xavier, Dyrhol‐Riise, Anne Margarita, Ean, Sim Choon, Echeverria‐Villalobos, Marco, Egan, Siobhan, Eggesbø, Linn Margrete, Eira, Carla, El Sanharawi, Mohammed, Elapavaluru, Subbarao, Elharrar, Brigitte, Ellerbroek, Jacobien, Ellingjord‐Dale, Merete, Eloy, Philippine, Elshazly, Tarek, Elyazar, Iqbal, Enderle, Isabelle, Endo, Tomoyuki, Eng, Chan Chee, Engelmann, Ilka, Enouf, Vincent, Epaulard, Olivier, Escher, Martina, Esperatti, Mariano, Esperou, Hélène, Esposito‐Farese, Marina, Estevão, João, Etienne, Manuel, Ettalhaoui, Nadia, Everding, Anna Greti, Evers, Mirjam, Fabre, Marc, Fabre, Isabelle, Faheem, Amna, Fahy, Arabella, Fairfield, Cameron J.; Fakar, Zul, Fareed, Komal, Faria, Pedro, Farooq, Ahmed, Fateena, Hanan, Fatoni, Arie Zainul, Faure, Karine, Favory, Raphaël, Fayed, Mohamed, Feely, Niamh, Feeney, Laura, Fernandes, Jorge, Fernandes, Marília Andreia, Fernandes, Susana, Ferrand, François‐Xavier, Devouge, Eglantine Ferrand, Ferrão, Joana, Ferraz, Mário, Ferreira, Sílvia, Ferreira, Isabel, Ferreira, Benigno, Ferrer‐Roca, Ricard, Ferriere, Nicolas, Ficko, Céline, Figueiredo‐Mello, Claudia, Finlayson, William, Fiorda, Juan, Flament, Thomas, Flateau, Clara, Fletcher, Tom, Florio, Letizia Lucia, Flynn, Deirdre, Foley, Claire, Foley, Jean, Fomin, Victor, Fonseca, Tatiana, Fontela, Patricia, Forsyth, Simon, Foster, Denise, Foti, Giuseppe, Fourn, Erwan, Fowler, Robert A.; Fraher, Marianne, Franch‐Llasat, Diego, Fraser, John F.; Fraser, Christophe, Freire, Marcela Vieira, Ribeiro, Ana Freitas, Friedrich, Caren, Fry, Stéphanie, Fuentes, Nora, Fukuda, Masahiro, Argin, G.; Gaborieau, Valérie, Gaci, Rostane, Gagliardi, Massimo, Gagnard, Jean‐Charles, Gagneux‐Brunon, Amandine, Gaião, Sérgio, Skeie, Linda Gail, Gallagher, Phil, Gamble, Carrol, Gani, Yasmin, Garan, Arthur, Garcia, Rebekha, Barrio, Noelia García, Garcia‐Diaz, Julia, Garcia‐Gallo, Esteban, Garimella, Navya, Garot, Denis, Garrait, Valérie, Gauli, Basanta, Gault, Nathalie, Gavin, Aisling, Gavrylov, Anatoliy, Gaymard, Alexandre, Gebauer, Johannes, Geraud, Eva, Morlaes, Louis Gerbaud, Germano, Nuno, Ghisulal, Praveen Kumar, Ghosn, Jade, Giani, Marco, Gibson, Jess, Gigante, Tristan, Gilg, Morgane, Gilroy, Elaine, Giordano, Guillermo, Girvan, Michelle, Gissot, Valérie, Glikman, Daniel, Glybochko, Petr, Gnall, Eric, Goco, Geraldine, Goehringer, François, Goepel, Siri, Goffard, Jean‐Christophe, Goh, Jin Yi, Golob, Jonathan, Gomez, Kyle, Gómez‐Junyent, Joan, Gominet, Marie, Gonçalves, Bronner P.; Gonzalez, Alicia, Gordon, Patricia, Gorenne, Isabelle, Goubert, Laure, Goujard, Cécile, Goulenok, Tiphaine, Grable, Margarite, Graf, Jeronimo, Grandin, Edward Wilson, Granier, Pascal, Grasselli, Giacomo, Green, Christopher A.; Greene, Courtney, Greenhalf, William, Greffe, Segolène, Grieco, Domenico Luca, Griffee, Matthew, Griffiths, Fiona, Grigoras, Ioana, Groenendijk, Albert, Lordemann, Anja Grosse, Gruner, Heidi, Gu, Yusing, Guedj, Jérémie, Guego, Martin, Guellec, Dewi, Guerguerian, Anne‐Marie, Guerreiro, Daniela, Guery, Romain, Guillaumot, Anne, Guilleminault, Laurent, Guimarães de Castro, Maisa, Guimard, Thomas, Haalboom, Marieke, Haber, Daniel, Habraken, Hannah, Hachemi, Ali, Hackmann, Amy, Hadri, Nadir, Haidri, Fakhir, Hakak, Sheeba, Hall, Adam, Hall, Matthew, Halpin, Sophie, Hameed, Jawad, Hamer, Ansley, Hamers, Raph L.; Hamidfar, Rebecca, Hammarström, Bato, Hammond, Terese, Han, Lim Yuen, Haniffa, Rashan, Hao, Kok Wei, Hardwick, Hayley, Harrison, Ewen M.; Harrison, Janet, Harrison, Samuel Bernard Ekow, Hartman, Alan, Hasan, Mohd Shahnaz, Hashmi, Junaid, Hayat, Muhammad, Hayes, Ailbhe, Hays, Leanne, Heerman, Jan, Heggelund, Lars, Hendry, Ross, Hennessy, Martina, Henriquez‐Trujillo, Aquiles, Hentzien, Maxime, Hernandez‐Montfort, Jaime, Hershey, Andrew, Hesstvedt, Liv, Hidayah, Astarini, Higgins, Eibhilin, Higgins, Dawn, Higgins, Rupert, Hinchion, Rita, Hinton, Samuel, Hiraiwa, Hiroaki, Hirkani, Haider, Hitoto, Hikombo, Ho, Yi Bin, Ho, Antonia, Hoctin, Alexandre, Hoffmann, Isabelle, Hoh, Wei Han, Hoiting, Oscar, Holt, Rebecca, Holter, Jan Cato, Horby, Peter, Horcajada, Juan Pablo, Hoshino, Koji, Houas, Ikram, Hough, Catherine L.; Houltham, Stuart, Hsu, Jimmy Ming‐Yang, Hulot, Jean‐Sébastien, Huo, Stella, Hurd, Abby, Hussain, Iqbal, Ijaz, Samreen, Illes, Hajnal‐Gabriela, Imbert, Patrick, Imran, Mohammad, Sikander, Rana Imran, Imtiaz, Aftab, Inácio, Hugo, Dominguez, Carmen Infante, Ing, Yun Sii, Iosifidis, Elias, Ippolito, Mariachiara, Isgett, Sarah, Isidoro, Tiago, Ismail, Nadiah, Isnard, Margaux, Istre, Mette Stausland, Itai, Junji, Ivulich, Daniel, Jaafar, Danielle, Jaafoura, Salma, Jabot, Julien, Jackson, Clare, Jamieson, Nina, Jaquet, Pierre, Jaud‐Fischer, Coline, Jaureguiberry, Stéphane, Jaworsky, Denise, Jego, Florence, Jelani, Anilawati Mat, Jenum, Synne, Jimbo‐Sotomayor, Ruth, Joe, Ong Yiaw, Jorge García, Ruth N.; Jørgensen, Silje Bakken, Joseph, Cédric, Joseph, Mark, Joshi, Swosti, Jourdain, Mercé, Jouvet, Philippe, Jung, Hanna, Jung, Anna, Juzar, Dafsah, Kafif, Ouifiya, Kaguelidou, Florentia, Kaisbain, Neerusha, Kaleesvran, Thavamany, Kali, Sabina, Kalicinska, Alina, Kalleberg, Karl Trygve, Kalomoiri, Smaragdi, Kamaluddin, Muhammad Aisar Ayadi, Kamaruddin, Zul Amali Che, Kamarudin, Nadiah, Kamineni, Kavita, Kandamby, Darshana Hewa, Kandel, Chris, Kang, Kong Yeow, Kanwal, Darakhshan, Karpayah, Pratap, Kartsonaki, Christiana, Kasugai, Daisuke, Kataria, Anant, Katz, Kevin, Kaur, Aasmine, Kay, Christy, Keane, Hannah, Keating, Seán, Kedia, Pulak, Kelly, Claire, Kelly, Yvelynne, Kelly, Andrea, Kelly, Niamh, Kelly, Aoife, Kelly, Sadie, Kelsey, Maeve, Kennedy, Ryan, Kennon, Kalynn, Kernan, Maeve, Kerroumi, Younes, Keshav, Sharma, Khalid, Imrana, Khalid, Osama, Khalil, Antoine, Khan, Coralie, Khan, Irfan, Khan, Quratul Ain, Khanal, Sushil, Khatak, Abid, Khawaja, Amin, Kherajani, Krish, Kho, Michelle E.; Khoo, Ryan, Khoo, Denisa, Khoo, Saye, Khoso, Nasir, Kiat, Khor How, Kida, Yuri, Kiiza, Peter, Granerud, Beathe Kiland, Kildal, Anders Benjamin, Kim, Jae Burm, Kimmoun, Antoine, Kindgen‐Milles, Detlef, King, Alexander, Kitamura, Nobuya, Kjetland, Eyrun Floerecke Kjetland, Klenerman, Paul, Klont, Rob, Bekken, Gry Kloumann, Knight, Stephen R.; Kobbe, Robin, Kodippily, Chamira, Vasconcelos, Malte Kohns, Koirala, Sabin, Komatsu, Mamoru, Kosgei, Caroline, Kpangon, Arsène, Krawczyk, Karolina, Krishnan, Vinothini, Krishnan, Sudhir, Kruglova, Oksana, Kumar, Ganesh, Kumar, Deepali, Kumar, Mukesh, Vecham, Pavan Kumar, Kuriakose, Dinesh, Kurtzman, Ethan, Kutsogiannis, Demetrios, Kutsyna, Galyna, Kyriakoulis, Konstantinos, Lachatre, Marie, Lacoste, Marie, Laffey, John G.; Lagrange, Marie, Laine, Fabrice, Lairez, Olivier, Lakhey, Sanjay, Lalueza, Antonio, Lambert, Marc, Lamontagne, François, Langelot‐Richard, Marie, Langlois, Vincent, Lantang, Eka Yudha, Lanza, Marina, Laouénan, Cédric, Laribi, Samira, Lariviere, Delphine, Lasry, Stéphane, Lath, Sakshi, Latif, Naveed, Launay, Odile, Laureillard, Didier, Lavie‐Badie, Yoan, Law, Andy, Lawrence, Teresa, Lawrence, Cassie, Le, Minh, Le Bihan, Clément, Le Bris, Cyril, Le Falher, Georges, Le Fevre, Lucie, Le Hingrat, Quentin, Le Maréchal, Marion, Le Mestre, Soizic, Le Moal, Gwenaël, Le Moing, Vincent, Le Nagard, Hervé, Le Turnier, Paul, Leal, Ema, Santos, Marta Leal, Lee, Heng Gee, Lee, Biing Horng, Lee, Yi Lin, Lee, Todd C.; Lee, James, Lee, Jennifer, Lee, Su Hwan, Leeming, Gary, Lefebvre, Laurent, Lefebvre, Bénédicte, Lefèvre, Benjamin, LeGac, Sylvie, Lelievre, Jean‐Daniel, Lellouche, François, Lemaignen, Adrien, Lemee, Véronique, Lemeur, Anthony, Lemmink, Gretchen, Lene, Ha Sha, Lennon, Jenny, León, Rafael, Leone, Marc, Leone, Michela, Lepiller, Quentin, Lescure, François‐Xavier, Lesens, Olivier, Lesouhaitier, Mathieu, Lester‐Grant, Amy, Levy, Yves, Levy, Bruno, Levy‐Marchal, Claire, Lewandowska, Katarzyna, L'Her, Erwan, Bassi, Gianluigi Li, Liang, Janet, Liaquat, Ali, Liegeon, Geoffrey, Lim, Kah Chuan, Lim, Wei Shen, Lima, Chantre, Lina, Lim, Lina, Bruno, Lind, Andreas, Lingad, Maja Katherine, Lingas, Guillaume, Lion‐Daolio, Sylvie, Lissauer, Samantha, Liu, Keibun, Livrozet, Marine, Lizotte, Patricia, Loforte, Antonio, Lolong, Navy, Loon, Leong Chee, Lopes, Diogo, Lopez‐Colon, Dalia, Lopez‐Revilla, Jose W.; Loschner, Anthony L.; Loubet, Paul, Loufti, Bouchra, Louis, Guillame, Lourenco, Silvia, Lovelace‐Macon, Lara, Low, Lee Lee, Lowik, Marije, Loy, Jia Shyi, Lucet, Jean Christophe, Bermejo, Carlos Lumbreras, Luna, Carlos M.; Lungu, Olguta, Luong, Liem, Luque, Nestor, Luton, Dominique, Lwin, Nilar, Lyons, Ruth, Maasikas, Olavi, Mabiala, Oryane, Machado, Moïse, Macheda, Gabriel, Madiha, Hashmi, Maestro de la Calle, Guillermo, Mahieu, Rafael, Mahy, Sophie, Maia, Ana Raquel, Maier, Lars S.; Maillet, Mylène, Maitre, Thomas, Malfertheiner, Maximilian, Malik, Nadia, Mallon, Paddy, Maltez, Fernando, Malvy, Denis, Manda, Victoria, Mandelbrot, Laurent, Manetta, Frank, Mankikian, Julie, Manning, Edmund, Manuel, Aldric, Sant'Ana Malaque, Ceila Maria, Marino, Flávio, Marino, Daniel, Markowicz, Samuel, Maroun Eid, Charbel, Marques, Ana, Marquis, Catherine, Marsh, Brian, Marsh, Laura, Marshal, Megan, Marshall, John, Martelli, Celina Turchi, Martin, Dori‐Ann, Martin, Emily, Martin‐Blondel, Guillaume, Martin‐Loeches, Ignacio, Martinot, Martin, Martin‐Quiros, Alejandro, Martins, João, Martins, Ana, Martins, Nuno, Rego, Caroline Martins, Martucci, Gennaro, Martynenko, Olga, Marwali, Eva Miranda, Marzukie, Marsilla, Maslove, David, Mason, Sabina, Masood, Sobia, Nor, Basri Mat, Matan, Moshe, Mathew, Meghena, Mathieu, Daniel, Mattei, Mathieu, Matulevics, Romans, Maulin, Laurence, Maxwell, Michael, Maynar, Javier, Mazzoni, Thierry, Evoy, Natalie Mc, Sweeney, Lisa Mc, McArthur, Colin, McArthur, Colin, McCarthy, Anne, McCarthy, Aine, McCloskey, Colin, McConnochie, Rachael, McDermott, Sherry, McDonald, Sarah E.; McElroy, Aine, McElwee, Samuel, McEneany, Victoria, McGeer, Allison, McKay, Chris, McKeown, Johnny, McLean, Kenneth A.; McNally, Paul, McNicholas, Bairbre, McPartlan, Elaine, Meaney, Edel, Mear‐Passard, Cécile, Mechlin, Maggie, Meher, Maqsood, Mehkri, Omar, Mele, Ferruccio, Melo, Luis, Memon, Kashif, Mendes, Joao Joao, Menkiti, Ogechukwu, Menon, Kusum, Mentré, France, Mentzer, Alexander J.; Mercier, Noémie, Mercier, Emmanuelle, Merckx, Antoine, Mergeay‐Fabre, Mayka, Mergler, Blake, Merson, Laura, Mesquita, António, Meta, Roberta, Metwally, Osama, Meybeck, Agnès, Meyer, Dan, Meynert, Alison M.; Meysonnier, Vanina, Meziane, Amina, Mezidi, Mehdi, Michelanglei, Céline, Michelet, Isabelle, Mihelis, Efstathia, Mihnovit, Vladislav, Miranda‐Maldonado, Hugo, Misnan, Nor Arisah, Mohamed, Tahira Jamal, Mohamed, Nik Nur Eliza, Moin, Asma, Molina, David, Molinos, Elena, Molloy, Brenda, Mone, Mary, Monteiro, Agostinho, Montes, Claudia, Montrucchio, Giorgia, Moore, Shona C.; Moore, Sarah, Cely, Lina Morales, Moro, Lucia, Morton, Ben, Motherway, Catherine, Motos, Ana, Mouquet, Hugo, Perrot, Clara Mouton, Moyet, Julien, Mudara, Caroline, Mufti, Aisha Kalsoom, Muh, Ng Yong, Muhamad, Dzawani, Mullaert, Jimmy, Müller, Fredrik, Müller, Karl Erik, Munblit, Daniel, Muneeb, Syed, Munir, Nadeem, Munshi, Laveena, Murphy, Aisling, Murphy, Lorna, Murphy, Aisling, Murris, Marlène, Murthy, Srinivas, Musaab, Himed, Muvindi, Himasha, Muyandy, Gugapriyaa, Myrodia, Dimitra Melia, Mohd‐Hanafiah, Farah Nadia, Nagpal, Dave, Nagrebetsky, Alex, Narasimhan, Mangala, Narayanan, Nageswaran, Khan, Rashid Nasim, Nazerali‐Maitland, Alasdair, Neant, Nadège, Neb, Holger, Nekliudov, Nikita, Nelwan, Erni, Neto, Raul, Neumann, Emily, Ng, Pauline Yeung, Ng, Wing Yiu, Nghi, Anthony, Nguyen, Duc, Choileain, Orna Ni, Leathlobhair, Niamh Ni, Nichol, Alistair, Nitayavardhana, Prompak, Nonas, Stephanie, Noordin, Nurul Amani Mohd, Noret, Marion, Norharizam, Nurul Faten Izzati, Norman, Lisa, Notari, Alessandra, Noursadeghi, Mahdad, Nowicka, Karolina, Nowinski, Adam, Nseir, Saad, Nunez, Jose I.; Nurnaningsih, Nurnaningsih, Nusantara, Dwi Utomo, Nyamankolly, Elsa, Nygaard, Anders Benteson, Brien, Fionnuala O.; Callaghan, Annmarie O.; O'Callaghan, Annmarie, Occhipinti, Giovanna, Oconnor, Derbrenn, O'Donnell, Max, Ogston, Tawnya, Ogura, Takayuki, Oh, Tak‐Hyuk, O'Halloran, Sophie, O'Hearn, Katie, Ohshimo, Shinichiro, Oldakowska, Agnieszka, Oliveira, João, Oliveira, Larissa, Olliaro, Piero L.; Ong, Jee Yan, Ong, David S. Y.; Oosthuyzen, Wilna, Opavsky, Anne, Openshaw, Peter, Orakzai, Saijad, Orozco‐Chamorro, Claudia Milena, Ortoleva, Jamel, Osatnik, Javier, O'Shea, Linda, O'Sullivan, Miriam, Othman, Siti Zubaidah, Ouamara, Nadia, Ouissa, Rachida, Oziol, Eric, Pagadoy, Maïder, Pages, Justine, Palacios, Mario, Palacios, Amanda, Palmarini, Massimo, Panarello, Giovanna, Panda, Prasan Kumar, Paneru, Hem, Pang, Lai Hui, Panigada, Mauro, Pansu, Nathalie, Papadopoulos, Aurélie, Parke, Rachael, Parker, Melissa, Parra, Briseida, Pasha, Taha, Pasquier, Jérémie, Pastene, Bruno, Patauner, Fabian, Patel, Drashti, Pathmanathan, Mohan Dass, Patrão, Luís, Patricio, Patricia, Patrier, Juliette, Patterson, Lisa, Pattnaik, Rajyabardhan, Paul, Mical, Paul, Christelle, Paulos, Jorge, Paxton, William A.; Payen, Jean‐François, Peariasamy, Kalaiarasu, Jiménez, Miguel Pedrera, Peek, Giles J.; Peelman, Florent, Peiffer‐Smadja, Nathan, Peigne, Vincent, Pejkovska, Mare, Pelosi, Paolo, Peltan, Ithan D.; Pereira, Rui, Perez, Daniel, Periel, Luis, Perpoint, Thomas, Pesenti, Antonio, Pestre, Vincent, Petrou, Lenka, Petrovic, Michele, Petrov‐Sanchez, Ventzislava, Pettersen, Frank Olav, Peytavin, Gilles, Pharand, Scott, Picard, Walter, Picone, Olivier, de Piero, Maria, Pierobon, Carola, Piersma, Djura, Pimentel, Carlos, Pinto, Raquel, Pires, Catarina, Pironneau, Isabelle, Piroth, Lionel, Pitaloka, Ayodhia, Pius, Riinu, Plantier, Laurent, Png, Hon Shen, Poissy, Julien, Pokeerbux, Ryadh, Pokorska‐Spiewak, Maria, Poli, Sergio, Pollakis, Georgios, Ponscarme, Diane, Popielska, Jolanta, Porto, Diego Bastos, Post, Andra‐Maris, Postma, Douwe F.; Povoa, Pedro, Póvoas, Diana, Powis, Jeff, Prapa, Sofia, Preau, Sébastien, Prebensen, Christian, Preiser, Jean‐Charles, Prinssen, Anton, Pritchard, Mark G.; Priyadarshani, Gamage Dona Dilanthi, Proença, Lucia, Pudota, Sravya, Puéchal, Oriane, Semedi, Bambang Pujo, Pulicken, Mathew, Purcell, Gregory, Quesada, Luisa, Quinones‐Cardona, Vilmaris, González, Víctor Quirós, Quist‐Paulsen, Else, Quraishi, Mohammed, Rabaa, Maia, Rabaud, Christian, Rabindrarajan, Ebenezer, Rafael, Aldo, Rafiq, Marie, Rahardjani, Mutia, Rahman, Rozanah Abd, Rahman, Ahmad Kashfi Haji Ab, Rahutullah, Arsalan, Rainieri, Fernando, Rajahram, Giri Shan, Ramachandran, Pratheema, Ramakrishnan, Nagarajan, Ramli, Ahmad Afiq, Rammaert, Blandine, Ramos, Grazielle Viana, Rana, Asim, Rangappa, Rajavardhan, Ranjan, Ritika, Rapp, Christophe, Rashan, Aasiyah, Rashan, Thalha, Rasheed, Ghulam, Rasmin, Menaldi, Rätsep, Indrek, Rau, Cornelius, Ravi, Tharmini, Raza, Ali, Real, Andre, Rebaudet, Stanislas, Redl, Sarah, Reeve, Brenda, Rehman, Attaur, Reid, Liadain, Reikvam, Dag Henrik, Reis, Renato, Rello, Jordi, Remppis, Jonathan, Remy, Martine, Ren, Hongru, Renk, Hanna, Resseguier, Anne‐Sophie, Revest, Matthieu, Rewa, Oleksa, Reyes, Luis Felipe, Reyes, Tiago, Ribeiro, Maria Ines, Ricchiuto, Antonia, Richardson, David, Richardson, Denise, Richier, Laurent, Ridzuan, Siti Nurul Atikah Ahmad, Riera, Jordi, Rios, Ana L.; Rishu, Asgar, Rispal, Patrick, Risso, Karine, Nuñez, Maria Angelica Rivera, Rizer, Nicholas, Robba, Chiara, Roberto, André, Roberts, Stephanie, Robertson, David L.; Robineau, Olivier, Roche‐Campo, Ferran, Rodari, Paola, Rodeia, Simão, Abreu, Julia Rodriguez, Roessler, Bernhard, Roger, Pierre‐Marie, Roger, Claire, Roilides, Emmanuel, Rojek, Amanda, Romaru, Juliette, Roncon‐Albuquerque, Roberto, Roriz, Mélanie, Rosa‐Calatrava, Manuel, Rose, Michael, Rosenberger, Dorothea, Roslan, Nurul Hidayah Mohammad, Rossanese, Andrea, Rossetti, Matteo, Rossignol, Bénédicte, Rossignol, Patrick, Rousset, Stella, Roy, Carine, Roze, Benoît, Rusmawatiningtyas, Desy, Russell, Clark D.; Ryan, Maria, Ryan, Maeve, Ryckaert, Steffi, Holten, Aleksander Rygh, Saba, Isabela, Sadaf, Sairah, Sadat, Musharaf, Sahraei, Valla, Saint‐Gilles, Maximilien, Sakiyalak, Pranya, Salahuddin, Nawal, Salazar, Leonardo, Saleem, Jodat, Sales, Gabriele, Sallaberry, Stéphane, Salmon Gandonniere, Charlotte, Salvator, Hélène, Sanchez, Olivier, Sanchez‐Miralles, Angel, Sancho‐Shimizu, Vanessa, Sandhu, Gyan, Sandhu, Zulfiqar, Sandrine, Pierre‐François, Sandulescu, Oana, Santos, Marlene, Sarfo‐Mensah, Shirley, Banheiro, Bruno Sarmento, Sarmiento, Iam Claire E.; Sarton, Benjamine, Satya, Ankana, Satyapriya, Sree, Satyawati, Rumaisah, Saviciute, Egle, Savvidou, Parthena, Saw, Yen Tsen, Schaffer, Justin, Schermer, Tjard, Scherpereel, Arnaud, Schneider, Marion, Schroll, Stephan, Schwameis, Michael, Schwartz, Gary, Scott, Janet T.; Scott‐Brown, James, Sedillot, Nicholas, Seitz, Tamara, Selvanayagam, Jaganathan, Selvarajoo, Mageswari, Semaille, Caroline, Semple, Malcolm G.; Senian, Rasidah Bt, Senneville, Eric, Sequeira, Filipa, Sequeira, Tânia, Neto, Ary Serpa, Balazote, Pablo Serrano, Shadowitz, Ellen, Shahidan, Syamin Asyraf, Shamsah, Mohammad, Shankar, Anuraj, Sharjeel, Shaikh, Sharma, Pratima, Shaw, Catherine A.; Shaw, Victoria, Sheharyar, Ashraf, Shetty, Rohan, Shetty, Rajesh Mohan, Shi, Haixia, Shiekh, Mohiuddin, Shime, Nobuaki, Shimizu, Keiki, Shrapnel, Sally, Shrestha, Pramesh Sundar, Shrestha, Shubha Kalyan, Shum, Hoi Ping, Mohammed, Nassima Si, Siang, Ng Yong, Sibiude, Jeanne, Siddiqui, Atif, Sigfrid, Louise, Sillaots, Piret, Silva, Catarina, Silva, Rogério, Silva, Maria Joao, Heng, Benedict Sim Lim, Sin, Wai Ching, Sinatti, Dario, Singh, Punam, Singh, Budha Charan, Sitompul, Pompini Agustina, Sivam, Karisha, Skogen, Vegard, Smith, Sue, Smood, Benjamin, Smyth, Coilin, Smyth, Michelle, Snacken, Morgane, So, Dominic, Soh, Tze Vee, Solberg, Lene Bergendal, Solomon, Joshua, Solomon, Tom, Somers, Emily, Sommet, Agnès, Song, Rima, Song, Myung Jin, Song, Tae, Chia, Jack Song, Sonntagbauer, Michael, Soom, Azlan Mat, Søraas, Arne, Søraas, Camilla Lund, Sotto, Alberto, Soum, Edouard, Sousa, Marta, Sousa, Ana Chora, Uva, Maria Sousa, Souza‐Dantas, Vicente, Sperry, Alexandra, Spinuzza, Elisabetta, Darshana, B. P. Sanka Ruwan Sri, Sriskandan, Shiranee, Stabler, Sarah, Staudinger, Thomas, Stecher, Stephanie‐Susanne, Steinsvik, Trude, Stienstra, Ymkje, Stiksrud, Birgitte, Stolz, Eva, Stone, Amy, Streinu‐Cercel, Adrian, Streinu‐Cercel, Anca, Stuart, David, Stuart, Ami, Subekti, Decy, Suen, Gabriel, Suen, Jacky Y.; Sultana, Asfia, Summers, Charlotte, Supic, Dubravka, Suppiah, Deepashankari, Surovcová, Magdalena, Suwarti, Suwarti, Svistunov, Andrey, Syahrin, Sarah, Syrigos, Konstantinos, Sztajnbok, Jaques, Szuldrzynski, Konstanty, Tabrizi, Shirin, Taccone, Fabio S.; Tagherset, Lysa, Taib, Shahdattul Mawarni, Talarek, Ewa, Taleb, Sara, Talsma, Jelmer, Tamisier, Renaud, Tampubolon, Maria Lawrensia, Tan, Kim Keat, Tan, Yan Chyi, Tanaka, Taku, Tanaka, Hiroyuki, Taniguchi, Hayato, Taqdees, Huda, Taqi, Arshad, Tardivon, Coralie, Tattevin, Pierre, Taufik, M. Azhari, Tawfik, Hassan, Tedder, Richard S.; Tee, Tze Yuan, Teixeira, João, Tejada, Sofia, Tellier, Marie‐Capucine, Teoh, Sze Kye, Teotonio, Vanessa, Téoulé, François, Terpstra, Pleun, Terrier, Olivier, Terzi, Nicolas, Tessier‐Grenier, Hubert, Tey, Adrian, Thabit, Alif Adlan Mohd, Thakur, Anand, Tham, Zhang Duan, Thangavelu, Suvintheran, Thibault, Vincent, Thiberville, Simon‐Djamel, Thill, Benoît, Thirumanickam, Jananee, Thompson, Shaun, Thomson, Emma C.; Thurai, Surain Raaj Thanga, Thwaites, Ryan S.; Tierney, Paul, Tieroshyn, Vadim, Timashev, Peter S.; Timsit, Jean‐François, Vijayaraghavan, Bharath Kumar Tirupakuzhi, Tissot, Noémie, Toh, Jordan Zhien Yang, Toki, Maria, Tonby, Kristian, Tonnii, Sia Loong, Torres, Margarida, Torres, Antoni, Santos‐Olmo, Rosario Maria Torres, Torres‐Zevallos, Hernando, Towers, Michael, Trapani, Tony, Treoux, Théo, Tromeur, Cécile, Trontzas, Ioannis, Trouillon, Tiffany, Truong, Jeanne, Tual, Christelle, Tubiana, Sarah, Tuite, Helen, Turmel, Jean‐Marie, Turtle, Lance C. W.; Tveita, Anders, Twardowski, Pawel, Uchiyama, Makoto, Udayanga, P. G. Ishara, Udy, Andrew, Ullrich, Roman, Uribe, Alberto, Usman, Asad.
Influenza and Other Respiratory Viruses ; 2022.
Article in English | Web of Science | ID: covidwho-2019369

ABSTRACT

Introduction: Case definitions are used to guide clinical practice, surveillance and research protocols. However, how they identify COVID-19-hospitalised patients is not fully understood. We analysed the proportion of hospitalised patients with laboratory-confirmed COVID-19, in the ISARIC prospective cohort study database, meeting widely used case definitions. Methods: Patients were assessed using the Centers for Disease Control (CDC), European Centre for Disease Prevention and Control (ECDC), World Health Organization (WHO) and UK Health Security Agency (UKHSA) case definitions by age, region and time. Case fatality ratios (CFRs) and symptoms of those who did and who did not meet the case definitions were evaluated. Patients with incomplete data and non-laboratory-confirmed test result were excluded. Results: A total of 263,218 of the patients (42%) in the ISARIC database were included. Most patients (90.4%) were from Europe arid Central Asia. The proportions of patients meeting the case definitions were 56.8% (WHO), 74.4% (UKHSA), 81.6% (ECDC) and 82.3% (CDC). For each case definition, patients at the extremes of age distribution met the criteria less frequently than those aged 30 to 70 years;geographical and time variations were also observed. Estimated CFRs were similar for the patients who met the case definitions. However, when more patients did riot meet the case definition, the CFR increased. Conclusions: The performance of case definitions might be different in different regions and may change over time. Similarly concerning is the fact that older patients often did not meet case definitions, risking delayed medical care. While epidemiologists must balance their analytics with field applicability, ongoing revision of case definitions is necessary to improve patient care through early diagnosis and limit potential nosocomial spread.

3.
Intensive Care Med ; 48(5): 580-589, 2022 05.
Article in English | MEDLINE | ID: covidwho-1797659

ABSTRACT

PURPOSE: We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. METHODS: We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which randomised 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero. RESULTS: We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention-to-treat population, EQ-5D-5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference - 4.3%; 99% confidence interval (CI) - 11.7-3.0; relative risk 0.89; 0.72-1.09; P = 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ-5D-5L index values were 0.06 (99% CI - 0.01 to 0.12; P = 0.10) and in EQ VAS scores 4 (- 3 to 10; P = 0.22). CONCLUSION: Among patients with COVID-19 and severe hypoxaemia, dexamethasone 12 mg compared with 6 mg did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose.


Subject(s)
COVID-19 , Dexamethasone , Hypoxia , Adult , COVID-19/complications , COVID-19/drug therapy , Dexamethasone/administration & dosage , Dose-Response Relationship, Drug , Humans , Hypoxia/complications , Hypoxia/drug therapy , Patient Acuity , Quality of Life , Surveys and Questionnaires , Treatment Outcome
4.
Intensive Care Med ; 48(1): 45-55, 2022 01.
Article in English | MEDLINE | ID: covidwho-1605102

ABSTRACT

PURPOSE: We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation. METHODS: We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone. RESULTS: The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses. CONCLUSION: We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.


Subject(s)
COVID-19 , Bayes Theorem , COVID-19/drug therapy , Dexamethasone , Humans , Hypoxia , SARS-CoV-2 , Steroids
5.
JAMA ; 326(18): 1807-1817, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1527380

ABSTRACT

Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.


Subject(s)
COVID-19/drug therapy , Dexamethasone/administration & dosage , Glucocorticoids/administration & dosage , Life Support Care , Aged , COVID-19/complications , COVID-19/mortality , Dexamethasone/adverse effects , Dose-Response Relationship, Drug , Female , Glucocorticoids/adverse effects , Humans , Hypoxia/etiology , Hypoxia/therapy , Male , Middle Aged , Mycoses/etiology , Respiration, Artificial , Shock, Septic/etiology , Single-Blind Method
6.
JAMA ; 326(18): 1807-1817, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1482066

ABSTRACT

Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.


Subject(s)
COVID-19/drug therapy , Dexamethasone/administration & dosage , Glucocorticoids/administration & dosage , Life Support Care , Aged , COVID-19/complications , COVID-19/mortality , Dexamethasone/adverse effects , Dose-Response Relationship, Drug , Female , Glucocorticoids/adverse effects , Humans , Hypoxia/etiology , Hypoxia/therapy , Male , Middle Aged , Mycoses/etiology , Respiration, Artificial , Shock, Septic/etiology , Single-Blind Method
7.
Acta Anaesthesiol Scand ; 65(5): 702-710, 2021 05.
Article in English | MEDLINE | ID: covidwho-1081822

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID-19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID-19 and severe hypoxia. METHODS: This protocol outlines the rationale and statistical methods for a secondary, pre-planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle-negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre-defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors. DISCUSSION: This secondary, pre-planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04509973; EudraCT: 2020-003363-25.


Subject(s)
COVID-19/drug therapy , Dexamethasone/administration & dosage , Hypoxia/drug therapy , Randomized Controlled Trials as Topic , SARS-CoV-2 , Bayes Theorem , Humans
8.
Indian J Crit Care Med ; 24(4): 242-244, 2020 Apr.
Article in English | MEDLINE | ID: covidwho-611652

ABSTRACT

How to cite this article: Vijayaraghavan BKT, Venkataraman R, Ramakrishnan N. Critical Care Epidemiology and Research in the Face of a Pandemic: An Opportunity in a Crisis. Indian J Crit Care Med 2020;24(4):242-244.

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